AN EXAMINATION OF DEVELOPMENTAL AND SEX DIFFERENCES IN ETHANOL CONSUMPTION BY LOW ALCOHOL-CONSUMING RAT LINES

poster abstractIn the United States, alcohol use and dependence is a major health issue affecting 4-5% of the population (Hasin et al., 2007). Research indicates ad-olescents ages 12-20 drink 11% of all alcohol consumed nationally, with more than 90% consumed in the form of binge drinking (Center for Disease Control and Prevention, 2010). Similar to the human condition, adolescent rodents generally consume more ethanol than their adult counterparts. Current rat animal model studies on alcoholism remain weighted toward examining Family History Positive (FHP), selectively bred, alcohol-preferring lines. Also, research has generally been focused on ethanol consumption be-havior of male rodents. However, female rodents tend to consume more al-cohol than male rodents (e.g., Adams et al., 1991). In addition, existing re-search on adolescent vs. adult alcohol abuse using “FHP” rats is not paral-leled by research with “Family History Negative” (FHN) rats, which might re-veal factors that prevent/protect an individual from excessive ethanol intake during this crucial stage of development. The purpose of this study was to evaluate ethanol consumption by male and female FHN, selectively bred, alcohol-nonpreferring rats during adoles-cence and adulthood. Studying adolescent vs. adult behavior may reveal de-velopmentally-specific, protective factors. Also, examining male versus fe-male behavior may reveal sex-by-development factors guarding against al-cohol abuse. Animals were placed in cages and assigned to experimental conditions defined by the following independent variables: line of rodent, rodent’s sex and age of ethanol exposure. The following dependent measures were exam-ined: changes in body weight as well as water and ethanol consumption. These measures were taken at least 5 days per week. We hypothesized that there would be elevated levels of ethanol con-sumption (g ethanol/kg body weight/day) in (a) adolescent vs. adult rats and (b) female vs. male rats. Future research might focus on gene and/or protein expression differences within certain nuclei of the brain’s reward neurocircuit between the FHP and FHN lines of rats. Currently, some data has been collected and statistically analyzed. Upon completion the study re-sults will be prepared for presentation and manuscript submission. Funded in part by the Indiana University-Purdue University Indianapolis, Undergraduate Re-search Opportunities Program (UROP

Socioeconomic Impacts on Survival Differ by Race/Ethnicity among Adolescents and Young Adults with Non-Hodgkin's Lymphoma

Shorter survival has been associated with low socioeconomic status (SES) among elderly non-Hodgkin's lymphoma (NHL) patients; however it remains unknown whether the same relationship holds for younger patients. We explored the California Cancer Registry (CCR), to investigate this relationship in adolescent and young adult (AYA) NHL patients diagnosed from 1996 to 2005. A case-only survival analysis was conducted to examine demographic and clinical variables hypothesized to be related to survival. Included in the final analysis were 3,489 incident NHL cases. In the multivariate analyses, all-cause mortality (ACM) was higher in individuals who had later stage at diagnosis (P < .05) or did not receive first-course chemotherapy (P < .05). There was also a significant gradient decrease in survival, with higher ACM at each decreasing quintile of SES (P < .001). Overall results were similar for lymphoma-specific mortality. In the race/ethnicity stratified analyses, only non-Hispanic Whites (NHWs) had a significant SES-ACM trend (P < .001). Reduced overall and lymphoma-specific survival was associated with lower SES in AYAs with NHL, although a significant trend was only observed for NHWs

Kids, Adolescents, and Young Adult Cancer Study—A Methodologic Approach in Cancer Epidemiology Research

Advances have been made in treatment and outcomes for pediatric cancer. However adolescents and young adults (AYAs) with cancer have not experienced similar relative improvements. We undertook a study to develop the methodology necessary for epidemiologic cancer research in these age groups. Our goal was to create the Kids, Adolescents, and Young Adults Cancer (KAYAC) project to create a resource to address research questions relevant to this population. We used a combination of clinic and population-based ascertainment to enroll 111 cases aged 0–39 for this methodology development study. The largest groups of cancer types enrolled include: breast cancer, leukemia, lymphoma, and melanoma. The overall participation rate is 69.8% and varies by age and tumor type. The study included patients, mothers, and fathers. The methods used to establish this resource are described, and the values of the resource in studies of childhood and young adult cancer are outlined

InAsP/AlGaInP/GaAs QD laser operating at ∼770 nm

We present a study of metalorganic vapour phase epitaxy of ternary InAsP quantum dots in AlGaInP/GaAs for application in laser diodes. The properties of InAsP QD laser structures were compared with reference samples containing binary InP QDs. Based on X-ray diffraction, the molar fraction of arsenic in InAsP QDs was estimated to be ~25%. Room temperature liquid contact electro-luminescence measurements revealed a long wavelength shift of the InAsP QD emission to ~775 nm as compared with the InP QD emission at 716 nm and an increased full width at half maximum of the spontaneous emission (71 meV vs 50 meV). As cleaved, 4 mm long and 50 µm wide InAsP QD lasers operated in a pulsed regime at room temperature at ~770 nm with a threshold current density of 155 A/cm and a maximum output optical power of at least 200 mW. The maximum operation temperature was at least 380 K

N,N′,N′′-Triphenyl­guanidinium 5-nitro-2,4-dioxo-1,2,3,4-tetra­hydro­pyrimidin-1-ide

In the title compound, C19H18N3 +.C4H2N3O4 −, the dihedral angles between the phenyl rings and the plane defined by the central guanidinium fragment are in the range 41.3 (1)–66.6 (1)°. The pyrimidine ring of the anion is distorted towards a boat conformation and the nitro group is rotated 11.4 (2)° out of the uracil plane. Hydrogen bonds assemble the ions in infinite helical chains along the b axis

Modeling mycorrhizal fungi dispersal by the mycophagous swamp wallaby (Wallabia bicolor)

Despite the importance of mammal-fungal interactions, tools to estimate the mammal-assisted dispersal distances of fungi are lacking. Many mammals actively consume fungal fruiting bodies, the spores of which remain viable after passage through their digestive tract. Many of these fungi form symbiotic relationships with trees and provide an array of other key ecosystem functions. We present a flexible, general model to predict the distance a mycophagous mammal would disperse fungal spores. We modelled the probability of spore dispersal by combining animal movement data from GPS-telemetry with data on spore gut-retention time. We test this model using an exemplar generalist mycophagist, the swamp wallaby (Wallabia bicolor). We show that swamp wallabies disperse fungal spores hundreds of metres—and occasionally up to 1265 m—from the point of consumption, distances that are ecologically significant for many mycorrhizal fungi. In addition to highlighting the ecological importance of swamp wallabies as dispersers of mycorrhizal fungi in eastern Australia, our simple modelling approach provides a novel and effective way of empirically describing spore dispersal by a mycophagous animal. This approach is applicable to the study of other animal-fungi interactions in other ecosystems.Funding provided by: Hermon Slade FoundationCrossref Funder Registry ID: http://dx.doi.org/10.13039/501100001109Award Number: HSF08-6Funding provided by: Australian Research CouncilCrossref Funder Registry ID: http://dx.doi.org/10.13039/501100000923Award Number: DP0557022Methods are described in the published article

Acute visceral pain relief mediated by A(3)AR agonists in rats: involvement of N-type voltage-gated calcium channels

Pharmacological tools for chronic visceral pain management are still limited and inadequate. A(3) adenosine receptor (A(3)AR) agonists are effective in different models of persistent pain. Recently, their activity has been related to the block of N-type voltage-gated Ca(2+) channels (Ca(v)2.2) in dorsal root ganglia (DRG) neurons. The present work aimed to evaluate the efficacy of A(3)AR agonists in reducing postinflammatory visceral hypersensitivity in both male and female rats. Colitis was induced by the intracolonic instillation of 2,4-dinitrobenzenesulfonic acid (DNBS; 30 mg in 0.25 mL 50% EtOH). Visceral hypersensitivity was assessed by measuring the visceromotor response and the abdominal withdrawal reflex to colorectal distension. The effects of A(3)AR agonists (MRS5980 and Cl-IB-MECA) were evaluated over time after DNBS injection and compared to that of the selective Ca(v)2.2 blocker PD173212, and the clinically used drug linaclotide. A(3)AR agonists significantly reduced DNBS-evoked visceral pain both in the postinflammatory (14 and 21 days after DNBS injection) and persistence (28 and 35 days after DNBS) phases. Efficacy was comparable to effects induced by linaclotide. PD173212 fully reduced abdominal hypersensitivity to control values, highlighting the role of Ca(v)2.2. The effects of MRS5980 and Cl-IB-MECA were completely abolished by the selective A(3)AR antagonist MRS1523. Furthermore, patch-clamp recordings showed that A(3)AR agonists inhibited Ca(v)2.2 in dorsal root ganglia neurons isolated from either control or DNBS-treated rats. The effect on Ca(2+) current was PD173212-sensitive and prevented by MRS1523. A(3)AR agonists are effective in relieving visceral hypersensitivity induced by DNBS, suggesting a potential therapeutic role against abdominal pain

Patient organization involvement and the challenge of securing access to treatments for rare diseases:Report of a policy engagement workshop

Plain English summary Patients with rare diseases often help to develop new treatments for their conditions. But once developed, those treatments are sometimes priced too high for many patients to access them. We became aware that this is a problem in the course of a social science research project that examines the place of rare diseases in health policy. We therefore organized a two-day workshop to try and understand why this problem occurs and what might be done about it. The people who participated in our workshop were: representatives of rare disease patient organizations, experts in matters of drug regulation and assessment of new health technologies, consultants involved with companies producing treatments for rare diseases, and social scientists researching related issues. The main conclusions to emerge from the discussions were as follows: Problems of access to treatments for rare diseases are not just due to high prices; procedures for regulating, assessing and delivering new treatments also need to be better organized. Patients and patient organizations have much to contribute to this process. However, their resources are often very limited. Consequently, more needs to be done to help them use those resources as effectively as possible. In particular, regulators and healthcare providers need to ensure that their procedures are clear and efficiently managed, so as not to waste patient organizations’ time and money. Clearer guidance is needed on what patient organizations can do to provide evidence of the effectiveness of new drugs. Insights gained in tackling rare diseases might also be applicable to common disorders. Finally, the consequences of Brexit for UK policies on rare diseases urgently need to be assessed. Abstract Since the enactment of orphan drug legislation in the USA, Europe and several other countries, an increasing number of treatments for rare diseases have been developed and many of them been approved for marketing. However, such treatments tend to be priced very high, and access to effective treatments remains a major challenge for patients with rare diseases – despite active involvement of patients and their support organizations in various stages of basic and applied research and commercial development. In order to allow patients to benefit from treatments proved effective for their diseases, we need to better understand why this challenge persists, and what steps might be taken to address it. To that end, we organized a policy-engagement workshop, bringing together individuals and organizations with direct experience of trying to secure access to a treatment for a rare disease along with individuals with relevant expertise in regulatory and commissioning processes for new medicines. With additional input from social scientists who offered different perspectives on the value of patient involvement, the workshop aimed to initiate a dialogue among the participants about how to address the challenge in a sustainable manner. Discussions at the workshop stressed that active involvement of patients is as valuable in the regulatory and commissioning processes as in the research and development of new medicines. However, it also highlighted certain risks and costs associated with such involvement. These include the costs of adjusting to abrupt changes in regulatory and commissioning processes, and the risk of being perceived as too close to commercial interests. To optimize use of scarce resources and ensure continuing active involvement, such risks and costs need to be better managed. Participants also noted that, owing to advances in genomic technologies, common diseases are also becoming divided into rare sub-categories, which are equally eligible for orphan drug designation. Consequently, involvement of wider patient communities beyond rare disease communities will be critical for continuing discussions about patients’ involvement in regulatory and commissioning processes, and to consider how patients and their support organizations can best work with other stakeholders – including companies, regulators and policymakers – to ensure access to effective medicines

A qualitative investigation of breast cancer survivors’ experiences with breastfeeding

This is an exploratory, qualitative investigation of breast cancer survivors’ experiences with breastfeeding. Previous studies have focused on the physiology of lactation after surgery and treatment, but have not explored factors influencing breastfeeding decisions and behavior. We used purposeful sampling to identify 11 breast cancer survivors who had a child after their diagnosis and treatment. Participants were recruited from among those in the Women’s Healthy Eating and Living (WHEL) study and a Young Survival Coalition (YSC) affiliate. We conducted semi-structured, open-ended telephone interviews lasting 45–75 min. We used social cognitive theory (SCT) to structure questions regarding influences on breastfeeding behavior. We transcribed interviews and used cross-case, inductive analysis to identify themes. Ten of 11 participants initiated breastfeeding. The following main themes emerged: 1) Cautiously hopeful, 2) Exhausting to rely on one breast, 3) Motivated despite challenges, 4) Support and lack of support, and 5) Encouraging to others. Study participants were highly motivated to breastfeed but faced considerable challenges. Participants described problems that are not unique to women with breast cancer, but experienced these to a much greater degree because they relied mostly or entirely on one lactating breast. This study revealed a need for improved access to information and support and greater sensitivity to the obstacles faced by breast cancer survivors. Results of this qualitative analysis indicate that interventions to support the efforts of breast cancer survivors who are interested in breastfeeding are warranted. Additional research would aid in the development of such interventions

Do Asian breast cancer patients have poorer survival than their western counterparts? A comparison between Singapore and Stockholm

10.1186/bcr2219Breast Cancer Research111-BCRR