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Adeno-associated virus (AAV) vectors are showing promise in gene therapy trials and have proven to be extremely efficient biological tools in basic neuroscience research. One major limitation to their widespread use in the neuroscience laboratory is the cost, labor, skill and time-intense purification process of AAV. We have recently shown that AAV can associate with exosomes (exo-AAV) when the vector is isolated from conditioned media of producer cells, and the exo-AAV is more resistant to neutralizing anti-AAV antibodies compared with standard AAV. Here, we demonstrate that simple pelleting of exo-AAV from media via ultracentrifugation results in high-titer vector preparations capable of efficient transduction of central nervous system (CNS) cells after systemic injection in mice. We observed that exo-AAV is more efficient at gene delivery to the brain at low vector doses relative to conventional AAV, even when derived from a serotype that does not normally efficiently cross the blood–brain barrier. Similar cell types were transduced by exo-AAV and conventionally purified vector. Importantly, no cellular toxicity was noted in exo-AAV-transduced cells. We demonstrated the utility and robustness of exo-AAV-mediated gene delivery by detecting direct GFP fluorescence after systemic injection, allowing three-dimensional reconstruction of transduced Purkinje cells in the cerebellum using ex vivo serial two-photon tomography. The ease of isolation combined with the high efficiency of transgene expression in the CNS, may enable the widespread use of exo-AAV as a neuroscience research tool. Furthermore, the ability of exo-AAV to evade neutralizing antibodies while still transducing CNS after peripheral delivery is clinically relevant.

Introduction/BackgroundTo compare the diagnostic accuracy of ultrasound (US), CT and WB-DWI/MRI in preoperative staging and assessment of optimal operability in patients with ovarian cancer.MethodologyPatients planned for ovarian cancer surgery were enrolled. They underwent preoperative work-up with US, CT, and WB-DWI/MRI, following evaluation form. Findings were compared to the reference standard (intraoperative and histopathological evaluation forms).ResultsFrom 67 patients enrolled, 51 (76%) had advanced and 16 (24%) early stage ovarian cancer. Ultrasound showed the best results in the detection of pelvic carcinomatosis, in contrast with MRI and CT (AUC 0.94, 0.91, and 0.82, respectively), and in the evaluation of the depth of rectosigmoid infiltration (AUC 0.96, 0.81, and 0.85). In the upper abdomen, all three methods showed comparable results in the detection of liver involvement (AUC 0.78, 0.79 and 0.76 for US, CT and WB-DWI/MRI), while US had the lowest AUC in the assessment of diaphragm (AUC 0.73, 0.84, 0.81). In the middle abdomen, ultrasound reached the highest AUC in the assessment of greater omentum and anterior wall (AUC of 0.87 and 0.76), in comparison with MRI (AUC 0.85 and 0.74), followed by CT (AUC 0.80 and 0.66). Ultrasound, MRI and CT showed comparable results in the assessment of bowel surface involvement (AUC 0.70, 0.69, 0.71), and ultrasound and MRI were better than CT (AUC 0.64, 0.71 and 0.76) in mesenterial involvement detection. In the assessment of retroperitoneal LNs, ultrasound and MRI were comparable (AUC 0.83), followed by CT (AUC of 0.76). All three modalities showed similar AUC in the prediction of optimal operability (AUC of 0.79 for US and CT and 0.80 for MRI).ConclusionThis is the first prospective study documenting the potential role of ultrasound in ovarian cancer staging, compared to the method of choice (CT) and a novel technique (WB-DWI/MRI).DisclosureThis work was supported by a grant from the Czech Research Council (AZV NV19- 03-00552).

Background The presence of myocardial fibrosis is associated with adverse outcome in dilated cardiomyopathy (DCM). Delayed contrast-enhanced cardiac magnetic resonance (DE-CMR) currently represents the gold standard in noninvasive evaluation of myocardial scarring. However, a significant number of patients are unable to undergo DE-CMR study for various reasons. We sought to determine the diagnostic accuracy of cardiac CT (CCT) compared with CMR in the investigation of the presence of delayed contrast enhancement (DCE) in subjects with DCM. Methods We prospectively enrolled 17 consecutive patients with DCM, who were initially referred to our institution because of recently manifested heart failure due to unexplained left ventricular systolic dysfunction. In all subjects, CCT and DE-CMR were performed within 1 week. Results CCT and DE-CMR showed satisfactory agreement in detecting DCE (agreement in 82% cases, κ = 0.56) with 50% sensitivity, 100% specificity, and a positive predictive value of 100%. Conclusion CCT may be a valuable method for detecting DCE in patients with DCM. CCT thus might be considered as an alternative method to DE-CMR in the assessment of the presence and extent of myocardial fibrosis in subjects who are not suitable for DE-CMR examination.

Correction to: Gene Therapy (2016) 23, 380–392; doi:10.1038/gt.2016.11 The initial Figure 2a was erroneously generated from a file from a mouse injected with conventional AAV9-GFP and not exo-AAV9-GFP, as described in the manuscript. We have therefore reformatted this specific panel, and corrected Figure 2a and the figure legend accordingly, now showing an image of the GFP signal detected by 2-photon microscopy after intravenous injection of exo-AAV9-GFP in a mouse.

This paper is an extension of our previous paper (Mašek and Rohlena, 2015), where we applied a transform method for the solution of Vlasov–Maxwell set of equations in a one-dimensional geometry to describe the Raman backscattering of the heating ns laser wave in the external corona of the generated laser plasma in a strongly non-linear regime. The method is stabilized by a simplified Fokker–Planck collision term, which, in turn, is used for a study of the influence of collisional and collisionless damping mechanisms of the daughter electron plasma wave (EPW) on the instability development and their competition resulting in a different instability behavior in various plasma configurations. The physics of trapped electrons is studied in detail and compared to the resulting Raman reflectivity. The Raman reflectivity was found to depend strongly on the intensity of laser irradiation in the different regions of the plasma corona. This is discussed in detail from the point of view of trapped electrons behavior in the EPW. Moreover, a study of the Raman reflectivity dependence on the electron–ion collision frequency (average plasma ionization) is presented, too. The results supplement the physical picture of the collision and collisionless processes influencing the Raman instability non-linear development.

Metabolic syndrome (MS) is frequent clinical condition in patients with hypertension. Primary aldosteronism (PA) is a common form of secondary hypertension. This study was aimed at investigating the prevalence of the MS and its components in the two major forms of PA, in unilateral aldosterone-producing adenoma (APA) and bilateral aldosterone overproduction because of idiopathic hyperaldosteronism (IHA). The diagnosis of the particular form of PA was based on adrenal venous sampling and/or successful surgery confirmed by histopathological examination. We analyzed clinical and laboratory data from 100 patients with PA (50 patients with IHA and 50 patients with APA) and from 90 patients with essential hypertension (EH). Metabolic profiles of patients with bilateral form of PA (because of IHA) were similar to EH, but differed from those in patients with unilateral form of PA (APA). The prevalence of the MS (62% in IHA, 34% in APA and 56% in EH), the body mass index value (30±4 kg m –2 in IHA, 27±5 kg m –2 in APA and 29±5 kg m –2 in EH) and triglycerides levels (1.9±0.9 mmol l –1 in IHA,1.4±0.8 mmol l –1 in APA and 2.01±1.39 mmol l –1 in EH) were all significantly ( P <0.05) higher in IHA compared with APA patients. Metabolic profile of patients with bilateral form of PA (because of IHA) is similar to EH in contrast to unilateral form of PA (APA).

Given that healthcare costs in the U.S. continue to climb, engineering managers can help address this situation by identifying designs for cost savings. Using discrete-event simulation, the layout of four different healthcare clinic scenarios considered in a redesign program named Patient Aligned Care Teams were studied. Model 1 is an existing layout in many clinics and Model 2 is staff-centered, while Models 3 and 4 provide additional space including common hallway(s). Our main conclusion is that Model 4 reduces patient travel distances and average queueing waits, while also providing the best privacy in accordance with HIPAA and the most security for the staff.

Monitoring maritime traffic has become an important task for ensuring the safety of vessels, as well as the goods, and persons that they may be transporting. An active area of research is the modelling of expected normal vessel behaviour so as to detect subsequent anomalies in new data. Anomalies indicate that a vessel is not behaving in an expected manner and their detection can be flagged for further investigation to identify whether the vessel needs assistance or intervention. An important factor for some vessels in determining normal behaviour is seasonal context. However, current approaches typically do not incorporate seasonality into the model.In this paper, an approach is presented where seasonal context is incorporated into the behaviour model. Seasonal context is first incorporated into vessel trajectory data by encoding the month of year into a historic dataset. Following this, a model of normal behaviour is generated using a clustering approach, with DBSCAN used in this paper. Details of setting the DBSCAN parameters appropriately for vessel trajectory data are provided and four distance metrics explored. Resulting cluster models are evaluated in the context of using the model to classify previously unseen data as either fitting the model or constituting an anomaly. The experiments focus on using fishing vessels within two identified seasons to build the normal model, which is evaluated with a mixture of in season and out of season fishing and non-fishing vessel behaviour.

Invasive meningococcal disease (IMD) is a serious, vaccine-preventable infectious disease that can be life-threatening. Teaching adolescents about the early detection and prevention of IMD can be challenging in a school environment, with educators reporting they lack confidence or expertise to cover this in the classroom environment. Professional guest educators are an alternative to cover specialist topics such as IMD; however, time and resourcing constraints can mean that these educators are not always available. Serious games may be an alternative to face-to-face education, where complex health information may be delivered via self-directed gameplay. This study aims to develop a serious game that can replace a face-to-face educator in a classroom setting to educate adolescents aged 12 years to 15 years. This study evaluates the efficacy of the Meningococcal Immunisation Awareness, Prevention and Protection app (MIApp), a serious game designed to replicate the information provided in a 30-minute face-to-face presentation provided by a trained educator. This clustered, randomized controlled equivalence trial involved students (Years 7-10) from 6 secondary schools across metropolitan Western Australia who completed pre- and postintervention questionnaires with a follow-up at 3 months postintervention to measure the primary outcome of IMD knowledge acquisition following this self-guided intervention. The findings were compared with changes in an active control (comparison) group who received an in-class educational presentation about IMD transmission and protection. A questionnaire was developed to assess 9 key areas of knowledge. Median scores for knowledge pre- and postintervention were collected from a self-administered assessment of this questionnaire and, at 3 months postintervention, were compared between groups. A knowledge score of +/-2/16 was determined a priori to meet the criteria for equivalence. Participants who used MIApp were also asked a series of questions to assess the enjoyment of and engagement with the game. Of the 788 participating students, the median postintervention correct score in both the MIApp and control cohorts was 14/16 (87.5% correct responses), compared with the median pre-intervention correct score of 6/16 (37.5% correct responses), representing a significant (P<.001) increase in IMD knowledge in both groups. Improvements were retained in both groups 3 months after the initial intervention (median correct score: 11/16 in the intervention group; 12/16 in the control group; P=.86), demonstrating the efficacy of MIApp to deliver health education about IMD transmission and protection, although response rates in the follow-up cohort were low (255/788, 32.4%). MIApp met the predetermined threshold for equivalence, demonstrating similar improvements in knowledge posttrial and at the 3-month follow-up. Participating adolescents considered the MIApp game more enjoyable than a presentation, with equivalent improvements in knowledge. Serious games could represent a constructive tool to help teachers impart specialized health education.