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IntroductionMucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N-acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs lysosomal degradation of keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations of MPS IVA present numerous challenges for management and necessitate the need for individualised treatment. Although treatment guidelines are available, the methodology used to develop this guidance has come under increased scrutiny. This programme was conducted to provide evidence-based, expert-agreed recommendations to optimise management of MPS IVA.MethodsTwenty six international healthcare professionals across multiple disciplines, with expertise in managing MPS IVA, and three patient advocates formed the Steering Committee (SC) and contributed to the development of this guidance. Representatives from six Patient Advocacy Groups (PAGs) were interviewed to gain insights on patient perspectives. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with experience managing patients with MPS IVA and the manuscript was evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers.ResultsA total of 87 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) disease-modifying interventions (enzyme replacement therapy [ERT] and haematopoietic stem cell transplantation [HSCT]); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions (including spinal, limb, ophthalmic, cardio-thoracic and ear-nose-throat [ENT] surgeries). Consensus was reached on all statements after two rounds of voting. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance).ConclusionThis manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS IVA and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps.

IntroductionMucopolysaccharidosis (MPS) VI or Maroteaux-Lamy syndrome (253200) is an autosomal recessive lysosomal storage disorder caused by deficiency in N-acetylgalactosamine-4-sulfatase (arylsulfatase B). The heterogeneity and progressive nature of MPS VI necessitates a multidisciplinary team approach and there is a need for robust guidance to achieve optimal management. This programme was convened to develop evidence-based, expert-agreed recommendations for the general principles of management, routine monitoring requirements and the use of medical and surgical interventions in patients with MPS VI.Methods26 international healthcare professionals from various disciplines, all with expertise in managing MPS VI, and three patient advocates formed the Steering Committee group (SC) and contributed to the development of this guidance. Members from six Patient Advocacy Groups (PAGs) acted as advisors and attended interviews to ensure representation of the patient perspective. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with expertise and experience managing patients with MPS VI and the manuscript has been evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers.ResultsA total of 93 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions. Consensus was reached on all statements after two rounds of voting. The greatest challenges faced by patients as relayed by consultation with PAGs were deficits in endurance, dexterity, hearing, vision and respiratory function. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance).ConclusionThis manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS VI and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps.

The global nephrology community recognizes the need for a cohesive strategy to address the growing problem of end-stage kidney disease (ESKD). In March 2018, the International Society of Nephrology hosted a summit on integrated ESKD care, including 92 individuals from around the globe with diverse expertise and professional backgrounds. The attendees were from 41 countries, including 16 participants from 11 low- and lower-middle-income countries. The purpose was to develop a strategic plan to improve worldwide access to integrated ESKD care, by identifying and prioritizing key activities across 8 themes: (i) estimates of ESKD burden and treatment coverage, (ii) advocacy, (iii) education and training/workforce, (iv) financing/funding models, (v) ethics, (vi) dialysis, (vii) transplantation, and (viii) conservative care. Action plans with prioritized lists of goals, activities, and key deliverables, and an overarching performance framework were developed for each theme. Examples of these key deliverables include improved data availability, integration of core registry measures and analysis to inform development of health care policy; a framework for advocacy; improved and continued stakeholder engagement; improved workforce training; equitable, efficient, and cost-effective funding models; greater understanding and greater application of ethical principles in practice and policy; definition and application of standards for safe and sustainable dialysis treatment and a set of measurable quality parameters; and integration of dialysis, transplantation, and comprehensive conservative care as ESKD treatment options within the context of overall health priorities. Intended users of the action plans include clinicians, patients and their families, scientists, industry partners, government decision makers, and advocacy organizations. Implementation of this integrated and comprehensive plan is intended to improve quality and access to care and thereby reduce serious health-related suffering of adults and children affected by ESKD worldwide.

In this study, we examined the impact of online learning on children's educational progress during the Covid-19 pandemic, particularly focusing on migrant children attending a primary school in Hangzhou, China. Through a combination of student and parent questionnaires (n = 537) and in-depth interviews with teachers and parents, we found that migrant children faced challenges such as poor connectivity, inadequate equipment, and lack of parental supervision when participating in online teaching. These challenges were exacerbated by pre-existing digital disparities and economic insecurities brought about by the pandemic, which further marginalised socially excluded families. As a result, children's ability to benefit from online instruction was compromised, highlighting the urgent need for remedial assistance and support for these vulnerable populations. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common type of bone cancer. Some patients eventually develop recurrent or metastatic diseases and treatment options are extremely limited. Discoidin domain receptor 1 (DDR1) is a unique collagen‐activated tyrosine kinase that participates in various human diseases, including cancer. DDR1 promotes adhesion, proliferation, differentiation, migration, and metastasis of cancer cells. The purpose of this study is to assess the expression, clinical prognostic relationship and functional roles of DDR1 in osteosarcoma. The correlation between DDR1 expression in tumor tissues and clinicopathological features, and prognosis was assessed via immunohistochemical staining of a unique tissue microarray (TMA) constructed from osteosarcoma specimens. DDR1‐specific siRNA and a highly selective DDR1 inhibitor, 7rh, were applied to determine the impact of DDR1 expression on osteosarcoma cell growth and proliferation. Furthermore, the effect of DDR1 inhibition on clonogenicity was evaluated using a clonogenic assay, and a 3D cell culture model was used to mimic DDR1 effects in an in vivo environment. The results demonstrate that higher DDR1 expression significantly correlates with recurrence, metastasis, and shorter overall survival in osteosarcoma patients. The expression of DDR1 is also inversely correlated to the response to neoadjuvant chemotherapy. Therapeutically, DDR1 knockdown with siRNA or selective inhibition with 7rh decreases the proliferation and growth of osteosarcoma cells. In conclusion, our study supports DDR1 expression as an independent predictor of poor prognosis and a promising therapeutic target for osteosarcoma. [ABSTRACT FROM AUTHOR]

The investigation of the subscriber lists of eighteenth-century books is a relatively new subgenre in the scholarly world, in part because quite often the names appearing in such lists are now obscure. But subscribers were hardly unknown when they subscribed, and a recovery of their identities can often be useful to other scholarly pursuits. This essay focusses on the subscribers to the works of Laurence Sterne and Samuel Derrick, one author well known today and one little known. A relatively large number of the subscribers in both were members of the eighteenth-century theatrical world. Furthermore, the essay looks at eighteenth-century annotations of the subscription list in Derrick's Works (1755) with an eye toward using them to provide further information about the evolving relationship between Derrick and a far more famous figure of the time, Samuel Johnson. [ABSTRACT FROM AUTHOR]

Herbaspirillum spp. is a common environmental bacterium usually found in soil, plant roots, and water. It is rarely associated with infection in immunocompromised patients, and rarely reported infections in immunocompetent patients. We report the first case of a Herbaspirillum huttiense bacteraemia in a non‐neutropenic home haemodialysis patient. A 57‐year‐old male presented to our hospital with a 3‐day history of malaise, fevers, rigours, and anorexia following dialysis through his central line. On examination, he was pyrexic (temperature 38.7°C) with splinter haemorrhages noted, but no other signs of infection were present. Blood cultures revealed a polymicrobial infection, with Serratia liquefaciens and Corynebacterium jeikeium isolated from the central line and Herbaspirillum sp. was isolated from both the central line and a peripheral culture. A later peripheral blood culture following central line removal isolated Herbaspirillum huttiense. Regular biological testing of his home water supply and dialysate detected no colony forming units of non‐fermenting gram‐negative bacilli. He was initially treated with ceftriaxone and vancomycin initially, followed by ertapenem and vancomycin. Intravenous antibiotics were ceased following 5 days after central line removal and he made an uneventful recovery. [ABSTRACT FROM AUTHOR]

Rising rates of incarceration in the United States and continuing use of the death penalty in over half of the states in the United States signal a need for more involvement of social workers in forensic roles to mitigate unjust sentencing. The National Association of Social Workers has consistently maintained a professional policy stance in opposition to the death penalty and in support for alternative sentencing plans, citing that the death penalty disproportionately impacts communities affected by poverty and communities of color, and is prone to error. The purpose of this article is to highlight the importance of educating social workers to mitigation as a primary role among forensic social workers, with a focus on death penalty mitigation with its critical skills and knowledge. After describing mitigation in death penalty cases, we examine four major social work roles in capital cases that expanded education should cover: (1) mitigation investigation, (2) consulting expert, (3) expert witness, (4) teaching expert. This article also addresses important ethical considerations when working as a member of capital defense teams and provides recommendations for social work graduate curricula to tailor content to better prepare students for capital mitigation practice.

An African American teacher and students engaged in meaningful reading and writing that included African American literature. These literacy experiences allowed the development of cultural models through exploring identity, questioning dominant narratives, and building capacity for literary analysis. This study shows how meaningful literacy pedagogy for African American students can be implemented during the school day despite the pressures of a heavily constrained curriculum.

Author(s): TK Logan [sup.1] , Kellie Lynch [sup.1] , Robert Walker [sup.1] Author Affiliations: (1) grid.266539.d, 0000 0004 1936 8438, University of Kentucky, , 333 Waller Ave, Suite 480, 40504, [...], Firearms are used in over half of partner violence victim homicides, and many victims experience firearm-related threats from their abusive partners. It is unclear whether, and to what extent, abusers who make firearm-related threats also engage in other forms of control and violence. An online community-based sample of women whose abusive partners caused them to experience fear because of their access to guns or threats to use them were recruited for the study. This study examined coercive control, threats, violence, and help-seeking for women whose partner held them at gunpoint (n = 112) compared to women whose partners did not hold them at gunpoint (n = 125). Women whose partners held them at gunpoint experienced more severe and frequent firearm and non-firearm related threats and physical/sexual violence. Additionally, abusers used a variety of strategies to control victims including tactics to increase dependency, debility, and dread-all of which were more frequent and severe among women held at gunpoint by the abuser. Only about half of the women held at gunpoint, and 30% of those not held at gunpoint, talked to police or sought a civil protective order. Among those that sought help through the justice system, only about 70% told police or the court about the firearm threats. Current legal remedies that restrict firearms may reduce some lethality risk, but safety is far from guaranteed by solely restricting gun ownership underscoring the importance of assessment and safety planning for partner violence victims who experience firearm-related threats.