462 research outputs found
Government munificence and the struggle to be poor. Politics, power and the Local State in Vietnam’s Northwest Borderlands
Successive regimes since colonial times have sought to develop
and incorporate the lands and people of northwestern Vietnam
under a biopolitical imaginary: to nurture and render the state
periphery productive and integrated into a unified nation state.
However, local people of the region have always had their own
‘projects’, which they pursue on the ‘margins’ of this
state project of power (Ortner 2006). This thesis sets out to
understand, through an ethnographic study of Vĩnh Thủy, an
ethnic minority commune in northwestern Vietnam, how the
different projects of power at work in Vĩnh Thủy commune come
together in (and through) the local state.
I theorise the local state as a political space created through
the coming together of the projects of power of four vectors in
Vĩnh Thủy: the centre state, the local community, local
officials, and the translocal flows, actors and institutions that
are increasingly prevalent in the northwestern uplands. These
projects of power meet around the governmental narratives,
technologies and everyday rituals of state that permeate the
commune, and through which the biopolitical imaginary of
integrating the uplands into the wider nation state is projected,
and enacted. Prominent governmental processes in Vĩnh Thủy
commune include regulating the division of political office
between ethnic minority groups; identifying ‘the poor’ and
delivering poverty reduction support; and attempting to modernise
the uplands through ‘the market’. Projects of power congeal
around these governmental processes and are contested, negotiated
and made anew in the local state space.
Governmental schemes are themselves productive of power, as
through them local ethnic minority people exercise a particular,
dexterous and constantly learning form of political agency, what
James Scott (1998) has called metis. However, where Scott saw
metis operating independently of the systems of state power, in
Vĩnh Thủy metis instead flourishes within the governmental
processes of state, and is sustained and nurtured by them. Local
elites in the commune, and local people in so far as they are
connected to these elites and therefore to power, pursue their
projects within and through the regulating technologies of state.
They reshape them as they are applied in the local state space,
even as they are themselves shaped by them.
It is through the local state too, that ideas of state are
locally re-imagined, and thereby achieve relevance and potency
for the people of Vĩnh Thủy. State ideas are shaped in the
local state space through an intense politics of intimacy, which
recognises that local elites pursue projects of power for the
benefit of themselves, their lineage groups and their wider
networks, but which also privileges notions of general provision,
obligation and duty to the unfortunate, and to the community as a
whole. Hopes, dreams and desires for development also crystallise
around the state and ensure that local people remain bound in to
locally imagined ideas of state, despite these dreams and desires
frequently being frustrated
Knowledge, attitudes and experiences of self-harm and suicide in low-income and middle-income countries: protocol for a systematic review.
From Europe PMC via Jisc Publications RouterHistory: ppub 2021-06-01, epub 2021-06-22Publication status: PublishedIntroductionOver 800 000 people die due to suicide each year and suicide presents a huge psychological, economic and social burden for individuals, communities and countries as a whole. Low-income and middle-income countries (LMICs) are disproportionately affected by suicide. The strongest risk factor for suicide is a previous suicide attempt, and other types of self-harm have been found to be robust predictors of suicidal behaviour. An approach that brings together multiple sectors, including education, labour, business, law, politics and the media is crucial to tackling suicide and self-harm. The WHO highlights that evaluations of the knowledge and attitudes that priority groups, not only healthcare staff, have of mental health and suicidal behaviour are key to suicide prevention strategies. The aim of this systematic review is to examine the knowledge, attitudes and experiences different stakeholders in LMICs have of self-harm and suicide.Methods and analysisMEDLINE, Embase, PsycINFO, CINAHL, BNI, Social Sciences and Cochrane Library will be searched. Reviewers working independently of each other will screen search results, select studies for inclusion, extract and check extracted data, and rate the quality of the studies using the Strengthening the Reporting of Observational studies in Epidemiology and Critical Appraisals Skills Programme checklists. In anticipation of heterogeneity, a narrative synthesis of quantitative studies will be provided and metaethnography will be used to synthesise qualitative studies.Ethics and disseminationEthical approval is not required. A report will be provided for the funding body, and the systematic review will be submitted for publication in a high-impact, peer-reviewed, open access journal. Results will also be disseminated at conferences, seminars, congresses and symposia, and to relevant stakeholders.Prospero registration numberCRD42019135323
Leptin and Associated Mediators of Immunometabolic Signaling: Novel Molecular Outcome Measures for Neurostimulation to Treat Chronic Pain
Chronic pain is a devastating condition affecting the physical, psychological, and socioeconomic status of the patient. Inflammation and immunometabolism play roles in the pathophysiology of chronic pain disorders. Electrical neuromodulation approaches have shown a meaningful success in otherwise drug-resistant chronic pain conditions, including failed back surgery, neuropathic pain, and migraine. A literature review (PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles) was performed using the following search terms: chronic pain disorders, systemic inflammation, immunometabolism, prediction, biomarkers, metabolic disorders, and neuromodulation for chronic pain. Experimental studies indicate a relationship between the development and maintenance of chronic pain conditions and a deteriorated immunometabolic state mediated by circulating cytokines, chemokines, and cellular components. A few uncontrolled in-human studies found increased levels of pro-inflammatory cytokines known to drive metabolic disorders in chronic pain patients undergoing neurostimulation therapies. In this narrative review, we summarize the current knowledge and possible relationships of available neurostimulation therapies for chronic pain with mediators of central and peripheral neuroinflammation and immunometabolism on a molecular level. However, to address the needs for predictive factors and biomarkers, large-scale databank driven clinical trials are needed to determine the clinical value of molecular profiling
Characterization of the gene encoding human sarcolipin (SLN), a proteolipid associated with SERCA1: Absence of structural mutations in five patients with brody disease
Sarcolipin (SLN) is a low-molecular-weight protein that copurifies with the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase (SERCA1). Genomic DNA and cDNA encoding human sarcolipin (SLN) were isolated and characterized and the SLN gene was mapped to chromosome 11q22-q23. Human, rabbit, and mouse cDNAs encode a protein of 31 amino acids. Homology of SLN with phospholamban (PLN) suggests that the first 7 hydrophilic amino acids are cytoplasmic, the next 19 hydrophobic amino acids form a single transmembrane helix, and the last 5 hydrophilic amino acids are lumenal. The cytoplasmic and transmembrane sequences are not well conserved among the three species, but the lumenal sequence is highly conserved. Like SERCA1, SLN is highly expressed in rabbit fast-twitch skeletal muscle, but it is expressed to a lower extent in slow-twitch muscle and to an even lower extent in cardiac muscle, where SERCA2a and PLN are highly expressed. It is expressed in only trace amounts in pancreas and prostate. SLN and PLN genes resemble each other in having two small exons, with their entire coding sequences lying in exon 2 and a large intron separating the two segments. Brody disease is an inherited disorder of skeletal muscle function, characterized by exercise-induced impairment of muscle relaxation. Mutations in the ATP2A1 gene encoding SERCA1 have been associated with the autosomal recessive inheritance of Brody disease in three families, but not with autosomal dominant inheritance of the disease. A search for mutations in the SLN gene in five Brody families, four of which were not linked to ATP2A1, did not reveal any alterations in coding, splice junction or promoter sequences. The homozygous deletion of C438 in the coding sequence of ATP2A1 in Brody disease family 3, leading to a frameshift and truncation following Pro147 in SERCA1, is the fourth ATP2A1 mutation to be associated with autosomal recessive Brody disease
Processing of thymine glycol in a clustered DNA damage site: mutagenic or cytotoxic
Localized clustering of damage is a hallmark of certain DNA-damaging agents, particularly ionizing radiation. The potential for genetic change arising from the effects of clustered damage sites containing combinations of AP sites, 8-oxo-7,8-dihydroguanine (8-oxoG) or 5,6-dihydrothymine is high. To date clusters containing a DNA base lesion that is a strong block to replicative polymerases, have not been explored. Since thymine glycol (Tg) is non-mutagenic but a strong block to replicative polymerases, we have investigated whether clusters containing Tg are highly mutagenic or lead to potentially cytotoxic lesions, when closely opposed to either 8-oxoG or an AP site. Using a bacterial plasmid-based assay and repair assays using cell extracts or purified proteins, we have shown that DNA double-strand breaks (DSBs) arise when Tg is opposite to an AP site, either through attempted base excision repair or at replication. In contrast, 8-oxoG opposite to Tg in a cluster ‘protects’ against DSB formation but does enhance the mutation frequency at the site of 8-oxoG relative to that at a single 8-oxoG, due to the decisive role of endonucleases in the initial stages of processing Tg/8-oxoG clusters, removing Tg to give an intermediate with an abasic site or single-strand break
Establishing a Target Exposure for Once-Daily Intravenous Busulfan Given with Fludarabine and Thymoglobulin before Allogeneic Transplantation
AbstractA combination of fludarabine (Flu) and daily i.v. busulfan (Bu) is well tolerated and effective in patients undergoing allogeneic hematopoietic stem cell transplantation. Although there is some evidence that Bu exposures exceeding 6000 μM/min may lead to excessive toxicity, there is little information on the effect of exposures below this level on outcomes. We studied Bu exposure, as measured by area under the concentration-time curve (AUC), in 158 patients with various hematologic malignancies in an attempt to identify an optimal range for targeted therapy. The preparative chemotherapy regimen comprised Flu 50 mg/m2 on days -6 to -2 and i.v. Bu 3.2 mg/kg on days -5 to -2 inclusive. Graft-versus-host disease (GVHD) prophylaxis included methotrexate, cyclosporin A, and antithymocyte globulin. Patients with Bu exposures below the median AUC of 4439 μM/min were at increased risk for acute GVHD grade II-IV (hazard ratio [HR], 2.30; 95% confidence interval [CI], 1.19 to 4.49; P = .014). Those in the highest and lowest Bu exposure quartiles (daily AUC <3814 μM/min and >4993 μM/min) had an increased risk of nonrelapse mortality (subdistribution HR, 3.32; 95% CI, 1.46 to 7.54; P = .004), as well as worse disease-free survival (HR, 1.81; 95% CI, 1.09 to 2.99; P = .021) and overall survival (HR, 1.94; 95% CI, 1.12 to 3.37; P = .018). Bu exposures between 4440 and 4993 μM/min were accompanied by the lowest risk of both nonrelapse mortality and acute GVHD
A web-accessible computer program for calculating electrical potentials and ion activities at cell-membrane surfaces
Increasing evidence indicates that plant responses to ions (uptake/transport, inhibition, and alleviation of inhibition) are dependent upon ion activities at the outer surface of root-cell plasma membranes (PMs) rather than activities in the bulk-phase rooting medium
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