Imaging of cancer with 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) has become a standard component of diagnosis and staging in oncology, and is becoming more important as a ...quantitative monitor of individual response to therapy. In this article we investigate the challenging problem of predicting a patient's response to neoadjuvant chemotherapy from a single 18F-FDG PET scan taken prior to treatment. We take a "radiomics" approach whereby a large amount of quantitative features is automatically extracted from pretherapy PET images in order to build a comprehensive quantification of the tumor phenotype. While the dominant methodology relies on hand-crafted texture features, we explore the potential of automatically learning low- to high-level features directly from PET scans. We report on a study that compares the performance of two competing radiomics strategies: an approach based on state-of-the-art statistical classifiers using over 100 quantitative imaging descriptors, including texture features as well as standardized uptake values, and a convolutional neural network, 3S-CNN, trained directly from PET scans by taking sets of adjacent intra-tumor slices. Our experimental results, based on a sample of 107 patients with esophageal cancer, provide initial evidence that convolutional neural networks have the potential to extract PET imaging representations that are highly predictive of response to therapy. On this dataset, 3S-CNN achieves an average 80.7% sensitivity and 81.6% specificity in predicting non-responders, and outperforms other competing predictive models.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In 2006 and 2007, multiple deployments of current meters and optical sensors on landers and moorings were made in the first detailed in situ study of the particle supply to the coral community in the ...Mingulay Reef complex in the Sea of Hebrides at 140-m water depth. Two distinct and predictable supply mechanisms were resolved. One mechanism consisted of the rapid downwelling of surface water caused by hydraulic control of tidal flow that transports particles from the surface to the corals in less than an hour. The rapid downwelling was recorded on the reef top as a pulse of warm, fluorescent, and relatively clear water at the onset of the flood and ebb tides. The pulse was strongest after flood tide and lasted for up to 3 h. The second mechanism consisted of advection onto the reef of deep bottom water with a high suspended matter load. This advection occurred during peak tides and was combined with topographical current acceleration on the reef top, enhancing delivery of particles to the corals.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Populations of the invasive alga
Sargassum muticum
were sampled along a time-since-invasion (TSI) gradient to test the hypothesis that chemical defences would increase with TSI, and diversity of ...native mesoherbivores. Algal chemical defences, phlorotannins, were quantified as a proxy for top-down-pressure, and these were compared with both native enemy diversity and time-since-invasion at each of seven sites along the west coast of the UK. The defences in the annual fronds showed a strong positive correlation with the biodiversity of native mesoherbivores. The defences in the perennial holdfasts, whilst generally higher than those in the fronds, showed no relationship. In contrast, defences in neither the fronds nor the holdfasts showed any relationship with TSI. The majority of mesoherbivores found in this survey were small and probably juvenile. Many of these individuals are known to occupy the fronds of
S. muticum
for shelter or to feed on its epiphytes, and are probably less likely to feed directly on its tissues than adults. The low probability that any one species of grazer was feeding on
S. muticum
tissues may explain why the alga contained a greater level of phlorotannin when the diversity of potential enemies was high. This study highlights the importance of enemy diversity in invasion ecology.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Follicular lymphoma is an incurable malignancy, with transformation to an aggressive subtype representing a critical event during disease progression. Here we performed whole-genome or whole-exome ...sequencing on 10 follicular lymphoma-transformed follicular lymphoma pairs followed by deep sequencing of 28 genes in an extension cohort, and we report the key events and evolutionary processes governing tumor initiation and transformation. Tumor evolution occurred through either a 'rich' or 'sparse' ancestral common progenitor clone (CPC). We identified recurrent mutations in linker histone, JAK-STAT signaling, NF-κB signaling and B cell developmental genes. Longitudinal analyses identified early driver mutations in chromatin regulator genes (CREBBP, EZH2 and KMT2D (MLL2)), whereas mutations in EBF1 and regulators of NF-κB signaling (MYD88 and TNFAIP3) were gained at transformation. Collectively, this study provides new insights into the genetic basis of follicular lymphoma and the clonal dynamics of transformation and suggests that personalizing therapies to target key genetic alterations in the CPC represents an attractive therapeutic strategy.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
IMPORTANCE Systematic reviews suggest adult patients in intensive care units (ICUs) with relative contraindications to early enteral nutrition (EN) may benefit from parenteral nutrition (PN) provided ...within 24 hours of ICU admission. OBJECTIVE To determine whether providing early PN to critically ill adults with relative contraindications to early EN alters outcomes. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, single-blind clinical trial conducted between October 2006 and June 2011 in ICUs of 31 community and tertiary hospitals in Australia and New Zealand. Participants were critically ill adults with relative contraindications to early EN who were expected to remain in the ICU longer than 2 days. INTERVENTIONS Random allocation to pragmatic standard care or early PN. MAIN OUTCOMES AND MEASURES Day-60 mortality; quality of life, infections, and body composition. RESULTS A total of 1372 patients were randomized (686 to standard care, 686 to early PN). Of 682 patients receiving standard care, 199 patients (29.2%) initially commenced EN, 186 patients (27.3%) initially commenced PN, and 278 patients (40.8%) remained unfed. Time to EN or PN in patients receiving standard care was 2.8 days (95% CI, 2.3 to 3.4). Patients receiving early PN commenced PN a mean of 44 minutes after enrollment (95% CI, 36 to 55). Day-60 mortality did not differ significantly (22.8% for standard care vs 21.5% for early PN; risk difference, −1.26%; 95% CI, −6.6 to 4.1; P = .60). Early PN patients rated day-60 quality of life (RAND-36 General Health Status) statistically, but not clinically meaningfully, higher (45.5 for standard care vs 49.8 for early PN; mean difference, 4.3; 95% CI, 0.95 to 7.58; P = .01). Early PN patients required fewer days of invasive ventilation (7.73 vs 7.26 days per 10 patient × ICU days, risk difference, −0.47; 95% CI, −0.82 to −0.11; P = .01) and, based on Subjective Global Assessment, experienced less muscle wasting (0.43 vs 0.27 score increase per week; mean difference, −0.16; 95% CI, −0.28 to −0.038; P = .01) and fat loss (0.44 vs 0.31 score increase per week; mean difference, −0.13; 95% CI, −0.25 to −0.01; P = .04). CONCLUSIONS AND RELEVANCE The provision of early PN to critically ill adults with relative contraindications to early EN, compared with standard care, did not result in a difference in day-60 mortality. The early PN strategy resulted in significantly fewer days of invasive ventilation but not significantly shorter ICU or hospital stays. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN012605000704695
Idelalisib, which inhibits PI3K isoform delta, produced antitumor responses in nearly 60% of pretreated patients with indolent non-Hodgkin's lymphomas. Responses lasted a median of 11 months. Grade 3 ...or higher toxic effects were seen in 13 to 27% of patients.
Indolent non-Hodgkin's lymphomas constitute approximately one third of all cases of non-Hodgkin's lymphoma and include follicular lymphoma, small lymphocytic lymphoma, marginal-zone lymphoma, and lymphoplasmacytic lymphoma with or without Waldenström's macroglobulinemia.
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–
3
It was estimated that approximately 20,000 people in the United States were diagnosed with indolent non-Hodgkin's lymphoma in 2012 and that approximately 7000 died of this disease.
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,
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The mainstay of treatment for indolent non-Hodgkin's lymphoma is an anti-CD20 antibody (primarily rituximab) in combination with chemotherapy consisting of alkylating agents, anthracyclines, antimitotic agents, or purine analogues. Although the current treatments for indolent non-Hodgkin's lymphomas are initially effective in inducing . . .
At present, crude oil and natural gas comprise ∼54.3% of the global energy supply. Rapidly replacing this with lower carbon sources is challenging, resulting in oil and gas forming a significant part ...of the energy mix in future predictions, even in scenarios that strive to meet the goals of the Paris Agreement. To assess the likely future demand, an analysis of multiple, recently published, rapid energy transition scenarios was conducted, indicating that 943.3 Bbbl of oil and 4,733.5 Tcf of gas will be required in the next three decades. Furthermore, analysis of different supply estimates indicates that 357.1–284.1 Bbbl of oil and 2,274.6–2,170.2 Tcf of gas will need to be found to complement existing recoverable reserves. To meet this demand will require the exploration and production of low carbon intensity ‘advantaged hydrocarbons’, combined with significant carbon sequestration activity. As hydrocarbon recovery becomes more difficult and energy intensive with time, it may be preferable to replace some existing ‘disadvantaged’ fields with new ‘advantaged’ hydrocarbons, implying the supply gap may be underestimated. Energy strategy at a national and global level must account for the large demand for hydrocarbons in coming decades and exploration and production companies need to align with the advantaged hydrocarbon paradigm. Stimulus is required to realise the carbon capture and storage capacity required to mitigate the consequences of the ongoing reliance on fossil fuels.
•943.3 Bbbl of oil and 4,733.5 Tcf of gas will be required by 2050 in a mean rapid energy transition scenario.•Between 357.1–284.1 Bbbl of oil and 2,274.6–2,170.2 Tcf of gas will need to be found.•A low-carbon ‘advantaged hydrocarbons’ strategy is needed in combination with significant carbon sequestration activity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Nitrogen dioxide (NO
) is a major air pollutant causing significant environmental
and health problems
. We report reversible adsorption of NO
in a robust metal-organic framework. Under ambient ...conditions, MFM-300(Al) exhibits a reversible NO
isotherm uptake of 14.1 mmol g
, and, more importantly, exceptional selective removal of low-concentration NO
(5,000 to <1 ppm) from gas mixtures. Complementary experiments reveal five types of supramolecular interaction that cooperatively bind both NO
and N
O
molecules within MFM-300(Al). We find that the in situ equilibrium 2NO
↔ N
O
within the pores is pressure-independent, whereas ex situ this equilibrium is an exemplary pressure-dependent first-order process. The coexistence of helical monomer-dimer chains of NO
in MFM-300(Al) could provide a foundation for the fundamental understanding of the chemical properties of guest molecules within porous hosts. This work may pave the way for the development of future capture and conversion technologies.
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IJS, KISLJ, NUK, SBMB, UL, UM, UPUK
The Multinational Association of Supportive Care in Cancer (MASCC) defines supportive care as "the prevention and management of the adverse effects of cancer and its treatment. This includes ...management of physical and psychological symptoms and side effects across the continuum of the cancer journey from diagnosis through treatment to post-treatment care. Supportive care aims to improve the quality of rehabilitation, secondary cancer prevention, survivorship, and end-of-life care". This article will provide an overview of modern supportive care in cancer, discussing its definition, its relationship with palliative care, models of care, "core" service elements (multi-professional/multidisciplinary involvement), the evidence that supportive care improves morbidity, quality of life, and mortality in various groups of patients with cancer, and the health economic benefits of supportive care. The article will also discuss the current and future challenges to providing optimal supportive care to all oncology patients.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In the present study we characterize the properties of the potent MCT1 (monocarboxylate transporter 1) inhibitor AR-C155858. Inhibitor titrations of L-lactate transport by MCT1 in rat erythrocytes ...were used to determine the Ki value and number of AR-C155858-binding sites (Et) on MCT1 and the turnover number of the transporter (kcat). Derived values were 2.3+/-1.4 nM, 1.29+/-0.09 nmol per ml of packed cells and 12.2+/-1.1 s-1 respectively. When expressed in Xenopus laevis oocytes, MCT1 and MCT2 were potently inhibited by AR-C155858, whereas MCT4 was not. Inhibition of MCT1 was shown to be time-dependent, and the compound was also active when microinjected, suggesting that AR-C155858 probably enters the cell before binding to an intracellular site on MCT1. Measurement of the inhibitor sensitivity of several chimaeric transporters combining different domains of MCT1 and MCT4 revealed that the binding site for AR-C155858 is contained within the C-terminal half of MCT1, and involves TM (transmembrane) domains 7-10. This is consistent with previous data identifying Phe360 (in TM10) and Asp302 plus Arg306 (TM8) as key residues in substrate binding and translocation by MCT1. Measurement of the Km values of the chimaeras for L-lactate and pyruvate demonstrate that both the C- and N-terminal halves of the molecule influence transport kinetics consistent with our proposed molecular model of MCT1 and its translocation mechanism that requires Lys38 in TM1 in addition to Asp302 and Arg306 in TM8 Wilson, Meredith, Bunnun, Sessions and Halestrap (2009) J. Biol. Chem. 284, 20011-20021.
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