Conditional Restricted Boltzmann Machines for Structured Output Prediction

Conditional Restricted Boltzmann Machines (CRBMs) are rich probabilistic models that have recently been applied to a wide range of problems, including collaborative filtering, classification, and modeling motion capture data. While much progress has been made in training non-conditional RBMs, these algorithms are not applicable to conditional models and there has been almost no work on training and generating predictions from conditional RBMs for structured output problems. We first argue that standard Contrastive Divergence-based learning may not be suitable for training CRBMs. We then identify two distinct types of structured output prediction problems and propose an improved learning algorithm for each. The first problem type is one where the output space has arbitrary structure but the set of likely output configurations is relatively small, such as in multi-label classification. The second problem is one where the output space is arbitrarily structured but where the output space variability is much greater, such as in image denoising or pixel labeling. We show that the new learning algorithms can work much better than Contrastive Divergence on both types of problems

Effect of variations in atelectasis on tumor displacement during radiation therapy for locally advanced lung cancer

Purpose Atelectasis (AT), or collapsed lung, is frequently associated with central lung tumors. We investigated the variation of atelectasis volumes during radiation therapy and analyzed the effect of AT volume changes on the reproducibility of the primary tumor (PT) position. Methods and materials Twelve patients with lung cancer who had AT and 10 patients without AT underwent repeated 4-dimensional fan beam computed tomography (CT) scans during radiation therapy per protocols that were approved by the institutional review board. Interfraction volume changes of AT and PT were correlated with PT displacements relative to bony anatomy using both a bounding box (BB) method and change in center of mass (COM). Linear regression modeling was used to determine whether PT and AT volume changes were independently associated with PT displacement. PT displacement was compared between patients with and without AT. Results The mean initial AT volume on the planning CT was 189 cm3 (37-513 cm3), and the mean PT volume was 93 cm3 (12-176 cm3). During radiation therapy, AT and PT volumes decreased on average 136.7 cm3 (20-369 cm3) for AT and 40 cm3 (−7 to 131 cm3) for PT. Eighty-three percent of patients with AT had at least one unidirectional PT shift that was greater than 0.5 cm outside of the initial BB during treatment. In patients with AT, the maximum PT COM shift was ≥0.5 cm in all patients and \u3e1 cm in 58% of patients (0.5-2.4 cm). Changes in PT and AT volumes were independently associated with PT displacement (P \u3c .01), and the correlation was smaller with COM (R2 = 0.58) compared with the BB method (R2 = 0.80). The median root mean squared PT displacement with the BB method was significantly less for patients without AT (0.45 cm) compared with those with AT (0.8cm, P = .002). Conclusions Changes in AT and PT volumes during radiation treatment were significantly associated with PT displacements that often exceeded standard setup margins. Repeated 3-dimensional imaging is recommended in patients with AT to evaluate for PT displacements during treatment. Summary This study analyzed 12 patients with atelectasis and 10 patients without atelectasis who underwent repeat 4-dimensional fan beam computed tomography during radiation therapy. Patients with atelectasis had significantly greater tumor displacements than patients without atelectasis, and these tumor displacements often exceeded standard setup margins. Patients with atelectasis may benefit from repeated 3-dimensional imaging during radiation therapy and possible replanning for large tumor displacements

Effect of variations in atelectasis on tumor displacement during radiation therapy for locally advanced lung cancer

Purpose Atelectasis (AT), or collapsed lung, is frequently associated with central lung tumors. We investigated the variation of atelectasis volumes during radiation therapy and analyzed the effect of AT volume changes on the reproducibility of the primary tumor (PT) position. Methods and materials Twelve patients with lung cancer who had AT and 10 patients without AT underwent repeated 4-dimensional fan beam computed tomography (CT) scans during radiation therapy per protocols that were approved by the institutional review board. Interfraction volume changes of AT and PT were correlated with PT displacements relative to bony anatomy using both a bounding box (BB) method and change in center of mass (COM). Linear regression modeling was used to determine whether PT and AT volume changes were independently associated with PT displacement. PT displacement was compared between patients with and without AT. Results The mean initial AT volume on the planning CT was 189 cm3 (37-513 cm3), and the mean PT volume was 93 cm3 (12-176 cm3). During radiation therapy, AT and PT volumes decreased on average 136.7 cm3 (20-369 cm3) for AT and 40 cm3 (−7 to 131 cm3) for PT. Eighty-three percent of patients with AT had at least one unidirectional PT shift that was greater than 0.5 cm outside of the initial BB during treatment. In patients with AT, the maximum PT COM shift was ≥0.5 cm in all patients and \u3e1 cm in 58% of patients (0.5-2.4 cm). Changes in PT and AT volumes were independently associated with PT displacement (P \u3c .01), and the correlation was smaller with COM (R2 = 0.58) compared with the BB method (R2 = 0.80). The median root mean squared PT displacement with the BB method was significantly less for patients without AT (0.45 cm) compared with those with AT (0.8cm, P = .002). Conclusions Changes in AT and PT volumes during radiation treatment were significantly associated with PT displacements that often exceeded standard setup margins. Repeated 3-dimensional imaging is recommended in patients with AT to evaluate for PT displacements during treatment. Summary This study analyzed 12 patients with atelectasis and 10 patients without atelectasis who underwent repeat 4-dimensional fan beam computed tomography during radiation therapy. Patients with atelectasis had significantly greater tumor displacements than patients without atelectasis, and these tumor displacements often exceeded standard setup margins. Patients with atelectasis may benefit from repeated 3-dimensional imaging during radiation therapy and possible replanning for large tumor displacements

An Investigation of the Application of the Golden Ratio and Fibonacci Sequence Associated with the Chart of Nuclides

The aim of this investigation was to examine the relationship between the golden ratio and atomic structure. The chart of nuclides was evaluated for evidence of a true golden ratio. That is, the neutron number divided by the proton number needed to equal 1.618 and the atomic number (neutrons plus protons) divided by the neutron number needed to equal 1.618. Across the chart of nuclides, this ratio approximated the golden ratio to a varying degree of accuracy for some nuclides but rarely for both calculations. This relationship (golden ratio in the chart of nuclides) has not been previously reported. It was determined that specific nuclides exhibit the golden ratio between protons and neutrons, and that these produce a trend line on the chart of nuclides. The Fibonacci sequence is mathematically evident and this information can be used to postulate new nuclides or elements

Understanding the Role of Culture and Heritage in Community Festivals: An Importance-Performance Analysis

Festivals can support local communities by bringing in unique visitors who will inject new revenue into the economy. Continued evaluation of festivals is necessary to ensure they are meeting customer expectations, which will generate positive word-of-mouth advertising and repeat visitation. The research reported here used an importance-performance analysis to evaluate a regional festival in South Carolina. Particular attention was paid to the importance of the cultural aspects of the festival. Based on a survey of 212 festival attendees, several recommendations are made to festival planners. Results indicate that cultural aspects of the festival were not very important to attendees

Geological evolution of western H.U. Sverdrupfjella, Dronning Maud land, Antarctica.

Thesis (Ph.D.)-University of Natal, Pietermaritzburg, 1992.The oldest rocks of western H.U. Sverdrupfjella, the Jutulrora Formation, consist of interlayered mafic to felsic ortho- and paragneisses thought to represent calc-alkaline volcanic and clastic sedimentary rocks. These rocks are structurally overlain by the largely paragneissic, carbonate- dominated Fuglefjellet Formation which may represent a miogeosynclinal shelf facies. This sequence is structurally overlain by the dominantly para-gneissic Sveabreen Formation which may comprise a eugeosynclinal facies. Three granitic bodies, the Roerkulten, Jutulrora and Brekkerista Granites intrude the Jutulrora Formation. The trace element chemistry of these granites suggest that accessory minerals played significant roles during their generation and crystallization. Various mafic intrusions, now discordant amphibolites, and a phase of diorite veining are present. The Dalmatian Granite was emplaced syntectonically with the 470Ma Pan-African (or Ross) orogeny during D3. This granite was generated by crustal anatexis at >5kb. Jurassic age intrusions include alkaline complexes at Straumsvola and Tvora and numerous dolerite dykes, some of which postdate the alkali intrusions. Five episodes of deformation are recognised. The first two resulted in folds (F1 and F2) which are co-planar and coaxial resulting in type 3 interference structures. Low angle thrust faulting occurred during D2. Fold vergence and associated lineations suggest tectonic transport from the southeast during D1 and D2, D3 involved folding and reverse faulting. The orientations of the fault and axial planes of these structures suggest transport from the west and north-west. D4 involved open dome and basin folding. D6 involved normal faulting and jointing, adjacent and parallel to the Jutulstraumen Glacier in the west. The joints affect the Tvora Alkaline Complex. Three phases of metamorphism, related to the deformation, are recognised. The dominant mineral assemblages are typical of medium to high grade metamorphism and define S1 and S2 planar fabrics. Discordant mafic intrusions provide evidence of a long history of metamorphism. M3 mineral development, commonly represented by biotite, is oriented axial planar to D3 folds. Comparison of the geology of the area with that of southern Mozambique reveals many similarities. These support reconstructions based on geophysical data which juxtapose Dronning Maud Land and southern Africa prior to the break up of Gondwanaland

Respiratory motion variability of primary tumors and lymph nodes during radiotherapy of locally advanced non-small-cell lung cancers

Background and purpose The need for target adjustment due to respiratory motion variation and the value of carina as a motion surrogate is evaluated for locally advanced non-small-cell lung cancer. Material and methods Using weekly 4D CTs (with audio-visual biofeedback) of 12 patients, respiratory motion variation of primary tumors (PT), lymph nodes (LN) and carina (C) were determined. Results Mean (SD) 3D respiratory motion ranges of PT, LN and C were 4 (3), 5 (3) and 5 (3) mm. PT and LN (p = 0.003), and LN and C motion range were correlated (p = 0.03). Only 20 %/5 % of all scans had variations \u3e3 mm/5 mm. Large respiratory motion range on the initial scan was associated with larger during-treatment variations for PT (p = 0.03) and LN (p = 0.001). Mean (SD) 3D relative displacements of PT-C, LN-C and PT-LN were each 6 (2) mm. Variations of displacements \u3e3 mm/5 mm were observed in 28 %/6 % of scans for PT-LN, 20 %/9 % for PT-C, and 20 %/8 % for LN-C. Conclusions Motion reassessment is recommended in patients with large initial motion range. Relative motion-related displacements between PT and LN were larger than PT and LN motion alone. Both PT and C appear to be comparable surrogates for LN respiratory motion

Interobserver Reliability in Describing Radiographic Lung Changes After Stereotactic Body Radiation Therapy

Purpose Radiographic lung changes after stereotactic body radiation therapy (SBRT) vary widely between patients. Standardized descriptions of acute (≤6 months after treatment) and late (\u3e6 months after treatment) benign lung changes have been proposed but the reliable application of these classification systems has not been demonstrated. Herein, we examine the interobserver reliability of classifying acute and late lung changes after SBRT. Methods and materials A total of 280 follow-up computed tomography scans at 3, 6, and 12 months post-treatment were analyzed in 100 patients undergoing thoracic SBRT. Standardized descriptions of acute lung changes (3- and 6-month scans) include diffuse consolidation, patchy consolidation and ground glass opacity (GGO), diffuse GGO, patchy GGO, and no change. Late lung change classifications (12-month scans) include modified conventional pattern, mass-like pattern, scar-like pattern, and no change. Five physicians scored the images independently in a blinded fashion. Fleiss\u27 kappa scores quantified the interobserver agreement. Results The Kappa scores were 0.30 at 3 months, 0.20 at 6 months, and 0.25 at 12 months. The proportion of patients in each category at 3 and 6 months was as follows: Diffuse consolidation 11% and 21%; patchy consolidation and GGO 15% and 28%; diffuse GGO 10% and 11%; patchy GGO 15% and 15%; and no change 49% and 25%, respectively. The percentage of patients in each category at 12 months was as follows: Modified conventional 46%; mass-like 16%; scar-like 26%; and no change 12%. Uniform scoring between the observers occurred in 26, 8, and 14 cases at 3, 6, and 12 months, respectively. Conclusions Interobserver reliability scores indicate a fair agreement to classify radiographic lung changes after SBRT. Qualitative descriptions are insufficient to categorize these findings because most patient scans do not fit clearly into a single classification. Categorization at 6 months may be the most difficult because late and acute lung changes can arise at that time

Understanding how neutrophils self-organise their migration to sites of inflammation in vivo

Neutrophils are major effectors of acute inflammation and microbial defence. Their infiltration and migration in injured tissue are critical for the inflammatory response. They are often observed navigating in a highly co-ordinated and directed manner leading to their aggregation at the target site of infection. This self-organised cell gathering is referred to as swarming. It is known that neutrophil swarming is driven by autocrine attractant production, notably of the lipid leukotriene B4 (LTB4). The decision to release attractants at the single-cell level is important and impacts the magnitude of the entire immune response. However, the precise mechanisms triggering this decision remain unclear. In this study, I employed in vivo imaging of zebrafish larvae to reveal the molecular processes that trigger the release of LTB4 and initiation of swarms. I developed a 2-Photon laser wound assay to elicit and visualise neutrophil swarming. A major limitation in previous studies of neutrophil swarms was the lack of tools to understand cell signalling dynamics during the response. To overcome this, I generated a new biosensor to probe for calcium levels in neutrophils as it correlates with the production of chemoattractants. Using this new tool, I revealed that neutrophils clustering at the target inflammatory site are experiencing sustained high calcium elevation. Using a new probe to follow the production dynamics of LTB4, I demonstrated that the rise of intracellular calcium promotes the biosynthesis of this key attractant. I further demonstrated that these calcium fluxes are triggered upon contact with necrotic tissue. This prompted me to interrogate the damage molecules driving these calcium signals in neutrophils. I discovered that the calcium fluxes were mediated by ATP that binds gated ion channels (P2X1) leading to rapid intracellular calcium uptake. Surprisingly, I found that live neutrophils can also trigger this calcium flux in other neutrophils upon mutual contact. Using chemical and genetic inhibition, I found that connexin-43 (Cx43) hemichannels, through their ability to release ATP, enable amplification of the calcium signal leading to chemoattractant production and subsequent neutrophil recruitment. I concluded that activation of LTB4 synthesis is a group decision reached via Cx43-dependent communication in pioneer clustering neutrophils. As Cx43 inhibition significantly reduced neutrophil aggregation at the target site, I investigated if this inhibition could have consequences for wound defence. For this, I developed a wound colonisation assay with Pseudomonas aeruginosa. Using this approach, I showed that Cx43 was crucial for the protection of wounds from opportunistic bacteria. Finally, I designed and generated an optogenetic tool to manipulate LTB4 biosynthesis dynamics in vivo. I demonstrated the effectiveness of this tool in immortalised cells and zebrafish larvae. The unique features of this tool make it very useful for a wide range of research applications on signalling dynamics. In conclusion, I have shown that by reinforcing damage signalling, Cx43 channels coordinate attractant biosynthesis in pioneer neutrophils. This generates an effective chemoattractant gradient source and promotes targeted aggregation and defence. This study, therefore, reveals a new mechanistic principle of collective behaviour that could be exploited in future pathological research.Wellcome trust four-year programm