Blocking of LFA-1 enhances expansion of Th17 cells induced by human CD14(+) CD16(++) nonclassical monocytes.

Among human peripheral blood (PB) monocyte (Mo) subsets, the classical CD14(++) CD16(-) (cMo) and intermediate CD14(++) CD16(+) (iMo) Mos are known to activate pathogenic Th17 responses, whereas the impact of nonclassical CD14(+) CD16(++) Mo (nMo) on T-cell activation has been largely neglected. The aim of this study was to obtain new mechanistic insights on the capacity of Mo subsets from healthy donors (HDs) to activate IL-17(+) T-cell responses in vitro, and assess whether this function was maintained or lost in states of chronic inflammation. When cocultured with autologous CD4(+) T cells in the absence of TLR-2/NOD2 agonists, PB nMos from HDs were more efficient stimulators of IL-17-producing T cells, as compared to cMo. These results could not be explained by differences in Mo lifespan and cytokine profiles. Notably, however, the blocking of LFA-1/ICAM-1 interaction resulted in a significant increase in the percentage of IL-17(+) T cells expanded in nMo/T-cell cocultures. As compared to HD, PB Mo subsets of patients with rheumatoid arthritis were hampered in their T-cell stimulatory capacity. Our new insights highlight the role of Mo subsets in modulating inflammatory T-cell responses and suggest that nMo could become a critical therapeutic target against IL-17-mediated inflammatory diseases.

Non-metastatic castrate-resistant prostate cancer: a call for improved guidance on clinical management.

BACKGROUND Guidelines on the clinical management of non-metastatic castrate-resistant prostate cancer (nmCRPC) generally focus on the need to continue androgen deprivation therapy and enrol patients into clinical trials of investigational agents. This guidance reflects the lack of clinical trial data with established agents in the nmCRPC patient population and the need for trials of new agents. AIM To review the evidence base and consider ways of improving the management of nmCRPC. CONCLUSION Upon the development of castrate resistance, it is essential to rule out the presence of metastases or micrometastases by optimising the use of bone scans and possibly newer procedures and techniques. When nmCRPC is established, management decisions should be individualised according to risk, but risk stratification in this diverse population is poorly defined. Currently, prostate-specific antigen (PSA) levels and PSA doubling time remain the best method of assessing the risk of progression and response to treatment in nmCRPC. However, optimising imaging protocols can also help assess the changing metastatic burden in patients with CRPC. Clinical trials of novel agents in nmCRPC are limited and have problems with enrolment, and therefore, improved risk stratification and imaging may be crucial to the improved management. The statements presented in this paper, reflecting the views of the authors, provide a discussion of the most recent evidence in nmCRPC and provide some advice on how to ensure these patients receive the best management available. However, there is an urgent need for more data on the management of nmCRPC.

Correction of aberrant FGFR1 RNA splicing through blocking intronic regulatory elements

Analysis of the human genome has revealed that more than 74% of human genes undergo alternative RNA splicing. Aberrations in alternative RNA splicing have been associated with several human disorders, including cancer. ^ We studied the aberrant expression of alternative RNA splicing isoforms of the Fibroblast Growth Factor Receptor 1 (FGFR1) gene in a human glioblastoma cancer model. Normal glial cells express the FGFR1α, which contains three extracellular domains. In tumors the most abundant isoform is the FGFR1β, which lacks the first extracellular domain due to the skipping of a single exon, termed alpha. The skipping of the α-exon is regulated by two intronic silencing sequences within the precursor mRNA. Since we observed no mutations on these elements in tumor cells, we hypothesized that the over-expression of regulatory proteins that recognize these sequences is responsible for the aberrant expression of splicing isoforms. Hence, we blocked the formation of protein complexes on the ISS using antisense RNA oligonucleotides in vitro. We also evaluated the impact of the ISS antisense oligonucleotides on the endogenous FGFR1 splicing, in a glioblastoma cell model. By targeting intronic regulatory elements we were able to increase the level of alpha exon inclusion up to 90% in glioblastoma cells. The effect was dose dependent, sequence specific and reproducible in glioblastoma and other cancer cells, which also exhibit an alpha exon skipping phenotype. Targeting FGFR1 endogenous ISS1 and ISS2 sequences did not have an additive or synergistic effect, which suggest a regulatory splicing mechanism that requires the interaction of complexes formed on these elements. An increase in the levels of the FGFR1α isoform resulted in a reduction in cell invasiveness. Also, a significant increase in the levels of caspase 3/7 activities, which is indicative of an elevation in apoptosis levels, suggests that expression of FGFR1β might be relevant for tumor survival. These studies demonstrate that it is possible to prevent aberrant expression of exon skipping events through the targeting of intronic regulatory elements, providing an important new therapeutic tool for the correction of human disease caused by alternative RNA splicing. ^

Perhaps Triangulation Isn’t Enough: a Call for Crystallization as a Methodological Referent in NOS Research

This research compares the methodological tools employed in NOS research, with analysis of what the comparison implies about the structure of nature of science knowledge. Descriptions of practicing teachers’ nature of science conceptions were compared based on data collected from forced choice responses, responses to a qualitative survey, and course writing samples. Participants’ understandings were scored differently on the Views of Nature of Science Questionnaire (VNOS) than the forced-choice measure, Scientific Thinking and Internet Learning Technologies (STILT). In addition, analysis of the writing samples and observations combined with interviews portrayed more sophisticated, but more variable, understandings of the nature of science than was evidenced by either the survey or the forced-choice measure. The differences between data collection measures included the degree to which they drew upon context bound or context general reasoning, the degree to which they required students to move beyond the simple intelligibility of their responses and allowed students to explore the fruitfulness of the constructs, as well as the degree to which they revealed the interconnection of participants NOS conceptions. In light of the different portrayals of a participants NOS conceptions yielded by these different measures, we call for the use of crystallization as a methodological referent in research.

If we call them, will they change? Feasibility of a telephone adaptation of motivational interviewing aimed at parents to reduce television time among 2nd and 4th grade children

Television viewing is a sedentary behavior that is modifiable. Reducing media-related behaviors via parent-focused interventions may hold promise for decreasing childhood obesity. This feasibility study examines a novel parent-centered brief telephone-delivered Motivational Enhancement Interview (MEI) to encourage parents of 2nd and 4th graders to set a rules limiting TV time or remove the TV from the child's bedroom. This quasi-experimental sub-study was part of the larger CATCH: En Vivo pilot study conducted in a Hispanic population in the Texas Rio Grande Valley. Parents in the MEI condition were contacted via telephone and encouraged to meet the American Academy of Pediatrics (AAP) recommended 2 hours per day or less of TV. Unconditional logistic regression was used to analyze the data. At post-test, 85% of parents of 4th graders in the MEI group (compared to 71% at pre-test) reported having a rule limiting TV time. The adjusted odds ratio for the MEI group compared to the control group was 3.88, 95% CI (0.72-20.99). At pre-test, 63.16% of 2nd graders had a television in their bedrooms. The 2nd grade MEI intervention reduced that number to 41.03% (OR=0.25, 95%CI (0.08-0.82)). This first look at using MEI to target parents of children to modify TV behavior presents evidence on a promising strategy for modifying children's home media environment and warrants further investigation. ^

Changes in 911 call volume and type during Hurricane Ike and the implementation and usefulness of the TeleHealth Nurse system for the Houston Fire Department

This study examined both changing call volume and type with resulting effect of TeleHealth Nurse, the Houston Fire Department's (HFD) telephone nurse line, on call burden during Hurricane Ike. On September 13, 2008, Hurricane Ike made landfall in the Galveston area and continued north through Houston resulting in catastrophic damages in infrastructure and posing a public health threat. The overall goal of this study looked at data from Houston Fire Department to obtain a better understanding of the needs of citizens before, during, and after a hurricane. This study looked at four aspects of emergency response from HFD. The first section looked at call volumes surrounding the time of Hurricane Ike in 2008 compared to the same time period in 2007. The data showed a 12% increase in calls surrounding Hurricane Ike compared to previous years with a p value <.001. Next, the study evaluated the types of calls prevalent during Hurricane Ike compared to the same time period in 2007. The data showed a statistically significant increase in chronic health problems such as diabetes and cardiac events, Obstetric calls and an increase in breathing problems, falls, and lacerations during the days following Hurricane Ike. There was also a statistically significant increase in auto med alerts and check patients surrounding Hurricane Ike's landfall. The third section analyzed the change in call volume sent to HFD's Telephone Nurse Line during Hurricane Ike and compares this to earlier time periods while the fourth and final section looks at the types of calls sent to the nurse line during Hurricane Ike. The data showed limited use of the TeleHealth Nurse line before Hurricane Ike, but when the winds were at their strongest and ambulances were unable to leave the station, the nurse line was the only functioning medical help some people were able to receive. These studies bring a better understanding to the number and types of calls that a city might experience during a natural disaster, such as a hurricane. This study also shows the usefulness of an EMS Telephone Nurse Line during a natural disaster.^

Implementing and evaluating a Web -based close call reporting system at an urban hospital

Medical errors and close calls are pervasive in health care. It is hypothesized that the causes of close calls are the same as for medical errors; therefore learning about close calls can help prevent errors and increase patient safety. Yet despite efforts to encourage close call reporting, close calls as well as medical errors are under-reported in health care. The purpose of this dissertation was to implement and evaluate a web-based anonymous close call reporting system in three units at an urban hospital. ^ The study participants were physicians, nurses and medical technicians (N = 187) who care for patients in the Medical Intermediate Care Unit, the Surgical Intermediate Care Unit, and the Coronary Catheterization Laboratory in the hospital. We provided educational information to the participants on how to use the system and e-mailed and delivered paper reminders to report to the participants throughout the 19-month project. We surveyed the participants at the beginning and at the end of the study to assess their attitudes and beliefs regarding incident reporting. We found that the majority of the health care providers in our study are supportive of incident reporting in general but in practice very few had actually reported an error or a close call, semi-structured interview 20 weeks after we made the close call reporting system available. The purpose of the interviews was to further assess the participants' attitudes regarding incident reporting and the reporting system. Our findings suggest that the health care providers are supportive of medical error reporting in general, but are not convinced of the benefit of reporting close calls. Barriers to close call reporting cited include lack of time, heavy workloads, preferring to take care of close calls "on the spot", and not seeing the benefits of close call reporting. Consequently only two = close calls were reported via the system by two separate caregivers during the project. ^ The findings suggest that future efforts to increase close call reporting must address barriers to reporting, especially the belief among care givers that it is not worth taking time from their already busy schedules to report close calls. ^

Call centers terciarizados : Los desafíos para la organización de los trabajadores en una actividad económica emergente

En el presente trabajo pretendemos explorar cuáles son las posibilidades de organización de los trabajadores en una actividad económica emergente como son los call centers terciarizados. En este sentido, nuestra meta principal será identificar ciertos dilemas y ejes problemáticos en el campo de la organización colectiva para estos espacios laborales atravesados por estrategias de flexibilización empresarial tales como la subcontratación y la deslocalización. En este marco de reflexión, indagamos hacia dónde se dirigen las estrategias de los sindicatos ante las transformaciones productivas en marcha -que han sido muy aceleradas en el sector de las telecomunicaciones-, cuál es la dinámica de estos actores y cuáles son los obstáculos mayores a su accionar. Asimismo, exploramos la existencia de nuevas formas de organización colectiva alternativas que dan voz a los intereses de los trabajadores por fuera de los sindicatos tradicionales. Describimos sus rasgos distintivos, sus condiciones de surgimiento y las ventajas y limitaciones respecto de los sindicatos clásicos. Finalmente, examinamos de qué manera ciertos aspectos ligados a los trabajadores y a la conformación de experiencias subjetivas en estos espacios laborales se relacionan con un mayor o menor grado de inclinación hacia la organización colectiva

Inversiones en servicios : Nuevas territorialidades en la expansión de call centers en el interior de la Argentina, 2002-2010

En la Argentina, el año 2002 marca el inicio de una serie de transformaciones productivas con fuerte impacto sobre las dinámicas territoriales, a partir de la llegada de inversiones extranjeras directas. Una importante porción de dichas inversiones se orienta a desarrollar actividades de baja jerarquización, en donde la competitividad se obtiene vía la reducción de los costos laborales y el otorgamiento de ventajas impositivas y subsidios hacia las empresas. La significativa expansión de la actividad de los call centers tercerizadores -que, en los últimos años, se localizan masiva y vertiginosamente en las principales ciudades del interior de nuestro país- es la evidencia empírica de este fenómeno. Analizar sus características, junto con una detallada descripción de las interacciones de los organismos estatales y los sectores políticos, sociales y económicos involucrados en la instalación de los call centers, no solo permite observar las transformaciones territoriales -en tanto se insertan nuevas actividades productivas y de empleo- sino que visibiliza mecanismos de cooperación y/o conflicto mediante los cuales los actores nacionales y foráneos posibilitan y modelan la inserción de lo global en lo local, materializando así novedosas lógicas de organización territorial, que representamos bajo el concepto "nuevas territorialidades". A lo largo de todo el trabajo, intentamos que nuestra mirada de estos procesos pueda dar cuenta de las (a)simetrías de poder entre los agentes económicos y actores estatales y extraestatales, en el marco de espacios locales periféricos en una época de globalización

Call centers terciarizados : Los desafíos para la organización de los trabajadores en una actividad económica emergente

En el presente trabajo pretendemos explorar cuáles son las posibilidades de organización de los trabajadores en una actividad económica emergente como son los call centers terciarizados. En este sentido, nuestra meta principal será identificar ciertos dilemas y ejes problemáticos en el campo de la organización colectiva para estos espacios laborales atravesados por estrategias de flexibilización empresarial tales como la subcontratación y la deslocalización. En este marco de reflexión, indagamos hacia dónde se dirigen las estrategias de los sindicatos ante las transformaciones productivas en marcha -que han sido muy aceleradas en el sector de las telecomunicaciones-, cuál es la dinámica de estos actores y cuáles son los obstáculos mayores a su accionar. Asimismo, exploramos la existencia de nuevas formas de organización colectiva alternativas que dan voz a los intereses de los trabajadores por fuera de los sindicatos tradicionales. Describimos sus rasgos distintivos, sus condiciones de surgimiento y las ventajas y limitaciones respecto de los sindicatos clásicos. Finalmente, examinamos de qué manera ciertos aspectos ligados a los trabajadores y a la conformación de experiencias subjetivas en estos espacios laborales se relacionan con un mayor o menor grado de inclinación hacia la organización colectiva

Inversiones en servicios : Nuevas territorialidades en la expansión de call centers en el interior de la Argentina, 2002-2010

En la Argentina, el año 2002 marca el inicio de una serie de transformaciones productivas con fuerte impacto sobre las dinámicas territoriales, a partir de la llegada de inversiones extranjeras directas. Una importante porción de dichas inversiones se orienta a desarrollar actividades de baja jerarquización, en donde la competitividad se obtiene vía la reducción de los costos laborales y el otorgamiento de ventajas impositivas y subsidios hacia las empresas. La significativa expansión de la actividad de los call centers tercerizadores -que, en los últimos años, se localizan masiva y vertiginosamente en las principales ciudades del interior de nuestro país- es la evidencia empírica de este fenómeno. Analizar sus características, junto con una detallada descripción de las interacciones de los organismos estatales y los sectores políticos, sociales y económicos involucrados en la instalación de los call centers, no solo permite observar las transformaciones territoriales -en tanto se insertan nuevas actividades productivas y de empleo- sino que visibiliza mecanismos de cooperación y/o conflicto mediante los cuales los actores nacionales y foráneos posibilitan y modelan la inserción de lo global en lo local, materializando así novedosas lógicas de organización territorial, que representamos bajo el concepto "nuevas territorialidades". A lo largo de todo el trabajo, intentamos que nuestra mirada de estos procesos pueda dar cuenta de las (a)simetrías de poder entre los agentes económicos y actores estatales y extraestatales, en el marco de espacios locales periféricos en una época de globalización