Gender differences in contributions of emotion to psychopathy and antisocial personality disorder.

PubMed

Rogstad, Jill E; Rogers, Richard

2008-12-01

Traditional conceptualizations of psychopathy highlight the importance of affective features as they relate to social deviance; however, little empirical research has actually investigated specific roles of emotion and emotion processing with respect to antisocial conduct. Antisocial personality disorder (APD), prevalent in forensic populations, is commonly associated with psychopathy despite the notable omission of such core affective features in its diagnosis. In this paper, we review the empirical literature on the contribution of emotion to psychopathy and APD, highlighting in particular research on emotion processing and various facets of emotional expression, including empathy and alexithymia. Research findings are discussed on gender differences in emotional functioning and their likely effects on the assessment of psychopathy and APD. Given the known gender differences in the expressions of emotion, the article concludes with recommendations to bridge research for different offender groups, including psychopathy and APD.

Differential effects of psychopathy and antisocial personality disorder symptoms on cognitive and fear processing in female offenders

PubMed Central

Anton, Marja E.; Vitale, Jennifer E.; Curtin, John J.; Newman, Joseph P.

2012-01-01

Psychopathy and antisocial personality disorder (APD) have long been considered important risk factors for criminal behavior and incarceration. However, little is known about the psychobiological underpinnings that give rise to the disinhibited behavior of female offenders. Using an instructed fear-conditioning paradigm and a sample of incarcerated female offenders, we manipulated attentional focus and cognitive load to characterize and differentiate between the dysfunctional cognitive and affective processes associated with these syndromes. We used fear-potentiated startle (FPS) and event-related potentials as measures of affective and cognitive processing, respectively. After controlling for APD symptoms, psychopathic women displayed greater FPS while attending directly to threat-relevant stimuli and displayed less FPS while performing a demanding task that directed attention to threat-irrelevant information. Conversely, controlling for psychopathy, women with high APD symptoms displayed less overall FPS, especially when instructed to focus on threat-relevant stimuli. However, as the demands on cognitive resources increased, they displayed greater FPS. For both psychopathy and APD, analysis of the event-related potentials qualified these findings and further specified the abnormal cognitive processes associated with these two syndromes. Overall, simultaneous analysis of psychopathy and APD revealed distinct patterns of cognitive processing and fear reactivity. PMID:22886692

Relation between Working Memory Capacity and Auditory Stream Segregation in Children with Auditory Processing Disorder.

PubMed

Lotfi, Yones; Mehrkian, Saiedeh; Moossavi, Abdollah; Zadeh, Soghrat Faghih; Sadjedi, Hamed

2016-03-01

This study assessed the relationship between working memory capacity and auditory stream segregation by using the concurrent minimum audible angle in children with a diagnosed auditory processing disorder (APD). The participants in this cross-sectional, comparative study were 20 typically developing children and 15 children with a diagnosed APD (age, 9-11 years) according to the subtests of multiple-processing auditory assessment. Auditory stream segregation was investigated using the concurrent minimum audible angle. Working memory capacity was evaluated using the non-word repetition and forward and backward digit span tasks. Nonparametric statistics were utilized to compare the between-group differences. The Pearson correlation was employed to measure the degree of association between working memory capacity and the localization tests between the 2 groups. The group with APD had significantly lower scores than did the typically developing subjects in auditory stream segregation and working memory capacity. There were significant negative correlations between working memory capacity and the concurrent minimum audible angle in the most frontal reference location (0° azimuth) and lower negative correlations in the most lateral reference location (60° azimuth) in the children with APD. The study revealed a relationship between working memory capacity and auditory stream segregation in children with APD. The research suggests that lower working memory capacity in children with APD may be the possible cause of the inability to segregate and group incoming information.

Antisocial Personality as a Neurodevelopmental Disorder.

PubMed

Raine, Adrian

2018-05-07

Although antisocial personality disorder (APD) is one of the most researched personality disorders, it is still surprisingly resistant to treatment. This lack of clinical progress may be partly due to the failure to view APD as a neurodevelopmental disorder and to consider early interventions. After first defining what constitutes a neurodevelopmental disorder, this review evaluates the extent to which APD meets neurodevelopmental criteria, covering structural and functional brain imaging, neurocognition, genetics and epigenetics, neurochemistry, and early health risk factors. Prevention and intervention strategies for APD are then outlined, focusing on addressing early biological and health systems, followed by forensic and clinical implications. It is argued both that APD meets criteria for consideration as a neurodevelopmental disorder and that consideration should be given both to the possibility that early onset conduct disorder is neurodevelopmental in nature, and also to the inclusion of psychopathy as a specifier in future Diagnostic and Statistical Manual revisions of APD.

Auditory Processing Disorders

MedlinePlus

... Loss Hearing Loss in Seniors Hearing Aids General Information Types Features Fittings Assistive Listening & Alerting Devices Cochlear Implants Aural Rehabilitation Auditory Processing Disorders (APDs) Common Conditions Dizziness Tinnitus Who Are ...

Psychometric Evaluation of Children with Auditory Processing Disorder (APD): Comparison with Normal-Hearing and Clinical Non-APD Groups

ERIC Educational Resources Information Center

Iliadou, Vasiliki; Bamiou, Doris Eva

2012-01-01

Purpose: To investigate the clinical utility of the Children's Auditory Processing Performance Scale (CHAPPS; Smoski, Brunt, & Tannahill, 1992) to evaluate listening ability in 12-year-old children referred for auditory processing assessment. Method: This was a prospective case control study of 97 children (age range = 11;4 [years;months] to…

Evidence-based interventions of dichotic listening training, compensatory strategies and combined therapies in managing pupils with auditory processing disorders.

PubMed

Osisanya, Ayo; Adewunmi, Abiodun T

2018-02-01

The need to develop a measure of managing children with a single profile of auditory processing disorders (APDs), and differentiate between true and artefactual improvements necessitated the study. The study also sought to determine the efficacy of interventions - both single and combined on APD, against no-treatment. A randomised controlled trial of interventions (RCT) was adopted. Participants were randomly allocated to each of the intervention groups or the no intervention group. The 10 weeks intervention included 45 minutes three times a week therapeutic intervention on listening with noise and sound localisation ability in the home and school environments. 80 pupils (7-11 years) with a single profile of APD participated in the study. Treatments were effective on the cocktail party and sound localisation. The best result was realised with the combined therapy (CT), and there was no significant difference in performance in the remaining treatment groups. The intervention groups were beneficial to pupils with APD and should be adopted by clinicians.

Applicability of central auditory processing disorder models.

PubMed

Jutras, Benoît; Loubert, Monique; Dupuis, Jean-Luc; Marcoux, Caroline; Dumont, Véronique; Baril, Michèle

2007-12-01

Central auditory processing disorder ([C]APD) is a relatively recent construct that has given rise to 2 theoretical models: the Buffalo Model and the Bellis/Ferre Model. These models describe 4 and 5 (C)APD categories, respectively. The present study examines the applicability of these models to clinical practice. Neither of these models was based on data from peer-reviewed sources. This is a retrospective study that reviewed 178 records of children diagnosed with (C)APD, of which 48 were retained for analysis. More than 80% of the children could be classified into one of the Buffalo Model categories, while more than 90% remained unclassified under the Bellis/Ferre Model. This discrepancy can be explained by the fact that the classification of the Buffalo Model is based primarily on a single central auditory test (Staggered Spondaic Word), whereas the Bellis/Ferre Model classification uses a combination of auditory test results. The 2 models provide a conceptual framework for (C)APD, but they must be further refined to be fully applicable in clinical settings.

Relation between Working Memory Capacity and Auditory Stream Segregation in Children with Auditory Processing Disorder

PubMed Central

Lotfi, Yones; Mehrkian, Saiedeh; Moossavi, Abdollah; Zadeh, Soghrat Faghih; Sadjedi, Hamed

2016-01-01

Background: This study assessed the relationship between working memory capacity and auditory stream segregation by using the concurrent minimum audible angle in children with a diagnosed auditory processing disorder (APD). Methods: The participants in this cross-sectional, comparative study were 20 typically developing children and 15 children with a diagnosed APD (age, 9–11 years) according to the subtests of multiple-processing auditory assessment. Auditory stream segregation was investigated using the concurrent minimum audible angle. Working memory capacity was evaluated using the non-word repetition and forward and backward digit span tasks. Nonparametric statistics were utilized to compare the between-group differences. The Pearson correlation was employed to measure the degree of association between working memory capacity and the localization tests between the 2 groups. Results: The group with APD had significantly lower scores than did the typically developing subjects in auditory stream segregation and working memory capacity. There were significant negative correlations between working memory capacity and the concurrent minimum audible angle in the most frontal reference location (0° azimuth) and lower negative correlations in the most lateral reference location (60° azimuth) in the children with APD. Conclusion: The study revealed a relationship between working memory capacity and auditory stream segregation in children with APD. The research suggests that lower working memory capacity in children with APD may be the possible cause of the inability to segregate and group incoming information. PMID:26989281

The practices, challenges and recommendations of South African audiologists regarding managing children with auditory processing disorders

PubMed Central

Govender, Samantha; Khan, Nasim

2016-01-01

Audiologists managing children with auditory processing disorders (APD) encounter challenges that include conflicting definitions, several classification profiles, problems with differential diagnosis and a lack of standardised guidelines. The heterogeneity of the disorder and its concomitant childhood disorders makes diagnosis difficult. Linguistic and cultural issues are additional challenges faced by South African audiologists. The study aimed to describe the practices, challenges and recommendations of South African audiologists managing children with APD. A quantitative, non-experimental descriptive survey was used to obtain data from 156 audiologists registered with the Health Professions of South Africa. Findings revealed that 67% screened for APD, 42% assessed while 43% provided intervention. A variety of screening and assessment procedures were being administered, with no standard test battery identified. A range of intervention strategies being used are discussed. When the relationship between the number of years of experience and the audiologists’ level of preparedness to practice in the field of APD was compared, a statistically significant difference (p = 0.049) was seen in that participants with more than 10 years of experience were more prepared to practice in this area. Those participants having qualified as speech-language therapists and audiologists were significantly more prepared (p = 0.03) to practice than the audiologists who comprised the sample. Challenges experienced by the participants included the lack of linguistically and culturally appropriate screening and assessment tools and limited normative data. Recommendations included reviewing the undergraduate audiology training programmes, reinstituting the South African APD Taskforce, developing linguistically and culturally appropriate normative data, creating awareness among educators and involving them in the multidisciplinary team. PMID:27380913

Perception of Small Frequency Differences in Children with Auditory Processing Disorder or Specific Language Impairment

PubMed Central

Rota-Donahue, Christine; Schwartz, Richard G.; Shafer, Valerie; Sussman, Elyse S.

2016-01-01

Background Frequency discrimination is often impaired in children developing language atypically. However, findings in the detection of small frequency changes in these children are conflicting. Previous studies on children’s auditory perceptual abilities usually involved establishing differential sensitivity thresholds in sample populations who were not tested for auditory deficits. To date, there are no data comparing suprathreshold frequency discrimination ability in children tested for both auditory processing and language skills. Purpose This study examined the perception of small frequency differences (Δf) in children with auditory processing disorder (APD) and/or specific language impairment (SLI). The aim was to determine whether children with APD and children with SLI showed differences in their behavioral responses to frequency changes. Results were expected to identify different degrees of impairment and shed some light on the auditory perceptual overlap between pediatric APD and SLI. Research Design An experimental group design using a two-alternative forced-choice procedure was used to determine frequency discrimination ability for three magnitudes of Δf from the 1000-Hz base frequency. Study Sample Thirty children between 10 years of age and 12 years, 11 months of age: 17 children with APD and/or SLI, and 13 typically developing (TD) peers participated. The clinical groups included four children with APD only, four children with SLI only, and nine children with both APD and SLI. Data Collection and Analysis Behavioral data collected using headphone delivery were analyzed using the sensitivity index d′, calculated for three Δf was 2%, 5%, and 15% of the base frequency or 20, 50, and 150 Hz. Correlations between the dependent variable d′ and the independent variables measuring auditory processing and language skills were also obtained. A stepwise regression analysis was then performed. Results TD children and children with APD and/or SLI differed in the detection of small-tone Δf. In addition, APD or SLI status affected behavioral results differently. Comparisons between auditory processing test scores or language test scores and the sensitivity index d′ showed different strengths of correlation based on the magnitudes of the Δf. Auditory processing scores showed stronger correlation to the sensitivity index d′ for the small Δf, while language scores showed stronger correlation to the sensitivity index d′ for the large Δf. Conclusion Although children with APD and/or SLI have difficulty with behavioral frequency discrimination, this difficulty may stem from two different levels: a basic auditory level for children with APD and a higher language processing level for children with SLI; the frequency discrimination performance seemed to be affected by the labeling demands of the same versus different frequency discrimination task for the children with SLI. PMID:27310407

Perception of Small Frequency Differences in Children with Auditory Processing Disorder or Specific Language Impairment.

PubMed

Rota-Donahue, Christine; Schwartz, Richard G; Shafer, Valerie; Sussman, Elyse S

2016-06-01

Frequency discrimination is often impaired in children developing language atypically. However, findings in the detection of small frequency changes in these children are conflicting. Previous studies on children's auditory perceptual abilities usually involved establishing differential sensitivity thresholds in sample populations who were not tested for auditory deficits. To date, there are no data comparing suprathreshold frequency discrimination ability in children tested for both auditory processing and language skills. : This study examined the perception of small frequency differences (∆ƒ) in children with auditory processing disorder (APD) and/or specific language impairment (SLI). The aim was to determine whether children with APD and children with SLI showed differences in their behavioral responses to frequency changes. Results were expected to identify different degrees of impairment and shed some light on the auditory perceptual overlap between pediatric APD and SLI. An experimental group design using a two-alternative forced-choice procedure was used to determine frequency discrimination ability for three magnitudes of ∆ƒ from the 1000-Hz base frequency. Thirty children between 10 years of age and 12 years, 11 months of age: 17 children with APD and/or SLI, and 13 typically developing (TD) peers participated. The clinical groups included four children with APD only, four children with SLI only, and nine children with both APD and SLI. Behavioral data collected using headphone delivery were analyzed using the sensitivity index d', calculated for three ∆ƒ was 2%, 5%, and 15% of the base frequency or 20, 50, and 150 Hz. Correlations between the dependent variable d' and the independent variables measuring auditory processing and language skills were also obtained. A stepwise regression analysis was then performed. TD children and children with APD and/or SLI differed in the detection of small-tone ∆ƒ. In addition, APD or SLI status affected behavioral results differently. Comparisons between auditory processing test scores or language test scores and the sensitivity index d' showed different strengths of correlation based on the magnitudes of the ∆ƒ. Auditory processing scores showed stronger correlation to the sensitivity index d' for the small ∆ƒ, while language scores showed stronger correlation to the sensitivity index d' for the large ∆ƒ. Although children with APD and/or SLI have difficulty with behavioral frequency discrimination, this difficulty may stem from two different levels: a basic auditory level for children with APD and a higher language processing level for children with SLI; the frequency discrimination performance seemed to be affected by the labeling demands of the same versus different frequency discrimination task for the children with SLI. American Academy of Audiology.

Diagnosis and subtypes of adolescent antisocial personality disorder.

PubMed

Jones, Meredith; Westen, Drew

2010-04-01

The present study examined the application of the Antisocial Personality Disorder (APD) diagnosis to adolescents and investigated the possibility of subtypes of APD adolescents. As part of a broader study of adolescent personality in clinically-referred patients, experienced clinicians provided personality data on a randomly selected patient in their care using the SWAP-II-A personality pathology instrument. Three hundred thirteen adolescents met adult DSM-IV diagnostic criteria for APD. To characterize adolescents with the disorder, we aggregated the data to identify the items most descriptive and distinctive of APD adolescents relative to other teenagers in the sample (N = 950). Q-factor analysis identified five personality subtypes: psychopathic-like, socially withdrawn, impulsive-histrionic, emotionally dysregulated, and attentionally dysregulated. The five subtypes differed in predictable ways on a set of external criteria related to global adaptive functioning, childhood family environment, and family history of psychiatric illness. Both the APD diagnosis and the empirically derived APD subtypes provided incremental validity over and above the DSM-IV disruptive behavior disorders in predicting global adaptive functioning, number of arrests, early-onset severe externalizing pathology, and quality of peer relationships. Although preliminary, these results provide support for the use of both APD and personality-based subtyping systems in adolescents.

Auditory Processing Disorders: An Overview. ERIC Digest.

ERIC Educational Resources Information Center

Ciocci, Sandra R.

This digest presents an overview of children with auditory processing disorders (APDs), children who can typically hear information but have difficulty attending to, storing, locating, retrieving, and/or clarifying that information to make it useful for academic and social purposes. The digest begins by describing central auditory processing and…

Referral and Diagnosis of Developmental Auditory Processing Disorder in a Large, United States Hospital-Based Audiology Service.

PubMed

Moore, David R; Sieswerda, Stephanie L; Grainger, Maureen M; Bowling, Alexandra; Smith, Nicholette; Perdew, Audrey; Eichert, Susan; Alston, Sandra; Hilbert, Lisa W; Summers, Lynn; Lin, Li; Hunter, Lisa L

2018-05-01

Children referred to audiology services with otherwise unexplained academic, listening, attention, language, or other difficulties are often found to be audiometrically normal. Some of these children receive further evaluation for auditory processing disorder (APD), a controversial construct that assumes neural processing problems within the central auditory nervous system. This study focuses on the evaluation of APD and how it relates to diagnosis in one large pediatric audiology facility. To analyze electronic records of children receiving a central auditory processing evaluation (CAPE) at Cincinnati Children's Hospital, with a broad goal of understanding current practice in APD diagnosis and the test information which impacts that practice. A descriptive, cross-sectional analysis of APD test outcomes in relation to final audiologist diagnosis for 1,113 children aged 5-19 yr receiving a CAPE between 2009 and 2014. Children had a generally high level of performance on the tests used, resulting in marked ceiling effects on about half the tests. Audiologists developed the diagnostic category "Weakness" because of the large number of referred children who clearly had problems, but who did not fulfill the AAA/ASHA criteria for diagnosis of a "Disorder." A "right-ear advantage" was found in all tests for which each ear was tested, irrespective of whether the tests were delivered monaurally or dichotically. However, neither the side nor size of the ear advantage predicted the ultimate diagnosis well. Cooccurrence of CAPE with other learning problems was nearly universal, but neither the number nor the pattern of cooccurring problems was a predictor of APD diagnosis. The diagnostic patterns of individual audiologists were quite consistent. The number of annual assessments decreased dramatically during the study period. A simple diagnosis of APD based on current guidelines is neither realistic, given the current tests used, nor appropriate, as judged by the audiologists providing the service. Methods used to test for APD must recognize that any form of hearing assessment probes both sensory and cognitive processing. Testing must embrace modern methods, including digital test delivery, adaptive testing, referral to normative data, appropriate testing for young children, validated screening questionnaires, and relevant objective (physiological) methods, as appropriate. Audiologists need to collaborate with other specialists to understand more fully the behaviors displayed by children presenting with listening difficulties. To achieve progress, it is essential for clinicians and researchers to work together. As new understanding and methods become available, it will be necessary to sort out together what works and what doesn't work in the clinic, both from a theoretical and a practical perspective. American Academy of Audiology.

Auditory Processing Disorder in Relation to Developmental Disorders of Language, Communication and Attention: A Review and Critique

ERIC Educational Resources Information Center

Dawes, Piers; Bishop, Dorothy

2009-01-01

Background: Auditory Processing Disorder (APD) does not feature in mainstream diagnostic classifications such as the "Diagnostic and Statistical Manual of Mental Disorders, 4th Edition" (DSM-IV), but is frequently diagnosed in the United States, Australia and New Zealand, and is becoming more frequently diagnosed in the United Kingdom. Aims: To…

[Auditory processing and high frequency audiometry in students of São Paulo].

PubMed

Ramos, Cristina Silveira; Pereira, Liliane Desgualdo

2005-01-01

Auditory processing and auditory sensibility to high Frequency sounds. To characterize the localization processes, temporal ordering, hearing patterns and detection of high frequency sounds, looking for possible relations between these factors. 32 hearing fourth grade students, born in city of São Paulo, were submitted to: a simplified evaluation of the auditory processing; duration pattern test; high frequency audiometry. Three (9,4%) individuals presented auditory processing disorder (APD) and in one of them there was the coexistence of lower hearing thresholds in high frequency audiometry. APD associated to an auditory sensibility loss in high frequencies should be further investigated.

Speech Processing to Improve the Perception of Speech in Background Noise for Children With Auditory Processing Disorder and Typically Developing Peers.

PubMed

Flanagan, Sheila; Zorilă, Tudor-Cătălin; Stylianou, Yannis; Moore, Brian C J

2018-01-01

Auditory processing disorder (APD) may be diagnosed when a child has listening difficulties but has normal audiometric thresholds. For adults with normal hearing and with mild-to-moderate hearing impairment, an algorithm called spectral shaping with dynamic range compression (SSDRC) has been shown to increase the intelligibility of speech when background noise is added after the processing. Here, we assessed the effect of such processing using 8 children with APD and 10 age-matched control children. The loudness of the processed and unprocessed sentences was matched using a loudness model. The task was to repeat back sentences produced by a female speaker when presented with either speech-shaped noise (SSN) or a male competing speaker (CS) at two signal-to-background ratios (SBRs). Speech identification was significantly better with SSDRC processing than without, for both groups. The benefit of SSDRC processing was greater for the SSN than for the CS background. For the SSN, scores were similar for the two groups at both SBRs. For the CS, the APD group performed significantly more poorly than the control group. The overall improvement produced by SSDRC processing could be useful for enhancing communication in a classroom where the teacher's voice is broadcast using a wireless system.

[Acquired perforating dermatosis in the patient with chronic kidney disease – case report and literature review].

PubMed

Steć, Anna; Paluch-Oleś, Jolanta; Korolczuk, Agnieszka; Magdalena Grzebalska, Agnieszka; Kozioł-Montewka, Maria; Książek, Andrzej

Acquired perforating dermatosis (APD) represents a heterogenous group of skin disorders characterized histopathologically by transepithelial elimination (TEE) of dermal structures. APD is manifested clinically as multi-localized, papulo-nodular skin lesions accompanied by a refractory pruritus. APD typically coexists with long-term disorders, most often diabetic kidney disease (DKD). The paper presents a case of a 56-year-old male patient with chronic kidney disease (CKD) and concomitant acquired reactive perforating collagenosis (ARPC), which is a subtype of APD. Etiological theories of ARPC as well as current diagnostic and treatment principles in dermatosis were described. On the basis of the presented case report and the literature review attention was paid to diagnostic difficulties associated with APD. The assumption was made that APD can be an underdiagnosed disease and thus it is not treated correctly. According to the authors’ opinion, this is an important circumstance to popularize the knowledge about APD.

Neutron diffraction study of the formation kinetics of ordered antiphase domains in titanium carbohydride TiC x H y

NASA Astrophysics Data System (ADS)

Khidirov, I.

2015-09-01

The kinetics of formation and growth of ordered antiphase domains (APDs) in titanium carbohydride TiC0.50H0.21 has been investigated by neutron diffraction. A model of ordered APDs is proposed. It is established that the pronounced ordering of interstitial atoms and APDs begin at 450°C. It is shown that the period of ordered APDs ( Р ≈ 10-12) is independent of the exposure time at a constant temperature. It is found that the temperature of ordered APDs, T OAPD, increases nonlinearly with an increase in the carbon concentration in the range 0.50 ≤ C/Ti ≤ 0.70. The formation temperature of ordered APDs is found to correlate with the concentration dependence of the order-disorder transition temperature and be 0.60 of the order-disorder transition temperature: T APD = 0.60 Т С.

Readability of Questionnaires Assessing Listening Difficulties Associated with (Central) Auditory Processing Disorders

ERIC Educational Resources Information Center

Atcherson, Samuel R.; Richburg, Cynthia M.; Zraick, Richard I.; George, Cassandra M.

2013-01-01

Purpose: Eight English-language, student- or parent proxy-administered questionnaires for (central) auditory processing disorders, or (C)APD, were analyzed for readability. For student questionnaires, readability levels were checked against the approximate reading grade levels by intended administration age per the questionnaires' developers. For…

Changes in Low-Frequency Fluctuations in Patients with Antisocial Personality Disorder Revealed by Resting-State Functional MRI

PubMed Central

Jiang, Weixiong; Wang, Wei

2014-01-01

Antisocial Personality Disorder (APD) is a personality disorder that is most commonly associated with the legal and criminal justice systems. The study of the brain in APD has important implications in legal contexts and in helping ensure social stability. However, the neural contribution to the high prevalence of APD is still unclear. In this study, we used resting-state functional magnetic resonance imaging (fMRI) to investigate the underlying neural mechanisms of APD. Thirty-two healthy individuals and thirty-five patients with APD were recruited. The amplitude of low-frequency fluctuations (ALFF) was analyzed for the whole brain of all subjects. Our results showed that APD patients had a significant reduction in the ALFF in the right orbitofrontal cortex, the left temporal pole, the right inferior temporal gyrus, and the left cerebellum posterior lobe compared to normal controls. We observed that the right orbitofrontal cortex had a negative correlation between ALFF values and MMPI psychopathic deviate scores. Alterations in ALFF in these specific brain regions suggest that APD patients may be associated with abnormal activities in the fronto-temporal network. We propose that our results may contribute in a clinical and forensic context to a better understanding of APD. PMID:24598769

Predicting Future Antisocial Personality Disorder in Males from a Clinical Assessment in Childhood

ERIC Educational Resources Information Center

Lahey, Benjamin B.; Loeber, Rolf; Burke, Jeffrey D.; Applegate, Brooks

2005-01-01

It is essential to identify childhood predictors of adult antisocial personality disorder (APD) to target early prevention. It has variously been hypothesized that APD is predicted by childhood conduct disorder (CD), attention-deficit/hyperactivity disorder (ADHD), or both disorders. To test these competing hypotheses, the authors used data from a…

Daily Stress, Hearing-Specific Stress and Coping: Self-reports from Deaf or Hard of Hearing Children and Children With Auditory Processing Disorder.

PubMed

Eschenbeck, Heike; Gillé, Vera; Heim-Dreger, Uwe; Schock, Alexandra; Schott, Andrea

2017-01-01

This study evaluated stressors and coping strategies in 70 children who are deaf or hard of hearing (D/HH) or with auditory processing disorder (APD) attending Grades 5 and 6 of a school for deaf and hard-of-hearing children. Everyday general stressors and more hearing-specific stressors were examined in a hearing-specific modified stress and coping questionnaire. Reports were compared with normative data for hearing children. Regarding everyday general stressors, stress levels for children who are D/HH or with APD did not differ from those of hearing children. Within children with hearing problems, everyday stressors were experienced as more stressful than hearing-specific stressors. For coping strategies, differences between children with hearing problems (D/HH, APD) and hearing children were shown (i.e., problem solving, anger-related emotion regulation). Girls scored higher in seeking social support whereas boys reported higher amounts of media use as a way of coping. Differences regarding stress and coping between children who are D/HH and children with APD were minor; D/HH children reported more social support seeking. Implications for assessment and resource promotion are discussed. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The Danish test battery for auditory processing disorder evaluated with patient and control data.

PubMed

Raben Pedersen, Ellen

2018-06-10

This study evaluates the Danish test battery for auditory processing disorder (APD). The battery consists of four behavioural tests, two speech and two non-speech stimuli tests. The evaluation includes determination of: (1) new cut-off values (pass-fail criteria), (2) the sensitivity and the specificity of the entire test battery and (3) the failure rate of different test combinations. For each test in the battery, cut-off values were determined using the weighted Youden index. Applying the newly derived cut-off values, the distribution of failing specific test combinations was determined. A group of 112 children diagnosed with APD (57 boys, 55 girls, aged 6-16 years) and a control group containing 158 children without auditory problems (75 boys, 83 girls, aged 6-16 years). Cut-off values for different weights of the sensitivity and the specificity have been determined. Using the criterion that at least two tests have to be failed for APD to be suspected, the sensitivity and the specificity of the entire test battery were 95.3% and 91.6%, respectively. Some test combinations were found to have higher failure rates than others. Due to the high sensitivity and specificity the test battery has good predictive value in APD assessment.

Clinical characteristics of self-mutilating behavior in Turkish male subjects with antisocial personality disorder: relationship to psychopathy.

PubMed

Alpay Ates, M; Algul, Ayhan; Semiz, Umit B; Gecici, Omer; Basoglu, Cengiz; Ebrinc, Servet; Cetin, Mesut

2011-05-01

The aims of this study were to determine the characteristics of self-mutilation (SM) and examine the relationship between SM and psychopathy in male subjects with antisocial personality disorder (APD). APD diagnosis was established by the Structured Clinical Interview for DSM-III-R Axis II Disorders. Subjects (N = 116) were assessed using the Psychopathy Checklist-Revised and a semi-structured self-mutilation questionnaire form. In males with APD, the percentages of psychopathy and SM were 48.3% (N =56) and 96.6% (N = 112), respectively. There were positive correlations between severity of psychopathy and severity, number, and frequency of SM. Considerably high rates of SM and psychopathy were found in Turkish males with APD. The features of SM were associated with comorbidity of psychopathy. These results showed the importance of exploring the self-injurious behavior and psychopathy when diagnosed with APD.

Auditory-Motor Interactions in Pediatric Motor Speech Disorders: Neurocomputational Modeling of Disordered Development

PubMed Central

Terband, H.; Maassen, B.; Guenther, F.H.; Brumberg, J.

2014-01-01

Background/Purpose Differentiating the symptom complex due to phonological-level disorders, speech delay and pediatric motor speech disorders is a controversial issue in the field of pediatric speech and language pathology. The present study investigated the developmental interaction between neurological deficits in auditory and motor processes using computational modeling with the DIVA model. Method In a series of computer simulations, we investigated the effect of a motor processing deficit alone (MPD), and the effect of a motor processing deficit in combination with an auditory processing deficit (MPD+APD) on the trajectory and endpoint of speech motor development in the DIVA model. Results Simulation results showed that a motor programming deficit predominantly leads to deterioration on the phonological level (phonemic mappings) when auditory self-monitoring is intact, and on the systemic level (systemic mapping) if auditory self-monitoring is impaired. Conclusions These findings suggest a close relation between quality of auditory self-monitoring and the involvement of phonological vs. motor processes in children with pediatric motor speech disorders. It is suggested that MPD+APD might be involved in typically apraxic speech output disorders and MPD in pediatric motor speech disorders that also have a phonological component. Possibilities to verify these hypotheses using empirical data collected from human subjects are discussed. PMID:24491630

Development of Antisocial Personality Disorder in Detained Youths: The Predictive Value of Mental Disorders

ERIC Educational Resources Information Center

Washburn, Jason J.; Romero, Erin Gregory; Welty, Leah J.; Abram, Karen M.; Teplin, Linda A.; McClelland, Gary M.; Paskar, Leah D.

2007-01-01

Antisocial personality disorder (APD) is a serious public and mental health concern. Understanding how well conduct disorder (CD) and other mental disorders predict the development of APD among youths involved in the juvenile justice system is critical for prevention. The authors used a stratified random sample of 1,112 detained youths to examine…

Auditory Processing Disorder and Auditory/Language Interventions: An Evidence-Based Systematic Review

ERIC Educational Resources Information Center

Fey, Marc E.; Richard, Gail J.; Geffner, Donna; Kamhi, Alan G.; Medwetsky, Larry; Paul, Diane; Ross-Swain, Deborah; Wallach, Geraldine P.; Frymark, Tobi; Schooling, Tracy

2011-01-01

Purpose: In this systematic review, the peer-reviewed literature on the efficacy of interventions for school-age children with auditory processing disorder (APD) is critically evaluated. Method: Searches of 28 electronic databases yielded 25 studies for analysis. These studies were categorized by research phase (e.g., exploratory, efficacy) and…

Neutron diffraction study of the formation kinetics of ordered antiphase domains in titanium carbohydride TiC{sub x}H{sub y}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khidirov, I., E-mail: khidirov@inp.uz

2015-09-15

The kinetics of formation and growth of ordered antiphase domains (APDs) in titanium carbohydride TiC{sub 0.50}H{sub 0.21} has been investigated by neutron diffraction. A model of ordered APDs is proposed. It is established that the pronounced ordering of interstitial atoms and APDs begin at 450°C. It is shown that the period of ordered APDs (P ≈ 10–12) is independent of the exposure time at a constant temperature. It is found that the temperature of ordered APDs, T{sub OAPD}, increases nonlinearly with an increase in the carbon concentration in the range 0.50 ≤ C/Ti ≤ 0.70. The formation temperature of orderedmore » APDs is found to correlate with the concentration dependence of the order–disorder transition temperature and be 0.60 of the order–disorder transition temperature: T{sub APD} = 0.60Τ{sub C}.« less

Overt versus covert conduct disorder symptoms and the prospective prediction of antisocial personality disorder.

PubMed

Le Corff, Yann; Toupin, Jean

2014-12-01

Studies have shown strong continuity between conduct disorder (CD) in adolescence and antisocial personality disorder (APD) in adulthood. Researchers have been trying to explain why some adolescents with CD persist into adult APD and others do not. A few studies reported that overt and covert CD symptoms have a differential predictive power for APD, with mixed results. The present study aimed to evaluate the prospective association of overt and covert CD symptoms with APD in a sample of male adolescents with CD (N = 128, mean age = 15.6, SD = 1.6). Participants were recruited at intake in Quebec Youth Centers and reassessed 3 years later (n = 73). CD and ADHD symptoms were assessed at intake with the DISC-R while APD was assessed 3 years later with the SCID-II. Logistic regression results showed that, contrary to previous prospective studies (Lahey, Loeber, Burke, & Applegate, 2005; Washburn et al., 2007), overt (OR = 2.12, 95% CI [1.29, 3.50]) but not covert (OR = 1.04, 95% CI [0.69, 1.56]) symptoms predicted later APD, controlling for ADHD symptoms and socioeconomic status. It is hypothesized that the divergence with previous studies may be explained by the higher mean number and wider range of overt CD symptoms in our sample.

A randomized control trial of interventions in school-aged children with auditory processing disorders.

PubMed

Sharma, Mridula; Purdy, Suzanne C; Kelly, Andrea S

2012-07-01

The primary purpose of the study was to compare intervention approaches for children with auditory processing disorder (APD): bottom-up training including activities focused on auditory perception, discrimination, and phonological awareness, and top-down training including a range of language activities. Another purpose was to determine the benefits of personal FM systems. The study is a randomized control trial where participants were allocated to groups receiving one of the two interventions, with and without personal FM, or to the no intervention group. The six-week intervention included weekly one-hour sessions with a therapist in the clinic, plus 1-2 hours per week of parent-directed homework. 55 children (7 to 13 years) with APD participated in the study. Intervention outcomes included reading, language, and auditory processing. Positive outcomes were observed for both training approaches and personal FM systems on several measures. Pre-intervention nonverbal IQ, age, and severity of APD did not influence outcomes. Performance of control group participants did not change when retested after the intervention period. Both intervention approaches were beneficial and there were additional benefits with the use of personal FM. Positive results were not limited to the areas specifically targeted by the interventions.

Modified Therapeutic Community Treatment for Offenders with MICA Disorders: Antisocial Personality Disorder and Treatment Outcomes

ERIC Educational Resources Information Center

McKendrick, Karen; Sullivan, Christopher; Banks, Steven; Sacks, Stanley

2006-01-01

Treatment outcomes 1 year after release from prison were compared for two subgroups of male inmates with co-occurring serious mental illness and chemical abuse (MICA) disorders, those with a diagnosis for Antisocial Personality Disorder (APD), and those without a diagnosis of APD. The foundation study had randomly assigned inmates to either…

Psychopathy, Antisocial Personality Disorder, and Reconviction in an Australian Sample of Forensic Patients.

PubMed

Shepherd, Stephane M; Campbell, Rachel E; Ogloff, James R P

2018-02-01

This study identified the presence of psychopathy (as measured by the PCL-R/PCL:SV instruments) and antisocial personality disorder (APD) and their relationship with future reconviction in an Australian forensic sample ( N = 136) of patients with a mental disorder. Patients were tracked for over 4 years postrelease to determine associations between a diagnosis of APD/psychopathy and reoffense. Patients with higher psychopathy scores were found to have an increased likelihood of reincarceration, a higher rate of reconviction, and were reconvicted earlier compared with patients with lower psychopathy scores. Patients with APD were more likely to be reconvicted and reincarcerated during the follow-up period than patients without an APD diagnosis. Despite demonstrating associations with general reconviction, the PCL instruments did not exhibit statistically significant relationships with violence. Implications for the clinical identification of personality disordered patients in forensic settings are discussed.

Intelligibility of degraded speech and the relationship between symptoms of inattention, hyperactivity/impulsivity and language impairment in children with suspected auditory processing disorder.

PubMed

Ahmmed, Ansar Uddin

2017-10-01

To compare the sensitivity and specificity of Auditory Figure Ground sub-tests of the SCAN-3 battery, using signal to noise ratio (SNR) of +8 dB (AFG+8) and 0 dB (AFG0), in identifying auditory processing disorder (APD). A secondary objective was to evaluate any difference in auditory processing (AP) between children with symptoms of inattention versus combined sub-types of Attention Deficit Hyperactivity Disorder (ADHD). Data from 201 children, aged 6 to 16 years (mean: 10 years 6 months, SD: 2 years 8 months), who were assessed for suspected APD were reviewed retrospectively. The outcomes of the SCAN-3 APD test battery, Swanson Nolan and Pelham-IV parental rating (SNAP-IV) and Children's Communication Checklist-2 (CCC-2) were analysed. AFG0 had a sensitivity of 56.3% and specificity of 100% in identifying children performing poorly in at least two of six SCAN-3 sub-tests or one of the two questionnaires, in contrast to 42.1% and 80% respectively for AFG+8. Impaired AP was mostly associated with symptoms of ADHD and /or language impairment (LI). LI was present in 92.9% of children with ADHD symptoms. Children with symptoms of combined ADHD plus LI performed significantly poorly (p < 0.05) compared to inattention ADHD plus LI in Filtered Words (FW) sub-test, but not in the rest of the SCAN-3 sub-tests. Speech in noise tests using SNR of 0 dB is better than +8 dB in assessing APD. The better FW performance of the inattention ADHD plus LI group can be speculated to be related to known difference in activity in a neural network between different sub-types of ADHD. The findings of the study and existing literature suggest that neural networks connecting the cerebral hemispheres, basal ganglia and cerebellum are involved in APD, ADHD and LI. Copyright © 2017 Elsevier B.V. All rights reserved.

Factors influencing tests of auditory processing: a perspective on current issues and relevant concerns.

PubMed

Cacace, Anthony T; McFarland, Dennis J

2013-01-01

Tests of auditory perception, such as those used in the assessment of central auditory processing disorders ([C]APDs), represent a domain in audiological assessment where measurement of this theoretical construct is often confounded by nonauditory abilities due to methodological shortcomings. These confounds include the effects of cognitive variables such as memory and attention and suboptimal testing paradigms, including the use of verbal reproduction as a form of response selection. We argue that these factors need to be controlled more carefully and/or modified so that their impact on tests of auditory and visual perception is only minimal. To advocate for a stronger theoretical framework than currently exists and to suggest better methodological strategies to improve assessment of auditory processing disorders (APDs). Emphasis is placed on adaptive forced-choice psychophysical methods and the use of matched tasks in multiple sensory modalities to achieve these goals. Together, this approach has potential to improve the construct validity of the diagnosis, enhance and develop theory, and evolve into a preferred method of testing. Examination of methods commonly used in studies of APDs. Where possible, currently used methodology is compared to contemporary psychophysical methods that emphasize computer-controlled forced-choice paradigms. In many cases, the procedures used in studies of APD introduce confounding factors that could be minimized if computer-controlled forced-choice psychophysical methods were utilized. Ambiguities of interpretation, indeterminate diagnoses, and unwanted confounds can be avoided by minimizing memory and attentional demands on the input end and precluding the use of response-selection strategies that use complex motor processes on the output end. Advocated are the use of computer-controlled forced-choice psychophysical paradigms in combination with matched tasks in multiple sensory modalities to enhance the prospect of obtaining a valid diagnosis. American Academy of Audiology.

Effects of speech in noise and dichotic listening intervention programs on central auditory processing disorders.

PubMed

Putter-Katz, Hanna; Adi-Bensaid, Limor; Feldman, Irit; Hildesheimer, Minka

2008-01-01

Twenty children with central auditory processing disorders [(C)APD] were subjected to a structured intervention program of listening skills in quiet and in noise. Their performance was compared to that of a control group of 10 children with (C)APD with no special treatment. Pretests were conducted in quiet and in degraded listening conditions (speech noise and competing speech). The (C)APD management approach was integrative and included top-down and bottom-up strategies. It focused on environmental modifications, remediation techniques, and compensatory strategies. Training was conducted with monosyllabic and polysyllabic words, sentences and phrases in quiet and in noise. Comparisons of pre- and post-management measures indicated increase in speech recognition performance in background noise and competing speech for the treatment group. This improvement was exhibited for both ears. A significant difference between ears was found with the left ear showing improvement in both the short and the long versions of competing sentence tests and the right ear performing better in the long competing sentences only following intervention. No changes were documented for the control group. These findings add to a growing body of literature suggesting that interactive auditory training can improve listening skills.

Olanzapine treatment of adolescent rats alters adult reward behaviour and nucleus accumbens function

PubMed Central

Vinish, Monika; Elnabawi, Ahmed; Milstein, Jean A.; Burke, Jesse S.; Kallevang, Jonathan K.; Turek, Kevin C.; Lansink, Carien S.; Merchenthaler, Istvan; Bailey, Aileen M.; Kolb, Bryan; Cheer, Joseph F.; Frost, Douglas O.

2018-01-01

Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug (APD) treatment. Most APDs are potent antagonists or partial agonists of dopamine (DA) D2 receptors ; atypical APDs also have multiple serotonergic activities. DA and serotonin regulate many neurodevelopmental processes. Thus, early life APD treatment can, potentially, perturb these processes, causing long-term behavioural and neurobiological sequelae. We treated adolescent, male rats with olanzapine (Ola) on post-natal days 28–49, under dosing conditions that approximate those employed therapeutically in humans. As adults, they exhibited enhanced conditioned place preference for amphetamine, as compared to vehicle-treated rats. In the nucleus accumbens core, DA D1 receptor binding was reduced, D2 binding was increased and DA release evoked by electrical stimulation of the ventral tegmental area was reduced. Thus, adolescent Ola treatment enduringly alters a key behavioural response to rewarding stimuli and modifies DAergic neurotransmission in the nucleus accumbens. The persistence of these changes suggests that even limited periods of early life Ola treatment may induce enduring changes in other reward-related behaviours and in behavioural and neurobiological responses to therapeutic and illicit psychotropic drugs. These results underscore the importance of improved understanding of the enduring sequelae of paediatric APD treatment as a basis for weighing the benefits and risks of adolescent APD therapy, especially prophylactic treatment in high-risk, asymptomatic patients. PMID:23351612

Reliability of self-reported antisocial personality disorder symptoms among substance abusers.

PubMed

Cottler, L B; Compton, W M; Ridenour, T A; Ben Abdallah, A; Gallagher, T

1998-02-01

It is estimated that from 20 to 60% of substance abusers meet criteria for Antisocial Personality Disorder (APD). An accurate and reliable diagnosis is important because persons meeting criteria for APD, by the nature of their disorder, are less likely to change behaviors and more likely to relapse to both substance abuse and high risk behaviors. To understand more about the reliability of the disorder and symptoms of APD, the Diagnostic Interview Schedule Version III-R (DIS) was administered to 453 substance abusers ascertained from treatment programs and from the general population (St Louis Epidemiological Catchment Area (ECA) follow-up study). Estimates of the 1 week, test-retest reliability for the childhood conduct disorder criterion, the adult antisocial behavior criterion, and APD diagnosis fell in the good agreement range, as measured by kappa. The internal consistency of these DIS symptoms was adequate to acceptable. Individual DIS criteria designed to measure childhood conduct disorder ranged from fair to good for most items; reliability was slightly higher for the adult antisocial behavior symptom items. Finally, self-reported 'liars' were no more unreliable in their reports of their behaviors than 'non-liars'.

Daily Stress, Hearing-Specific Stress and Coping: Self-Reports from Deaf or Hard of Hearing Children and Children with Auditory Processing Disorder

ERIC Educational Resources Information Center

Eschenbeck, Heike; Gillé, Vera; Heim-Dreger, Uwe; Schock, Alexandra; Schott, Andrea

2017-01-01

This study evaluated stressors and coping strategies in 70 children who are deaf or hard of hearing (D/HH) or with auditory processing disorder (APD) attending Grades 5 and 6 of a school for deaf and hard-of-hearing children. Everyday general stressors and more hearing-specific stressors were examined in a hearing-specific modified stress and…

Attachment priming and avoidant personality features as predictors of social-evaluation biases.

PubMed

Bowles, David P; Meyer, Björn

2008-02-01

Personality research has shown that negativity in social situations (e.g., negative evaluations of others) can be reduced by the activation of participants' sense of attachment security. Individuals with avoidant personality disorder (APD), however, are theoretically less responsive to context or situational cues because of the inflexible nature of their personality disposition. This idea of individual differences in context-responsiveness was tested in a sample of 169 undergraduates who were assessed for APD features and assigned to positive, negative, or neutral attachment priming conditions. More pronounced APD features were associated with more negative responses to vignettes describing potentially distressing social situations. A significant interaction showed that participants with more avoidant features consistently appraised the vignettes relatively more negatively, regardless of priming condition. Those without APD features, by contrast, did not exhibit negative appraisals/evaluations unless negatively primed (curvilinear effect). This effect could not be explained by depression, current mood, or attachment insecurity, all of which related to negative evaluative biases, but none of which related to situation inflexibility. These findings provide empirical support for the notion that negative information-processing is unusually inflexible and context-unresponsive among individuals with more pronounced features of APD.

Auditory-motor interactions in pediatric motor speech disorders: neurocomputational modeling of disordered development.

PubMed

Terband, H; Maassen, B; Guenther, F H; Brumberg, J

2014-01-01

Differentiating the symptom complex due to phonological-level disorders, speech delay and pediatric motor speech disorders is a controversial issue in the field of pediatric speech and language pathology. The present study investigated the developmental interaction between neurological deficits in auditory and motor processes using computational modeling with the DIVA model. In a series of computer simulations, we investigated the effect of a motor processing deficit alone (MPD), and the effect of a motor processing deficit in combination with an auditory processing deficit (MPD+APD) on the trajectory and endpoint of speech motor development in the DIVA model. Simulation results showed that a motor programming deficit predominantly leads to deterioration on the phonological level (phonemic mappings) when auditory self-monitoring is intact, and on the systemic level (systemic mapping) if auditory self-monitoring is impaired. These findings suggest a close relation between quality of auditory self-monitoring and the involvement of phonological vs. motor processes in children with pediatric motor speech disorders. It is suggested that MPD+APD might be involved in typically apraxic speech output disorders and MPD in pediatric motor speech disorders that also have a phonological component. Possibilities to verify these hypotheses using empirical data collected from human subjects are discussed. The reader will be able to: (1) identify the difficulties in studying disordered speech motor development; (2) describe the differences in speech motor characteristics between SSD and subtype CAS; (3) describe the different types of learning that occur in the sensory-motor system during babbling and early speech acquisition; (4) identify the neural control subsystems involved in speech production; (5) describe the potential role of auditory self-monitoring in developmental speech disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

[Cognitive and emotional impairments in patients with protracted anxiety-phobic disorders].

PubMed

Chutko, L S; Surushkina, S Iu; Iakovenko, E A; Nikishena, I S; Anisimova, T I; Bondarchuk, Iu L

2014-01-01

To study cognitive and emotional impairments in patients with anxiety-phobic disorders (APDs), to comparatively analyze the clinical manifestations of acute (less than one-year) and protracted (1-to-5-year) forms of this disease, and to evaluate the efficacy of noofen used to treat this pathology. Sixty-two patients aged 18 to 50 years with APDs were examined. The investigators collected clinical history data, performed neurological examination, and assessed autonomic disorders in accordance with the questionnaire to reveal their signs, anxiety using the Hamilton anxiety rating scale, memory impairment employing the methods developed by A.R. Luria, attention disorders applying the test of variables of attention, and diagnosed emotional intelligence using the Mayer-Salovey-Caruso emotional intelligence test. Noofen 1000 mg/day was used to treat the patients. Protracted APDs were shown to be characterized by the higher degree of psychosomatic symptoms and by more pronounced impairments in attention, memory, and emotional intelligence. The data of posttreatment clinical and psychological studiesare indicative of improvements in 73.3% of cases. The findings may lead to the conclusion that noofen is highly effective in the treatment of patients with protracted APDs.

Relations among symptoms of social phobia subtypes, avoidant personality disorder, panic, and depression.

PubMed

Carter, Shawn A; Wu, Kevin D

2010-03-01

This study's primary goal was to examine relations between symptoms of specific social phobia (SSP), generalized social phobia (GSP), avoidant personality disorder (APD), and panic and depression. Past research has suggested a single social phobia continuum in which SSP displays less symptom severity than GSP or APD. We found SSP symptoms correlated less strongly with depression but more strongly with panic relative to both GSP and APD symptoms. These findings challenge a unidimensional model of social phobia, suggesting a multidimensional model may be more appropriate. These findings also inform current research aimed at classifying mood and anxiety disorders more broadly by identifying that the different factors of fear versus distress appear to underlie different subtypes of social phobia. 2008. Published by Elsevier Ltd.

Cognitive Control Deficits Associated with Antisocial Personality Disorder and Psychopathy

PubMed Central

Zeier, Joshua D.; Baskin-Sommers, Arielle R.; Newman, Joseph P.; Racer, Kristina Hiatt

2011-01-01

Antisociality has been linked to a variety of executive functioning deficits, including poor cognitive control. Surprisingly, cognitive control deficits are rarely found in psychopathic individuals, despite their notoriously severe and persistent antisocial behavior. In fact, primary (low-anxious) psychopathic individuals display superior performance on cognitive control-type tasks under certain circumstances. To clarify these seemingly contradictory findings, we administered a response competition (i.e. flanker) task to incarcerated offenders, who were assessed for Antisocial Personality Disorder (APD) symptoms and psychopathy. As hypothesized, APD related to poorer accuracy, especially on incongruent trials. Contrary to expectation, however, the same pattern of results was found in psychopathy. Additional analyses indicated that these effects of APD and psychopathy were associated with overlapping variance. The findings suggest that psychopathy and APD symptoms are both associated with deficits in cognitive control, and that this deficit relates to general antisociality as opposed to a specific antisocial syndrome. PMID:22452754

A magnetic resonance spectroscopy study of antisocial behaviour disorder, psychopathy and violent crime among military conscripts.

PubMed

Basoglu, Cengiz; Semiz, Umit; Oner, Ozgur; Gunay, Huseyin; Ebrinc, Servet; Cetin, Mesut; Sildiroglu, Onur; Algul, Ayhan; Ates, Alpay; Sonmez, Guner

2008-04-01

Prefrontal and/or temporo-limbic abnormalities associated with antisocial personality disorder (APD), high psychopathy scores and violent behaviours can readily be evaluated by neuroimaging methods. In this study, we compared the brain metabolites in adult male military conscripts with APD, high psychopathy scores and serious violent crimes (n = 15) with age- and educational-level-matched healthy controls (n = 15) by means of magnetic resonance spectroscopy. All cases were diagnosed by means of the Diagnostic Statistical Manual-IV APD module of the Structured Clinical Interview for DSM III-R Axis II Disorders (SCID-II) semistructured questionnaire in Turkish. The psychopathy scores were evaluated by means of the Hare Psychopathy Checklist-Revised translated into Turkish (PCL-R). PCL-R is a 20-item, reliable and valid instrument for assessment of psychopathy, both in categorical and dimensional natures. All patients had a total score of 29 (of possible 40) or higher from PCL-R, indicating a high degree of psychopathy. Our results showed no significant differences in ratio of N-acetyl aspartate (NAA), creatine (Cr) and choline-related compounds in the right dorsolateral prefrontal cortex, anterior cingulate cortex (ACC) and amygdala-hippocampus regions of cases compared with controls. ACC NAA/Cr was significantly negatively correlated with both the PCL-R total score and the PCL-R factor I score (interpersonal/affective problems) among the cases. As ACC plays an important role in decision-making and emotional information processing, we postulate that the lower NAA/Cr ratio, suggesting impaired neural integrity, may increase the severity of interpersonal/affective problems of the psychopathy factor in male subjects exhibiting APD, high psychopathy overall scores and violent crimes.

Use of Questionnaire-Based Measures in the Assessment of Listening Difficulties in School-Aged Children

PubMed Central

Tomlin, Danielle; Moore, David R.; Dillon, Harvey

2015-01-01

Objectives: In this study, the authors assessed the potential utility of a recently developed questionnaire (Evaluation of Children’s Listening and Processing Skills [ECLiPS]) for supporting the clinical assessment of children referred for auditory processing disorder (APD). Design: A total of 49 children (35 referred for APD assessment and 14 from mainstream schools) were assessed for auditory processing (AP) abilities, cognitive abilities, and symptoms of listening difficulty. Four questionnaires were used to capture the symptoms of listening difficulty from the perspective of parents (ECLiPS and Fisher’s auditory problem checklist), teachers (Teacher’s Evaluation of Auditory Performance), and children, that is, self-report (Listening Inventory for Education). Correlation analyses tested for convergence between the questionnaires and both cognitive and AP measures. Discriminant analyses were performed to determine the best combination of tests for discriminating between typically developing children and children referred for APD. Results: All questionnaires were sensitive to the presence of difficulty, that is, children referred for assessment had significantly more symptoms of listening difficulty than typically developing children. There was, however, no evidence of more listening difficulty in children meeting the diagnostic criteria for APD. Some AP tests were significantly correlated with ECLiPS factors measuring related abilities providing evidence for construct validity. All questionnaires correlated to a greater or lesser extent with the cognitive measures in the study. Discriminant analysis suggested that the best discrimination between groups was achieved using a combination of ECLiPS factors, together with nonverbal Intelligence Quotient (cognitive) and AP measures (i.e., dichotic digits test and frequency pattern test). Conclusions: The ECLiPS was particularly sensitive to cognitive difficulties, an important aspect of many children referred for APD, as well as correlating with some AP measures. It can potentially support the preliminary assessment of children referred for APD. PMID:26002277

Consensus on the Definition of Advanced Parkinson's Disease: A Neurologists-Based Delphi Study (CEPA Study).

PubMed

Luquin, Maria-Rosario; Kulisevsky, Jaime; Martinez-Martin, Pablo; Mir, Pablo; Tolosa, Eduardo S

2017-01-01

To date, no consensus exists on the key factors for diagnosing advanced Parkinson disease (APD). To obtain consensus on the definition of APD, we performed a prospective, multicenter, Spanish nationwide, 3-round Delphi study (CEPA study). An ad hoc questionnaire was designed with 33 questions concerning the relevance of several clinical features for APD diagnosis. In the first-round, 240 neurologists of the Spanish Movement Disorders Group participated in the study. The results obtained were incorporated into the questionnaire and both, results and questionnaire, were sent out to and fulfilled by 26 experts in Movement Disorders. Review of results from the second-round led to a classification of symptoms as indicative of "definitive," "probable," and "possible" APD. This classification was confirmed by 149 previous participating neurologists in a third-round, where 92% completely or very much agreed with the classification. Definitive symptoms of APD included disability requiring help for the activities of daily living, presence of motor fluctuations with limitations to perform basic activities of daily living without help, severe dysphagia, recurrent falls, and dementia. These results will help neurologists to identify some key factors in APD diagnosis, thus allowing users to categorize the patients for a homogeneous recognition of this condition.

FDG PET/CT findings in acquired perforating dermatosis.

PubMed

Shinmura, Akiko; Abe, Koichiro; Baba, Shingo; Isoda, Takuro; Maruoka, Yasuhiro; Yasukawa, Fumiko; Kiryu, Hiromaro; Sasaki, Masayuki; Furue, Masutaka; Honda, Hiroshi

2012-10-01

Acquired perforating dermatosis (APD) is an uncommon cutaneous perforating disorder. We report a patient on hemodialysis who developed skin eruption and jaundice. He underwent FDG PET/CT under suspicion of biliary malignancies. PET/CT showed no significant abnormal uptake except of multiple FDG-avid nodules in the skin. The eruption he had was histopathologically diagnosed as APD by skin biopsy. His case suggests that APD should be considered as a differential diagnosis when multiple cutaneous FDG accumulations are found in a patient on hemodialysis. To the best of our knowledge, this is the first report showing the FDG PET/CT findings of APD.

Association between violent behaviour and impaired prepulse inhibition of the startle response in antisocial personality disorder and schizophrenia.

PubMed

Kumari, Veena; Das, Mrigen; Hodgins, Sheilagh; Zachariah, Elizabeth; Barkataki, Ian; Howlett, Michael; Sharma, Tonmoy

2005-03-07

Violent behaviour has a strong association with antisocial personality disorder (APD) and schizophrenia. Although developments in the understanding of socio-environmental factors associated with violence should not be ignored, advances in prevention and treatment of violent behaviour would benefit by improved understanding of its neurobiological and cognitive basis. The authors, therefore, investigated prepulse inhibition (PPI) of the startle response in APD and schizophrenia in relation to a history of serious violence. The neural substrates of PPI, especially the hippocampus, amygdala, thalamus and basal ganglia, are implicated in violence as well as in APD and schizophrenia. The study included four groups: (i) patients with APD and a history of violence, (ii) patients with schizophrenia and a history of violence, (iii) patients with schizophrenia without a history of violence, and (iv) healthy subjects with no history of violence or a mental disorder. All subjects were assessed identically on acoustic PPI. Compared to healthy subjects, significantly reduced PPI occurred in APD, violent schizophrenia and non-violent schizophrenia patients. Although PPI did not significantly differentiate the three clinical groups, high ratings of violence were modestly associated with reduced PPI across the entire study sample. Violent patients with impulsive and premeditated violence showed comparable PPI. The association between violent behaviour and impaired PPI suggests that neural structures and functions underlying PPI are implicated in (inhibition of) violence.

A Comparison of Psychoanalytic Therapy and Cognitive Behavioral Therapy for Anxiety (Panic/Agoraphobia) and Personality Disorders (APD Study): Presentation of the RCT Study Design.

PubMed

Benecke, Cord; Huber, Dorothea; Staats, Hermann; Zimmermann, Johannes; Henkel, Miriam; Deserno, Heinrich; Wiegand-Grefe, Silke; Schauenburg, Henning

2016-09-01

Anxiety disorders, most notably panic disorders and agoraphobia, are common mental disorders, and there is a high comorbidity with personality disorders. Randomized controlled trails addressing this highly relevant group of patients are missing. The multicenter Anxiety and Personality Disorders (APD) study investigates 200 patients with panic disorder and/or agoraphobia with comorbid personality disorder in a randomized control-group comparison of psychoanalytic therapy (PT) and cognitive behavioral therapy (CBT), including 100 patients in each group. Each patient will be examined over a period of six years, regardless of the duration of the individual treatment. The main issues that are addressed in this study are the comparison of the efficacy of PT and CBT in this special patient population, the comparison of the sustainability of the effects of PT and CBT, the comparison of the long-term cost-benefit-ratios of PT and CBT as well as the investigation of prescriptive patient characteristics for individualized treatment recommendations (differential indication). The APD study compares efficacy, sustainability, and cost-benefit-ratios of CBT and PT for anxiety plus personality disorders in a randomized controlled trail. The study design meets the requirements for an efficacy study for PT, which were recently defined. Current Controlled Trials ISRCTN12449681.

Multivariate dependencies between difficult childhood, temperament and antisocial personality disorder in a population of French male prisoners.

PubMed

Pousset, M; Tremblay, R E; Falissard, B

2011-06-01

The aim of this study was to contribute to clarification of the relations between antisocial personality disorder (APD) and its potential risk factors in a population of 560 French male prisoners. Adverse childhood was assessed as a latent variable determined by several traumatic events. APD (MINI), character and temperament (Cloninger's model), WAIS®-III similarities subtest and psychosocial characteristics were assessed by two clinicians. The WAIS®-III subtest accounts for verbal and cognitive performance. We used a structural model to determine the weight of the different pathways between adverse childhood and APD. Study confirmed the major and direct role of adverse childhood (standardized coefficient=0.48). An intermediate effect mediated by character (considered as a global variable) and novelty-seeking was also shown, confirming previous results from the literature. This study emphasizes the role of adverse childhood in APD, suggesting the potential benefit of early intervention in the prevention of antisocial behaviours. Copyright © 2011. Published by Elsevier Masson SAS.

Cognitive control deficits associated with antisocial personality disorder and psychopathy.

PubMed

Zeier, Joshua D; Baskin-Sommers, Arielle R; Hiatt Racer, Kristina D; Newman, Joseph P

2012-07-01

Antisociality has been linked to a variety of executive functioning deficits, including poor cognitive control. Surprisingly, cognitive control deficits are rarely found in psychopathic individuals, despite their notoriously severe and persistent antisocial behavior. In fact, primary (low-anxious) psychopathic individuals display superior performance on cognitive control-type tasks under certain circumstances. To clarify these seemingly contradictory findings, we administered a response competition (i.e., flanker) task to incarcerated offenders, who were assessed for Antisocial Personality Disorder (APD) symptoms and psychopathy. As hypothesized, APD related to poorer accuracy, especially on incongruent trials. Contrary to expectation, however, the same pattern of results was found in psychopathy. Additional analyses indicated that these effects of APD and psychopathy were associated with overlapping variance. The findings suggest that psychopathy and APD symptoms are both associated with deficits in cognitive control, and that this deficit relates to general antisociality as opposed to a specific antisocial syndrome. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Self-esteem and other-esteem in college students with borderline and avoidant personality disorder features: An experimental vignette study.

PubMed

Bowles, David P; Armitage, Chris J; Drabble, Jennifer; Meyer, Björn

2013-11-01

An experimental study investigated self-esteem and other-esteem responses to either fully supportive or less supportive interpersonal feedback in college students with avoidant and borderline personality disorder features (APD and BPD respectively). Disturbances in self-esteem and in evaluations of others are central to definitions of both APD and BPD, but the extent to which such interpersonal appraisals are responsive to contextual features, such as evaluative feedback from others, is not yet clear. In theory, we would expect that individuals with pronounced PD features would show more inflexible and more negative self-evaluations and others- evaluations than those without PD features. In this study with 169 undergraduates, APD but not BPD features were associated with other-contingent state self-esteem and other-esteem. A significant interaction indicated that highly avoidant respondents felt particularly negatively about themselves and their close others in situations that conveyed subtle criticism but not in situations signalling unequivocal support. This suggests that their self-esteem and other-esteem, rather than being rigidly negative, are instead highly contingent upon interpersonal feedback. Such context contingency has implications for the trait-like description of diagnostic characteristics within current taxonomies and is in line with contemporary dynamic models of personality structure and process. Copyright © 2013 John Wiley & Sons, Ltd.

What Can We Learn about Auditory Processing from Adult Hearing Questionnaires?

PubMed

Bamiou, Doris-Eva; Iliadou, Vasiliki Vivian; Zanchetta, Sthella; Spyridakou, Chrysa

2015-01-01

Questionnaires addressing auditory disability may identify and quantify specific symptoms in adult patients with listening difficulties. (1) To assess validity of the Speech, Spatial, and Qualities of Hearing Scale (SSQ), the (Modified) Amsterdam Inventory for Auditory Disability (mAIAD), and the Hyperacusis Questionnaire (HYP) in adult patients experiencing listening difficulties in the presence of a normal audiogram. (2) To examine which individual questionnaire items give the worse scores in clinical participants with an auditory processing disorder (APD). A prospective correlational analysis study. Clinical participants (N = 58) referred for assessment because of listening difficulties in the presence of normal audiometric thresholds to audiology/ear, nose, and throat or audiovestibular medicine clinics. Normal control participants (N = 30). The mAIAD, HYP, and the SSQ were administered to a clinical population of nonneurological adults who were referred for auditory processing (AP) assessment because of hearing complaints, in the presence of normal audiogram and cochlear function, and to a sample of age-matched normal-hearing controls, before the AP testing. Clinical participants with abnormal results in at least one ear and in at least two tests of AP (and at least one of these tests to be nonspeech) were classified as clinical APD (N = 39), and the remaining (16 of whom had a single test abnormality) as clinical non-APD (N = 19). The SSQ correlated strongly with the mAIAD and the HYP, and correlation was similar within the clinical group and the normal controls. All questionnaire total scores and subscores (except sound distinction of mAIAD) were significantly worse in the clinical APD versus the normal group, while questionnaire total scores and most subscores indicated greater listening difficulties for the clinical non-APD versus the normal subgroups. Overall, the clinical non-APD group tended to give better scores than the APD in all questionnaires administered. Correlation was strong for the worse-ear gaps-in-noise threshold with the SSQ, mAIAD, and HYP; strong to moderate for the speech in babble and left-ear dichotic digit test scores (at p < 0.01); and weak to moderate for the remaining AP tests except the frequency pattern test that did not correlate. The worse-scored items in all three questionnaires concerned speech-in-noise questions. This is similar to worse-scored items by hearing-impaired participants as reported in the literature. Worse-scored items of the clinical group also included quality aspects of listening questions from the SSQ, which most likely pertain to cognitive aspects of listening, such as ability to ignore other sounds and listening effort. Hearing questionnaires may help assess symptoms of adults with APD. The listening difficulties and needs of adults with APD to some extent overlap with those of hearing-impaired listeners, but there are significant differences. The correlation of the gaps-in-noise and duration pattern (but not frequency pattern) tests with the questionnaire scores indicates that temporal processing deficits may play an important role in clinical presentation. American Academy of Audiology.

75 FR 66319 - State Systems Advance Planning Document (APD) Process

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

...) equipment and services. The APD process was designed to mitigate financial risks, avoid incompatibilities... develop a General Systems Design (GSD). Implementation APD means a recorded plan of action to request Federal financial participation (FFP) in the costs of designing, developing and implementing the system...

Assessing Auditory Processing Abilities in Typically Developing School-Aged Children.

PubMed

McDermott, Erin E; Smart, Jennifer L; Boiano, Julie A; Bragg, Lisa E; Colon, Tiffany N; Hanson, Elizabeth M; Emanuel, Diana C; Kelly, Andrea S

2016-02-01

Large discrepancies exist in the literature regarding definition, diagnostic criteria, and appropriate assessment for auditory processing disorder (APD). Therefore, a battery of tests with normative data is needed. The purpose of this study is to collect normative data on a variety of tests for APD on children aged 7-12 yr, and to examine effects of outside factors on test performance. Children aged 7-12 yr with normal hearing, speech and language abilities, cognition, and attention were recruited for participation in this normative data collection. One hundred and forty-seven children were recruited using flyers and word of mouth. Of the participants recruited, 137 children qualified for the study. Participants attended schools located in areas that varied in terms of socioeconomic status, and resided in six different states. Audiological testing included a hearing screening (15 dB HL from 250 to 8000 Hz), word recognition testing, tympanometry, ipsilateral and contralateral reflexes, and transient-evoked otoacoustic emissions. The language, nonverbal IQ, phonological processing, and attention skills of each participant were screened using the Clinical Evaluation of Language Fundamentals-4 Screener, Test of Nonverbal Intelligence, Comprehensive Test of Phonological Processing, and Integrated Visual and Auditory-Continuous Performance Test, respectively. The behavioral APD battery included the following tests: Dichotic Digits Test, Frequency Pattern Test, Duration Pattern Test, Random Gap Detection Test, Compressed and Reverberated Words Test, Auditory Figure Ground (signal-to-noise ratio of +8 and +0), and Listening in Spatialized Noise-Sentences Test. Mean scores and standard deviations of each test were calculated, and analysis of variance tests were used to determine effects of factors such as gender, handedness, and birth history on each test. Normative data tables for the test battery were created for the following age groups: 7- and 8-yr-olds (n = 49), 9- and 10-yr-olds (n = 40), and 11- and 12-yr-olds (n = 48). No significant effects were seen for gender or handedness on any of the measures. The data collected in this study are appropriate for use in clinical diagnosis of APD. Use of a low-linguistically loaded core battery with the addition of more language-based tests, when language abilities are known, can provide a well-rounded picture of a child's auditory processing abilities. Screening for language, phonological processing, attention, and cognitive level can provide more information regarding a diagnosis of APD, determine appropriateness of the test battery for the individual child, and may assist with making recommendations or referrals. It is important to use a multidisciplinary approach in the diagnosis and treatment of APD due to the high likelihood of comorbidity with other language, learning, or attention deficits. Although children with other diagnoses may be tested for APD, it is important to establish previously made diagnoses before testing to aid in appropriate test selection and recommendations. American Academy of Audiology.

Animal cruelty and psychiatric disorders.

PubMed

Gleyzer, Roman; Felthous, Alan R; Holzer, Charles E

2002-01-01

Animal cruelty in childhood, although generally viewed as abnormal or deviant, for years was not considered symptomatic of any particular psychiatric disorder. Although animal cruelty is currently used as a diagnostic criterion for conduct disorder, research establishing the diagnostic significance of this behavior is essentially nonexistent. In the current study, investigators tested the hypothesis that a history of substantial animal cruelty is associated with a diagnosis of antisocial personality disorder (APD) and looked for associations with other disorders commonly diagnosed in a population of criminal defendants. Forty-eight subjects, criminal defendants who had histories of substantial animal cruelty, were matched with defendants without this history. Data were systematically obtained from the files by using four specifically designed data retrieval outlines. A history of animal cruelty during childhood was significantly associated with APD, antisocial personality traits, and polysubstance abuse. Mental retardation, psychotic disorders, and alcohol abuse showed no such association.

Blood-based NfL

PubMed Central

Janelidze, Shorena; Hall, Sara; Magdalinou, Nadia; Lees, Andrew J.; Andreasson, Ulf; Norgren, Niklas; Linder, Jan; Forsgren, Lars; Constantinescu, Radu; Zetterberg, Henrik; Blennow, Kaj

2017-01-01

Objective: To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, and can therefore improve the diagnostic workup of parkinsonian disorders. Methods: The study included 3 independent prospective cohorts: the Lund (n = 278) and London (n = 117) cohorts, comprising healthy controls and patients with PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), as well as an early disease cohort (n = 109) of patients with PD, PSP, MSA, or CBS with disease duration ≤3 years. Blood NfL concentration was measured using an ultrasensitive single molecule array (Simoa) method, and the diagnostic accuracy to distinguish PD from APD was investigated. Results: We found strong correlations between blood and CSF concentrations of NfL (ρ ≥ 0.73–0.84, p ≤ 0.001). Blood NfL was increased in patients with MSA, PSP, and CBS (i.e., all APD groups) when compared to patients with PD as well as healthy controls in all cohorts (p < 0.001). Furthermore, in the Lund cohort, blood NfL could accurately distinguish PD from APD (area under the curve [AUC] 0.91) with similar results in both the London cohort (AUC 0.85) and the early disease cohort (AUC 0.81). Conclusions: Quantification of blood NfL concentration can be used to distinguish PD from APD. Blood-based NfL might consequently be included in the diagnostic workup of patients with parkinsonian symptoms in both primary care and specialized clinics. Classification of evidence: This study provides Class III evidence that blood NfL levels discriminate between PD and APD. PMID:28179466

Police-registered offenses and psychiatric disorders among young males : the Finnish "From a boy to a man" birth cohort study.

PubMed

Elonheimo, Henrik; Niemelä, Solja; Parkkola, Kai; Multimäki, Petteri; Helenius, Hans; Nuutila, Ari-Matti; Sourander, Andre

2007-06-01

To study associations between crime and psychiatric disorders among adolescent males in a representative population-based cohort study. The sample includes 2,712 Finnish boys born in 1981. Information on criminality consists of offenses registered in the Finnish National Police Register 1998-2001. Crime was classified according to frequency and type (drug, violent, property, traffic, and drunk driving offenses). Information on psychiatric diagnoses between 1999 and 2004 was collected from the Finnish National Military Register. Of the 2,712 boys, 22% had a crime registration during the 4-year period, and 10% had at least one psychiatric disorder according to the Military Register. Those with psychiatric disorders accounted for 49% of all crimes. Of those with more than five crimes (n = 98), 59% had psychiatric diagnoses. After adjusting for other crime types and childhood socio-economic status, property crime was independently associated with several diagnoses: antisocial personality (APD), substance use (SUD), psychotic, anxiety, and adjustment disorders. Drug offending was independently associated with APD, SUD, and psychotic disorder, and traffic offenses with APD. Youth crime is predominantly associated with antisocial personality and substance use disorders. Crime prevention efforts should focus on boys showing a risk for antisocial and substance use problems. In particular, property, drug, and repeat offenders need mental health and substance use assessment. There is a need to develop integrated mental health and substance use treatment services for young offenders within or alongside the criminal justice system.

Group schema therapy versus group cognitive behavioral therapy for social anxiety disorder with comorbid avoidant personality disorder: study protocol for a randomized controlled trial.

PubMed

Baljé, Astrid; Greeven, Anja; van Giezen, Anne; Korrelboom, Kees; Arntz, Arnoud; Spinhoven, Philip

2016-10-08

Social anxiety disorder (SAD) with comorbid avoidant personality disorder (APD) has a high prevalence and is associated with serious psychosocial problems and high societal costs. When patients suffer from both SAD and APD, the Dutch multidisciplinary guidelines for personality disorders advise offering prolonged cognitive behavioral therapy (CBT). Recently there is increasing evidence for the effectiveness of schema therapy (ST) for personality disorders such as borderline personality disorder and cluster C personality disorders. Since ST addresses underlying personality characteristics and maladaptive coping strategies developed in childhood, this treatment might be particularly effective for patients with SAD and comorbid APD. To our knowledge, there are no studies comparing CBT with ST in this particular group of patients. This superiority trial aims at comparing the effectiveness of these treatments. As an additional goal, predictors and underlying mechanisms of change will be explored. The design of the study is a multicentre two-group randomized controlled trial (RCT) in which the treatment effect of group cognitive behavioral therapy (GCBT) will be compared to that of group schema therapy (GST) in a semi-open group format. A total of 128 patients aged 18-65 years old will be enrolled. Patients will receive 30 sessions of GCBT or GST during a period of approximately 9 months. Primary outcome measures are the Liebowitz Social Anxiety Scale Self-Report (LSAS-SR) for social anxiety disorder and the newly developed Avoidant Personality Disorder Severity Index (AVPDSI) for avoidant personality disorder. Secondary outcome measures are the MINI section SAD, the SCID-II section APD, the Schema Mode Inventory (SMI-2), the Inventory of Depressive Symptomatology Self-Report (IDS-SR), the World Health Organization Quality of Life-BREF (WHOQOL-BREF), the Difficulties in Emotion Regulation Scale (DERS), the Rosenberg Self-Esteem Scale (RSES) and the Acceptance and Action Questionnaire (AAQ-II). Data will be collected at the start, halfway and at the end of the treatment, followed by measurements at 3, 6 and 12 months post-treatment. The trial will increase our knowledge on the effectiveness and applicability of both treatment modalities for patients suffering from both diagnoses. Dutch Trial Register: NTR3921 . Registered on 25 March 2013.

Comparing the constructs of antisocial personality disorder and psychopathy in a sample of incarcerated women.

PubMed

Warren, Janet I; South, Susan C

2006-01-01

Our study examines the relationship between Antisocial Personality Disorder (APD) and psychopathy among a sample of 137 female offenders. Drawing from a historical review of the evolution of these two concepts, we explore their differential relationship to patterns of criminal behavior, psychological adjustment, co-morbidity with other personality disorders, victimization, and institutional adjustment. Findings suggest that the two disorders share a common foundation of social norm violations and deception; however, APD is associated with impulsive, aggressive, and irresponsible behavior, higher rates of childhood abuse, and greater co-morbidity with Cluster A PDs, while psychopathy is better characterized by higher rates of property crimes, previous incarceration, and the manifestation of remorselessness. Results contribute to a further understanding of the etiology and phenomenology of these two disorders and suggest different types of treatment and intervention. Copyright (c) 2006 John Wiley & Sons, Ltd.

Effects of listening ability on speaking, writing and reading skills of children who were suspected of auditory processing difficulty.

PubMed

Yalçinkaya, Fulya; Muluk, Nuray Bayar; Sahin, Semra

2009-08-01

The aim of this study was to investigate the effects of listening ability on speaking, writing and reading skills of children who was suspected of auditory processing difficulty (APD). This research was conducted with 67 children in 1st or 2nd grade of primary school. The first group (Group I-control) was comprised of 41 children without APD. The second group (Group II-study group) was comprised of 26 children with APD. Listening, speaking, reading and writing skills were evaluated by Observational Rating Scale (ORS) and analyzed in both groups. Listening value of ORS in APD group was significantly lower; and, speaking, reading and writing values of ORS in APD group were significantly higher than control group (p=0.000). It was also found that, the main effect of listening skills was on speaking in normal childs, and on writing ability in children with APD. It was concluded that, for school-aged children, APD can lead to or is associated with difficulties in written language.

Predictive validity of childhood oppositional defiant disorder and conduct disorder: implications for the DSM-V.

PubMed

Burke, Jeffrey D; Waldman, Irwin; Lahey, Benjamin B

2010-11-01

Data are presented from 3 studies of children and adolescents to evaluate the predictive validity of childhood oppositional defiant disorder (ODD) and conduct disorder (CD) as defined in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV; American Psychiatric Association, 1994) and the International Classification of Diseases, Version 10 (ICD-10; World Health Organization, 1992). The present analyses strongly support the predictive validity of these diagnoses by showing that they predict both future psychopathology and enduring functional impairment. Furthermore, the present findings generally support the hierarchical developmental hypothesis in DSM-IV that some children with ODD progress to childhood-onset CD, and some youth with CD progress to antisocial personality disorder (APD). Nonetheless, they reveal that CD does not always co-occur with ODD, particularly during adolescence. Importantly, the present findings suggest that ICD-10 diagnostic criteria for ODD, which treat CD symptoms as ODD symptoms when diagnostic criteria for CD are not met, identify more functionally impaired children than the more restrictive DSM-IV definition of ODD. Filling this "hole" in the DSM-IV criteria for ODD should be a priority for the DSM-V. In addition, the present findings suggest that although the psychopathic trait of interpersonal callousness in childhood independently predicts future APD, these findings do not confirm the hypothesis that callousness distinguishes a subset of children with CD with an elevated risk for APD. PsycINFO Database Record (c) 2010 APA, all rights reserved

The effect of sampling, diagnostic criteria and assessment procedures on the observed prevalence of DSM-III-R personality disorders among treated alcoholics.

PubMed

Verheul, R; Hartgers, C; Van den Brink, W; Koeter, M W

1998-03-01

OBJECTIVE. In a recent review of empirical studies on the prevalence of DSM-III-R personality disorders among substance abusers, wide ranges of prevalence rates for overall Axis II, antisocial personality disorder (APD) and borderline personality disorder (BPD) were shown. Utilizing subsamples from within a single study population, the current report explores the effect of sampling, diagnostic criteria and assessment procedures on the observed prevalence of DSM-III-R personality disorders among treated alcoholics. Personality disorders were assessed with the Personality Diagnostic Questionnaire Revised (PDQR) at two times of measurement (Time 1 n = 459; Time 2 n = 90). In addition, APD was measured with the Composite International Diagnostic Interview (CIDI; n = 587). Finally, an unselected subgroup (n = 136) was interviewed with the International Personality Disorder Examination (IPDE). There were few differences between inpatients or outpatients or between males and females. Using the IPDE, the exclusion of substance-related pathology did not affect the prevalence estimate. However, the prevalence rates according to the PDQR varied greatly across age groups. In a representative subsample (n = 109), the prevalence rates also varied greatly across assessment methods (PDQR, 52% vs IPDE, 31%). The prevalence estimate of APD according to the CIDI was related to setting, gender, age group and the applied time-frame. These findings indicate the examined factors to be necessary qualifiers of prevalence estimates and, consequently, support the use of a multiple-criteria/multimethod assessment battery in research as well as in clinical work.

Epstein–Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS) Immunodeficiency

PubMed Central

Carpier, Jean-Marie; Lucas, Carrie L.

2018-01-01

Activated PI3Kδ Syndrome (APDS) is an inherited immune disorder caused by heterozygous, gain-of-function mutations in the genes encoding the phosphoinositide 3-kinase delta (PI3Kδ) subunits p110δ or p85δ. This recently described primary immunodeficiency disease (PID) is characterized by recurrent sinopulmonary infections, lymphoproliferation, and susceptibility to herpesviruses, with Epstein–Barr virus (EBV) infection being most notable. A broad range of PIDs having disparate, molecularly defined genetic etiology can cause susceptibility to EBV, lymphoproliferative disease, and lymphoma. Historically, PID patients with loss-of-function mutations causing defective cell-mediated cytotoxicity or antigen receptor signaling were found to be highly susceptible to pathological EBV infection. By contrast, the gain of function in PI3K signaling observed in APDS patients paradoxically renders these patients susceptible to EBV, though the underlying mechanisms are incompletely understood. At a cellular level, APDS patients exhibit deranged B lymphocyte development and defects in class switch recombination, which generally lead to defective immunoglobulin production. Moreover, APDS patients also demonstrate an abnormal skewing of T cells toward terminal effectors with short telomeres and senescence markers. Here, we review APDS with a particular focus on how the altered lymphocyte biology in these patients may confer EBV susceptibility. PMID:29387064

A study of chemokines, chemokine receptors and interleukin-6 in patients with panic disorder, personality disorders and their co-morbidity.

PubMed

Ogłodek, Ewa A; Szota, Anna M; Just, Marek J; Szromek, Adam R; Araszkiewicz, Aleksander

2016-08-01

Stress may induce inflammatory changes in the immune system and activate pro-inflammatory cytokines and their receptors by activating the hypothalamic-pituitary-adrenal axis. 460 hospitalized patients with panic disorders (PD) and/or personality disorders (P) were studied. The study group comprised subjects with PD, avoidant personality disorder (APD), borderline personality disorder (BPD), obsessive-compulsive personality disorder (OCPD), and concomitant (PD+APD; PD+BPD; PD+OCPD). Each study group consisted of 60 subjects (30 females and 30 males). The control group included 20 females and 20 males without any history of mental disorder. ELISA was used to assess the levels of chemokines: CCL-5/RANTES (regulated on activation, normal T-cell expressed and secreted), CXCL-12/SDF-1 (stromal derived factor), their receptors CXCR-5 (C-C chemokine receptor type-5), CXCR-4 (chemokine C-X-C motif receptor-4), and IL-6. Statistically significant differences in the levels of CCL-5 and CCR-5 were revealed between all study groups. The greatest differences were found between the groups with PD+OCPD and PD+APD. Moreover, concomitance of PD with P significantly increased the level of chemokines and their receptors in all study groups versus the subjects with P alone. The results of the study show differences between the groups. To be specific, inflammatory markers were more elevated in the study groups than the controls. Therefore, chemokines and chemokine receptors may be used as inflammatory markers in patients with PD co-existent with P to indicate disease severity. PD was found to be a factor in maintaining inflammatory activity in the immune system in patients with P. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Recent advances in very large area avalanche photodiodes

NASA Astrophysics Data System (ADS)

Squillante, Michael R.; Christian, James; Entine, Gerald; Farrell, Richard; Karger, Arieh M.; McClish, Mickel; Myers, Richard; Shah, Kanai S.; Taylor, David; Vanderpuye, Kofi; Waer, Peter; Woodring, Mitchell

2003-09-01

The Avalanche Photodiode (APD) is a unique device that combines the advantages of solid state photodetectors with those of high gain devices such as photomultiplier tubes (PMTs). APDs have internal gain that provides a high signal-to-noise ratio. APDs have high quantum efficiency, are fast, compact, and rugged. These properties make them suitable detectors for important applications such as LADAR, detection and identification toxic chemicals and bio-warfare agents, LIDAR fluorescence detection, stand-off laser induced breakdown spectroscopy (LIBS), and nuclear detectors and imagers. Recently there have been significant technical breakthroughs in fabricating very large APDs, APD arrays, and position sensitive APD arrays (PSAPD). Signal gain of over 10,000 has been achieved, single element APDs have been fabricated with active area greater than 40 cm2, monolithic pixelated arrays with up to 28 x 28 elements have been fabricated, and position sensitive APDs have been developed and tested. Additionally, significant progress has been made in improving the fabrication process to provide better uniformity and high yield, permitting cost effective manufacturing of APDs for reduced cost.

Predictor Variables of Developing Anterior Pituitary Deficiencies in a Group of Paediatric Patients with Central Diabetes Insipidus and Langerhans Cell Histiocytosis.

PubMed

Vaiani, Elisa; Malossetti, Carmen; Vega, Lina Margarita; Zubizarreta, Pedro; Braier, Jorge; Belgorosky, Alicia

2017-01-01

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder of unknown etiopathogenesis. Central diabetes insipidus (CDI) is the most frequent endocrine manifestation and is a known risk factor for the development of further anterior pituitary hormone deficiencies (APD). However, not all CDI patients develop APD, as observed during prolonged periods of follow-up. To find predictors of developing APD in LCH children with CDI followed in our institution. We retrospectively analysed 44 patients over a median period (quartiles) of 12.3 years (8.79-14.24). Patients were subdivided into group 1 and group 2, according to absence or presence of APD, respectively. The main variables studied were: (1) chronological age (CA) at LCH diagnosis, (2) the primary site of LCH at diagnosis: low risk (LR) and multisystemic risk organs, and (3) the presence of reactivation. Multivariate Cox regression analysis showed that APD was positively associated with CA at LCH diagnosis [relative risk (RR) 1.14, p < 0.01], the LR clinical form (RR 8.6, p < 0.03), and negatively associated with the presence of reactivations (RR 0.3, p < 0.01). Patients with older CA at LCH diagnosis, LR clinical forms, and fewer reactivation episodes might represent a subgroup of paediatric LCH CDI patients with a higher risk of developing APD. © 2016 S. Karger AG, Basel.

Amygdala reactivity and negative emotionality: divergent correlates of antisocial personality and psychopathy traits in a community sample.

PubMed

Hyde, Luke W; Byrd, Amy L; Votruba-Drzal, Elizabeth; Hariri, Ahmad R; Manuck, Stephen B

2014-02-01

Previous studies have emphasized that antisocial personality disorder (APD) and psychopathy overlap highly but differ critically in several features, notably negative emotionality (NEM) and possibly amygdala reactivity to social signals of threat and distress. Here we examined whether dimensions of psychopathy and APD correlate differentially with NEM and amygdala reactivity to emotional faces. Testing these relationships among healthy individuals, dimensions of psychopathy and APD were generated by the profile matching technique of Lynam and Widiger (2001), using facet scales of the NEO Personality Inventory-Revised, and amygdala reactivity was measured using a well-established emotional faces task, in a community sample of 103 men and women. Higher psychopathy scores were associated with lower NEM and lower amygdala reactivity, whereas higher APD scores were related to greater NEM and greater amygdala reactivity, but only after overlapping variance in APD and psychopathy was adjusted for in the statistical model. Amygdala reactivity did not mediate the relationship of APD and psychopathy scores to NEM. Supplemental analyses also compared other measures of factors within psychopathy in predicting NEM and amygdala reactivity and found that Factor 2 psychopathy was positively related to NEM and amygdala reactivity across measures of psychopathy. The overall findings replicate seminal observations on NEM in psychopathy by Hicks and Patrick (2006) and extend this work to neuroimaging in a normative population. They also suggest that one critical way in which APD and psychopathy dimensions may differ in their etiology is through their opposing levels of NEM and amygdala reactivity to threat. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Amygdala Reactivity and Negative Emotionality: Divergent Correlates of Antisocial Personality and Psychopathy Traits in a Community Sample

PubMed Central

Hyde, Luke W.; Byrd, Amy L.; Votruba-Drzal, Elizabeth; Hariri, Ahmad R.; Manuck, Stephen B.

2014-01-01

Previous studies have emphasized that antisocial personality disorder (APD) and psychopathy overlap highly but differ critically in several features, notably negative emotionality (NEM) and possibly amygdala reactivity to social signals of threat and distress. Here we examined whether dimensions of psychopathy and APD correlate differentially with NEM and amygdala reactivity to emotional faces. Testing these relationships among healthy individuals, dimensions of psychopathy and APD were generated by the profile matching technique of Lynam and Widiger (2001), using facet scales of the NEO Personality Inventory-Revised, and amygdala reactivity was measured using a well-established emotional faces task, in a community sample of 103 men and women. Higher psychopathy scores were associated with lower NEM and lower amygdala reactivity, whereas higher APD scores were related to greater NEM and greater amygdala reactivity, but only after overlapping variance in APD and psychopathy was adjusted for in the statistical model. Amygdala reactivity did not mediate the relationship of APD and psychopathy scores to NEM. Supplemental analyses also compared other measures of factors within psychopathy in predicting NEM and amygdala reactivity and found that Factor 2 psychopathy was positively related to NEM and amygdala reactivity across measures of psychopathy. The overall findings replicate seminal observations on NEM in psychopathy by Hicks and Patrick (2006) and extend this work to neuroimaging in a normative population. They also suggest that one critical way in which APD and psychopathy dimensions may differ in their etiology is through their opposing levels of NEM and amygdala reactivity to threat. PMID:24661171

Evaluation of selected auditory tests in school-age children suspected of auditory processing disorders.

PubMed

Vanniasegaram, Iyngaram; Cohen, Mazal; Rosen, Stuart

2004-12-01

To compare the auditory function of normal-hearing children attending mainstream schools who were referred for an auditory evaluation because of listening/hearing problems (suspected auditory processing disorders [susAPD]) with that of normal-hearing control children. Sixty-five children with a normal standard audiometric evaluation, ages 6-14 yr (32 of whom were referred for susAPD, with the rest age-matched control children), completed a battery of four auditory tests: a dichotic test of competing sentences; a simple discrimination of short tone pairs differing in fundamental frequency at varying interstimulus intervals (TDT); a discrimination task using consonant cluster minimal pairs of real words (CCMP), and an adaptive threshold task for detecting a brief tone presented either simultaneously with a masker (simultaneous masking) or immediately preceding it (backward masking). Regression analyses, including age as a covariate, were performed to determine the extent to which the performance of the two groups differed on each task. Age-corrected z-scores were calculated to evaluate the effectiveness of the complete battery in discriminating the groups. The performance of the susAPD group was significantly poorer than the control group on all but the masking tasks, which failed to differentiate the two groups. The CCMP discriminated the groups most effectively, as it yielded the lowest number of control children with abnormal scores, and performance in both groups was independent of age. By contrast, the proportion of control children who performed poorly on the competing sentences test was unacceptably high. Together, the CCMP (verbal) and TDT (nonverbal) tasks detected impaired listening skills in 56% of the children who were referred to the clinic, compared with 6% of the control children. Performance on the two tasks was not correlated. Two of the four tests evaluated, the CCMP and TDT, proved effective in differentiating the two groups of children of this study. The application of both tests increased the proportion of susAPD children who performed poorly compared with the application of each test alone, while reducing the proportion of control subjects who performed poorly. The findings highlight the importance of carrying out a complete auditory evaluation in children referred for medical attention, even if their standard audiometric evaluation is unremarkable.

Auditory processing theories of language disorders: past, present, and future.

PubMed

Miller, Carol A

2011-07-01

The purpose of this article is to provide information that will assist readers in understanding and interpreting research literature on the role of auditory processing in communication disorders. A narrative review was used to summarize and synthesize the literature on auditory processing deficits in children with auditory processing disorder (APD), specific language impairment (SLI), and dyslexia. The history of auditory processing theories of these 3 disorders is described, points of convergence and controversy within and among the different branches of research literature are considered, and the influence of research on practice is discussed. The theoretical and clinical contributions of neurophysiological methods are also reviewed, and suggested approaches for critical reading of the research literature are provided. Research on the role of auditory processing in communication disorders springs from a variety of theoretical perspectives and assumptions, and this variety, combined with controversies over the interpretation of research results, makes it difficult to draw clinical implications from the literature. Neurophysiological research methods are a promising route to better understanding of auditory processing. Progress in theory development and its clinical application is most likely to be made when researchers from different disciplines and theoretical perspectives communicate clearly and combine the strengths of their approaches.

Patient request for pharmacist counseling and satisfaction: Automated prescription delivery system versus regular pick-up counter.

PubMed

Hirsch, Jan D; Oen, Austin; Robertson, Suzie; Nguyen, Nancy; Daniels, Charles

2009-01-01

To assess the rate of patient-requested pharmacist counseling for refill prescriptions and satisfaction with pick-up process for patients using an automated prescription delivery system (APDS) versus those using a regular pick-up counter and to explore patient willingness to use an APDS as a tool for pharmacist monitoring of medication therapy outcomes. In this uncontrolled, cross-sectional, survey study, we assessed use of APDS or the regular counter by 116 patients picking up refill prescriptions at two community pharmacies. The main outcome measures were number of patients requesting pharmacist counseling for refill prescriptions, patient satisfaction with pick-up process, and patient willingness to use an APDS to report medication therapy outcomes. None of the regular counter users and only two APDS users (3.7%) requested counseling for their refill prescription (P = 0.126). Almost all patients agreed that they were able to talk to a pharmacist about their prescription if they wanted to do so (95.1% regular counter and 92.3% APDS; P = 0.268). The majority (75%) of patients using APDS indicated that they would be willing to use the system to answer questions or perform simple tests to provide information that the pharmacist could use to improve medication effectiveness or reduce adverse effects. Very few patients (ADPS or regular counter) asked to speak to a pharmacist about their refill medications, although it appeared that no perceived barriers to pharmacist access existed. Most APDS patients were willing to use this new technology to provide information about therapy outcomes to the pharmacist. Further exploration and testing of the APDS as a data collection tool to enhance pharmacist access to therapy outcomes is warranted.

Computerized Auditory Training in Students: Electrophysiological and Subjective Analysis of Therapeutic Effectiveness.

PubMed

Melo, Ândrea de; Mezzomo, Carolina Lisbôa; Garcia, Michele Vargas; Biaggio, Eliara Pinto Vieira

2018-01-01

Introduction  Computerized auditory training (CAT) has been building a good reputation in the stimulation of auditory abilities in cases of auditory processing disorder (APD). Objective  To measure the effects of CAT in students with APD, with typical or atypical phonological acquisition, through electrophysiological and subjective measures, correlating them pre- and post-therapy. Methods  The sample for this study includes14 children with APD, subdivided into children with APD and typical phonological acquisition (G1), and children with APD and atypical phonological acquisition (G2). Phonological evaluation of children (PEC), long latency auditory evoked potential (LLAEP) and scale of auditory behaviors (SAB) were conducted to help with the composition of the groups and with the therapeutic intervention. The therapeutic intervention was performed using the software Escuta Ativa (CTS Informática, Pato Branco, Brazil) in 12 sessions of 30 minutes, twice a week. For data analysis, the appropriate statistical tests were used. Results  A decrease in the latency of negative wave N2 and the positive wave P3 in the left ear in G1, and a decrease of P2 in the right ear in G2 were observed. In the analysis comparing the pre- and post-CAT groups, there was a significant difference in P1 latency in the left ear and P2 latency in the right ear, pre-intervention. Furthermore, eight children had an absence of the P3 wave, pre-CAT, but after the intervention, all of them presented the P3 wave. There were changes in the SAB score pre- and post-CAT in both groups. The presence of correlation between the scale and some LLAEP components was observed. Conclusion  The CAT produced an electrophysiological modification, which became evident in the effects of the effects of neural plasticity after CAT. The SAB proved to be useful in measuring the therapeutic effects of the intervention. Moreover, there were behavioral changes in the SAB (higher scores) and correlation with LLAEP.

Acoustic Reflexes in Normal-Hearing Adults, Typically Developing Children, and Children with Suspected Auditory Processing Disorder: Thresholds, Real-Ear Corrections, and the Role of Static Compliance on Estimates.

PubMed

Saxena, Udit; Allan, Chris; Allen, Prudence

2017-06-01

Previous studies have suggested elevated reflex thresholds in children with auditory processing disorders (APDs). However, some aspects of the child's ear such as ear canal volume and static compliance of the middle ear could possibly affect the measurements of reflex thresholds and thus impact its interpretation. Sound levels used to elicit reflexes in a child's ear may be higher than predicted by calibration in a standard 2-cc coupler, and lower static compliance could make visualization of very small changes in impedance at threshold difficult. For this purpose, it is important to evaluate threshold data with consideration of differences between children and adults. A set of studies were conducted. The first compared reflex thresholds obtained using standard clinical procedures in children with suspected APD to that of typically developing children and adults to test the replicability of previous studies. The second study examined the impact of ear canal volume on estimates of reflex thresholds by applying real-ear corrections. Lastly, the relationship between static compliance and reflex threshold estimates was explored. The research is a set of case-control studies with a repeated measures design. The first study included data from 20 normal-hearing adults, 28 typically developing children, and 66 children suspected of having an APD. The second study included 28 normal-hearing adults and 30 typically developing children. In the first study, crossed and uncrossed reflex thresholds were measured in 5-dB step size. Reflex thresholds were analyzed using repeated measures analysis of variance (RM-ANOVA). In the second study, uncrossed reflex thresholds, real-ear correction, ear canal volume, and static compliance were measured. Reflex thresholds were measured using a 1-dB step size. The effect of real-ear correction and static compliance on reflex threshold was examined using RM-ANOVA and Pearson correlation coefficient, respectively. Study 1 replicated previous studies showing elevated reflex thresholds in many children with suspected APD when compared to data from adults using standard clinical procedures, especially in the crossed condition. The thresholds measured in children with suspected APD tended to be higher than those measured in the typically developing children. There were no significant differences between the typically developing children and adults. However, when real-ear calibrated stimulus levels were used, it was found that children's thresholds were elicited at higher levels than in the adults. A significant relationship between reflex thresholds and static compliance was found in the adult data, showing a trend for higher thresholds in ears with lower static compliance, but no such relationship was found in the data from the children. This study suggests that reflex measures in children should be adjusted for real-ear-to-coupler differences before interpretation. The data in children with suspected APD support previous studies suggesting abnormalities in reflex thresholds. The lack of correlation between threshold and static compliance estimates in children as was observed in the adults may suggest a nonmechanical explanation for age and clinically related effects. American Academy of Audiology

Development of novel technologies to enhance performance and reliability of III-Nitride avalanche photodiodes

NASA Astrophysics Data System (ADS)

Suvarna, Puneet Harischandra

Solar-blind ultraviolet avalanche photodiodes are an enabling technology for applications in the fields of astronomy, communication, missile warning systems, biological agent detection and particle physics research. Avalanche photodiodes (APDs) are capable of detecting low-intensity light with high quantum efficiency and signal-to-noise ratio without the need for external amplification. The properties of III-N materials (GaN and AlGaN) are promising for UV photodetectors that are highly efficient, radiation-hard and capable of visible-blind or solar-blind operation without the need for external filters. However, the realization of reliable and high performance III-N APDs and imaging arrays has several technological challenges. The high price and lack of availability of bulk III-N substrates necessitates the growth of III-Ns on lattice mismatched substrates leading to a high density of dislocations in the material that can cause high leakage currents, noise and premature breakdown in APDs. The etched sidewalls of III-N APDs and high electric fields at contact edges are also detrimental to APD performance and reliability. In this work, novel technologies have been developed and implemented that address the issues of performance and reliability in III-Nitride based APDs. To address the issue of extended defects in the bulk of the material, a novel pulsed MOCVD process was developed for the growth of AlGaN. This process enables growth of high crystal quality AlxGa1-xN with excellent control over composition, doping and thickness. The process has also been adapted for the growth of high quality III-N materials on silicon substrate for devices such as high electron mobility transistors (HEMTs). A novel post-growth defect isolation technique is also discussed that can isolate the impact of conductive defects from devices. A new sidewall passivation technique using atomic layer deposition (ALD) of dielectric materials was developed for III-N APDs that is effective in reducing the dark-current and trap states at sidewalls by close to an order of magnitude, leading to improved APD performance. Development and implementation of an ion implantation based contact edge termination technique for III-N APDs that helps prevent premature breakdown from the contact edge of the devices, has further lead to improved reliability. Finally novel improved III-N APD device designs are proposed using preliminary experiments and numerical simulations for future implementations.

Diagnostic accuracy of combined FP-CIT, IBZM, and MIBG scintigraphy in the differential diagnosis of degenerative parkinsonism: a multidimensional statistical approach.

PubMed

Südmeyer, Martin; Antke, Christina; Zizek, Tanja; Beu, Markus; Nikolaus, Susanne; Wojtecki, Lars; Schnitzler, Alfons; Müller, Hans-Wilhelm

2011-05-01

In vivo molecular imaging of pre- and postsynaptic nigrostriatal neuronal degeneration and sympathetic cardiac innervation with SPECT is used to distinguish idiopathic Parkinson disease (PD) from atypical parkinsonian disorder (APD). However, the diagnostic accuracy of these imaging approaches as stand-alone procedures is often unsatisfying. The aim of this study was therefore to evaluate to which extent diagnostic accuracy can be increased by their combined use together with a multidimensional statistical algorithm. The SPECT radiotracers (123)I-(S)-2-hydroxy-3-iodo-6-methoxy-N-[1-ethyl-2-pyrrodinyl)-methyl]benzamide (IBZM), (123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropan (FP-CIT), and meta-(123)I-iodobenzylguanidine (MIBG) were used to assess striatal postsynaptic D(2) receptor binding, striatal presynaptic dopamine transporter binding, and myocardial adrenergic innervation, respectively. Thirty-one PD and 17 APD patients were prospectively investigated. PD and APD diagnoses were established using consensus criteria and reevaluated after 37.4 ± 12.4 and 26 ± 11.6 mo in PD and APD, respectively. Test accuracy (TA) for PD-APD differentiation was computed for all logical (Boolean) combinations of imaging modalities by receiver-operating-characteristic analysis--that is, after multidimensional optimization of cutoff values. Analysis showed moderate TA for PD-APD differentiation using each molecular approach alone (IBZM, 79%; MIBG, 73%; and FP-CIT, 73%). For combined use, the highest TA resulted under the assumption that at least 2 of the 3 biologic markers had to be positive for APD using the following cutoff values: 1.46 or less for IBZM, less than 2.10 for FP-CIT, and greater than 1.43 for MIBG. This algorithm distinguished APD from PD with a sensitivity of 94%, specificity of 94% (TA, 94%), positive predictive value of 89%, and negative predictive value of 97%. Results suggest that the multidimensional combination of FP-CIT, IBZM, and MIBG scintigraphy is likely to significantly increase TA in differentiating PD from APD. The differential diagnosis of degenerative parkinsonism may thus be facilitated.

Examining the prevalence, role and impact of evidence regarding Antisocial Personality, sociopathy and psychopathy in capital cases: a survey of defense team members.

PubMed

Edens, John F; Cox, Jennifer

2012-01-01

Although anecdotal case accounts suggest that evidence concerning Antisocial Personality Disorder (APD), sociopathy and psychopathy is frequently introduced by the prosecution in capital murder trials, to date there has been no systematic research to determine the actual prevalence, role, or perceived impact of such evidence in these cases. Survey data collected from attendees at a national capital mitigation conference (n=41) indicated that prosecution evidence concerning APD was quite prevalent, with "sociopath" and "psychopath" labels being introduced less frequently. Evidence concerning these disorders, which were assessed primarily via DSM criteria and self-report personality inventories, was most often introduced by the prosecution in the sentencing phase to address a defendant's ostensible risk of future dangerousness and/or to rebut mitigating evidence-although it was also introduced frequently in the guilt/innocence phase of these trials to rebut mental health evidence offered by the defense. Survey respondents believed that evidence concerning APD, sociopathy, and psychopathy had a considerable impact on trial outcomes. Also, although defense objections were common, such evidence was rarely ruled to be inadmissible in these cases. Copyright © 2012 John Wiley & Sons, Ltd.

Synaptosomal-associated protein 25 gene polymorphisms and antisocial personality disorder: association with temperament and psychopathy.

PubMed

Basoglu, Cengiz; Oner, Ozgur; Ates, Alpay; Algul, Ayhan; Bez, Yasin; Cetin, Mesut; Herken, Hasan; Erdal, Mehmet Emin; Munir, Kerim M

2011-06-01

The molecular genetic of personality disorders has been investigated in several studies; however, the association of antisocial behaviours with synaptosomal-associated protein 25 (SNAP25) gene polymorphisms has not. This association is of interest as SNAP25 gene polymorphism has been associated with attention-deficit hyperactivity disorder and personality. We compared the distribution of DdeI and MnII polymorphisms in 91 young male offenders and in 38 sex-matched healthy control subjects. We also investigated the association of SNAP25 gene polymorphisms with severity of psychopathy and with temperament traits: novelty seeking, harm avoidance, and reward dependence. The MnII T/T and DdeI T/T genotypes were more frequently present in male subjects with antisocial personality disorder (APD) than in sex-matched healthy control subjects. The association was stronger when the frequency of both DdeI and MnII T/T were taken into account. In the APD group, the genotype was not significantly associated with the Psychopathy Checklist-Revised scores, measuring the severity of psychopathy. However, the APD subjects with the MnII T/T genotype had higher novelty seeking scores; whereas, subjects with the DdeI T/T genotype had lower reward dependence scores. Again, the association between genotype and novelty seeking was stronger when both DdeI and MnII genotypes were taken into account. DdeI and MnII T/T genotypes may be a risk factor for antisocial behaviours. The association of the SNAP25 DdeI T/T and MnII T/T genotypes with lower reward dependence and higher novelty seeking suggested that SNAP25 genotype might influence other personality disorders, as well.

Synaptosomal-Associated Protein 25 Gene Polymorphisms and Antisocial Personality Disorder: Association With Temperament and Psychopathy

PubMed Central

Basoglu, Cengiz; Oner, Ozgur; Ates, Alpay; Algul, Ayhan; Bez, Yasin; Cetin, Mesut; Herken, Hasan; Erdal, Mehmet Emin; Munir, Kerim M

2011-01-01

Objective The molecular genetic of personality disorders has been investigated in several studies; however, the association of antisocial behaviours with synaptosomal-associated protein 25 (SNAP25) gene polymorphisms has not. This association is of interest as SNAP25 gene polymorphism has been associated with attention-deficit hyperactivity disorder and personality. Methods We compared the distribution of DdeI and MnlI polymorphisms in 91 young male offenders and in 38 sex-matched healthy control subjects. We also investigated the association of SNAP25 gene polymorphisms with severity of psychopathy and with temperament traits: novelty seeking, harm avoidance, and reward dependence. Results The MnlI T/T and DdeI T/T genotypes were more frequently present in male subjects with antisocial personality disorder (APD) than in sex-matched healthy control subjects. The association was stronger when the frequency of both DdeI and MnlI T/T were taken into account. In the APD group, the genotype was not significantly associated with the Psychopathy Checklist–Revised scores, measuring the severity of psychopathy. However, the APD subjects with the MnlI T/T genotype had higher novelty seeking scores; whereas, subjects with the DdeI T/T genotype had lower reward dependence scores. Again, the association between genotype and novelty seeking was stronger when both DdeI and MnlI genotypes were taken into account. Conclusion DdeI and MnlI T/T genotypes may be a risk factor for antisocial behaviours. The association of the SNAP25 DdeI T/T and MnlI T/T genotypes with lower reward dependence and higher novelty seeking suggested that SNAP25 genotype might influence other personality disorders, as well. PMID:21756448

Towards on-chip integration of brain imaging photodetectors using standard CMOS process.

PubMed

Kamrani, Ehsan; Lesage, Frederic; Sawan, Mohamad

2013-01-01

The main effects of on-chip integration on the performance and efficiency of silicon avalanche photodiode (SiAPD) and photodetector front-end is addressed in this paper based on the simulation and fabrication experiments. Two different silicon APDs are fabricated separately and also integrated with a transimpedance amplifier (TIA) front-end using standard CMOS technology. SiAPDs are designed in p+/n-well structure with guard rings realized in different shapes. The TIA front-end has been designed using distributed-gain concept combined with resistive-feedback and common-gate topology to reach low-noise and high gain-bandwidth product (GBW) characteristics. The integrated SiAPDs show higher signal-to-noise ratio (SNR), sensitivity and detection efficiency comparing to the separate SiAPDs. The integration does not show a significant effect on the gain and preserves the low power consumption. Using APDs with p-well guard-ring is preferred due to the higher observed efficiency after integration.

Setting appropriate pass or fail cut-off criteria for tests to reflect real life listening difficulties in children with suspected auditory processing disorder.

PubMed

Ahmmed, Ansar U; Ahmmed, Afsara A

2016-05-01

This paper explores the pass or fail cut-off criteria, the number of test fails, and the nature of tests that are most appropriate in predicting listening difficulties (LiD) in children with suspected APD (SusAPD). One hundred and nine English-speaking children (67 males, 42 females) aged between 6 and 11 years with SusAPD were assessed. The Children's Auditory Performance Scale (CHAPS) scores 2 SD below the mean were taken as markers of LiD in different listening conditions. Binary logistic regression analyses were carried out to evaluate the cut-off criterion (2 SD or 1.5 SD or 1 SD below the mean) of failing at least two tests, from the SCAN-C and IMAP test batteries, which significantly predicted LiD. Analyses were also carried out to assess if the group of auditory processing (AP) or cognitive or combination of AP plus cognitive tests were significant in predicting LiD. Receiver Operative Characteristic (ROC) curves were also explored to evaluate how the sensitivity and specificity in confirming LiD varied with the number of test fails. Filtered Words, Competing Words, Competing Sentences, VCV in ICRA noise, Digit Span, Sight Word Reading and the Cued Auditory Attention tests correlated with one or more of the CHAPS domains. Failing at least two of these tests 1.5 SD below the mean significantly predicted (p<.05) CHAPS Ideal scores 2 SD below the mean, and failing at least two of the tests 1 SD below the mean significantly predicted (p<.05) CHAPS Memory and CHAPS Attention scores 2 SD below the mean. The combination of AP plus cognitive tests had significantly higher ability to predict CHAPS Ideal, Memory and Attention scores, compared to the group of AP or cognitive tests separately. ROC curves showed that failing at least two of the tests was associated with the best sensitivity and specificity in predicting LiD. Of the different CHAPS domains only the CHAPS Ideal, Memory and Attention correlated with the APD tests. Failing at least two APD tests from a combination of AP and cognitive tests 1 SD and 1.5 SD below the mean, but not 2 SD, is more appropriate in confirming LiD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Advanced Parkinson disease patients have impairment in prosody processing.

PubMed

Albuquerque, Luisa; Martins, Maurício; Coelho, Miguel; Guedes, Leonor; Ferreira, Joaquim J; Rosa, Mário; Martins, Isabel Pavão

2016-01-01

The ability to recognize and interpret emotions in others is a crucial prerequisite of adequate social behavior. Impairments in emotion processing have been reported from the early stages of Parkinson's disease (PD). This study aims to characterize emotion recognition in advanced Parkinson's disease (APD) candidates for deep-brain stimulation and to compare emotion recognition abilities in visual and auditory domains. APD patients, defined as those with levodopa-induced motor complications (N = 42), and healthy controls (N = 43) matched by gender, age, and educational level, undertook the Comprehensive Affect Testing System (CATS), a battery that evaluates recognition of seven basic emotions (happiness, sadness, anger, fear, surprise, disgust, and neutral) on facial expressions and four emotions on prosody (happiness, sadness, anger, and fear). APD patients were assessed during the "ON" state. Group performance was compared with independent-samples t tests. Compared to controls, APD had significantly lower scores on the discrimination and naming of emotions in prosody, and visual discrimination of neutral faces, but no significant differences in visual emotional tasks. The contrasting performance in emotional processing between visual and auditory stimuli suggests that APD candidates for surgery have either a selective difficulty in recognizing emotions in prosody or a general defect in prosody processing. Studies investigating early-stage PD, and the effect of subcortical lesions in prosody processing, favor the latter interpretation. Further research is needed to understand these deficits in emotional prosody recognition and their possible contribution to later behavioral or neuropsychiatric manifestations of PD.

The Role of Structural and Compositional Heterogeneities in the Insulator-to-Metal Transition in Hole-Doped APd3O4 (A = Ca, Sr).

PubMed

Lamontagne, Leo K; Laurita, Geneva; Knight, Michael; Yusuf, Huma; Hu, Jerry; Seshadri, Ram; Page, Katharine

2017-05-01

The cubic semiconducting compounds APd 3 O 4 (A = Ca, Sr) can be hole-doped by Na substitution on the A site and driven toward more conducting states. This process has been followed here by a number of experimental techniques to understand the evolution of electronic properties. While an insulator-to-metal transition is observed in Ca 1-x Na x Pd 3 O 4 for x ≥ 0.15, bulk metallic behavior is not observed for Sr 1-x Na x Pd 3 O 4 up to x = 0.20. Given the very similar crystal and (calculated) electronic structures of the two materials, the distinct behavior is a matter of interest. We present evidence of local disorder in the A = Sr materials through the analysis of the neutron pair distribution function, which is potentially at the heart of the distinct behavior. Solid-state 23 Na nuclear magnetic resonance studies additionally suggest a percolative insulator-to-metal transition mechanism, wherein presumably small regions with a signal resembling metallic NaPd 3 O 4 form almost immediately upon Na substitution, and this signal grows monotonically with substitution. Some signatures of increased local disorder and a propensity for Na clustering are seen in the A = Sr compounds.

Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits.

PubMed

Odening, Katja E; Jung, Bernd A; Lang, Corinna N; Cabrera Lozoya, Rocio; Ziupa, David; Menza, Marius; Relan, Jatin; Franke, Gerlind; Perez Feliz, Stefanie; Koren, Gideon; Zehender, Manfred; Bode, Christoph; Brunner, Michael; Sermesant, Maxime; Föll, Daniela

2013-10-01

Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias. To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS. Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities. In the same rabbits' hearts, monophasic APDs were assessed in corresponding segments. In LQT2 and E4031-treated rabbits, APD was longer in all left ventricular segments (P < .01) and APD dispersion was greater than that in LMC rabbits (P < .01). In diastole, peak radial velocities (Vr) were reduced in LQT2 and E4031-treated compared to LMC rabbits in LV base and mid (LQT2: -3.36 ± 0.4 cm/s, P < .01; E4031-treated: -3.24 ± 0.6 cm/s, P < .0001; LMC: -4.42 ± 0.5 cm/s), indicating an impaired diastolic function. Regionally heterogeneous diastolic Vr correlated with APD (LQT2: correlation coefficient [CC] 0.38, P = .01; E4031-treated: CC 0.42, P < .05). Time-to-diastolic peak Vr were prolonged in LQT2 rabbits (LQT2: 196.8 ± 2.9 ms, P < .001; E4031-treated: 199.5 ± 2.2 ms, P < .0001, LMC 183.1 ± 1.5), indicating a prolonged contraction duration. Moreover, in transgenic LQT2 rabbits, diastolic time-to-diastolic peak Vr correlated with APD (CC 0.47, P = .001). In systole, peak Vr were reduced in LQT2 and E4031-treated rabbits (P < .01) but longitudinal velocities or ejection fraction did not differ. Finally, random forest machine learning algorithms enabled a differentiation between LQT2, E4031-treated, and LMC rabbits solely based on "mechanical" magnetic resonance imaging data. The prolongation of APD led to impaired diastolic and systolic function in transgenic and drug-induced LQT2 rabbits. APD correlated with regional diastolic dysfunction, indicating that LQTS is not purely an electrical but an electromechanical disorder. © 2013 Heart Rhythm Society. All rights reserved.

Assessing Auditory Processing Deficits in Tinnitus and Hearing Impaired Patients with the Auditory Behavior Questionnaire

PubMed Central

Diges, Isabel; Simón, Francisco; Cobo, Pedro

2017-01-01

Background and Purpose: Auditory processing disorders (APD), tinnitus and hearing loss (HL) are typical issues reported by patients in audiologic clinics. These auditory impairments can be concomitant or mutually excluding. APD are not necessarily accompanied by significant HL, whereas many adults exhibit peripheral HL and typical cognitive deficits often associated with APD. Since HL, tinnitus and APD affects to several parts of the ascending auditory pathway from the periphery to the auditory cortex, there could be some interrelationship between them. For instance, tinnitus has been reported to degrade the auditory localization capacity. Tinnitus is believed to be triggered by deafferentation of normal peripheral input to the central auditory system. This peripheral deficit can be accompanied by HL or not, since a type of permanent cochlear damage (thus deafferentation) without an elevation of hearing thresholds might persist. Therefore, a combined study of APD, tinnitus and HL on the same cohort of patients can be audiologically relevant and worthy. Methods: Statistical analysis is applied to a cohort of 305 patients attending an audiology clinic in Madrid (Spain). This group of patients is first categorized in four subgroups, namely, HLTG (with tinnitus and HL), NHLTG (with tinnitus and without HL), HLNTG (with HL but no tinnitus), and NHLNTG (neither tinnitus nor HL). The statistical variables include Age, Average Auditory Threshold (ATT), for assessing HL, Tinnitus Handicap Inventory (THI), for measuring tinnitus, and a new 25-item Auditory Behavior Questionnaire (ABQ), for scoring APD. Factor analysis is applied to arrange these items into 4 subscales. The internal consistency reliability of this ABQ is confirmed by calculating Cronbach's coefficients α. The test-retest reliability is assessed by the intraclass correlation coefficients, ICC. Statistical techniques applied to the data set include descriptive analysis of variables and Spearman rank correlations (ρ) between them. Results: Overall reliability of ABQ is confirmed by an α value of 0.89 and by an ICC of 0.91. Regarding the internal consistency reliability, the four subscales prove a fairly good consistency with α coefficients above 0.7. Average values of statistical variables show significantly lower age of patients with tinnitus and no HL, which can provide a cue of noise overexposure of this segment of population. These younger patients show also decreased ABQ and similar THI in comparison with patients in the other subgroups. A strong correlation (ρ = 0.63) was found between AAT and Age for the HLNTG subgroup. For the HLTG subgroup, a moderate correlation (ρ = 0.44) was found between ABQ and THI. Conclusion: The utilized questionnaire (ABQ), together with AAT and THI, can help to study comorbid hearing impairments in patients regularly attending an audiological clinic. PMID:28428741

An amorphous silicon photodiode with 2 THz gain-bandwidth product based on cycling excitation process

NASA Astrophysics Data System (ADS)

Yan, Lujiang; Yu, Yugang; Zhang, Alex Ce; Hall, David; Niaz, Iftikhar Ahmad; Raihan Miah, Mohammad Abu; Liu, Yu-Hsin; Lo, Yu-Hwa

2017-09-01

Since impact ionization was observed in semiconductors over half a century ago, avalanche photodiodes (APDs) using impact ionization in a fashion of chain reaction have been the most sensitive semiconductor photodetectors. However, APDs have relatively high excess noise, a limited gain-bandwidth product, and high operation voltage, presenting a need for alternative signal amplification mechanisms of superior properties. As an amplification mechanism, the cycling excitation process (CEP) was recently reported in a silicon p-n junction with subtle control and balance of the impurity levels and profiles. Realizing that CEP effect depends on Auger excitation involving localized states, we made the counter intuitive hypothesis that disordered materials, such as amorphous silicon, with their abundant localized states, can produce strong CEP effects with high gain and speed at low noise, despite their extremely low mobility and large number of defects. Here, we demonstrate an amorphous silicon low noise photodiode with gain-bandwidth product of over 2 THz, based on a very simple structure. This work will impact a wide range of applications involving optical detection because amorphous silicon, as the primary gain medium, is a low-cost, easy-to-process material that can be formed on many kinds of rigid or flexible substrates.

Auditory Training Effects on the Listening Skills of Children With Auditory Processing Disorder.

PubMed

Loo, Jenny Hooi Yin; Rosen, Stuart; Bamiou, Doris-Eva

2016-01-01

Children with auditory processing disorder (APD) typically present with "listening difficulties,"' including problems understanding speech in noisy environments. The authors examined, in a group of such children, whether a 12-week computer-based auditory training program with speech material improved the perception of speech-in-noise test performance, and functional listening skills as assessed by parental and teacher listening and communication questionnaires. The authors hypothesized that after the intervention, (1) trained children would show greater improvements in speech-in-noise perception than untrained controls; (2) this improvement would correlate with improvements in observer-rated behaviors; and (3) the improvement would be maintained for at least 3 months after the end of training. This was a prospective randomized controlled trial of 39 children with normal nonverbal intelligence, ages 7 to 11 years, all diagnosed with APD. This diagnosis required a normal pure-tone audiogram and deficits in at least two clinical auditory processing tests. The APD children were randomly assigned to (1) a control group that received only the current standard treatment for children diagnosed with APD, employing various listening/educational strategies at school (N = 19); or (2) an intervention group that undertook a 3-month 5-day/week computer-based auditory training program at home, consisting of a wide variety of speech-based listening tasks with competing sounds, in addition to the current standard treatment. All 39 children were assessed for language and cognitive skills at baseline and on three outcome measures at baseline and immediate postintervention. Outcome measures were repeated 3 months postintervention in the intervention group only, to assess the sustainability of treatment effects. The outcome measures were (1) the mean speech reception threshold obtained from the four subtests of the listening in specialized noise test that assesses sentence perception in various configurations of masking speech, and in which the target speakers and test materials were unrelated to the training materials; (2) the Children's Auditory Performance Scale that assesses listening skills, completed by the children's teachers; and (3) the Clinical Evaluation of Language Fundamental-4 pragmatic profile that assesses pragmatic language use, completed by parents. All outcome measures significantly improved at immediate postintervention in the intervention group only, with effect sizes ranging from 0.76 to 1.7. Improvements in speech-in-noise performance correlated with improved scores in the Children's Auditory Performance Scale questionnaire in the trained group only. Baseline language and cognitive assessments did not predict better training outcome. Improvements in speech-in-noise performance were sustained 3 months postintervention. Broad speech-based auditory training led to improved auditory processing skills as reflected in speech-in-noise test performance and in better functional listening in real life. The observed correlation between improved functional listening with improved speech-in-noise perception in the trained group suggests that improved listening was a direct generalization of the auditory training.

Longitudinal effects of dysfunctional perfectionism and avoidant personality style on postpartum mental disorders: Pathways through antepartum depression and anxiety.

PubMed

Oddo-Sommerfeld, Silvia; Hain, Sarah; Louwen, Frank; Schermelleh-Engel, Karin

2016-02-01

There is first evidence that some personality characteristics raise the risk of postpartum depression (PPD). The present longitudinal study investigates whether dysfunctional perfectionism and avoidant personality style predict PPD, postpartum anxiety (PPA) and bonding impairment (BI) directly or indirectly through antepartum anxiety (APA) and antepartum depression (APD). Pregnant women were recruited in two obstetric departments in Germany. The assessment occurred at two measurement time points: In the third trimester of pregnancy (N=297) and twelve weeks postpartum (N=266). Six questionnaires were administered during pregnancy: perfectionism, personality styles, anxiety, and depression. Postpartum, data on PPA, PPD and BI were collected. We conducted two path analyses in order to examine direct and indirect effects of the two personality characteristics on postpartum disorders. Testing for direct effects of dysfunctional perfectionism and avoidant personality style on PPD, PPA, and BI did not yield significant results. Instead, significant indirect effects were found: PPD, PPA, and BI were influenced indirectly by dysfunctional perfectionism and avoidant personality style via APD and APA. This model explained high portions of the variance of PPD, PPA, and impaired bonding. Each of the two personality characteristics explained a unique part of the outcome measures. The influence on BI was mediated by PPD. APD affected PPD and PPA more strongly than APA. Path models with manifest (observed) variables may lead to measurement errors. Self-rating questionnaires may raise the problem of social desirability. Dysfunctional perfectionism and avoidant personality style are significant risk factors for PPD, PPA, and BI. Screenings of both variables, as well as of APA and APD, which mediated the effect of personality traits on postpartum syndromes, are necessary. Copyright © 2015 Elsevier B.V. All rights reserved.

Antepartum and postpartum exposure to maternal depression: different effects on different adolescent outcomes.

PubMed

Hay, Dale F; Pawlby, Susan; Waters, Cerith S; Sharp, Deborah

2008-10-01

Postpartum depression (PPD) is considered a major public health problem that conveys risk to mothers and offspring. Yet PPD typically occurs in the context of a lifelong episodic illness, and its putative effects might derive from the child's exposure to other episodes, in pregnancy or later childhood. The aim of the study is to test two hypotheses: (1) that the effects of PPD on adolescent outcomes are partly explained by antepartum depression (APD) and (2) that the effects of APD and PPD are both explained by later exposure to the mother's depression. A random sample of 178 antenatal patients was drawn from two general medical practices in South London; 171 gave birth to live infants, and 150 (88%) were assessed at 3 months post partum, with 121 of their offspring (81%) assessed for emotional disorders (ED), disruptive behaviour disorders (DBD) and IQ, at 11 and 16 years of age. When APD and subsequent episodes of depression were taken into account, PPD had a significant effect on adolescent IQ, especially for boys, but did not predict psychopathology. ED and DBD in adolescence were predicted by the extent of exposure to maternal depression after 3 months post partum; a significant effect of APD on ED in girls was accounted for by later exposure to the mother's illness. Mothers' symptoms of anxiety, smoking and alcohol use in pregnancy did not predict adolescent outcomes, once maternal depression was taken into account. Some effects attributed to mothers' mental health problems in pregnancy or post partum may be mediated by cumulative exposure to maternal illness, probably reflecting genetic influence and gene-environment correlation. However, PPD has a direct effect on cognition. Clinicians should endeavour to identify women with depression in pregnancy (31% of this sample) and help them to manage their lifelong illness.

Determination of the excess noise of avalanche photodiodes integrated in 0.35-μm CMOS technologies

NASA Astrophysics Data System (ADS)

Jukić, Tomislav; Brandl, Paul; Zimmermann, Horst

2018-04-01

The excess noise of avalanche photodiodes (APDs) integrated in a high-voltage (HV) CMOS process and in a pin-photodiode CMOS process, both with 0.35-μm structure sizes, is described. A precise excess noise measurement technique is applied using a laser source, a spectrum analyzer, a voltage source, a current meter, a cheap transimpedance amplifier, and a personal computer with a MATLAB program. In addition, usage for on-wafer measurements is demonstrated. The measurement technique is verified with a low excess noise APD as a reference device with known ratio k = 0.01 of the impact ionization coefficients. The k-factor of an APD developed in HV CMOS is determined more accurately than known before. In addition, it is shown that the excess noise of the pin-photodiode CMOS APD depends on the optical power for avalanche gains above 35 and that modulation doping can suppress this power dependence. Modulation doping, however, increases the excess noise.

Arctigenin, a potential anti-arrhythmic agent, inhibits aconitine-induced arrhythmia by regulating multi-ion channels.

PubMed

Zhao, Zhenying; Yin, Yongqiang; Wu, Hong; Jiang, Min; Lou, Jianshi; Bai, Gang; Luo, Guo'an

2013-01-01

Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms. A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD), sodium current (I(Na)), L-type calcium current (I(Ca, L)) and transient outward potassium current (I(to)) were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by. Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD50 and APD90) were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD50 and APD90 caused by 1 µM aconitine. Arctigenin inhibited I(Na) and I(Ca,L) and attenuated the aconitine-increased I(Na) and I(Ca,L) by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced Ito by facilitating the activation process and delaying the inactivation process, and recoverd the decreased Ito induced by aconitine. Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, I(Na), I(Ca, L), and I(to) may be multiple targets of arctigenin, leading to its antiarrhythmic effect. © 2013 S. Karger AG, Basel.

The technology on noise reduction of the APD detection circuit

NASA Astrophysics Data System (ADS)

Wu, Xue-ying; Zheng, Yong-chao; Cui, Jian-yong

2013-09-01

The laser pulse detection is widely used in the field of laser range finders, laser communications, laser radar, laser Identification Friend or Foe, et al, for the laser pulse detection has the advantage of high accuracy, high sensitivity and strong anti-interference. The avalanche photodiodes (APD) has the advantage of high quantum efficiency, high response speed and huge gain. The APD is particularly suitable for weak signal detection. The technology that APD acts as the photodetector for weak signal reception and amplification is widely used in laser pulse detection. The APD will convert the laser signal to weak electrical signal. The weak signal is amplified, processed and exported by the circuit. In the circuit design, the optimal signal detection is one key point in photoelectric detection system. The issue discusses how to reduce the noise of the photoelectric signal detection circuit and how to improve the signal-to-noise ratio, related analysis and practice included. The essay analyzes the mathematical model of the signal-to-noise ratio for photoelectric conversion and the noise of the APD photoelectric detection system. By analysis the bandwidth of the detection system is determined, and the circuit devices are selected that match the APD. In the circuit design separated devices with low noise are combined with integrated operational amplifier for the purpose of noise reduction. The methods can effectively suppress the noise, and improve the detection sensitivity.

Cerebrospinal Fluid Biomarker Candidates for Parkinsonian Disorders

PubMed Central

Constantinescu, Radu; Mondello, Stefania

2013-01-01

The Parkinsonian disorders are a large group of neurodegenerative diseases including idiopathic Parkinson’s disease (PD) and atypical Parkinsonian disorders (APD), such as multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies. The etiology of these disorders is not known although it is considered to be a combination of genetic and environmental factors. One of the greatest obstacles for developing efficacious disease-modifying treatment strategies is the lack of biomarkers. Reliable biomarkers are needed for early and accurate diagnosis, to measure disease progression, and response to therapy. In this review several of the most promising cerebrospinal biomarker candidates are discussed. Alpha-synuclein seems to be intimately involved in the pathogenesis of synucleinopathies and its levels can be measured in the cerebrospinal fluid and in plasma. In a similar way, tau protein accumulation seems to be involved in the pathogenesis of tauopathies. Urate, a potent antioxidant, seems to be associated to the risk of developing PD and with its progression. Neurofilament light chain levels are increased in APD compared with PD and healthy controls. The new “omics” techniques are potent tools offering new insights in the patho-etiology of these disorders. Some of the difficulties encountered in developing biomarkers are discussed together with future perspectives. PMID:23346074

Mental disorders and delivery motorcycle drivers (motoboys): a dangerous association.

PubMed

Kieling, R R; Szobot, C M; Matte, B; Coelho, R S; Kieling, C; Pechansky, F; Rohde, L A

2011-01-01

Low and middle-income countries experience an expressive growth in the number of circulating motorcycles, paralleled by an increasing number of traffic accidents. Delivery motorcycles drivers ("motoboys") are generally perceived as accountable for this scenario. Although traffic accidents have a multivariate etiology, mental disorders, such as substance use disorders (SUD) and attention deficit/hyperactivity disorder (ADHD), are often involved. This paper aims at investigating the prevalence of ADHD, SUD and other mental disorders in a sample of Brazilian motoboys, and additionally, to evaluate the association between psychiatric diagnoses, motorcycle accidents and traffic violation tickets. A convenient sample of subjects was invited to participate in a cross-sectional assessment including an inventory of traffic accidents and violations. Psychiatric diagnoses were based on semi-structured and clinical interviews. A sample of 101 motoboys was assessed. Overall, 75% of subjects had a positive lifetime history of at least one psychiatric disorder. SUD was the most frequent diagnosis (43.6% for alcohol, 39.6% for cannabis). ADHD was associated with a higher number of traffic accidents (p=0.002), and antisocial personality disorder (APD) was associated with a greater number of traffic violations (p=0.007). The prevalence of mental disorders was much higher in our sample than in the general population. ADHD and APD, but not SUD, were associated with negative traffic outcomes. These findings have implications for public mental health planning since mental disorders can be both prevented and treated, improving driving behavior and increasing road safety. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

7 CFR 277.18 - Establishment of an Automated Data Processing (ADP) and Information Retrieval System.

Code of Federal Regulations, 2010 CFR

2010-01-01

... activities and expenditures in relation to the approved Planning APD or Implementation APD. An APDU may also... organizations other than the State agency to perform such tasks as feasibility studies, system studies, system... requirements of § 277.18(c). Feasibility Study means a preliminary study to determine whether it is...

The role of defense mechanisms in borderline and antisocial personalities.

PubMed

Presniak, Michelle D; Olson, Trevor R; Macgregor, Michael Wm

2010-03-01

We examined whether borderline personality disorder (BPD) and antisocial personality disorder (APD) could be differentiated based on defense mechanisms as measured by observer (Defense-Q; MacGregor, Olson, Presniak, & Davidson, 2008) and self-report (Defense Style Questionnaire; Andrews, Singh, & Bond, 1993) measures. We conducted 2 studies whereby nonclinical participants were divided into borderline and antisocial groups based on scores from the Personality Assessment Inventory (Morey, 1991). Multivariate analysis of variance results revealed significant overall group differences in defense use. Univariate analyses further showed group differences on several individual defenses (e.g., acting out, denial, and turning against self). Together, the findings suggest that in BPD, the defenses may emphasize interpersonal dependency and a tendency to direct aggression toward the self; whereas in APD, the defenses may emphasize egocentricity, interpersonal exploitation, and a tendency to direct aggression toward others. Overall, this study demonstrates important differences in defense use between borderline and antisocial personality groups across both observer and self-report measures.

Active quench and reset integrated circuit with novel hold-off time control logic for Geiger-mode avalanche photodiodes.

PubMed

Deng, Shijie; Morrison, Alan P

2012-09-15

This Letter presents an active quench-and-reset circuit for Geiger-mode avalanche photodiodes (GM-APDs). The integrated circuit was fabricated using a conventional 0.35 μm complementary metal oxide semiconductor process. Experimental results show that the circuit is capable of linearly setting the hold-off time from several nanoseconds to microseconds with a resolution of 6.5 ns. This allows the selection of the optimal afterpulse-free hold-off time for the GM-APD via external digital inputs or additional signal processing circuitry. Moreover, this circuit resets the APD automatically following the end of the hold-off period, thus simplifying the control for the end user. Results also show that a minimum dead time of 28.4 ns is achieved, demonstrating a saturated photon-counting rate of 35.2 Mcounts/s.

Changes in auditory memory performance following the use of frequency-modulated system in children with suspected auditory processing disorders.

PubMed

Umat, Cila; Mukari, Siti Z; Ezan, Nurul F; Din, Normah C

2011-08-01

To examine the changes in the short-term auditory memory following the use of frequency-modulated (FM) system in children with suspected auditory processing disorders (APDs), and also to compare the advantages of bilateral over unilateral FM fitting. This longitudinal study involved 53 children from Sekolah Kebangsaan Jalan Kuantan 2, Kuala Lumpur, Malaysia who fulfilled the inclusion criteria. The study was conducted from September 2007 to October 2008 in the Department of Audiology and Speech Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. The children's age was between 7-10 years old, and they were assigned into 3 groups: 15 in the control group (not fitted with FM); 19 in the unilateral; and 19 in the bilateral FM-fitting group. Subjects wore the FM system during school time for 12 weeks. Their working memory (WM), best learning (BL), and retention of information (ROI) were measured using the Rey Auditory Verbal Learning Test at pre-fitting, post (after 12 weeks of FM usage), and at long term (one year after the usage of FM system ended). There were significant differences in the mean WM (p=0.001), BL (p=0.019), and ROI (p=0.005) scores at the different measurement times, in which the mean scores at long-term were consistently higher than at pre-fitting, despite similar performances at the baseline (p>0.05). There was no significant difference in performance between unilateral- and bilateral-fitting groups. The use of FM might give a long-term effect on improving selected short-term auditory memories of some children with suspected APDs. One may not need to use 2 FM receivers to receive advantages on auditory memory performance.

Development of a 32-channel ASIC for an X-ray APD detector onboard the ISS

NASA Astrophysics Data System (ADS)

Arimoto, Makoto; Harita, Shohei; Sugita, Satoshi; Yatsu, Yoichi; Kawai, Nobuyuki; Ikeda, Hirokazu; Tomida, Hiroshi; Isobe, Naoki; Ueno, Shiro; Mihara, Tatehiro; Serino, Motoko; Kohmura, Takayoshi; Sakamoto, Takanori; Yoshida, Atsumasa; Tsunemi, Hiroshi; Hatori, Satoshi; Kume, Kyo; Hasegawa, Takashi

2018-02-01

We report on the design and performance of a mixed-signal application specific integrated circuit (ASIC) dedicated to avalanche photodiodes (APDs) in order to detect hard X-ray emissions in a wide energy band onboard the International Space Station. To realize wide-band detection from 20 keV to 1 MeV, we use Ce:GAGG scintillators, each coupled to an APD, with low-noise front-end electronics capable of achieving a minimum energy detection threshold of 20 keV. The developed ASIC has the ability to read out 32-channel APD signals using 0.35 μm CMOS technology, and an analog amplifier at the input stage is designed to suppress the capacitive noise primarily arising from the large detector capacitance of the APDs. The ASIC achieves a performance of 2099 e- + 1.5 e-/pF at root mean square (RMS) with a wide 300 fC dynamic range. Coupling a reverse-type APD with a Ce:GAGG scintillator, we obtain an energy resolution of 6.7% (FWHM) at 662 keV and a minimum detectable energy of 20 keV at room temperature (20 °C). Furthermore, we examine the radiation tolerance for space applications by using a 90 MeV proton beam, confirming that the ASIC is free of single-event effects and can operate properly without serious degradation in analog and digital processing.

Characterization of Geiger mode avalanche photodiodes for fluorescence decay measurements

NASA Astrophysics Data System (ADS)

Jackson, John C.; Phelan, Don; Morrison, Alan P.; Redfern, R. Michael; Mathewson, Alan

2002-05-01

Geiger mode avalanche photodiodes (APD) can be biased above the breakdown voltage to allow detection of single photons. Because of the increase in quantum efficiency, magnetic field immunity, robustness, longer operating lifetime and reduction in costs, solid-state detectors capable of operating at non-cryogenic temperatures and providing single photon detection capabilities provide attractive alternatives to the photomultiplier tube (PMT). Shallow junction Geiger mode APD detectors provide the ability to manufacture photon detectors and detector arrays with CMOS compatible processing steps and allows the use of novel Silicon-on-Insulator(SoI) technology to provide future integrated sensing solutions. Previous work on Geiger mode APD detectors has focused on increasing the active area of the detector to make it more PMT like, easing the integration of discrete reaction, detection and signal processing into laboratory experimental systems. This discrete model for single photon detection works well for laboratory sized test and measurement equipment, however the move towards microfluidics and systems on a chip requires integrated sensing solutions. As we move towards providing integrated functionality of increasingly nanoscopic sized emissions, small area detectors and detector arrays that can be easily integrated into marketable systems, with sensitive small area single photon counting detectors will be needed. This paper will demonstrate the 2-dimensional and 3-dimensional simulation of optical coupling that occurs in Geiger mode APDs. Fabricated Geiger mode APD detectors optimized for fluorescence decay measurements were characterized and preliminary results show excellent results for their integration into fluorescence decay measurement systems.

Sci-Sat AM(1): Imaging-08: Small animal APD PET detector with submillimetric resolution for molecular imaging.

PubMed

Bérard, P; Bergeron, M; Pepin, C M; Cadorette, J; Tétrault, M-A; Viscogliosi, N; Fontaine, R; Dautet, H; Davies, M; Lecomte, R

2008-07-01

Visualization and quantification of biological processes in mice, the preferred animal model in most preclinical studies, require the best possible spatial resolution in positron emission tomography (PET). A new 64-channel avalanche photodiode (APD) detector module was developed to achieve submillimeter spatial resolution for this purpose. The module consists of dual 4 × 8 APD arrays mounted in a custom ceramic holder. Individual APD pixels having an active area of 1.1 × 1.1 mm2 at a 1.2 mm pitch can be fitted to an 8 × 8 LYSO scintillator block designed to accommodate one-to-one coupling. An analog test board with four 16-channel preamplifier ASICs was designed to be interfaced with the existing LabPET digital processing electronics. At a standard APD operating bias, a mean energy resolution of 27.5 ± 0.6% was typically obtained at 511 keV with a relative standard deviation of 13.8% in signal amplitude for the 64 individual pixels. Crosstalk between pixels was found to be well below the typical lower energy threshold used for PET imaging applications. With two modules in coincidence, a global timing resolution of 5.0 ns FWHM was measured. Finally, an intrinsic spatial resolution of 0.8 mm FWHM was measured by sweeping a 22Na point source between two detector arrays. The proposed detector module demonstrates promising characteristics for dedicated mouse PET imaging at submillimiter resolution. © 2008 American Association of Physicists in Medicine.

Computer-based auditory training (CBAT): benefits for children with language- and reading-related learning difficulties.

PubMed

Loo, Jenny Hooi Yin; Bamiou, Doris-Eva; Campbell, Nicci; Luxon, Linda M

2010-08-01

This article reviews the evidence for computer-based auditory training (CBAT) in children with language, reading, and related learning difficulties, and evaluates the extent it can benefit children with auditory processing disorder (APD). Searches were confined to studies published between 2000 and 2008, and they are rated according to the level of evidence hierarchy proposed by the American Speech-Language Hearing Association (ASHA) in 2004. We identified 16 studies of two commercially available CBAT programs (13 studies of Fast ForWord (FFW) and three studies of Earobics) and five further outcome studies of other non-speech and simple speech sounds training, available for children with language, learning, and reading difficulties. The results suggest that, apart from the phonological awareness skills, the FFW and Earobics programs seem to have little effect on the language, spelling, and reading skills of children. Non-speech and simple speech sounds training may be effective in improving children's reading skills, but only if it is delivered by an audio-visual method. There is some initial evidence to suggest that CBAT may be of benefit for children with APD. Further research is necessary, however, to substantiate these preliminary findings.

Development of high-sensitivity SWIR APD receivers

NASA Astrophysics Data System (ADS)

Bai, Xiaogang; Yuan, Ping; Chang, James; Sudharsanan, Rengarajan; Krainak, Michael; Yang, Guangning; Sun, Xiaoli; Lu, Wei

2013-06-01

Emerging short wavelength infrared (SWIR) LIght Detection And Ranging (LIDAR) and long range laser rangefinder systems, require large optical aperture avalanche photodiodes (APDs) receivers with high sensitivity and high bandwidth. A large optical aperture is critical to increase the optical coupling efficiency and extend the LIDAR sensing range of the above systems. Both APD excess noise and transimpedance amplifier (TIA) noise need to be reduced in order to achieve high receiver sensitivity. The dark current and capacitance of large area APDs increase with APD aperture and thus limit the sensitivity and bandwidth of receivers. Spectrolab has been developing low excess noise InAlAs/InGaAs APDs with impact ionization engineering (I2E) designs for many years and has demonstrated APDs with optical gain over 100 utilizing multiple period I2E structures in the APD multiplier. These high gain I2E APDs have an excess noise factor less than 0.15. With an optical aperture of 200 μm, low excess noise multiple periods I2E APDs have capacitances about 1.7 pF. In addition, optical gains of InAlAs based APDs show very little temperature dependence and will enable APD photoreceivers without thermal electric cooling.

Development of an integrated four-channel fast avalanche-photodiode detector system with nanosecond time resolution

NASA Astrophysics Data System (ADS)

Li, Zhenjie; Li, Qiuju; Chang, Jinfan; Ma, Yichao; Liu, Peng; Wang, Zheng; Hu, Michael Y.; Zhao, Jiyong; Alp, E. E.; Xu, Wei; Tao, Ye; Wu, Chaoqun; Zhou, Yangfan

2017-10-01

A four-channel nanosecond time-resolved avalanche-photodiode (APD) detector system is developed at Beijing Synchrotron Radiation. It uses a single module for signal processing and readout. This integrated system provides better reliability and flexibility for custom improvement. The detector system consists of three parts: (i) four APD sensors, (ii) four fast preamplifiers and (iii) a time-digital-converter (TDC) readout electronics. The C30703FH silicon APD chips fabricated by Excelitas are used as the sensors of the detectors. It has an effective light-sensitive area of 10 × 10 mm2 and an absorption layer thickness of 110 μm. A fast preamplifier with a gain of 59 dB and bandwidth of 2 GHz is designed to readout of the weak signal from the C30703FH APD. The TDC is realized by a Spartan-6 field-programmable-gate-array (FPGA) with multiphase method in a resolution of 1ns. The arrival time of all scattering events between two start triggers can be recorded by the TDC. The detector has been used for nuclear resonant scattering study at both Advanced Photon Source and also at Beijing Synchrotron Radiation Facility. For the X-ray energy of 14.4 keV, the time resolution, the full width of half maximum (FWHM) of the detector (APD sensor + fast amplifier) is 0.86 ns, and the whole detector system (APD sensors + fast amplifiers + TDC readout electronics) achieves a time resolution of 1.4 ns.

Release of non-methane organic compounds during simulated landfilling of aerobically pretreated municipal solid waste.

PubMed

Zhang, Yuanyuan; Yue, Dongbei; Liu, Jianguo; Lu, Peng; Wang, Ying; Liu, Jing; Nie, Yongfeng

2012-06-30

Characteristics of non-methane organic compounds (NMOCs) emissions during the anaerobic decomposition of untreated (APD-0) and four aerobically pretreated (APD-20, APD-39, APD-49, and APD-63) samples of municipal solid waste (MSW) were investigated in laboratory. The cumulative mass of the NMOCs of APD-20, APD-39, APD-49, and APD-63 accounted for 15%, 9%, 16%, and 15% of that of APD-0, respectively. The intensities of the NMOC emissions calculated by dividing the cumulative NMOC emissions by the quantities of organic matter removed (Q(VS)) decreased from 4.1 mg/kg Q(VS) for APD-0 to 0.8-3.4 mg/kg Q(VS) for aerobically pretreated MSW. The lipid and starch contents might have significant impact on the intensity of the NMOC emissions. Alkanes dominated the NMOCs released from the aerobically pretreated MSW, while oxygenated compounds were the chief component of the NMOCs generated from untreated MSW. Aerobic pretreatment of MSW prior to landfilling reduces the organic content of the waste and the intensity of the NMOC emissions, and increases the odor threshold, thereby reducing the environmental impact of landfills. Copyright © 2012 Elsevier Ltd. All rights reserved.

Silicone-containing aqueous polymer dispersions with hybrid particle structure.

PubMed

Kozakiewicz, Janusz; Ofat, Izabela; Trzaskowska, Joanna

2015-09-01

In this paper the synthesis, characterization and application of silicone-containing aqueous polymer dispersions (APD) with hybrid particle structure are reviewed based on available literature data. Advantages of synthesis of dispersions with hybrid particle structure over blending of individual dispersions are pointed out. Three main processes leading to silicone-containing hybrid APD are identified and described in detail: (1) emulsion polymerization of organic unsaturated monomers in aqueous dispersions of silicone polymers or copolymers, (2) emulsion copolymerization of unsaturated organic monomers with alkoxysilanes or polysiloxanes with unsaturated functionality and (3) emulsion polymerization of alkoxysilanes (in particular with unsaturated functionality) and/or cyclic siloxanes in organic polymer dispersions. The effect of various factors on the properties of such hybrid APD and films as well as on hybrid particles composition and morphology is presented. It is shown that core-shell morphology where silicones constitute either the core or the shell is predominant in hybrid particles. Main applications of silicone-containing hybrid APD and related hybrid particles are reviewed including (1) coatings which show specific surface properties such as enhanced water repellency or antisoiling or antigraffiti properties due to migration of silicone to the surface, and (2) impact modifiers for thermoplastics and thermosets. Other processes in which silicone-containing particles with hybrid structure can be obtained (miniemulsion polymerization, polymerization in non-aqueous media, hybridization of organic polymer and polysiloxane, emulsion polymerization of silicone monomers in silicone polymer dispersions and physical methods) are also discussed. Prospects for further developments in the area of silicone-containing hybrid APD and related hybrid particles are presented. Copyright © 2015. Published by Elsevier B.V.

Single-Photon-Sensitive HgCdTe Avalanche Photodiode Detector

NASA Technical Reports Server (NTRS)

Huntington, Andrew

2013-01-01

The purpose of this program was to develop single-photon-sensitive short-wavelength infrared (SWIR) and mid-wavelength infrared (MWIR) avalanche photodiode (APD) receivers based on linear-mode HgCdTe APDs, for application by NASA in light detection and ranging (lidar) sensors. Linear-mode photon-counting APDs are desired for lidar because they have a shorter pixel dead time than Geiger APDs, and can detect sequential pulse returns from multiple objects that are closely spaced in range. Linear-mode APDs can also measure photon number, which Geiger APDs cannot, adding an extra dimension to lidar scene data for multi-photon returns. High-gain APDs with low multiplication noise are required for efficient linear-mode detection of single photons because of APD gain statistics -- a low-excess-noise APD will generate detectible current pulses from single photon input at a much higher rate of occurrence than will a noisy APD operated at the same average gain. MWIR and LWIR electron-avalanche HgCdTe APDs have been shown to operate in linear mode at high average avalanche gain (M > 1000) without excess multiplication noise (F = 1), and are therefore very good candidates for linear-mode photon counting. However, detectors fashioned from these narrow-bandgap alloys require aggressive cooling to control thermal dark current. Wider-bandgap SWIR HgCdTe APDs were investigated in this program as a strategy to reduce detector cooling requirements.

The Heritability of Cluster B Personality Disorders Assessed both by Personal Interview and Questionnaire

PubMed Central

Torgersen, Svenn; Myers, John; Reichborn-Kjennerud, Ted; Røysamb, Espen; Kubarych, Thomas S.; Kendler, Kenneth S.

2013-01-01

Whereas the heritability of common personality traits has been firmly established, the results of the few published studies on personality disorders (PDs) are highly divergent, with some studies finding high heredity and others very low. A problem with assessing personality disorders by means of interview is errors connected with interviewer bias. A way to overcome the problem is to use self-report questionnaires in addition to interviews. This study used both interview and questionnaire for assessing DSM-IV Cluster B personality disorders: antisocial personality disorder (APD), borderline (BPD), narcissistic (NPD), and histrionic (HPD). We assessed close to 2,800 twins from the Norwegian Institute of Public Health Twin Panel using a self-report questionnaire and, a few years later, the Structured Interview for DSM-IV Personality (SIDP-IV). Items from the self-report questionnaire that best predicted the PDs captured by the interview were then selected. Measurement models combining questionnaire and interview information were applied and were fitted using Mx. Whereas the heritability of Cluster B PDs assessed by interview was around .30, and around .40–.50 when assessed by self-report questionnaire, the heritability of the convergent latent factor, including information from both interview and self-report questionnaire was .69 for APD, .67 for BPD, .71 for NPD, and .63 for HPD. As is usually found for personality, the effect of shared-in families (familial) environment was zero. In conclusion, when both interview and self-report questionnaire are taken into account, the heritability of Cluster B PD appears to be in the upper range of previous findings for mental disorders. PMID:23281671

The heritability of Cluster B personality disorders assessed both by personal interview and questionnaire.

PubMed

Torgersen, Svenn; Myers, John; Reichborn-Kjennerud, Ted; Røysamb, Espen; Kubarych, Thomas S; Kendler, Kenneth S

2012-12-01

Whereas the heritability of common personality traits has been firmly established, the results of the few published studies on personality disorders (PDs) are highly divergent, with some studies finding high heredity and others very low. A problem with assessing personality disorders by means of interview is errors connected with interviewer bias. A way to overcome the problem is to use self-report questionnaires in addition to interviews. This study used both interview and questionnaire for assessing DSM-IV Cluster B personality disorders: antisocial personality disorder (APD), borderline (BPD), narcissistic (NPD), and histrionic (HPD). We assessed close to 2,800 twins from the Norwegian Institute of Public Health Twin Panel using a self-report questionnaire and, a few years later, the Structured Interview for DSM-IV Personality (SIDP-IV). Items from the self-report questionnaire that best predicted the PDs captured by the interview were then selected. Measurement models combining questionnaire and interview information were applied and were fitted using Mx. Whereas the heritability of Cluster B PDs assessed by interview was around .30, and around .40-.50 when assessed by self-report questionnaire, the heritability of the convergent latent factor, including information from both interview and self-report questionnaire was .69 for APD, .67 for BPD, .71 for NPD, and .63 for HPD. As is usually found for personality, the effect of shared-in families (familial) environment was zero. In conclusion, when both interview and self-report questionnaire are taken into account, the heritability of Cluster B PD appears to be in the upper range of previous findings for mental disorders.

Offender Characteristics in Lethal Violence with Special Reference to Antisocial and Autistic Personality Traits

ERIC Educational Resources Information Center

Wahlund, Katarina; Kristiansson, Marianne

2006-01-01

The objective of the study is to assess the relationships between personality traits, lifetime psychosocial functioning, and crime scene behavior. Thirty-five male offenders referred for forensic psychiatric assessment in Sweden (1996-2001) and assigned a main diagnosis of either antisocial personality disorder (APD) or autism spectrum disorder…

Design of a Multi-Channel Front-End Readout ASIC With Low Noise and Large Dynamic Input Range for APD-Based PET Imaging

NASA Astrophysics Data System (ADS)

Fang, X. C.; Hu-Guo, Ch.; Ollivier-Henry, N.; Brasse, D.; Hu, Y.

2010-06-01

This paper represents the design of a low-noise, wide band multi-channel readout integrated circuit (IC) used as front end readout electronics of avalanche photo diodes (APD) dedicated to a small animal positron emission tomography (PET) system. The first ten-channel prototype chip (APD-Chip) of the analog parts has been designed and fabricated in a 0.35 μm CMOS process. Every channel of the APD_Chip includes a charge-sensitive preamplifier (CSA), a CR-(RC)2 shaper, and an analog buffer. In a channel, the CSA reads charge signals (10 bits dynamic range) from an APD array having 10 pF of capacitance per pixel. A linearized degenerated differential pair which ensures high linearity in all dynamical range is used as the high feedback resistor for preventing pile up of signals. The designed CSA has the capability of compensating automatically up to 200 nA leakage current from the detector. The CR-(RC)2 shaper filters and shapes the output signal of the CSA. An equivalent input noise charge obtained from test is 275 e -+ 10 e-/pF. In this paper the prototype is presented for both its theoretical analysis and its test results.

Theory of the development of alternans in the heart during controlled diastolic interval pacing

NASA Astrophysics Data System (ADS)

Otani, Niels F.

2017-09-01

The beat-to-beat alternation in action potential durations (APDs) in the heart, called APD alternans, has been linked to the development of serious cardiac rhythm disorders, including ventricular tachycardia and fibrillation. The length of the period between action potentials, called the diastolic interval (DI), is a key dynamical variable in the standard theory of alternans development. Thus, methods that control the DI may be useful in preventing dangerous cardiac rhythms. In this study, we examine the dynamics of alternans during controlled-DI pacing using a series of single-cell and one-dimensional (1D) fiber models of alternans dynamics. We find that a model that combines a so-called memory model with a calcium cycling model can reasonably explain two key experimental results: the possibility of alternans during constant-DI pacing and the phase lag of APDs behind DIs during sinusoidal-DI pacing. We also find that these results can be replicated by incorporating the memory model into an amplitude equation description of a 1D fiber. The 1D fiber result is potentially concerning because it seems to suggest that constant-DI control of alternans can only be effective over only a limited region in space.

Clarifying the Role of Defensive Reactivity Deficits in Psychopathy and Antisocial Personality Using Startle Reflex Methodology

PubMed Central

Vaidyanathan, Uma; Hall, Jason R.; Patrick, Christopher J.; Bernat, Edward M.

2010-01-01

Prior research has demonstrated deficits in defensive reactivity (indexed by potentiation of the startle blink reflex) in psychopathic individuals. However, the basis of this association remains unclear, as diagnostic criteria for psychopathy encompass two distinct phenotypic components that may reflect differing neurobiological mechanisms – an affective-interpersonal component, and an antisocial deviance component. Likewise, the role of defensive response deficits in antisocial personality disorder (APD), a related but distinct syndrome, remains to be clarified. The current study examined affective priming deficits in relation to factors of psychopathy and symptoms of APD using startle reflex methods in 108 adult male prisoners. Deficits in blink reflex potentiation during aversive picture viewing were found in relation to the affective-interpersonal (Factor 1) component of psychopathy, and to a lesser extent in relation to the antisocial deviance (Factor 2) component of psychopathy and symptoms of APD—but only as a function of their overlap with affective-interpersonal features of psychopathy. These findings provide clear evidence that deficits in defensive reactivity are linked specifically to the affective-interpersonal features of psychopathy, and not the antisocial deviance features represented most strongly in APD. PMID:20973594

Application of simple negative feedback model for avalanche photodetectors investigation

NASA Astrophysics Data System (ADS)

Kushpil, V. V.

2009-10-01

A simple negative feedback model based on Miller's formula is used to investigate the properties of Avalanche Photodetectors (APDs). The proposed method can be applied to study classical APD as well as new type of devices, which are operating in the Internal Negative Feedback (INF) regime. The method shows a good sensitivity to technological APD parameters making it possible to use it as a tool to analyse various APD parameters. It also allows better understanding of the APD operation conditions. The simulations and experimental data analysis for different types of APDs are presented.

Do antipsychotic drugs increase seizure frequency in epilepsy patients?

PubMed

Okazaki, Mitsutoshi; Adachi, Naoto; Akanuma, Nozomi; Hara, Koichiro; Ito, Masumi; Kato, Masaaki; Onuma, Teiichi

2014-11-01

To investigate whether addition of antipsychotic drugs (APD) would increase seizure frequency in epilepsy patients who were already treated with anti-epileptic drugs (AED), we compared a one-year seizure control outcome in 150 epilepsy patients with APD treatment for psychiatric conditions and 309 epilepsy patients without APD treatment matched for ages at epilepsy onset and the baseline evaluation and types of epilepsy. The seizure frequency was recorded at the baseline (immediately before the start of APD) and after the 1st, 3rd, 6th and 12th months. The seizure outcome at each of the four follow-up points was compared with the baseline. The seizure outcome was compared between the two groups as a whole and according to the types of epilepsy (idiopathic generalized and partial epilepsies). In the APD group, the seizure outcome was also analyzed according to the types of APD (first and second generation APD and combination of first and second generation APD) and the types of psychiatric conditions (psychosis and non-psychosis). The seizure outcome was significantly better in the APD group than control group at all the four follow-up points. According to the epilepsy types, the improvement in the seizure outcome was only observed in the patients with partial epilepsy. Of the APD group, there was no significant difference in the seizure outcome according to the types of APD or the psychiatric conditions. In epilepsy patients who are already treated with AED, APD treatment seems safe in seizure control outcome for treatment of psychiatric conditions. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

CMOS integrated avalanche photodiodes and frequency-mixing optical sensor front end for portable NIR spectroscopy instruments.

PubMed

Yun, Ruida; Sthalekar, Chirag; Joyner, Valencia M

2011-01-01

This paper presents the design and measurement results of two avalanche photodiode structures (APDs) and a novel frequency-mixing transimpedance amplifier (TIA), which are key building blocks towards a monolithically integrated optical sensor front end for near-infrared (NIR) spectroscopy applications. Two different APD structures are fabricated in an unmodified 0.18 \\im CMOS process, one with a shallow trench isolation (STI) guard ring and the other with a P-well guard ring. The APDs are characterized in linear mode. The STI bounded APD demonstrates better performance and exhibits 3.78 A/W responsivity at a wavelength of 690 nm and bias voltage of 10.55 V. The frequency-mixing TIA (FM-TIA) employs a T-feedback network incorporating gate-controlled transistors for resistance modulation, enabling the simultaneous down-conversion and amplification of the high frequency modulated photodiode (PD) current. The TIA achieves 92 dS Ω conversion gain with 0.5 V modulating voltage. The measured IIP(3) is 10.6/M. The amplifier together with the 50 Ω output buffer draws 23 mA from a1.8 V power supply.

Extraction of bioactives from Orthosiphon stamineus using microwave and ultrasound-assisted techniques: Process optimization and scale up.

PubMed

Chan, Chung-Hung; See, Tiam-You; Yusoff, Rozita; Ngoh, Gek-Cheng; Kow, Kien-Woh

2017-04-15

This work demonstrated the optimization and scale up of microwave-assisted extraction (MAE) and ultrasonic-assisted extraction (UAE) of bioactive compounds from Orthosiphon stamineus using energy-based parameters such as absorbed power density and absorbed energy density (APD-AED) and response surface methodology (RSM). The intensive optimum conditions of MAE obtained at 80% EtOH, 50mL/g, APD of 0.35W/mL, AED of 250J/mL can be used to determine the optimum conditions of the scale-dependent parameters i.e. microwave power and treatment time at various extraction scales (100-300mL solvent loading). The yields of the up scaled conditions were consistent with less than 8% discrepancy and they were about 91-98% of the Soxhlet extraction yield. By adapting APD-AED method in the case of UAE, the intensive optimum conditions of the extraction, i.e. 70% EtOH, 30mL/g, APD of 0.22W/mL, AED of 450J/mL are able to achieve similar scale up results. Copyright © 2016 Elsevier Ltd. All rights reserved.

Personality disorder in convicted Jamaican murderers.

PubMed

Hickling, F W; Walcott, G

2013-01-01

To establish the aetiology and historical prevalence of personality disorder in violent homicidal men in Jamaica. Examination and analysis of primary data from the psychosocial case study interviews of 36 convicted murderers from the Jamaican Government Barnett Commission of Enquiry in 1976. The disaggregated social and clinical data were analysed using a Chi-square statistical analysis. The mean age at time of arrest for the male convicted murderers was 24.26 ± 8.48 years. Twenty-three (66%) of the subjects had loving relationships with mothers, particularly in those men reared in the rural areas. Twenty-one (59%) cases showed marked paternal rejection and absence of integrated family life. Twenty-four (69%) of the cases experienced severe parental disciplinary methods, and two-thirds were illiterate or barely literate. Twenty-nine (83%) were from very poor socio-economic conditions. Thirty (86%) of all the murder victims were adult males. There were significant differences between the urban reared murderers (URM) and rural reared murderers (RRM). Sixteen (94%) of the victims of the URM ensued from robbery and police confrontation, while 13 (72%) of the victims of the RRM resulted from domestic disputes (p < 0.00). Seventeen (49%) of the men had normal personalities; 18 (51%) were diagnosed as having antisocial and inadequate personalities. Diagnosis of primary data using Diagnostic and Statistical Manual of Mental Disorders fourth edition, text revision (DSM-IV-TR) criteria revealed 23 (66%) men with Antisocial Personality Disorder (APD). There were significantly more APD in the URM than the RRM (p < 0.01). Antisocial personality disorder as an aetiological precursor of homicidal violence represents a major public health problem in contemporary Jamaica.

Central and Peripheral Mechanisms of Antipsychotic Medication Induced Metabolic Dysregulation

DTIC Science & Technology

2016-10-01

consumption in hypothalamus-specific D2R (and wildtype littermate controls) treated with either with first-generation APD haloperidol or second-generation APD...wildtype littermate controls) treated with either with first-generation APD haloperidol or second-generation APD olanzapine (via i.p. administration

Economic costs of automated and continuous ambulatory peritoneal dialysis in Taiwan: a combined survey and retrospective cohort analysis.

PubMed

Tang, Chao-Hsiun; Wu, Yu-Ting; Huang, Siao-Yuan; Chen, Hsi-Hsien; Wu, Ming-Ju; Hsu, Bang-Gee; Tsai, Jer-Chia; Chen, Tso-Hsiao; Sue, Yuh-Mou

2017-03-21

Taiwan succeeded in raising the proportion of peritoneal dialysis (PD) usage after the National Health Insurance (NHI) payment scheme introduced financial incentives in 2005. This study aims to compare the economic costs between automated PD (APD) and continuous ambulatory PD (CAPD) modalities from a societal perspective. A retrospective cohort of patients receiving PD from the NHI Research Database was identified during 2004-2011. The 1:1 propensity score matched 1749 APD patients and 1749 CAPD patients who were analysed on their NHI-financed medical costs and utilisation. A multicentre study by face-to-face interviews on 117 APD and 129 CAPD patients from five hospitals located in four regions of Taiwan was further carried out to collect data on their out-of-pocket payments, productivity losses and quality of life with EuroQol-5D-5L. The NHI-financed medical costs, out-of-pocket payments and productivity losses of APD and CAPD patients. The total NHI-financed medical costs per patient-year after 5 years of follow-up were significantly higher with APD than CAPD (US$23 005 vs US$19 237; p<0.01). In terms of dialysis-related costs, APD had higher costs resulting from the use of APD machines (US$795) and APD sets (US$2913). Significantly lower productivity losses were found with APD (US$2619) than CAPD (US$6443), but the out-of-pocket payments were not significantly different. The differences in NHI-financed medical costs and productivity losses between APD and CAPD remained robust in the bootstrap analysis. The total economic costs of APD (US$30 401) were similar to those of CAPD (US$29 939), even after bootstrap analysis (APD, US$28 399; CAPD, US$27 960). No discernable differences were found in the results of mortality and quality of life between the APD and CAPD patients. APD had higher annual dialysis-related costs and lower annual productivity losses than CAPD, which made the economic costs of APD very close to those of CAPD in Taiwan. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Design and Development of 256x256 Linear Mode Low-Noise Avalanche Photodiode Arrays

NASA Technical Reports Server (NTRS)

Yuan, Ping; Sudharsanan, Rengarajan; Bai, Xiaogang; Boisvert, Joseph; McDonald, Paul; Chang, James

2011-01-01

A larger format photodiode array is always desirable for many LADAR imaging applications. However, as the array format increases, the laser power or the lens aperture has to increase to maintain the same flux per pixel thus increasing the size, weight and power of the imaging system. In order to avoid this negative impact, it is essential to improve the pixel sensitivity. The sensitivity of a short wavelength infrared linear-mode avalanche photodiode (APD) is a delicate balance of quantum efficiency, usable gain, excess noise factor, capacitance, and dark current of APD as well as the input equivalent noise of the amplifier. By using InA1As as a multiplication layer in an InP-based APD, the ionization coefficient ratio, k, is reduced from 0.40 (lnP) to 0.22, and the excess noise is reduced by about 50%. An additional improvement in excess noise of 25% was achieved by employing an impact-ionization-engineering structure with a k value of 0.15. Compared with the traditional InP structure, about 30% reduction in the noise-equivalent power with the following amplifier can be achieved. Spectrolab demonstrated 30-um mesa APD pixels with a dark current less than 10 nA and a capacitance of 60 fF at gain of 10. APD gain uninformity determines the usable gain of most pixels in an array, which is critical to focal plane array sensitivity. By fine tuning the material growth and device process, a break-down-voltage standard deviation of 0.1 V and gain of 30 on individual pixels were demonstrated in our 256x256 linear-mode APD arrays.

β1-Adrenoceptor autoantibodies affect action potential duration and delayed rectifier potassium currents in guinea pigs.

PubMed

Zhao, Yuhui; Huang, Haixia; Du, Yunhui; Li, Xiao; Lv, Tingting; Zhang, Suli; Wei, Hua; Shang, Jianyu; Liu, Ping; Liu, Huirong

2015-01-01

β1-Adrenoceptor autoantibodies (β1-AAs) affect the action potential duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The delayed rectifier potassium current (I K) plays a crucial role in APD, but the effects of β1-AAs on I K have not been completely illuminated. This work aimed to observe the effects of β1-AAs on I K and APD and further explore the mechanisms of β1-AA-mediated ventricular arrhythmias. β1-AAs were obtained from sera of patients with coronary heart disease (CHD) and nonsustained ventricular tachycardia. With whole-cell patch clamp technique, action potentials and I K were recorded. The results illustrated 0.1 μmol/L β1-AAs shortened APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01 μmol/L, β1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001 μmol/L, β1-AAs significantly prolonged APD90 and APD50. Moreover, β1-AAs (0.001, 0.01, 0.1 μmol/L) dose-dependently increased the rapidly activating delayed rectifier potassium current (I Kr), but similarly decreased the slowly activating delayed rectifier potassium current (I Ks) and increased L-type calcium currents at the different concentrations. Taken together, the IKr increase induced by high β1-AA concentrations is responsible for a significant APD reduction which would contribute to repolarization changes and trigger the malignant ventricular arrhythmias in CHD patients.

Sub-electron read noise and millisecond full-frame readout with the near infrared eAPD array SAPHIRA

NASA Astrophysics Data System (ADS)

Finger, Gert; Baker, Ian; Alvarez, Domingo; Dupuy, Christophe; Ives, Derek; Meyer, Manfred; Mehrgan, Leander; Stegmeier, Jörg; Weller, Harald J.

2016-07-01

In 2007 ESO started a program at SELEX (now LEONARDO) to develop noiseless near infrared HgCdTe electron avalanche photodiode arrays (eAPD)[1][2][3]. This eAPD technology is only way to overcome the limiting CMOS noise barrier of near infrared sensors used for wavefront sensing and fringe tracking. After several development cycles of solid state engineering techniques which can be easily applied to the chosen growth technology of metal organic vapour phase epitaxy (MOVPE), the eAPD arrays have matured and resulted in the SAPHIRA arrays. They have a format of 320x256 pixels with a pitch of 24 μm. They now offer an unmatched combination of sub-electron read noise at millisecond frame readout rates. The first generation of SAPHIRA arrays were only sensitive in H and K-band. With the removal of a wide bandgap buffer layer the arrays are now sensitive from λ=0.8 μm to 2.5 μm with high quantum efficiency over the entire wavelength range. The high temperature anneal applied during the growth process produces material with superb cosmetic quality at an APD gain of over 600. The design of the SAPHIRA ROIC has also been revised and the new ME1000 ROIC has an optimized analogue chain and more flexible readout modes. The clock for the vertical shift register is now under external control. The advantage of this is that correlated-double-sampling and uncorrelated readout in the rolling shutter mode now have a duty cycle of 100% at the maximum frame rate. Furthermore, to reduce the readout noise rows can be read several times before and after row reset. Since the APD gain is sufficiently high that one photon produces many more electrons than the square root of kTC which is the charge uncertainty after reset, signals of one photon per exposure can be easily detected without the need for double correlated sampling. First results obtained with the fringe tracker in GRAVITY and the four SAPHIRA wavefront sensors installed in the CIAO adaptive optics systems of the four 8 meter telescopes of the VLTI have proven the unrivaled performance of the SAPHIRA eAPD technology. A future program is being assembled to develop eAPD arrays having a larger format of 1Kx1K capable of frame rates of 1.2 KHz. There are also good prospects to offer low dark current eAPD technology for large format science focal planes as well.

Nutritional Knowledge and Attitudes in Athletes With Physical Disabilities

PubMed Central

Rastmanesh, Reza; Taleban, Furugh Azam; Kimiagar, Masood; Mehrabi, Yadolah; Salehi, Moosa

2007-01-01

Context: Little is known about sport nutritional problems and requirements of athletes with physical disabilities. Objective: To compare the nutritional knowledge and attitudes of Iranian athletes with physical disabilities (APDs) after nutrition education. Because proper nutrition is important for both performance and injury healing, learning about the nutritional areas in which APDs are deficient may assist professionals in educating them. Design: Nested case-control study. Setting: Sport camp. Patients or Other Participants: Seventy-two APDs (42 APDs in the intervention group and 30 age-matched and sex-matched control APDs) and 10 coaches completed the study. Intervention(s): The APDs in the intervention group and their coaches were given nutrition education, which included a booklet with a simplified food guide pyramid, simple concepts about nutrition and weight loss, and four 3-hour courses. The APDs in the control group and their coaches were not given nutrition education. Main Outcome Measure(s): Subjects completed 2 nutritional questionnaires with both quantitative and qualitative components. Nutritional questionnaires were administered at 2 consecutive camps, 30 days apart, before and after nutrition education. Our questionnaires included a demographics section; 88 Likert scale and true-false questions; and 18 open-ended questions, 13 of which were specifically designed for APDs. Each APD completed two 3-day food records. Results: The APDs in the intervention group scored significantly higher after nutrition education and higher than the control group on the knowledge subscales and interest in nutrition. Although the nutrition knowledge score in this study was moderate, several specific areas of deficient nutritional knowledge were identified that are critical for the health of APDs. Our model of nutrition education was more effective than the usual instructions presented irregularly by coaches. Conclusions: Our findings suggest that Iranian APDs lack nutritional knowledge in areas critical to preventing nutrition-related health problems, especially components related to nutrition for athletes with disabilities. PMID:17597950

Use of antiparkinson medications among elderly Medicare beneficiaries with Parkinson's disease.

PubMed

Wei, Yu-Jung Jenny; Stuart, Bruce; Zuckerman, Ilene H

2010-08-01

Antiparkinson drugs (APDs) are the mainstay in the management of Parkinson's disease (PD). However, the use of APDs has not been investigated in a nationally representative sample. This study aimed to describe the prevalence and patterns of APD use and to identify determinants of APD use among elderly Medicare beneficiaries with PD. Data from the Medicare Current Beneficiary Survey and Medicare claims from 2000 to 2003 were used to identify beneficiaries ≥65 years of age with PD. The APDs included in the study were levodopa, dopamine agonists, monoamine oxidase-B inhibitors, amantadine, anticholinergic agents, and catechol-O-methyltransferase inhibitors. The annual prevalence of APD use was calculated; patterns of APD use were measured by drug class and type of drug regimens (monotherapy or combination therapy). Potential determinants of APD use included sociodemographic characteristics (age, sex, race, education, marital status, and annual income), self-reported health status, residential status (institution or community), prescription drug coverage, disability (functional, physical, and mental), and disease-specific factors (dementia, depression, and other comorbidities). Multivariate logistic regression analyses with generalized estimating equations were used to estimate odds ratios (ORs) of any APD use associated with the determinants. The data revealed 571 beneficiaries with PD (30.1% aged ≥85 years, 55.0% female, 88.3% white), who were observed for a total of 924 person-years. The annual prevalence of APD use was 58.2% (538/924). Levodopa was the most frequently used agent, either as monotherapy or in combination with other APDs (85.5%; 460/538). Multivariate analyses found that patients 65 to 74 years of age (OR = 0.70; 95% CI, 0.49-0.99; P < 0.05) and those ≥85 years of age (OR = 0.57; 95% CI, 0.40-0.81; P < 0.01) were less likely to use APDs than were patients aged 75 to 84 years of age. Patients who had attained a high level of education (more than a high school diploma) were more likely to use APDs than were patients with a low level of education (a high school diploma or less) (OR = 1.51; 95% CI, 1.04-2.19; P < 0.05). In addition, institutionalization (OR = 1.78; 95% CI, 1.17-2.71; P < 0.01), prescription drug coverage (OR = 1.50; 95% CI, 1.15-1.94; P < 0.01), activities of daily living (ADLs) (OR = 1.47; 95% CI, 1.16-1.87; P < 0.01), and depression (OR = 1.25; 95% CI, 1.02-1.53; P < 0.05) were significantly associated with use of APDs. The probability of APD use was lower among those with dementia than among those without dementia (OR = 0.62; 95% CI, 0.48-0.80; P < 0.001). Almost half of the elderly Medicare beneficiaries with PD in this study did not use any APD between 2000 and 2003. Levodopa was the most frequently used APD, either as monotherapy or in combination with other APDs. The identified determinants of APD use (age, education, prescription drug coverage, ADLs, dementia, depression, and residing in an institution) may be helpful in developing interventions for this population. Copyright © 2010 Excerpta Medica Inc. All rights reserved.

Neutron diffraction study of the formation of ordered antiphase domains in cubic titanium carbide TiC{sub 0.60}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khidirov, I., E-mail: khidirov@inp.uz; Parpiev, A. S.

2013-05-15

A series of superstructural reflections (described within the sp. gr. Fd3m) are found to be split into three symmetric parts in the neutron powder diffraction pattern of titanium carbide TiC{sub 0.60} annealed at a temperature of 600 Degree-Sign C. No splitting of superstructural reflections is observed in the neutron diffraction pattern of TiC{sub 0.60} annealed at relatively high temperatures (780 Degree-Sign C). This phenomenon can be explained by that fact that the ordering of carbon atoms at relatively high temperatures (780 Degree-Sign C) is accompanied by the formation of randomly oriented rather large antiphase domains (APDs) (450 A). At relativelymore » low temperatures (600 Degree-Sign C), stacking faults arise in the arrangement of partially ordered carbon atoms. In this case, relatively small ordered APDs (290 A) are formed, along with disordered ones.« less

Predictors of Percutaneous Catheter Drainage (PCD) after Abdominal Paracentesis Drainage (APD) in Patients with Moderately Severe or Severe Acute Pancreatitis along with Fluid Collections

PubMed Central

Liu, Wei-hui; Wang, Tao; Yan, Hong-tao; Chen, Tao; Xu, Chuan; Ye, Ping; Zhang, Ning; Liu, Zheng-cai; Tang, Li-jun

2015-01-01

Aims Although we previously demonstrated abdominal paracentesis drainage (APD) preceding percutaneous catheter drainage (PCD) as the central step for treating patients with moderately severe (MSAP) or severe acute pancreatitis (SAP), the predictors leading to PCD after APD have not been studied. Methods Consecutive patients with MSAP or SAP were recruited between June 2011 and June 2013. As a step-up approach, all patients initially received medical management, later underwent ultrasound-guided APD before PCD, if necessary, followed by endoscopic necrosectomy through the path formed by PCD. APD primarily targeted fluid in the abdominal or pelvic cavities, whereas PCD aimed at (peri)pancreatic fluid. Results Of the 92 enrolled patients, 40 were managed with APD alone and 52 received PCD after APD (14 required necrosectomy after initial PCD). The overall mortality was 6.5%. Univariate analysis showed that among the 20 selected parameters, 13 factors significantly affected PCD intervention after APD. Multivariate analysis revealed that infected (peri)pancreatic collections (P = -0.001), maximum extent of necrosis of more than 30% of the pancreas (P = -0.024), size of the largest necrotic peri(pancreatic) collection (P = -0.007), and reduction of (peri)pancreatic fluid collections by <50% after APD (P = -0.008) were all independent predictors of PCD. Conclusions Infected (peri)pancreatic collections, a largest necrotic peri(pancreatic) collection of more than 100 ml, and reduction of (peri)pancreatic fluid collections by <50% after APD could effectively predict the need for PCD in the early course of the disease. PMID:25659143

Peritoneal dialysis technique success during the initial 90 days of therapy.

PubMed

Guest, Steven; Hayes, Andrew C; Story, Kenneth; Davis, Ira D

2012-01-01

Comparisons of technique success by peritoneal dialysis (PD) modality have typically excluded the initial 90 days of therapy. We analyzed a database of 51,469 new PD starts from 2004 to 2008 in the United States. The analysis concentrated on the initial 90 days of therapy to determine technique success and the impact of the continuous ambulatory PD (CAPD) and automated PD (APD) modalities. Overall, 13.3% of patients stopped PD within 90 days. Of patients starting directly on APD, 14.3% stopped PD within 90 days. Of patients starting on CAPD, 12.6% stopped PD within 90 days, and 63.4% changed to APD within 90 days. Only 3.3% of the latter patients failed to reach 90 days of therapy. By comparison, technique failure occurred in 28.8% of those initiating with and remaining on CAPD. We conclude that initial training to perform CAPD, with timely transfer to APD within the first 3 months, was associated with the greatest technique success at 90 days. The reasons for that success are unclear, and further research should be directed to determining factors responsible. It is possible that patients trained initially to CAPD but converted to APD have a greater understanding of the total therapy, which improves confidence. Those converted to APD may be more appreciative of the lifestyle benefits of APD, which translates into improved compliance; alternatively, technical factors associated with APD may be responsible. Those technical factors may include improved catheter function in the recumbent position during APD or the reduced infection risk associated with just 2 connect/disconnect procedures in APD compared with 8 in CAPD.

Use of active personal dosimeters in hospitals: EURADOS survey.

PubMed

Ciraj-Bjelac, Olivera; Carinou, Eleftheria; Vanhavere, Filip

2018-06-01

Considering that occupational exposure in medicine is a matter of growing concern, active personal dosimeters (APDs) are also increasingly being used in different fields of application of ionising radiation in medicine. An extensive survey to collect relevant information regarding the use of APDs in medical imaging applications of ionising radiation was organised by the EURADOS (European Radiation Dosimetry Group) Working Group 12. The objective was to collect data about the use of APDs and to identify the basic problems in the use of APDs in hospitals. APDs are most frequently used in interventional radiology and cardiology departments (54%), in nuclear medicine (29%), and in radiotherapy (12%). Most types of APDs use silicon diodes as the detector; however, in many cases their calibration is not given proper attention, as radiation beam qualities in which they are calibrated differ significantly from those in which they are actually used. The survey revealed problems related to the use of APDs, including their reliability in pulsed x-ray fields that are widely used in hospitals. Guidance from regulatory authorities and professional organisations on the testing and calibration of APDs used in hospital would likely improve the situation.

Progress in low light-level InAs detectors- towards Geiger-mode detection

NASA Astrophysics Data System (ADS)

Tan, Chee Hing; Ng, Jo Shien; Zhou, Xinxin; David, John; Zhang, Shiyong; Krysa, Andrey

2017-05-01

InAs avalanche photodiodes (APDs) can be designed such that only electrons are allowed to initiate impact ionization, leading to the lowest possible excess noise factor. Optimization of wet chemical etching and surface passivation produced mesa APDs with bulk dominated dark current and responsivity that are comparable and higher, respectively, than a commercial InAs detector. Our InAs electron-APDs also show high stability with fluctuation of 0.1% when operated at a gain of 11.2 over 60 s. These InAs APDs can detect very weak signal down to 35 photons per pulse. Fabrication of planar InAs by Be implantation produced planar APDs with bulk dominated dark current. Annealing at 550 °C was necessary to remove implantation damage and to activate Be dopants. Due to minimal diffusion of Be, thick depletion of 8 μm was achieved. Since the avalanche gain increases exponentially with the thickness of avalanche region, our planar APD achieved high gain > 300 at 200 K. Our work suggest that both mesa and planar InAs APDs can exhibit high gain. When combined with a suitable preamplifier, single photon detection using InAs electron-APDs could be achieved.

Single Photon Counting Detectors for Low Light Level Imaging Applications

NASA Astrophysics Data System (ADS)

Kolb, Kimberly

2015-10-01

This dissertation presents the current state-of-the-art of semiconductor-based photon counting detector technologies. HgCdTe linear-mode avalanche photodiodes (LM-APDs), silicon Geiger-mode avalanche photodiodes (GM-APDs), and electron-multiplying CCDs (EMCCDs) are compared via their present and future performance in various astronomy applications. LM-APDs are studied in theory, based on work done at the University of Hawaii. EMCCDs are studied in theory and experimentally, with a device at NASA's Jet Propulsion Lab. The emphasis of the research is on GM-APD imaging arrays, developed at MIT Lincoln Laboratory and tested at the RIT Center for Detectors. The GM-APD research includes a theoretical analysis of SNR and various performance metrics, including dark count rate, afterpulsing, photon detection efficiency, and intrapixel sensitivity. The effects of radiation damage on the GM-APD were also characterized by introducing a cumulative dose of 50 krad(Si) via 60 MeV protons. Extensive development of Monte Carlo simulations and practical observation simulations was completed, including simulated astronomical imaging and adaptive optics wavefront sensing. Based on theoretical models and experimental testing, both the current state-of-the-art performance and projected future performance of each detector are compared for various applications. LM-APD performance is currently not competitive with other photon counting technologies, and are left out of the application-based comparisons. In the current state-of-the-art, EMCCDs in photon counting mode out-perform GM-APDs for long exposure scenarios, though GM-APDs are better for short exposure scenarios (fast readout) due to clock-induced-charge (CIC) in EMCCDs. In the long term, small improvements in GM-APD dark current will make them superior in both long and short exposure scenarios for extremely low flux. The efficiency of GM-APDs will likely always be less than EMCCDs, however, which is particularly disadvantageous for moderate to high flux rates where dark noise and CIC are insignificant noise sources. Research into decreasing the dark count rate of GM-APDs will lead to development of imaging arrays that are competitive for low light level imaging and spectroscopy applications in the near future.

Restitution slope is principally determined by steady-state action potential duration.

PubMed

Shattock, Michael J; Park, Kyung Chan; Yang, Hsiang-Yu; Lee, Angela W C; Niederer, Steven; MacLeod, Kenneth T; Winter, James

2017-06-01

The steepness of the action potential duration (APD) restitution curve and local tissue refractoriness are both thought to play important roles in arrhythmogenesis. Despite this, there has been little recognition of the apparent association between steady-state APD and the slope of the restitution curve. The objective of this study was to test the hypothesis that restitution slope is determined by APD and to examine the relationship between restitution slope, refractoriness and susceptibility to VF. Experiments were conducted in isolated hearts and ventricular myocytes from adult guinea pigs and rabbits. Restitution curves were measured under control conditions and following intervention to prolong (clofilium, veratridine, bretylium, low [Ca]e, chronic transverse aortic constriction) or shorten (catecholamines, rapid pacing) ventricular APD. Despite markedly differing mechanisms of action, all interventions that prolonged the action potential led to a steepening of the restitution curve (and vice versa). Normalizing the restitution curve as a % of steady-state APD abolished the difference in restitution curves with all interventions. Effects on restitution were preserved when APD was modulated by current injection in myocytes pre-treated with the calcium chelator BAPTA-AM - to abolish the intracellular calcium transient. The non-linear relation between APD and the rate of repolarization of the action potential is shown to underpin the common influence of APD on the slope of the restitution curve. Susceptibility to VF was found to parallel changes in APD/refractoriness, rather than restitution slope. Steady-state APD is the principal determinant of the slope of the ventricular electrical restitution curve. In the absence of post-repolarization refractoriness, factors that prolong the action potential would be expected to steepen the restitution curve. However, concomitant changes in tissue refractoriness act to reduce susceptibility to sustained VF. Dependence on steady-state APD may contribute to the failure of restitution slope to predict sudden cardiac death. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology

Restitution slope is principally determined by steady-state action potential duration

PubMed Central

Shattock, Michael J.; Park, Kyung Chan; Yang, Hsiang-Yu; Lee, Angela W. C.; Niederer, Steven; MacLeod, Kenneth T.

2017-01-01

Aims The steepness of the action potential duration (APD) restitution curve and local tissue refractoriness are both thought to play important roles in arrhythmogenesis. Despite this, there has been little recognition of the apparent association between steady-state APD and the slope of the restitution curve. The objective of this study was to test the hypothesis that restitution slope is determined by APD and to examine the relationship between restitution slope, refractoriness and susceptibility to VF. Methods and results Experiments were conducted in isolated hearts and ventricular myocytes from adult guinea pigs and rabbits. Restitution curves were measured under control conditions and following intervention to prolong (clofilium, veratridine, bretylium, low [Ca]e, chronic transverse aortic constriction) or shorten (catecholamines, rapid pacing) ventricular APD. Despite markedly differing mechanisms of action, all interventions that prolonged the action potential led to a steepening of the restitution curve (and vice versa). Normalizing the restitution curve as a % of steady-state APD abolished the difference in restitution curves with all interventions. Effects on restitution were preserved when APD was modulated by current injection in myocytes pre-treated with the calcium chelator BAPTA-AM – to abolish the intracellular calcium transient. The non-linear relation between APD and the rate of repolarization of the action potential is shown to underpin the common influence of APD on the slope of the restitution curve. Susceptibility to VF was found to parallel changes in APD/refractoriness, rather than restitution slope. Conclusion(s) Steady-state APD is the principal determinant of the slope of the ventricular electrical restitution curve. In the absence of post-repolarization refractoriness, factors that prolong the action potential would be expected to steepen the restitution curve. However, concomitant changes in tissue refractoriness act to reduce susceptibility to sustained VF. Dependence on steady-state APD may contribute to the failure of restitution slope to predict sudden cardiac death. PMID:28371805

Comparison of cost-utility between automated peritoneal dialysis and continuous ambulatory peritoneal dialysis.

PubMed

Cortés-Sanabria, Laura; Paredes-Ceseña, Carlos A; Herrera-Llamas, Rebeca M; Cruz-Bueno, Yolanda; Soto-Molina, Herman; Pazarín, Leonardo; Cortés, Margarita; Martínez-Ramírez, Héctor R

2013-11-01

The use of automated peritoneal dialysis (APD) is increasing compared to continuous ambulatory peritoneal dialysis (CAPD). Surprisingly, little data about health benefits and cost of APD exist, and virtually no information comparing the cost-utility between CAPD and APD is available. We undertook this study to evaluate and compare the health-related quality of life (HRQOL) and cost-utility indexes in patients on CAPD vs. This was a prospective cohort of patients initiating dialysis (2008-2009). Two questionnaires were self-administered: European Research Questionnaire Quality of Life (EQ-5D) and Kidney Disease Quality of Life (short form, KDQOL-SF, Rand, Santa Monica, CA). Direct medical costs (DMC) were determined from the health provider perspective including the following medical resource utilization: outpatient clinic/emergency care, dialysis procedures, medications, laboratory tests, hospitalization, and surgery. Cost-utility indexes were calculated dividing total mean cost by indicators of the HRQOL. One hundred twenty-three patients were evaluated: 77 on CAPD and 46 on APD. Results of the EQ-5D and KDQOL-SF questionnaires were significantly better in APD compared to the CAPD group. Main costs in both APD and CAPD were attributed to hospitalization and dialysis procedures followed by medication and surgery. Outpatient clinic visits and laboratory tests were significantly more costly in CAPD than in APD, whereas dialysis procedures were more expensive in the latter. Cost-utility indexes were significantly better in APD compared to CAPD. A significant cost-utility advantage of APD vs. CAPD was observed. The annual DMC per-patient were not different between groups but the HRQOL was better in the APD compared to the CAPD group. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

APD Response Time Measurements for Future TOF-E Systems

NASA Astrophysics Data System (ADS)

Starkey, M. J.; Ogasawara, K.; Dayeh, M. A.; Desai, M. I.

2017-12-01

In space physics, the ability to detect ions is crucial to understanding plasma distributions in the solar wind. This usually typically requires the determination of the particle's mass, charge, and total energy. Current ion detection schemes are implemented in three sequential parts; an electrostatic analyzer for energy per charge (E/Q) measurements, a time-of-flight (TOF) for mass per charge (M/Q) measurements, and a solid-state detector (SSD) for total energy (E) measurements. Recent work has suggested the use of avalanche photodiode detectors (APD) for a simultaneous TOF and total energy (TOF-E) measurement system, which would replace traditional SSDs, simplify design, and reduce costs. Although TOF based ion spectrometry typically requires timing resolution of <1ns, the timing profile for ion detection by APDs is not well understood. In this study we examine the timing profile of 3 different APDs for ion measurements over a suprathermal energy range of 50-300 keV. The three APDs differ by their doping type (N or P) and their detector thickness (30 μm or 150 μm). We find that APD P30, which is P doped and 30μm thick, provides the fastest rise times of the three APDs. Furthermore, these rise times are species independent and less than 1 ns. Our study shows that APDs are capable of sub-nanosecond response times for low energy ions and thus supports the future use of APDs in replacing SSDs in some TOF-E systems.

Spatiotemporal differentiation in auditory and motor regions during auditory phoneme discrimination.

PubMed

Aerts, Annelies; Strobbe, Gregor; van Mierlo, Pieter; Hartsuiker, Robert J; Corthals, Paul; Santens, Patrick; De Letter, Miet

2017-06-01

Auditory phoneme discrimination (APD) is supported by both auditory and motor regions through a sensorimotor interface embedded in a fronto-temporo-parietal cortical network. However, the specific spatiotemporal organization of this network during APD with respect to different types of phonemic contrasts is still unclear. Here, we use source reconstruction, applied to event-related potentials in a group of 47 participants, to uncover a potential spatiotemporal differentiation in these brain regions during a passive and active APD task with respect to place of articulation (PoA), voicing and manner of articulation (MoA). Results demonstrate that in an early stage (50-110 ms), auditory, motor and sensorimotor regions elicit more activation during the passive and active APD task with MoA and active APD task with voicing compared to PoA. In a later stage (130-175 ms), the same auditory and motor regions elicit more activation during the APD task with PoA compared to MoA and voicing, yet only in the active condition, implying important timing differences. Degree of attention influences a frontal network during the APD task with PoA, whereas auditory regions are more affected during the APD task with MoA and voicing. Based on these findings, it can be carefully suggested that APD is supported by the integration of early activation of auditory-acoustic properties in superior temporal regions, more perpetuated for MoA and voicing, and later auditory-to-motor integration in sensorimotor areas, more perpetuated for PoA.

Central and Peripheral Mechanisms of Antipsychotic Medication-Induced Metabolic Dysregulation

DTIC Science & Technology

2016-10-01

generation APD haloperidol or second-generation APD olanzapine (via i.p. administration). We will also measure serum fasting glucose and insulin levels...food consumption in beta cell-specific D2R (and wildtype littermate controls) treated with either with first- generation APD haloperidol or second...effects of D2R agonists (dopamine, quinpirole) versus APD antagonists ( haloperidol and olanzapine). § We will treat pancreatic islets from wildtype

APD in the developing world: is there a future?

PubMed

Correa-Rotter, Ricardo

2002-01-01

Automated peritoneal dialysis (APD) has experienced significant growth in highly developed nations in the last few years, while in developing countries with important social, educational, and financial constraints this treatment modality is, at best, trying to emerge. APD offers advantages that make it popular. Some of these advantages include increased adequacy for some patient groups, enhanced patient well-being and positive changes in lifestyle, as well as a reduction in peritonitis rates attributed to fewer connect-disconnect procedures. The development of APD in developing nations has been very poor mainly due to educational and financial constraints. APD growth as a treatment modality in the developing world requires multiple approaches, some of them general and others related to the specific needs of each nation. There is a need to develop APD research projects and pilot programs to demonstrate the benefits for specific subpopulations. In addition, the development of research and industry-market strategies directed at reducing costs related to this form of treatment are required. The relatively low use of APD in developing nations is primarily influenced by nonmedical factors. Given the financial and educational constraints, APD programs may need to be directed toward specific subpopulations such as young working adults, individuals who require assistance to perform procedures, or patients who require an increased dialysis dose in order to reach adequate clearances.

Avalanche photodiode photon counting receivers for space-borne lidars

NASA Technical Reports Server (NTRS)

Sun, Xiaoli; Davidson, Frederic M.

1991-01-01

Avalanche photodiodes (APD) are studied for uses as photon counting detectors in spaceborne lidars. Non-breakdown APD photon counters, in which the APD's are biased below the breakdown point, are shown to outperform: (1) conventional APD photon counters biased above the breakdown point; (2) conventional APD photon counters biased above the breakdown point; and (3) APD's in analog mode when the received optical signal is extremely weak. Non-breakdown APD photon counters were shown experimentally to achieve an effective photon counting quantum efficiency of 5.0 percent at lambda = 820 nm with a dead time of 15 ns and a dark count rate of 7000/s which agreed with the theoretically predicted values. The interarrival times of the counts followed an exponential distribution and the counting statistics appeared to follow a Poisson distribution with no after pulsing. It is predicted that the effective photon counting quantum efficiency can be improved to 18.7 percent at lambda = 820 nm and 1.46 percent at lambda = 1060 nm with a dead time of a few nanoseconds by using more advanced commercially available electronic components.

Prospective test of the developmental propensity model of antisocial behavior: from childhood and adolescence into early adulthood.

PubMed

Lahey, Benjamin B; Class, Quetzal A; Zald, David H; Rathouz, Paul J; Applegate, Brooks; Waldman, Irwin D

2018-06-01

The developmental propensity model of antisocial behavior posits that several dispositional characteristics of children transact with the environment to influence the likelihood of learning antisocial behavior across development. Specifically, greater dispositional negative emotionality, greater daring, and lower prosociality-operationally, the inverse of callousness- and lower cognitive abilities are each predicted to increase risk for developing antisocial behavior. Prospective tests of key predictions derived from the model were conducted in a high-risk sample of 499 twins who were assessed on dispositions at 10-17 years of age and assessed for antisocial personality disorder (APD) symptoms at 22-31 years of age. Predictions were tested separately for parent and youth informants on the dispositions using multiple regressions that adjusted for oversampling, nonresponse, and clustering within twin pairs, controlling demographic factors and time since the first assessment. Consistent with predictions, greater numbers of APD symptoms in adulthood were independently predicted over a 10-15 year span by higher youth ratings on negative emotionality and daring and lower youth ratings on prosociality, and by parent ratings of greater negative emotionality and lower prosociality. A measure of working memory did not predict APD symptoms. These findings support future research on the role of these dispositions in the development of antisocial behavior. © 2017 Association for Child and Adolescent Mental Health.

[Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles].

PubMed

Li, S N; Zhang, K Y

1992-11-01

Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD < 1; P < 0.01), but did not affect APD20 and other parameters. In the late stage, Dau prolonged APD100, ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P < 0.01), greatly diminished APA and OS of SAP induced by isoprenaline (P < 0.01), and remarkably inhibited Isi (P < 0.01). The results suggested that Dau exerted an inhibitory effect on Na+, Ca2+, and K+ channels.

Testing limits to airflow perturbation device (APD) measurements.

PubMed

Lopresti, Erika R; Johnson, Arthur T; Koh, Frank C; Scott, William H; Jamshidi, Shaya; Silverman, Nischom K

2008-10-31

The Airflow Perturbation Device (APD) is a lightweight, portable device that can be used to measure total respiratory resistance as well as inhalation and exhalation resistances. There is a need to determine limits to the accuracy of APD measurements for different conditions likely to occur: leaks around the mouthpiece, use of an oronasal mask, and the addition of resistance in the respiratory system. Also, there is a need for resistance measurements in patients who are ventilated. Ten subjects between the ages of 18 and 35 were tested for each station in the experiment. The first station involved testing the effects of leaks of known sizes on APD measurements. The second station tested the use of an oronasal mask used in conjunction with the APD during nose and mouth breathing. The third station tested the effects of two different resistances added in series with the APD mouthpiece. The fourth station tested the usage of a flexible ventilator tube in conjunction with the APD. All leaks reduced APD resistance measurement values. Leaks represented by two 3.2 mm diameter tubes reduced measured resistance by about 10% (4.2 cmH2O.sec/L for control and 3.9 cm H2O.sec/L for the leak). This was not statistically significant. Larger leaks given by 4.8 and 6.4 mm tubes reduced measurements significantly (3.4 and 3.0 cm cmH2O.sec/L, respectively). Mouth resistance measured with a cardboard mouthpiece gave an APD measurement of 4.2 cm H2O.sec/L and mouth resistance measured with an oronasal mask was 4.5 cm H2O.sec/L; the two were not significantly different. Nose resistance measured with the oronasal mask was 7.6 cm H2O.sec/L. Adding airflow resistances of 1.12 and 2.10 cm H2O.sec/L to the breathing circuit between the mouth and APD yielded respiratory resistance values higher than the control by 0.7 and 2.0 cm H2O.sec/L. Although breathing through a 52 cm length of flexible ventilator tubing reduced the APD measurement from 4.0 cm H2O.sec/L for the control to 3.6 cm H2O.sec/L for the tube, the difference was not statistically significant. The APD can be adapted for use in ventilated, unconscious, and uncooperative patients with use of a ventilator tube and an oronasal mask without significantly affecting measurements. Adding a resistance in series with the APD mouthpiece has an additive effect on resistance measurements, and can be used for qualitative calibration. A leak size of at least the equivalent of two 3.2 mm diameter tubes can be tolerated without significantly affecting APD measurements.

Comparison of peritonitis rates and patient survival in automated and continuous ambulatory peritoneal dialysis: a 10-year single center experience.

PubMed

El-Reshaid, Wael; Al-Disawy, Hanan; Nassef, Hossameldeen; Alhelaly, Usama

2016-09-01

Peritonitis is a common complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). In this retrospective study, peritonitis rates and patient survival of 180 patients on CAPD and 128 patients on APD were compared in the period from January 2005 to December 2014 at Al-Nafisi Center in Kuwait. All patients had prophylactic topical mupirocin at catheter exit site. Patients on CAPD had twin bag system with Y transfer set. The peritonitis rates were 1 in 29 months in CAPD and 1 in 38 months in APD (p < 0.05). Percentage of peritonitis free patients over 10-year period in CAPD and APD were 49 and 60%, respectively (p < 0.05). Time to develop peritonitis was 10.25 ± 3.1 months in CAPD compared to 16.1 ± 4 months in APD (p < 0.001). Relapse and recurrence rates were similar in both groups. Median patient survival in CAPD and APD groups with peritonitis was 13.1 ± 1 and 14 ± 1.4 months respectively (p = 0.3) whereas in peritonitis free patients it was 15 ± 1.4 months in CAPD and 23 ± 3.1 months in APD (p = 0.025). APD had lower incidence rate of peritonitis than CAPD. Patient survival was better in APD than CAPD in peritonitis free patients but was similar in patients who had peritonitis.

Use of Fall-Risk Inducing Drugs in Patients Using Anti-Parkinson Drugs (APD): A Swedish Register-Based Study.

PubMed

Haasum, Ylva; Fastbom, Johan; Johnell, Kristina

2016-01-01

Many drugs increase the risk of falls in old age. Although persons with Parkinson's disease (PD) are at increased risk of experiencing falls and fractures, the use of fall-risk inducing drugs (FRIDs) in this population has not previously been investigated. The objective of this study was to investigate the burden of use of FRIDs in older persons treated with anti-Parkinson drugs (APD; used as a proxy for PD), compared to persons without APD. We analyzed individual data on age, sex, type of housing and drug use in 1 346 709 persons aged ≥ 65 years in the Swedish Prescribed Drug Register on the date of 30 September 2008. Main outcome measure was the use of FRIDs. FRIDs were used by 79% of persons with APD and 75% of persons without APD. Persons with APD were more likely to use ≥ 1 FRIDs compared to persons without APD (adjusted OR: 1.09; 95% CI: 1.06-1-12). The association was stronger for concomitant use of ≥ 5 FRIDS (adjusted OR: 1.49; 95% CI: 1.44-1.55). The high use of FRIDs among persons with APD indicates that these patients may be at increased risk of drug-induced falls. Further studies are needed to investigate how these drugs affect the risk of falling in persons with PD.

Use of Fall-Risk Inducing Drugs in Patients Using Anti-Parkinson Drugs (APD): A Swedish Register-Based Study

PubMed Central

Haasum, Ylva; Fastbom, Johan; Johnell, Kristina

2016-01-01

Objectives Many drugs increase the risk of falls in old age. Although persons with Parkinson’s disease (PD) are at increased risk of experiencing falls and fractures, the use of fall-risk inducing drugs (FRIDs) in this population has not previously been investigated. The objective of this study was to investigate the burden of use of FRIDs in older persons treated with anti-Parkinson drugs (APD; used as a proxy for PD), compared to persons without APD. Methods We analyzed individual data on age, sex, type of housing and drug use in 1 346 709 persons aged ≥ 65 years in the Swedish Prescribed Drug Register on the date of 30 September 2008. Main outcome measure was the use of FRIDs. Results FRIDs were used by 79% of persons with APD and 75% of persons without APD. Persons with APD were more likely to use ≥ 1 FRIDs compared to persons without APD (adjusted OR: 1.09; 95% CI: 1.06-1-12). The association was stronger for concomitant use of ≥ 5 FRIDS (adjusted OR: 1.49; 95% CI: 1.44–1.55). Conclusions The high use of FRIDs among persons with APD indicates that these patients may be at increased risk of drug-induced falls. Further studies are needed to investigate how these drugs affect the risk of falling in persons with PD. PMID:27537366

Comparison of Respiratory Resistance Measurements Made with an Airflow Perturbation Device with Those from Impulse Oscillometry

PubMed Central

Pan, J.; Saltos, A.; Smith, D.; Johnson, A.; Vossoughi, J.

2013-01-01

The airflow perturbation device (APD) has been developed as a portable, easy to use, and a rapid response instrument for measuring respiratory resistance in humans. However, the APD has limited data validating it against the established techniques. This study used a mechanical system to simulate the normal range of human breathing to validate the APD with the clinically accepted impulse oscillometry (IOS) technique. The validation system consisted of a sinusoidal flow generator with ten standardized resistance configurations that were shown to represent a total range of resistances from 0.12 to 0.95 kPa·L−1 ·s (1.2–9.7 cm H2O·L−1 ·s). Impulse oscillometry measurements and APD measurements of the mechanical system were recorded and compared at a constant airflow of 0.15 L·s−1. Both the IOS and APD measurments were accurate in assessing nominal resistance. In addition, a strong linear relationship was observed between APD measurements and IOS measurements (R 2 = 0.999). A second series of measurements was made on ten human volunteers with external resistors added in their respiratory flow paths. Once calibrated with the mechanical system, the APD gave respiratory resistance measurements within 5% of IOS measurements. Because of their comparability to IOS measurements, APD measurements are shown to be valid representations of respiratory resistance. PMID:27006908

Human stem cell-derived cardiomyocytes detect drug-mediated changes in action potentials and ion currents.

PubMed

Gibson, John K; Yue, Yimei; Bronson, Jared; Palmer, Cassie; Numann, Randy

2014-01-01

It has been proposed that proarrhythmia assessment for safety pharmacology testing includes the use of human pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) to detect drug-induced changes in cardiac electrophysiology. This study measured the actions of diverse agents on action potentials (AP) and ion currents recorded from hiPSC-CM. During AP experiments, the hiPSC-CM were paced at 1Hz during a baseline period, and when increasing concentrations of test compound were administered at 4-minute intervals. AP parameters, including duration (APD60 and APD90), resting membrane potential, rate of rise, and amplitude, were measured throughout the entire experiment. Voltage clamp experiments with E-4031 and nifedipine were similarly conducted. E-4031 produced a dose-dependent prolongation of cardiac action potential and blocked the hERG/IKr current with an IC50 of 17nM. At 3nM, dofetilide significantly increased APD90. Astemizole significantly increased APD60 and APD90 at 30nM. Terfenadine significantly increased APD90 at concentrations greater than 10nM. Fexofenadine, a metabolite of terfenadine, did not produce any electrophysiologic changes in cardiac action potentials. Flecainide produced a dose-dependent prolongation of the cardiac action potential at 1 and 3μM. Acute exposure to nifedipine significantly decreased APD60 and APD90 and produced a dose-dependent block of calcium current with an IC50 of 0.039μM. Verapamil first shortened APD60 and APD90 in a dose-dependent manner, until a compensating increase in APD90, presumably via hERG blockade, was observed at 1 and 3μM. Following a chronic exposure (20-24h) to clinically relevant levels of pentamidine, a significant increase in action potential duration was accompanied by early afterdepolarizations (EADs). These experiments show the ability of AP measured from hiPSC-CM to record the interactions of various ion channels via AP recording and avoid the limitations of using several single ion channel assays in a noncardiac tissue. Copyright © 2014 Elsevier Inc. All rights reserved.

Atrial Premature Depolarization-Induced Changes in QRS and T Wave Morphology on Resting Electrocardiograms in Horses.

PubMed

Broux, B; De Clercq, D; Decloedt, A; Van Der Vekens, N; Verheyen, T; Ven, S; Pardon, B; van Loon, G

2016-07-01

The electrocardiographic differentiation between atrial (APDs) and ventricular (VPDs) premature depolarizations is important. P wave prematurity and normal QRS and T wave morphology generally are used as discriminating criteria for APDs. The aim of this study was to determine whether P, Q, R, S, and T wave amplitude, PQ interval, QRS and P wave duration and P and T wave morphology differ between APDs and sinus beats. To determine the relationship between the RR coupling interval and the change in S wave amplitude between sinus beats and APDs. Case-control study. From a modified base-apex configuration of 30 horses with APDs at rest, sinus beat and APD associated preceding RR interval, P, PQ and QRS duration and P, R, S, and T wave amplitudes were measured. Linear mixed models and logistic regression were used to determine the effect of APDs on the ECG variables studied. In comparison to sinus beats, APDs were associated with a significant (P < .001) change in P amplitude (-0.03 ± 0.01 mV) and increase in S (0.20 ± 0.02 mV) and T (0.08 ± 0.03 mV) amplitude. PQ (-20.3 ± 5.2 ms) and RR (-519 ± 14 ms) interval and P duration (-21.1 ± 3.0 ms) decreased (P < .001). APDs were significantly associated with a singular positive P wave (OR: 11.0, P < .001) and were more likely to have a monophasic positive T wave (OR: 9.2, P < .001). A smaller RR coupling interval was associated with an increased relative difference in S amplitude (P < .01). Atrial premature depolarizations may lead to changes in QRS and T wave morphology. Knowledge of these changes is important to avoid interpreting certain APDs as VPDs. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Clinical, biochemical, and radiographic effects of aminohydroxypropylidene bisphosphonate treatment in rheumatoid arthritis.

PubMed Central

Ralston, S H; Hacking, L; Willocks, L; Bruce, F; Pitkeathly, D A

1989-01-01

A placebo controlled, double blind study of aminohydroxypropylidene bisphosphonate (APD), given by monthly intravenous infusion, was conducted in 40 patients with rheumatoid arthritis. Biochemical markers of increased bone resorption, such as fasting urinary calcium/creatinine ratio and hydroxyproline/creatinine ratio, were suppressed significantly in the APD group to approximately 50% and 60% of the pretreatment level respectively, and serum calcium fell transiently after the first APD infusion. There was no significant effect on disease activity in either the APD or placebo groups as judged by clinical (grip strength, morning stiffness, visual analogue score) or laboratory (haemoglobin, platelet count, erythrocyte sedimentation rate, C reactive protein) criteria. An exception was the articular index which improved to a similar degree in both groups, falling from (mean (SEM] 13.8 (1.8) to 7.2 (2.2) in the APD group and from 13.7 (1.9) to 6.8 (1.5) in the placebo group. Radiological progression occurred to a similar degree in both groups as assessed by the Sharp index (mean (SEM) 86 (13.1) v 95 (12.9)-APD group; 103 (15.1) v 110 (15.8)-placebo group), but there was no significant change in the Larsen index in either group (mean (SEM) 53 (4.2) v 57 (3.8)-APD; 62 (5.8) v 63 (5.6)-placebo). The lack of effect on radiological progression in the APD group indicates that focal erosive disease may either have progressed as the result of a non-osteoclast related mechanism, or that the intensity of bone resorption was too great to be inhibited by the doses of APD used. The biochemical response to APD presumably reflected inhibition of bone resorption at other sites, suggesting that further studies of the effects of bisphosphates on periarticular and systemic osteoporosis in rheumatoid arthritis may be of the interest. PMID:2658875

Correction of differential renal function for asymmetric renal area ratio in unilateral hydronephrosis.

PubMed

Aktaş, Gul Ege; Sarıkaya, Ali

2015-11-01

Children with unilateral hydronephrosis are followed up with anteroposterior pelvic diameter (APD), hydronephrosis grade, mercaptoacetyltriglycine (MAG-3) drainage pattern and differential renal function (DRF). Indeterminate drainage preserved DRF in higher grades of hydronephrosis, in some situations, complicating the decision-making process. Due to an asymmetric renal area ratio, falsely negative DRF estimations can result in missed optimal surgery times. This study was designed to assess whether correcting the DRF estimation according to kidney area could reflect the clinical situation of a hydronephrotic kidney better than a classical DRF calculation, concurrently with the hydronephrosis grade, APD and MAG-3 drainage pattern. We reviewed the MAG-3, dimercaptosuccinic acid (DMSA) scans and ultrasonography (US) of 23 children (6 girls, 17 boys, mean age: 29 ± 50 months) with unilateral hydronephrosis. MAG-3 and DMSA scans were performed within 3 months (mean 25.4 ± 30.7 days). The closest US findings (mean 41.5 ± 28.2 days) were used. DMSA DRF estimations were obtained using the geometric mean method. Secondary calculations were performed to correct the counts (the total counts divided by the number of pixels in ROI) according to kidney area. The renogram patterns of patients were evaluated and separated into subgroups. The visual assessment of DMSA scans was noted and the hydronephrotic kidney was classified in comparison to the normal contralateral kidney's uptake. The correlations of the DRF values of classical and area-corrected methods with MAG-3 renogram patterns, the visual classification of DMSA scan, the hydronephrosis grade and the APD were assessed. DRF estimations of two methods were statistically different (p: 0.001). The categories of 12 hydronephrotic kidneys were changed. There were no correlations between classical DRF estimations and the hydronephrosis grade, APD, visual classification of the DMSA scan and uptake evaluation. The DRF distributions according to MAG-3 drainage patterns were not different. Area-corrected DRF estimations correlated with all: with an increasing hydronephrosis grade and APD, DRF estimations decreased and MAG-3 drainage patterns worsened. A decrease in DRF (< 45 %) was determined when APD was ≥ 10 mm. When APD was ≥ 26 mm, a reduction of DRF below 40 % was determined. Our results suggest that correcting DRF estimation for asymmetric renal area ratio in unilateral hydronephrosis can be more robust than the classical method, especially for higher grades of hydronephrotic kidneys, under equivocal circumstances.

76 FR 41799 - Agency Information Collection Activities: Proposed Collection; Comment Request; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-15

... Checklist: Medicaid Eligibility & Enrollment Systems--Advance Planning Document (E&E-APD); Use: Under... Eligibility/Enrollment Systems APD approval assignment. The information requested on the Checklist will be... an Expedited Checklist: Medicaid Eligibility & Enrollment Systems--Advance Planning Document (E& -APD...

Explicit and inferred motives for nonsuicidal self-injurious acts and urges in borderline and avoidant personality disorders.

PubMed

Snir, Avigal; Rafaeli, Eshkol; Gadassi, Reuma; Berenson, Kathy; Downey, Geraldine

2015-07-01

Nonsuicidal self-injury (NSSI) is a perplexing phenomenon that may have differing motives. The present study used experience sampling methods (ESM) which inquired explicitly about the motives for NSSI, but also enabled a temporal examination of the antecedents/consequences of NSSI; these allow us to infer other motives which were not explicitly endorsed. Adults (n = 152, aged 18-65) with borderline personality disorder (BPD), avoidant personality disorder (APD), or no psychopathology participated in a 3-week computerized diary study. We examined 5 classes of explicit motives for engaging in NSSI, finding support primarily for internally directed rather than interpersonally directed ones. We then used multilevel regression to examine changes in affect, cognition, and behavior surrounding moments of NSSI acts/urges compared with control moments (i.e., without NSSI). We examined changes in 5 scales of inferred motives, designed to correspond to the 5 classes of explicit motives. The results highlight differing motives for NSSI among individuals with BPD and APD, with some similarities (mostly in the explicit motives) and some differences (mostly in the inferred motives) between the disorders. Despite their infrequent explicit endorsement, fluctuations in interpersonally oriented scales were found surrounding NSSI acts/urges. This highlights the need to continue attending to interpersonal aspects of NSSI in research and in clinical practice. Additionally, NSSI urges, like acts, were followed by decline in affective/interpersonal distress (although in a delayed manner). Thus, interventions that build distress tolerance and enhance awareness for affective changes, and for antecedent/consequence patterns in NSSI, could help individuals resist the urge to self-injure. (c) 2015 APA, all rights reserved).

Near-IR photon number resolving detector design

NASA Astrophysics Data System (ADS)

Bogdanski, Jan; Huntington, Elanor H.

2013-05-01

Photon-Number-Resolving-Detection (PNRD) capability is crucial for many Quantum-Information (QI) applications, e.g. for Coherent-State-Quantum-Computing, Linear-Optics-Quantum-Computing. In Quantum-Key-Distribution and Quantum-Secret-Sharing over 1310/1550 nm fiber, two other important, defense and information security related, QI applications, it's crucial for the information transmission security to guarantee that the information carriers (photons) are single. Thus a PNRD can provide an additional security level against eavesdropping. Currently, there are at least a couple of promising PNRD technologies in the Near-Infrared, but all of them require cryogenic cooling. Thus a compact, portable PNRD, based on commercial Avalanche-Photo-Diodes (APDs), could be a very useful instrument for many QI experiments. For an APD-based PNRD, it is crucial to measure the APD-current in the beginning of the avalanche. Thus an efficient cancellation of the APD capacitive spikes is a necessary condition for the very weak APD current measurement. The detector's principle is based on two commercial, pair-matched InGaAs/InP APDs, connected in series. It leads to a great cancelation of the capacitive spikes caused by the narrow (300 ps), differential gate-pulses of maximum 4V amplitude assuming that both pulses are perfectly matched in regards to their phases, amplitudes, and shapes. The cancellation scheme could be used for other APD-technologies, e.g. Silicon, extending the detection spectrum from visible to NIR. The design distinguishes itself from other, APD-based, schemes by its scalability feature and its computer controlled cancellation of the capacitive spikes. Furthermore, both APDs could be equally used for the detection purpose, which opens a possibility for the odd-even photon number parity detection.

Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry

PubMed Central

Maccari, Maria Elena; Abolhassani, Hassan; Aghamohammadi, Asghar; Aiuti, Alessandro; Aleinikova, Olga; Bangs, Catherine; Baris, Safa; Barzaghi, Federica; Baxendale, Helen; Buckland, Matthew; Burns, Siobhan O.; Cancrini, Caterina; Cant, Andrew; Cathébras, Pascal; Cavazzana, Marina; Chandra, Anita; Conti, Francesca; Coulter, Tanya; Devlin, Lisa A.; Edgar, J. David M.; Faust, Saul; Fischer, Alain; Garcia-Prat, Marina; Hammarström, Lennart; Heeg, Maximilian; Jolles, Stephen; Karakoc-Aydiner, Elif; Kindle, Gerhard; Kiykim, Ayca; Kumararatne, Dinakantha; Grimbacher, Bodo; Longhurst, Hilary; Mahlaoui, Nizar; Milota, Tomas; Moreira, Fernando; Moshous, Despina; Mukhina, Anna; Neth, Olaf; Neven, Benedicte; Nieters, Alexandra; Olbrich, Peter; Ozen, Ahmet; Schmid, Jana Pachlopnik; Picard, Capucine; Prader, Seraina; Rae, William; Reichenbach, Janine; Rusch, Stephan; Savic, Sinisa; Scarselli, Alessia; Scheible, Raphael; Sediva, Anna; Sharapova, Svetlana O.; Shcherbina, Anna; Slatter, Mary; Soler-Palacin, Pere; Stanislas, Aurelie; Suarez, Felipe; Tucci, Francesca; Uhlmann, Annette; van Montfrans, Joris; Warnatz, Klaus; Williams, Anthony Peter; Wood, Phil; Kracker, Sven; Condliffe, Alison Mary; Ehl, Stephan

2018-01-01

Activated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS), caused by autosomal dominant mutations in PIK3CD (APDS1) or PIK3R1 (APDS2), is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions about long-term disease evolution and response to therapy remain. The prospective European Society for Immunodeficiencies (ESID)-APDS registry aims to characterize the disease course, identify outcome predictors, and evaluate treatment responses. So far, 77 patients have been recruited (51 APDS1, 26 APDS2). Analysis of disease evolution in the first 68 patients pinpoints the early occurrence of recurrent respiratory infections followed by chronic lymphoproliferation, gastrointestinal manifestations, and cytopenias. Although most manifestations occur by age 15, adult-onset and asymptomatic courses were documented. Bronchiectasis was observed in 24/40 APDS1 patients who received a CT-scan compared with 4/15 APDS2 patients. By age 20, half of the patients had received at least one immunosuppressant, but 2–3 lines of immunosuppressive therapy were not unusual before age 10. Response to rapamycin was rated by physician visual analog scale as good in 10, moderate in 9, and poor in 7. Lymphoproliferation showed the best response (8 complete, 11 partial, 6 no remission), while bowel inflammation (3 complete, 3 partial, 9 no remission) and cytopenia (3 complete, 2 partial, 9 no remission) responded less well. Hence, non-lymphoproliferative manifestations should be a key target for novel therapies. This report from the ESID-APDS registry provides comprehensive baseline documentation for a growing cohort that will be followed prospectively to establish prognostic factors and identify patients for treatment studies. PMID:29599784

Disease Evolution and Response to Rapamycin in Activated Phosphoinositide 3-Kinase δ Syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry.

PubMed

Maccari, Maria Elena; Abolhassani, Hassan; Aghamohammadi, Asghar; Aiuti, Alessandro; Aleinikova, Olga; Bangs, Catherine; Baris, Safa; Barzaghi, Federica; Baxendale, Helen; Buckland, Matthew; Burns, Siobhan O; Cancrini, Caterina; Cant, Andrew; Cathébras, Pascal; Cavazzana, Marina; Chandra, Anita; Conti, Francesca; Coulter, Tanya; Devlin, Lisa A; Edgar, J David M; Faust, Saul; Fischer, Alain; Garcia-Prat, Marina; Hammarström, Lennart; Heeg, Maximilian; Jolles, Stephen; Karakoc-Aydiner, Elif; Kindle, Gerhard; Kiykim, Ayca; Kumararatne, Dinakantha; Grimbacher, Bodo; Longhurst, Hilary; Mahlaoui, Nizar; Milota, Tomas; Moreira, Fernando; Moshous, Despina; Mukhina, Anna; Neth, Olaf; Neven, Benedicte; Nieters, Alexandra; Olbrich, Peter; Ozen, Ahmet; Schmid, Jana Pachlopnik; Picard, Capucine; Prader, Seraina; Rae, William; Reichenbach, Janine; Rusch, Stephan; Savic, Sinisa; Scarselli, Alessia; Scheible, Raphael; Sediva, Anna; Sharapova, Svetlana O; Shcherbina, Anna; Slatter, Mary; Soler-Palacin, Pere; Stanislas, Aurelie; Suarez, Felipe; Tucci, Francesca; Uhlmann, Annette; van Montfrans, Joris; Warnatz, Klaus; Williams, Anthony Peter; Wood, Phil; Kracker, Sven; Condliffe, Alison Mary; Ehl, Stephan

2018-01-01

Activated phosphoinositide 3-kinase (PI3K) δ Syndrome (APDS), caused by autosomal dominant mutations in PIK3CD (APDS1) or PIK3R1 (APDS2), is a heterogeneous primary immunodeficiency. While initial cohort-descriptions summarized the spectrum of clinical and immunological manifestations, questions about long-term disease evolution and response to therapy remain. The prospective European Society for Immunodeficiencies (ESID)-APDS registry aims to characterize the disease course, identify outcome predictors, and evaluate treatment responses. So far, 77 patients have been recruited (51 APDS1, 26 APDS2). Analysis of disease evolution in the first 68 patients pinpoints the early occurrence of recurrent respiratory infections followed by chronic lymphoproliferation, gastrointestinal manifestations, and cytopenias. Although most manifestations occur by age 15, adult-onset and asymptomatic courses were documented. Bronchiectasis was observed in 24/40 APDS1 patients who received a CT-scan compared with 4/15 APDS2 patients. By age 20, half of the patients had received at least one immunosuppressant, but 2-3 lines of immunosuppressive therapy were not unusual before age 10. Response to rapamycin was rated by physician visual analog scale as good in 10, moderate in 9, and poor in 7. Lymphoproliferation showed the best response (8 complete, 11 partial, 6 no remission), while bowel inflammation (3 complete, 3 partial, 9 no remission) and cytopenia (3 complete, 2 partial, 9 no remission) responded less well. Hence, non-lymphoproliferative manifestations should be a key target for novel therapies. This report from the ESID-APDS registry provides comprehensive baseline documentation for a growing cohort that will be followed prospectively to establish prognostic factors and identify patients for treatment studies.

Acquired perforating dermatosis: a report of 8 cases.

PubMed

González-Lara, L; Gómez-Bernal, S; Vázquez-López, F; Vivanco-Allende, B

2014-01-01

Acquired perforating dermatosis (APD) is an uncommon disease characterized by lesions exhibiting transepidermal elimination of collagen or elastic fibers. APD affects adults and is associated with systemic diseases, mainly diabetes mellitus and renal failure. We present 8 cases of APD. Seven patients had concomitant diabetes mellitus with or without chronic renal failure, and 1 had alcoholic cirrhosis. In the patients with chronic renal failure, the onset of APD coincided with transient worsening of renal function. The mean increase in creatinine concentrations above baseline was 1.14mg/dL. Acute deterioration of renal function may be involved in APD. Further studies are needed to investigate this association. Copyright © 2013 Elsevier España, S.L. y AEDV. All rights reserved.

HgCdTe APD-based linear-mode photon counting components and ladar receivers

NASA Astrophysics Data System (ADS)

Jack, Michael; Wehner, Justin; Edwards, John; Chapman, George; Hall, Donald N. B.; Jacobson, Shane M.

2011-05-01

Linear mode photon counting (LMPC) provides significant advantages in comparison with Geiger Mode (GM) Photon Counting including absence of after-pulsing, nanosecond pulse to pulse temporal resolution and robust operation in the present of high density obscurants or variable reflectivity objects. For this reason Raytheon has developed and previously reported on unique linear mode photon counting components and modules based on combining advanced APDs and advanced high gain circuits. By using HgCdTe APDs we enable Poisson number preserving photon counting. A metric of photon counting technology is dark count rate and detection probability. In this paper we report on a performance breakthrough resulting from improvement in design, process and readout operation enabling >10x reduction in dark counts rate to ~10,000 cps and >104x reduction in surface dark current enabling long 10 ms integration times. Our analysis of key dark current contributors suggest that substantial further reduction in DCR to ~ 1/sec or less can be achieved by optimizing wavelength, operating voltage and temperature.

Putative cognitive enhancers in preclinical models related to schizophrenia: the search for an elusive target.

PubMed

Barak, Segev; Weiner, Ina

2011-08-01

Several developments have converged to drive what may be called "the cognitive revolution" in drug discovery in schizophrenia (SCZ), including the emphasis on cognitive deficits as a core disabling aspect of SCZ, the increasing consensus that cognitive deficits are not treated satisfactorily by the available antipsychotic drugs (APDs), and the failure of animal models to predict drug efficacy for cognitive deficits in clinical trials. Consequently, in recent years, a paradigm shift has been encouraged in animal modeling, triggered by the NIMH sponsored Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative, and intended to promote the development and use of behavioral measures in animals that can generate valid (clinically relevant) measures of cognition and thus promote the identification of cognition enhancers for SCZ. Here, we provide a non-exhaustive survey of the effects of putative cognition enhancers (PCEs) representing 10 pharmacological targets as well as antipsychotic drugs (APDs), on SCZ-mimetic drugs (NMDA antagonists, muscarinic antagonist scopolamine and dopaminergic agonist amphetamine), in several tasks considered to measure cognitive processes/domains that are disrupted in SCZ (the five choice serial reaction time task, sustain attention task, working and/or recognition memory (delayed (non)matching to sample, delayed alternation task, radial arm maze, novel object recognition), reversal learning, attentional set shifting, latent inhibition and spatial learning and memory). We conclude that most of the available models have no capacity to distinguish between PCEs and APDs and that there is a need to establish models based on tasks whose perturbations lead to performance impairments that are resistant to APDs, and/or to accept APDs as a "weak gold standard". Several directions derived from the surveyed data are suggested. Copyright © 2011 Elsevier Inc. All rights reserved.

Integrated three-dimensional optical MEMS for chip-based fluorescence detection

NASA Astrophysics Data System (ADS)

Hung, Kuo-Yung; Tseng, Fan-Gang; Khoo, Hwa-Seng

2009-04-01

This paper presents a novel fluorescence sensing chip for parallel protein microarray detection in the context of a 3-in-1 protein chip system. This portable microchip consists of a monolithic integration of CMOS-based avalanche photo diodes (APDs) combined with a polymer micro-lens, a set of three-dimensional (3D) inclined mirrors for separating adjacent light signals and a low-noise transformer-free dc-dc boost mini-circuit to power the APDs (ripple below 1.28 mV, 0-5 V input, 142 V and 12 mA output). We fabricated our APDs using the planar CMOS process so as to facilitate the post-CMOS integration of optical MEMS components such as the lenses. The APD arrays were arranged in unique circular patterns appropriate for detecting the specific fluorescently labelled protein spots in our study. The array-type APDs were designed so as to compensate for any alignment error as detected by a positional error signal algorithm. The condenser lens was used as a structure for light collection to enhance the fluorescent signals by about 25%. This element also helped to reduce the light loss due to surface absorption. We fabricated an inclined mirror to separate two adjacent fluorescent signals from different specimens. Excitation using evanescent waves helped reduce the interference of the excitation light source. This approach also reduced the number of required optical lenses and minimized the complexity of the structural design. We achieved detection floors for anti-rabbit IgG and Cy5 fluorescent dye as low as 0.5 ng/µl (~3.268 nM). We argue that the intrinsic nature of point-to-point and batch-detection methods as showcased in our chip offers advantages over the serial-scanning approach used in traditional scanner systems. In addition, our system is low cost and lightweight.

Expected radiation damage of reverse-type APDs for the Astro-H mission

NASA Astrophysics Data System (ADS)

Kataoka, J.; Saito, T.; Yoshino, M.; Mizoma, H.; Nakamori, T.; Yatsu, Y.; Ishikawa, Y.; Matsunaga, Y.; Tajima, H.; Kokubun, M.; Edwards, P. G.

2012-06-01

Scheduled for launch in 2014, Astro-H is the sixth Japanese X-ray astronomy satellite mission. More than 60 silicon avalanche photodiodes (Si-APDs; hereafter APDs) will be used to read out BGO scintillators, which are implemented to generate a veto signal to reduce background contamination for the hard X-ray imager (HXI) and a soft gamma-ray detector (SGD). To date, however, APDs have rarely been used in space experiments. Moreover, strict environmental tests are necessary to guarantee APD performance for missions expected to extend beyond five years. The radiation hardness of APDs, as for most semiconductors, is particularly crucial, since radiation in the space environment is severe. In this paper, we present the results of radiation tests conducted on reverse-type APDs (provided by Hamamatsu Photonics) irradiated by gamma rays (60Co) and 150 MeV protons. We show that, even under the same 100 Gy dose, high energy protons can cause displacement (bulk) damage in the depletion region and possibly change the activation energy, whereas gamma-ray irradiation is less prone to cause damage, because ionization damage dominates only the surface region. We also present quantitative guidance on how to estimate APD noise deterioration over a range of temperatures and radiation doses. As a practical example, we discuss the expected degradation of the BGO energy threshold for the generation of veto signals, following several years of Astro-H operation in Low Earth Orbit (LEO), and directly compare it to experimental results obtained using a small BGO crystal.

Spectral dependence of the main parameters of ITE silicon avalanche photodiodes

NASA Astrophysics Data System (ADS)

Wegrzecka, Iwona; Grynglas, Maria; Wegrzecki, Maciej

2001-08-01

New applications for avalanche photodiodes (APDs) as in systems using visible radiation, have prompted the need for the evaluation of detection properties of ITE APDs in the 400 divided by 700 nm spectral range. The paper presents the method and result of studies on the spectral dependence of the gain, dark and noise currents, sensitivity and excess noise factor of ITE APDs. The studies have shown that ITE APDs optimized for the near IR radiation can be effectively applied in the detection of radiation above the 500 nm wavelength.

Gain properties of doped GaAs/AlGaAs multiple quantum well avalanche photodiode structures

NASA Technical Reports Server (NTRS)

Menkara, H. M.; Wagner, B. K.; Summers, C. J.

1995-01-01

A comprehensive characterization has been made of the static and dynamical response of conventional and multiple quantum well (MQW) avalanche photodiodes (APDs). Comparison of the gain characteristics at low voltages between the MQW and conventional APDs show a direct experimental confirmation of a structure-induced carrier multiplication due to interband impact ionization. Similar studies of the bias dependence of the excess noise characteristics show that the low-voltage gain is primarily due to electron ionization in the MQW-APDS, and to both electron and hole ionization in the conventional APDS. For the doped MQW APDS, the average gain per stage was calculated by comparing gain data with carrier profile measurements, and was found to vary from 1.03 at low bias to 1.09 near avalanche breakdown.

Ventricular action potential adaptation to regular exercise: role of β-adrenergic and KATP channel function.

PubMed

Wang, Xinrui; Fitts, Robert H

2017-08-01

Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K + (K ATP ) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6-8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca 2+ transient durations reflected the changes in APD, while Ca 2+ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β 1 -AR blocker atenolol, but not the β 2 -AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β 1 -AR. At 10 Hz, the K ATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β 1 -AR responsiveness and K ATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca 2+ influx; during exercise, an increase in K ATP channel activity would shorten APD and, thus, protect the heart against Ca 2+ overload or inadequate filling. NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca 2+ transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the β-adrenergic receptor agonist dose-response curve rightward compared with controls by reducing β 1 -adrenergic receptor responsiveness and that, at the high activation rate, myocytes from trained animals showed higher K ATP channel function. Copyright © 2017 the American Physiological Society.

High-performance fused indium gallium arsenide/silicon photodiode

NASA Astrophysics Data System (ADS)

Kang, Yimin

Modern long haul, high bit rate fiber-optic communication systems demand photodetectors with high sensitivity. Avalanche photodiodes (APDs) exhibit superior sensitivity performance than other types of photodetectors by virtual of its internal gain mechanism. This dissertation work further advances the APD performance by applying a novel materials integration technique. It is the first successful demonstration of wafer fused InGaAs/Si APDs with low dark current and low noise. APDs generally adopt separate absorption and multiplication (SAM) structure, which allows independent optimization of materials properties in two distinct regions. While the absorption material needs to have high absorption coefficient in the target wavelength range to achieve high quantum efficiency, it is desirable for the multiplication material to have large discrepancy between its electron and hole ionization coefficients to reduce noise. According to these criteria, InGaAs and Si are the ideal materials combination. Wafer fusion is the enabling technique that makes this theoretical ideal an experimental possibility. APDs fabricated on the fused InGaAs/Si wafer with mesa structure exhibit low dark current and low noise. Special device fabrication techniques and high quality wafer fusion reduce dark current to nano ampere level at unity gain, comparable to state-of-the-art commercial III/V APDs. The small excess noise is attributed to the large difference in ionization coefficients between electrons and holes in silicon. Detailed layer structure designs are developed specifically for fused InGaAs/Si APDs based on principles similar to those used in traditional InGaAs/InP APDs. An accurate yet straightforward technique for device structural parameters extraction is also proposed. The extracted results from the fabricated APDs agree with device design parameters. This agreement also confirms that the fusion interface has negligible effect on electric field distributions for devices fabricated from high quality fusion materials. The feasibility of fused InGaAs/Si APD for analog systems is also explored. Preliminary two-tone measurement shows that a moderately high dynamic range of 70 dBc/Hz1/2 for broadband Spur Free Dynamic Range (SFDR) or 82 dBc/Hz2/3 suboctave SFDR, up to 50 muA of optical current, can be achieved. The theoretical analyses of SNR show that fused InGaAs/Si APD receivers can provide larger Signal-to-Noise Ratio (SNR) than their III/V counterparts.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Fan; Wang, Yuanqing, E-mail: yqwang@nju.edu.cn; Li, Fenfang

The avalanche-photodiode-array (APD-array) laser detection and ranging (LADAR) system has been continually developed owing to its superiority of nonscanning, large field of view, high sensitivity, and high precision. However, how to achieve higher-efficient detection and better integration of the LADAR system for real-time three-dimensional (3D) imaging continues to be a problem. In this study, a novel LADAR system using four linear mode APDs (LmAPDs) is developed for high-efficient detection by adopting a modulation and multiplexing technique. Furthermore, an automatic control system for the array LADAR system is proposed and designed by applying the virtual instrumentation technique. The control system aimsmore » to achieve four functions: synchronization of laser emission and rotating platform, multi-channel synchronous data acquisition, real-time Ethernet upper monitoring, and real-time signal processing and 3D visualization. The structure and principle of the complete system are described in the paper. The experimental results demonstrate that the LADAR system is capable of achieving real-time 3D imaging on an omnidirectional rotating platform under the control of the virtual instrumentation system. The automatic imaging LADAR system utilized only 4 LmAPDs to achieve 256-pixel-per-frame detection with by employing 64-bit demodulator. Moreover, the lateral resolution is ∼15 cm and range accuracy is ∼4 cm root-mean-square error at a distance of ∼40 m.« less

Studies of Avalanche Photodiodes (APDS) as Readout Devices for Scintillating Fibers for High Energy Gamma-Ray Astronomy Telescopes

NASA Technical Reports Server (NTRS)

Vasile, Stefan; Shera, Suzanne; Shamo, Denis

1998-01-01

New gamma ray and charged particle telescope designs based on scintillating fiber arrays could provide low cost, high resolution, lightweight, very large area and multi radiation length instrumentation for planned NASA space exploration. The scintillating fibers low visible light output requires readout sensors with single photon detection sensitivity and low noise. The sensitivity of silicon Avalanche Photodiodes (APDS) matches well the spectral output of the scintillating fibers. Moreover, APDs have demonstrated single photon capability. The global aim of our work is to make available to NASA a novel optical detector concept to be used as scintillating fiber readouts and meeting the requirements of the new generations of space-borne gamma ray telescopes. We proposed to evaluate the feasibility of using RMD's small area APDs ((mu)APD) as scintillating fiber readouts and to study possible alternative (mu)APD array configurations for space borne readout scintillating fiber systems, requiring several hundred thousand to one million channels. The evaluation has been conducted in accordance with the task description and technical specifications detailed in the NASA solicitation "Studies of Avalanche Photodiodes (APD as readout devices for scintillating fibers for High Energy Gamma-Ray Astronomy Telescopes" (#8-W-7-ES-13672NAIS) posted on October 23, 1997. The feasibility study we propose builds on recent developments of silicon APD arrays and light concentrators advances at RMD, Inc. and on more than 5 years of expertise in scintillating fiber detectors. In a previous program we carried out the initial research to develop a high resolution, small pixel, solid-state, silicon APD array which exhibited very high sensitivity in the UV-VIS spectrum. This (mu)APD array is operated in Geiger mode and results in high gain (greater than 10(exp 8)), extremely low noise, single photon detection capability, low quiescent power (less than 10 (mu)W/pixel for 30 micrometers sensitive area diameter) and output in the 1-5 volt range. If successful, this feasibility study will make possible the development of a scintillating fiber detector with unsurpassed sensitivity, extremely low power usage, a crucial factor of merit for space based sensors and telescopes.

A positron emission tomograph based on LSO-APD modules with a sampling ADC read-out system for a students' advanced laboratory course.

PubMed

Schneider, Florian R; Mann, Alexander B; Konorov, Igor; Delso, Gaspar; Paul, Stephan; Ziegler, Sibylle I

2012-06-01

A one-day laboratory course on positron emission tomography (PET) for the education of physics students and PhD students in medical physics has been set up. In the course, the physical background and the principles of a PET scanner are introduced. Course attendees set the system in operation, calibrate it using a (22)Na point source and reconstruct different source geometries filled with (18)F. The PET scanner features an individual channel read-out of 96 lutetium oxyorthosilicate (LSO) scintillator crystals coupled to avalanche photodiodes (APD). The analog data of each APD are digitized by fast sampling analog to digital converters (SADC) and processed within field programmable gate arrays (FPGA) to extract amplitudes and time stamps. All SADCs are continuously sampling with a precise rate of 80MHz, which is synchronous for the whole system. The data is transmitted via USB to a Linux PC, where further processing and the image reconstruction are performed. The course attendees get an insight into detector techniques, modern read-out electronics, data acquisition and PET image reconstruction. In addition, a short introduction to some common software applications used in particle and high energy physics is part of the course. Copyright © 2011. Published by Elsevier GmbH.

45 CFR 307.5 - Mandatory computerized support enforcement systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

.... Waiver requests must be submitted and approved as part of the State's APD or APD update. (c) Conditions... chapter; and either: (2) The waiver request meets the criteria set forth in section 1115(c) (1), (2) and... system configuration. APDs submitted by States which include requests for waiver for an alternative...

45 CFR 307.5 - Mandatory computerized support enforcement systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... Waiver requests must be submitted and approved as part of the State's APD or APD update. (c) Conditions... chapter; and either: (2) The waiver request meets the criteria set forth in section 1115(c) (1), (2) and... system configuration. APDs submitted by States which include requests for waiver for an alternative...

Application of dot-matrix illumination of liquid crystal phase space light modulator in 3D imaging of APD array

NASA Astrophysics Data System (ADS)

Wang, Shuai; Sun, Huayan; Guo, Huichao

2018-01-01

Aiming at the problem of beam scanning in low-resolution APD array in three-dimensional imaging, a method of beam scanning with liquid crystal phase-space optical modulator is proposed to realize high-resolution imaging by low-resolution APD array. First, a liquid crystal phase spatial light modulator is used to generate a beam array and then a beam array is scanned. Since the sub-beam divergence angle in the beam array is smaller than the field angle of a single pixel in the APD array, the APD's pixels respond only to the three-dimensional information of the beam illumination position. Through the scanning of the beam array, a single pixel is used to collect the target three-dimensional information multiple times, thereby improving the resolution of the APD detector. Finally, MATLAB is used to simulate the algorithm in this paper by using two-dimensional scalar diffraction theory, which realizes the splitting and scanning with a resolution of 5 x 5. The feasibility is verified theoretically.

Theoretical Studies on InGaAs/InAlAs SAGCM Avalanche Photodiodes

NASA Astrophysics Data System (ADS)

Cao, Siyu; Zhao, Yue; ur Rehman, Sajid; Feng, Shuai; Zuo, Yuhua; Li, Chuanbo; Zhang, Lichun; Cheng, Buwen; Wang, Qiming

2018-05-01

In this paper, we provide a detailed insight on InGaAs/InAlAs separate absorption, grading, charge, and multiplication avalanche photodiodes (SAGCM APDs) and a theoretical model of APDs is built. Through theoretical analysis and two-dimensional (2D) simulation, the influence of charge layer and tunneling effect on the APDs is fully understood. The design of charge layer (including doping level and thickness) can be calculated by our predictive model for different multiplication thickness. We find that as the thickness of charge layer increases, the suitable doping level range in charge layer decreases. Compared to thinner charge layer, performance of APD varies significantly via several percent deviations of doping concentrations in thicker charge layer. Moreover, the generation rate ( G btt ) of band-to-band tunnel is calculated, and the influence of tunneling effect on avalanche field was analyzed. We confirm that avalanche field and multiplication factor ( M n ) in multiplication will decrease by the tunneling effect. The theoretical model and analysis are based on InGaAs/InAlAs APD; however, they are applicable to other APD material systems as well.

Effect of action potential duration on Tpeak-Tend interval, T-wave area and T-wave amplitude as indices of dispersion of repolarization: Theoretical and simulation study in the rabbit heart.

PubMed

Arteyeva, Natalia V; Azarov, Jan E

The aim of the study was to differentiate the effect of dispersion of repolarization (DOR) and action potential duration (APD) on T-wave parameters being considered as indices of DOR, namely, Tpeak-Tend interval, T-wave amplitude and T-wave area. T-wave was simulated in a wide physiological range of DOR and APD using a realistic rabbit model based on experimental data. A simplified mathematical formulation of T-wave formation was conducted. Both the simulations and the mathematical formulation showed that Tpeak-Tend interval and T-wave area are linearly proportional to DOR irrespectively of APD range, while T-wave amplitude is non-linearly proportional to DOR and inversely proportional to the minimal repolarization time, or minimal APD value. Tpeak-Tend interval and T-wave area are the most accurate DOR indices independent of APD. T-wave amplitude can be considered as an index of DOR when the level of APD is taken into account. Copyright © 2017 Elsevier Inc. All rights reserved.

Gastrin producing G-cells after chronic ethanol and low protein nutrition.

PubMed

Koko, V; Todorović, V; Varagić, J; Micev, M; Korać, A; Bajcetić, M; Cakić-Milosević, M; Nedeljković, M; Drndarević, N

1998-11-01

Male Wistar rats, (2 months old), randomly divided according to the diet offered to four groups (C-control; A- alcoholized, PD-protein-deprived, A-PD- alcoholized protein-deprived). In group A and A-PD rats, the number of gastrin producing G-cells was significantly lower. The volume density of G-cells was significantly decreased in alcoholic rats. Fasting serum gastrin level (FSGL) significantly raised due to combined effect of alcohol consumption and protein malnutrition. In group A rats, the profile area of G-cells and their nuclei increased. In PD rats, the profile area of G cells also increased. There were no differences in nucleus/cell ratio due to alcohol ingestion alone, but it decreased significantly in PD and A-PD rats. Pale and lucent types of granules were predominantly seen in G-cells of animals of group A and A-PD. Mean diameter of granules increased in A, PD and A-PD rats. Other endocrine cells (ECL, D, EC) also decreased in number in A rats. Somatostatin producing D-cells decreased significantly in A-PD rats, both in fundic and pyloric mucosa.

Safety of long-term clozapine administration. Frequency of cardiomyopathy and hyponatraemia: two cross-sectional, naturalistic studies.

PubMed

Serrano, Ana; Rangel, Nairy; Carrizo, Edgardo; Uzcátegui, Euderruh; Sandia, Ignacio; Zabala, Angélica; Fernández, Erika; Tálamo, Eduardo; Servigna, Mercedes; Prieto, Dexi; Connell, Lisette; Baptista, Trino

2014-02-01

The antipsychotic drug (APD) clozapine (CLZ) is under-prescribed because of concerns about its safety. We evaluated in separate protocols the frequency of cardiomyopathy and hyponatraemia, which are adverse drug effects, where few comparative studies are available. Cross-sectional studies in subjects treated for at least 3 consecutive months with the same drug were conducted. Cardiomyopathy: Patients undergoing treatment either with CLZ (n = 125) or with other typical or atypical APDs (n = 59) were examined by a cardiologist who also recorded echocardiograms and electrocardiograms in order to diagnose cardiomyopathy. Hyponatraemia: Fasting sodium levels were assessed in patients receiving any of the following treatments: CLZ (n = 88), other atypical APDs (n = 61), typical APDs (n = 23), typical + atypical APDs (n = 11), and other drugs/drug-free (n = 36). Cardiomyopathy: No case of cardiomyopathy was detected. The frequency of abnormal ventricular ejection fraction (< 55%) was similar in both treatment groups (p = 1). Hyponatraemia: The frequency of hyponatraemia (percentage; 95% CI) was: CLZ (3.4%; -0.7, 7.1); other atypical APDs (4.9%; -0.5, 10.3); typical APDs (26.1%; 8.2, 44.0); typical + atypical APDs (9.1%; -7.8, 26.0); other drugs/drug-free (0%). None of the CLZ hyponatraemia subjects were on monotherapy. Our results are at odds with previous studies of CLZ-associated cardiomyopathy. However, they must be compared to further cross-sectional or prospective studies because most published data come from either case reports or pharmacovigilance systems. The frequency of hyponatraemia during CLZ administration was similar to that observed with other atypical APDs, and it was significantly lower than that recorded with typical agents. These results, along with numerous case reports on the effects of CLZ in patients with polydipsia and water intoxication, point to a safe or even positive profile of CLZ on electrolytic regulation.

30 CFR 250.418 - What additional information must I submit with my APD?

Code of Federal Regulations, 2012 CFR

2012-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Applying for A Permit to Drill § 250.418 What additional information must I submit with my APD? You must include the following with the APD: (a) Rated capacities of the drilling rig...

30 CFR 250.418 - What additional information must I submit with my APD?

Code of Federal Regulations, 2014 CFR

2014-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Applying for A Permit to Drill § 250.418 What additional information must I submit with my APD? You must include the following with the APD: (a) Rated capacities of the drilling rig...

30 CFR 250.418 - What additional information must I submit with my APD?

Code of Federal Regulations, 2013 CFR

2013-07-01

..., DEPARTMENT OF THE INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Applying for A Permit to Drill § 250.418 What additional information must I submit with my APD? You must include the following with the APD: (a) Rated capacities of the drilling rig...

30 CFR 250.418 - What additional information must I submit with my APD?

Code of Federal Regulations, 2010 CFR

2010-07-01

... INTERIOR OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Oil and Gas Drilling Operations Applying for A Permit to Drill § 250.418 What additional information must I submit with my APD? You must include the following with the APD: (a) Rated capacities of the drilling rig and major...

A Highly Sensitive Multi-Element HgCdTe E-APD Detector for IPDA Lidar Applications

NASA Technical Reports Server (NTRS)

Beck, Jeff; Welch, Terry; Mitra, Pradip; Reiff, Kirk; Sun, Xiaoli; Abshire, James

2014-01-01

An HgCdTe electron avalanche photodiode (e-APD) detector has been developed for lidar receivers, one application of which is integrated path differential absorption lidar measurements of such atmospheric trace gases as CO2 and CH4. The HgCdTe APD has a wide, visible to mid-wave-infrared, spectral response, high dynamic range, substantially improved sensitivity, and an expected improvement in operational lifetime. A demonstration sensor-chip assembly consisting of a 4.3 lm cutoff HgCdTe 4 9 4 APD detector array with 80 micrometer pitch pixels and a custom complementary metal-oxide-semiconductor readout integrated circuit was developed. For one typical array the APD gain was 654 at 12 V with corresponding gain normalized dark currents ranging from 1.2 fA to 3.2 fA. The 4 9 4 detector system was characterized at 77 K with a 1.55 micrometer wavelength, 1 microsecond wide, laser pulse. The measured unit gain detector photon conversion efficiency was 91.1%. At 11 V bias the mean measured APD gain at 77 K was 307.8 with sigma/mean uniformity of 1.23%. The average, noise-bandwidth normalized, system noise-equivalent power (NEP) was 1.04 fW/Hz(exp 1/2) with a sigma/mean of 3.8%. The measured, electronics-limited, bandwidth of 6.8 MHz was more than adequate for 1 microsecond pulse detection. The system had an NEP (3 MHz) of 0.4 fW/Hz(exp 1/2) at 12 V APD bias and a linear dynamic range close to 1000. A gain-independent quantum-limited SNR of 80% of full theoretical was indicative of a gain-independent excess noise factor very close to 1.0 and the expected APD mode quantum efficiency.

Monoacylglycerol lipase inhibitor JZL184 reduces neuroinflammatory response in APdE9 mice and in adult mouse glial cells.

PubMed

Pihlaja, Rea; Takkinen, Jatta; Eskola, Olli; Vasara, Jenni; López-Picón, Francisco R; Haaparanta-Solin, Merja; Rinne, Juha O

2015-04-28

Recently, the role of monoacylglycerol lipase (MAGL) as the principal regulator of simultaneous prostaglandin synthesis and endocannabinoid receptor activation in the CNS was demonstrated. To expand upon previously published research in the field, we observed the effect of the MAGL inhibitor JZL184 during the early-stage proinflammatory response and formation of beta-amyloid (Aβ) in the Alzheimer's disease mouse model APdE9. We also investigated its effects in proinflammatory agent - induced astrocytes and microglia isolated from adult mice. Transgenic APdE9 mice (5 months old) were treated with JZL184 (40 mg/kg) or vehicle every day for 1 month. In vivo binding of the neuroinflammation-related, microglia-specific translocator protein (TSPO) targeting radioligand [(18) F]GE-180 decreased slightly but statistically non-significantly in multiple brain areas compared to vehicle-treated mice. JZL184 treatment induced a significant decrease in expression levels of inflammation-induced, Iba1-immunoreactive microglia in the hippocampus (P < 0.01) and temporal and parietal (P < 0.05) cortices. JZL184 also induced a marked decrease in total Aβ burden in the temporal (P < 0.001) and parietal (P < 0.01) cortices and, to some extent, in the hippocampus. Adult microglial and astrocyte cultures pre-treated with JZL184 and then exposed to the neuroinflammation-inducing agents lipopolysaccharide (LPS), interferon-gamma (IFN-γ), and Aβ42 had significantly reduced proinflammatory responses compared to cells without JZL184 treatment. JZL184 decreased the proinflammatory reactions of microglia and reduced the total Aβ burden and its precursors in the APdE9 mouse model. It also reduced the proinflammatory responses of microglia and astrocytes isolated from adult mice.

Microstructural observations in rapidly-solidified and heat-treated Ni3Al-Cr alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carro, G.; Flanagan, W.F.

1992-08-01

The microstructural development following heat treatments of several rapidly-solidified Ni3Al-Cr and Ni3Al-Cr-B alloys is presented. Depending on composition, the as-solidified samples were either 100 percent gamma-prime phase - in the form of fine antiphase domains (APD) - or a mixture of gamma-prime (APDs) and beta phases. Upon annealing, the as-solidified microstructures transform to either APD-free gamma-prime or mixtures of gamma and gamma-prime phases. For those compositions where the quenched microstructures were 100 percent gamma-prime it was observed that APD coarsening followed conventional grain-growth kinetics, but when gamma phase precipitated on the APD boundaries the rate constant changed abruptly while themore » time exponent remained unaffected. It was also found that alloys containing critical amounts of chromium and boron are susceptible to precipitation of the boride Cr5B3. 14 refs.« less

Microstructural observations in rapidly-solidified and heat-treated Ni sub 3 Al-Cr alloys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carro, G.; Flanagan, W.F.

1992-01-01

In this paper , the microstructural development following heat treatments of several rapidly-solidified Ni{sub 3}Al-Cr and Ni{sub 3}Al-Cr-B alloys is presented. Depending on composition, the as-solidified samples were either 100% {gamma} phase-in the form of fine anti-phase domains (APD)-or a mixture of {gamma} (APDs) and {beta} phases. Upon annealing, the as-solidified microstructures transform to either APD-free {gamma}or mixtures of {gamma}and {gamma}{prime} phases. For those compositions where the quenched microstructures were 100{gamma}{prime} it was observed that APD coarsening followed conventional grain-growth kinetics, but when {gamma} phase precipitated on the APD boundaries the rate constant changed abruptly while the time exponent remainedmore » unaffected. It was also found that alloys containing critical amounts of chromium and boron are susceptible to precipitation of the boride Cr{sub 5}B{sub 3}.« less

Microstructural observations in rapidly-solidified and heat-treated Ni3Al-Cr alloys

NASA Technical Reports Server (NTRS)

Carro, G.; Flanagan, W. F.

1992-01-01

The microstructural development following heat treatments of several rapidly-solidified Ni3Al-Cr and Ni3Al-Cr-B alloys is presented. Depending on composition, the as-solidified samples were either 100 percent gamma-prime phase - in the form of fine antiphase domains (APD) - or a mixture of gamma-prime (APDs) and beta phases. Upon annealing, the as-solidified microstructures transform to either APD-free gamma-prime or mixtures of gamma and gamma-prime phases. For those compositions where the quenched microstructures were 100 percent gamma-prime it was observed that APD coarsening followed conventional grain-growth kinetics, but when gamma phase precipitated on the APD boundaries the rate constant changed abruptly while the time exponent remained unaffected. It was also found that alloys containing critical amounts of chromium and boron are susceptible to precipitation of the boride Cr5B3.

Effect of electron irradiation dose on the performance of avalanche photodiode electron detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kawauchi, Taizo; Wilde, Markus; Fukutani, Katsuyuki

2009-01-01

Avalanche photodiodes (APDs) are efficient detectors for electrons with energies below 100 keV. The damaging effects of 8 keV electron beam irradiation on the dark current and the output signal of the APD detector were investigated in this study. The APD dark current increases after electron doses exceeding 1.4x10{sup 13} cm{sup -2}. Preirradiation by high doses of 8 keV electrons further causes a deformation of the pulse height distribution of the APD output in the subsequent detection of low-flux electrons. This effect is particularly prominent when the energy of the detected electrons is lower than that of the damaging electrons.more » By comparing the experimental data with results of a simulation based on an electron trapping model, we conclude that the degradation of the APD performance is attributable to an enhancement of secondary-electron trapping at irradiation induced defects.« less

42 CFR 433.112 - FFP for design, development, installation or enhancement of mechanized claims processing and...

Code of Federal Regulations, 2014 CFR

2014-10-01

... enhancement of mechanized claims processing and information retrieval systems. 433.112 Section 433.112 Public... processing and information retrieval systems. (a) Subject to paragraph (c) of this section, FFP is available... enhancement of a mechanized claims processing and information retrieval system only if the APD is approved by...

42 CFR 433.112 - FFP for design, development, installation or enhancement of mechanized claims processing and...

Code of Federal Regulations, 2012 CFR

2012-10-01

... enhancement of mechanized claims processing and information retrieval systems. 433.112 Section 433.112 Public... processing and information retrieval systems. (a) Subject to paragraph (c) of this section, FFP is available... enhancement of a mechanized claims processing and information retrieval system only if the APD is approved by...

42 CFR 433.112 - FFP for design, development, installation or enhancement of mechanized claims processing and...

Code of Federal Regulations, 2011 CFR

2011-10-01

... enhancement of mechanized claims processing and information retrieval systems. 433.112 Section 433.112 Public... processing and information retrieval systems. (a) Subject to paragraph (c) of this section, FFP is available... enhancement of a mechanized claims processing and information retrieval system only if the APD is approved by...

42 CFR 433.112 - FFP for design, development, installation or enhancement of mechanized claims processing and...

Code of Federal Regulations, 2013 CFR

2013-10-01

... enhancement of mechanized claims processing and information retrieval systems. 433.112 Section 433.112 Public... processing and information retrieval systems. (a) Subject to paragraph (c) of this section, FFP is available... enhancement of a mechanized claims processing and information retrieval system only if the APD is approved by...

Research on APD-based non-line-of-sight UV communication system

NASA Astrophysics Data System (ADS)

Wang, Rongyang; Wang, Ling; Li, Chao; Zhang, Wenjing; Yuan, Yonggang; Xu, Jintong; Zhang, Yan; Li, Xiangyang

2010-10-01

In this paper, specific issues in designing an avalanche photodiode (APD)-based non-line-of-sight (NLOS) ultraviolet (UV) communication system are investigated. A proper wavelength of the UV LEDs and a system configuration should be considered carefully to assure the feasibility of this system. Using the single scattering model, the received optical power at the sensitive area of the APD can be calculated. According to the calculation, it revealed that the scattered ultraviolet signal level was very low; therefore, a post signal processing circuit was necessary. The authors put forward the key components of the circuit based on the compromise between signal bandwidth and gain. The performance of this circuit was evaluated by means of software simulation, and continued work was involved to improve its signal noise ratio (SNR). The transmitter used in this system was 365 nm UV LED array. Strictly speaking, this was not the practical outdoor UV communication system. Since the scattering coefficient of 365 nm UV only drops a little compared with solar blind UV, the research-grade UV communication could be carried out in a darkroom without a great influence. By combining an APD with a compound parabolic concentrator (CPC) optical system, the effective collection area and field of view (FOV) of the detector could be adjusted. Several issues were also raised to improve the performance of UV communication system, including using more powerful UV LEDs and choosing suitable modulation schemes.

Performance of normal adults and children on central auditory diagnostic tests and their corresponding visual analogs.

PubMed

Bellis, Teri James; Ross, Jody

2011-09-01

It has been suggested that, in order to validate a diagnosis of (C)APD (central auditory processing disorder), testing using direct cross-modal analogs should be performed to demonstrate that deficits exist solely or primarily in the auditory modality (McFarland and Cacace, 1995; Cacace and McFarland, 2005). This modality-specific viewpoint is controversial and not universally accepted (American Speech-Language-Hearing Association [ASHA], 2005; Musiek et al, 2005). Further, no such analogs have been developed to date, and neither the feasibility of such testing in normally functioning individuals nor the concurrent validity of cross-modal analogs has been established. The purpose of this study was to investigate the feasibility of cross-modal testing by examining the performance of normal adults and children on four tests of central auditory function and their corresponding visual analogs. In addition, this study investigated the degree to which concurrent validity of auditory and visual versions of these tests could be demonstrated. An experimental repeated measures design was employed. Participants consisted of two groups (adults, n=10; children, n=10) with normal and symmetrical hearing sensitivity, normal or corrected-to-normal visual acuity, and no family or personal history of auditory/otologic, language, learning, neurologic, or related disorders. Visual analogs of four tests in common clinical use for the diagnosis of (C)APD were developed (Dichotic Digits [Musiek, 1983]; Frequency Patterns [Pinheiro and Ptacek, 1971]; Duration Patterns [Pinheiro and Musiek, 1985]; and the Random Gap Detection Test [RGDT; Keith, 2000]). Participants underwent two 1 hr test sessions separated by at least 1 wk. Order of sessions (auditory, visual) and tests within each session were counterbalanced across participants. ANOVAs (analyses of variance) were used to examine effects of group, modality, and laterality (for the Dichotic/Dichoptic Digits tests) or response condition (for the auditory and visual Frequency Patterns and Duration Patterns tests). Pearson product-moment correlations were used to investigate relationships between auditory and visual performance. Adults performed significantly better than children on the Dichotic/Dichoptic Digits tests. Results also revealed a significant effect of modality, with auditory better than visual, and a significant modality×laterality interaction, with a right-ear advantage seen for the auditory task and a left-visual-field advantage seen for the visual task. For the Frequency Patterns test and its visual analog, results revealed a significant modality×response condition interaction, with humming better than labeling for the auditory version but the reversed effect for the visual version. For Duration Patterns testing, visual performance was significantly poorer than auditory performance. Due to poor test-retest reliability and ceiling effects for the auditory and visual gap-detection tasks, analyses could not be performed. No cross-modal correlations were observed for any test. Results demonstrated that cross-modal testing is at least feasible using easily accessible computer hardware and software. The lack of any cross-modal correlations suggests independent processing mechanisms for auditory and visual versions of each task. Examination of performance in individuals with central auditory and pan-sensory disorders is needed to determine the utility of cross-modal analogs in the differential diagnosis of (C)APD. American Academy of Audiology.

The Association between Peritoneal Dialysis Modality and Peritonitis

PubMed Central

Johnson, David W.; McDonald, Stephen P.; Boudville, Neil; Borlace, Monique; Badve, Sunil V.; Sud, Kamal; Clayton, Philip A.

2014-01-01

Background and objectives There is conflicting evidence comparing peritonitis rates among patients treated with continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD). This study aims to clarify the relationship between peritoneal dialysis (PD) modality (APD versus CAPD) and the risk of developing PD-associated peritonitis. Design, setting, participants, & measurements This study examined the association between PD modality (APD versus CAPD) and the risks, microbiology, and clinical outcomes of PD-associated peritonitis in 6959 incident Australian PD patients between October 1, 2003, and December 31, 2011, using data from the Australia and New Zealand Dialysis and Transplant Registry. Median follow-up time was 1.9 years. Results Patients receiving APD were younger (60 versus 64 years) and had fewer comorbidities. There was no association between PD modality and time to first peritonitis episode (adjusted hazard ratio [HR] for APD versus CAPD, 0.98; 95% confidence interval [95% CI], 0.91 to 1.07; P=0.71). However, there was a lower hazard of developing Gram-positive peritonitis with APD than CAPD, which reached borderline significance (HR, 0.90; 95% CI, 0.80 to 1.00; P=0.05). No statistically significant difference was found in the risk of hospitalizations (odds ratio, 1.12; 95% CI, 0.93 to 1.35; P=0.22), but there was a nonsignificant higher likelihood of 30-day mortality (odds ratio, 1.33; 95% CI, 0.93 to 1.88; P=0.11) at the time of the first episode of peritonitis for patients receiving APD. For all peritonitis episodes (including subsequent episodes of peritonitis), APD was associated with lower rates of culture-negative peritonitis (incidence rate ratio [IRR], 0.81; 95% CI, 0.69 to 0.94; P=0.002) and higher rates of gram-negative peritonitis (IRR, 1.28; 95% CI, 1.13 to 1.46; P=0.01). Conclusions PD modality was not associated with a higher likelihood of developing peritonitis. However, APD was associated with a borderline reduction in the likelihood of a first episode of Gram-positive peritonitis compared with CAPD, and with lower rates of culture-negative peritonitis and higher rates of Gram-negative peritonitis. Peritonitis outcomes were comparable between both modalities. PMID:24626434

Photodiode Preamplifier for Laser Ranging With Weak Signals

NASA Technical Reports Server (NTRS)

Abramovici, Alexander; Chapsky, Jacob

2007-01-01

An improved preamplifier circuit has been designed for processing the output of an avalanche photodiode (APD) that is used in a high-resolution laser ranging system to detect laser pulses returning from a target. The improved circuit stands in contrast to prior such circuits in which the APD output current pulses are made to pass, variously, through wide-band or narrow-band load networks before preamplification. A major disadvantage of the prior wide-band load networks is that they are highly susceptible to noise, which degrades timing resolution. A major disadvantage of the prior narrow-band load networks is that they make it difficult to sample the amplitudes of the narrow laser pulses ordinarily used in ranging. In the improved circuit, a load resistor is connected to the APD output and its value is chosen so that the time constant defined by this resistance and the APD capacitance is large, relative to the duration of a laser pulse. The APD capacitance becomes initially charged by the pulse of current generated by a return laser pulse, so that the rise time of the load-network output is comparable to the duration of the return pulse. Thus, the load-network output is characterized by a fast-rising leading edge, which is necessary for accurate pulse timing. On the other hand, the resistance-capacitance combination constitutes a lowpass filter, which helps to suppress noise. The long time constant causes the load network output pulse to have a long shallow-sloping trailing edge, which makes it easy to sample the amplitude of the return pulse. The output of the load network is fed to a low-noise, wide-band amplifier. The amplifier must be a wide-band one in order to preserve the sharp pulse rise for timing. The suppression of noise and the use of a low-noise amplifier enable the ranging system to detect relatively weak return pulses.

APD125, a Selective Serotonin 5-HT2A Receptor Inverse Agonist, Significantly Improves Sleep Maintenance in Primary Insomnia

PubMed Central

Rosenberg, Russell; Seiden, David J.; Hull, Steven G.; Erman, Milton; Schwartz, Howard; Anderson, Christen; Prosser, Warren; Shanahan, William; Sanchez, Matilde; Chuang, Emil; Roth, Thomas

2008-01-01

Introduction: Insomnia is a condition affecting 10% to 15% of the adult population and is characterized by difficulty falling asleep, difficulty staying asleep, or nonrestorative sleep, accompanied by daytime impairment or distress. This study evaluates APD125, a selective inverse agonist of the 5-HT2A receptor, for treatment of chronic insomnia, with particular emphasis on sleep maintenance. In phase 1 studies, APD125 improved sleep maintenance and was well tolerated. Methodology: Adult subjects (n = 173) with DSM-IV defined primary insomnia were randomized into a multicenter, double-blind, placebo-controlled, 3-way crossover study to compare 2 doses of APD125 (10 mg and 40 mg) with placebo. Each treatment period was 7 days with a 7- to 9-day washout period between treatments. Polysomnographic recordings were performed at the initial 2 screening nights and at nights (N) 1/2 and N 6/7 of each treatment period. Results: APD125 was associated with significant improvements in key sleep maintenance parameters measured by PSG. Wake time after sleep onset decreased (SEM) by 52.5 (3.2) min (10 mg) and 53.5 (3.5) min (40 mg) from baseline to N 1/2 vs. 37.8 (3.4) min for placebo, (P < 0.0001 for both doses vs placebo), and by 51.7 (3.4) min (P = 0.01) and 48.0 (3.6) min (P = 0.2) at N 6/7 vs. 44.0 (3.8) min for placebo. Significant APD125 effects on wake time during sleep were also seen (P < 0.0001 N 1/2, P < 0.001 N 6/7). The number of arousals and number of awakenings decreased significantly with APD125 treatment compared to placebo. Slow wave sleep showed a statistically significant dose-dependent increase. There was no significant decrease in latency to persistent sleep. No serious adverse events were reported, and no meaningful differences in adverse event profiles were observed between either dose of APD125 and placebo. APD125 was not associated with next-day psychomotor impairment as measured by Digit Span, Digit Symbol Copy, and Digit Symbol Coding Tests. Conclusions: APD125 produced statistically significant improvements in objective parameters of sleep maintenance and sleep consolidation and was well tolerated in adults with primary chronic insomnia. Citation: Rosenberg R; Seiden DJ; Hull SG; Erman M; Schwartz H; Anderson C; Prosser W; Shanahan W; Sanchez M; Chuang E; Roth T. APD125, a selective serotonin 5-HT2A receptor inverse agonist, significantly improves sleep maintenance in primary insomnia. SLEEP 2008;31(12):1663–1671. PMID:19090322

Response of CMS avalanche photo-diodes to low energy neutrons

NASA Astrophysics Data System (ADS)

Brown, R. M.; Deiters, K.; Ingram, Q.; Renker, D.

2012-12-01

The response of the Avalanche Photo-diodes (APDs) installed in the CMS detector at the LHC to neutrons from 241AmBe and 252Cf sources is reported. Signals in size equivalent to those of up to 106 photo-electrons with the nominal APD gain are observed. Measurements with an APD with the protective epoxy coating removed and with the source placed behind the APD show that there is an important response due to recoil protons from neutron interactions with the hydrogen in the epoxy, in addition to signals from neutron interactions with the silicon of the diode. The effective gain of these signals is much smaller than the diode's nominal gain.

42 CFR 433.112 - FFP for design, development, installation or enhancement of mechanized claims processing and...

Code of Federal Regulations, 2010 CFR

2010-10-01

... enhancement of mechanized claims processing and information retrieval systems. 433.112 Section 433.112 Public... processing and information retrieval systems. (a) FFP is available at the 90 percent rate in State... information retrieval system only if the APD is approved by CMS prior to the State's expenditure of funds for...

Propagation of Electrical Excitation in a Ring of Cardiac Cells: A Computer Simulation Study

NASA Technical Reports Server (NTRS)

Kogan, B. Y.; Karplus, W. J.; Karpoukhin, M. G.; Roizen, I. M.; Chudin, E.; Qu, Z.

1996-01-01

The propagation of electrical excitation in a ring of cells described by the Noble, Beeler-Reuter (BR), Luo-Rudy I (LR I), and third-order simplified (TOS) mathematical models is studied using computer simulation. For each of the models it is shown that after transition from steady-state circulation to quasi-periodicity achieved by shortening the ring length (RL), the action potential duration (APD) restitution curve becomes a double-valued function and is located below the original ( that of an isolated cell) APD restitution curve. The distributions of APD and diastolic interval (DI) along a ring for the entire range of RL corresponding to quasi-periodic oscillations remain periodic with the period slightly different from two RLs. The 'S' shape of the original APD restitution curve determines the appearance of the second steady-state circulation region for short RLs. For all the models and the wide variety of their original APD restitution curves, no transition from quasi-periodicity to chaos was observed.

Investigation of Avalanche Photodiodes and Multipixel Photon Counters as Light Detectors for Cosmic Rays

NASA Astrophysics Data System (ADS)

Vasquez, Jaime; Saavedra, Arthur; Ramos, Roxana; Tavares, Pablo; Wade, Marcus; Fan, Sewan; Haag, Brooke

2013-04-01

Through the Research Scholars Institute, students of Hartnell Community College experimented with the application of avalanche photodiodes (APDs) as cosmic ray detectors during the summer of 2012. An APD detector was coupled with a 10 meter long wavelength shifting fiber (WSF) wrapped around a cylindrical plastic scintillator to maximize signal detection. A photomultiplier tube (PMT) was used in conjunction to detect the same scintillation light caused by incoming cosmic rays. Two APD detectors were evaluated to confirm the viability of the setup. In addition, a similar setup was recently utilized to implement multi-pixel photon counters (MPPCs) as readout detectors. Under this configuration, a high gain preamplifier was used to amplify the signals for both the MPPC and APD detectors. We report on our results characterizing the MPPC and discuss its overall performance. Compared to the APD, our findings suggest that the MPPC detector has greater sensitivity in detecting weak light signals, and can be used in place of the PMT for certain counting applications.

Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

PubMed

Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

2017-10-01

Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

APDS: Autonomous Pathogen Detection System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Langlois, R G; Brown, S; Burris, L

An early warning system to counter bioterrorism, the Autonomous Pathogen Detection System (APDS) continuously monitors the environment for the presence of biological pathogens (e.g., anthrax) and once detected, it sounds an alarm much like a smoke detector warns of a fire. Long before September 11, 2001, this system was being developed to protect domestic venues and events including performing arts centers, mass transit systems, major sporting and entertainment events, and other high profile situations in which the public is at risk of becoming a target of bioterrorist attacks. Customizing off-the-shelf components and developing new components, a multidisciplinary team developed APDS,more » a stand-alone system for rapid, continuous monitoring of multiple airborne biological threat agents in the environment. The completely automated APDS samples the air, prepares fluid samples in-line, and performs two orthogonal tests: immunoassay and nucleic acid detection. When compared to competing technologies, APDS is unprecedented in terms of flexibility and system performance.« less

Patient-reported speech in noise difficulties and hyperacusis symptoms and correlation with test results.

PubMed

Spyridakou, Chrysa; Luxon, Linda M; Bamiou, Doris E

2012-07-01

To compare self-reported symptoms of difficulty hearing speech in noise and hyperacusis in adults with auditory processing disorders (APDs) and normal controls; and to compare self-reported symptoms to objective test results (speech in babble test, transient evoked otoacoustic emission [TEOAE] suppression test using contralateral noise). A prospective case-control pilot study. Twenty-two participants were recruited in the study: 10 patients with reported hearing difficulty, normal audiometry, and a clinical diagnosis of APD; and 12 normal age-matched controls with no reported hearing difficulty. All participants completed the validated Amsterdam Inventory for Auditory Disability questionnaire, a hyperacusis questionnaire, a speech in babble test, and a TEOAE suppression test using contralateral noise. Patients had significantly worse scores than controls in all domains of the Amsterdam Inventory questionnaire (with the exception of sound detection) and the hyperacusis questionnaire (P < .005). Patients also had worse TEOAE suppression test results in both ears than controls; however, this result was not significant after Bonferroni correction. Strong correlations were observed between self-reported symptoms of difficulty hearing speech in noise and speech in babble test results in the right ear (ρ = 0.624, P = .002), and between self-reported symptoms of hyperacusis and TEOAE suppression test results in the right ear (ρ = -0.597 P = .003). There was no significant correlation between the two tests. A strong correlation was observed between right ear speech in babble and patient-reported intelligibility of speech in noise, and right ear TEOAE suppression by contralateral noise and hyperacusis questionnaire. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

Heart rate variability alters cardiac repolarization and electromechanical dynamics.

PubMed

Phadumdeo, Vrishti M; Weinberg, Seth H

2018-04-07

Heart rate continuously varies due to autonomic regulation, stochasticity in pacemaking, and circadian rhythm, collectively termed heart rate variability (HRV), during normal physiological conditions. Low HRV is clinically associated with an elevated risk of cardiac arrhythmias. Alternans, a beat-to-beat alternation in action potential duration (APD) and/or intracellular calcium (Ca) transient, is a well-known risk factor associated with cardiac arrhythmias that is typically studied under conditions of a constant pacing rate, i.e., the absence of HRV. In this study, we investigate the effects of HRV on the interplay between APD, Ca, and electromechanical properties, employing a nonlinear discrete-time map model that governs APD and intracellular Ca cycling with a stochastic pacing period. We find that HRV can decrease variation in APD and peak Ca at fast pacing rates for which alternans is present. Further, increased HRV typically disrupts the alternating pattern for both APD and peak Ca and weakens the correlation between APD and peak Ca, thus decoupling Ca-mediated instabilities from repolarization alternation. We find that the efficacy of these effects is regulated by the sarcoplasmic reticulum Ca uptake rate. Overall, these results demonstrate that HRV disrupts arrhythmogenic alternans and suggests that HRV may be a significant factor in preventing life-threatening arrhythmias. Copyright © 2018 Elsevier Ltd. All rights reserved.

NASA Program Office Technology Investments to Enable Future Missions

NASA Astrophysics Data System (ADS)

Thronson, Harley; Pham, Thai; Ganel, Opher

2018-01-01

The Cosmic Origins (COR) and Physics of the Cosmos (PCOS) Program Offices (POs) reside at NASA GSFC and implement priorities for the NASA HQ Astrophysics Division (APD). One major aspect of the POs’ activities is managing our Strategic Astrophysics Technology (SAT) program to mature technologies for future strategic missions. The Programs follow APD guidance on which missions are strategic, currently informed by the NRC’s 2010 Decadal Survey report, as well as APD’s Implementation Plan and the Astrophysics Roadmap.In preparation for the upcoming 2020 Decadal Survey, the APD has established Science and Technology Definition Teams (STDTs) to study four large-mission concepts: the Origins Space Telescope (née, Far-IR Surveyor), Habitable Exoplanet Imaging Mission, Large UV/Optical/IR Surveyor, and Lynx (née, X-ray Surveyor). The STDTs will develop the science case and design reference mission, assess technology development needs, and estimate the cost of their concept. A fifth team, the L3 Study Team (L3ST), was charged to study potential US contributions to ESA’s planned Laser Interferometer Space Antenna (LISA) gravitational-wave observatory.The POs use a rigorous and transparent process to solicit technology gaps from the scientific and technical communities, and prioritize those entries based on strategic alignment, expected impact, cross-cutting applicability, and urgency. For the past two years, the technology-gap assessments of the four STDTs and the L3ST are included in our process. Until a study team submits its final report, community-proposed changes to gaps submitted or adopted by a study team are forwarded to that study team for consideration.We discuss our technology development process, with strategic prioritization informing calls for SAT proposals and informing investment decisions. We also present results of the 2017 technology gap prioritization and showcase our current portfolio of technology development projects. To date, 96 COR and 86 PCOS SAT proposals have been received, of which 22 COR and 28 PCOS projects were awarded. For more information, see the Program Annual Technology Reports available through the PO Technology web page at https://apd440.gsfc.nasa.gov/technology.html .

Comparative analysis of high-performance infrared avalanche InxGa1-xAsyP1-y and Hg1-xCdxTe heterophotodiodes

NASA Astrophysics Data System (ADS)

Kholodnov, Viacheslav; Drugova, Albina; Nikitin, Mikhail; Chekanova, Galina

2012-10-01

Technology of infrared (IR) avalanche photodiodes (APDs) gradually moves from simple single element APD to 2D focal plane arrays (FPA). Spectral covering of APDs is expanded continuously from classic 1.3 μm to longer wavelengths due to using of narrow-gap semiconductor materials like Hg1-xCdxTe. APDs are of great interest to developers and manufacturers of different optical communication, measuring and 3D reconstruction thermal imaging systems. Major IR detector materials for manufacturing of high-performance APDs became heteroepitaxial structures InxGa1-xAsyP1-y and Hg1-xCdxTe. Progress in IR APD technology was achieved through serious improvement in material growing techniques enabling forming of multilayer heterostuctures with separate absorption and multiplication regions (SAM). Today SAM-APD design can be implemented both on InxGa1-xAsyP1-y and Hg1-xCdxTe multilayer heteroepitaxial structures. To create the best performance optimal design avalanche heterophotodiode (AHPD) it is necessary to carry out a detailed theoretical analysis of basic features of generation, avalanche breakdown and multiplication of charge carriers in proper heterostructure. Optimization of AHPD properties requires comprehensive estimation of AHPD's pixel performance depending on pixel's multi-layer structure design, layers doping, distribution of electric field in the structure and operating temperature. Objective of the present article is to compare some features of 1.55 μm SAM-AHPDs based on InxGa1-xAsyP1-y and Hg1-xCdxTe.

Impaired Na⁺-dependent regulation of acetylcholine-activated inward-rectifier K⁺ current modulates action potential rate dependence in patients with chronic atrial fibrillation.

PubMed

Voigt, Niels; Heijman, Jordi; Trausch, Anne; Mintert-Jancke, Elisa; Pott, Lutz; Ravens, Ursula; Dobrev, Dobromir

2013-08-01

Shortened action-potential duration (APD) and blunted APD rate adaptation are hallmarks of chronic atrial fibrillation (cAF). Basal and muscarinic (M)-receptor-activated inward-rectifier K(+) currents (IK1 and IK,ACh, respectively) contribute to regulation of human atrial APD and are subject to cAF-dependent remodeling. Intracellular Na(+) ([Na(+)]i) enhances IK,ACh in experimental models but the effect of [Na(+)]i-dependent regulation of inward-rectifier K(+) currents on APD in human atrial myocytes is currently unknown. Here, we report a [Na(+)]i-dependent inhibition of outward IK1 in atrial myocytes from sinus rhythm (SR) or cAF patients. In contrast, IK,ACh activated by carbachol, a non-selective M-receptor agonist, increased with elevation of [Na(+)]i in SR. This [Na(+)]i-dependent IK,ACh regulation was absent in cAF. Including [Na(+)]i dependence of IK1 and IK,ACh in a recent computational model of the human atrial myocyte revealed that [Na(+)]i accumulation at fast rates inhibits IK1 and blunts physiological APD rate dependence in both groups. [Na(+)]i-dependent IK,ACh augmentation at fast rates increased APD rate dependence in SR, but not in cAF. These results identify impaired Na(+)-sensitivity of IK,ACh as one potential mechanism contributing to the blunted APD rate dependence in patients with cAF. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes". Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Correlation between human ether‐a‐go‐go‐related gene channel inhibition and action potential prolongation

PubMed Central

Saxena, P; Hortigon‐Vinagre, M P; Beyl, S; Baburin, I; Andranovits, S; Iqbal, S M; Costa, A; IJzerman, A P; Kügler, P; Timin, E

2017-01-01

Background and Purpose Human ether‐a‐go‐go‐related gene (hERG; Kv11.1) channel inhibition is a widely accepted predictor of cardiac arrhythmia. hERG channel inhibition alone is often insufficient to predict pro‐arrhythmic drug effects. This study used a library of dofetilide derivatives to investigate the relationship between standard measures of hERG current block in an expression system and changes in action potential duration (APD) in human‐induced pluripotent stem cell‐derived cardiomyocytes (hiPSC‐CMs). The interference from accompanying block of Cav1.2 and Nav1.5 channels was investigated along with an in silico AP model. Experimental Approach Drug‐induced changes in APD were assessed in hiPSC‐CMs using voltage‐sensitive dyes. The IC50 values for dofetilide and 13 derivatives on hERG current were estimated in an HEK293 expression system. The relative potency of each drug on APD was estimated by calculating the dose (D150) required to prolong the APD at 90% (APD90) repolarization by 50%. Key Results The D150 in hiPSC‐CMs was linearly correlated with IC50 of hERG current. In silico simulations supported this finding. Three derivatives inhibited hERG without prolonging APD, and these compounds also inhibited Cav1.2 and/or Nav1.5 in a channel state‐dependent manner. Adding Cav1.2 and Nav1.2 block to the in silico model recapitulated the direction but not the extent of the APD change. Conclusions and Implications Potency of hERG current inhibition correlates linearly with an index of APD in hiPSC‐CMs. The compounds that do not correlate have additional effects including concomitant block of Cav1.2 and/or Nav1.5 channels. In silico simulations of hiPSC‐CMs APs confirm the principle of the multiple ion channel effects. PMID:28681507

Spatial gradients in action potential duration created by regional magnetofection of hERG are a substrate for wavebreak and turbulent propagation in cardiomyocyte monolayers.

PubMed

Campbell, Katherine; Calvo, Conrado J; Mironov, Sergey; Herron, Todd; Berenfeld, Omer; Jalife, José

2012-12-15

Spatial dispersion of action potential duration (APD) is a substrate for the maintenance of cardiac fibrillation, but the mechanisms are poorly understood. We investigated the role played by spatial APD dispersion in fibrillatory dynamics. We used an in vitro model in which spatial gradients in the expression of ether-à-go-go-related (hERG) protein, and thus rapid delayed rectifying K(+) current (I(Kr)) density, served to generate APD dispersion, high-frequency rotor formation, wavebreak and fibrillatory conduction. A unique adenovirus-mediated magnetofection technique generated well-controlled gradients in hERG and green fluorescent protein (GFP) expression in neonatal rat ventricular myocyte monolayers. Computer simulations using a realistic neonatal rat ventricular myocyte monolayer model provided crucial insight into the underlying mechanisms. Regional hERG overexpression shortened APD and increased rotor incidence in the hERG overexpressing region. An APD profile at 75 percent repolarization with a 16.6 ± 0.72 ms gradient followed the spatial profile of hERG-GFP expression; conduction velocity was not altered. Rotors in the infected region whose maximal dominant frequency was 12.9 Hz resulted in wavebreak at the interface (border zone) between infected and non-infected regions; dominant frequency distribution was uniform when the maximal dominant frequency was <12.9 Hz or the rotors resided in the uninfected region. Regularity at the border zone was lowest when rotors resided in the infected region. In simulations, a fivefold regional increase in I(Kr) abbreviated the APD and hyperpolarized the resting potential. However, the steep APD gradient at the border zone proved to be the primary mechanism of wavebreak and fibrillatory conduction. This study provides insight at the molecular level into the mechanisms by which spatial APD dispersion contributes to wavebreak, rotor stabilization and fibrillatory conduction.

Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

PubMed

Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

2018-01-01

We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus, our study links electrical restitution remodeling to a defining mechanical characteristic of heart failure, the reduced ability to respond to an increase in demand.

Atrial Heterogeneity Generates Re-entrant Substrate during Atrial Fibrillation and Anti-arrhythmic Drug Action: Mechanistic Insights from Canine Atrial Models

PubMed Central

Varela, Marta; Hancox, Jules C.; Aslanidi, Oleg V.

2016-01-01

Anti-arrhythmic drug therapy is a frontline treatment for atrial fibrillation (AF), but its success rates are highly variable. This is due to incomplete understanding of the mechanisms of action of specific drugs on the atrial substrate at different stages of AF progression. We aimed to elucidate the role of cellular, tissue and organ level atrial heterogeneities in the generation of a re-entrant substrate during AF progression, and their modulation by the acute action of selected anti-arrhythmic drugs. To explore the complex cell-to-organ mechanisms, a detailed biophysical models of the entire 3D canine atria was developed. The model incorporated atrial geometry and fibre orientation from high-resolution micro-computed tomography, region-specific atrial cell electrophysiology and the effects of progressive AF-induced remodelling. The actions of multi-channel class III anti-arrhythmic agents vernakalant and amiodarone were introduced in the model by inhibiting appropriate ionic channel currents according to experimentally reported concentration-response relationships. AF was initiated by applied ectopic pacing in the pulmonary veins, which led to the generation of localized sustained re-entrant waves (rotors), followed by progressive wave breakdown and rotor multiplication in both atria. The simulated AF scenarios were in agreement with observations in canine models and patients. The 3D atrial simulations revealed that a re-entrant substrate was typically provided by tissue regions of high heterogeneity of action potential duration (APD). Amiodarone increased atrial APD and reduced APD heterogeneity and was more effective in terminating AF than vernakalant, which increased both APD and APD dispersion. In summary, the initiation and sustenance of rotors in AF is linked to atrial APD heterogeneity and APD reduction due to progressive remodelling. Our results suggest that anti-arrhythmic strategies that increase atrial APD without increasing its dispersion are effective in terminating AF. PMID:27984585

Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values.

PubMed

Meltzer, H Y; Matsubara, S; Lee, J C

1989-10-01

The pKi values of 13 reference typical and 7 reference atypical antipsychotic drugs (APDs) for rat striatal dopamine D-1 and D-2 receptor binding sites and cortical serotonin (5-HT2) receptor binding sites were determined. The atypical antipsychotics had significantly lower pKi values for the D-2 but not 5-HT2 binding sites. There was a trend for a lower pKi value for the D-1 binding site for the atypical APD. The 5-HT2 and D-1 pKi values were correlated for the typical APD whereas the 5-HT2 and D-2 pKi values were correlated for the atypical APD. A stepwise discriminant function analysis to determine the independent contribution of each pKi value for a given binding site to the classification as a typical or atypical APD entered the D-2 pKi value first, followed by the 5-HT2 pKi value. The D-1 pKi value was not entered. A discriminant function analysis correctly classified 19 of 20 of these compounds plus 14 of 17 additional test compounds as typical or atypical APD for an overall correct classification rate of 89.2%. The major contributors to the discriminant function were the D-2 and 5-HT2 pKi values. A cluster analysis based only on the 5-HT2/D2 ratio grouped 15 of 17 atypical + one typical APD in one cluster and 19 of 20 typical + two atypical APDs in a second cluster, for an overall correct classification rate of 91.9%. When the stepwise discriminant function was repeated for all 37 compounds, only the D-2 and 5-HT2 pKi values were entered into the discriminant function.(ABSTRACT TRUNCATED AT 250 WORDS)

Spatial gradients in action potential duration created by regional magnetofection of hERG are a substrate for wavebreak and turbulent propagation in cardiomyocyte monolayers

PubMed Central

Campbell, Katherine; Calvo, Conrado J; Mironov, Sergey; Herron, Todd; Berenfeld, Omer; Jalife, José

2012-01-01

Spatial dispersion of action potential duration (APD) is a substrate for the maintenance of cardiac fibrillation, but the mechanisms are poorly understood. We investigated the role played by spatial APD dispersion in fibrillatory dynamics. We used an in vitro model in which spatial gradients in the expression of ether-à-go-go-related (hERG) protein, and thus rapid delayed rectifying K+ current (IKr) density, served to generate APD dispersion, high-frequency rotor formation, wavebreak and fibrillatory conduction. A unique adenovirus-mediated magnetofection technique generated well-controlled gradients in hERG and green fluorescent protein (GFP) expression in neonatal rat ventricular myocyte monolayers. Computer simulations using a realistic neonatal rat ventricular myocyte monolayer model provided crucial insight into the underlying mechanisms. Regional hERG overexpression shortened APD and increased rotor incidence in the hERG overexpressing region. An APD profile at 75 percent repolarization with a 16.6 ± 0.72 ms gradient followed the spatial profile of hERG-GFP expression; conduction velocity was not altered. Rotors in the infected region whose maximal dominant frequency was ≥12.9 Hz resulted in wavebreak at the interface (border zone) between infected and non-infected regions; dominant frequency distribution was uniform when the maximal dominant frequency was <12.9 Hz or the rotors resided in the uninfected region. Regularity at the border zone was lowest when rotors resided in the infected region. In simulations, a fivefold regional increase in IKr abbreviated the APD and hyperpolarized the resting potential. However, the steep APD gradient at the border zone proved to be the primary mechanism of wavebreak and fibrillatory conduction. This study provides insight at the molecular level into the mechanisms by which spatial APD dispersion contributes to wavebreak, rotor stabilization and fibrillatory conduction. PMID:23090949

Equivalent circuit model of Ge/Si separate absorption charge multiplication avalanche photodiode

NASA Astrophysics Data System (ADS)

Wang, Wei; Chen, Ting; Yan, Linshu; Bao, Xiaoyuan; Xu, Yuanyuan; Wang, Guang; Wang, Guanyu; Yuan, Jun; Li, Junfeng

2018-03-01

The equivalent circuit model of Ge/Si Separate Absorption Charge Multiplication Avalanche Photodiode (SACM-APD) is proposed. Starting from the carrier rate equations in different regions of device and considering the influences of non-uniform electric field, noise, parasitic effect and some other factors, the equivalent circuit model of SACM-APD device is established, in which the steady-state and transient current voltage characteristics can be described exactly. In addition, the proposed Ge/Si SACM APD equivalent circuit model is embedded in PSpice simulator. The important characteristics of Ge/Si SACM APD such as dark current, frequency response, shot noise are simulated, the simulation results show that the simulation with the proposed model are in good agreement with the experimental results.

Flammability and oxidation kinetics of hydrophobic silica aerogels.

PubMed

Li, Zhi; Cheng, Xudong; Shi, Long; He, Song; Gong, Lunlun; Li, Congcong; Zhang, Heping

2016-12-15

Silica aerogels (SAs) present great application prospects especially on thermal insulation, but their flammability is usually ignored. A combined study on the combustion behaviors and oxidation kinetics of hydrophobic silica aerogels prepared by ambient pressure drying (SA-apd) and supercritical drying (SA-sd) was performed by employing cone calorimeter and thermal analysis. The whole combustion process for SAs could be divided into three stages in which a fire propagation phenomenon was observed with the radial propagation velocity of 6.6-8.3cms -1 . Current investigations forcefully demonstrated that hydrophobic SAs were combustible and easy to flashover when exposed to a heat flux higher than 25kWm -2 . Compared between the two SAs, the SA-sd owned a less fire risk with presenting a less fire hazard and a lower smoke toxicity than those of SA-apd. The oxidation kinetics by Ozawa-Flynn-Wall method revealed that SA-sd had larger apparent activation energies than those of SA-apd which conformed to the thermal stability analysis by TG-DSC. Furthermore, a two-step combustion mechanism was proposed to explain the combustion behaviors of SAs. Copyright © 2016 Elsevier B.V. All rights reserved.

An integrated fluorescence detection system in poly(dimethylsiloxane) for microfluidic applications.

PubMed

Chabinyc, M L; Chiu, D T; McDonald, J C; Stroock, A D; Christian, J F; Karger, A M; Whitesides, G M

2001-09-15

This paper describes a prototype of an integrated fluorescence detection system that uses a microavalanche photodiode (microAPD) as the photodetector for microfluidic devices fabricated in poly(dimethylsiloxane) (PDMS). The prototype device consisted of a reusable detection system and a disposable microfluidic system that was fabricated using rapid prototyping. The first step of the procedure was the fabrication of microfluidic channels in PDMS and the encapsulation of a multimode optical fiber (100-microm core diameter) in the PDMS; the tip of the fiber was placed next to the side wall of one of the channels. The optical fiber was used to couple light into the microchannel for the excitation of fluorescent analytes. The photodetector, a prototype solid-state microAPD array, was embedded in a thick slab (1 cm) of PDMS. A thin (80 microm) colored polycarbonate filter was placed on the top of the embedded microAPD to absorb scattered excitation light before it reached the detector. The microAPD was placed below the microchannel and orthogonal to the axis of the optical fiber. The close proximity (approximately 200 microm) of the microAPD to the microchannel made it unnecessary to incorporate transfer optics; the pixel size of the microAPD (30 microm) matched the dimensions of the channels (50 microm). A blue light-emitting diode was used for fluorescence excitation. The microAPD was operated in Geiger mode to detect the fluorescence. The detection limit of the prototype (approximately 25 nM) was determined by finding the minimum detectable concentration of a solution of fluorescein. The device was used to detect the separation of a mixture of proteins and small molecules by capillary electrophoresis; the separation illustrated the suitability of this integrated fluorescence detection system for bioanalytical applications.

Large Diameter, High Speed InGaAs Receivers for Free-Space Lasercom

DTIC Science & Technology

2007-01-01

appropriate transimpedance amplifier and limiting amplifier . Development and testing of the APD receivers will be described below. 15. SUBJECT TERMS 16...available transimpedance amplifiers (TIA) from Maxim of Dallas. There have also been several devices built in house by NRL in 8-pin TO-39 headers...manufacture a large area, high speed InGaAs APD with an effective ionization ratio of < 0.2 and by matching the APD device with an appropriate transimpedance

Use of antidepressants in Parkinson's disease: A Swedish register-based study of over 1.5 million older people.

PubMed

Haasum, Ylva; Fastbom, Johan; Johnell, Kristina

2016-06-01

It has been suggested that depression in Parkinson's Disease (PD) is often unrecognized and undertreated. However, few previous studies have studied the use of antidepressants in a large sample of both home-dwelling and institutionalized elderly persons with PD. We aimed to study the use of antidepressants in older persons using anti-parkinson drugs (APD, used as a proxy for PD), stratified by residential setting. We analyzed individual data on age, sex, residential setting and drug use in over 1.5 million older persons in the Swedish Prescribed Drug Register on 31th of December 2013. Twenty-two percent of the home-dwellers and 50% of the institutionalized elderly persons with APD used antidepressants. Persons with APD had a higher probability of use of any antidepressant compared to persons without APD. A selective serotonin reuptake inhibitor (SSRI) was the most commonly used antidepressants in both settings followed by mirtazapin. The high use of antidepressants among older persons with APD warrants further studies on the quality of treatment of depression in PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Geiger mode avalanche photodiodes for microarray systems

NASA Astrophysics Data System (ADS)

Phelan, Don; Jackson, Carl; Redfern, R. Michael; Morrison, Alan P.; Mathewson, Alan

2002-06-01

New Geiger Mode Avalanche Photodiodes (GM-APD) have been designed and characterized specifically for use in microarray systems. Critical parameters such as excess reverse bias voltage, hold-off time and optimum operating temperature have been experimentally determined for these photon-counting devices. The photon detection probability, dark count rate and afterpulsing probability have been measured under different operating conditions. An active- quench circuit (AQC) is presented for operating these GM- APDs. This circuit is relatively simple, robust and has such benefits as reducing average power dissipation and afterpulsing. Arrays of these GM-APDs have already been designed and together with AQCs open up the possibility of having a solid-state microarray detector that enables parallel analysis on a single chip. Another advantage of these GM-APDs over current technology is their low voltage CMOS compatibility which could allow for the fabrication of an AQC on the same device. Small are detectors have already been employed in the time-resolved detection of fluorescence from labeled proteins. It is envisaged that operating these new GM-APDs with this active-quench circuit will have numerous applications for the detection of fluorescence in microarray systems.

Geiger-Mode Avalanche Photodiode Arrays Integrated to All-Digital CMOS Circuits

DTIC Science & Technology

2016-01-20

Figure 7 4×4 GMAPD array wire bonded to CMOS timing circuits Figure 8 Low‐fill‐factor APD design used in lidar sensors The APD doping...epitaxial growth and the pixels are isolated by mesa etch. 128×32 lidar image sensors were built by bump bonding the APD arrays to a CMOS timing...passive image sensor with this large a format based on hybridization of a GMAPD array to a CMOS readout. Fig. 14 shows one of the first images taken

Autoimmune progesterone dermatitis.

PubMed

Detrixhe, A; Nikkels, A F; Dezfoulian, B

2017-11-01

Autoimmune progesterone dermatitis (APD) is an exceptional condition affecting young women of childbearing age with a high prevalence during the third decade of life. The diagnosis should be confirmed using an intradermal skin test to progesterone, during the follicular phase of the menstrual cycle. APD represents an early manifestation of autoimmune disease. A case of APD is presented who after curative treatment did not develop other autoimmune diseases during a 6-year follow-up. Dermatologists, gynecologists and obstetricians should be aware of this rare but highly invalidating entity.

Evaluation of the acute electrophysiologic effects of intravenous dronedarone, an amiodarone-like agent, with special emphasis on ventricular repolarization and acquired torsade de pointes arrhythmias.

PubMed

Verduyn, S C; Vos, M A; Leunissen, H D; van Opstal, J M; Wellens, H J

1999-02-01

In the anesthetized dog with complete chronic AV block (CAVB), we evaluated and compared the acute electrophysiologic effects of dronedarone i.v. (Dron, 2 times 2.5 mg/kg/10 min) and amiodarone i.v. (Amio, 2 times 5 mg/kg/10 min). This canine model with a high sensitivity for acquired torsade de pointes (TdP) provides an ideal substrate to evaluate ventricular repolarization abnormalities. Six ECG leads and two endocardial monophasic action potential (MAP) recordings in the left and right ventricle (LV and RV) were simultaneously recorded to measure QT time, action-potential duration (APD), interventricular dispersion (deltaAPD = LV(APD) - RV(APD)), early afterdepolarizations (EADs), ectopic beats (EBs), and TdP. Measurements were made at the spontaneous idioventricular rhythm (IVR) and 1,000-ms steady-state pacing. To investigate its short-term, antiarrhythmic properties, Dron was given after almokalant (0.12 mg/kg)-induced TdP. Furthermore, in another set of experiments, oral Dron (20 mg/kg, b.i.d) was given for 3 weeks to conscious CAVB dogs. Dron, i.v., shortened ventricular repolarization (QT, 435 +/- 60 to 360 +/- 55; LV(APD) 395 +/- 75 to 335 +/- 60 ms; p < 0.05), whereas IVR and ventricular effective refractory period (VERP, 225 +/- 30 to 230 +/- 30 ms) remained similar. Therefore the VERP/QT ratio increased (0.55 +/- 0.04 to 0.61 +/- 0.03; p < 0.05). Similar results were obtained with Amio, i.v.. Almokalant-induced TdP was characterized by an increased repolarization duration, deltaAPD, and EADs. Dron, i.v., suppressed the EADs, EBs, and TdP by a reduction and homogenization of repolarization (LV(APD), 505 +/- 110 to 455 +/- 80 ms, and deltaAPD, 110 +/- 55 to 65 +/- 40 ms). Long-term oral Dron increased the PP interval, CL-IVR, and QT(c) time. In contrast to oral treatment, Dron i.v. shortens ventricular repolarization parameters, resulting in suppression of EAD-dependent acquired TdP. The increased VERP/QT ratio after Dron i.v. may indicate an important second antiarrhythmic property.

Comparison of relative and actual chest compression depths during cardiac arrest in children, adolescents, and young adults☆

PubMed Central

Niles, Dana E.; Nishisaki, Akira; Sutton, Robert M.; Nysæther, Jon; Eilevstjønn, Joar; Leffelman, Jessica; Maltese, Matthew R.; Arbogast, Kristy B.; Abella, Benjamin S.; Helfaer, Mark A.; Berg, Robert A.; Nadkarni, Vinay M.

2013-01-01

Aim Cardiopulmonary resuscitation (CPR) guidelines recommend specific chest compression (CC) target depths for children. We quantitatively describe relative anterior–posterior diameter (APD) depth, actual depth, and force of CCs during real CPR events in children. Methods CC depth and force were recorded during real CPR events in children ≥8 years using FDA-approved CC sensor. Patient chest APD was measured at conclusion of each CPR event. CC data was stratified and analyzed according to age (pre-puberty, 8–14 years; post-puberty, 15+ years). Relative (% APD) and actual CC depth, corrected for mattress deflection, were assessed and compared with American Heart Association (AHA) 2005 and 2010 pediatric CPR guidelines. Results 35 events in 32 subjects included 16,158 CCs for data analysis: 16 pre-puberty (CCs = 7484, age 11.9 ± 2 years, APD 164.6 ± 25.1 mm); 19 post-puberty (CCs = 8674, age 18.0 ± 2.7 years, APD 196.5 ± 30.4 mm). After correction for mattress deflection, 92% of CC delivered to pre-puberty were <1/3 relative APD and 60% of CC were <38 mm actual depth. Mean actual CC depth (36.2 ± 9.6 mm vs. 36.8 ± 9.9 mm, p = 0.64), mean relative APD (22.5% ± 7.0% vs. 19.5 ± 6.7%, p = 0.13), and mean CC force (30.7 ± 7.6 kg vs. 33.6 ± 9.4 kg, p = 0.07) were not significantly less in pre-puberty vs. post-puberty. Conclusions During in-hospital cardiac arrest of children ≥8 years, CCs delivered by resuscitation teams were frequently <1/3 relative APD and <38 mm actual depth after mattress deflection correction, below pediatric and adult target guidelines. Mean CC actual depth and force were not significantly different in pre-puberty and post-puberty. Additional investigation to determine depth of CCs to optimize hemodynamics and outcomes is needed to inform future CPR guidelines. PMID:22079410

Predictors for the need of surgery in antenatally detected hydronephrosis due to UPJ obstruction--a prospective multivariate analysis.

PubMed

Arora, S; Yadav, P; Kumar, M; Singh, S Kumar; Sureka, S Kumar; Mittal, V; Ansari, M S

2015-10-01

Disagreement exists over the ability of different diagnostic tests to define obstruction, indications and timing of surgery and which patients will benefit from surgical intervention in antenatal hydronephrosis (ANH) due to ureteropelvic junction obstruction (UPJO). We try to find a way to predict which patients of ANH due to UPJO will eventually need surgery during conservative management. Prospective single centre study involving 122 renal units at a referral centre in India. Patients on conservative management were followed using a standard protocol and operated for pre-defined indications defining failure of conservative management. Patients who underwent surgery were compared with the non-operated group in terms of sex, side, baseline grade of hydronephrosis, maximum anterioposterior diameter on first postnatal ultrasound and differential renal function on first renal scan. A total of 109 renal units qualified for conservative management. Of those, 23.9% required operative intervention during follow-up. Median time to failure of conservative management was 37 weeks. The median follow-up of non-operated cases was 54 months. Univariate analysis revealed that society of fetal urology (SFU) grade of hydronephrosis, anteroposterior diameter (APD), cortical thickness (CT), and pre-operative differential renal function (DRF) had a significant association with surgery (P < 0.05). Multivariate analysis revealed APD and pre-operative DRF as the only independent predictors for requiring surgery, while CT and initial SFU grade of hydronephrosis were not. Receiver operating curve analysis showed that an APD of 24.3 mm could predict the need for surgery, with a sensitivity of 73.1% and a specificity of 88.0%. APD and DRF are the predictive factors for surgery. We stop short of recommending surgery only on the basis of APD. Instead we recommend that efforts be made to improve the specificity of this criterion, or by using APD in perspective with the differential renal function. We can reduce the burden of investigations in those with APD <24 mm while those with APD >24 mm can be more comprehensively monitored. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model.

PubMed

Sun, Juan; Yan, Huang; Wugeti, Najina; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi

2015-01-01

Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 μm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P < 0.05). 4-AP superfusion significantly prolonged FAPD. In pace/amiodarone groups, 4-Ap superfusion extended fAPD. MEA was a sensitive and stable reporter for the measurement of the tissue action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical remodeling. Amiodarone alter potassium ion channel activity (Ito, IKur, IK1 and IKs), shortening fAPD.

Central auditory processing effects induced by solvent exposure.

PubMed

Fuente, Adrian; McPherson, Bradley

2007-01-01

Various studies have demonstrated that organic solvent exposure may induce auditory damage. Studies conducted in workers occupationally exposed to solvents suggest, on the one hand, poorer hearing thresholds than in matched non-exposed workers, and on the other hand, central auditory damage due to solvent exposure. Taking into account the potential auditory damage induced by solvent exposure due to the neurotoxic properties of such substances, the present research aimed at studying the possible auditory processing disorder (APD), and possible hearing difficulties in daily life listening situations that solvent-exposed workers may acquire. Fifty workers exposed to a mixture of organic solvents (xylene, toluene, methyl ethyl ketone) and 50 non-exposed workers matched by age, gender and education were assessed. Only subjects with no history of ear infections, high blood pressure, kidney failure, metabolic and neurological diseases, or alcoholism were selected. The subjects had either normal hearing or sensorineural hearing loss, and normal tympanometric results. Hearing-in-noise (HINT), dichotic digit (DD), filtered speech (FS), pitch pattern sequence (PPS), and random gap detection (RGD) tests were carried out in the exposed and non-exposed groups. A self-report inventory of each subject's performance in daily life listening situations, the Amsterdam Inventory for Auditory Disability and Handicap, was also administered. Significant threshold differences between exposed and non-exposed workers were found at some of the hearing test frequencies, for both ears. However, exposed workers still presented normal hearing thresholds as a group (equal or better than 20 dB HL). Also, for the HINT, DD, PPS, FS and RGD tests, non-exposed workers obtained better results than exposed workers. Finally, solvent-exposed workers reported significantly more hearing complaints in daily life listening situations than non-exposed workers. It is concluded that subjects exposed to solvents may acquire an APD and thus the sole use of pure-tone audiometry is insufficient to assess hearing in solvent-exposed populations.

Age- and Gender-Specific Normative Information from Children Assessed with a Dichotic Words Test.

PubMed

Moncrieff, Deborah

2015-01-01

The most widely used assessment in the clinical auditory processing disorder (APD) battery is the dichotic listening test. New tests with normative information are helpful for assessment and cross-check of results for reliable diagnosis. The Dichotic Words Test was developed for use in the clinical test battery for diagnosis of APD. The test stimuli were common single syllable words matched for average root-mean-square amplitude and each pair was temporally aligned at both onset and offset. The study was conducted to collect performance results from typically developing children to create normative information for the test. The study follows a cross-sectional design. Typically developing children (n = 416) between the ages of 5 and 12 yr were recruited from schools in the community. There were 217 males and 199 females in the study sample. Only children who passed a hearing screening were eligible to participate. Scores for each ear were recorded during administration of the first free recall version of the test. Ear advantages based on results recorded for left and right ears were used to measure prevalence of right, left, and no ear advantages. Results for each listener's dominant and non-dominant ears and the absolute difference between them were put into the data analysis. Results were analyzed for normality and because no results were normally distributed, all further analyses were done with nonparametric statistical tests. Normative data for dominant and non-dominant ear scores and ear advantages were determined at the 95% confidence interval through bootstrapping methods with 1,000 samples. Children were divided into four age groups based on results in their dominant ears. Females generally performed better than males and the prevalence of a right-ear advantage was ∼60% across all children tested. Normative lower-bound cut-off scores were established for males and females within each age group for dominant and non-dominant ear scores. Normative upper-bound cut-off scores were established for males and females within each age group for ear advantage scores. Normative information specific to age group and gender will be useful in clinical assessment for APD. Prevalence of left-ear advantage results in the sample may have been partly due to uncontrolled influences of voice-onset time in arranging the dichotic pairs. American Academy of Audiology.

Temperature Control of Avalanche Photodiode Using Thermoelectric Cooler

NASA Technical Reports Server (NTRS)

Refaat, Tamer F.; Luck, William S., Jr.; DeYoung, Russell J.

1999-01-01

Avalanche photodiodes (APDS) are quantum optical detectors that are used for visible and near infrared optical detection applications. Although APDs are compact, rugged, and have an internal gain mechanism that is suitable for low light intensity; their responsivity, and therefore their output, is strongly dependent on the device temperature. Thermoelectric coolers (TEC) offers a suitable solution to this problem. A TEC is a solid state cooling device, which can be controlled by changing its current. TECs are compact and rugged, and they can precisely control the temperature to within 0.1 C with more than a 150 C temperature gradient between its surfaces. In this Memorandum, a proportional integral (PI) temperature controller for APDs using a TEC is discussed. The controller is compact and can successfully cool the APD to almost 0 C in an ambient temperature environment of up to 27 C.

Characterisation of Geiger-mode avalanche photodiodes for medical imaging applications

NASA Astrophysics Data System (ADS)

Britvitch, I.; Johnson, I.; Renker, D.; Stoykov, A.; Lorenz, E.

2007-02-01

Recently developed multipixel Geiger-mode avalanche photodiodes (G-APDs) are very promising candidates for the detection of light in medical imaging instruments (e.g. positron emission tomography) as well as in high-energy physics experiments and astrophysical applications. G-APDs are especially well suited for morpho-functional imaging (multimodality PET/CT, SPECT/CT, PET/MRI, SPECT/MRI). G-APDs have many advantages compared to conventional photosensors such as photomultiplier tubes because of their compact size, low-power consumption, high quantum efficiency and insensitivity to magnetic fields. Compared to avalanche photodiodes and PIN diodes, they are advantageous because of their high gain, reduced sensitivity to pick up and the so-called nuclear counter effect and lower noise. We present measurements of the basic G-APD characteristics: photon detection efficiency, gain, inter-cell crosstalk, dynamic range, recovery time and dark count rate.

Degradation and Its Control of Ultraviolet Avalanche Photodiodes Using PEDOT:PSS/ZnSSe Organic-Inorganic Hybrid Structure

NASA Astrophysics Data System (ADS)

Abe, Tomoki; Uchida, Shigeto; Tanaka, Keita; Fujisawa, Takanobu; Kasada, Hirofumi; Ando, Koshi; Akaiwa, Kazuaki; Ichino, Kunio

2018-05-01

We investigated device degradation in PEDOT:PSS/ZnSSe organic-inorganic hybrid ultraviolet avalanche photodiodes (UV-APDs). ZnSSe/n-GaAs wafers were grown by molecular beam epitaxy, and PEDOT:PSS window layers were formed by inkjet technique. We observed rapid degradation with APD-mode stress (˜ 30 V) in the N2 (4 N) atmosphere, while we observed no marked change in forward bias current stress and photocurrent stress. In the case of a vacuum condition, we observed no detectable degradation in the dark avalanche current with APD-mode stress. Therefore, the degradation in the PEDOT:PSS/ZnSSe interface under the APD-mode stress was caused by the residual water vapor or oxygen in the N2 atmosphere and could be controlled by vacuum packaging.

Computational model based approach to analysis ventricular arrhythmias: Effects of dysfunction calcium channels

NASA Astrophysics Data System (ADS)

Gulothungan, G.; Malathi, R.

2018-04-01

Disturbed sodium (Na+) and calcium (Ca2+) handling is known to be a major predisposing factor for life-threatening cardiac arrhythmias. Cardiac contractility in ventricular tissue is prominent by Ca2+ channels like voltage dependent Ca2+ channels, sodium-calcium exchanger (Na+-Ca2+x) and sacroplasmicrecticulum (SR) Ca2+ pump and leakage channels. Experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. Our aim of this article is to study the impact on action potential (AP) generation and propagation in single ventricular myocyte and ventricular tissue under different dysfunction Ca2+ channels condition. In enhanced activity of Na+-Ca2+x, single myocyte produces AP duration (APD90) and APD50 is significantly smaller (266 ms and 235 ms). Its Na+-Ca2+x current at depolarization is increases 60% from its normal level and repolarization current goes more negative (nonfailing= -0.28 pA/pF and failing= -0.47 pA/pF). Similarly, same enhanced activity of Na+-Ca2+x in 10 mm region of ventricular sheet, raises the plateau potential abruptly, which ultimately affects the diastolic repolarization. Compare with normal ventricular sheet region of 10 mm, 10% of ventricular sheet resting state is reduces and ventricular sheet at time 250 ms is goes to resting state very early. In hypertrophy condition, single myocyte produces APD90 and APD50 is worthy of attention smaller (232 mS and 198 ms). Its sodium-potassium (Na+-K+) pump current is 75% reduces from its control conditions (0.13 pA/pF). Hypertrophy condition, 50% of ventricular sheet is reduces to minimum plateau potential state, that starts the repolarization process very early and reduces the APD. In a single failing SR Ca2+ channels myocyte, recovery of Ca2+ concentration level in SR reduces upto 15% from its control myocytes. At time 290 ms, 70% of ventricular sheet is in dysfunction resting potential state in the range -83 mV and ventricular sheet at time 295 ms is goes to 65% dysfunction resting state. Therefore we concluded that shorter APD, instability resting potential and affected calcium induced calcium release (CICR) due to dysfunction Ca2+ channels is potentially have a substantial effect on cardiac contractility and relaxation. Computational study on ventricular tissue AP and its underlying ionic channel currents could help to elucidate possible arrhythmogenic mechanism on a cellular level.

Carrier trajectory tracking equations for Simple-band Monte Carlo simulation of avalanche multiplication processes

NASA Astrophysics Data System (ADS)

Ong, J. S. L.; Charin, C.; Leong, J. H.

2017-12-01

Avalanche photodiodes (APDs) with steep electric field gradients generally have low excess noise that arises from carrier multiplication within the internal gain of the devices, and the Monte Carlo (MC) method is among popular device simulation tools for such devices. However, there are few articles relating to carrier trajectory modeling in MC models for such devices. In this work, a set of electric-field-gradient-dependent carrier trajectory tracking equations are developed and used to update the positions of carriers along the path during Simple-band Monte Carlo (SMC) simulations of APDs with non-uniform electric fields. The mean gain and excess noise results obtained from the SMC model employing these equations show good agreement with the results reported for a series of silicon diodes, including a p+n diode with steep electric field gradients. These results confirm the validity and demonstrate the feasibility of the trajectory tracking equations applied in SMC models for simulating mean gain and excess noise in APDs with non-uniform electric fields. Also, the simulation results of mean gain, excess noise, and carrier ionization positions obtained from the SMC model of this work agree well with those of the conventional SMC model employing the concept of a uniform electric field within a carrier free-flight. These results demonstrate that the electric field variation within a carrier free-flight has an insignificant effect on the predicted mean gain and excess noise results. Therefore, both the SMC model of this work and the conventional SMC model can be used to predict the mean gain and excess noise in APDs with highly non-uniform electric fields.

GHz low noise short wavelength infrared (SWIR) photoreceivers

NASA Astrophysics Data System (ADS)

Bai, Xiaogang; Yuan, Ping; McDonald, Paul; Boisvert, Joseph; Chang, James; Woo, Robyn; Labios, Eduardo; Sudharsanan, Rengarajan; Krainak, Michael; Yang, Guangning; Sun, Xiaoli; Lu, Wei; McIntosh, Dion; Zhou, Qiugui; Campbell, Joe

2011-06-01

Next generation LIDAR mapping systems require multiple channels of sensitive photoreceivers that operate in the wavelength region of 1.06 to 1.55 microns, with GHz bandwidth and sensitivity less than 300 fW/√Hz. Spectrolab has been developing high sensitivity photoreceivers using InAlAs impact ionization engineering (I2E) avalanche photodiodes (APDs) structures for this application. APD structures were grown using metal organic vapor epitaxy (MOVPE) and mesa devices were fabricated using these structures. We have achieved low excess noise at high gain in these APD devices; an impact ionization parameter, k, of about 0.15 has been achieved at gains >20 using InAlAs/InGaAlAs as a multiplier layer. Electrical characterization data of these devices show dark current less than 2 nA at a gain of 20 at room temperature; and capacitance of 0.4 pF for a typical 75 micron diameter APD. Photoreceivers were built by integrating I2E APDs with a low noise GHz transimpedance amplifier (TIA). The photoreceivers showed a bandwidth of 1 GHz and a noise equivalent power (NEP) of 150 fW/rt(Hz) at room temperature.

Pulse oximeter using a gain-modulated avalanche photodiode operated in a pseudo lock-in light detection mode

NASA Astrophysics Data System (ADS)

Miyata, Tsuyoshi; Iwata, Tetsuo; Araki, Tsutomu

2006-01-01

We propose a reflection-type pulse oximeter, which employs two pairs of a light-emitting diode (LED) and a gated avalanche photodiode (APD). One LED is a red one with an emission wavelength λ = 635 nm and the other is a near-infrared one with that λ = 945 nm, which are both driven with a pulse mode at a frequency f (=10 kHz). Superposition of a transistor-transistor-logic (TTL) gate pulse on a direct-current (dc) bias, which is set so as not exceeding the breakdown voltage of each APD, makes the APD work in a gain-enhanced operation mode. Each APD is gated at a frequency 2f (=20 kHz) and its output signal is fed into a laboratory-made lock-in amplifier that works in synchronous with the pulse modulation signal of each LED at a frequency f (=10 kHz). A combination of the gated APD and the lock-in like signal detection scheme is useful for the reflection-type pulse oximeter thanks to the capability of detecting a weak signal against a large background (BG) light.

APDS: the autonomous pathogen detection system.

PubMed

Hindson, Benjamin J; Makarewicz, Anthony J; Setlur, Ujwal S; Henderer, Bruce D; McBride, Mary T; Dzenitis, John M

2005-04-15

We have developed and tested a fully autonomous pathogen detection system (APDS) capable of continuously monitoring the environment for airborne biological threat agents. The system was developed to provide early warning to civilians in the event of a bioterrorism incident and can be used at high profile events for short-term, intensive monitoring or in major public buildings or transportation nodes for long-term monitoring. The APDS is completely automated, offering continuous aerosol sampling, in-line sample preparation fluidics, multiplexed detection and identification immunoassays, and nucleic acid-based polymerase chain reaction (PCR) amplification and detection. Highly multiplexed antibody-based and duplex nucleic acid-based assays are combined to reduce false positives to a very low level, lower reagent costs, and significantly expand the detection capabilities of this biosensor. This article provides an overview of the current design and operation of the APDS. Certain sub-components of the ADPS are described in detail, including the aerosol collector, the automated sample preparation module that performs multiplexed immunoassays with confirmatory PCR, and the data monitoring and communications system. Data obtained from an APDS that operated continuously for 7 days in a major U.S. transportation hub is reported.

The performance of Geiger mode avalanche photo-diodes in free space laser communication links

NASA Astrophysics Data System (ADS)

Farrell, Thomas C.

2018-05-01

Geiger mode avalanche photo-diode (APD) arrays, when used as detectors in laser communication (lasercom) receivers, promise better performance at lower signal levels than APDs operated in the linear mode. In this paper, we describe the basic operation of the Geiger mode APD array as a lasercom detector, concentrating on aspects relevant to the link design engineer (rather than, for example, describing the details of the physics of the basic device operation itself). Equations are developed that describe the effects of defocus and hold-off time on the relation between the number of photons detected by the array and the output of photo-electron counts. We show how to incorporate these equations into a link budget. The resulting predictions are validated by comparison against simulation results. Finally, we compare the performance of linear mode APD based receivers and Geiger mode APD array based receivers. Results show the Geiger mode receivers yield better performance, in terms of probability of bit error, at lower signal levels, except on links where there is an exceptionally large amount of background noise. Under those conditions, not surprisingly, the hold-off time degrades performance.

Effect of Intermolecular Distance on Surface-Plasmon-Assisted Catalysis.

PubMed

Wu, Shiwei; Liu, Yu; Ma, Caiqing; Wang, Jing; Zhang, Yao; Song, Peng; Xia, Lixin

2018-06-26

4-Aminothiophenol (PATP) and 4-aminophenyl disulfide (APDS) in contact with silver will form H 2 N-C 6 H 4 -S-Ag (PATP-Ag), and under the conditions of surface-enhanced Raman spectroscopy (SERS), a coupling reaction will generate 4,4-dimercaptoazobenzene (DMAB). DMAB is strongly Raman-active, showing strong peaks at ν ≈ 1140, 1390, and 1432 cm -1 , and is widely used in surface-plasmon-assisted catalysis. Using APDS, PATP, p-nitrothiophenol (PNTP), and p-nitrodiphenyl disulfide (NPDS) as probe molecules, Raman spectroscopy and imaging techniques have been used to study the effect of intermolecular distance on surface-plasmon-assisted catalysis. Theoretically, PATP-Ag formed from APDS will be bound at proximal Ag atoms on the Ag surface due to S-S bond cleavage. The results show that APDS is more prone to surface-plasmon-assisted catalytic coupling due to the smaller distance between surface PATP-Ag moieties than those derived from PATP. Therefore, APDS has a higher reaction efficiency, better Raman activity, and better Raman imaging than does PATP. Analogous experiments with PNTP and NPDS gave similar results. Thus, this technique has great application prospects in the fields of surface chemistry and materials chemistry.

The Autonomous Pathogen Detection System (APDS)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morris, J; Dzenitis, J

2004-09-22

Shaped like a mailbox on wheels, it's been called a bioterrorism ''smoke detector.'' It can be found in transportation hubs such as airports and subways, and it may be coming to a location near you. Formally known as the Autonomous Pathogen Detection System, or APDS, this latest tool in the war on bioterrorism was developed at Lawrence Livermore National Laboratory to continuously sniff the air for airborne pathogens and toxins such as anthrax or plague. The APDS is the modern day equivalent of the canaries miners took underground with them to test for deadly carbon dioxide gas. But this canarymore » can test for numerous bacteria, viruses, and toxins simultaneously, report results every hour, and confirm positive samples and guard against false positive results by using two different tests. The fully automated system collects and prepares air samples around the clock, does the analysis, and interprets the results. It requires no servicing or human intervention for an entire week. Unlike its feathered counterpart, when an APDS unit encounters something deadly in the air, that's when it begins singing, quietly. The APDS unit transmits a silent alert and sends detailed data to public health authorities, who can order evacuation and begin treatment of anyone exposed to toxic or biological agents. It is the latest in a series of biodefense detectors developed at DOE/NNSA national laboratories. The manual predecessor to APDS, called BASIS (for Biological Aerosol Sentry and Information System), was developed jointly by Los Alamos and Lawrence Livermore national laboratories. That system was modified to become BioWatch, the Department of Homeland Security's biological urban monitoring program. A related laboratory instrument, the Handheld Advanced Nucleic Acid Analyzer (HANAA), was first tested successfully at LLNL in September 1997. Successful partnering with private industry has been a key factor in the rapid advancement and deployment of biodefense instruments such as these. The APDS technology has been licensed and is currently undergoing commercialization.« less

Electrophysiological effects of Chinese medicine Shen song Yang xin (SSYX) on Chinese miniature swine heart and isolated guinea pig ventricular myocytes.

PubMed

Feng, Li; Gong, Jing; Jin, Zhen-yi; Li, Ning; Sun, Li-ping; Wu, Yi-ling; Pu, Jie-lin

2009-07-05

Shen song Yang xin (SSYX) is a compound of Chinese medicine with the effect of increasing heart rate (HR). This study aimed to evaluate its electrophysiological properties at heart and cellular levels. The Chinese miniature swines were randomly assigned to two groups, administered with SSYX or placebo for 4 weeks (n = 8 per group). Cardiac electrophysiological study (EPS) was performed before and after drug administration. The guinea pig ventricular myocytes were enzymatically isolated and whole cell voltage-clamp technique was used to evaluate the effect of SSYX on cardiac action potential (AP). SSYX treatment accelerated the HR from (141.8 +/- 36.0) beats per minute to (163.0 +/- 38.0) beats per minute (P = 0.013) without changing the other parameters in surface electrocardiogram. After blockage of the autonomic nervous system with metoprolol and atropin, SSYX had no effect on intrinsic HR (IHR), but decreased corrected sinus node recovery time (CSNRT) and sinus atrium conducting time (SACT). Intra cardiac EPS showed that SSYX significantly decreased the A-H and A-V intervals as well as shortened the atrial (A), atrioventricular node (AVN) and ventricular (V) effective refractory period (ERP). In isolated guinea pig ventricular myocytes, the most obvious effect of SSYX on action potential was a shortening of the action potential duration (APD) without change in shape of action potential. The shortening rates of APD(30), APD(50) and APD(90) were 19.5%, 17.8% and 15.3%, respectively. The resting potential (Em) and the interval between the end of APD(30) and APD(90) did not significantly change. The present study demonstrates that SSYX increases the HR and enhances the conducting capacity of the heart in the condition of the intact autonomic nervous system. SSYX homogenously decreases the ERP of the heart and shortens the APD of the myocytes, suggesting its antiarrhythmic effect without proarrhythmia.

Electrophysiological and structural determinants of electrotonic modulation of repolarization by the activation sequence

PubMed Central

Walton, Richard D.; Benson, Alan P.; Hardy, Matthew E. L.; White, Ed; Bernus, Olivier

2013-01-01

Spatial dispersion of repolarization is known to play an important role in arrhythmogenesis. Electrotonic modulation of repolarization by the activation sequence has been observed in some species and tissue preparations, but to varying extents. Our study sought to determine the mechanisms underlying species- and tissue-dependent electrotonic modulation of repolarization in ventricles. Epi-fluorescence optical imaging of whole rat hearts and pig left ventricular wedges were used to assess epicardial spatial activation and repolarization characteristics. Experiments were supported by computer simulations using realistic geometries. Tight coupling between activation times (AT) and action potential duration (APD) were observed in rat experiments but not in pig. Linear correlation analysis found slopes of −1.03 ± 0.59 and −0.26 ± 0.13 for rat and pig, respectively (p < 0.0001). In rat, maximal dispersion of APD was 11.0 ± 3.1 ms but dispersion of repolarization time (RT) was relatively homogeneous (8.2 ± 2.7, p < 0.0001). However, in pig no such difference was observed between the dispersion of APD and RT (17.8 ± 6.1 vs. 17.7 ± 6.5, respectively). Localized elevations of APD (12.9 ± 8.3%) were identified at ventricular insertion sites of rat hearts both in experiments and simulations. Tissue geometry and action potential (AP) morphology contributed significantly to determining influence of electrotonic modulation. Simulations of a rat AP in a pig geometry decreased the slope of AT and APD relationships by 70.6% whereas slopes were increased by 75.0% when implementing a pig AP in a rat geometry. A modified pig AP, shortened to match the rat APD, showed little coupling between AT and APD with greatly reduced slope compared to the rat AP. Electrotonic modulation of repolarization by the activation sequence is especially pronounced in small hearts with murine-like APs. Tissue architecture and AP morphology play an important role in electrotonic modulation of repolarization. PMID:24115934

Arrhythmogenic drugs can amplify spatial heterogeneities in the electrical restitution in perfused guinea-pig heart: An evidence from assessments of monophasic action potential durations and JT intervals

PubMed Central

2018-01-01

Non-uniform shortening of the action potential duration (APD90) in different myocardial regions upon heart rate acceleration can set abnormal repolarization gradients and promote arrhythmia. This study examined whether spatial heterogeneities in APD90 restitution can be amplified by drugs with clinically proved proarrhythmic potential (dofetilide, quinidine, procainamide, and flecainide) and, if so, whether these effects can translate to the appropriate changes of the ECG metrics of ventricular repolarization, such as JT intervals. In isolated, perfused guinea-pig heart preparations, monophasic action potentials and volume-conducted ECG were recorded at progressively increased pacing rates. The APD90 measured at distinct ventricular sites, as well as the JTpeak and JTend values were plotted as a function of preceding diastolic interval, and the maximum slopes of the restitution curves were determined at baseline and upon drug administration. Dofetilide, quinidine, and procainamide reverse rate-dependently prolonged APD90 and steepened the restitution curve, with effects being greater at the endocardium than epicardium, and in the right ventricular (RV) vs. the left ventricular (LV) chamber. The restitution slope was increased to a greater extent for the JTend vs. the JTpeak interval. In contrast, flecainide reduced the APD90 restitution slope at LV epicardium without producing effect at LV endocardium and RV epicardium, and reduced the JTpeak restitution slope without changing the JTend restitution. Nevertheless, with all agents, these effects translated to the amplified epicardial-to-endocardial and the LV-to-RV non-uniformities in APD90 restitution, paralleled by the increased JTend vs. JTpeak difference in the restitution slope. In summary, these findings suggest that arrhythmic drug profiles are partly attributable to the accentuated regional heterogeneities in APD90 restitution, which can be indirectly determined through ECG assessments of the JTend vs. JTpeak dynamics at variable pacing rates. PMID:29352276

Arrhythmogenic drugs can amplify spatial heterogeneities in the electrical restitution in perfused guinea-pig heart: An evidence from assessments of monophasic action potential durations and JT intervals.

PubMed

Osadchii, Oleg E

2018-01-01

Non-uniform shortening of the action potential duration (APD90) in different myocardial regions upon heart rate acceleration can set abnormal repolarization gradients and promote arrhythmia. This study examined whether spatial heterogeneities in APD90 restitution can be amplified by drugs with clinically proved proarrhythmic potential (dofetilide, quinidine, procainamide, and flecainide) and, if so, whether these effects can translate to the appropriate changes of the ECG metrics of ventricular repolarization, such as JT intervals. In isolated, perfused guinea-pig heart preparations, monophasic action potentials and volume-conducted ECG were recorded at progressively increased pacing rates. The APD90 measured at distinct ventricular sites, as well as the JTpeak and JTend values were plotted as a function of preceding diastolic interval, and the maximum slopes of the restitution curves were determined at baseline and upon drug administration. Dofetilide, quinidine, and procainamide reverse rate-dependently prolonged APD90 and steepened the restitution curve, with effects being greater at the endocardium than epicardium, and in the right ventricular (RV) vs. the left ventricular (LV) chamber. The restitution slope was increased to a greater extent for the JTend vs. the JTpeak interval. In contrast, flecainide reduced the APD90 restitution slope at LV epicardium without producing effect at LV endocardium and RV epicardium, and reduced the JTpeak restitution slope without changing the JTend restitution. Nevertheless, with all agents, these effects translated to the amplified epicardial-to-endocardial and the LV-to-RV non-uniformities in APD90 restitution, paralleled by the increased JTend vs. JTpeak difference in the restitution slope. In summary, these findings suggest that arrhythmic drug profiles are partly attributable to the accentuated regional heterogeneities in APD90 restitution, which can be indirectly determined through ECG assessments of the JTend vs. JTpeak dynamics at variable pacing rates.

Avalanche photodiode based time-of-flight mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ogasawara, Keiichi, E-mail: kogasawara@swri.edu; Livi, Stefano A.; Desai, Mihir I.

2015-08-15

This study reports on the performance of Avalanche Photodiodes (APDs) as a timing detector for ion Time-of-Flight (TOF) mass spectroscopy. We found that the fast signal carrier speed in a reach-through type APD enables an extremely short timescale response with a mass or energy independent <2 ns rise time for <200 keV ions (1−40 AMU) under proper bias voltage operations. When combined with a microchannel plate to detect start electron signals from an ultra-thin carbon foil, the APD comprises a novel TOF system that successfully operates with a <0.8 ns intrinsic timing resolution even using commercial off-the-shelf constant-fraction discriminators. Bymore » replacing conventional total-energy detectors in the TOF-Energy system, APDs offer significant power and mass savings or an anti-coincidence background rejection capability in future space instrumentation.« less

Advances in HgCdTe APDs and LADAR Receivers

NASA Technical Reports Server (NTRS)

Bailey, Steven; McKeag, William; Wang, Jinxue; Jack, Michael; Amzajerdian, Farzin

2010-01-01

Raytheon is developing NIR sensor chip assemblies (SCAs) for scanning and staring 3D LADAR systems. High sensitivity is obtained by integrating high performance detectors with gain i.e. APDs with very low noise Readout Integrated Circuits. Unique aspects of these designs include: independent acquisition (non-gated) of pulse returns, multiple pulse returns with both time and intensity reported to enable full 3D reconstruction of the image. Recent breakthrough in device design has resulted in HgCdTe APDs operating at 300K with essentially no excess noise to gains in excess of 100, low NEP <1nW and GHz bandwidths and have demonstrated linear mode photon counting. SCAs utilizing these high performance APDs have been integrated and demonstrated excellent spatial and range resolution enabling detailed 3D imagery both at short range and long ranges. In this presentation we will review progress in high resolution scanning, staring and ultra-high sensitivity photon counting LADAR sensors.

HgCdTe Avalanche Photodiode Detectors for Airborne and Spaceborne Lidar at Infrared Wavelengths

NASA Technical Reports Server (NTRS)

Sun, Xiaoli; Abshire, James B.; Beck, Jeffrey D.; Mitra, Pradip; Reiff, Kirk; Yang, Guangning

2017-01-01

We report results from characterizing the HgCdTe avalanche photodiode (APD) sensorchip assemblies (SCA) developed for lidar at infrared wavelength using the high density vertically integrated photodiodes (HDVIP) technique. These devices demonstrated high quantum efficiency, typically greater than 90 between 0.8 micrometers and the cut-off wavelength, greater than 600 APD gain, near unity excess noise factor, 6-10 MHz electrical bandwidth and less than 0.5 fW/Hz(exp.1/2) noise equivalent power (NEP). The detectors provide linear analog output with a dynamic range of 2-3 orders of magnitude at a fixed APD gain without averaging, and over 5 orders of magnitude by adjusting the APD and preamplifier gain settings. They have been successfully used in airborne CO2 and CH4 integrated path differential absorption (IPDA) lidar as a precursor for space lidar applications.

InAlAs/InGaAs avalanche photodiode arrays for free space optical communication.

PubMed

Ferraro, Mike S; Clark, William R; Rabinovich, William S; Mahon, Rita; Murphy, James L; Goetz, Peter G; Thomas, Linda M; Burris, Harris R; Moore, Christopher I; Waters, William D; Vaccaro, Kenneth; Krejca, Brian D

2015-11-01

In free space optical communication, photodetectors serve not only as communications receivers but also as position sensitive detectors (PSDs) for pointing, tracking, and stabilization. Typically, two separate detectors are utilized to perform these tasks, but recent advances in the fabrication and development of large-area, low-noise avalanche photodiode (APD) arrays have enabled these devices to be used both as PSDs and as communications receivers. This combined functionality allows for more flexibility and simplicity in optical system design without sacrificing the sensitivity and bandwidth performance of smaller, single-element data receivers. This work presents the development of APD arrays rated for bandwidths beyond 1 GHz with measured carrier ionization ratios of approximately 0.2 at moderate APD gains. We discuss the fabrication and characterization of three types of APD arrays along with their performance as high-speed photodetectors.

Automated Predictive Diagnosis (APD): A 3-tiered shell for building expert systems for automated predictions and decision making

NASA Technical Reports Server (NTRS)

Steib, Michael

1991-01-01

The APD software features include: On-line help, Three level architecture, (Logic environments, Setup/Application environment, Data environment), Explanation capability, and File handling. The kinds of experimentation and record keeping that leads to effective expert systems is facilitated by: (1) a library of inferencing modules (in the logic environment); (2) an explanation capability which reveals logic strategies to users; (3) automated file naming conventions; (4) an information retrieval system; and (5) on-line help. These aid with effective use of knowledge, debugging and experimentation. Since the APD software anticipates the logical rules becoming complicated, it is embedded in a production system language (CLIPS) to insure the full power of the production system paradigm of CLIPS and availability of the procedural language C. The development is discussed of the APD software and three example applications: toy, experimental, and operational prototype for submarine maintenance predictions.

Detecting Bioaerosols When Time Is of the Essence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hazi, A

About seven years ago, Livermore researchers received seed funding from the Laboratory Directed Research and Development Program to develop an instrument that counters bioterrorism by providing a rapid early warning system for pathogens, such as anthrax. (See S&TR, January/February 2002, pp. 24-26.) That instrument, the Autonomous Pathogen Detection System (APDS), is now ready for deployment to better protect the public from a bioaerosol attack, and the development team has been honored with a 2004 R&D 100 Award. The lectern-size APDS can be placed in airports, office buildings, performing arts centers, mass transit systems, sporting arenas--anywhere an attack might be launched.more » APDS was designed to get results fast and get them right, without false positives. Biological scientist Richard Langlois, who spearheaded the APDS development effort, explains, ''The system provides results on the spot. Faster results allow a faster emergency response, which in the end means saving lives.''« less

Advances in LADAR Components and Subsystems at Raytheon

NASA Technical Reports Server (NTRS)

Jack, Michael; Chapman, George; Edwards, John; McKeag, William; Veeder, Tricia; Wehner, Justin; Roberts, Tom; Robinson, Tom; Neisz, James; Andressen, Cliff;

Analytically based photon scatter modeling for a multipinhole cardiac SPECT camera.

PubMed

Pourmoghaddas, Amir; Wells, R Glenn

2016-11-01

Dedicated cardiac SPECT scanners have improved performance over standard gamma cameras allowing reductions in acquisition times and/or injected activity. One approach to improving performance has been to use pinhole collimators, but this can cause position-dependent variations in attenuation, sensitivity, and spatial resolution. CT attenuation correction (AC) and an accurate system model can compensate for many of these effects; however, scatter correction (SC) remains an outstanding issue. In addition, in cameras using cadmium-zinc-telluride-based detectors, a large portion of unscattered photons is detected with reduced energy (low-energy tail). Consequently, application of energy-based SC approaches in these cameras leads to a higher increase in noise than with standard cameras due to the subtraction of true counts detected in the low-energy tail. Model-based approaches with parallel-hole collimator systems accurately calculate scatter based on the physics of photon interactions in the patient and camera and generate lower-noise estimates of scatter than energy-based SC. In this study, the accuracy of a model-based SC method was assessed using physical phantom studies on the GE-Discovery NM530c and its performance was compared to a dual energy window (DEW)-SC method. The analytical photon distribution (APD) method was used to calculate the distribution of probabilities that emitted photons will scatter in the surrounding scattering medium and be subsequently detected. APD scatter calculations for 99m Tc-SPECT (140 ± 14 keV) were validated with point-source measurements and 15 anthropomorphic cardiac-torso phantom experiments and varying levels of extra-cardiac activity causing scatter inside the heart. The activity inserted into the myocardial compartment of the phantom was first measured using a dose calibrator. CT images were acquired on an Infinia Hawkeye (GE Healthcare) SPECT/CT and coregistered with emission data for AC. For comparison, DEW scatter projections (120 ± 6 keV ) were also extracted from the acquired list-mode SPECT data. Either APD or DEW scatter projections were subtracted from corresponding 140 keV measured projections and then reconstructed with AC (APD-SC and DEW-SC). Quantitative accuracy of the activity measured in the heart for the APD-SC and DEW-SC images was assessed against dose calibrator measurements. The difference between modeled and acquired projections was measured as the root-mean-squared-error (RMSE). APD-modeled projections for a clinical cardiac study were also evaluated. APD-modeled projections showed good agreement with SPECT measurements and had reduced noise compared to DEW scatter estimates. APD-SC reduced mean error in activity measurement compared to DEW-SC in images and the reduction was statistically significant where the scatter fraction (SF) was large (mean SF = 28.5%, T-test p = 0.007). APD-SC reduced measurement uncertainties as well; however, the difference was not found to be statistically significant (F-test p > 0.5). RMSE comparisons showed that elevated levels of scatter did not significantly contribute to a change in RMSE (p > 0.2). Model-based APD scatter estimation is feasible for dedicated cardiac SPECT scanners with pinhole collimators. APD-SC images performed better than DEW-SC images and improved the accuracy of activity measurement in high-scatter scenarios.

CT-1-CP-induced ventricular electrical remodeling in mice.

PubMed

Chen, Shu-fen; Wei, Tao-zhi; Rao, Li-ya; Xu, Ming-guang; Dong, Zhan-ling

2015-02-01

The chronic effects of carboxyl-terminal polypeptide of Cardiotrophin-1 (CT-1-CP) on ventricular electrical remodeling were investigated. CT-1-CP, which contains 16 amino acids in sequence of the C-terminal of Cardiotrophin-1, was selected and synthesized, and then administered to Kunming mice (aged 5 weeks) by intraperitoneal injection (500 ng·g⁻¹·day⁻¹) (4 groups, n=10 and female: male=1:1 in each group) for 1, 2, 3 and 4 weeks, respectively. The control group (n=10, female: male=1:1) was injected by physiological saline for 4 weeks. The epicardial monophasic action potential (MAP) was recorded by using a contact-type MAP electrode placed vertically on the left ventricular (LV) epicardium surface, and the electrocardiogram (ECG) signal in lead II was monitored synchronously. ECG intervals (RR, PR, QRS and QT) and the amplitude of MAP (Am), the maximum upstroke velocity (Vmax), as well as action potential durations (APDs) at different repolarization levels (APD30, APD50, APD70, and APD90) of MAP were determined and analyzed in detail. There were no significant differences in RR and P intervals between CT-1-CP-treated groups and control group, but the PR segment and the QRS complex were greater in the former than in the latter (F=2.681 and 5.462 respectively, P<0.05). Though QT interval and the corrected QT interval (QTc) were shorter in CT-1-CP-treated groups than in control group, the QT dispersion (QTd) of them was greater in the latter than in the former (F=3.090, P<0.05) and increased with the time. The ECG monitoring synchronously with the MAP showed that the compression of MAP electrode on the left ventricular epicardium induced performance similar to myocardium ischemia. As compared with those before chest-opening, the PR segment and QT intervals remained basically unchanged in control group, but prolonged significantly in all CT-1-CP-treated groups and the prolongation of QT intervals increased gradually along with the time of exposure to CT-1-CP. The QRS complex had no significant change in control group, one-week and three-week CT-1-CP-treated groups, but prolonged significantly in two-week and four-week CT-1-CP-treated groups. Interestingly, the QTd after chest-opening was significantly greater than that before chest-opening in control group (t=5.242, P<0.01), but decreased along with the time in CT-1-CP-treated groups. The mean MAP amplitude, Vmax and APD were greater in CT-1-CP-treated groups than those in control group, and became more obvious along with the time. The APD in four CT-1-CP-treat groups was prolonged mainly in middle to final repolarization phase. The difference among these groups became significant in middle phase (APD50) (F=6.076, P<0.01) and increased furthermore in late and final phases (APD70: F=10.054; APD90: F=18.691, P<0.01) along with the time of injection of CT-1-CP. The chronic action of CT-1-CP might induce the adapting alteration in cardiac conductivity and ventricular repolarization. The amplitude and the Vmax of the anterior LV epicardial MAP increased obviously, and the APD prolonged mainly in late and final phase of repolarization.

Electrophysiological effects of haloperidol on isolated rabbit Purkinje fibers and guinea pigs papillary muscles under normal and simulated ischemia.

PubMed

Yan, Dong; Cheng, Lu-feng; Song, Hong-Yan; Turdi, Subat; Kerram, Parhat

2007-08-01

Overdoses of haloperidol are associated with major ventricular arrhythmias, cardiac conduction block, and sudden death. The aim of this experiment was to study the effect of haloperidol on the action potentials in cardiac Purkinje fibers and papillary muscles under normal and simulated ischemia conditions in rabbits and guinea pigs. Using the standard intracellular microelectrode technique, we examined the effects of haloperidol on the action potential parameters [action potential amplitude (APA), phase 0 maximum upstroke velocity (V(max)), action potential amplitude at 90% of repolarization (APD(90)), and effective refractory period (ERP)] in rabbit cardiac Purkinje fibers and guinea pig cardiac papillary cells, in which both tissues were under simulated ischemic conditions. Under ischemic conditions, different concentrations of haloperidol depressed APA and prolonged APD(90) in a concentration-dependent manner in rabbit Purkinje fibers. Haloperidol (3 micromol/L) significantly depressed APA and prolonged APD(90), and from 1 micromol/L, haloperidol showed significant depression on V(max); ERP was not significantly affected. In guinea pig cardiac papillary muscles, the thresholds of significant reduction in APA, V(max), EPR, and APD(90) were 10, 0.3, 1, and 1 mumol/L, respectively, for haloperidol. Compared with cardiac conductive tissues, papillary muscles were more sensitive to ischemic conditions. Under ischemia, haloperidol prolonged ERP and APD(90) in a concentration-dependent manner and precipitated the decrease in V(max) induced by ischemia. The shortening of ERP and APD(90) in papillary muscle action potentials may be inhibited by haloperidol.

Development of HgCdTe single-element APDs based detectors for low flux short wave infrared applications

NASA Astrophysics Data System (ADS)

Foubert, K.; Lasfargues, G.; Mathieu, L.; Benahmed, S.; Vojetta, G.; Rothman, J.; Benoît à la Guillaume, Q.; Calvo, Vincent; Picot-Clemente, Jérémy; Le Mounier, Florent; Gibert, Fabien

2013-03-01

The remarkable properties (internal gain larger than 100 and close to unity excess noise factor) of Short Wave Infrared (SWIR) HgCdTe electron-initiated Avalanche Photodiodes (e-APDs) are put to good use to demanding applications, i.e. spectroscopy and LIDAR. Knowing the requirements of both situations, we have designed specific models based on highly sensitive single elements APDs and adapted proximity electronics. On one hand, we use the e-APDs low noise equivalent power (NEP) at 180K (few fW/Hz1/2). We simultaneously designed a specific Transimpedance Amplifier (TIA) which allows us to take advantage of the low APD NEP. The combination of both elements along with a dedicated cryostat enables direct LIDAR detection at moderate bandwidth (BW = 20 MHz) without the need for long time averaging, which is crucial in far field (>= 5 km) analysis. One the other hand, we have optimized a low-noise and low-frequency LN2 cooled prototype operating with an external commercial amplifier. It allows us to observe the photoluminescence of Ge nanostructures in the range 1.5-2.5 μm with a significantly increased SNR along with a reduce pump laser power. The possibility to use these detectors in the photon counting limit will be discussed in light of our recent results. In parallel, we present preliminary time response measurements performed on SWIR APD suggesting that a higher GHz BW could be reached with this type of detector. This is however subjected to optical optimization at the moment.

Slow adaptation of ventricular repolarization as a cause of arrhythmia?

PubMed

Bueno-Orovio, A; Hanson, B M; Gill, J S; Taggart, P; Rodriguez, B

2014-01-01

This article is part of the Focus Theme of Methods of Information in Medicine on "Biosignal Interpretation: Advanced Methods for Studying Cardiovascular and Respiratory Systems". Adaptation of the QT-interval to changes in heart rate reflects on the body-surface electrocardiogram the adaptation of action potential duration (APD) at the cellular level. The initial fast phase of APD adaptation has been shown to modulate the arrhythmia substrate. Whether the slow phase is potentially proarrhythmic remains unclear. To analyze in-vivo human data and use computer simulations to examine effects of the slow APD adaptation phase on dispersion of repolarization and reentry in the human ventricle. Electrograms were acquired from 10 left and 10 right ventricle (LV/RV) endocardial sites in 15 patients with normal ventricles during RV pacing. Activation-recovery intervals, as a surrogate for APD, were measured during a sustained increase in heart rate. Observed dynamics were studied using computer simulations of human tissue electrophysiology. Spatial heterogeneity of rate adaptation was observed in all patients. Inhomogeneity in slow APD adaptation time constants (Δτ(s)) was greater in LV than RV (Δτ(s)(LV) = 31.8 ± 13.2, Δτ(s)(RV) = 19.0 ± 12.8 s , P< 0.01). Simulations showed that altering local slow time constants of adaptation was sufficient to convert partial wavefront block to block with successful reentry. Using electrophysiological data acquired in-vivo in human and computer simulations, we identify heterogeneity in the slow phase of APD adaptation as an important component of arrhythmogenesis.

Acute alteration of cardiac ECG, action potential, I{sub Kr} and the human ether-a-go-go-related gene (hERG) K{sup +} channel by PCB 126 and PCB 77

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Mi-Hyeong; Park, Won Sun; Jo, Su-Hyun, E-mail: suhyunjo@kangwon.ac.kr

2012-07-01

Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K{sup +} current (I{sub Kr}) of guinea pigs' hearts, and hERG K{sup +} current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD{sub 90}), and 50% of repolarization (APD{sub 50}) (P < 0.05) without changing the action potential duration at 20% (APD{submore » 20}). PCB 77 decreased APD{sub 20} (P < 0.05) without affecting QTc, APD{sub 90}, and APD{sub 50}. The PCB 126 increased the I{sub Kr} in guinea-pig ventricular myocytes held at 36 °C and hERG K{sup +} current amplitude at the end of the voltage steps in voltage-dependent mode (P < 0.05); however, PCB 77 did not change the hERG K{sup +} current amplitude. The PCB 77 increased the diastolic Ca{sup 2+} and decreased Ca{sup 2+} transient amplitude (P < 0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD{sub 90} possibly by increasing I{sub Kr}, while PCB 77 decreased the APD{sub 20} possibly by other modulation related with intracellular Ca{sup 2+}. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca{sup 2+}, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body. -- Highlights: ► PCBs are known as serious environmental pollutants and developmental disruptors. ► PCB 126 shortened QT interval of ECG and action potential duration. ► PCB 126 increased human ether-a-go-go-related K{sup +} current and I{sub Kr}. ► PCB 77 decreased action potential duration and increased intracellular Ca{sup 2+} content. ► PCBs acutely change cardiac electrophysiology and rhythmicity.« less

Is low affect consciousness related to the severity of psychopathology? A cross-sectional study of patients with avoidant and borderline personality disorder.

PubMed

Normann-Eide, Eivind; Johansen, Merete Selsbakk; Normann-Eide, Tone; Egeland, Jens; Wilberg, Theresa

2013-02-01

This study examined the relationships between affect consciousness (AC) and symptom distress, interpersonal problems, low self-esteem, and the number of PD traits in patients with avoidant personality disorder (APD) and borderline personality disorder (BPD). Within the setting of a treatment trial, 52 patients with APD or BPD were examined with structured interviews and self-report questionnaires before treatment and at 3-year follow-up. The evaluations included the Affect Consciousness Interview, the SCID-II interview, the Symptom Checklist 90-R, the Circumplex of Interpersonal Problems, and the Index of Self-esteem. A low global level of AC was expected to be associated with the severity of psychopathology; a low AC for interest, joy, and tenderness was expected to be associated with social detachment; and a low AC for anger, contempt, and disgust was expected to be associated with nonassertiveness. A low AC was associated with interpersonal problems and low self-esteem, but not symptom distress or the number of fulfilled SCID-II criteria. Despite a significant reduction in the psychopathology based on most clinical variables, the associations measured at baseline were maintained after 3years. Examination of specific affect categories showed a pattern of convergent and discriminative relationships with different types of interpersonal problems. A low AC for pleasant affects was specifically related to communion problems, like cold, detached behavior, both at baseline and follow-up. In contrast, a low AC for self-boundary affects was specifically related to agency problems, like non-assertiveness, at follow-up. Our results showed that a low AC was associated with central domains of psychopathology in patients with PDs. This suggested that AC would be an important focus for treatment and further research in PDs. Future studies are needed to examine how AC is related to various forms of personality pathology. Copyright © 2013 Elsevier Inc. All rights reserved.

Flecainide attenuates rate adaptation of ventricular repolarization in guinea-pig heart.

PubMed

Osadchii, Oleg E

2016-01-01

Flecainide is class Ic antiarrhythmic agent that was found to increase the risk of sudden cardiac death. Arrhythmic responses to flecainide could be precipitated by exercise, suggesting a role played by inappropriate rate adaptation of ventricular repolarization. This study therefore examined flecainide effect on adaptation of the QT interval and ventricular action potential duration (APD) to abrupt reductions of the cardiac cycle length. ECG and ventricular epicardial and endocardial monophasic APD were recorded in isolated, perfused guinea-pig heart preparations upon a sustained cardiac acceleration (rapid pacing for 30 s), and following a single perturbation of the cycle length evoked by extrasystolic stimulation. Sustained increase in heart rate was associated with progressive bi-exponential shortening of the QT interval and APD. Flecainide prolonged ventricular repolarization, delayed its rate adaptation, and decreased the amplitude of QT interval and APD shortening upon rapid cardiac pacing. During extrasystolic stimulation, flecainide attenuated APD shortening in premature ventricular beats, with effect being greater upon using a longer basic drive cycle length (S1-S1=550 ms versus S1-S1=300 ms). Flecainide-induced arrhythmia may be partly accounted for by attenuated adaptation of ventricular repolarization to sudden changes in cardiac cycle length provoked by transient tachycardia or ectopic beats.

Update on Linear Mode Photon Counting with the HgCdTe Linear Mode Avalanche Photodiode

NASA Technical Reports Server (NTRS)

Beck, Jeffrey D.; Kinch, Mike; Sun, Xiaoli

2014-01-01

The behavior of the gain-voltage characteristic of the mid-wavelength infrared cutoff HgCdTe linear mode avalanche photodiode (e-APD) is discussed both experimentally and theoretically as a function of the width of the multiplication region. Data are shown that demonstrate a strong dependence of the gain at a given bias voltage on the width of the n- gain region. Geometrical and fundamental theoretical models are examined to explain this behavior. The geometrical model takes into account the gain-dependent optical fill factor of the cylindrical APD. The theoretical model is based on the ballistic ionization model being developed for the HgCdTe APD. It is concluded that the fundamental theoretical explanation is the dominant effect. A model is developed that combines both the geometrical and fundamental effects. The model also takes into account the effect of the varying multiplication width in the low bias region of the gain-voltage curve. It is concluded that the lower than expected gain seen in the first 2 × 8 HgCdTe linear mode photon counting APD arrays, and higher excess noise factor, was very likely due to the larger than typical multiplication region length in the photon counting APD pixel design. The implications of these effects on device photon counting performance are discussed.

Interplanetary Space Weather Effects on Lunar Reconnaissance Orbiter Avalanche Photodiode Performance

NASA Technical Reports Server (NTRS)

Clements, E. B.; Carlton, A. K.; Joyce, C. J.; Schwadron, N. A.; Spence, H. E.; Sun, X.; Cahoy, K.

2016-01-01

Space weather is a major concern for radiation-sensitive space systems, particularly for interplanetary missions, which operate outside of the protection of Earth's magnetic field. We examine and quantify the effects of space weather on silicon avalanche photodiodes (SiAPDs), which are used for interplanetary laser altimeters and communications systems and can be sensitive to even low levels of radiation (less than 50 cGy). While ground-based radiation testing has been performed on avalanche photodiode (APDs) for space missions, in-space measurements of SiAPD response to interplanetary space weather have not been previously reported. We compare noise data from the Lunar Reconnaissance Orbiter (LRO) Lunar Orbiter Laser Altimeter (LOLA) SiAPDs with radiation measurements from the onboard Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument. We did not find any evidence to support radiation as the cause of changes in detector threshold voltage during radiation storms, both for transient detector noise and long-term average detector noise, suggesting that the approximately 1.3 cm thick shielding (a combination of titanium and beryllium) of the LOLA detectors is sufficient for SiAPDs on interplanetary missions with radiation environments similar to what the LRO experienced (559 cGy of radiation over 4 years).

Reliable InP-based Geiger-mode avalanche photodiode arrays

NASA Astrophysics Data System (ADS)

Smith, Gary M.; McIntosh, K. Alex; Donnelly, Joseph P.; Funk, Joseph E.; Mahoney, Leonard J.; Verghese, Simon

2009-05-01

Arrays as large as 256 x 64 of single-photon counting avalanche photodiodes have been developed for defense applications in free-space communication and laser radar. Focal plane arrays (FPAs) sensitive to both 1.06 and 1.55 μm wavelength have been fabricated for these applications. At 240 K and 4 V overbias, the dark count rate (DCR) of 15 μm diameter devices is typically 250 Hz for 1.06 μm sensitive APDs and 1 kHz for 1.55 μm APDs. Photon detection efficiencies (PDE) at 4 V overbias are about 45% for both types of APDs. Accounting for microlens losses, the full FPA has a PDE of 30%. The reset time needed for a pixel to avoid afterpulsing at 240 K is about 3-4 μsec. These devices have been used by system groups at Lincoln Laboratory and other defense contractors for building operational systems. For these fielded systems the device reliability is a strong concern. Individual APDs as well as full arrays have been run for over 1000 hrs of accelerated testing to verify their stability. The reliability of these GM-APDs is shown to be under 10 FITs at operating temperatures of 250 K, which also corresponds to an MTTF of 17,100 yrs.

Characterization of Advanced Avalanche Photodiodes for Water Vapor Lidar Receivers

NASA Technical Reports Server (NTRS)

Refaat, Tamer F.; Halama, Gary E.; DeYoung, Russell J.

2000-01-01

Development of advanced differential absorption lidar (DIAL) receivers is very important to increase the accuracy of atmospheric water vapor measurements. A major component of such receivers is the optical detector. In the near-infrared wavelength range avalanche photodiodes (APD's) are the best choice for higher signal-to-noise ratio, where there are many water vapor absorption lines. In this study, characterization experiments were performed to evaluate a group of silicon-based APD's. The APD's have different structures representative of different manufacturers. The experiments include setups to calibrate these devices, as well as characterization of the effects of voltage bias and temperature on the responsivity, surface scans, noise measurements, and frequency response measurements. For each experiment, the setup, procedure, data analysis, and results are given and discussed. This research was done to choose a suitable APD detector for the development of an advanced atmospheric water vapor differential absorption lidar detection system operating either at 720, 820, or 940 nm. The results point out the benefits of using the super low ionization ratio (SLIK) structure APD for its lower noise-equivalent power, which was found to be on the order of 2 to 4 fW/Hz(sup (1/2)), with an appropriate optical system and electronics. The water vapor detection systems signal-to-noise ratio will increase by a factor of 10.

Detection of cat-eye effect echo based on unit APD

NASA Astrophysics Data System (ADS)

Wu, Dong-Sheng; Zhang, Peng; Hu, Wen-Gang; Ying, Jia-Ju; Liu, Jie

2016-10-01

The cat-eye effect echo of optical system can be detected based on CCD, but the detection range is limited within several kilometers. In order to achieve long-range even ultra-long-range detection, it ought to select APD as detector because of the high sensitivity of APD. The detection system of cat-eye effect echo based on unit APD is designed in paper. The implementation scheme and key technology of the detection system is presented. The detection performances of the detection system including detection range, detection probability and false alarm probability are modeled. Based on the model, the performances of the detection system are analyzed using typical parameters. The results of numerical calculation show that the echo signal-to-noise ratio is greater than six, the detection probability is greater than 99.9% and the false alarm probability is less tan 0.1% within 20 km detection range. In order to verify the detection effect, we built the experimental platform of detection system according to the design scheme and carry out the field experiments. The experimental results agree well with the results of numerical calculation, which prove that the detection system based on the unit APD is feasible to realize remote detection for cat-eye effect echo.

C-RED One : the infrared camera using the Saphira e-APD detector

NASA Astrophysics Data System (ADS)

Greffe, Timothée.; Feautrier, Philippe; Gach, Jean-Luc; Stadler, Eric; Clop, Fabien; Lemarchand, Stephane; Boutolleau, David; Baker, Ian

2016-08-01

Name for Person Card: Observatoire de la Côte d'Azur First Light Imaging' C-RED One infrared camera is capable of capturing up to 3500 full frames per second with a sub-electron readout noise and very low background. This breakthrough has been made possible thanks to the use of an e- APD infrared focal plane array which is a real disruptive technology in imagery. C-RED One is an autonomous system with an integrated cooling system and a vacuum regeneration system. It operates its sensor with a wide variety of read out techniques and processes video on-board thanks to an FPGA. We will show its performances and expose its main features. The project leading to this application has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement N° 673944.

78 FR 40745 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-08

.... Description: The Advance Planning Document (APD) process, established in the rules at 45 CFR part 95, subpart F, is the procedure by which States request and obtain approval for Federal financial participation... Advance Planning Document 34 1.2 120 4,896 Operational Advance Planning Document 20 1 30 600 Estimated...

42 CFR 433.117 - Initial approval of replacement systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... and Information Retrieval Systems § 433.117 Initial approval of replacement systems. (a) A replacement system must meet all conditions of initial approval of a mechanized claims processing and information retrieval system. (b) The agency must submit a APD that includes— (1) The date the replacement system will...

78 FR 14556 - Proposed Information Collection Activity; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-06

... for ACF. OMB No.: 0992-0005. Description: The Advance Planning Document (APD) process, established in... Biennial Reports 54 1 1.50 81 Advance Planning Document 34 1.2 120 4,896 Operational Advance Planning... for the proper performance of the functions of the agency, including whether the information shall...

Increased Late Sodium Current Contributes to the Electrophysiological Effects of Chronic, but Not Acute, Dofetilide Administration.

PubMed

Qiu, Xiaoliang S; Chauveau, Samuel; Anyukhovsky, Evgeny P; Rahim, Tania; Jiang, Ya-Ping; Harleton, Erin; Feinmark, Steven J; Lin, Richard Z; Coronel, Ruben; Janse, Michiel J; Opthof, Tobias; Rosen, Tove S; Cohen, Ira S; Rosen, Michael R

2016-04-01

Drugs are screened for delayed rectifier potassium current (IKr) blockade to predict long QT syndrome prolongation and arrhythmogenesis. However, single-cell studies have shown that chronic (hours) exposure to some IKr blockers (eg, dofetilide) prolongs repolarization additionally by increasing late sodium current (INa-L) via inhibition of phosphoinositide 3-kinase. We hypothesized that chronic dofetilide administration to intact dogs prolongs repolarization by blocking IKr and increasing INa-L. We continuously infused dofetilide (6-9 μg/kg bolus+6-9 μg/kg per hour IV infusion) into anesthetized dogs for 7 hours, maintaining plasma levels within the therapeutic range. In separate experiments, myocardial biopsies were taken before and during 6-hour intravenous dofetide infusion, and the level of phospho-Akt was determined. Acute and chronic dofetilide effects on action potential duration (APD) were studied in canine left ventricular subendocardial slabs using microelectrode techniques. Dofetilide monotonically increased QTc and APD throughout 6.5-hour exposure. Dofetilide infusion during ≥210 minutes inhibited Akt phosphorylation. INa-L block with lidocaine shortened QTc and APD more at 6.5 hours than at 50 minutes (QTc) or 30 minutes (APD) dofetilide administration. In comparison, moxifloxacin, an IKr blocker with no effects on phosphoinositide 3-kinase and INa-L prolonged APD acutely but no additional prolongation occurred on chronic superfusion. Lidocaine shortened APD equally during acute and chronic moxifloxacin superfusion. Increased INa-L contributes to chronic dofetilide effects in vivo. These data emphasize the need to include time and INa-L in evaluating the phosphoinositide 3-kinase inhibition-derived proarrhythmic potential of drugs and provide a mechanism for benefit from lidocaine administration in clinical acquired long QT syndrome. © 2016 American Heart Association, Inc.

Contrasting effects of increased and decreased dopamine transmission on latent inhibition in ovariectomized rats and their modulation by 17beta-estradiol: an animal model of menopausal psychosis?

PubMed

Arad, Michal; Weiner, Ina

2010-06-01

Women with schizophrenia have later onset and better response to antipsychotic drugs (APDs) than men during reproductive years, but the menopausal period is associated with increased symptom severity and reduced treatment response. Estrogen replacement therapy has been suggested as beneficial but clinical data are inconsistent. Latent inhibition (LI), the capacity to ignore irrelevant stimuli, is a measure of selective attention that is disrupted in acute schizophrenia patients and in rats and humans treated with the psychosis-inducing drug amphetamine and can be reversed by typical and atypical APDs. Here we used amphetamine (1 mg/kg)-induced disrupted LI in ovariectomized rats to model low levels of estrogen along with hyperfunction of the dopaminergic system that may be occurring in menopausal psychosis, and tested the efficacy of APDs and estrogen in reversing disrupted LI. 17beta-Estradiol (50, 150 microg/kg), clozapine (atypical APD; 5, 10 mg/kg), and haloperidol (typical APD; 0.1, 0.3 mg/kg) effectively reversed amphetamine-induced LI disruption in sham rats, but were much less effective in ovariectomized rats; 17beta-estradiol and clozapine were effective only at high doses (150 microg/kg and 10 mg/kg, respectively), whereas haloperidol failed at both doses. Haloperidol and clozapine regained efficacy if coadministered with 17beta-estradiol (50 microg/kg, an ineffective dose). Reduced sensitivity to dopamine (DA) blockade coupled with spared/potentiated sensitivity to DA stimulation after ovariectomy may provide a novel model recapitulating the combination of increased vulnerability to psychosis with reduced response to APD treatment in female patients during menopause. In addition, our data show that 17beta-estradiol exerts antipsychotic activity.

Enhanced basal late sodium current appears to underlie the age-related prolongation of action potential duration in guinea pig ventricular myocytes.

PubMed

Song, Yejia; Belardinelli, Luiz

2017-12-14

Aging hearts have prolonged QT interval and are vulnerable to oxidative stress. Because the QT interval indirectly reflects the action potential duration (APD), we examined the hypotheses that 1) the APD of ventricular myocytes increases with age; 2) the age-related prolongation of APD is due to an enhancement of basal late Na + current (I NaL ); 3) inhibition of I NaL may protect aging hearts from arrhythmogenic effects of hydrogen peroxide (H 2 O 2 ). Experiments were performed on ventricular myocytes isolated from one-month (young) and one-year (old) guinea pigs (GPs). The APD of myocytes from old GPs was significantly longer than that from young GPs and was shortened by the I NaL inhibitors GS967 and tetrodotoxin. The magnitude of I NaL was significantly larger in myocytes from old than from young GPs. The CaMKII inhibitors KN-93 and AIP and the Na V 1.5-channel blocker MTSEA blocked the I NaL . There were no significant differences between myocytes from young and old GPs in L-type Ca 2+ current and the rapidly- and slowly-activating delayed rectifier K + currents, although the inward rectifier K + current was slightly decreased in myocytes from old GPs. H 2 O 2 induced more early afterdepolarizations in myocytes from old than from young GPs. The effect of H 2 O 2 was attenuated by GS967. The results suggest that 1) the APD of myocytes from old GPs is prolonged, 2) a CaMKII-mediated increase in Na V 1.5-channel I NaL is responsible for the prolongation of APD, and 3) Inhibition of I NaL may be beneficial for maintaining electrical stability under oxidative stress in myocytes of old GPs.

An Acoustic Charge Transport Imager for High Definition Television Applications: Reliability Modeling and Parametric Yield Prediction of GaAs Multiple Quantum Well Avalanche Photodiodes. Degree awarded Oct. 1997

NASA Technical Reports Server (NTRS)

Hunt, W. D.; Brennan, K. F.; Summers, C. J.; Yun, Ilgu

1994-01-01

Reliability modeling and parametric yield prediction of GaAs/AlGaAs multiple quantum well (MQW) avalanche photodiodes (APDs), which are of interest as an ultra-low noise image capture mechanism for high definition systems, have been investigated. First, the effect of various doping methods on the reliability of GaAs/AlGaAs multiple quantum well (MQW) avalanche photodiode (APD) structures fabricated by molecular beam epitaxy is investigated. Reliability is examined by accelerated life tests by monitoring dark current and breakdown voltage. Median device lifetime and the activation energy of the degradation mechanism are computed for undoped, doped-barrier, and doped-well APD structures. Lifetimes for each device structure are examined via a statistically designed experiment. Analysis of variance shows that dark-current is affected primarily by device diameter, temperature and stressing time, and breakdown voltage depends on the diameter, stressing time and APD type. It is concluded that the undoped APD has the highest reliability, followed by the doped well and doped barrier devices, respectively. To determine the source of the degradation mechanism for each device structure, failure analysis using the electron-beam induced current method is performed. This analysis reveals some degree of device degradation caused by ionic impurities in the passivation layer, and energy-dispersive spectrometry subsequently verified the presence of ionic sodium as the primary contaminant. However, since all device structures are similarly passivated, sodium contamination alone does not account for the observed variation between the differently doped APDs. This effect is explained by the dopant migration during stressing, which is verified by free carrier concentration measurements using the capacitance-voltage technique.

Properties and ionic mechanisms of action potential adaptation, restitution, and accommodation in canine epicardium.

PubMed

Decker, Keith F; Heijman, Jordi; Silva, Jonathan R; Hund, Thomas J; Rudy, Yoram

2009-04-01

Computational models of cardiac myocytes are important tools for understanding ionic mechanisms of arrhythmia. This work presents a new model of the canine epicardial myocyte that reproduces a wide range of experimentally observed rate-dependent behaviors in cardiac cell and tissue, including action potential (AP) duration (APD) adaptation, restitution, and accommodation. Model behavior depends on updated formulations for the 4-aminopyridine-sensitive transient outward current (I(to1)), the slow component of the delayed rectifier K(+) current (I(Ks)), the L-type Ca(2+) channel current (I(Ca,L)), and the Na(+)-K(+) pump current (I(NaK)) fit to data from canine ventricular myocytes. We found that I(to1) plays a limited role in potentiating peak I(Ca,L) and sarcoplasmic reticulum Ca(2+) release for propagated APs but modulates the time course of APD restitution. I(Ks) plays an important role in APD shortening at short diastolic intervals, despite a limited role in AP repolarization at longer cycle lengths. In addition, we found that I(Ca,L) plays a critical role in APD accommodation and rate dependence of APD restitution. Ca(2+) entry via I(Ca,L) at fast rate drives increased Na(+)-Ca(2+) exchanger Ca(2+) extrusion and Na(+) entry, which in turn increases Na(+) extrusion via outward I(NaK). APD accommodation results from this increased outward I(NaK). Our simulation results provide valuable insight into the mechanistic basis of rate-dependent phenomena important for determining the heart's response to rapid and irregular pacing rates (e.g., arrhythmia). Accurate simulation of rate-dependent phenomena and increased understanding of their mechanistic basis will lead to more realistic multicellular simulations of arrhythmia and identification of molecular therapeutic targets.

Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate.

PubMed

Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O'Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

2014-06-01

Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Activation recovery intervals measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady-state pacing, whilst subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Hemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (P=0.001). APD decreased during the stressful parts of the film clip, for example, for global right ventricular activation recovery interval at end of film clip 193.8 ms (SD, 14) versus 198.0 ms (SD, 13) during the matched breathing control (end film left ventricle 199.8 ms [SD, 16] versus control 201.6 ms [SD, 15]; P=0.004). Respiration rate increased during the stressful part of the film clip (by 2 breaths per minute) and was well matched in the respective control period without any hemodynamic or activation recovery interval changes. Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular APD in conscious humans. The effect of mental challenge on APD was not secondary to emotionally induced altered respiration or heart rate. © 2014 American Heart Association, Inc.

Evaluation of a HgCdTe e-APD based detector for 2  μm CO2 DIAL application.

PubMed

Dumas, Arnaud; Rothman, Johan; Gibert, Fabien; Édouart, Dimitri; Lasfargues, Gilles; Cénac, Claire; Mounier, Florian Le; Pellegrino, Jessica; Zanatta, Jean-Paul; Bardoux, Alain; Tinto, Francesc; Flamant, Pierre

2017-09-20

Benefiting from close to ideal amplification properties (high gain, low dark current, and low excess noise factor), HgCdTe electron initiated avalanche photodiode (e-APD) technology exhibits state of the art sensitivity, thus being especially relevant for applications relying on low light level detection, such as LIDAR (Light Detection And Ranging). In addition, the tunable gap of the Hg 1-x Cd x Te alloy enables coverage of the short wavelength infrared (SWIR) and especially the 2 μm spectral range. For these two reasons, a HgCdTe e-APD based detector is a promising candidate for future differential absorption LIDAR missions targeting greenhouse gas absorption bands in SWIR. In this study, we report on the design and evaluation of such a HgCdTe e-APD based detector. The first part focuses on detector architecture and performance. Key figures of merit are: 2.8 μm cutoff wavelength, 200 μm diameter almost circular sensitive area, 185 K operating temperature (thermo-electric cooling), 22 APD gain (at 12 V reverse bias), 360  kΩ transimpedance gain, and 60  fWHz -0.5 noise equivalent power (at 12 V reverse bias). The second part presents an analysis of atmospheric LIDAR signals obtained by mounting the HgCdTe e-APD based detector on the 2 μm differential absorption LIDAR developed at the Laboratoire de Météorologie Dynamique and dedicated to CO 2 monitoring. Discussion emphasizes random and systematic errors in LIDAR measurements regarding breadboard detector characterization. In particular, we investigate the influence of parasitic tails in detector impulse response on short range DIAL measurements.

Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study.

PubMed

Coulter, Tanya I; Chandra, Anita; Bacon, Chris M; Babar, Judith; Curtis, James; Screaton, Nick; Goodlad, John R; Farmer, George; Steele, Cathal Laurence; Leahy, Timothy Ronan; Doffinger, Rainer; Baxendale, Helen; Bernatoniene, Jolanta; Edgar, J David M; Longhurst, Hilary J; Ehl, Stephan; Speckmann, Carsten; Grimbacher, Bodo; Sediva, Anna; Milota, Tomas; Faust, Saul N; Williams, Anthony P; Hayman, Grant; Kucuk, Zeynep Yesim; Hague, Rosie; French, Paul; Brooker, Richard; Forsyth, Peter; Herriot, Richard; Cancrini, Caterina; Palma, Paolo; Ariganello, Paola; Conlon, Niall; Feighery, Conleth; Gavin, Patrick J; Jones, Alison; Imai, Kohsuke; Ibrahim, Mohammad A A; Markelj, Gašper; Abinun, Mario; Rieux-Laucat, Frédéric; Latour, Sylvain; Pellier, Isabelle; Fischer, Alain; Touzot, Fabien; Casanova, Jean-Laurent; Durandy, Anne; Burns, Siobhan O; Savic, Sinisa; Kumararatne, D S; Moshous, Despina; Kracker, Sven; Vanhaesebroeck, Bart; Okkenhaug, Klaus; Picard, Capucine; Nejentsev, Sergey; Condliffe, Alison M; Cant, Andrew James

2017-02-01

Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described combined immunodeficiency resulting from gain-of-function mutations in PIK3CD, the gene encoding the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ). We sought to review the clinical, immunologic, histopathologic, and radiologic features of APDS in a large genetically defined international cohort. We applied a clinical questionnaire and performed review of medical notes, radiology, histopathology, and laboratory investigations of 53 patients with APDS. Recurrent sinopulmonary infections (98%) and nonneoplastic lymphoproliferation (75%) were common, often from childhood. Other significant complications included herpesvirus infections (49%), autoinflammatory disease (34%), and lymphoma (13%). Unexpectedly, neurodevelopmental delay occurred in 19% of the cohort, suggesting a role for PI3Kδ in the central nervous system; consistent with this, PI3Kδ is broadly expressed in the developing murine central nervous system. Thoracic imaging revealed high rates of mosaic attenuation (90%) and bronchiectasis (60%). Increased IgM levels (78%), IgG deficiency (43%), and CD4 lymphopenia (84%) were significant immunologic features. No immunologic marker reliably predicted clinical severity, which ranged from asymptomatic to death in early childhood. The majority of patients received immunoglobulin replacement and antibiotic prophylaxis, and 5 patients underwent hematopoietic stem cell transplantation. Five patients died from complications of APDS. APDS is a combined immunodeficiency with multiple clinical manifestations, many with incomplete penetrance and others with variable expressivity. The severity of complications in some patients supports consideration of hematopoietic stem cell transplantation for severe childhood disease. Clinical trials of selective PI3Kδ inhibitors offer new prospects for APDS treatment. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Short-term action potential memory and electrical restitution: A cellular computational study on the stability of cardiac repolarization under dynamic pacing

PubMed Central

2018-01-01

Electrical restitution (ER) is a major determinant of repolarization stability and, under fast pacing rate, it reveals memory properties of the cardiac action potential (AP), whose dynamics have never been fully elucidated, nor their ionic mechanisms. Previous studies have looked at ER mainly in terms of changes in AP duration (APD) when the preceding diastolic interval (DI) changes and described dynamic conditions where this relationship shows hysteresis which, in turn, has been proposed as a marker of short-term AP memory and repolarization stability. By means of numerical simulations of a non-propagated human ventricular AP, we show here that measuring ER as APD versus the preceding cycle length (CL) provides additional information on repolarization dynamics which is not contained in the companion formulation. We focus particularly on fast pacing rate conditions with a beat-to-beat variable CL, where memory properties emerge from APD vs CL and not from APD vs DI and should thus be stored in APD and not in DI. We provide an ion-currents characterization of such conditions under periodic and random CL variability, and show that the memory stored in APD plays a stabilizing role on AP repolarization under pacing rate perturbations. The gating kinetics of L-type calcium current seems to be the main determinant of this safety mechanism. We also show that, at fast pacing rate and under otherwise identical pacing conditions, a periodically beat-to-beat changing CL is more effective than a random one in stabilizing repolarization. In summary, we propose a novel view of short-term AP memory, differentially stored between systole and diastole, which opens a number of methodological and theoretical implications for the understanding of arrhythmia development. PMID:29494628

Characterization of irradiated APDs for picosecond time measurements

NASA Astrophysics Data System (ADS)

Centis Vignali, M.; Dalal, R.; Gallinaro, M.; Harrop, B.; Jain, G.; Lu, C.; McClish, M.; McDonald, K. T.; Moll, M.; Newcomer, F. M.; Ugobono, S. Otero; White, S.

2018-01-01

For their operation at the CERN High Luminosity Large Hadron Collider (HL-LHC), the ATLAS and CMS experiments are planning to implement dedicated systems to measure the time of arrival of minimum ionizing particles with an accuracy of about 30 ps. The timing detectors will be subjected to radiation levels corresponding up to a 1-MeV neutrons fluence (Φeq) of 1015 cm-2 for the goal integrated luminosity of HL-LHC of 3000 fb-1. In this paper, deep-diffused Avalanche Photo Diodes (APDs) produced by Radiation Monitoring Devices are examined as candidate timing detectors for HL-LHC applications. These APDs are operated at 1.8 kV, resulting in a gain of up to 500. The timing performance of the detectors is evaluated using a pulsed laser. The effects of radiation damage on current, signal amplitude, noise, and timing performance of the APDs are evaluated using detectors irradiated with neutrons up to Φeq = 1015 cm-2.

A retrospective cohort study on the association between periapical abscess, advanced periodontal disease, and the national oral health screening program among Korean adults.

PubMed

Ha, Jung-Eun; Jung, Se-Hwan; Jin, Bo-Hyoung; Lee, Byoung-Jin; Bae, Kwang-Hak

2013-09-01

The National Oral Health Screening Program (NOHSP) is a general population-based program in Korea. The objective of this study was to assess the association between participation in the NOHSP and dental visit for periapical abscess (PA) and advanced periodontal disease (APD) among Korean adults. Data were obtained for subjects from the National Health Insurance database. The authors conducted a retrospective cohort study of 9358 randomly selected subjects who were between 40 and 64 years old in 2002. The outcomes of dental visit for PA or APD from the years 2003 to 2007 were compared between the screening and nonscreening groups. The nonscreening group had 19% higher risk of PA and 15% higher risk of APD. This study suggests that the NOHSP may decrease the risk of dental visit because of PA and APD by preventing the progress of lesion to the advanced stage among Korean adults.

Current 2-μm dial measurements of atmospheric CO2 and expected results from space using new MCT APDS

NASA Astrophysics Data System (ADS)

Dumas, A.; Gibert, F.; Rothman, J.; Édouart, D.; Le Mounier, F.; Cénac, C.

2017-11-01

In the framework of CO2 monitoring in the Atmospheric Boundary Layer (ABL), a ground-based 2-μm Differential Absorption Lidar (DIAL) has been developed at the Laboratoire de Météorologie Dynamique (LMD) in Palaiseau. In order to derive flux information, this system has been set up with coherent detection, which allows to combine CO2 density measurements with wind velocity measurements. On the other hand, new advances in the field of Mercury Cadmium Tellure (MCT) Avalanche Photodiodes (APDs) open the way for high-precision measurements in direct detection ultimately from space. In this study, we first report on state of the art measurements obtained with the current coherent DIAL system before presenting expected results for a similar laser transmitter equipped with MCT APDs. For this latter part, we use a numerical model which relies on APDs performance data provided by the Laboratoire d'Électronique et de Technologie de l'Information (LETI).

Environmental Radiation Measurements on MIR Station

NASA Astrophysics Data System (ADS)

Benton, E. V.; Frank, A. L.; Benton, E. R.

1997-04-01

Environmental radiation levels on the Russian space station Mir are being monitored under differing shielding conditions by a series of six area passive dosimeters (APDs) placed at individual locations inside the Core and Kvant 2 modules, and by an External Dosimeter Array (EDA) to be-deployed on the exterior surface of the Kvant 2 module. Each APD and the EDA contains CR-39 plastic nuclear track detectors (PNTDs) for measurement of LET spectra and TLDs for absorbed dose measurements. Two of the missions, NASA-2/Mir-21 and NASA-3/Mir-22 have been completed and the six APDs from each mission returned to Earth from Mir. This report covers progress to date on the analysis of TLDs and PNTDs from these two missions. For NASA-2/Mir-21, average mission absorbed dose rates varied from 271 to 407 micro-Gy/d at the APDS. For NASA-3/Mir-22, average mission absorbed dose rates varied from 265 to 421 micro-Gy/d.

The histopathologic features of autoimmune progesterone dermatitis.

PubMed

James, Travis; Ghaferi, Jessica; LaFond, Ann

2017-01-01

The histologic features of autoimmune progesterone dermatitis (APD) are generally non-specific and have been described only in brief case reports. We present a case of APD and review the literature with a focus on the histologic findings described. A review of the English literature on APD was performed using PubMed and MEDLINE. A total of 39 patients, including our patient are included in this review. The most consistent histologic finding reported was a perivascular inflammatory infiltrate, being seen in 72% of cases. A non-specific or interstitial inflammatory infiltrate was described in 31% of the cases, with 41% having an eosinophilic component and 21% having a neutrophilic component mixed with the predominant lymphocytic infiltrate. Interface dermatitis was the second most common finding with 36% showing a mild to exaggerated interface dermatitis. Although histopathologic changes are non-specific, perivascular dermatitis with eosinophils and interface changes are common in APD. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Environmental Radiation Measurements on MIR Station. Program 1; Internal Experiment

NASA Technical Reports Server (NTRS)

Benton, E. V.; Frank, A. L.; Benton, E. R.

1997-01-01

Environmental radiation levels on the Russian space station Mir are being monitored under differing shielding conditions by a series of six area passive dosimeters (APDs) placed at individual locations inside the Core and Kvant 2 modules, and by an External Dosimeter Array (EDA) to be-deployed on the exterior surface of the Kvant 2 module. Each APD and the EDA contains CR-39 plastic nuclear track detectors (PNTDs) for measurement of LET spectra and TLDs for absorbed dose measurements. Two of the missions, NASA-2/Mir-21 and NASA-3/Mir-22 have been completed and the six APDs from each mission returned to Earth from Mir. This report covers progress to date on the analysis of TLDs and PNTDs from these two missions. For NASA-2/Mir-21, average mission absorbed dose rates varied from 271 to 407 micro-Gy/d at the APDS. For NASA-3/Mir-22, average mission absorbed dose rates varied from 265 to 421 micro-Gy/d.

White noise effects of U.S. crude oil spot prices on stock prices of a publicly traded company: A case study cross-correlation analysis based on green energy management theory

NASA Astrophysics Data System (ADS)

Roberts, Peter M.

The purpose of this study was to examine white noise effects of U.S. crude oil spot prices on the stock prices of a green energy company. Epistemological, Phenomenological, Axiological and Ontological assumptions of Green Energy Management (GEM) Theory were utilized for selecting Air Products and Chemicals Inc. (APD) as the case study. Exxon Mobil (XOM) was used as a control for triangulation purposes. The period of time examined was between January of 1999 and December of 2008. Monthly stock prices for APD and XOM for the ten year period of time were collected from the New York Stock Exchange. Monthly U.S. crude oil spot prices for the ten year period of time were collected from the US Energy Information Administration. The data was entered into SPSS 17.0 software in order to conduct cross-correlation analysis. The six cross-correlation assumptions were satisfied in order to conduct a Cross-correlation Mirror Test (CCMT). The CCMT established the lag time direction and verified that U.S. crude oil spot prices serve as white noise for stock prices of APD and XOM. The Theory of Relative Weakness was employed in order to analyze the results. A 2 year period of time between December, 2006 and December, 2008 was examined. The correlation coefficient r = - .155 indicates that U.S. crude oil spot prices lead APD stock prices by 4 months. During the same 2 year period of time, U.S. crude oil spot prices lead XOM stock prices by 4 months at r = -.283. XOM stock prices and APD stock prices were positively correlated with 0 lag in time with a positive r = .566. The 4 month cycle was an exact match between APD stock prices, XOM stock prices and U.S. crude oil spot prices. The 4 month cycle was due to the random price fluctuation of U.S. crude oil spot prices that obscured the true stock prices of APD and XOM for the 2 year period of time.

III-V strain layer superlattice based band engineered avalanche photodiodes (Presentation Recording)

NASA Astrophysics Data System (ADS)

Ghosh, Sid

2015-08-01

Laser detection and ranging (LADAR)-based systems operating in the Near Infrared (NIR) and Short Wave Infrared (SWIR) have become popular optical sensors for remote sensing, medical, and environmental applications. Sophisticated laser-based radar and weapon systems used for long-range military and astronomical applications need to detect, recognize, and track a variety of targets under a wide spectrum of atmospheric conditions. Infrared APDs play an important role in LADAR systems by integrating the detection and gain stages in a single device. Robust silicon-APDs are limited to visible and very near infrared region (< 1 um), while InGaAs works well up to wavelengths of about 1.5um. Si APDs have low multiplication or excess noise but are limited to below 1um due very poor quantum efficiency above 0.8um. InGaAs and Ge APDs operate up to wavelengths of 1.5um but have poor multiplication or excess noise due to a low impact ionization coefficient ratio between electrons and holes. For the past several decades HgCdTe has been traditionally used in longer wavelength (> 3um) infrared photon detection applications. Recently, various research groups (including Ghosh et. al.) have reported SWIR and MWIR HgCdTe APDs on CdZnTe and Si substrates. However, HgCdTe APDs suffer from low breakdown fields due to material defects, and excess noise increases significantly at high electric fields. During the past decade, InAs/GaSb Strain Layer Superlattice (SLS) material system has emerged as a potential material for the entire infrared spectrum because of relatively easier growth, comparable absorption coefficients, lower tunneling currents and longer Auger lifetimes resulting in enhanced detectivities (D*). Band engineering in type II SLS allows us to engineer avalanche properties of electrons and holes. This is a great advantage over bulk InGaAs and HgCdTe APDs where engineering avalanche properties is not possible. The talk will discuss the evolution of superlattice based avalanche photodiodes and some of the recent results on the work being done at Raytheon on SWIR avalanche photodiodes.

Simultaneous Quantification of Spatially Discordant Alternans in Voltage and Intracellular Calcium in Langendorff-Perfused Rabbit Hearts and Inconsistencies with Models of Cardiac Action Potentials and Ca Transients

PubMed Central

Uzelac, Ilija; Ji, Yanyan C.; Hornung, Daniel; Schröder-Scheteling, Johannes; Luther, Stefan; Gray, Richard A.; Cherry, Elizabeth M.; Fenton, Flavio H.

2017-01-01

Rationale: Discordant alternans, a phenomenon in which the action potential duration (APDs) and/or intracellular calcium transient durations (CaDs) in different spatial regions of cardiac tissue are out of phase, present a dynamical instability for complex spatial dispersion that can be associated with long-QT syndrome (LQTS) and the initiation of reentrant arrhythmias. Because the use of numerical simulations to investigate arrhythmic effects, such as acquired LQTS by drugs is beginning to be studied by the FDA, it is crucial to validate mathematical models that may be used during this process. Objective: In this study, we characterized with high spatio-temporal resolution the development of discordant alternans patterns in transmembrane voltage (Vm) and intracellular calcium concentration ([Cai]+2) as a function of pacing period in rabbit hearts. Then we compared the dynamics to that of the latest state-of-the-art model for ventricular action potentials and calcium transients to better understand the underlying mechanisms of discordant alternans and compared the experimental data to the mathematical models representing Vm and [Cai]+2 dynamics. Methods and Results: We performed simultaneous dual optical mapping imaging of Vm and [Cai]+2 in Langendorff-perfused rabbit hearts with higher spatial resolutions compared with previous studies. The rabbit hearts developed discordant alternans through decreased pacing period protocols and we quantified the presence of multiple nodal points along the direction of wave propagation, both in APD and CaD, and compared these findings with results from theoretical models. In experiments, the nodal lines of CaD alternans have a steeper slope than those of APD alternans, but not as steep as predicted by numerical simulations in rabbit models. We further quantified several additional discrepancies between models and experiments. Conclusions: Alternans in CaD have nodal lines that are about an order of magnitude steeper compared to those of APD alternans. Current action potential models lack the necessary coupling between voltage and calcium compared to experiments and fail to reproduce some key dynamics such as, voltage amplitude alternans, smooth development of calcium alternans in time, conduction velocity and the steepness of the nodal lines of APD and CaD. PMID:29104543

Efficient entanglement distribution over 200 kilometers.

PubMed

Dynes, J F; Takesue, H; Yuan, Z L; Sharpe, A W; Harada, K; Honjo, T; Kamada, H; Tadanaga, O; Nishida, Y; Asobe, M; Shields, A J

2009-07-06

Here we report the first demonstration of entanglement distribution over a record distance of 200 km which is of sufficient fidelity to realize secure communication. In contrast to previous entanglement distribution schemes, we use detection elements based on practical avalanche photodiodes (APDs) operating in a self-differencing mode. These APDs are low-cost, compact and easy to operate requiring only electrical cooling to achieve high single photon detection efficiency. The self-differencing APDs in combination with a reliable parametric down-conversion source demonstrate that entanglement distribution over ultra-long distances has become both possible and practical. Consequently the outlook is extremely promising for real world entanglement-based communication between distantly separated parties.

45 CFR 95.605 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Equipment and Services-Conditions for Federal Financial Participation (FFP) General § 95.605 Definitions. As... acquiring ADP equipment or services from commercial sources or from State or local government resources... use of ADP services or equipment. The term APD refers to a Planning APD, or to a planning and/or...

A human ventricular cell model for investigation of cardiac arrhythmias under hyperkalaemic conditions.

PubMed

Carro, Jesús; Rodríguez, José Félix; Laguna, Pablo; Pueyo, Esther

2011-11-13

In this study, several modifications were introduced to a recently proposed human ventricular action potential (AP) model so as to render it suitable for the study of ventricular arrhythmias. These modifications were driven by new sets of experimental data available from the literature and the analysis of several well-established cellular arrhythmic risk biomarkers, namely AP duration at 90 per cent repolarization (APD(90)), AP triangulation, calcium dynamics, restitution properties, APD(90) adaptation to abrupt heart rate changes, and rate dependence of intracellular sodium and calcium concentrations. The proposed methodology represents a novel framework for the development of cardiac cell models. Five stimulation protocols were applied to the original model and the ventricular AP model developed here to compute the described arrhythmic risk biomarkers. In addition, those models were tested in a one-dimensional fibre in which hyperkalaemia was simulated by increasing the extracellular potassium concentration, [K(+)](o). The effective refractory period (ERP), conduction velocity (CV) and the occurrence of APD alternans were investigated. Results show that modifications improved model behaviour as verified by: (i) AP triangulation well within experimental limits (the difference between APD at 50 and 90 per cent repolarization being 78.1 ms); (ii) APD(90) rate adaptation dynamics characterized by fast and slow time constants within physiological ranges (10.1 and 105.9 s); and (iii) maximum S1S2 restitution slope in accordance with experimental data (S(S1S2)=1.0). In simulated tissues under hyperkalaemic conditions, APD(90) progressively shortened with the degree of hyperkalaemia, whereas ERP increased once a threshold in [K(+)](o) was reached ([K(+)](o)≈6 mM). CV decreased with [K(+)](o), and conduction was blocked for [K(+)](o)>10.4 mM. APD(90) alternans were observed for [K(+)](o)>9.8 mM. Those results adequately reproduce experimental observations. This study demonstrated the value of basing the development of AP models on the computation of arrhythmic risk biomarkers, as opposed to joining together independently derived ion channel descriptions to produce a whole-cell AP model, with the new framework providing a better picture of the model performance under a variety of stimulation conditions. On top of replicating experimental data at single-cell level, the model developed here was able to predict the occurrence of APD(90) alternans and areas of conduction block associated with high [K(+)](o) in tissue, which is of relevance for the investigation of the arrhythmogenic substrate in ischaemic hearts.

Attenuated subjective ratings and skin conductance responses to neutral and negative pictures in non-psychopathic mentally disordered offenders with various diagnoses.

PubMed

Wahlund, Katarina; Sorman, Karolina; Gavazzeni, Joachim; Fischer, Håkan; Kristiansson, Marianne

2010-11-30

Altered autonomic arousal in relation to offending behavior has mainly been investigated in subjects with varying degrees of psychopathic traits. The present study sets out to investigate subjective ratings and skin conductance responses (SCRs) in mentally disordered offenders with various diagnoses but without psychopathy, specifically recruited from the forensic psychiatric system. Two subgroups were investigated; an antisocial group with antisocial personality disorder (APD) or antisocial traits (n=16) and a non-antisocial group with various diagnoses (n=25), in relation to a healthy non-criminal control group (n=20). All participants were male. SCRs and subjective ratings of arousal and valence were measured for neutral and negative pictures from the International Affective Picture System (IAPS). The offenders showed significantly lower SCRs and subjective ratings than the control group. Moreover, there was no significant difference between antisocial and non-antisocial offenders, indicating that antisocial behavior might not be a differential factor. Thus, attenuated emotional responses may be a characteristic shared by mentally disordered offenders overall. Copyright © 2009 Elsevier Ltd. All rights reserved.

Temporal dependence of transient dark counts in an avalanche photodiode: A solution for power-law behavior of afterpulsing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akiba, M., E-mail: akiba@nict.go.jp; Tsujino, K.

This paper offers a theoretical explanation of the temperature and temporal dependencies of transient dark count rates (DCRs) measured for a linear-mode silicon avalanche photodiode (APD) and the dependencies of afterpulsing that were measured in Geiger-mode Si and InGaAs/InP APDs. The temporal dependencies exhibit power-law behavior, at least to some extent. For the transient DCR, the value of the DCR for a given time period increases with decreases in temperature, while the power-law behavior remains unchanged. The transient DCR is attributed to electron emissions from traps in the multiplication layer of the APD with a high electric field, and itsmore » temporal dependence is explained by a continuous change in the electron emission rate as a function of the electric field strength. The electron emission rate is calculated using a quantum model for phonon-assisted tunnel emission. We applied the theory to the temporal dependence of afterpulsing that was measured for Si and InGaAs/InP APDs. The power-law temporal dependence is attributed to the power-law function of the electron emission rate from the traps as a function of their position across the p–n junction of the APD. Deviations from the power-law temporal dependence can be derived from the upper and lower limits of the electric field strength.« less

FACT - Status and experience from five years of operation of the first G-APD Cherenkov Telescope

NASA Astrophysics Data System (ADS)

Neise, D.; Adam, J.; Ahnen, M. L.; Baack, D.; Balbo, M.; Bergmann, M.; Biland, A.; Blank, M.; Bretz, T.; Brügge, K. A.; Buss, J.; Dmytriiev, A.; Dorner, D.; Einecke, S.; Hempfling, C.; Hildebrand, D.; Hughes, G.; Linhoff, L.; Mannheim, K.; Müller, S.; Neronov, A.; Nöthe, M.; Paravac, A.; Pauss, F.; Rhode, W.; Shukla, A.; Temme, F.; Thaele, J.; Walter, R.

2017-12-01

The First G-APD Cherenkov Telescope (FACT) demonstrates the usability of novel Geiger-mode operated Avalanche Photo Diodes (G-APD, often called SiPM) for Imaging Atmospheric Cherenkov Telescopes (IACT). The camera consists of 1440 pixels with dedicated electronics operating at 2 Giga samples per second. It is installed on the refurbished HEGRA telescope with a mirror area of ≈ 9.5m2 on the Canary Island La Palma. FACT is taking data almost every night since the camera was installed in October 2011. It was possible to improve the data taking efficiency to very high values due to the very stable and reliable operation. This also allows to operate FACT remotely without any need for operators on site. Even remote human intervention became less and less frequent over the years, allowing operation to become mostly automatic. FACT is monitoring the long-term behavior of some very-high energy variable extra-galactic sources with unparalleled sampling density as well as testing the behavior of the sensors under severe weather conditions. Due to the long exposure of FACT's G-APDs under strong moonlight conditions it was possible to evaluate the aging effects of G-APDs due to collected charge. No indication of aging was found. No external calibration device is needed to operate FACT since the properties of the sensors themselves allow for a high precision self-calibration of the camera.

Paradoxical Effects of Sodium-Calcium Exchanger Inhibition on Torsade de Pointes and Early Afterdepolarization in a Heart Failure Rabbit Model.

PubMed

Chang, Po-Cheng; Lu, Yu-Ying; Lee, Hui-Ling; Lin, Shien-Fong; Chu, Yen; Wen, Ming-Shien; Chou, Chung-Chuan

2018-05-03

Calcium homeostasis plays an important role in development of early afterdepolarizations (EADs) and torsade de pointes (TdP). The role of sodium-calcium exchanger (NCX) inhibition in genesis secondary Ca rise and EADs-TdP is still debated. Dual voltage and intracellular Ca optical mapping were conducted in 6 control and 9 failing rabbit hearts. After baseline electrophysiological and optical mapping studies, E4031 was given to simulate long QT syndrome. ORM-10103 was then administrated to examine the electrophysiological effects on EAD-TdP development. E4031 enhanced secondary Ca rise, EADs development and TdP inducibility in both control and failing hearts. The results showed that ORM-10103 reduced premature ventricular beats (PVBs) but was unable to suppress the inducibility of TdP or EADs. The electrophysiological effects of ORM-10103 included prolongation of action potential duration (APD) and increased APD heterogeneity in failing hearts. ORM10103 had a neutral effect on the amplitude of secondary Cai rise in control and HF groups. In this model, most EADs generated from the long-short APD junction area. In conclusion, highly selective NCX inhibition with ORM-10103 reduced PVB burden but was unable to suppress secondary Ca rise, EADs development nor inducibility of TdP. The possible electrophysiological mechanisms include APD prolongation and increased APD heterogeneity.

Ultra-violet avalanche photodiode based on AlN/GaN periodically-stacked-structure

NASA Astrophysics Data System (ADS)

Wu, Xingzhao; Zheng, Jiyuan; Wang, Lai; Brault, Julien; Matta, Samuel; Hao, Zhibiao; Sun, Changzheng; Xiong, Bing; Luo, Yi; Han, Yianjun; Wang, Jian; Li, Hongtao; Khalfioui, Mohamed A.; Li, Mo; Kang, Jianbin; Li, Qian

2018-02-01

The high-gain photomultiplier tube (PMT) is the most popular method to detect weak ultra-violet signals which attenuate quickly in atmosphere, although the vacuum tube makes it fragile and difficult to integrate. To overcome the disadvantage of PMT, an AlN/GaN periodically-stacked-structure (PSS) avalanche photodiode (APD) has been proposed, finally achieving good quality of high gain and low excessive noise. As there is a deep g valley only in the conduction band of both GaN and AlN, the electron transfers suffering less scattering and thus becomes easier to obtain the threshold of ionization impact. Because of unipolar ionization in the PSS APD, it works in linear mode. Four prototype devices of 5-period, 10-period, 15-period, and 20-period were fabricated to verify that the gain of APD increases exponentially with period number. And in 20-period device, a recorded high and stable gain of 104 was achieved under constant bias. In addition, it is proved both experimentally and theoretically, that temperature stability on gain is significantly improved in PSS APD. And it is found that the resonant enhancement in interfacial ionization may bring significant enhancement of electron ionization performance. To make further progress in PSS APD, the device structure is investigated by simulation. Both the gain and temperature stability are optimized alternatively by a proper design of periodical thickness and AlN layer occupancy.

78 FR 37819 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

.... Description: The Advance Planning Document (APD) process, established in the rules at 45 CFR Part 95, Subpart F, is the procedure by which States request and obtain approval for Federal financial participation... Advance Planning Document 34 1.2 120 4,896 Operational Advance Planning Document 20 1 30 600 [[Page 37820...

45 CFR 205.35 - Mechanized claims processing and information retrieval systems; definitions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... software and hardware used: (1) To introduce, control and account for data items in providing public... undertaken, and the resources required to complete the project; (2) The preparation of an APD; (3) The preparation of a detailed project plan describing when and how the computer system will be designed and...

Analysis and modeling of optical crosstalk in InP-based Geiger-mode avalanche photodiode FPAs

NASA Astrophysics Data System (ADS)

Chau, Quan; Jiang, Xudong; Itzler, Mark A.; Entwistle, Mark; Piccione, Brian; Owens, Mark; Slomkowski, Krystyna

2015-05-01

Optical crosstalk is a major factor limiting the performance of Geiger-mode avalanche photodiode (GmAPD) focal plane arrays (FPAs). This is especially true for arrays with increased pixel density and broader spectral operation. We have performed extensive experimental and theoretical investigations on the crosstalk effects in InP-based GmAPD FPAs for both 1.06-μm and 1.55-μm applications. Mechanisms responsible for intrinsic dark counts are Poisson processes, and their inter-arrival time distribution is an exponential function. In FPAs, intrinsic dark counts and cross talk events coexist, and the inter-arrival time distribution deviates from purely exponential behavior. From both experimental data and computer simulations, we show the dependence of this deviation on the crosstalk probability. The spatial characteristics of crosstalk are also demonstrated. From the temporal and spatial distribution of crosstalk, an efficient algorithm to identify and quantify crosstalk is introduced.

Growth of antiphase-domain-free GaP on Si substrates by metalorganic chemical vapor deposition using an in situ AsH{sub 3} surface preparation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, Emily L., E-mail: emily.warren@nrel.gov; Kibbler, Alan E.; France, Ryan M.

2015-08-24

Antiphase-domain (APD) free GaP films were grown on Si(100) substrates prepared by annealing under dilute AsH{sub 3} in situ in an MOCVD reactor. LEED and AES surface analysis of Si(100) surfaces prepared by this treatment show that AsH{sub 3} etching quickly removes O and C contaminants at a relatively low temperature (690–740 °C), and creates a single-domain “A-type” As/Si surface reconstruction. The resulting GaP epilayers grown at the same temperature are APD-free, and could thereby serve as templates for direct growth of III-V semiconductors on Si. This single chamber process has a low thermal budget, and can enable heteroepitaxial integration ofmore » III-Vs and Si at an industrial scale.« less

Orbiter Docking System/Spacelab-Mir Module in Atlantis

NASA Technical Reports Server (NTRS)

1995-01-01

The STS-71 mission payload is in its final flight configuration after integration into the payload bay of the Space Shuttle orbiter Atlantis and prior to payload bay door closing and rollover of the spaceplane from Orbiter Processing Facility Bay 3 to the Vehicle Assembly Building. In the foreground is the Orbiter Docking System (ODS) that is topped with the red Russian- built Androgynous Peripheral Docking System (APDS). During the 11-day mission, the APDS will lock together with a similar system on the Russian Mir Space Station so that the two spacecraft can remain docked together for four days. The ODS features an airlock that will provide access to and from both the Mir and orbiter for the U.S. and Russian flight crews. A Spacelab transfer tunnel runs from the ODS to the Spacelab-Mir module, where joint U.S. medical experiments will be conducted during the 11-day spaceflight.

45 CFR 307.15 - Approval of advance planning documents for computerized support enforcement systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES COMPUTERIZED SUPPORT ENFORCEMENT SYSTEMS..., organization, services and constraints related to the computerized support enforcement system; (4) The APD must... design, development, installation or enhancement; (5) The APD must contain a description of each...

45 CFR 307.15 - Approval of advance planning documents for computerized support enforcement systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES COMPUTERIZED SUPPORT ENFORCEMENT SYSTEMS..., organization, services and constraints related to the computerized support enforcement system; (4) The APD must... design, development, installation or enhancement; (5) The APD must contain a description of each...

45 CFR 307.15 - Approval of advance planning documents for computerized support enforcement systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES COMPUTERIZED SUPPORT ENFORCEMENT SYSTEMS..., organization, services and constraints related to the computerized support enforcement system; (4) The APD must... design, development, installation or enhancement; (5) The APD must contain a description of each...

Automatic Channel Fault Detection on a Small Animal APD-Based Digital PET Scanner

NASA Astrophysics Data System (ADS)

Charest, Jonathan; Beaudoin, Jean-François; Cadorette, Jules; Lecomte, Roger; Brunet, Charles-Antoine; Fontaine, Réjean

2014-10-01

Avalanche photodiode (APD) based positron emission tomography (PET) scanners show enhanced imaging capabilities in terms of spatial resolution and contrast due to the one to one coupling and size of individual crystal-APD detectors. However, to ensure the maximal performance, these PET scanners require proper calibration by qualified scanner operators, which can become a cumbersome task because of the huge number of channels they are made of. An intelligent system (IS) intends to alleviate this workload by enabling a diagnosis of the observational errors of the scanner. The IS can be broken down into four hierarchical blocks: parameter extraction, channel fault detection, prioritization and diagnosis. One of the main activities of the IS consists in analyzing available channel data such as: normalization coincidence counts and single count rates, crystal identification classification data, energy histograms, APD bias and noise thresholds to establish the channel health status that will be used to detect channel faults. This paper focuses on the first two blocks of the IS: parameter extraction and channel fault detection. The purpose of the parameter extraction block is to process available data on individual channels into parameters that are subsequently used by the fault detection block to generate the channel health status. To ensure extensibility, the channel fault detection block is divided into indicators representing different aspects of PET scanner performance: sensitivity, timing, crystal identification and energy. Some experiments on a 8 cm axial length LabPET scanner located at the Sherbrooke Molecular Imaging Center demonstrated an erroneous channel fault detection rate of 10% (with a 95% confidence interval (CI) of [9, 11]) which is considered tolerable. Globally, the IS achieves a channel fault detection efficiency of 96% (CI: [95, 97]), which proves that many faults can be detected automatically. Increased fault detection efficiency would be advantageous but, the achieved results would already benefit scanner operators in their maintenance task.

Development of Si-APD Timing Detectors for Nuclear Resonant Scattering using High-energy Synchrotron X-rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kishimoto, Shunji; Zhang Xiaowei; Yoda, Yoshitaka

2007-01-19

A timing detector with silicon avalanche photodiodes (Si-APDs) has been developed for nuclear resonant scattering using synchrotron x-rays. The detector had four pairs of a germanium plate 0.1mm thick and a Si-APD (3 mm in dia., a depletion layer of 30-{mu}m thickness). Using synchrotron x-rays of 67.4 keV, the efficiency increased to 1.5% for the incident beam, while the efficiency was 0.76 % without the germanium converters. A measurement of SR-PAC on Ni-61 was executed by using the detector. Some other types of timing detectors are planned for x-rays of E>20 keV.

Performance enhancement of GaN ultraviolet avalanche photodiodes with p-type δ-doping

NASA Astrophysics Data System (ADS)

Bayram, C.; Pau, J. L.; McClintock, R.; Razeghi, M.

2008-06-01

High quality δ-doped p-GaN is used as a means of improving the performance of back-illuminated GaN avalanche photodiodes (APDs). Devices with δ-doped p-GaN show consistently lower leakage current and lower breakdown voltage than those with bulk p-GaN. APDs with δ-doped p-GaN also achieve a maximum multiplication gain of 5.1×104, more than 50 times higher than that obtained in devices with bulk p-GaN. The better device performance of APDs with δ-doped p-GaN is attributed to the higher structural quality of the p-GaN layer achieved via δ-doping.

AlInAsSb separate absorption, charge, and multiplication avalanche photodiodes

NASA Astrophysics Data System (ADS)

Ren, Min; Maddox, Scott J.; Woodson, Madison E.; Chen, Yaojia; Bank, Seth R.; Campbell, Joe C.

2016-05-01

We report AlxIn1-xAsySb1-y separate absorption, charge, and multiplication avalanche photodiodes (APDs) that operate in the short-wavelength infrared spectrum. They exhibit excess noise factor less or equal to that of Si and the low dark currents typical of III-V compound APDs.

45 CFR 1355.56 - Failure to meet the conditions of the approved APD.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 4 2012-10-01 2012-10-01 false Failure to meet the conditions of the approved APD. 1355.56 Section 1355.56 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF..., YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND FAMILY SERVICES...

45 CFR 1355.56 - Failure to meet the conditions of the approved APD.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 4 2014-10-01 2014-10-01 false Failure to meet the conditions of the approved APD. 1355.56 Section 1355.56 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF..., YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND FAMILY SERVICES...

45 CFR 1355.56 - Failure to meet the conditions of the approved APD.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 4 2011-10-01 2011-10-01 false Failure to meet the conditions of the approved APD. 1355.56 Section 1355.56 Public Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF..., YOUTH AND FAMILIES, FOSTER CARE MAINTENANCE PAYMENTS, ADOPTION ASSISTANCE, AND CHILD AND FAMILY SERVICES...

Magnetic Properties and Moessbauer Spectra of Several Iron(III) Dicarboxylic Acid Complexes.

DTIC Science & Technology

1980-10-01

model CS-202 Displex Cryogenic refrigerator with a model APD-E temperature controller manufactured by Air Products and Chemicals , Inc ., Allentown, Pa...coupled tL a special, helium gas filled shroud, Model DMX-20, supplied by Air Products and Chemicals , Inc . Infrared spectra were obtained on a Beckman IR

Study of gain and photoresponse characteristics for back-illuminated separate absorption and multiplication GaN avalanche photodiodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xiaodong; Pan, Ming; Hou, Liwei

2014-01-07

The gain and photoresponse characteristics have been numerically studied for back-illuminated separate absorption and multiplication (SAM) GaN avalanche photodiodes (APDs). The parameters of fundamental models are calibrated by simultaneously comparing the simulated dark and light current characteristics with the experimental results. Effects of environmental temperatures and device dimensions on gain characteristics have been investigated, and a method to achieve the optimum thickness of charge layer is obtained. The dependence of gain characteristics and breakdown voltage on the doping concentration of the charge layer is also studied in detail to get the optimal charge layer. The bias-dependent spectral responsivity and quantummore » efficiency are then presented to study the photoresponse mechanisms inside SAM GaN APDs. It is found the responsivity peak red-shifts at first due to the Franz-Keldysh effect and then blue-shifts due to the reach-through effect of the absorption layer. Finally, a new SAM GaN/AlGaN heterojunction APD structure is proposed for optimizing SAM GaN APDs.« less

Precautionary measures reduce risk of definite neuroleptic malignant syndrome in newly typical neuroleptic-treated schizophrenia inpatients.

PubMed

Shiloh, Roni; Valevski, Avi; Bodinger, Liron; Misgav, Sagit; Aizenberg, Dov; Dorfman-Etrog, Pnina; Weizman, Abraham; Munitz, Hanan

2003-05-01

Neuroleptic malignant syndrome (NMS) is a potentially lethal antipsychotic drug (APD)-induced thermoregulatory disturbance. We hypothesized that several precautionary measures taken after administeration of APDs might prevent progression to definite NMS. The study group included 657 consecutively admitted drug-free schizophrenia inpatients who received various typical APDs for 28 days. Specific predefined precautionary measures were employed for this group. The comparison group (n=192) consisted of typical APD-treated schizophrenia inpatients in whom such precautionary measures were not imposed. The study group exhibited a significantly lower incidence of definite NMS (1/657=0.2% versus 4/192=2.1%; P=0.01, odds ratio=13.96; 95% confidence interval 1.55-125.63). Antipsychotics were discontinued in 28 patients (28/657=4.3%) from the study group due to NMS (n=1) or early detection of potential NMS-related signs (probable abortive NMS) (n=27). Our findings suggest that specific precautionary measures can effectively reduce the incidence of definite NMS by approximately one order in newly medicated schizophrenia inpatients.

Further Characterization of the Predictive Validity of the Brattleboro Rat Model for Antipsychotic Efficacy

PubMed Central

Feifel, D.; Shilling, P. D.; Melendez, G.

2014-01-01

Our laboratory and others have reported that Brattleboro (BRAT) rats, a Long Evans (LE) strain with a single gene mutation, have inherent deficits in prepulse inhibition (PPI) homologous to those observed in schizophrenia patients and that these deficits are reversed by antipsychotic drugs (APDs). To further evaluate the potential predictive validity of BRAT rat PPI for APDs, we compared the effects of acute subcutaneous administration of the typical APD chlorpromazine to that of three psychotropic drugs without antipsychotic efficacy, the antidepressant imipramine, the anxiolytic diazepam and the anticonvulsant mood stabilizer valproic acid on male and female BRAT rat PPI. Male and female BRAT rats exhibited baseline (saline treatment) PPI that was not different from each other (21.1 % and 21.3 %, respectively) and low compared to those historically exhibited by LE rats (approximately 59 %). Chlorpromazine facilitated PPI in male and female BRAT rats, whereas imipramine, diazepam, and valproic acid had no significant effect on PPI. These results suggest that PPI in the BRAT rat responds specifically to drugs with APD efficacy but not psychotropic drugs of different therapeutic families. PMID:21106605

The 1.06 optical receiver. [avalanche photodiodes for laser range finders

NASA Technical Reports Server (NTRS)

Tomasetta, L. R.; Law, H. D.; Nakano, K.; Scholl, F. W.; Harris, J. S., Jr.

1978-01-01

High performance 1.06 micron m avalanche photodetectors (APDs), fabricated in the GaAlSb system, have high quantum efficiency (90 percent), high speed (risetime less than 60 ps) and low leakage currents (less than 50 na). The dark current represents more than an order of magnitude reduction compared to previously reported results. The high speed avalanche gain of these devices is between 20 and 50. The area uniformity is better than + or - 10 percent. GaAlAs APDs at 0.53 micron m have even faster speed, lower dark currents, and high speed gains of 100 to 200. Optical rangefinders based on measured APD performance parameters have far superior performance when compared to even ideal photomultiplier tubes in either a one color or two color rangefinder system. For a one color system, f factor of two lower time jitter can be achieved with identical transmitted power. The superiority of the APD based two color receiver is significant and exists in the entire range of desired time jitters (less than 100 ps) and received power levels.

Risk of antenatal psychosocial distress in indigenous women and its management at primary health care centres in Australia.

PubMed

Gausia, Kaniz; Thompson, Sandra C; Nagel, Tricia; Schierhout, Gill; Matthews, Veronica; Bailie, Ross

2015-01-01

This study explored the risk of antenatal psychosocial distress (APD) and associated potential factors and examined management aspects of risk of APD in women attending Aboriginal primary health care services in Australia. Audits of medical records of 797 pregnant women from 36 primary health centres in five jurisdictions (NSW, QLD, SA, WA and NT) were undertaken as part of a quality improvement programme. Information collected included mental health assessed by a standard screening tools, enquiry regarding social and emotional well-being (SEWB), depression management (including antidepressant medications) and referral. Around 18% (n=141) of women were at risk of APD based on assessment using a standard screening tool or by SEWB enquiry. There was a significant association between risk of distress and women's life style behaviours (e.g., alcohol, illicit drug use) and health centre characteristics. Of the 141 women, 16% (n= 22) were prescribed antidepressant drugs during pregnancy. A range of nonpharmaceutical mental health interventions were also recorded, including brief intervention of 61% (n=86), counselling of 57% (n=80) and cognitive behaviour therapy of 5% (n=7). About 39% (n=55) of women with APD were referred to external services for consultations with a psychiatrist, psychologist or social worker or to a women's refuge centre. The higher risk of APD associated with women's life style behaviour indicates that the better understanding of mental health in its cultural context is essential. Copyright © 2015 Elsevier Inc. All rights reserved.

Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes.

PubMed

Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W

2015-01-01

Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

Costs of home assistance for peritoneal dialysis: results of a European survey.

PubMed

Dratwa, M

2008-04-01

Assisted peritoneal dialysis (aPD) was 'invented' in France in 1977 and was immediately very well reimbursed. This has since helped to maintain a high French peritoneal dialysis (PD) penetration rate among elderly dependent patients who might enjoy a better quality of life by remaining in their own environment. The aim of this study was to investigate the present status of aPD funding in European countries through a questionnaire sent in 2006 to health authorities and commercial PD providers asking about reimbursement modalities (in euro ([euro]) per patient per year) for nurse aPD. Specific funding for aPD only exists in Belgium, Denmark, France, Switzerland, and one region of Spain (Canary Islands). Germany and the United Kingdom are testing pilot schemes. Compared to France, all other countries exhibit significant differences in reimbursement for similar services (performing bag exchanges or disconnections from/to a cycler, exit site care, monitoring weight as well as blood pressure and ultrafiltration, and also including transportation costs) both for continuous ambulatory peritoneal dialysis (CAPD) (23 400 vs 7280 \\[euro] per patient per year in Spain) and automated peritoneal dialysis (APD) (18 200 vs 5356 euro per patient per year in Belgium); these differences are difficult to understand and might reflect disparities in cost of living, national health-care budget, and/or mean nurses' salaries. Also, there is no correlation between these rates and the reimbursement for PD therapy itself. Only France and Belgium differentiate assisted CAPD and APD, but these differences do not reflect the time really spent at the patient's home. It is concluded that high reimbursement rates for assistance add significant extra cost to PD, but allow granting many dependent patients all the advantages of home therapy, instead of treating them with in-center hemodialysis which in any case still remains more expensive for our societies.

Renal, metabolic, and hormonal responses to proteins of different origin in normotensive, nonproteinuric type I diabetic patients.

PubMed

Kontessis, P A; Bossinakou, I; Sarika, L; Iliopoulou, E; Papantoniou, A; Trevisan, R; Roussi, D; Stipsanelli, K; Grigorakis, S; Souvatzoglou, A

1995-09-01

Whether the differences in renal function found in vegetarian compared with omnivorous subjects are related to quantity or quality of the protein is unknown. We have studied the renal function of nine normotensive, nonproteinuric type I diabetic patients who were fed in random order for 4 weeks either an animal protein diet (APD) (protein intake 1.1 g . kg-1 . day-1) or a vegetable protein diet VPD (protein intake 0.95 g . kg-1 . day-1). The two diets were isocaloric. In a crossover study, we measured glomerular filtration rate (GFR) (inulin clearance), renal plasma flow (RPF) (p-aminohippurate clearance), plasma amino acids, growth hormone, glucagon, insulin-like growth factor I-(IGF-I), and microalbuminuria. GFR and RPF were lower with the VPD than with the APD (89.9 +/- 4.1 vs. 105.6 +/- 5.1 ml . min-1 . 1.73 m-2, P < 0.05, and 425.7 +/- 22.2 vs. 477.8 +/- 32.2 ml . min-1 1.73m-2, P < 0.05, respectively). Renal vascular resistance (RVR) was higher with the VPD than with the APD (101 +/- 25 vs. 91 +/- 10 mmHg . min-1 . ml-1, P < 0.05). Filtration fraction (FF) remained unchanged after either diet. Fractional clearance of albumin fell with the VPD to 2.0 +/- 0.65 from 3.4 +/- 1.15 x 10-6 (P < 0.05). At the end of the APD and VPD, the plasma levels of growth hormone and glucagon did not differ significantly. Plasma levels of IGF-I were higher with the APD than with the VPD (1.1 +/- 0.6 vs. 0.9 +/- 0.13 U/ml, P < 0.05). Plasma concentrations of valine and lysine were significantly higher with the APD than with the VPD (234.6 +/- 30.3 vs. 164.5 +/- 25.4 mm1/1, P < 0.05, and 565 +/- 45.1 vs. 430 +/- 56.1 mmol/l, P < 0.05, respectively), whereas plasma valine was strongly correlated to the GFR (r = 0.832, P < 0.01). No differences were found in other amino acids. A VPD has significantly different renal effects from an APD equal in protein intake in normotensive type I diabetic patients. This could be explained partly by differences in plasma concentrations of amino acids and IGF-I.

Ultraviolet Light Curves of Gaia16apd in Superluminous Supernova Models

NASA Astrophysics Data System (ADS)

Tolstov, Alexey; Zhiglo, Andrey; Nomoto, Ken'ichi; Sorokina, Elena; Kozyreva, Alexandra; Blinnikov, Sergei

2017-08-01

Observations of Gaia16apd revealed extremely luminous ultraviolet emission among superluminous supernovae (SLSNe). Using radiation hydrodynamics simulations, we perform a comparison of UV light curves, color temperatures, and photospheric velocities between the most popular SLSN models: pair-instability supernova, magnetar, and interaction with circumstellar medium. We find that the interaction model is the most promising to explain the extreme UV luminosity of Gaia16apd. The differences in late-time UV emission and in color evolution found between the models can be used to link an observed SLSN event to the most appropriate model. Observations at UV wavelengths can be used to clarify the nature of SLSNe and more attention should be paid to them in future follow-up observations.

A Comprehensive Analysis of the Physical Properties of Advanced GaAs/AlGaAs Junctions

NASA Technical Reports Server (NTRS)

Menkara, Hicham M.

1996-01-01

Extensive studies have been performed on MQW junctions and structures because of their potential applications as avalanche photodetectors in optical communications and imaging systems. The role of the avalanche photodiode is to provide for the conversion of an optical signal into charge. Knowledge of junction physics, and the various carrier generation/recombination mechanisms, is crucial for effectively optimizing the conversion process and increasing the structure's quantum efficiency. In addition, the recent interest in the use of APDs in imaging systems has necessitated the development of semiconductor junctions with low dark currents and high gains for low light applications. Because of the high frame rate and high pixel density requirements in new imaging applications, it is necessary to provide some front-end gain in the imager to allow operation under reasonable light conditions. Understanding the electron/hole impact ionization process, as well as diffusion and surface leakage effects, is needed to help maintain low dark currents and high gains for such applications. In addition, the APD must be capable of operating with low power, and low noise. Knowledge of the effects of various doping configurations and electric field profiles, as well as the excess noise resulting from the avalanche process, are needed to help maintain low operating bias and minimize the noise output.

On the feasibility of utilizing active personal dosimeters worn on the chest to estimate occupational eye lens dose in x-ray angiography.

PubMed

Omar, Artur; Marteinsdottir, Maria; Kadesjö, Nils; Fransson, Annette

2015-06-01

The International Commission on Radiological Protection (ICRP) has recommended that the occupational dose limit to the eye lens be substantially reduced. To ensure compliance with these recommendations, monitoring of the occupational eye lens dose is essential in certain hospital work environments. For assessment of the eye lens dose it is recommended to use a supplementary dosimeter placed at a position adjacent to the eye(s). Wearing a dosimeter at eye level can, however, be impractical and distributing and managing additional dosimeters over long periods of time is cumbersome and costly for large clinical sites. An attractive alternative is to utilize active personal dosimeters (APDs), which are routinely used by clinical staff for real-time monitoring of the personal dose equivalent rate (H(p)(10)). In this work, a formalism for the determination of eye lens dose from the response of such APD's worn on the chest is proposed and evaluated. The evaluation is based on both phantom and clinical measurements performed in an x-ray angiography suite for interventional cardiology. The main results show that the eye lens dose to the primary operator and to the assisting clinical staff can be conservatively estimated from the APD response as D(eye)(conductor) = 2.0 APD chest and D(eye)(assisting) = 1.0 APD chest, respectively. However, care should be exercised for particularly short assisting staff and if radiation protection shields are misused. These concerns can be greatly mitigated if the clinical staff are provided with adequate radiation protection training.

Vulnerability to re-entry in simulated two-dimensional cardiac tissue: effects of electrical restitution and stimulation sequence.

PubMed

Tran, Diana X; Yang, Ming-Jim; Weiss, James N; Garfinkel, Alan; Qu, Zhilin

2007-12-01

Ventricular fibrillation is a lethal arrhythmia characterized by multiple wavelets usually starting from a single or figure-of-eight re-entrant circuit. Understanding the factors regulating vulnerability to the re-entry is essential for developing effective therapeutic strategies to prevent ventricular fibrillation. In this study, we investigated how pre-existing tissue heterogeneities and electrical restitution properties affect the initiation of re-entry by premature extrastimuli in two-dimensional cardiac tissue models. We studied two pacing protocols for inducing re-entry following the "sinus" rhythm (S1) beat: (1) a single premature (S2) extrastimulus in heterogeneous tissue; (2) two premature extrastimuli (S2 and S3) in homogeneous tissue. In the first case, the vulnerable window of re-entry is determined by the spatial dimension and extent of the heterogeneity, and is also affected by electrical restitution properties and the location of the premature stimulus. The vulnerable window first increases as the action potential duration (APD) difference between the inside and outside of the heterogeneous region increases, but then decreases as this difference increases further. Steeper APD restitution reduces the vulnerable window of re-entry. In the second case, electrical restitution plays an essential role. When APD restitution is flat, no re-entry can be induced. When APD restitution is steep, re-entry can be induced by an S3 over a range of S1S2 intervals, which is also affected by conduction velocity restitution. When APD restitution is even steeper, the vulnerable window is reduced due to collision of the spiral tips.

Diagnostic accuracy of neonatal kidney ultrasound in children having antenatal hydronephrosis without ureter and bladder abnormalities.

PubMed

Rianthavorn, Pornpimol; Limwattana, Sorawan

2015-10-01

To determine the diagnostic accuracy of anteroposterior renal pelvic diameter (APD) measurement and the society for fetal urology (SFU) grading in neonatal ultrasonography (USG) for detecting uropathy in newborns having antenatal isolated hydronephrosis (IH), characterized by hydronephrosis without ureter and bladder abnormalities, and to study time to resolution and factors predicting resolution of insignificant hydronephrosis. Ninety-six healthy newborns (129 kidneys) with IH, who underwent USG at age 7-30 days and voiding cystourethrography (VCUG) in conjunction with diuretic renography (DR) if APD > 10 mm or SFU grade 3-4 in neonatal USG, and at least a 12-month follow-up were divided into significant and insignificant hydronephrosis using the combined data of sequential USG, VCUG, and DR as the reference standard. Areas under the receiver operating characteristic plots (95 % CI) were 0.86 (0.79-0.94) versus 0.81 (0.73-0.89); p = 0.08, and 87.6 versus 79.8 % of cases were correctly classified, for APD ≥ 16 mm versus SFU grade 4, respectively. Ureteropelvic junction obstruction (UPJO) was the most common uropathy diagnosed. Of 85 kidneys with insignificant hydronephrosis, 57 underwent spontaneous resolution. The resolution rates were 24, 40, and 68 % at age 6, 12, and 24 months, respectively. APD was the only independent factor predicting resolution with the hazard ratio of 0.83 (95 % CI 0.74-0.92; p = 0.001). In IH, neonatal USG was a useful diagnostic tool to detect uropathy, mainly UPJO. Further investigation should be recommended when APD ≥ 16 mm or SFU grade 4.

Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour.

PubMed

Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Noble, Denis; Giles, Wayne

2017-11-01

In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, AP height and duration are key physiological variables. In addition, rate-dependent changes in ventricular AP duration (APD), and variations in APD at a fixed heart rate are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q-T intervals as criteria for safety pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence draws attention to the early repolarization phase of the action potential (and the J-wave of the ECG) as an additional important biomarker for arrhythmogenesis. Here we provide a mechanistic background to this early repolarization syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time- and voltage-dependent thresholds, and also demonstrating that both can show regenerative all-or-none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as 'repolarization reserve'. For example, the complex pattern of cell-to-cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q-T interval of the electrocardiogram alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti-arrhythmic drugs). © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Low extracellular potassium prolongs repolarization and evokes early afterdepolarization in human induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Kuusela, Jukka; Larsson, Kim; Shah, Disheet; Prajapati, Chandra; Aalto-Setälä, Katriina

2017-06-15

Long QT syndrome (LQTS) is characterized by a prolonged QT-interval on electrocardiogram and by increased risk of sudden death. One of the most common and potentially life-threatening electrolyte disturbances is hypokalemia, characterized by low concentrations of K + Using a multielectrode array platform and current clamp technique, we investigated the effect of low extracellular K + concentration ([K + ] Ex ) on the electrophysiological properties of hiPSC-derived cardiomyocytes (CMs) generated from a healthy control subject (WT) and from two symptomatic patients with type 1 of LQTS carrying G589D (LQT1A) or IVS7-2A>G mutation (LQT1B) in KCNQ1 The baseline prolongations of field potential durations (FPDs) and action potential durations (APDs) were longer in LQT1-CMs than in WT-CMs. Exposure to low [K + ] Ex prolonged FPDs and APDs in a concentration-dependent fashion. LQT1-CMs were found to be more sensitive to low [K + ] Ex compared to WT-CMs. At baseline, LQT1A-CMs had more prolonged APDs than LQT1B-CMs, but low [K + ] Ex caused more pronounced APD prolongation in LQT1B-CMs. Early afterdepolarizations in the action potentials were observed in a subset of LQT1A-CMs with further prolonged baseline APDs and triangular phase 2 profiles. This work demonstrates that the hiPSC-derived CMs are sensitive to low [K + ] Ex and provide a platform to study acquired LQTS. © 2017. Published by The Company of Biologists Ltd.

Short-Wave Infrared HgCdTe Electron Avalanche Photodiodes for Gated Viewing

NASA Astrophysics Data System (ADS)

Sieck, A.; Benecke, M.; Eich, D.; Oelmaier, R.; Wendler, J.; Figgemeier, H.

2018-06-01

Short-wave infrared (SWIR) HgCdTe electron avalanche photodiodes (eAPDs) with different doping profiles have been characterized for use in SWIR gated viewing systems. Gated viewing offers enhanced image contrast in scenes with clutter from the foreground or background. HgCdTe-based eAPDs show exponential gain-voltage characteristics and low excess noise and are, therefore, well suited for active imaging applications. The gain achievable at a fixed reverse voltage varies with the bandgap of the Hg1-xCdxTe detector material. We analyze current-voltage and gain-voltage plots measured on SWIR Hg1-xCdxTe eAPDs with x = 0.45, corresponding to a cutoff wavelength of 2.55 μm at 150 K. The cutoff has been chosen as a trade-off between achievable APD gain and operating temperature for SWIR gated-viewing systems with target distances of about 1000 m. Focal plane arrays with a readout-integrated circuit featuring a fast internal clock have been built and their performance with respect to gated viewing applications has been evaluated on a laboratory demonstrator for short distances. Future plans for a field demonstrator for distances up to 1000 m are described briefly at the end.

The transfer functions of cardiac tissue during stochastic pacing.

PubMed

de Lange, Enno; Kucera, Jan P

2009-01-01

The restitution properties of cardiac action potential duration (APD) and conduction velocity (CV) are important factors in arrhythmogenesis. They determine alternans, wavebreak, and the patterns of reentrant arrhythmias. We developed a novel approach to characterize restitution using transfer functions. Transfer functions relate an input and an output quantity in terms of gain and phase shift in the complex frequency domain. We derived an analytical expression for the transfer function of interbeat intervals (IBIs) during conduction from one site (input) to another site downstream (output). Transfer functions can be efficiently obtained using a stochastic pacing protocol. Using simulations of conduction and extracellular mapping of strands of neonatal rat ventricular myocytes, we show that transfer functions permit the quantification of APD and CV restitution slopes when it is difficult to measure APD directly. We find that the normally positive CV restitution slope attenuates IBI variations. In contrast, a negative CV restitution slope (induced by decreasing extracellular [K(+)]) amplifies IBI variations with a maximum at the frequency of alternans. Hence, it potentiates alternans and renders conduction unstable, even in the absence of APD restitution. Thus, stochastic pacing and transfer function analysis represent a powerful strategy to evaluate restitution and the stability of conduction.

Performance Analysis of OCDMA Based on AND Detection in FTTH Access Network Using PIN & APD Photodiodes

NASA Astrophysics Data System (ADS)

Aldouri, Muthana; Aljunid, S. A.; Ahmad, R. Badlishah; Fadhil, Hilal A.

2011-06-01

In order to comprise between PIN photo detector and avalanche photodiodes in a system used double weight (DW) code to be a performance of the optical spectrum CDMA in FTTH network with point-to-multi-point (P2MP) application. The performance of PIN against APD is compared through simulation by using opt system software version 7. In this paper we used two networks designed as follows one used PIN photo detector and the second using APD photo diode, both two system using with and without erbium doped fiber amplifier (EDFA). It is found that APD photo diode in this system is better than PIN photo detector for all simulation results. The conversion used a Mach-Zehnder interferometer (MZI) wavelength converter. Also we are study, the proposing a detection scheme known as AND subtraction detection technique implemented with fiber Bragg Grating (FBG) act as encoder and decoder. This FBG is used to encode and decode the spectral amplitude coding namely double weight (DW) code in Optical Code Division Multiple Access (OCDMA). The performances are characterized through bit error rate (BER) and bit rate (BR) also the received power at various bit rate.

[Influence exogenous nicotinamide adenine dinucleotide (NAD+) on contractile and bioelectric activity of the rat heart].

PubMed

Pustovit, K B; Kuz'min, V S; Sukhova, G S

2014-04-01

This study is aimed to the investigation of the nicotinamide adenine dinucleotide (NAD+) effects and mechanisms of action in a heart. NAD+ (mcM) induces multiphase alternation of contractile activity of isolated rat heart: short positive inotropic action is followed by a negative inotropic phase. NAD+ (1-100 mcM) induces decreasing of action potential duration (APD) in rat atrial myocardium (from 45 +/- 0.82 ms in control experiments to 39 +/- 1.05 (n = 8) and 32 +/- 2 (n = 8) during application of 10 and 100 mcM of NAD+, respectively). Significant APD increase (from 45 +/- 0.82 ms to 74 +/- 1.89 (n = 8) ms) was observed during washing out of NAD+ (100 mcM). ATP or adenosine was unable to increase APD both during application or washing out. NAD+ induced APD decrease was not suppressed by P1-antagonist theophylline. P1-purinoreceptor and metabolite independent direct action of NAD+ in rat heart is suggested. Activation of P2X or P2Y receptors, cyclic ADP-ribose accumulation in cardiomyocytes is proposed as a main mechanism of NAD(+)-induced effects in the heart.

A near-Infrared SETI Experiment: Alignment and Astrometric precision

NASA Astrophysics Data System (ADS)

Duenas, Andres; Maire, Jerome; Wright, Shelley; Drake, Frank D.; Marcy, Geoffrey W.; Siemion, Andrew; Stone, Remington P. S.; Tallis, Melisa; Treffers, Richard R.; Werthimer, Dan

2016-06-01

Beginning in March 2015, a Near-InfraRed Optical SETI (NIROSETI) instrument aiming to search for fast nanosecond laser pulses, has been commissioned on the Nickel 1m-telescope at Lick Observatory. The NIROSETI instrument makes use of an optical guide camera, SONY ICX694 CCD from PointGrey, to align our selected sources into two 200µm near-infrared Avalanche Photo Diodes (APD) with a field-of-view of 2.5"x2.5" each. These APD detectors operate at very fast bandwidths and are able to detect pulse widths extending down into the nanosecond range. Aligning sources onto these relatively small detectors requires characterizing the guide camera plate scale, static optical distortion solution, and relative orientation with respect to the APD detectors. We determined the guide camera plate scale as 55.9+- 2.7 milli-arcseconds/pixel and magnitude limit of 18.15mag (+1.07/-0.58) in V-band. We will present the full distortion solution of the guide camera, orientation, and our alignment method between the camera and the two APDs, and will discuss target selection within the NIROSETI observational campaign, including coordination with Breakthrough Listen.

An excess noise measurement system for weak responsivity avalanche photodiodes

NASA Astrophysics Data System (ADS)

Qiao, Liang; Dimler, Simon J.; Baharuddin, Aina N. A. P.; Green, James E.; David, John P. R.

2018-06-01

A system for measuring, with reduced photocurrent, the excess noise associated with the gain in avalanche photodiodes (APDs), using a transimpedance amplifier front-end and based on phase-sensitive detection is described. The system can reliably measure the excess noise power of devices, even when the un-multiplied photocurrent is low (~10 nA). This is more than one order of magnitude better than previously reported systems and represents a significantly better noise signal to noise ratio. This improvement in performance has been achieved by increasing the value of the feedback resistor and reducing the op-amp bandwidth. The ability to characterise APD performance with such low photocurrents enables the use of low power light sources such as light emitting diode rather than lasers to investigate the APD noise performance.

Ultraviolet Light Curves of Gaia16apd in Superluminous Supernova Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tolstov, Alexey; Zhiglo, Andrey; Nomoto, Ken’ichi

2017-08-10

Observations of Gaia16apd revealed extremely luminous ultraviolet emission among superluminous supernovae (SLSNe). Using radiation hydrodynamics simulations, we perform a comparison of UV light curves, color temperatures, and photospheric velocities between the most popular SLSN models: pair-instability supernova, magnetar, and interaction with circumstellar medium. We find that the interaction model is the most promising to explain the extreme UV luminosity of Gaia16apd. The differences in late-time UV emission and in color evolution found between the models can be used to link an observed SLSN event to the most appropriate model. Observations at UV wavelengths can be used to clarify the naturemore » of SLSNe and more attention should be paid to them in future follow-up observations.« less

Best-Practice Criteria for Practical Security of Self-Differencing Avalanche Photodiode Detectors in Quantum Key Distribution

NASA Astrophysics Data System (ADS)

Koehler-Sidki, A.; Dynes, J. F.; Lucamarini, M.; Roberts, G. L.; Sharpe, A. W.; Yuan, Z. L.; Shields, A. J.

2018-04-01

Fast-gated avalanche photodiodes (APDs) are the most commonly used single photon detectors for high-bit-rate quantum key distribution (QKD). Their robustness against external attacks is crucial to the overall security of a QKD system, or even an entire QKD network. We investigate the behavior of a gigahertz-gated, self-differencing (In,Ga)As APD under strong illumination, a tactic Eve often uses to bring detectors under her control. Our experiment and modeling reveal that the negative feedback by the photocurrent safeguards the detector from being blinded through reducing its avalanche probability and/or strengthening the capacitive response. Based on this finding, we propose a set of best-practice criteria for designing and operating fast-gated APD detectors to ensure their practical security in QKD.

Single photon detection in a waveguide-coupled Ge-on-Si lateral avalanche photodiode.

PubMed

Martinez, Nicholas J D; Gehl, Michael; Derose, Christopher T; Starbuck, Andrew L; Pomerene, Andrew T; Lentine, Anthony L; Trotter, Douglas C; Davids, Paul S

2017-07-10

We examine gated-Geiger mode operation of an integrated waveguide-coupled Ge-on-Si lateral avalanche photodiode (APD) and demonstrate single photon detection at low dark count for this mode of operation. Our integrated waveguide-coupled APD is fabricated using a selective epitaxial Ge-on-Si growth process resulting in a separate absorption and charge multiplication (SACM) design compatible with our silicon photonics platform. Single photon detection efficiency and dark count rate is measured as a function of temperature in order to understand and optimize performance characteristics in this device. We report single photon detection of 5.27% at 1310 nm and a dark count rate of 534 kHz at 80 K for a Ge-on-Si single photon avalanche diode. Dark count rate is the lowest for a Ge-on-Si single photon detector in this range of temperatures while maintaining competitive detection efficiency. A jitter of 105 ps was measured for this device.

Compact and high-sensitivity 100-Gb/s (4 × 25 Gb/s) APD-ROSA with a LAN-WDM PLC demultiplexer.

PubMed

Yoshimatsu, Toshihide; Nada, Masahiro; Oguma, Manabu; Yokoyama, Haruki; Ohno, Tetsuichiro; Doi, Yoshiyuki; Ogawa, Ikuo; Takahashi, Hiroshi; Yoshida, Eiji

2012-12-10

We demonstrate an integrated 100 GbE receiver optical sub-assembly (ROSA) that incorporates a monolithic four-channel avalanche photodiode (APD) array and a planer lightwave circuit (PLC) based LAN-WDM demultiplexer. A record minimum receiver sensitivity of -20 dBm and 50-km error-free SMF transmission without an optical amplifier have been achieved.

Ranolazine improves abnormal repolarization and contraction in left ventricular myocytes of dogs with heart failure by inhibiting late sodium current

PubMed Central

Undrovinas, Albertas I.; Belardinelli, Luiz; Undrovinas, Nidas A.; Sabbah, Hani N.

2005-01-01

Background Ventricular repolarization and contractile function are frequently abnormal in ventricular myocytes from human failing hearts as well as canine hearts with experimentally induced heart failure (HF). These abnormalities have been attributed to dysfunction involving various steps of the excitation-contraction coupling process, leading to impaired intracellular sodium and calcium homeostasis. We previously reported that the slow inactivating component of the Na+ current (late INa) is augmented in myocytes from failing hearts, and this appears to play a significant role in abnormal ventricular myocytes repolarization and function. We tested the effect of ranolazine, a novel drug being developed to treat angina, on 1) action potential duration (APD), 2) peak transient and late INa (INaT and INaL respectively), 3) early afterdepolarizations (EADs), and 4) twitch contraction (TC) including aftercontractions and contracture. Methods: Myocytes were isolated from the left ventricle of normal dogs and of dogs with chronic HF caused by multiple sequential intracoronary microembolizations. INaT and INaL were recorded using conventional whole-cell patch-clamp techniques. APs were recorded using the β-escin perforated patch-clamp configuration at frequencies of 0.25 and 0.5 Hz. TCs were recorded using an edge movement detector at stimulation frequencies ranging from 0.5 to 2.0 Hz. Results Ranolazine significantly (p < 0.05) and reversibly shortened the APD of myocytes stimulated at either 0.5 or 0.25 Hz in a concentration-dependent manner. At a stimulation frequency of 0.5 Hz, 5, 10 and 20 μM ranolazine shortened the APD90 (APD measured at 90% repolarization) from 516 ± 51 to 304 ± 22, 212 ± 34 and 160 ± 11 ms, respectively, and markedly decreased beat-to-beat variability of APD90, EADs and dispersion of APDs. Ranolazine preferentially blocked INaL relative to INaT in a state-dependent manner; with a ~ 38-fold greater potency against INaL to produce tonic block (IC50 = 6.5 μ M) than INaT (IC50 =294 μM). When we evaluated inactivated state blockade of INaL from the steady-state inactivation mid-potential shift using a theoretical model, ranolazine was found to bind more tightly to the inactivated state than the resting state of the sodium channel underlying INaL, with apparent dissociation constants Kdr=7.47μ M and Kdi=1.71μ M, respectively. TCs of myocytes stimulated at 0.5 Hz were characterized by an initial spike followed by a dome-like aftercontraction, which was observed in75% of myocytes from failing hearts and coincided with the long AP plateau and EADs. Ranolazine at 5, and 10 μM reversibly shortened duration of TCs and abolished the aftercontraction. When the rate of myocyte stimulation was increased from 1.0 to 2.0 Hz, there was a progressive increase in diastolic “tension”, i.e., contracture. Ranolazine at 5, and 10 μM reversibly prevented this frequency-dependent contracture. PMID:16686675

Relative to typical antipsychotic drugs, aripiprazole is a safer alternative for alleviating behavioral disturbances after experimental brain trauma

PubMed Central

Phelps, Thomas I.; Bondi, Corina O.; Mattiola, Vincent V.; Kline, Anthony E.

2016-01-01

Background Antipsychotic drugs (APDs) are used to manage traumatic brain injury (TBI)-induced behavioral disturbances, such as agitation and aggression. However, APDs exhibiting D2 receptor antagonism impede cognitive recovery after experimental TBI. Hence, empirical evaluation of APDs with different mechanistic actions is warranted. Aripiprazole (ARIP) is a D2 and 5-HT1A receptor agonist; pharmacotherapies with these properties enhance cognition after TBI. Objective To test the hypothesis that ARIP would increase behavioral performance and decrease histopathology after TBI. Methods Adult male rats were subjected to either a controlled cortical impact (CCI) or sham injury and then randomly assigned to ARIP (0.1 or 1.0 mg/kg) or VEH (1.0 mL/kg, saline vehicle) groups. Treatments began 24 hr after surgery and were administered once daily for 19 days. Motor (beam-balance/beam-walk) and cognitive (Morris water maze) performance was assessed on post-operative days 1-5 and 14-19, respectively, followed by quantification of hippocampal CA1/3 neuron survival and cortical lesion volume. Results Beam-balance was significantly improved in the CCI + ARIP (1.0 mg/kg) group vs. CCI + ARIP (0.1 mg/kg) and CCI + VEH [p<0.05]. Spatial learning and memory retention were significantly improved in the CCI + ARIP (0.1 mg/kg) group vs. the CCI + ARIP (1.0 mg/kg) and CCI + VEH groups [p<0.05]. Both doses of ARIP reduced lesion size and CA3 cell loss vs. VEH [p<0.05]. Importantly, neither dose of ARIP impeded functional recovery as previously reported with other APDs. Conclusion These findings support the hypothesis and endorse ARIP as a safer APD for alleviating behavioral disturbances after TBI. PMID:27225976

Action potentials and amphetamine release antipsychotic drug from dopamine neuron synaptic VMAT vesicles.

PubMed

Tucker, Kristal R; Block, Ethan R; Levitan, Edwin S

2015-08-11

Based on lysotracker red imaging in cultured hippocampal neurons, antipsychotic drugs (APDs) were proposed to accumulate in synaptic vesicles by acidic trapping and to be released in response to action potentials. Because many APDs are dopamine (DA) D2 receptor (D2R) antagonists, such a mechanism would be particularly interesting if it operated in midbrain DA neurons. Here, the APD cyamemazine (CYAM) is visualized directly by two-photon microscopy in substantia nigra and striatum brain slices. CYAM accumulated slowly into puncta based on vacuolar H(+)-ATPase activity and dispersed rapidly upon dissipating organelle pH gradients. Thus, CYAM is subject to acidic trapping and released upon deprotonation. In the striatum, Ca(2+)-dependent reduction of the CYAM punctate signal was induced by depolarization or action potentials. Striatal CYAM overlapped with the dopamine transporter (DAT). Furthermore, parachloroamphetamine (pCA), acting via vesicular monoamine transporter (VMAT), and a charged VMAT, substrate 1-methyl-4-phenylpyridinium (MPP(+)), reduced striatal CYAM. In vivo CYAM administration and in vitro experiments confirmed that clinically relevant CYAM concentrations result in vesicular accumulation and pCA-dependent release. These results show that some CYAM is in DA neuron VMAT vesicles and suggests a new drug interaction in which amphetamine induces CYAM deprotonation and release as a consequence of the H(+) countertransport by VMAT that accompanies vesicular uptake, but not by inducing exchange or acting as a weak base. Therefore, in the striatum, APDs are released with DA in response to action potentials and an amphetamine. This synaptic corelease is expected to enhance APD antagonism of D2Rs where and when dopaminergic transmission occurs.

Design and performance of single photon APD focal plane arrays for 3-D LADAR imaging

NASA Astrophysics Data System (ADS)

Itzler, Mark A.; Entwistle, Mark; Owens, Mark; Patel, Ketan; Jiang, Xudong; Slomkowski, Krystyna; Rangwala, Sabbir; Zalud, Peter F.; Senko, Tom; Tower, John; Ferraro, Joseph

2010-08-01

×We describe the design, fabrication, and performance of focal plane arrays (FPAs) for use in 3-D LADAR imaging applications requiring single photon sensitivity. These 32 × 32 FPAs provide high-efficiency single photon sensitivity for three-dimensional LADAR imaging applications at 1064 nm. Our GmAPD arrays are designed using a planarpassivated avalanche photodiode device platform with buried p-n junctions that has demonstrated excellent performance uniformity, operational stability, and long-term reliability. The core of the FPA is a chip stack formed by hybridizing the GmAPD photodiode array to a custom CMOS read-out integrated circuit (ROIC) and attaching a precision-aligned GaP microlens array (MLA) to the back-illuminated detector array. Each ROIC pixel includes an active quenching circuit governing Geiger-mode operation of the corresponding avalanche photodiode pixel as well as a pseudo-random counter to capture per-pixel time-of-flight timestamps in each frame. The FPA has been designed to operate at frame rates as high as 186 kHz for 2 μs range gates. Effective single photon detection efficiencies as high as 40% (including all optical transmission and MLA losses) are achieved for dark count rates below 20 kHz. For these planar-geometry diffused-junction GmAPDs, isolation trenches are used to reduce crosstalk due to hot carrier luminescence effects during avalanche events, and we present details of the crosstalk performance for different operating conditions. Direct measurement of temporal probability distribution functions due to cumulative timing uncertainties of the GmAPDs and ROIC circuitry has demonstrated a FWHM timing jitter as low as 265 ps (standard deviation is ~100 ps).

HgCdTe APDs for time-resolved space applications

NASA Astrophysics Data System (ADS)

Rothman, J.; Lasfargues, G.; Delacourt, B.; Dumas, A.; Gibert, F.; Bardoux, A.; Boutillier, M.

2017-12-01

The use of HgCdTe avalanche photodiodes (APDs) for resolving the temporal variation of faint light level signals is analyzed. The analysis is based on the performance characteristics such as the gain, the response time, and dark currents in the APDs, measured as a function of operating temperature and Cd composition, and on recently developed detector demonstrator modules. The choice of Cd composition in the APDs is strongly dependent on the application needs in terms of electrical bandwidth and signal-to-noise ratio. A performance model has been developed and used to predict the performance of the future detector modules for different applications such as high bandwidth and/or deep space free space optical telecommunications and lidar, associated with sensitivities down to single photon level at low operating temperature and close to single-photon operation at bandwidth of 10 GHz at room temperature. The predictions are corroborated by the results obtained on detector modules that have been developed and used in lidar and deep space optical communications. In a first lidar prototype, integrating a 200 µm APD, we obtained a maximum sensitivity of 25 fW/√Hz at T = 190 K operating temperature. The detector has been used for differential absorption lidar estimations of the absorption due to presence of CO2 in the atmosphere. A random error of 3-10% was obtained for the estimation of the optical thickness at a distance of 100-3000 m, for a range resolution of 100 m and using and averaging time of 4 s. The pursuit of this development is pending on the space qualification of the technology. Results from first proton and irradiation tests are reported that shows on a close to constant performance during and after the irradiation and endurance tests.

Glucose absorption in acute peritoneal dialysis.

PubMed

Podel, J; Hodelin-Wetzel, R; Saha, D C; Burns, G

2000-04-01

During acute peritoneal dialysis (APD), it is known that glucose found in the dialysate solution contributes to the provision of significant calories. It has been well documented in continuous ambulatory peritoneal dialysis (CAPD) that glucose absorption occurs. In APD, however, it remains unclear how much glucose absorption actually does occur. Therefore, the purpose of this study was to determine whether it is appropriate to use the formula used to calculate glucose absorption in CAPD (Grodstein et al) among patients undergoing APD. Actual measurements of glucose absorption (Method I) were calculated in 9 patients undergoing APD treatment for >24 hours who were admitted to the intensive care unit. Glucose absorption using the Grodstein et al formula (Method II) was also determined and compared with the results of actual measurements. The data was then further analyzed based on the factors that influence glucose absorption, specifically dwell time and concentration. The mean total amount of glucose absorbed was 43% +/- 15%. However, when dwell time and concentration were further examined, significant differences were noted. Method I showed a cumulative increase over time. Method II showed that absorption was fixed. This suggests that with the variation in dwell time commonly seen in the acute care setting, the use of Method II may not be accurate. In each of the 2 methods, a significant difference in glucose absorption was noted when comparing the use of 1.5% and 4.25% dialysate concentrations. The established formula designed for CAPD should not be used for calculating glucose absorption in patients receiving APD because variation in dwell time and concentration should be taken into account. Because of the time constraints and staffing required to calculate each exchange individually, combined with the results of the study, we recommend the use of the percentage estimate of 40% to 50%.

Time Course of Peritoneal Function in Automated and Continuous Peritoneal Dialysis

PubMed Central

Michels, Wieneke M.; Verduijn, Marion; Parikova, Alena; Boeschoten, Elisabeth W.; Struijk, Dirk G.; Dekker, Friedo W.; Krediet, Raymond T.

2012-01-01

♦ Background and Objectives: In automated peritoneal dialysis (APD), a patient’s peritoneal membrane is more intensively exposed to fresh dialysate than it is in continuous ambulatory peritoneal dialysis (CAPD). Our aim was to study, in incident peritoneal dialysis (PD) patients, the influence of APD—compared with that of CAPD—on peritoneal transport over 4 years. ♦ Design, Setting, Participants, and Measurements: Patients were included if at least 2 annual standard permeability analyses (SPAs) performed with 3.86% glucose were available while the patient was using the same modality with which they had started PD (APD or CAPD). Patients were followed until their first modality switch. Differences in the pattern of SPA outcomes over time were tested using repeated-measures models adjusted for age, sex, comorbidity, primary kidney disease, and year of PD start. ♦ Results: The 59 CAPD patients enrolled were older than the 47 APD patients enrolled (mean age: 58 ± 14 years vs 49 ± 14 years; p < 0.01), and they had started PD earlier (mean start year: 2000 vs 2002). Over time, no differences in solute (p > 0.19) or fluid transport (p > 0.13) were observed. Similarly, free water transport (p = 0.43) and small-pore transport (p = 0.31) were not different between the modalities. Over time, patients on APD showed a faster decline in effective lymphatic absorption rate (ELAR: p = 0.02) and in transcapillary ultrafiltration (TCUF: p = 0.07, adjusted p = 0.05). Further adjustment did not change the results. ♦ Conclusions: Compared with patients starting on CAPD, those starting on APD experienced a faster decline in ELAR and TCUF. Other transport parameters were not different over time between the groups. PMID:22473037

Changes in Ca(2+) cycling proteins underlie cardiac action potential prolongation in a pressure-overloaded guinea pig model with cardiac hypertrophy and failure.

PubMed

Ahmmed, G U; Dong, P H; Song, G; Ball, N A; Xu, Y; Walsh, R A; Chiamvimonvat, N

2000-03-17

Ventricular arrhythmias are common in both cardiac hypertrophy and failure; cardiac failure in particular is associated with a significant increase in the risk of sudden cardiac death. We studied the electrophysiologic changes in a guinea pig model with aortic banding resulting in cardiac hypertrophy at 4 weeks and progressing to cardiac failure at 8 weeks using whole-cell patch-clamp and biochemical techniques. Action potential durations (APDs) were significantly prolonged in banded animals at 4 and 8 weeks compared with age-matched sham-operated animals. APDs at 50% and 90% repolarization (APD(50) and APD(90) in ms) were the following: 4 week, banded, 208+/-51 and 248+/-49 (n = 15); 4 week, sham, 189+/-68 and 213+/-69 (n = 16); 8 week, banded, 197+/-40 and 226+/-40 (n = 21); and 8 week, sham, 156+/-42 and 189+/-45 (n = 22), respectively; P<0.05 comparing banded versus sham-operated animals. We observed no significant differences in the K(+) currents between the 2 groups of animals at 4 and 8 weeks. However, banded animals exhibited a significant increase in Na(+) and Na(+)-Ca(2+) exchange current densities compared with controls. Furthermore, we have found a significant attenuation in the Ca(2+)-dependent inactivation of the L-type Ca(2+) current in the banded compared with sham-operated animals, likely as a result of the significant downregulation of the sarcoplasmic reticulum Ca(2+) ATPase, which has been documented previously in the heart failure animals. Our data provide an alternate mechanism for APD prolongation in cardiac hypertrophy and failure and support the notion that there is close interaction between Ca(2+) handling and action potential profile.

Sex differences in repolarization and slow delayed rectifier potassium current and their regulation by sympathetic stimulation in rabbits.

PubMed

Zhu, Yujie; Ai, Xun; Oster, Robert A; Bers, Donald M; Pogwizd, Steven M

2013-06-01

Slow delayed rectifier potassium current (IKs) is important in action potential (AP) repolarization and repolarization reserve. We tested the hypothesis that there are sex-specific differences in IKs, AP, and their regulation by β-adrenergic receptors (β-AR's) using whole-cell patch-clamp. AP duration (APD90) was significantly longer in control female (F) than in control male (M) myocytes. Isoproterenol (ISO, 500 nM) shortened APD90 comparably in M and F, and was largely reversed by β1-AR blocker CGP 20712A (CGP, 300 nM). Inhibition of IKs with chromanol 293B (10 μM) resulted in less APD prolongation in F at baseline (3.0 vs 8.9 %, p < 0.05 vs M) and even in the presence of ISO (5.4 vs 20.9 %, p < 0.05). This suggests that much of the ISO-induced APD abbreviation in F is independent of IKs. In F, baseline IKs was 42 % less and was more weakly activated by ISO (19 vs 68 % in M, p < 0.01). ISO enhancement of IKs was comparably attenuated by CGP in M and F. After ovariectomy, IKs in F had greater enhancement by ISO (72 %), now comparable to control M. After orchiectomy, IKs in M was only slightly enhanced by ISO (23 %), comparable to control F. Pretreatment with thapsigargin (to block SR Ca release) had bigger impact on ISO-induced APD shortening in F than that in M (p < 0.01). In conclusion, we found that there are sex differences in IKs, AP, and their regulation by β-AR's that are modulated by sex hormones, suggesting the potential for sex-specific antiarrhythmic therapy.

Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate

PubMed Central

Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O’Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

2014-01-01

Background Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Methods and Results Activation recovery intervals (ARI) measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady state pacing while subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Haemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (p=0.001). APD decreased during the stressful parts of the film clip, eg for global RV ARI at end of film clip 193.8ms (SD 14) vs 198.0ms (SD13) during the matched breathing control (end film LV 199.8ms (SD16) vs control 201.6ms (SD15), p=0.004. Respiration rate increased during the stressful part of the film clip (by 2 breaths/minute), and was well matched in the respective control period without any haemodynamic or ARI changes. Conclusions Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular action potential duration in conscious humans. The effect of mental challenge on APD was not secondary to emotionally-induced altered respiration or heart rate. PMID:24833641

The Relative Influences of Phosphometabolites and pH on Action Potential Morphology during Myocardial Reperfusion: A Simulation Study

PubMed Central

Roberts, Byron N.; Christini, David J.

2012-01-01

Myocardial ischemia-reperfusion (IR) injury represents a constellation of pathological processes that occur when ischemic myocardium experiences a restoration of perfusion. Reentrant arrhythmias, which represent a particularly lethal manifestation of IR injury, can result when ischemic tissue exhibits decreased excitability and/or changes of action potential duration (APD), conditions that precipitate unidirectional conduction block. Many of the cellular components that are involved with IR injury are modulated by pH and/or phosphometabolites such as ATP and phosphocreatine (PCr), all of which can be manipulated in vivo and potentially in the clinical setting. Using a mathematical model of the cardiomyocyte that we previously developed to study ischemia and reperfusion, we performed a series of simulations with the aim of determining whether pH- or phosphometabolite-related processes play a more significant role in generating changes in excitability and action potential morphology that are associated with the development of reentry. In our simulations, persistent shortening of APD, action potential amplitude (APA), and depolarization of the resting membrane potential were more severe when ATP and PCr availability were suppressed during reperfusion than when extracellular pH recovery was inhibited. Reduced phosphometabolite availability and pH recovery affected multiple ion channels and exchangers. Some of these effects were the result of direct modulation by phosphometabolites and/or acidosis, while others resulted from elevated sodium and calcium loads during reperfusion. In addition, increasing ATP and PCr availability during reperfusion was more beneficial in terms of increasing APD and APA than was increasing the amount of pH recovery. Together, these results suggest that therapies directed at increasing ATP and/or PCr availability during reperfusion may be more beneficial than perturbing pH recovery with regard to mitigating action potential changes that increase the likelihood of reentrant arrhythmias. PMID:23144801

HgCdTe APDS for time resolved space applications

NASA Astrophysics Data System (ADS)

Rothman, J.; Lasfargues, G.; Delacourt, B.; Dumas, A.; Gibert, F.; Bardoux, A.; Boutillier, M.

2017-09-01

HgCdTe APDs have opened a new horizon in photon starved applications due to their exceptional performance in terms of high linear gain, low excess noise and high quantum efficiency. Both focal plane arrays (FPAs) and large array single element using HgCdTe (MCT) APDs have been developed at CEA/Leti and Sofradir and high performance devices are at present available to detect without deterioration the spatial and/or temporal information in photon fluxes with a low number of photon in each spatio-temporal bin. The enhancement in performance that can be achieved with MCT has subsequently been demonstrated in a wide scope of applications such as astronomical observations, active imaging, deep space telecommunications, atmospheric LIDAR and mid-IR (MIR) time resolved photoluminescence measurements. Most of these applications can be used in space borne platforms.

Harsh-Environment Solid-State Gamma Detector for Down-hole Gas and Oil Exploration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peter Sandvik; Stanislav Soloviev; Emad Andarawis

2007-08-10

The goal of this program was to develop a revolutionary solid-state gamma-ray detector suitable for use in down-hole gas and oil exploration. This advanced detector would employ wide-bandgap semiconductor technology to extend the gamma sensor's temperature capability up to 200 C as well as extended reliability, which significantly exceeds current designs based on photomultiplier tubes. In Phase II, project tasks were focused on optimization of the final APD design, growing and characterizing the full scintillator crystals of the selected composition, arranging the APD device packaging, developing the needed optical coupling between scintillator and APD, and characterizing the combined elements asmore » a full detector system preparing for commercialization. What follows is a summary report from the second 18-month phase of this program.« less

NASA Astrophysics Prioritizes Technology Development Funding for Strategic Missions

NASA Astrophysics Data System (ADS)

Thronson, Harley A.; Pham, Bruce; Ganel, Opher

2017-01-01

The Cosmic Origins (COR) and Physics of the Cosmos (PCOS) Program Offices (POs) reside at NASA GSFC and implement priorities for the NASA HQ Astrophysics Division (APD). One major aspect of the POs’ activities is managing our Strategic Astrophysics Technology (SAT) program to mature technologies for future strategic missions. The Programs follow APD guidance on which missions are strategic, currently informed by the NRC’s 2010 Decadal Survey report, as well as APD’s Implementation Plan and the Astrophysics Roadmap.In preparation for the upcoming 2020 Decadal Survey, the APD has established Science and Technology Definition Teams (STDTs) to study four large-mission concepts: the Origins Space Telescope, Habitable Exoplanet Imaging Mission, Large UV/Optical/IR Surveyor, and X-ray Surveyor. The STDTs will develop the science case and design reference mission, assess technology development needs, and estimate the cost of their concept. A fifth team, the L3 Study Team (L3ST), was charged to study potential US contributions to ESA’s planned L3 gravitational-wave observatory.The POs use a rigorous and transparent process to solicit technology gaps from the scientific and technical communities, and prioritize those entries based on strategic alignment, expected impact, cross-cutting applicability, and urgency. Starting in 2016, the technology-gap assessments of the four STDTs and the L3ST are included in our process. Until a study team submits its final report, community-proposed changes to gaps submitted or adopted by a study team are forwarded to that study team for consideration.We discuss our technology development process, with strategic prioritization informing calls for SAT proposals and informing investment decisions. We also present results of this year’s technology gap prioritization and showcase our current portfolio of technology development projects. To date, 77 COR and 80 PCOS SAT proposals have been received, of which 18 COR and 22 PCOS projects were funded (PCOS awards starting in 2017 have yet to be announced). For more information, see the respective Program Annual Technology Reports under the technology tabs of the COR website at cor.gsfc.nasa.gov and the PCOS website at pcos.gsfc.nasa.gov.

Estimating random errors due to shot noise in backscatter lidar observations.

PubMed

Liu, Zhaoyan; Hunt, William; Vaughan, Mark; Hostetler, Chris; McGill, Matthew; Powell, Kathleen; Winker, David; Hu, Yongxiang

2006-06-20

We discuss the estimation of random errors due to shot noise in backscatter lidar observations that use either photomultiplier tube (PMT) or avalanche photodiode (APD) detectors. The statistical characteristics of photodetection are reviewed, and photon count distributions of solar background signals and laser backscatter signals are examined using airborne lidar observations at 532 nm using a photon-counting mode APD. Both distributions appear to be Poisson, indicating that the arrival at the photodetector of photons for these signals is a Poisson stochastic process. For Poisson- distributed signals, a proportional, one-to-one relationship is known to exist between the mean of a distribution and its variance. Although the multiplied photocurrent no longer follows a strict Poisson distribution in analog-mode APD and PMT detectors, the proportionality still exists between the mean and the variance of the multiplied photocurrent. We make use of this relationship by introducing the noise scale factor (NSF), which quantifies the constant of proportionality that exists between the root mean square of the random noise in a measurement and the square root of the mean signal. Using the NSF to estimate random errors in lidar measurements due to shot noise provides a significant advantage over the conventional error estimation techniques, in that with the NSF, uncertainties can be reliably calculated from or for a single data sample. Methods for evaluating the NSF are presented. Algorithms to compute the NSF are developed for the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations lidar and tested using data from the Lidar In-space Technology Experiment.

Hard-X-Ray/Soft-Gamma-Ray Imaging Sensor Assembly for Astronomy

NASA Technical Reports Server (NTRS)

Myers, Richard A.

2008-01-01

An improved sensor assembly has been developed for astronomical imaging at photon energies ranging from 1 to 100 keV. The assembly includes a thallium-doped cesium iodide scintillator divided into pixels and coupled to an array of high-gain avalanche photodiodes (APDs). Optionally, the array of APDs can be operated without the scintillator to detect photons at energies below 15 keV. The array of APDs is connected to compact electronic readout circuitry that includes, among other things, 64 independent channels for detection of photons in various energy ranges, up to a maximum energy of 100 keV, at a count rate up to 3 kHz. The readout signals are digitized and processed by imaging software that performs "on-the-fly" analysis. The sensor assembly has been integrated into an imaging spectrometer, along with a pair of coded apertures (Fresnel zone plates) that are used in conjunction with the pixel layout to implement a shadow-masking technique to obtain relatively high spatial resolution without having to use extremely small pixels. Angular resolutions of about 20 arc-seconds have been measured. Thus, for example, the imaging spectrometer can be used to (1) determine both the energy spectrum of a distant x-ray source and the angular deviation of the source from the nominal line of sight of an x-ray telescope in which the spectrometer is mounted or (2) study the spatial and temporal development of solar flares, repeating - ray bursters, and other phenomena that emit transient radiation in the hard-x-ray/soft- -ray region of the electromagnetic spectrum.

Estimating Random Errors Due to Shot Noise in Backscatter Lidar Observations

NASA Technical Reports Server (NTRS)

Liu, Zhaoyan; Hunt, William; Vaughan, Mark A.; Hostetler, Chris A.; McGill, Matthew J.; Powell, Kathy; Winker, David M.; Hu, Yongxiang

2006-01-01

In this paper, we discuss the estimation of random errors due to shot noise in backscatter lidar observations that use either photomultiplier tube (PMT) or avalanche photodiode (APD) detectors. The statistical characteristics of photodetection are reviewed, and photon count distributions of solar background signals and laser backscatter signals are examined using airborne lidar observations at 532 nm using a photon-counting mode APD. Both distributions appear to be Poisson, indicating that the arrival at the photodetector of photons for these signals is a Poisson stochastic process. For Poisson-distributed signals, a proportional, one-to-one relationship is known to exist between the mean of a distribution and its variance. Although the multiplied photocurrent no longer follows a strict Poisson distribution in analog-mode APD and PMT detectors, the proportionality still exists between the mean and the variance of the multiplied photocurrent. We make use of this relationship by introducing the noise scale factor (NSF), which quantifies the constant of proportionality that exists between the root-mean-square of the random noise in a measurement and the square root of the mean signal. Using the NSF to estimate random errors in lidar measurements due to shot noise provides a significant advantage over the conventional error estimation techniques, in that with the NSF uncertainties can be reliably calculated from/for a single data sample. Methods for evaluating the NSF are presented. Algorithms to compute the NSF are developed for the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) lidar and tested using data from the Lidar In-space Technology Experiment (LITE). OCIS Codes:

A multi-MHz single-shot data acquisition scheme with high dynamic range: pump-probe X-ray experiments at synchrotrons.

PubMed

Britz, Alexander; Assefa, Tadesse A; Galler, Andreas; Gawelda, Wojciech; Diez, Michael; Zalden, Peter; Khakhulin, Dmitry; Fernandes, Bruno; Gessler, Patrick; Sotoudi Namin, Hamed; Beckmann, Andreas; Harder, Manuel; Yavaş, Hasan; Bressler, Christian

2016-11-01

The technical implementation of a multi-MHz data acquisition scheme for laser-X-ray pump-probe experiments with pulse limited temporal resolution (100 ps) is presented. Such techniques are very attractive to benefit from the high-repetition rates of X-ray pulses delivered from advanced synchrotron radiation sources. Exploiting a synchronized 3.9 MHz laser excitation source, experiments in 60-bunch mode (7.8 MHz) at beamline P01 of the PETRA III storage ring are performed. Hereby molecular systems in liquid solutions are excited by the pulsed laser source and the total X-ray fluorescence yield (TFY) from the sample is recorded using silicon avalanche photodiode detectors (APDs). The subsequent digitizer card samples the APD signal traces in 0.5 ns steps with 12-bit resolution. These traces are then processed to deliver an integrated value for each recorded single X-ray pulse intensity and sorted into bins according to whether the laser excited the sample or not. For each subgroup the recorded single-shot values are averaged over ∼10 7  pulses to deliver a mean TFY value with its standard error for each data point, e.g. at a given X-ray probe energy. The sensitivity reaches down to the shot-noise limit, and signal-to-noise ratios approaching 1000 are achievable in only a few seconds collection time per data point. The dynamic range covers 100 photons pulse -1 and is only technically limited by the utilized APD.

Optical Communications With A Geiger Mode APD Array

DTIC Science & Technology

2016-02-09

spurious fires from numerous sources, including crosstalk from other detectors in the same array . Additionally, after a 9 successful detection, the...be combined into arrays with large numbers of detectors , allowing for scaling of dynamic range with relatively little overhead on space and power...overall higher rate of dark counts than a single detector , this is more than compensated for by the extra detectors . A sufficiently large APD array could

Single photon counting linear mode avalanche photodiode technologies

NASA Astrophysics Data System (ADS)

Williams, George M.; Huntington, Andrew S.

2011-10-01

The false count rate of a single-photon-sensitive photoreceiver consisting of a high-gain, low-excess-noise linear-mode InGaAs avalanche photodiode (APD) and a high-bandwidth transimpedance amplifier (TIA) is fit to a statistical model. The peak height distribution of the APD's multiplied dark current is approximated by the weighted sum of McIntyre distributions, each characterizing dark current generated at a different location within the APD's junction. The peak height distribution approximated in this way is convolved with a Gaussian distribution representing the input-referred noise of the TIA to generate the statistical distribution of the uncorrelated sum. The cumulative distribution function (CDF) representing count probability as a function of detection threshold is computed, and the CDF model fit to empirical false count data. It is found that only k=0 McIntyre distributions fit the empirically measured CDF at high detection threshold, and that false count rate drops faster than photon count rate as detection threshold is raised. Once fit to empirical false count data, the model predicts the improvement of the false count rate to be expected from reductions in TIA noise and APD dark current. Improvement by at least three orders of magnitude is thought feasible with further manufacturing development and a capacitive-feedback TIA (CTIA).

Cost and logistics of implementing a tissue-based American College of Surgeons/Association of Program Directors in Surgery surgical skills curriculum for general surgery residents of all clinical years.

PubMed

Henry, Brandon; Clark, Philip; Sudan, Ranjan

2014-02-01

The cost and logistics of deploying the American College of Surgeons (ACS)/Association of Program Directors in Surgery (APDS) National Technical Skills Curriculum across all training years are not known. This information is essential for residency programs choosing to adopt similar curricula. A task force evaluated the authors' institution's existing simulation curriculum and enhanced it by implementing the ACS/APDS modules. A 35-module curriculum was administered to 35 general surgery residents across all 5 clinical years. The costs and logistics were noted, and resident satisfaction was assessed. The annual operational cost was $110,300 ($3,150 per resident). Cost per module, per resident was $940 for the cadaveric module compared with $220 and $240 for dry simulation and animal tissue-based modules, respectively. Resident satisfaction improved from 2.45 to 4.78 on a 5-point, Likert-type scale after implementing the ACS/APDS modules. The ACS/APDS skills curriculum was implemented successfully across all clinical years. Cadaveric modules were the most expensive. Animal and dry simulation modules were equivalent in cost. The addition of tissue-based modules was associated with high satisfaction. Copyright © 2014 Elsevier Inc. All rights reserved.

Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration.

PubMed

Kistamás, Kornél; Hegyi, Bence; Váczi, Krisztina; Horváth, Balázs; Bányász, Tamás; Magyar, János; Szentandrássy, Norbert; Nánási, Péter P

2015-07-01

Profound changes in tissue redox potential occur in the heart under conditions of oxidative stress frequently associated with cardiac arrhythmias. Since beat-to-beat variability (short term variability, SV) of action potential duration (APD) is a good indicator of arrhythmia incidence, the aim of this work was to study the influence of redox changes on SV in isolated canine ventricular cardiomyocytes using a conventional microelectrode technique. The redox potential was shifted toward a reduced state using a reductive cocktail (containing dithiothreitol, glutathione, and ascorbic acid) while oxidative changes were initiated by superfusion with H2O2. Redox effects were evaluated as changes in "relative SV" determined by comparing SV changes with the concomitant APD changes. Exposure of myocytes to the reductive cocktail decreased SV significantly without any detectable effect on APD. Application of H2O2 increased both SV and APD, but the enhancement of SV was the greater, so relative SV increased. Longer exposure to H2O2 resulted in the development of early afterdepolarizations accompanied by tremendously increased SV. Pretreatment with the reductive cocktail prevented both elevation in relative SV and the development of afterdepolarizations. The results suggest that the increased beat-to-beat variability during an oxidative stress contributes to the generation of cardiac arrhythmias.

Hematopoietic Stem Cell Transplantation for Progressive Combined Immunodeficiency and Lymphoproliferation in Activated PI3K Syndrome Type 1.

PubMed

Okano, Tsubasa; Imai, Kohsuke; Tsujita, Yuki; Mitsuiki, Noriko; Yoshida, Kenichi; Kamae, Chikako; Honma, Kenichi; Mitsui-Sekinaka, Kanako; Sekinaka, Yujin; Kato, Tamaki; Hanabusa, Katsuyuki; Endo, Eri; Takashima, Takehiro; Hiroki, Haruka; Yeh, Tzu-Wen; Tanaka, Keisuke; Nagahori, Masakazu; Tsuge, Ikuya; Bando, Yuki; Iwasaki, Fuminori; Shikama, Yoshiaki; Inoue, Masami; Kimoto, Tomiko; Moriguchi, Naohiko; Yuza, Yuki; Kaneko, Takashi; Suzuki, Kyoko; Matsubara, Tomoyo; Maruo, Yoshihiro; Kunitsu, Tomoaki; Waragai, Tomoko; Sano, Hideki; Hashimoto, Yuko; Tasaki, Kazuhiro; Suzuki, Osamu; Shirakawa, Toshihiko; Kato, Motohiro; Uchiyama, Toru; Ishimura, Masataka; Tauchi, Tetsuzo; Yagasaki, Hiroshi; Jou, Shiann-Tarng; Yu, Hsin-Hui; Kanegane, Hirokazu; Kracker, Sven; Durandy, Anne; Kojima, Daiei; Muramatsu, Hideki; Wada, Taizo; Inoue, Yuzaburo; Takada, Hidetoshi; Kojima, Seiji; Ogawa, Seishi; Ohara, Osamu; Nonoyama, Shigeaki; Morio, Tomohiro

2018-05-17

Activated phosphatidylinositol-3-OH kinase-delta (PI3Kδ) syndrome type 1 (APDS1) is a recently described primary immunodeficiency syndrome characterized by recurrent respiratory infections, lymphoid hyperplasia, and herpesviridae infections due to germline gain-of-function mutations of PIK3CD. Hematopoietic stem cell transplantation (HSCT) may be considered to ameliorate progressive immunodeficiency and associated malignancy, but appropriate indications, method, and outcomes of HSCT for APDS1 remain undefined. Our objective was to analyze the clinical manifestations, laboratory findings, prognosis, and treatment of APDS1 and explore appropriate indications and methods of HSCT. We retrospectively reviewed the medical records of cohorts undergoing HSCT at collaborating facilities. Thirty-year overall survival was 86.1%, but event-free survival was 39.6%. Life-threatening events, such as severe infections or lymphoproliferation, were frequent in childhood and adolescence, and were common indications for HSCT. Nine patients underwent HSCT with fludarabine-based reduced intensity conditioning (RIC). Seven patients survived after frequent adverse complications and engraftment failure. Most symptoms improved after HSCT. Patients with APDS1 showed variable clinical manifestations. Life-threatening progressive combined immunodeficiency and massive lymphoproliferation were common indications for HSCT. Fludarabine-based RIC-HSCT ameliorated clinical symptoms, but transplant-related complications were frequent, including graft failure. Copyright © 2018. Published by Elsevier Inc.

Microencapsulation of hydrophilic drug substances using biodegradable polyesters. Part II: Implants allowing controlled drug release--a feasibility study using bisphosphonates.

PubMed

Weidenauer, U; Bodmer, D; Kissel, T

2004-03-01

The prolonged delivery of hydrophilic drug salts from hydrophobic polymer carriers at high drug loading is an ambitious goal. Pamidronate disodium salt (APD) containing implants prepared from spray-dried microparticles were investigated using a laboratory ram extruder. An APD-containing polymer matrix consisting of an APD-chitosan implant embedded in the biodegradable polymer D,L-poly(lactide-co-glycolide acid-glucose) (PLG-GLU) was compared with a matrix system with the micronized drug distributed in the PLG-GLU. The APD-chitosan matrix system showed a triphasic release behaviour at loading levels of 6.86 and 15.54% (w/w) over 36 days under in-vitro conditions. At higher loading (31.92%), a drug burst was observed within 6 days due to the formation of pores and channels in the polymeric matrix. In contrast, implants containing the micronized drug showed a more continuous release profile over 48 days up to a loading of 31.78% (w/w). At a drug loading of 46.17% (w/w), a drug burst was observed. Using micronized drug salts and reducing the surface area available for diffusion, parenteral delivery systems for highly water-soluble drug candidates were shown to be technically feasible at high drug loadings.

Acidogenesis and Two-Phase Codigestion of Fats, Oils, and Greases and Municipal Biosolids.

PubMed

Varin, Ross; Novak, John; Bott, Charles

2016-11-01

  Acidogenic codigestion of fats, oils, and greases (FOG) was studied using suspended growth sludge digesters operated as batch fed reactors that were fed twice daily. The digesters were maintained at a 2-day retention time and at 37 °C to mimic the acid phase of an acid-gas digestion system. As FOG loading rates increased, volatile fatty acid (VFA) production was found to increase, although the percentage of VFA production compared to theoretical values decreased exponentially to just 20% at the highest loading rates. FOG matter was found to have accumulated in the reactor vessel in semi-solid balls that floated near the liquid surface. Two-phase codigestion of FOG was studied at 37 °C using Continuously Stirred Tank Reactors (CSTRs) as acid phase digesters (APD) operated with 2-day retention times, followed by gas phase digesters (GPD) with 15-day retention times. The two-phase systems were compared by FOG addition to the APD versus GPD. FOG addition to the APD resulted in 88% destruction of LCFAs, whereas FOG addition to the GPD resulted in 95% destruction of LCFAs. Accumulated LCFAs were found in the APD receiving FOG and were primarily composed palmitic acid (16:0), followed by oleic acid (18:1) and stearic acid (18:0).

Surfactant-free synthesis of silica aerogel microspheres with hierarchically porous structure.

PubMed

Zhang, Yulu; Wang, Jin; Zhang, Xuetong

2018-04-01

In this work, we developed a new method to synthesize silica aerogel microspheres via ambient pressure drying (APD) process without applying any surfactants and mechanical stirring. An ethanol solution of partially hydrolyzed, partially condensed silica (CS) was used as precursor in the synthesis, the water-repellent n-Heptane as solvent, while the water-soluble ammonia gas (NH 3 ) as catalyst. After a fast sol-gel process and APD process, aerogel microspheres were obtained in the form of white powder with packing density ranged from 62 mg/cm 3 to 230 mg/cm 3 for different samples. The SEM images exhibited fine spherical morphology for these aerogel microparticles, and their statistical average particle diameter ranged from 0.8 μm to 1.5 μm. Besides, according to the analysis of N 2 adsorption-desorption isotherms, the BET surface area of these aerogel microspheres was in the range of 800-960 m 2 /g, and a considerable volume of micropores was detected along with the abundant mesospores in these microspheres, which was further confirmed by the TEM image and SAXS curve. Based on the very limited solubility of NH 3 in the reaction system, a non-emulsion formation mechanism was proposed to illustrate the formation of these aerogel microspheres. Copyright © 2018 Elsevier Inc. All rights reserved.

Low-temperature photoluminescence study of thin epitaxial GaAs films on Ge substrates

NASA Astrophysics Data System (ADS)

Brammertz, Guy; Mols, Yves; Degroote, Stefan; Motsnyi, Vasyl; Leys, Maarten; Borghs, Gustaaf; Caymax, Matty

2006-05-01

Thin epitaxial GaAs films, with thickness varying from 140 to 1000 nm and different Si doping levels, were grown at 650 °C by organometallic vapor phase epitaxy on Ge substrates and analyzed by low-temperature photoluminescence (PL) spectroscopy. All spectra of thin GaAs on Ge show two different structures, one narrow band-to-band (B2B) structure at an energy of ~1.5 eV and a broad inner-band-gap (IB) structure at an energy of ~1.1 eV. Small strain in the thin GaAs films causes the B2B structure to be separated into a light-hole and a heavy-hole peak. At 2.5 K the good structural quality of the thin GaAs films on Ge can be observed from the narrow excitonic peaks. Peak widths of less than 1 meV are measured. GaAs films with thickness smaller than 200 nm show B2B PL spectra with characteristics of an n-type doping level of approximately 1018 at./cm3. This is caused by heavy Ge diffusion from the substrate into the GaAs at the heterointerface between the two materials. The IB structure observed in all films consists of two Gaussian peaks with energies of 1.04 and 1.17 eV. These deep trapping states arise from Ge-based complexes formed within the GaAs at the Ge-GaAs heterointerface, due to strong diffusion of Ge atoms into the GaAs. Because of similarities with Si-based complexes, the peak at 1.04 eV was identified to be due to a GeGa-GeAs complex, whereas the peak at 1.17 eV was attributed to the GeGa-VGa complex. The intensity of the IB structure decreases strongly as the GaAs film thickness is increased. PL intensity of undoped GaAs films containing antiphase domains (APDs) is four orders of magnitude lower than for similar films without APDs. This reduction in intensity is due to the electrically active Ga-Ga and As-As bonds at the boundaries between the different APDs. When the Si doping level is increased, the PL intensity of the APD-containing films is increased again as well. A film containing APDs with a Si doping level of ~1018 at./cm3 has only a factor 10 reduced intensity. We tentatively explain this observation by Si or Ge clustering at antiphase boundaries, which eliminates the effects of the Ga-Ga and As-As bonds. This assumption is confirmed by the fact that, at 77 K, the ratio between the intensity of the IB peak at 1.17 eV to the intensity of the peak at 1.04 eV is smaller than 1.4 for all films containing APDs, whereas it is larger than 1.4 for all films without APDs. This shows stronger clustering of Si or Ge in the material with APDs. For future electronic applications, Ge diffusion into the GaAs will have to be reduced. PL analysis will be a rapid tool for studying the Ge diffusion into the GaAs thin films.

Receiver design, performance analysis, and evaluation for space-borne laser altimeters and space-to-space laser ranging systems

NASA Technical Reports Server (NTRS)

Davidson, Frederic M.; Sun, Xiaoli; Field, Christopher T.

1994-01-01

This interim report consists of two reports: 'Space Radiation Effects on Si APDs for GLAS' and 'Computer Simulation of Avalanche Photodiode and Preamplifier Output for Laser Altimeters.' The former contains a detailed description of our proton radiation test of Si APD's performed at the Brookhaven National Laboratory. The latter documents the computer program subroutines which were written for the upgrade of NASA's GLAS simulator.

Acquired perforating dermatosis in a patient with Poland syndrome.

PubMed

Fistarol, Susanna K; Itin, Peter H

2003-01-01

Acquired perforating dermatosis (APD) is characterized by umbilicated 1- to 10-mm-measuring papulonodules with a central adherent oystershell-like keratotic plug, typically on the dorsa of the hands, forearms and over the knees. APD is associated with systemic diseases, especially diabetes mellitus and/or renal failure. Histologically the lesions show transepidermal elimination of altered dermal components into a cup-shaped epidermal depression. We present a 69-year-old man with coexisting APD and Poland syndrome (PS), an association not yet described. PS (OMIM 173800) is a rare congenital anomaly consisting of unilateral partial or total absence of the greater pectoralis muscle and ipsilateral symbrachydactyly. Most cases of PS are sporadic as it was in our case. Our patient had, in addition, an untreated diabetic condition, hyperuricaemia, dilated cardiomyopathy and a very recent pulmonary embolism. He responded to therapy with allopurinol. Copyright 2003 S. Karger AG, Basel

Environmental Radiation Measurements on the Mir Space Station. Program 1; Internal Experiment Program

NASA Technical Reports Server (NTRS)

Benton, E. V.; Frank, A. L.; Benton, E. R.

1998-01-01

As part of the NASA/Mir Phase 1B Science Program, the ionizing radiation environment inside and outside the Russian Mir's Space Station was monitored using a combination of Thermoluminescent Detectors (TLD) and CR-39 Plastic Nuclear Track Detectors (PNTD). Radiation measurements inside the Mir station were carried out using six Area Passive Dosimeters (APD), four located inside the Mir Base Block and two located inside the Kvant 2 module, during the NASA-2/Mir-21, NASA-3/Mir-22 and NASA-4/Mir-23 missions. The radiation environment under low shielding was measured using an External Dosimeter Array (EDA) mounted on the outer surface of the Kvant 2 module. The external radiation environment and a location inside the Kvant 2 roughly corresponding to the location of the EDA were monitored for 130 days during the NASA- 4/Mir-23 and NASA-5/Mir-24 missions. Dose rates measured by APD TLDs ranged from 271 to 407 microGy/d during the NASA-2/Mir-21 mission, from 265 to 378 microGy/d during the NASA-3/Mir-22 mission, and from 287 to 421 microGy/d during the NASA-4/Mir-23 mission. APD PNTDs have been analyzed and LET spectra have been Cenerated for the five APDs exposed on the NASA-2/Mir-21 mission and for two APD PNTDs exposed on the NASA-3/Mir-22 mission. Dose equivalent rates on the NASA-2/Mir-21 mission ranged from 513 microSv/d in the Kvant 2 module to 710 microSv/d on the floor of the Base Block. Dose as a function of shielding depth in TLDs has been measured in the thin TLD stacks including in the EDA. EDA dose range from 72.5 Gy under 0.0146 g/sq cm to 0.093 Gy under 3.25 g/sq cm of shielding. Readout and analysis of the reaming PNTDs form the NASA-3/Mir-22 mission and PNTDs from the NASA-4/Mir-23 mission (including those from the EDA) is ongoing and will be completed during the final year of this experiment. Dose equivalent rates for the NASA-3/Mir-22 and NASA-4/Mir-23 APDs will then be determined and comparisons will be made with both model calculations and with results from similar measurements.

Beat-to-Beat Variability of Ventricular Action Potential Duration Oscillates at Low Frequency During Sympathetic Provocation in Humans

PubMed Central

Porter, Bradley; van Duijvenboden, Stefan; Bishop, Martin J.; Orini, Michele; Claridge, Simon; Gould, Justin; Sieniewicz, Benjamin J.; Sidhu, Baldeep; Razavi, Reza; Rinaldi, Christopher A.; Gill, Jaswinder S.; Taggart, Peter

2018-01-01

Background: The temporal pattern of ventricular repolarization is of critical importance in arrhythmogenesis. Enhanced beat-to-beat variability (BBV) of ventricular action potential duration (APD) is pro-arrhythmic and is increased during sympathetic provocation. Since sympathetic nerve activity characteristically exhibits burst patterning in the low frequency range, we hypothesized that physiologically enhanced sympathetic activity may not only increase BBV of left ventricular APD but also impose a low frequency oscillation which further increases repolarization instability in humans. Methods and Results: Heart failure patients with cardiac resynchronization therapy defibrillator devices (n = 11) had activation recovery intervals (ARI, surrogate for APD) recorded from left ventricular epicardial electrodes alongside simultaneous non-invasive blood pressure and respiratory recordings. Fixed cycle length was achieved by right ventricular pacing. Recordings took place during resting conditions and following an autonomic stimulus (Valsalva). The variability of ARI and the normalized variability of ARI showed significant increases post Valsalva when compared to control (p = 0.019 and p = 0.032, respectively). The oscillatory behavior was quantified by spectral analysis. Significant increases in low frequency (LF) power (p = 0.002) and normalized LF power (p = 0.019) of ARI were seen following Valsalva. The Valsalva did not induce changes in conduction variability nor the LF oscillatory behavior of conduction. However, increases in the LF power of ARI were accompanied by increases in the LF power of systolic blood pressure (SBP) and the rate of systolic pressure increase (dP/dtmax). Positive correlations were found between LF-SBP and LF-dP/dtmax (rs = 0.933, p < 0.001), LF-ARI and LF-SBP (rs = 0.681, p = 0.001) and between LF-ARI and LF-dP/dtmax (rs = 0.623, p = 0.004). There was a strong positive correlation between the variability of ARI and LF power of ARI (rs = 0.679, p < 0.001). Conclusions: In heart failure patients, physiological sympathetic provocation induced low frequency oscillation (~0.1 Hz) of left ventricular APD with a strong positive correlation between the LF power of APD and the BBV of APD. These findings may be of importance in mechanisms underlying stability/instability of repolarization and arrhythmogenesis in humans. PMID:29670531

Avalanche photodiode for measurement of low-energy electrons

NASA Astrophysics Data System (ADS)

Ogasawara, K.; Asamura, K.; Mukai, T.; Saito, Y.

2005-06-01

We report on the performance of an Avalanche Photodiode (APD) produced by Hamamatsu Photonics Co. Ltd. (Type Z7966-20) for measurements of low energy electrons. We have set up an electron gun, which can generate a 1-20 keV electron beam impinging onto the APD in a vacuum chamber. The result shows that the pulse height distribution (PHD) of the APD signal exhibits a significant peak for electrons with energies above 8 keV, and the variation of the PHD peak shows a good linearity with the energy of incident electrons. The energy resolution is quite good, though it slightly depends on the electron energy. In the case of low-energies (lower than 10 keV), the pulse height distribution has a characteristic tail on the low energy side, and the energy resolution becomes a little worse. The position of the peak appears on a slightly lower channel than is expected from data at higher energies (near 20 keV). Qualitatively, the low-energy tail is caused by the dead-layer on the surface of the device. The nonlinearity and the worse resolution of the peaks for higher energy electrons may have resulted from a space-charge effect due to created e-h pairs. For a quantitative understanding, we have made a Monte Carlo particle simulation of charge transport and collection inside the APD.

[A comparative study of complications after vagotomy-pyloroplasty using Sugiura-Futagawa procedure and surgery of acid peptic disease].

PubMed

Orozco, H; Mercado, M A; Morales-Linares, J C; Gómez-Méndez, T J

1996-01-01

The frequency of complications of vagotomy and pyloroplasty for treating peptic disease is considerable. The modification of the Sugiura-Futagawa procedure includes bilateral truncal vagotomy and pyloroplasty as part of the devascularization, with a low frequency of related complications. To study the effects after VP in the outcome of both groups of patients. The results of a retrospective, comparative, not randomized, controlled trial of 153 medical records of patients who underwent our modification of the Sugiura-Futagawa operation (SFO) due to Hemorrhagic Portal Hypertension (HPH), and 100 patients with bilateral truncal vagotomy and pyloroplasty (VP) due to Acid-Peptic Disease (APD) are presented. In both groups VP was done. The first group as part of SFO, and the second to treat their disease. We found 47 complications; 40 (40%) were observed in patients who underwent VP for APD and 7 (4%) in SFO: Post-vagotomy Diarrhea (PVD): 11% after APD and 2% after SFO. Dumping Syndrome (DS): 22% and 1%, and Alkaline Reflux Gastritis (ARG): 7% and 0.5% respectively. The calculated risk of developing complications related to vagotomy and pyloroplasty in peptic ulcer disease was 14 times higher. The incidence of these post VP complications at the SFO group was low (4%), in relation to 40% for the APD; the outcomes were statistically significative (p < 0.05).

Geiger-mode APD camera system for single-photon 3D LADAR imaging

NASA Astrophysics Data System (ADS)

Entwistle, Mark; Itzler, Mark A.; Chen, Jim; Owens, Mark; Patel, Ketan; Jiang, Xudong; Slomkowski, Krystyna; Rangwala, Sabbir

2012-06-01

The unparalleled sensitivity of 3D LADAR imaging sensors based on single photon detection provides substantial benefits for imaging at long stand-off distances and minimizing laser pulse energy requirements. To obtain 3D LADAR images with single photon sensitivity, we have demonstrated focal plane arrays (FPAs) based on InGaAsP Geiger-mode avalanche photodiodes (GmAPDs) optimized for use at either 1.06 μm or 1.55 μm. These state-of-the-art FPAs exhibit excellent pixel-level performance and the capability for 100% pixel yield on a 32 x 32 format. To realize the full potential of these FPAs, we have recently developed an integrated camera system providing turnkey operation based on FPGA control. This system implementation enables the extremely high frame-rate capability of the GmAPD FPA, and frame rates in excess of 250 kHz (for 0.4 μs range gates) can be accommodated using an industry-standard CameraLink interface in full configuration. Real-time data streaming for continuous acquisition of 2 μs range gate point cloud data with 13-bit time-stamp resolution at 186 kHz frame rates has been established using multiple solid-state storage drives. Range gate durations spanning 4 ns to 10 μs provide broad operational flexibility. The camera also provides real-time signal processing in the form of multi-frame gray-scale contrast images and single-frame time-stamp histograms, and automated bias control has been implemented to maintain a constant photon detection efficiency in the presence of ambient temperature changes. A comprehensive graphical user interface has been developed to provide complete camera control using a simple serial command set, and this command set supports highly flexible end-user customization.

Limitations in electrophysiological model development and validation caused by differences between simulations and experimental protocols.

PubMed

Carro, Jesús; Rodríguez-Matas, José F; Monasterio, Violeta; Pueyo, Esther

2017-10-01

Models of ion channel dynamics are usually built by fitting isolated cell experimental values of individual parameters while neglecting the interaction between them. Another shortcoming regards the estimation of ionic current conductances, which is often based on quantification of Action Potential (AP)-derived markers. Although this procedure reduces the uncertainty in the calculation of conductances, many studies evaluate electrophysiological AP-derived markers from single cell simulations, whereas experimental measurements are obtained from tissue preparations. In this work, we explore the limitations of these approaches to estimate ion channel dynamics and maximum current conductances and how they could be overcome by using multiscale simulations of experimental protocols. Four human ventricular cell models, namely ten Tusscher and Panfilov (2006), Grandi et al. (2010), O'Hara et al. (2011), and Carro et al. (2011), were used. Two problems involving scales from ion channels to tissue were investigated: 1) characterization of L-type calcium voltage-dependent inactivation I Ca,L ; 2) identification of major ionic conductance contributors to steady-state AP markers, including APD 90 , APD 75 , APD 50 , APD 25 , Triangulation and maximal and minimal values of V and dV/dt during the AP (V max , V min , dV/dt max , dV/dt min ). Our results show that: 1) I Ca,L inactivation characteristics differed significantly when calculated from model equations and from simulations reproducing the experimental protocols. 2) Large differences were found in the ionic currents contributors to APD 25 , Triangulation, V max , dV/dt max and dV/dt min between single cells and 1D-tissue. When proposing any new model formulation, or evaluating an existing model, consistency between simulated and experimental data should be verified considering all involved effects and scales. Copyright © 2016 Elsevier Ltd. All rights reserved.

Blonanserin reverses the phencyclidine (PCP)-induced impairment in novel object recognition (NOR) in rats: role of indirect 5-HT(1A) partial agonism.

PubMed

Horiguchi, M; Meltzer, H Y

2013-06-15

Blonanserin is an atypical antipsychotic drug (APD) which, compared to other atypical APDs, is a relatively selective serotonin (5-HT)2A and dopamine D2 antagonist. Comparing blonanserin with more broadly acting atypical APDs could be useful to test the contributions of actions at other monoamine receptors, e.g. 5-HT1A receptors, to the reversal of PCP-induced novel object recognition (NOR) deficit. In this study, we tested the effect of blonanserin alone, and in combination with 5-HT1A agents, on NOR deficit induced by subchronic treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP; 2 mg/kg), b.i.d., for 7 days. Blonanserin, 1mg/kg, but not 0.3mg/kg, improved the PCP-induced NOR deficit. However, at 1mg/kg, object exploration was diminished. Co-administration of sub-effective doses of blonanserin (0.3 mg/kg) and the 5-HT1A partial agonist, tandospirone (0.2 mg/kg), significantly reversed the NOR deficit without diminishing activity during the acquisition or retention periods. The combination of WAY100635 (0.6 mg/kg), a 5-HT1A antagonist, and blonanserin (1 mg/kg), also diminished object exploration which prevented assessment of the effect of this combination on NOR. WAY100635 (0.6 mg/kg) blocked the ameliorating effect of risperidone (0.1 mg/kg), another atypical APD with low affinity for 5-HT1A receptors, but did not impair exploration. These results suggest that blonansein and risperidone, atypical APDs which lack a direct action on 5-HT1A receptors require 5-HT1A receptor stimulation to reverse the subchronic PCP-induced NOR deficit and provide a support for clinical trial of blonanserin in combination with tandospirone to ameliorate cognitive impairment in schizophrenia and to have fewer side effects. Copyright © 2013 Elsevier B.V. All rights reserved.

Can body surface microvolt T-wave alternans distinguish concordant and discordant intracardiac alternans?

PubMed

Floré, Vincent; Claus, Piet; Symons, Rolf; Smith, Godfrey L; Sipido, Karin R; Willems, Rik

2013-08-01

There is convincing experimental evidence that cellular action potential duration (APD) alternans is arrhythmogenic but its relationship with body surface microvolt T-wave alternans (MTWA) remains unclear. We investigated the relationship between MTWA and APD alternans induced by alternating cycle length (CL) pacing in a pig model. In 10 pigs, catheters in the right atrium (RA) and right (RV) and left ventricle (LV) allowed pacing and recording of monophasic action potentials (MAP). During RA pacing at stable 500-ms CL, LV was paced at alternating CL (505 ms and 495 ms). Changing the alternating LV (A-LV) pacing delay changes the size of the region with alternating ventricular activation. Spectral analysis of intracardiac MAP was correlated with body surface MTWA. In a similar setup (during alternating pacing in RV and LV), we investigated concordant versus discordant APD alternans. Pacing the LV with subtle alternating cycle lengths at short A-LV delay leads to broad QRS (97 ± 10 ms), body surface MTWA (mean Valt 4.2 ± 1.8 µV), and positive RR-interval alternans. At longer A-LV delay, not resulting in QRS widening (68 ± 5 ms), body surface RR alternans was absent but MTWA remained detectable and was even more pronounced (8.7 ± 5.1 µV, P < 0.01). During both concordant and discordant pacing MTWA was present. The precordial leads were better for detecting discordant APD alternans (8.0 ± 2.9 µV and 12.8 ± 4.52 µV, P = 0.02). MTWA is a potent technique to detect subtle and isolated intracardiac APD alternans that is artificially induced by alternating pacing. In the same model, discordant activation alternans can only be discriminated from concordant when using a quantifying approach of MTWA analysis. ©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.

Free Fatty Acid Effects on the Atrial Myocardium: Membrane Ionic Currents Are Remodeled by the Disruption of T-Tubular Architecture

PubMed Central

O’Connell, Ryan P.; Musa, Hassan; Gomez, Mario San Martin; Avula, Uma Mahesh; Herron, Todd J.; Kalifa, Jerome; Anumonwo, Justus M. B.

2015-01-01

Background Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown. Objective To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes. Methods We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4–6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs). Results Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p≤0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ~60% reduction (p<0.01) of the L-type calcium current (ICa-L) and ~30% reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001). Conclusions SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis. PMID:26274906

Free Fatty Acid Effects on the Atrial Myocardium: Membrane Ionic Currents Are Remodeled by the Disruption of T-Tubular Architecture.

PubMed

O'Connell, Ryan P; Musa, Hassan; Gomez, Mario San Martin; Avula, Uma Mahesh; Herron, Todd J; Kalifa, Jerome; Anumonwo, Justus M B

2015-01-01

Epicardial adiposity and plasma levels of free fatty acids (FFAs) are elevated in atrial fibrillation, heart failure and obesity, with potentially detrimental effects on myocardial function. As major components of epicardial fat, FFAs may be abnormally regulated, with a potential to detrimentally modulate electro-mechanical function. The cellular mechanisms underlying such effects of FFAs are unknown. To determine the mechanisms underlying electrophysiological effects of palmitic (PA), stearic (SA) and oleic (OA) FFAs on sheep atrial myocytes. We used electrophysiological techniques, numerical simulations, biochemistry and optical imaging to examine the effects of acutely (≤ 15 min), short-term (4-6 hour) or 24-hour application of individual FFAs (10 μM) on isolated ovine left atrial myocytes (LAMs). Acute and short-term incubation in FFAs resulted in no differences in passive or active properties of isolated left atrial myocytes (LAMs). 24-hour application had differential effects depending on the FFA. PA did not affect cellular passive properties but shortened (p<0.05) action potential duration at 30% repolarization (APD30). APD50 and APD80 were unchanged. SA had no effect on resting membrane potential but reduced membrane capacitance by 15% (p<0.05), and abbreviated APD at all values measured (p≤0.001). OA did not significantly affect passive or active properties of LAMs. Measurement of the major voltage-gated ion channels in SA treated LAMs showed a ~60% reduction (p<0.01) of the L-type calcium current (ICa-L) and ~30% reduction (p<0.05) in the transient outward potassium current (ITO). A human atrial cell model recapitulated SA effects on APD. Optical imaging showed that SA incubated for 24 hours altered t-tubular structure in isolated cells (p<0.0001). SA disrupts t-tubular architecture and remodels properties of membrane ionic currents in sheep atrial myocytes, with potential implications in arrhythmogenesis.

Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria

PubMed Central

Colman, Michael A; Aslanidi, Oleg V; Kharche, Sanjay; Boyett, Mark R; Garratt, Clifford; Hancox, Jules C; Zhang, Henggui

2013-01-01

Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF-induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche–Ramirez–Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF-induced changes of major ionic channel currents (ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca2+ handling. The single cell models for control and AF-remodelled conditions were incorporated into multicellular three-dimensional (3D) atrial tissue models. Effects of the AF-induced electrical remodelling were quantified as the changes of AP profile, AP duration (APD) and its dispersion across the atria, and the vulnerability of atrial tissue to the initiation of re-entry. The dynamic behaviour of re-entrant excitation waves in the 3D models was characterised. In our simulations, AF-induced electrical remodelling abbreviated atrial APD non-uniformly across the atria; this resulted in relatively short APDs co-existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium. As a result, the measured tissue vulnerability to re-entry initiation at these tissue junctions was increased. The AF-induced electrical remodelling also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. Under the AF-remodelled condition, re-entrant scroll waves in the 3D model degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, realistic 3D atrial tissue models indicate that AF-induced electrical remodelling produces regionally heterogeneous and shortened APD; these respectively facilitate initiation and maintenance of re-entrant excitation waves. PMID:23732649

Pro-arrhythmogenic effects of atrial fibrillation-induced electrical remodelling: insights from the three-dimensional virtual human atria.

PubMed

Colman, Michael A; Aslanidi, Oleg V; Kharche, Sanjay; Boyett, Mark R; Garratt, Clifford; Hancox, Jules C; Zhang, Henggui

2013-09-01

Chronic atrial fibrillation (AF) is associated with structural and electrical remodelling in the atria, which are associated with a high recurrence of AF. Through biophysically detailed computer modelling, this study investigated mechanisms by which AF-induced electrical remodelling promotes and perpetuates AF. A family of Courtemanche-Ramirez-Nattel variant models of human atrial cell action potentials (APs), taking into account of intrinsic atrial electrophysiological properties, was modified to incorporate various experimental data sets on AF-induced changes of major ionic channel currents (ICaL, IKur, Ito, IK1, IKs, INaCa) and on intracellular Ca(2+) handling. The single cell models for control and AF-remodelled conditions were incorporated into multicellular three-dimensional (3D) atrial tissue models. Effects of the AF-induced electrical remodelling were quantified as the changes of AP profile, AP duration (APD) and its dispersion across the atria, and the vulnerability of atrial tissue to the initiation of re-entry. The dynamic behaviour of re-entrant excitation waves in the 3D models was characterised. In our simulations, AF-induced electrical remodelling abbreviated atrial APD non-uniformly across the atria; this resulted in relatively short APDs co-existing with marked regional differences in the APD at junctions of the crista terminalis/pectinate muscle, pulmonary veins/left atrium. As a result, the measured tissue vulnerability to re-entry initiation at these tissue junctions was increased. The AF-induced electrical remodelling also stabilized and accelerated re-entrant excitation waves, leading to rapid and sustained re-entry. Under the AF-remodelled condition, re-entrant scroll waves in the 3D model degenerated into persistent and erratic wavelets, leading to fibrillation. In conclusion, realistic 3D atrial tissue models indicate that AF-induced electrical remodelling produces regionally heterogeneous and shortened APD; these respectively facilitate initiation and maintenance of re-entrant excitation waves.

Gaia16apd - a link between fast and slowly declining type I superluminous supernovae

NASA Astrophysics Data System (ADS)

Kangas, T.; Blagorodnova, N.; Mattila, S.; Lundqvist, P.; Fraser, M.; Burgaz, U.; Cappellaro, E.; Carrasco Martínez, J. M.; Elias-Rosa, N.; Hardy, L. K.; Harmanen, J.; Hsiao, E. Y.; Isern, J.; Kankare, E.; Kołaczkowski, Z.; Nielsen, M. B.; Reynolds, T. M.; Rhodes, L.; Somero, A.; Stritzinger, M. D.; Wyrzykowski, Ł.

2017-07-01

We present ultraviolet (UV), optical and infrared photometry and optical spectroscopy of the type Ic superluminous supernova (SLSN) Gaia16apd (=SN 2016eay), covering its evolution from 26 d before the g-band peak to 234.1 d after the peak. Gaia16apd was followed as a part of the NOT Unbiased Transient Survey (NUTS). It is one of the closest SLSNe known (z = 0.102 ± 0.001), with detailed optical and UV observations covering the peak. Gaia16apd is a spectroscopically typical type Ic SLSN, exhibiting the characteristic blue early spectra with O II absorption, and reaches a peak Mg = -21.8 ± 0.1 mag. However, photometrically it exhibits an evolution intermediate between the fast and slowly declining type Ic SLSNe, with an early evolution closer to the fast-declining events. Together with LSQ12dlf, another SLSN with similar properties, it demonstrates a possible continuum between fast and slowly declining events. It is unusually UV-bright even for an SLSN, reaching a non-K-corrected Muvm2 ≃ -23.3 mag, the only other type Ic SLSN with similar UV brightness being SN 2010gx. Assuming that Gaia16apd was powered by magnetar spin-down, we derive a period of P = 1.9 ± 0.2 ms and a magnetic field of B = 1.9 ± 0.2 × 1014 G for the magnetar. The estimated ejecta mass is between 8 and 16 M⊙, and the kinetic energy between 1.3 and 2.5 × 1052 erg, depending on opacity and assuming that the entire ejecta is swept up into a thin shell. Despite the early photometric differences, the spectra at late times are similar to slowly declining type Ic SLSNe, implying that the two subclasses originate from similar progenitors.

Far-ultraviolet to Near-infrared Spectroscopy of a Nearby Hydrogen-poor Superluminous Supernova Gaia16apd

NASA Astrophysics Data System (ADS)

Yan, Lin; Quimby, R.; Gal-Yam, A.; Brown, P.; Blagorodnova, N.; Ofek, E. O.; Lunnan, R.; Cooke, J.; Cenko, S. B.; Jencson, J.; Kasliwal, M.

2017-05-01

We report the first maximum-light far-ultraviolet (FUV) to near-infrared (NIR) spectra (1000 Å - 1.62 μm, rest) of a hydrogen-poor superluminous supernova, Gaia16apd. At z = 0.1018, it is the second closest and the UV brightest SLSN-I, with 17.4 mag in Swift UVW2 band at -11 days pre-maximum. The coordinated observations with HST, Palomar, and Keck were taken at -2 to +25 days. Assuming an exponential (or t 2) form, we derived the rise time of 33 days and the peak bolometric luminosity of 3 × 1044 erg s-1. At the maximum, the photospheric temperature and velocity are 17,000 K and 14,000 km s-1, respectively. The inferred radiative and kinetic energy are roughly 1 × 1051 and 2 × 1052 erg. Gaia16apd is extremely UV luminous, and emits 50% of its total luminosity at 1000-2500 Å. Compared to the UV spectra (normalized at 3100 Å) of well studied SN1992A (Ia), SN2011fe (Ia), SN1999em (IIP), and SN1993J (IIb), it has orders of magnitude more FUV emission. This excess is interpreted primarily as a result of weaker metal-line blanketing due to a much lower abundance of iron group elements in the outer ejecta. Because these elements originate either from the natal metallicity of the star, or have been newly produced, our observation provides direct evidence that little of these freshly synthesized material, including 56Ni, were mixed into the outer ejecta, and the progenitor metallicity is likely sub-solar. This disfavors Pair-instability Supernova models with helium core masses ≥slant 90 {M}⊙ , where substantial 56Ni material is produced. A higher photospheric temperature definitely contributes to the FUV excess from Gaia16apd. Compared with Gaia16apd, we find PS1-11bam is also UV luminous.

Dark Current Degradation of Near Infrared Avalanche Photodiodes from Proton Irradiation

NASA Technical Reports Server (NTRS)

Becker, Heidi N.; Johnston, Allan H.

2004-01-01

InGaAs and Ge avalanche photodiodes (APDs) are examined for the effects of 63-MeV protons on dark current. Dark current increases were large and similar to prior results for silicon APDs, despite the smaller size of InGaAs and Ge devices. Bulk dark current increases from displacement damage in the depletion regions appeared to be the dominant contributor to overall dark current degradation. Differences in displacement damage factors are discussed as they relate to structural and material differences between devices.

NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure.

PubMed

Maleckar, Mary M; Lines, Glenn T; Koivumäki, Jussi T; Cordeiro, Jonathan M; Calloe, Kirstine

2014-11-01

The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore the intracellular Ca(2) (+) transient (CaT), due to HF-induced remodelling of Ca(2+) handling. An existing mathematical model of the canine ventricular myocyte was modified to incorporate recent experimental data from healthy and failing myocytes, resulting in models of both healthy and HF epicardial, midmyocardial, and endocardial cell variants. Affects of NS5806 were also included in HF models through its direct interaction with Kv4.3 and Kv1.4. Single-cell simulations performed in all models (control, HF, and HF + drug) and variants (epi, mid, and endo) assessed AP morphology and underlying ionic processes with a focus on calcium transients (CaT), how these were altered in HF across the ventricular wall, and the subsequent effects of varying compound concentration in HF. Heart failure model variants recapitulated a characteristic increase in AP duration (APD) in the disease. The qualitative effects of application of half-maximal effective concentration (EC50) of NS5806 on APs and CaT are heterogeneous and non-linear. Deepening in the AP notch with drug is a direct effect of the activation of Ito; both Ito and consequent alteration of IK1 kinetics cause decrease in AP plateau potential. Decreased APD50 and APD90 are both due to altered IK1. Analysis revealed that drug effects depend on transmurality. Ca(2+) transient morphology changes-increased amplitude and shorter time to peak-are due to direct increase in ICa,L and indirect larger SR Ca(2+) release subsequent to Ito activation. Downstream effects of a compound acting exclusively on sarcolemmal ion channels are difficult to predict. Remediation of APD to pre-failing state does not ameliorate dysfunction in CaT; however, restoration of notch depth appears to impart modest benefit and a likelihood of therapeutic value in modulating early repolarization. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

The New APD Based Readout for the Crystal Barrel Calorimeter

NASA Astrophysics Data System (ADS)

Urban, M.; Honisch, Ch; Steinacher, M.; CBELSA/TAPS Collaboration

2015-02-01

The CBELSA/TAPS experiment at ELSA measures double polarization observables in meson photoproduction off protons and neutrons. To be able to measure purely neutral reactions off polarized neutrons with high efficiency, the main calorimeter has to be integrated into the first level trigger. This requires to exchange the existing PIN photo diode by a new avalanche photo diode (APD) readout. The newly developed readout electronics will provide an energy resolution compatible to the previous set-up and a fast trigger signal down to 10 MeV energy deposit per crystal. After the successful final tests with a 3x3 CsI crystal matrix in Bonn at ELSA and in Mainz at MAMI all front-end electronics were produced in fall 2013. Automated test routines for the front-end electronics were developed and the characterization measurements of all APDs were successfully accomplished in Bonn. The project is supported by the Deutsche Forschungsgemeinschaft (SFB/TR16) and Schweizerischer Nationalfonds.

X-ray spectroscopy with silicon pin and avalanche photo diodes

NASA Technical Reports Server (NTRS)

Desai, U. D.

1992-01-01

Results of an evaluation of silicon P-Intrinsic-N (PIN) photodiodes and Avalanche Photodiodes (APD) for the direct detection of soft x rays from 1 to 20 keV and for the detection of scintillation light output from CsI(TI) for higher x ray energies (30 to 1000 keV) are presented. About one keV resolution was achieved at room temperature for both the PIN and APD detectors for soft x rays (1 to 20 keV). Commercially available, low power (18 mV), low noise, hybrid preamplifiers, were used. These photodiodes were also coupled to CsI(TI) scintillator and obtained about 6 resolution at 662 keV. The photodiode frequency response matches well with the emission spectrum of the CsI(TI) scintillator providing good spectral resolution and a higher signal than NaI(TI) when viewed by conventional photomultipliers. A PIN-CsI(TI) combination provides a low energy threshold of around 60 keV while for the APD-CsI(TI) it is 15 keV.

Analysis of edge density fluctuation measured by trial KSTAR beam emission spectroscopy systema)

NASA Astrophysics Data System (ADS)

Nam, Y. U.; Zoletnik, S.; Lampert, M.; Kovácsik, Á.

2012-10-01

A beam emission spectroscopy (BES) system based on direct imaging avalanche photodiode (APD) camera has been designed for Korea Superconducting Tokamak Advanced Research (KSTAR) and a trial system has been constructed and installed for evaluating feasibility of the design. The system contains two cameras, one is an APD camera for BES measurement and another is a fast visible camera for position calibration. Two pneumatically actuated mirrors were positioned at front and rear of lens optics. The front mirror can switch the measurement between edge and core region of plasma and the rear mirror can switch between the APD and the visible camera. All systems worked properly and the measured photon flux was reasonable as expected from the simulation. While the measurement data from the trial system were limited, it revealed some interesting characteristics of KSTAR plasma suggesting future research works with fully installed BES system. The analysis result and the development plan will be presented in this paper.

Upgrades to improve the usability, reliability, and spectral range of the MST Thomson scattering diagnostic

NASA Astrophysics Data System (ADS)

Kubala, S. Z.; Borchardt, M. T.; Den Hartog, D. J.; Holly, D. J.; Jacobson, C. M.; Morton, L. A.; Young, W. C.

2016-11-01

The Thomson scattering diagnostic on MST records both equilibrium and fluctuating electron temperature with a range capability of 10 eV-5 keV. Standard operation with two modified commercial Nd:YAG lasers allows measurements at rates of 1 kHz-25 kHz. Several subsystems of the diagnostic are being improved. The power supplies for the avalanche photodiode detectors (APDs) that record the scattered light are being replaced to improve usability, reliability, and maintainability. Each of the 144 APDs will have an individual rack mounted switching supply, with bias voltage adjustable to match the APD. Long-wavelength filters (1140 nm center, 80 nm bandwidth) have been added to the polychromators to improve capability to resolve non-Maxwellian distributions and to enable directed electron flow measurements. A supercontinuum (SC) pulsed white light source has replaced the tungsten halogen lamp previously used for spectral calibration of the polychromators. The SC source combines substantial brightness produced in nanosecond pulses with a spectrum that covers the entire range of the polychromators.

Upgrades to improve the usability, reliability, and spectral range of the MST Thomson scattering diagnostic.

PubMed

Kubala, S Z; Borchardt, M T; Den Hartog, D J; Holly, D J; Jacobson, C M; Morton, L A; Young, W C

2016-11-01

The Thomson scattering diagnostic on MST records both equilibrium and fluctuating electron temperature with a range capability of 10 eV-5 keV. Standard operation with two modified commercial Nd:YAG lasers allows measurements at rates of 1 kHz-25 kHz. Several subsystems of the diagnostic are being improved. The power supplies for the avalanche photodiode detectors (APDs) that record the scattered light are being replaced to improve usability, reliability, and maintainability. Each of the 144 APDs will have an individual rack mounted switching supply, with bias voltage adjustable to match the APD. Long-wavelength filters (1140 nm center, 80 nm bandwidth) have been added to the polychromators to improve capability to resolve non-Maxwellian distributions and to enable directed electron flow measurements. A supercontinuum (SC) pulsed white light source has replaced the tungsten halogen lamp previously used for spectral calibration of the polychromators. The SC source combines substantial brightness produced in nanosecond pulses with a spectrum that covers the entire range of the polychromators.

Scroll wave dynamics in a three-dimensional cardiac tissue model: roles of restitution, thickness, and fiber rotation.

PubMed Central

Qu, Z; Kil, J; Xie, F; Garfinkel, A; Weiss, J N

2000-01-01

Scroll wave (vortex) breakup is hypothesized to underlie ventricular fibrillation, the leading cause of sudden cardiac death. We simulated scroll wave behaviors in a three-dimensional cardiac tissue model, using phase I of the Luo-Rudy (LR1) action potential model. The effects of action potential duration (APD) restitution, tissue thickness, filament twist, and fiber rotation were studied. We found that APD restitution is the major determinant of scroll wave behavior and that instabilities arising from APD restitution are the main determinants of scroll wave breakup in this cardiac model. We did not see a "thickness-induced instability" in the LR1 model, but a minimum thickness is required for scroll breakup in the presence of fiber rotation. The major effect of fiber rotation is to maintain twist in a scroll wave, promoting filament bending and thus scroll breakup. In addition, fiber rotation induces curvature in the scroll wave, which weakens conduction and further facilitates wave break. PMID:10827961

Novel Photon-Counting Detectors for Free-Space Communication

NASA Technical Reports Server (NTRS)

Krainak, M. A.; Yang, G.; Sun, X.; Lu, W.; Merritt, S.; Beck, J.

2016-01-01

We present performance data for novel photon-counting detectors for free space optical communication. NASA GSFC is testing the performance of two types of novel photon-counting detectors 1) a 2x8 mercury cadmium telluride (HgCdTe) avalanche array made by DRS Inc., and a 2) a commercial 2880-element silicon avalanche photodiode (APD) array. We present and compare dark count, photon-detection efficiency, wavelength response and communication performance data for these detectors. We successfully measured real-time communication performance using both the 2 detected-photon threshold and AND-gate coincidence methods. Use of these methods allows mitigation of dark count, after-pulsing and background noise effects. The HgCdTe APD array routinely demonstrated photon detection efficiencies of greater than 50% across 5 arrays, with one array reaching a maximum PDE of 70%. We performed high-resolution pixel-surface spot scans and measured the junction diameters of its diodes. We found that decreasing the junction diameter from 31 micrometers to 25 micrometers doubled the e- APD gain from 470 for an array produced in the year 2010 to a gain of 1100 on an array delivered to NASA GSFC recently. The mean single-photon SNR was over 12 and the excess noise factors measurements were 1.2-1.3. The commercial silicon APD array exhibited a fast output with rise times of 300 ps and pulse widths of 600 ps. On-chip individually filtered signals from the entire array were multiplexed onto a single fast output.

Novel Photon-Counting Detectors for Free-Space Communication

NASA Technical Reports Server (NTRS)

Krainak, Michael A.; Yang, Guan; Sun, Xiaoli; Lu, Wei; Merritt, Scott; Beck, Jeff

2016-01-01

We present performance data for novel photon counting detectors for free space optical communication. NASA GSFC is testing the performance of three novel photon counting detectors 1) a 2x8 mercury cadmium telluride avalanche array made by DRS Inc. 2) a commercial 2880 silicon avalanche photodiode array and 3) a prototype resonant cavity silicon avalanche photodiode array. We will present and compare dark count, photon detection efficiency, wavelength response and communication performance data for these detectors. We discuss system wavelength trades and architectures for optimizing overall communication link sensitivity, data rate and cost performance. The HgCdTe APD array has photon detection efficiencies of greater than 50 were routinely demonstrated across 5 arrays, with one array reaching a maximum PDE of 70. High resolution pixel-surface spot scans were performed and the junction diameters of the diodes were measured. The junction diameter was decreased from 31 m to 25 m resulting in a 2x increase in e-APD gain from 470 on the 2010 array to 1100 on the array delivered to NASA GSFC. Mean single photon SNRs of over 12 were demonstrated at excess noise factors of 1.2-1.3.The commercial silicon APD array has a fast output with rise times of 300ps and pulse widths of 600ps. Received and filtered signals from the entire array are multiplexed onto this single fast output. The prototype resonant cavity silicon APD array is being developed for use at 1 micron wavelength.

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

PubMed Central

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-01-01

Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Results Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (Ito), the rapidly activated omponent of delayed rectifier potassium current (IKr), the slowly activated component of delayed rectifier potassium current (IKs), and the L-type calcium current (ICaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Conclusions Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca2+ current are likely the underlying mechanism of action. PMID:23610573

Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction.

PubMed

Lan, Yun-Feng; Zhang, Jian-Cheng; Gao, Jin-Lao; Wang, Xue-Ping; Fang, Zhou; Fu, Yi-Cheng; Chen, Mei-Yan; Lin, Min; Xue, Qiao; Li, Yang

2013-03-01

To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (I to), the rapidly activated omponent of delayed rectifier potassium current (I Kr), the slowly activated component of delayed rectifier potassium current (I Ks), and the L-type calcium current (I CaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca(2+) current are likely the underlying mechanism of action.

STS-89 tunnel adapter in OPF bay 1

NASA Technical Reports Server (NTRS)

1997-01-01

The tunnel adapter (left) which will be flown on the STS-89 mission is being installed in the Space Shuttle orbiter Endeavour's payload bay in Orbiter Processing Facility bay 1. To the right is the Orbiter Docking System (ODS), with its distinctive red Russian-built Androgynous Peripheral Docking System (APDS). STS-89 will be the eighth U.S. docking mission with the Russian Mir space station. The nine-day space flight is scheduled for launch in mid-January 1998.

HgCdTe avalanche photodiodes: A review

NASA Astrophysics Data System (ADS)

Singh, Anand; Srivastav, Vanya; Pal, Ravinder

2011-10-01

This paper presents a comprehensive review of fundamental issues, device architectures, technology development and applications of HgCdTe based avalanche photodiodes (APD). High gain, above 5×10 3, a low excess noise factor close to unity, THz gain-bandwidth product, and fast response in the range of pico-seconds has been achieved by electron-initiated avalanche multiplication for SWIR, MWIR, and LWIR detector applications involving low optical signals. Detector arrays with good element-to-element uniformity have been fabricated paving the way for fabrication of HgCdTe-APD FPAs.

Effective amplifier noise for an optical receiver based on linear mode avalanche photodiodes

NASA Technical Reports Server (NTRS)

Chen, C.-C.

1989-01-01

The rms noise charge induced by the amplifier for an optical receiver based on the linear-mode avalanche photodiode (APD) was analyzed. It is shown that for an amplifier with a 1-pF capacitor and a noise temperature of 100 K, the rms noise charge due to the amplifier is about 300. Since the noise charge must be small compared to the signal gain, APD gains on the order of 1000 will be required to operate the receiver in the linear mode.

Kvβ1.1 (AKR6A8) senses pyridine nucleotide changes in the mouse heart and modulates cardiac electrical activity.

PubMed

Tur, Jared; Chapalamadugu, Kalyan C; Katnik, Christopher; Cuevas, Javier; Bhatnagar, Aruni; Tipparaju, Srinivas M

2017-03-01

The present study investigates the physiological role of Kvβ1 subunit for sensing pyridine nucleotide (NADH/NAD+) changes in the heart. We used Kvβ1.1 knockout (KO) or wild-type (WT) mice and established that Kvβ1.1 preferentially binds with Kv4.2 and senses the pyridine nucleotide changes in the heart. The cellular action potential duration (APD) obtained from WT cardiomyocytes showed longer APDs with lactate perfusion, which increases intracellular NADH levels, while the APDs remained unaltered in the Kvβ1.1 KO. Ex vivo monophasic action potentials showed a similar response, in which the APDs were prolonged in WT mouse hearts with lactate perfusion; however, the Kvβ1.1 KO mouse hearts did not show APD changes upon lactate perfusion. COS-7 cells coexpressing Kv4.2 and Kvβ1.1 were used for whole cell patch-clamp recordings to evaluate changes caused by NADH (lactate). These data reveal that Kvβ1.1 is required in the mediated inactivation of Kv4.2 currents, when NADH (lactate) levels are increased. In vivo, isoproterenol infusion led to increased NADH in the heart along with QTc prolongation in wild-type mice; regardless of the approach, our data show that Kvβ1.1 recognizes NADH changes and modulates Kv4.2 currents affecting AP and QTc durations. Overall, this study uses multiple levels of investigation, including the heterologous overexpression system, cardiomyocyte, ex vivo, and ECG, and clearly depicts that Kvβ1.1 is an obligatory sensor of NADH/NAD changes in vivo, with a physiological role in the heart. NEW & NOTEWORTHY Cardiac electrical activity is mediated by ion channels, and Kv4.2 plays a significant role, along with its binding partner, the Kvβ1.1 subunit. In the present study, we identify Kvβ1.1 as a sensor of pyridine nucleotide changes and as a modulator of Kv4.2 gating, action potential duration, and ECG in the mouse heart. Copyright © 2017 the American Physiological Society.

Menstrual hygiene management among Bangladeshi adolescent schoolgirls and risk factors affecting school absence: results from a cross-sectional survey

PubMed Central

Luby, Stephen P; Halder, Amal K; Islam, Khairul; Opel, Aftab; Shoab, Abul K; Ghosh, Probir K; Rahman, Mahbubur; Mahon, Therese; Unicomb, Leanne

2017-01-01

Background Many adolescent girls in low-income and middle-income countries lack appropriate facilities and support in school to manage menstruation. Little research has been conducted on how menstruation affects school absence. This study examines the association of menstrual hygiene management knowledge, facilities and practice with absence from school during menstruation among Bangladeshi schoolgirls. Methods We conducted a nationally representative, cross-sectional study in Bangladeshi schools from March to June 2013 among girls 11 to 17 years old who reached menarche. We sampled 700 schools from 50 urban and 50 rural clusters using a probability proportional to size technique. We interviewed 2332 schoolgirls and conducted spot checks in each school for menstrual hygiene facilities. To assess factors associated with reported school absence, we estimated adjusted prevalence difference (APD) for controlling confounders’ effect using generalised estimating equations to account for school-level clustering. Results Among schoolgirls who reached menarche, 41% (931) reported missing school, an average of 2.8 missed days per menstrual cycle. Students who felt uncomfortable at school during menstruation (99% vs 32%; APD=58%; CI 54 to 63) and who believed menstrual problems interfere with school performance (64% vs 30%; APD=27; CI 20 to 33) were more likely to miss school during menstruation than those who did not. School absence during menstruation was less common among girls attending schools with unlocked toilet for girls (35% vs 43%; APD=−5.4; CI −10 to –1.6). School absence was more common among girls who were forbidden from any activities during menstruation (41% vs 33%; APD=9.1; CI 3.3 to 14). Conclusion Risk factors for school absence included girl’s attitude, misconceptions about menstruation, insufficient and inadequate facilities at school, and family restriction. Enabling girls to manage menstruation at school by providing knowledge and management methods prior to menarche, privacy and a positive social environment around menstrual issues has the potential to benefit students by reducing school absence. PMID:28694347

Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart.

PubMed

Winter, James; Bishop, Martin J; Wilder, Catherine D E; O'Shea, Christopher; Pavlovic, Davor; Shattock, Michael J

2018-01-01

Rationale: Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS) on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart. The present study sought to address this, by application of voltage and Ca optical mapping for the simultaneous study of APD and Ca alternans in the intact guinea pig heart during direct SNS. Objective : To determine the effects of SNS on APD and Ca alternans in the intact guinea pig heart and to examine the mechanism(s) by which the effects of SNS are mediated. Methods and Results : Studies utilized simultaneous voltage and Ca optical mapping in isolated guinea pig hearts with intact innervation. Alternans were induced using a rapid dynamic pacing protocol. SNS was associated with rate-independent shortening of action potential duration (APD) and the suppression of APD and Ca alternans, as indicated by a shift in the alternans threshold to faster pacing rates. Qualitatively similar results were observed with exogenous noradrenaline perfusion. In contrast with previous reports, both SNS and noradrenaline acted to flatten the slope of the electrical restitution curve. Pharmacological block of the slow delayed rectifying potassium current (I Ks ), sufficient to abolish I Ks -mediated APD-adaptation, partially reversed the effects of SNS on pacing-induced alternans. Treatment with cyclopiazonic acid, an inhibitor of the sarco(endo)plasmic reticulum ATPase, had opposite effects to that of SNS, acting to increase susceptibility to alternans, and suggesting that accelerated Ca reuptake into the sarcoplasmic reticulum is a major mechanism by which SNS suppresses alternans in the guinea pig heart. Conclusions : SNS suppresses calcium and action potential alternans in the intact guinea pig heart by an action mediated through accelerated Ca handling and via increased I Ks .

Menstrual hygiene management among Bangladeshi adolescent schoolgirls and risk factors affecting school absence: results from a cross-sectional survey.

PubMed

Alam, Mahbub-Ul; Luby, Stephen P; Halder, Amal K; Islam, Khairul; Opel, Aftab; Shoab, Abul K; Ghosh, Probir K; Rahman, Mahbubur; Mahon, Therese; Unicomb, Leanne

2017-07-09

Many adolescent girls in low-income and middle-income countries lack appropriate facilities and support in school to manage menstruation. Little research has been conducted on how menstruation affects school absence. This study examines the association of menstrual hygiene management knowledge, facilities and practice with absence from school during menstruation among Bangladeshi schoolgirls. We conducted a nationally representative, cross-sectional study in Bangladeshi schools from March to June 2013 among girls 11 to 17 years old who reached menarche. We sampled 700 schools from 50 urban and 50 rural clusters using a probability proportional to size technique. We interviewed 2332 schoolgirls and conducted spot checks in each school for menstrual hygiene facilities. To assess factors associated with reported school absence, we estimated adjusted prevalence difference (APD) for controlling confounders' effect using generalised estimating equations to account for school-level clustering. Among schoolgirls who reached menarche, 41% (931) reported missing school, an average of 2.8 missed days per menstrual cycle. Students who felt uncomfortable at school during menstruation (99% vs 32%; APD=58%; CI 54 to 63) and who believed menstrual problems interfere with school performance (64% vs 30%; APD=27; CI 20 to 33) were more likely to miss school during menstruation than those who did not. School absence during menstruation was less common among girls attending schools with unlocked toilet for girls (35% vs 43%; APD=-5.4; CI -10 to -1.6). School absence was more common among girls who were forbidden from any activities during menstruation (41% vs 33%; APD=9.1; CI 3.3 to 14). Risk factors for school absence included girl's attitude, misconceptions about menstruation, insufficient and inadequate facilities at school, and family restriction. Enabling girls to manage menstruation at school by providing knowledge and management methods prior to menarche, privacy and a positive social environment around menstrual issues has the potential to benefit students by reducing school absence. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Predicting the performance of linear optical detectors in free space laser communication links

NASA Astrophysics Data System (ADS)

Farrell, Thomas C.

2018-05-01

While the fundamental performance limit for optical communications is set by the quantum nature of light, in practical systems background light, dark current, and thermal noise of the electronics also degrade performance. In this paper, we derive a set of equations predicting the performance of PIN diodes and linear mode avalanche photo diodes (APDs) in the presence of such noise sources. Electrons generated by signal, background, and dark current shot noise are well modeled in PIN diodes as Poissonian statistical processes. In APDs, on the other hand, the amplifying effects of the device result in statistics that are distinctly non-Poissonian. Thermal noise is well modeled as Gaussian. In this paper, we appeal to the central limit theorem and treat both the variability of the signal and the sum of noise sources as Gaussian. Comparison against Monte-Carlo simulation of PIN diode performance (where we do model shot noise with draws from a Poissonian distribution) validates the legitimacy of this approximation. On-off keying, M-ary pulse position, and binary differential phase shift keying modulation are modeled. We conclude with examples showing how the equations may be used in a link budget to estimate the performance of optical links using linear receivers.

Wideband LTE power amplifier with integrated novel analog pre-distorter linearizer for mobile wireless communications.

PubMed

Uthirajoo, Eswaran; Ramiah, Harikrishnan; Kanesan, Jeevan; Reza, Ahmed Wasif

2014-01-01

For the first time, a new circuit to extend the linear operation bandwidth of a LTE (Long Term Evolution) power amplifier, while delivering a high efficiency is implemented in less than 1 mm2 chip area. The 950 µm × 900 µm monolithic microwave integrated circuit (MMIC) power amplifier (PA) is fabricated in a 2 µm InGaP/GaAs process. An on-chip analog pre-distorter (APD) is designed to improve the linearity of the PA, up to 20 MHz channel bandwidth. Intended for 1.95 GHz Band 1 LTE application, the PA satisfies adjacent channel leakage ratio (ACLR) and error vector magnitude (EVM) specifications for a wide LTE channel bandwidth of 20 MHz at a linear output power of 28 dBm with corresponding power added efficiency (PAE) of 52.3%. With a respective input and output return loss of 30 dB and 14 dB, the PA's power gain is measured to be 32.5 dB while exhibiting an unconditional stability characteristic from DC up to 5 GHz. The proposed APD technique serves to be a good solution to improve linearity of a PA without sacrificing other critical performance metrics.

Wideband LTE Power Amplifier with Integrated Novel Analog Pre-Distorter Linearizer for Mobile Wireless Communications

PubMed Central

Uthirajoo, Eswaran; Ramiah, Harikrishnan; Kanesan, Jeevan; Reza, Ahmed Wasif

2014-01-01

For the first time, a new circuit to extend the linear operation bandwidth of a LTE (Long Term Evolution) power amplifier, while delivering a high efficiency is implemented in less than 1 mm2 chip area. The 950 µm × 900 µm monolithic microwave integrated circuit (MMIC) power amplifier (PA) is fabricated in a 2 µm InGaP/GaAs process. An on-chip analog pre-distorter (APD) is designed to improve the linearity of the PA, up to 20 MHz channel bandwidth. Intended for 1.95 GHz Band 1 LTE application, the PA satisfies adjacent channel leakage ratio (ACLR) and error vector magnitude (EVM) specifications for a wide LTE channel bandwidth of 20 MHz at a linear output power of 28 dBm with corresponding power added efficiency (PAE) of 52.3%. With a respective input and output return loss of 30 dB and 14 dB, the PA’s power gain is measured to be 32.5 dB while exhibiting an unconditional stability characteristic from DC up to 5 GHz. The proposed APD technique serves to be a good solution to improve linearity of a PA without sacrificing other critical performance metrics. PMID:25033049

Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart.

PubMed

Sung, Derrick; Mills, Robert W; Schettler, Jan; Narayan, Sanjiv M; Omens, Jeffrey H; McCulloch, Andrew D

2003-07-01

Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

The Role of Transmural Repolarization Gradient in the Inversion of Cardiac Electric Field: Model Study of ECG in Hypothermia.

PubMed

Arteyeva, Natalia V; Azarov, Jan E

2017-01-01

The changes in ventricular repolarization gradients lead to significant alterations of the electrocardiographic body surface T waves up to the T wave inversion. However, the contribution of a specific gradient remains to be elucidated. The objective of the present investigation was to study the role of the transmural repolarization gradient in the inversion of the body surface T wave with a mathematical model of the hypothermia-induced changes of ventricular repolarization. By means of mathematical simulation, we set the hypothermic action potential duration (APD) distribution on the rabbit ventricular epicardium as it was previously experimentally documented. Then the parameters of the body surface potential distribution were tested with the introduction of different scenarios of the endocardial and epicardial APD behavior in hypothermia resulting in the unchanged, reversed or enlarged transmural repolarization gradient. The reversal of epicardial repolarization gradients (apicobasal, anterior-posterior and interventricular) caused the inversion of the T waves regardless of the direction of the transmural repolarization gradient. However, the most realistic body surface potentials were obtained when the endocardial APDs were not changed under hypothermia while the epicardial APDs prolonged. This produced the reversed and increased transmural repolarization gradient in absolute magnitude. The body surface potentials simulated under the unchanged transmural gradient were reduced in comparison to those simulated under the reversed transmural gradient. The simulations demonstrated that the transmural repolarization gradient did not play a crucial role in the cardiac electric field inversion under hypothermia, but its magnitude and direction contribute to the T wave amplitude. © 2016 Wiley Periodicals, Inc.

Determinants of ante-partum depression: a multicenter study.

PubMed

Balestrieri, Matteo; Matteo, Balestrieri; Isola, Miriam; Miriam, Isola; Bisoffi, Giulia; Giulia, Bisoffi; Calò, Salvatore; Salvatore, Calò; Conforti, Anita; Anita, Conforti; Driul, Lorenza; Lorenza, Driul; Marchesoni, Diego; Diego, Marchesoni; Petrosemolo, Paola; Paola, Petrosemolo; Rossi, Michela; Michela, Rossi; Zito, Adriana; Adriana, Zito; Zorzenone, Stefania; Stefania, Zorzenone; Di Sciascio, Guido; Guido, Di Sciascio; Leone, Roberto; Roberto, Leone; Bellantuono, Cesario; Cesario, Bellantuono

2012-12-01

Ante-partum depression (APD) is usually defined as a non-psychotic depressive episode of mild to moderate severity, beginning in or extending into pregnancy. APD has received less attention than postpartum depression. This is a cross-sectional study carried out in the Obstetrics and Gynaecology (OG) departments of four different general hospitals in Italy. Women attending consecutively the OG departments for their first ultrasound examination were asked to fill in the Edinburgh Postnatal Depression Scale (EPDS) in its Italian validated version. We used the total scores of the EPDS as a continuous variable for univariate and linear regression analyses; in accordance with the literature, the item analysis of EPDS was carried out by classifying the sample as women with "no depression" (scores 0-9), "possible depression" (scores 10-12), "probable depression" (scores 13+) and "probable APD" (scores 15+). The number of women recruited was 1,608. The EPDS assessment classified 10.9 % of the women as possibly depressed, 8.3 % as probably depressed and 4.7 % probably affected from an APD. EPDS score distribution was associated with nationality (higher scores for foreigners), cohabitation (higher scores for women living with friends or in a community), occupation (higher scores for housewives), past episodes of depression and use of herbal drugs. Non-depressed women had significantly lower values on all ten items as compared with depressed women, however, the pattern of item distribution on the EPDS scale remained similar across depression severity groups. In all four groups item 4 (anxious depression) attained the highest scores, while item 10 (suicidality) attained the lowest scores.

Development of HgCdTe large format MBE arrays and noise-free high speed MOVPE EAPD arrays for ground based NIR astronomy

NASA Astrophysics Data System (ADS)

Finger, G.; Baker, I.; Downing, M.; Alvarez, D.; Ives, D.; Mehrgan, L.; Meyer, M.; Stegmeier, J.; Weller, H. J.

2017-11-01

Large format near infrared HgCdTe 2Kx2K and 4Kx4K MBE arrays have reached a level of maturity which meets most of the specifications required for near infrared (NIR) astronomy. The only remaining problem is the persistence effect which is device specific and not yet fully under control. For ground based multi-object spectroscopy on 40 meter class telescopes larger pixels would be advantageous. For high speed near infrared fringe tracking and wavefront sensing the only way to overcome the CMOS noise barrier is the amplification of the photoelectron signal inside the infrared pixel by means of the avalanche gain. A readout chip for a 320x256 pixel HgCdTe eAPD array will be presented which has 32 parallel video outputs being arranged in such a way that the full multiplex advantage is also available for small sub-windows. In combination with the high APD gain this allows reducing the readout noise to the subelectron level by applying nondestructive readout schemes with subpixel sampling. Arrays grown by MOVPE achieve subelectron readout noise and operate with superb cosmetic quality at high APD gain. Efforts are made to reduce the dark current of those arrays to make this technology also available for large format focal planes of NIR instruments offering noise free detectors for deep exposures. The dark current of the latest MOVPE eAPD arrays is already at a level adequate for noiseless broad and narrow band imaging in scientific instruments.

AlInAsSb/GaSb staircase avalanche photodiode

NASA Astrophysics Data System (ADS)

Ren, Min; Maddox, Scott; Chen, Yaojia; Woodson, Madison; Campbell, Joe C.; Bank, Seth

2016-02-01

Over 30 years ago, Capasso and co-workers [IEEE Trans. Electron Devices 30, 381 (1982)] proposed the staircase avalanche photodetector (APD) as a solid-state analog of the photomultiplier tube. In this structure, electron multiplication occurs deterministically at steps in the conduction band profile, which function as the dynodes of a photomultiplier tube, leading to low excess multiplication noise. Unlike traditional APDs, the origin of staircase gain is band engineering rather than large applied electric fields. Unfortunately, the materials available at the time, principally AlxGa1-xAs/GaAs, did not offer sufficiently large conduction band offsets and energy separations between the direct and indirect valleys to realize the full potential of the staircase gain mechanism. Here, we report a true staircase APD operation using alloys of a rather underexplored material, AlxIn1-xAsySb1-y, lattice-matched to GaSb. Single step "staircase" devices exhibited a constant gain of ˜2×, over a broad range of applied bias, operating temperature, and excitation wavelengths/intensities, consistent with Monte Carlo calculations.

Gigahertz-gated InGaAs/InP single-photon detector with detection efficiency exceeding 55% at 1550 nm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Comandar, L. C.; Engineering Department, Cambridge University, 9 J J Thomson Ave, Cambridge CB3 0FA; Fröhlich, B.

We report on a gated single-photon detector based on InGaAs/InP avalanche photodiodes (APDs) with a single-photon detection efficiency exceeding 55% at 1550 nm. Our detector is gated at 1 GHz and employs the self-differencing technique for gate transient suppression. It can operate nearly dead time free, except for the one clock cycle dead time intrinsic to self-differencing, and we demonstrate a count rate of 500 Mcps. We present a careful analysis of the optimal driving conditions of the APD measured with a dead time free detector characterization setup. It is found that a shortened gate width of 360 ps together with anmore » increased driving signal amplitude and operation at higher temperatures leads to improved performance of the detector. We achieve an afterpulse probability of 7% at 50% detection efficiency with dead time free measurement and a record efficiency for InGaAs/InP APDs of 55% at an afterpulse probability of only 10.2% with a moderate dead time of 10 ns.« less

Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion.

PubMed

Mbonile, Lumuli

2016-03-17

Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated. APD symptoms usually start 3 - 10 days before menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old woman presented with urticaria, petechiae and palpable pinpoint purpura lesions of the legs, forearms, neck and buttocks 1 week prior to her menses starting and 2 months after a medical abortion. She was diagnosed with allergic contact dermatitis and topical steroids were prescribed. Her skin conditions did not improve and were associated with her menstrual cycle. We performed an intradermal test using progesterone, which was positive. She was treated with oral contraceptive pills and the symptoms were resolved. This is a typical case of APD triggered by increased sensitivity to endogenous progesterone induced a few months after medical abortion.

Bifurcation theory and cardiac arrhythmias

PubMed Central

Karagueuzian, Hrayr S; Stepanyan, Hayk; Mandel, William J

2013-01-01

In this paper we review two types of dynamic behaviors defined by the bifurcation theory that are found to be particularly useful in describing two forms of cardiac electrical instabilities that are of considerable importance in cardiac arrhythmogenesis. The first is action potential duration (APD) alternans with an underlying dynamics consistent with the period doubling bifurcation theory. This form of electrical instability could lead to spatially discordant APD alternans leading to wavebreak and reentrant form of tachyarrhythmias. Factors that modulate the APD alternans are discussed. The second form of bifurcation of importance to cardiac arrhythmogenesis is the Hopf-homoclinic bifurcation that adequately describes the dynamics of the onset of early afterdepolarization (EAD)-mediated triggered activity (Hopf) that may cause ventricular tachycardia and ventricular fibrillation (VT/VF respectively). The self-termination of the triggered activity is compatible with the homoclinic bifurcation. Ionic and intracellular calcium dynamics underlying these dynamics are discussed using available experimental and simulation data. The dynamic analysis provides novel insights into the mechanisms of VT/VF, a major cause of sudden cardiac death in the US. PMID:23459417

Genetic defects in PI3Kδ affect B-cell differentiation and maturation leading to hypogammaglobulineamia and recurrent infections.

PubMed

Wentink, Marjolein; Dalm, Virgil; Lankester, Arjan C; van Schouwenburg, Pauline A; Schölvinck, Liesbeth; Kalina, Tomas; Zachova, Radana; Sediva, Anna; Lambeck, Annechien; Pico-Knijnenburg, Ingrid; van Dongen, Jacques J M; Pac, Malgorzata; Bernatowska, Ewa; van Hagen, Martin; Driessen, Gertjan; van der Burg, Mirjam

2017-03-01

Mutations in PIK3CD and PIK3R1 cause activated PI3K-δ syndrome (APDS) by dysregulation of the PI3K-AKT pathway. We studied precursor and peripheral B-cell differentiation and apoptosis via flowcytometry. Furthermore, we performed AKT-phosphorylation assays and somatic hypermutations (SHM) and class switch recombination (CSR) analysis. We identified 13 patients of whom 3 had new mutations in PIK3CD or PIK3R1. Patients had low total B-cell numbers with increased frequencies of transitional B cells and plasmablasts, while the precursor B-cell compartment in bone marrow was relatively normal. Basal AKT phosphorylation was increased in lymphocytes from APDS patients and natural effector B cells where most affected. PI3K mutations resulted in altered SHM and CSR and increased apoptosis. The B-cell compartment in APDS patients is affected by the mutations in PI3K. There is reduced differentiation beyond the transitional stage, increased AKT phosphorylation and increased apoptosis. This B-cell phenotype contributes to the clinical phenotype. Copyright © 2017. Published by Elsevier Inc.

Direct detection optical intersatellite link at 220 Mbps using AlGaAs laser diode and silicon APD with 4-ary PPM signaling

NASA Technical Reports Server (NTRS)

Sun, Xiaoli; Davidson, Frederic M.

1990-01-01

A newly developed 220 Mbps free-space 4-ary pulse position modulation (PPM) direct detection optical communication system is described. High speed GaAs integrated circuits were used to construct the PPM encoder and receiver electronic circuits. Both PPM slot and word timing recovery were provided in the PPM receiver. The optical transmitter consisted of an AlGaAs laser diode (Mitsubishi ML5702A, lambda=821nm) and a high speed driver unit. The photodetector consisted of a silicon avalanche photodiode (APD) (RCA30902S) preceded by an optical interference filter (delta lambda=10nm). Preliminary tests showed that the self-synchronized PPM receiver could achieve a receiver bit error rate of less than 10(exp -6) at 25 nW average received optical signal power or 360 photons per transmitted information bit. The relatively poor receiver sensitivity was believed to be caused by the insufficient electronic bandwidth of the APD preamplifier and the poor linearity of the preamplifier high frequency response.

Performance Dependences of Multiplication Layer Thickness for InP/InGaAs Avalanche Photodiodes Based on Time Domain Modeling

NASA Technical Reports Server (NTRS)

Xiao, Yegao; Bhat, Ishwara; Abedin, M. Nurul

2005-01-01

InP/InGaAs avalanche photodiodes (APDs) are being widely utilized in optical receivers for modern long haul and high bit-rate optical fiber communication systems. The separate absorption, grading, charge, and multiplication (SAGCM) structure is an important design consideration for APDs with high performance characteristics. Time domain modeling techniques have been previously developed to provide better understanding and optimize design issues by saving time and cost for the APD research and development. In this work, performance dependences on multiplication layer thickness have been investigated by time domain modeling. These performance characteristics include breakdown field and breakdown voltage, multiplication gain, excess noise factor, frequency response and bandwidth etc. The simulations are performed versus various multiplication layer thicknesses with certain fixed values for the areal charge sheet density whereas the values for the other structure and material parameters are kept unchanged. The frequency response is obtained from the impulse response by fast Fourier transformation. The modeling results are presented and discussed, and design considerations, especially for high speed operation at 10 Gbit/s, are further analyzed.

Performances of a HGCDTE APD based direct detection lidar at 2 μm. Application to dial measurements

NASA Astrophysics Data System (ADS)

Gibert, Fabien; Dumas, Arnaud; Rothman, Johan; Edouart, Dimitri; Cénac, Claire; Pellegrino, Jessica

2018-04-01

A lidar receiver with a direct detection chain adapted to a HgCdTe APD based detector with electric cooling is associated to a 2.05 μm Ho :YLF pulsed dual wavelength single mode transmitter to provide the first atmospheric lidar measurements using this technology. Experiments confirm the outstanding sensitivity of the detector and hightligth its huge potential for DIAL measurements of trace gas (CO2 and H2O) in this spectral domain. Performances of coherent vs direct detection at 2.05 μm is assessed.

KATP channel inhibition blunts electromechanical decline during hypoxia in left ventricular working rabbit hearts

PubMed Central

Garrott, Kara; Kuzmiak‐Glancy, Sarah; Wengrowski, Anastasia; Zhang, Hanyu; Rogers, Jack

2017-01-01

Key points Heart function is critically dependent upon the balance of energy production and utilization. Sarcolemmal ATP‐sensitive potassium channels (KATP channels) in cardiac myocytes adjust contractile function to compensate for the level of available energy.Understanding the activation of KATP channels in working myocardium during high‐stress situations is crucial to the treatment of cardiovascular disease, especially ischaemic heart disease.Using a new optical mapping approach, we measured action potentials from the surface of excised contracting rabbit hearts to assess when sarcolemmal KATP channels were activated during physiologically relevant workloads and during gradual reductions in myocardial oxygenation.We demonstrate that left ventricular pressure is closely linked to KATP channel activation and that KATP channel inhibition with a low concentration of tolbutamide prevents electromechanical decline when oxygen availability is reduced. As a result, KATP channel inhibition probably exacerbates a mismatch between energy demand and energy production when myocardial oxygenation is low. Abstract Sarcolemmal ATP‐sensitive potassium channel (KATP channel) activation in isolated cells is generally understood, although the relationship between myocardial oxygenation and KATP activation in excised working rabbit hearts remains unknown. We optically mapped action potentials (APs) in excised rabbit hearts to test the hypothesis that hypoxic changes would be more severe in left ventricular (LV) working hearts (LWHs) than Langendorff (LANG) perfused hearts. We further hypothesized that KATP inhibition would prevent those changes. Optical APs were mapped when measuring LV developed pressure (LVDP), coronary flow rate and oxygen consumption in LANG and LWHs. Hearts were paced to increase workload and perfusate was deoxygenated to study the effects of myocardial hypoxia. A subset of hearts was perfused with 1 μm tolbutamide (TOLB) to identify the level of AP duration (APD) shortening attributed to KATP channel activation. During sinus rhythm, APD was shorter in LWHs compared to LANG hearts. APD in both LWHs and LANG hearts dropped steadily during deoxygenation. With TOLB, APDs in LWHs were longer at all workloads and APD reductions during deoxygenation were blunted in both LWHs and LANG hearts. At 50% perfusate oxygenation, APD and LVDP were significantly higher in LWHs perfused with TOLB (199 ± 16 ms; 92 ± 5.3 mmHg) than in LWHs without TOLB (109 ± 14 ms, P = 0.005; 65 ± 6.5 mmHg, P = 0.01). Our results indicate that KATP channels are activated to a greater extent in perfused hearts when the LV performs pressure–volume work. The results of the present study demonstrate the critical role of KATP channels in modulating myocardial function over a wide range of physiological conditions. PMID:28177123

A 1.5k x 1.5k class photon counting HgCdTe linear avalanche photo-diode array for low background space astronomy in the 1-5micron infrared

NASA Astrophysics Data System (ADS)

Hall, Donald

Under a current award, NASA NNX 13AC13G "EXTENDING THE ASTRONOMICAL APPLICATION OF PHOTON COUNTING HgCdTe LINEAR AVALANCHE PHOTODIODE ARRAYS TO LOW BACKGROUND SPACE OBSERVATIONS" UH has used Selex SAPHIRA 320 x 256 MOVPE L-APD HgCdTe arrays developed for Adaptive Optics (AO) wavefront (WF) sensing to investigate the potential of this technology for low background space astronomy applications. After suppressing readout integrated circuit (ROIC) glow, we have placed upper limits on gain normalized dark current of 0.01 e-/sec at up to 8 volts avalanche bias, corresponding to avalanche gain of 5, and have operated with avalanche gains of up to several hundred at higher bias. We have also demonstrated detection of individual photon events. The proposed investigation would scale the format to 1536 x 1536 at 12um (the largest achievable in a standard reticule without requiring stitching) while incorporating reference pixels required at these low dark current levels. The primary objective is to develop, produce and characterize a 1.5k x 1.5k at 12um pitch MOVPE HgCdTe L-APD array, with nearly 30 times the pixel count of the 320 x 256 SAPHIRA, optimized for low background space astronomy. This will involve: 1) Selex design of a 1.5k x 1.5k at 12um pitch ROIC optimized for low background operation, silicon wafer fabrication at the German XFab foundry in 0.35 um 3V3 process and dicing/test at Selex, 2) provision by GL Scientific of a 3-side close-buttable carrier building from the heritage of the HAWAII xRG family, 3) Selex development and fabrication of 1.5k x 1.5k at 12 um pitch MOVPE HgCdTe L-APD detector arrays optimized for low background applications, 4) hybridization, packaging into a sensor chip assembly (SCA) with initial characterization by Selex and, 5) comprehensive characterization of low background performance, both in the laboratory and at ground based telescopes, by UH. The ultimate goal is to produce and eventually market a large format array, the L-APD equivalent of the Teledyne H1RG and H2RG, able to achieve sub-electron read noise and count 1 - 5 um photons with high quantum efficiency and low dark count rate while preserving their Poisson statistics and noise.

Long-wavelength photonic integrated circuits and avalanche photodetectors

NASA Astrophysics Data System (ADS)

Tsou, Yi-Jen D.; Zaytsev, Sergey; Pauchard, Alexandre; Hummel, Steve; Lo, Yu-Hwa

2001-10-01

Fast-growing internet traffic volume require high data communication bandwidth over longer distances. Access network bottlenecks put pressure on short-range (SR) telecommunication systems. To effectively address these datacom and telecom market needs, low-cost, high-speed laser modules at 1310 to 1550 nm wavelengths and avalanche photodetectors are required. The great success of GaAs 850nm VCSEls for Gb/s Ethernet has motivated efforts to extend VCSEL technology to longer wavelengths in the 1310 and 1550 nm regimes. However, the technological challenges associated with materials for long wavelength VCSELs are tremendous. Even with recent advances in this area, it is believed that significant additional development is necessary before long wavelength VCSELs that meet commercial specifications will be widely available. In addition, the more stringent OC192 and OC768 specifications for single-mode fiber (SMF) datacom may require more than just a long wavelength laser diode, VCSEL or not, to address numerous cost and performance issues. We believe that photonic integrated circuits (PICs), which compactly integrate surface-emitting lasers with additional active and passive optical components with extended functionality, will provide the best solutions to today's problems. Photonic integrated circuits have been investigated for more than a decade. However, they have produced limited commercial impact to date primarily because the highly complicated fabrication processes produce significant yield and device performance issues. In this presentation, we will discuss a new technology platform of InP-based PICs compatible with surface-emitting laser technology, as well as a high data rate externally modulated laser module. Avalanche photodetectors (APDs) are the key component in the receiver to achieve high data rate over long transmission distance because of their high sensitivity and large gain- bandwidth product. We have used wafer fusion technology to achieve InGaAs/Si APDs with much greater potential than the traditional InGaAs/InP APDs. Preliminary results on their performance will be presented.

SWIR HgCdTe avalanche photiode focal plane array performances evaluation

NASA Astrophysics Data System (ADS)

de Borniol, E.; Rothman, J.; Salveti, F.; Feautrier, P.

2017-11-01

One of the main challenges of modern astronomical instruments like adaptive optics (AO) systems or fringe trackers is to deal with the very low photons flux detection scenarios. The typical timescale of atmospheric turbulences being in the range of some tens of milliseconds, infrared wavefront sensors for AO systems needs frame rates higher than 1 KHz leading to integration times lower than 1 ms. This integration time associated with a low irradiance results in a few number of integrated photons per frame per pixel. To preserve the information coming from this weak signal, the focal plane array (FPA) has to present a low read out noise, a high quantum efficiency and a low dark current. Up to now, the output noise of high speed near infrared sensors is limited by the silicon read out circuit noise. The use of HgCdTe avalanche photodiodes with high gain at moderate reverse bias and low excess noise seems then a logical way to reduce the impact of the read noise on images signal to noise ratio. These low irradiance passive imaging applications with integration times in the millisecond range needs low photodiode dark current and low background current. These requirements lead to the choice of the photodiode cut off wavelength. The short wave infrared (SWIR) around 3 μm is a good compromise between the gain that can be obtain for a given APD bias and the background and dark current. The CEA LETI HgCdTe APD technology, and a fine analysis of the gain curve characteristic are presented in [1] and won't be detailed here. The response time of the APD is also a key factor for a high frame rate FPA. This parameter has been evaluated in [2] and the results shows cut off frequencies in the GHz range. In this communication we report the performances of a SWIR APD FPA designed and fabricated by CEA LETI and SOFRADIR for astrophysical applications. This development was made in the frame of RAPID, a 4 years R&D project funded by the French FUI (Fond Unique Interministériel). This project involves industrial and academic partners from the field of advanced infrared focal plane arrays fabrication (SOFRADIR and CEA LETI) and of astronomical/defense institutes (IPAG, LAM, ONERA). The goal of this program is to develop a fast and low noise SWIR camera for astronomical fast applications like adaptive optics wavefront sensing and fringe tracking for astronomical interferometers [3]. The first batch of FPA's was based on liquid-phase epitaxy (LPE) grown photodiode arrays with 3 μm cut off wavelength. In order to get higher avalanche gain for a given photodiode reverse bias voltage, we have made a second batch with a cadmium composition leading to 3.3 μm cut off wavelength (λc). This paper described the read out circuit in the next section. The aim section III is to find the critical parameter that has to be measured to evaluate the signal to noise ratio (SNR) of an APD FPA. The main electro optical characteristics of an FPA based on 3.3μm cut off wavelength APDs are reported in "Rapid FPAs characterisation" section. The dark current evolution with temperature of a 3 μm FPA high and low APD bias is also detailed in this section.

Development of a Monte Carlo Simulation for APD-Based PET Detectors Using a Continuous Scintillating Crystal

NASA Astrophysics Data System (ADS)

Clowes, P.; Mccallum, S.; Welch, A.

2006-10-01

We are currently developing a multilayer avalanche photodiode (APD)-based detector for use in positron emission tomography (PET), which utilizes thin continuous crystals. In this paper, we developed a Monte Carlo-based simulation to aid in the design of such detectors. We measured the performance of a detector comprising a single thin continuous crystal (3.1 mm times 9.5 mm times 9.5 mm) of lutetium yttrium ortho-silicate (LYSO) and an APD array (4times4) elements; each element 1.6 mm2 and on a 2.3 mm pitch. We showed that a spatial resolution of better than 2.12 mm is achievable throughout the crystal provided that we adopt a Statistics Based Positioning (SBP) Algorithm. We then used Monte Carlo simulation to model the behavior of the detector. The accuracy of the Monte Carlo simulation was verified by comparing measured and simulated parent datasets (PDS) for the SBP algorithm. These datasets consisted of data for point sources at 49 positions uniformly distributed over the detector area. We also calculated the noise in the detector circuit and verified this value by measurement. The noise value was included in the simulation. We show that the performance of the simulation closely matches the measured performance. The simulations were extended to investigate the effect of different noise levels on positioning accuracy. This paper showed that if modest improvements could be made in the circuit noise then positioning accuracy would be greatly improved. In summary, we have developed a model that can be used to simulate the performance of a variety of APD-based continuous crystal PET detectors

A Controlled Study of the Effectiveness of an Adaptive Closed-Loop Algorithm to Minimize Corticosteroid-Induced Stress Hyperglycemia in Type 1 Diabetes

PubMed Central

Youssef, Joseph El; Castle, Jessica R; Branigan, Deborah L; Massoud, Ryan G; Breen, Matthew E; Jacobs, Peter G; Bequette, B Wayne; Ward, W Kenneth

2011-01-01

To be effective in type 1 diabetes, algorithms must be able to limit hyperglycemic excursions resulting from medical and emotional stress. We tested an algorithm that estimates insulin sensitivity at regular intervals and continually adjusts gain factors of a fading memory proportional-derivative (FMPD) algorithm. In order to assess whether the algorithm could appropriately adapt and limit the degree of hyperglycemia, we administered oral hydrocortisone repeatedly to create insulin resistance. We compared this indirect adaptive proportional-derivative (APD) algorithm to the FMPD algorithm, which used fixed gain parameters. Each subject with type 1 diabetes (n = 14) was studied on two occasions, each for 33 h. The APD algorithm consistently identified a fall in insulin sensitivity after hydrocortisone. The gain factors and insulin infusion rates were appropriately increased, leading to satisfactory glycemic control after adaptation (premeal glucose on day 2, 148 ± 6 mg/dl). After sufficient time was allowed for adaptation, the late postprandial glucose increment was significantly lower than when measured shortly after the onset of the steroid effect. In addition, during the controlled comparison, glycemia was significantly lower with the APD algorithm than with the FMPD algorithm. No increase in hypoglycemic frequency was found in the APD-only arm. An afferent system of duplicate amperometric sensors demonstrated a high degree of accuracy; the mean absolute relative difference of the sensor used to control the algorithm was 9.6 ± 0.5%. We conclude that an adaptive algorithm that frequently estimates insulin sensitivity and adjusts gain factors is capable of minimizing corticosteroid-induced stress hyperglycemia. PMID:22226248

Can non‐clinical repolarization assays predict the results of clinical thorough QT studies? Results from a research consortium

PubMed Central

Park, Eunjung; Gintant, Gary A; Bi, Daoqin; Kozeli, Devi; Pettit, Syril D; Skinner, Matthew; Willard, James; Wisialowski, Todd; Koerner, John; Valentin, Jean‐Pierre

2018-01-01

Background and Purpose Translation of non‐clinical markers of delayed ventricular repolarization to clinical prolongation of the QT interval corrected for heart rate (QTc) (a biomarker for torsades de pointes proarrhythmia) remains an issue in drug discovery and regulatory evaluations. We retrospectively analysed 150 drug applications in a US Food and Drug Administration database to determine the utility of established non‐clinical in vitro IKr current human ether‐à‐go‐go‐related gene (hERG), action potential duration (APD) and in vivo (QTc) repolarization assays to detect and predict clinical QTc prolongation. Experimental Approach The predictive performance of three non‐clinical assays was compared with clinical thorough QT study outcomes based on free clinical plasma drug concentrations using sensitivity and specificity, receiver operating characteristic (ROC) curves, positive (PPVs) and negative predictive values (NPVs) and likelihood ratios (LRs). Key Results Non‐clinical assays demonstrated robust specificity (high true negative rate) but poor sensitivity (low true positive rate) for clinical QTc prolongation at low‐intermediate (1×–30×) clinical exposure multiples. The QTc assay provided the most robust PPVs and NPVs (ability to predict clinical QTc prolongation). ROC curves (overall test accuracy) and LRs (ability to influence post‐test probabilities) demonstrated overall marginal performance for hERG and QTc assays (best at 30× exposures), while the APD assay demonstrated minimal value. Conclusions and Implications The predictive value of hERG, APD and QTc assays varies, with drug concentrations strongly affecting translational performance. While useful in guiding preclinical candidates without clinical QT prolongation, hERG and QTc repolarization assays provide greater value compared with the APD assay. PMID:29181850

Glutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs.

PubMed

Xie, Chaoqin; Biary, Nora; Tocchetti, Carlo G; Aon, Miguel A; Paolocci, Nazareno; Kauffman, Justin; Akar, Fadi G

2013-04-01

Chronic hyperglycemia in type-1 diabetes mellitus is associated with oxidative stress (OS) and sudden death. Mechanistic links remain unclear. We investigated changes in electrophysiological (EP) properties in a model of chronic hyperglycemia before and after challenge with OS by GSH oxidation and tested reversibility of EP remodeling by insulin. Guinea pigs survived for 1 mo following streptozotocin (STZ) or saline (sham) injection. A treatment group received daily insulin for 2 wk to reverse STZ-induced hyperglycemia (STZ + Ins). EP properties were measured using high-resolution optical action potential mapping before and after challenge of hearts with diamide. Despite elevation of glucose levels in STZ compared with sham-operated (P = 0.004) and STZ + Ins (P = 0.002) animals, average action potential duration (APD) and arrhythmia propensity were not altered at baseline. Diamide promoted early (<10 min) formation of arrhythmic triggers reflected by a higher arrhythmia scoring index in STZ (P = 0.045) and STZ + Ins (P = 0.033) hearts compared with sham-operated hearts. APD heterogeneity underwent a more pronounced increase in response to diamide in STZ and STZ + Ins hearts compared with sham-operated hearts. Within 30 min, diamide resulted in spontaneous incidence of ventricular tachycardia and ventricular fibrillation (VT/VF) in 3/6, 2/5, 1/5, and 0/4 STZ, STZ + Ins, sham-operated, and normal hearts, respectively. Hearts prone to VT/VF exhibited greater APD heterogeneity (P = 0.010) compared with their VT/VF-free counterparts. Finally, altered EP properties in STZ were not rescued by insulin. In conclusion, GSH oxidation enhances APD heterogeneity and increases arrhythmia scoring index in a guinea pig model of chronic hyperglycemia. Despite normalization of glycemic levels by insulin, these proarrhythmic properties are not reversed, suggesting the importance of targeting antioxidant defenses for arrhythmia suppression.

Ventricular stimulus site influences dynamic dispersion of repolarization in the intact human heart

PubMed Central

Orini, Michele; Simon, Ron B.; Providência, Rui; Khan, Fakhar Z.; Segal, Oliver R.; Babu, Girish G.; Bradley, Richard; Rowland, Edward; Ahsan, Syed; Chow, Anthony W.; Lowe, Martin D.; Taggart, Peter

2016-01-01

The spatial variation in restitution properties in relation to varying stimulus site is poorly defined. This study aimed to investigate the effect of varying stimulus site on apicobasal and transmural activation time (AT), action potential duration (APD) and repolarization time (RT) during restitution studies in the intact human heart. Ten patients with structurally normal hearts, undergoing clinical electrophysiology studies, were enrolled. Decapolar catheters were placed apex to base in the endocardial right ventricle (RVendo) and left ventricle (LVendo), and an LV branch of the coronary sinus (LVepi) for transmural recording. S1–S2 restitution protocols were performed pacing RVendo apex, LVendo base, and LVepi base. Overall, 725 restitution curves were analyzed, 74% of slopes had a maximum slope of activation recovery interval (ARI) restitution (Smax) > 1 (P < 0.001); mean Smax = 1.76. APD was shorter in the LVepi compared with LVendo, regardless of pacing site (30-ms difference during RVendo pacing, 25-ms during LVendo, and 48-ms during LVepi; 50th quantile, P < 0.01). Basal LVepi pacing resulted in a significant transmural gradient of RT (77 ms, 50th quantile: P < 0.01), due to loss of negative transmural AT-APD coupling (mean slope 0.63 ± 0.3). No significant transmural gradient in RT was demonstrated during endocardial RV or LV pacing, with preserved negative transmural AT-APD coupling (mean slope −1.36 ± 1.9 and −0.71 ± 0.4, respectively). Steep ARI restitution slopes predominate in the normal ventricle and dynamic ARI; RT gradients exist that are modulated by the site of activation. Epicardial stimulation to initiate ventricular activation promotes significant transmural gradients of repolarization that could be proarrhythmic. PMID:27371682

Dopamine D3 receptor antagonism contributes to blonanserin-induced cortical dopamine and acetylcholine efflux and cognitive improvement.

PubMed

Huang, Mei; Kwon, Sunoh; Oyamada, Yoshihiro; Rajagopal, Lakshmi; Miyauchi, Masanori; Meltzer, Herbert Y

2015-11-01

Blonanserin is a novel atypical antipsychotic drug (APD), which, unlike most atypical APDs, has a slightly higher affinity for dopamine (DA) D2 than serotonin (5-HT)2A receptors, and is an antagonist at both, as well as at D3 receptors. The effects of atypical APDs to enhance rodent cortical, hippocampal, limbic, and dorsal striatal (dSTR) DA and acetylcholine (ACh) release, contribute to their ability to improve novel object recognition (NOR) in rodents treated with sub-chronic (sc) phencyclidine (PCP) and cognitive impairment associated with schizophrenia (CIAS). Here we determined the ability of blonanserin, the D3 antagonist NGB 2904, and the typical APD, haloperidol, a D2 antagonist, to enhance neurotransmitter efflux in the medial prefrontal cortex (mPFC) and dSTR of mice, and to ameliorate the scPCP-induced deficit in NOR in rats. Blonanserin, 10mg/kg, i.p., increased DA, norepinephrine (NE), and ACh efflux in mPFC and dSTR. NGB 2904, 3mg/kg, increased DA and ACh, but not NE, efflux in mPFC, and DA, but not ACh, efflux in dSTR. Haloperidol increased DA and NE efflux in dSTR only. The selective D3 agonist PD 128907 partially blocked the blonanserin-induced cortical ACh, DA, NE and striatal DA efflux. NGB 2904, 3mg/kg, like blonanserin, 1mg/kg, and the combination of sub-effective doses of NGB 2904 and blonanserin (both 0.3mg/kg), ameliorated the scPCP-induced NOR deficit in rats. These results suggest that D3 receptor blockade may contribute to the ability of blonanserin to increase cortical DA and ACh efflux, as well as to restore NOR and improve CIAS. Copyright © 2015 Elsevier Inc. All rights reserved.

Electrophysiological characteristics of embryonic stem cell-derived cardiomyocytes are cell line-dependent.

PubMed

Hannes, Tobias; Wolff, Marie; Doss, Michael Xavier; Pfannkuche, Kurt; Haustein, Moritz; Müller-Ehmsen, Jochen; Sachinidis, Agapios; Hescheler, Jürgen; Khalil, Markus; Halbach, Marcel

2015-01-01

Modelling of cardiac development, physiology and pharmacology by differentiation of embryonic stem cells (ESCs) requires comparability of cardiac differentiation between different ESC lines. To investigate whether the outcome of cardiac differentiation is consistent between different ESC lines, we compared electrophysiological properties of ESC-derived cardiomyocytes (ESC-CMs) of different murine ESC lines. Two wild-type (D3 and R1) and two transgenic ESC lines (D3/aPIG44 and CGR8/AMPIGX-7) were differentiated under identical culture conditions. The transgenic cell lines expressed enhanced green fluorescent protein (eGFP) and puromycin-N-acetyltransferase under control of the cardiac specific α-myosin heavy chain (αMHC) promoter. Action potentials (APs) were recorded using sharp electrodes and multielectrode arrays in beating clusters of ESC-CMs. Spontaneous AP frequency and AP duration (APD) as well as maximal upstroke velocity differed markedly between unpurified CMs of the four ESC lines. APD heterogeneity was negligible in D3/aPIG44, moderate in D3 and R1 and extensive in CGR8/AMPIGX-7. Interspike intervals calculated from long-term recordings showed a high degree of variability within and between recordings in CGR8/AMPIGX-7, but not in D3/aPIG44. Purification of the αMHC+ population by puromycin treatment posed only minor changes to APD in D3/aPIG44, but significantly shortened APD in CGR8/AMPIGX-7. Electrophysiological properties of ESC-CMs are strongly cell line-dependent and can be influenced by purification of cardiomyocytes by antibiotic selection. Thus, conclusions on cardiac development, physiology and pharmacology derived from single stem cell lines have to be interpreted carefully. © 2015 S. Karger AG, Basel.

Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

NASA Technical Reports Server (NTRS)

Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

2003-01-01

INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

Human ex-vivo action potential model for pro-arrhythmia risk assessment.

PubMed

Page, Guy; Ratchada, Phachareeya; Miron, Yannick; Steiner, Guido; Ghetti, Andre; Miller, Paul E; Reynolds, Jack A; Wang, Ken; Greiter-Wilke, Andrea; Polonchuk, Liudmila; Traebert, Martin; Gintant, Gary A; Abi-Gerges, Najah

2016-01-01

While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-arrhythmic risk in man. Human ventricular trabeculae from ethically consented organ donors were used to evaluate the effects of dofetilide, d,l-sotalol, quinidine, paracetamol and verapamil on AP duration (APD) and recognized pro-arrhythmia predictors (short-term variability of APD at 90% repolarization (STV(APD90)), triangulation (ADP90-APD30) and incidence of early afterdepolarizations at 1 and 2Hz to quantitatively identify the pro-arrhythmic risk. Each drug was blinded and tested separately with 3 concentrations in triplicate trabeculae from 5 hearts, with one vehicle time control per heart. Electrophysiological stability of the model was not affected by sequential applications of vehicle (0.1% dimethyl sulfoxide). Paracetamol and verapamil did not significantly alter anyone of the AP parameters and were classified as devoid of pro-arrhythmic risk. Dofetilide, d,l-sotalol and quinidine exhibited an increase in the manifestation of pro-arrhythmia markers. The model provided quantitative and actionable activity flags and the relatively low total variability in tissue response allowed for the identification of pro-arrhythmic signals. Power analysis indicated that a total of 6 trabeculae derived from 2 hearts are sufficient to identify drug-induced pro-arrhythmia. Thus, the human ex-vivo AP-based model provides an integrative translational assay assisting in shaping clinical development plans that could be used in conjunction with the new CiPA-proposed approach. Copyright © 2016 Elsevier Inc. All rights reserved.

The cost-effectiveness of levodopa/carbidopa intestinal gel compared to standard care in advanced Parkinson's disease.

PubMed

Lowin, Julia; Sail, Kavita; Baj, Rakhi; Jalundhwala, Yash J; Marshall, Thomas S; Konwea, Henrietta; Chaudhuri, K R

2017-11-01

Parkinson's disease (PD) is an incurable, progressive neurological condition, with symptoms impacting movement, walking, and posture that eventually become severely disabling. Advanced PD (aPD) has a significant impact on quality-of-life (QoL) for patients and their caregivers/families. Levodopa/carbidopa intestinal gel (LCIG) is indicated for the treatment of advanced levodopa-responsive PD with severe motor fluctuations and hyper-/dyskinesia when available combinations of therapy have not given satisfactory results. To determine the cost-effectiveness of LCIG vs standard of care (SoC) for the treatment of aPD patients. A Markov model was used to evaluate LCIG vs SoC in a hypothetical cohort of 100 aPD patients with severe motor fluctuations from an Irish healthcare perspective. Model health states were defined by Hoehn & Yahr (H&Y) scale-combined with amount of time in OFF-time-and death. SoC comprised of standard oral therapy ± subcutaneous apomorphine infusion and standard follow-up visits. Clinical efficacy, utilities, and transition probabilities were derived from published studies. Resource use was estimated from individual patient-level data from Adelphi 2012 UK dataset, using Irish costs, where possible. Time horizon was 20 years. Costs and outcomes were discounted at 4%. Both one-way and probabilistic sensitivity analyses were conducted. The incremental cost-effectiveness ratio for LCIG vs SOC was €26,944/quality adjusted life year (QALY) (total costs and QALYs for LCIG vs SoC: €537,687 vs €514,037 and 4.37 vs 3.49, respectively). LCIG is cost-effective at a payer threshold of €45,000. The model was most sensitive to health state costs. LCIG is a cost-effective treatment option compared with SoC in patients with aPD.

Elevated heart rate triggers action potential alternans and sudden death. translational study of a homozygous KCNH2 mutation.

PubMed

Schweigmann, Ulrich; Biliczki, Peter; Ramirez, Rafael J; Marschall, Christoph; Takac, Ina; Brandes, Ralf P; Kotzot, Dieter; Girmatsion, Zenawit; Hohnloser, Stefan H; Ehrlich, Joachim R

2014-01-01

Long QT syndrome (LQTS) leads to arrhythmic events and increased risk for sudden cardiac death (SCD). Homozygous KCNH2 mutations underlying LQTS-2 have previously been termed "human HERG knockout" and typically express severe phenotypes. We studied genotype-phenotype correlations of an LQTS type 2 mutation identified in the homozygous index patient from a consanguineous Turkish family after his brother died suddenly during febrile illness. Clinical work-up, DNA sequencing, mutagenesis, cell culture, patch-clamp, in silico mathematical modelling, protein biochemistry, confocal microscopy were performed. Genetic analysis revealed a homozygous C-terminal KCNH2 mutation (p.R835Q) in the index patient (QTc ∼506 ms with notched T waves). Parents were I° cousins - both heterozygous for the mutation and clinically unremarkable (QTc ∼447 ms, father and ∼396 ms, mother). Heterologous expression of KCNH2-R835Q showed mildly reduced current amplitudes. Biophysical properties of ionic currents were also only nominally changed with slight acceleration of deactivation and more negative V50 in R835Q-currents. Protein biochemistry and confocal microscopy revealed similar expression patterns and trafficking of WT and R835Q, even at elevated temperature. In silico analysis demonstrated mildly prolonged ventricular action potential duration (APD) compared to WT at a cycle length of 1000 ms. At a cycle length of 350 ms M-cell APD remained stable in WT, but displayed APD alternans in R835Q. Kv11.1 channels affected by the C-terminal R835Q mutation display mildly modified biophysical properties, but leads to M-cell APD alternans with elevated heart rate and could precipitate SCD under specific clinical circumstances associated with high heart rates.

Quetiapine and aripiprazole signal differently to ERK, p90RSK and c-Fos in mouse frontal cortex and striatum: role of the EGF receptor

PubMed Central

2014-01-01

Background Signaling pathways outside dopamine D2 receptor antagonism may govern the variable clinical profile of antipsychotic drugs (APD) in schizophrenia. One postulated mechanism causal to APD action may regulate synaptic plasticity and neuronal connectivity via the extracellular signal-regulated kinase (ERK) cascade that links G-protein coupled receptors (GPCR) and ErbB growth factor signaling, systems disturbed in schizophrenia. This was based upon our finding that the low D2 receptor affinity APD clozapine induced initial down-regulation and delayed epidermal growth factor receptor (EGFR or ErbB1) mediated activation of the cortical and striatal ERK response in vivo distinct from olanzapine or haloperidol. Here we map whether the second generation atypical APDs aripiprazole and quetiapine affect the EGFR-ERK pathway and its substrates p90RSK and c-Fos in mouse brain, given their divergent agonist and antagonist properties on dopaminergic transmission, respectively. Results In prefrontal cortex, aripiprazole triggered triphasic ERK phosphorylation that was EGFR-independent but had no significant effect in striatum. Conversely quetiapine did not alter cortical ERK signaling but elevated striatal ERK levels in an EGFR-dependent manner. Induction of ERK by aripiprazole did not affect p90RSK signaling but quetiapine decreased RSK phosphorylation within 1-hour of administration. The transcription factor c-Fos by comparison was a direct target of ERK phosphorylation induced by aripiprazole in cortex and quetiapine in striatum with protein levels in temporal alignment with that of ERK. Conclusions These data indicate that aripiprazole and quetiapine signal to specific nuclear targets of ERK, which for quetiapine occurs via an EGFR-linked mechanism, possibly indicating involvement of this system in its action. PMID:24552586

Influence of Zoledronic Acid on Atrial Electrophysiological Parameters and Electrocardiographic Measurements.

PubMed

Tisdale, James E; Allen, Matthew R; Overholser, Brian R; Jaynes, Heather A; Kovacs, Richard J

2015-06-01

Our objective was to determine effects of zoledronic acid (ZA) on atrial electrophysiological parameters and electrocardiographic measurements. Ex vivo perfusion study: Isolated guinea pig hearts were perfused with modified Krebs-Henseleit (K-H) buffer with or without ZA 0.07 mg/kg/L (each n = 6). In ZA-perfused hearts, atrial action potential at 90% repolarization (APD90 ) decreased more from baseline than in controls (-23.2% ± -5.1% vs. -2.1% ± -8.1%, P < 0 .0001), as did APD30 (-28.8% ± -3.8% vs. -2.1% ± -2.1%, P < 0.0001). In vivo dose-response study: Guinea pigs underwent intraperitoneal injections every 2 weeks in 1 of 4 groups (each n = 8): ZA 0.007 mg/kg (low-dose), ZA 0.07 mg/kg (medium-dose), ZA 0.7 mg/kg (high-dose), or placebo. Hearts were excised at 8 weeks and perfused with modified K-H. Atrial effective refractory period (ERP) was lower with medium- and high-dose ZA versus placebo (P = 0.004). Atrial APD30 was lower with high-dose ZA versus placebo, low and medium doses (P < 0.001). Canine ECG study: Mature female beagles received intravenous ZA 0.067 mg/kg or saline (placebo; each n = 6) every 2 weeks for 12 weeks. P wave dispersion was greater in the ZA group (7.7 ± 3.7 vs. 3.4 ± 2.6 ms, P = 0.04). There were no significant differences in P wave index, maximum or minimum P wave duration, or PR interval. ZA shortens left atrial APD and ERP and increases P wave dispersion. © 2015 Wiley Periodicals, Inc.

Gated IR imaging with 128 × 128 HgCdTe electron avalanche photodiode FPA

NASA Astrophysics Data System (ADS)

Beck, Jeff; Woodall, Milton; Scritchfield, Richard; Ohlson, Martha; Wood, Lewis; Mitra, Pradip; Robinson, Jim

2007-04-01

The next generation of IR sensor systems will include active imaging capabilities. One example of such a system is a gated-active/passive system. The gated-active/passive system promises long-range target detection and identification. A detector that is capable of both active and passive modes of operation opens up the possibility of a self-aligned system that uses a single focal plane. The detector would need to be sensitive in the 3-5 μm band for passive mode operation. In the active mode, the detector would need to be sensitive in eye-safe range, e.g. 1.55 μm, and have internal gain to achieve the required system sensitivity. The MWIR HgCdTe electron injection avalanche photodiode (e-APD) not only provides state-of-the-art 3-5 μm spectral sensitivity, but also high avalanche photodiode gain without minimal excess noise. Gains of greater than 1000 have been measured in MWIR e-APDs with a gain independent excess noise factor of 1.3. This paper reports the application of the mid-wave HgCdTe e-APD for near-IR gated-active/passive imaging. Specifically a 128x128 FPA composed of 40 μm pitch, 4.2 μm to 5 μm cutoff, APD detectors with a custom readout integrated circuit was designed, fabricated, and tested. Median gains as high as 946 at 11 V bias with noise equivalent inputs as low as 0.4 photon were measured at 80 K. A gated imaging demonstration system was designed and built using commercially available parts. High resolution gated imagery out to 9 km was obtained with this system that demonstrated predicted MTF, precision gating, and sub 10 photon sensitivity.

Human ex-vivo action potential model for pro-arrhythmia risk assessment

PubMed Central

Page, Guy; Ratchada, Phachareeya; Miron, Yannick; Steiner, Guido; Ghetti, Andre; Miller, Paul E; Reynolds, Jack A; Wang, Ken; Greiter-Wilke, Andrea; Polonchuk, Liudmila; Traebert, Martin; Gintant, Gary A; Abi-Gerges, Najah

2016-01-01

While current S7B/E14 guidelines have succeeded in protecting patients from QT-prolonging drugs, the absence of a predictive paradigm identifying pro-arrhythmic risks has limited the development of valuable drug programs. We investigated if a human ex-vivo action potential (AP)-based model could provide a more predictive approach for assessing pro-arrhythmic risk in man. Human ventricular trabeculae from ethically consented organ donors were used to evaluate the effects of dofetilide, d,l-sotalol, quinidine, paracetamol and verapamil on AP duration (APD) and recognized pro-arrhythmia predictors (short-term variability of APD at 90% repolarization (STV(APD90)), triangulation (ADP90-APD30) and incidence of early afterdepolarizations at 1 and 2 Hz to quantitatively identify the pro-arrhythmic risk. Each drug was blinded and tested separately with 3 concentrations in triplicate trabeculae from 5 hearts, with one vehicle time control per heart. Electrophysiological stability of the model was not affected by sequential applications of vehicle (0.1% dimethyl sulfoxide). Paracetamol and verapamil did not significantly alter anyone of the AP parameters and were classified as devoid of pro-arrhythmic risk. Dofetilide, d,l-sotalol and quinidine exhibited an increase in the manifestation of pro-arrhythmia markers. The model provided quantitative and actionable activity flags and the relatively low total variability in tissue response allowed for the identification of pro-arrhythmic signals. Power analysis indicated that a total of 6 trabeculae derived from 2 hearts are sufficient to identify drug-induced pro-arrhythmia. Thus, the human ex-vivo AP-based model provides an integrative translational assay assisting in shaping clinical development plans that could be used in conjunction with the new CiPA-proposed approach. PMID:27235787

Acute ivabradine treatment reduces heart rate without increasing atrial fibrillation inducibility irrespective of underlying vagal activity in dogs.

PubMed

Uemura, Kazunori; Inagaki, Masashi; Zheng, Can; Kawada, Toru; Li, Meihua; Fukumitsu, Masafumi; Sugimachi, Masaru

2017-04-01

Ivabradine, a bradycardic agent, has been shown to stably reduce patient's heart rate (HR) in the setting of acute cardiac care. However, an association between atrial fibrillation (AF) risk and acute ivabradine treatment remains a controversial clinical issue, and has not been thoroughly investigated. Bradycardia and abnormal atrial refractoriness induced by ivabradine treatment may enhance vulnerability to AF induction, especially when vagal nerve is concurrently activated. We aimed to experimentally investigate the effects of acute ivabradine treatment with/without concurrent vagal activation on AF inducibility. In 16 anesthetized dogs, cervical vagal nerves were prepared for electrical stimulation (VS). AF induction rate (AFIR) was determined by atrial burst pacing. HR, atrial action potential duration (APD), atrial effective refractory period (ERP), and AFIR were obtained consecutively at baseline, during delivery of VS (VS alone), after intravenous injection of ivabradine 0.5 mg/kg (n = 8, ivabradine group) or saline (n = 8, saline group), and again during VS delivery (drug+VS). In the ivabradine group, ivabradine alone significantly lowered HR compared to baseline, while ivabradine+VS significantly lowered HR compared to VS alone. Contrary to expectations, there were no significant differences in trends of APD, temporal dispersion of APD, ERP, and AFIR between ivabradine and saline groups. Irrespective of whether ivabradine or saline was injected, VS significantly shortened APD and ERP, and increased AFIR. Interestingly, although bradycardia in response to ivabradine injection was more intense than that to VS alone, AFIR was significantly lower after ivabradine injection than during VS alone. We conclude that, despite its intense bradycardic effect, acute ivabradine treatment does not increase AF inducibility irrespective of underlying vagal activity. This study may constitute support for the safety of using ivabradine in the setting of acute cardiac care.

Renal sympathetic denervation modulates ventricular electrophysiology and has a protective effect on ischaemia-induced ventricular arrhythmia.

PubMed

Huang, Bing; Yu, Lilei; He, Bo; Lu, Zhibing; Wang, Songyun; He, Wenbo; Yang, Kang; Liao, Kai; Zhang, Ling; Jiang, Hong

2014-11-01

Recently, a beneficial effect of renal sympathetic denervation (RSD) has been seen in patients with ventricular electrical storm. However, the effect of RSD on ventricular electrophysiology remains unclear. Thirty-three mongrel dogs were included in the present study. Renal sympathetic denervation was performed by radiofrequency ablation of the adventitial surface of the renal artery. In group 1 (n = 8), programmed stimulation was performed before and after RSD to determine the ventricular effective refractory period (ERP) and action potential duration (APD) restitution properties. The same parameters were measured in five other animals that underwent sham RSD to serve as controls. In group 2 (n = 10), acute myocardial ischaemia (AMI) was induced by ligating the proximal left anterior descending coronary artery after the performance of RSD, and the incidence of ventricular arrhythmia (VA) was calculated during 1 h of recording. In another 10 dogs (group 3), AMI was induced and VA was measured with sham RSD. In group 1, RSD significantly prolonged ventricular ERP and APD, reduced the maximal slope (Smax) of the restitution curve and suppressed APD alternans at each site. Renal sympathetic denervation also significantly decreased the spatial dispersion of ERP, APD and Smax. In the five control animals, no significant electrophysiological change was detected after sham RSD. The occurrence of spontaneous VA during 1 h of AMI in group 2 was significantly lower than that in group 3. These data suggest that RSD stabilizes ventricular electrophysiological properties in normal hearts and reduces the occurrence of VA in hearts experiencing AMI. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Smaller, Lower-Power Fast-Neutron Scintillation Detectors

NASA Technical Reports Server (NTRS)

Patel, Jagdish; Blaes, Brent

2008-01-01

Scintillation-based fast-neutron detectors that are smaller and less power-hungry than mainstream scintillation-based fast-neutron detectors are undergoing development. There are numerous applications for such detectors in monitoring fast-neutron fluxes from nuclear reactors, nuclear materials, and natural sources, both on Earth and in outer space. A particularly important terrestrial application for small, low-power, portable fast-neutron detectors lies in the requirement to scan for nuclear materials in cargo and baggage arriving at international transportation facilities. The present development of miniature, low-power scintillation-based fast-neutron detectors exploits recent advances in the fabrication of avalanche photodiodes (APDs). Basically, such a detector includes a plastic scintillator, typically between 300 and 400 m thick with very thin silver mirror coating on all its faces except the one bonded to an APD. All photons generated from scintillation are thus internally reflected and eventually directed to the APD. This design affords not only compactness but also tight optical coupling for utilization of a relatively large proportion of the scintillation light. The combination of this tight coupling and the avalanche-multiplication gain (typically between 750 and 1,000) of the APD is expected to have enough sensitivity to enable monitoring of a fast-neutron flux as small as 1,000 cm(exp -2)s(exp -1). Moreover, pulse-height analysis can be expected to provide information on the kinetic energies of incident neutrons. It has been estimated that a complete, fully developed fast-neutron detector of this type, would be characterized by linear dimensions of the order of 10 cm or less, a mass of no more than about 0.5 kg, and a power demand of no more than a few watts.

Glutathione oxidation unmasks proarrhythmic vulnerability of chronically hyperglycemic guinea pigs

PubMed Central

Xie, Chaoqin; Biary, Nora; Tocchetti, Carlo G.; Aon, Miguel A.; Paolocci, Nazareno; Kauffman, Justin

2013-01-01

Chronic hyperglycemia in type-1 diabetes mellitus is associated with oxidative stress (OS) and sudden death. Mechanistic links remain unclear. We investigated changes in electrophysiological (EP) properties in a model of chronic hyperglycemia before and after challenge with OS by GSH oxidation and tested reversibility of EP remodeling by insulin. Guinea pigs survived for 1 mo following streptozotocin (STZ) or saline (sham) injection. A treatment group received daily insulin for 2 wk to reverse STZ-induced hyperglycemia (STZ + Ins). EP properties were measured using high-resolution optical action potential mapping before and after challenge of hearts with diamide. Despite elevation of glucose levels in STZ compared with sham-operated (P = 0.004) and STZ + Ins (P = 0.002) animals, average action potential duration (APD) and arrhythmia propensity were not altered at baseline. Diamide promoted early (<10 min) formation of arrhythmic triggers reflected by a higher arrhythmia scoring index in STZ (P = 0.045) and STZ + Ins (P = 0.033) hearts compared with sham-operated hearts. APD heterogeneity underwent a more pronounced increase in response to diamide in STZ and STZ + Ins hearts compared with sham-operated hearts. Within 30 min, diamide resulted in spontaneous incidence of ventricular tachycardia and ventricular fibrillation (VT/VF) in 3/6, 2/5, 1/5, and 0/4 STZ, STZ + Ins, sham-operated, and normal hearts, respectively. Hearts prone to VT/VF exhibited greater APD heterogeneity (P = 0.010) compared with their VT/VF-free counterparts. Finally, altered EP properties in STZ were not rescued by insulin. In conclusion, GSH oxidation enhances APD heterogeneity and increases arrhythmia scoring index in a guinea pig model of chronic hyperglycemia. Despite normalization of glycemic levels by insulin, these proarrhythmic properties are not reversed, suggesting the importance of targeting antioxidant defenses for arrhythmia suppression. PMID:23376824

Electrophysiological determinants of arrhythmic susceptibility upon endocardial and epicardial pacing in guinea-pig heart.

PubMed

Osadchii, O E

2012-08-01

Endocardial pacing instituted to treat symptomatic bradycardia may nevertheless promote tachyarrhythmia in some pacemaker-implanted patients. We sought to determine the contributing electrophysiological mechanisms. Left ventricular (LV) monophasic action potential duration (APD(90)) and effective refractory periods were determined in perfused guinea-pig hearts along with volume-conducted ECG recordings during epicardial and endocardial stimulations. Consistent with electrotonic modulation of repolarization, APD(90) at a given (either epicardial or endocardial) recording site tended to be longer while pacing from the ipsilateral LV site as compared to stimulations applied at the opposite side of ventricular wall. As a result, the intrinsic transmural repolarization gradient was amplified during endocardial pacing while being significantly reduced upon epicardial stimulations. The maximum slope of APD(90) restitution was greater upon endocardial than epicardial pacing. The excitability was found to recur at earlier repolarization time point at endocardium than epicardium, thereby contributing to increased endocardial critical intervals for re-excitation. Premature extrasystolic beats could have been elicited at shorter coupling stimulation intervals and propagated with greater transmural conduction delay upon endocardial than epicardial stimulations. Endocardial site exhibited lower ventricular fibrillation thresholds and greater inducibility of tachyarrhythmia upon extrasystolic stimulations as compared to epicardium. Arrhythmic susceptibility in guinea-pig heart is greater during endocardial than epicardial pacing because of greater transmural APD(90) dispersion, steeper electrical restitution slopes, greater critical intervals for LV re-excitation and slower transmural conduction of the earliest premature ectopic beats. Further studies are warranted to determine whether these effects may contribute to proarrhythmia in paced human patients. © 2012 The Author Acta Physiologica © 2012 Scandinavian Physiological Society.

Antiarrhythmic effect of IKr activation in a cellular model of LQT3.

PubMed

Diness, Jonas Goldin; Hansen, Rie Schultz; Nissen, Jakob Dahl; Jespersen, Thomas; Grunnet, Morten

2009-01-01

Long QT syndrome type 3 (LQT3) is an inherited cardiac disorder caused by gain-of-function mutations in the cardiac voltage-gated sodium channel, Na(v)1.5. LQT3 is associated with the polymorphic ventricular tachycardia torsades de pointes (TdP), which can lead to syncope and sudden cardiac death. The sea anemone toxin ATX-II has been shown to inhibit the inactivation of Na(v)1.5, thereby closely mimicking the underlying cause of LQT3 in patients. The hypothesis for this study was that activation of the I(Kr) current could counteract the proarrhythmic effects of ATX-II. Two different activators of I(Kr), NS3623 and mallotoxin (MTX), were used in patch clamp studies of ventricular cardiac myocytes acutely isolated from guinea pig to test the effects of selective I(Kr) activation alone and in the presence of ATX-II. Action potentials were elicited at 1 Hz by current injection and the cells were kept at 32 degrees C to 35 degrees C. NS3623 significantly shortened action potential duration at 90% repolarization (APD(90)) compared with controls in a dose-dependent manner. Furthermore, it reduced triangulation, which is potentially antiarrhythmic. Application of ATX-II (10 nM) was proarrhythmic, causing a profound increase of APD(90) as well as early afterdepolarizations and increased beat-to-beat variability. Two independent I(Kr) activators attenuated the proarrhythmic effects of ATX-II. NS3623 did not affect the late sodium current (I(NaL)) in the presence of ATX-II. Thus, the antiarrhythmic effect of NS3623 is likely to be caused by selective I(Kr) activation. The present data show the antiarrhythmic potential of selective I(Kr) activation in a cellular model of the LQT3 syndrome.

Performances of a HGCDTE APD Based Detector with Electric Cooling for 2-μm DIAL/IPDA Applications

NASA Astrophysics Data System (ADS)

Dumas, A.; Rothman, J.; Gibert, F.; Lasfargues, G.; Zanatta, J.-P.; Edouart, D.

2016-06-01

In this work we report on design and testing of an HgCdTe Avalanche Photodiode (APD) detector assembly for lidar applications in the Short Wavelength Infrared Region (SWIR : 1,5 - 2 μm). This detector consists in a set of diodes set in parallel -making a 200 μm large sensitive area- and connected to a custom high gain TransImpedance Amplifier (TIA). A commercial four stages Peltier cooler is used to reach an operating temperature of 185K. Crucial performances for lidar use are investigated : linearity, dynamic range, spatial homogeneity, noise and resistance to intense illumination.

Performance measurement results for a 220 Mbps QPPM optical communication receiver with an EG/G Slik APD

NASA Technical Reports Server (NTRS)

Davidson, Frederic M.; Sun, Xiaoli

1992-01-01

The performance of a 220 Mbps quaternary pulse position modulation (QPPM) optical communication receiver with a 'Slik' silicon avalanche photodiode (APD) and a wideband transimpedance preamplifier in a small hybrid circuit module was measured. The receiver performance had been poor due to the lack of a wideband and low noise transimpedance preamplifier. With the new APB preamplifier module, the receiver achieved a bit error rate (BER) of 10 exp -6 at an average received input optical signal power of 4.2 nW, which corresponds to an average of 80 received (incident) signal photons per information bit.

Low-Noise Free-Running High-Rate Photon-Counting for Space Communication and Ranging

NASA Technical Reports Server (NTRS)

Lu, Wei; Krainak, Michael A.; Yang, Guangning; Sun, Xiaoli; Merritt, Scott

2016-01-01

We present performance data for low-noise free-running high-rate photon counting method for space optical communication and ranging. NASA GSFC is testing the performance of two types of novel photon-counting detectors 1) a 2x8 mercury cadmium telluride (HgCdTe) avalanche array made by DRS Inc., and a 2) a commercial 2880-element silicon avalanche photodiode (APD) array. We successfully measured real-time communication performance using both the 2 detected-photon threshold and logic AND-gate coincidence methods. Use of these methods allows mitigation of dark count, after-pulsing and background noise effects without using other method of Time Gating The HgCdTe APD array routinely demonstrated very high photon detection efficiencies ((is) greater than 50%) at near infrared wavelength. The commercial silicon APD array exhibited a fast output with rise times of 300 ps and pulse widths of 600 ps. On-chip individually filtered signals from the entire array were multiplexed onto a single fast output. NASA GSFC has tested both detectors for their potential application for space communications and ranging. We developed and compare their performances using both the 2 detected photon threshold and coincidence methods.

Low-Noise Free-Running High-Rate Photon-Counting for Space Communication and Ranging

NASA Technical Reports Server (NTRS)

Lu, Wei; Krainak, Michael A.; Yang, Guan; Sun, Xiaoli; Merritt, Scott

2016-01-01

We present performance data for low-noise free-running high-rate photon counting method for space optical communication and ranging. NASA GSFC is testing the performance of two types of novel photon-counting detectors 1) a 2x8 mercury cadmium telluride (HgCdTe) avalanche array made by DRS Inc., and a 2) a commercial 2880-element silicon avalanche photodiode (APD) array. We successfully measured real-time communication performance using both the 2 detected-photon threshold and logic AND-gate coincidence methods. Use of these methods allows mitigation of dark count, after-pulsing and background noise effects without using other method of Time Gating The HgCdTe APD array routinely demonstrated very high photon detection efficiencies (50) at near infrared wavelength. The commercial silicon APD array exhibited a fast output with rise times of 300 ps and pulse widths of 600 ps. On-chip individually filtered signals from the entire array were multiplexed onto a single fast output. NASA GSFC has tested both detectors for their potential application for space communications and ranging. We developed and compare their performances using both the 2 detected photon threshold and coincidence methods.

Revised guidelines on management of antenatal hydronephrosis.

PubMed

Sinha, Aditi; Bagga, Arvind; Krishna, Anurag; Bajpai, Minu; Srinivas, M; Uppal, Rajesh; Agarwal, Indira

2013-02-01

Widespread antenatal screening has resulted in increased detection of anomalies of the kidneys and urinary tract. The present guidelines update the recommendations published in 2000. Antenatal hydronephrosis (ANH) is transient and resolves by the third trimester in almost one-half cases. The presence of oligohydramnios and additional renal or extrarenal anomalies suggests significant pathology. All patients with ANH should undergo postnatal ultrasonography; the intensity of subsequent evaluation depends on anteroposterior diameter (APD) of the renal pelvis and/or Society for Fetal Urology (SFU) grading. Patients with postnatal APD exceeding 10 mm and/or SFU grade 3-4 should be screened for upper or lower urinary tract obstruction and vesicoureteric reflux. Infants with vesicoureteric reflux should receive antibiotic prophylaxis through the first year of life, and their parents counseled regarding the risk of urinary tract infections. The management of patients with pelviureteric junction or vesicoureteric junction obstruction depends on clinical features and results of sequential ultrasonography and radionuclide renography. Surgery is considered in patients with increasing renal pelvic APD and/or an obstructed renogram with differential renal function <35-40% or its subsequent decline. Further studies are necessary to clarify the role of prenatal intervention, frequency of follow up investigations and indications for surgery in these patients.

Synthesis of ent-BE-43547A1 reveals a potent hypoxia-selective anticancer agent and uncovers the biosynthetic origin of the APD-CLD natural products.

PubMed

Villadsen, Nikolaj L; Jacobsen, Kristian M; Keiding, Ulrik B; Weibel, Esben T; Christiansen, Bjørn; Vosegaard, Thomas; Bjerring, Morten; Jensen, Frank; Johannsen, Mogens; Tørring, Thomas; Poulsen, Thomas B

2017-03-01

Tumour hypoxia is speculated to be a key driver of therapeutic resistance and metastatic dissemination. Consequently, the discovery of new potent agents that selectively target the hypoxic cell population may reveal new and untapped antitumour mechanisms. Here we demonstrate that the BE-43547 subclass of the APD-CLD (amidopentadienoate-containing cyclolipodepsipeptides) natural products possesses highly hypoxia-selective growth-inhibitory activity against pancreatic cancer cells. To enable this discovery, we have developed the first synthesis of the BE-43547-macrocyclic scaffold in 16 steps (longest linear sequence), which also allowed access to the full panel of relative stereoisomers and ultimately to the assignment of stereochemical configuration. Discrepancies between the spectroscopic signatures of the synthetic compounds with that originally reported for the BE-43547 members stimulated us to re-isolate the natural product from a BE-43547-producing microorganism during which we elucidated the biosynthetic gene clusters for the BE-43547 family as well as for all other known APD-CLDs. Our studies underline the exciting possibilities for the further development of the anticancer activities of these natural products.

Synthesis of ent-BE-43547A1 reveals a potent hypoxia-selective anticancer agent and uncovers the biosynthetic origin of the APD-CLD natural products

NASA Astrophysics Data System (ADS)

Villadsen, Nikolaj L.; Jacobsen, Kristian M.; Keiding, Ulrik B.; Weibel, Esben T.; Christiansen, Bjørn; Vosegaard, Thomas; Bjerring, Morten; Jensen, Frank; Johannsen, Mogens; Tørring, Thomas; Poulsen, Thomas B.

2017-03-01

Tumour hypoxia is speculated to be a key driver of therapeutic resistance and metastatic dissemination. Consequently, the discovery of new potent agents that selectively target the hypoxic cell population may reveal new and untapped antitumour mechanisms. Here we demonstrate that the BE-43547 subclass of the APD-CLD (amidopentadienoate-containing cyclolipodepsipeptides) natural products possesses highly hypoxia-selective growth-inhibitory activity against pancreatic cancer cells. To enable this discovery, we have developed the first synthesis of the BE-43547-macrocyclic scaffold in 16 steps (longest linear sequence), which also allowed access to the full panel of relative stereoisomers and ultimately to the assignment of stereochemical configuration. Discrepancies between the spectroscopic signatures of the synthetic compounds with that originally reported for the BE-43547 members stimulated us to re-isolate the natural product from a BE-43547-producing microorganism during which we elucidated the biosynthetic gene clusters for the BE-43547 family as well as for all other known APD-CLDs. Our studies underline the exciting possibilities for the further development of the anticancer activities of these natural products.

Development of the hard x-ray monitor onboard WF-MAXI

NASA Astrophysics Data System (ADS)

Arimoto, Makoto; Yatsu, Yoichi; Kawai, Nobuyuki; Ikeda, Hirokazu; Harayama, Atsushi; Takeda, Shin'ichiro; Takahashi, Tadayuki; Tomida, Hiroshi; Ueno, Shiro; Kimura, Masashi; Mihara, Tatehiro; Serino, Motoko; Tsunemi, Hiroshi; Yoshida, Atsumasa; Sakamoto, Takanori; Kohmura, Tadayoshi; Negoro, Hitoshi; Ueda, Yoshihiro

2014-07-01

WF-MAXI is a mission to detect and localize X-ray transients with short-term variability as gravitational-wave (GW) candidates including gamma-ray bursts, supernovae etc. We are planning on starting observations by WF-MAXI to be ready for the initial operation of the next generation GW telescopes (e.g., KAGRA, Advanced LIGO etc.). WF-MAXI consists of two main instruments, Soft X-ray Large Solid Angle Camera (SLC) and Hard X-ray Monitor (HXM) which totally cover 0.7 keV to 1 MeV band. HXM is a multi-channel array of crystal scintillators coupled with APDs observing photons in the hard X-ray band with an effective area of above 100 cm2. We have developed an analog application specific integrated circuit (ASIC) dedicated for the readout of 32-channel APDs' signals using 0.35 μm CMOS technology based on Open IP project and an analog amplifier was designed to achieve a low-noise readout. The developed ASIC showed a low-noise performance of 2080 e- + 2.3 e-/pF at root mean square and with a reverse-type APD coupled to a Ce:GAGG crystal a good FWHM energy resolution of 6.9% for 662 keV -rays.

Self-triggering readout system for the neutron lifetime experiment PENeLOPE

NASA Astrophysics Data System (ADS)

Gaisbauer, D.; Bai, Y.; Konorov, I.; Paul, S.; Steffen, D.

2016-02-01

PENeLOPE is a neutron lifetime measurement developed at the Technische Universität München and located at the Forschungs-Neutronenquelle Heinz Maier-Leibnitz (FRM II) aiming to achieve a precision of 0.1 seconds. The detector for PENeLOPE consists of about 1250 Avalanche Photodiodes (APDs) with a total active area of 1225 cm2. The decay proton detector and electronics will be operated at a high electrostatic potential of -30 kV and a magnetic field of 0.6 T. This includes shaper, preamplifier, ADC and FPGA cards. In addition, the APDs will be cooled to 77 K. The 1250 APDs are divided into 14 groups of 96 channels, including spares. A 12-bit ADC digitizes the detector signals with 1 MSps. A firmware was developed for the detector including a self-triggering readout with continuous pedestal calculation and configurable signal detection. The data transmission and configuration is done via the Switched Enabling Protocol (SEP). It is a time-division multiplexing low layer protocol which provides determined latency for time critical messages, IPBus, and JTAG interfaces. The network has a n:1 topology, reducing the number of optical links.

Revised guidelines on management of antenatal hydronephrosis

PubMed Central

Sinha, A.; Bagga, A.; Krishna, A; Bajpai, M.; Srinivas, M.; Uppal, R.; Agarwal, I.

2013-01-01

Widespread antenatal screening has resulted in increased detection of anomalies of the kidneys and urinary tract. The present guidelines update the recommendations published in 2000. Antenatal hydronephrosis (ANH) is transient and resolves by the third trimester in almost one-half cases. The presence of oligohydramnios and additional renal or extrarenal anomalies suggests significant pathology. All patients with ANH should undergo postnatal ultrasonography; the intensity of subsequent evaluation depends on anteroposterior diameter (APD) of the renal pelvis and/or Society for Fetal Urology (SFU) grading. Patients with postnatal APD exceeding 10 mm and/or SFU grade 3-4 should be screened for upper or lower urinary tract obstruction and vesicoureteric reflux (VUR). Infants with VUR should receive antibiotic prophylaxis through the first year of life, and their parents counseled regarding the risk of urinary tract infections. The management of patients with pelviureteric junction or vesicoureteric junction obstruction depends on clinical features and results of sequential ultrasonography and radionuclide renography. Surgery is considered in patients with increasing renal pelvic APD and/or an obstructed renogram with differential renal function <35-40% or its subsequent decline. Further studies are necessary to clarify the role of prenatal intervention, frequency of follow-up investigations and indications for surgery in these patients. PMID:23716913

A Hybrid Readout Solution for GaN-Based Detectors Using CMOS Technology.

PubMed

Padmanabhan, Preethi; Hancock, Bruce; Nikzad, Shouleh; Bell, L Douglas; Kroep, Kees; Charbon, Edoardo

2018-02-03

Gallium nitride (GaN) and its alloys are becoming preferred materials for ultraviolet (UV) detectors due to their wide bandgap and tailorable out-of-band cutoff from 3.4 eV to 6.2 eV. GaN based avalanche photodiodes (APDs) are particularly suitable for their high photon sensitivity and quantum efficiency in the UV region and for their inherent insensitivity to visible wavelengths. Challenges exist however for practical utilization. With growing interests in such photodetectors, hybrid readout solutions are becoming prevalent with CMOS technology being adopted for its maturity, scalability, and reliability. In this paper, we describe our approach to combine GaN APDs with a CMOS readout circuit, comprising of a linear array of 1 × 8 capacitive transimpedance amplifiers (CTIAs), implemented in a 0.35 µm high voltage CMOS technology. Further, we present a simple, yet sustainable circuit technique to allow operation of APDs under high reverse biases, up to ≈80 V with verified measurement results. The readout offers a conversion gain of 0.43 µV/e - , obtaining avalanche gains up to 10³. Several parameters of the CTIA are discussed followed by a perspective on possible hybridization, exploiting the advantages of a 3D-stacked technology.

Evaluation of Space Radiation Effects on HgCdTe Avalanche Photodiode Arrays for Lidar Applications

NASA Technical Reports Server (NTRS)

Sun, Xiaoli; Abshire, James B.; Lauenstein, Jean-Marie; Sullivan, William III; Beck, Jeff; Hubbs, John E.

2018-01-01

We report the results from proton and gamma ray radiation testing of HgCdTe avalanche photodiode (APD) arrays developed by Leonardo DRS for space lidar detectors. We tested these devices with both approximately 60 MeV protons and gamma rays, with and without the read out integrated circuit (ROIC). We also measured the transient responses with the device fully powered and with the APD gain from unity to greater than 1000. The detectors produced a large current impulse in response to each proton hit but the response completely recovered within 1 microsecond. The devices started to have persistent damage at a proton fluence of 7e10 protons/cm2, equivalent to 10 krad(Si) total ionization dose. The dark current became much higher after the device was warmed to room temperature and cooled to 80K again, but it completely annealed after baking at 85 C for several hours. These results showed the HgCdTe APD arrays are suitable for use in space lidar for typical Earth orbiting and planetary missions provided that provisions are made to heat the detector chip to 85 C for several hours after radiation damage becomes evident that system performance is impacted.

Curvature effects on activation speed and repolarization in an ionic model of cardiac myocytes

NASA Astrophysics Data System (ADS)

Comtois, P.; Vinet, A.

1999-10-01

Reentry is a major mechanism underlying the initiation and perpetuation of many cardiac arrhythmias 12345. Stimulated ventricular myocytes give action potential characterized by a fast upstroke, a long-lasting plateau, and a late repolarization phase. The plateau phase determines the action potential duration (APD) during which the system remains refractory, a property essential to the synchronization of the heart cycle. The APD varies much with prematurity and this change has been shown to be the main determinant of the dynamics in models of paced cells and cable, and during reentry in the one-dimensional loop. Curvature has also been shown to be an important factor for propagation in experimental and theoretical cardiac extended tissue. The objective of this paper is to combine both curvature and prematurity effects in a kinematical model of propagation in cardiac tissue. First, an approximation of the ionic model is used to obtain the effects of curvature and prematurity on the speed of propagation, the APD, and the absolute refractory period. Two versions of the ionic model are studied that differ in their rate of excitability recovery. The functions are used in a kinematical model describing the propagation of period-1 solutions around an annulus.

Emergent Start Peritoneal Dialysis for End-Stage Renal Disease: Outcomes and Advantages.

PubMed

Nayak, K Shivanand; Subhramanyam, Sreepada V; Pavankumar, Navva; Antony, Sinoj; Sarfaraz Khan, M A

2018-01-01

Initiating renal replacement therapy in late referred patients with central venous catheter (CVC) hemodialysis (HD) causes serious complications. In urgent start peritoneal dialysis, initiating peritoneal dialysis (PD) within 14 days of catheter insertion still needs HD with CVC. We initiated Emergent start PD (ESPD) with Automated PD (APD) at our center within 48 h from the time of presentation. A prospective, case-controlled, intention-to-treat study with 56 patients was conducted between March 2016 and August 2017. Group A (24 patients) underwent conventional PD 14 days after catheter insertion. Group B (32 patients), underwent ESPD with APD. Exit site leak (ESL), catheter blockage, and peritonitis at 90 days were primary outcomes. Technique survival was secondary outcome. Baseline characteristics were similar with 3 episodes of ESLs (9.4%) in the study group and none in the control group (p = 0.123). Catheter blockage (16.7%-Group A, 25%-Group B) and peritonitis (none vs. 9.4% in study group) were similar in terms of statistical details just as technique survival (95%-Group A, 88.2%-Group B at 90 days). ESPD with APD in the unplanned patient is an appropriate approach. © 2018 S. Karger AG, Basel.

Single-photon semiconductor photodiodes for distributed optical fiber sensors: state of the art and perspectives

NASA Astrophysics Data System (ADS)

Ripamonti, Giancarlo; Lacaita, Andrea L.

1993-03-01

The extreme sensitivity and time resolution of Geiger-mode avalanche photodiodes (GM- APDs) have already been exploited for optical time domain reflectometry (OTDR). Better than 1 cm spatial resolution in Rayleigh scattering detection was demonstrated. Distributed and quasi-distributed optical fiber sensors can take advantage of the capabilities of GM-APDs. Extensive studies have recently disclosed the main characteristics and limitations of silicon devices, both commercially available and developmental. In this paper we report an analysis of the performance of these detectors. The main characteristics of GM-APDs of interest for distributed optical fiber sensors are briefly reviewed. Command electronics (active quenching) is then introduced. The detector timing performance sets the maximum spatial resolution in experiments employing OTDR techniques. We highlight that the achievable time resolution depends on the physics of the avalanche spreading over the device area. On the basis of these results, trade-off between the important parameters (quantum efficiency, time resolution, background noise, and afterpulsing effects) is considered. Finally, we show first results on Germanium devices, capable of single photon sensitivity at 1.3 and 1.5 micrometers with sub- nanosecond time resolution.

Artificial Pancreas Device Systems for the Closed-Loop Control of Type 1 Diabetes

PubMed Central

Trevitt, Sara; Simpson, Sue; Wood, Annette

2015-01-01

Background: Closed-loop artificial pancreas device (APD) systems are externally worn medical devices that are being developed to enable people with type 1 diabetes to regulate their blood glucose levels in a more automated way. The innovative concept of this emerging technology is that hands-free, continuous, glycemic control can be achieved by using digital communication technology and advanced computer algorithms. Methods: A horizon scanning review of this field was conducted using online sources of intelligence to identify systems in development. The systems were classified into subtypes according to their level of automation, the hormonal and glycemic control approaches used, and their research setting. Results: Eighteen closed-loop APD systems were identified. All were being tested in clinical trials prior to potential commercialization. Six were being studied in the home setting, 5 in outpatient settings, and 7 in inpatient settings. It is estimated that 2 systems may become commercially available in the EU by the end of 2016, 1 during 2017, and 2 more in 2018. Conclusions: There are around 18 closed-loop APD systems progressing through early stages of clinical development. Only a few of these are currently in phase 3 trials and in settings that replicate real life. PMID:26589628

Bradycardia alters Ca2+ dynamics enhancing dispersion of repolarization and arrhythmia risk

PubMed Central

Kim, Jong J.; Němec, Jan; Papp, Rita; Strongin, Robert; Abramson, Jonathan J.

2013-01-01

Bradycardia prolongs action potential (AP) durations (APD adaptation), enhances dispersion of repolarization (DOR), and promotes tachyarrhythmias. Yet, the mechanisms responsible for enhanced DOR and tachyarrhythmias remain largely unexplored. Ca2+ transients and APs were measured optically from Langendorff rabbit hearts at high (150 × 150 μm2) or low (1.5 × 1.5 cm2) magnification while pacing at a physiological (120 beats/min) or a slow heart rate (SHR = 50 beats/min). Western blots and pharmacological interventions were used to elucidate the regional effects of bradycardia. As a result, bradycardia (SHR 50 beats/min) increased APDs gradually (time constant τf→s = 48 ± 9.2 s) and caused a secondary Ca2+ release (SCR) from the sarcoplasmic reticulum during AP plateaus, occurring at the base on average of 184.4 ± 9.7 ms after the Ca2+ transient upstroke. In subcellular imaging, SCRs were temporally synchronous and spatially homogeneous within myocytes. In diastole, SHR elicited variable asynchronous sarcoplasmic reticulum Ca2+ release events leading to subcellular Ca2+ waves, detectable only at high magnification. SCR was regionally heterogeneous, correlated with APD prolongation (P < 0.01, n = 5), enhanced DOR (r = 0.9277 ± 0.03, n = 7), and was gradually reversed by pacing at 120 beats/min along with APD shortening (P < 0.05, n = 5). A stabilizer of leaky ryanodine receptors (RyR2), 3-(4-benzylcyclohexyl)-1-(7-methoxy-2,3-dihydrobenzo[f][1,4]thiazepin-4(5H)-yl)propan-1-one (K201; 1 μM), suppressed SCR and reduced APD at the base, thereby reducing DOR (P < 0.02, n = 5). Ventricular ectopy induced by bradycardia (n = 5/15) was suppressed by K201. Western blot analysis revealed spatial differences of voltage-gated L-type Ca2+ channel protein (Cav1.2α), Na+-Ca2+ exchange (NCX1), voltage-gated Na+ channel (Nav1.5), and rabbit ether-a-go-go-related (rERG) protein [but not RyR2 or sarcoplasmic reticulum Ca2+ ATPase 2a] that correlate with the SCR distribution and explain the molecular basis for SCR heterogeneities. In conclusion, acute bradycardia elicits synchronized subcellular SCRs of sufficient magnitude to overcome the source-sink mismatch and to promote afterdepolarizations. PMID:23316064

Development of a paper based roll-to-roll nanoimprinting machine

NASA Astrophysics Data System (ADS)

Son, Byungwook

Nanoimprint lithography (NIL) has been developed and studied since 1995. It is a technique where micro- or nanoscale patterns are transferred to soft materials such as polymer through pressing a stamp with certain patterns into this materials and then solidifying it by cooling at lower temperature or curing under ultra violet excitement. High Cost and low throughput of batch mode nanoimprint lithography (NIL) processes are limiting its wide range of applications in meeting industry manufacturing requirements. The roll-to-roll (R2R) nanoimprinting technology is emerged as a solution to this issue. This thesis study presents the design, build and test of an innovative R2R T-NIL process machine for nanofabrication and MEMS fabrication applications, which consists of individual modules of heating, inking, pressuring, and rotational speed control. The system utilizes PDMS as mold material, PMMA as imprinting material, and paper as substrate material. In order to achieve a uniform pressure on PMMA during imprinting process, an innovative air pressure device (APD) was developed and integrated with R2R machine. The APD replaces the conventional 2-roll line contact pressure approach and can cover one third of the surface of the imprinting roller with a uniform pressure (1-3 psi). During the imprinting experiment, a mixture of PMMA (20w %) and 2-Ethoxyethyl acetate is applied on the paper substrate by an inking roller using capillary force and an IR heater is used for pre-heating and drying of polymer layers before it is fed into the imprinting module. Two 500-Watt cartridge heaters are installed on the roller and provide the heat to raise the PMMA film temperature during the imprinting.

Allele-specific RNA interference rescues the long-QT syndrome phenotype in human-induced pluripotency stem cell cardiomyocytes.

PubMed

Matsa, Elena; Dixon, James E; Medway, Christopher; Georgiou, Orestis; Patel, Minal J; Morgan, Kevin; Kemp, Paul J; Staniforth, Andrew; Mellor, Ian; Denning, Chris

2014-04-01

Long-QT syndromes (LQTS) are mostly autosomal-dominant congenital disorders associated with a 1:1000 mutation frequency, cardiac arrest, and sudden death. We sought to use cardiomyocytes derived from human-induced pluripotency stem cells (hiPSCs) as an in vitro model to develop and evaluate gene-based therapeutics for the treatment of LQTS. We produced LQTS-type 2 (LQT2) hiPSC cardiomyocytes carrying a KCNH2 c.G1681A mutation in a IKr ion-channel pore, which caused impaired glycosylation and channel transport to cell surface. Allele-specific RNA interference (RNAi) directed towards the mutated KCNH2 mRNA caused knockdown, while leaving the wild-type mRNA unaffected. Electrophysiological analysis of patient-derived LQT2 hiPSC cardiomyocytes treated with mutation-specific siRNAs showed normalized action potential durations (APDs) and K(+) currents with the concurrent rescue of spontaneous and drug-induced arrhythmias (presented as early-afterdepolarizations). These findings provide in vitro evidence that allele-specific RNAi can rescue diseased phenotype in LQTS cardiomyocytes. This is a potentially novel route for the treatment of many autosomal-dominant-negative disorders, including those of the heart.

Gray matter changes in right superior temporal gyrus in criminal psychopaths. Evidence from voxel-based morphometry.

PubMed

Müller, Jürgen L; Gänssbauer, Susanne; Sommer, Monika; Döhnel, Katrin; Weber, Tatjana; Schmidt-Wilcke, Tobias; Hajak, Göran

2008-08-30

"Psychopathy" according to the PCL-R describes a specific subgroup of antisocial personality disorder with a high risk for criminal relapses. Lesion and imaging studies point towards frontal or temporal brain regions connected with disturbed social behavior, antisocial personality disorder (APD) and psychopathy. Morphologically, some studies described a reduced prefrontal brain volume, whereas others reported on temporal lobe atrophy. To further investigate whether participants with psychopathy according to the Psychopathy Checklist-Revised Version (PCL-R) show abnormalities in brain structure, we used voxel-based morphometry (VBM) to investigate region-specific changes in gray matter in 17 forensic male inpatients with high PCL-R scores (PCL-R>28) and 17 male control subjects with low PCL-R scores (PCL<10). We found significant gray matter reductions in frontal and temporal brain regions in psychopaths compared with controls. In particular, we found a highly significant volume loss in the right superior temporal gyrus. This is the first study to show that psychopathy is associated with a decrease in gray matter in both frontal and temporal brain regions, in particular in the right superior temporal gyrus, supporting the hypothesis that a disturbed frontotemporal network is critically involved in the pathogenesis of psychopathy.

Advanced Parkinson's or "complex phase" Parkinson's disease? Re-evaluation is needed.

PubMed

Titova, Nataliya; Martinez-Martin, Pablo; Katunina, Elena; Chaudhuri, K Ray

2017-12-01

Holistic management of Parkinson's disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson's from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson's which may manifest in a motor dominant or nonmotor dominant manner. The "advanced" stages of Parkinson's disease qualify for advanced treatments such as with continuous infusion or stereotactic surgery yet the concept of "advanced Parkinson's disease" (APD) remains controversial in spite of growing knowledge of the natural history of the motor syndrome of PD. Advanced PD is currently largely defined on the basis of consensus opinion and thus with several caveats. Nonmotor aspects of PD may also reflect advancing course of the disorder, so far not reflected in usual scale based assessments which are largely focussed on motor symptoms. In this paper, we discuss the problems with current definitions of "advanced" PD and also propose the term "complex phase" Parkinson's disease as an alternative which takes into account a multimodal symptoms and biomarker based approach in addition to patient preference.

Allele-specific RNA interference rescues the long-QT syndrome phenotype in human-induced pluripotency stem cell cardiomyocytes

PubMed Central

Matsa, Elena; Dixon, James E.; Medway, Christopher; Georgiou, Orestis; Patel, Minal J.; Morgan, Kevin; Kemp, Paul J.; Staniforth, Andrew; Mellor, Ian; Denning, Chris

2014-01-01

Aims Long-QT syndromes (LQTS) are mostly autosomal-dominant congenital disorders associated with a 1:1000 mutation frequency, cardiac arrest, and sudden death. We sought to use cardiomyocytes derived from human-induced pluripotency stem cells (hiPSCs) as an in vitro model to develop and evaluate gene-based therapeutics for the treatment of LQTS. Methods and results We produced LQTS-type 2 (LQT2) hiPSC cardiomyocytes carrying a KCNH2 c.G1681A mutation in a IKr ion-channel pore, which caused impaired glycosylation and channel transport to cell surface. Allele-specific RNA interference (RNAi) directed towards the mutated KCNH2 mRNA caused knockdown, while leaving the wild-type mRNA unaffected. Electrophysiological analysis of patient-derived LQT2 hiPSC cardiomyocytes treated with mutation-specific siRNAs showed normalized action potential durations (APDs) and K+ currents with the concurrent rescue of spontaneous and drug-induced arrhythmias (presented as early-afterdepolarizations). Conclusions These findings provide in vitro evidence that allele-specific RNAi can rescue diseased phenotype in LQTS cardiomyocytes. This is a potentially novel route for the treatment of many autosomal-dominant-negative disorders, including those of the heart. PMID:23470493

Autoimmune Progesterone Dermatitis: A Diagnosis to Consider in a Patient With Cyclical Cutaneous Eruptions.

PubMed

Steuer, Alexa B; Scherl, Sharon; Ashinoff, Robin

2017-10-01

Autoimmune progesterone dermatitis (APD) is a cyclical cutaneous reaction to progesterone, with symptoms that typically begin 3-10 days before the onset of menstrual flow and end 1-2 days into menses. The symptoms vary in severity from barely visible to anaphylaxis, but most often include an eczematous eruption, erythema multiforme, urticaria, folliculitis, and angioedema. This is a rare disorder with only a handful of documented cases. The pathogenesis of this condition remains unknown and significant variations in the presentation and severity of symptoms complicates its diagnosis. Treatment seeks to inhibit progesterone secretion through suppression of ovulation, but it may be unsuccessful. We present a case of autoimmune progesterone dermatitis that eluded diagnosis for several years, and subsequently the patient was completely controlled with oral contraceptive pills.

J Drugs Dermatol. 2017;16(10):1040-1042.

[Design of Complex Cavity Structure in Air Route System of Automated Peritoneal Dialysis Machine].

PubMed

Quan, Xiaoliang

2017-07-30

This paper introduced problems about Automated Peritoneal Dialysis machine(APD) that the lack of technical issues such as the structural design of the complex cavities. To study the flow characteristics of this special structure, the application of ANSYS CFX software is used with k-ε turbulence model as the theoretical basis of fluid mechanics. The numerical simulation of flow field simulation result in the internal model can be gotten after the complex structure model is imported into ANSYS CFX module. Then, it will present the distribution of complex cavities inside the flow field and the flow characteristics parameter, which will provide an important reference design for APD design.

SNR characteristics of 850-nm OEIC receiver with a silicon avalanche photodetector.

PubMed

Youn, Jin-Sung; Lee, Myung-Jae; Park, Kang-Yeob; Rücker, Holger; Choi, Woo-Young

2014-01-13

We investigate signal-to-noise ratio (SNR) characteristics of an 850-nm optoelectronic integrated circuit (OEIC) receiver fabricated with standard 0.25-µm SiGe bipolar complementary metal-oxide-semiconductor (BiCMOS) technology. The OEIC receiver is composed of a Si avalanche photodetector (APD) and BiCMOS analog circuits including a transimpedance amplifier with DC-balanced buffer, a tunable equalizer, a limiting amplifier, and an output buffer with 50-Ω loads. We measure APD SNR characteristics dependence on the reverse bias voltage as well as BiCMOS circuit noise characteristics. From these, we determine the SNR characteristics of the entire OEIC receiver, and finally, the results are verified with bit-error rate measurement.

Range imaging pulsed laser sensor with two-dimensional scanning of transmitted beam and scanless receiver using high-aspect avalanche photodiode array for eye-safe wavelength

NASA Astrophysics Data System (ADS)

Tsuji, Hidenobu; Imaki, Masaharu; Kotake, Nobuki; Hirai, Akihito; Nakaji, Masaharu; Kameyama, Shumpei

2017-03-01

We demonstrate a range imaging pulsed laser sensor with two-dimensional scanning of a transmitted beam and a scanless receiver using a high-aspect avalanche photodiode (APD) array for the eye-safe wavelength. The system achieves a high frame rate and long-range imaging with a relatively simple sensor configuration. We developed a high-aspect APD array for the wavelength of 1.5 μm, a receiver integrated circuit, and a range and intensity detector. By combining these devices, we realized 160×120 pixels range imaging with a frame rate of 8 Hz at a distance of about 50 m.

Embryo recovery from mares exposed to a year-to-year artificially prolonged daylength.

PubMed

Kot, K; Tischner, M

1991-09-01

The aim of the experiment was to determine the effect of a year-to-year prolonged daylength on the patterns of equine reproductive activity and results of embryo recovery. Experiments using Konik Polski mares were conducted over four reproduction seasons. Five mares were exposed to a regimen of artificially prolonged daylength (APD) and another five mares in a control group were kept under conditions of natural daylight. Both the control and experimental groups were examined for appearance of estrus, ovulation and also for the state of their coats. A single stallion was used for breeding all of the mares. The embryos were recovered nonsurgically 6 to 9 days after ovulation. All of the mares exposed to APD showed increased ovarian activity, which commenced earlier than in the control group. About 19% more ovulations were detected in the experimental group. The average number of ovulations per lighted mare per year was 15.3, while in the control group it was 12.4 ovulations (P<0.05). However, the embryo recovery rate and total number of embryos obtained from the mares exposed to APD did not exceed the number of embryos collected from the control mares (P<0.05). Modification of daylength had a visible effect on the mares by producing a change in their coats.

A Hybrid Readout Solution for GaN-Based Detectors Using CMOS Technology †

PubMed Central

Hancock, Bruce; Nikzad, Shouleh; Bell, L. Douglas; Kroep, Kees; Charbon, Edoardo

2018-01-01

Gallium nitride (GaN) and its alloys are becoming preferred materials for ultraviolet (UV) detectors due to their wide bandgap and tailorable out-of-band cutoff from 3.4 eV to 6.2 eV. GaN based avalanche photodiodes (APDs) are particularly suitable for their high photon sensitivity and quantum efficiency in the UV region and for their inherent insensitivity to visible wavelengths. Challenges exist however for practical utilization. With growing interests in such photodetectors, hybrid readout solutions are becoming prevalent with CMOS technology being adopted for its maturity, scalability, and reliability. In this paper, we describe our approach to combine GaN APDs with a CMOS readout circuit, comprising of a linear array of 1 × 8 capacitive transimpedance amplifiers (CTIAs), implemented in a 0.35 µm high voltage CMOS technology. Further, we present a simple, yet sustainable circuit technique to allow operation of APDs under high reverse biases, up to ≈80 V with verified measurement results. The readout offers a conversion gain of 0.43 µV/e−, obtaining avalanche gains up to 103. Several parameters of the CTIA are discussed followed by a perspective on possible hybridization, exploiting the advantages of a 3D-stacked technology. PMID:29401655

Artificial Pancreas Device Systems for the Closed-Loop Control of Type 1 Diabetes: What Systems Are in Development?

PubMed

Trevitt, Sara; Simpson, Sue; Wood, Annette

2016-05-01

Closed-loop artificial pancreas device (APD) systems are externally worn medical devices that are being developed to enable people with type 1 diabetes to regulate their blood glucose levels in a more automated way. The innovative concept of this emerging technology is that hands-free, continuous, glycemic control can be achieved by using digital communication technology and advanced computer algorithms. A horizon scanning review of this field was conducted using online sources of intelligence to identify systems in development. The systems were classified into subtypes according to their level of automation, the hormonal and glycemic control approaches used, and their research setting. Eighteen closed-loop APD systems were identified. All were being tested in clinical trials prior to potential commercialization. Six were being studied in the home setting, 5 in outpatient settings, and 7 in inpatient settings. It is estimated that 2 systems may become commercially available in the EU by the end of 2016, 1 during 2017, and 2 more in 2018. There are around 18 closed-loop APD systems progressing through early stages of clinical development. Only a few of these are currently in phase 3 trials and in settings that replicate real life. © 2015 Diabetes Technology Society.

Continuous ambulatory peritoneal dialysis is better than automated peritoneal dialysis as first-line treatment in renal replacement therapy.

PubMed

Li, Philip Kam-Tao; Chung, Kwok Yi; Chow, Kai Ming

2007-06-01

This article examines the roles of continuous ambulatory peritoneal dialysis (CAPD) versus automated peritoneal dialysis (APD) as first-line renal replacement therapy. To date, no high-quality large-scale randomized controlled studies have compared CAPD with APD as first-line therapy. However, a discussion on this issue is important so that nephrologists can decide and patients can have a choice of modality on which to start dialysis, especially in the context of health care economics. We review the literature and present Hong Kong as the model of a "CAPD first" policy, an appealing, cost-effective approach for any country. An ideal renal replacement therapy should provide optimal survival, lowest possible risk for comorbidity, highest level of quality of life, and equally important, acceptable cost to society. When we consider this subject in the context that all patients should be started on one first-line modality, the data suggest that a "CAPD first" policy has all these advantages, with APD probably having the edge only with regard to patient preference. The present review highlights preservation of residual renal function, removal and balancing of sodium, incidence of peritonitis, peritoneal membrane transport status, patient rehabilitation, and financial issues in demonstrating that a "CAPD first" policy is the model that should be adopted.

The Role of Spatial Dispersion of Repolarization in Inherited and Acquired Sudden Cardiac Death Syndromes

PubMed Central

Antzelevitch, Charles

2007-01-01

This review examines the role of spatial electrical heterogeneity within ventricular myocardium on the function of the heart in health and disease. The cellular basis for transmural dispersion of repolarization (TDR) is reviewed and the hypothesis that amplification of spatial dispersion of repolarization underlies the development of life-threatening ventricular arrhythmias associated with inherited ion channelopathies is evaluated. The role of TDR in the long QT, short QT and Brugada syndromes as well as catecholaminergic polymorphic ventricular tachycardia (CPVT) are critically examined. In the long QT Syndrome, amplification of TDR is often secondary to preferential prolongation of the action potential duration (APD) of M cells, whereas in the Brugada Syndrome, it is thought to be due to selective abbreviation of the APD of right ventricular (RV) epicardium. Preferential abbreviation of APD of either endocardium or epicardium appears to be responsible for amplification of TDR in the short QT syndrome. In catecholaminergic polymorphic VT, reversal of the direction of activation of the ventricular wall is responsible for the increase in TDR. In conclusion, the long QT, short QT, Brugada and catecholaminergic polymorphic VT syndromes are pathologies with very different phenotypes and etiologies, but which share a common final pathway in causing sudden cardiac death. PMID:17586620

Effects of astragaloside IV on action potentials and ionic currents in guinea-pig ventricular myocytes.

PubMed

Zhao, Meimi; Zhao, Jinsheng; He, Guilin; Sun, Xuefei; Huang, Xueshi; Hao, Liying

2013-01-01

Astragaloside IV (AS-IV) is one of the main active constituents of Astragalus membranaceus, which has various actions on the cardiovascular system. However, its electrophysiological mechanisms are not clear. In the present study, we investigated the effects of AS-IV on action potentials and membrane currents using the whole-cell patch clamp technique in isolated guinea-pig ventricular myocytes. AS-IV prolonged the action potential duration (APD) at all three tested concentrations. The peak effect was achieved with 1×10(-6) M, at which concentration AS-IV significantly prolonged the APD at 95% repolarization from 313.1±38.9 to 785.3±83.7 ms. AS-IV at 1×10(-6) M also enhanced the inward rectifier K(+) currents (I(K1)) and inhibited the delayed rectifier K(+) currents (I(K)). AS-IV (1×10(-6) M) strongly depressed the peak of voltage-dependent Ca(2+) channel current (I(CaL)) from -607.3±37.5 to -321.1±38.3 pA. However, AS-IV was not found to affect the Na(+) currents. Taken together, AS-IV prolonged APD of guinea-pig ventricular myocytes, which might be explained by its inhibition of I(K). AS-IV also influences Ca(2+) signaling through suppressing ICaL.

Flecainide-induced proarrhythmia is attributed to abnormal changes in repolarization and refractoriness in perfused guinea-pig heart.

PubMed

Osadchii, Oleg E

2012-11-01

Flecainide is nonselective Na(+) channel blocker which may also inhibit I(Kr), the rapid component of the delayed rectifier. This study was designed to explore if proarrhythmic responses to flecainide noted in cardiac patients may be partly attributed to abnormal changes in repolarization and refractoriness. Monophasic action potential duration (APD) and effective refractory periods (ERP) were assessed at distinct epicardial and endocardial sites along with volume-conducted ECG recordings in isolated perfused guinea-pig heart preparations. Flecainide was found to prolong ventricular repolarization, with effect being greater at the left ventricular compared with the right ventricular epicardium. This change translated to reversal of the normal right ventricular-to-left ventricular transepicardial APD difference determined before drug infusion. An inverse correlation between local epicardial APD and corresponding activation time values seen at baseline was eliminated in flecainide-treated hearts, indicating the activation-to-repolarization uncoupling. Over transmural plane, flecainide produced a greater ERP lengthening at endocardium than epicardium, thus markedly increasing ERP dispersion across ventricular wall. Spontaneous short-lasting episodes of monomorphic ventricular tachycardia were observed in 45% of heart preparations upon flecainide infusion. In conclusion, in nonischemic guinea-pig heart, flecainide-induced proarrhythmia may be partly attributed to abnormal spatial gradients in repolarization and refractoriness and impaired transepicardial activation-to-repolarization coupling.

Chiral recognition of pinacidil and its 3-pyridyl isomer by canine cardiac and smooth muscle: Antagonism by sulfonylureas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Steinberg, M.I.; Wiest, S.A.; Zimmerman, K.M.

1991-01-01

Pinacidil, a potassium channel opener (PCO), relaxes vascular smooth muscle by increasing potassium ion membrane conductance, thereby causing membrane hyperpolarization. PCOs also act on cardiac muscle to decrease action potential duration (APD) selectively. To examine the enantiomeric selectivity of pinacidil, the stereoisomers of pinacidil (a 4-pyridylcyanoguanidine) and its 3-pyridyl isomer (LY222675) were synthesized and studied in canine Purkinje fibers and cephalic veins. The (-)-enantiomers of both pinacidil and LY222675 were more potent in relaxing phenylephrine-contracted cephalic veins and decreasing APD than were their corresponding (+)-enantiomers. The EC50 values for (-)-pinacidil and (-)-LY222675 in relaxing cephalic veins were 0.44 and 0.09more » microM, respectively. In decreasing APD, the EC50 values were 3.2 microM for (-)-pinacidil and 0.43 microM for (-)-LY222675. The eudismic ratio was greater for the 3-pyridyl isomer than for pinacidil in both cardiac (71 vs. 22) and vascular (53 vs. 17) tissues. (-)-LY222675 and (-)-pinacidil (0.1-30 microM) also increased 86Rb efflux from cephalic veins to a greater extent than did their respective optical antipodes. The antidiabetic sulfonylurea, glyburide (1-30 microM), shifted the vascular concentration-response curve of (-)-pinacidil to the right by a similar extent at each inhibitor concentration. Glipizide also antagonized the response to (-)-pinacidil, but was about 1/10 as potent with a maximal shift occurring at 10 and 30 microM. Glyburide antagonized the vascular relaxant effects of 0.3 microM (-)-LY222675 (EC50, 2.3 microM) and reversed the decrease in APD caused by 3 microM (-)-LY222675 (EC50, 1.9 microM). Nitroprusside did not alter 86Rb efflux, and vascular relaxation induced by sodium nitroprusside was unaffected by sulfonylureas.« less

Differential responses of rabbit ventricular and atrial transient outward current (Ito) to the Ito modulator NS5806.

PubMed

Cheng, Hongwei; Cannell, Mark B; Hancox, Jules C

2017-03-01

Transient outward potassium current (I to ) in the heart underlies phase 1 repolarization of cardiac action potentials and thereby affects excitation-contraction coupling. Small molecule activators of I to may therefore offer novel treatments for cardiac dysfunction, including heart failure and atrial fibrillation. NS5806 has been identified as a prototypic activator of canine I to This study investigated, for the first time, actions of NS5806 on rabbit atrial and ventricular I to Whole cell patch-clamp recordings of I to and action potentials were made at physiological temperature from rabbit ventricular and atrial myocytes. 10  μ mol/L NS5806 increased ventricular I to with a leftward shift in I to activation and accelerated restitution. At higher concentrations, stimulation of I to was followed by inhibition. The EC 50 for stimulation was 1.6  μ mol/L and inhibition had an IC 50 of 40.7  μ mol/L. NS5806 only inhibited atrial I to (IC 50 of 18  μ mol/L) and produced a modest leftward shifts in I to activation and inactivation, without an effect on restitution. 10  μ mol/L NS5806 shortened ventricular action potential duration (APD) at APD 20 -APD 90 but prolonged atrial APD NS5806 also reduced atrial AP upstroke and amplitude, consistent with an additional atrio-selective effect on Na + channels. In contrast to NS5806, flecainide, which discriminates between Kv1.4 and 4.x channels, produced similar levels of inhibition of ventricular and atrial I to NS5806 discriminates between rabbit ventricular and atrial I to, with mixed activator and inhibitor actions on the former and inhibitor actions against the later. NS5806 may be of significant value for pharmacological interrogation of regional differences in native cardiac I to . © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Capacity of Pulse-Position Modulation (PPM) on Gaussian and Webb Channels

NASA Technical Reports Server (NTRS)

Dolinar, S.; Divsalar, D.; Hamkins, J.; Pollara, F.

2000-01-01

This article computes the capacity of various idealized soft-decision channels modeling an optical channel using an avalanche photodiode detector (APD) and pulse-position modulation (PPM). The capacity of this optical channel depends in a complicated way on the physical parameters of the APD and the constraints imposed by the PPM orthogonal signaling set. This article attempts to identify and separate the effects of several fundamental parameters on the capacity of the APD-detected optical PPM channel. First, an overall signal-to-noise ratio (SNR) parameter is de ned such that the capacity as a function of a bit-normalized version of this SNR drops precipitously toward zero at quasi-brick-wall limits on bit SNR that are numerically the same as the well-understood brick-wall limits for the standard additive white Gaussian noise (AWGN) channel. A second parameter is used to quantify the effects on capacity of one unique facet of the optical PPM channel (as compared with the standard AWGN channel) that causes the noise variance to be higher in signal slots than in nonsignal slots. This nonuniform noise variance yields interesting capacity effects even when the channel model is AWGN. A third parameter is used to measure the effects on capacity of the difference between an AWGN model and a non-Gaussian model proposed by Webb (see reference in [2]) for approximating the statistics of the APD-detected optical channel. Finally, a fourth parameter is used to quantify the blending of a Webb model with a pure AWGN model to account for thermal noise. Numerical results show that the capacity of M-ary orthogonal signaling on the Webb channel exhibits the same brick-wall Shannon limit, (M ln 2)=(M 1), as on the AWGN channel ( 1:59 dB for large M). Results also compare the capacity obtained by hard- and soft-output channels and indicate that soft-output channels o er a 3-dB advantage.

Computational modeling for cardiac safety pharmacology analysis: Contribution of fibroblasts.

PubMed

Gao, Xin; Engel, Tyler; Carlson, Brian E; Wakatsuki, Tetsuro

2017-09-01

Drug-induced proarrhythmic potential is an important regulatory criterion in safety pharmacology. The application of in silico approaches to predict proarrhythmic potential of new compounds is under consideration as part of future guidelines. Current approaches simulate the electrophysiology of a single human adult ventricular cardiomyocyte. However, drug-induced proarrhythmic potential can be different when cardiomyocytes are surrounded by non-muscle cells. Incorporating fibroblasts in models of myocardium is important particularly for predicting a drugs cardiac liability in the aging population - a growing population who take more medications and exhibit increased cardiac fibrosis. In this study, we used computational models to investigate the effects of fibroblast coupling on the electrophysiology and response to drugs of cardiomyocytes. A computational model of cardiomyocyte electrophysiology and ion handling (O'Hara, Virag, Varro, & Rudy, 2011) is coupled to a passive model of fibroblast electrophysiology to test the effects of three compounds that block cardiomyocyte ion channels. Results are compared to model results without fibroblast coupling to see how fibroblasts affect cardiomyocyte action potential duration at 90% repolarization (APD 90 ) and propensity for early after depolarization (EAD). Simulation results show changes in cardiomyocyte APD 90 with increasing concentration of three drugs that affect cardiac function (dofetilide, vardenafil and nebivolol) when no fibroblasts are coupled to the cardiomyocyte. Coupling fibroblasts to cardiomyocytes markedly shortens APD 90 . Moreover, increasing the number of fibroblasts can augment the shortening effect. Coupling cardiomyocytes and fibroblasts are predicted to decrease proarrhythmic susceptibility under dofetilide, vardenafil and nebivolol block. However, this result is sensitive to parameters which define the electrophysiological function of the fibroblast. Fibroblast membrane capacitance and conductance (C FB and G FB ) have less of an effect on APD 90 than the fibroblast resting membrane potential (E FB ). This study suggests that in both theoretical models and experimental tissue constructs that represent cardiac tissue, both cardiomyocytes and non-muscle cells should be considered when testing cardiac pharmacological agents. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of Selegiline and Rasagiline Therapies in Parkinson Disease: A Real-life Study

PubMed Central

Peretz, Chava; Segev, Hagar; Rozani, Violet; Gurevich, Tanya; El-Ad, Baruch; Tsamir, Judith; Giladi, Nir

2016-01-01

Background We aimed to compare indicators of Parkinson disease (PD) progression between patients first prescribed either selegiline or rasagiline as their antiparkinsonian drugs (APDs) on the basis of real-life data. Methods Pharmacy data on members of a large Israeli health maintenance organization, treated as patients with PD during 2001–2012 and prescribed selegiline or rasagiline as their first APD, were analyzed. The first APD was selegiline for 349 patients (2001–2006) and rasagiline for 485 patients (2007–2012). Time from monoamine oxidase type B inhibitor prescription until initiating treatment with dopamine agonists (DAs) or levodopa was compared between the groups using Cox regression adjusted to sex and age at initiation of APD. Results The selegiline group was significantly older at first monoamine oxidase type B inhibitor purchase. In a similar follow-up time (3.0 [1.7] year for selegiline group, 3.1 y [1.4] for rasagiline group), the time to initiation of levodopa treatment did not differ between the 2 groups (adjusted hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.86–1.31). The time to initiation of DA treatment was longer in the selegiline group (adjusted HR, 1.93; 95% CI, 1.49–2.53). For those who were treated with DA before levodopa (n = 276), the time to initiation of levodopa treatment was longer in the rasagiline group (adjusted HR, 0.77; 95% CI, 0.56–1.07). Conclusions The similarity in time to levodopa in both groups suggests no differences between selegiline and rasagiline in their effect on the natural history of PD. A possible interaction effect between rasagiline and DA might exist. A better symptomatic profile of selegiline more than that of rasagiline in the earlier stages of PD may explain the difference between the 2 groups in time to DA initiation. PMID:27438181

Evaluation of the Cardiotoxicity of Mitragynine and Its Analogues Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

PubMed Central

Wu, Jianjun; Jamil, Mohd Fadzly Amar; Tan, Mei Lan; Adenan, Mohd Ilham; Wong, Philip; Shim, Winston

2014-01-01

Introduction Mitragynine is a major bioactive compound of Kratom, which is derived from the leave extracts of Mitragyna speciosa Korth or Mitragyna speciosa (M. speciosa), a medicinal plant from South East Asia used legally in many countries as stimulant with opioid-like effects for the treatment of chronic pain and opioid-withdrawal symptoms. Fatal incidents with Mitragynine have been associated with cardiac arrest. In this study, we determined the cardiotoxicity of Mitragynine and other chemical constituents isolated using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Methods and Results The rapid delayed rectifier potassium current (I Kr), L-type Ca2+ current (I Ca,L) and action potential duration (APD) were measured by whole cell patch-clamp. The expression of KCNH2 and cytotoxicity was determined by real-time PCR and Caspase activity measurements. After significant I Kr suppression by Mitragynine (10 µM) was confirmed in hERG-HEK cells, we systematically examined the effects of Mitragynine and other chemical constituents in hiPSC-CMs. Mitragynine, Paynantheine, Speciogynine and Speciociliatine, dosage-dependently (0.1∼100 µM) suppressed I Kr in hiPSC-CMs by 67% ∼84% with IC50 ranged from 0.91 to 2.47 µM. Moreover, Mitragynine (10 µM) significantly prolonged APD at 50 and 90% repolarization (APD50 and APD90) (439.0±11.6 vs. 585.2±45.5 ms and 536.0±22.6 vs. 705.9±46.1 ms, respectively) and induced arrhythmia, without altering the L-type Ca2+ current. Neither the expression,and intracellular distribution of KCNH2/Kv11.1, nor the Caspase 3 activity were significantly affected by Mitragynine. Conclusions Our study indicates that Mitragynine and its analogues may potentiate Torsade de Pointes through inhibition of I Kr in human cardiomyocytes. PMID:25535742

The outcome of antenatal ultrasound diagnosed anomalies of the kidney and urinary tract in a large Danish birth cohort.

PubMed

Andrés-Jensen, Liv; Jørgensen, Finn Stener; Thorup, Jorgen; Flachs, Julie; Madsen, Jan Lysgaard; Maroun, Lisa Leth; Nørgaard, Pernille; Vinicoff, Pablo Gustavo; Olsen, Beth Härstedt; Cortes, Dina

2016-09-01

Antenatal ultrasound diagnosed anomalies of the kidney and urinary tract (AUDAKUT) are reported in 0.3%-5% on prenatal ultrasound (US) and 0.3%-4.5% on postnatal US. The anterior-posterior diameter of the renal pelvis (APD) is an essential measurement. Series with low threshold values of APD prenatally and postnatally will include healthy infants. It is important to avoid follow-up of such infants. In 2006, new Danish guidelines for AUDAKUT were introduced. Investigations of incidences and type of AUDAKUT based on Danish guidelines, including long-term follow-up. Cohort study. Copenhagen University Hospital Hvidovre and Copenhagen University Hospital Rigshospitalet, Denmark. Consecutive cases with AUDAKUT in the second and third trimesters, which were either terminated before 22 completed weeks of gestation or born in the 8-year period January 2006-December 2013. Patients were followed until June 2014. 50 193 live born children and 24 terminated fetuses (0.05%) were included. The prevalence of AUDAKUT was only 0.39% prenatally, 0.29% at first postnatal US and 0.22% at the end of follow-up, including terminated cases. The greater the prenatal and postnatal APD, the higher risk of febrile urinary tract infection (fUTI) and surgical intervention, and lower probability of resolution. 25% of the identified patients had fUTI and/or surgery. We recommend threshold values of APD at least 10 mm in the third trimester and in general at least 12 mm at first postnatal US for intensive follow-up. In this largest to date unselected birth cohort of AUDAKUT, the incidences of clinically significant AUDAKUT were in the lowest range of those previously published. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Upregulation of K(2P)3.1 K+ Current Causes Action Potential Shortening in Patients With Chronic Atrial Fibrillation.

PubMed

Schmidt, Constanze; Wiedmann, Felix; Voigt, Niels; Zhou, Xiao-Bo; Heijman, Jordi; Lang, Siegfried; Albert, Virginia; Kallenberger, Stefan; Ruhparwar, Arjang; Szabó, Gábor; Kallenbach, Klaus; Karck, Matthias; Borggrefe, Martin; Biliczki, Peter; Ehrlich, Joachim R; Baczkó, István; Lugenbiel, Patrick; Schweizer, Patrick A; Donner, Birgit C; Katus, Hugo A; Dobrev, Dobromir; Thomas, Dierk

2015-07-14

Antiarrhythmic management of atrial fibrillation (AF) remains a major clinical challenge. Mechanism-based approaches to AF therapy are sought to increase effectiveness and to provide individualized patient care. K(2P)3.1 (TASK-1 [tandem of P domains in a weak inward-rectifying K+ channel-related acid-sensitive K+ channel-1]) 2-pore-domain K+ (K(2P)) channels have been implicated in action potential regulation in animal models. However, their role in the pathophysiology and treatment of paroxysmal and chronic patients with AF is unknown. Right and left atrial tissue was obtained from patients with paroxysmal or chronic AF and from control subjects in sinus rhythm. Ion channel expression was analyzed by quantitative real-time polymerase chain reaction and Western blot. Membrane currents and action potentials were recorded using voltage- and current-clamp techniques. K(2P)3.1 subunits exhibited predominantly atrial expression, and atrial K(2P)3.1 transcript levels were highest among functional K(2P) channels. K(2P)3.1 mRNA and protein levels were increased in chronic AF. Enhancement of corresponding currents in the right atrium resulted in shortened action potential duration at 90% of repolarization (APD90) compared with patients in sinus rhythm. In contrast, K(2P)3.1 expression was not significantly affected in subjects with paroxysmal AF. Pharmacological K(2P)3.1 inhibition prolonged APD90 in atrial myocytes from patients with chronic AF to values observed among control subjects in sinus rhythm. Enhancement of atrium-selective K(2P)3.1 currents contributes to APD shortening in patients with chronic AF, and K(2P)3.1 channel inhibition reverses AF-related APD shortening. These results highlight the potential of K(2P)3.1 as a novel drug target for mechanism-based AF therapy. © 2015 American Heart Association, Inc.

On-chip integrated functional near infra-red spectroscopy (fNIRS) photoreceiver for portable brain imaging

NASA Astrophysics Data System (ADS)

Kamrani, Ehsan

Optical brain imaging using functional near infra-red spectroscopy (fNIRS) offers a direct and noninvasive tool for monitoring of blood oxygenation. fNIRS is a noninvasive, safe, minimally intrusive, and high temporal-resolution technique for real-time and long-term brain imaging. It allows detecting both fast-neuronal and slow-hemodynamic signals. Besides the significant advantages of fNIRS systems, they still suffer from few drawbacks including low spatial-resolution, moderately high-level noise and high-sensitivity to movement. In order to overcome the limitations of currently available non-portable fNIRS systems, we have introduced a new low-power, miniaturized on-chip photodetector front-end intended for portable fNIRS systems. It includes silicon avalanche photodiode (SiAPD), Transimpedance amplifier (TIA), and Quench- Reset circuitry implemented using standard CMOS technologies to operate in both linear and Geiger modes. So it can be applied for both continuous-wave fNIRS (CW-fNIRS) and also single-photon counting applications. Several SiAPDs have been implemented in novel structures and shapes (Rectangular, Octagonal, Dual, Nested, Netted, Quadratic and Hexadecagonal) using different premature edge breakdown prevention techniques. The main characteristics of the SiAPDs are validated and the impact of each parameter and the device simulators (TCAD, COMSOL, etc.) have been studied based on the simulation and measurement results. Proposed techniques exhibit SiAPDs with high avalanche-gain (up to 119), low breakdown-voltage (around 12V) and high photon-detection efficiency (up to 72% in NIR region) in additional to a low dark-count rate (down to 30Hz at 1V excess bias voltage). Three new high gain-bandwidth product (GBW) and low-noise TIAs are introduced and implemented based on distributed-gain concept, logarithmic-amplification and automatic noise-rejection and have been applied in linear-mode of operation. The implemented TIAs offer a power-consumption around 0.4 mW, transimpedance gain of 169 dBO, and input-output current/voltage noises in fA/pV range accompanied with ability to tune the gain, bandwidth and power-consumption in a wide range. The implemented mixed quench-reset circuit (MQC) and controllable MQC (CMQC) front-ends offer a quench-time of 10ns, a maximum power-consumption of 0.4 mW, with a controllable hold-off and reset-times. The on-chip integration of SiAPDs with TIA and photon-counting circuitries has been demonstrated showing improvement of the photodetection-efficiency, specially regarding to the sensitivity, power-consumption and signal-to-noise ratio (SNR) characteristics.

Imaging performance of LabPET APD-based digital PET scanners for pre-clinical research

NASA Astrophysics Data System (ADS)

Bergeron, Mélanie; Cadorette, Jules; Tétrault, Marc-André; Beaudoin, Jean-François; Leroux, Jean-Daniel; Fontaine, Réjean; Lecomte, Roger

2014-02-01

The LabPET is an avalanche photodiode (APD) based digital PET scanner with quasi-individual detector read-out and highly parallel electronic architecture for high-performance in vivo molecular imaging of small animals. The scanner is based on LYSO and LGSO scintillation crystals (2×2×12/14 mm3), assembled side-by-side in phoswich pairs read out by an APD. High spatial resolution is achieved through the individual and independent read-out of an individual APD detector for recording impinging annihilation photons. The LabPET exists in three versions, LabPET4 (3.75 cm axial length), LabPET8 (7.5 cm axial length) and LabPET12 (11.4 cm axial length). This paper focuses on the systematic characterization of the three LabPET versions using two different energy window settings to implement a high-efficiency mode (250-650 keV) and a high-resolution mode (350-650 keV) in the most suitable operating conditions. Prior to measurements, a global timing alignment of the scanners and optimization of the APD operating bias have been carried out. Characteristics such as spatial resolution, absolute sensitivity, count rate performance and image quality have been thoroughly investigated following the NEMA NU 4-2008 protocol. Phantom and small animal images were acquired to assess the scanners' suitability for the most demanding imaging tasks in preclinical biomedical research. The three systems achieve the same radial FBP spatial resolution at 5 mm from the field-of-view center: 1.65/3.40 mm (FWHM/FWTM) for an energy threshold of 250 keV and 1.51/2.97 mm for an energy threshold of 350 keV. The absolute sensitivity for an energy window of 250-650 keV is 1.4%/2.6%/4.3% for LabPET4/8/12, respectively. The best count rate performance peaking at 362 kcps is achieved by the LabPET12 with an energy window of 250-650 keV and a mouse phantom (2.5 cm diameter) at an activity of 2.4 MBq ml-1. With the same phantom, the scatter fraction for all scanners is about 17% for an energy threshold of 250 keV and 10% for an energy threshold of 350 keV. The results obtained with two energy window settings confirm the relevance of high-efficiency and high-resolution operating modes to take full advantage of the imaging capabilities of the LabPET scanners for molecular imaging applications.

Neuropsychological correlates of cognitive, emotional-affective and auto-activation apathy in Alzheimer's disease.

PubMed

Perri, Roberta; Turchetta, Chiara Stella; Caruso, Giulia; Fadda, Lucia; Caltagirone, Carlo; Carlesimo, Augusto Giovanni

2018-01-31

Apathy symptoms include different dimensions: cognitive (C), emotional-affective (E-Aff) and auto-activation; they have been related to dysfunctions of the dorsolateral, orbito-basal prefrontal cortex and the subcortical frontal connections to the basal ganglia, respectively. In Alzheimer's disease (AD), an association has been found between apathy severity and both executive deficits and atrophy of the dorso-lateral prefrontal cortex; however, it is not clear whether these associations concern only the cognitive aspects of apathy. Furthermore, whether there is an association in AD between E-aff apathy and theory of mind (ToM),the cognitive functions subsumed by the orbito-basal prefrontal cortex, has not been investigated. Aim of the study was to investigate the relationship between C, E-Aff and auto-activation apathy and performance on tasks investigating executive and ToM cognitive functions in AD. For this purpose, 20 AD patients with apathy and 20 matched controls were submitted to an executive and ToM neuropsychological assessment. Apathy was assessed with a weekly diary (ApD) created specifically to assist caregivers in quantifying the C, E-Aff and auto-activation symptomatology of apathy. Correlational analyses showed that AD patients' scores on the Modified Card Sorting Test (MCST) and Emotion Attribution tasks were correlated with most ApD scores. However, regression analyses showed that C diary scores were predicted by MCST performance, E-Aff diary scores by performance on the E-Attribution task and ApD scores measuring auto-activation apathy were predicted by both the MCST and the Emotion Attribution scores. These results confirm the co-occurrence of apathy and executive-function deficits in AD and suggest a specific association between AD patients' executive deficits and the cognitive component of apathy. Furthermore, they document, for the first time, an association between poor performance on tests assessing ToM abilities and the emotional-affective component of apathy in AD patients. Finally, these results are in line with the view that auto-activation apathy reflects the sum of emotional and cognitive processing deficits. Copyright © 2018 Elsevier Ltd. All rights reserved.

Complex aberrant splicing in the induced pluripotent stem cell-derived cardiomyocytes from a patient with long-QT syndrome carrying KCNQ1-A344Aspl mutation.

PubMed

Wuriyanghai, Yimin; Makiyama, Takeru; Sasaki, Kenichi; Kamakura, Tsukasa; Yamamoto, Yuta; Hayano, Mamoru; Harita, Takeshi; Nishiuchi, Suguru; Chen, Jiarong; Kohjitani, Hirohiko; Hirose, Sayako; Yokoi, Fumika; Gao, Jingshan; Chonabayashi, Kazuhisa; Watanabe, Ken; Ohno, Seiko; Yoshida, Yoshinori; Kimura, Takeshi; Horie, Minoru

2018-05-29

Long-QT syndrome type 1 (LQT1) is caused by mutations in KCNQ1, which encodes the α-subunit of the slow delayed rectifier potassium current (I Ks ) channel. We previously reported that a synonymous mutation, c.1032G>A, p.A344Aspl in KCNQ1 is most commonly identified in the genotyped LQT1 Japanese patients, and the aberrant splicing was analyzed in the lymphocytes isolated from patients' blood samples. However, the mechanisms underlying the observed processes in human cardiomyocytes remains unclear. To establish and analyze patient-specific human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model carrying KCNQ1-A344Aspl. We generated hiPSCs from the peripheral blood mononuclear cells obtained from an LQT1 patient carrying KCNQ1-A344Aspl. Using the differentiated cardiomyocytes, we analyzed splicing variants and performed electrophysiological studies. We identified seven aberrant RNA variants in A344Aspl-hiPSC-CMs, more complex compared with those in the peripheral lymphocytes. Multi-electrode array analysis revealed that 1 μM isoproterenol significantly prolonged the duration of corrected field potential in A344Aspl-hiPSC-CMs, compared with that in the controls. Additionally, 100 nM E-4031, I Kr blocker, was shown to induce early afterdepolarization-like waveforms in A344Aspl-hiPSC-CMs. Action potential durations (APDs) did not significantly differ between the hiPSC-CM groups. After administrating 500 nM isoproterenol, APDs of A344Aspl-hiPSC-CMs were significantly longer than those of the controls. ML277 and phenylboronic acid, I Ks activators, ameliorated the APDs of hiPSC-CMs. We identified complex aberrant mRNA variants in the A344Aspl-hiPSC-CM model, and successfully recapitulated the clinical phenotypes of the patient with concealed LQT1. This model allows the investigation of the underlying mechanisms and development of novel therapies. Copyright © 2018. Published by Elsevier Inc.

A novel biasing dependent circuit model of resonant cavity enhanced avalanche photodetectors (RCE-APDs)

NASA Astrophysics Data System (ADS)

Abdelhamid, Mostafa R.; El-Batawy, Yasser M.; Deen, M. Jamal

2018-02-01

In Resonant Cavity Enhanced Photodetectors (RCE-PDs), the trade-off between the bandwidth and the quantum efficiency in the conventional photodetectors is overcome. In RCE-PDs, large bandwidth can be achieved using a thin absorption layer while the use of a resonant cavity allows for multiple passes of light in the absorption which boosts the quantum efficiency. In this paper, a complete bias-dependent model for the Resonant Cavity Enhanced-Separated Absorption Graded Charge Multiplication-Avalanche Photodetector (RCE-SAGCM-APD) is presented. The proposed model takes into account the case of drift velocities other than the saturation velocity, thus modeling this effect on the photodetector different design parameters such as Gain, Bandwidth and Gain-Bandwidth product.