Percutaneous screw fixation of the iliosacral joint: optimal screw pathways are frequently not completely intraosseous

INTRODUCTION In iliosacral screw fixation, the dimensions of solely intraosseous (secure) pathways, perpendicular to the ilio-sacral articulation (optimal) with corresponding entry (EP) and aiming points (AP) on lateral fluoroscopic projections, and the factors (demographic, anatomic) influencing these have not yet been described. METHODS In 100 CTs of normal pelvises, the height and width of the secure and optimal pathways were measured on axial and coronal views bilaterally (total measurements: n=200). Corresponding EP and AP were defined as either the location of the screw head or tip at the crossing of lateral innominate bones' cortices (EP) and sacral midlines (AP) within the centre of the pathway, respectively. EP and AP were transferred to the sagittal pelvic view using a coordinate system with the zero-point in the centre of the posterior cortex of the S1 vertebral body (x-axis parallel to upper S1 endplate). Distances are expressed in relation to the anteroposterior distance of the S1 upper endplate (in %). The influence of demographic (age, gender, side) and/or anatomic (PIA=pelvic incidence angle; TCA=transversal curvature angle, PID-Index=pelvic incidence distance-index; USW=unilateral sacral width-index) parameters on pathway dimensions and positions of EP and AP were assessed (multivariate analysis). RESULTS The width, height or both factors of the pathways were at least 7mm or more in 32% and 53% or 20%, respectively. The EP was on average 14±24% behind the centre of the posterior S1 cortex and 41±14% below it. The AP was on average 53±7% in the front of the centre of the posterior S1 cortex and 11±7% above it. PIA influenced the width, TCA, PID-Index the height of the pathways. PIA, PID-Index, and USW-Index significantly influenced EP and AP. Age, gender, and TCA significantly influenced EP. CONCLUSION Secure and optimal placement of screws of at least 7mm in diameter will be unfeasible in the majority of patients. Thoughtful preoperative planning of screw placement on CT scans is advisable to identify secure pathways with an optimal direction. For this purpose, the presented methodology of determining and transferring EPs and APs of corresponding pathways to the sagittal pelvic view using a coordinate system may be useful.

Early versus delayed application of Thomas splints in patients with isolated femur shaft fractures: The benefits quantified

AIMS To investigate and quantify the clinical benefits of early versus delayed application of Thomas splints in patients with isolated femur shaft fractures. MATERIALS AND METHODS Level IV retrospective clinical and radiological analysis of patients presenting from January to December 2012 at a Level 1 Trauma Unit. All skeletally mature patients with isolated femur shaft fractures independently of their mechanism of injury were included. Exclusion criteria were: ipsilateral fracture of the lower limb, neck and supracondylar femur fractures, periprosthetic and incomplete fractures. Their clinical records were analysed for blood transfusion requirements, pulmonary complications, surgery time, duration of hospital stay and analgesic requirements. RESULTS A total of 106 patients met our inclusion criteria. There were 74 males and 32 females. Fifty seven (54%) patients were in the 'early splinted' group and 49 patients (46%) were in the 'delayed splinted' group (P>0.05). The need for blood transfusion was significantly reduced in the 'early splinted' group (P=0.04). There was a significantly higher rate of pulmonary complications in the 'delayed splinted' group (P=0.008). All other parameters were similar between the two groups. CONCLUSION The early application of Thomas splints for isolated femur fractures in non-polytraumatised patients has a clinically and statistically significant benefit of reducing the need for blood transfusions and the incidence of pulmonary complications.

Automatic assessment of time-resolved OCT images for selective retina therapy

Purpose In recent years, selective retina laser treatment (SRT), a sub-threshold therapy method, avoids widespread damage to all retinal layers by targeting only a few. While these methods facilitate faster healing, their lack of visual feedback during treatment represents a considerable shortcoming as induced lesions remain invisible with conventional imaging and make clinical use challenging. To overcome this, we present a new strategy to provide location-specific and contact-free automatic feedback of SRT laser applications. Methods We leverage time-resolved optical coherence tomography (OCT) to provide informative feedback to clinicians on outcomes of location-specific treatment. By coupling an OCT system to SRT treatment laser, we visualize structural changes in the retinal layers as they occur via time-resolved depth images. We then propose a novel strategy for automatic assessment of such time-resolved OCT images. To achieve this, we introduce novel image features for this task that when combined with standard machine learning classifiers yield excellent treatment outcome classification capabilities. Results Our approach was evaluated on both ex vivo porcine eyes and human patients in a clinical setting, yielding performances above 95 % accuracy for predicting patient treatment outcomes. In addition, we show that accurate outcomes for human patients can be estimated even when our method is trained using only ex vivo porcine data. Conclusion The proposed technique presents a much needed strategy toward noninvasive, safe, reliable, and repeatable SRT applications. These results are encouraging for the broader use of new treatment options for neovascularization-based retinal pathologies.

The inhibition of NF-kappaB activation pathways and the induction of apoptosis by dithiocarbamates in T cells are blocked by the glutathione precursor N-acetyl-L-cysteine

Nuclear factor-kappaB regulates genes that control immune and inflammatory responses and are involved in the pathogenesis of several diseases, including AIDS and cancer. It has been proposed that reactive oxygen intermediates participate in NF-kappaB activation pathways, and compounds with putative antioxidant activity such as N-acetyl-L-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) have been used interchangeably to demonstrate this point. We examined their effects, separately and combined, on different stages of the NF-kappaB activation pathway, in primary and in transformed T cells. We show that NAC, contrary to its reported role as an NF-kappaB inhibitor, can actually enhance rather than inhibit IkappaB degradation and, most importantly, show that in all cases NAC exerts a dominant antagonistic effect on PDTC-mediated NF-kappaB inhibition. This was observed at the level of IkappaB degradation, NF-kappaB DNA binding, and HIV-LTR-driven reporter gene expression. NAC also counteracted growth arrest and apoptosis induced by dithiocarbamates. Antagonistic effects were further observed at the level of jun-NH2-terminal kinase, p38 and ATF-2 activation. Our findings argue against the widely accepted assumption that NAC inhibits all NF-kappaB activation pathways and shows that two compounds, previously thought to function through a common inhibitory mechanism, can also have antagonistic effects.

Deterrence, Incapacitation, and Repeat Offenders

This paper develops an economic model of criminal enforcement that combines the goals of deterrence and incapacitation. Potential offenders commit an initial criminal act if the present value of net private gains is positive. A fraction of these offenders become habitual and commit further crimes immediately upon release from their initial prison term (if any). The optimal punishment scheme in this setting generally involves a finite prison term for first-time offenders (based on the goal of deterrence), and an infinite (life) sentence for repeat offenders (based on the goal of incapacitation).

PIM KINASE INHIBITION: SINGLE AGENT AND COMBINATION APPROACHES IN B-CELL LYMPHOMA

Proviral integration site for Moloney murine leukemia virus (Pim) kinases are Ser/Thr/Tyr kinases. They modulate B-cell development but become oncoproteins and promote cancer development once overexpressed. Containing three isoforms, Pim-1, -2 and -3 are known to phosphorylate various substrates that regulate transcription, translation, cell cycle, and survival pathways in both hematological and solid tumors. Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma. Elevated Pim kinase levels are common in MCL, and it negatively correlates with patient outcome. SGI-1776 is a small molecule inhibitor selective for Pim-1/-3. We hypothesize that SGI-1776 treatment in MCL will inhibit Pim kinase function, and inhibition of downstream substrates phosphorylation will disrupt transcriptional, translational, and cell cycle processes while promoting apoptosis. SGI-1776 treatment induced moderate to high levels of apoptosis in four MCL cell lines (JeKo-1, Mino, SP-53 and Granta-519) and peripheral blood mononuclear cells (PBMCs) from MCL patients. Phosphorylation of transcription and translation regulators, c-Myc and 4E-BP1 declined in both model systems. Additionally, levels of short-lived Mcl-1 mRNA and protein also decreased and correlated with decline of global RNA synthesis. Collectively, our investigations highlight Pim kinases as viable drug targets in MCL and emphasize their roles in transcriptional and translational regulation. We further investigated a combination strategy using SGI-1776 with bendamustine, an FDA-approved DNA-damaging alkylating agent for treating non-Hodgkin’s lymphoma. We hypothesized this combination will enhance SGI-1776-induced transcription and translation inhibition, while promoting bendamustine-triggered DNA damage and inducing additive to synergistic cytotoxicity in B-cell lymphoma. Bendamustine alone resulted in moderate levels of apoptosis induction in MCL cell lines (JeKo-1 and Mino), and in MCL and splenic marginal zone lymphoma (a type of B-cell lymphoma) primary cells. An additive effect in cell killing was observed when combined with SGI-1776. Expectedly, SGI-1776 effectively decreased global RNA and protein synthesis levels, while bendamustine significantly inhibited DNA synthesis and generated DNA damage response. In combination, intensified inhibitory effects in DNA, RNA and protein syntheses were observed. Together, these data suggested feasibility of using Pim kinase inhibitor in combination with chemotherapeutic agents such as bendamustine in B-cell lymphoma, and provided foundation of their mechanism of actions in lymphoma cells.

Horizontal profiles of longwave and shortwave radiation components over sea ice near Barrow, Alaska during the 2011 melt

An integrated instrument package for measuring and understanding the surface radiation budget of sea ice is presented, along with results from its first deployment. The setup simultaneously measures broadband fluxes of upwelling and downwelling terrestrial and solar radiation (four components separately), spectral fluxes of incident and reflected solar radiation, and supporting data such as air temperature and humidity, surface temperature, and location (GPS), in addition to photographing the sky and observed surface during each measurement. The instruments are mounted on a small sled, allowing measurements of the radiation budget to be made at many locations in the study area to see the effect of small-scale surface processes on the large-scale radiation budget. Such observations have many applications, from calibration and validation of remote sensing products to improving our understanding of surface processes that affect atmosphere-snow-ice interactions and drive feedbacks, ultimately leading to the potential to improve climate modelling of ice-covered regions of the ocean. The photographs, spectral data, and other observations allow for improved analysis of the broadband data. An example of this is shown by using the observations made during a partly cloudy day, which show erratic variations due to passing clouds, and creating a careful estimate of what the radiation budget along the observed line would have been under uniform sky conditions, clear or overcast. Other data from the setup's first deployment, in June 2011 on fast ice near Point Barrow, Alaska, are also shown; these illustrate the rapid changes of the radiation budget during a cold period that led to refreezing and new snow well into the melt season.

Psicoanálisis y lingüística : Delimitación de fronteras, delimitación de problemas. Enunciación e interpretación

El presente trabajo se enmarca en el proyecto de investigación 'Lógica y alcance de las operaciones del analista según Freud: colegir (erraten), interpretar, construir'. En esta oportunidad nos interesa delimitar la categoría de enunciación, en la dirección de establecer algunas de las particularidades que presenta en el campo de la lingüística y el campo del psicoanálisis. Por su parte, esto nos permitirá pensar si la articulación entre enunciación e interpretación presenta diferencias entre los dos campos mencionados Comenzamos entonces situando la categoría de enunciación en psicoanálisis a partir de la reformulación hecha por J. Lacan a la categoría de signo lingüístico presentado por Saussure, en cuanto a sus componentes y a su modo de operación. Ya que es a partir de estas reformulaciones que es posible pensar la articulación entre la significación y el sentido. Luego haremos un breve rastreo, vale decir, no exhaustivo de la noción de sentido o enunciación en Lingüística, intentando establecer sus particularidades en el terreno de este campo de la ciencia. Inevitablemente haremos una, también breve, mención a algunos de los problemas que en la lingüística surgen al intentar delimitarla dicha noción. A través de diferentes referencias bibliográficas se trabajaran las propuestas que al respecto presentan O. Ducrot, E. Benveniste, C. Kebrat Orechioni, G. Reyes y A. Bertorello. Se recortan así los problemas de 'intención enunciativa' y 'subjetividad' en la Lingüística. Estos serán contrastados y/o comparados con la noción de sujeto que se desprende de la enseñanza de Lacan, al menos en un período de la misma. Esta noción, entendida como sujeto intervalar se anuda a la re conceptualización mencionada en primer lugar del signo lingüístico y su operatoria. Nos referimos a la elaboración realizada por J. Lacan en su Seminario 11 'Los Cuatro Conceptos Fundamentales' respecto a lo que allí denomina las operaciones de 'Alienación' y 'Separación'. Es en torno a estas operaciones que puede pensarse al sujeto como el efecto del intervalo entre dos significantes. La operación de 'Separación' permitirá una dimensión de rescate de la dimensión 'no yo' de la 'Alienación' primera. Allí se juega para el sujeto la posibilidad de incluirse y hacerse representar en el lenguaje, mostrando al mismo tiempo los límites del campo de lo simbólico para otorgar identidad. Es en esta dirección que se piensa también la eficacia de la interpretación en Psicoanálisis. De este modo, llegamos al último tramo de nuestro recorrido donde intentaremos precisar a partir de estos desarrollos cuál es la articulación entre interpretación y enunciación en Psicoanálisis lo que nos llevará al problema de la convicción en un análisis o al problema de la producción de 'Efectos de verdad'. Tomando como herramienta la noción de verdad que allí se pone en juego, la diferenciaremos de otros modos de entender esta categoría. Para esto la referencia bibliográfica a la que hemos recurrido es el Seminario 17 'El revés del Psicoanálisis' de J. Lacan. Será entonces el lugar de la verdad en la articulación entre interpretación y enunciación, lo que nos permitirá delimitar la especificidad de estas categorías en el campo del Psicoanálisis. El presente trabajo se enmarca en el proyecto de investigación 'Lógica y alcance de las operaciones del analista según Freud: colegir (erraten), interpretar, construir' En esta oportunidad nos interesa delimitar la categoría de enunciación, en la dirección de establecer algunas de las particularidades que presenta en el campo de la lingüística y el campo del psicoanálisis. Por otro lado, la categoría de enunciación convoca a la de interpretación. Es por esto, que nuestra exploración sobre la primera nos ha llevado a preguntarnos por las diferencias en la articulación entre enunciación e interpretación entre los campos lingüístico y psicoanalítico. Estos entrecruzamientos delimitarán problemas para ambos campos que nos permitirán definir especificidades. Por un lado, nos saldrá al cruce desde la lingüística la noción de intención enunciativa y de subjetividad, las que diferentes autores recorren en términos de lo incognosible, o como disfuncionamiento lingüístico o como el 'aparato formal de la enunciación en el enunciado'. Por otro lado, desde el psicoanálisis, la noción de sujeto como sujeto intervalar, nos llevará a pensar la articulación clínica de la enunciación y la interpretación. Será entonces luego de pensar la noción de sujeto que cada campo articula con las categorías de enunciación e interpretación que les compete, que podremos avanzar en algunas delimitaciones especificas