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The Ethics of Taxing Sugar-Sweetened Beverages to Improve Public Health
No full textThe World Health Organization highlights fiscal policies as priority interventions for the promotion of healthy eating in its Action Plan for the Prevention and Control of Non-communicable Diseases. The taxation of sugar sweetened beverages (SSBs) in particular is noted to be an effective measure, and SSBs taxes have already been implemented in several countries worldwide. However, although the evidence base suggests that this will be effective in helping to combat rising obesity rates, opponents of SSBs taxation argue that it is illiberal and paternalistic, and therefore should be avoided. Bioethical analysis may play an essential role in clarifying whether policymakers should adopt SSBs taxes as part of wider obesity strategy. In this article we argue that no single ethical theory can account for the complexities inherent in obesity prevention strategy, especially the liberal theories relied upon by opponents of SSBs taxation. We contend that a pluralist approach to the ethics of SSBs taxation must be adopted as the only suitable way of accounting for the multiple overlapping, and sometimes, conflicting factors that are relevant to determining the moral acceptability of such an intervention
Multi-parametric single cell evaluation defines distinct drug responses in healthy hematological cells that are retained in corresponding malignant cell types.
No full textInnate drug sensitivity in healthy cells aids identification of lineage
specific anti-cancer therapies and reveals off-target effects. To characterize the diversity in drug responses in the major hematopoietic cell
types, we simultaneously assessed their sensitivity to 71 small molecules
utilizing a multi-parametric flow cytometry assay and mapped their proteomic and basal signaling profiles. Unsupervised hierarchical clustering
identified distinct drug responses in healthy cell subsets based on their
cellular lineage. Compared to other cell types, CD19+
/B and CD56+
/NK
cells were more sensitive to dexamethasone, venetoclax and midostaurin, while monocytes were more sensitive to trametinib. Venetoclax
exhibited dose-dependent cell selectivity that inversely correlated to
STAT3 phosphorylation. Lineage specific effect of midostaurin was similarly detected in CD19+
/B cells from healthy, acute myeloid leukemia
and chronic lymphocytic leukemia samples. Comparison of drug
responses in healthy and neoplastic cells showed that healthy cell
responses are predictive of the corresponding malignant cell response.
Taken together, understanding drug sensitivity in the healthy cell-of-origin provides opportunities to obtain a new level of therapy precision and
avoid off-target toxicity
Targeting histone deacetylase 3 (HDAC3) in the bone marrow microenvironment inhibits multiple myeloma proliferation by modulating exosomes and IL-6 trans-signaling
No full textMultiple myeloma (MM) is an incurable cancer that derives pro-survival/proliferative signals from the bone marrow (BM)
niche. Novel agents targeting not only cancer cells, but also the BM-niche have shown the greatest activity in MM. Histone
deacetylases (HDACs) are therapeutic targets in MM and we previously showed that HDAC3 inhibition decreases MM
proliferation both alone and in co-culture with bone marrow stromal cells (BMSC). In this study, we investigate the effects
of HDAC3 targeting in BMSCs. Using both BMSC lines as well as patient-derived BMSCs, we show that HDAC3
expression in BMSCs can be induced by co-culture with MM cells. Knock-out (KO), knock-down (KD), and pharmacologic
inhibition of HDAC3 in BMSCs results in decreased MM cell proliferation; including in autologous cultures of patient MM
cells with BMSCs. We identified both quantitative and qualitative changes in exosomes and exosomal miRNA, as well as
inhibition of IL-6 trans-signaling, as molecular mechanisms mediating anti-MM activity. Furthermore, we show that
HDAC3-KD in BM endothelial cells decreases neoangiogenesis, consistent with a broad effect of HDAC3 targeting in the
BM-niche. Our results therefore support the clinical development of HDAC3 inhibitors based not only on their direct anti-
MM effects, but also their modulation of the BM microenvironment
Targeting adhesion in fungal pathogen Candida albicans
No full textFungal infections with increasing resistance to conventional therapies are a growing concern. Candida albicans is a major opportunistic yeast responsible for mucosal and invasive infections. Targeting the initial step of the infection process (i.e., C. albicans adhesion to the host cell) is a promising strategy. A wide variety of molecules can interfere with adhesion processes via an assortment of mechanisms. Herein, we focus on how small molecules disrupt biosynthesis of fungal cell wall components and membrane structure, prevent the localization of GPI-anchor proteins, inhibit production of enzymes involved in adhesion, downregulate genes encoding adhesins and competitively inhibit receptor interactions. As a result, adhesion of C. albicans to host cells is reduced, paving the way to new classes of antifungal agents
Graphene modified composites and electrodes and their potential applications in the Electro-Fenton process
No full textIn recent years, graphene-based materials have been identified as an emerging and promising new material in electro-Fenton, with the potential to form highly efficient metal-free catalysts that can be employed in the removal of contaminants from water, conserving precious water resources. In this review, the recent applications of graphene-based materials in electro-Fenton are described and discussed. Initially, homogenous and heterogenous electro-Fenton methods are briefly introduced, highlighting the importance of the generation of H2O2 from the two-electron reduction of dissolved oxygen and its catalysed decomposition to produce reactive and oxidising hydroxy radicals. Next, the promising applications of graphene-based electrodes in promoting this two-electron oxygen reduction reaction are considered and this is followed by an account of the various graphene-based materials that have been used successfully to give highly efficient graphene-based cathodes in electro-Fenton. In particular, graphene-based composites that have been combined with other carbonaceous materials, doped with nitrogen, formed as highly porous aerogels, three-dimensional materials and porous gas diffusion electrodes, used as supports for iron oxides and functionalised with ferrocene and employed in the more effective heterogeneous electro-Fenton, are all reviewed. It is perfectly clear that graphene-based materials have the potential to degrade and mineralise dyes, pharmaceutical compounds, antibiotics, phenolic compounds and show tremendous potential in electro-Fenton and other advanced oxidation processes
Developing a world view through a diversity of voices: A Reflection
No full textThe poems in this book give us the unique opportunity to explore the thoughts and imagination of people from a diversity of backgrounds and experiences. Some were born and raised in Ireland; some have come to live in Ireland from different countries including Nigeria, America, and Cyprus, while others currently live in other countries around the world. Many of the poets share a common sentiment of how tired, distressed and enraged they are by the vast array of social problems smattered across our globe. These voices resonated with me, reminding me of stories I heard in the United States, my home country. The global North and the global South share an unjust and lopsided history, yet we, those of us reading this book, those of us who are activists, those of us who are poets and writers and academics, we are coming together to demand justice, equality, and to save our planet
Extraction and transport of sulfate using macrocyclic squaramide receptors
No full textThe selective extraction of the hydrophilic sulfate ion from water is highly challenging because the high free
energy of hydration of this ion makes it more difficult to extract than less hydrophilic ions such as chloride
and nitrate. Lipophilic macrocyclic squaramide receptors 1 and 2 were synthesized. Receptor 2 efficiently
extracted sulfate from aqueous sodium sulfate solutions into a chloroform phase, via exchange with
nitrate ions, overcoming the Hofmeister bias. The resulting 2$SO4
2� complex was readily recycled
through precipitation of BaSO4. Transport of sulfate across a bulk chloroform membrane by 2 was
demonstrated across a wide pH range (pH 3.2–9.4) and in the presence of high concentrations of
competing anions (chloride, nitrate and dihydrogenphosphate), opening the door to the use of 2 for the
selective removal of sulfate from water across a range of applications
Analysis of multi-mode waveguide cavities containing free space gaps for use in future far-infrared telescopes
No full textIn order to investigate the formation and evolution of galaxies, stars and planetary systems, it is necessary to carry out astronomical observations in the far-infrared portion of the electromagnetic spectrum. Missions such as the Herschel Space Observatory (European Space Agency) have already completed observations in this region with great success. Proposed high resolution spectrometer instruments such as SAFARI (a joined European/Japanese (ESA/JAXA) proposal as part of the SPICA mission), aim to build upon the work of previous missions by carrying out observations in the 1.5–10 THz band with unprecedented levels of sensitivity. Spica (SPace Infrared telescope for Cosmology and Astrophysics) is currently a candidate mission as part of ESA’s Cosmic Vision 2015–2025.
Future far-IR missions must realise higher levels of sensitivity, limited only by the cosmic microwave background. One solution in achieving these sensitivity goals is to use waveguide coupled Transition Edge Sensor (TES) detectors, arranged in a densely packed focal plane. Additionally, multi-mode pixels can be used in order to maximise the optical throughput and coupling while still defining a definite beam shape. For the SAFARI instrument multimoded horns coupling into integrating waveguide cavities that house the TES detectors and associated absorbing layer are envisioned. This represents a significant technological challenge in terms of accurate manufacture tolerances relative to the short wavelength, however in the case of the SAFARI instrument pixel much work has already been carried out, with prototype pixels having undergone extensive testing at SRON (Space Research Organisation of the Netherlands) Groningen. In order to fully characterise the experimental results, it is necessary also to carry out comprehensive electromagnetic modelling of these structures which is also computationally intensive and requires novel approaches. These waveguide structures (horn and cavity) are typically electrically large however, and so analysis techniques using commercial finite element software prove inefficient (particularly as the structures are multimoded).
The mode-matching technique with new analytical features offer a computationally efficient and reliable alternative to full electromagnetic solvers, and in this paper we outline the additions to this technique that were necessary in order to allow typical SAFARI far-infrared pixels to be modeled, including the complete optical coupling calculation of the measurement test setup at SRON and the inclusion of the free space gap within the horn antenna and the integrating cavity. Optical coupling efficiencies simulated using this developed technique show excellent agreement with the experimental measurements
A universal Standardized Precipitation Index candidate distribution function for observations and simulations
No full textThe Standardized Precipitation Index (SPI) is awidely accepted drought index. Its calculation algorithm nor-malizes the index via a distribution function. Which distribu-tion function to use is still disputed within the literature. Thisstudy illuminates that long-standing dispute and proposes asolution that ensures the normality of the index for all com-mon accumulation periods in observations and simulations.We compare the normality of SPI time series derived withthe gamma, Weibull, generalized gamma, and the exponenti-ated Weibull distribution. Our normality comparison is basedon a complementary evaluation. Actual compared to theo-retical occurrence probabilities of SPI categories evaluatethe absolute performance of candidate distribution functions.Complementary, the Akaike information criterion evaluatescandidate distribution functions relative to each other whileanalytically punishing complexity. SPI time series, span-ning 1983–2013, are calculated from the Global PrecipitationClimatology Project’s monthly precipitation dataset, and sea-sonal precipitation hindcasts are from the Max Planck Insti-tute Earth System Model. We evaluate these SPI time seriesover the global land area and for each continent individuallyduring winter and summer. While focusing on regional per-formance disparities between observations and simulationsthat manifest in an accumulation period of 3 months, we ad-ditionally test the drawn conclusions for other common ac-cumulation periods (1, 6, 9, and 12 months).Our results suggest that calculating SPI with the com-monly used gamma distribution leads to deficiencies in theevaluation of ensemble simulations. Replacing it with theexponentiated Weibull distribution reduces the area of thoseregions where the index does not have any skill for precip-itation obtained from ensemble simulations by more than one magnitude. The exponentiated Weibull distribution max-imizes also the normality of SPI obtained from observationaldata and a single ensemble simulation. We demonstrate thatcalculating SPI with the exponentiated Weibull distributiondelivers better results for each continent and every investi-gated accumulation period, irrespective of the heritage of theprecipitation data. Therefore, we advocate the employmentof the exponentiated Weibull distribution as the basis for SPI
The forgotten drought of 1765–1768: Reconstructing and re-evaluating historical droughts in the British and Irish Isles
No full textHistorical precipitation records are fundamental for the management of
water resources, yet rainfall observations typically span 100–15 0 years at
most, with considerable uncertainties surrounding earlier records. Here, we
analyse some of the longest a vailabl e precipitation records globally, for
England and Wales, Scotland and Ireland. To assess the credibility of these
records and extend them further back in time, we statistically reconstruct
(using independent predictors) monthly precipitation series representing
these regions for the period 1748–2000. By applying the Standardized Precipi-
tation Index at 12-month accumulations (SPI-12) to the observed and our
reconstructed series we re-evaluate historical meteorological droughts. We
find strong agreement between observed and reconstructed drought chronol-
ogies in post-1870 records, but divergence in e arlier series due to biases in
early precipitation observations. Hence, the 1800s decade was less drought
prone in our reconstructions relative to observations. Overall, the drought of
1834–1836 was the most intense SPI-12 event in our reconstruction for
England and Wales. Newspaper accounts and documentary sources confirm
the extent of impacts across England in particular. We also identify a major,
“forgotten” drought in 1765–1768 that affected the British-Irish Isles. This
was the most intense event in our reconstructions for Ireland and Scotland,
and ranks first for accumulated deficits a cross all three regional series.
Moreover, the 1765–1768 event was also the most extreme multi-year drought
across all regional series when considering 36-month a ccumulations (SPI-36).
Newspaper and other sources confirm the occurrence and major socio-
economic impact of this drought, such as major rivers like the Shannon being
fordable by foot. Our results provide new insights into historical droughts
across the British Irish Isles. Given the importance of historical droughts for
stress-testing the resilience of water resources, drought plans and supply sys-
tems, the forgotten drought of 1765–1 768 offers perhaps the most extreme
benchmark scenario in more than 250-years