Effect of the COVID-19 Pandemic on Seizure Control Status in Patients With Epilepsy

Background: Previous studies have shown that patients with epilepsy (PWE) perceived significant disruption in the quality and provision of care due to the coronavirus disease 2019 (COVID-19) pandemic. The present study aimed to investigate the effect of this pandemic on seizure control status and changes in seizure frequency in PWE. Methods:A consecutive sample of adult PWE registered in the database of Shiraz Epilepsy Center (Shiraz, Iran) was included in the study. In July 2021, phone interviews were conducted with all selected patients. Information such as age, sex, last seizure, seizure type, and frequency during the 12 months before the study, and history of COVID-19 contraction was extracted. The seizure control status of the patients in 2019 (pre-pandemic) was compared with that during the COVID-19 pandemic. Data were analyzed using SPSS software with the Fisher’s exact test and Pearson’s Chi squared test. P Results: A total of 158 patients were included in the study, out of which 62 (39.2%) patients had a stable seizure control status, 47 (29.7%) had fewer seizures, and 50 (31.6%) had more seizures. Breakthrough seizures were reported by 32 (34.4%) patients. Seizure frequency increased in 18 (27.7%) and decreased in 46 (70.7%) patients. Conclusion: Overall, the COVID-19 pandemic has not been a major precipitating factor nor has it affected the seizure control status of PWE. In treated epilepsy, a fluctuating course with periods of seizure freedom followed by relapses is part of its natural history

Evaluation of nanocarrier targeted drug delivery of capecitabine-PAMAM dendrimer complex in a mice colorectal cancer model

Capecitabine, an effective anticancer drug in colorectal cancer chemotherapy, may create adverse side effects on healthy tissues. In the present study, we first induced colon adenocarcinoma with azoxymethane, a carcinogen agent, and then investigated the potentiality of polyamidoamine (PAMAM) dendrimer to improve capecitabine therapeutic index and decrease its adverse side effects on healthy tissues like liver and bone marrow. Other variables such as nanoparticle concentrations have also been investigated. Drug loading concentration (DLC) and encapsulation efficiency (EE) were calculated for capecitabine/dendrimer complex. Experimental results showed an increase in DLC percentage resulted from elevated capecitabine/dendrimer ratio. Capecitabine/dendrimer complex could reduce tumor size and adverse side effects in comparison with free capecitabine form. © 2016 Tehran University of Medical Sciences. All rights reserved

Mayo Adhesive Probability Score Does Not Have Prognostic Ability in Locally Advanced Renal Cell Carcinoma

Nephrectomy remains standard treatment for renal cell carcinoma (RCC). The Mayo Adhesive Probability (MAP) score is predictive of adherent perinephric fat and associated surgical complexity, and is determined by assessing perinephric fat and stranding. MAP has additionally predicted progression-free survival (PFS), though primarily reported in stage T1-T2 RCC. Here, we examine MAP’s ability to predict overall survival (OS) and PFS in T3-T4 RCC. From our prospectively maintained RCC database, patients that underwent radical nephrectomy (2009-2016) with available abdominal imaging (<90 days preop) and T3/T4 RCC underwent MAP scoring. Survival analyses were conducted with MAP scores as individual (0-5) and dichotomized (0-3 vs 4-5) using Kaplan-Meier method. Multivariable Cox proportional hazard regression models for PFS and OS were built with backward elimination. 141 patients were included. 134 (95%) and 7 (5%) had pT3 and pT4 disease, respectively. 46.1% of patients had an inferior vena cava thrombus. Mean MAP score was 3.22±1.52, with 75 (53%) patients having a score between 0-3 and 66 (47%) having a score of 4-5. Both male gender (p=0.006) and clear cell histology (p=0.012) were associated with increased MAP scores. On Kaplan-Meier and multivariable analysis, no significant associations were identified between MAP and PFS (HR=1.01, 95% CI 0.85-1.20, p=0.93) or OS (HR=1.01, 95% CI 0.84-1.21, p=0.917). In this cohort of patients with locally advanced RCC, high MAP scores were not predictive of worse PFS or OS

Clinical outcome and prognostic factors for central neurocytoma: twenty year institutional experience

Central neurocytomas are uncommon intraventricular neoplasms whose optimal management remains controversial due to their rarity. We assessed outcomes for a historical cohort of neurocytoma patients and evaluated effects of tumor atypia, size, resection extent, and adjuvant radiotherapy. Progression-free survival (PFS) was measured by Kaplan-Meier and Cox proportional hazards methods. A total of 28 patients (15 males, 13 females) were treated between 1995 and 2014, with a median age at diagnosis of 26 years (range 5-61). Median follow-up was 62.2 months and 3 patients were lost to follow-up postoperatively. Thirteen patients experienced recurrent/progressive disease and 2-year PFS was 75% (95% CI 53-88%). Two-year PFS was 48% for MIB-1 labeling >4% versus 90% for ≤4% (HR 5.4, CI 2.2-27.8, p = 0.0026). Nine patients (32%) had gross total resections (GTR) and 19 (68%) had subtotal resections (STR). PFS for >80% resection was 83 versus 67% for ≤80% resection (HR 0.67, CI 0.23-2.0, p = 0.47). Three STR patients (16%) received adjuvant radiation which significantly improved overall PFS (p = 0.049). Estimated 5-year PFS was 67% for STR with radiotherapy versus 53% for STR without radiotherapy. Salvage therapy regimens were diverse and resulted in stable disease for 54% of patients and additional progression for 38 %. Two patients with neuropathology-confirmed atypical neurocytomas died at 4.3 and 113.4 months after initial surgery. For central neurocytomas, MIB-1 labeling index >4% is predictive of poorer outcome and our data suggest that adjuvant radiotherapy after STR may improve PFS. Most patients requiring salvage therapy will be stabilized and multiple modalities can be effectively utilized

Generating Bessel beams with broad depth-of-field by using phase-only acoustic holograms

[EN] We report zero-th and high-order acoustic Bessel beams with broad depth-of-field generated using acoustic holograms. While the transverse field distribution of Bessel beams generated using traditional passive methods is correctly described by a Bessel function, these methods present a common drawback: the axial distribution of the field is not constant, as required for ideal Bessel beams. In this work, we experimentally, numerically and theoretically report acoustic truncated Bessel beams of flat-intensity along their axis in the ultrasound regime using phase-only holograms. In particular, the beams present a uniform field distribution showing an elongated focal length of about 40 wavelengths, while the transverse width of the beam remains smaller than 0.7 wavelengths. The proposed acoustic holograms were compared with 3D-printed fraxicons, a blazed version of axicons. The performance of both phase-only holograms and fraxicons is studied and we found that both lenses produce Bessel beams in a wide range of frequencies. In addition, high-order Bessel beam were generated. We report first order Bessel beams that show a clear phase dislocation along their axis and a vortex with single topological charge. The proposed method may have potential applications in ultrasonic imaging, biomedical ultrasound and particle manipulation applications using passive lenses.This work was supported by the Spanish Ministry of Economy and Innovation (MINECO) through Project TEC2016-80976-R. NJ and SJ acknowledge financial support from Generalitat Valenciana through grants APOSTD/2017/042, ACIF/2017/045 and GV/2018/11. FC acknowledges financial support from Agencia Valenciana de la Innovacio through grant INNCON00/18/9 and European Regional Development Fund (IDIFEDER/2018/022).Jiménez-Gambín, S.; Jimenez, N.; Benlloch Baviera, JM.; Camarena Femenia, F. (2019). Generating Bessel beams with broad depth-of-field by using phase-only acoustic holograms. Scientific Reports. 9:1-13. https://doi.org/10.1038/s41598-019-56369-zS1139Durnin, J. Exact solutions for nondiffracting beams. i. the scalar theory. J. Opt. Soc. Am. A 4, 651 (1987).Durnin, J., Miceli, J. Jr & Eberly, J. Diffraction-free beams. Physical review letters 58, 1499 (1987).Chu, X. Analytical study on the self-healing property of Bessel beam. Eur. Phys. J. D 66, 259 (2012).McLeod, E., Hopkins, A. B. & Arnold, C. B. Multiscale Bessel beams generated by a tunable acoustic gradient index of refraction lens. Opt. Lett. 31, 3155 (2006).Li, Z., Alici, K. B., Caglayan, H. & Ozbay, E. Generation of an axially asymmetric Bessel-like beam from a metallic subwavelength aperture. Phys. Rev. Lett. 102, 143901 (2009).Fahrbach, F. & Rohrbach, A. Propagation stability of self-reconstructing Bessel beams enables contrast-enhanced imaging in thick media. Nat. Commun. 3, 632 (2011).Lu, J.-y, Zou, H. & Greenleaf, J. F. Biomedical ultrasound beam forming. Ultrasound in medicine & biology 20, 403–428 (1994).Marston, P. L. Scattering of a Bessel beam by a sphere. J. Acous. Soc. Am. 121, 753 (2007).Marston, P. L. Scattering of a Bessel beam by a sphere: Ii. helicoidal case and spherical shell example. The Journal of the Acoustical Society of America 124, 2905–2910 (2008).Lu, J. & Greenleaf, F. Ultrasonic nondiffracting transducer for medical imaging. IEEE Trans. Ultrason. Ferroelec. Freq. Contr. 37, 438 (1990).Lu, J.-Y. & Greenleaf, J. F. Pulse-echo imaging using a nondiffracting beam transducer. Ultrasound in medicine & biology 17, 265–281 (1991).Lu, J.-y, Song, T.-K., Kinnick, R. R. & Greenleaf, J. F. In vitro and in vivo real-time imaging with ultrasonic limited diffraction beams. IEEE transactions on medical imaging 12, 819–829 (1993).Lu, J.-y, Xu, X.-L., Zou, H. & Greenleaf, J. F. Application of Bessel beam for doppler velocity estimation. IEEE transactions on ultrasonics, ferroelectrics, and frequency control 42, 649–662 (1995).Nabavizadeh, A., Greenleaf, J. F., Fatemi, M. & Urban, M. W. Optimized shear wave generation using hybrid beamforming methods. Ultrasound in medicine & biology 40, 188–199 (2014).Marston, P. L. Axial radiation force of a Bessel beam on a sphere and direction reversal of the force. The Journal of the Acoustical Society of America 120, 3518–3524 (2006).Marston, P. L. Negative axial radiation forces on solid spheres and shells in a Bessel beam. The Journal of the Acoustical Society of America 122, 3162–3165 (2007).Marston, P. L. Radiation force of a helicoidal Bessel beam on a sphere. The Journal of the Acoustical Society of America 125, 3539–3547 (2009).Thomas, J.-L. & Marchiano, R. Pseudo angular momentum and topological charge conservation for nonlinear acoustical vortices. Physical review letters 91, 244302 (2003).Volke-Sepúlveda, K., Santillán, A. O. & Boullosa, R. R. Transfer of angular momentum to matter from acoustical vortices in free space. Phys. Rev. Lett. 100, 024302 (2008).Zhang, L. & Marston, P. L. Geometrical interpretation of negative radiation forces of acoustical Bessel beams on spheres. Physical Review E 84, 035601 (2011).Courtney, C. R. et al. Dexterous manipulation of microparticles using Bessel-function acoustic pressure fields. Applied Physics Letters 102, 123508 (2013).Hong, Z., Zhang, J. & Drinkwater, B. W. Observation of orbital angular momentum transfer from Bessel-shaped acoustic vortices to diphasic liquid-microparticle mixtures. Phys. Rev. Lett. 114, 214301 (2015).Baresch, D., Thomas, J.-L. &Marchiano, R. Observation of a single-beam gradient force acoustical trap for elastic particles: Acoustical tweezers. Phys. Rev. Lett. 116 (2016).Marzo, A., Caleap, M. & Drinkwater, B. W. Acoustic virtual vortices with tunable orbital angular momentum for trapping of mie particles. Phys. Rev. Lett. 120, 044301 (2018).Li, Y. et al. Acoustic radiation torque of an acoustic-vortex spanner exerted on axisymmetric objects. Applied Physics Letters 112, 254101 (2018).Riaud, A., Baudoin, M., Thomas, J.-L. & Matar, O. B. Cyclones and attractive streaming generated by acoustical vortices. Physical Review E 90, 013008 (2014).Shi, C., Dubois, M., Wang, Y. & Zhang, X. High-speed acoustic communication by multiplexing orbital angular momentum. Proceedings of the National Academy of Sciences 114, 7250–7253 (2017).Jiang, X., Liang, B., Cheng, J.-C. & Qiu, C.-W. Twisted acoustics: metasurface-enabled multiplexing and demultiplexing. Advanced Materials 30, 1800257 (2018).Hsu, D., Margetan, F. & Thompson, D. O. Bessel beam ultrasonic transducer: fabrication method and experimental results. Appl. Phys. Lett. 55, 2066 (1989).Campbell, J. A. & Soloway, S. Generation of a nondiffracting beam with frequency-independent beamwidth. The Journal of the Acoustical Society of America 88, 2467–2477 (1990).Masuyama, H., Yokoyama, T., Nagai, K. & Mizutani, K. Generation of Bessel beam from equiamplitude-driven annular transducer array consisting of a few elements. Jpn. J. Appl. Phys. 38, 3080 (1999).Fjield, T., Fan, X. & Hynynen, K. A parametric study of the concentric-ring transducer design for mri guided ultrasound surgery. J. Acoust. Soc. Am. 100, 1220 (1996).Chillara, V. K., Pantea, C. & Sinha, D. N. Low-frequency ultrasonic Bessel-like collimated beam generation from radial modes of piezoelectric transducers. Applied Physics Letters 110, 064101 (2017).Burckhardt, C., Hoffmann, H. & Grandchamp, P.-A. Ultrasound axicon: A device for focusing over a large depth. The Journal of the Acoustical Society of America 54, 1628–1630 (1973).Foster, F., Patterson, M., Arditi, M. & Hunt, J. The conical scanner: a two transducer ultrasound scatter imaging technique. Ultrasonic imaging 3, 62–82 (1981).McLeod, J. H. The axicon: A new type of optical element. J. Opt. Soc. Am. 44, 592 (1954).Arlt, J. & Dholakia, K. Generation of high-order Bessel beams by use of an axicon. Optics Communications 177, 297–301 (2000).Golub, I. Fresnel axicon. Optics letters 31, 1890–1892 (2006).Lirette, R. & Mobley, J. Broadband wave packet dynamics of minimally diffractive ultrasonic fields from axicon and stepped fraxicon lenses. The Journal of the Acoustical Society of America 146, 103–108 (2019).Jiménez, N. et al. Acoustic Bessel-like beam formation by an axisymmetric grating. Europhys. Lett. 106, 24005 (2014).Xu, Z., Xu, W., Qian, M., Cheng, Q. & Liu, X. A flat acoustic lens to generate a Bessel-like beam. Ultrasonics 80, 66–71 (2017).Li, Y., Liang, B., Gu, Z.-M., Zou, X.-Y. & Cheng, J.-C. Reflected wavefront manipulation based on ultrathin planar acoustic metasurfaces. Scientific Reports 3, 2546 (2013).Nye, J. & Berry, M. Dislocations in wave trains. Proc. R. Soc. London, Ser. A 336, 165–190 (1974).Jiménez, N. et al. Formation of high-order acoustic Bessel beams by spiral diffraction gratings. Physical Review E 94, 053004 (2016).Wang, T. et al. Particle manipulation with acoustic vortex beam induced by a brass plate with spiral shape structure. Applied Physics Letters 109, 123506 (2016).Jia, Y.-R., Wei, Q., Wu, D.-J., Xu, Z. & Liu, X.-J. Generation of fractional acoustic vortex with a discrete archimedean spiral structure plate. Applied Physics Letters 112, 173501 (2018).Jiménez, N., Romero-Garca, V., Garca-Raffi, L. M., Camarena, F. & Staliunas, K. Sharp acoustic vortex focusing by fresnel-spiral zone plates. Applied Physics Letters 112, 204101 (2018).Baudoin, M. et al. Folding a focalized acoustical vortex on a flat holographic transducer: miniaturized selective acoustical tweezers. Science advances 5, eaav1967 (2019).Muelas-Hurtado, R. D., Ealo, J. L., Pazos-Ospina, J. F. & Volke-Sepúlveda, K. Acoustic analysis of a broadband spiral source for the simultaneous generation of multiple Bessel vortices in air. The Journal of the Acoustical Society of America 144, 3252–3261 (2018).Muelas-Hurtado, R. D., Ealo, J. L., Pazos-Ospina, J. F. & Volke-Sepúlveda, K. Generation of multiple vortex beam by means of active diffraction gratings. Applied Physics Letters 112, 084101 (2018).Wunenburger, R., Lozano, J. I. V. & Brasselet, E. Acoustic orbital angular momentum transfer to matter by chiral scattering. New Journal of Physics 17, 103022 (2015).Terzi, M., Tsysar, S., Yuldashev, P., Karzova, M. & Sapozhnikov, O. Generation of a vortex ultrasonic beam with a phase plate with an angular dependence of the thickness. Moscow University Physics Bulletin 72, 61–67 (2017).Hefner, B. T. & Marston, P. L. An acoustical helicoidal wave transducer with applications for the alignment of ultrasonic and underwater systems. Jour. Acous. Soc. Am. 106, 3313–3316 (1999).Ealo, J. L., Prieto, J. C. & Seco, F. Airborne ultrasonic vortex generation using flexible ferroelectrets. IEEE transactions on ultrasonics, ferroelectrics, and frequency control 58, 1651–1657 (2011).Naify, C. J. et al. Generation of topologically diverse acoustic vortex beams using a compact metamaterial aperture. Applied Physics Letters 108, 223503 (2016).Ye, L. et al. Making sound vortices by metasurfaces. AIP Advances 6, 085007 (2016).Jiang, X., Li, Y., Liang, B., Cheng, J.-C. & Zhang, L. Convert acoustic resonances to orbital angular momentum. Physical review letters 117, 034301 (2016).Esfahlani, H., Lissek, H. & Mosig, J. R. Generation of acoustic helical wavefronts using metasurfaces. Physical Review B 95, 024312 (2017).Jiménez-Gambn, S., Jiménez, N., Benlloch, J. M. & Camarena, F. Holograms to focus arbitrary ultrasonic fields through the skull. Physical Review Applied 12, 014016 (2019).Maimbourg, G., Houdouin, A., Deffieux, T., Tanter, M. & Aubry, J.-F. 3d-printed adaptive acoustic lens as a disruptive technology for transcranial ultrasound therapy using single-element transducers. Physics in Medicine & Biology 63, 025026 (2018).Ferri, M. et al. On the evaluation of the suitability of the materials used to 3d print holographic acoustic lenses to correct transcranial focused ultrasound aberrations. Polymers 11, 1521 (2019).Melde, K., Mark, A. G., Qiu, T. & Fischer, P. Holograms for acoustics. Nature 537, 518 (2016).Brown, M. D., Cox, B. T. & Treeby, B. E. Design of multi-frequency acoustic kinoforms. Applied Physics Letters 111, 244101 (2017).Brown, M., Nikitichev, D., Treeby, B. & Cox, B. Generating arbitrary ultrasound fields with tailored optoacoustic surface profiles. Applied Physics Letters 110, 094102 (2017).Zhu, Y. et al. Fine manipulation of sound via lossy metamaterials with independent and arbitrary reflection amplitude and phase. Nature communications 9, 1632 (2018).Brown, M. D. Phase and amplitude modulation with acoustic holograms. Applied Physics Letters 115, 053701 (2019).Jiménez, N., Romero-Garca, V., Pagneux, V. & Groby, J.-P. Quasiperfect absorption by subwavelength acoustic panels in transmission using accumulation of resonances due to slow sound. Physical Review B 95, 014205 (2017).Tsang, P. W. M. & Poon, T.-C. Novel method for converting digital fresnel hologram to phase-only hologram based on bidirectional error diffusion. Optics Express 21, 23680–23686 (2013).Soret, J. Ueber die durch kreisgitter erzeugten diffractionsphänomene. Annalen der Physik 232, 99–113 (1875).Turunen, J., Vasara, A. & Friberg, A. T. Holographic generation of diffraction-free beams. Applied Optics 27, 3959–3962 (1988).Vasara, A., Turunen, J. & Friberg, A. T. Realization of general nondiffracting beams with computer-generated holograms. JOSA A 6, 1748–1754 (1989).Cunningham, K. B. & Hamilton, M. F. Bessel beams of finite amplitude in absorbing fluids. J. Acous. Soc. Am. 108, 519 (2000).Ding, D. & Y. Lu, J. Higher-order harmonics of limited diffraction Bessel beams. J. Acous. Soc. Am. 107, 1212 (2000).Skeldon, K., Wilson, C., Edgar, M. & Padgett, M. An acoustic spanner and its associated rotational Doppler shift. New J. Phys. 10, 013018 (2008).Wu, J. Acoustical tweezers. J. Acoust. Soc. Am. 89, 2140–2143 (1991).Zhang, L. & Marston, P. L. Angular momentum flux of nonparaxial acoustic vortex beams and torques on axisymmetric objects. Physical Review E 84, 065601 (2011).Yoon, C., Kang, B. J., Lee, C., Kim, H. H. & Shung, K. K. Multi-particle trapping and manipulation by a high-frequency array transducer. Appl. Phys. Lett. 105, 214103 (2014).Marzo, A. et al. Holographic acoustic elements for manipulation of levitated objects. Nat. Commun. 6 (2015).Blackstock, D. T. Fundamentals of physical acoustics (John Wiley & Sons, 2000).Treeby, B. E. & Cox, B. Modeling power law absorption and dispersion for acoustic propagation using the fractional laplacian. The Journal of the Acoustical Society of America 127, 2741–2748 (2010).Treeby, B. E., Jaros, J., Rendell, A. P. & Cox, B. Modeling nonlinear ultrasound propagation in heterogeneous media with power law absorption using a k-space pseudospectral method. The Journal of the Acoustical Society of America 131, 4324–4336 (2012).Jiménez, N. et al. Time-domain simulation of ultrasound propagation in a tissue-like medium based on the resolution of the nonlinear acoustic constitutive relations. Acta Acustica united with Acustica 102, 876–892 (2016)

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10-14 and 50-54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings The global TFR decreased from 2.72 (95% uncertainty interval [UI] 2.66-2.79) in 2000 to 2.31 (2.17-2.46) in 2019. Global annual livebirths increased from 134.5 million (131.5-137.8) in 2000 to a peak of 139.6 million (133.0-146.9) in 2016. Global livebirths then declined to 135.3 million (127.2-144.1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2.1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27.1% (95% UI 26.4-27.8) of global livebirths. Global life expectancy at birth increased from 67.2 years (95% UI 66.8-67.6) in 2000 to 73.5 years (72.8-74.3) in 2019. The total number of deaths increased from 50.7 million (49.5-51.9) in 2000 to 56.5 million (53.7-59.2) in 2019. Under-5 deaths declined from 9.6 million (9.1-10.3) in 2000 to 5.0 million (4.3-6.0) in 2019. Global population increased by 25.7%, from 6.2 billion (6.0-6.3) in 2000 to 7.7 billion (7.5-8.0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58.6 years (56.1-60.8) in 2000 to 63.5 years (60.8-66.1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.Peer reviewe

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

Global, regional and national burden of bladder cancer and its attributable risk factors in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease study 2019

Introduction The current study determined the level and trends associated with the incidence, death and disability rates for bladder cancer and its attributable risk factors in 204 countries and territories, from 1990 to 2019, by age, sex and sociodemographic index (SDI; a composite measure of sociodemographic factors). Methods Various data sources from different countries, including vital registration and cancer registries were used to generate estimates. Mortality data and incidence data transformed to mortality estimates using the mortality to incidence ratio (MIR) were used in a cause of death ensemble model to estimate mortality. Mortality estimates were divided by the MIR to produce incidence estimates. Prevalence was calculated using incidence and MIR-based survival estimates. Age-specific mortality and standardised life expectancy were used to estimate years of life lost (YLLs). Prevalence was multiplied by disability weights to estimate years lived with disability (YLDs), while disability-adjusted life years (DALYs) are the sum of the YLLs and YLDs. All estimates were presented as counts and age-standardised rates per 100 000 population. Results Globally, there were 524 000 bladder cancer incident cases (95% uncertainty interval 476 000 to 569 000) and 229 000 bladder cancer deaths (211 000 to 243 000) in 2019. Age-standardised death rate decreased by 15.7% (8.6 to 21.0), during the period 1990–2019. Bladder cancer accounted for 4.39 million (4.09 to 4.70) DALYs in 2019, and the age-standardised DALY rate decreased significantly by 18.6% (11.2 to 24.3) during the period 1990–2019. In 2019, Monaco had the highest age-standardised incidence rate (31.9 cases (23.3 to 56.9) per 100 000), while Lebanon had the highest age-standardised death rate (10.4 (8.1 to 13.7)). Cabo Verde had the highest increase in age-standardised incidence (284.2% (214.1 to 362.8)) and death rates (190.3% (139.3 to 251.1)) between 1990 and 2019. In 2019, the global age-standardised incidence and death rates were higher among males than females, across all age groups and peaked in the 95+ age group. Globally, 36.8% (28.5 to 44.0) of bladder cancer DALYs were attributable to smoking, more so in males than females (43.7% (34.0 to 51.8) vs 15.2% (10.9 to 19.4)). In addition, 9.1% (1.9 to 19.6) of the DALYs were attributable to elevated fasting plasma glucose (FPG) (males 9.3% (1.6 to 20.9); females 8.4% (1.6 to 19.1)). Conclusions There was considerable variation in the burden of bladder cancer between countries during the period 1990–2019. Although there was a clear global decrease in the age-standardised death, and DALY rates, some countries experienced an increase in these rates. National policy makers should learn from these differences, and allocate resources for preventative measures, based on their country-specific estimates. In addition, smoking and elevated FPG play an important role in the burden of bladder cancer and need to be addressed with prevention programmes.publishedVersio

Real-time prostate motion assessment: image-guidance and the temporal dependence of intra-fraction motion

BACKGROUND: The rapid adoption of image-guidance in prostate intensity-modulated radiotherapy (IMRT) results in longer treatment times, which may result in larger intrafraction motion, thereby negating the advantage of image-guidance. This study aims to qualify and quantify the contribution of image-guidance to the temporal dependence of intrafraction motion during prostate IMRT. METHODS: One-hundred and forty-three patients who underwent conventional IMRT (n=67) or intensity-modulated arc therapy (IMAT/RapidArc, n=76) for localized prostate cancer were evaluated. Intrafraction motion assessment was based on continuous RL (lateral), SI (longitudinal), and AP (vertical) positional detection of electromagnetic transponders at 10 Hz. Daily motion amplitudes were reported as session mean, median, and root-mean-square (RMS) displacements. Temporal effect was evaluated by categorizing treatment sessions into 4 different classes: IMRT(c) (transponder only localization), IMRT(cc) (transponder + CBCT localization), IMAT(c) (transponder only localization), or IMAT(cc) (transponder + CBCT localization). RESULTS: Mean/median session times were 4.15/3.99 min (IMAT(c)), 12.74/12.19 min (IMAT(cc)), 5.99/5.77 min (IMRT(c)), and 12.98/12.39 min (IMRT(cc)), with significant pair-wise difference (p<0.0001) between all category combinations except for IMRT(cc) vs. IMAT(cc) (p>0.05). Median intrafraction motion difference between CBCT and non-CBCT categories strongly correlated with time for RMS (t-value=17.29; p<0.0001), SI (t-value=−4.25; p<0.0001), and AP (t-value=2.76; p<0.0066), with a weak correlation for RL (t-value=1.67; p=0.0971). Treatment time reduction with non-CBCT treatment categories showed reductions in the observed intrafraction motion: systematic error (Σ)<0.6 mm and random error (σ)<1.2 mm compared with ≤0.8 mm and <1.6 mm, respectively, for CBCT-involved treatment categories. CONCLUSIONS: For treatment durations >4-6 minutes, and without any intrafraction motion mitigation protocol in place, patient repositioning is recommended, with at least the acquisition of the lateral component of an orthogonal image pair in the absence of volumetric imaging