Practice variation in the diagnosis of acute rejection among pediatric heart transplant centers: An analysis of the pediatric heart transplant society (PHTS) registry.

BACKGROUND: Freedom from rejection in pediatric heart transplant recipients is highly variable across centers. This study aimed to assess the center variation in methods used to diagnose rejection in the first-year post-transplant and determine the impact of this variation on patient outcomes. METHODS: The PHTS registry was queried for all rejection episodes in the first-year post-transplant (2010-2019). The primary method for rejection diagnosis was determined for each event as surveillance biopsy, echo diagnosis, or clinical. The percentage of first-year rejection events diagnosed by surveillance biopsy was used to approximate the surveillance strategy across centers. Methods of rejection diagnosis were described and patient outcomes were assessed based on surveillance biopsy utilization among centers. RESULTS: A total of 3985 patients from 56 centers were included. Of this group, 873 (22%) developed rejection within the first-year post-transplant. Surveillance biopsy was the most common method of rejection diagnosis (71.7%), but practices were highly variable across centers. The majority (73.6%) of first rejection events occurred within 3-months of transplantation. Diagnosis modality in the first-year was not independently associated with freedom from rejection, freedom from rejection with hemodynamic compromise, or overall graft survival. CONCLUSIONS: Rejection in the first-year after pediatric heart transplant occurs in 22% of patients and most commonly in the first 3 months post-transplant. Significant variation exists across centers in the methods used to diagnose rejection in pediatric heart transplant recipients, however, these variable strategies are not independently associated with freedom from rejection, rejection with hemodynamic compromise, or overall graft survival.

Limits on the Existence of sub-MeV Sterile Neutrinos from the Decay of

Sterile neutrinos are natural extensions to the standard model of particle physics and provide a possible portal to the dark sector. We report a new search for the existence of sub-MeV sterile neutrinos using the decay-momentum reconstruction technique in the decay of ^{7}Be. The experiment measures the total energy of the ^{7}Li daughter atom from the electron capture decay of ^{7}Be implanted into sensitive superconducting tunnel junction (STJ) quantum sensors. This first experiment presents data from a single STJ operated at a low count rate for a net total of 28 days, and provides exclusion limits on sterile neutrinos in the mass range from 100 to 850 keV that improve upon previous work by up to an order of magnitude.

Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis.

Uterine leiomyomata (UL) are the most common neoplasms of the female reproductive tract and primary cause for hysterectomy, leading to considerable morbidity and high economic burden. Here we conduct a GWAS meta-analysis in 35,474 cases and 267,505 female controls of European ancestry, identifying eight novel genome-wide significant (P < 5 × 10-8) loci, in addition to confirming 21 previously reported loci, including multiple independent signals at 10 loci. Phenotypic stratification of UL by heavy menstrual bleeding in 3409 cases and 199,171 female controls reveals genome-wide significant associations at three of the 29 UL loci: 5p15.33 (TERT), 5q35.2 (FGFR4) and 11q22.3 (ATM). Four loci identified in the meta-analysis are also associated with endometriosis risk; an epidemiological meta-analysis across 402,868 women suggests at least a doubling of risk for UL diagnosis among those with a history of endometriosis. These findings increase our understanding of genetic contribution and biology underlying UL development, and suggest overlapping genetic origins with endometriosis.

Obesity and obesogenic growth are both highly heritable and modified by diet in a nonhuman primate model, the African green monkey (Chlorocebus aethiops sabaeus).

OBJECTIVE: In humans, the ontogeny of obesity throughout the life course and the genetics underlying it has been historically difficult to study. We compared, in a non-human primate model, the lifelong growth trajectories of obese and non-obese adults to assess the heritability of and map potential genomic regions implicated in growth and obesity. STUDY POPULATION: A total of 905 African green monkeys, or vervets (Chlorocebus aethiops sabaeus) (472 females, 433 males) from a pedigreed captive colony. METHODS: We measured fasted body weight (BW), crown-to-rump length (CRL), body-mass index (BMI) and waist circumference (WC) from 2000 to 2015. We used a longitudinal clustering algorithm to detect obesogenic growth, and logistic growth curves implemented in nonlinear mixed effects models to estimate three growth parameters. We used maximum likelihood variance decomposition methods to estimate the genetic contributions to obesity-related traits and growth parameters, including a test for the effects of a calorie-restricted dietary intervention. We used multipoint linkage analysis to map implicated genomic regions. RESULTS: All measurements were significantly influenced by sex, and with the exception of WC, also influenced by maternal and post-natal diet. Chronic obesity outcomes were significantly associated with a pattern of extended growth duration with slow growth rates for BW. After accounting for environmental influences, all measurements were found to have a significant genetic component to variability. Linkage analysis revealed several regions suggested to be linked to obesity-related traits that are also implicated in human obesity and metabolic disorders. CONCLUSIONS: As in humans, growth patterns in vervets have a significant impact on adult obesity and are largely under genetic control with some evidence for maternal and dietary programming. These results largely mirror findings from human research, but reflect shorter developmental periods, suggesting that the vervet offers a strong genetic model for elucidating the ontogeny of human obesity.

ASD restricted and repetitive behaviors associated at 17q21.33: genes prioritized by expression in fetal brains.

Autism spectrum disorder (ASD) is a behaviorally defined condition that manifests in infancy or early childhood as deficits in communication skills and social interactions. Often, restricted and repetitive behaviors (RRBs) accompany this disorder. ASD is polygenic and genetically complex, so we hypothesized that focusing analyses on intermediate core component phenotypes, such as RRBs, can reduce genetic heterogeneity and improve statistical power. Applying this approach, we mined Caucasian genome-wide association studies (GWAS) data from two of the largest ASD family cohorts, the Autism Genetics Resource Exchange and Autism Genome Project (AGP). Of the 12 RRBs measured by the Autism Diagnostic Interview-Revised, seven were found to be significantly familial and substantially variable, and hence, were tested for genome-wide association in 3104 ASD-affected children from 2045 families. Using a stringent significance threshold (P<7.1 × 10-9), GWAS in the AGP revealed an association between 'the degree of the repetitive use of objects or interest in parts of objects' and rs2898883 (P<6.8 × 10-9), which resides within the sixth intron of PHB. To identify the candidate target genes of the associated single-nucleotide polymorphisms at that locus, we applied chromosome conformation studies in developing human brains and implicated three additional genes: SLC35B1, CALCOCO2 and DLX3. Gene expression, brain imaging and fetal brain expression quantitative trait locus studies prioritize SLC35B1 and PHB. These analyses indicate that GWAS of single heritable features of genetically complex disorders followed by chromosome conformation studies in relevant tissues can be successful in revealing novel risk genes for single core features of ASD.

Genome-wide association study of NMDA receptor coagonists in human cerebrospinal fluid and plasma.

The N-methyl-D-aspartate receptor (NMDAR) coagonists glycine, D-serine and L-proline play crucial roles in NMDAR-dependent neurotransmission and are associated with a range of neuropsychiatric disorders. We conducted the first genome-wide association study of concentrations of these coagonists and their enantiomers in plasma and cerebrospinal fluid (CSF) of human subjects from the general population (N=414). Genetic variants at chromosome 22q11.2, located in and near PRODH (proline dehydrogenase), were associated with L-proline in plasma (ß=0.29; P=6.38 × 10(-10)). The missense variant rs17279437 in the proline transporter SLC6A20 was associated with L-proline in CSF (ß=0.28; P=9.68 × 10(-9)). Suggestive evidence of association was found for the D-serine plasma-CSF ratio at the D-amino-acid oxidase (DAO) gene (ß=-0.28; P=9.08 × 10(-8)), whereas a variant in SRR (that encodes serine racemase and is associated with schizophrenia) constituted the most strongly associated locus for the L-serine to D-serine ratio in CSF. All these genes are highly expressed in rodent meninges and choroid plexus, anatomical regions relevant to CSF physiology. The enzymes and transporters they encode may be targeted to further construe the nature of NMDAR coagonist involvement in NMDAR gating. Furthermore, the highlighted genetic variants may be followed up in clinical populations, for example, schizophrenia and 22q11 deletion syndrome. Overall, this targeted metabolomics approach furthers the understanding of NMDAR coagonist concentration variability and sets the stage for non-targeted CSF metabolomics projects.

Generalist red velvet mite predator (Balaustium sp.) performs better on a mixed diet.

Generalist predators have the potential advantage to control more than one pest and to be more persistent than specialist predators because they can survive on different foods. Moreover, their population growth rate may be elevated when offered a mixture of prey species. We studied a generalist predatory mite Balaustium sp. that shows promise for biological control of thrips and whiteflies in protected rose cultures in Colombia. Although starting its life in the soil, this predator makes excursions onto plants where it feeds on various arthropods. We quantified life history parameters of the predator, offering high densities of three pest species: first-instar larvae of Frankliniella occidentalis, eggs of Trialeurodes vaporariorum and Tetranychus urticae, either alone or in combination. The predators completed their life cycle on each diet. The egg-to-egg period was c. 2 months. All eggs were laid in one batch in 1-2 days, indicating a pronounced semelparous reproduction pattern. In general, females reproduced earlier and laid more eggs on mixed diets, and these early reproducers consequently had higher population growth rates than late reproducers. The best diet in terms of egg-to-egg period and juvenile survival was the combination of eggs from whiteflies and spider mites. Spider mite eggs alone and western flower thrips larvae alone were the worst diets. It remains to be investigated whether mixed diets promote the population growth rate of Balaustium sufficiently for biocontrol of whiteflies and thrips in the presence of alternative prey, such as spider mites, to become effective.

Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid.

Studying genetic determinants of intermediate phenotypes is a powerful tool to increase our understanding of genotype-phenotype correlations. Metabolic traits pertinent to the central nervous system (CNS) constitute a potentially informative target for genetic studies of intermediate phenotypes as their genetic underpinnings may elucidate etiological mechanisms. We therefore conducted a genome-wide association study (GWAS) of monoamine metabolite (MM) levels in cerebrospinal fluid (CSF) of 414 human subjects from the general population. In a linear model correcting for covariates, we identified one locus associated with MMs at a genome-wide significant level (standardized ß=0.32, P=4.92 × 10(-8)), located 20 kb from SSTR1, a gene involved with brain signal transduction and glutamate receptor signaling. By subsequent whole-genome expression quantitative trait locus (eQTL) analysis, we provide evidence that this variant controls expression of PDE9A (ß=0.21; P unadjusted=5.6 × 10(-7); P corrected=0.014), a gene previously implicated in monoaminergic transmission, major depressive disorder and antidepressant response. A post hoc analysis of loci significantly associated with psychiatric disorders suggested that genetic variation at CSMD1, a schizophrenia susceptibility locus, plays a role in the ratio between dopamine and serotonin metabolites in CSF. The presented DNA and mRNA analyses yielded genome-wide and suggestive associations in biologically plausible genes, two of which encode proteins involved with glutamate receptor functionality. These findings will hopefully contribute to an exploration of the functional impact of the highlighted genes on monoaminergic transmission and neuropsychiatric phenotypes.

Horn-coupled, commercially-fabricated aluminum lumped-element kinetic inductance detectors for millimeter wavelengths.

We discuss the design, fabrication, and testing of prototype horn-coupled, lumped-element kinetic inductance detectors (LEKIDs) designed for cosmic microwave background studies. The LEKIDs are made from a thin aluminum film deposited on a silicon wafer and patterned using standard photolithographic techniques at STAR Cryoelectronics, a commercial device foundry. We fabricated 20-element arrays, optimized for a spectral band centered on 150 GHz, to test the sensitivity and yield of the devices as well as the multiplexing scheme. We characterized the detectors in two configurations. First, the detectors were tested in a dark environment with the horn apertures covered, and second, the horn apertures were pointed towards a beam-filling cryogenic blackbody load. These tests show that the multiplexing scheme is robust and scalable, the yield across multiple LEKID arrays is 91%, and the measured noise-equivalent temperatures for a 4 K optical load are in the range 26±6 µK√s.

Seasonal variation of serotonin turnover in human cerebrospinal fluid, depressive symptoms and the role of the 5-HTTLPR.

Studying monoaminergic seasonality is likely to improve our understanding of neurobiological mechanisms underlying season-associated physiological and pathophysiological behavior. Studies of monoaminergic seasonality and the influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on serotonin seasonality have yielded conflicting results, possibly due to lack of power and absence of multi-year analyses. We aimed to assess the extent of seasonal monoamine turnover and examined the possible involvement of the 5-HTTLPR. To determine the influence of seasonality on monoamine turnover, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the cerebrospinal fluid of 479 human subjects collected during a 3-year period. Cosine and non-parametric seasonal modeling were applied to both metabolites. We computed serotonin (5-HT) seasonality values and performed an association analysis with the s/l alleles of the 5-HTTLPR. Depressive symptomatology was assessed using the Beck Depression Inventory-II. Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074). Season of sampling explained 5.4% (P=1.57 × 10(-7)) of the variance in 5-HIAA concentrations. The 5-HTTLPR s-allele was associated with increased 5-HIAA seasonality (standardized regression coefficient=0.12, P=0.020, N=393). 5-HIAA seasonality correlated with depressive symptoms (Spearman's rho=0.13, P=0.018, N=345). In conclusion, we highlight a dose-dependent association of the 5-HTTLPR with 5-HIAA seasonality and a positive correlation between 5-HIAA seasonality and depressive symptomatology. The presented data set the stage for follow-up in clinical populations with a role for seasonality, such as affective disorders.

INTERACCIÓN ENTRE DOS ÁCAROS DEPREDADORES DE Tetranychus urticae KOCH (ACARIFORMES: TETRANYCHIDAE) EN LABORATORIO / Interaction Between Two Predator Mites of Tetranychus urticae Koch (Acariformes: Tetranychidae) in Laboratory

Tetranychus urticae (Acari: Tetranychidae) es una de las principales plagas de cultivos ornamentales, entre las especies más utilizadas para su control se encuentran Neoseiulus californicus y Phytoseiulus persimilis (Parasitiformes: Phytoseiidae). En el presente trabajo se propone el manejo de la plaga mediante el empleo de liberaciones simultáneas de los dos fitoseidos. Se evaluaron varias situaciones, por un lado se estudiaron las interacciones cuando un depredador se encuentra en una densidad baja mientras que el otro depredador se presenta en alta densidad (esta situación se analizó tanto en presencia como en ausencia de la presa). Por otro lado, se evaluaron las interacciones cuando los P. persimilis y N. californicus dos están presentes en igual densidad y en presencia de T. urticae. Cuando uno de los depredadores está en mayor densidad y hay presencia de la presa, se observa que al incrementar la edad del depredador que tiene menor densidad, aumenta también la interferencia en el consumo de presas por parte de los depredadores que están en mayor densidad. Además cuando disminuye el consumo de T. urticae se incrementa el consumo intraguilda. Phytoseiulus persimilis en ausencia de T. urticae y en presencia de N. californicus adopta un comportamiento de depredación intraguilda sobre todos los estados de desarrollo de su conespecifico, mientras que N. californicus únicamente consume larvas de conespecíficos en ausencia del fitófago y en presencia de P. persimilis. Cuando se encontraban los dos depredadores en el mismo montaje y la misma densidad de población, no se observó un mayor consumo de T. urticae que cuando cada depredador es empleado por separado.

Tetranychus urticae (Acari: Tetranychidae) is an important pest of ornamental crops. A species of predatory mite used for its control is Neoseiulus californicus and Phytoseiulus persimilis (Acari: Phytoseiidae). This research proposes the use of joint releases of the two cited predators for the control of the pest. Several situations leading to interaction were evaluated: High density of one predator and low density of the other one, being the prey present or absent. The scenario with predators in equal densities and in presence of the prey was also evaluated. When a predator is in higher density and the prey present, the predator with the lower density increases the interference with the comsumption of preys by the predator with higher density. On the other hand, when the comsumption of T. urticae reduces, intraguild predation increases. P. persimilis shows intraguild predation behaviour when T. urticae is absent and N. californicus is present, consuming all developmental stages of its conspecific. Instead, N. californicus only feed on conspecific larvae, when the fitofagous was absent and P. persimilis was present. When the two predators were present in the same assemblage and with the same population density, the quantity of T. urticae consumed by both of them was not higher than the consumed one when each predator was present in separate way.

QTL replication and targeted association highlight the nerve growth factor gene for nonverbal communication deficits in autism spectrum disorders.

Autism Spectrum Disorder (ASD) has a heterogeneous etiology that is genetically complex. It is defined by deficits in communication and social skills and the presence of restricted and repetitive behaviors. Genetic analyses of heritable quantitative traits that correlate with ASD may reduce heterogeneity. With this in mind, deficits in nonverbal communication (NVC) were quantified based on items from the Autism Diagnostic Interview Revised. Our previous analysis of 228 families from the Autism Genetics Research Exchange (AGRE) repository reported 5 potential quantitative trait loci (QTL). Here we report an NVC QTL replication study in an independent sample of 213 AGRE families. One QTL was replicated (P<0.0004). It was investigated using a targeted-association analysis of 476 haplotype blocks with 708 AGRE families using the Family Based Association Test (FBAT). Blocks in two QTL genes were associated with NVC with a P-value of 0.001. Three associated haplotype blocks were intronic to the Nerve Growth Factor (NGF) gene (P=0.001, 0.001, 0.002), and one was intronic to KCND3 (P=0.001). Individual haplotypes within the associated blocks drove the associations (0.003, 0.0004 and 0.0002) for NGF and 0.0001 for KCND3. Using the same methods, these genes were tested for association with NVC in an independent sample of 1517 families from an Autism Genome Project (AGP). NVC was associated with a haplotype in an adjacent NGF block (P=0.0005) and one 46 kb away from the associated block in KCND3 (0.008). These analyses illustrate the value of QTL and targeted association studies for genetically complex disorders such as ASD. NGF is a promising risk gene for NVC deficits.

Allowing for sex differences increases power in a GWAS of multiplex Autism families.

Current genomewide association studies account for only a small fraction of the estimated heritabilities of genetically complex neuropsychiatric disorders, indicating they are likely to result from the small effects of numerous predisposing variants, many of which have gone undetected. The statistical power to detect associations of common variants with small effects is increased by conducting joint association tests of a single nucleotide polymorphism (SNP), an additional risk factor (F), and their interaction. F can represent an environmental exposure, another genotype or any source of genetic heterogeneity. In case and control studies, logistic regression makes joint tests straightforward. This analytic method cannot be employed directly when SNP transmission tests are used to detect associations in parent/affected child trios and multiplex families. However, the method can be implemented using the case/pseudocontrol approach. We applied this approach to analyze data from a genomewide association study of multiplex families ascertained for Autism Spectrum Disorder, where sex was used to define the F. Joint analyses revealed two associations exceeding genomewide significance. One novel gene, Ryandine Receptor 2, implicated in calcium channel defects, was identified with a joint P-value of 3.9E-11. Calcium channel defects have been connected to Autism spectrum disorder (ASD) by Timothy Syndrome, which is Mendelian, and a previous targeted sex-specific association analysis of idiopathic Autism. A second gene, uridine phosphorylase 2, with a joint P-value of 2.3E-9, has been previously linked and associated with Autism in independent samples. These findings highlight two Autism candidate genes for follow-up studies.

Association between genetic variation in a region on chromosome 11 and schizophrenia in large samples from Europe.

Recent molecular studies have implicated common alleles of small to moderate effect and rare alleles with larger effect sizes in the genetic architecture of schizophrenia (SCZ). It is expected that the reliable detection of risk variants with very small effect sizes can only be achieved through the recruitment of very large samples of patients and controls (that is tens of thousands), or large, potentially more homogeneous samples that have been recruited from confined geographical areas using identical diagnostic criteria. Applying the latter strategy, we performed a genome-wide association study (GWAS) of 1169 clinically well characterized and ethnically homogeneous SCZ patients from a confined area of Western Europe (464 from Germany, 705 from The Netherlands) and 3714 ethnically matched controls (1272 and 2442, respectively). In a subsequent follow-up study of our top GWAS results, we included an additional 2569 SCZ patients and 4088 controls (from Germany, The Netherlands and Denmark). Genetic variation in a region on chromosome 11 that contains the candidate genes AMBRA1, DGKZ, CHRM4 and MDK was significantly associated with SCZ in the combined sample (n=11 540; P=3.89 × 10(-9), odds ratio (OR)=1.25). This finding was replicated in 23 206 independent samples of European ancestry (P=0.0029, OR=1.11). In a subsequent imaging genetics study, healthy carriers of the risk allele exhibited altered activation in the cingulate cortex during a cognitive control task. The area of interest is a critical interface between emotion regulation and cognition that is structurally and functionally abnormal in SCZ and bipolar disorder.

GWA study data mining and independent replication identify cardiomyopathy-associated 5 (CMYA5) as a risk gene for schizophrenia.

We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values ≤0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611-rs10043986, r(2)=0.008; rs10043986-rs4704591, r(2)=0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR)=1.11, 95% confidence interval (CI)=1.04-1.18, P=8.2 × 10(-4) and rs4704591, OR=1.07, 95% CI=1.03-1.11, P=3.0 × 10(-4)). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR=1.11, 95% CI=1.03-1.17, P=0.0026 and rs4704591, OR=1.07, 95% CI=1.02-1.11, P=0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed at these two markers are independent. On the basis of these results, we concluded that CMYA5 is associated with schizophrenia and further investigation of the gene is warranted.

CRITERIOS PARA LA PRODUCCIÓN DE Phytoseiulus persimilis (PARASITIFORMES: PHYTOSEIIDAE) BAJO CONDICIONES DE INVERNADERO / Criteria or the production of phytoseiuls persimilis (parasitiformes: pphytoseiidae) under greenhouse conditinns

El ácaro depredador Phytoseiulus persimilis ha sido usado con éxito para el control del ácaro fitófago Tetranychus urticae, el cual constituye una de las plagas mas importantes en los cultivos de rosa de la Sabana de Bogotá. En Colombia esta estrategia de control se ha visto limitada por la falta de disponibilidad de los depredadores en el comercio del producto. En el presente trabajo se proponen criterios para estandarizar las bases para la producción de P. persimilis en plantas de frijol infestadas con poblaciones de T. urticae de diferentes tiempos de desarrollo, utilizando una proporción constante de depredadores liberados. Se encontró que plantas infestadas con poblaciones de T. urticae por más de tres semanas permiten obtener mayores incrementos de población de los depredadores y que aproximadamente a los 25 días después de realizada la liberación, de los depredadores en las plantas infestadas, se obtienen los mayores poblaciones del depredador en estado de ninfa y adulto para cosechar y usar como estrategia de control en los cultivos.

The predatory mite Phytoseiulus persimilis has been used successfully to control the phytophagous mite Tetranychus urticae in rose crops, in what is one of the most important pests. In Colombia , this control strategy has been limited by the lack of predators in the trade of the product. Here was proposed to standardize the basis for the production of P. persimilis on bean plants infested with populations of T. urticae of different development times, using a constant proportion of predators released. We found that populations of plants infested with T. urticae for more than three weeks resulted in higher population increase of predators and at approximately 25 days after the release of predators on plants infested, you get the largest predator populations in a state of nymph and adult to harvest and use as a strategy control in crops.

High-density SNP association study of the 17q21 chromosomal region linked to autism identifies CACNA1G as a novel candidate gene.

Chromosome 17q11-q21 is a region of the genome likely to harbor susceptibility to autism (MIM(209850)) based on earlier evidence of linkage to the disorder. This linkage is specific to multiplex pedigrees containing only male probands (MO) within the Autism Genetic Resource Exchange (AGRE). Earlier, Stone et al.(1) completed a high-density single nucleotide polymorphism association study of 13.7 Mb within this interval, but common variant association was not sufficient to account for the linkage signal. Here, we extend this single nucleotide polymorphism-based association study to complete the coverage of the two-LOD support interval around the chromosome 17q linkage peak by testing the majority of common alleles in 284 MO trios. Markers within an interval containing the gene, CACNA1G, were found to be associated with Autism Spectrum Disorder at a locally significant level (P=1.9 × 10(-5)). While establishing CACNA1G as a novel candidate gene for autism, these alleles do not contribute a sufficient genetic effect to explain the observed linkage, indicating that there is substantial genetic heterogeneity despite the clear linkage signal. The region thus likely harbors a combination of multiple common and rare alleles contributing to the genetic risk. These data, along with earlier studies of chromosomes 5 and 7q3, suggest few if any major common risk alleles account for Autism Spectrum Disorder risk under major linkage peaks in the AGRE sample. This provides important evidence for strategies to identify Autism Spectrum Disorder genes, suggesting that they should focus on identifying rare variants and common variants of small effect.

Measuring tissue heat penetration by scattered light measurements.

BACKGROUND AND OBJECTIVES: The monitoring of tissue morphological changes during clinical procedure such as laser thermotherapy, laser hair removal and others is important in order to prevent damage to healthy tissue. An optical system and method for the assessment of real time in vivo tissue morphological changes is proposed. MATERIALS AND METHODS: We used ex vivo chicken breast as tissue samples. The samples were irradiated by CO(2) laser to create thermal structural changes. The optical properties of the tissue samples were measured using an integrating sphere method. We measured the tissue heat penetration and the scattered light from the tissue and compared the results to Monte-Carlo simulation. RESULTS: Thermal interaction causes structural changes in the tissue. Therefore changing (increasing) the scattering properties of the tissue. We relate the structural changes to the scattered light pattern and proposed a method for controlling the thermal interaction. CONCLUSION: It is possible to design a real time in vivo controlling system for laser tissue thermal interaction that utilizes the changes in the scattered light pattern.