22 resultados para Safety of pre-exposure prophylaxis

em Aston University Research Archive


Relevância:

100.00% 100.00%

Publicador:

Resumo:

Objectives: This study measured and compared the pharmacokinetics of CMPD167, a small molecule antiretroviral CCR5 inhibitor with potential as an HIV microbicide, following vaginal, rectal and oral administration in rhesus macaques. Methods: Avaginal hydroxyethylcellulose (HEC) gel, a rectal HEC gel, a silicone elastomer matrix-type vaginal ring and an oral solution, each containing CMPD167, were prepared and administered to rhesus macaques pretreated with Depo-Provera. CMPD167 concentrations in vaginal fluid, vaginal tissue (ring only), rectal fluid and blood plasma were quantified by HPLC-mass spectrometry. Results: CMPD167 concentrations measured in rectal fluid, vaginal fluid and blood plasma were highly dependent on both the route of administration and the formulation type. Although rectal and vaginal fluid concentrations were highest when CMPD167 was administered locally (via either gel or ring), lower concentrations of the drug were also measured in these compartments following administration at the remote mucosal site or orally. CMPD167 levels in the vaginal and rectal fluid following oral administration were relatively low compared with local administration. Conclusions: The study provides clear evidence for vaginal-rectal and rectal-vaginal drug transfer pathways and suggests that oral pre-exposure prophylaxis with CMPD167 may be less efficacious at preventing sexual transmission of HIV-1 than topically applied products. ©The Author 2013.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The overall objective of this work was to compare the effect of pre-treatment and catalysts on the quality of liquid products from fast pyrolysis of biomass. This study investigated the upgrading of bio-oil in terms of its quality as a bio-fuel and/or source of chemicals. Bio-oil used directly as a biofuel for heat or power needs to be improved particularly in terms of temperature sensitivity, oxygen content, chemical instability, solid content, and heating values. Chemicals produced from bio-oil need to be able to meet product specifications for market acceptability. There were two main objectives in this research. The first was to examine the influence of pre-treatment of biomass on the fast pyrolysis process and liquid quality. The relationship between the method of pre-treatment of biomass feedstock to fast pyrolysis oil quality was studied. The thermal decomposition behaviour of untreated and pretreated feedstocks was studied by using a TGA (thermogravimetric analysis) and a Py-GC/MS (pyroprobe-gas chromatography/mass spectrometry). Laboratory scale reactors (100g/h, 300g/h, 1kg/h) were used to process untreated and pretreated feedstocks by fast pyrolysis. The second objective was to study the influence of numerous catalysts on fast pyrolysis liquids from wheat straw. The first step applied analytical pyrolysis (Py-GC/MS) to determine which catalysts had an effect on fast pyrolysis liquid, in order to select catalysts for further laboratory fast pyrolysis. The effect of activation, temperature, and biomass pre-treatment on catalysts were also investigated. Laboratory experiments were also conducted using the existing 300g/h fluidised bed reactor system with a secondary catalytic fixed bed reactor. The screening of catalysts showed that CoMo was a highly active catalyst, which particularly reduced the higher molecular weight products of fast pyrolysis. From these screening tests, CoMo catalyst was selected for larger scale laboratory experiments. With reference to the effect of pre-treatment work on fast pyrolysis process, a significant effect occurred on the thermal decomposition of biomass, as well as the pyrolysis products composition, and the proportion of key components in bio-oil. Torrefaction proved to have a mild influence on pyrolysis products, when compared to aquathermolysis and steam pre-treatment.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The Biased Competition Model (BCM) suggests both top-down and bottom-up biases operate on selective attention (e.g., Desimone & Duncan, 1995). It has been suggested that top-down control signals may arise from working memory. In support, Downing (2000) found faster responses to probes presented in the location of stimuli held vs. not held in working memory. Soto, Heinke, Humphreys, and Blanco (2005) showed the involuntary nature of this effect and that shared features between stimuli were sufficient to attract attention. Here we show that stimuli held in working memory had an influence on the deployment of attentional resources even when: (1) It was detrimental to the task, (2) there was equal prior exposure, and (3) there was no bottom-up priming. These results provide further support for involuntary top-down guidance of attention from working memory and the basic tenets of the BCM, but further discredit the notion that bottom-up priming is necessary for the effect to occur.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

The thesis examines and explains the development of occupational exposure limits (OELs) as a means of preventing work related disease and ill health. The research focuses on the USA and UK and sets the work within a certain historical and social context. A subsidiary aim of the thesis is to identify any short comings in OELs and the methods by which they are set and suggest alternatives. The research framework uses Thomas Kuhn's idea of science progressing by means of paradigms which he describes at one point, `lq ... universally recognised scientific achievements that for a time provide model problems and solutions to a community of practitioners. KUHN (1970). Once learned individuals in the community, `lq ... are committed to the same rules and standards for scientific practice. Ibid. Kuhn's ideas are adapted by combining them with a view of industrial hygiene as an applied science-based profession having many of the qualities of non-scientific professions. The great advantage of this approach to OELs is that it keeps the analysis grounded in the behaviour and priorities of the groups which have forged, propounded, used, benefited from, and defended, them. The development and use of OELs on a larger scale is shown to be connected to the growth of a new profession in the USA; industrial hygiene, with the assistance of another new profession; industrial toxicology. The origins of these professions, particularly industrial hygiene, are traced. By examining the growth of the professions and the writings of key individuals it is possible to show how technical, economic and social factors became embedded in the OEL paradigm which industrial hygienists and toxicologists forged. The origin, mission and needs of these professions and their clients made such influences almost inevitable. The use of the OEL paradigm in practice is examined by an analysis of the process of the American Conference of Governmental Industrial Hygienists, Threshold Limit Value (ACGIH, TLV) Committee via the Minutes from 1962-1984. A similar approach is taken with the development of OELs in the UK. Although the form and definition of TLVs has encouraged the belief that they are health-based OELs the conclusion is that they, and most other OELs, are, and always have been, reasonably practicable limits: the degree of risk posed by a substance is weighed against the feasibility and cost of controlling exposure to that substance. The confusion over the status of TLVs and other OELs is seen to be a confusion at the heart of the OEL paradigm and the historical perspective explains why this should be. The paradigm has prevented the creation of truly health-based and, conversely, truly reasonably practicable OELs. In the final part of the thesis the analysis of the development of OELs is set in a contemporary context and a proposal for a two-stage, two-committee procedure for producing sets of OELs is put forward. This approach is set within an alternative OEL paradigm. The advantages, benefits and likely obstacles to these proposals are discussed.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Background The role of applied theatre in engaging both lay and professional publics with debate on health policy and practice is an emergent field. This paper discusses the development, production performance and discussion of ‘Inside View’.1 Objectives The objectives were to produce applied theatre from research findings of a completed study on genetic prenatal screening, exploring the dilemmas for women and health professionals of prenatal genetic screening, and to engage audiences in debate and reflection on the dilemmas of prenatal genetic screening. Methods ‘Inside View’ was developed from a multidisciplinary research study through identification of emergent themes from qualitative interviews, and development of these by the writer, theatre producer and media technologist with input from the researchers. Findings Inside View was performed in London and the Midlands to varied audiences with a panel discussion and evaluation post performance. The audiences were engaged in debate that was relevant to them professionally and personally. Knowledge translation through applied theatre is an effective tool for engaging the public but the impact subsequently is unclear. There are ethical issues of unexpected disclosure during discussion post performance and the process of transforming research findings into applied theatre requires time and trust within the multidisciplinary team as well as adequate resourcing.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Objective - To evaluate long-term safety of intravitreal ranibizumab 0.5-mg injections in neovascular age-related macular degeneration (nAMD). Design - Twenty-four–month, open-label, multicenter, phase IV extension study. Participants - Two hundred thirty-four patients previously treated with ranibizumab for 12 months in the EXCITE/SUSTAIN study. Methods - Ranibizumab 0.5 mg administered at the investigator's discretion as per the European summary of product characteristics 2007 (SmPC, i.e., ranibizumab was administered if a patient experienced a best-corrected visual acuity [BCVA] loss of >5 Early Treatment Diabetic Retinopathy Study letters measured against the highest visual acuity [VA] value obtained in SECURE or previous studies [EXCITE and SUSTAIN], attributable to the presence or progression of active nAMD in the investigator's opinion). Main Outcome Measures - Incidence of ocular or nonocular adverse events (AEs) and serious AEs, mean change in BCVA from baseline over time, and the number of injections. Results - Of 234 enrolled patients, 210 (89.7%) completed the study. Patients received 6.1 (mean) ranibizumab injections over 24 months. Approximately 42% of patients had 7 or more visits at which ranibizumab was not administered, although they had experienced a VA loss of more than 5 letters, indicating either an undertreatment or that factors other than VA loss were considered for retreatment decision by the investigator. The most frequent ocular AEs (study eye) were retinal hemorrhage (12.8%; 1 event related to study drug), cataract (11.5%; 1 event related to treatment procedure), and increased intraocular pressure (6.4%; 1 event related to study drug). Cataract reported as serious due to hospitalization for cataract surgery occurred in 2.6% of patients; none was suspected to be related to study drug or procedure. Main nonocular AEs were hypertension and nasopharyngitis (9.0% each). Arterial thromboembolic events were reported in 5.6% of the patients. Five (2.1%) deaths occurred during the study, none related to the study drug or procedure. At month 24, mean BCVA declined by 4.3 letters from the SECURE baseline. Conclusions - The SECURE study showed that ranibizumab administered as per a VA-guided flexible dosing regimen recommended in the European ranibizumab SmPC at the investigator's discretion was well tolerated over 2 years. No new safety signals were identified in patients who received ranibizumab for a total of 3 years. On average, patients lost BCVA from the SECURE study baseline, which may be the result of disease progression or possible undertreatment.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

It has been proposed that either excessive inflammation or an imbalance in angiogenic factors cause pre-eclampsia. In the present review, the arguments for and against the role of inflammation and/or angiogenic imbalance as the cause of pre-eclampsia are discussed on the basis of the Bradford-Hill criteria for disease causation. Although both angiogenic imbalance and systemic inflammation are implicated in pre-eclampsia, the absence of temporality of inflammatory markers with pre-eclampsia challenges the concept that excessive inflammation is the cause of pre-eclampsia. In contrast, the elevation of anti-angiogenic factors that precede the clinical signs of pre-eclampsia fulfils the criterion of temporality. The second most important criterion is the dose-response relationship. Although such a relationship has not been proven between pro-inflammatory cytokines and pre-eclampsia, high levels of anti-angiogenic factors have been shown to correlate with increased incidence and disease severity, hence satisfying this condition. Finally, as the removal of circulating sFlt-1 (soluble Fms-like tyrosine kinase receptor-1) from pre-eclamptic patients significantly improves the clinical outcome, it fulfils the Hill's experiment principle, which states that removal of the cause by an appropriate experimental regimen should ameliorate the condition. In contrast, treatment with high doses of corticosteroid fails to improve maternal outcome in pre-eclampsia, despite suppressing inflammation. Inflammation may enhance the pathology induced by the imbalance in the angiogenic factors, but does not by itself cause pre-eclampsia. Development of therapies based on the angiogenic and cytoprotective mechanisms seems more promising.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

In this paper we examine the impact that the new trading system SETSmm had on market quality measures such as firm value, liquidity and pricing efficiency. This system was introduced for mid-cap securities on the London Stock Exchange in 2003. We show that there is a small SETSmm return premium associated with the announcement that securities are to migrate to the new trading system. We find that migration to SETSmm also improves liquidity and pricing efficiency and these changes are related to the return premium. We also find that these gains are stronger for firms with high pre SETSmm liquidity and weaker for firms with low SETSmm liquidity.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

OBJECTIVE - A 12-week study assessed the efficacy and safety of a new oral antidiabetic agent, imeglimin, as add-on therapy in type 2 diabetes patients inadequately controlled with metformin alone. RESEARCH DESIGN AND METHODS - A total of 156 patients were randomized 1:1 to receive imeglimin (1,500mg twice a day) or placebo added to a stable dose of metformin (1,500-2,000 mg/day). Change in A1C from baseline was the primary efficacy outcome; secondary outcomes included fasting plasma glucose (FPG) and proinsulin/insulin ratio. RESULTS - After 12 weeks, the placebo-subtracted decrease in A1C with metformin-imeglimin was 20.44% (P <0.001). Metformin-imeglimin also significantly improved FPG and the proinsulin/insulin ratio from baseline (20.91 mg/dL and 27.5, respectively) compared with metformin-placebo (0.36 mg/dL and 11.81). Metformin-imeglimin therapy was generally welltolerated with a comparable safety profile to metformin-placebo. CONCLUSIONS - Addition of imeglimin to metformin improved glycemic control and offers potential as a new treatment for type 2 diabetes. Copyright © 2013 by the American Diabetes Association.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Relevância:

100.00% 100.00%

Publicador:

Resumo:

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

In this paper we examine the impact that the new trading system SETSmm had on market quality measures such as firm value, liquidity and pricing efficiency. This system was introduced for mid-cap securities on the London Stock Exchange in 2003. We show that there is a small SETSmm return premium associated with the announcement that securities are to migrate to the new trading system. We find that migration to SETSmm also improves liquidity and pricing efficiency and these changes are related to the return premium. We also find that these gains are stronger for firms with high pre SETSmm liquidity and weaker for firms with low SETSmm liquidity. © 2013 John Wiley & Sons Ltd.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

For more than a century it has been known that the eye is not a perfect optical system, but rather a system that suffers from aberrations beyond conventional prescriptive descriptions of defocus and astigmatism. Whereas traditional refraction attempts to describe the error of the eye with only two parameters, namely sphere and cylinder, measurements of wavefront aberrations depict the optical error with many more parameters. What remains questionable is the impact these additional parameters have on visual function. Some authors have argued that higher-order aberrations have a considerable effect on visual function and in certain cases this effect is significant enough to induce amblyopia. This has been referred to as ‘higher-order aberration-associated amblyopia’. In such cases, correction of higher-order aberrations would not restore visual function. Others have reported that patients with binocular asymmetric aberrations display an associated unilateral decrease in visual acuity and, if the decline in acuity results from the aberrations alone, such subjects may have been erroneously diagnosed as amblyopes. In these cases, correction of higher-order aberrations would restore visual function. This refractive entity has been termed ‘aberropia’. In order to investigate these hypotheses, the distribution of higher-order aberrations in strabismic, anisometropic and idiopathic amblyopes, and in a group of visual normals, was analysed both before and after wavefront-guided laser refractive correction. The results show: (i) there is no significant asymmetry in higher-order aberrations between amblyopic and fixing eyes prior to laser refractive treatment; (ii) the mean magnitude of higher-order aberrations is similar within the amblyopic and visually normal populations; (iii) a significant improvement in visual acuity can be realised for adult amblyopic patients utilising wavefront-guided laser refractive surgery and a modest increase in contrast sensitivity was observed for the amblyopic eye of anisometropes following treatment (iv) an overall trend towards increased higher-order aberrations following wavefront-guided laser refractive treatment was observed for both visually normal and amblyopic eyes. In conclusion, while the data do not provide any direct evidence for the concepts of either ‘aberropia’ or ‘higher-order aberration-associated amblyopia’, it is clear that gains in visual acuity and contrast sensitivity may be realised following laser refractive treatment of the amblyopic adult eye. Possible mechanisms by which these gains are realised are discussed.

Relevância:

100.00% 100.00%

Publicador:

Resumo:

Pre-eclampsia is a vascular disorder of pregnancy where anti-angiogenic factors, systemic inflammation and oxidative stress predominate, but none can claim to cause pre-eclampsia. This review provides an alternative to the 'two-stage model' of pre-eclampsia in which abnormal spiral arteries modification leads to placental hypoxia, oxidative stress and aberrant maternal systemic inflammation. Very high maternal soluble fms-like tyrosine kinase-1 (sFlt-1 also known as sVEGFR) and very low placenta growth factor (PlGF) are unique to pre-eclampsia; however, abnormal spiral arteries and excessive inflammation are also prevalent in other placental disorders. Metaphorically speaking, pregnancy can be viewed as a car with an accelerator and brakes, where inflammation, oxidative stress and an imbalance in the angiogenic milieu act as the 'accelerator'. The 'braking system' includes the protective pathways of haem oxygenase 1 (also referred as Hmox1 or HO-1) and cystathionine-γ-lyase (also known as CSE or Cth), which generate carbon monoxide (CO) and hydrogen sulphide (H2S) respectively. The failure in these pathways (brakes) results in the pregnancy going out of control and the system crashing. Put simply, pre-eclampsia is an accelerator-brake defect disorder. CO and H2S hold great promise because of their unique ability to suppress the anti-angiogenic factors sFlt-1 and soluble endoglin as well as to promote PlGF and endothelial NOS activity. The key to finding a cure lies in the identification of cheap, safe and effective drugs that induce the braking system to keep the pregnancy vehicle on track past the finishing line.