Counterflow dielectrophoresis for trypanosome enrichment and detection in blood

Human African trypanosomiasis or sleeping sickness is a deadly disease endemic in sub-Saharan Africa, caused by single-celled protozoan parasites. Although it has been targeted for elimination by 2020, this will only be realized if diagnosis can be improved to enable identification and treatment of afflicted patients. Existing techniques of detection are restricted by their limited field-applicability, sensitivity and capacity for automation. Microfluidic-based technologies offer the potential for highly sensitive automated devices that could achieve detection at the lowest levels of parasitemia and consequently help in the elimination programme. In this work we implement an electrokinetic technique for the separation of trypanosomes from both mouse and human blood. This technique utilises differences in polarisability between the blood cells and trypanosomes to achieve separation through opposed bi-directional movement (cell counterflow). We combine this enrichment technique with an automated image analysis detection algorithm, negating the need for a human operator

Beyond the culture effect on credibility perception on microblogs

We investigated the credibility perception of tweet readers from the USA and by readers from eight Arabic countries; our aim was to understand if credibility was affected by country and/or by culture. Results from a crowd-sourcing experiment, showed a wide variety of factors affected credibility perception, including a tweet author's gender, profile image, username style, location, and social network overlap with the reader. We found that culture determines readers' credibility perception, but country has no effect. We discuss the implications of our findings for user interface design and social media systems

Induction immunosuppression in adults undergoing liver transplantation: a network meta-analysis

BACKGROUND: Liver transplantation is considered the definitive treatment for people with liver failure. As part of post-liver transplantation management, immunosuppression (suppressing the host immunity) is given to prevent graft rejections. Immunosuppressive drugs can be classified into those that are used for a short period during the beginning phase of immunosuppression (induction immunosuppression) and those that are used over the entire lifetime of the individual (maintenance immunosuppression), because it is widely believed that graft rejections are more common during the first few months after liver transplantation. Some drugs such as glucocorticosteroids may be used for both induction and maintenance immunosuppression because of their multiple modalities of action. There is considerable uncertainty as to whether induction immunosuppression is necessary and if so, the relative efficacy of different immunosuppressive agents. OBJECTIVES: To assess the comparative benefits and harms of different induction immunosuppressive regimens in adults undergoing liver transplantation through a network meta-analysis and to generate rankings of the different induction immunosuppressive regimens according to their safety and efficacy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until July 2019 to identify randomised clinical trials in adults undergoing liver transplantation. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or status) in adults undergoing liver transplantation. We excluded randomised clinical trials in which participants had multivisceral transplantation and those who already had graft rejections. DATA COLLECTION AND ANALYSIS: We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, and hazard ratio (HR) with 95% credible intervals (CrIs) based on an available case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS: We included a total of 25 trials (3271 participants; 8 treatments) in the review. Twenty-three trials (3017 participants) were included in one or more outcomes in the review. The trials that provided the information included people undergoing primary liver transplantation for various indications and excluded those with HIV and those with renal impairment. The follow-up in the trials ranged from three to 76 months, with a median follow-up of 12 months among trials. All except one trial were at high risk of bias, and the overall certainty of evidence was very low. Overall, approximately 7.4% of people who received the standard regimen of glucocorticosteroid induction died and 12.2% developed graft failure. All-cause mortality and graft failure was lower with basiliximab compared with glucocorticosteroid induction: all-cause mortality (HR 0.53, 95% CrI 0.31 to 0.93; network estimate, based on 2 direct comparison trials (131 participants; low-certainty evidence)); and graft failure (HR 0.44, 95% CrI 0.28 to 0.70; direct estimate, based on 1 trial (47 participants; low-certainty evidence)). There was no evidence of differences in all-cause mortality and graft failure between other induction immunosuppressants and glucocorticosteroids in either the direct comparison or the network meta-analysis (very low-certainty evidence). There was also no evidence of differences in serious adverse events (proportion), serious adverse events (number), renal failure, any adverse events (proportion), any adverse events (number), liver retransplantation, graft rejections (any), or graft rejections (requiring treatment) between other induction immunosuppressants and glucocorticosteroids in either the direct comparison or the network meta-analysis (very low-certainty evidence). However, because of the wide CrIs, clinically important differences in these outcomes cannot be ruled out. None of the studies reported health-related quality of life. FUNDING: the source of funding for 14 trials was drug companies who would benefit from the results of the study; two trials were funded by neutral organisations who have no vested interests in the results of the study; and the source of funding for the remaining nine trials was unclear. AUTHORS' CONCLUSIONS: Based on low-certainty evidence, basiliximab induction may decrease mortality and graft failure compared to glucocorticosteroids induction in people undergoing liver transplantation. However, there is considerable uncertainty about this finding because this information is based on small trials at high risk of bias. The evidence is uncertain about the effects of different induction immunosuppressants on other clinical outcomes, including graft rejections. Future randomised clinical trials should be adequately powered, employ blinding, avoid post-randomisation dropouts (or perform intention-to-treat analysis), and use clinically important outcomes such as mortality, graft failure, and health-related quality of life

Marginalization of end-use technologies in energy innovation for climate protection

Mitigating climate change requires directed innovation efforts to develop and deploy energy technologies. Innovation activities are directed towards the outcome of climate protection by public institutions, policies and resources that in turn shape market behaviour. We analyse diverse indicators of activity throughout the innovation system to assess these efforts. We find efficient end-use technologies contribute large potential emission reductions and provide higher social returns on investment than energy-supply technologies. Yet public institutions, policies and financial resources pervasively privilege energy-supply technologies. Directed innovation efforts are strikingly misaligned with the needs of an emissions-constrained world. Significantly greater effort is needed to develop the full potential of efficient end-use technologies

Omanicotyle heterospina n. gen. et n. comb. (Monogenea: Microcotylidae) from the gills of Argyrops spinifer (Forsskal) (Teleostei: Sparidae) from the Sea of Oman

Background: The Sultanate of Oman's aquaculture industry is expanding with an on-going assessment of potential new fish species for culture. The king soldier bream, Argyrops spinifer (Forsskål) (Sparidae), is one such species that is under consideration. During a routine health assessment of specimens caught in the Sea of Oman throughout the period November 2009 to March 2011, a number of gill polyopisthocotylean monogeneans were recovered. Methods: A subsequent study of the monogeneans using a range of morphology-based approaches indicated that these were Bivagina heterospina Mamaev et Parukhin, 1974. In the absence of pre-existing molecular data, an expanded description of this species is provided, including a differential diagnosis with other species and genera belonging to the subfamily Microcotylinae Monticelli, 1892 with the subsequent movement of this species to a new genus to accommodate it. Results: The polyopisthocotyleans collected from the gills of A. spinifer appear to be unique within the family Microcotylidae Taschenberg, 1879 in that, morphologically, they possess a pair of large, muscular vaginae each armed with a full crown of 16-18 robust spines and a unique dorsal region of folded tegument, which permits their discrimination from species of Bivagina Yamaguti, 1963. Sequencing of the SSU rDNA (complete 1968 bp) and LSU rDNA (partial 949 bp) places the specimens collected during this study within the subfamily Microcotylinae, but the LSU rDNA sequence differs from Bivagina and also from other microcotylid genera. Morphological features of B. heterospina sensu Mamaev et Parukhin, 1974 and the specimens collected from the current study are consistent with one another and represent a single species. The vaginal armature of these worms is unique and differs from all other genera within the Microcotylinae, including Bivagina, and its movement to Omanicotyle n. gen. to accommodate this species is proposed. Conclusions: A new genus, Omanicotyle n. gen., is erected to accommodate Omanicotyle [Bivagina] heterospina n. comb. which represents the first monogenean to be described from Omani marine waters. Given the pathogenic potential of microcotylids on captive held fish stocks, a full assessment of Omanicotyle heterospina n. gen. et n. comb. is now required before large-scale production commences

Nutritional supplementation for nonalcohol-related fatty liver disease: a network meta-analysis.

BACKGROUND: The prevalence of non-alcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases risks of liver cirrhosis, hepatocellular carcinoma, and the requirement for liver transplantation. Uncertainty surrounds relative benefits and harms of various nutritional supplements in NAFLD. Currently no nutritional supplement is recommended for people with NAFLD. OBJECTIVES: • To assess the benefits and harms of different nutritional supplements for treatment of NAFLD through a network meta-analysis • To generate rankings of different nutritional supplements according to their safety and efficacy SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index-Science, the World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or status) for people with NAFLD, irrespective of method of diagnosis, age and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS: We performed a network meta-analysis with OpenBUGS using Bayesian methods whenever possible and calculated differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios with 95% credible intervals (CrIs) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. MAIN RESULTS: We included in the review a total of 202 randomised clinical trials (14,200 participants). Nineteen trials were at low risk of bias. A total of 32 different interventions were compared in these trials. A total of 115 trials (7732 participants) were included in one or more comparisons. The remaining trials did not report any of the outcomes of interest for this review. Follow-up ranged from 1 month to 28 months. The follow-up period in trials that reported clinical outcomes was 2 months to 28 months. During this follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. We did not calculate effect estimates for mortality because of sparse data (zero events for at least one of the groups in the trial). None of the trials reported that they measured overall health-related quality of life using a validated scale. The evidence is very uncertain about effects of interventions on serious adverse events (number of people or number of events). We are very uncertain about effects on adverse events of most of the supplements that we investigated, as the evidence is of very low certainty. However, people taking PUFA (polyunsaturated fatty acid) may be more likely to experience an adverse event than those not receiving an active intervention (network meta-analysis results: OR 4.44, 95% CrI 2.40 to 8.48; low-certainty evidence; 4 trials, 203 participants; direct evidence: OR 4.43, 95% CrI 2.43 to 8.42). People who take other supplements (a category that includes nutritional supplements other than vitamins, fatty acids, phospholipids, and antioxidants) had higher numbers of adverse events than those not receiving an active intervention (network meta-analysis: rate ratio 1.73, 95% CrI 1.26 to 2.41; 6 trials, 291 participants; direct evidence: rate ratio 1.72, 95% CrI 1.25 to 2.40; low-certainty evidence). Data were sparse (zero events in all groups in the trial) for liver transplantation, liver decompensation, and hepatocellular carcinoma. So, we did not perform formal analysis for these outcomes. The evidence is very uncertain about effects of other antioxidants (antioxidants other than vitamins) compared to no active intervention on liver cirrhosis (HR 1.68, 95% CrI 0.23 to 15.10; 1 trial, 99 participants; very low-certainty evidence). The evidence is very uncertain about effects of interventions in any of the remaining comparisons, or data were sparse (with zero events in at least one of the groups), precluding formal calculations of effect estimates. Data were probably because of the very short follow-up period (2 months to 28 months). It takes follow-up of 8 to 28 years to detect differences in mortality between people with NAFLD and the general population. Therefore, it is unlikely that differences in clinical outcomes are noted in trials providing less than 5 to 10 years of follow-up. AUTHORS' CONCLUSIONS: The evidence indicates considerable uncertainty about effects of nutritional supplementation compared to no additional intervention on all clinical outcomes for people with non-alcohol-related fatty liver disease. Accordingly, high-quality randomised comparative clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (study design in which multiple interventions are trialed within large longitudinal cohorts of patients to gain efficiencies and align trials more closely to standard clinical practice) comparing interventions such as vitamin E, prebiotics/probiotics/synbiotics, PUFAs, and no nutritional supplementation. The reason for the choice of interventions is the impact of these interventions on indirect outcomes, which may translate to clinical benefit. Outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource utilisation measures including costs of intervention and decreased healthcare utilisation after minimum follow-up of 8 years (to find meaningful differences in clinically important outcomes)

Lifestyle modifications for nonalcohol-related fatty liver disease: a network meta-analysis

BACKGROUND: The prevalence of nonalcohol-related fatty liver disease (NAFLD) varies between 19% and 33% in different populations. NAFLD decreases life expectancy and increases the risks of liver cirrhosis, hepatocellular carcinoma, and requirement for liver transplantation. There is uncertainty surrounding the relative benefits and harms of various lifestyle interventions for people with NAFLD. OBJECTIVES: To assess the comparative benefits and harms of different lifestyle interventions in the treatment of NAFLD through a network meta-analysis, and to generate rankings of the different lifestyle interventions according to their safety and efficacy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, World Health Organization International Clinical Trials Registry Platform, and trials registers until February 2021 to identify randomised clinical trials in people with NAFLD. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or status) in people with NAFLD, whatever the method of diagnosis, age, and diabetic status of participants, or presence of non-alcoholic steatohepatitis (NASH). We excluded randomised clinical trials in which participants had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS: We planned to perform a network meta-analysis with OpenBUGS using Bayesian methods and to calculate the differences in treatments using hazard ratios (HRs), odds ratios (ORs), and rate ratios (RaRs) with 95% credible intervals (CrIs) based on an available-participant analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. However, the data were too sparse for the clinical outcomes. We therefore performed only direct comparisons (head-to-head comparisons) with OpenBUGS using Bayesian methods. MAIN RESULTS: We included a total of 59 randomised clinical trials (3631 participants) in the review. All but two trials were at high risk of bias. A total of 33 different interventions, ranging from advice to supervised exercise and special diets, or a combination of these and no additional intervention were compared in these trials. The reference treatment was no active intervention. Twenty-eight trials (1942 participants) were included in one or more comparisons. The follow-up ranged from 1 month to 24 months. The remaining trials did not report any of the outcomes of interest for this review. The follow-up period in the trials that reported clinical outcomes was 2 months to 24 months. During this short follow-up period, clinical events related to NAFLD such as mortality, liver cirrhosis, liver decompensation, liver transplantation, hepatocellular carcinoma, and liver-related mortality were sparse. This is probably because of the very short follow-up periods. It takes a follow-up of 8 years to 28 years to detect differences in mortality between people with NAFLD and the general population. It is therefore unlikely that differences by clinical outcomes will be noted in trials with less than 5 years to 10 years of follow-up. In one trial, one participant developed an adverse event. There were no adverse events in any of the remaining participants in this trial, or in any of the remaining trials, which seemed to be directly related to the intervention. AUTHORS' CONCLUSIONS: The evidence indicates considerable uncertainty about the effects of the lifestyle interventions compared with no additional intervention (to general public health advice) on any of the clinical outcomes after a short follow-up period of 2 months to 24 months in people with nonalcohol-related fatty liver disease. Accordingly, high-quality randomised clinical trials with adequate follow-up are needed. We propose registry-based randomised clinical trials or cohort multiple randomised clinical trials (a study design in which multiple interventions are trialed within large longitudinal cohorts of participants to gain efficiencies and align trials more closely to standard clinical practice), comparing aerobic exercise and dietary advice versus standard of care (exercise and dietary advice received as part of national health promotion). The reason for the choice of aerobic exercise and dietary advice is the impact of these interventions on indirect outcomes which may translate to clinical benefit. The outcomes in such trials should be mortality, health-related quality of life, decompensated liver cirrhosis, liver transplantation, and resource use measures including costs of intervention and decreased healthcare use after a minimum follow-up of eight years, to find meaningful differences in the clinically important outcomes

Antibiotic treatment for spontaneous bacterial peritonitis in people with decompensated liver cirrhosis:a network meta-analysis

Background: Approximately 2.5% of all hospitalisations in people with cirrhosis are for spontaneous bacterial peritonitis (SBP). Antibiotics, in addition to supportive treatment (fluid and electrolyte balance, treatment of shock), form the mainstay treatments of SBP. Various antibiotics are available for the treatment of SBP, but there is uncertainty regarding the best antibiotic for SBP. Objectives: To compare the benefits and harms of different antibiotic treatments for spontaneous bacterial peritonitis (SBP) in people with decompensated liver cirrhosis. Search methods: We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until November 2018 to identify randomised clinical trials on people with cirrhosis and SBP. Selection criteria: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adults with cirrhosis and SBP. We excluded randomised clinical trials in which participants had previously undergone liver transplantation. Data collection and analysis: Two review authors independently identified eligible trials and collected data. The outcomes for this review included mortality, serious adverse events, any adverse events, resolution of SBP, liver transplantation, and other decompensation events. We performed a network meta‐analysis with OpenBUGS using Bayesian methods and calculated the odds ratio, rate ratio, and hazard ratio with 95% credible intervals (CrIs) based on an available‐case analysis, according to the National Institute of Health and Care Excellence (NICE) Decision Support Unit guidance. Main results: We included a total of 12 trials (1278 participants; 13 antibiotics) in the review. Ten trials (893 participants) were included in one or more outcomes in the review. The trials that provided the information included patients having cirrhosis with or without other features of decompensation of varied aetiologies. The follow‐up in the trials ranged from one week to three months. All the trials were at high risk of bias. Only one trial was included under each comparison for most of the outcomes. Because of these reasons, there is very low certainty in all the results. The majority of the randomised clinical trials used third‐generation cephalosporins, such as intravenous ceftriaxone, cefotaxime, or ciprofloxacin as one of the interventions. Overall, approximately 75% of trial participants recovered from SBP and 25% of people died within three months. There was no evidence of difference in any of the outcomes for which network meta‐analysis was possible: mortality (9 trials; 653 participants), proportion of people with any adverse events (5 trials; 297 participants), resolution of SBP (as per standard definition, 9 trials; 873 participants), or other features of decompensation (6 trials; 535 participants). The effect estimates in the direct comparisons (when available) were very similar to those of network meta‐analysis. For the comparisons where network meta‐analysis was not possible, there was no evidence of difference in any of the outcomes (proportion of participants with serious adverse events, number of adverse events, and proportion of participants requiring liver transplantation). Due to the wide CrIs and the very low‐certainty evidence for all the outcomes, significant benefits or harms of antibiotics are possible. None of the trials reported health‐related quality of life, number of serious adverse events, or symptomatic recovery from SBP. Funding: the source of funding for two trials were industrial organisations who would benefit from the results of the trial; the source of funding for the remaining 10 trials was unclear. Authors' conclusions: Short‐term mortality after SBP is about 25%. There is significant uncertainty about which antibiotic therapy is better in people with SBP. We need adequately powered randomised clinical trials, with adequate blinding, avoiding post‐randomisation dropouts (or performing intention‐to‐treat analysis), and using clinically important outcomes, such as mortality, health‐related quality of life, and adverse events

Decreased expression of breast cancer resistance protein in the duodenum in patients with obstructive cholestasis

Background/Aims: The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Since the drug efflux transporter breast cancer resistance protein (BCRP) is known to transport bile acids, we investigated whether duodenal BCRP expression could be altered during cholestasis. Methods: Using real-time RT-PCR analysis we determined mRNA expression levels in duodenal tissue of 19 cholestatic patients. Expression levels were compared to 14 healthy subjects. BCRP protein staining was determined in biopsies of 6 cholestatic and 6 healthy subjects by immunohistochemistry. Results: We found that in patients with obstructive cholestasis mean duodenal BCRP mRNA levels were significantly reduced to 53% and mean protein staining was reduced to 57%. Conclusions: BCRP, a transporter for bile acids and numerous drugs, appears to be down-regulated in the human duodenum during cholestasis. The clinical impact of these results has to be investigated in further studies. Copyright (c) 2006 S. Karger AG, Basel