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Embracing nature’s complexity: Immunoparasitology in the wild
No full textA wealth of research is dedicated to understanding how resistance against parasites is conferred and how parasite-driven pathology is regulated. This research is in part driven by the hope to better treatments for parasitic diseases of humans and livestock, and in part by immunologists who use parasitic infections as biomedical tools to evoke physiological immune responses. Much of the current mechanistic knowledge has been discovered in laboratory studies using model organisms, especially the laboratory mouse. However, wildlife are also hosts to a range of parasites. Through the study of host-parasite interactions in these non-laboratory systems we can gain a deeper understanding of parasite immunology in a more natural, complex environment. With a focus on helminth parasites, we here explore the insights gained into parasite-induced immune responses through (for immunologists) non-conventional experimental systems, and how current core findings from laboratory studies are reflected in these more natural conditions. The quality of the immune response is undoubtedly a central player in susceptibility versus resistance, as many laboratory studies have shown. Yet, in the wild, parasite infections tend to be chronic diseases. Whilst reading our review, we encourage the reader to consider the following questions which may (only) be answered by studying naturally occurring parasites in the wild: a) what type of immune responses are mounted against parasites in different hosts in the wild, and how do they vary within an individual over time, between individuals of the same species and between species? b) can we use wild or semi-wild study systems to understand the evolutionary drivers for tolerance versus resistance towards a parasite? c) what determines the ability of the host to cope with an infection and is there a link with the type of immune response mounted? d) can we modulate environmental factors to manipulate a wild animal’s immune response to parasitic infections, with translation potential for humans, wildlife, and livestock? and e) in context of this special issue, what lessons for type 2 immunity can we glean from studying animals in their natural environments? Further, we aim to integrate some of the knowledge gained in semi-wild and wild settings with knowledge gained from traditional laboratory-based research, and to raise awareness for the opportunities (and challenges) that come with integrating a multitude of naturally-occurring variables into immunoparasitological research
Pore Distortion in a Metal-Organic Framework for Regulated Separation of Propane and Propylene
No full textThe development of porous solids for adsorptive separation of propylene and propane remains an important and challenging line of research. State-of-the-art sorbent materials often suffer from the trade-off between adsorption capacity and selectivity. Here, we report the regulated separation of propylene and propane in a metal-organic framework via designed pore distortion. The distorted pore structure of HIAM-301 successfully excludes propane and thus achieved simultaneously high selectivity (>150) and large capacity (~3.2 mmol/g) of propylene at 298 K and 1 bar. Dynamic breakthrough measurements validated the excellent separation of propane and propylene. In situ neutron powder diffraction and inelastic neutron scattering revealed the binding domains of adsorbed propylene molecules in HIAM-301 as well as host-guest interaction dynamics. This study presents a new benchmark for the adsorptive separation of propylene and propane
Synthesis of 2D anatase TiO2 with Highly Reactive Facets by Fluorine-free Topochemical Conversion of 1T-TiS2 nanosheets
No full textTwo-dimensional (2D) anatase titanium dioxide (TiO2) is expected to exhibit different properties as compared to anatase nanocrystallites, due to its highly reactive exposed facets. However, access to 2D anatase TiO2 is limited by the non-layered nature of the bulk crystal, which does not allow to use top-down chemical exfoliation. Large effort has been dedicated to the growth of 2D anatase TiO2 with high reactive facets by bottom-up approaches, which relies on the use of harmful chemical reagents. Here, we demonstrate a novel fluorine-free strategy based on topochemical conversion of 2D 1T-TiS2 for the production of single crystalline 2D anatase TiO2, exposing the {001} facet on top and bottom and {100} at the sides of the nanosheet. The exposure of these faces, with no additional defects or doping, gives rise to a significant activity enhancement in the hydrogen evolution reaction, as compared to commercially available Degussa P25 TiO2 nanoparticles.Because of the strong potential of TiO2 in many energy-based applications, our topochemical approach offers a low cost, green and mass scalable route for production of highly crystalline anatase TiO2 with well controlled and highly reactive exposed facets
Exploratory study of the association in the United Kingdom between hypertension and inorganic arsenic (iAs) intake from rice and rice products
No full textHypertension risks arising from chronic exposure to inorganic arsenic (iAs) are well documented. Consumption of rice is a major iAs exposure route for over 3 billion people, however, there is a lack of epidemiological evidence demonstrating an association of hypertension risks with iAs intake from rice, especially in areas where there is little exposure from drinking water but a growing demand for rice intake.To address this, we conducted an individual-level cross-sectional analysis to quantify the extent to which daily iAs intake from rice & rice products (E-iAsing,rice) modifies the association between hypertension risks and previously well-established risk factors. The analysis was based on secondary dietary, socio-demographic and health status data of 598 participants recorded in the UK National Diet and Nutrition Survey 2014 - 2016. E-iAsing, rice and five blood pressure endpoints were derived with potential associations explored through generalized linear models. According to the results, a negative but not significant relationship was found between hypertension risks and E-iAsing, rice after adjusting for major risk factors, notably age, gender, diabetes and obesity, with relatively higher risks being observed for male, middle-aged, overweight, alcohol consumer or Asian or Asian British, Black or Black British and mixed ethnic groups.Though inconclusive and mainly limited by potential incomplete adjustment for major confounders and intrinsic disadvantages of a cross-sectional design, this study was the first quantifying the individual level dose-response relationship between E-iAsing, rice and hypertension risks, and is consistent with previous studies on the limited associations of hypertension with low level arsenic exposure from drinking water. Larger scale cohort studies are indicated to quantify the association but in any event it is likely to be weak
Understanding Refractory Rheumatoid Arthritis:Implications for a Therapeutic Approach
No full textRefractory rheumatoid arthritis (RA) has emerged as an area of unmet need in a landscape of generally well-controlled disease. Whilst most patients are adequately treated on methotrexate and other first-line disease-modifying anti-rheumatic drugs (DMARDs), a proportion requires biologic (b) and targeted synthetic (ts) DMARDs, with a further subsection failing multiple agents. Recent observational studies have adopted working definitions of refractory RA based on number of failed DMARDs, with prevalence estimates of 6–21% depending on threshold and study population. Risk factors include treatment delay, baseline disease activity and function, female gender, smoking, obesity and lower socioeconomic status. Practical and conceptual challenges in defining refractory RA arise from limitations of disease activity scores used to assess response, with attendant misclassification risk of co-existent non-inflammatory pathology, and failure to capture additional outcomes, such as fatigue, that have variable treatment response. Time is an important factor in defining refractory disease; registry studies show that growing treatment options have resulted in rapid b/tsDMARD cycling and earlier refractory status, and refractory RA is itself a dynamic concept, evolving with each new therapeutic class. Whilst the biology underpinning refractory RA remains largely unknown, a general overview of biomarker studies and clinical trials old and new offers insights into prediction of response and treatment failure. Whilst the future holds promise, current data are insufficient to personalise or meaningfully sequence b/tsDMARDs. Therefore, avoidance of a refractory course is best achieved by following proven management paradigms (e.g. early diagnosis and treat-to-target), addressing modifiable risk factors, and considering enrolment in novel trials.</p
Cause of intrauterine and neonatal Death in Twin Pregnancies (CoDiT): development of a novel classification system
No full textObjective: Twin pregnancies have a significantly higher perinatal mortality than singleton pregnancies and current classification systems for perinatal death lack twin-specific categories, potentially leading to loss of important information regarding cause of death. We introduce and test a classification system designed to assign a cause of death in twin pregnancies (CoDiT).Design: Retrospective cross-sectional study.Setting: Tertiary maternity unit in England with a perinatal pathology service.Population: Twin pregnancies in the West Midlands affected by fetal or neonatal demise of one or both twins between 1st January 2005 and 31st December 2016 in which post-mortem examination was undertaken.Methods: A multidisciplinary panel designed CoDiT by adapting the most appropriate elements of singleton classification systems. The system was tested by assigning cause of death in 265 fetal and neonatal deaths from 144 twin pregnancies. Cause of death was validated by another obstetrician blinded to the original classification.Main Outcome Measures: Inter-rater, intra-rater, inter-disciplinary agreement and cause of death.Results: Cohen’s Kappa demonstrated “strong” (>0.8) inter-rater, intra-rater and inter-disciplinary agreement (95% CI 0.70-0.91). The commonest cause of death irrespective of chorionicity was the placenta; twin-to-twin transfusion syndrome (TTTS) was the commonest placental cause in monochorionic twins and acute chorioamnionitis in dichorionic twins.Conclusions: This novel classification system records causes of death in twin pregnancies from postmortem reports with high inter-user agreement. We highlight differences in aetiology of deathbetween monochorionic and dichorionic twins
Circular Economy Financing: Clear Winner or Risky Proposition?
No full textA major shift in private and public investment is needed to forge a transition to a circular economy. A recent surge of activity from policy makers, the financial industry, and other stakeholders suggests commitment and progress toward providing resources to facilitate this process. In this forum article, we provide a measured, and in some respects critical and corrective, assessment of these developments. We highlight the risk that progress toward a circular economy will be curtailed by strategic decisions based on contestable understanding, fuzzy indicators, and inadequate information. Before major industry actors implement international investment standards and innovative financing vehicles and ramp up investment, we call for more effective oversight to prevent the circular economy from becoming yet another compromised and ultimately ineffectual sustainability concept
The predictive value of signs and symptoms in predicting adverse maternal and perinatal outcomes in severe preeclampsia in a low-resource setting, findings from a cross-sectional study at Mpilo Central Hospital, Bulawayo, Zimbabwe.
No full textObjectives In low resource settings symptoms and signs may be used to identify which women require intervention to mitigate the risks of severe preeclampsia. This study aimed to report the frequency of signs and symptoms in women with severe preeclampsia and to determine their predictive value for adverse maternal and perinatal outcomes. Study design A retrospective cross-sectional study of women with severe preeclampsia from 01/01/2016 to 31/12/2018 at Mpilo Central Hospital, Bulawayo, Zimbabwe. Multivariate logistic regression was used to determine whether symptoms and signs were independently associated with the co-primary outcomes. Main outcome measures The co-primary outcome measures were a composite of maternal complications including major organ dysfunction or mortality and a composite measure of severe perinatal morbidity or mortality. Results Symptoms were present in 58.8% of women with severe preeclampsia; headache and epigastric pain were most commonly reported (47.9% and 22.4% of women respectively). Most symptoms and signs were not independently predictive of adverse maternal or perinatal outcomes. Vaginal bleeding with abdominal pain reduced odds of adverse maternal outcome (Adjusted Odds Ratio (AOR) 0.16, 95% Confidence Interval (CI) 0.03, 0.84; p=0.03), systolic blood pressure of 161-180 mmHg increased odds of adverse maternal outcome (AOR 2.71, 95% CI 1.14, 6.41, p=0.03) and birthweight ≤1500g increased odds of adverse perinatal outcome (AOR 23.21, 95% CI 7.70, 69.92, p<0.001). Conclusions Maternal signs and symptoms are ineffective predictors of maternal or perinatal morbidity and mortality; as such they cannot be used alone to predict which women would benefit from intervention in severe preeclampsia
Quartet states in two-electron quantum dots in bilayer graphene
No full textTrapping electrons in quantum dots and controlling their quantum states is crucial for converting semiconductor structures into bits of quantum information processing. Here, we study single- and two-particle states in electrostatically induced quantum dots in gapped bilayer graphene (BLG), where the electron’s valley states appear in pair with their spin quantum number. Moreover, the features of BLG’s electronic structure, such as the three mini-valleys around each valley, and the corresponding orbital magnetic moment, modify the characteristics of the dot states. In the weakly gapped case, the single-particle level scheme is that of an almost quadratic band. For a sufficiently strong gap, an additional threefold ”mini-valley degeneracy” emerges. Based on these single-particle states, we analyze the orbital, spin- and valley states of two interacting electrons in the dot. We find spin and valley singlets and triplet states depending on the BLG and dot parameters, as well as two-particle interaction strength and external magnetic field. The multiplicity and the spin/valley configuration of the single and two-particle states are essential for using these degrees of freedom in quantum transport and quantum computing with BLG QD devices