The Structure of VOPc on Cu(111): Does V=O Point Up, or Down, or Both?

The local structure of the nonplanar phthalocyanine, vanadyl phthalocyanine (VOPc), adsorbed on Cu(111) at a coverage of approximately one-half of a saturated molecular layer, has been investigated by a combination of normal-incidence X-ray standing waves (NIXSW), scanned-energy mode photoelectron diffraction (PhD), and density-functional theory (DFT), complemented by scanning tunnelling microscopy (STM). Qualitative assessment of the NIXSW data clearly shows that both "up" and "down" orientations of the molecule (with V=O pointing out of, and into, the surface) must coexist on the surface. O 1s PhD proves to be inconclusive regarding the molecular orientation. DFT calculations, using two different dispersion correction schemes, show good quantitative agreement with the NIXSW structural results for equal co-occupation of the two different molecular orientations and clearly favor the many body dispersion (MBD) method to deal with long-range dispersion forces. The calculated relative adsorption energies of the differently oriented molecules at the lowest coverage show a strong preference for the "up" orientation, but at higher local coverages, this energetic difference decreases, and mixed orientation phases are almost energetically equivalent to pure "up"-oriented phases. DFT-based Tersoff-Hamann simulations of STM topographs for the two orientations cast some light on the extent to which such images provide a reliable guide to molecular orientation.

Re-evaluating how charge transfer modifies the conformation of adsorbed molecules.

The archetypal electron acceptor molecule, TCNQ, is generally believed to become bent into an inverted bowl shape upon adsorption on the coinage metal surfaces on which it becomes negatively charged. New quantitative experimental structural measurements show that this is not the case for TCNQ on Ag(111). DFT calculations show that the inclusion of dispersion force corrections reduces not only the molecule-substrate layer spacing but also the degree of predicted molecular bonding. However, complete agreement between experimentally-determined and theoretically-predicted structural parameters is only achieved with the inclusion of Ag adatoms into the molecular layer, which is also the energetically favoured configuration. The results highlight the need for both experimental and theoretical quantitative structural methods to reliably understand similar metal-organic interfaces and highlight the need to re-evaluate some previously-investigated systems.

Probing the interplay between geometric and electronic structure in a two-dimensional K-TCNQ charge transfer network.

Scanning tunnelling microscopy (STM), low energy electron diffraction (LEED), ultraviolet and soft X-ray photoelectron spectroscopy (UPS and SXPS) have been used to characterise the formation of a coadsorption phase of TCNQ and K on Ag(111), while the normal incident X-ray standing waves (NIXSW) technique has been used to obtain quantitative structural information. STM and LEED show that an ordered incommensurate phase is formed in which the K atoms are surrounded by four TCNQ molecules in a 'windmill' motif, characteristic of other metal/TCNQ phases, in which the nominal TCNQ : K stoichiometry is 1 : 1. UPS and SXPS data indicate the TCNQ is in a negatively-charged state. NIXSW results show that the carbon core of the TCNQ is essentially planar at a height above the Ag(111) surface closely similar to that found without coadsorbed K. In the presence of TCNQ the height of the K ions above the surface is significantly larger than on clean Ag(111), and the ions occupy sites above 'holes' in the TCNQ network. NIXSW data also show that the N atoms in the molecules must occupy sites with at least two different heights above the surface, which can be reconciled by a tilt or twist of the TCNQ molecules, broadly similar to the geometry that occurs in bulk TCNQ/K crystals.

A randomized double-blind placebo-controlled cross-over trial of the impact on quality of life of continuing dexamethasone beyond 24 h following adjuvant chemotherapy for breast cancer.

Uncertainty remains about the optimal anti-emetic regimen for control of delayed nausea and vomiting after adjuvant chemotherapy for breast cancer. Many patients receive dexamethasone but complain of insomnia, anxiety/agitation, and indigestion. The aim was to determine if patients receiving chemotherapy for breast cancer prefer treatment with dexamethasone or placebo for prophylaxis against delayed nausea and vomiting, and to compare quality of life (QOL) between the two treatments. In this randomized, double-blind, cross-over trial, we compared oral dexamethasone (4 mg twice daily for 2 days) versus placebo for chemotherapy-naïve patients with breast cancer. All patients received intravenous granisetron and dexamethasone pre-chemotherapy and oral granisetron on day 2. Primary endpoints were: (i) patient preference; (ii) difference between cycles in change of QOL from days 1 to 8. Median age of the 94 women was 51 years (range 27-76): 79 received fluorouracil/epirubicin/cyclophosphamide and 15 received doxorubicin/cyclophosphamide. Thirteen withdrew pre-cycle 2 with no differences between arms. Of 80 patients stating a preference, 31 preferred placebo (39 %, 95 % CI: 28-50 %) and 37 (46 %, 95 % CI: 35-58 %) preferred dexamethasone; 12 had no preference. There were no differences in intensity of vomiting, nausea, or time to onset of vomiting. There was greater decrease in global QOL (p = 0.06) when patients received dexamethasone. No other symptom/QOL domains differed significantly. In conclusion, no significant difference was found in patient preference, QOL, or symptoms regardless of whether dexamethasone or placebo was used after adjuvant chemotherapy.

Chemotherapy-and cancer-related nausea and vomiting.

Approximately one half of cancer patients will experience nausea or vomiting during the course of their disease either because of the cancer itself or because of their treatment. Emesis attributable to cancer warrants a careful investigation to determine whether a treatable underlying cause is responsible. Interventions using dexamethasone and octreotide may reduce vomiting attributable to bowel obstruction. In the absence of a bowel obstruction or a correctable cause, the usual approach is a sequential trial of antiemetics guided by considerations of cost and side effects.Major progress in managing chemotherapy-induced emesis followed from the use of a combination of a corticosteroid and 5-hydroxytryptamine(3) (5-HT(3)) receptor antagonist for moderately to highly emetogenic chemotherapy. Nevertheless, vomiting still occurred in approximately 40% of women receiving chemotherapy containing an anthracycline plus cyclophosphamide and in approximately 50% of patients receiving high-dose cisplatin. The addition of aprepitant, a neurokinin 1 receptor antagonist, improved control of emesis by a further 15%-20%, and that agent is now recommended as part of standard antiemetic therapy for patients at high risk of emesis. Based largely on anecdotal experience, cannabinoids and olanzapine are sometimes also recommended in patients with refractory emesis. Phase III trials are required to confirm their efficacy as add-ons to a corticosteroid, a 5-HT(3) receptor antagonist, and possibly aprepitant.

Implementing evidence based antiemetic guidelines in the oncology setting: results of a 4-month prospective intervention study.

There is a considerable gap between obtaining results in randomized trials and implementing them into practice. This is particularly relevant with the high-cost 5HT3 antiemetics, which include ondansetron, dolasetron and granisetron. Randomized trial data suggests that they should be used as a single daily dose during only the first 24 h of chemotherapy because they offer little benefit over less costly agents beyond this period. In this study, six intervention methods (i.e. multifaceted approach) were combined to change physicians' 5HT3 prescribing patterns to comply with evidence-based antiemetic guidelines. A six-step implementation process was adopted, consisting of guideline dissemination, the use of opinion leaders, interactive educational workshops, therapeutic reminders in the form of preprinted orders, clinical interventions by pharmacists for the event of inappropriate antiemetic orders, and physician audit and feedback. Once implemented, the control of emesis was collected in all patients who were enrolled in the intervention program. Multivariable regression analysis was then used to assess whether prescribing within antiemetic guidelines compromised patient care. A total of 195 inpatients were enrolled in the study over the 4-month intervention period. Overall, 88.7% of granisetron prescriptions fulfilled the guidelines with respect to appropriate indication, dosage, and duration of therapy. The multivariable analysis suggested that granisetron prescribing within guidelines did not compromise the control of acute and delayed emesis. In addition, patients who received evidence-based antiemetic therapy experienced a significant reduction in the severity of acute nausea [risk ratio (RR) = 0.69; P=0.03]. The results of this guideline implementation study revealed that a pharmacist-driven multifaceted intervention program for such high-cost agents as 5HT3 antiemetics can promote their use in a clinically appropriate manner and can save unnecessary drug costs without compromising the quality of patient care.

Randomized trial of intensive cyclophosphamide, epirubicin, and fluorouracil chemotherapy compared with cyclophosphamide, methotrexate, and fluorouracil in premenopausal women with node-positive breast cancer. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To determine the relative efficacy of an intensive cyclophosphamide, epirubicin, and fluorouracil (CEF) adjuvant chemotherapy regimen compared with cyclophosphamide, methotrexate, and fluorouracil (CMF) in node-positive breast cancer. PATIENTS AND METHODS: Premenopausal women with node-positive breast cancer were randomly allocated to receive either cyclophosphamide 100 mg/m2 orally days 1 through 14; methotrexate 40 mg/m2 intravenously (i.v.) days 1 and 8; and fluorouracil 600 mg/m2 i.v. days 1 and 8 or cyclophosphomide 75 mg/m2 orally days 1 through 14; epirubicin 60 mg/m2 i.v. days 1 and 8; and fluorouracil 500 mg/m2 i.v. days 1 and 8. Each cycle was administered monthly for 6 months. Patients administered CEF received antibiotic prophylaxis with cotrimoxazole two tablets twice a day for the duration of chemotherapy. RESULTS: The median follow-up was 59 months. One hundred sixty-nine of the 359 CMF patients developed recurrence compared with 132 of the 351 CEF patients. The corresponding 5-year relapse-free survival rates were 53% and 63%, respectively (P = .009). One hundred seven CMF patients died compared with 85 CEF patients. The corresponding 5-year actuarial survival rates were 70% and 77%, respectively (P = .03). The rate of hospitalization for febrile neutropenia was 1.1% in the CMF group compared with 8.5% in the CEF group. There was one case of congestive heart failure in a patient who received CMF compared with none in the CEF group. Acute leukemia occurred in five patients in the CEF group. CONCLUSION: The results of this trial show the superiority of CEF over CMF in terms of both disease-free and overall survival in premenopausal women with axillary node-positive breast cancer.

Rural youth: HIV/STD knowledge levels and sources of information.

Though it is recognised that a sound knowledge of HIV/STD transmission is insufficient on its own to ensure that young people practise safer sex, knowledge of this sort is a necessary prerequisite to safe sex behaviours. Research on the HIV/STD knowledge levels of young people has shown that, while they have high levels of HIV knowledge, they generally have little idea about the transmission of other STDs. Moreover, most of this research has been conducted with more accessible youth in large urban centres. The research reported in this paper focused on HIV/STD knowledge levels, awareness of safe and unsafe sexual practices, and the information sources accessed by 1168 young people living in small rural towns in Queensland, Tasmania and Victoria. As with mainstream youth, the participants in this study had high levels of HIV knowledge and very low levels of knowledge about the transmission of other STDs, their names and symptoms. Practical knowledge of the safety of sexual practices was good, although a number of students confused high risk practices with high risk groups. Students mainly accessed informal information sources such as parents, peers and magazines and took little advantage of more formal sources even when they were available in their towns. There were few gender differences in levels of knowledge; however, girls accessed more information sources and knew more names of STDs. The implications of these findings are discussed in relation to young people developing critical attitudes towards more informal sources, and the better use of more formal sources.

Consensus proposal for 5HT3 antagonists in the prevention of acute emesis related to highly emetogenic chemotherapy. Dose, schedule, and route of administration.

Selective antagonists to the Type 3 serotonin receptor (5HT3) in combination with corticosteroids are now considered the standard of care for the prevention of emesis from moderately to highly emetogenic chemotherapy. Here we address issues of optimal dose, schedule and route of administration of four currently available selectable 5HT3 antagonists. This paper utilizes an evidence based medicine approach to the literature regarding this class of drugs, emphasizing the results large, randomized, controlled trials to make formal recommendations concerning optimal use of this important new class of anti-emetic agents. We conclude that for each drug there is a plateau in therapeutic efficacy at a definable dose level above which further dose escalation does not improve outcome. Furthermore, a single dose is as effective as multiple doses or continuous infusion, and finally, emerging data demonstrate that the oral route is equally efficacious as the intravenous route of administration, even with highly emetogenic chemotherapy.

Phase II study of dexverapamil plus anthracycline in patients with metastatic breast cancer who have progressed on the same anthracycline regimen.

The purpose of this study is to evaluate whether metastatic breast cancer that has progressed on an anthracycline-containing drug regimen will subsequently respond to that identical regimen if dexverapamil, a modulator of P-glycoprotein-mediated drug resistance, is given concomitantly. Eligible patients received 180 mg/m2 dexverapamil every 6 h for 15 doses with the anthracycline administered 30 min after the seventh dose. Blood for dexverapamil levels was drawn before and 30 min after this dose. When possible, biopsies were obtained to measure mdr-1 expression by reverse transcription-PCR and by image cytometry. Of the 21 patients entered onto the trial, 20 were evaluable for response. There were two partial responses (10%) that both lasted for 6 months, and two additional patients had stable disease. Seven patients had asymptomatic cardiotoxicity consisting of hypotension (24%), bradycardia (5%), or prolongation of the P-R interval (14%). Two patients developed acute congestive heart failure, one on dexverapamil and one 10 days after stopping it. Dexverapamil did not seem to increase anthracycline toxicity. The median trough dexverapamil plus norverapamil level on day 3 was 1110 ng/ml (range, 186-3385 ng/ml), and the median peak level was 2164 ng/ml (range, 964-8382 ng/ml). There was poor correlation between reverse transcription-PCR and image cytometry for the level of mdr-1 expression. Because dexverapamil has been shown to affect doxorubicin pharmacokinetics subsequent to the initiation of this trial, it cannot be concluded that the responses seen were necessarily due to P-glycoprotein inhibition. Additional studies are necessary to determine whether mdr-1 modulators can reverse clinical drug resistance in breast cancer patients. The intrinsic cardiotoxicity of dexverapamil makes it less suitable for such studies than several other available agents.

Use of dexamethasone and granisetron in the control of delayed emesis for patients who receive highly emetogenic chemotherapy. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To evaluate the roles of granisetron and dexamethasone for emesis control on days 2 through 7 after the administration of cisplatin in doses of 50 mg/m2 or greater to patients who had not previously received chemotherapy. PATIENTS AND METHODS: Four hundred thirty-five eligible and assessable patients were randomized to one of two arms in a double-blind fashion: arm A; granisetron 3 mg intravenous (i.v.) plus dexamethasone 10 mg i.v. prechemotherapy followed by granisetron 1 mg orally at 6 and 12 hours, then granisetron 1 mg orally and dexamethasone 8 mg orally twice daily on days 2 through 7 (219 patients); arm B; as in arm A but with placebo substituted for granisetron on days 2 through 7 (216 patients). All patients completed diaries in which episodes of emesis and severity of nausea were recorded. RESULTS: The addition of granisetron on days 2 through 7 had no discernable impact on nausea and vomiting during this period. CONCLUSION: The administration of a 5-hydroxytryptamine3, receptor (5-HT3) antagonist, in this case granisetron, after 24 hours conferred no benefit. This negative result needs to be assessed in light of conflicting literature, but at present it does not appear that the routine use of these drugs in this setting is justified.

"When you carry condoms all the boys think you want it": negotiating competing discourses about safe sex.

With the advent of HIV, sexual health campaigns and formal sex education in schools have worked to instil the concept of safe sex into the collective minds of Australia's youth. However the concept in its present guise is a fairly limited one. We argue in this paper that the predominant emphasis in education programmes on safe sex as condom use may be counter-productive for some young heterosexuals for two reasons. First, this strategy is male-focused and may not extrapolate well to young women who face special risks around pregnancy and rigid societal gender norms which govern sexual behaviour. Second, health promotion strategies aimed at young heterosexuals are based on an assumption of rational decision-making in sexual encounters and obscure the non-rational nature of arousal and desire, and the unequal power relations that exist between young men and women engaging in sex. Five hundred and twelve senior rural students participated in the study which included group discussions about sexuality and survey items which focused on the meanings of safe sex and the accessibility and use of condoms. The results showed that though most students identified condoms with safe sex, many were ambivalent about using them. Reasons given related to problems of negotiation, difficulties of access, and the risks which condoms gave no protection from, such as a sullied reputation. Perhaps, partly because of this, some students were looking to less secure methods of protection such as informal history-taking and monogamy. It is argued that successful sexual health promotion strategies must address the broad spectrum of concerns facing young men and women when they become sexually active and that consideration be given to the social context in which young people conduct their sexual lives.

A randomized controlled trial of the effects of group psychological therapy on survival in women with metastatic breast cancer.

In order to test the effect of a psychological intervention on survival from cancer, 66 women with metastatic breast cancer, all receiving standard medical care, were randomly assigned into two groups; one group (n = 30) attended the psychological intervention, consisting of 35 weekly, 2 h sessions of supportive plus cognitive behavioral therapy; the control group (n = 36) received only a home study cognitive behavioral package. No significant difference was found in survival post-randomization between the groups as assessed by a log rank test 5 years after the commencement of the study. As expected, several prognostic factors were significant predictors of survival: metastatic site, hormonal receptor status, and chemotherapy prior to randomization. While many personal and demographic variables did not influence survival, there was a significant effect of self-reported exercise (possibly due to better health). A small subgroup of intervention subjects who attended outside support groups also survived significantly longer than those who did not. The strengths and limitations of the present study are discussed, and the results contrasted with those of a well known study by Spiegel et al. (Spiegel, D., Bloom, J.R., Kraemer, H.C. and Gottheil, E. (1989) Lancet ii, 888-891). We propose that a different experimental design (correlative) may be needed to show any effect of self-help behaviors and psychological attributes in a small minority of patients.

Vulnerability on the streets: female sex workers and HIV risk.

In-depth interviews were conducted with 24 purposively selected female sex workers who were perceived to be vulnerable to risks associated with their lifestyle and occupation. Brothel workers were found to be considerably less exposed to risk than the women working on the streets. Client resistance was the major obstacle to women maintaining safe sex practices. Physical threats and coercion from clients, the absence of legal protection for street workers, the workers' extreme social isolation and lack of community support added to the difficulties experienced by women in their attempts to insist on condoms for all sex services. Youth, homelessness and heavy drug use had contributed to women being at times even more vulnerable because they had less capacity to manage situations of potential violence or STD risk. Whether through sex work or in their private relationships, HIV remains a risk for some of these women. This study highlights the dangers associated with illegal sex work. While decriminalization of prostitution would reduce some of the dangers to which women were exposed and increase women's capacity to insist on safe sex practices, it is also important for community education programmes to address men's failure to accept responsibility for condom use when seeking the services of sex workers.

'That's the problem with living in a small town': privacy and sexual health issues for young rural people.

Survey and focus group discussions examining sexual health issues for young people were conducted with 1168 year 8 and year 10 secondary school students living in small rural communities across Australia. Growing up in the country was generally perceived as a positive experience; however, many young people felt that they had little privacy. Two main areas of concern emerged in relation to sexual health issues: worries about being recognised in public venues such as doctor's surgeries and chemists, and the informal mechanisms among peer groups that appraised and regulated sexual behaviour and attitudes. There were some significant gender differences evident in the expectations and experiences attached to these concerns, with girls expressing more awareness of and concern towards their public reputations when accessing sexual health services. They also felt that their sexual reputations among peers were closely monitored by way of their behaviour and appearance. This can militate against confident and assertive safer sex strategies such as condom use, when initiating or insisting upon condom use is construed as evidence of promiscuity or a preparedness to engage in sex. Concerns around privacy may be acutely experienced by young rural women, and health services providers need to be aware of these issues and efforts need to be made to address and allay the apprehensions of young people in this sensitive area.

Effect of postchemotherapy nausea and vomiting on health-related quality of life. The Quality of Life and Symptom Control Committees of the National Cancer Institute of Canada Clinical Trials Group.

The purpose was to measure the effects of postchemotherapy nausea and vomiting (PCNV) on health-related quality of life (HQL) in patients receiving either moderately or highly emetogenic chemotherapy. The study sample consisted of 832 chemotherapy-naive patients with cancer who received either moderately or highly emetogenic chemotherapy as part of multicenter trials of new antiemetics. The patients completed the self-report European Organization for Research and Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) before chemotherapy (baseline) and 1 week (day 8) and 2-4 weeks after chemotherapy. They also completed a self-report nausea and vomiting (NV) diary for 5-7 days after chemotherapy. To determine the effects of PCNV on HQL, the change in scores between the baseline and day 8 HQL assessments was calculated for each domain and symptom in the QLQ-C30 and compared in four subgroups of patients: those with both nausea and vomiting, those with nausea but no vomiting, those with no nausea but with vomiting, and those with neither nausea nor vomiting. The group with both nausea and vomiting showed statistically significantly worse physical, cognitive and social functioning, global quality of life, fatigue, anorexia, insomnia and dyspnea as compared to the group with neither nausea nor vomiting (0.0001 < P < 0.05). Patients with only nausea but no vomiting tended to have less worsening in functioning and symptoms than those having both nausea and vomiting. Increased severity of vomiting (> 2 episodes) was associated with worsening of only global quality of life and anorexia as compared with 1-2 episodes of vomiting (0.0001 < P < 0.01). By 2-4 weeks after chemotherapy all HQL scores had either returned to their baseline levels or were better than baseline. PCNV adversely affects several quality-of-life domains, but patients with only nausea experience less disruption than do those with both nausea and vomiting. Patients with 1-2 episodes of vomiting experience almost the same degree of disruption of HQL as do patients with more than 2 episodes of vomiting.