Current Perspectives on the Use of off the Shelf CAR-T/NK Cells for the Treatment of Cancer

CAR T cells have revolutionised the treatment of haematological malignancies. Despite this, several obstacles still prohibit their widespread use and efficacy. One of these barriers is the use of autologous T cells as the carrier of the CAR. The individual production of CAR T cells results in large variation in the product, greater wait times for treatment and higher costs. To overcome this several novel approaches have emerged that utilise allogeneic cells, so called “off the shelf” CAR T cells. In this Review, we describe the different approaches that have been used to produce allogeneic CAR T to date, as well as their current pre-clinical and clinical progress

Effects of a Tailored Follow-Up Intervention on Health Behaviors, Beliefs, and Attitudes

Background: The high rates of relapse that tend to occur after short-term behavioral interventions indicate the need for maintenance programs that promote long-term adherence to new behavior patterns. Computer-tailored health messages that are mailed to participants or given in brief telephone calls offer an innovative and time-efficient alternative to ongoing face-to-face contact with healthcare providers. Methods: Following a 1-year behavior change program, 22 North Carolina health departments were randomly assigned to a follow-up intervention or control condition. Data were collected from 1999 to 2001 by telephone-administered surveys at preintervention and postintervention for 511 low-income, midlife adult women enrolled in the Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) program at local North Carolina health departments. During the year after the behavior change program, intervention participants were mailed six sets of computer-tailored health messages and received two computer-tailored telephone counseling sessions. Main outcomes of dietary and physical activity behaviors, beliefs, and attitudes were measured. Results: Intervention participants were more likely to move forward into more advanced stages of physical activity change (p = 0.02); control participants were more likely to increase their level of dietary social support at follow-up (p = 0.05). Both groups maintained low levels of reported saturated fat and cholesterol intake at follow-up. No changes were seen in physical activity in either group. Conclusions: Mailed computer-tailored health messages and telephone counseling calls favorably modified forward physical activity stage movement but did not appreciably affect any other psychosocial or behavioral outcomes

Land degradation and climate change: opportunities for building climate resilience in agriculture

Land degradation and climate change pose enormous risks to global food security. Land degradation increases the vulnerability of agroecological systems to climate change and reduces the effectiveness of adaptation options. Yet these interactions have largely been omitted from climate impact assessments and adaptation planning. We examine how land degradation can influence climate-change impacts and the adaptive capacity of crop and livestock producers across agroecological systems. We then present novel strategies for climate-resilient agriculture that support opportunities to integrate responses to these challenges. Forward-looking, climate-resilient agriculture requires: (1) incorporation of land degradation processes, and their linkages with adaptive capacity, into adaptation planning; (2) identification of key vulnerabilities to prioritize adaptation responses; (3) improved knowledge exchange across local to global scales to support strategies for developing the adaptive capacity of producers; and (4) innovative management and policy options that provide multiple “wins” for land, climate, and biodiversity, thus enabling global development and food security goals to be achieved

Haptoglobin Phenotype, Preeclampsia Risk and the Efficacy of Vitamin C and E Supplementation to Prevent Preeclampsia in a Racially Diverse Population

Haptoglobin's (Hp) antioxidant and pro-angiogenic properties differ between the 1-1, 2-1, and 2-2 phenotypes. Hp phenotype affects cardiovascular disease risk and treatment response to antioxidant vitamins in some non-pregnant populations. We previously demonstrated that preeclampsia risk was doubled in white Hp 2-1 women, compared to Hp 1-1 women. Our objectives were to determine whether we could reproduce this finding in a larger cohort, and to determine whether Hp phenotype influences lack of efficacy of antioxidant vitamins in preventing preeclampsia and serious complications of pregnancy-associated hypertension (PAH). This is a secondary analysis of a randomized controlled trial in which 10,154 low-risk women received daily vitamin C and E, or placebo, from 9-16 weeks gestation until delivery. Hp phenotype was determined in the study prediction cohort (n = 2,393) and a case-control cohort (703 cases, 1,406 controls). The primary outcome was severe PAH, or mild or severe PAH with elevated liver enzymes, elevated serum creatinine, thrombocytopenia, eclampsia, fetal growth restriction, medically indicated preterm birth or perinatal death. Preeclampsia was a secondary outcome. Odds ratios were estimated by logistic regression. Sampling weights were used to reduce bias from an overrepresentation of women with preeclampsia or the primary outcome. There was no relationship between Hp phenotype and the primary outcome or preeclampsia in Hispanic, white/other or black women. Vitamin supplementation did not reduce the risk of the primary outcome or preeclampsia in women of any phenotype. Supplementation increased preeclampsia risk (odds ratio 3.30; 95% confidence interval 1.61-6.82, p<0.01) in Hispanic Hp 2-2 women. Hp phenotype does not influence preeclampsia risk, or identify a subset of women who may benefit from vitamin C and E supplementation to prevent preeclampsia

Overview of a formal scoping review on health system report cards

Background: There is an extensive body of literature on health system quality reporting that has yet to be characterized. Scoping is a novel methodology for systematically assessing the breadth of a body of literature in a particular research area. Our objectives were to showcase the scoping review methodology in the review of health system quality reporting, and to report on the extent of the literature in this area.Methods: A scoping review was performed based on the York methodology outlined by Arksey and O'Malley from the University of York, United Kingdom. We searched 14 peer reviewed and grey literature databases limiting the search to English language and non-English language articles with English abstracts published between 1980 and June 2006 with an update to November 2008. We also searched specific websites, reference lists, and key journals for relevant material and solicited input from key stakeholders. Inclusion/exclusion criteria were applied to select relevant material and qualitative information was charted from the selected literature.Results: A total of 10,102 articles were identified from searching the literature databases, 821 were deemed relevant to our scoping review. An additional 401 were identified from updates, website searching, references lists, key journals, and stakeholder suggestions for a total of 1,222 included articles. These were categorized and catalogued according to the inclusion criteria, and further subcategories were identified through the charting process. Topic areas represented by this review included the effectiveness of health system report cards (n = 194 articles), methodological issues in their development (n = 815 articles), stakeholder views on report cards (n = 144 articles), and ethical considerations around their development (n = 69 articles).Conclusions: The scoping review methodology has permitted us to characterize and catalogue the extensive body of literature pertaining to health system report cards. The resulting literature repository that our review has created can be of use to researchers and health system stakeholders interested in the topic of health system quality measurement and reporting. © 2010 Brien et al; licensee BioMed Central Ltd

Modulation of enhancer looping and differential gene targeting by Epstein-Barr virus transcription factors directs cellular reprogramming

Epstein-Barr virus (EBV) epigenetically reprogrammes B-lymphocytes to drive immortalization and facilitate viral persistence. Host-cell transcription is perturbed principally through the actions of EBV EBNA 2, 3A, 3B and 3C, with cellular genes deregulated by specific combinations of these EBNAs through unknown mechanisms. Comparing human genome binding by these viral transcription factors, we discovered that 25% of binding sites were shared by EBNA 2 and the EBNA 3s and were located predominantly in enhancers. Moreover, 80% of potential EBNA 3A, 3B or 3C target genes were also targeted by EBNA 2, implicating extensive interplay between EBNA 2 and 3 proteins in cellular reprogramming. Investigating shared enhancer sites neighbouring two new targets (WEE1 and CTBP2) we discovered that EBNA 3 proteins repress transcription by modulating enhancer-promoter loop formation to establish repressive chromatin hubs or prevent assembly of active hubs. Re-ChIP analysis revealed that EBNA 2 and 3 proteins do not bind simultaneously at shared sites but compete for binding thereby modulating enhancer-promoter interactions. At an EBNA 3-only intergenic enhancer site between ADAM28 and ADAMDEC1 EBNA 3C was also able to independently direct epigenetic repression of both genes through enhancer-promoter looping. Significantly, studying shared or unique EBNA 3 binding sites at WEE1, CTBP2, ITGAL (LFA-1 alpha chain), BCL2L11 (Bim) and the ADAMs, we also discovered that different sets of EBNA 3 proteins bind regulatory elements in a gene and cell-type specific manner. Binding profiles correlated with the effects of individual EBNA 3 proteins on the expression of these genes, providing a molecular basis for the targeting of different sets of cellular genes by the EBNA 3s. Our results therefore highlight the influence of the genomic and cellular context in determining the specificity of gene deregulation by EBV and provide a paradigm for host-cell reprogramming through modulation of enhancer-promoter interactions by viral transcription factors

Dental management considerations for the patient with an acquired coagulopathy. Part 1: Coagulopathies from systemic disease

Current teaching suggests that many patients are at risk for prolonged bleeding during and following invasive dental procedures, due to an acquired coagulopathy from systemic disease and/or from medications. However, treatment standards for these patients often are the result of long-standing dogma with little or no scientific basis. The medical history is critical for the identification of patients potentially at risk for prolonged bleeding from dental treatment. Some time-honoured laboratory tests have little or no use in community dental practice. Loss of functioning hepatic, renal, or bone marrow tissue predisposes to acquired coagulopathies through different mechanisms, but the relationship to oral haemostasis is poorly understood. Given the lack of established, science-based standards, proper dental management requires an understanding of certain principles of pathophysiology for these medical conditions and a few standard laboratory tests. Making changes in anticoagulant drug regimens are often unwarranted and/or expensive, and can put patients at far greater risk for morbidity and mortality than the unlikely outcome of postoperative bleeding. It should be recognised that prolonged bleeding is a rare event following invasive dental procedures, and therefore the vast majority of patients with suspected acquired coagulopathies are best managed in the community practice setting

Identidad étnica y redes personales entre jóvenes de Sarajevo

After fieldwork conducted among young people in Sarajevo, we found a relation between the discourses sustained by them and the ethnic categories they use to classify people and to identify themselves. Also we have found that people self-affiliated as "Bosnians" play an important role in the network of multiethnic relationships, in which strong ties, surprisingly, are still very important. Finally we found a relationship between the composition of personal networks and the ethnic discourses that are maintained.Después de un trabajo de campo realizado con un grupo de jóvenes en Sarajevo, hemos constatado la existencia de una relación entre los discursos que sostienen y las categorías étnicas que utilizan tanto para clasificar a los demás como para auto-identificarse. Asimismo hemos encontrado que los jóvenes que se autodenominan "Bosnios" juegan un rol importante en la red de relaciones multiétnicas, en la que los lazos fuertes, sorprendentemente, son muy importantes. Finalmente hemos hallado una relación entre la composición de las redes personales y los discursos étnicos que se sostienen. Vivimos, o creemos vivir, en múltiples "comunidades", imaginadas o no. Al mismo tiempo, el individuo y no el lugar, la familia o el grupo, se sitúa en el centro de la vida social y de las comunicaciones (Cf. Wellman, 2001). En este contexto, inducido por el avance del capitalismo flexible (Castells, 1996), pensamos que para entender adecuadamente la identidad o identidades postuladas por los individuos es necesario estudiar las redes personales y su dinámica. Desde esta perspectiva no podemos hablar de "etnias" o "multietnicidad" sin más precisiones, pues son conceptos basados en una concepción esencialista y estática de la identidad individual. El concepto de "sociedad multiétnica" es utilizado de una manera engañosamente progresista y objetiva, pues lo que en realidad legitima es la existencia de diferencias esenciales entre personas, alejando en lugar de acercar. Sin embargo, somos plenamente conscientes que los discursos esencialistas de la identidad étnica son omnipresentes, con enormes efectos políticos e individuales. Que planteemos que la concepción esencialista de la identidad sea inapropiada desde un punto de vista académico, no significa que ésta no se utilice políticamente y por lo tanto tenga consecuencias formidables en las relaciones sociales. Precisamente el estudio de las redes personales nos permite situarnos en una perspectiva que no utiliza con pretensiones analíticas conceptos "folk", como son los de "etnia", "pueblo" o "nación", sino que los sitúa en el terreno de los discursos sustentados por los actores (y los estados y medios de comunicación) y nos permite contextualizarlos mediante conceptos etic, es decir, impuestos por los investigadores. Sólo así podemos superar las tautologías que abundan en los discursos étnicos