Police lethal force and accountability : monitoring deaths in Western Europe

The use of force by the police and other law enforcement officers has long been a significant topic of concern, especially when it results in death. This issue and the controversies around it have recently been highlighted by a series of high-profile deaths in 2020. Police Lethal Force and Accountability assesses the frequency of deaths, and the availability and reliability of information regarding deaths, associated with the application of force by law enforcement agencies in four jurisdictions: Belgium, England & Wales, France and the Netherlands. By adopting a common set of considerations for assessing the policies and practices within these individual jurisdictions, this report enables comparisons to be made across them. In doing so, we look to provide those in policing agencies, campaigning groups, government ministries and others, with sound information with which they can identify priorities to ensure uses of force are being accurately recorded and investigated. By enabling those concerned to understand how uses of force are recorded and addressed in comparison with other jurisdictions, we hope this report will help them to build a stronger case when holding public institutions accountable and identifying points for improvement. As documented, while deaths from the use of force appear relatively rare across these four jurisdictions when compared to countries such as the US the procedures and policies for recording, investigating and disclosing details associated with deaths are wanting. The availability of official information on the number of deaths associated with the use of force, its reliability, and the extent of details collected on those that die at the hands of the state vary from country to country. While there are elements of good practice, the procedures and policies are often lacking in critical respects. As a result of such deficiencies, it is difficult to assess many important dimensions of policing, including whether some communities are disproportionality subjected to the lethal use of force. Ultimately, reducing the extent of police force requires addressing underlying societal conditions associated with employment, health, housing and education. However, more can be done by law enforcement agencies, as well as by their oversight bodies and government ministers. Assembling data and evidence that is accessible, relevant and useful to those concerned with lethal force is a necessary step to enhance accountability for, and possibly prevent, deaths. In the context of democratic societies, the police and police-related bodies not only need to act on what they know in order to learn lessons, but also to demonstrate they are doing so to the populations they are meant to serve. Every death associated with the use of force by law enforcement officials should be recorded, recognised and investigated. No one’s death should go unacknowledged and unexamined

Police lethal force and accountability :Monitoring deaths in Western Europe

The use of force by the police and other law enforcement officers has long been a significant topic of concern, especially when it results in death. This issue and the controversies around it have recently been highlighted by a series of high-profile deaths in 2020. Police Lethal Force and Accountability assesses the frequency of deaths, and the availability and reliability of information regarding deaths, associated with the application of force by law enforcement agencies in four jurisdictions: Belgium, England & Wales, France and the Netherlands. By adopting a common set of considerations for assessing the policies and practices within these individual jurisdictions, this report enables comparisons to be made across them. In doing so, we look to provide those in policing agencies, campaigning groups, government ministries and others, with sound information with which they can identify priorities to ensure uses of force are being accurately recorded and investigated. By enabling those concerned to understand how uses of force are recorded and addressed in comparison with other jurisdictions, we hope this report will help them to build a stronger case when holding public institutions accountable and identifying points for improvement. As documented, while deaths from the use of force appear relatively rare across these four jurisdictions when compared to countries such as the US the procedures and policies for recording, investigating and disclosing details associated with deaths are wanting. The availability of official information on the number of deaths associated with the use of force, its reliability, and the extent of details collected on those that die at the hands of the state vary from country to country. While there are elements of good practice, the procedures and policies are often lacking in critical respects. As a result of such deficiencies, it is difficult to assess many important dimensions of policing, including whether some communities are disproportionality subjected to the lethal use of force. Ultimately, reducing the extent of police force requires addressing underlying societal conditions associated with employment, health, housing and education. However, more can be done by law enforcement agencies, as well as by their oversight bodies and government ministers. Assembling data and evidence that is accessible, relevant and useful to those concerned with lethal force is a necessary step to enhance accountability for, and possibly prevent, deaths. In the context of democratic societies, the police and police-related bodies not only need to act on what they know in order to learn lessons, but also to demonstrate they are doing so to the populations they are meant to serve. Every death associated with the use of force by law enforcement officials should be recorded, recognised and investigated. No one’s death should go unacknowledged and unexamined

Nox2-deficient Tregs improve heart transplant outcomes via their increased graft recruitment and enhanced potency.

Nox2 is a ROS-generating enzyme, deficiency of which increases suppression by Tregs in vitro and in an in vivo model of cardiac remodelling. Since Tregs have emerged as a candidate therapy in autoimmunity and transplantation, we hypothesised that Nox2 deficiency in Tregs in recipient mice may improve outcomes in a heart transplant model. A novel B6129 mouse model with Treg-targeted Nox2 deletion (Nox2fl/flFoxP3Cre+) was generated and transplanted with hearts from CB6F1 donors. As compared to littermate controls, Nox2fl/flFoxP3Cre+ mice had lower plasma levels of alloantibodies and troponin-I, reduced levels of IFN-γ in heart allograft homogenates and diminished cardiomyocyte necrosis and allograft fibrosis. Single cell analyses of allografts revealed higher absolute numbers of Tregs and lower CD8+ T cell infiltration in Nox2-deficient recipients compared to Nox2-replete mice. Mechanistically, in addition to a greater suppression of CD8+CD25- T effector cell proliferation and IFN-γ production, Nox2-deficient Tregs expressed higher levels of CCR4 and CCR8, driving cell migration to allografts; this was associated with increased expression of miR214-3p. These data indicate that Nox2 deletion in Tregs enhances their suppressive ability and migration to heart allografts. Therefore, Nox2 inhibition in Tregs may be a useful approach to improve their therapeutic efficacy

Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma

30siopenMelanoma prognosis is dictated by tumor-infiltrating lymphocytes, the migratory and functional behavior of which is guided by chemokine or cytokine gradients. Here, we retrospectively analyzed the expression patterns of 9 homing receptors (CCR/CXCR) in naive and memory CD4(+) and CD8(+) T lymphocytes in 57 patients with metastatic melanoma (MMel) with various sites of metastases to evaluate whether T cell CCR/CXCR expression correlates with intratumoral accumulation, metastatic progression, and/or overall survival (OS). Homing receptor expression on lymphocytes strongly correlated with MMel dissemination. Loss of CCR6 or CXCR3, but not cutaneous lymphocyte antigen (CLA), on circulating T cell subsets was associated with skin or lymph node metastases, loss of CXCR4, CXCR5, and CCR9 corresponded with lung involvement, and a rise in CCR10 or CD103 was associated with widespread dissemination. High frequencies of CD8(+)CCR9(+) naive T cells correlated with prolonged OS, while neutralizing the CCR9/CCL25 axis in mice stimulated tumor progression. The expansion of CLA-expressing effector memory CD8(+) T cells in response to a single administration of CTLA4 blockade predicted disease control at 3 months in 47 patients with MMel. Thus, specific CCR/CXCR expression patterns on circulating T lymphocytes may guide potential diagnostic and therapeutic approaches.openJacquelot N.; Enot D.P.; Flament C.; Vimond N.; Blattner C.; Pitt J.M.; Yamazaki T.; Roberti M.P.; Daillere R.; Vetizou M.; Poirier-Colame V.; Semeraro M.; Caignard A.; Slingluff C.L.; Sallusto F.; Rusakiewicz S.; Weide B.; Marabelle A.; Kohrt H.; Dalle S.; Cavalcanti A.; Kroemer G.; DI Giacomo A.M.; Maio M.; Wong P.; Yuan J.; Wolchok J.; Umansky V.; Eggermont A.; Zitvogel L.Jacquelot, N.; Enot, D. P.; Flament, C.; Vimond, N.; Blattner, C.; Pitt, J. M.; Yamazaki, T.; Roberti, M. P.; Daillere, R.; Vetizou, M.; Poirier-Colame, V.; Semeraro, M.; Caignard, A.; Slingluff, C. L.; Sallusto, F.; Rusakiewicz, S.; Weide, B.; Marabelle, A.; Kohrt, H.; Dalle, S.; Cavalcanti, A.; Kroemer, G.; DI Giacomo, A. M.; Maio, M.; Wong, P.; Yuan, J.; Wolchok, J.; Umansky, V.; Eggermont, A.; Zitvogel, L

Description of the fecal microbiota of siblings from Costa Rica with and without affective and psychotic disorders

Peer reviewe

Drug-microbiota interactions and treatment response: Relevance to rheumatoid arthritis

Knowledge about associations between changes in the structure and/or function of intestinal microbes (the microbiota) and the pathogenesis of various diseases is expanding. However, interactions between the intestinal microbiota and different pharmaceuticals and the impact of these on responses to treatment are less well studied. Several mechanisms are known by which drug-microbiota interactions can influence drug bioavailability, efficacy, and/or toxicity. This includes direct activation or inactivation of drugs by microbial enzymes which can enhance or reduce drug effectiveness. The extensive metabolic capabilities of the intestinal microbiota make it a hotspot for drug modification. However, drugs can also influence the microbiota profoundly and change the outcome of interactions with the host. Additionally, individual microbiota signatures are unique, leading to substantial variation in host responses to particular drugs. In this review, we describe several known and emerging examples of how drug-microbiota interactions influence the responses of patients to treatment for various diseases, including inflammatory bowel disease, type 2 diabetes and cancer. Focussing on rheumatoid arthritis (RA), a chronic inflammatory disease of the joints which has been linked with microbial dysbiosis, we propose mechanisms by which the intestinal microbiota may affect responses to treatment with methotrexate which are highly variable. Furthering our knowledge of this subject will eventually lead to the adoption of new treatment strategies incorporating microbiota signatures to predict or improve treatment outcomes

Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma

Melanoma prognosis is dictated by tumor-infiltrating lymphocytes, the migratory and functional behavior of which is guided by chemokine or cytokine gradients. Here, we retrospectively analyzed the expression patterns of 9 homing receptors (CCR/CXCR) in naive and memory CD4+ and CD8+ T lymphocytes in 57 patients with metastatic melanoma (MMel) with various sites of metastases to evaluate whether T cell CCR/CXCR expression correlates with intratumoral accumulation, metastatic progression, and/or overall survival (OS). Homing receptor expression on lymphocytes strongly correlated with MMel dissemination. Loss of CCR6 or CXCR3, but not cutaneous lymphocyte antigen (CLA), on circulating T cell subsets was associated with skin or lymph node metastases, loss of CXCR4, CXCR5, and CCR9 corresponded with lung involvement, and a rise in CCR10 or CD103 was associated with widespread dissemination. High frequencies of CD8+CCR9+ naive T cells correlated with prolonged OS, while neutralizing the CCR9/CCL25 axis in mice stimulated tumor progression. The expansion of CLA-expressing effector memory CD8+ T cells in response to a single administration of CTLA4 blockade predicted disease control at 3 months in 47 patients with MMel. Thus, specific CCR/CXCR expression patterns on circulating T lymphocytes may guide potential diagnostic and therapeutic approaches