Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Pharmaceutical Sciences after peer review and technical editing by the publisher. Under embargo. Embargo end date: 9 November 2017. The version of record, Joanna Muddle, Stewart B. Kirton, Irene Parisini, Andrew Muddle, Darragh Murnane, Jogoth Ali, Marc Brown, Clive Page and Ben Forbes, ‘Predicting the Fine Particle Fraction of Dry Powder Inhalers Using Artificial Neural Networks’, Journal of Pharmaceutical Sciences, Vol 106(1): 313-321, first published online on 9 November 2016, is available online via doi: http://dx.doi.org/10.1016/j.xphs.2016.10.002 0022-3549/© 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.Dry powder inhalers are increasingly popular for delivering drugs to the lungs for the treatment of respiratory diseases, but are complex products with multivariate performance determinants. Heuristic product development guided by in vitro aerosol performance testing is a costly and time-consuming process. This study investigated the feasibility of using artificial neural networks (ANNs) to predict fine particle fraction (FPF) based on formulation device variables. Thirty-one ANN architectures were evaluated for their ability to predict experimentally determined FPF for a self-consistent dataset containing salmeterol xinafoate and salbutamol sulfate dry powder inhalers (237 experimental observations). Principal component analysis was used to identify inputs that significantly affected FPF. Orthogonal arrays (OAs) were used to design ANN architectures, optimized using the Taguchi method. The primary OA ANN r2 values ranged between 0.46 and 0.90 and the secondary OA increased the r2 values (0.53-0.93). The optimum ANN (9-4-1 architecture, average r2 0.92 ± 0.02) included active pharmaceutical ingredient, formulation, and device inputs identified by principal component analysis, which reflected the recognized importance and interdependency of these factors for orally inhaled product performance. The Taguchi method was effective at identifying successful architecture with the potential for development as a useful generic inhaler ANN model, although this would require much larger datasets and more variable inputs.Peer reviewe

Clinical Oncology Society of Australia position statement on exercise in cancer care

Introduction: Clinical research has established exercise as a safe and effective intervention to counteract the adverse physical and psychological effects of cancer and its treatment. This article summarises the position of the Clinical Oncology Society of Australia (COSA) on the role of exercise in cancer care, taking into account the strengths and limitations of the evidence base. It provides guidance for all health professionals involved in the care of people with cancer about integrating exercise into routine cancer care. Main recommendations: COSA calls for: - exercise to be embedded as part of standard practice in cancer care and to be viewed as an adjunct therapy that helps counteract the adverse effects of cancer and its treatment; - all members of the multidisciplinary cancer team to promote physical activity and recommend that people with cancer adhere to exercise guidelines; and - best practice cancer care to include referral to an accredited exercise physiologist or physiotherapist with experience in cancer care. Changes in management as a result of the guideline: COSA encourages all health professionals involved in the care of people with cancer to: - discuss the role of exercise in cancer recovery; - recommend their patients adhere to exercise guidelines (avoid inactivity and progress towards at least 150 minutes of moderate intensity aerobic exercise and two to three moderate intensity resistance exercise sessions each week); and - refer their patients to a health professional who specialises in the prescription and delivery of exercise (ie, accredited exercise physiologist or physiotherapist with experience in cancer care)

The Grizzly, February 24, 1997

Dr. Gaede Receives $28,500 Grant • Organist and Dancer to Perform at Ursinus • Dr. Goetz to Lecture • Greek Life Discussion at Common Hour • Opinion: Things That Make Me Go Hmmm; Letters from Great Britain; A Non-Greek Speaks Back; Go Out and Do Something; Student Ponders Greek Life; Politicians\u27 Greed Outweighs Desires of Constituents • Daniel Pipes to Lecture on the Middle East • Torsone Wins 118-Pound Regional Title • Women\u27s Basketball Drops Two in a Row • Larkin Honored Twice • Gymnastics Place Third at Ithaca Invitational • Buyse Scores 1,000th Pointhttps://digitalcommons.ursinus.edu/grizzlynews/1398/thumbnail.jp

Understanding TERT promoter mutations: a common path to immortality

Telomerase (TERT) activation is a fundamental step in tumorigenesis. By maintaining telomere length, telomerase relieves a main barrier on cellular lifespan, enabling limitless proliferation driven by oncogenes. The recently discovered, highly recurrent mutations in the promoter of TERT are found in over 50 cancer types, and are the most common mutation in many cancers. Transcriptional activation of TERT, via promoter mutation or other mechanisms, is the rate-limiting step in production of active telomerase. Although TERT is expressed in stem cells, it is naturally silenced upon differentiation. Thus, the presence of TERT promoter mutations may shed light on whether a particular tumor arose from a stem cell or more differentiated cell type. It is becoming clear that TERT mutations occur early during cellular transformation, and activate the TERT promoter by recruiting transcription factors that do not normally regulate TERT gene expression. This review highlights the fundamental and widespread role of TERT promoter mutations in tumorigenesis, including recent progress on their mechanism of transcriptional activation. These somatic promoter mutations, along with germline variation in the TERT locus also appear to have significant value as biomarkers of patient outcome. Understanding the precise molecular mechanism of TERT activation by promoter mutation and germline variation may inspire novel cancer cell-specific targeted therapies for a large number of cancer patients.Support was provided from a generous gift from the Dabbiere family(RJB,AM,JFC), the Hana Jabsheh Research Initiative (RJB,AM,JFC), and NIH grants NCI P50CA097257 (RJB,AM,JFC), P01CA118816-06 (RJB,AM,JFC), R01HG003008 (HTR), and R01CA163336 (JSS). Additional support was provided from the Sontag Foundation Distinguished Scientist Award (JSS), Fundação para a Ciência e Tecnologia SFRH/BD/88220/2012 (AXM), IF/00601/2012 (BMC), Programa Operacional Regional do Norte (ON.2—O Novo Norte) (BMC), Quadro de Referência Estratégico Nacional (BMC), and Fundo Europeu de Desenvolvimento Regional (BMC).info:eu-repo/semantics/publishedVersio

Ocean biogeochemical response to phytoplankton-light feedback in a global model

Oceanic phytoplankton, absorbing solar radiation, can influence the bio-optical properties of seawater and hence upper ocean physics. We include this process in a global ocean general circulation model (OGCM) coupled to a dynamic green ocean model (DGOM) based on multiple plankton functional types (PFT). We not only study the impact of this process on ocean physics but we also explore the biogeochemical response due to this biophysical feedback. The phytoplankton-light feedback (PLF) impacts the dynamics of the upper tropical and subtropical oceans. The change in circulation enhances both the vertical supply in the tropics and the lateral supply of nutrients from the tropics to the subtropics boosting the subtropical productivity by up to 60 gC m(-2) a(-1). Physical changes, due to the PLF, impact on light and nutrient availability causing shifts in the ocean ecosystems. In the extratropics, increased stratification favors calcifiers (by up to similar to 8%) at the expense of mixed phytoplankton. In the Southern Ocean, silicifiers increase their biomass (by up to similar to 10%) because of the combined alleviation of iron and light limitation. The PLF has a small effect globally on air-sea fluxes of carbon dioxide (CO2, 72 TmolC a(-1) outgassing) and oxygen (O-2, 46 TmolO(2) a(-1) ingassing) because changes in biogeochemical processes (primary production, biogenic calcification, and export production) highly vary regionally and can also oppose each other. From our study it emerges that the main impact of the PLF is an amplification of the seasonal cycle of physical and biogeochemical properties of the high-latitude oceans mostly driven by the amplification of the SST seasonal cycle

Roadmap on spatiotemporal light fields

Spatiotemporal sculpturing of light pulse with ultimately sophisticated structures represents the holy grail of the human everlasting pursue of ultrafast information transmission and processing as well as ultra-intense energy concentration and extraction. It also holds the key to unlock new extraordinary fundamental physical effects. Traditionally, spatiotemporal light pulses are always treated as spatiotemporally separable wave packet as solution of the Maxwell's equations. In the past decade, however, more generalized forms of spatiotemporally nonseparable solution started to emerge with growing importance for their striking physical effects. This roadmap intends to highlight the recent advances in the creation and control of increasingly complex spatiotemporally sculptured pulses, from spatiotemporally separable to complex nonseparable states, with diverse geometric and topological structures, presenting a bird's eye viewpoint on the zoology of spatiotemporal light fields and the outlook of future trends and open challenges.Comment: This is the version of the article before peer review or editing, as submitted by an author to Journal of Optics. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from i

Proceedings of Abstracts, School of Physics, Engineering and Computer Science Research Conference 2022

© 2022 The Author(s). This is an open-access work distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. For further details please see https://creativecommons.org/licenses/by/4.0/. Plenary by Prof. Timothy Foat, ‘Indoor dispersion at Dstl and its recent application to COVID-19 transmission’ is © Crown copyright (2022), Dstl. This material is licensed under the terms of the Open Government Licence except where otherwise stated. To view this licence, visit http://www.nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: [email protected] present proceedings record the abstracts submitted and accepted for presentation at SPECS 2022, the second edition of the School of Physics, Engineering and Computer Science Research Conference that took place online, the 12th April 2022

Copy number signatures and mutational processes in ovarian carcinoma.

The genomic complexity of profound copy number aberrations has prevented effective molecular stratification of ovarian cancers. Here, to decode this complexity, we derived copy number signatures from shallow whole-genome sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were validated on 527 independent cases. We show that HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in known patterns of genomic aberration. Copy number signature exposures at diagnosis predict both overall survival and the probability of platinum-resistant relapse. Measurement of signature exposures provides a rational framework to choose combination treatments that target multiple mutational processes.NIHR, Ovarian Cancer Action, Cancer Research UK Cambridge Centre, Cambridge Experimental Cancer Medicine Centr