The excess burden of obesity among African–American women is well documented. However, the behavioural weight loss intervention literature often does not report results by ethnic group or gender. The ...purpose of this article is to conduct a systematic review of all behavioural weight loss intervention trials published between 1990 and 2010 that included and reported results separately for African–American women. The criteria for inclusion included (i) participants age ≥18 years; (ii) a behavioural weight loss intervention; (iii) weight as an outcome variable; (iv) inclusion of African–American women; and (v) weight loss results reported separately by ethnicity and gender. The literature search identified 25 studies that met inclusion criteria. Our findings suggest that more intensive randomized behavioural weight loss trials with medically at‐risk populations yield better results. Well‐designed and more intensive multi‐site trials with medically at‐risk populations currently offer the most promising results for African–American women. Still, African–American women lose less weight than other subgroups in behavioural weight loss interventions. It is now critical to expand on individual‐level approaches and incorporate the biological, social and environmental factors that influence obesity. This will help enable the adoption of healthier behaviours for this group of women disproportionately affected by obesity.
In recent years, sea spray as well as the biological material it contains has received increased attention as a source of ice-nucleating particles (INPs). Such INPs may play a role in remote marine ...regions, where other sources of INPs are scarce or absent. In the Arctic, these INPs can influence water–ice partitioning in low-level clouds and thereby the cloud lifetime, with consequences for the surface energy budget, sea ice formation and melt, and climate. Marine aerosol is of a diverse nature, so identifying sources of INPs is challenging. One fraction of marine bioaerosol (phytoplankton and their exudates) has been a particular focus of marine INP research. In our study we attempt to address three main questions. Firstly, we compare the ice-nucleating ability of two common phytoplankton species with Arctic seawater microlayer samples using the same instrumentation to see if these phytoplankton species produce ice-nucleating material with sufficient activity to account for the ice nucleation observed in Arctic microlayer samples. We present the first measurements of the ice-nucleating ability of two predominant phytoplankton species: Melosira arctica, a common Arctic diatom species, and Skeletonema marinoi, a ubiquitous diatom species across oceans worldwide. To determine the potential effect of nutrient conditions and characteristics of the algal culture, such as the amount of organic carbon associated with algal cells, on the ice nucleation activity, Skeletonema marinoi was grown under different nutrient regimes. From comparison of the ice nucleation data of the algal cultures to those obtained from a range of sea surface microlayer (SML) samples obtained during three different field expeditions to the Arctic (ACCACIA, NETCARE, and ASCOS), we found that they were not as ice active as the investigated microlayer samples, although these diatoms do produce ice-nucleating material. Secondly, to improve our understanding of local Arctic marine sources as atmospheric INPs we applied two aerosolization techniques to analyse the ice-nucleating ability of aerosolized microlayer and algal samples. The aerosols were generated either by direct nebulization of the undiluted bulk solutions or by the addition of the samples to a sea spray simulation chamber filled with artificial seawater. The latter method generates aerosol particles using a plunging jet to mimic the process of oceanic wave breaking. We observed that the aerosols produced using this approach can be ice active, indicating that the ice-nucleating material in seawater can indeed transfer to the aerosol phase. Thirdly, we attempted to measure ice nucleation activity across the entire temperature range relevant for mixed-phase clouds using a suite of ice nucleation measurement techniques – an expansion cloud chamber, a continuous-flow diffusion chamber, and a cold stage. In order to compare the measurements made using the different instruments, we have normalized the data in relation to the mass of salt present in the nascent sea spray aerosol. At temperatures above 248 K some of the SML samples were very effective at nucleating ice, but there was substantial variability between the different samples. In contrast, there was much less variability between samples below 248 K. We discuss our results in the context of aerosol–cloud interactions in the Arctic with a focus on furthering our understanding of which INP types may be important in the Arctic atmosphere.
An emerging strategy for the treatment of monogenic diseases uses genetic engineering to precisely correct the mutation(s) at the genome level. Recent advancements in this technology have ...demonstrated therapeutic levels of gene correction using a zinc-finger nuclease (ZFN)-induced DNA double-strand break in conjunction with an exogenous DNA donor substrate. This strategy requires efficient nucleic acid delivery and among viral vectors, recombinant adeno-associated virus (rAAV) has demonstrated clinical success without pathology. However, a major limitation of rAAV is the small DNA packaging capacity and to date, the use of rAAV for ZFN gene delivery has yet to be reported. Theoretically, an ideal situation is to deliver both ZFNs and the repair substrate in a single vector to avoid inefficient gene targeting and unwanted mutagenesis, both complications of a rAAV co-transduction strategy. Therefore, a rAAV format was generated in which a single polypeptide encodes the ZFN monomers connected by a ribosome skipping 2A peptide and furin cleavage sequence. On the basis of this arrangement, a DNA repair substrate of 750 nucleotides was also included in this vector. Efficient polypeptide processing to discrete ZFNs is demonstrated, as well as the ability of this single vector format to stimulate efficient gene targeting in a human cell line and mouse model derived fibroblasts. Additionally, we increased rAAV-mediated gene correction up to sixfold using a combination of Food and Drug Administration-approved drugs, which act at the level of AAV vector transduction. Collectively, these experiments demonstrate the ability to deliver ZFNs and a repair substrate by a single AAV vector and offer insights for the optimization of rAAV-mediated gene correction using drug therapy.
SummaryBackgroundPopulation-based cancer survival estimates provide valuable insights into the effectiveness of cancer services and can reflect the prospects of cure. As part of the second phase of ...the International Cancer Benchmarking Partnership (ICBP), the Cancer Survival in High-Income Countries (SURVMARK-2) project aims to provide a comprehensive overview of cancer survival across seven high-income countries and a comparative assessment of corresponding incidence and mortality trends. MethodsIn this longitudinal, population-based study, we collected patient-level data on 3·9 million patients with cancer from population-based cancer registries in 21 jurisdictions in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK) for seven sites of cancer (oesophagus, stomach, colon, rectum, pancreas, lung, and ovary) diagnosed between 1995 and 2014, and followed up until Dec 31, 2015. We calculated age-standardised net survival at 1 year and 5 years after diagnosis by site, age group, and period of diagnosis. We mapped changes in incidence and mortality to changes in survival to assess progress in cancer control. FindingsIn 19 eligible jurisdictions, 3 764 543 cases of cancer were eligible for inclusion in the study. In the 19 included jurisdictions, over 1995–2014, 1-year and 5-year net survival increased in each country across almost all cancer types, with, for example, 5-year rectal cancer survival increasing more than 13 percentage points in Denmark, Ireland, and the UK. For 2010–14, survival was generally higher in Australia, Canada, and Norway than in New Zealand, Denmark, Ireland, and the UK. Over the study period, larger survival improvements were observed for patients younger than 75 years at diagnosis than those aged 75 years and older, and notably for cancers with a poor prognosis (ie, oesophagus, stomach, pancreas, and lung). Progress in cancer control (ie, increased survival, decreased mortality and incidence) over the study period was evident for stomach, colon, lung (in males), and ovarian cancer. InterpretationThe joint evaluation of trends in incidence, mortality, and survival indicated progress in four of the seven studied cancers. Cancer survival continues to increase across high-income countries; however, international disparities persist. While truly valid comparisons require differences in registration practice, classification, and coding to be minimal, stage of disease at diagnosis, timely access to effective treatment, and the extent of comorbidity are likely the main determinants of patient outcomes. Future studies are needed to assess the impact of these factors to further our understanding of international disparities in cancer survival. FundingCanadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; The Scottish Government; Western Australia Department of Health; and Wales Cancer Network.
Diets rich in saturated fatty acids (SFAs) produce a form of tissue inflammation driven by “metabolically activated” macrophages. We show that SFAs, when in excess, induce a unique transcriptional ...signature in both mouse and human macrophages that is enriched by a subset of ER stress markers, particularly IRE1α and many adaptive downstream target genes. SFAs also activate the NLRP3 inflammasome in macrophages, resulting in IL-1β secretion. We found that IRE1α mediates SFA-induced IL-1β secretion by macrophages and that its activation by SFAs does not rely on unfolded protein sensing. We show instead that the ability of SFAs to stimulate either IRE1α activation or IL-1β secretion can be specifically reduced by preventing their flux into phosphatidylcholine (PC) or by increasing unsaturated PC levels. Thus, IRE1α is an unrecognized intracellular PC sensor critical to the process by which SFAs stimulate macrophages to secrete IL-1β, a driver of diet-induced tissue inflammation.
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•Saturated fatty acids induce an ER stress transcriptional signature in macrophages•Flux of saturated fatty acids into phospholipids activates the ER stress sensor IRE1α•IRE1α mediates saturated fatty-acid-induced activation of the NLRP3 inflammasome
Excessive saturated fat consumption promotes tissue inflammation driven by “metabolically activated” macrophages. Here, Robblee et al. use transcriptomic profiling to identify the ER stress sensor IRE1α as a key component of metabolic activation that senses phospholipid saturation to mediate inflammatory activation in macrophages exposed to saturated fat.
Hidradenitis suppurativa (HS) affects predominantly women of reproductive age and frequently flares during the perimenstrual period, indicating a hormonal influence. Studies on the effect of ...pregnancy on HS disease severity have reported improvement, no change and worsening during pregnancy. We aimed to assess changes in HS disease course during pregnancy and postpartum and identify potential predictors of HS pregnancy outcomes.
Understanding hydraulic fracturing: a multi-scale problem Hyman, J. D.; Jiménez-Martínez, J.; Viswanathan, H. S. ...
Philosophical transactions of the Royal Society of London. Series A: Mathematical, physical, and engineering sciences,
10/2016, Letnik:
374, Številka:
2078
Journal Article
Recenzirano
Odprti dostop
Despite the impact that hydraulic fracturing has had on the energy sector, the physical mechanisms that control its efficiency and environmental impacts remain poorly understood in part because the ...length scales involved range from nanometres to kilometres. We characterize flow and transport in shale formations across and between these scales using integrated computational, theoretical and experimental efforts/methods. At the field scale, we use discrete fracture network modelling to simulate production of a hydraulically fractured well from a fracture network that is based on the site characterization of a shale gas reservoir. At the core scale, we use triaxial fracture experiments and a finite-discrete element model to study dynamic fracture/crack propagation in low permeability shale. We use lattice Boltzmann pore-scale simulations and microfluidic experiments in both synthetic and shale rock micromodels to study pore-scale flow and transport phenomena, including multi-phase flow and fluids mixing. A mechanistic description and integration of these multiple scales is required for accurate predictions of production and the eventual optimization of hydrocarbon extraction from unconventional reservoirs. Finally, we discuss the potential of CO2 as an alternative working fluid, both in fracturing and re-stimulating activities, beyond its environmental advantages.
This article is part of the themed issue ‘Energy and the subsurface’.
This work follows Lykins et al. discussion of classic plasma cooling function at low density and solar metallicity. Here, we focus on how the cooling function changes over a wide range of density (n
...H <1012 cm−3) and metallicity (Z < 30 Z⊙). We find that high densities enhance the ionization of elements such as hydrogen and helium until they reach local thermodynamic equilibrium. By charge transfer, the metallicity changes the ionization of hydrogen when it is partially ionized. We describe the total cooling function as a sum of four parts: those due to H&He, the heavy elements, electron–electron bremsstrahlung and grains. For the first three parts, we provide a low-density limit cooling function, a density dependence function, and a metallicity-dependent function. These functions are given with numerical tables and analytical fit functions. We discuss grain cooling only in the interstellar medium case. We then obtain a total cooling function that depends on density, metallicity and temperature. As expected, collisional de-excitation suppresses the heavy elements cooling. Finally, we provide a function giving the electron fraction, which can be used to convert the cooling function into a cooling rate.
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