Injury prevention among friends: the benefits of school connectedness.

Unsafe road behaviors, violence and alcohol use, are primary contributors to adolescent injury. Research suggests that adolescents look out for their friends and engage in protective behavior to reduce others' risk-taking and that school connectedness is associated with reduced injury-risks. This study examined the role of school connectedness in willingness to protect and prevent friends from involvement in alcohol use, fights and unlicensed driving. Surveys were completed at two time points, six months apart, by 545 13-14 year olds from seven Australian high schools. Females were significantly more likely than males to report willingness to protect their friends. School connectedness significantly and positively predicted willingness to protect across all three injury-risk behaviors, after accounting for sex and own involvement in injury-risk behaviors. School connectedness may therefore be an important factor to target in school-based prevention programs, both to reduce adolescents' own injury-risk behavior and to increase injury prevention among friends.

PROSPER: a randomised comparison of surgical treatments for rectal prolapse.

AIM: Rectal prolapse is a profoundly disabling condition, occurring mainly in elderly and parous women. There is no accepted standard surgical treatment, with previous studies limited in methodological quality and size. PROSPER aimed to address these deficiencies by comparing the relative merits of different procedures. METHOD: In a pragmatic, factorial (2 × 2) design trial, patients could be randomised between abdominal and perineal surgery (i), and suture vs resection rectopexy for those receiving an abdominal procedure (ii) or Altemeier's vs Delorme's for those receiving a perineal procedure (iii). Primary outcome measures were recurrence of the prolapse, incontinence, bowel function and quality of life scores (Vaizey, bowel thermometer and EQ-5D) measured up to 3 years. RESULTS: Two hundred and ninety-three patients were recruited: 49 were randomised between surgical approaches (i); 78 between abdominal procedures (ii); and 213 between perineal procedures (iii). Recurrence rates were higher than anticipated, but not significantly different in any comparison: Altemeier's vs Delorme's 24/102 (24%) and 31/99 (31%) [hazard ratio (HR) 0.81; 95% CI 0.47, 1.38; P = 0.4]; resection vs suture rectopexy 4/32 (13%) and 9/35 (26%) (HR 0.45; 95% CI 0.14, 1.46; P = 0.2); perineal vs abdominal 5/25 (20%) and 5/19 (26%) (HR 0.83; 95% CI 0.24, 2.86; P = 0.8). Vaizey, bowel thermometer and EQ-5D scores were not significantly different in any of the comparisons. CONCLUSION: No significant differences were seen in any of the randomised comparisons, although substantial improvements from baseline in quality of life were noted following all procedures.

Pilot evaluation of an adolescent risk and injury prevention programme incorporating curriculum and school connectedness components.

School connectedness is an important protective factor for adolescent risk-taking behaviour. This study examined a pilot version of the Skills for Preventing Injury in Youth (SPIY) programme, combining teacher professional development (PD) for increasing school connectedness (connectedness component) with a risk and injury prevention curriculum for early adolescents (curriculum component). A process evaluation was conducted on the connectedness component, involving assessments of programme reach, participant receptiveness and initial use, and a preliminary impact evaluation was conducted on the combined connectedness and curriculum programme. The connectedness component was well received by teacher participants, who saw benefits for both themselves and their students. Classroom observation also showed that teachers who received PD made use of the programme strategies. Grade 8 students who participated in the SPIY programme were less likely to report violent behaviour at 6-month follow-up than were control students, and trends also suggested reduced transport injuries. The results of this research support the use of the combined SPIY connectedness and curriculum components in a large-scale effectiveness trial to assess the impact of the programme on students' connectedness, risk-taking and associated injuries.

The use of conditioned place preference to determine broiler preferences for quantitative or qualitative dietary restriction.

1. Calcium propionate (CAP) may improve the welfare of feed restricted broiler breeders by improving their satiety when included within the feed ration. However, the evidence for this is mixed. 2. This study used a closed economy conditioned place preference (CPP) task and aimed to identify whether broilers (as a model for broiler breeders) preferred an environment associated with quantitative food restriction (QFR) or an environment associated with a diet quality-adjusted by the inclusion of CAP. Birds taught to associate different environments with QFR and ad libitum (AL) access to feed were used to validate the methodology. 3. The two treatment groups were (1) QFR/AL (n = 12) in which birds alternated every 2 d between QFR and ad libitum access to food, and (2) QFR/CAP (n = 12) in which birds alternated every 2 d between QFR and QFR + calcium propionate (increased from 3-9% over the study period). Birds were taught to associate one diet option with vertical stripes and the other with horizontal black and white stripes. Each bird was tested twice for a CPP (once per diet). 4. QFR/AL birds showed a significant preference for the pen associated with ad libitum access to feed, but only when tested hungry (i.e. fed QFR on day of testing). QFR/CAP birds did not show a preference under either hunger state. 5. Reasons for the failure of QFR/CAP birds to show a preference are unclear but could include a lack of preference or failure to learn the task. 6. The existence of state-dependent effects indicates that care is needed in the design of future CPP studies and that the effect of calcium propionate and level of hunger on ability to learn a CPP needs further investigation.

Altered monocyte cyclo-oxygenase response in non-obese diabetic mice.

Monocytes infiltrate islets in non-obese diabetic (NOD) mice. Activated monocyte/macrophages express cyclo-oxygenase-2 (COX-2) promoting prostaglandin-E(2) (PGE(2)) secretion, while COX-1 expression is constitutive. We investigated in female NOD mice: (i) natural history of monocyte COX expression basally and following lipopolysaccharide (LPS) stimulation; (ii) impact of COX-2 specific inhibitor (Vioxx) on PGE(2), insulitis and diabetes. CD11b(+) monocytes were analysed for COX mRNA expression from NOD (n = 48) and C57BL/6 control (n = 18) mice. NOD mice were treated with either Vioxx (total dose 80 mg/kg) (n = 29) or methylcellulose as control (n = 29) administered by gavage at 4 weeks until diabetes developed or age 30 weeks. In all groups, basal monocyte COX mRNA and PGE(2) secretion were normal, while following LPS, after 5 weeks of age monocyte/macrophage COX-1 mRNA decreased (P < 0.01) and COX-2 mRNA increased (P < 0.01). However, diabetic NOD mice had reduced COX mRNA response (P = 0.03). Vioxx administration influenced neither PGE(2), insulitis nor diabetes. We demonstrate an isoform switch in monocyte/macrophage COX mRNA expression following LPS, which is altered in diabetic NOD mice as in human diabetes. However, Vioxx failed to affect insulitis or diabetes. We conclude that monocyte responses are altered in diabetic NOD mice but COX-2 expression is unlikely to be critical to disease risk.

Epithelial ovarian cancer: role of pegylated liposomal Doxorubicin in prolonging the platinum-free interval and cancer antigen 125 trends during treatment.

BACKGROUND: Epithelial ovarian cancer's response to platinum retreatment depends on the duration of response to first-line platinum therapy. Platinum-free interval predicts subsequent platinum sensitivity and is a prognostic factor. Little has been published on the effect of pegylated liposomal doxorubicin (PLD) in the prolongation of treatment-free interval. METHODS: Patients treated with PLD were reviewed to assess response to platinum retreatment after PLD and to establish the use of cancer antigen 125 (Ca125) trends. All patients treated with PLD had progressed within 12 months of prior platinum therapy. Cancer antigen 125 fluctuations were categorized as the variances from the baseline (+/-10%, +/-10%-25%, and >25%). The response to chemotherapy was defined as Ca125 reduction from the baseline of more than 50%, clinical, or radiological response. RESULTS: Fifty-nine women were identified. The response rate (RR) to PLD was 28.9%, and the median overall survival from PLD initiation was 62 weeks. The number of women demonstrating more than 25% reduction in Ca125 from the baseline increased progressively with each cycle; at cycle 2, 11%; cycle 3, 18%; cycle 4, 22%; and cycle 5, 27% (trend significant between cycles 2 and 4, P = 0.004). Fifteen patients were re-treated with platinum after progression after PLD with 80% (12/15) of the patients responding. The RR to platinum retreatment after PLD compares favorably with the historical data on the response to second-line platinum retreatment. CONCLUSIONS: The sole use of early Ca125 trends in PLD treatment before cycle 4 may result in an erroneous discontinuation of PLD in potential responders. Retreatment with platinum after PLD may yield a good RR in selected patients even those with disease progression within 12 months after prior platinum treatment.

Prosthodontic rehabilitation of hypophosphatasia using dental implants: a review of the literature and two case reports.

There are reports in the literature of the various dental features of hypophosphatasia, especially where it affects the deciduous dentition. The descriptions include both the manifestations of the disorder and the subsequent patterns of tooth loss. There are fewer descriptions of the effects of hypophosphatasia on the permanent dentition and little information on the subsequent prosthodontic management of these patients, particularly in relation to the use of dental implants. The aim of this paper was to review the literature on the dental effects of hypophosphatasia, present two cases and describe how one of those patients, a young adult, was successfully rehabilitated using dental implants. That latter patient's pattern of tooth loss as well as some histological and scanning electron microscopic findings of root cementum from the other case is also described.

Radiotherapy dosimetry using a commercial OSL system.

A commercial optically stimulated luminescence (OSL) system developed for radiation protection dosimetry by Landauer, Inc., the InLight microStar reader, was tested for dosimetry procedures in radiotherapy. The system uses carbon-doped aluminum oxide, Al2O3:C, as a radiation detector material. Using this OSL system, a percent depth dose curve for 60Co gamma radiation was measured in solid water. Field size and SSD dependences of the detector response were also evaluated. The dose response relationship was investigated between 25 and 400 cGy. The decay of the response with time following irradiation and the energy dependence of the Al2O3:C OSL detectors were also measured. The results obtained using OSL dosimeters show good agreement with ionization chamber and diode measurements carried out under the same conditions. Reproducibility studies show that the response of the OSL system to repeated exposures is 2.5% (1sd), indicating a real possibility of applying the Landauer OSL commercial system for radiotherapy dosimetric procedures.

Selective axillary node sampling and radiotherapy to the axilla in the management of breast cancer.

AIMS: Axillary treatment for patients with early-stage breast cancer can be associated with considerable morbidity. Techniques, such as axillary node sampling (ANS) and, more recently, sentinel node biopsy, in combination with radiotherapy have the potential to reduce toxicity. A retrospective review of axillary treatment in patients with early-stage breast cancer treated at our institution between 1997 and 2003 was carried out to assess the outcome and morbidity of ANS in combination with radiotherapy. MATERIALS AND METHODS: The treatment policy was to carry out four-node, Edinburgh-style ANS except in those cases with either palpably enlarged nodes or cytological confirmation of involvement or with clinically obvious node involvement at surgery when level 2 axillary node clearance (ANC) was carried out. Patients with involved nodes after ANS received postoperative axillary radiotherapy. RESULTS: In total, 381 patients were included, 331 received ANS and 50 received ANC. The median follow-up was 6.5 years and overall survival at 5 years was 84%. Pathologically involved nodes were found in 152/331 (50%) ANS patients and 43/50 (86%) ANC patients. The rate of local recurrence (breast or chest wall) at 5 years was 4% (95% confidence interval 1-17%) in the ANC group and 2% (95% confidence interval 1-4%) in the ANS group. The nodal recurrence rate of those undergoing ANS was 3% (11/331) compared with 6% (3/50) for those treated by ANC. The rate of clinically significant lymphoedema at 5 years was significantly higher (P=0.01) in the ANC arm: 18% (95% confidence interval 9-32%) compared with 5% (95% confidence interval 3-8%) in those treated by ANS. Thirty-one cases received additional supraclavicular fossa irradiation because of the involvement of more than four nodes on ANS, which may not have been available with sentinel node biopsy and has implications for current practice. CONCLUSIONS: Selective ANS with the removal of a minimum of four nodes guides optimal locoregional treatment with good local control rates, low overall morbidity and may obviate the need for a second surgical procedure.

Nonclinical aspects of biopharmaceutical development: discussion of case studies at a PhRMA-FDA workshop.

Robust assessments of the nonclinical safety profile of biopharmaceuticals are best developed on a scientifically justified, case-by-case basis, with consideration of the therapeutic molecule, molecular target, and differences/similarities between nonclinical species and humans (ICH S6). Significant experience has been gained in the 10 years ensuing since publication of the ICH S6 guidance. In a PhRMA-FDA-sponsored workshop, "Nonclinical Aspects of Biopharmaceutical Development," industry and US regulatory representatives engaged in exploration of current scientific and regulatory issues relating to the nonclinical development of biopharmaceuticals in order to share scientific learning and experience and to work towards establishing consistency in application of general principles and approaches. The proceedings and discussions of this workshop confirm general alignment of strategy and tactics in development of biopharmaceuticals with regard to such areas as species selection, selection of high doses in toxicology studies, selection of clinical doses, the conduct of developmental and reproductive toxicity (DART) studies, and assessment of carcinogenic potential. However, several important aspects, including, for example, appropriate use of homologues, nonhuman primates, and/or in vitro models in the assessment of risk for potential developmental and carcinogenic effects, were identified as requiring further scientific exploration and discussion.

Supportive therapy for schizophrenia.

BACKGROUND: Supportive therapy is often used in everyday clinical care and in evaluative studies of other treatments. OBJECTIVES: To estimate the effects of supportive therapy for people with schizophrenia. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register of trials (January 2004), supplemented by manual reference searching and contact with authors of relevant reviews or studies. SELECTION CRITERIA: All randomised trials involving people with schizophrenia and comparing supportive therapy with any other treatment or standard care. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated these and extracted data. For dichotomous data, we estimated the relative risk (RR) fixed effect with 95% confidence intervals (CI). Where possible, we undertook intention-to-treat analyses. For statistically significant results, we calculated the number needed to treat/harm (NNT/H). We estimated heterogeneity (I-square technique) and publication bias. MAIN RESULTS: We included 21 relevant studies. We found no significant differences in the primary outcomes between supportive therapy and standard care. There were, however, significant differences favouring other psychological or psychosocial treatments over supportive therapy. These included hospitalisation rates (3 RCTs, n=241, RR 2.12 CI 1.2 to 3.6, NNT 8) but not relapse rates (5 RCTs, n=270, RR 1.18 CI 0.9 to 1.5). We found that the results for general functioning significantly favoured cognitive behavioural therapy compared with supportive therapy in the short (1 RCT, n=70, WMD -9.50 CI -16.1 to -2.9), medium (1 RCT, n=67, WMD -12.6 CI -19.4 to -5.8) and long term (2 RCTs, n=78, SMD -0.50 CI -1.0 to -0.04), but the clinical significance of these findings based on few data is unclear. Participants were less likely to be satisfied with care if receiving supportive therapy compared with cognitive behavioural treatment (1 RCT, n=45, RR 3.19 CI 1.0 to 10.1, NNT 4 CI 2 to 736). The results for mental state and symptoms were unclear in the comparisons with other therapies. No data were available to assess the impact of supportive therapy on engagement with structured activities. AUTHORS' CONCLUSIONS: There are insufficient data to identify a difference in outcome between supportive therapy and standard care. There are several outcomes, including hospitalisation and general mental state, indicating advantages for other psychological therapies over supportive therapy but these findings are based on a few small studies. Future research would benefit from larger trials that use supportive therapy as the main treatment arm rather than the comparator.

Supportive therapy for schizophrenia.

BACKGROUND: Supportive therapy is often used in everyday clinical care and in evaluative studies of other treatments. OBJECTIVES: To estimate the effects of supportive therapy for people with schizophrenia. SEARCH STRATEGY: We searched the Cochrane Schizophrenia Group's register of trials (January 2004), supplemented by manual reference searching and contact with authors of relevant reviews or studies. SELECTION CRITERIA: All randomised trials involving people with schizophrenia and comparing supportive therapy with any other treatment or standard care. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated these and extracted data. For dichotomous data, we estimated the relative risk (RR) fixed effect with 95% confidence intervals (CI). Where possible, we undertook intention-to-treat analyses. For statistically significant results, we calculated the number needed to treat/harm (NNT/H). We estimated heterogeneity (I-square technique) and publication bias. MAIN RESULTS: We included 21 relevant studies. We found no significant differences in the primary outcomes between supportive therapy and standard care. There were, however, significant differences favouring other psychological or psychosocial treatments over supportive therapy. These included hospitalisation rates (3 RCTs, n=241, RR 2.12 CI 1.2 to 3.6, NNT 8) but not relapse rates (5 RCTs, n=270, RR 1.18 CI 0.9 to 1.5). We found that the results for general functioning significantly favoured cognitive behavioural therapy compared with supportive therapy in the short (1 RCT, n=70, WMD -9.50 CI -16.1 to -2.9), medium (1 RCT, n=67, WMD -12.6 CI -19.4 to -5.8) and long term (2 RCTs, n=78, SMD -0.50 CI -1.0 to -0.04), but the clinical significance of these findings based on few data is unclear. Participants were less likely to be satisfied with care if receiving supportive therapy compared with cognitive behavioural treatment (1 RCT, n=45, RR 3.19 CI 1.0 to 10.1, NNT 4 CI 2 to 736). The results for mental state and symptoms were unclear in the comparisons with other therapies. No data were available to assess the impact of supportive therapy on engagement with structured activities. AUTHORS' CONCLUSIONS: There are insufficient data to identify a difference in outcome between supportive therapy and standard care. There are several outcomes, including hospitalisation and general mental state, indicating advantages for other psychological therapies over supportive therapy but these findings are based on a few small studies. Future research would benefit from larger trials that use supportive therapy as the main treatment arm rather than the comparator.

Carcinogenicity of 2',3'-dideoxycytidine in mice.

2',3'-dideoxycytidine (ddC) is a synthetic pyrimidine nucleoside analogue approved for treatment of HIV-positive patients. Previous studies indicated that ddC has the potential to cause thymic lymphoma in C57BL/6 x C3H F1 (hereafter called B6C3F1) mice. In this study, we evaluated the carcinogenic potential of ddC in two different mouse models. B6C3F1 hybrid mice carry ecotropic endogenous proviral sequences that may be activated to cause lymphoma, whereas NIH Swiss mice lack proviral sequences that can be expressed. The mice were treated with ddC by gavage at 500 and 1000 mg/kg/day for up to 6 months (human dose, 2.25 mg/day) and evaluated for toxicity, plasma levels of ddC, and pathological changes. Lymphocyte cell markers from the thymic lymphomas were assessed by immunophenotyping. Expression of p53 protein was evaluated using immunohistochemical staining. Treatment-related thymic lymphomas were present in both mouse models with a higher incidence in NIH Swiss than in B6C3F1 mice. The lymphomas were more prevalent in females than in males of both mouse models. Most mice with thymic lymphoma died during the course of the study. In addition to the thymus, lymphoma was often present in lymph nodes, spleen, and other organs. Lymphomas arose more frequently in mice that lack endogenous ecotropic retroviral sequences and thus were not due to activation of endogenous provirus. During the third month of the study, a few NIH Swiss mice that died had granulosa cell tumors of the ovary. Treatment-related but reversible thymic atrophy was observed in both mouse models. There was a very high correlation between the internal dose of ddC and the incidence of thymic lymphoma in both mouse models. Most of the lymphocytes from control thymuses and ddC-induced lymphomas were positive for Thy-1.2 (pan-T), heat stable antigen, and CD4 and CD8 markers, with no marked differences in the lymphocyte markers of the tumors between sexes or dose groups. p53 protein was detected in only 20% (23/115) of the ddC-induced lymphomas with mostly minimal expression in scattered cells. Because ddC induced lymphomas in two different mouse models, the potential carcinogenic risk should be considered in long-term treatment of HIV-positive patients, especially children and adolescent patients treated with ddC.

Presentation, clinical pathological and post-mortem findings in three related Scottish terriers with ligneous membranitis.

Ligneous conjunctivitis and gingivitis were diagnosed in three related Scottish terrier dogs presented for investigation of severe conjunctivitis and respiratory signs. Hypoplasminogenaemia was confirmed in one of the three affected dogs. Supportive treatment was not effective, and the dogs died or were euthanased because of the disease. Post-mortem analysis of two of the dogs revealed multiple abnormalities including severe proliferative fibrinous lesions affecting the conjunctiva, gingiva, trachea, larynx and epicardium and multiple fibrous adhesions throughout the thoracic and abdominal cavities. One dog had internal hydrocephalus and lacked a cerebellar vermis. Ligneous membranitis was confirmed on histopathology. This is a rare condition in dogs but an important differential diagnosis for severe conjunctivitis and gingivitis.

Tamoxifen and cardiac risk factors in healthy women: Suggestion of an anti-inflammatory effect.

-Tamoxifen reduces the incidence of breast cancer in women at risk for that disease. Because heart disease is the leading cause of death in women and because tamoxifen is also associated with venous thrombosis, an improved understanding of the association of tamoxifen with cardiovascular disease risk factors is required. In 111 healthy women at a single center, who were participating in a randomized double-blind breast cancer prevention trial, the 6-month effects of oral tamoxifen (20 mg/d) compared with placebo on factors related to inflammation, hemostasis, and lipids were studied. Tamoxifen was associated with reductions of 26% in median C-reactive protein, 22% in median fibrinogen, and 9% in cholesterol (all P:<0.01 compared with placebo). There were no differences in treatment effects on factor VII coagulant activity, fragment 1-2, and triglycerides. In secondary analyses, the effect of tamoxifen on C-reactive protein was larger in postmenopausal women and in women with higher waist-to-hip ratios. The effect on fibrinogen was larger in women with higher baseline cholesterol. Tamoxifen demonstrated effects on inflammatory markers that were consistent with reduced cardiovascular risk. These findings are in contrast to recent reports of increased C-reactive protein associated with postmenopausal estrogen. The potential for beneficial cardiovascular effects of tamoxifen in healthy women is suggested.

Attitudes of clinical faculty about career progress, career success and recognition, and commitment to academic medicine. Results of a survey.

OBJECTIVE: To assess attitudes about career progress, resources for career development, and commitment to academic medicine in physician faculty at an academic medical center who spend more than 50% of their time in clinical care. DESIGN: Faculty survey. SETTING: Academic medical center and associated Veterans Affairs medical center. RESULTS: A total of 310 physician faculty responded to the survey. Half of the faculty reported spending 50% or less of their time in clinical care (mean, 31% of time) (group 1) and half reported spending more than 50% of their time in clinical care (mean, 72% of time) (group 2). Group 2 faculty had one third of the time for scholarly activities, reported slower career progress, and were less likely to be at the rank of professor (40% and 16% for groups 1 and 2, respectively; P<.001) or to be tenured (52% and 26%, respectively; P<.001) despite similar age and years on faculty. Group 2 faculty were 50% more likely to report that tenure and promotion criteria were not reviewed at their annual progress report (P =.003) and that they did not understand the criteria (P<.001). Group 2 faculty valued excellence in patient care over scholarship and national visibility. Group 2 faculty reported greater dissatisfaction with academic medicine and less commitment to a career in academic medicine. CONCLUSIONS: Physician faculty who spend more than 50% of their time in clinical care have less time, mentoring, and resources needed for development of an academic career. These obstacles plus differences in their attitudes about career success and recognition contribute to significant differences in promotion. These factors are associated with greater dissatisfaction with academic medicine and lower commitment to academic careers.

Ehlers-Danlos syndrome associated with fatal spontaneous vascular rupture in a dog.

A 7-month-old male cross breed dog was presented with hyperextensible skin and atrophic scarring. A diagnosis of Ehlers-Danlos syndrome was made based on clinical signs, histopathology and electron microscopy. Two weeks after presentation, the dog died suddenly. Post-mortem examination revealed haemothorax and rupture of the left subclavian artery. Histological findings, including Goldner's modified Masson's trichrome staining and transmission electron microscopy of the subclavian artery, revealed abnormalities in the structure and arrangement of collagen fibrils, suggesting that the defective collagen formation extended to the vasculature. To the authors' knowledge, this is the first report of Ehlers-Danlos syndrome with vascular involvement in animals.

GHS-R1A antagonism reduces alcohol but not sucrose preference in prairie voles.

RATIONALE: Ghrelin has been shown to mediate food and drug reward in rats and mice, and the rewarding properties of sweet foods and alcohol are known to contribute to overconsumption of these substances. OBJECTIVE: To investigate the effects of GHS-R1A antagonism in a novel animal model of high alcohol consumption, the prairie vole, and to characterize the role of ghrelin in limited access consumption of a drug (alcohol) and non-drug (sucrose) reward. METHODS: Female prairie voles were given four 2-h two-bottle drinking sessions, occurring every other day. During drinking sessions, animals had access to 20% ethanol vs water or 10% sucrose vs water. Pre-treatment with the GHS-R1A antagonist JMV 2959 (i.p.; 0.0, 9.0mg/kg Experiments 1 and 2; 0.0, 9.0, 12.0mg/kg Experiments 3 and 4.) occurred 30-min before the fourth session. To determine if the amount of exposure to sucrose sessions affected the efficacy of JMV 2959, in Experiment 5 animals were given 16 daily 2-hr drinking sessions with 10% sucrose vs water. JMV 2959 treatment (0.0 or 9.0mg/kg) occurred 30-min prior to the 16th session. RESULTS: JMV 2959 reduced alcohol but not sucrose preference. Even after extended experience with sucrose sessions, JMV 2959 had no effect on sucrose preference or consumption. CONCLUSION: These findings demonstrate that GHS-R1A antagonism reduces alcohol preference, but suggest limitations on the role of ghrelin in the preference for and consumption of naturally rewarding substances.

DNA phylogeny of the marsupial wolf resolved.

The phylogenetic position of the recently extinct marsupial 'wolf', or thylacine (Thylacinus cynocephalus), has been a source of contention in mammalian systematics for nearly a century. Thylacines were endemic to Australasia, but possessed striking anatomical similarities to Oligo-Miocene borhyaenid marsupials of South America. At issue has been whether these features are indicative of common ancestry or convergent adaptation to carnivory. Recent morphological studies have supported both conclusions. Although current marsupial classifications group thylacines with Australian dasyuromorphians, this putative clade is characterized by mostly primitive morphological features. Attempts to determine thylacine affinities with ancient protein and DNA analyses have supported, but not resolved, a dasyuromorphian placement. We report 1546 bp of mitochondrial DNA sequence (from cytochrome b and 12S rRNA genes) and 841 bp of nuclear protamine gene sequence from the thylacine and representatives of all or most other marsupial orders. Phylogenetic analysis of these sequences shows unambiguously that thylacines are members of Dasyuromorphia, and suggests a late Oligocene or very early Miocene divergence of familial lineages.