On the nature of the speech perception deficits in children with autism spectrum disorders.

Previous studies have claimed to show deficits in the perception of speech sounds in autism spectrum disorders (ASD). The aim of the current study was to clarify the nature of such deficits. Children with ASD might only exhibit a lesser amount of precision in the perception of phoneme categories (CPR deficit). However, these children might further present an allophonic mode of speech perception, similar to the one evidenced in dyslexia, characterised by enhanced discrimination of acoustic differences within phoneme categories. Allophonic perception usually gives rise to a categorical perception (CP) deficit, characterised by a weaker coherence between discrimination and identification of speech sounds. The perceptual performance of ASD children was compared to that of control children of the same chronological age. Identification and discrimination data were collected for continua of natural vowels, synthetic vowels, and synthetic consonants. Results confirmed that children with ASD exhibit a CPR deficit for the three stimulus continua. These children further exhibited a trend toward allophonic perception that was, however, not accompanied by the usual CP deficit. These findings confirm that the commonly found CPR deficit is also present in ASD. Whether children with ASD also present allophonic perception requires further investigations.

Genetic variation within the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways as risk factors for venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is highly heritable (estimated heritability [h(2)]=0.62) and likely to be a result of multigenic action. OBJECTIVE: To systematically test variation within genes encoding for important components of the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways for an independent association with VTE. METHODS: Non-Hispanic adults of European ancestry with objectively-diagnosed VTE, and age- and sex- matched controls, were genotyped for 13 031 single nucleotide polymorphisms (SNPs) within 764 genes. Analyses (n=12296 SNPs) were performed with plink using an additive genetic model and adjusted for age, sex, state of residence, and myocardial infarction or stroke. RESULTS: Among 2927 individuals, one or more SNPs within ABO, F2, F5, F11, KLKB1, SELP and SCUBE1 were significantly associated with VTE, including factor (F) V Leiden, prothrombin G20210A, ABO non-O blood type, and a novel association with ABO rs2519093 (OR=1.68, P-value=8.08×10(-16) ) that was independent of blood type. In stratified analyses, SNPs in the following genes were significantly associated with VTE: F5 and ABO among both genders and LY86 among women; F2, ABO and KLKB1 among FV Leiden non-carriers; F5, F11, KLKB1 and GFRA1 in those with ABO non-O blood type; and ABO, F5, F11, KLKB1, SCUBE1 and SELP among prothrombin G20210A non-carriers. The ABO rs2519093 population-attributable risk (PAR) exceeded that of FV Leiden and prothrombin G20210A, and the joint PAR of FV Leiden, prothrombin G20210A, ABO non-O and ABO rs2519093 was 0.40. CONCLUSIONS: Anticoagulant, procoagulant, fibrinolytic and innate immunity pathway genetic variation accounts for a large proportion of VTE among non-Hispanic adults of European ancestry.

Comparative analysis of detoxification enzymes in Acyrthosiphon pisum and Myzus persicae.

Herbivorous insects use detoxification enzymes, including cytochrome P450 monooxygenases, glutathione S-transferases, and carboxy/cholinesterases, to metabolize otherwise deleterious plant secondary metabolites. Whereas Acyrthosiphon pisum (pea aphid) feeds almost exclusively from the Fabaceae, Myzus persicae (green peach aphid) feeds from hundreds of species in more than forty plant families. Therefore, M. persicae as a species would be exposed to a greater diversity of plant secondary metabolites than A. pisum, and has been predicted to require a larger complement of detoxification enzymes. A comparison of M. persicae cDNA and A. pisum genomic sequences is partially consistent with this hypothesis. There is evidence of at least 40% more cytochrome P450 genes in M. persicae than in A. pisum. In contrast, no major differences were found between the two species in the numbers of glutathione S-transferases, and carboxy/cholinesterases. However, given the incomplete M. persicae cDNA data set, the number of identified detoxification genes in this species is likely to be an underestimate.

Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis.

BACKGROUND: Dysregulation of the cell cycle is a hallmark of many cancers including ovarian cancer, a leading cause of gynaecologic cancer mortality worldwide. METHODS: We examined single nucleotide polymorphisms (SNPs) (n=288) from 39 cell cycle regulation genes, including cyclins, cyclin-dependent kinases (CDKs) and CDK inhibitors, in a two-stage study. White, non-Hispanic cases (n=829) and ovarian cancer-free controls (n=941) were genotyped using an Illumina assay. RESULTS: Eleven variants in nine genes (ABL1, CCNB2, CDKN1A, CCND3, E2F2, CDK2, E2F3, CDC2, and CDK7) were associated with risk of ovarian cancer in at least one genetic model. Seven SNPs were then assessed in four additional studies with 1689 cases and 3398 controls. Association between risk of ovarian cancer and ABL1 rs2855192 found in the original population [odds ratio, OR(BB vs AA) 2.81 (1.29-6.09), P=0.01] was also observed in a replication population, and the association remained suggestive in the combined analysis [OR(BB vs AA) 1.59 (1.08-2.34), P=0.02]. No other SNP associations remained suggestive in the replication populations. CONCLUSION: ABL1 has been implicated in multiple processes including cell division, cell adhesion and cellular stress response. These results suggest that characterization of the function of genetic variation in this gene in other ovarian cancer populations is warranted.

Eggs of the stink bug Acrosternum (Chinavia) marginatum (Hemiptera: Pentatomidae): a scanning electron microscopy study.

The morphology of the outer face of the eggshell, its appearance in cross fractures and the surface morphology of the inner face are described in the green stink bug Acrosternum (Chinavia) marginatum (Hemiptera: Pentatomidae) using scanning electron microscopy. Deposited eggs are barrel-shaped and the surface consists of hexagonally arranged, funnel-shaped pits that possess transverse diaphragms in their slender, basal portions. Only minor differences are detectable between the central portion of the anterior plate (the operculum) and the lateral wall together with the basal portion of the eggshell. The rim at the anterior pole of the egg carries processes with a bulbous end, the aero-micropylar processes. A narrow band of the anterior plate bordering these processes shows hexagonally arranged elements. These differ from those of the operculum and the lateral wall, in that cylindrical pits are abundant. During hatching, the operculum is lifted precisely at the rim of this area. Inspection of the periphery of the inner face of the operculum reveals slender, radially arranged grooves. Their arrangement and spacing indicate that they bear a spatial relationship with the aero-micropylar processes. Their role may lie in guiding the sperm to the site where fertilization occurs and in facilitating the gas exchange of the embryo. The remainder of the eggshell carries shallow elevations at its inner face. Exterior and interior features of the eggshell, as well as its appearance in cross-fractures, are discussed.

Tropospheric emission spectrometer for the Earth Observing System's Aura satellite.

The Tropospheric Emission Spectrometer (TES) is an imaging infrared Fourier-transform spectrometer scheduled to be launched into polar Sun-synchronous orbit aboard the Earth Observing System's Aura satellite in June 2003. The primary objective of the TES is to make global three-dimensional measurements of tropospheric ozone and of the physical-chemical factors that control its formation, destruction, and distribution. Such an ambitious goal requires a highly sophisticated cryogenic instrument operating over a wide frequency range, which, in turn, demands state-of-the-art infrared detector arrays. In addition, the measurements require an instrument that can operate in both nadir and limb-sounding modes with a precision pointing system. The way in which these mission objectives flow down to the specific science and measurement requirements and in turn are implemented in the flight hardware are described. A brief overview of the data analysis approach is provided.

Thirty years of Batten disease research: present status and future goals.

From a meager beginning in 1968, when Batten disease or neuronal ceroid lipofuscinosis was practically unheard of, tremendous advances have been made. It is now recognized worldwide as the most common neurodegenerative disease in children and young adults. It is recognized as a genetic disease. The infantile form has been localized to chromosome 1 p32 and the juvenile form, to 16p12.1; the gene for the late infantile is on chromosome 11p15 and for a variant form of the late infantile, the gene lies on chromosome 15q21-23. Finally, the molecular basis of the late infantile form is probably a pepstatin-insensitive lysomal peptidase. The future is to identify carriers, prevent the disease, and develop treatment by gene and enzyme replacement.

The Genome Sequence DataBase version 1.0 (GSDB): from low pass sequences to complete genomes.

The Genome Sequence DataBase (GSDB) has completed its conversion to an improved relational database. The new database, GSDB 1.0, is fully operational and publicly available. Data contributions, including both original sequence submissions and community annotation, are being accomplished through the use of a graphical client-server interface tool, the GSDB Annotator, and via GIO (GSDB Input/Output) files. Data retrieval services are being provided through a new Web Query Tool and direct SQL. All methods of data contribution and data retrieval fully support the new data types that have been incorporated into GSDB, including discontiguous sequences, multiple sequence alignments, and community annotation.

The Genome Sequence DataBase (GSDB): meeting the challenge of genomic sequencing.

The genome sequence database (GSDB) is a complete, publicly available relational database of DNA sequences and annotation maintained by the National Center for Genome Resources (NCGR) under a Cooperative Agreement with the US Department of Energy (DOE). GSDB provides direct, client- server access to the database for data contributions, community annotation and SQL queries. The GSDB Annotator, a multi-platform graphic user interface, is freely available. Automatically updated relational replicates of GSDB are also freely available.

The speciation of behavior analysis.

The relationship between the Experimental Analysis of Behavior (EAB) and Applied Behavior Analysis (ABA) has been the subject of several editorials and commentaries in recent years. Various authors have argued that researchers in these two fields (a) have become isolated from each other, (b) face different requirements for survival in their respective fields, and (c) possess different skills to meet those requirements. The present paper provides an allegory for the relationship between EAB and ABA in terms of biological speciation. The conditions that have changed the relationship between EAB and ABA are parallel to those responsible for biological speciation: (a) isolation of some members of a species from the rest of the population, (b) different contingencies of survival for members of the two separate groups, and (c) divergence in the adaptive characteristics displayed by the two groups. When members of two different groups, descendants of common ancestors, no longer are capable of producing viable offspring by interbreeding, the different groups then represent different species. To the extent that members of the EAB group and members of the ABA group interact with each other only trivially, they each represent allegorically different species. Changes in the relationship between EAB and ABA are part of a natural process that takes place in many other sciences, and the course of that process can hardly be reversed by us.

The effects of reinforcement frequency and response requirements on the maintenance of behavior.

Six rats responded under fixed-interval and tandem fixed-interval fixed-ratio schedules of food reinforcement. Basic fixed-interval schedules alternated over experimental conditions with tandem fixed-interval fixed-ratio schedules with the same fixed-interval value. Fixed-interval length was varied within subjects over pairs of experimental conditions; the ratio requirement of the tandem schedules was varied across subjects. For both subjects with a ratio requirement of 10, overall response rates and running response rates typically were higher under the tandem schedules than under the corresponding basic fixed-interval schedules. For all subjects with ratio requirements of 30 or 60, overall response rates and running response rates were higher under the tandem schedules than under the corresponding basic fixed-interval schedules only with relatively short fixed intervals. At longer fixed intervals, higher overall response rates and running rates were maintained by the basic fixed-interval schedules than by the tandem schedules. These findings support Zeiler and Buchman's (1979) reinforcement-theory account of response strength as an increasing monotonic function of both the response requirement and reinforcement frequency. Small response requirements added in tandem to fixed-interval schedules have little effect on reinforcement frequency and so their net effect is to enhance responding. Larger response requirements reduce reinforcement frequency more substantially; therefore their net effect depends on the length of the fixed interval, which limits overall reinforcement frequency. At the longest fixed intervals studied in the present experiment, reinforcement frequency under the tandem schedules was sufficiently low that responding weakened or ceased altogether.

Initial treatment of ventricular fibrillation: defibrillation or drug therapy.

The belief that defibrillation of unwitnessed ventricular fibrillation frequently results in asystole, combined with perceived low survival rates, led to deviation from "standard" advanced cardiac life support (ACLS) by physicians directing paramedics in the field. In nonstandard ACLS, intubation or drug therapy preceded defibrillation. This study retrospectively compared standard and nonstandard ACLS for ventricular fibrillation. The long-term survival rates were 12.3% (7/57) and 3.6% (6/168) for the two forms of ACLS, respectively (p = 0.03). The incidence of postcountershock asystole was 35% and 28% (p = 0.45). The survival rates for patients with a postcountershock rhythm and a pulse were 83% and 17% after standard and nonstandard ACLS (p less than 0.0001). Other factors reported to have a significant effect on survival were compared, and no significant differences (p greater than 0.05) were noted for mean age, sex, cardiopulmonary resuscitation (CPR) initiated by a bystander, ACLS response time, time to CPR, lay-witnessed arrest, or time to definitive care. The significant difference in the time to defibrillation (14 and 26 minutes) was expected. This is the first clinical study to clearly confirm the ACLS recommendation of early defibrillation before drug therapy in ventricular fibrillation.

Batten disease: past, present, and future.

The name Batten disease (or neuronal ceroid lipofuscinosis) is used to unify the spectrum of clinical and pathological conditions covered by the names infantile, late infantile, juvenile, and adult variants with their respective eponyms. The past was largely devoted to clinical diagnosis. The present is devoted to specific diagnostic tests. The future will be devoted to prevention and treatment. Treatment may consist of specific drug treatment, enzyme replacement, or gene replacement. Early diagnosis is important in order to provide genetic counseling and to establish family support for those patients who have a protracted, progressive disabling and ultimate fatal course.

Intermittent reinforcement of a continuous response.

Six rats were trained with food deliveries contingent upon their pressing a lever and holding it down for either fixed or variable cumulative durations. Fixed-hold requirements ranged from 15 s to 90 s over experimental conditions; variable-hold requirements ranged from 15 s to 120 s. At most long and intermediate values, variable-hold requirements maintained more lever holding than fixed requirements. At the longest hold requirements studied, more lever holding was maintained by variable requirements than by fixed requirements of equivalent mean length for each rat. Postreinforcement-pause duration increased with lever-holding time for both fixed- and variable-hold requirements. At comparable lever-holding times per reinforcer, longer pauses typically were produced by fixed requirements than by variable requirements. Data from this study on the maintenance of responding, temporal response patterns, and postreinforcement pausing are comparable to those obtained with intermittent reinforcement of discrete responses. These findings suggest that the response-reinforcer relation specified by a reinforcement schedule is a fundamental determinant of responding, whether responding consists of discrete units or of continuous activity.

Effects of hematoporphyrin derivative and photodynamic therapy on atherosclerotic rabbits.

This study was performed to demonstrate selective uptake of hematoporphyrin derivative (HPD) within actively developing atheroma, to localize the site of uptake of HPD within the atheroma, and to determine the potential for photodynamic therapy (PDT) of atherosclerosis in the rabbit model. Fifteen rabbits were rendered atherosclerotic. Five rabbits received neither HPD nor PDT and 2 rabbits received HPD, 10 mg/kg intravenously, without subsequent irradiation. Eight other rabbits received 5 to 20 mg of HPD intravenously and subsequent intravascular 636-nm laser radiation to either the thoracic aorta or the aortic arch. A total of 32 to 288 J of laser energy was delivered through a 300-mu quartz fiber. All rabbits that received in vivo HPD had red fluorescence of their aortas when placed under ultraviolet light. The pattern of fluorescence corresponded precisely to the pattern of atheroma. In segments that received PDT, light microscopic examination revealed an accumulation of smooth muscle cells at the intimal surface. Fluorescence microscopy revealed a diminishing concentration gradient of HPD from intimal surface layers towards the media. Assessment of treated thoracic aortic segments revealed quantitative and qualitative differences compared with control segments. In the arch-treated segments, however, no changes were seen. It is concluded that HPD localizes within rabbit atheroma, can be detected by fluorescence and is deposited in a diminishing concentration gradient from lumen toward media. Irradiation with 636-nm light may induce qualitative and quantitative changes in atheroma.