Non-state space: The strategic ejection of dangerous and high maintenance urban space

Some commentators have characterised so-called ‘no-go’ areas as sites in which the exercise of authority is prevented. Here we suggest that many such spaces are produced by state, policing and citizen repertoires that aim to minimise the costs and risks of engaging, supporting and servicing such spaces and their populations. In this article we locate strategies of public spending, policing and political action that offer a governing logic in which neighbourhoods are essentially subtracted from the constitution of the city. During such designations the assurances of citizenship, vitality of civic institutions and presence of policing may be partially or wholly suspended. We present a framework for the identification of such strategies in which these forms of social, political and spatial exiting are described as being autotomic in nature – spaces that are ejected in order to avoid losses or further damage to the body politic of the city in ways akin to the response of certain animals that protect themselves from predation by shedding a limb or body part. This term adds force and depth to assessments of the ways in which both temporary and more sustained exits by policing, management and state servicing are designed in order to avoid responsibility over, or engagement with, spaces that are deemed a threat in order to maintain the integrity of the remaining, included city

Caregiver Recognition of Childhood Diarrhea, Care Seeking Behaviors and Home Treatment Practices in Rural Burkina Faso: A Cross-Sectional Survey

Introduction: To design effective national diarrhea control programs, including oral rehydration solution (ORS) and therapeutic zinc supplementation, information is needed on local perceptions of illness, external care seeking behaviors, and home treatment practices. Methods: A cross-sectional, community-based household survey was conducted in the Orodara Health District, Burkina Faso. Caregivers of 10,490 children,27 months were interviewed to assess child diarrhea prevalence and related car

Assembly of the LongSHOT cohort: Public record linkage on a grand scale

Background: Virtually all existing evidence linking access to firearms to elevated risks of mortality and morbidity comes from ecological and case-control studies. To improve understanding of the health risks and benefits of firearm ownership, we launched a cohort study: the Longitudinal Study of Handgun Ownership and Transfer (LongSHOT). Methods: Using probabilistic matching techniques we linked three sources of individual-level, state-wide data in California: official voter registration records, an archive of lawful handgun transactions and all-cause mortality data. There were nearly 28.8 million unique voter registrants, 5.5 million handgun transfers and 3.1 million deaths during the study period (18 October 2004 to 31 December 2016). The linkage relied on several identifying variables (first, middle and last names; date of birth; sex; residential address) that were available in all three data sets, deploying them in a series of bespoke algorithms. Results: Assembly of the LongSHOT cohort commenced in January 2016 and was completed in March 2019. Approximately three-quarters of matches identified were exact matches on all link variables. The cohort consists of 28.8 million adult residents of California followed for up to 12.2 years. A total of 1.2 million cohort members purchased at least one handgun during the study period, and 1.6 million died. Conclusions: Three steps taken early may be particularly useful in enhancing the efficiency of large-scale data linkage: thorough data cleaning; assessment of the suitability of off-the-shelf data linkage packages relative to bespoke coding; and careful consideration of the minimum sample size and matching precision needed to support rigorous investigation of the study questions

HSP90 inhibitors disrupt a transient HSP90-HSF1 interaction and identify a noncanonical model of HSP90-mediated HSF1 regulation

Heat shock factor 1 (HSF1) initiates a broad transcriptional response to proteotoxic stress while also mediating a cancer-specific transcriptional program. HSF1 is thought to be regulated by molecular chaperones, including Heat Shock Protein 90 (HSP90). HSP90 is proposed to sequester HSF1 in unstressed cells, but visualization of this interaction in vivo requires protein crosslinking. In this report, we show that HSP90 binding to HSF1 depends on HSP90 conformation and is only readily visualized for the ATP-dependent, N-domain dimerized chaperone, a conformation only rarely sampled by mammalian HSP90. We have used this mutationally fixed conformation to map HSP90 binding sites on HSF1. Further, we show that ATP-competitive, N-domain targeted HSP90 inhibitors disrupt this interaction, resulting in the increased duration of HSF1 occupancy of the hsp70 promoter and significant prolongation of both the constitutive and heat-induced HSF1 transcriptional activity. While our data do not support a role for HSP90 in sequestering HSF1 monomers to suppress HSF1 transcriptional activity, our findings do identify a noncanonical role for HSP90 in providing dynamic modulation of HSF1 activity by participating in removal of HSF1 trimers from heat shock elements in DNA, thus terminating the heat shock response

Does the Community-based Combined Meeting Center Support Programme (MCSP) Make the Pathway to Day-care Activities Easier for People Living with Dementia? A Comparison Before and After Implementation of MCSP in Three European Countries

The "pathway to care" concept offers a helpful framework for preparing national dementia plans and strategies and provides a structure to explore the availability and accessibility of timely and effective care for people with dementia and support for their informal carers. Within the framework of the JPND-MEETINGDEM implementation project the pathways to regular day-care activities and the Meeting Centers Support Programme (MCSP), an innovative combined support form for people with dementia and carers, was explored. An exploratory, descriptive, qualitative, cross-country design was applied to investigate the pathways to day care in several regions in four European countries (Italy, Poland, United Kingdom, and the Netherlands). Before implementation of MCSP, of the four countries the United Kingdom had the most structured pathway to post-diagnostic support for people with dementia. MCSP introduction had a positive impact on the pathways to day-care activities in all countries. MCSP filled an important gap in post-diagnostic care, increasing the accessibility to support for both people with dementia and carers. Key elements such as program of activities, target group, and collaboration between healthcare and social services were recognized as success factors. This study shows that MCSP fills (part of) the gap between diagnosis and residential care and can therefore be seen as a pillar of post-diagnostic care and support. Further dissemination of Meeting Centers in Europe may have a multiple impact on the structure of dementia services in European countries and the pathways to day care for people with dementia and their carer(s)

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

Building a tuberculosis-free world: The Lancet Commission on tuberculosis

___Key messages___ The Commission recommends five priority investments to achieve a tuberculosis-free world within a generation. These investments are designed to fulfil the mandate of the UN High Level Meeting on tuberculosis. In addition, they answer