A novel vision-based multi-functional sensor for normality and position measurements in precise robotic manufacturing

Cobots play an essential role in the fourth industrial revolution and the automation of complex manufacturing processes. However, cobots still face challenges in achieving high precision, which obstructs their usage in precise applications such as the aerospace industry. Nonetheless, advances in perception systems unlock new cobot manufacturing capabilities. This paper presents a novel multi-functional sensor that combines visual and tactile feedback using a single optical sensor, featuring a moving gate mechanism. This work also marks the first integration of Vision-Based Tactile Sensing (VBTS) into a robotic machining end-effector. The sensor provides vision-based tactile perception capabilities for precise normality control and exteroceptive perception for robot localization and positioning. Its performance is experimentally demonstrated in a precise robotic deburring application, where the sensor achieves the high-precision requirements of the aerospace industry with a mean normality error of 0.13° and a mean positioning error of 0.2 mm. These results open a new paradigm for using vision-based sensing for precise robotic manufacturing, which surpasses conventional approaches in terms of precision, weight, size, and cost-effectiveness

The Topical Ocular Delivery of Rapamycin to Posterior Eye Tissues and the Suppression of Retinal Inflammatory Disease

Treatment of posterior eye diseases with intravitreal injections of drugs, while effective, is invasive and associated with side effects such as retinal detachment and endophthalmitis. In this work, we have formulated a model compound, rapamycin (RAP), in nanoparticle-based eye drops and evaluated the delivery of RAP to the posterior eye tissues in a healthy rabbit. We have also studied the formulation in experimental autoimmune uveitis (EAU) mouse model with retinal inflammation. Aqueous RAP eye drops were prepared using N-palmitoyl-N-monomethyl-N,N-dimethyl-N,N,N-trimethyl-6-O-glycolchitosan (Molecular Envelope Technology - MET) containing 0.23 ± 0.001% w/v RAP with viscosity, osmolarity, and pH within the ocular comfort range, and the formulation (MET-RAP) was stable in terms of drug content at both refrigeration and room temperature for one month. The MET-RAP eye drops delivered RAP to the choroid-retina with a Cmax of 145 ± 49 ng/g (tmax = 1 hour). The topical application of the MET-RAP eye drops to the EAU mouse model resulted in significant disease suppression compared to controls, with activity similar to dexamethasone eye drops. The MET-RAP eye drops also resulted in a reduction of RORγt and an increase in both Foxp3 expression and IL-10 secretion, indicating a mechanism involving the inhibition of Th17 cells and the up-regulation of T-reg cells. The MET-RAP formulation delivers RAP to the posterior eye segments, and the formulation is active in EAU

COVID-19 Delta Variant: Perceptions, Worries, and Vaccine-Booster Acceptability among Healthcare Workers

Background: As the COVID-19 Delta variant has spread across the globe, healthcare workers’ (HCWs) knowledge, worries, and vaccine booster acceptance should be assessed. Methods: Online questionnaires aimed at HCWs in Saudi Arabia were distributed between 9 and 12 August 2021, aiming to evaluate HCWs’ perceptions and worries about the Delta variant as well as their feelings about receiving a booster-vaccine. Results: A total of 1279 HCWs participated, with 51.1% being physicians and 41.7% nurses. 92.5% were aware of the emergence of the Delta variant. Still, only 28.7% were found to have sufficient knowledge of the variant, and their level of worry about it was higher than their level of worry about the Alpha variant (2.32/5 versus 1.79/5). The main information sources cited by the participants were social media (50.5%), while 30.5% used scientific journals. Overall, 55.3% were willing to receive a vaccine booster, while one third would have preferred to receive a new mRNA vaccine specifically developed for the Delta variant. Factors associated with vaccine booster acceptance were receiving both vaccination doses (p = 0.008), believing that the Pfizer-BioNTech BNT162b2 vaccine is effective against variants (p < 0.001), and agreement that mixing/matching vaccines is effective against variants (p < 0.001). Conclusions: A high percentage of HCWs were aware of the Delta variant, but only a small fraction had decent quality of knowledge about it. The participants exhibited high worry levels and showed a modest acceptance of receiving a vaccine booster dose. These results should encourage public health officials to scale up educational efforts to disseminate reliable information about the different variants and provide recommendations about receiving a vaccine booster. Further research on methods to alleviate HCWs’ worries about emerging variants is warranted

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019 : a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dosespecific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in countryreported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81.6% [95% uncertainty interval 80.4-82 .7]) more than doubled from levels estimated in 1980 (39.9% [37.5-42.1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38.5% [35.4-41.3] in 1980 to 83.6% [82.3-84.8] in 2019). Third- dose polio vaccine (Pol3) coverage also increased, from 42.6% (41.4-44.1) in 1980 to 79.8% (78.4-81.1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56.8 million (52.6-60. 9) to 14.5 million (13.4-15.9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

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. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Development of Pharmaceutical Nanomedicines: From the Bench to the Market

Nanotechnology plays a significant role in the field of medicine and in drug delivery, mainly due to the major limitations affecting the conventional pharmaceutical agents, and older formulations and delivery systems. The effect of nanotechnology on healthcare is already being felt, as various nanotechnology applications have been developed, and several nanotechnology-based medicines are now on the market. Across many parts of the world, nanotechnology draws increasing investment from public authorities and the private sector. Most conventional drug-delivery systems (CDDSs) have an immediate, high drug release after administration, leading to increased administration frequency. Thus, many studies have been carried out worldwide focusing on the development of pharmaceutical nanomedicines for translation into products manufactured by local pharmaceutical companies. Pharmaceutical nanomedicine products are projected to play a major role in the global pharmaceutical market and healthcare system. Our objectives were to examine the nanomedicines approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the global market, to briefly cover the challenges faced during their development, and to look at future perspectives. Additionally, the importance of nanotechnology in developing pharmaceutical products, the ideal properties of nanocarriers, the reasons behind the failure of some nanomedicines, and the important considerations in the development of nanomedicines will be discussed in brief

Gum Acacia Functionalized Colloidal Gold Nanoparticles of Letrozole as Biocompatible Drug Delivery Carrier for Treatment of Breast Cancer

The most prevalent malignancy among postmenopausal women is breast cancer. It is one of the leading causes of cancer-related mortality among women. Letrozole (LTZ) is a clinically approved inhibitor for breast cancer in postmenopausal women. However, due to poor aqueous solubility, non-specific binding, unwanted toxicity, and poor blood circulation hampered its clinical applications. To maximize the pharmacological effects and minimize the side effects, inorganic nanoparticles are a good alternative. Due to excellent biocompatibility and minimum cytotoxicity, gold nanoparticles (AuNPs) offer distinct benefits over other metal nanoparticles. Emerging as attractive components, AuNPs and Gum acacia (GA) have been extensively studied as biologically safe nanomaterials for the treatment of cancers. This study reports the synthesis and characterization of GA stabilized gold nanoparticles (GA-AuNPs) of LTZ for breast cancer treatment. The observed particle size of optimized LTZ @ GA-AuNPs was 81.81 ± 4.24 nm in size, 0.286 ± 0.143 of polydispersity index (PDI) and −14.6 ± −0.73 mV zeta potential. The biologically synthesized LTZ @ GA-AuNPs also demonstrated dose-dependent cytotoxicity against the human breast cancer cell line MCF-7, with an inhibitory concentration (IC50) of 3.217 ± 0.247. We determined the hemolytic properties of the LTZ @ GA-AuNPs to evaluate the interaction between the nanoparticles and blood components. Results showed that there is no interaction between LTZ @ GA-AuNPs and blood. In conclusion, the findings indicate that LTZ @ GA-AuNPs has significant potential as a promising drug delivery carrier for treating breast cancer in postmenopausal women

Antimicrobial Resistance Awareness, Antibiotics Prescription Errors and Dispensing Patterns by Community Pharmacists in Saudi Arabia

Background: Antibiotic overuse and misuse have greatly facilitated the development of antimicrobial resistance (AMR). The Kingdom of Saudi Arabia is one of the countries that took a strategic approach, beginning with the prohibition of over-the-counter antibiotic dispensing, followed by the implementation of antimicrobial stewardship programs and various educational and awareness governmental activities and plans. However, the status of antibiotic prescriptions and dispensing in Saudi community pharmacies is still unclear. As a result, this study investigates community pharmacists' antibiotic dispensing practices and their knowledge of their role in fighting AMR, in addition to the status of antibiotic prescribing errors by physicians. Method: This is an online-based survey study of 671 participants distributed among community pharmacists of large pharmacy chains throughout the Saudi Arabia. Result: A number of 671 community pharmacists were participated in total, with a response rate of 96.57% (648 responses). The majority of community pharmacists (67%) had a long experience (>5 years) in this field. An antibiotic prescribing error was prevalent, with a mean of 3.32 per month in each pharmacy. Dentists (36.7%) and general practitioners (28.7%) were the most prescribers associated with antibiotic prescription errors. Most community pharmacists had a generally good practice of dispensing antibiotics, accounting for 71.5% of daily antibiotic dispensing. However, more than one-third of those pharmacists (35.2%) agreed on dispensing topical antibiotics without a prescription, based on their evaluation of the case presented in the pharmacy, as the majority of community pharmacists demonstrated a significant understanding of AMR. Conclusion: The current study demonstrated that there is a good antibiotic dispensing practice in the community pharmacies in Saudi Arabia, in addition to a substantial understanding of the community pharmacist’s vital role in fighting AMR. This study could inform decision-makers on antibiotic usage in Saudi community pharmacies to improve the current inappropriate antibiotic use and dispensing situation and, thus, control AMR spread in Saudi Arabia