Subcellular localization of monoglyceride acyltransferase, xanthine oxidation, NADP: isocitrate dehydrogenase and alkaline phosphatase in the mucosa of the guinea-pig small intestine.

1. Rate dependent and isopycnic banding in a zonal rotor were used to analyse the subcellular sites of enzymes in homogenates of guinea-pig small intestinal mucosa. 2, The results demonstrate the following localizations: monoglyceride acyltransferase-microsomal; xanthine oxidase and dehydrogenase-soluble phase, and NADP: isocitrate dehydrogenase-soluble phase and mitochondrial. 3, Alkaline phosphatase is confined to brush borders and is absent from the basolateral plasma membrane. A variable proportion of the activity, up to 40%, is on brush borders which during homogenization break up into particles of reduced density and slow sedimentation rate

Intestinal peroxisomes of goldfish (Carrassius auratus) - examination for hydrolase, dehydrogenase and carnitine acetyltransferase activities.

1. Rate sedimentation and isopycnic centrifugation were used to analyse the subcellular sites of enzymes in homogenates of goldfish intestinal mucosa. 2. The results allowed the following allocations to be made: carnitine acetyl transferase-mitochondrial and peroxisomal, xanthine dehydrogenase and NAD: :x-glycerophosphate dehydrogenase soluble phase; NADP: isocitrate dehydrogenase soluble phase and mitochondrial, and 2-naphthyl laurate hydrolase microsomal and/or brush border. 3. Histochemistry confirmed the use of alkaline phosphatase and I-naphthyl acetate esterase as brush border and microsome markers respectively. 4. Urate oxidase, allantoinase, allantoicase, xanthine oxidase and glycollatejlactate oxidase, activities were undetectable, and I-naphthyl palmilale hydrolase was present only as a contaminant from pancreas

Zonal rotor study of the subcellular distribution of acyl-CoA synthetases, carnitine acyl transferases and phosphatidate phosphatase in the guinea-pig small intestine.

Homogenates made from the mucosa of the guinea pig small intestine were fractionated in a zonal rotor by rate and isopycnic centrifugation in sucrose gradients. Density perturbation of endoplasmic reticulum vesicles was done by treating homogenate with pyrophosphate and was analysed by isopyenic centrifugation. Subcellular fractions were analysed for the distribution of markers for brush borders. basolateral plasma membrane. Iysosomes. peroxi. somes. mitochondria. nuclei and endoplasmic reliculum. Fractions werc also analysed for the distribution ofpropionyl-. butyryl-. and palmityl. CoA synthetases. for carnitine acetyl and palmityltransferases. and for phosphatidate phosphatase. Comparison of marker and unknown distributions shows that palmityl- CoA synthetase is located on the endoplasmic reticulum. while propionyl- and butyryl-CoA synthetases and carnitine acetyl and pal. mit)'l transferases are exclusively mitochondrial. I'hosphatidate phosphatase has complex subcellular localisation with activity in brush borders. microsomes (possibly not the endoplasmic reticulum component) and possibly Iysosomes

Optimising video for e-commerce

An e-commerce video is an online video which offers one or more items for the viewer to directly buy. It is a new type of media content, resulting from the fusion of the retail, content creation and digital marketing industries, and it is enjoying rapid, global growth. But what kind of video works best in e-commerce? How is such video best produced and distributed? What are the optimal strategies for content in e-commerce video?Through his critical analysis of a set of works published from 2013-18, the author has sought to break new ground through answering these questions. He sets three specific objectives, around which the narrative of this thesis is built, in looking to provide a better understanding of the route to optimization of video content for e-commerce. First, he evaluates what literature already exists, in both the parent category of branded content, and in the new, fast-growth sub-category of e-commerce video itself - around the drivers of success in shoppable video content creation. He finds that coverage is quite substantial around e-commerce and social media, and in the technical routes to successful e-commerce sales through video distribution. But it is sparse with respect to the content itself, which allows him the space to make a meaningful contribution. Second, he considers and contextualises his own original research into the existence of a ‘cliff-edge’ in branded content including e-commerce video. In a piece of video content, there is a point beyond which greater brand integration has a negative effect on customer engagement and sales. Knowing that point is vital to the advertiser. Here the author’s original, new research provides useful insight into the gradations of in-content branding that are effective, and this cut-off moment where the audience begins to respond negatively. Third, the author considers and contextualises his own additional new, original research into which specific styles of e-commerce video are most likely to deliver results. Here he provides multiple new findings - such as the fact that multi-product videos are more likely to sell goods than ones featuring single products alone; or that mute videos are better sales tools than videos with presenters, or using user-generated content. By answering the three research questions, the author provides focus and nuance to an academic topic which is barely a decade old, and in a developing media content genre which is commercially powerful, global and evolving fast. As a reflection on that rapid change, the author adds a postscript chapter where he reviews all the technologies that are driving the growth of e-commerce video into the future, including Artificial Intelligence

Total hip replacement for the treatment of end stage arthritis of the hip : a systematic review and meta-analysis

Background: Evolvements in the design, fixation methods, size, and bearing surface of implants for total hip replacement (THR) have led to a variety of options for healthcare professionals to consider. The need to determine the most optimal combinations of THR implant is warranted. This systematic review evaluated the clinical effectiveness of different types of THR used for the treatment of end stage arthritis of the hip. Methods: A comprehensive literature search was undertaken in major health databases. Randomised controlled trials (RCTs) and systematic reviews published from 2008 onwards comparing different types of primary THR in patients with end stage arthritis of the hip were included. Results: Fourteen RCTs and five systematic reviews were included. Patients experienced significant post-THR improvements in Harris Hip scores, but this did not differ between impact types. There was a reduced risk of implant dislocation after receiving a larger femoral head size (36 mm vs. 28 mm; RR = 0.17, 95% CI: 0.04, 0.78) or cemented cup (vs. cementless cup; pooled odds ratio: 0.34, 95% CI: 0.13, 0.89). Recipients of cross-linked vs. conventional polyethylene cup liners experienced reduced femoral head penetration and revision. There was no impact of femoral stem fixation and cup shell design on implant survival rates. Evidence on mortality and complications (aseptic loosening, femoral fracture) was inconclusive. Conclusions: The majority of evidence was inconclusive due to poor reporting, missing data, or uncertainty in treatment estimates. The findings warrant cautious interpretation given the risk of bias (blinding, attrition), methodological limitations (small sample size, low event counts, short follow-up), and poor reporting. Long-term pragmatic RCTs are needed to allow for more definitive conclusions. Authors are encouraged to specify the minimal clinically important difference and power calculation for their primary outcome(s) as well CONSORT, PRISMA and STROBE guidelines to ensure better reporting and more reliable production and assessment of evidence

Belimumab : a technological advance for systemic lupus erythematosus patients? Report of a systematic review and meta-analysis

Objectives: To undertake a systematic review and meta-analysis to investigate clinical effectiveness of belimumab for patients with systemic lupus erythematosus (SLE) and antinuclear and/or anti-double-stranded DNA (dsDNA) autoantibodies. Methods: We searched eight electronic databases and reference lists for randomised controlled trials (RCTs) of belimumab against placebo or best supportive care. Quality assessment and random effects meta-analysis were undertaken. Design: A meta-analysis of RCTs. Participants: 2133 SLE patients. Primary and secondary outcome measures: SLE Responder Index (SRI) at week 52. Results: Three double-blind placebo-controlled RCTs (L02, BLISS-52 BLISS-76) investigated 2133 SLE patients. BLISS-52 and BLISS-76 trials recruited patients with antinuclear and/or anti-dsDNA autoantibodies and demonstrated belimumab effectiveness for the SRI at week 52. Ethnicity and geographical location of participants varied considerably between BLISS trials. Although tests for statistical heterogeneity were negative, BLISS-52 results were systematically more favourable for all measured outcomes. Meta-analysis of pooled 52-week SRI BLISS results showed benefit for belimumab (OR 1.63, 95% CI 1.27 to 2.09). By week 76, the primary SRI outcome in BLISS-76 was not statistically significant (OR 1.31, 95% CI 0.919 to 1.855)

Is monitoring of plasma 5-fluorouracil levels in metastatic / advanced colorectal cancer clinically effective? A systematic review

Background: Pharmacokinetic guided dosing of 5-fluorouracil chemotherapies to bring plasma 5-fluorouracil into a desired therapeutic range may lead to fewer side effects and better patient outcomes. High performance liquid chromatography and a high throughput nanoparticle immunoassay (My5-FU) have been used in conjunction with treatment algorithms to guide dosing. The objective of this study was to assess accuracy, clinical effectiveness and safety of plasma 5-fluorouracil guided dose regimen(s) versus standard regimens based on body surface area in colorectal cancer. Methods: We undertook a systematic review. MEDLINE; MEDLINE In-Process & Other Non-Indexed Citations; EMBASE; Cochrane Library; Science Citation Index and Conference Proceedings (Web of Science); and NIHR Health Technology Assessment Programme were searched from inception to January 2014. We reviewed evidence on accuracy of My5-FU for estimating plasma 5-fluorouracil and on the clinical effectiveness of pharmacokinetic dosing compared to body surface area dosing. Estimates of individual patient data for overall survival and progression-free survival were reconstructed from published studies. Survival and adverse events data were synthesised and examined for consistency across studies. Results: My5-FU assays were found to be consistent with reference liquid chromatography tandem mass spectrometry. Comparative studies pointed to gains in overall survival and in progression-free survival with pharmacokinetic dosing, and were consistent across multiple studies. Conclusions: Although our analyses are encouraging, uncertainties remain because evidence is mainly from outmoded 5-fluorouracil regimens; a randomised controlled trial is urgently needed to investigate new dose adjustment methods in modern treatment regimens

Test accuracy of drug and antibody assays for predicting response to anti-Tumour Necrosis Factor treatment in Crohn’s disease : a systematic review and meta-analysis

Objective: To present meta-analytic test accuracy estimates of levels of anti-TNF and antibodies to anti-TNF to predict loss of response or lack of regaining response in anti-TNF managed Crohn’s disease patients. Methods: MEDLINE, Embase, the Cochrane Library and Science Citation Index were searched from inception to October / November 2014 to identify studies which reported 2x2 table data of the association between levels of anti-TNF or its antibodies and clinical status. Hierarchical / bivariate meta-analysis was undertaken with the user-written “metandi” package of Harbord and Whiting using Stata 11 software, for Infliximab, Adalimumab, anti-Infliximab and anti-Adalimumab levels as predictors of loss of response. Prevalence of Crohn’s disease in included studies was meta-analysed using a random effects model in MetaAnalyst software to calculate positive and negative predictive values. The search was updated in January 2017. Results: 31 studies were included in the review. Studies were heterogeneous with respect to type of test used, criteria for establishing response and loss of response, population examined, and results. Metaanalytic summary point estimates for sensitivity and specificity were 65.7% and 80.6% for Infliximab trough levels and 56% and 79% for antibodies to Infliximab, respectively. Pooled results for Adalimumab trough levels and antibodies to Adalimumab were similar. Pooled positive and negative predictive values ranged between 70% and 80% implying that between 20% and 30% of both positive and negative test results may be incorrect in predicting loss of response. Conclusion: The available evidence suggests that these tests have modest predictive accuracy for clinical status, direct test accuracy comparisons in the same population are needed. More clinical trial evidence from test-treat studies is required before the clinical utility of the tests can be reliably evaluated

Primary care management for optimized antithrombotic treatment [PICANT]: study protocol for a cluster-randomized controlled trial

Background: Antithrombotic treatment is a continuous therapy that is often performed in general practice and requires careful safety management. The aim of this study is to investigate whether a best practice model that applies major elements of case management, including patient education, can improve antithrombotic management in primary health care in terms of reducing major thromboembolic and bleeding events. Methods: This 24-month cluster-randomized trial will be performed in 690 adult patients from 46 practices. The trial intervention will be a complex intervention involving general practitioners, health care assistants and patients with an indication for oral anticoagulation. To assess adherence to medication and symptoms in patients, as well as to detect complications early, health care assistants will be trained in case management and will use the Coagulation-Monitoring-List (Co-MoL) to regularly monitor patients. Patients will receive information (leaflets and a video), treatment monitoring via the Co-MoL and be motivated to perform self-management. Patients in the control group will continue to receive treatment-as-usual from their general practitioners. The primary endpoint is the combined endpoint of all thromboembolic events requiring hospitalization, and all major bleeding complications. Secondary endpoints are mortality, hospitalization, strokes, major bleeding and thromboembolic complications, severe treatment interactions, the number of adverse events, quality of anticoagulation, health-related quality of life and costs. Further secondary objectives will be investigated to explain the mechanism by which the intervention is effective: patients' assessment of chronic illness care, self-reported adherence to medication, general practitioners' and health care assistants' knowledge, patients' knowledge and satisfaction with shared decision making. Practice recruitment is expected to take place between July and December 2012. Recruitment of eligible patients will start in July 2012. Assessment will occur at three time points: baseline (T0), follow-up after 12 (T1) and after 24 months (T2). Discussion: The efficacy and effectiveness of individual elements of the intervention, such as antithrombotic interventions, self-management concepts in orally anticoagulated patients and the methodological tool, case-management, have already been extensively demonstrated. This project foresees the combination of several proven instruments, as a result of which we expect to profit from a reduction in the major complications associated with antithrombotic treatment