Secondary injury in traumatic brain injury patients - A prospective Study

Objective. Secondary insults of hypotension and hypoxia significantly impact on outcome in patients  with traumatic brain injury (TBI). More than 4 hours' delay in evacuation of intracranial haematomas has  been demonstrated to have an additional impact on outcome. The objective of this study was to document the incidence of these preventable secondary insults in patients admitted with moderate or severe brain  injury.Methodology. All moderate and severe head injury patients admitted to Groote Schuur Hospital over a  3-month period were studied prospectively. Data were obtained from ambulance dockets, referral letters, patient charts and attending medical staff. Preventable secondary insults (hypotension, hypoxia) and time delay to assessment and surgery were documented. Outcome was assessed using the Glasgow outcome scale (GOS) at discharge or outpatient follow-up.Results. Ninety-six patients were studied. Forty-nine patients experienced at least one recorded  preventable event of hypoxia or hypotension. Seventeen had an intracranial haematoma requiring  evacuation. The mean time interval between injury and surgery was 455 minutes. No haematoma was evacuated within 4 hours of injury. Patients referred via a primary or secondary care facility experienced a mean additional delay of 70 minutes. These results demonstrated a significant incidence of secondary injury and delay to assessment and surgery. We believe that education and a raised awa reness of the impact of secondary insults may have a positive impact on TBI outcome in our referral area

Inquiry in Technology Education

Technology education involves much more than instruction of the artifacts and methods of technology. The increasing amount and complexity of technology require students to know how to use, manage, assess, and understand technology. Inquiry is a cognitive instructional strategy that can help students learn about current technologies and also provide them with tools for investigating emerging technologies as they are encountered

PPARδ status and mismatch repair mediated neoplasia in the mouse intestine

BACKGROUND: Therapeutic regulation of PPARδ activity using selective agonists has been proposed for various disorders. However, the consequences of altered peroxisome proliferator-activated receptor delta (PPARδ) activity in the context of intestinal tumourigenesis remain somewhat unclear. Contradictory evidence suggesting PPARδ either attenuates or potentiates intestinal neoplasia. To further investigate the PPARδ dependency of intestinal tumourigenesis, we have analysed the consequences of PPARδ deficiency upon intestinal neoplasia occurring in mice with impaired mismatch DNA repair. METHODS: Mice deficient for both PPARδ and the mismatch repair gene Mlh1 were produced and the incidence and severity of intestinal neoplasia recorded. RESULTS: No significant differences between the control genotypes and the double mutant genotypes were recorded indicating that deficiency of PPARδ does not modify impaired mismatch repair induced neoplasia. CONCLUSION: In contrast with the previously observed acceleration of intestinal neoplasia in the context of the Apc(Min/+ )mouse, PPARδ deficiency does not alter the phenotype of mismatch repair deficiency. This data supports the notion that PPARδ is not required for adenoma formation and indicate that any pro-tumourigenic effect of PPARδ inactivation may be highly context dependent

SOX10 directly modulates ERBB3 transcription via an intronic neural crest enhancer

<p>Abstract</p> <p>Background</p> <p>The <it>ERBB3 </it>gene is essential for the proper development of the neural crest (NC) and its derivative populations such as Schwann cells. As with all cell fate decisions, transcriptional regulatory control plays a significant role in the progressive restriction and specification of NC derived lineages during development. However, little is known about the sequences mediating transcriptional regulation of <it>ERBB3 </it>or the factors that bind them.</p> <p>Results</p> <p>In this study we identified three transcriptional enhancers at the <it>ERBB3 </it>locus and evaluated their regulatory potential <it>in vitro </it>in NC-derived cell types and <it>in vivo </it>in transgenic zebrafish. One enhancer, termed <it>ERBB3</it>_MCS6, which lies within the first intron of <it>ERBB3</it>, directs the highest reporter expression <it>in vitro </it>and also demonstrates epigenetic marks consistent with enhancer activity. We identify a consensus SOX10 binding site within <it>ERBB3</it>_MCS6 and demonstrate, <it>in vitro</it>, its necessity and sufficiency for the activity of this enhancer. Additionally, we demonstrate that transcription from the endogenous <it>Erbb3 </it>locus is dependent on Sox10. Further we demonstrate <it>in vitro </it>that Sox10 physically interacts with that <it>ERBB3</it>_MCS6. Consistent with its <it>in vitro </it>activity, we also show that <it>ERBB3</it>_MCS6 drives reporter expression in NC cells and a subset of its derivative lineages <it>in vivo </it>in zebrafish in a manner consistent with <it>erbb3b </it>expression. We also demonstrate, using morpholino analysis, that Sox10 is necessary for <it>ERBB3</it>_MCS6 expression <it>in vivo </it>in zebrafish.</p> <p>Conclusions</p> <p>Taken collectively, our data suggest that <it>ERBB3 </it>may be directly regulated by SOX10, and that this control may in part be facilitated by <it>ERBB3</it>_MCS6.</p

Anaesthesia – what has the University of Cape Town contributed?

From humble beginnings, the University of Cape Town’s Department of Anaesthesia has played a major role in the development of anaesthesia as a speciality, in South Africa and internationally. We highlight these contributions in clinical service, teaching and research, with particular emphasis on the department’s leading role in the evolution of anaesthetic safety in adults and children: from the development of the treatment of malignant hyperthermia, to unique studies in mortality associated with anaesthesia, and modern contributions to improved drug safety. Innovations in anaesthetic techniques have contributed to significant surgical developments, including the first heart transplant. Furthermore, our research has contributed to major advances in obstetric and endocrine anaesthesia, and training in the department is recognised as being among the best in the world

Wave-driven inner-shelf motions on the Oregon coast

Author Posting. © American Meteorological Society, 2009. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 39 (2009): 2942-2956, doi:10.1175/2009JPO4041.1.Recent work by S. Lentz et al. documents offshore transport in the inner shelf due to a wave-driven return flow associated with the Hasselmann wave stress (the Stokes–Coriolis force). This analysis is extended using observations from the central Oregon coast to identify the wave-driven return flow present and quantify the potential bias of wind-driven across-shelf exchange by unresolved wave-driven circulation. Using acoustic Doppler current profiler (ADCP) measurements at six stations, each in water depths of 13–15 m, observed depth-averaged, across-shelf velocities were generally correlated with theoretical estimates of the proposed return flow. During times of minimal wind forcing, across-shelf velocity profiles were vertically sheared, with stronger velocities near the top of the measured portion of the water column, and increased in magnitude with increasing significant wave height, consistent with circulation due to the Hasselmann wave stress. Yet velocity magnitudes and vertical shears were stronger than that predicted by linear wave theory, and more similar to the stratified “summer” velocity profiles described by S. Lentz et al. Additionally, substantial temporal and spatial variability of the wave-driven return flow was found, potentially due to changing wind and wave conditions as well as local bathymetric variability. Despite the wave-driven circulation found, subtracting estimates of the return flow from the observed across-shelf velocity had no significant effect on estimates of the across-shelf exchange due to along-shelf wind forcing at these water depths along the Oregon coast during summer.This work was performed with the Partnership for Interdisciplinary Studies of Coastal Oceans (PISCO), funded primarily by the Gordon and Betty Moore Foundation and David and Lucile Packard Foundation. SL acknowledges support from NSF Ocean Science Grant #OCE-0548961. AK acknowledges support from the WHOI Coastal Ocean Institute Fellowship

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11

First radial velocity results from the MINiature Exoplanet Radial Velocity Array (MINERVA)

The MINiature Exoplanet Radial Velocity Array (MINERVA) is a dedicated observatory of four 0.7m robotic telescopes fiber-fed to a KiwiSpec spectrograph. The MINERVA mission is to discover super-Earths in the habitable zones of nearby stars. This can be accomplished with MINERVA's unique combination of high precision and high cadence over long time periods. In this work, we detail changes to the MINERVA facility that have occurred since our previous paper. We then describe MINERVA's robotic control software, the process by which we perform 1D spectral extraction, and our forward modeling Doppler pipeline. In the process of improving our forward modeling procedure, we found that our spectrograph's intrinsic instrumental profile is stable for at least nine months. Because of that, we characterized our instrumental profile with a time-independent, cubic spline function based on the profile in the cross dispersion direction, with which we achieved a radial velocity precision similar to using a conventional "sum-of-Gaussians" instrumental profile: 1.8 m s$^{-1}$ over 1.5 months on the RV standard star HD 122064. Therefore, we conclude that the instrumental profile need not be perfectly accurate as long as it is stable. In addition, we observed 51 Peg and our results are consistent with the literature, confirming our spectrograph and Doppler pipeline are producing accurate and precise radial velocities.Comment: 22 pages, 9 figures, submitted to PASP, Peer-Reviewed and Accepte

Carina OB Stars: X-ray Signatures of Wind Shocks and Magnetic Fields

The Chandra Carina Complex contains 200 known O- and B type stars. The Chandra survey detected 68 of the 70 O stars and 61 of 127 known B0-B3 stars. We have assembled a publicly available optical/X-ray database to identify OB stars that depart from the canonical Lx/Lbol relation, or whose average X-ray temperatures exceed 1 keV. Among the single O stars with high kT we identify two candidate magnetically confined wind shock sources: Tr16-22, O8.5 V, and LS 1865, O8.5 V((f)). The O4 III(fc) star HD 93250 exhibits strong, hard, variable X-rays, suggesting it may be a massive binary with a period of >30 days. The visual O2 If* binary HD 93129A shows soft 0.6 keV and hard 1.9 keV emission components, suggesting embedded wind shocks close to the O2 If* Aa primary, and colliding wind shocks between Aa and Ab. Of the 11 known O-type spectroscopic binaries, the long orbital-period systems HD 93343, HD 93403 and QZ Car have higher shock temperatures than short-period systems such as HD 93205 and FO 15. Although the X-rays from most B stars may be produced in the coronae of unseen, low-mass pre-main-sequence companions, a dozen B stars with high Lx cannot be explained by a distribution of unseen companions. One of these, SS73 24 in the Treasure Chest cluster, is a new candidate Herbig Be star.Comment: To be published in a special issue of the Astrophysical Journal Supplement on the Chandra Carina Complex Projec

Applying Superfluid Helium to Light Dark Matter Searches: Demonstration of the HeRALD Detector Concept

The SPICE/HeRALD collaboration is performing R&D to enable studies of sub-GeV dark matter models using a variety of target materials. Here we report our recent progress on instrumenting a superfluid $^4$He target mass with a transition-edge sensor based calorimeter to detect both atomic signals (e.g. scintillation) and $^4$He quasiparticle (phonon and roton) excitations. The sensitivity of HeRALD to the critical "quantum evaporation" signal from $^4$He quasiparticles requires us to block the superfluid film flow to the calorimeter. We have developed a heat-free film-blocking method employing an unoxidized Cs film, which we implemented in a prototype "HeRALD v0.1" detector of $\sim$10~g target mass. This article reports initial studies of the atomic and quasiparticle signal channels. A key result of this work is the measurement of the quantum evaporation channel's gain of $0.15 \pm 0.012$, which will enable $^4$He-based dark matter experiments in the near term. With this gain the HeRALD detector reported here has an energy threshold of 145~eV at 5 sigma, which would be sensitive to dark matter masses down to 220~MeV/c$^2$.Comment: 14 pages, 9 figure