Improved methods for the analysis of circadian rhythms in correlated gene expression data

Circadian clocks regulate biological behaviours, such as sleeping and waking times, that recur naturally on an approximately 24-hour cycle. These clocks tend to be influenced by a variety of external factors, sometimes to the extent that it can have an impact on health. As an example in pharmacology, the effects of chemicals on the circadian rhythm in patients can be key in clarifying the relationship of drug efficacy and toxicity with dosing times. While pre-clinical experiments conducted to elucidate these effects may produce correlated data measured over time, such as gene expression profiles, existing methods for fitting parametric nonlinear regression models are however inadequate and can lead to unreliable, inconsistent parameter estimates and invalid inference. A de-trending method is widely used as a pre-processing step to address the non-stationary problem in the data before fitting models based on the assumption of independence. However, as it is unclear that this approach properly accounts for the correlation structure, alternative methods that specifically model the correlation in the data based on conditional least squares and a two-stage estimation procedure are proposed and evaluated. A simulation study covering a wide range of scenarios and models show that the proposed methods more efficient and robust to model mis-specification than de-trending and, furthermore, they lead to reduced bias in estimation of the circadian period and more reliable confidence intervals

Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students

Background: Genetic factors impact alcohol use behaviors and these factors may become increasingly evident during emerging adulthood. Examination of the effects of individual variants as well as aggregate genetic variation can clarify mechanisms underlying risk. Methods: We conducted genome-wide association studies (GWAS) in an ethnically diverse sample of college students for three quantitative outcomes including typical monthly alcohol consumption, alcohol problems, and maximum number of drinks in 24 h. Heritability based on common genetic variants (h2SNP) was assessed. We also evaluated whether risk variants in aggregate were associated with alcohol use outcomes in an independent sample of young adults. Results: Two genome-wide significant markers were observed: rs11201929 in GRID1 for maximum drinks in 24 h, with supportive evidence across all ancestry groups; and rs73317305 in SAMD12 (alcohol problems), tested only in the African ancestry group. The h2SNP estimate was 0.19 (SE = 0.11) for consumption, and was non-significant for other outcomes. Genome-wide polygenic scores were significantly associated with alcohol outcomes in an independent sample. Conclusions: These results robustly identify genetic risk for alcohol use outcomes at the variant level and in aggregate. We confirm prior evidence that genetic variation in GRID1impacts alcohol use, and identify novel loci of interest for multiple alcohol outcomes in emerging adults. These findings indicate that genetic variation influencing normative and problematic alcohol use is, to some extent, convergent across ancestry groups. Studying college populations represents a promising avenue by which to obtain large, diverse samples for gene identification

Efektivitas Penggunaan Metode Iqra’ Untuk Meningkatkan Kemampuan Membaca Al-Qur’an Bagi Siswa Muallaf

This study examines the effectiveness of using the iqra' method to improve the ability to read the Qur'an to convert students at Assalam Islamic Solidarity School in Jantho City. Based on the facts in the field, the convert students who are already young have not been able to read the Qur'an well. This institution seeks to improve the quality of convert students in the Qur'an reading, which aims to be one of the motivations for other students to study the Qur'an well. This research has two objectives, namely: How is the ability to read the Qur’an, and the use of the iqra' method to convert students at Assalam Islamic Solidarity School in Jantho City. This research uses a descriptive qualitative approach. Respondents in this study were teachers and students. Data collection techniques in this study are using observation and interviews. From the results of the study found by researchers that the use of iqra' method has been effective against the ability to read for convert students, although there are difficulties in the learning process, caused by lughat (pronunciation) their tongues are still stiff. From this study it can be concluded that every educational institution that is specifically in charge of the education of the Qur'an must be able to improve its quality in carrying out the Qur'anic learning process especially in terms of reading the letters, so that every student, especially converts, can learn the Qur'an 's well and correctly so that they can instill Islamic laws based on the Qur'an and as-Sunnah

Using Patterns of Genetic Association to Elucidate Shared Genetic Etiologies Across Psychiatric Disorders

Twin studies indicate that latent genetic factors overlap across comorbid psychiatric disorders. In this study, we used a novel approach to elucidate shared genetic factors across psychiatric outcomes by clustering single nucleotide polymorphisms based on their genome-wide association patterns. We applied latent profile analysis (LPA) to p-values resulting from genome-wide association studies across three phenotypes: symptom counts of alcohol dependence (AD), antisocial personality disorder (ASP), and major depression (MD), using the European–American case-control genome-wide association study subsample of the collaborative study on the genetics of alcoholism (N = 1399). In the 3-class model, classes were characterized by overall low associations (85.6% of SNPs), relatively stronger association only with MD (6.8%), and stronger associations with AD and ASP but not with MD (7.6%), respectively. These results parallel the genetic factor structure identified in twin studies. The findings suggest that applying LPA to association results across multiple disorders may be a promising approach to identify the specific genetic etiologies underlying shared genetic variance

Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis.

Background and aimsThe associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis).DesignPolygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families.SettingSix sites in the United States.ParticipantsEuropean ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample.MeasurementsOutcomes included criterion counts for DSM-5 alcohol use disorder (AUDSX), Fagerström nicotine dependence (NDSX) and DSM-5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears-GPS) using summary statistics from a large (> 1 million) genome-wide association study of educational attainment.FindingsIn polygenic association analyses, higher EduYears-GPS predicted lower AUDSX, NDSX and CUDSX [P < 0.01, effect sizes (R2 ) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears-GPS predicted all three SUDs (P < 0.05, R2 0.13-0.20%).ConclusionsIndividuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio-economic status, urban-rural residency and parental education)

Komunikasi Interpersonal Wanita Bercadar: Studi di Dayah Darul Mu’arrif Al-Aziziyyah Kota Lhokseumawe

Penelitian ini berjudul Komunikasi Interpersonal Wanita Bercadar (di Dayah Darul Mu’arrif Al-Aziziyyah Kota Lhokseumawe)dalam proses interaksi eksklusivitas dan ketutupan komunitas cadar dapat menghambat proses sosialisasi. Setiap individu tidak lepas dari sebuah komunikasi dalam hal ini adalah komunikasi interpersonal yang juga sangat di pengaruhi oleh adanya persepsi interpersonal di antara berbagai petunjuk non verbal dan petunjuk wajah. Penelitian ini  bertujuan untuk mengetahui dan mendeskripsikan bagaimana komunikasi yang terjadi antara santriwati bercadar dengan santriwati yang tidak bercadar di Dayah Darul Mu’arrif Al-Aziziyyah Kota Lhokseumawe. Fokus penelitian ini adalah bentuk komunikasi verbal dan non verbal dengan proses diadik atau triadik dari komunikasi interpersonal antara wanita bercadar. Pendekatan penelitian yang digunakan adalah kualitatif dengan tipe penelitian deskriptif. Data didapati dengan cara observasi, wawancara dan kajian pustaka dengan enam informan di dayah. Hasil penelitian menunjukkan bahwa komunikasi yang berlangsung antara santriwati bercadar dan santriwati yang tidak bercadar adalah komunikasi efektif dalam kontek tertutup seperti bertingkah laku  dan menjaga image dalam berbicara dan berbeda pengalaman dengan santriwati yang tidak bercadar. Dengan sifat tertutup dari santriwati bercadar terhadap santriwati yang tidak bercadar, sehingga melahirkan komunikasi yang efektif dalam kontek tertutup

Scanning Electron Microscopic Study of Effect of Various Agents on Urinary Crystal Morphology

Crystals seen in human urinary stones namely whewellite, weddellite, brushite, octocalcium phosphate, apatite, struvite and newberyite were grown in vitro in silica gel medium. The crystal growth medium was reproduced with addition of known inhibitors of crystallisation namely tartaric acid and citric acid and urine samples of stone patients and normal controls. The size and shape of the crystals were studied in the original setup and on addition of various agents as observed under the scanning electron microscope (SEM). The SEM appearance of crystals was uniformly reproducible. Addition of known inhibitors produced alteration of crystal habit and stunting of growth. Urine of stone patients produced changes in crystal appearance. Normal urine samples produced reduction in size of crystals and altered shapes. It is surmised from the observations that normal urine contains inhibitors of crystallisation and these are absent in the urine of certain stone formers

Lage ciclosporinespiegel na kort rifampicinegebruik : immuunsuppressie kan langdurig tekortschieten

Cyclosporin is an immunosuppressive agent with a wide range of therapeutic uses. In transplant patients, it is used for the prevention of rejection and graft-versus-host reactions. The metabolism and bioavailability of cyclosporin can be significantly and persistently influenced through induction of CYP3A4 caused by the concomitant use of rifampicin. However, awareness of the need for the timely and frequent monitoring of cyclosporin levels during and especially after treatment with rifampicin has not fully been addressed. Here, we describe 3 patient cases concerning significant episodes of sub-therapeutic cyclosporin levels after short-term rifampicin therapy. Rifampicin was administered for three to five days and decreased cyclosporin levels were observed ± 7 days after the initiation of rifampicin, and continued during the following weeks even after the cessation of rifampicin therapy. Cyclosporin dosage-adjustments were made based on the cyclosporin blood levels and all 3 patients showed good therapeutic and clinical responses.Zelfs kortdurend gebruik van het antibioticum rifampicine kan de ciclosporineconcentratie in het bloed verlagen. Daarom moet de bloedspiegel van dit immunosuppressivum goed gemonitord worden bij patiënten die ook rifampicine krijgen, ook als de patiënt al gestopt is met het middel. Om afstoting van transplantaten of graft-versus-hostreacties te voorkómen, is het vaak nodig de ciclosporinedosering aan te passen

How phenotype and developmental stage affect the genes we find: GABRA2 and impulsivity

CONTEXT: The detection and replication of genes involved in psychiatric outcome has been notoriously difficult. Phenotypic measurement has been offered as one explanation, although most of this discussion has focused on problems with binary diagnoses. OBJECTIVE: This article focuses on two additional components of phenotypic measurement that deserve further consideration in evaluating genetic associations: (1) the measure used to reflect the outcome of interest, and (2) the developmental stage of the study population. We focus our discussion of these issues around the construct of impulsivity and externalizing disorders, and the association of these measures with a specific gene, GABRA2. DESIGN, SETTING, AND PARTICIPANTS: Data were analyzed from the Collaborative Study on the Genetics of Alcoholism Phase IV assessment of adolescents and young adults (ages 12–26; N = 2,128). MAIN OUTCOME MEASURES: Alcohol dependence, illicit drug dependence, childhood conduct disorder, and adult antisocial personality disorder symptoms were measured by psychiatric interview; Achenbach youth/adult self-report externalizing scale; Zuckerman Sensation-Seeking scale; Barratt Impulsivity scale; NEO extraversion and consciousness. RESULTS: GABRA2 was associated with subclinical levels of externalizing behavior as measured by the Achenbach in both the adolescent and young adult samples. Contrary to previous associations in adult samples, it was not associated with clinical-level DSM symptom counts of any externalizing disorders in these younger samples. There was also association with sensation-seeking and extraversion, but only in the adolescent sample. There was no association with the Barratt impulsivity scale or conscientiousness. CONCLUSIONS: Our results suggest that the pathway by which GABRA2 initially confers risk for eventual alcohol problems begins with a predisposition to sensation-seeking early in adolescence. The findings support the heterogeneous nature of impulsivity and demonstrate that both the measure used to assess a construct of interest and the age of the participants can have profound implications for the detection of genetic associations