Dynamic simulation modelling of policy responses to reduce alcohol-related harms: Rationale and procedure for a participatory approach

Development of effective policy responses to address complex public health problems can be challenged by a lack of clarity about the interaction of risk factors driving the problem, differing views of stakeholders on the most appropriate and effective intervention approaches, a lack of evidence to support commonly implemented and acceptable intervention approaches, and a lack of acceptance of effective interventions. Consequently, political considerations, community advocacy and industry lobbying can contribute to a hotly contested debate about the most appropriate course of action; this can hinder consensus and give rise to policy resistance. The problem of alcohol misuse and its associated harms in New South Wales (NSW), Australia, provides a relevant example of such challenges. Dynamic simulation modelling is increasingly being valued by the health sector as a robust tool to support decision making to address complex problems. It allows policy makers to ask ‘what-if’ questions and test the potential impacts of different policy scenarios over time, before solutions are implemented in the real world. Participatory approaches to modelling enable researchers, policy makers, program planners, practitioners and consumer representatives to collaborate with expert modellers to ensure that models are transparent, incorporate diverse evidence and perspectives, are better aligned to the decision-support needs of policy makers, and can facilitate consensus building for action. This paper outlines a procedure for embedding stakeholder engagement and consensus building in the development of dynamic simulation models that can guide the development of effective, coordinated and acceptable policy responses to complex public health problems, such as alcohol-related harms in NSW

UV Photo-Oxidation of Polybenzimidazole (PBI)

Since polybenzimidazole (PBI) is often used in the aerospace industry and in high temperature fuel cells, this research investigated the surface modification of PBI film with 253.7 and 184.9 nm UV photo-oxidation. As observed by X-ray photoelectron spectroscopy (XPS), the oxygen concentration on the surface increased up to a saturation level of 20.2 ± 0.7 at %. With increasing treatment time, there were significant decreases in the concentrations of C-C sp2 and C=N groups and increases in the concentration of C=O, O-C=O, O-(C=O)-O, C-N, N-O, and N-C=O containing moieties due to 253.7 nm photo-oxidation of the aromatic groups of PBI and reaction with ozone produced by 184. 9 nm photo-dissociation of oxygen. Because no significant changes in surface topography were detected by AFM and SEM measurements, the observed decrease in the water contact angle down to ca. 44°, i.e., increase in hydrophilic, was due to the chemical changes on the surface

AVIATR - Aerial Vehicle for In-situ and Airborne Titan Reconnaissance A Titan Airplane Mission Concept

We describe a mission concept for a stand-alone Titan airplane mission: Aerial Vehicle for In-situ and Airborne Titan Reconnaissance (AVIATR). With independent delivery and direct-to-Earth communications, AVIATR could contribute to Titan science either alone or as part of a sustained Titan Exploration Program. As a focused mission, AVIATR as we have envisioned it would concentrate on the science that an airplane can do best: exploration of Titan's global diversity. We focus on surface geology/hydrology and lower-atmospheric structure and dynamics. With a carefully chosen set of seven instruments-2 near-IR cameras, 1 near-IR spectrometer, a RADAR altimeter, an atmospheric structure suite, a haze sensor, and a raindrop detector-AVIATR could accomplish a significant subset of the scientific objectives of the aerial element of flagship studies. The AVIATR spacecraft stack is composed of a Space Vehicle (SV) for cruise, an Entry Vehicle (EV) for entry and descent, and the Air Vehicle (AV) to fly in Titan's atmosphere. Using an Earth-Jupiter gravity assist trajectory delivers the spacecraft to Titan in 7.5 years, after which the AVIATR AV would operate for a 1-Earth-year nominal mission. We propose a novel 'gravity battery' climb-then-glide strategy to store energy for optimal use during telecommunications sessions. We would optimize our science by using the flexibility of the airplane platform, generating context data and stereo pairs by flying and banking the AV instead of using gimbaled cameras. AVIATR would climb up to 14 km altitude and descend down to 3.5 km altitude once per Earth day, allowing for repeated atmospheric structure and wind measurements all over the globe. An initial Team-X run at JPL priced the AVIATR mission at FY10 $715M based on the rules stipulated in the recent Discovery announcement of opportunity. Hence we find that a standalone Titan airplane mission can achieve important science building on Cassini's discoveries and can likely do so within a New Frontiers budget

Candidate Massive Galaxies at z~4 in the Dark Energy Survey

Using stellar population models, we predicted that the Dark Energy Survey (DES) - due to its special combination of area (5000 deg. sq.) and depth ($i = 24.3$) - would be in the position to detect massive ($\gtrsim 10^{11}$ M$_{\odot}$) galaxies at $z \sim 4$. We confront those theoretical calculations with the first $\sim 150$ deg. sq. of DES data reaching nominal depth. From a catalogue containing $\sim 5$ million sources, $\sim26000$ were found to have observed-frame $g-r$ vs $r-i$ colours within the locus predicted for $z \sim 4$ massive galaxies. We further removed contamination by stars and artefacts, obtaining 606 galaxies lining up by the model selection box. We obtained their photometric redshifts and physical properties by fitting model templates spanning a wide range of star formation histories, reddening and redshift. Key to constrain the models is the addition, to the optical DES bands $g$, $r$, $i$, $z$, and $Y$, of near-IR $J$, $H$, $K_{s}$ data from the Vista Hemisphere Survey. We further applied several quality cuts to the fitting results, including goodness of fit and a unimodal redshift probability distribution. We finally select 233 candidates whose photometric redshift probability distribution function peaks around $z\sim4$, have high stellar masses ($\log($M$^{*}$/M$_{\odot})\sim 11.7$ for a Salpeter IMF) and ages around 0.1 Gyr, i.e. formation redshift around 5. These properties match those of the progenitors of the most massive galaxies in the local universe. This is an ideal sample for spectroscopic follow-up to select the fraction of galaxies which is truly at high redshift. These initial results and those at the survey completion, which we shall push to higher redshifts, will set unprecedented constraints on galaxy formation, evolution, and the re-ionisation epoch

Dietary docosahexaenoic acid alleviates autistic-like behaviors resulting from maternal immune activation in mice

The prevalence of autism spectrum disorders over the last several decades has risen at an alarming rate. Factors such as broadened clinical definitions and increased parental age only partially account for this precipitous increase, suggesting that recent changes in environmental factors may also be responsible. One such factor could be the dramatic decrease in consumption of anti-inflammatory dietary omega-3 (n-3) polyunsaturated fatty acids (PUFAs) relative to the amount of pro-inflammatory omega-6 (n-6) PUFAs and saturated fats in the Western diet. Docosahexaenoic acid (DHA) is the principle n-3 PUFA found in neural tissue and is important for optimal brain development, especially during late gestation when DHA rapidly and preferentially accumulates in the brain. In this study, we tested whether supplementation of a low n-3 PUFA diet with DHA throughout development could improve measures related to autism in a mouse model of maternal immune activation. We found that dietary DHA protected offspring from the deleterious effects of gestational exposure to the viral mimetic polyriboinosinic-polyribocytidilic acid on behavioral measures of autism and subsequent adulthood immune system reactivity. These data suggest that elevated dietary levels of DHA, especially during pregnancy and nursing, may help protect normal neurodevelopment from the potentially adverse consequences of environmental insults like maternal infection

Dartmoor National Park Traffic management strategy

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FIGURE 4 from Functional Heterogeneity in MET Pathway Activation in PDX Models of Osimertinib-resistant EGFR-driven Lung Cancer

Heterogeneity in MET polysomy and MET amplification in osimertinib-resistant EGFR-mutant NSCLC. A, Representative phospho-MET IHC (several are reused from Fig. 2D), MET FISH images and MET FISH scoring from PDXs with MET polysomy. B, Representative phospho-MET IHC, MET FISH images and MET FISH scoring from longitudinally collected tumor samples from patient LAT006 at first progression on osimertinib, second progression after osimertinib rechallenge, and upon further progression on chemoimmunotherapy. Scale bars, 50 µm.</p

FIGURE 1 from Functional Heterogeneity in MET Pathway Activation in PDX Models of Osimertinib-resistant EGFR-driven Lung Cancer

Generation of spatial and temporally heterogenous osimertinib-resistant EGFR-mutant NSCLC PDX models and treatment study design. A, Schematic diagram of the prospective clinical trial of LAT for osimertinib-treated EGFR-mutant lung cancer (RT: radiotherapy). PDXs were generated from osimertinib-resistant tumor tissue either at first or second progression on osimertinib or after standard of care (S.O.C) therapy. B, Multi-region and temporal tumor samples from surgical resections or biopsies used for PDX generation are shown for each individual patient. Putative mechanism of resistance to osimertinib as evidenced by exome and or transcriptome sequencing (Roper et al., Cell Reports Medicine 2020) is shown below each set of PDXs. Color denotes timing of sample acquisition. Red: first progression on osimertinib; Green: second progression on osimertinib; Blue: progression on S.O.C treatment. C, Illustrations of PDX generation from 3 patients with EGFR-mutant lung cancer with MET polysomy by FISH (MET ≥ 4.0 and MET/CEP7 ratio is MET amplification by FISH (MET/CEP7 ratio ≥2.0 or ≥6 MET copies per cell) as a mechanism of resistance to osimertinib. D, Study design for treatment with MET inhibitor (savolitinib) with a third-generation EGFR TKI (osimertinib). PDXs with spatial heterogeneity in MET pathway activation (LAT001_6B and LAT001_9B), PDXs with temporal heterogeneity in MET pathway activation (LAT006_2B and LAT006_0118) and an additional validation PDX (LAT015_6B) were treated with vehicle, osimertinib, savolitinib, and osimertinib plus savolitinib combination followed by assessment of efficacy and identification of predictive markers.</p