Derjaguin-Landau-Verwey-Overbeek Energy Landscape of a Janus Particle with a Nonuniform Cap

A colloidal particle is often termed “Janus” when some portion of its surface is coated by a second material which has distinct properties from the native particle. The anisotropy of Janus particles enables unique behavior at interfaces. However, rigorous methodologies to predict Janus particle dynamics at interfaces are required to implement these particles in complex fluid applications. Previous work studying Janus particle dynamics does not consider van der Waals interactions and realistic, nonuniform coating morphology. Here we develop semianalytic equations to accurately calculate the potential landscape, including van der Waals interactions, of a Janus particle with nonuniform coating thickness above a solid boundary. The effects of both nonuniform coating thickness and van der Waals interactions significantly influence the potential landscape of the particle, particularly in high ionic strength solutions, where the particle samples positions very close to the solid boundary. The equations developed herein facilitate more simple, accurate, and less computationally expensive characterization of conservative interactions experienced by a confined Janus particle than previous methods

Sleep disturbance in dementia or mild cognitive impairment: a realist review of general practice

Background: Sleep disturbance (SD) is a prevalent condition among people living with dementia (PLwD) or mild cognitive impairment (MCI). Its assessment and management within primary care is complex due to the comorbidities, older age and cognitive impairment typical of this patient group. Aim: This study aimed to explore how primary care clinicians assess, understand, and manage SD for PLwD or MCI; if and why such initiatives work; and how people and their carers experience SD and its treatment. Design and setting: A realist review of existing literature was conducted in 2022. Methods: Six bibliographic databases were searched. Context-Mechanism-Outcome Configurations (CMOCs) were developed and refined. Results: Sixty records were included from 1,869 retrieved hits and 19 CMOCs were developed. Low awareness of and confidence in the treatment of SD among primary care clinicians and service users, combined with time and resource constraints, meant that identifying SD was difficult and not prioritised. Medication was perceived by clinicians and service users as the primary management tool, resulting in inappropriate or long-term prescription. Rigid nursing routines in care homes were reportedly not conducive to good quality sleep. Conclusion: In primary care, SD among PLwD or MCI is not adequately addressed. Over-reliance on medication, under-utilisation of non-pharmacological strategies, and inflexible care home routines were reported due to low confidence and resource constraints. This does not constitute effective and person-centred care. Future work should consider ways to tailor the assessment and management of SD to the needs of individuals and their informal carers without overstretching services

HER2-Specific Chimeric Antigen Receptor–Modified Virus-Specific T Cells for Progressive Glioblastoma: A Phase 1 Dose-Escalation Trial

Glioblastoma is an incurable tumor, and the therapeutic options for patients are limited. To determine whether the systemic administration of HER2-specific chimeric antigen receptor (CAR)-modified virus-specific T cells (VSTs) is safe and whether these cells have antiglioblastoma activity. In this open-label phase 1 dose-escalation study conducted at Baylor College of Medicine, Houston Methodist Hospital, and Texas Children's Hospital, patients with progressive HER2-positive glioblastoma were enrolled between July 25, 2011, and April 21, 2014. The duration of follow-up was 10 weeks to 29 months (median, 8 months). Monotherapy with autologous VSTs specific for cytomegalovirus, Epstein-Barr virus, or adenovirus and genetically modified to express HER2-CARs with a CD28.ζ-signaling endodomain (HER2-CAR VSTs). Primary end points were feasibility and safety. The key secondary end points were T-cell persistence and their antiglioblastoma activity. A total of 17 patients (8 females and 9 males; 10 patients ≥18 years [median age, 60 years; range, 30-69 years] and 7 patients <18 years [median age, 14 years; range, 10-17 years]) with progressive HER2-positive glioblastoma received 1 or more infusions of autologous HER2-CAR VSTs (1 × 106/m2 to 1 × 108/m2) without prior lymphodepletion. Infusions were well tolerated, with no dose-limiting toxic effects. HER2-CAR VSTs were detected in the peripheral blood for up to 12 months after the infusion by quantitative real-time polymerase chain reaction. Of 16 evaluable patients (9 adults and 7 children), 1 had a partial response for more than 9 months, 7 had stable disease for 8 weeks to 29 months, and 8 progressed after T-cell infusion. Three patients with stable disease are alive without any evidence of progression during 24 to 29 months of follow-up. For the entire study cohort, median overall survival was 11.1 months (95% CI, 4.1-27.2 months) from the first T-cell infusion and 24.5 months (95% CI, 17.2-34.6 months) from diagnosis. Infusion of autologous HER2-CAR VSTs is safe and can be associated with clinical benefit for patients with progressive glioblastoma. Further evaluation of HER2-CAR VSTs in a phase 2b study is warranted as a single agent or in combination with other immunomodulatory approaches for glioblastoma

Cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life years for 29 cancer groups from 2010 to 2019 a systematic analysis for the global burden of disease study 2019

IMPORTANCE The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world. © 2022 American Medical Association. All rights reserved. **Please note that there are multiple authors for this article therefore only the name of the first 30 including Federation University Australia affiliate “Muhammad Aziz Rahman" is provided in this record*

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021:a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed.FundingBill &amp; Melinda Gates Foundation.<br/

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

An international survey of the structure and process of care for traumatic spinal cord injury in acute and rehabilitation facilities : lessons learned from a pilot study

BACKGROUND: To describe the key findings and lessons learned from an international pilot study that surveyed spinal cord injury programs in acute and rehabilitation facilities to understand the status of spinal cord injury care. METHODS: An online survey with two questionnaires, a 74-item for acute care and a 51-item for rehabilitation, was used. A subset of survey items relevant to the themes of specialized care, timeliness, patient-centeredness, and evidence-based care were operationalized as structure or process indicators. Percentages of facilities reporting the structure or process to be present, and percentages of indicators met by each facility were calculated and reported separately for facilities from high-income countries (HIC) and from low and middle-income countries (LMIC) to identify "hard to meet" indicators defined as those met by less than two-thirds of facilities and to describe performance level. RESULTS: A total of 26 acute and 26 rehabilitation facilities from 25 countries participated in the study. The comparison of the facilities based on the country income level revealed three general observations: 1) some indicators were met equally well by both HIC and LMIC, such as 24-hour access to CT scanners in acute care and out-patient services at rehabilitation facilities; 2) some indicators were hard to meet for LMIC but not for HIC, such as having a multidisciplinary team for both acute and rehabilitation settings; and 3) some indicators were hard to meet by both HIC and LMIC, including having peer counselling programs. Variability was also observed for the same indicator between acute and rehabilitation facilities, and a wide range in the total number of indicators met among HIC facilities (acute 59-100%; rehabilitation 36-100%) and among LMIC facilities (acute: 41-82%; rehabilitation: 36-93%) was reported. CONCLUSIONS: Results from this international pilot study found that the participating acute and rehabilitation facilities on average adhered to 74% of the selected indicators, suggesting that the structure and processes to provide ideal traumatic spinal cord injury care were broadly available. Recruiting a representative sample of SCI facilities and incorporating regional attributes in future surveys will be helpful to examine factors affecting adherence to indicators.publishedVersionPeer reviewe

Moving in the anthropocene: global reductions in terrestrial mammalian movements

Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016