1,156 research outputs found
Adults With Type 2 Diabetes Mellitus Exhibit a Greater Exercise-Induced Increase in Arterial Stiffness and Vessel Hemodynamics
Individuals with type 2 diabetes mellitus (T2DM) have a greater blood pressure (BP) response to acute maximal exercise compared to those without T2DM; however, whether they exhibit a different arterial stiffness response to maximal exercise has yet to be explored. Adults with (n=66) and without T2DM (n=61) underwent an arterial stress test: at rest and immediately postexercise, carotid-femoral pulse wave velocity, the gold standard measure of arterial stiffness, brachial BP, heart rate, and other hemodynamic measurements were assessed. Linear regression models were used to evaluate between-group differences at rest, and the response to exercise (postexercise value), adjusting for covariates including BP and heart rate when relevant, and the corresponding baseline value of each parameter. All participants (mean +/- SD: age 59.3 +/- 10.6 years; body mass index 31.2 +/- 3.9 kg/m(2)) had hypertension (mean BP 130 +/- 14/80 +/- 9 mm Hg). At rest, participants with T2DM had significantly higher carotid-femoral pulse wave velocity (10.3 +/- 2.7 versus 9.1 +/- 1.9 m/s), heart rate (69 +/- 11 versus 66 +/- 10 beats/min), and lower diastolic BP (79 +/- 9 versus 83 +/- 9 mm Hg), but systolic BP (129 +/- 15 versus 131 +/- 13 mm Hg) was similar. In response to exercise, participants with T2DM showed greater increases in carotid-femoral pulse wave velocity (1.6 [95% CI, 0.4-2.9 m/s]) and systolic BP (9 [95% CI, 1-17 mm Hg]) than participants without T2DM. A greater proportion of participants with T2DM had a hypertensive response to exercise compared to participants without T2DM (n=23, 35% versus n=11, 18%; P=0.033). By incorporating exercise as a vascular stressor, we provide evidence of a greater increase in arterial stiffness in individuals with T2DM, independently of resting arterial stiffness, and the BP postexercise.</p
What are the impacts of within-field farmland management practices on the flux of greenhouse gases from arable cropland in temperate regions? A systematic map protocol
Background: Reducing greenhouse gas emissions is a vital step in limiting climate change and meeting the goals outlined in the COP 21 Paris Agreement of 2015. Studies have suggested that agriculture accounts for around 11% of total greenhouse gas emissions and the industry has a significant role in meeting international and national climate change reduction objectives. However, there is currently little consensus on the mechanisms that regulate the production and assimilation of greenhouse gases in arable land and the practical factors that affect the process. Practical advice for farmers is often overly general, and models based on the amount of nitrogen fertiliser applied, for example, are used despite a lack of knowledge of how local conditions affect the process, such as the importance of humus content and soil types. Here, we propose a systematic map of the evidence relating to the impact on greenhouse gas flux from the agricultural management of arable land in temperate regions. Methods: Using established methods for systematic mapping in environmental sciences we will search for, collate and catalogue research studies relating to the impacts of farming in temperate systems on greenhouse gas emissions. We will search 6 bibliographic databases using a tested search string, and will hand search a web-based search engine and a list of organisational web sites. Furthermore, evidence will be sought from key stakeholders. Search results will then be screened for relevance at title, abstract and full text levels according to a predefined set of eligibility criteria. Consistency checking will be employed to ensure the criteria are being applied accurately and consistently. Relevant studies will then be subjected to coding and meta-data extraction, which will be used to populate a systematic map database describing each relevant study's settings, methods and measured outcomes. The mapping process will help to identify knowledge gaps (subjects lacking in evidence warranting further primary research) and knowledge clusters (subjects with sufficient studies to allow a useful full systematic review), and will highlight best and suboptimal research methods
Experimental conditions affect the outcome of Plasmodium falciparum platelet-mediated clumping assays
<p>Abstract</p> <p>Background</p> <p>Platelet-mediated clumping of <it>Plasmodium falciparum</it>-infected erythrocytes (IE) is a parasite adhesion phenotype that has been associated with severe malaria in some, but not all, field isolate studies. A variety of experimental conditions have been used to study clumping <it>in vitro</it>, with substantial differences in parasitaemia (Pt), haematocrit (Ht), and time of reaction between studies. It is unknown whether these experimental variables affect the outcome of parasite clumping assays.</p> <p>Methods</p> <p>The effects of Pt (1, 4 and 12%), Ht (2, 5 and 10%) and time (15 min, 30 min, 1 h, 2 h) on the clumping of <it>P. falciparum </it>clone HB3 were examined. The effects of platelet freshness and parasite maturity were also studied.</p> <p>Results</p> <p>At low Ht (2%), the Pt of the culture has a large effect on clumping, with significantly higher clumping occurring at 12% Pt (mean 47% of IE in clumps) compared to 4% Pt (mean 26% IE in clumps) or 1% Pt (mean 7% IE in clumps) (ANOVA, p = 0.0004). Similarly, at low Pt (1%), the Ht of the culture has a large effect on clumping, with significantly higher clumping occurring at 10% Ht (mean 62% IE in clumps) compared to 5% Ht (mean 25% IE in clumps) or 2% Ht (mean 10% IE in clumps) (ANOVA, p = 0.0004). Combinations of high Ht and high Pt were impractical because of the difficulty assessing clumping in densely packed IE and the rapid formation of enormous clumps that could not be counted accurately. There was no significant difference in clumping when fresh platelets were used compared to platelets stored at 4°C for 10 days. Clumping was a property of mature pigmented-trophozoites and schizonts but not ring stage parasites.</p> <p>Conclusion</p> <p>The Pt and Ht at which <it>in vitro </it>clumping assays are set up have a profound effect on the outcome. All previous field isolate studies on clumping and malaria severity suffer from potential problems in experimental design and methodology. Future studies of clumping should use standardized conditions and control for Pt, and should take into account the limitations and variability inherent in the assay.</p
Recommended from our members
A systematic review of frameworks for the interrelationships of mental health evidence and policy in low- and middle-income countries
Background: The interrelationships between research evidence and policy-making are complex. Different theoretical frameworks exist to explain general evidence–policy interactions. One largely unexplored element of these interrelationships is how evidence interrelates with, and influences, policy/political agenda-setting. This review aims to identify the elements and processes of theories, frameworks and models on interrelationships of research evidence and health policy-making, with a focus on actionability and agenda-setting in the context of mental health in low- and middle-income countries (LMICs).
Methods: A systematic review of theories was conducted based on the BeHeMOTh search method, using a tested and refined search strategy. Nine electronic databases and other relevant sources were searched for peer-reviewed and grey literature. Two reviewers screened the abstracts, reviewed full-text articles, extracted data and performed quality assessments. Analysis was based on a thematic analysis. The included papers had to present an actionable theoretical framework/model on evidence and policy interrelationships, such as knowledge translation or evidence-based policy, specifically target the agenda-setting process, focus on mental health, be from LMICs and published in English.
Results: From 236 publications included in the full text analysis, no studies fully complied with our inclusion criteria. Widening the focus by leaving out ‘agenda-setting’, we included ten studies, four of which had unique conceptual frameworks focusing on mental health and LMICs but not agenda-setting. The four analysed frameworks confirmed research gaps from LMICs and mental health, and a lack of focus on agenda-setting. Frameworks and models from other health and policy areas provide interesting conceptual approaches and lessons with regards to agenda-setting.
Conclusion: Our systematic review identified frameworks on evidence and policy interrelations that differ in their elements and processes. No framework fulfilled all inclusion criteria. Four actionable frameworks are applicable to mental health and LMICs, but none specifically target agenda-setting. We have identified agenda-setting as a research theory gap in the context of mental health knowledge translation in LMICs. Frameworks from other health/policy areas could offer lessons on agenda-setting and new approaches for creating policy impact for mental health and to tackle the translational gap in LMICs
Elite Suppressor–Derived HIV-1 Envelope Glycoproteins Exhibit Reduced Entry Efficiency and Kinetics
Elite suppressors (ES) are a rare subset of HIV-1–infected individuals who are able to maintain HIV-1 viral loads below the limit of detection by ultra-sensitive clinical assays in the absence of antiretroviral therapy. Mechanism(s) responsible for this elite control are poorly understood but likely involve both host and viral factors. This study assesses ES plasma-derived envelope glycoprotein (env) fitness as a function of entry efficiency as a possible contributor to viral suppression. Fitness of virus entry was first evaluated using a novel inducible cell line with controlled surface expression levels of CD4 (receptor) and CCR5 (co-receptor). In the context of physiologic CCR5 and CD4 surface densities, ES envs exhibited significantly decreased entry efficiency relative to chronically infected viremic progressors. ES envs also demonstrated slow entry kinetics indicating the presence of virus with reduced entry fitness. Overall, ES env clones were less efficient at mediating entry than chronic progressor envs. Interestingly, acute infection envs exhibited an intermediate phenotypic pattern not distinctly different from ES or chronic progressor envs. These results imply that lower env fitness may be established early and may directly contribute to viral suppression in ES individuals
Intestinal Damage Determines the Inflammatory Response and Early Complications in Patients Receiving Conditioning for a Stem Cell Transplantation
Contains fulltext :
87954.pdf (publisher's version ) (Open Access)BACKGROUND: Stem cell transplantation (SCT) is still complicated by the occurrence of fever and inflammatory complications attributed to neutropenia and subsequent infectious complications. The role of mucosal barrier injury (MBI) of the intestinal tract therein has received little attention. METHODS: We performed a retrospective analysis in 163 SCT recipients of which data had been collected prospectively on intestinal damage (citrulline), inflammation (C-reactive protein), and neutrophil count. Six different conditioning regimens were studied; 5 myeloablative (MA) and 1 non-myeloablative (NMA). Linear mixed model multivariate and AUC analyses were used to define the role of intestinal damage in post-SCT inflammation. We also studied the relationship between the degree of intestinal damage and the occurrence of early post-SCT complications. RESULTS: In the 5 MA regimen there was a striking pattern of inflammatory response that coincided with the occurrence of severe intestinal damage. This contrasted with a modest inflammatory response seen in the NMA regimen in which intestinal damage was limited. With linear mixed model analysis the degree of intestinal damage was shown the most important determinant of the inflammatory response, and both neutropenia and bacteremia had only a minor impact. AUC analysis revealed a strong correlation between citrulline and CRP (Pearson correlation r = 0.96). Intestinal damage was associated with the occurrence of bacteremia and acute lung injury, and influenced the kinetics of acute graft-versus-host disease. CONCLUSION: The degree of intestinal damage after myeloablative conditioning appeared to be the most important determined the inflammatory response following SCT, and was associated with inflammatory complications. Studies should explore ways to ameliorate cytotoxic therapy-induced intestinal damage in order to reduce complications associated with myeloablative conditioning therapy
Damaged Intestinal Epithelial Integrity Linked to Microbial Translocation in Pathogenic Simian Immunodeficiency Virus Infections
The chronic phase of HIV infection is marked by pathological activation of the immune system, the extent of which better predicts disease progression than either plasma viral load or CD4+ T cell count. Recently, translocation of microbial products from the gastrointestinal tract has been proposed as an underlying cause of this immune activation, based on indirect evidence including the detection of microbial products and specific immune responses in the plasma of chronically HIV-infected humans or SIV-infected Asian macaques. We analyzed tissues from SIV-infected rhesus macaques (RMs) to provide direct in situ evidence for translocation of microbial constituents from the lumen of the intestine into the lamina propria and to draining and peripheral lymph nodes and liver, accompanied by local immune responses in affected tissues. In chronically SIV-infected RMs this translocation is associated with breakdown of the integrity of the epithelial barrier of the gastrointestinal (GI) tract and apparent inability of lamina propria macrophages to effectively phagocytose translocated microbial constituents. By contrast, in the chronic phase of SIV infection in sooty mangabeys, we found no evidence of epithelial barrier breakdown, no increased microbial translocation and no pathological immune activation. Because immune activation is characteristic of the chronic phase of progressive HIV/SIV infections, these findings suggest that increased microbial translocation from the GI tract, in excess of capacity to clear the translocated microbial constituents, helps drive pathological immune activation. Novel therapeutic approaches to inhibit microbial translocation and/or attenuate chronic immune activation in HIV-infected individuals may complement treatments aimed at direct suppression of viral replication
Multilocus Sequence Typing as a Replacement for Serotyping in Salmonella enterica
Salmonella enterica subspecies enterica is traditionally subdivided into serovars by serological and nutritional characteristics. We used Multilocus Sequence Typing (MLST) to assign 4,257 isolates from 554 serovars to 1092 sequence types (STs). The majority of the isolates and many STs were grouped into 138 genetically closely related clusters called eBurstGroups (eBGs). Many eBGs correspond to a serovar, for example most Typhimurium are in eBG1 and most Enteritidis are in eBG4, but many eBGs contained more than one serovar. Furthermore, most serovars were polyphyletic and are distributed across multiple unrelated eBGs. Thus, serovar designations confounded genetically unrelated isolates and failed to recognize natural evolutionary groupings. An inability of serotyping to correctly group isolates was most apparent for Paratyphi B and its variant Java. Most Paratyphi B were included within a sub-cluster of STs belonging to eBG5, which also encompasses a separate sub-cluster of Java STs. However, diphasic Java variants were also found in two other eBGs and monophasic Java variants were in four other eBGs or STs, one of which is in subspecies salamae and a second of which includes isolates assigned to Enteritidis, Dublin and monophasic Paratyphi B. Similarly, Choleraesuis was found in eBG6 and is closely related to Paratyphi C, which is in eBG20. However, Choleraesuis var. Decatur consists of isolates from seven other, unrelated eBGs or STs. The serological assignment of these Decatur isolates to Choleraesuis likely reflects lateral gene transfer of flagellar genes between unrelated bacteria plus purifying selection. By confounding multiple evolutionary groups, serotyping can be misleading about the disease potential of S. enterica. Unlike serotyping, MLST recognizes evolutionary groupings and we recommend that Salmonella classification by serotyping should be replaced by MLST or its equivalents
A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns.
In cancer, the primary tumour's organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA
The double-design dilemma : political science, parliamentary crisis and disciplinary justifications
Two separate, but inter-linked, dilemmas have highlighted the importance of design-led thinking. First, the crumbling physical fabric of the Palace of Westminster has prompted a multi-billion rebuilding project, which will require the parliamentary studies specialism to engage with questions of design, space, and architecture. Separately, political science more generally has been challenged to utilize the insights of design-thinking and design-practice: a challenge to which it is culturally and methodological ill-equipped. This article considers what a design-led approach to political science looks like in theory, and in practice, in the case study of the Restoration and Renewal of the Palace of Westminster. This represents a first attempt at how such a fusion could be beneficial for both politics as theory and politics as practice. The main conclusion is that although design-orientated political science is not a panacea for the challenges of modern democratic governance – in intellectual or practical terms – it does appear to offer significant potential in terms of theoretically-informed but solution focused research
- …