Use of Motion Pictures in Laboratory Dynamical Studies

In student laboratory experiments in dynamics, as, for example, Newton\u27s second law of motion or the conservation of momentum, it is, of course, highly desirable to allow motion with the least possible constraint and to observe the displacements of moving parts without using perturbing markers. This circumstance has led us to use motion pictures in the student laboratory for quantitative observation of rapid dynamic processes, a technique which is used in a well-known textbook.\u27 The photographic method combines maximum freedom of movement with accurate observation of position as a function of time, if the camera frame speed is sufficiently high. A double pendulum apparatus, with which we have studied the conservation of momentum in the student laboratory, is shown in Fig. 1. It consists of two wooden blocks, each suspended by a steel rod from a common free-swing pivot and counter-weighted in such a way that the center of mass of each pendulum is at the center of its wooden block. A spring is compressed between the two blocks, and they are tied together with a thread. When this thread is burned, the pendulums recoil. The mass of each block can be varied at will. The motion is photographed with a motion picture camera at 64 frames per second. The camera used in this work was a war-surplus gun-point aiming camera, adapted only to the extent of adding a viewfinder. Since there is a coordinate screen behind the pendulums, the student can determine the heights to which the blocks rise by examining the film with a magnifying viewer

Use of Motion Pictures in Laboratory Dynamical Studies

In student laboratory experiments in dynamics, as, for example, Newton\u27s second law of motion or the conservation of momentum, it is, of course, highly desirable to allow motion with the least possible constraint and to observe the displacements of moving parts without using perturbing markers. This circumstance has led us to use motion pictures in the student laboratory for quantitative observation of rapid dynamic processes, a technique which is used in a well-known textbook.\u27 The photographic method combines maximum freedom of movement with accurate observation of position as a function of time, if the camera frame speed is sufficiently high. A double pendulum apparatus, with which we have studied the conservation of momentum in the student laboratory, is shown in Fig. 1. It consists of two wooden blocks, each suspended by a steel rod from a common free-swing pivot and counter-weighted in such a way that the center of mass of each pendulum is at the center of its wooden block. A spring is compressed between the two blocks, and they are tied together with a thread. When this thread is burned, the pendulums recoil. The mass of each block can be varied at will. The motion is photographed with a motion picture camera at 64 frames per second. The camera used in this work was a war-surplus gun-point aiming camera, adapted only to the extent of adding a viewfinder. Since there is a coordinate screen behind the pendulums, the student can determine the heights to which the blocks rise by examining the film with a magnifying viewer

Thick target preparation and isolation of 186Re from high current production via the 186W(d,2n)186Re reaction

Rhenium-186 has a half-life (t1/2 = 3.72 days) and emission of both gamma and beta particles that make it very attractive for use as a theranostic agent in targeted radionuclide therapy. 186Re can be readily prepared by the 185Re(n,γ)186Re reac-tion1. However, that reaction results in low specific activity, severely limiting the use of reactor produced 186Re in radiopharmaceuticals. It has previously been shown that high specific activity 186Re can be produced by cyclotron irradiations of 186W with protons and deuterons2,3. In this investigation we evaluated the 186W(d,2n)186Re reaction using thick target irradiations at higher incident deuteron energies and beam currents than previously reported. We elected not to use copper or aluminum foils in the preparation of our 186W targets due to their activation in the deuteron beam, so part of the investigation was an evaluation of an alternate method for preparing thick targets that withstand μA beam currents. Irradiation of 186W. Initial thick targets (~600-1100 mg) were prepared using 96.86% enriched 186W by hydraulic pressing (6.9 MPa) of tungsten metal powder into an aluminum target support. Those thick targets were irradiated for 10 minu-tes at 10 µA with nominal extracted deuteron energies of 15, 17, 20, 22, and 24 MeV. Isolation of 186Re. Irradiated targets were dissolved with H2O2 and basified with (NH4)2CO3 prior to separation using column(s) of ~100–300 mg Analig Tc-02 resin. Columns were washed with (NH4)2CO3 and the rhenium was eluted with ~80˚C H2O. Gamma-ray spectroscopy was per-formed to assess production yields, extraction yields, and radionuclidic byproducts. Recycling target material. When tested on a natural abundance W target, recovery of the oxidized WO4- target material from the resin was found to proceed rapidly with the addition of 4M HCl in the form of hydrated WO3. The excess water in the WO3 was then removed by calcination at 800 °C for 4 hours. This material was found to undergo reduction to metallic W at elevated temperatures (~1550 °C) in a tube furnace under an inert atmosphere (Ar). Quanti-fication of % reduction and composition analyses were accomplished with SEM, EDS, and XRD and were used to characterize and compare both the WO3 and reduced Wmetal products to a sample of commercially available material. Structural enhancement by surface annealing. In some experiments ~1 g WO3 pellets were prepared from Wmetal that had been chemically treated to simulate the target material recovery process described above. Following calcination, the WO3 was allowed to cool to ambient temperature, pulverized with a mortar and pestle and then uniaxially pressed at 13.8 MPa into 13 mm pellets. Conversion of the WO3 back to Wmetal in pellet form was accomplished in a tube furnace under flowing Ar at 1550 °C for 8 hours. Material characterization and product composition analyses were conducted with SEM, EDS, and XRD spectroscopy. Graphite-encased W targets. Irradiations were conducted at 20 μA with a nominal extracted deuteron energy of 17 MeV using thick targets (~750 mg) of natural abundance tungsten metal powder uniaxially pressed into an aluminum target support between layers of graphite pow-der (100 mg on top, 50 mg on the bottom). Targets were then dissolved as previously described and preliminary radiochemical isola-tion yields obtained by counting in a dose calibrator. Although irradiations of W targets were possible at 10 μA currents, difficulties were encountered in maintaining the structural integrity of the full-thickness pressed target pellets under higher beam currents. This led to further investigation of the target design for irradiations conducted at higher beam currents. Comprehensive target material characterization via analysis by SEM, EDS, XRD, and Raman Spectroscopy allowed for a complete redesign of the target maximizing the structural integrity of the pressed target pellet without impacting production or isolation. At the 10 A current, target mass loss following irradiation of an enriched 186W target was < 1 % and typical separation yields in excess of 70 % were observed. Saturated yields and percent of both 183Re (t½ = 70 days) and 184gRe (t½ = 35 days) relative to 186gRe (decay corrected to EOB) are reported in TABLE 1 below. The reason for the anomalously low yield at 24 MeV is unknown, but might be explained by poor beam alignment and/or rhenium volatility during irradiation. Under these irradiation conditions, recovery yields of the W target material from the recycling process were found to be in excess of 90% with no discernable differences noted when compared to commercially available Wmetal and WO3. Conceptually, increasing the structural integrity of pressed WO3 targets by high temperature heat treatment under an inert atmosphere is intriguing. However, the treated pellets lacked both density and structural stability resulting in disintegration upon manipulation , despite the initially encouraging energy dispersive X-ray spectroscopy (EDS) determination that 94.9% percent of the WO3 material in each pellet had been reduced to metallic W. The use of powdered graphite as a target stabi-lizing agent provided successful irradiation of natural abundance W under conditions where non-stabilized targets failed (20 µA at 17 MeV for 10 minutes). Target mass loss following irradiation of a natW target was < 1 % and a separation yield in excess of 97 % was obtained. In conclusion, the theranostic radionuclide 186Re was produced in thick targets via the 186W(d,2n) reaction. It was found that pressed W metal could be used for beam currents of 10 μA or less. For deuteron irradiations at higher beam currents, a method involving pressing W metal between two layers of graphite provides increased target stability. Both target configurations allow high recovery of radioactivity from the W target material, and a solid phase extraction method allows good recovery of 186Re. An effective approach to the recycling of enriched W has been developed using elevated temperature under an inert atmosphere. Further studies are underway with 186W targets sandwiched by graphite to assess 186Re production yields, levels of contaminant radiorhenium, power deposition, and enriched 186W material requirements under escalated irradiation conditions (20 µA and 17 MeV for up to 2 hours)

Targetry investigations of 186Re production via proton induced reactions on natural Osmium disulfide and Tungsten disulfide targets

Introduction Radioisotopes play an important role in nuclear medicine and represent powerful tools for imaging and therapy. With the extensive use of 99mTc-based imaging agents, therapeutic rhenium analogues are highly desirable. Rhenium-186 emits therapeutic − particles with an endpoint-energy of 1.07 MeV, allowing for a small, targeted tissue range of 3.6 mm. Additionally, its low abundance γ-ray emission of 137.2 keV (9.42 %) allows for in vivo tracking of a radiolabeled compounds and dosimetry calculations. With a longer half-life of 3.718 days, synthesis and shipment of Re-186 based radiopharmaceuticals is not limited. Rhenium-186 can be produced either in a reactor or in an accelerator. Currently, Re-186 is produced in a reactor via the 185Re(n,γ) reaction resulting in low specific activity which makes its therapeutic application limited.[1] Production in an accelerator, such as the PETtrace at the University of Missouri Research Reactor (MURR), can theoretically provide a specific activity of 34,600 Ci.mmol−1 Re[2], which represents a 62 fold increase over reactor produced 186Re. The studies reported herein focused on the evaluation of accelerator-based reaction pathways to produce high specific activity (HSA) 186Re. Those pathways include proton and deuteron bombardment of tungsten and osmium targets by the following reactions: 186W(p,n)186Re, 186W(d,2n) 186Re, 189Os(p,α)186Re, and 192Os(p,α3n)186Re. Additional information on target design related to the determination and optimization of production rates, radionuclidic purity, and yield are presented. Material and Methods Osmium and tungsten metals are very hard and thus very brittle. Attempts at pressing the pure metal into aluminum backings resulted in chalky targets, which easily crumbled during handling. Osmium disulfide (OsS2) and tungsten disulfide (WS2) were identified to provide a softer, less brittle chemical form for targets. OsS2 and WS2 targets were prepared using a unilateral press with a 13 mm diameter die to form pressed powder discs. A simple target holder design (FIG. 1) was implemented to provide a stabilizing platform for the pressed discs. The target material was sealed in place with epoxy using a thin aluminum foil pressed over the target face. Initial irradiations of OsS2 were performed using the 16 MeV GE PETtrace cyclotron at MURR. Irradiations were performed for 30–60 minutes with proton beam currents of 10–20 µA. Following irradiation, the OsS2 targets were dissolved in NaOCl and the pH adjusted using NaOH. The resultant aqueous solution was mixed with methyl ethyl ketone (MEK), with the lipophilic perrhenate being extracted into the MEK layer and the osmium and iridium remaining in the aqueous layer. The MEK extracts were then passed through an acidic alumina column to remove any remaining osmium and iridium. Determination of rhenium and iridium activities was done by gamma spectroscopy on an HPGe detector. Preliminary irradiations on WS2 targets were performed at MURR with the beam degraded to 14 MeV with a proton beam current of 10 µA for 60 minutes. After irradiation, WS2 was dissolved using 30% H2O2 with gentle heating and counted on an HPGe detector to determine the radio-nuclides produced. Results and Conclusion Thin natOsS2 targets were produced, irradiated at 16 MeV for 10 µAh, and analyzed for radiorhenium. Under these irradiation conditions, rhenium isotopes were produced in nanocurie quantities while iridium isotopes were produced in microcurie quantities. Future studies with higher proton energies are planned to increase the production of rhenium and decrease the production of iridium. After optimizing irradiation conditions, enriched 189Os will be used for irradiations to reduce the production of unwanted radionuclides. A liquid-liquid extraction method separated the bulk of the rhenium from the iridium. The majority of the rhenium produced was recovered in the first organic aliquot with little iridium observed while the majority of the iridium and osmium was retained in the first aqueous aliquot. Target production with WS2 was successful. A thin target of natWS2 was produced and irradiated at 14 MeV for 10 µAh. Under these irradiation conditions, several rhenium isotopes were produced in microcurie quantities. Target parameters to maximize 186Re production remain to be determined before enriched 186W targets are used for irradiations to reduce the production of unwanted radionuclides. In conclusion, the potential production routes for accelerator-produced high specific activity 186Re are being evaluated. Cyclotron-based irradiations of natOsS2 targets established the feasibility of producing rhenium via the natOs(p,αxn)Re reaction. Current results indicate higher proton energies are necessary to reduce the production of unwanted iridium isotopes while increasing the production of rhenium isotopes. Preliminary irradiations were performed using the 50.5 MeV Scanditronix MC50 clinical cyclotron at the University of Washington to determine irradiation parameters for future higher energy irradiations (20–30 MeV). A rapid liquid-liquid extraction method isolated rhenium from the bulk of the iridium and osmium following irradiation. Preliminary studies indicate WS2 may also provide a suitable target material to produce 186Re via the (p,n) reaction pathway

Hydrophilic and lipophilic radiopharmaceuticals as tracers in pharmaceutical development: In vitro – In vivo studies

BACKGROUND: Scintigraphic studies have been performed to assess the release, both in vitro and in vivo, of radiotracers from tablet formulations. Four different tracers with differing physicochemical characteristics have been evaluated to assess their suitability as models for drug delivery. METHODS: In-vitro disintegration and dissolution studies have been performed at pH 1, 4 and 7. In-vivo studies have been performed by scintigraphic imaging in healthy volunteers. Two hydrophilic tracers, ((99m)Tc-DTPA) and ((99m)Tc-MDP), and two lipophilic tracers, ((99m)Tc-ECD) and ((99m)Tc-MIBI), were used as drug models. RESULTS: Dissolution and disintegration profiles, differed depending on the drug model chosen. In vitro dissolution velocity constants indicated a probable retention of the radiotracer in the formulation. In vivo disintegration velocity constants showed important variability for each radiopharmaceutical. Pearson statistical test showed no correlation between in vitro drug release, and in vivo behaviour, for (99m)Tc-DTPA, (99m)Tc-ECD and (99m)Tc-MIBI. High correlation coefficients were found for (99m)Tc-MDP not only for in vitro dissolution and disintegration studies but also for in vivo scintigraphic studies. CONCLUSION: Scintigraphic studies have made a significant contribution to the development of drug delivery systems. It is essential, however, to choose the appropriate radiotracers as models of drug behaviour. This study has demonstrated significant differences in release patterns, depending on the model chosen. It is likely that each formulation would require the development of a specific model, rather than being able to use a generic drug model on the basis of its physicochemical characteristics

A Systematic Literature Review with Meta-Analyses of Within- and Between-Day Differences in Objectively Measured Physical Activity in School-Aged Children

Background: Targeting specific time periods of the day or week may enhance physical activity (PA) interventions in youth. The most prudent time segments to target are currently unclear.  Objectives: To systematically review the literature describing differences in young people’s objectively measured PA on weekdays vs. weekends, in school vs. out of school, weekends vs. out of school and lesson time vs. break time.  Methods: Electronic databases were searched for English-language, cross-sectional studies of school-aged children (4–18 years) reporting time-segment-specific accelerometer-measured PA from 01/1990 to 01/2013. We meta-analysed standardised mean differences (SMD) between time segments for mean accelerometer counts per minute (TPA) and minutes in moderate-to-vigorous PA (MVPA). SMD is reported in units of standard deviation; 0.2, 0.5 and 0.8 represent small, moderate and large effects. Heterogeneity was explored using meta-regression (potential effect modifiers: age, sex and study setting).  Results: Of the 54 included studies, 37 were eligible for meta-analyses. Children were more active on weekdays than weekends [pooled SMD (95 % CI) TPA 0.14 (0.08; 0.20), MVPA 0.42 (0.35; 0.49)]. On school days, TPA was lower in school than out of school; however, marginally more MVPA was accumulated in school [TPA −0.24 (−0.40; −0.08), MVPA 0.17 (−0.03; 0.38)]. TPA was slightly lower on weekends than out of school on school days, but a greater absolute volume of MVPA was performed on weekends [TPA −0.10 (−0.19; −0.01), MVPA 1.02 (0.82; 1.23)]. Heterogeneity between studies was high (I2 73.3–96.3 %), with 20.3–53.1 % of variance between studies attributable to potential moderating factors.  Conclusions: School-aged children are more active on weekdays than weekend days. The outcome measure influences the conclusions for other comparisons. Findings support the tailoring of intervention strategies to specific time periods

Comparative oncology and clinical translation of glyco protein conjugated gold nano therapeutic agent (GA-198AuNP) [abstract]

Nanoscience Poster SessionAs part of our efforts toward clinical translation of GA-198AuNP, our studies are focused on therapeutic efficacy of nanoparticulate GA198AuNP agent in dogs with prostatic carcinoma. The overall goal is to gain clinical insights on therapeutic efficacy of GA198AuNP in a large animal model. We have performed a phase I clinical trial using GA-AuNP administered intravenously or intratumorally by injection or infusion. CT scans were performed prior to injection and 24 hours post injection in 3 of the 4 dogs. Following injections, dogs were allowed further treatment as recommended by the primary attending clinician. Four dogs have been treated to date. Complications related to GA-AuNP treatment were not observed, and all 4 dogs received adjunctive treatment with radiation therapy and/ or chemotherapy. These preliminary studies have clearly provided compelling evidence on the therapeutic potential of biocompatible GA-AuNP for their utility as novel therapeutic agents in treating various types of inoperable solid tumors. Intra-tumoral and intravenous administration of GA-AuNP is safe in dogs with spontaneously occurring tumors. As further therapeutic efficacy studies continue, the outcome of this clinical trial in a large animal model will generate therapeutic efficacy data which will be used for filing IND application for Phase I clinical trial studies. This clinical translation effort provides significant advances in terms of delivering optimum therapeutic payloads into prostate cancers with subsequent reduction in tumor volume, thus may effectively reduce/eliminate the need for surgical resection. This presentation will include details of clinical translation of GA198AuNP in prostate tumor bearing dogs

Burden of non-communicable diseases among adolescents aged 10–24 years in the EU, 1990–2019: a systematic analysis of the Global Burden of Diseases Study 2019

Background: Disability and mortality burden of non-communicable diseases (NCDs) have risen worldwide; however, the NCD burden among adolescents remains poorly described in the EU. Methods: Estimates were retrieved from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Causes of NCDs were analysed at three different levels of the GBD 2019 hierarchy, for which mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were extracted. Estimates, with the 95% uncertainty intervals (UI), were retrieved for EU Member States from 1990 to 2019, three age subgroups (10–14 years, 15–19 years, and 20–24 years), and by sex. Spearman's correlation was conducted between DALY rates for NCDs and the Socio-demographic Index (SDI) of each EU Member State. Findings: In 2019, NCDs accounted for 86·4% (95% uncertainty interval 83·5–88·8) of all YLDs and 38·8% (37·4–39·8) of total deaths in adolescents aged 10–24 years. For NCDs in this age group, neoplasms were the leading causes of both mortality (4·01 [95% uncertainty interval 3·62–4·25] per 100 000 population) and YLLs (281·78 [254·25–298·92] per 100 000 population), whereas mental disorders were the leading cause for YLDs (2039·36 [1432·56–2773·47] per 100 000 population) and DALYs (2040·59 [1433·96–2774·62] per 100 000 population) in all EU Member States, and in all studied age groups. In 2019, among adolescents aged 10–24 years, males had a higher mortality rate per 100 000 population due to NCDs than females (11·66 [11·04–12·28] vs 7·89 [7·53–8·23]), whereas females presented a higher DALY rate per 100 000 population due to NCDs (8003·25 [5812·78–10 701·59] vs 6083·91 [4576·63–7857·92]). From 1990 to 2019, mortality rate due to NCDs in adolescents aged 10–24 years substantially decreased (–40·41% [–43·00 to –37·61), and also the YLL rate considerably decreased (–40·56% [–43·16 to –37·74]), except for mental disorders (which increased by 32·18% [1·67 to 66·49]), whereas the YLD rate increased slightly (1·44% [0·09 to 2·79]). Positive correlations were observed between DALY rates and SDIs for substance use disorders (rs=0·58, p=0·0012) and skin and subcutaneous diseases (rs=0·45, p=0·017), whereas negative correlations were found between DALY rates and SDIs for cardiovascular diseases (rs=–0·46, p=0·015), neoplasms (rs=–0·57, p=0·0015), and sense organ diseases (rs=–0·61, p=0·0005). Interpretation: NCD-related mortality has substantially declined among adolescents in the EU between 1990 and 2019, but the rising trend of YLL attributed to mental disorders and their YLD burden are concerning. Differences by sex, age group, and across EU Member States highlight the importance of preventive interventions and scaling up adolescent-responsive health-care systems, which should prioritise specific needs by sex, age, and location. Funding: Bill &amp; Melinda Gates Foundation

Burden of injury along the development spectrum: Associations between the Socio-demographic Index and disability-adjusted life year estimates from the Global Burden of Disease Study 2017

Background: The epidemiological transition of non-communicable diseases replacing infectious diseases as the main contributors to disease burden has been well documented in global health literature. Less focus, however, has been given to the relationship between sociodemographic changes and injury. The aim of this study was to examine the association between disability-adjusted life years (DALYs) from injury for 195 countries and territories at different levels along the development spectrum between 1990 and 2017 based on the Global Burden of Disease (GBD) 2017 estimates. Methods: Injury mortality was estimated using the GBD mortality database, corrections for garbage coding and CODEm-the cause of death ensemble modelling tool. Morbidity estimation was based on surveys and inpatient and outpatient data sets for 30 cause-of-injury with 47 nature-of-injury categories each. The Socio-demographic Index (SDI) is a composite indicator that includes lagged income per capita, average educational attainment over age 15 years and total fertility rate. Results: For many causes of injury, age-standardised DALY rates declined with increasing SDI, although road injury, interpersonal violence and self-harm did not follow this pattern. Particularly for self-harm opposing patterns were observed in regions with similar SDI levels. For road injuries, this effect was less pronounced. Conclusions: The overall global pattern is that of declining injury burden with increasing SDI. However, not all injuries follow this pattern, which suggests multiple underlying mechanisms influencing injury DALYs. There is a need for a detailed understanding of these patterns to help to inform national and global efforts to address injury-related health outcomes across the development spectrum

The global burden of adolescent and young adult cancer in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15–39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods: Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15–39 years to define adolescents and young adults. Findings: There were 1·19 million (95% UI 1·11–1·28) incident cancer cases and 396 000 (370 000–425 000) deaths due to cancer among people aged 15–39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59·6 [54·5–65·7] per 100 000 person-years) and high-middle SDI countries (53·2 [48·8–57·9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14·2 [12·9–15·6] per 100 000 person-years) and middle SDI (13·6 [12·6–14·8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23·5 million (21·9–25·2) DALYs to the global burden of disease, of which 2·7% (1·9–3·6) came from YLDs and 97·3% (96·4–98·1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation: Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Funding: Bill &amp; Melinda Gates Foundation, American Lebanese Syrian Associated Charities, St Baldrick's Foundation, and the National Cancer Institute