Greening academia: developing sustainable waste management at Higher Education Institutions.

Higher Education Institutions (HEIs) are often the size of small municipalities. Worldwide, the higher education (HE) sector has expanded phenomenally; for example, since the 1960s, the United Kingdom (UK) HE system has expanded sixfold to >2.4 million students. As a consequence, the overall production of waste at HEIs throughout the world is very large and presents significant challenges as the associated legislative, economic and environmental pressures can be difficult to control and manage. This paper critically reviews why sustainable waste management has become a key issue for the worldwide HE sector to address and describes some of the benefits, barriers, practical and logistical problems. As a practical illustration of some of the issues and problems, the four-phase waste management strategy developed over 15 years by one of the largest universities in Southern England--the University of Southampton (UoS)--is outlined as a case study. The UoS is committed to protecting the environment by developing practices that are safe, sustainable and environmentally friendly and has developed a practical, staged approach to manage waste in an increasingly sustainable fashion. At each stage, the approach taken to the development of infrastructure (I), service provision (S) and behavior change (B) is explained, taking into account the Political, Economic, Social, Technological, Legal and Environmental (PESTLE) factors. Signposts to lessons learned, good practice and useful resources that other institutions--both nationally and internationally--can access are provided. As a result of the strategy developed at the UoS, from 2004 to 2008 waste costs fell by around £125k and a recycling rate of 72% was achieved. The holistic approach taken--recognizing the PESTLE factors and the importance of a concerted ISB approach--provides a realistic, successful and practical example for other institutions wishing to effectively and sustainably manage their waste.

Modulation of erlotinib pharmacokinetics in mice by a novel cytochrome P450 3A4 inhibitor, BAS 100.

Administration of BAS 100, a novel mechanism-based CYP3A4 inhibitor isolated from grapefruit juice, resulted in a 2.1-fold increase in erlotinib exposure following oral administration to wild-type and humanized CYP3A4 transgenic mice. This study illustrates the potential of BAS 100 to increase the low and variable oral bioavailability of erlotinib in cancer patients.

Variants in the SLCO1B3 gene: interethnic distribution and association with paclitaxel pharmacokinetics.

To explore retrospectively the relationships between paclitaxel pharmacokinetics and three known, non-synonymous single-nucleotide polymorphisms (SNPs) in SLCO1B3, the gene encoding organic anion transporting polypeptide (OATP)1B3. Accumulation of [(3)H]paclitaxel was studied in Xenopus laevis oocytes injected with cRNA of Oatp1b2, OATP1A2, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, and NTCP. The 334T>G (Ser112Ala), 699G>A (Met233Ile), and 1564G>T (Gly522Cys) loci of SLCO1B3 were screened in 475 individuals from five ethnic groups and 90 European Caucasian cancer patients treated with paclitaxel. Only OATP1B3 was capable of transporting paclitaxel to a significant extent (P=0.003). The 334T>G and 699G>A SNPs were less common in the African-American and Ghanaian populations (P<0.000001). Paclitaxel pharmacokinetics were not associated with the studied SNPs or haplotypes (P>0.3). The studied SNPs in SLCO1B3 appear to play a limited role in the disposition of paclitaxel, although their clinical significance in other ethnic populations remains to be investigated.

Preclinical pharmacokinetics and metabolism of a novel prototype DNA-PK inhibitor NU7026.

In this study we investigated the in vitro time dependence of radiosensitisation, pharmacokinetics and metabolism of NU7026, a novel inhibitor of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). At a dose of 10 muM, which is nontoxic to cells per se, a minimum NU7026 exposure of 4 h in combination with 3 Gy radiation is required for a significant radiosensitisation effect in CH1 human ovarian cancer cells. Following intravenous administration to mice at 5 mg kg(-1), NU7026 underwent rapid plasma clearance (0.108 l h(-1)) and this was largely attributed to extensive metabolism. Bioavailability following interperitoneal (i.p.) and p.o. administration at 20 mg kg(-1) was 20 and 15%, respectively. Investigation of NU7026 metabolism profiles in plasma and urine indicated that the compound undergoes multiple hydroxylations. A glucuronide conjugate of a bis-hydroxylated metabolite represented the major excretion product in urine. Identification of the major oxidation site as C-2 of the morpholine ring was confirmed by the fact that the plasma clearance of NU7107 (an analogue of NU7026 methylated at C-2 and C-6 of the morpholine ring) was four-fold slower than that of NU7026. The pharmacokinetic simulations performed predict that NU7026 will have to be administered four times per day at 100 mg kg(-1) i.p. in order to obtain the drug exposure required for radiosensitisation.

Evaluation of the cassette dosing approach for assessing the pharmacokinetics of geldanamycin analogues in mice.

PURPOSE: There is currently much interest in developing analogues of the benzoquinone ansamycin geldanamycin that may overcome the limitations of 17-(allylamino)-17-demethoxygeldanamycin (17AAG), which is the first known inhibitor of heat shock protein 90 (Hsp90) to enter clinical trials. Studies were performed to assess whether cassette dosing, the coadministration of several compounds to a single animal, is a suitable approach to evaluate the preclinical pharmacokinetics of geldanamycin analogues in high throughput. METHODS: Five geldanamycin analogues (17AAG, NSC 255110, NSC 682300, NSC 683661, NSC 683663) were administered intravenously to mice in combination at 5 mg/kg each and as single agents at 5 mg/kg and 50 mg/kg, or 12.5 mg/kg for NSC 682300. The compounds were also incubated with mouse liver microsomes individually and in combination at 15 microM each. Quantitative analysis was performed by LC/MS/MS. Plasma and tissue pharmacokinetic parameters were evaluated by non-compartmental analysis. In vitro metabolic stability was assessed by monitoring disappearance of the parent compound. RESULTS: Of the compounds that were detectable following individual administration at 5 mg/kg, 17AAG and NSC 683661 exhibited nonlinear pharmacokinetics. In addition, the plasma area under the curve (AUC) and the half-life of these compounds was greater following cassette dosing at 5 mg/kg compared to single administration at the same dose. When pharmacokinetic parameters were calculated up to the same time point following cassette and individual administration at the higher dose, three of the compounds displayed non-linear increases in AUC and slower clearances following cassette compared to single compound dosing. When all measurable concentrations at the higher dose were included, the half-life of NSC 683663 was nine-fold longer following individual compared to cassette administration. 17AAG displayed the highest AUC following cassette dosing, whereas NSC 683663 displayed the highest AUC following single-compound dosing. Excluding NSC 683663, the rank order from the highest to the lowest AUC was the same; however, NSC 682300, which ranked fifth, was administered at a four-fold lower individual dose than the other compounds. Exposure of the liver and kidneys to the compounds was greater than that of plasma. Despite being administered at a lower dose, NSC 682300 displayed the highest kidney AUC of the five compounds. The same ranking was maintained between cassette and single compound dosing in the kidney. With the exception of NSC 682300, in vitro metabolic stability was predictive of in vivo pharmacokinetics in the plasma and liver. The extent of metabolism of four of the five compounds was lower following microsomal incubation in combination compared to incubation alone, suggestive of likely drug-drug interaction in the cassette. However, for 17AAG this may be partly due to metabolism of NSC 683661 and NSC 683663 to this compound. CONCLUSIONS: Whilst cassette dosing has advantages for use in drug discovery, it is probably unsuitable to evaluate the pharmacokinetics of geldanamycin analogues due to non-linear pharmacokinetics and drug-drug interaction. The issues identified for this compound series should also be considered in assessing the suitability of cassette dosing for other chemotypes.

Stages of acquisition and cessation for adolescent smoking: an empirical integration.

Adolescent cigarette smoking acquisition and cessation were integrated into a single nine-stages-of-change continuum using the transtheoretical model of change framework. Findings in a high school student sample (n > 700) showed that a few of the never smokers were planning to try smoking, and half of the current smokers were contemplating quitting. More than half of former smokers were long-term quitters. The high pros of smoking scores assessing coping benefits of cigarettes were related to smoking acquisition and the high con (disadvantages) scores to long-term abstinence. Never smokers were most tempted to try smoking when they anticipated that smoking would help reduce negative and increase positive mood. Current and former smokers were tempted due to peer cigarette offers and negative mood. These temptations were significantly reduced among ex-smokers.

Computer-based smoking cessation interventions in adolescents: description, feasibility, and six-month follow-up findings.

The impact of adolescent smoking cessation clinics has been disappointing due to low participation rates, high attrition, and low quit rates. This paper describes two computerized self-help adolescent smoking cessation intervention programs: 1) a program utilizing the expert system which is based on the transtheoretical model of change and 2) a popular action-oriented smoking cessation clinic program for teens which was modified for computer presentation. High participation rates in the program among 132 smokers demonstrate the high feasibility and acceptability of the programs. Quit rates of up to 20% were observed during the intervention, and an additional 30% made unsuccessful quit attempt(s). The 6-month follow-up findings indicated that adolescents were poorly prepared to maintain abstinence.

A preliminary resolution of the retention of distributed vs massed response prevention in rats.

This study consisted of two experiments conducted to investigate the difference in efficacy and retention of distributed response prevention when compared to massed response prevention using an animal model of avoidance learning. The purpose was to obtain an estimate of the over-all treatment time for response prevention that begins to be affected by the treatment, either distributed or massed. In Exp. 1, 50 rats were given two trials of escape learning in a one-way black-white shuttle-box. Groups received response-prevention treatment or nontreatment in 9 1-min. distributed sessions or 1 9-min. massed session. Subjects were tested using a passive-avoidance paradigm immediately following treatment, 24 hours, and 720 hours (30 days) later. Analysis showed that with an over-all response-prevention time of 9 min., response-prevention treatment was effective in reducing avoidance behavior, that the effect was retained, and that there were no differences between distributed and massed groups. These results led to Exp. II in which 50 rats were exposed to the same training procedure as in Exp. I. These groups received response-prevention treatment or nontreatment in 12 15-sec. distributed sessions or one 3-min. massed session. Analysis of passive-avoidance testing immediately following treatment, 24 hr., and 720 hr. later showed that, when the over-all response-prevention time was 3 min., only groups with distributed treatment showed reduction of avoidance behavior and retention of the treatment effects. Since past studies have produced inconsistent findings in comparing distributed vs massed delivery of response-prevention treatment these two experiments are intended to serve as a preliminary resolution of the past differing results. When the over-all treatment time is longer than 3 min., there is no delivery of treatment effect. However, with 3 min. of over-all treatment time, distributed delivery was necessary to facilitate the treatment effects. Implications for animals and humans are discussed.

Retention of massed vs distributed response-prevention treatments in rats and a revised training procedure.

Two experiments were conducted to estimate the retention of response-prevention effects using massed vs distributed treatments in a model of animal avoidance-learning. In Exp. I, 120 rats were trained to avoid shock in a one-way platform avoidance apparatus. Groups received response-prevention treatment or nontreatment in a 36-min. massed session or in several sessions distributed over a four-day period. In Exp. II, 160 rats were given two trials of escape training in a one-way shuttle box. Groups received response-prevention treatment or nontreatment in a 24-min. session of massed or distributed treatments delivered in one day. Subjects in both studies were tested using a passive-avoidance paradigm immediately following treatment, 24 hours later, and 30 days later. Analysis showed that response-prevention treatments were effective in reducing avoidance behavior and there were no significant differences in retention of avoidance associated with massed vs distributed response-prevention treatments. Implications for animals and humans are discussed, and researchers are encouraged to change from a criterion training procedure to an escape procedure since the latter is a closer analogue to the human condition.

Circulatory and ionoregulatory effects of atrial natriuretic peptide on rainbow trout (Salmo gairdneri Richardson) fed normal or high levels of dietary salt.

Rainbow trout fed a normal salt diet (1.3% NaCl) or a high salt diet (12% NaCl for at least 6 months) were chronically cannulated in the dorsal aorta and received 10 µg kg(-1) ANP (1-28 human, UBC-Bioproducts) infused over a 10 min period. This had an insignificant influence on sodium balance, blood electrolytes and branchial sodium fluxes. In fish given a normal diet, the blood pressure and heart rate were uninfluenced by ANP, but pulse pressure was reduced by on average 60% and in some cases was not evident at all. Blood pressure in the fish fed a high salt diet was significantly higher than in the control fish; this together with heart rate and pulse pressure was not affected by ANP administration.

Rate-dependency and hyperactivity: methylphenidate effects on operant responding.

The two most common treatment for hyperactivity are psychopharmacological regimens and behavior therapy. Although the concurrent use of stimulant medication has been purported to enhance a child's rate of responding under a behavior management program, studies examining the interaction of the two treatments have been unable to confirm this hypothesis. The present investigation sought to examine the effects of differing levels of methylphenidate hydrochloride (Ritalin) upon operant responding with hyperactive children. After an initial drug-free training period, 10 first through fourth grade hyperactive males performed an operant key-pressing task under a mult VR 5 FI 30 sec reinforcement schedule across four randomly determined, double-blind drug conditions (placebo, 5, 10, 15 mg). Only VR responding changed significantly during medication conditions; however, rate-dependent psychostimulant effects were found within both reinforcement schedules. Discrepancies with animal rate-dependency and implications for treatment and future research are discussed. Medication effects on operant responding appear to depend upon the reinforcement schedule and dose employed.

Residual fear of the conditioned stimulus as a function of response prevention after avoidance or classical defensive conditioning in the rat.

Studies employing response prevention (RP) are reviewed. Considering assessment difficulties and conflicting findings, it is questionable whether RP actually reduces fear to a conditioned stimulus (CS). This study measured fear after RP via a conditioned emotional response (CER) paradigm. Hypotheses were that fear of an auditory CS (conditioned in an avoidance paradigm) is reduced during RP, and that fear conditioning would occur to aspects of the conditioning environment per se. Also evaluated was the effectiveness of RP when fear had been learned under two different conditions: (a) avoidance or (b) classical defensive conditioning. Seven groups of 10 experimentally naive female rats were run. Animals were initially trained to bar press for food pellets on a variable interval (VI) 2 schedule. Three groups were then avoidance trained in a two-way shuttle box to a criterion of 10 successive avoidances. Immediately following acquisition, one group received RP (blocking) in the shuttle box (Condition A-B). This consisted of placing a door between the two sides of the box and presenting the 85 dB (A) white noise CS for 15 20-sec periods with a variable 1-min interstimulus interval. One group did not receive RP (nonblocked) and was instead immediately returned to its home cage (Condition A-NBHC). The third group was treated as was A-B except the CS was not presented (Condition A-NBSB). Two other groups were trained in a classical defensive paradigm. These animals were matched to A-B animals in terms of number, order, and duration of CSs and USs. Following conditioning, one group received the same treatment as A-B (Condition CD-B), and the other received the same treatment as A-NBHC (Condition CD-NBHC). Two groups served as controls. A backward control (Condition BC-NBHC) was matched to A-NBHC in terms of number, order, and duration of CSs and USs. A sensitization control (Condition SC-NBHC) was matched to A-NBHC in terms of number, order, and duration of CS presentations. Immediately following conditioning trials, control animals received the same treatment as A-NBHC animals. After differential treatments all animals were immediately returned to the lever box in which they had learned to bar press, a VI 2 schedule was reinstated, and the CER was measured. A-B showed significant suppression initially but significantly less than A-NBHC, suggesting that although RP was effective in reducing fear to the CS, some fear remained. Controls showed essentially no suppression and did not differ. A-B did not differ from A-NBSB, suggesting that conditioning of fear did occur to the environment and that this fear was subsequently reduced in A-NBSB. A-B suppressed significantly more than CD-B, suggesting that RP was more effective when fear was learned in a classical as compared to an avoidance paradigm. Theoretical implications and generalizations to implosive therapy are discussed.

Ability of rats with ventromedial hypothalamic lesions to work: effects of ambient temperature.

Rats with bilateral ventromedial hypothalamic lesions decreased bar pressing at FR 64 at high ambient temperatures. No significant decrease was noted at low temperatures for VMH rats. Controls evidence no response suppression at any temperature. Pause time for the VMH rats at high temperatures suggest a VMH lesion-ambient temperature interaction.