Conjunctival melanoma copy number alterations and correlation with mutation status, tumor features, and clinical outcome.

Relatively little is known about the genetic aberrations of conjunctival melanomas (CoM) and their correlation with clinical and histomorphological features as well as prognosis. The aim of this large collaborative multicenter study was to determine potential key biomarkers for metastatic risk and any druggable targets for high metastatic risk CoM. Using Affymetrix single nucleotide polymorphism genotyping arrays on 59 CoM, we detected frequent amplifications on chromosome (chr) 6p and deletions on 7q, and characterized mutation-specific copy number alterations.

Early Adolescent Trajectories of Impulsiveness and Sensation Seeking in Children of Fathers with Histories of Alcohol and Other Substance Use Disorders.

Background: Problem substance use often begins in adolescence. This vulnerability likely stems, at least partially, from relatively rapid increases in sensation seeking occurring in early to mid-adolescence and more gradual improvements in impulse control occurring through later adolescence. Better understanding how these processes develop in high-risk youth may lead to enhanced substance use disorder treatment and prevention strategies.

Pubertal Maturation Compression and Behavioral Impulsivity among Boys at Increased Risk for Substance Use.

Objectives: While early onset of puberty among girls has been related to substance use involvement and other adverse outcomes, less research has examined pubertal development and outcomes in boys. Further, research on puberty has not been conducted in the context of other risk factors for substance use involvement such as impulsivity. To address these gaps, this study characterized boys' pubertal development from preadolescence to mid-adolescence and related it to substance use risk and behavioral impulsivity.

Family Functioning as a Mediator of Relations between Family History of Substance Use Disorder and Impulsivity.

Unlabelled: Impulsivity is strongly related to the development of adolescent substance use. Therefore, understanding factors that influence impulsive characteristics is important for the development of prevention and intervention programs. Intervention and prevention programs focused on factors that influence impulsive characteristics are especially important for those at particularly high risk for the expression of impulsivity - those with a family history of substance use disorder.

Clinical and Social/Environmental Characteristics in a Community Sample of Children With and Without Family Histories of Substance Use Disorder in the San Antonio Area: A Descriptive Study.

This is a descriptive study of the recruitment and clinical/environmental characteristics of a child cohort (ages 10-12) established to test transmission of impulsivity in children with (FH+; n = 305) and without (FH-; n = 81) family history of substance use disorder. Among this cohort FH children had more emotional and behavioral symptoms, worse family relationships, and more deviant peers compared to FH children. This cohort of children was established prior to the initiation of regular substance use and significant clinical problems, which will allow the opportunity to examine reciprocal relations between development of impulse control and substance use development.

Insights into genetic alterations of liver metastases from uveal melanoma.

The liver is the organ usually affected by metastatic uveal melanoma (MUM). Current treatments are almost always ineffective and mortality remains high. In this study, copy number variations (CNVs) were identified in 12 metastatic and five matched primary UMs (PUMs).

The Potential Clinical Utility of Transdermal Alcohol Monitoring Data to Estimate the Number of Alcoholic Drinks Consumed.

Objectives: Transdermal alcohol monitoring is used extensively in forensic settings to identify whether individuals have violated court-ordered mandates to abstain from drinking. Despite widespread use in that setting, comparatively few studies have explored the clinical utility of transdermal alcohol monitoring. Furthermore, of the few studies conducted, most have relied on the forensically established conservative criteria to identify whether or not a drinking episode has occurred.

Behavioral Impulsivity and Risk-Taking Trajectories Across Early Adolescence in Youths With and Without Family Histories of Alcohol and Other Drug Use Disorders.

Background: Youths with family histories of alcohol and other drug use disorders (FH+) are at increased susceptibility for developing substance use disorders relative to those without such histories (FH-). This vulnerability may be related to impaired adolescent development of impulse control and elevated risk-taking. However, no previous studies have prospectively examined impulse control and risk-taking in FH+ youth across adolescence.

Using contingency management procedures to reduce at-risk drinking in heavy drinkers.

Background: Treatments for alcohol use disorders typically have been abstinence based, but harm reduction approaches that encourage drinkers to alter their drinking behavior to reduce the probability of alcohol-related consequences, have gained in popularity. This study used a contingency management procedure to determine its effectiveness in reducing alcohol consumption among heavy drinkers.

Methods: Eighty-two nontreatment-seeking heavy drinkers (ages 21 to 54, M = 30.

Increased Pre- and Early-Adolescent Stress in Youth with a Family History of Substance Use Disorder and Early Substance Use Initiation.

Individuals with a family history of substance use disorders (Family History Positive) are more likely to have early-onset substance use (i.e., prior to age 15), which may contribute to their higher rates of substance use disorders.

Assessing the Validity of Participant-Derived Compared to Staff-Derived Values to Compute a Binge Score.

Aims: This study examined the validity of two methods of classifying binge drinkers.

Methods: Adult drinkers (n = 166) completed the Alcohol Use Questionnaire (AUQ) and a Timeline Followback (TLFB) interview to characterize drinking during the past 28 days. Using Townshend and Duka's (2005) recommendations, answers on three AUQ items (average drinks per hour, number of times drunk within the prior 6 months and percentage of times drunk when drinking) were used to derive a binge score that was then used to classify drinkers as Binge, Non-Binge and Unclassifiable.

Effects of tryptophan depletion and a simulated alcohol binge on impulsivity.

Researchers have suggested binge drinkers experience disproportionate increases in impulsivity during the initial period of drinking, leading to a loss of control over further drinking, and that serotonergic mechanisms may underlie such effects. We examined the effects of a simulated alcohol binge and tryptophan depletion on 3 types of impulsivity-response initiation (immediate memory task [IMT]), response inhibition (GoStop task), and delay discounting (single key impulsivity paradigm [SKIP])-and tested whether observed effects were related to real-world binging. Adults (N = 179) with diverse drinking histories completed a within-subject crossover design over 4 experimental days.

Transdermal alcohol concentration data collected during a contingency management program to reduce at-risk drinking.

Background: Recently, we demonstrated that transdermal alcohol monitors could be used in a contingency management procedure to reduce problematic drinking; the frequency of self-reported heavy/moderate drinking days decreased and days of no to low drinking increased. These effects persisted for three months after intervention. In the current report, we used the transdermal alcohol concentration (TAC) data collected prior to and during the contingency management procedure to provide a detailed characterization of objectively measured alcohol use.

Mechanisms of the pellagragenic effect of leucine: stimulation of hepatic tryptophan oxidation by administration of branched-chain amino acids to healthy human volunteers and the role of plasma free tryptophan and total kynurenines.

The pellagragenic effect of leucine (Leu) has been proposed to involve modulation of L-tryptophan (Trp) metabolism along the hepatic kynurenine pathway. Here, we discuss some of the mechanisms suggested and report the effects in healthy volunteers of single doses of Leu (4.05-6.

Do variable rates of alcohol drinking alter the ability to use transdermal alcohol monitors to estimate peak breath alcohol and total number of drinks?

Background: Transdermal alcohol monitoring is a noninvasive method that continuously gathers transdermal alcohol concentrations (TAC) in real time; thus, its use is becoming increasingly more common in alcohol research. In previous studies, we developed models that use TAC data to estimate peak breath alcohol concentration (BrAC) and standard units consumed when the rate of consumption was tightly controlled.

Methods: Twenty-two healthy participants aged 21 to 52 who reported consuming alcohol on 1 to 4 days per week were recruited from the community.

Mutations in g protein encoding genes and chromosomal alterations in primary leptomeningeal melanocytic neoplasms.

Limited data is available on the genetic features of primary leptomeningeal melanocytic neoplasms (LMNs). Similarities with uveal melanoma were recently suggested as both entities harbor oncogenic mutations in GNAQ and GNA11. Whether primary LMNs share additional genetic alterations with uveal melanoma including copy number variations is unknown.

Use of continuous transdermal alcohol monitoring during a contingency management procedure to reduce excessive alcohol use.

Background: Research on contingency management to treat excessive alcohol use is limited due to feasibility issues with monitoring adherence. This study examined the effectiveness of using transdermal alcohol monitoring as a continuous measure of alcohol use to implement financial contingencies to reduce heavy drinking.

Methods: Twenty-six male and female drinkers (from 21 to 39 years old) were recruited from the community.

Transcriptome analysis of a parasitic clade V nematode: comparative analysis of potential molecular anthelmintic targets in Cylicostephanus goldi.

Clade V nematodes comprise several parasitic species that include the cyathostomins, primary helminth pathogens of horses. Next generation transcriptome datasets are available for eight parasitic clade V nematodes, although no equine parasites are included in this group. Here, we report next generation transcriptome sequencing analysis for the common cyathostomin species, Cylicostephanus goldi.

Static and dynamic approaches yield similar estimates of the thermal sensitivity of insect metabolism.

Thermal sensitivity of metabolism (estimated by the temperature coefficient, Q10) is important for understanding ectotherm responses to temperature, but can only be measured empirically. Several strategies can be used to estimate thermal sensitivity. Static temperature respirometry uses measurements of metabolic rate taken at a series of temperatures, either by using different individuals at each temperature (independent STR, iSTR), or the same individual at several different temperatures (repeated STR, rSTR).

Pharmacotherapy of impulsive aggression: a quality comparison of controlled studies.

The present study assessed the quality of pharmacotherapy trials to treat impulsive aggressive behavior. While a search of the literature found 55 peer-reviewed published studies on the pharmacotherapy of aggression, only 23 met criteria for inclusion in the quality analysis. To be included in this review, the study must have had at least one comparison group to control for placebo effects.

Single nucleotide polymorphism array analysis of uveal melanomas reveals that amplification of CNKSR3 is correlated with improved patient survival.

Metastatic death from uveal melanoma occurs almost exclusively with tumors showing monosomy of chromosome 3. However, approximately 5% of patients with a disomy 3 uveal melanoma develop metastases, and a further 5% of monosomy 3 uveal melanoma patients exhibit disease-free survival for >5 years. In the present study, whole-genome microarrays were used to interrogate four clinically well-defined subgroups of uveal melanoma: i) disomy 3 uveal melanoma with long-term survival; ii) metastasizing monosomy 3 uveal melanoma; iii) metastasizing disomy 3 uveal melanoma; and iv) monosomy 3 uveal melanoma with long-term survival.

Comparison of formalin-fixed and snap-frozen samples analyzed by multiplex ligation-dependent probe amplification for prognostic testing in uveal melanoma.

Purpose: Survival of patients with uveal melanoma (UM) correlates strongly with chromosomal abnormalities, such as monosomy 3 and polysomy 8q. Studies have shown multiplex ligation-dependent probe amplification (MLPA) to detect reliably chromosomal aberrations in UM using frozen samples. To date, the concordance between MLPA data generated from frozen and fixed samples has not been investigated.