Fraction-variant beam orientation optimization for non-coplanar IMRT

Conventional beam orientation optimization (BOO) algorithms for IMRT assume that the same set of beam angles is used for all treatment fractions. In this paper we present a BOO formulation based on group sparsity that simultaneously optimizes non-coplanar beam angles for all fractions, yielding a fraction-variant (FV) treatment plan. Beam angles are selected by solving a multi-fraction FMO problem involving 500-700 candidate beams per fraction, with an additional group sparsity term that encourages most candidate beams to be inactive. The optimization problem is solved using the Fast Iterative Shrinkage-Thresholding Algorithm. Our FV BOO algorithm is used to create non-coplanar, five-fraction treatment plans for prostate and lung cases, as well as a non-coplanar 30-fraction plan for a head and neck case. A homogeneous PTV dose coverage is maintained in all fractions. The treatment plans are compared with fraction-invariant plans that use a fixed set of beam angles for all fractions. The FV plans reduced mean and max OAR dose on average by 3.3% and 3.7% of the prescription dose, respectively. Notably, mean OAR dose was reduced by 14.3% of prescription dose (rectum), 11.6% (penile bulb), 10.7% (seminal vesicle), 5.5% (right femur), 3.5% (bladder), 4.0% (normal left lung), 15.5% (cochleas), and 5.2% (chiasm). Max OAR dose was reduced by 14.9% of prescription dose (right femur), 8.2% (penile bulb), 12.7% (prox. bronchus), 4.1% (normal left lung), 15.2% (cochleas), 10.1% (orbits), 9.1% (chiasm), 8.7% (brainstem), and 7.1% (parotids). Meanwhile, PTV homogeneity defined as D95/D5 improved from .95 to .98 (prostate case) and from .94 to .97 (lung case), and remained constant for the head and neck case. Moreover, the FV plans are dosimetrically similar to conventional plans that use twice as many beams per fraction. Thus, FV BOO offers the potential to reduce delivery time for non-coplanar IMRT

Evaluating solar radiation forecast uncertainty

The presence of clouds and their characteristics have a strong impact on the radiative balance of the Earth and on the amount of solar radiation reaching the Earth's surface. Many applications require accurate forecasts of surface radiation on weather timescales, for example solar energy and UV radiation forecasts. Here we investigate how operational forecasts of low and mid-level clouds affect the accuracy of solar radiation forecasts. A total of 4 years of cloud and solar radiation observations from one site in Helsinki, Finland, are analysed. Cloud observations are obtained from a ceilometer and therefore we first develop algorithms to reliably detect cloud base, precipitation, and fog. These new algorithms are widely applicable for both operational use and research, such as in-cloud icing detection for the wind energy industry and for aviation. The cloud and radiation observations are compared to forecasts from the Integrated Forecast System (IFS) run operationally and developed by the European Centre for Medium-Range Weather Forecasts (ECMWF). We develop methods to evaluate the skill of the cloud and radiation forecasts. These methods can potentially be extended to hundreds of sites globally. Over Helsinki, the measured global horizontal irradiance (GHI) is strongly influenced by its northerly location and the annual variation in cloudiness. Solar radiation forecast error is therefore larger in summer than in winter, but the relative error in the solar radiation forecast is more or less constant throughout the year. The mean overall bias in the GHI forecast is positive (8 W m(-2)). The observed and forecast distributions in cloud cover, at the spatial scales we are considering, are strongly skewed towards clear-sky and overcast situations. Cloud cover forecasts show more skill in winter when the cloud cover is predominantly overcast; in summer there are more clear-sky and broken cloud situations. A negative bias was found in forecast GHI for correctly forecast clear-sky cases and a positive bias in correctly forecast overcast cases. Temporal averaging improved the cloud cover forecast and hence decreased the solar radiation forecast error. The positive bias seen in overcast situations occurs when the model cloud has low values of liquid water path (LWP). We attribute this bias to the model having LWP values that are too low or the model optical properties for clouds with low LWP being incorrect.Peer reviewe

Ohio State University's Wetlands Watercolors Eco Art Exhibition Proposal

Course Code: ENR 2367A proposal for the implementation of an environmental art show at the Ohio State University's Wetlands.Academic Major: Agribusiness and Applied EconomicsAcademic Major: Environment, Economy, Development, and SustainabilityAcademic Major: Environmental ScienceAcademic Major: ExplorationAcademic Major: Financ

Low-Level Jets over Utö, Finland, Based on Doppler Lidar Observations

Over two years of meteorological observations from Utö, a small island in the Finnish outer archipelago in the Baltic Sea, were used to investigate the occurrence and characteristics of low-level jets (LLJs) and the diurnal and seasonal variations in these properties. An objective LLJ identification algorithm that is suitable for high-temporal-and-vertical-resolution Doppler lidar data was created and applied to wind profiles obtained from a combination of Doppler lidar data and two-dimensional sonic anemometer observations. This algorithm was designed to identify coherent LLJ structures and requires that they persist for at least 1 h. The long-term mean LLJ frequency of occurrence at Utö was 12%, the mean LLJ wind speed was 11.6 m s−1, and the vast majority of identified LLJs occurred below 150 m above ground level. The LLJ frequency of occurrence was much higher during summer (21%) and spring (18%) than in autumn (8%) and winter (3%). During winter and spring, the LLJ frequency of occurrence is evenly distributed throughout the day. In contrast, the LLJ frequency of occurrence peaks at night (1900–0100 UTC) during summer and during the evening hours (1700–1900 UTC) in autumn. The highest and strongest LLJs come from the southwest, which is also the predominant LLJ direction in all seasons. LLJs below 100 m are common in spring and summer, are weaker, and do not show a strong directional dependence.Peer reviewe

Identification of iridoid glucoside transporters in Catharanthus roseus

Monoterpenoid indole alkaloids (MIAs) are plant defense compounds and high-value pharmaceuticals. Biosynthesis of the universal MIA precursor, secologanin, is organized between internal phloem-associated parenchyma (IPAP) and epidermis cells. Transporters for intercellular transport of proposed mobile pathway intermediates have remained elusive. Screening of an Arabidopsis thaliana transporter library expressed in Xenopus oocytes identified AtNPF2.9 as a putative iridoid glucoside importer. Eight orthologs were identified in Catharanthus roseus, of which three, CrNPF2.4, CrNPF2.5 and CrNPF2.6, were capable of transporting the iridoid glucosides 7-deoxyloganic acid, loganic acid, loganin and secologanin into oocytes. Based on enzyme expression data and transporter specificity, we propose that several enzymes of the biosynthetic pathway are present in both IPAP and epidermis cells, and that the three transporters are responsible for transporting not only loganic acid, as previously proposed, but multiple intermediates. Identification of the iridoid glucoside-transporting CrNPFs is an important step toward understanding the complex orchestration of the seco-iridioid pathway

Alzheimer's Disease-Related Dementias Summit 2022: National Research Priorities for the Investigation of Post-Traumatic Brain Injury Alzheimer's Disease and Related Dementias

Traumatic Brain Injury (TBI) is a risk factor for Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD) and otherwise classified post-traumatic neurodegeneration (PTND). Targeted research is needed to elucidate the circumstances and mechanisms through which TBI contributes to the initiation, development, and progression of AD/ADRD pathologies including multiple etiology dementia (MED). The National Institutes of Health hosts triennial ADRD summits to inform a national research agenda, and TBI was included for a second time in 2022. A multidisciplinary expert panel of TBI and dementia researchers was convened to re-evaluate the 2019 research recommendations for understanding TBI as an AD/ADRD risk factor and to assess current progress and research gaps in understanding post-TBI AD/ADRD. Refined and new recommendations were presented during the MED special topic session at the virtual ADRD Summit in March 2022. Final research recommendations incorporating broad stakeholder input are organized into four priority areas as follows: (1) Promote interdisciplinary collaboration and data harmonization to accelerate progress of rigorous, clinically meaningful research; (2) Characterize clinical and biological phenotypes of PTND associated with varied lifetime TBI histories in diverse populations to validate multimodal biomarkers; (3) Establish and enrich infrastructure to support multimodal longitudinal studies of individuals with varied TBI exposure histories and standardized methods including common data elements (CDEs) for ante-mortem and post-mortem clinical and neuropathological characterization; and (4) Support basic and translational research to elucidate mechanistic pathways, development, progression, and clinical manifestations of post-TBI AD/ADRDs. Recommendations conceptualize TBI as a contributor to MED and emphasize the unique opportunity to study AD/ADRD following known exposure, to inform disease mechanisms and treatment targets for shared common AD/ADRD pathways

Combined Oxygen-enhanced MRI and perfusion imaging detect hypoxia modification from banoxantrone and atovaquone and track their differential mechanisms of action

Oxygen-enhanced MRI (OE-MRI) has shown promise for quantifying and spatially mapping tumor hypoxia, either alone or in combination with perfusion imaging. Previous studies have validated the technique in mouse models and in patients with cancer. Here, we report the first evidence that OE-MRI can track change in tumor oxygenation induced by two drugs designed to modify hypoxia. Mechanism of action of banoxantrone and atovaquone were confirmed using in vitro experiments. Next, in vivo OE-MRI studies were performed in Calu6 and U87 xenograft tumor models, alongside [18F] FAZA PET and immunohistochemistry assays of hypoxia. Neither drug altered tumor size. Banoxantrone reduced OE-MRI hypoxic fraction in Calu6 tumors by 52.5% +/- 12.0% (p=0.008) and in U87 tumors by 29.0% +/- 15.8% (p=0.004) after 3 days treatment. Atovaquone reduced OE-MRI hypoxic fraction in Calu6 tumors by 53.4% +/- 15.3% (p=0.002) after 7 days therapy. PET and immunohistochemistry provided independent validation of the MRI findings. Finally, combined OE-MRI and perfusion imaging showed that hypoxic tissue was converted into necrotic tissue when treated by the hypoxia-activated cytotoxic prodrug banoxantrone, whereas hypoxic tissue became normoxic when treated by atovaquone, an inhibitor of mitochondrial complex III of the electron transport chain. OE-MRI detected and quantified hypoxia reduction induced by two hypoxia-modifying therapies and could distinguish between their differential mechanisms of action. These data support clinical translation of OE-MRI biomarkers in clinical trials of hypoxia-modifying agents, to identify patients demonstrating biological response and to optimize treatment timing and scheduling

Buprenorphine versus dihydrocodeine for opiate detoxification in primary care: a randomised controlled trial

Background Many drug users present to primary care requesting detoxification from illicit opiates. There are a number of detoxification agents but no recommended drug of choice. The purpose of this study is to compare buprenorphine with dihydrocodeine for detoxification from illicit opiates in primary care. Methods Open label randomised controlled trial in NHS Primary Care (General Practices), Leeds, UK. Sixty consenting adults using illicit opiates received either daily sublingual buprenorphine or daily oral dihydrocodeine. Reducing regimens for both interventions were at the discretion of prescribing doctor within a standard regimen of not more than 15 days. Primary outcome was abstinence from illicit opiates at final prescription as indicated by a urine sample. Secondary outcomes during detoxification period and at three and six months post detoxification were recorded. Results Only 23% completed the prescribed course of detoxification medication and gave a urine sample on collection of their final prescription. Risk of non-completion of detoxification was reduced if allocated buprenorphine (68% vs 88%, RR 0.58 CI 0.35–0.96, p = 0.065). A higher proportion of people allocated to buprenorphine provided a clean urine sample compared with those who received dihydrocodeine (21% vs 3%, RR 2.06 CI 1.33–3.21, p = 0.028). People allocated to buprenorphine had fewer visits to professional carers during detoxification and more were abstinent at three months (10 vs 4, RR 1.55 CI 0.96–2.52) and six months post detoxification (7 vs 3, RR 1.45 CI 0.84–2.49). Conclusion Informative randomised trials evaluating routine care within the primary care setting are possible amongst drug using populations. This small study generates unique data on commonly used treatment regimens

The importance of form field validation: lessons learnt from a feasibility study of an mHealth application in Malawi, Africa

Measuring adherence to clinical guidelines using mobile health (mHealth) technologies when form field validation is enforced or turned on could potentially be viewed as skewing the dataset, leading to 100% adherence to the clinical rule base. In theory, healthcare providers should fully abide by clinical guidelines, whether in paper or digital format, to ensure that the patient receives appropriate care. However, what happens when mHealth form field validation is turned off? As part of a feasibility study in Malawi, Africa, we explored this phenomenon. Switching off validation on the mHealth artefact served its purpose within the context of a feasibility study where a parallel paper-based clinical assessment process remained in place. The design of this technical artefact with the turnkey validation feature afforded us the opportunity to turn validation on and off seamlessly. Ultimately, from an ethical, clinical and technical perspective the optimum approach is to ensure that form field validation is switched on. With form field validation on adherence to the clinical guidelines is enforced which minimises incomplete assessment and the potential for suboptimal clinical decisions that could adversely affect patient care

Long-term safety and efficacy of teriflunomide : nine-year follow-up of the randomized TEMSO study

This study was funded by Sanofi Genzyme.OBJECTIVE: To report safety and efficacy outcomes from up to 9 years of treatment with teriflunomide in an extension (NCT00803049) of the pivotal phase 3 Teriflunomide Multiple Sclerosis Oral (TEMSO) trial (NCT00134563). METHODS: A total of 742 patients entered the extension. Teriflunomide-treated patients continued the original dose; those previously receiving placebo were randomized 1:1 to teriflunomide 14 mg or 7 mg. RESULTS: By June 2013, median (maximum) teriflunomide exposure exceeded 190 (325) weeks per patient; 468 patients (63%) remained on treatment. Teriflunomide was well-tolerated with continued exposure. The most common adverse events (AEs) matched those in the core study. In extension year 1, first AEs of transient liver enzyme increases or reversible hair thinning were generally attributable to patients switching from placebo to teriflunomide. Approximately 11% of patients discontinued treatment owing to AEs. Twenty percent of patients experienced serious AEs. There were 3 deaths unrelated to teriflunomide. Soon after the extension started, annualized relapse rates and gadolinium-enhancing T1 lesion counts fell in patients switching from placebo to teriflunomide, remaining low thereafter. Disability remained stable in all treatment groups (median Expanded Disability Status Scale score ≤2.5; probability of 12-week disability progression ≤0.48). CONCLUSIONS: In the TEMSO extension, safety observations were consistent with the core trial, with no new or unexpected AEs in patients receiving teriflunomide for up to 9 years. Disease activity decreased in patients switching from placebo and remained low in patients continuing on teriflunomide. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that long-term treatment with teriflunomide is well-tolerated and efficacy of teriflunomide is maintained long-term.Publisher PDFPeer reviewe