Ionic liquids containing tricyanomethanide anions: physicochemical characterisation and performance as electrochemical double-layer capacitor electrolytes

We investigated the use of fluorine free ionic liquids (ILs) containing the tricyanomethanide anion ([C(CN)3]) as an electrolyte in electrochemical double-layer capacitors (EDLCs). Three cations were used; 1-butyl-3-methylimidazolium ([Im1,4]), N-butyl-N-methylpyrrolidinium ([Pyr1,4]) and N-butyl-N-methylpiperidinium ([Pip1,4]). Their physicochemical properties are discussed alongside with their performance as electrolytes. We found that the cyano-based ILs present higher ionic conductivity (9.4, 8.7 and 4.2 mS cm−1 at 25 °C for [Im1,4], [Pyr1,4] and [Pip1,4], respectively) than the widely studied IL containing the bis(trifluoromethylsulfonyl)imide anion, namely [Pyr1,4][Tf2N] (2.7 mS cm−1 at 25 °C). Of the three ILs investigated, [Pip1,4][C(CN)3] presents the widest electrochemical stability window, 3.0 V, while [Pyr1,4][C(CN)3] is stable up to 2.9 V and its [Tf2N] analogue can operate at 3.5 V. Despite operating at a lower voltage, [Pyr1,4][C(CN)3] EDLC is capable of delivering up to 4.5 W h kg−1 when operating at high specific power of 7.2 kW kg−1, while its [Pyr1,4][Tf2N] counterpart only delivered 3.0 W h kg−1 when operated at similar power

Heterosexual HIV-1 infectiousness and antiretroviral use : systematic review of prospective studies of discordant couples

Background: Recent studies have estimated the reduction in HIV-1 infectiousness with antiretroviral therapy (ART), but high-quality studies such as randomized controlled trials, accompanied by rigorous adherence counseling, are likely to overestimate the effectiveness of treatment-as-prevention in real-life settings. Methods: We attempted to summarize the effect of ART on HIV transmission by undertaking a systematic review and meta-analysis of HIV-1 infectiousness per heterosexual partnership (incidence rate and cumulative incidence over study follow-up) estimated from prospective studies of discordant couples. We used random-effects Poisson regression models to obtain summary estimates. When possible, the analyses were further stratified by direction of transmission (man-to-woman or woman-to-man) and economic setting (high- or low-income countries). Potential causes of heterogeneity of estimates were explored through subgroup analyses. Results: Fifty publications were included. Nine allowed comparison between ART and non-ART users within studies (ART-stratified studies), in which summary incidence rates were 3.6/100 person-years (95% confidence interval = 2.0-6.5) and 0.2/100 person-years (0.07-0.7) for non-ART- and ART-using couples, respectively (P < 0.001), constituting a 91% (79-96%) reduction in per-partner HIV-1 incidence rate with ART use. The 41 studies that did not stratify by ART use provided estimates with high levels of heterogeneity (I2 statistic) and few reported levels of ART use, making interpretation difficult. Nevertheless, estimates tended to be lower with ART use. Infectiousness tended to be higher for low-income than high-income settings, but there was no clear pattern by direction of transmission (man-to-woman and woman-to-man). Conclusions: ART substantially reduces HIV-1 infectiousness within discordant couples, based on observational studies, and could play a major part in HIV-1 prevention efforts. However, the non-zero risk from partners receiving ART demonstrates that appropriate counseling and other risk-reduction strategies for discordant couples are still required. Additional estimates of ART effectiveness by adherence level from real-life settings will be important, especially for persons starting treatment early without symptoms

The Physics of the Colloidal Glass Transition

As one increases the concentration of a colloidal suspension, the system exhibits a dramatic increase in viscosity. Structurally, the system resembles a liquid, yet motions within the suspension are slow enough that it can be considered essentially frozen. This kinetic arrest is the colloidal glass transition. For several decades, colloids have served as a valuable model system for understanding the glass transition in molecular systems. The spatial and temporal scales involved allow these systems to be studied by a wide variety of experimental techniques. The focus of this review is the current state of understanding of the colloidal glass transition. A brief introduction is given to important experimental techniques used to study the glass transition in colloids. We describe features of colloidal systems near and in glassy states, including tremendous increases in viscosity and relaxation times, dynamical heterogeneity, and ageing, among others. We also compare and contrast the glass transition in colloids to that in molecular liquids. Other glassy systems are briefly discussed, as well as recently developed synthesis techniques that will keep these systems rich with interesting physics for years to come.Comment: 56 pages, 18 figures, Revie

Economic integration and security in the Middle East and North Africa: what prospects for a liberal peace?

Since the late 1980s governments in the Middle East and North Africa (MENA) have created commercial institutions in order to promote regional economic integration. The primary aim of this policy has been regarded as the promotion of economic welfare gains at the national level. A second, albeit less-emphasized goal, has been to promote regional peace through economic interdependence. This study examines the prospects for a liberal peace in the MENA by analyzing two stages of the commercial institutional peace. Firstly, the study considers whether commercial institutions have promoted intra-regional trade in the MENA. Secondly, it examines if economic interaction has had an impact on promoting peace within the region. Twenty states are considered here and the unit of analysis is the dyad-year over a 25-year period from 1990-2014. This study finds that commercial institutions in the MENA have only a limited positive correlation with trade volume and while there is a direct positive correlation between economic integration and peace in the region, this is quite limited. These findings suggest that the conclusions made by previous studies that demonstrate a direct positive correlation between commercial institutions (and economic integration more generally) and peace, may be less applicable to some regions such as MENA

Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells

Thyroid hormones (THs) 3,3′,5-triiodo-L-thyronine (T3) and L-thyroxine (T4) are important regulators of the metabolism and physiology of most normal tissues.Cytochrome P450 family 3A members are drug metabolizing enzymes involved in theactivation and detoxification of several drugs. CYP3A4 is the major enzyme involvedin the metabolism of chemotherapeutic drugs. In this work, we demonstrate thatTHs induce a significant increase in CYP3A4 mRNA levels, protein expression andmetabolic activity through the membrane receptor integrin αvβ3 and the activation ofsignalling pathways through Stat1 and NF-κB. We reasoned that TH-induced CYP3A4modulation may act as an important regulator in the metabolism of doxorubicin(Doxo). Experiments in vitro demonstrated that in CYP3A4-knocked down cells, noTH-mediated chemosensitivity to Doxo was observed. We also found that THs modulatethese functions by activating the membrane receptor integrin αvβ3. In addition, weshowed that the thyroid status can modulate CYP450 mRNA levels in tumor and livertissues, and the tumor volume in response to chemotherapy in vivo. In fact, Doxotreatment in hypothyroid mice was associated with lower tumors, displaying lowerlevels of CYP enzymes, than euthyroid mice. However, higher mRNA levels of CYPenzymes were found in livers from Doxo treated hypothyroid mice respect to control.These results present a new mechanism by which TH could modulate chemotherapyresponse. These findings highlight the importance of evaluating thyroid status inpatients during application of T-cell lymphoma therapeutic regimens.Fil: Díaz Flaqué, María Celeste. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Cayrol, Maria Florencia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Sterle, Helena Andrea. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Aschero, María del Rosario. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Díaz Albuja, Johanna Abigail. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Isse, Blanca Alicia de Los Angeles G.. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Farias, Ricardo Norberto. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Cornell University; Estados UnidosFil: Rosemblit, Cinthia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Cremaschi, Graciela Alicia. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentin

The global biopharma industry and the rise of Indian drug multinationals: implications for Australian generics policy

This article provides a synopsis of the new dynamics of the global biopharma industry. The emergence of global generics companies with capabilities approximating those of 'big pharma' has accelerated the blurring of boundaries between the innovator and generics sectors. Biotechnology-based products form a large and growing segment of prescription drug markets and regulatory pathways for biogenerics are imminent. Indian biopharma multinationals with large-scale efficient manufacturing plants and growing R&D capabilities are now major suppliers of Active Pharmaceutical Ingredients (APIs) and generic drugs across both developed and developing countries. In response to generic competition, innovator companies employ a range of life cycle management techniques, including the launch of 'authorised generics'. The generics segment in Australia will see high growth rates in coming years but the prospect for local manufacturing is bleak. The availability of cheap generics in international markets has put pressure on Pharmaceutical Benefits Scheme (PBS) pricing arrangements, and a new policy direction was announced in November 2006. Lower generics prices will have a negative impact on some incumbent suppliers but industrial renewal policies for the medicines industry in Australia are better focused on higher value R&D activities and niche manufacturing of sophisticated products

Obstacles to researching the researchers: A case study of the ethical challenges of undertaking methodological research investigating the reporting of randomised controlled trials

<p>Abstract</p> <p>Background</p> <p>Recent cohort studies of randomised controlled trials have provided evidence of within-study selective reporting bias; where statistically significant outcomes are more likely to be more completely reported compared to non-significant outcomes. Bias resulting from selective reporting can impact on meta-analyses, influencing the conclusions of systematic reviews, and in turn, evidence based clinical practice guidelines.</p> <p>In 2006 we received funding to investigate if there was evidence of within-study selective reporting in a cohort of RCTs submitted to New Zealand Regional Ethics Committees in 1998/99. This research involved accessing ethics applications, their amendments and annual reports, and comparing these with corresponding publications. We did not plan to obtain informed consent from trialists to view their ethics applications for practical and scientific reasons.</p> <p>In November 2006 we sought ethical approval to undertake the research from our institutional ethics committee. The Committee declined our application on the grounds that we were not obtaining informed consent from the trialists to view their ethics application. This initiated a seventeen month process to obtain ethical approval. This publication outlines what we planned to do, the issues we encountered, discusses the legal and ethical issues, and presents some potential solutions.</p> <p>Discussion and conclusion</p> <p>Methodological research such as this has the potential for public benefit and there is little or no harm for the participants (trialists) in undertaking it. Further, in New Zealand, there is freedom of information legislation, which in this circumstance, unambiguously provided rights of access and use of the information in the ethics applications. The decision of our institutional ethics committee defeated this right and did not recognise the nature of this observational research.</p> <p>Methodological research, such as this, can be used to develop processes to improve quality in research reporting. Recognition of the potential benefit of this research in the broader research community, and those who sit on ethics committees, is perhaps needed. In addition, changes to the ethical review process which involve separation between those who review proposals to undertake methodological research using ethics applications, and those with responsibility for reviewing ethics applications for trials, should be considered. Finally, we contend that the research community could benefit from quality improvement approaches used in allied sectors.</p

The contrasting effects of diethylmethylamine during reduction of protons and oxidation of formic acid in diethylmethylammonium-based protic ionic liquids

Ionic liquids are formally defined as liquids that consist entirely of ions, and which are liquid below 100 C. As these liquids are being proposed for use in a range of electrochemical devices and applications, understanding the electrochemical behaviour of these is increasingly important. In this contribution, we describe the effects of parent amine molecules on electrocatalysis in the protic ionic liquids diethylmethylammonium trifluoromethanesulfonate and diethylmethylammonium heptafluorobutanoate. We first show that diethylmethylamine can adsorb onto Pt electrodes during electrocatalytic reduction of trifluoromethanesulfonic acid in diethylmethylammonium trifluoromethanesulfonate. In contrast, diethylmethylamine promotes the oxidation of formic acid in this ionic liquid, by deprotonating the acid to the active formate species. Therefore, the neutral base can either inhibit or enhance electrocatalysis in the liquid, depending on the reaction under consideration. We also show that the mechanism of formic-acid oxidation in diethylmethylammonium heptafluorobutanoate differs significantly from that observed when using diethylmethylammonium trifluoromethanesulfonate. This phenomenon is attributed to adsorption of poisoning spectator species onto the electrode surface, demonstrating that changes to the structure of ionic-liquid anions can have drastic effects on the electrochemistry of these liquids

On deciding to have a lobotomy:either lobotomies were justified or decisions under risk should not always seek to maximise expected utility

In the 1940s and 1950s thousands of lobotomies were performed on people with mental disorders. These operations were known to be dangerous, but thought to offer great hope. Nowadays, the lobotomies of the 1940s and 1950s are widely condemned. The consensus is that the practitioners who employed them were, at best, misguided enthusiasts, or, at worst, evil. In this paper I employ standard decision theory to understand and assess shifts in the evaluation of lobotomy. Textbooks of medical decision making generally recommend that decisions under risk are made so as to maximise expected utility (MEU) I show that using this procedure suggests that the 1940s and 1950s practice of psychosurgery was justifiable. In making sense of this finding we have a choice: Either we can accept that psychosurgery was justified, in which case condemnation of the lobotomists is misplaced. Or, we can conclude that the use of formal decision procedures, such as MEU, is problematic

Carotid Baroreflex Activation: Past, Present, and Future

Electrical activation of the carotid baroreceptor system is an attractive therapy for the treatment of resistant hypertension. In the past, several attempts were made to directly activate the baroreceptor system in humans, but the method had to be restricted to a few selected patients. Adverse effects, the need for better electrical devices and better surgical techniques, and the lack of knowledge about long-term effects has greatly hampered developments in this area for many years. Recently, a new and promising device was evaluated in a multicenter feasibility trial, which showed a clinically and statistically significant reduction in office systolic blood pressure (>20 mm Hg). This reduction could be sustained for at least 2 years with an acceptable safety profile. In the future, this new device may stimulate further application of electrical activation of the carotid baroreflex in treatment-resistant hypertension