Use of diffusion tensor imaging to assess the impact of normobaric hyperoxia within at-risk pericontusional tissue after traumatic brain injury

Ischemia and metabolic dysfunction remain important causes of neuronal loss after head injury, and we have shown that normobaric hyperoxia may rescue such metabolic compromise. This study examines the impact of hyperoxia within injured brain using diffusion tensor imaging (DTI). Fourteen patients underwent DTI at baseline and after 1 hour of 80% oxygen. Using the apparent diffusion coefficient (ADC) we assessed the impact of hyperoxia within contusions and a 1 cm border zone of normal appearing pericontusion, and within a rim of perilesional reduced ADC consistent with cytotoxic edema and metabolic compromise. Seven healthy volunteers underwent imaging at 21%, 60%, and 100% oxygen. In volunteers there was no ADC change with hyperoxia, and contusion and pericontusion ADC values were higher than volunteers (P < 0.01). There was no ADC change after hyperoxia within contusion, but an increase within pericontusion (P < 0.05). We identified a rim of perilesional cytotoxic edema in 13 patients, and hyperoxia resulted in an ADC increase towards normal (P=0.02). We demonstrate that hyperoxia may result in benefit within the perilesional rim of cytotoxic edema. Future studies should address whether a longer period of hyperoxia has a favorable impact on the evolution of tissue injury

Normobaric hyperoxia does not improve derangements in diffusion tensor imaging found distant from visible contusions following acute traumatic brain injury

We have previously shown that normobaric hyperoxia may benefit peri-lesional brain and white matter following traumatic brain injury (TBI). This study examined the impact of brief exposure to hyperoxia using diffusion tensor imaging (DTI) to identify axonal injury distant from contusions. Fourteen patients with acute moderate/severe TBI underwent baseline DTI and following one hour of 80% oxygen. Thirty-two controls underwent DTI, with 6 undergoing imaging following graded exposure to oxygen. Visible lesions were excluded and data compared with controls. We used the 99% prediction interval (PI) for zero change from historical control reproducibility measurements to demonstrate significant change following hyperoxia. Following hyperoxia DTI was unchanged in controls. In patients following hyperoxia, mean diffusivity (MD) was unchanged despite baseline values lower than controls (p < 0.05), and fractional anisotropy (FA) was lower within the left uncinate fasciculus, right caudate and occipital regions (p < 0.05). 16% of white and 14% of mixed cortical and grey matter patient regions showed FA decreases greater than the 99% PI for zero change. The mechanistic basis for some findings are unclear, but suggest that a short period of normobaric hyperoxia is not beneficial in this context. Confirmation following a longer period of hyperoxia is required.Dr. Veenith was supported by clinical research training fellowship from National institute of Academic Anaesthesia and Raymond Beverly Sackler studentship. VFJN is supported by a Health Foundation/Academy of Medical Sciences Clinician Scientist Fellowship. JPC was supported by Wellcome trust project grant. DKM is supported by an NIHR Senior Investigator Award. This work was supported by a Wellcome Trust Project Grant (WT093267) and Medical Research Council (UK) Program Grant (Acute brain injury: heterogeneity of mechanisms, therapeutic targets and outcome effects (G9439390 ID 65883)), the UK National Institute of Health Research Biomedical Research Centre at Cambridge, and the Technology Platform funding provided by the UK Department of Health. The funders had no role in study design, data collection and analyses, decision to publish, or preparation of the manuscript

Isolated and dynamical horizons and their applications

Over the past three decades, black holes have played an important role in quantum gravity, mathematical physics, numerical relativity and gravitational wave phenomenology. However, conceptual settings and mathematical models used to discuss them have varied considerably from one area to another. Over the last five years a new, quasi-local framework was introduced to analyze diverse facets of black holes in a unified manner. In this framework, evolving black holes are modeled by dynamical horizons and black holes in equilibrium by isolated horizons. We review basic properties of these horizons and summarize applications to mathematical physics, numerical relativity and quantum gravity. This paradigm has led to significant generalizations of several results in black hole physics. Specifically, it has introduced a more physical setting for black hole thermodynamics and for black hole entropy calculations in quantum gravity; suggested a phenomenological model for hairy black holes; provided novel techniques to extract physics from numerical simulations; and led to new laws governing the dynamics of black holes in exact general relativity.Comment: 77 pages, 12 figures. Typos and references correcte

A behavioral comparison of male and female adults with high functioning autism spectrum conditions

Autism spectrum conditions (ASC) affect more males than females in the general population. However, within ASC it is unclear if there are phenotypic sex differences. Testing for similarities and differences between the sexes is important not only for clinical assessment but also has implications for theories of typical sex differences and of autism. Using cognitive and behavioral measures, we investigated similarities and differences between the sexes in age- and IQ-matched adults with ASC (high-functioning autism or Asperger syndrome). Of the 83 (45 males and 38 females) participants, 62 (33 males and 29 females) met Autism Diagnostic Interview-Revised (ADI-R) cut-off criteria for autism in childhood and were included in all subsequent analyses. The severity of childhood core autism symptoms did not differ between the sexes. Males and females also did not differ in self-reported empathy, systemizing, anxiety, depression, and obsessive-compulsive traits/symptoms or mentalizing performance. However, adult females with ASC showed more lifetime sensory symptoms (p = 0.036), fewer current socio-communication difficulties (p = 0.001), and more self-reported autistic traits (p = 0.012) than males. In addition, females with ASC who also had developmental language delay had lower current performance IQ than those without developmental language delay (p<0.001), a pattern not seen in males. The absence of typical sex differences in empathizing-systemizing profiles within the autism spectrum confirms a prediction from the extreme male brain theory. Behavioral sex differences within ASC may also reflect different developmental mechanisms between males and females with ASC. We discuss the importance of the superficially better socio-communication ability in adult females with ASC in terms of why females with ASC may more often go under-recognized, and receive their diagnosis later, than males

Intrinsic Shapes of Elliptical Galaxies

Tests for the intrinsic shape of the luminosity distribution in elliptical galaxies are discussed, with an emphasis on the uncertainties. Recent determinations of the ellipticity frequency function imply a paucity of nearly spherical galaxies, and may be inconsistent with the oblate hypothesis. Statistical tests based on the correlation of surface brightness, isophotal twisting, and minor axis rotation with ellipticity have so far not provided strong evidence in favor of the nearly oblate or nearly prolate hypothesis, but are at least qualitatively consistent with triaxiality. The possibility that the observed deviations of elliptical galaxy isophotes form ellipses are due to projection effects is evaluated. Dynamical instabilities may explain the absence of elliptical galaxies flatter than about E6, and my also play a role in the lack of nearly-spherical galaxies

Suturing training in Augmented Reality: gaining proficiency in suturing skills faster

Background: Providing informative feedback and setting goals tends to motivate trainees to practice more extensively. Augmented Reality simulators retain the benefit of realistic haptic feedback and additionally generate objective assessment and informative feedback during the training. This study researched the performance curve of the adapted suturing module on the ProMIS Augmented Reality simulator. Methods: Eighteen novice participants were pretrained on the MIST-VR to become acquainted with laparoscopy. Subsequently, they practiced 16 knots on the suturing module, of which the assessment scores were recorded to evaluate the gain in laparoscopic suturing skills. The scoring of the assessment method was calculated from the “time spent in the correct area” during the knot tying and the quality of the knot. Both the baseline knot and the knot at the top of the performance curve were assessed by two independent objective observers, by means of a standardized evaluation form, to objectify the gain in suturing skills. Results: There was a statistically significant difference between the scores of the second knot (mean 72.59, standard deviation (SD) 16.28) and the top of the performance curve (mean 95.82, SD 3.05; p < 0.001, paired t-test). The scoring of the objective observers also differed significantly (mean 11.83 and 22.11, respectively; SD 3.37 and 3.89, respectively; p < 0.001) (interobserver reliability Cronbach’s alpha = 0.96). The median amount of repetitions to reach the top of the performance curve was eight, which also showed significant differences between both the assessment score (mean 88.14, SD 13.53, p < 0.001) and scoring of the objective observers of the second knot (mean 20.51, SD 4.14; p < 0.001). Conclusions: This adapted suturing module on the ProMIS Augmented Reality laparoscopic simulator is a potent tool for gaining laparoscopic suturing skills.Industrial DesignIndustrial Design Engineerin

Renal angiomyolipoma in patients with tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increase disease Awareness

BACKGROUND: Renal angiomyolipoma occurs at a high frequency in patients with tuberous sclerosis complex (TSC) and is associated with potentially life-threatening complications. Despite this frequency and severity, there are no large population-based cohort studies. Here we present baseline and follow-up data of the international TuberOus SClerosis registry to increase disease Awareness (TOSCA) with an aim to provide detailed clinical characteristics of renal angiomyolipoma among patients with TSC. METHODS: Patients of any age with a documented clinic visit for TSC within 12 months or who were newly diagnosed with TSC before participation in the registry were eligible. Data specific to renal angiomyolipoma included physical tumour characteristics (multiple, bilateral, lesion size and growing lesions), clinical signs and symptoms, and management. The effects of age, gender and genotype on the prevalence of renal angiomyolipoma were also evaluated. RESULTS: Renal angiomyolipoma was reported in 51.8% of patients at baseline, with higher frequency in female patients (57.8% versus 42.2%). The median age at diagnosis was 12 years. Prevalence of angiomyolipoma was higher in patients with TSC2 compared with TSC1 mutations (59.2% versus 33.3%, P 3 cm in 34.3% of patients. Most patients were asymptomatic (82%). Frequently reported angiomyolipoma-related symptoms included bleeding, pain, elevated blood pressure and impaired renal function. Embolization and mammalian target of rapamycin inhibitors were the two most common treatment modalities. CONCLUSIONS: The TOSCA registry highlights the burden of renal angiomyolipoma in patients with TSC and shows that renal manifestations are initially asymptomatic and are influenced by gender and genotype. Furthermore, the occurrence of significant problems from angiomyolipoma in a minority of younger patients suggests that surveillance should begin in infancy or at initial diagnosis

TuberOus SClerosis registry to increAse disease awareness (TOSCA) Post-Authorisation Safety Study of Everolimus in Patients With Tuberous Sclerosis Complex

This non-interventional post-authorisation safety study (PASS) assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) who participated in the TuberOus SClerosis registry to increase disease Awareness (TOSCA) clinical study and received everolimus for the licensed indications in the European Union. The rate of adverse events (AEs), AEs that led to dose adjustments or treatment discontinuation, AEs of potential clinical interest, treatment-related AEs (TRAEs), serious AEs (SAEs), and deaths were documented. One hundred seventy-nine patients were included in the first 5 years of observation; 118 of 179 patients had an AE of any grade, with the most common AEs being stomatitis (7.8%) and headache (7.3%). AEs caused dose adjustments in 56 patients (31.3%) and treatment discontinuation in nine patients (5%). AEs appeared to be more frequent and severe in children. On Tanner staging, all patients displayed signs of age-appropriate sexual maturation. Twenty-two of 106 female (20.8%) patients had menstrual cycle disorders. The most frequent TRAEs were stomatitis (6.7%) and aphthous mouth ulcer (5.6%). SAEs were reported in 54 patients (30.2%); the most frequent SAE was pneumonia (>3% patients; grade 2, 1.1%, and grade 3, 2.8%). Three deaths were reported, all in patients who had discontinued everolimus for more than 28 days, and none were thought to be related to everolimus according to the treating physicians. The PASS sub-study reflects the safety and tolerability of everolimus in the management of TSC in real-world routine clinical practice

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Challenges in identifying barriers to adoption in a theory-based implementation study: lessons for future implementation studies

Background: Exploring barriers to the uptake of research based recommendations into practice is an important part of the development of implementation programmes. Techniques to identify barriers can include use of theory-informed questionnaires and qualitative interviews. Conceptualising and measuring theory-informed factors, and engaging health professionals’ to uncover all potential barriers, can be a difficult task. This paper presents a case study of the process of trying to identify, systematically, the key factors influencing health professionals’ referrals for women diagnosed with mild to moderate postnatal depression for psychological treatment. The paper illustrates how the factors were conceptualised and measured and explores the real world challenges experienced, with implications for future implementation studies. Methods: Theory-informed factors were conceptualised and measured using a questionnaire and interviews. The questionnaire was piloted, before being administered to general practitioners, practice nurses and health visitors working in general practices in one area of the UK NHS. The interviews were conducted with a small sample of general practitioners who had not completed the questionnaire, further exploring factors influencing their referral decisions in the local context. Results: The response rate to the questionnaire was low (19%), despite selecting the recommendation to target through engagement with local stakeholders and surveying local health professionals, and despite using two reminders, an incentive prize, and phone calls to practice managers to bolster response rates. Conclusions: Two significant challenges to achieving higher response rates and successfully exploring local context were identified: the difficulties of developing a robust- but feasible- questionnaire to explore theory-informed factors, and targeting recommendations that are important to policy makers, but which health professionals view as unimportant. This case study highlights the “trade-off” between scientifically rigorous collection of data against the pragmatism and flexibility requirements of “real world” implementation. Future implementation studies should explore different ways of identifying factors influencing the adoption of recommendations to bridge this gulf