Risk of infertility in female adolescents and young adults with cancer: a population-based cohort study.

STUDY QUESTION: Do female adolescents and young adults (AYAs) with cancer have a higher risk of subsequent infertility diagnosis than AYAs without cancer? SUMMARY ANSWER: Female AYAs with breast, hematological, thyroid and melanoma cancer have a higher risk of subsequent infertility diagnosis. WHAT IS KNOWN ALREADY: Cancer therapies have improved substantially, leading to dramatic increases in survival. As survival improves, there is an increasing emphasis on optimizing the quality of life among cancer survivors. Many cancer therapies increase the risk of infertility, but we lack population-based studies that quantify the risk of subsequent infertility diagnosis in female AYAs with non-gynecological cancers. The literature is limited to population-based studies comparing pregnancy or birth rates after cancer against unexposed women, or smaller studies using markers of the ovarian reserve as a proxy of infertility among female survivors of cancer. STUDY DESIGN, SIZE, DURATION: We conducted a population-based cohort study using universal health care databases in the province of Ontario, Canada. Using data from the Ontario Cancer Registry, we identified all women 15-39 years of age diagnosed with the most common cancers in AYAs (brain, breast, colorectal, leukemia, Hodgkin lymphoma, non-Hodgkin lymphoma, thyroid and melanoma) from 1992 to 2011 who lived at least 5 years recurrence-free (Exposed, n = 14,316). Women with a tubal ligation, bilateral oophorectomy or hysterectomy previous to their cancer diagnosis were excluded. We matched each exposed woman by age, census subdivision, and parity to five randomly selected unexposed women (n = 60,975) and followed subjects until 31 December 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Infertility diagnosis after 1 year of cancer was identified using information on physician billing codes through the Ontario Health Insurance Plan database (ICD-9 628). Modified Poisson regression models were used to assess the risk of infertility diagnosis (relative risk, RR) adjusted for income quintile and further stratified by parity at the time of cancer diagnosis (nulliparous and parous). MAIN RESULTS AND THE ROLE OF CHANCE: Mean age at cancer diagnosis was 31.4 years. Overall, the proportion of infertility diagnosis was higher in cancer survivors compared to unexposed women. Mean age of infertility diagnosis was similar among cancer survivors and unexposed women (34.8 years and 34.9 years, respectively). The overall risk of infertility diagnosis was higher in cancer survivors (RR 1.30; 95% CI 1.23-1.37). Differences in infertility risk varied by type of cancer. Survivors of breast cancer (RR 1.46; 95% CI 1.30-1.65), leukemia (RR 1.56; 95% CI 1.09-2.22), Hodgkin lymphoma (RR 1.49; 95% CI 1.28-1.74), non-Hodgkin lymphoma (RR 1.42; 95% CI 1.14, 1.76), thyroid cancer (RR 1.20; 95% CI 1.10-1.30) and melanoma (RR 1.17; 95% CI 1.01, 1.35) had a higher risk of infertility diagnosis compared to women without cancer. After stratification by parity, the association remained in nulliparous women survivors of breast cancer, leukemia, lymphoma and melanoma, whereas it was attenuated in parous women. In survivors of thyroid cancer, the association remained statistically significant in both nulliparous and parous women. In survivors of brain or colorectal cancer, the association was not significant, overall or after stratification by parity. LIMITATIONS, REASONS FOR CAUTION: Non-biological factors that may influence the likelihood of seeking a fertility assessment may not be captured in administrative databases. The effects of additional risk factors, including cancer treatment, which may modify the associations, need to be assessed in future studies. WIDER IMPLICATIONS OF THE FINDINGS: Reproductive health surveillance in female AYAs with cancer is a priority, especially those with breast cancer, leukemia and lymphoma. Our finding of a potential effects of thyroid cancer (subject to over-diagnosis) and, to a lesser extent, melanoma need to be further studied, and, if an effect is confirmed, possible mechanisms need to be elucidated. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the Faculty of Health Sciences and Department of Obstetrics and Gynecology, Queen's University. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Regioselective Synthesis of 1,2,3,4-Tetrasubstituted Arenes by Vicinal Functionalization of Arynes Derived from Aryl(Mes)iodonium Salts*.

Herein, the synthesis of 1,2,3,4-tetrasubstituted benzenoid rings, motifs found in pharmaceutical, agrochemical, and natural products, is described.[1] In the past, the regioselective syntheses of such compounds have been a significant challenge. This work reports a method using substituted arynes derived from aryl(Mes)iodonium salts to access a range of densely functionalized 1,2,3,4-tetrasubstituted benzenoid rings. Significantly, it was found that halide substituents are compatible under these conditions, enabling post-synthetic elaboration via palladium-catalyzed coupling. This concise strategy is predicated on two regioselective events: 1) ortho- deprotonation of aryl(Mes)iodonium salts to generate a substituted aryne intermediate, and 2) regioselective trapping of said arynes, thereby improving previously reported reaction conditions to generate arynes at room temperature and in shorter reaction times. Density functional theory (DFT) computations and linear free energy relationship (LFER) analysis suggest the regioselectivity of deprotonation is influenced by both proximal and distal ring substituents on the aryne precursor. A competition experiment further reveals the role of arene substituents on relative reactivity of aryl(Mes)iodoniums as aryne precursors.

Tuning Supramolecular Selectivity for Hydrosulfide: Linear Free Energy Relationships Reveal Preferential C-H Hydrogen Bond Interactions.

Supramolecular anion receptors can be used to study the molecular recognition properties of the reactive yet biologically critical hydrochalcogenide anions (HCh-). Achieving selectivity for HCh- over the halides is challenging but necessary for not only developing future supramolecular probes for HCh- binding and detection, but also for understanding the fundamental properties that govern these binding and recognition events. Here we demonstrate that linear free energy relationships (LFERs)-including Hammett and Swain-Lupton plots-reveal a clear difference in sensitivity to the polarity of an aryl C-H hydrogen bond (HB) donor for HS- over other HCh- and halides. Analysis using electrostatic potential maps highlights that this difference in sensitivity results from a preference of the aryl C-H HB donor for HS- in this host scaffold. From this study, we demonstrate that LFERs are a powerful tool to gain interpretative insight into motif design for future anion-selective supramolecular receptors and highlight the importance of C-H HB donors for HS- recognition. From our results, we suggest that aryl C-H HB donors should be investigated in the next generation of HS- selective receptors based on the enhanced HS- selectivity over other competing anions in this system.

Viscous placebo and carbohydrate breakfasts similarly decrease appetite and increase resistance exercise performance compared with a control breakfast in trained males.

Given the common view that pre-exercise nutrition/breakfast is important for performance, the present study investigated whether breakfast influences resistance exercise performance via a physiological or psychological effect. Twenty-two resistance-trained, breakfast-consuming men completed three experimental trials, consuming water-only (WAT), or semi-solid breakfasts containing 0 g/kg (PLA) or 1·5 g/kg (CHO) maltodextrin. PLA and CHO meals contained xanthan gum and low-energy flavouring (approximately 122 kJ), and subjects were told both 'contained energy'. At 2 h post-meal, subjects completed four sets of back squat and bench press to failure at 90 % ten repetition maximum. Blood samples were taken pre-meal, 45 min and 105 min post-meal to measure serum/plasma glucose, insulin, ghrelin, glucagon-like peptide-1 and peptide tyrosine-tyrosine concentrations. Subjective hunger/fullness was also measured. Total back squat repetitions were greater in CHO (44 (sd 10) repetitions) and PLA (43 (sd 10) repetitions) than WAT (38 (sd 10) repetitions; P < 0·001). Total bench press repetitions were similar between trials (WAT 37 (sd 7) repetitions; CHO 39 (sd 7) repetitions; PLA 38 (sd 7) repetitions; P = 0·130). Performance was similar between CHO and PLA trials. Hunger was suppressed and fullness increased similarly in PLA and CHO, relative to WAT (P < 0·001). During CHO, plasma glucose was elevated at 45 min (P < 0·05), whilst serum insulin was elevated (P < 0·05) and plasma ghrelin suppressed at 45 and 105 min (P < 0·05). These results suggest that breakfast/pre-exercise nutrition enhances resistance exercise performance via a psychological effect, although a potential mediating role of hunger cannot be discounted.

Enantioselective Synthesis of α-Amidoboronates Catalyzed by Planar-Chiral NHC-Cu(I) Complexes.

The first highly selective catalytic hydroboration of alkyl-substituted aldimines to provide medicinally relevant α-amidoboronates is disclosed. The Cu(I)-catalyzed borylation proceeds with excellent facial selectivity when a set of planar-chiral N-heterocyclic carbenes (NHCs) were employed as ligands. Density functional theory computations suggest that interactions between BPin and the planar-chiral catalyst are responsible for the observed stereoselectivity. Important pharmacophores, such as the boronate analogue of isoleucine, can be prepared using a chromatography-free protocol starting from commercially available reagents. The application of these NHC ligands in these Cu(I)-catalyzed processes offers a significant contribution to existing strategies for laboratory-scale preparation of enantioenriched α-amidoboronates.

Contribution of central and peripheral risk factors to prevalence, incidence and progression of knee pain: a community-based cohort study.

AIM: To explore risk factors that may influence knee pain (KP) through central or peripheral mechanisms. METHODS: A questionnaire-based prospective community cohort study with KP defined as pain in or around a knee on most days for at least a month. Baseline prevalence, and one year incidence and progression (KP worsening) were examined. Central (e.g., Pain Catastrophizing Scale (PCS)) and peripheral (e.g., significant injury) risk factors were examined. Adjusted odds ratio (OR) and 95% confidence interval (CI) were calculated using logistic regression. Proportional risk contribution (PRC) was estimated using receiver-operator-characteristic (ROC) analysis. RESULTS: Of 9506 baseline participants, 4288 (45%) had KP (men 1826; women, 2462). KP incidence was 12% (men 11%, women 13%), and KP progression 19% (men 16%, women 21%) at one year. While both central and peripheral factors contributed to prevalence, central factors contributed more to progression, and peripheral factors more to incidence of KP. For example, although PCS (OR 2.06, 95% CI 1.88-2.25) and injury (5.62, 4.92-6.42) associated with KP prevalence, PCS associated with progression (2.27, 1.83-2.83) but not incidence (1.14, 0.86-1.52), whereas injury more strongly associated with incidence (69.27, 24.15-198.7) than progression (2.52, 1.48-4.30). The PRC of central and peripheral factors were 19% and 23% for prevalence, 14% and 29% for incidence, and 29% and 5% for progression, respectively. CONCLUSIONS: Both central and peripheral risk factors influence KP but relative contributions may differ in terms of development (mainly peripheral) and progression (mainly central). Further study of such relative contributions may inform primary and secondary prevention strategies.

A C=O⋠⋠⋠Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols.

A combination of experimental and computational studies have identified a C=O⋅⋅⋅isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s factors up to >200). The reaction proceeds at low catalyst loadings (generally 1 mol %) with either isobutyric or acetic anhydride as the acylating agent under mild conditions.

Knee pain and related health in the community study (KPIC): a cohort study protocol.

BACKGROUND: The incidence, progression and related risk factors for recent-onset knee pain (KP) remain uncertain. This study aims to examine the natural history of KP including incidence and progression and to identify possible phenotypes and their associated risk factors. METHODS: A prospective community-based cohort of men and women aged 40 years or over within the East Midlands region (UK) will be recruited via a postal questionnaire from their general practices. The questionnaire will enquire about: presence and onset of KP; pain severity (0­10 numerical rating scale (NRS)); pain catastrophizing and neuropathic-like pain (NP) using the painDETECT questionnaires (definite NP scores ≥19­38); risk factors for KP and/ or osteoarthritis (OA) (age, body mass index, constitutional knee alignment, nodal OA, index: ring finger length (2D4D) ratio); quality of life (SF12); and mental health (Hospital Anxiety and Depression Scale). Clinical assessments will be undertaken in a sample of 400 participants comprising three groups: early KP (≤3 year's duration), established KP (>3 years) and no KP. Assessments will include knee radiographs (standing semi-flexed and 30(0) skyline views); knee ultrasound (synovial effusion, hypertrophy, and Doppler activity); quantitative sensory testing; muscle strength (quadriceps, hip abductor, and hand-grip); balance; gait analysis (GAITrite); and biomarker sampling. A repeat questionnaire will be sent to responders at years 1 and 3. The baseline early KP group will undergo repeat assessments at year 1 (apart from radiographs) and year 3 (with radiographs). Any incident KP individuals identified at year 1 or 3 questionnaires will have clinical and radiographic assessments at the respective time points. DISCUSSION: Baseline data will be used to examine risk factors for early onset KP and to identify KP phenotypes. Subsequent prospective data, at least to Year 3, will allow examination of the natural history of KP and risk factors for incidence and progression. TRIAL REGISTRATION: The study was registered on the clinicaltrials.gov portal: NCT02098070) on the 14th of March 2014.

Evaluation of self-swabbing coupled with a telephone health helpline as an adjunct tool for surveillance of influenza viruses in Ontario.

BACKGROUND: Calls to a telephone health helpline (THHL) have been previously evaluated for the ability to monitor specific syndromes, such as fever and influenza-like-illness or gastrointestinal illness. This method of surveillance has been shown to be highly correlated with traditional surveillance methods, and to have potential for early detection of community-based illness. Self-sampling, or having a person take his/her own nasal swab, has also proven successful as a useful method for obtaining a specimen, which may be used for respiratory virus detection. METHODS: This study describes a self-swabbing surveillance system mediated by a nurse-led THHL in Ontario whereby syndromic surveillance concepts are used to recruit and monitor participants with influenza-like illness. Once recruited, participants collect a nasal specimen obtained by self-swabbing and submit for testing and laboratory confirmation. Enumeration of weekly case counts was used to evaluate the timeliness of the self-swabbing surveillance system through comparison to other respiratory virus and influenza surveillance systems in Ontario. The operational efficiency of the system was also evaluated. RESULTS: The mean and median number of days between the day that a participant called the THHL, to the day a package was received at the laboratory for testing were approximately 10.4 and 8.6 days, respectively. The time between self-swab collection and package reception was 4.9 days on average, with a median of 4 days. The self-swabbing surveillance system adequately captured the 2014 influenza B season in a timely manner when compared to other Ontario-based sources of influenza surveillance data from the same year; however, the emergence of influenza B was not detected any earlier than with these other surveillance systems. Influenza A surveillance was also evaluated. Using the THHL self-swabbing system, a peak in the number of cases for influenza A was observed approximately one week after or during the same week as that reported by the other surveillance systems. CONCLUSION: This one-year pilot study suggests that the THHL self-swabbing surveillance system has significant potential as an adjunct tool for the surveillance of influenza viruses in Ontario. Recommendations for improving system efficacy are discussed.

Increased visual gamma power in schizoaffective bipolar disorder.

BACKGROUND: Electroencephalography and magnetoencephalography (MEG) studies have identified alterations in gamma-band (30-80 Hz) cortical activity in schizophrenia and mood disorders, consistent with neural models of disturbed glutamate (and GABA) neuron influence over cortical pyramidal cells. Genetic evidence suggests specific deficits in GABA-A receptor function in schizoaffective bipolar disorder (SABP), a clinical syndrome with features of both bipolar disorder and schizophrenia. This study investigated gamma oscillations in this under-researched disorder. METHOD: MEG was used to measure induced gamma and evoked responses to a visual grating stimulus, known to be a potent inducer of primary visual gamma oscillations, in 15 individuals with remitted SABP, defined using Research Diagnostic Criteria, and 22 age- and sex-matched healthy controls. RESULTS: Individuals with SABP demonstrated increased sustained visual cortical power in the gamma band (t 35 = -2.56, p = 0.015) compared to controls. There were no group differences in baseline gamma power, transient or sustained gamma frequency, alpha band responses or pattern onset visual-evoked responses. CONCLUSIONS: Gamma power is increased in remitted SABP, which reflects an abnormality in the cortical inhibitory-excitatory balance. Although an interaction between gamma power and medication can not be ruled out, there were no group differences in evoked responses or baseline measures. Further work is needed in other clinical populations and at-risk relatives. Pharmaco-magnetoencephalography studies will help to elucidate the specific GABA and glutamate pathways affected.

Neural correlates of theory of mind reasoning in congenitally blind children.

Vision is an important source of information about other minds for sighted children, especially prior to the onset of language. Visually observed actions, eye gaze, and facial expressions of others provide information about mental states, such as beliefs, desires, and emotions. Does such experience contribute causally to the development of cortical networks supporting social cognition? To address this question we compared functional development of brain regions supporting theory of mind (ToM), as well as behavioral ToM reasoning, across congenitally blind (n=17) and sighted (n=114) children and adolescents (4-17 years old). We find that blind children in this age range show slightly lower ToM behavioral performance relative to sighted children. Likewise, the functional profile of ToM brain regions is qualitatively similar, but quantitatively weaker in blind relative to sighted children. Alongside prior research, these data suggest that vision facilitates, but is not necessary for, ToM development.

A randomized, placebo-controlled trial (NCIC CTG MAP.2) examining the effects of exemestane on mammographic breast density, bone density, markers of bone metabolism and serum lipid levels in postmenopausal women.

We hypothesized that exemestane (EXE) would reduce mammographic breast density and have unique effects on biomarkers of bone and lipid metabolism. Healthy postmenopausal women were randomized to EXE (25 mg daily) or placebo (PLAC) for 12 months and followed for a total of 24 months. The primary endpoint was change in percent breast density (PD) between the baseline and 12-month mammograms and secondary endpoints were changes in serum lipid levels, bone biomarkers, and bone mineral density (BMD). Ninety-eight women were randomized (49 to EXE; 49 to PLAC) and 65 had PD data at baseline and 12 months. Among women treated with EXE, PD was not significantly changed from baseline at 6, 12, or 24 months and was not different from PLAC. EXE was associated with significant percentage increase from baseline in N-telopeptide at 12 months compared with PLAC. No differences in percent change from baseline in BMD (lumbar spine and femoral neck) were observed between EXE and PLAC at either 12 or 24 months. Patients on EXE had a significantly larger percent decrease in total cholesterol than in the PLAC arm at 6 months and in HDL cholesterol at 3, 6, and 12 months. No significant differences in percent change in LDL or triglycerides were noted at any time point between the two treatment arms. EXE administered for 1 year to healthy postmenopausal women did not result in significant changes in mammographic density. A reversible increase in the bone resorption marker N-telopeptide without significant change in bone specific alkaline phosphatase or BMD during the 12 months treatment period and 1 year later was noted. Changes in lipid parameters on this trial were modest and reversible.

Preferential responses to faces in superior temporal and medial prefrontal cortex in three-year-old children.

Perceiving faces and understanding emotions are key components of human social cognition. Prior research with adults and infants suggests that these social cognitive functions are supported by superior temporal cortex (STC) and medial prefrontal cortex (MPFC). We used functional near-infrared spectroscopy (fNIRS) to characterize functional responses in these cortical regions to faces in early childhood. Three-year-old children (n = 88, M(SD) = 3.15(.16) years) passively viewed faces that varied in emotional content and valence (happy, angry, fearful, neutral) and, for fearful and angry faces, intensity (100%, 40%), while undergoing fNIRS. Bilateral STC and MPFC showed greater oxygenated hemoglobin concentration values to all faces relative to objects. MPFC additionally responded preferentially to happy faces relative to neutral faces. We did not detect preferential responses to angry or fearful faces, or overall differences in response magnitude by emotional valence (100% happy vs. fearful and angry) or intensity (100% vs. 40% fearful and angry). In exploratory analyses, preferential responses to faces in MPFC were not robustly correlated with performance on tasks of early social cognition. These results link and extend adult and infant research on functional responses to faces in STC and MPFC and contribute to the characterization of the neural correlates of early social cognition.

A randomized, placebo-controlled trial (NCIC CTG MAP1) examining the effects of letrozole on mammographic breast density and other end organs in postmenopausal women.

Mammographically detected breast density has been correlated with breast cancer risk. Breast density appears to be influenced by hormonal factors including increasing age, postmenopausal status, number of pregnancies, lower body weight, hormone replacement therapy, and tamoxifen therapy. The aromatase inhibitor letrozole profoundly reduces breast and circulating estrogen levels in postmenopausal women. We hypothesize that letrozole may reduce breast density and report here on its effects on mammographic breast density, bone mineral density (BMD), bone biomarkers, plasma hormone, and serum lipid levels. MAP1 was a multicenter, randomized, double-blind, placebo-controlled, feasibility trial in which postmenopausal women with or without prior invasive breast cancer were randomized in a 2:1 ratio of letrozole (2.5 mg daily) or placebo for 12 months and followed for a total of 24 months. Eligible women had an estimated >25% breast density on baseline mammogram. The primary endpoint was change in percent breast density (PD) between the baseline and 12-month mammograms as estimated by a computer-assisted thresholding program. Baseline and 12-month mammographic density was also assessed in a blinded manner by visual inspection. Secondary endpoints included changes in serum hormones, plasma lipid levels, bone biomarkers, and BMD. Data are available for 67 women (44 on letrozole and 23 on placebo). No significant changes in PD were noted between the treatment arms at either 12 or 24 months. No distinguishable difference in density measurements by visual inspection were noted between baseline and 12-month mammograms. A significant decrease in percentage change in T-score of the femoral neck at 12 months was noted in the letrozole arm without other significant changes in BMD parameters. Lipid values did not differ between treatment groups except for a borderline significant decrease in total cholesterol at 3 months among women treated with letrozole. Letrozole therapy was associated with a significant reduction in mean serum estradiol, estrone, and estrone sulfate levels at 12 months, but not at 24 months. A significant increase in serum IGF-1 levels was also noted in the letrozole group compared to the placebo group at both 12 and 24 months. To conclude, compared with placebo, 12 months of letrozole therapy does not appear to have a significant effect on mammographic PD. Twelve months of letrozole was associated with a decrease of uncertain clinical significance in the T-score of the femoral neck at 12 months which was reversible at 24 months with recovery of estrogen levels. Letrozole therapy was found to increase IGF-1 levels at 12 and 24 months.

Debcl, a proapoptotic Bcl-2 homologue, is a component of the Drosophila melanogaster cell death machinery.

Bcl-2 family of proteins are key regulators of apoptosis. Both proapoptotic and antiapoptotic members of this family are found in mammalian cells, but no such proteins have been described in insects. Here, we report the identification and characterization of Debcl, the first Bcl-2 homologue in Drosophila melanogaster. Structurally, Debcl is similar to Bax-like proapoptotic Bcl-2 family members. Ectopic expression of Debcl in cultured cells and in transgenic flies causes apoptosis, which is inhibited by coexpression of the baculovirus caspase inhibitor P35, indicating that Debcl is a proapoptotic protein that functions in a caspase-dependent manner. debcl expression correlates with developmental cell death in specific Drosophila tissues. We also show that debcl genetically interacts with diap1 and dark, and that debcl-mediated apoptosis is not affected by gene dosage of rpr, hid, and grim. Biochemically, Debcl can interact with several mammalian and viral prosurvival Bcl-2 family members, but not with the proapoptotic members, suggesting that it may regulate apoptosis by antagonizing prosurvival Bcl-2 proteins. RNA interference studies indicate that Debcl is required for developmental apoptosis in Drosophila embryos. These results suggest that the main components of the mammalian apoptosis machinery are conserved in insects.

Free-radical oxidants in natural waters.

Photooxidation of cumene (isopropylbenzene) and pyridine in dilute solution in natural waters gives products characteristic of reactions with alkylperoxy (RO(2).) and hydroxyl (HO.) radicals. On the basis of the rates of formation of the products, the average concentrations of RO(2). and HO. are estimated to be about 10(-9) and 10(-17) mole per liter, respectively. The concentration of RO(2). is large enough that, for some classes of reactive chemicals, oxidation can be an important process in natural waters.

Fourier-transformed infrared photoacoustic spectroscopy of biological materials.

A new technique for measuring the infrared spectra of solids has been developed. The photoacoustic spectra of hemin, hemoglobin, protoporphyrin IX, and horseradish peroxidase show how this technique can be used to obtain structural information about biological materials which cannot readily be studied by normal transmission infrared spectroscopy. The method requires milligram quantities of material and involves no sample preparation.

Apollo 11 Laser Ranging Retro-Reflector: Initial Measurements from the McDonald Observatory.

Acquisition measurements of the round-trip travel time of light, from the McDonald Observatory to the Laser Ranging Retro-Reflector deployed on the moon by the Apollo 11 astronauts, were made on 20 August and on 3, 4, and 22 September 1969. The uncertainty in the round-trip travel time was +/- 15 nanoseconds, with the pulsed ruby laser and timing system used for the acquisition. The uncertainty in later measurements of a planned long-term sequence from this observatory is expected to be an order of magnitude smaller. The successful performance of the retro-reflector at several angles of solar illumination, as well as during and after a lunar night, confirms the prediction of thermal design analyses.

Dependence-induced alcohol drinking by alcohol-preferring (P) rats and outbred Wistar rats.

BACKGROUND: Chronic intermittent alcohol vapor exposure and selective breeding procedures have been used separately for many years to model specific aspects of alcohol dependence. The purpose of the present investigation was to combine these 2 approaches by exposing alcohol-preferring (P) rats to chronic intermittent alcohol vapor for extended periods of time and then testing them for operant alcohol responding in parallel with a group of outbred Wistar rats at multiple time points following the termination of vapor exposure. METHODS: P rats (n = 20) and Wistar rats (n = 18) were trained to respond for 10% (w/v) ethanol in an operant situation, then divided into groups matched for intake levels. Animals were then exposed to chronic intermittent alcohol vapor (14 hours ON/10 hours OFF) or air for 8 weeks. Rats were then tested for operant alcohol responding under various conditions and at multiple time points during alcohol withdrawal (6 hours) and protracted abstinence (1 to 15 days). RESULTS: Chronic alcohol vapor exposure produced similar increases in operant alcohol responding in P rats and Wistar rats during acute withdrawal and protracted abstinence. CONCLUSIONS: These results illustrate the separate and combined effects of genetic selection for high alcohol preference and dependence on alcohol drinking behavior. Furthermore, these results confirm past findings that dependent rats consume more alcohol than nondependent controls well into abstinence following extended periods of alcohol vapor exposure.