Real-time in vivo dosimetry in high dose rate prostate brachytherapy

Background and purpose: Single fraction treatments of 15 Gy or 19 Gy are common in HDR prostate brachytherapy. In vivo dosimetry (IVD) is therefore important to ensure patient safety. This study assesses clinical IVD and investigates error detection thresholds for real-time treatment monitoring. Materials and methods: IVD was performed for 40 treatments planned using intra-operative trans-rectal ultrasound (TRUS) with a MOSFET inserted into an additional needle. Post-treatment TRUS images were acquired for 20 patients to assess needle movement. Monte Carlo simulations of treatment plans were performed for 10 patients to assess impact of heterogeneities. Per-needle and total plan uncertainties were estimated and retrospectively applied to the measured data as error detection thresholds. Results: The mean measured dose was −6.4% compared to prediction (range + 5.1% to −15.2%). Needle movement and heterogeneities accounted for −1.8% and −1.6% of this difference respectively (mean values for the patients analysed). Total plan uncertainty (k = 2) ranged from 11% to 17% and per needle uncertainty (k = 2) ranged from 18% to 110% (mean 31%). One out of 40 plans and 5% of needles were outside k = 2 error detection threshold. Conclusions: IVD showed good agreement with predicted dose within measurement uncertainties, providing reassurance in the accuracy of dose delivery. Thresholds for real-time error detection should be calculated on an individual plan/needle basis

North Atlantic ocean circulation and abrupt climate change during the last glaciation.

The most recent ice age was characterized by rapid and hemispherically asynchronous climate oscillations, whose origin remains unresolved. Variations in oceanic meridional heat transport may contribute to these repeated climate changes, which were most pronounced during marine isotope stage 3, the glacial interval 25 thousand to 60 thousand years ago. We examined climate and ocean circulation proxies throughout this interval at high resolution in a deep North Atlantic sediment core, combining the kinematic tracer protactinium/thorium (Pa/Th) with the deep water-mass tracer, epibenthic δ(13)C. These indicators suggest reduced Atlantic overturning circulation during every cool northern stadial, with the greatest reductions during episodic Hudson Strait iceberg discharges, while sharp northern warming followed reinvigorated overturning. These results provide direct evidence for the ocean's persistent, central role in abrupt glacial climate change

A Systematic Review of the Clinical Implementation of Pelvic Magnetic Resonance Imaging (MR)-Only Planning for External Beam Radiation Therapy

The use of magnetic resonance imaging (MRI) scans alone for radiotherapy treatment planning (MR-only planning) has been highlighted as one method of improving patient outcomes. Recent technological advances have meant that introducing MR-only planning to the clinic is now becoming a reality, with several specialist radiotherapy clinics treating patients with this technique. As such, substantial efforts are being made to introduce this technique into wide-spread clinical implementation. A systematic review of publications investigating the clinical implementation of pelvic MR-only radiotherapy treatment planning was undertaken following the PRISMA guidelines. The Medline, Embase, Scopus, Science Direct, CINAHL and Web of Science databases were searched (timespan: all years to 2nd January 2019). Twenty six articles met the inclusion criteria. The studies were grouped into the following categories: 1. MR acquisition and synthetic-CT generation verification, 2. MR distortion quantification and phantom development, 3. Clinical validation of patient treatment positioning in an MR-only workflow and 4. MR-only commissioning processes. Key conclusions from this review are: i) MR-only planning has been clinically implemented for prostate cancer treatments; ii) A substantial amount of work remains to translate MR-only planning into wide spread clinical implementation for all pelvic sites; iii) MR scanner distortions are no longer a barrier to MR-only planning; however they must be managed appropriately; iv) MR-only based patient positioning verification shows promise, however limited evidence is reported in the literature and further investigation is required; and v) a number of MR-only commissioning processes have been reported which can aid centres as they undertake local commissioning, however this needs to be formalised in guidance from national bodies

Engineering the Fab fragment of the anti-IgE omalizumab to prevent Fab crystallization and permit IgE-Fc complex crystallization

Immunoglobulin E (IgE) plays a central role in the allergic response, in which cross-linking of allergen by Fc[epsilon]RI-bound IgE triggers mast cell and basophil degranulation and the release of inflammatory mediators. The high-affinity interaction between IgE and Fc[epsilon]RI is a long-standing target for therapeutic intervention in allergic disease. Omalizumab is a clinically approved anti-IgE monoclonal antibody that binds to free IgE, also with high affinity, preventing its interaction with Fc[epsilon]RI. All attempts to crystallize the pre-formed complex between the omalizumab Fab and the Fc region of IgE (IgE-Fc), to understand the structural basis for its mechanism of action, surprisingly failed. Instead, the Fab alone selectively crystallized in different crystal forms, but their structures revealed intermolecular Fab/Fab interactions that were clearly strong enough to disrupt the Fab/IgE-Fc complexes. Some of these interactions were common to other Fab crystal structures. Mutations were therefore designed to disrupt two recurring packing interactions observed in the omalizumab Fab crystal structures without interfering with the ability of the omalizumab Fab to recognize IgE-Fc; this led to the successful crystallization and subsequent structure determination of the Fab/IgE-Fc complex. The mutagenesis strategy adopted to achieve this result is applicable to other intractable Fab/antigen complexes or systems in which Fabs are used as crystallization chaperones

DeepBrain: Functional Representation of Neural In-Situ Hybridization Images for Gene Ontology Classification Using Deep Convolutional Autoencoders

This paper presents a novel deep learning-based method for learning a functional representation of mammalian neural images. The method uses a deep convolutional denoising autoencoder (CDAE) for generating an invariant, compact representation of in situ hybridization (ISH) images. While most existing methods for bio-imaging analysis were not developed to handle images with highly complex anatomical structures, the results presented in this paper show that functional representation extracted by CDAE can help learn features of functional gene ontology categories for their classification in a highly accurate manner. Using this CDAE representation, our method outperforms the previous state-of-the-art classification rate, by improving the average AUC from 0.92 to 0.98, i.e., achieving 75% reduction in error. The method operates on input images that were downsampled significantly with respect to the original ones to make it computationally feasible

Two in one: cryptic species discovered in biological control agent populations using molecular data and crossbreeding experiments

There are many examples of cryptic species that have been identified through DNA-barcoding or other genetic techniques. There are, however, very few confirmations of cryptic species being reproductively isolated. This study presents one of the few cases of cryptic species that has been confirmed to be reproductively isolated and therefore true species according to the biological species concept. The cryptic species are of special interest because they were discovered within biological control agent populations. Two geographically isolated populations of Eccritotarsus catarinensis (Carvalho) [Hemiptera: Miridae], a biological control agent for the invasive aquatic macrophyte, water hyacinth, Eichhornia crassipes (Mart.) Solms [Pontederiaceae], in South Africa, were sampled from the native range of the species in South America. Morphological characteristics indicated that both populations were the same species according to the current taxonomy, but subsequent DNA analysis and breeding experiments revealed that the two populations are reproductively isolated. Crossbreeding experiments resulted in very few hybrid offspring when individuals were forced to interbreed with individuals of the other population, and no hybrid offspring were recorded when a choice of mate from either population was offered. The data indicate that the two populations are cryptic species that are reproductively incompatible. Subtle but reliable diagnostic characteristics were then identified to distinguish between the two species which would have been considered intraspecific variation without the data from the genetics and interbreeding experiments. These findings suggest that all consignments of biological control agents from allopatric populations should be screened for cryptic species using genetic techniques and that the importation of multiple consignments of the same species for biological control should be conducted with caution

Chiral Dynamics in Photo-Pion Physics: Theory, Experiment, and Future Studies at the HIγ\gammaS Facility

A review of photo-pion experiments on the nucleon in the near threshold region is presented. Comparisons of the results are made with the predictions of the low energy theorems of QCD calculated using chiral perturbation theory (ChPT) which is based on the spontaneous breaking of chiral symmetry as well as its explicit breaking due to the finite quark masses. As a result of the vanishing of the threshold amplitudes in the chiral limit, the experiments are difficult since the cross sections are small. Nevertheless the field has been brought to a mature stage of accuracy and sensitivity. The accomplishments and limitations of past experiments are discussed. Future planned experiments at Mainz and HI$\gamma$S using polarization observables are discussed as a more rigorous test of theoretical calculations. Emphasis is given to the technical developments that are required for the HI$\gamma$S facility. It is shown that future experiments will provide more accurate tests of ChPT and will be sensitive to isospin breaking dynamics due to the mass difference of the up and down quarks.Comment: 61 pages, 10 figures, 2 table

Delayed onset of changes in soma action potential genesis in nociceptive A-beta DRG neurons in vivo in a rat model of osteoarthritis

<p>Abstract</p> <p>Background</p> <p>Clinical data on osteoarthritis (OA) suggest widespread changes in sensory function that vary during the progression of OA. In previous studies on a surgically-induced animal model of OA we have observed that changes in structure and gene expression follow a variable trajectory over the initial days and weeks. To investigate mechanisms underlying changes in sensory function in this model, the present electrophysiological study compared properties of primary sensory nociceptive neurons at one and two months after model induction with properties in naïve control animals. Pilot data indicated no difference in C- or Aδ-fiber associated neurons and therefore the focus is on Aβ-fiber nociceptive neurons.</p> <p>Results</p> <p>At one month after unilateral derangement of the knee by cutting the anterior cruciate ligament and removing the medial meniscus, the only changes observed in Aβ-fiber dorsal root ganglion (DRG) neurons were in nociceptor-like unresponsive neurons bearing a hump on the repolarization phase; these changes consisted of longer half width, reflecting slowed dynamics of AP genesis, a depolarized Vm and an increased AP amplitude. At two months, changes observed were in Aβ-fiber high threshold mechanoreceptors, which exhibited shorter AP duration at base and half width, shorter rise time and fall time, and faster maximum rising rate/maximum falling rate, reflecting accelerated dynamics of AP genesis.</p> <p>Conclusion</p> <p>These data indicate that Aβ nociceptive neurons undergo significant changes that vary in time and occur later than changes in structure and in nociceptive scores in this surgically induced OA model. Thus, if changes in Aβ-fiber nociceptive neurons in this model reflect a role in OA pain, they may relate to mechanisms underlying pain associated with advanced OA.</p

Penerapan Metode Field Trip dalam Pembelajaran Menulis Karangan Deskripsi pada Siswa Tunarungu

Penelitian ini bertujuan untuk meningkatkan aktivitas dalam proses pembelajaran menulis karangan deskripsi, meningkatkan kemampuan dalam menulis karangan dekripsi sesuai dengan penyusunan Subjek, Predikat, Objektif dan Keterangan  pada siswa tunarungu di SMPLB-B YPTB Malang.  Penelitian ini menggunakan Quasi Eksperimen dengan desain penelitian one-group-pretestposttest-design. Sampel dari penelitian ini 10 siswa SMPLB-B YPTB Malang dengan mata pelajaran Bahasa Indonesia. Teknik pengumpulan data dengan observasi, wawancara, tes dan dokumentasi. Analisis data menggunakan Uji Wilcoxon Signed Rank Test. Berdasarkan hasil penelitian penggunaan metode field trip dalam menulis karangan deskripsi dapat mempengaruhi hasil belajar siswa secara signifikan dibandingkan dengan prnggunaan metode konvensional.

Input-to-state stability of infinite-dimensional control systems

We develop tools for investigation of input-to-state stability (ISS) of infinite-dimensional control systems. We show that for certain classes of admissible inputs the existence of an ISS-Lyapunov function implies the input-to-state stability of a system. Then for the case of systems described by abstract equations in Banach spaces we develop two methods of construction of local and global ISS-Lyapunov functions. We prove a linearization principle that allows a construction of a local ISS-Lyapunov function for a system which linear approximation is ISS. In order to study interconnections of nonlinear infinite-dimensional systems, we generalize the small-gain theorem to the case of infinite-dimensional systems and provide a way to construct an ISS-Lyapunov function for an entire interconnection, if ISS-Lyapunov functions for subsystems are known and the small-gain condition is satisfied. We illustrate the theory on examples of linear and semilinear reaction-diffusion equations.Comment: 33 page