cells of many mucosal organs have adapted to coexist with microbes and microbial products. In general, most studies suggest that epithelial cells benefit from interactions with commensal microorganisms present at the lumenal surface. However, potentially injurious molecules found in this microenvironment also have the capacity to elicit local inflammatory responses and even systemic disease. We have recently demonstrated that epithelia cells express the anti-infective molecule bactericidal/ permeability-increasing protein (BPI). Here, we extend these findings to examine molecular mechanisms of intestinal epithelial cell (IEC) BPI expression and function. Initial experiments revealed a variance of BPI mRNA and protein expression among various IEC lines. Studies of BPI promoter expression in IECs identified regulatory regions of the BPI promoter and revealed a prominent role for CCAAT/enhancer binding protein and especially Sp1/Sp3 in the basal regulation of BPI. To assess the functional significance of this protein, we generated an IEC line stably transfected with full-length BPI. We demonstrated that, whereas epithelia express markedly less BPI protein than neutrophils, epithelial BPI contributes significantly to bacterial killing and attenuating bacterial-elicted proinflammatory signals. Additional studies in murine tissue ex vivo revealed that BPI is diffusely expressed along the crypt-villous axis and that epithelial BPI levels decrease along the length of the intestine. Taken together, these data confirm the transcriptional regulation of BPI in intestinal epithelia and provide insight into the relevance of BPI as an anti-infective molecule at intestinal surfaces. mucosa; infection; inflammation; transcription; intestine AMONG THE INNATE ANTI-INFECTIVE DEFENSE MOLECULES of humans is bactericidal/permeability-increasing protein (BPI), a 55-to 60-kDa protein originally found in neutrophil azurophilic granules (62), on the neutrophil cell surface (60), and, to a lesser extent, in specific granules of eosinophils (3). More recently, BPI has been shown to be expressed in epithelia (4) and by fibroblasts (49). BPI's high affinity for the lipid A region of lipopolysaccharide (LPS) (16) in the gram-negative bacterial outer membrane is followed by a time-dependent penetration of the molecule to the bacterial inner membrane, where damage results in a loss of membrane integrity, dissipation of electrochemical gradients, and bacterial death (39). In addition, BPI is capable of inhibiting all of the many proinflammatory activities of LPS, including the induction of cytokine release, activation of neutrophil oxidase enzymes, and nitric oxide formation (6,32,40,63). This protein can also serve as an opsonin for phagocytosis of gram-negative bacteria by neutrophils (9, 34). BPI's actions are amplified by extracellular factors including the complement system and secretory phospholipase A 2 (10), and members of the defensin and cathelicidin antimicrobial peptide families synergistically enhance BPI's antibacterial activity (33...

Article 19 of the UN Convention on the Rights of Persons with Disabilities requires states to ensure that disabled people can choose where and with whom they live with access to a range of services including personal assistance. Based on qualitative research of the implementation of Article 19 in Nordic countries, this paper focuses on Sweden, which was at the forefront of implementing personal assistance law and policy and has been the inspiration for many European countries. Instead of strengthening access to personal assistance, this study found that since the Swedish government ratified the Convention in 2008, there has been an increase in the numbers of people losing state-funded personal assistance and an increase in rejected applications. This paper examines the reasons for the deterioration of eligibility criteria for accessing personal assistance in Sweden. The findings shed light on how legal and administrative interpretations of "basic needs" are shifting from a social to a medical understanding. They also highlight a shift from collaborative policy making towards conflict, where courts have become the battleground for defining eligibility criteria. Drawing on the findings, we ask if Sweden is violating its obligations under the Convention.

Article 19 of the United Nations (UN) Convention on the Rights of Persons with Disabilities requires states to ensure that persons with disabilities have access to a range of support services, including personal assistance. The Convention is an agreement between state parties and the UN. However, in practice, disability services are often implemented at the local level. Drawing on the findings of qualitative research in Iceland, Norway and Sweden, this paper examines a paradox whereby states commit to ensure access to support services, but decentralize responsibility to autonomous and independent local governments. A multi-level governance framework is applied to analyse the findings of qualitative inquiry with policy-makers, local government officials and leaders of independent living organizations in all three Nordic countries. A multi-level analysis highlights the tensions and contradictions between decentralization and human rights commitments.

The global COVID-19 Disability Rights Monitor (COVID-19 DRM) has revealed major injustices suffered by disabled people around the world during the first stage of the pandemic, including enhanced institutionalisation, breakdown of essential services in the community, multiplication of intersectional harms, and denial of access to healthcare. In this paper, we present an overview of the COVID-19 DRM and its findings. We also offer a disability studies response by making recourse to the social model of disability, independent living philosophy, and analyses of biopolitics. We argue that the COVID-19 DRM illuminates systemic flaws that predate the pandemic, and that it is these flaws that need to be addressed in post-pandemic efforts at reconstruction.

This paper was inspired by a peculiar theme that emerged from qualitative interviews in Iceland, Norway and Sweden with leaders of Centres for Independent Living (CILs). CILs are peer-led organisations that maximise user-control of disability services. Paradoxically, the Nordic reputation as forerunners in deinstitutionalisation and independent living was considered an impediment to implementing Article 19 of the UN Convention on the Rights of Persons with Disabilities which requires "access to a range of support services, including personal assistance necessary to support living and inclusion in the community". This contradiction prompted the questions: How is Article 19 implemented in Nordic welfare services? And why is previous progress towards independent living and personal assistance seen as an impediment to implementing the rights-based approach required by the Convention? The findings suggest that it is difficult to change a developed welfare system in which there are vested interests in maintaining the status quo. The reputation of "being number one" conceals problems such as inflexible services and the imbalance of power where the control of services lies with the system and the professionals, not the users.