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There is a pressing need to identify non-opioid, evidence-based treatments to address the high prevalence of chronic pain in licensed opioid treatment programs (OTP). Yoga is an effective pain coping strategy but is not widely used by OTP patients. Few studies have examined underlying factors related to poor yoga utilization in this population. Seventy-one participants with and without chronic pain enrolled in a hospital-based OTP completed an acceptability survey assessing pain, current pain coping strategies, prior yoga experience, willingness to try yoga, and beliefs about yoga. Participants with and without chronic pain were compared, as were participants with and without prior yoga experience. The relationships between primary study variables in the chronic pain group were also explored. Participants reported using over-the-counter medications, meditation, stretching, and exercise to manage chronic pain, but yoga was not commonly used. Participants with prior yoga experience reported higher willingness to try yoga and more favorable beliefs about yoga than participants without prior yoga experience. There were no significant differences in willingness to try yoga between participants with and without chronic pain. Among participants with chronic pain, there was a positive association between total number of pain coping strategies used and willingness to try yoga. This study adds to the existing literature on the implementation of yoga programs into OTPs by demonstrating the acceptability of yoga in patients with opioid use disorder, including those experiencing chronic pain, and encourages additional research exploring implementation.

To better understand the relationship between faith and LGBTQ+ identity, we conducted a qualitative analysis of 86 respondents to a general question posed through the Dear Abby column. Responses were anonymized and analyzed using a grounded theory approach. Analysis revealed six themes, reflecting a diversity of lived experience from community rejection to acceptance, and self-rejection to feelings of acceptance by God. Despite frequent media portrayals of conflict between faith and LGBTQ+ identity, the reality is more complex, and faith and LGBTQ+ identity development can be complementary.

A circular economy relies on demonstrating the quality and environmental safety of wastes that are recovered and reused as products. Policy-level risk assessments, using generalised exposure scenarios, and informed by stakeholder communities have been used to appraise the acceptability of necessary changes to legislation, allowing wastes to be valued, reused and marketed. Through an extensive risk assessment exercise, summarised in this paper, we explore the burden of proof required to offer safety assurance to consumer and brand-sensitive food sectors in light of attempts to declassify, as wastes, quality-assured, source-segregated compost and anaerobic digestate products in the United Kingdom. We report the residual microbiological and chemical risks estimated for both products in land application scenarios and discuss these in the context of an emerging UK bioeconomy worth £52bn per annum. Using plausible worst case assumptions, as demanded by the quality food sector, risk estimates and hazard quotients were estimated to be low or negligible. For example, the human health risk of E. coli 0157 illness from exposure to microbial residuals in quality-assured composts, through a ready-to-eat vegetable consumption exposure route, was estimated at ~10−8 per person per annum. For anaerobic digestion residues, 7 × 10−3 cases of E. coli 0157 were estimated per annum, a potential contribution of 0.0007% of total UK cases. Hazard quotients for potential chemical contaminants in both products were insufficient in magnitude to merit detailed quantitative risk assessments. Stakeholder engagement and expert review was also a substantive feature of this study. We conclude that quality-assured, source-segregated products applied to land, under UK quality protocols and waste processing standards, pose negligible risks to human, animal, environmental and crop receptors, providing that risk management controls set within the standards and protocols are adhered to. Keywords: Compost, Digestate, Regulation, Risk, Bioeconomy, Quality

Preclinical studies demonstrate that sleep disruption diminishes morphine analgesia and modulates reward processing. We sought to translate these preclinical findings to humans by examining whether sleep disruption alters morphine’s analgesic and hedonic properties. We randomized 100 healthy adults to receive morphine versus placebo after two nights of undisturbed sleep (US) and two nights of forced awakening (FA) sleep disruption. Sleep conditions were counterbalanced, separated by a two-week washout. The morning after both sleep conditions, we tested cold pressor pain tolerance before and 40-min after double-blind injection of .08 mg/kg morphine or placebo. The primary outcome was the analgesia index, calculated as the change in cold pressor hand withdrawal latency (HWL) before and after drug injection. Secondary outcomes were ratings of feeling “high,” drug “liking,” and negative drug effects. We found a significant sleep condition by drug interaction on the analgesia index (95% CI − 0.57, − 0.001). After US, subjects receiving morphine demonstrated significantly longer HWL compared to placebo (95% CI 0.23, 0.65), but not after FA (95% CI − 0.05, 0.38). Morphine analgesia was diminished threefold under FA, relative to US. After FA, females (95% CI − 0.88, − 0.05), but not males (95% CI − 0.23, 0.72), reported decreased subjective “high” effects compared to US. After FA, females (95% CI 0.05, 0.27), but not males (95% CI − 0.10, 0.11), administered morphine reported increased negative drug effects compared to US. These data demonstrate that sleep disruption attenuates morphine analgesia in humans and suggest that sleep disturbed males may be at greatest risk for problematic opioid use.

In the aftermath of World War II, the Red Army as a symbol of power was supported in many other arenas so as to counteract the rival influence of the United States on Central Europe. The Soviet Union brought new urgency to these efforts from 1948, with music—and culture more broadly—providing a case for Russia’s attractiveness and superiority with respect to the West. This chapter discusses the nature and scope of Soviet influence in the Central European music world through the examples of East Germany and Poland, and through the prism of the music and persona of Sergei Prokofiev. After his return to the USSR in 1936, Prokofiev, along with Shostakovich, became associated with the very definition of what made music Soviet and thus worthy of emulation. And even more than Shostakovich, Prokofiev and his music functioned as powerful but malleable symbols that could be appropriated by all Soviet actors for their own ends.

An efficient synthesis of 6-oxo-1,2,3,4,5,7,12,12b-octahydroindolo[2,3-α]quinolizine from 2-acetylpyridine and phenylhydrazine is described. This derivative of the natural alkaloid desbromoarborescidine A is an important entry point to the sarpagine-vobasine family of plant alkaloids.

The goal of the Zagreb conference “The Tito-Stalin Split: 70 Years Later”, Zagreb-Goli Otok, 28-30 June 2018, as well as of the papers presented, was to show not only the new interpretations and takes on the subject, but to present the Yugoslav 1948 as a global event, one that touched lives of so many people around the world. It had a very significant impact not only on politics, international relations, prisoners, army cooperation and army relations, ideology, but also cultural life and production, especially in Yugoslavia and the Soviet Union. Most of the papers presented at the Faculty of Humanities and Social Sciences, University of Zagreb, which co-organized the whole event with colleagues from the University of Ljubljana, Slovenia, are published in this volume. A few papers were presented but the authors did not contribute the text (those were: Mark Kramer, Peter Ruggenthaler, Ondřej Vojtěchovský, Klaus Buchenau, Andreii Edemskii, Boris Stamenic, and Marie-Janine Calic). Also, one paper on China was not presented, but the text is here. We hope this volume will be an important contribution to the continuous dialogue that should be not only regional, but global. It should also be ongoing, since there is hardly an event in the history of the Cold War whose consequences were as important and as global as this one’s. (from the Preface)The book is co-published by the University of Zagreb, Faculty of Humanities and Social Sciences – Department of History (Postgraduate Doctoral Studies “Modern and Contemporary Croatian History In European and World Context”) & the University of Ljubljana Faculty of Arts – Department of History, as a volume 31 in the Historia series.

The number of persons on buprenorphine maintenance for opioid use disorder (OUD) is rising and these patients often have chronic pain. It is not clear whether the endogenous analgesic system, which is often dysregulated in chronic pain patients, is affected by buprenorphine maintenance. Conditioned pain modulation (CPM) can evaluate endogenous analgesia; CPM is tested by applying a primary noxious stimulus alone and then simultaneously with a conditioning noxious stimulus on a remote body part. An efficient CPM results in an increase in primary pain threshold in the presence of the conditioning stimulus. A less efficient CPM is pro-nociceptive and results in lower primary pain threshold in the presence of the conditioning stimulus. This study assessed CPM in persons without chronic pain maintained on buprenorphine. CPM was tested by measuring pressure pain threshold at baseline and while undergoing a cold pressor test. Further, this study examined whether adjunct hydromorphone and/or buprenorphine, compared to placebo, effected CPM. Participants (N=13) with OUD who were maintained on 12mg or 16mg buprenorphine performed three study sessions, at least one week apart, where they underwent CPM at baseline and after cumulative doses of 32mg IV hydromorphone, 32mg IV buprenorphine, or placebo. Thirty-one percent of participants displayed less efficient CPM in at least one session prior to drug administration based on lower pressure pain threshold during cold-pressor testing compared to baseline. There were no significant differences in the proportion of individuals with less efficient CPM following 32mg IV hydromorphone (69%), 32mg buprenorphine (54%), or placebo (62%) (p=0.779). Results suggest that some buprenorphine-maintained individuals experience less efficient CPM. High doses of hydromorphone or buprenorphine did not improve CPM compared to placebo. Non-opioid analgesic strategies should be developed to address chronic pain in persons maintained on buprenorphine. Study medications provided by Indivior, Inc.

Catastrophizing, a persistent negative mental set characterized by helplessness, rumination, and magnification of pain sensations, has a potent effect on pain report and clinical outcomes. Previous studies have documented an association between cognitive factors and central sensitization. The current analysis sought to test the potential modulating effect of pain catastrophizing on the association between capsaicin pain and the region of secondary hyperalgesia. Thirty-eight healthy individuals (50% women, mean age = 25.7, SD = 5.3) completed the Pain Catastrophizing Scale (PCS), then underwent topical application of 10% capsaicin, which was covered by a thermode maintained at 40°C for 90-min. Following removal of the capsaicin, the region of secondary hyperalgesia was determined. Hayes' PROCESS macro was employed to examine catastrophizing's potential moderating effect, which did not reveal a significant association between capsaicin pain ratings and the region of secondary hyperalgesia (β = 15.1, p = .06). Though PCS was not associated with area of secondary hyperalgesia (β = 23.9, p = .29), a significant interaction was present between PCS and capsaicin pain ratings (β = 3.7, p = .0004). Specifically, those endorsing higher catastrophizing levels and higher pain ratings experienced the greatest areas of secondary hyperalgesia. The Johnson-Neyman technique was used to determine the regional effect of the moderation, which indicated that when PCS scores were ≥10.6, capsaicin pain significantly moderated the association between pain and area of secondary hyperalgesia. These results suggest that catastrophizing plays an important role in the area of secondary hyperalgesia, and potentially central sensitization, warranting further testing in future research.

As the Eastern bloc coalesced in the later 1940s, its leaders sought to present themselves to their citizens as both building a socialist utopia and offering a model for the rest of the world. Mao’s 1949 victory in China, the world’s most populous country, seemed to prefigure this inexorable deepening and broadening of communism, and Central European communists sought to deploy a representation of the People’s Republic of China (PRC) in service of constructing a socialist society at home. Party officials, artists and intellectuals, and ordinary citizens helped to fashion this image of China, which circulated widely throughout the public sphere in the mass media of newspapers, popular magazines, fiction and non-fiction books, music, television, and film, as well as through the wide distribution of informational pamphlets and booklets. Public demonstrations and parades featured speeches and slogans thematizing China, as did more intense campaigns like the “Month of Chinese-German Friendship.” Posters and other public visual material, especially showpiece cultural exhibitions, also helped to construct and propagate an image of the PRC. A particularly compelling source is that of visiting delegations of artists, scientists, experts, and ordinary citizens, going in both directions, as these guests gathered and left impressions open to interpretation, both official and otherwise. This dynamic began to change with the Sino-Soviet split in the 1960s, but even as a problematic ally and then enemy, the image of China helped to build socialism in Central Europe.

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycoprotein present on the cancer cell plasma membrane, enhances fibroblast synthesis of matrix metalloproteinases (MMPs). The demonstration that peritumoral fibroblasts synthesize most of the MMPs in human tumors rather than the cancer cells themselves has ignited interest in the role of EMMPRIN in tumor dissemination. In this report we have demonstrated a role for EMMPRIN in cancer progression. Human MDA-MB-436 breast cancer cells, which are tumorigenic but slow growing in vivo, were transfected with EMMPRIN cDNA and injected orthotopically into mammary tissue of female NCr nu/nu mice. Green fluorescent protein was used to visualize metastases. In three experiments, breast cancer cell clones transfected with EMMPRIN cDNA were considerably more tumorigenic and invasive than plasmid-transfected cancer cells. Increased gelatinase A and gelatinase B expression (demonstrated by in situ hybridization and gelatin substrate zymography) was demonstrated in EMMPRIN-enhanced tumors. In contrast to de novo breast cancers in humans, human tumors transplanted into mice elicited minimal stromal or inflammatory cell reactions. Based on these experimental studies and our previous demonstration that EMMPRIN is prominently displayed in human cancer tissue, we propose that EMMPRIN plays an important role in cancer progression by increasing synthesis of MMPs.

Opioid-induced hyperalgesia (OIH), increased sensitivity to noxious stimuli after repeated opioid exposures, has been demonstrated in preclinical studies. However, there is no accepted, prospective model of OIH after repeated opioid exposures currently available in humans. This study assessed a potential prospective OIH model.Double-blind intramuscular injections of a short-acting opioid (alfentanil 15 mcg/kg; N=8) were compared to active placebo (diphenhydramine 25 mg; N=3) on cold and pressure pain testing and standard abuse liability measures in eight 10-hour sessions (1 injection/session) over 4 to 5 weeks in healthy, pain-free males. Decreases from session baseline pain threshold (PThr) and tolerance (PTol) were calculated to represent hyperalgesia, and were assessed both within and across sessions.Mean decreases in cold PTol were seen in the alfentanil group at 180 minutes (-3.8 s, ±26.5) and 480 minutes (-1.63 s, ±31.5) after drug administration. There was a trend for differences between conditions on cold PThr hyperalgesia but not for pressure PThr. Alfentanil participants had greater mean ratings on Liking and High visual analog scales at peak effects (30 min), but these scores did not change across sessions.Repeated alfentanil exposures over 4 to 5 weeks resulted in within session decreases in cold pain tolerance from baseline but these differences were not substantially different from diphenhydramine controls. The results did not support the phenomenon of OIH in this model, although definitive conclusions regarding the existence of OIH in humans likely requires a larger sample size or an alternative model.

Good sample preparation is an essential first step to almost all laboratory analytical procedures. The procedures presented are intended to stimulate interest in generic methods for performance testing of various steps in fertilizer sample preparation, including initial reduction of unground sample, grinding, and mixing. Sample reduction quality is measured by 2 types of procedures, the first using 2 sizes of glass beads for a more theoretical approach, and the second using 2 common fertilizer materials for a more empirical method. Grinding performance is measured by recovery and carryover methods, followed by particle size and uniformity estimates of the ground material. Mixing after grinding is tested by measuring time-to-blend of a segregated mixture.

Mucinous adenocarcinoma of the lung is a subtype of highly invasive pulmonary tumors and is associated with decreased or absent expression of the transcription factor NK2 homeobox 1 (NKX2-1; also known as TTF-1). Here, we show that haploinsufficiency of Nkx2-1 in combination with oncogenic Kras(G12D), but not with oncogenic EGFR(L858R), caused pulmonary tumors in transgenic mice that were phenotypically similar to human mucinous adenocarcinomas. Gene expression patterns distinguished tumor goblet (mucous) cells from nontumorigenic airway and intestinal goblet cells. Expression of NKX2-1 inhibited urethane and oncogenic Kras(G12D)-induced tumorigenesis in vivo. Haploinsufficiency of Nkx2-1 enhanced Kras(G12D)-mediated tumor progression, but reduced EGFR(L858R)-mediated progression. Genome-wide analysis of gene expression demonstrated that a set of genes induced in mucinous tumors was shared with genes induced in a nontumorigenic chronic lung disease, while a distinct subset of genes was specific to mucinous tumors. ChIP with massively parallel DNA sequencing identified a direct association of NKX2-1 with the genes induced in mucinous tumors. NKX2-1 associated with the AP-1 binding element as well as the canonical NKX2-1 binding element. NKX2-1 inhibited both AP-1 activity and tumor colony formation in vitro. These data demonstrate that NKX2-1 functions in a context-dependent manner in lung tumorigenesis and inhibits Kras(G12D)-driven mucinous pulmonary adenocarcinoma.

Composting of source-separated green waste (SSGW) is essential to meet the EU Landfill Directive target and agricultural land is considered a significant market for the resulting composts. A critical review of the literature was performed to evaluate the potential for pathogens to enter the composting process via SSGW feedstocks and the likelihood of their survival of the composting process and subsequent application to land. This is discussed in the context of application of other organic wastes to land. It was concluded that zoonoses such as verotoxigenic Escherichia coli and Salmonella spp. are unlikely to survive and effective composting process, whereas spore forming organisms are more resistant to composting but are also ubiquitous in the environment. Adherence to existing guidelines, such as those for farm yard manures, is likely to provide a rational degree of health protection for humans and livestock.

For decades Malaysia was the world's largest producer of Sn, but now the vast open cast mining operations have left a legacy of some 100 000 ha of what is effectively wasteland, covered with a mosaic of tailings and lagoons. Few plants naturally recolonise these areas. The demand for such land for both urban expansion and agricultural use has presented an urgent need for better characterisation. This study reports on the formation of artificial soils from alluvial Sn mining waste with a focus on the effects of experimental treatments on soil chemistry. Soil organic matter, clay, and pH were manipulated in a controlled environment. Adding both clay tailings and peat enhanced the cation exchange capacity of sand tailings but also reduced the pH. The addition of peat reduced the extractable levels of some elements but increased the availability of Ca and Mg, thus proving beneficial. The use of clay tailings increased the levels of macro and micronutrients but also released Al, As, La, Pb and U. Additionally, the effects of soil mix and mycorrhizal treatments on growth and foliar chemistry were studied. Two plant species were selected: Panicum milicaeum and Pueraria phaseoloides. Different growth patterns were observed with respect to the additions of peat and clay. The results for mycorrhizal treatment (live inoculum or sterile carrier medium) are more complex, but both resulted in improved growth. The use of mycorrhizal fungi could greatly enhance rehabilitation efforts on sand tailings.

Despite advances in the development of medications to treat alcohol dependence, few medications have been approved by the U.S. Food and Drug Administration. The use of certain anticonvulsant medications has demonstrated potential efficacy in treating alcohol dependence. Previous research suggests that the anticonvulsant levetiracetam may be beneficial in an alcohol-dependent population of very heavy drinkers.In this double-blind, randomized, placebo-controlled clinical trial, 130 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either levetiracetam extended-release (XR) or placebo and a Brief Behavioral Compliance Enhancement Treatment intervention. Levetiracetam XR was titrated during the first 4 weeks to 2,000 mg/d. This target dose was maintained during weeks 5 through 14 and was tapered during weeks 15 and 16.No significant differences were detected between the levetiracetam XR and placebo groups in either the primary outcomes (percent heavy drinking days and percent subjects with no heavy drinking days) or in other secondary drinking outcomes. Treatment groups did not differ on a number of nondrinking outcomes, including depression, anxiety, mood, and quality of life. The only difference observed was in alcohol-related consequences. The levetiracetam XR treatment group showed significantly fewer consequences than did the placebo group during the maintenance period (p = 0.02). Levetiracetam XR was well tolerated, with fatigue being the only significantly elevated adverse event, compared with placebo (53% vs. 24%, respectively; p = 0.001).This multisite clinical trial showed no efficacy for levetiracetam XR compared with placebo in reducing alcohol consumption in heavy drinking alcohol-dependent patients.

OBJECTIVES: To estimate, overall and by organism, the incidence of infectious intestinal disease (IID) in the community, presenting to general practice (GP) and reported to national surveillance. DESIGN: Prospective, community cohort study and prospective study of GP presentation conducted between April 2008 and August 2009. SETTING: Eighty-eight GPs across the UK recruited from the Medical Research Council General Practice Research Framework and the Primary Care Research Networks. PARTICIPANTS: 6836 participants registered with the 88 participating practices in the community study; 991 patients with UK-acquired IID presenting to one of 37 practices taking part in the GP presentation study. MAIN OUTCOME MEASURES: IID rates in the community, presenting to GP and reported to national surveillance, overall and by organism; annual IID cases and GP consultations by organism. RESULTS: The overall rate of IID in the community was 274 cases per 1000 person-years (95% CI 254 to 296); the rate of GP consultations was 17.7 per 1000 person-years (95% CI 14.4 to 21.8). There were 147 community cases and 10 GP consultations for every case reported to national surveillance. Norovirus was the most common organism, with incidence rates of 47 community cases per 1000 person-years and 2.1 GP consultations per 1000 person-years. Campylobacter was the most common bacterial pathogen, with a rate of 9.3 cases per 1000 person-years in the community, and 1.3 GP consultations per 1000 person-years. We estimate that there are up to 17 million sporadic, community cases of IID and 1 million GP consultations annually in the UK. Of these, norovirus accounts for 3 million cases and 130,000 GP consultations, and Campylobacter is responsible for 500,000 cases and 80,000 GP consultations. CONCLUSIONS: IID poses a substantial community and healthcare burden in the UK. Control efforts must focus particularly on reducing the burden due to Campylobacter and enteric viruses.

A generalized quantitative risk assessment for the use of source-segregated green waste (SSGW) compost use in livestock production is presented. This assessment focussed on potential risks associated with a specific product, PAS100 compost that meets the UK publicly available specification 100 and represents the majority of compost available for use in extensive Scottish livestock systems. A hazard screening approach was used to identify all potentially hazardous agents present in compost. A total of 497 potentially hazardous agents were screened, with 147 finally put forward for quantitative risk assessment. Scenarios modelled in the assessment included surface application of compost to grazing land and also incorporation into soil and subsequent uptake by fodder crops. Risk estimates were compared to those associated with six comparator materials, including various sludges, slurries and farm yard manures. Overall, five potentially hazardous agents (PCB28, PCB138, PCB153, 1,2,3,4,6,7,8-HpCDD, Clopyralid) returned a hazard quotient >1 but within margins of uncertainty, indicating that further investigation may be required. Within the limitations of available information, SSGW compost was found to pose less risk to grazing livestock, or the environment, than other commonly-used soil amendments. While this assessment relates to a specific product/standard used in the UK, the methodology could easily be applied to other composts/products/situations. Therefore these results have wider applicability.

Background: Deriving an appropriate differential diagnosis is a key clinical competency, but there is little data available on how medical students learn this skill. Software resources designed to complement clinical reasoning might be asset in helping them in this task. Aims: The goals of this study were to identify the resources third year medical students use to solve a challenging diagnostic case, and specifically to evaluate the usefulness of Isabel, a second-generation electronic diagnosis support system. Methods: Third year medical students (n ¼ 117) were presented a challenging case and asked to identify and prioritize their top 3 diagnoses, report the time devoted to the exercise, and list the resources they used and their relative usefulness. Students were randomized to receive (or not) free access, instruction, and encouragement to use to a web-based decision support system (Isabel). Results: Students who identified the correct diagnosis as their first choice spent significantly more time on the case than did the other students (3.75 � 0.28 hours vs 2.88 � 0.15 hours, p < 0.05). Students used electronic resources extensively, in particular Google. Students who self-reported use of Isabel had greater success identifying the correct diagnosis (24/33 ¼ 73% for users vs 45/84 ¼ 53% for non-users) a difference of borderline statistical significance. Conclusions: These findings indicate that medical trainees use a wide range of electronic decision support products to solve challenging cases. Medical education needs to adapt to this reality, and address the need to teach future clinicians how to use these tools to advantage.

The bronchioles of the murine lung are lined by a simple columnar epithelium composed of ciliated, Clara, and goblet cells that together mediate barrier function, mucociliary clearance and innate host defense, vital for pulmonary homeostasis. In the present work, we demonstrate that expression of Sox2 in Clara cells is required for the differentiation of ciliated, Clara, and goblet cells that line the bronchioles of the postnatal lung. The gene was selectively deleted in Clara cells utilizing Scgb1a1-Cre, causing the progressive loss of Sox2 in the bronchioles during perinatal and postnatal development. The rate of bronchiolar cell proliferation was decreased and associated with the formation of an undifferentiated, cuboidal-squamous epithelium lacking the expression of markers of Clara cells (Scgb1a1), ciliated cells (FoxJ1 and alpha-tubulin), and goblet cells (Spdef and Muc5AC). By adulthood, bronchiolar cell numbers were decreased and Sox2 was absent in extensive regions of the bronchiolar epithelium, at which time residual Sox2 expression was primarily restricted to selective niches of CGRP staining neuroepithelial cells. Allergen-induced goblet cell differentiation and mucus production was absent in the respiratory epithelium lacking Sox2. In vitro, Sox2 activated promoter-luciferase reporter constructs for differentiation markers characteristic of Clara, ciliated, and goblet cells, Scgb1a1, FoxJ1, and Agr2, respectively. Sox2 physically interacted with Smad3 and inhibited TGF-beta1/Smad3-mediated transcriptional activity in vitro, a pathway that negatively regulates proliferation. Sox2 is required for proliferation and differentiation of Clara cells that serve as the progenitor cells from which Clara, ciliated, and goblet cells are derived.

We have investigated S. aureus adherence to human endothelial cells utilizing an in vitro model. Staphylococcus binding to confluent endothelial cell monolayers was saturable in both dose and time response studies suggesting that the binding interaction was specific. We have developed a technique, based on the pH dependent affinity of iminobiotin for streptavidin, for the isolation of an endothelial cell membrane component that binds S. aureus, in vitro. A 50-kD membrane component was isolated and purified using this approach. This component was trypsin sensitive, periodate insensitive, and did not label with [3H]glucosamine. [35S]Methionine and [125I]iodine labeling confirmed that the protein was synthesized by and expressed on the endothelial cell surface. Functional binding studies demonstrated that staphylococci, but not endothelial cells, bound to the protein when immobilized on microtiter wells. Preincubation of staphylococci with the purified protein significantly (P less than 0.001) reduced staphylococcal binding to cultured endothelial cells. The capacity of S. aureus to colonize and invade endovascular surfaces may in part be a consequence of staphylococcal interaction with this endothelial cell membrane protein.

s / Drug and Alcohol Dependence 146 (2015) e2–e33 e5 and TM use patterns and preferences pertaining to their substance treatment. Results: Mobile phone ownership was common (93%) with no significant differences in ownership among self-reported homeless, recently incarcerated, and unemployed respondents. Most reported sending or receiving TM (93%) and reporting ‘very much’ or ‘somewhat’ comfort sending TM (79%). Contacting buprenorphine providers by phone (30%) or TM (17%) was uncommon, however most preferred to use either form of communication to reach their provider (67%). Older patients received less TM (25) compared to younger age groups (128) yet were as interested as the rest of the clinic population to have their provider’s mobile phone number (96%) and send TM if at risk of relapse (78%). Conclusions:Ourfindingshighlight the acceptability of enhancing patient-provider mobile phone and TM communications in a public sector, office-based buprenorphine clinic, even among respondents that were not comfortable in using TM. Although mobile phone ownership was very common, frequent turnover in phone ownership and changing phone numbers highlights challenges in feasibility for any future mhealth interventions in this clinical setting. Financial Support: Babak Tofighi is supported by a NRSA T32: Postdoctoral Primary Care Research Training Program (HRSA T32HP22238-01-00) and the Research in AddictionMedicine Scholars Program (R25DA03211). http://dx.doi.org/10.1016/j.drugalcdep.2014.09.694 What is the most cost-effective advertising strategy for alcohol pharmacotherapy clinical trials? David A. Tompkins, Joseph A. Harrison, Eric C. Strain Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United

If the deleterious effects of non-specific parasites are greater on vulnerable host species than on reservoir host species then exclusion of the vulnerable host through apparent competition is more likely. Evidence suggests that such a mechanism occurs in interactions between the ring-necked pheasant (Phasianus colchicus), the grey partridge (Perdix perdix), and their shared caecal nematode Heterakis gallinarum. Modelling of the system predicts that the reduced parasite impact on the pheasant compared to the partridge results in the force of infection transmitted from pheasants to partridges being sufficient to cause partridge exclusion. Since the parasite impacts are currently estimated from correlational work, controlled infections were conducted to experimentally compare the impact of H. gallinarum on the two hosts and verify cause and effect. While challenged partridges showed reduced mass gain, decreased food consumption, and impaired caecal activity, in comparison to controls, the only detectable effect of parasite challenge on the pheasant was impaired caecal activity. The impact of H. gallinarum on challenged partridges conforms with previous correlational data, supporting the prediction that parasite-mediated apparent competition with the ring-necked pheasant may result in grey partridge exclusion. However, the observed decrease in the caecal activity of challenged pheasants could imply that H. gallinarum may also have an impact on the fecundity and survival of pheasants in the wild, particularly if food is limiting. If this is the case, the associated decrease in the force of infection to which the partridge is exposed may be sufficient to change the model prediction from partridge exclusion to pheasant and partridge coexistence.

The primary objective of this study was to gain a clearer understanding of the barriers to adherence to highly active antiretroviral therapy (HAART) faced by people living with HIV/AIDS (PLWHIV/AIDS) on Long Island, New York. Focus group, a qualitative research method, was used to study these barriers. The study was conducted in 1998 on Long Island, NY, at five institutions that provide services to 1700 PLWHIV/AIDS. Five focus groups were conducted with 6 to 13 PLWHIV/AIDS in each group, a total of 39 subjects. PLWHIV/AIDS identified eight common barriers to adherence to HAART. In descending order, the barriers include: (1) frequency and severity of side effects, (2) conflicts with daily routines, (3) dietary requirements, (4) frequency of taking medications, (5) number and dosage of medications, (6) psychosocial factors (i.e., stress, feeling good, and bad news), (7) pharmacy refills, and (8) physiological needs (i.e., sleep, hunger, or thirst). Many factors play a role in the success or failure of HAART, including preexisting drug resistance, drug-drug interactions, and the ability of PLWHIV/AIDS to adhere to a rigid and frequently changing medication regimen. The information gleaned from focus groups is limited in that it may not be generalized to a larger population with any known reliability. However, clinicians sensitive to barriers to adherence to HAART, including those identified by PLWHIV/AIDS in this study, may play a more proactive role in supporting adherence to the medication regimen, increasing the durability of effective viral suppression, decreasing morbidity and mortality, and decreasing the selection and transmission of resistant strains of HIV.

The methyl esters of 2-methoxy-3, 6-dichlorobenzoic acid and three phenoxyacetic acids were prepared by the admixture of an excess of both methyl iodide and anhydrous alkali-metal carbonate to a solution of the carboxylic acids in acetone. The reaction was completed within the shortest period of time when cesium carbonate was used, and the reaction mixture was injected without further work-up into a gas chromatograph fitted with a flame ionization detector. Further reduction of reaction time was achieved by heating the mixture to 50°C and by ultrasonic treatment; this technique is also suitable for esterification of microliter quantities and obviates the need for a microrefluxer. Butylesters of 2, 4-D and 2, 4, 5-T were prepared in an analogous manner. The methyl esters of 2, 4-D and 2, 4, 5-T, and the butyl ester of 2, 4-D were obtained in better than 90% yield.