Bubble Raft Model for a Paraboloidal Crystal

We investigate crystalline order on a two-dimensional paraboloid of revolution by assembling a single layer of millimeter-sized soap bubbles on the surface of a rotating liquid, thus extending the classic work of Bragg and Nye on planar soap bubble rafts. Topological constraints require crystalline configurations to contain a certain minimum number of topological defects such as disclinations or grain boundary scars whose structure is analyzed as a function of the aspect ratio of the paraboloid. We find the defect structure to agree with theoretical predictions and propose a mechanism for scar nucleation in the presence of large Gaussian curvature.Comment: 4 pages, 4 figure

Inter-study reproducibility of arterial spin labelling magnetic resonance imaging for measurement of renal perfusion in healthy volunteers at 3 Tesla

Background: Measurement of renal perfusion is a crucial part of measuring kidney function. Arterial spin labelling magnetic resonance imaging (ASL MRI) is a non-invasive method of measuring renal perfusion using magnetised blood as endogenous contrast. We studied the reproducibility of ASL MRI in normal volunteers.<p></p> Methods: ASL MRI was performed in healthy volunteers on 2 occasions using a 3.0 Tesla MRI scanner with flow-sensitive alternating inversion recovery (FAIR) perfusion preparation with a steady state free precession (True-FISP) pulse sequence. Kidney volume was measured from the scanned images. Routine serum and urine biochemistry were measured prior to MRI scanning.<p></p> Results: 12 volunteers were recruited yielding 24 kidneys, with a mean participant age of 44.1 ± 14.6 years, blood pressure of 136/82 mmHg and chronic kidney disease epidemiology formula estimated glomerular filtration rate (CKD EPI eGFR) of 98.3 ± 15.1 ml/min/1.73 m2. Mean kidney volumes measured using the ellipsoid formula and voxel count method were 123.5 ± 25.5 cm3, and 156.7 ± 28.9 cm3 respectively. Mean kidney perfusion was 229 ± 41 ml/min/100 g and mean cortical perfusion was 327 ± 63 ml/min/100 g, with no significant differences between ASL MRIs. Mean absolute kidney perfusion calculated from kidney volume measured during the scan was 373 ± 71 ml/min. Bland Altman plots were constructed of the cortical and whole kidney perfusion measurements made at ASL MRIs 1 and 2. These showed good agreement between measurements, with a random distribution of means plotted against differences observed. The intra class correlation for cortical perfusion was 0.85, whilst the within subject coefficient of variance was 9.2%. The intra class correlation for whole kidney perfusion was 0.86, whilst the within subject coefficient of variance was 7.1%.<p></p> Conclusions: ASL MRI at 3.0 Tesla provides a repeatable method of measuring renal perfusion in healthy subjects without the need for administration of exogenous compounds. We have established normal values for renal perfusion using ASL MRI in a cohort of healthy volunteers.<p></p&gt

Cost-effectiveness of microendoscopic discectomy versus conventional open discectomy in the treatment of lumbar disc herniation

Background: Open discectomy is the standard surgical procedure in the treatment of patients with long-lasting sciatica caused by lumbar disc herniation. Minimally invasive approaches such as microendoscopic discectomy have gained attention in recent years. Reduced tissue trauma allows early ambulation, short hospital stay and quick resumption of daily activities. A comparative cost-effectiveness study has not been performed yet. We present the design of a randomised controlled trial on cost-effectiveness of microendoscopic discectomy versus conventional open discectomy in patients with lumbar disc herniation. Methods/Design: Patients (age 18-70 years) presenting with sciatica due to lumbar disc herniation lasting more than 6-8 weeks are included. Patients with disc herniation larger than 1/3 of the spinal canal diameter, or disc herniation less than 1/3 of the spinal canal diameter with concomitant lateral recess stenosis or sequestration, are eliglible for participation. Randomisation into microendoscopic discectomy or conventional unilateral transflaval discectomy will take place in the operating room after induction of anesthesia. The length of skin incision is equal in both groups. The primary outcome measure is the functional assessment of the patient, measured by the Roland Disability Questionnaire for Sciatica, at 8 weeks and 1 year after surgery. We will also evaluate several other outcome parameters, including perceived recovery, leg and back pain, incidence of re-operations, complications, serum creatine kinase, quality of life, medical consumption, absenteeism and costs. The study is a randomised prospective multi-institutional trial, in which two surgical techniques are compared in a parallel group design. Patients and research nurses are kept blinded of the allocated treatment during the follow-up period of 2 years. Discussion: Currently, open discectomy is the golden standard in the surgical treatment of lumbar disc herniation. Whether microendoscopic discectomy is more cost-effective than unilateral transflaval discectomy has to be determined by this trial

Multi-component physical activity interventions in the UK must consider determinants of activity to increase effectiveness

Interventions to increase physical activity in children have adopted broad approaches and achieved varying success. There is a need to adopt approaches underpinned with a theoretical basis. Accordingly, the aim here was to implement and evaluate a 12-week intervention designed using the concepts of the COM-B model to determine the effect this has on physical activity levels. One hundred and forty-seven school-age children (mean age 8.9 ± 1.3 years) took part in a 12-week program delivered in a school setting. Topics included physical activity, healthy eating, sleep quality and reducing screen time/sedentary activities when not in school. A sample of participants wore a wrist-worn accelerometer for seven days pre-and post-intervention (N = 11). The physical activity frequency was unchanged (2.9 ± 1.0 AU) when compared with post-intervention values (3.1 ± 0.8 AU, mean increase 6.8 ± 3.7%, p > 0.05). Changes were observed in the daily consumption of fruit and vegetables (pre-intervention 44.6% vs. post-intervention 60.2%, p p > 0.05). There is a need to adopt a broader approach that incorporates a theoretical basis and considers the complex ways by which physical activity behaviours are influenced

FISSA: A neuropil decontamination toolbox for calcium imaging signals

In vivo calcium imaging has become a method of choice to image neuronal population activity throughout the nervous system. These experiments generate large sequences of images. Their analysis is computationally intensive and typically involves motion correction, image segmentation into regions of interest (ROIs), and extraction of fluorescence traces of each ROI. Out of focus fluorescence from surrounding neuropil and other cells can strongly contaminate the signal assigned to a given ROI. In this study, we introduce the FISSA toolbox (Fast Image Signal Separation Analysis) for neuropil decontamination. Given pre-defined ROIs, the FISSA toolbox automatically extracts the surrounding local neuropil and performs blind-source separation with non-negative matrix factorization. Using both simulated and in vivo data, we show that this toolbox performs similarly or better than existing published methods. FISSA requires only little RAM, allowing for fast processing of large datasets even on a standard laptop. The FISSA toolbox is available in Python, with an option for MATLAB format outputs, and can easily be integrated into existing workflows. It is available from Github and the standard Python repositories

Threshold neutral pion photoproduction off the tri-nucleon to O(q^4)

We calculate electromagnetic neutral pion production off tri-nucleon bound states (3H, 3He) at threshold in chiral nuclear effective field theory to fourth order in the standard heavy baryon counting. We show that the fourth order two-nucleon corrections to the S-wave multipoles at threshold are very small. This implies that a precise measurement of the S-wave cross section for neutral pion production off 3He allows for a stringent test of the chiral perturbation theory prediction for the S-wave electric multipole E_{0+}^{pi0 n}.Comment: 17 pages, 5 figures, title changed, final version to appear in EPJA. arXiv admin note: substantial text overlap with arXiv:1103.340

Sequential Alcohol Septal Ablation to Resolve LV Outflow Tract Obstruction After Transcatheter Mitral Valve Replacement

Left ventricular outflow tract obstruction (LVOTO) is a notorious complication of transcatheter mitral valve replacement (TMVR). Computed tomography–derived simulations can predict neo-LVOTO post-TMVR, whereas alcohol septal ablation can mitigate neo-LVOTO risk. We report a case of sequential alcohol septal ablation of 2 adjacent septal branches to resolve unexpected neo-LVOTO post-TMVR.</p

First-line palliative HER2-targeted therapy in HER2-positive metastatic breast cancer is less effective after previous adjuvant trastuzumab-based therapy

Background. Survival of patients with human epidermal growth receptor 2 (HER2)-positive metastatic breast cancer (MBC) has improved dramatically since trastuzumab has become available, although the disease eventually progresses in most patients. This study investigates the outcome (overall survival [OS] and time to next treatment [TNT]) in MBC patients pretreated with trastuzumab in the adjuvant setting (TP-group) compared with trastuzumab-näive patients (TN-group) in order to investigate the possibility of trastuzumab resistance. Patients and Methods. Patients treated with first-line HER2-targeted- containing chemotherapy were eligible for the study. A power analysis was performed to estimate the minimum size of the TP-group. OS and TNT were estimated using Kaplan-Meier curves andmultivariable Cox proportional hazards models. Results. Between January 1, 2000, and June 1, 2014, 469 patients were included, of whom 82 were in the TP-group and 387 were in the TN-group. Median OS and TNT were significantly worse in the TP-group compared with the TN-group (17 vs. 30 months, adjusted hazard ratio [HR] 1.84 [1.15-2.96], p5.01 and 7 vs. 13 months, adjusted HR 1.65 [1.06-2.58], p5.03) after adjustment for age, year of diagnosis, diseasefree interval, hormone receptor status, metastatic site, and cytotoxic regimens. Conclusion. First-line trastuzumab-containing treatment regimens are less effective in patients with failure of adjuvant trastuzumab compared with trastuzumab-näive patients and might be due to trastuzumab resistance. The impact of trastuzumab resistance on the response on dual HER2 blockade with trastuzumab and pertuzumab and how resistance mechanisms can be used in the optimization of HER2-targeted treatment lines need further investigation.</p

Microclusters of inhibitory killer immunoglobulin–like receptor signaling at natural killer cell immunological synapses

We report the supramolecular organization of killer Ig–like receptor (KIR) phosphorylation using a technique applicable to imaging phosphorylation of any green fluorescent protein–tagged receptor at an intercellular contact or immune synapse. Specifically, we use fluorescence lifetime imaging (FLIM) to report Förster resonance energy transfer (FRET) between GFP-tagged KIR2DL1 and a Cy3-tagged generic anti-phosphotyrosine monoclonal antibody. Visualization of KIR phosphorylation in natural killer (NK) cells contacting target cells expressing cognate major histocompatibility complex class I proteins revealed that inhibitory signaling is spatially restricted to the immune synapse. This explains how NK cells respond appropriately when simultaneously surveying susceptible and resistant target cells. More surprising, phosphorylated KIR was confined to microclusters within the aggregate of KIR, contrary to an expected homogeneous distribution of KIR signaling across the immune synapse. Also, yellow fluorescent protein–tagged Lck, a kinase important for KIR phosphorylation, accumulated in a multifocal distribution at inhibitory synapses. Spatial confinement of receptor phosphorylation within the immune synapse may be critical to how activating and inhibitory signals are integrated in NK cells