Early Developmental Processes and the Continuity of Risk for Underage Drinking and Problem Drinking

Developmental pathways to underage drinking emerge before the second decade of life. Many scientists, however, as well as the general public, continue to focus on proximal influences surrounding the initiation of drinking in adolescence, such as social, behavioral, and genetic variables related to availability and ease of acquisition of the drug, social reinforcement for its use, and individual differences in drug responses. In the past 20 years, a considerable body of evidence has accumulated on the early (often much earlier than the time of the first drink) predictors and pathways of youthful alcohol use and abuse. These early developmental influences involve numerous risk, vulnerability, promotive, and protective processes. Some of these factors are not related directly to alcohol use, whereas others involve learning and expectancies about later drug use that are shaped by social experience. The salience of these factors (identifiable in early childhood) for understanding the course and development of adult alcohol and other drug use disorders is evident from the large and growing body of findings on their ability to predict adult clinical outcomes. This review summarizes the evidence on early pathways toward and away from underage drinking, with a particular focus on the risk and protective factors and the mediators and moderators of risk for underage drinking that become evident during the preschool and early school years. It is guided by a developmental perspective on the aggregation of risk and protection and examines the contributions of biological, psychological, and social processes within the context of normal development.Implications of this evidence for policy, intervention, and future research are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65125/1/UM 33 Zucker2008_EarlyDevelopmentalProc.Pediatrics_InPress_.pd

Cultural Resources Investigations Along Whiteoak Bayou, Harris County, Texas

In 1986, cultural resources investigations were carried out to prepare a synthesis of the archeology of the Whiteoak Bayou area in western Harris County, Texas, and to conduct subsurface testing at prehistoric sites that may be affected by the U.S. Army Corps of Engineers Upper Whiteoak Bayou Flood Damage Reduction Project. The tasks undertaken during these investigations are: (1) background research into the environment and archeology of the area; (2) historic/archival research and reconnaissance survey to summarize the historical development of Whiteoak Bayou and to identify any important sites in the project area; (3) intensive survey of Vogel Creek, a tributary to Whiteoak Bayou, to assess the potential for intact cultural remains; (4) National Register testing and assessment of nine aboriginal sites; (5) geoarcheological investigations to establish the geological context of the archeological remains, to identify the depositional environments represented, and to establish an alluvial sequence for the project area; and (6) analysis of a large collection of artifacts from 46 Whiteoak Bayou sites made prior to 1986 by members of the Houston Archeological Society, as well as the materials recovered during 1986. The nine archeological sites tesLed during this project are 41HR241, 4lHR259, 41HR273, 41HR278, 41HR279, 41HR283, 41HR290, 41HR298, and 41HR541. The testing showed that only three -- 41HR259, 41HR273, and 41HR541 -- have substantial, intact cultural deposits. Two of these -- 41HR273 and 41HR541 -- are judged to be eligible for listing on the National Register of Historic Places and for designation as State Archeological Landmarks. One site, 4lHR259, is currently listed on the National Register, although the remaining part of this site is judged to have a limited potential to yield additi0nal information. The other seven sites are judged to be ineligible for listing

Hormonal Contraception and Metabolic Outcomes in Women With or at Risk for HIV Infection

The use of hormonal contraception (HC) is increasing in HIV-infected women. Both HC and HIV infection have been associated with adverse metabolic outcomes. We investigated the association of progestin-only and combined (estrogen/progestin) HC with disorders of glucose and lipid metabolism in HIV-infected and uninfected women

The Lantern Vol. 34, No. 2, May 1968

• The Man Without a System • A Medal for Malcolm • On Hearing That Tonya Will Be Married • The Black Sea • Odyssey \u2767 • Second Poem to Chris • Singularity • Period 5-A Began • Long and Aching Ride • Souvenirs • My Eschatological Epitaph • Discotheque • Some Borrowed Words • False Breakthrough • Shore Morning • The Beholder • Thursday Childless • A Most Prominent Role • It Ran Out • Shades of the Living • The Dark Night of the Mind II • One Step Beyond the Doors • A Note of Thanks to My Parents and Teachers • To a Dead Hippie • A Scrap • Love • Haiku No. 30 • Rachel • There Is No Present • Winter Woods • One Hundred Per Cent Genuine • Heaven • Silence Is Like God • I Soaked Up Silence • Opened Letter From Whistler Homer, Insaned Assailant • Sol Clutch Rides Tonight • I Have Seen Destruction • Upon That Night • That\u27s Weird • Alone • Kathy\u27s Tune • On Walking Home • The Wheel • Some Excuse, at Least • Freedom to Flap • Awareness • Okay, You Guys • You Say You Dream • Bacci Miahttps://digitalcommons.ursinus.edu/lantern/1093/thumbnail.jp

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P &lt; 0.001) and PARP inhibitor therapy (P &lt; 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P &lt; 0.018) and WEE1 inhibitor (P &lt; 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P &lt; 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy