The active site behaviour of electrochemically synthesised gold nanomaterials

Even though gold is the noblest of metals, a weak chemisorber and is regarded as being quite inert, it demonstrates significant electrocatalytic activity in its nanostructured form. It is demonstrated here that nanostructured and even evaporated thin films of gold are covered with active sites which are responsible for such activity. The identification of these sites is demonstrated with conventional electrochemical techniques such as cyclic voltammetry as well as a large amplitude Fourier transformed alternating current (FT-ac) method under acidic and alkaline conditions. The latter technique is beneficial in determining if an electrode process is either Faradaic or capacitive in nature. The observed behaviour is analogous to that observed for activated gold electrodes whose surfaces have been severely disrupted by cathodic polarisation in the hydrogen evolution region. It is shown that significant electrochemical oxidation responses occur at discrete potential values well below that for the formation of the compact monolayer oxide of bulk gold and are attributed to the facile oxidation of surface active sites. Several electrocatalytic reactions are explored in which the onset potential is determined by the presence of such sites on the surface. Significantly, the facile oxidation of active sites is used to drive the electroless deposition of metals such as platinum, palladium and silver from their aqueous salts on the surface of gold nanostructures. The resultant surface decoration of gold with secondary metal nanoparticles not only indicates regions on the surface which are rich in active sites but also provides a method to form interesting bimetallic surfaces.

Large amplitude Fourier transformed AC voltammetric investigation of the active state electrochemistry of a copper/aqueous base interface and implications for electrocatalysis

The higher harmonic components available from large-amplitude Fourier-transformed alternating current (FT-ac) voltammetry enable the surface active state of a copper electrode in basic media to be probed in much more detail than possible with previously used dc methods. In particular, the absence of capacitance background current allows low-level Faradaic current contributions of fast electron-transfer processes to be detected; these are usually completely undetectable under conditions of dc cyclic voltammetry. Under high harmonic FT-ac voltammetric conditions, copper electrodes exhibit well-defined and reversible premonolayer oxidation responses at potentials within the double layer region in basic 1.0 M NaOH media. This process is attributed to oxidation of copper adatoms (Cu*) of low bulk metal lattice coordination numbers to surface-bonded, reactive hydrated oxide species. Of further interest is the observation that cathodic polarization in 1.0 M NaOH significantly enhances the current detected in each of the fundamental to sixth FT-ac harmonic components in the Cu*/Cu hydrous oxide electron-transfer process which enables the underlying electron transfer processes in the higher harmonics to be studied under conditions where the dc capacitance response is suppressed; the results support the incipient hydrous oxide adatom mediator (IHOAM) model of electrocatalysis. The underlying quasi-reversible interfacial Cu*/Cu hydrous oxide process present under these conditions is shown to mediate the reduction of nitrate at a copper electrode, while the mediator for the hydrazine oxidation reaction appears to involve a different mediator or active state redox couple. Use of FT-ac voltammetry offers prospects for new insights into the nature of active sites and electrocatalysis at the electrode/solution interface of Group 11 metals in aqueous media.

Reduction of Au3+ ions by activated surface atoms of platinum

In this work it is demonstrated that Pt electrodes can be activated by cathodic polarisation in the hydrogen evolution region which makes it prone to oxidation at potentials below that of bulk oxide formation. When an activated Pt electrode is placed in an aqueous HAuCl4 solution the electroless deposition of Au onto the surface of the electrode is observed and confirmed by cyclic voltammetry and XPS measurements. It is demonstrated that the oxidation of active Pt surface atoms provides the driving force for the spontaneous reduction of Au3+ ions into metallic Au to generate a Pt/Au surface which is highly active for the electro-oxidation of ethanol.

Understanding chronic pain complicating disability: Finding meaning through focus group methodology

Over the past few decades a major paradigm shift has occurred in the conceptualisation of chronic pain as a complex multidimensional phenomenon. Yet, pain experienced by individuals with a primary disability continues to be understood largely from a traditional biomedical model, despite its inherent limitations. This is reflected in the body of literature on the topic that is primarily driven by positivist assumptions and the search for etiologic pain mechanisms. Conversely, little is known about the experiences of and meanings attributed to, disability-related pain. Thus the purpose of this paper is to discuss the use of focus group methodology in elucidating the meanings and experiences of this population. Here, a distinction is made between the method of the focus group and focus group research as methodology. Typically, the focus group is presented as a seemingly atheoretical method of research. Drawing on research undertaken on the impact of chronic pain in people with multiple sclerosis, this paper seeks to theorise the focus group in arguing the methodological congruence of focus group research and the study of pain experience. It is argued that the contributions of group interaction and shared experiences in focus group discussions produce data and insights less accessible through more structured research methods. It is concluded that a biopsychosocial perspective of chronic pain may only ever be appreciated when the person-in-context is the unit of investigation.

Group interactions in science practical work

This study explored the interactions of a highly motivated group of students doing traditional practical work in science. Interest focussed on the social construction of understanding and how this could be described. Despite considerable collaboration in constructing an understanding of the task the students rarely focussed on the concepts the practical work was intended to illustrate. Collaboration was described in terms of social behaviours and discourse moves which supported the use of cognitive strategies.

The epidemiology of invasive group A streptococcal disease in Victoria, Australia

Objective To estimate the incidence and severity of invasive group A streptococcal infection in Victoria, Australia. Design Prospective active surveillance study. Setting Public and private laboratories, hospitals and general practitioners throughout Victoria. Patients eople in Victoria diagnosed with group A streptococcal disease notified to the surveillance system between 1 March 2002 and 31 August 2004. Main outcome measure Confirmed invasive group A streptococcal disease. Results We identified 333 confirmed cases: an average annualised incidence rate of 2.7 (95% CI, 2.3-3.2) per 100000 population per year. Rates were highest in people aged 65 years and older and those younger than 5 years. The case-fatality rate was 7.8%. Streptococcal toxic shock syndrome occurred in 48 patients (14.4%), with a case-fatality rate of 23%. Thirty cases of necrotising fasciitis were reported; five (17%) of these patients died. Type 1 (23%) was the most frequently identified emm sequence type in all, age groups. All tested isolates were susceptible to penicillin and clindamycin. Two isolates (4%) were resistant to erythromycin. Conclusion The incidence of invasive group A streptococcal disease in temperate Australia is greater than previously appreciated and warrants greater public health attention, including its designation as a notifiable disease.

A multilevel model of work-life : examining the impact of group structure and relational job design

One in five Australian workers believes that work doesn’t fit well with their family and social commitments. Concurrently, organisations are recognising that to stay competitive they need policies and practices that support the multiple aspects of employees’ lives. Many employees work in group environments yet there is currently little group level work-life balance research. This paper proposes a new theoretical framework developed to understand the design of work groups to better facilitate work-life balance. This new framework focuses on task and relational job designs, group structures and processes and workplace culture.

Platinum-based chemotherapy in metastatic breast cancer : the Leicester (UK) experience

Aims: After failure of anthracycline- and taxane-based chemotherapy in metastatic breast cancer, treatment options until recently were limited. Until the introduction of capecitabine and vinorelbine, no standard regimen was available. We conducted a retrospective study to determine the efficacy and toxicity of platinum-based chemotherapy in metastatic breast cancer. Materials and methods: Forty-two women with metastatic breast cancer previously treated with anthracyclines (93%) and/or taxanes (36%) received mitomycin-vinblastine-cisplatin (MVP) (n = 23), or cisplatin-etoposide (PE) (n = 19), as first-, second- and third-line treatment at a tertiary referral centre between 1997 and 2002. Chemotherapy was given every 3 weeks as follows: mitomycin-C (8 mg/m 2) (cycles 1, 2, 4, 6), vinblastine (6 mg/m 2), and cisplatin (50 mg/m 2) all on day 1; and cisplatin (75 mg/m 2) and etoposide (100 mg/m 2) on day 1 and (100 mg/m 2) orally twice a day on days 2-3. Results: The response rate for 40 evaluable patients (MVP: n = 23; PE: n = 17) was 18% (95% confidence interval [CI]: 9-32%). The response rate to MVP was 13% (95% CI: 5-32%, one complete and two partial responses) and to PE 24% (10-47%, four partial responses). Disease stabilised in 43% (26-63%) and 47% (26-69%) of women treated with MVP and PE, respectively. After a median follow-up of 18 months, 37 women (MVP: n = 19; PE: n = 18) died from their disease. Median (range) progression-free survival and overall survival were 6 months (0.4-18.7) and 9.9 months (1.3-40.8), respectively. Median progression-free survival for the MVP and PE groups was 5.5 and 6.2 months (Log-rank, P = 0.82), and median overall survival was 10.2 and 9.4 months (Log-rank, P = 0.46), respectively. The main toxicity was myelosuppression. Grades 3-4 neutropenia was more common in women treated with PE than in women treated with MVP (74% vs 30%; P = 0.012), but the incidence of neutropenic sepsis, relative to the number of chemotherapy cycles, was low (7% overall). The toxicity-related hospitalisation rate was 1.2 admissions per six cycles of chemotherapy. No treatment-related deaths occurred. MVP and PE chemotherapy have modest activity and are safe in women with metastatic breast cancer. © 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Advances in the systemic therapy of malignant pleural mesothelioma

Malignant pleural mesothelioma is an aggressive thoracic malignancy associated with exposure to asbestos, and its incidence is anticipated to increase during the first half of this century. Chemotherapy is the mainstay of treatment, yet sufficiently robust evidence to substantiate the current standard of care has emerged only in the past 5 years. This Review summarizes the evidence supporting the clinical activity of chemotherapy, discusses the use of end points for its assessment and examines the influence of clinical and biochemical prognostic factors on the natural history of malignant pleural mesothelioma. Early-phase clinical trials of second-line and novel agents are emerging from an increased understanding of mesothelioma cell biology. Coupled with high-quality translational research, such developments have real potential to improve the outlook of patients at a time of increasing incidence.

Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment : the M77001 study group

Purpose: This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Patients and Methods: Patients were randomly assigned to six cycles of docetaxel 100 mg/m 2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. Results: A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Conclusion: Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity. © 2005 by American Society of Clinical Oncology.

SRL 172 (killed Mycobacterium vaccae) in addition to standard chemotherapy improves quality of life without affecting survival, in patients with advanced non-small-cell lung cancer : phase III results

Background: This open-label, randomised phase III study was designed to further investigate the clinical activity and safety of SRL172 (killed Mycobacterium vaccae suspension) with chemotherapy in the treatment of non-small-cell lung cancer (NSCLC). Patients and methods: Patients were randomised to receive platinum-based chemotherapy, consisting of up to six cycles of MVP (mitomycin, vinblastine and cisplatin or carboplatin) with (210 patients) or without (209 patients) monthly SRL172. Results: There was no statistical difference between the two groups in overall survival (primary efficacy end point) over the course of the study (median overall survival of 223 days versus 225 days; P = 0.65). However, a higher proportion of patients were alive at the end of the 15-week treatment phase in the chemotherapy plus SRL172 group (90%), than in the chemotherapy alone group (83%) (P = 0.061). At the end of the treatment phase, the response rate was 37% in the combined group and 33% in the chemotherapy alone group. Patients in the chemotherapy alone group had greater deterioration in their Global Health Status score (-14.3) than patients in the chemotherapy plus SRL172 group (-6.6) (P = 0.02). Conclusion: In this non-placebo controlled trial, SRL172 when added to standard cancer chemotherapy significantly improved patient quality of life without affecting overall survival times. © 2004 European Society for Medical Oncology.

Combination therapy with gefitinib and rofecoxib in patients with platinum-pretreated relapsed non-small-cell lung cancer

Purpose: In non-small-cell lung cancer (NSCLC), the epidermal growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) play major roles in tumorigenesis. This phase I/II study evaluated combined therapy with the EGFR tyrosine kinase inhibitor (TKI) gefitinib and the COX-2 inhibitor rofecoxib in platinum-pretreated, relapsed, metastatic NSCLC (n = 45). Patients and Methods: Gefitinib 250 mg/d was combined with rofecoxib (dose escalated from 12.5 to 25 to 50 mg/d through three cohorts, each n = 6). Because the rofecoxib maximum-tolerated dose was not reached, the 50 mg/d cohort was expanded for efficacy evaluation (n = 33). Results: Among the 42 assessable patients, there was one complete response (CR) and two partial responses (PRs) and 12 patients with stable disease (SD); disease control rate was 35.7% (95% CI, 21.6% to 52.0%). Median time to tumor progression was 55 days (95% CI, 47 to 70 days), and median survival was 144 days (95% CI, 103 to 190 days). In a pilot study, matrix-assisted laser desorption/ionization (MALDI) proteomics analysis of baseline serum samples could distinguish patients with an objective response from those with SD or progressive disease (PD), and those with disease control (CR, PR, and SD) from those with PD. The regimen was generally well tolerated, with predictable toxicities including skin rash and diarrhea. Conclusion: Gefitinib combined with rofecoxib provided disease control equivalent to that expected with single-agent gefitinib and was generally well tolerated. Baseline serum proteomics may help identify those patients most likely to benefit from EGFR TKIs. © 2007 by American Society of Clinical Oncology.

Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX) : an open-label randomised phase III trial

Background: Use of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has the potential to increase survival in patients with advanced non-small-cell lung cancer. We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer. Methods: In a multinational, multicentre, open-label, phase III trial, chemotherapy-naive patients (≥18 years) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy. Chemotherapy was cisplatin 80 mg/m 2 intravenous infusion on day 1, and vinorelbine 25 mg/m 2 intravenous infusion on days 1 and 8 of every 3-week cycle) for up to six cycles. Cetuximab-at a starting dose of 400 mg/m 2 intravenous infusion over 2 h on day 1, and from day 8 onwards at 250 mg/m 2 over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred. The primary endpoint was overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00148798. Findings: Between October, 2004, and January, 2006, 1125 patients were randomly assigned to chemotherapy plus cetuximab (n=557) or chemotherapy alone (n=568). Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group (median 11·3 months vs 10·1 months; hazard ratio for death 0·871 [95% CI 0·762-0·996]; p=0·044). The main cetuximab-related adverse event was acne-like rash (57 [10%] of 548, grade 3). Interpretation: Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer. Funding: Merck KGaA. © 2009 Elsevier Ltd. All rights reserved.

Reversibility of liver failure secondary to metastatic breast cancer by vinorelbine and cisplatin chemotherapy

Purpose: The development of liver metastases from breast cancer is associated with a very poor prognosis, estimated at 4 months median survival. Since treatment with many chemotherapeutic agents is relatively contraindicated, we assessed the safety, tolerability and potential efficacy of combination chemotherapy with vinorelbine and cisplatin (ViP). Method: Pilot study in 11 patients with histologically confirmed breast carcinoma, radiological evidence of liver metastases and serum bilirubin greater than 1.5 times the upper limit of normal. Patients received up to six cycles of cisplatin (75 mg/m 2) every 21 days and vinorelbine (20 mg/m 2) on days 1 and 8 of every 21-day cycle. Measurement of liver lesions was performed on CT scan every 8 weeks into treatment. Results: The most frequently reported adverse event was myelosuppression. Other adverse effects included nausea, vomiting and mild neurotoxicity. Two patients died after one treatment with ViP, one of whom suffered an intracerebral haemorrhage that was possibly treatment-related. Improvement in liver function tests was observed in 10 patients, and mean time to normalization of bilirubin levels was 36 days. Partial responses were documented radiologically in 7 out of 11 patients treated. Median overall survival from trial entry was 6.5 months (range 11-364 days), with one patient alive 13 months from trial entry. Conclusion: Normalization of liver function is possible with ViP treatment of metastatic breast cancer, offering the potential to prolong survival. Phase II clinical trials of this regimen in this patient group should include measurement of quality of life in order to assess risk versus benefit.

Crizotinib versus chemotherapy in advanced ALK-positive lung cancer

BACKGROUND: In single-group studies, chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK ) have been associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting ALK. Whether crizotinib is superior to standard chemotherapy with respect to efficacy is unknown. METHODS: We conducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locally advanced or metastatic ALK-positive lung cancer who had received one prior platinum-based regimen. Patients were randomly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemotherapy with either pemetrexed (500 mg per square meter of body-surface area) or docetaxel (75 mg per square meter) every 3 weeks. Patients in the chemotherapy group who had disease progression were permitted to cross over to crizotinib as part of a separate study. The primary end point was progression-free survival. RESULTS: The median progression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy group (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to 0.64; P<0.001). The response rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with chemotherapy (P<0.001). An interim analysis of overall survival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54). Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, alopecia, and dyspnea. Patients reported greater reductions in symptoms of lung cancer and greater improvement in global quality of life with crizotinib than with chemotherapy. CONCLUSIONS: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement. (Funded by Pfizer; ClinicalTrials.gov number, NCT00932893.) Copyright © 2013 Massachusetts Medical Society.