Unraveling Forward and Backward Source Problems for a Nonlocal Integrodifferential Equation: A Journey through Operational Calculus for Dzherbashian-Nersesian Operator

This article primarily aims at introducing a novel operational calculus of Mikusi\'nski's type for the Dzherbashian-Nersesian operator. Using this calculus, we are able to derive exact solutions for the forward and backward source problems (BSPs) of a differential equation that features Dzherbashian-Nersesian operator in time and intertwined with nonlocal boundary conditions. The initial condition is expressed in terms of Riemann-Liouville integral (RLI). Solution is presented using Mittag-Leffler type functions (MLTFs). The outcomes related to the existence and uniqueness subject to certain conditions of regularity on the input data are established.Comment: 13 page

A thermogelling organic-inorganic hybrid hydrogel with excellent printability, shape fidelity and cytocompatibility for 3D bioprinting

Alginates are the most commonly used bioink in biofabrication, but their rheological profiles make it very challenging to perform real 3D printing. In this study, an advanced hybrid hydrogel ink was developed, a mixture of thermogelling diblock copolymer, alginate and clay i.e. Laponite XLG. The reversible thermogelling and shear thinning properties of the diblock copolymer in the ink system improves handling and 3D printability significantly. Various three-dimensional constructs, including suspended filaments, were printed successfully with high shape fidelity and excellent stackability. Subsequent ionic crosslinking of alginate fixates the printed scaffolds, while the diblock copolymer is washed out of the structure, acting as a fugitive material/porogen on the (macro)molecular level. Finally, cell-laden printing and culture over 21 d demonstrated good cytocompatibility and feasibility of the novel hybrid hydrogels for 3D bioprinting. We believe that the developed approach could be interesting for a wide range of bioprinting applications including tissue engineering and drug screening, potentially enabling also other biological bioinks such as collagen, hyaluronic acid, decellularized extracellular matrices or cellulose based bioinks.Peer reviewe

Thermal, electrochemical and mechanical properties of shape memory alloy developed by a conventional processing route

A Cu based shape memory alloy (Cu-Al-Ni) having a composition 83% Cu, 14% Al, 3% Ni, was developed and studied to determine the shape memory effect. Powder of Cu, Al and Ni was melted in a pit furnace at about 15500C, and casted alloy was heat treated at 8500C for a period of 50 minutes followed by water quenching. Microstructure characterization of alloy (Cu-Al-Ni) was carried out to determine the pre-quenched (cast structure) and quenched martensitic structure. The microstructure analysis of developed samples showed needle like structure of quenched martensite after heat treatment. It has a very good resemblance with structure of casted shape memory alloy obtained from the vacuum induction process. The Vickers hardness test was also performed. Quenched microstructure with improved hardness than pre-quenched structure was observed.Keywords: Shape Memory Alloy, Microstructure, Mechanical Propertie

Tuning the Thermogelation and Rheology of Poly(2-Oxazoline)/Poly(2-Oxazine)s Based Thermosensitive Hydrogels for 3D Bioprinting

As one kind of “smart” material, thermogelling polymers find applications in biofabrication, drug delivery and regenerative medicine. In this work, we report a thermosensitive poly(2-oxazoline)/poly(2-oxazine) based diblock copolymer comprising thermosensitive/moderately hydrophobic poly(2-N-propyl-2-oxazine) (pPrOzi) and thermosensitive/moderately hydrophilic poly(2-ethyl-2-oxazoline) (pEtOx). Hydrogels were only formed when block length exceeded certain length (≈100 repeat units). The tube inversion and rheological tests showed that the material has then a reversible sol-gel transition above 25 wt.% concentration. Rheological tests further revealed a gel strength around 3 kPa, high shear thinning property and rapid shear recovery after stress, which are highly desirable properties for extrusion based three-dimensional (3D) (bio) printing. Attributed to the rheology profile, well resolved printability and high stackability (with added laponite) was also possible. (Cryo) scanning electron microscopy exhibited a highly porous, interconnected, 3D network. The sol-state at lower temperatures (in ice bath) facilitated the homogeneous distribution of (fluorescently labelled) human adipose derived stem cells (hADSCs) in the hydrogel matrix. Post-printing live/dead assays revealed that the hADSCs encapsulated within the hydrogel remained viable (≈97%). This thermoreversible and (bio) printable hydrogel demonstrated promising properties for use in tissue engineering applications

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: an initiative of the Joint Programme for Neurodegenerative Disease Research

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention

Use of multidimensional item response theory methods for dementia prevalence prediction : an example using the Health and Retirement Survey and the Aging, Demographics, and Memory Study

Background Data sparsity is a major limitation to estimating national and global dementia burden. Surveys with full diagnostic evaluations of dementia prevalence are prohibitively resource-intensive in many settings. However, validation samples from nationally representative surveys allow for the development of algorithms for the prediction of dementia prevalence nationally. Methods Using cognitive testing data and data on functional limitations from Wave A (2001-2003) of the ADAMS study (n = 744) and the 2000 wave of the HRS study (n = 6358) we estimated a two-dimensional item response theory model to calculate cognition and function scores for all individuals over 70. Based on diagnostic information from the formal clinical adjudication in ADAMS, we fit a logistic regression model for the classification of dementia status using cognition and function scores and applied this algorithm to the full HRS sample to calculate dementia prevalence by age and sex. Results Our algorithm had a cross-validated predictive accuracy of 88% (86-90), and an area under the curve of 0.97 (0.97-0.98) in ADAMS. Prevalence was higher in females than males and increased over age, with a prevalence of 4% (3-4) in individuals 70-79, 11% (9-12) in individuals 80-89 years old, and 28% (22-35) in those 90 and older. Conclusions Our model had similar or better accuracy as compared to previously reviewed algorithms for the prediction of dementia prevalence in HRS, while utilizing more flexible methods. These methods could be more easily generalized and utilized to estimate dementia prevalence in other national surveys

The global, regional, and national burden of adult lip, oral, and pharyngeal cancer in 204 countries and territories:A systematic analysis for the Global Burden of Disease Study 2019

Importance Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.Objective To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.Evidence Review The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.Findings In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.Conclusions and Relevance In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts

Global, regional, and national burden of osteoarthritis, 1990–2020 and projections to 2050: a systematic analysis for the Global Burden of Disease Study 2021

Background Osteoarthritis is the most common form of arthritis in adults, characterised by chronic pain and loss of mobility. Osteoarthritis most frequently occurs after age 40 years and prevalence increases steeply with age. WHO has designated 2021–30 the decade of healthy ageing, which highlights the need to address diseases such as osteoarthritis, which strongly affect functional ability and quality of life. Osteoarthritis can coexist with, and negatively effect, other chronic conditions. Here we estimate the burden of hand, hip, knee, and other sites of osteoarthritis across geographies, age, sex, and time, with forecasts of prevalence to 2050. Methods In this systematic analysis for the Global Burden of Disease Study, osteoarthritis prevalence in 204 countries and territories from 1990 to 2020 was estimated using data from population-based surveys from 26 countries for knee osteoarthritis, 23 countries for hip osteoarthritis, 42 countries for hand osteoarthritis, and US insurance claims for all of the osteoarthritis sites, including the other types of osteoarthritis category. The reference case definition was symptomatic, radiographically confirmed osteoarthritis. Studies using alternative definitions from the reference case definition (for example self-reported osteoarthritis) were adjusted to reference using regression models. Osteoarthritis severity distribution was obtained from a pooled meta-analysis of sources using the Western Ontario and McMaster Universities Arthritis Index. Final prevalence estimates were multiplied by disability weights to calculate years lived with disability (YLDs). Prevalence was forecast to 2050 using a mixed-effects model. Findings Globally, 595 million (95% uncertainty interval 535–656) people had osteoarthritis in 2020, equal to 7·6% (95% UI 6·8–8·4) of the global population, and an increase of 132·2% (130·3–134·1) in total cases since 1990. Compared with 2020, cases of osteoarthritis are projected to increase 74·9% (59·4–89·9) for knee, 48·6% (35·9–67·1) for hand, 78·6% (57·7–105·3) for hip, and 95·1% (68·1–135·0) for other types of osteoarthritis by 2050. The global age-standardised rate of YLDs for total osteoarthritis was 255·0 YLDs (119·7–557·2) per 100 000 in 2020, a 9·5% (8·6–10·1) increase from 1990 (233·0 YLDs per 100 000, 109·3–510·8). For adults aged 70 years and older, osteoarthritis was the seventh ranked cause of YLDs. Age-standardised prevalence in 2020 was more than 5·5% in all world regions, ranging from 5677·4 (5029·8–6318·1) per 100 000 in southeast Asia to 8632·7 (7852·0–9469·1) per 100 000 in high-income Asia Pacific. Knee was the most common site for osteoarthritis. High BMI contributed to 20·4% (95% UI –1·7 to 36·6) of osteoarthritis. Potentially modifiable risk factors for osteoarthritis such as recreational injury prevention and occupational hazards have not yet been explored in GBD modelling. Interpretation Age-standardised YLDs attributable to osteoarthritis are continuing to rise and will lead to substantial increases in case numbers because of population growth and ageing, and because there is no effective cure for osteoarthritis. The demand on health systems for care of patients with osteoarthritis, including joint replacements, which are highly effective for late stage osteoarthritis in hips and knees, will rise in all regions, but might be out of reach and lead to further health inequity for individuals and countries unable to afford them. Much more can and should be done to prevent people getting to that late stage