Journal articles on the topic 'Feature location (FL)'

Most patients with follicular lymphoma (FL) have somatically mutated V genes with intraclonal variation, consistent with location in the germinal center site. Using our own and published sequences, we have investigated the frequency of potential N-glycosylation sites introduced into functional VH genes as a consequence of somatic mutation. FL cells were compared with normal memory B cells or plasma cells matched for similar levels of mutation. Strikingly, novel sites were detected in 55 of 70 (79%) patients with FL, compared to 7 of 75 (9%) in the normal B-cell population (P < .001). Diffuse large B-cell lymphoma (DLCL) showed an intermediate frequency (13 of 32 [41%] patients). Myeloma and the mutated subset of chronic lymphocytic leukemia showed frequencies similar to those of normal cells in 5 of 64 (8%) patients and 5 of 40 (13%) patients, respectively. In 3 of 3 random patients with FL, immunoglobulin was expressed as recombinant single-chain Fv inPichia pastoris, and glycosylation was demonstrated. These findings indicate that N-glycosylation of the variable region may be common in FL and in a subset of DLCL. Most novel sites are located in the complementarity-determining regions. VH sequences of nonfunctional VH genes contained few sites, arguing for positive selection in FL. One possibility is that the added carbohydrate in the variable region contributes to interaction with elements in the germinal center environment. This common feature of FL may be critical for tumor behavior.

Wireless fingerprinting localization (FL) systems identify locations by building radio fingerprint maps, aiming to provide satisfactory location solutions for the complex environment. However, the radio map is easy to change, and the cost of building a new one is high. One research focus is to transfer knowledge from the old radio maps to a new one. Feature-based transfer learning methods help by mapping the source fingerprint and the target fingerprint to a common hidden domain, then minimize the maximum mean difference (MMD) distance between the empirical distributions in the latent domain. In this paper, the optimal transport (OT)-based transfer learning is adopted to directly map the fingerprint from the source domain to the target domain by minimizing the Wasserstein distance so that the data distribution of the two domains can be better matched and the positioning performance in the target domain is improved. Two channel-models are used to simulate the transfer scenarios, and the public measured data test further verifies that the transfer learning based on OT has better accuracy and performance when the radio map changes in FL, indicating the importance of the method in this field.

Abstract Immunogenetic analysis of B-cell malignancies can provide important information that relates to the cellular origin and clonal history of these lymphomas and give clues as to possible pathogenic mechanisms. In follicular lymphoma (FL), immunoglobulin variable region (V) genes are commonly somatically mutated and display intraclonal heterogeneity consistent with location in the germinal centre (GC). In this analysis of 44 cases of FL we find that, with minor exceptions, both the VH and VL gene usage reflects that of the normal B cell repertoire, indicative of a common antigenic drive and in support of a final transforming event in the GC. We have previously reported a high incidence of potential N-glycosylation sites in the VH genes of FL, which have been introduced by the process of somatic mutation. Here we have assessed both the VH and VL genes and find that sites are universally present and further demonstrate that they are available for functional glycosylation. The majority of sites are found in VH (81%) and are located predominantly within CDR2 and CDR3, with few sites present in the FRs. Sites are also evident in VL (45%) where they are focused mainly in CDR3 and CDR1. A minor subset (10%) has sites in VL only. In total, 26 different N-glycosylation motifs were observed, with NIS being the most commonly used. The natural motif in the V4–34 germline gene appears unimportant, and can be lost. Scrutiny of the somatic mutations giving rise to these motifs reveals that the acquisition of sites was predominantly (73%) achieved by a single amino acid (aa) replacement to Asn at position 1 of the motif, either with or without an additional, non-essential aa replacement at another position. Common ‘hotspots’ were observed within the CDR2 for the VH gene segments V3–23, V3–48, V3–07 and V3–15. It appears likely that the acquisition of N-glycosylation sites in the antigen-binding site during somatic mutation in the GC and the subsequent addition of oligosaccharides is important to the lifestyle of FL and may provide a critical second tumorigenic event. In turn, it may be possible to exploit this seemingly essential feature to develop novel therapeutic approaches.

Landslide inventory mapping (LIM) is a key prerequisite for landslide susceptibility evaluation and disaster mitigation. It aims to record the location, size, and extent of landslides in each map scale. Machine learning algorithms, such as support vector machine (SVM) and random forest (RF), have been increasingly applied to landslide detection using remote sensing images in recent decades. However, their limitations have impeded their wide application. Furthermore, despite the widespread use of deep learning algorithms in remote sensing, for LIM, deep learning algorithms are limited to less unbalanced landslide samples. To this end, in this study, full convolution networks with focus loss (FCN-FL) were adopted to map historical landslides in regions with imbalanced samples using an improved symmetrically connected full convolution network and focus loss function to increase the feature level and reduce the contribution of the background loss value. In addition, K-fold cross-validation training models (FCN-FLK) were used to improve data utilization and model robustness. Results showed that the recall rate, F1-score, and mIoU of the model were improved by 0.08, 0.09, and 0.15, respectively, compared to FCN. It also demonstrated advantages over U-Net and SegNet. The results prove that the method proposed in this study can solve the problem of imbalanced sample in landslide inventory mapping. This research provides a reference for addressing imbalanced samples in the deep learning of LIM.

Abstract Follicular lymphoma (FL) is typically a nodal disease. Primary extranodal FLs, that represent less than 10% of the cases, might have differentiated clinicobiological features. The aim of the present study was to analyze the main clinicobiological characteristics, response to therapy and outcome of a series of patients with FL primarily extranodal in origin, and compare them with nodal FLs. Twenty two patients (12M/10F; median age, 59 years) with FL with primary origin in extranodal location diagnosed in a single institution during a 24-year period, with primary origin in extranodal location were the subject of the study. The control group was constituted by 212 patients with nodal FL diagnosed during the same period of time. Main clinicobiological features were recorded and analyzed. The sites of the primary disease were: skin, 5 cases; Waldeyer’s ring, 4; GI tract, 3; bone marrow, CNS and parotid (two cases each); and pancreas, thyroid, kidney and orbit (one case each). Main histological and clinical features are listed in the table. Treatment was given without considering the nodal or extranodal origin of the disease and consisted of: monotherapy with alkylating agents (38 cases), polychemotherapy (149), and fludarabine alone or with other drugs (14) and others, including surgery and observation (33). CR rate was higher in extranodal than in nodal FL (82% vs. 53%, respectively; p=0.02), but no differences were found in overall survival. FLIPI score was the most significant variable predicting overall survival in the global series as well as in either in nodal or extranodal FL. In conclusion, extranodal FL had some peculiar clinicobiological features with respect to nodal cases. Regarding the outcome, although patients with extranodal FL showed a higher CR rate, the overall survival was similar in both groups. Extranodal FL (N=22) Nodal FL (N=212) p Age (median, range) 59 (28–82) years 55 (24–93) years NS Sex (M/F) 12/10 100/112 NS Histological grade 3 (%) 12 10 NS CD10+(%) 85 90 NS Bcl2+ (%) 67 91 NS Bcl2/JH (%) 37 65 0.03 Stage IV (%) 50 64 NS Bone marrow + (%) 36 62 0.02 LDH > 450 IU/L (%) 15 24 NS B2-microglobulin > 2.3 mg/L (%) 7 41 0.058 High-risk FLIPI (%) 19 35 NS CR rate (%) 82 53 0.02 5-year OS (%) 75 74 NS 5-year FFS (%) 67 27 <0.02

Abstract. Fly-in-fl y-out personnel in the Far North are exposed to extreme climatic, geographic, and production factors, and also remain in conditions of group isolation, which makes demands on fl y-in-fl y-out worker’ body that oft en exceed its reserves. Th e full adaptation impossibility is associated with unfavorable functional states of workers, which lead to a decrease in the level of mental health, productivity and work effi ciency. Job tasks of workers in various industries diff er in physical and physiological stress and in the degree of harmful production factors expression. Th e purpose of this study is to identify and describe the psychological adaptation features in fl y-in-fl y-out personnel in industrial enterprises of the Far North. Th e study involved 145 fl y-in-fl y-out workers of oil, gas, and diamond mining industries in the Far North, 82 fl y-in-fl y-out builders in the south of the Russian Federation, who were a comparison group to identify the psychological adaptation features of fl y-in-fl y-out personnel in the Far North. Research methods are psychophysiological and psychological testing aimed at diagnosing conscious self-regulation of voluntary human activity and subjective control as key characteristics of psychological adaptation of workers. Th e results obtained allow us to conclude about the similarity of psychological characteristics that contribute to the successful adaptation of fl yin-fl y-out personnel, regardless of the region where the industrial facility is located. Th ese include internality in the areas of achievement, failure, family relationships, health and illness, as well as modeling, performance evaluation, and autonomy as regulatory processes. At the same time, their expression is specifi c, depending on the region of the object location and the industry.

Abstract During its first three years, the Tropical Rainfall Measuring Mission (TRMM) satellite observed nearly six million precipitation features. The population of precipitation features is sorted by lightning flash rate, minimum brightness temperature, maximum radar reflectivity, areal extent, and volumetric rainfall. For each of these characteristics, essentially describing the convective intensity or the size of the features, the population is broken into categories consisting of the top 0.001%, top 0.01%, top 0.1%, top 1%, top 2.4%, and remaining 97.6%. The set of “weakest/smallest” features composes 97.6% of the population because that fraction does not have detected lightning, with a minimum detectable flash rate of 0.7 flashes (fl) min−1. The greatest observed flash rate is 1351 fl min−1; the lowest brightness temperatures are 42 K (85 GHz) and 69 K (37 GHz). The largest precipitation feature covers 335 000 km2, and the greatest rainfall from an individual precipitation feature exceeds 2 × 1012 kg h−1 of water. There is considerable overlap between the greatest storms according to different measures of convective intensity. The largest storms are mostly independent of the most intense storms. The set of storms producing the most rainfall is a convolution of the largest and the most intense storms. This analysis is a composite of the global Tropics and subtropics. Significant variability is known to exist between locations, seasons, and meteorological regimes. Such variability will be examined in Part II. In Part I, only a crude land–ocean separation is made. The known differences in bulk lightning flash rates over land and ocean result from at least two differences in the precipitation feature population: the frequency of occurrence of intense storms and the magnitude of those intense storms that do occur. Even when restricted to storms with the same brightness temperature, same size, or same radar reflectivity aloft, the storms over water are considerably less likely to produce lightning than are comparable storms over land.

The fibrolamellar variant of hepatocellular carcinoma (FL-HCC) is distinguished from other hepatocellular carcinomas (HCC) by its unique clinical and pathologic features. Cytological features for this tumor on fine needle aspiration (FNA) of primary tumors have been described earlier. We present here a unique case of metastatic FL-HCC diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of mediastinal adenopathy. A 32-year-old woman with a history of oral contraceptive use presented with nausea and severe abdominal pain but no ascites or stigmata of cirrhosis. She had a past history of resection of a liver lesion. Serial computed tomography scans revealed mediastinal lymphadenopathy and the patient was referred for endoscopic ultrasound (EUS). A transesophageal EUS-FNA was performed and tissue was collected for cytological evaluation by an on-site pathologist with no knowledge of prior history. Based on morphology correlated with prior history received later, a final diagnosis of metastatic FL-HCC in the retrocardiac lymph node was rendered on the EUS-FNA samples. There are very few reports in the literature where a diagnosis of FL-HCC is rendered at unusual sites. This case highlights that EUS-FNA is a relatively non-invasive, rapid, accurate and effective modality in obtaining tissue from otherwise hard-to-reach areas. It also suggests that metastasis of FL-HCC can be observed in mediastinal nodes and that diagnosis based on cytological features can be rendered even when the tumor is identified at unusual locations.

To ensure the mission implementation of Autonomous Underwater Vehicles (AUVs), faults occurring on actuators should be detected and located promptly; therefore, reliable control strategies and inputs can be effectively provided. In this paper, faults occurring on the propulsion and attitude control systems of a torpedo-shaped AUV are analyzed and located while fault features may induce confusions for conventional fault localization (FL). Selective features of defined fault parameters are assorted as necessary conditions against different faulty actuators and synthesized in a fault tree subsequently to state the sufficiency towards possible abnormal parts. By matching fault features with those of estimated fault parameters, suspected faulty sections are located. Thereafter, active FL strategies that analyze the related fault parameters after executing purposive actuator control are proposed to provide precise fault location. Moreover, the generality of the proposed methods is analyzed to support extensive implementations. Simulations based on finite element analysis against a torpedo-shaped AUV with actuator faults are carried out to illustrate the effectiveness of the proposed methods.

To ensure the mission implementation of Autonomous Underwater Vehicles (AUVs), faults occurring on actuators should be detected and located promptly; therefore, reliable control strategies and inputs can be effectively provided. In this paper, faults occurring on the propulsion and attitude control systems of a torpedo-shaped AUV are analyzed and located while fault features may induce confusions for conventional fault localization (FL). Selective features of defined fault parameters are assorted as necessary conditions against different faulty actuators and synthesized in a fault tree subsequently to state the sufficiency towards possible abnormal parts. By matching fault features with those of estimated fault parameters, suspected faulty sections are located. Thereafter, active FL strategies that analyze the related fault parameters after executing purposive actuator control are proposed to provide precise fault location. Moreover, the generality of the proposed methods is analyzed to support extensive implementations. Simulations based on finite element analysis against a torpedo-shaped AUV with actuator faults are carried out to illustrate the effectiveness of the proposed methods.

In humans, neurofibroma and schwannoma are distinct entities within the group of benign peripheral nerve sheath tumors. In the veterinary literature, these tumors are often classified together simply as benign peripheral nerve sheath tumors, and diagnostic criteria for their subclassification are not well established. We describe peripheral nerve sheath tumors with microscopic, immunohistologic, and ultrastructural features similar to those in subtypes of human neurofibroma in 12 dogs, 2 horses, and 1 chicken. Dogs were of different breeds and were aged 2 months to 15 years. The canine tumors were located in the skin, peripheral nerve, tongue, and large intestine. The 2 horses were 11 and 12 years old. The equine tumors were located in the subcutis of the neck and axilla. The chicken was a mature white Leghorn chicken with an ocular neoplasm. Neurofibromas of this study had localized, plexiform, diffuse and combined plexiform and diffuse growth patterns, and microscopic features similar to those in classic, collagenous, cellular, myxoid, and pigmented neurofibromas of humans. One diffuse neurofibroma contained areas of schwannian differentiation (hybrid neurofibroma-schwannoma). Two plexiform neurofibromas occurred together with diffuse ganglioneuromatosis in the large intestine of young dogs, as has also been reported in humans. This investigation shows the existence of identical subtypes of neurofibroma in animals and humans and identifies similarities in tumor location and patient age between animals and humans. This report will allow a more discriminating classification of benign peripheral nerve sheath tumors and probably has a bearing on epidemiology, pathogenesis and prognosis.

Issues related to the design and hydraulic calculation of the transit part of a closed tubular water supply structure of the siphon type is considered. The operating conditions of the siphon with rectangular pipes in the transition mode are evaluated, in which the entrance section of the pipes of the culvert structure experiences increased hydrodynamic loads, often leading to certain destructions. The siphon design was modeled with two breaks along the length with a smooth inlet head and without a head. During the experiments, the absence of infl uence of the inlet head of the tubular HTS on the length of the free-flow section was noted. It has been established that the conditions of formation and features of the hydraulic operation of the siphon in the transient mode are largely determined by its design features. With the flooding of the inlet head, the flow of air into the pipe is hindered and a transition mode of the second type is formed with a slight fluctuation of the water level in the upper pool. The dependence of the location of the point of separation of the flow with a decrease in the passing water flow rate on its value is revealed, which made it possible to obtain a graph of the dependence of the relative length of the non-pressure end section on the square root of the Froude number. A comparison was made with the results of studies by other authors, which showed an increase in the relative length in tubular HTS of the siphon type in sections with reverse slopes at the same Froude numbers. Recommendations are given on the methodology for carrying out hydraulic calculation of tubular structures of the siphon type with minimal flow rates.

<p>Of the 27 species of orchids growing in the Kemerovoregion, 20 are included in the Red books of The Russian Federation and the Kemerovoregion. An objective assessment and development of effective protection measures involves consideration of the location, population assessment and evaluation of the conditions. The article features characteristics of species composition, biomorphs, ecological features of the protected Orchidaceae species in the Kemerovodistrict. The research focused on the population status of <em>Dactylorhiza fuchsii </em>(Druce) Soo and <em>Orchis militaris </em>L. at the time of their fl The process involved setting transects consisting of 25 adjacent square pads with an area of 1 m2 each. The number of specimen was calculated on each site; their age and status were determined; the height of fl plants, the length of the infl and leaf were measured. Juvenile, immature, virginile and generative specimen were defi in each population of orchids. The authors determined the vital status of specimens, characterized the age and vitality spectrum, as well as the spatial structure of the populations. The population status <em>Orchis militaris </em>L. is defi as satisfactory, whereas the population of <em>Dactylorhiza fuchsii </em>(Druce) Soo was assessed as bad.</p>

The study of engineering and geological properties of anthropogenic deposits, widespread in the city of Samara. Their main properties have been identifi ed and a classifi cation based on the genetic principle has been developed. The results of a petrographic study of samples from cultural layers taken at an archaeological site are presented. Archaeological excavations were carried out on the territory of Khlebnaya Square, located in the oldest part of the city, in 2019. The object represents the cultural layers that were formed in the XVIII-XIX centuries at the site of the alleged location of the second Samara fortress. Petrographic studies of the samples were carried out under a binocular microscope at 8.75 times magnifi cation, in transmitt ed light of a polarizing microscope at 72 times magnifi cation and under a digital microscope (USB DIGITAL) at 10 times magnifi cation. It has been determined that the pebble fraction is represented by quartz ite and jasper fl int, the sandy and silty fractions are angular quartz fragments with an admixture of undecomposed organic remains. The organic cultural layers, which reach 7-8 m and more in the ancient part of the city, are especially powerful. Their presence is a limiting factor in modern urban construction.

Several approaches have been applied to groundwater exploration. In some instances positive results occur, but this is not always the case. This led hydrogeologists to look for a credible approach upon which they can rely during preliminary surveys for groundwater exploration. The development of remote sensing tools along with GIS methodologies gave rise to many new approaches. Most significant among these is the mapping of linear features (lineaments), which appear on satellite images. These features mainly reflect fracture traces, faults or lithologic boundaries and, therefore, are considered as major hydrogeologic parameters to be taken into account. The aim of this paper is to define an empirical relationship between lineament morphometric properties and the productivity of water wells. The three major properties of lineaments, i.e. frequency (Lf), density (Ld) and fault-lineaments (Fl), were analysed using Landsat 7 ETM+ images and GIS techniques. The resultant maps were correlated with the location of water wells in 90 sites from different regions of Lebanon. The resulting output showed an obvious relationship between productive wells and their proximity to fault lineaments. The closer the location of water wells to a ault trace the higher the water productivity. However, this hypothesis can be preliminary utilized in surveys for groundwater exploration, notably in a terrain with intensive rock deformation like that in Lebanon.

Introduction: In young children, excessive cow’s milk intake causes iron-deficiency anemia, which is associated with hypercoagulable states. We present a case series of 4 toddlers with excessive milk intake iron-deficiency anemia and cerebral sinovenous thrombosis. Methods: Retrospective chart review of 4 patients was performed for patients with cerebral sinovenous thrombosis and iron-deficiency anemia secondary to excessive milk intake. Iron-deficiency anemia was defined as hemoglobin <11 mg/dL, mean corpuscular volume <70 fL, and serum ferritin <12 μg/L. Excessive milk intake was defined as consumption of >24 oz daily. Clinical, laboratory, and radiographic features were reviewed. Results: Age ranged from 12 to 24 months. Average hemoglobin, hematocrit, mean corpuscular volume, and ferritin levels were 6.1 g/dL, 22.7 g/dL, 52.7 fL, and 3.2 ng/mL, respectively. Daily milk consumption ranged from 40 to 60 oz. All patients presented with focal neurologic deficits, including seizures in 3. The location of cerebral sinovenous thrombosis varied, and 3 patients had venous infarcts, one of them hemorrhagic. All patients had a limited diet and were described as “picky eaters” by their parents, and only 1 had transitioned of a bottle. All patients were treated with anticoagulation, iron supplementation, and extensive dietary counseling to reduce cow’s milk intake. Conclusion: Iron-deficiency anemia due to excessive milk intake is an important and preventable etiology of pediatric cerebral sinovenous thrombosis. Focused anticipatory guidance is necessary for at-risk groups to prevent this neurologic emergency.

Abstract Abstract 439 Introduction: Follicular lymphoma (FL) is the most common indolent lymphoid malignancy in North America with approximately 20,000 new cases of this incurable cancer diagnosed each year. In approximately 85% of patients, FL is associated with the reciprocal translocation t(14;18)(q32;q21), which results in a fusion between IGH and BCL2 genes and consequent over-expression of the anti-apoptotic protein BCL2. This translocation likely represents an initiating event for FL, requiring additional mutational events for the onset of clinical disease. To investigate the relationship between genome rearrangements and FL we identified rearrangement locations in the genome followed by detailed, fine-structure analysis of the rearrangements to ascertain their effects on genes and other features of biological interest. Patients and Methods: We used a whole-genome bacterial artificial chromosome (BAC) fingerprint-based approach, termed Fingerprint Profiling (FPP, Krzywinski, M. et al. 2007), to detect genome rearrangements relative to the reference human genome in neoplastic B cells purified from 24 FL patient biopsies. Analysis of 2,640,707 BAC fingerprints revealed 721 candidate genomic rearrangements. To validate these observations and provide base-pair resolution of the rearrangement breakpoints we performed paired-end massively parallel sequencing, on the Illumina Genome Analyzer II platform, of the breakpoint-containing regions captured in the BAC clones. Sequence reads were assembled into contigs using our in-house de novo assembly algorithm ABySS (Assembly By Short Sequences, Simpson, J. et al. 2009) then aligned to the reference human genome. Following manual annotation of the breakpoint junctions PCR primers were designed to assay patient tumour and matched constitutional DNA and thus determine whether the observed genome rearrangements were somatic (acquired) or germline in origin. Results: 727 BACs with apparent large-scale genome rearrangements, representing 354 distinct genome rearrangements across 20 patients, were sequenced in 95 pools, generating 72 Gbp of sequence. The 354 distinct events include 163 deletions, 71 inversions, 27 insertions, 83 translocations and 10 duplications, ranging in size from 3 kb to 67 Mb. PCR assays for 194 of the distinct events have been performed thus far identifying 80 distinct somatic and 114 germline-derived structural variations at base-pair resolution. Of the somatic events 5 are present in two or more of the 20 patients analyzed including a 720 kb inversion of 3q27.3 that results in expression of a BCL6-ST6GAL1 fusion transcript. Identification at base-pair resolution of breakpoint sequences enabled a detailed study of breakpoint and fusion mechanisms. We classified breakpoint junctions into 4 groups; those with microhomology (48%), those with sequence additions (28%), those with blunt fusions (20%) and those with flanking low copy repeats (4%). We were particularly interested in establishing the origin of the observed nucleotide sequence additions in 97 breakpoint junctions. The sequence additions ranged in size from a single nucleotide to 454 bp. In one case we have unambiguously mapped a 53 bp sequence, lying within one of the 3q27.3 inversion breakpoints, to chromosome 5q12.3. This finding is consistent with the recently proposed fork stalling and template switching (FoSTeS) DNA replication-based mechanism and thus represents a novel mechanism in FL lymphomagenesis. Conclusions: We have successfully employed high-throughput clone fingerprinting and sequencing to identify numerous novel somatic and germline genome rearrangements from FL primary tumour samples. Furthermore, base-pair resolution of rearrangement breakpoints provides mechanistic insights. With the complete inventory of somatic and germline events in hand we will be able to propose recurrent structurally altered genes in FL patients for validation in independent datasets and improve our understanding of FL biology. Pathway analyses to identify emerging themes from somatic mutations are also being performed. The PCR assays we have developed will also be of utility in identifying germline predisposition alleles in larger FL patient cohorts. Disclosures: No relevant conflicts of interest to declare.

The lithic industry of the stratified site Go Da in Central Vietnam is described, and its place among the contemporaneous Early Paleolithic sites of East and Southeast Asia is determined. Results of a morphological technotypological analysis of the Go Da assemblage are provided. Go Da is attributed to the An Khe-type sites situated in the eponymous area of Vietnam. Cores and tools were made from pebbles, less often from fl akes. Primary reduction focused on simple pebble cores with natural striking-platforms, whereas radial cores were less common. Predom inant among the tools are picks, scrapers of various modifi cations, choppers, and chopping tools, as well as denticulate and notched tools; also, bifaces occur. These tools belong to a single homogeneous industry, showing common features in primary reduction, preparation, and design of key artifacts. On the basis of analysis of the stratigraphic sequence of Go Da and the absolute date of 806 ± 22 ka BP, generated by the potassium-argon analysis of tektites, it is proposed that the site is older than other dated locations with the An Khe industry. Apparently, it resulted from a convergent evolution of the pebble-fl ake industry introduced by the fi rst wave of Homo erectus from Africa. Go Da and other An Khe sites likely belong to a vast habitation zone of Southeast Asian hominins with technologically and typologically similar industries dating to the boundary between the Lower and the Middle Pleistocene.

It is shown that the application of the Internet technologies is relevant in the selection of crop production technologies and the formation of a rational composition of the machine-and-tractor fl eet taking into account the conditions and production resources of a particular agricultural enterprise. The work gives a short description of the web applications, namely “ExactFarming”, “Agrivi” and “AgCommand” that provide a possibility to select technologies and technical means of soil treatment, and their functions. “ExactFarming” allows to collect and store information about temperature, precipitation and weather forecast in certain areas, keep records of information about crops and make technological maps using expert templates. “Agrivi” allows to store and provide access to weather information in the fi elds with certain crops. It has algorithms to detect and make warnings about risks related to diseases and pests, as well as provides economic calculations of crop profi tability and crop planning. “AgCommand” allows to track the position of machinery and equipment in the fi elds and provides data on the weather situation in order to plan the use of agricultural machinery in the fi elds. The web applications presented hereabove do not show relation between the technologies applied and agro-climatic features of the farm location zone. They do not take into account the phytosanitary conditions in the previous years, or the relief and contour of the fi elds while drawing up technological maps or selecting the machine-and-tractor fl eet. Siberian Physical-Technical Institute of Agrarian Problems of Siberian Federal Scientifi c Center of AgroBioTechnologies of the Russian Academy of Sciences developed a software complex PIKAT for supporting machine agrotechnologies for production of spring wheat grain at an agricultural enterprise, on the basis of which there is a plan to develop a web application that will consider all the main factors limiting the yield of cultivated crops.

The frequency of occurrence and intensity of floods is a huge threat to environment, human existence, critical infrastructure and economy. Flood risk assessments depend on probabilistic approaches and suffer from non-existence of appropriate indices of acceptable risk, dearth of information and pieces of knowledge for explicit view and understanding of the characteristics and severity level of flood hazard. This paper proposes a hybridized intelligent framework comprising fuzzy logic (FL), neural network and genetic algorithm for clustering and visualization of flood data, prediction and classification of flood risks severity level. A multidimensional knowledge model of flood incidence using star, snowflake and facts constellation schemas was proposed for the knowledge warehouse. A six-layered adaptive neuro-fuzzy inference system implementing mamdani’s inference mechanism was design to evaluate input features based on fuzzy rules held in the multidimensional data model. The system is aimed at predicticting and classifying flood risk severity levels. The perception of emergency risk management is very important in modern society. Therefore, this work provides a framework for the practical applications of data mining techniques and tools to emergency risk management. The work would assist to identify locations with significant flood risk.

Abstract Background: The control of hemoglobin F (Hb F) expression has proven an elusive puzzle with several postulated but not mutually exclusive hypotheses. A silencing mechanism hypothesis, which predicts the existence of a regulatory element that suppresses HbF expression, has been supported by recent investigations into a 3.5 kb region upstream from the delta globin gene (HBD). To test this hypothesis, we have investigated our historical case files in a tertiary care high-throughput clinical laboratory and compared the patient phenotype (Hgb, MCV, MCH, RDW, Hb F %, and flow cytometry Hb F distribution) with the status of this 3.5 kb region. Methods: A query of clinical testing patient files from Mayo Clinic Metabolic Hematology Laboratory yielded 179 patients confirmed by Multiplex Ligation-dependent Probe Amplification (MLPA) to contain large deletions located within the epsilon through beta globin genes. Of these, 27 unrelated patients with breakpoints between the pseudobeta (HBBP1) and HBD genes were identified. Four additional MLPA probe pairs were placed in this region and the patient phenotypes were compared. Results: The interior two (of the four added) probes between HBBP1 and HBD stratified all 27 cases. The other two (flanking) probes were never discriminatory, thus refining the area of interest to 2.4 kb. Sixteen cases showed breakpoints within hg19 g.5260154-5259135 (5' region) and eleven cases showed breakpoints within hg19 g.5259136-5257692 (3' region) upstream of HBD. Patients who displayed a phenotype of HPFH (n = 9) contained breakpoints in the 5' region whereas those with a delta beta thalassemia (DBT) phenotype (n = 11) were associated with breakpoints in the 3' region. A subset (n = 7) with breakpoints in the 5' region had indefinite phenotypic features, but of these, all but one showed homocellular Hb F distribution. Conclusion: Our molecular and phenotypic correlation of 27 patients with large deletional breakpoints between HBBP1 and HBD supports the hypothesis of a silencing element located upstream of HBD and further narrows the area that segregates many HPFH and DBT patient phenotypes from 3.5 kb to 2.4 kb. Several potential silencing effectors with binding sites in this region include HDAC1, GATA1 and H3K27me3; interestingly, the BCL11A binding site may be outside of the regulatory area. Table 1. Phenotypic data of patients with deletions between HBBP1 and HBD. Case Age/Sex Hb F Hb A2 Hb X Hgb RBC MCV MCH MCHC RDW Hb F Flow (Y) (%) (%) (%) (g/dL) ( 10^12/L) (fL) (pg/cell) (hg/cell) (%) 3' Region 1 47 M 25.5 2.1 16.7 6.3 81.4 26.7 32.8 15.7 H 2 5 M 28.3 2.4 12.5 4.9 74.6 25.4 34 15.9 H 3 24 F 30.3 1.7 11.6 4.23 92.7 27.4 29.6 15.2 H 4 9 F 36.3 2.2 S = 62 13.1 5.2 69.9 NA NA 14.8 5 24 F 37.3 2.1 C = 61 12.9 5.1 72.9 25.5 35 14.3 6 3 M 39.7 2.1 12.4 4.4 88.7 28.1 31.7 16.3 7 27 F 40.2 3.4 S = 56 12.2 4.4 79.7 27.8 34.9 15 8 16 M 43.7 2.2 S = 54 15.9 6.8 71.5 23.5 32.9 14.1 9 7m M 100.0* 0.0 12.8 4.8 76 26.5 34.9 16.8 3' Region 10 28 F 20.9 2 10.11 4.4 70.9 22.7 32.1 19 H 11 64 M 21.4 2.3 10.51 4.1 81.1 25.8 31.8 18.1 12 2.5 M 24 2.1 10.21 5.3 59.4 19.3 32.5 20.9 H 13 58 F 24 2.1 9.51 4.4 72.2 21.5 29.8 17.7 H 14 14 F 25.4 1.5 10.81 4.9 69.4 22 31.8 17.6 H 15 52 F 26.9 1.8 8.42 3.6 72 23.5 32.7 19.4 T 16 34 M 38.7 1.7 S = 60 11.4 4.7 71.6 NA NA 21.6 5' Region 17 24 F 2.7 2.9 12.3 6.1 62.2 20 32.2 18.2 18 32 F 6.1 2.7 10.2 5.1 61.3 19.9 32.5 19.3 19 27 F 7.2 2.9 11 5.1 72.9 21.7 29.8 19.9 20 29 F 7.8 2.7 10.2 4.7 72.2 21.7 30 20.5 21 15 M 7.8 2.5 12.7 6.2 64.7 20.4 31.5 21.2 22 42 M 7.8 3.1 10.6 4.9 75.1 21.5 28.6 23.7 23 60 M 10.1 2.5 11 4.5 74.8 24.7 33 23.4 24 41 M 10.7 2.8 8.6 4.1 73.3 21.2 29 26.8 25 30 F 11.5 2.7 12.1 5.5 67.4 21.9 32.5 21.8 26 25 F 13.2 2.8 12.1 5.3 68.4 22.8 33.3 21.6 27 3 F 18.3 2.6 11.9 5.79 63.6 20.6 32.3 22.7 T Normal values <1 2-3.3 0 H = homocellular; T= heterocellular; I = indeterminate; *homozygous deletion -- = no deletion; + = deletion present (all alpha deletions were single -3.7 kb 'rightward' deletions) 1 = Suspected Fe deficiency; 2 = recent transfusion Disclosures No relevant conflicts of interest to declare.

In June 2007, approximately 8 km east of Belle Glade, FL, a rust disease was observed on a sugarcane (a complex hybrid of Saccharum L. species) cultivar (CP 80-1743) considered resistant to brown rust caused by Puccinia melanocephala Syd. & P. Syd. Approximately 10 km south of Canal Point, FL, another cultivar (CP 72-2086), also considered resistant to P. melanocephala, was found to be infected with a rust. Samples were sent to the USDA-APHIS National Mycologist and the USDA-ARS Systematic Mycology and Microbiology Laboratory in Beltsville, MD for identification. Observed morphological features were consistent with P. kuehnii E.J. Butler. Uredinial lesions were orange and variable in size, measuring 650 to 850 × 26 to 32 μm, hypophyllous, ellipsoidal to fusiform in shape, and distinctly lighter than pustules of P. melanocephala that were present in the area along with P. kuehnii. Urediniospores were mostly obovoid to pyriform or broadly ellipsoidal, variable in size, 32 to 45 × 25 to 30 μm, and moderately echinulate with mostly evenly distributed spines 2 to 4.5 μm apart. Walls were orange-to-light cinnamon brown, 1 to 2.5 μm thick with a pronounced apical wall thickening as much as 7 μm, and 4 to 5 equatorial pores. Similar orange uredinial lesions were subsequently observed on the same two cultivars and several other cultivars, including CPCL99-1777 and CPCL01-1055, at different locations in South Florida. Telia and teliospores were not observed. The nuclear large subunit rDNA region of the rust infecting cv. CP 80-1743 (BPI 878243, GenBank Accession No. EU164549) and the ITS1, 5.8S, and ITS2 rDNA regions of the rust infecting CP 80-1743 (GenBank Accession No. EU176009) and CP 72-2086 (GenBank Accession No. EU176008) were sequenced (1,4). All sequences were identical to sequences of P. kuehnii and distinct from known sequences of P. melanocephala (4). To our knowledge, this is the first confirmed record of P. kuehnii infecting sugarcane in the Western Hemisphere, and the disease appears to be distributed widely in the South Florida sugarcane-growing area. Although listed by P. Holliday (3) as occurring in Cuba, the Dominican Republic, and Mexico, CMI map no. 215 ed. 4 (2) does not include these three countries in the known distribution of P. kuehnii. P. kuehnii has also been reported in the literature as present in Hawaii (4). However, examination of the specimen label found that the specimen cited in those papers (BPI 079624) was actually collected in Tahiti. Therefore, the report from Hawaii is erroneous. References: (1) M. C. Aime. Mycoscience 47:112, 2006. (2) CMI. Distribution Maps of Plant Diseases. No. 215, ed. 4. CAB International, Wallingford, UK, 1981. (3) P. Holliday. Fungus Diseases of Tropical Crops. Cambridge University Press, Cambridge, 1980. (4) E. V. Virtudazo et al. Mycoscience 42:447, 2001.

Abstract Diffuse large B cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Both biologically and clinically, DLBCL represents a highly heterogeneous disease. DLBCL has been subdivided into germinal center B cell (GCB)-like and activated B cell (ABC)-like DLBCL, on the basis of gene expression profiling, which separates DLBCL according to the presumed cell of origin (COO). This COO-based classifier distinguishes sub-entities displaying distinct biological features, pathogenesis and clinical response to frontline therapy. In addition to this classic transcriptome-based stratifier, recent genomic analyses of human DLBCL samples led to the discovery of partially overlapping genetically-defined DLBCL subsets. A study by Schmitz et al. employed a supervised clustering approach, allowing the classification of ~50% of the cases into four genetically-defined DLBCL subtypes, one of which is being characterized by co-occurring MYD88- and CD79B mutations as well as high expression of BCL2 (termed MCD). In a second approach by Chapuy et al., patient samples were clustered in an unsupervised manner. Also in this study, a cluster with recurrent mutations in MYD88 (specifically p.L265P) and CD79B, as well as gains of 18q (the location of BCL2) was identified (termed C5). We previously reported the formation of B cell lymphoma in mice that were engineered to express Myd88 p.L252P in combination with overexpression of BCL2 (Myd88 p.L252P/wt;R26 LSL.BCL2/wt;Cd19 Cre/wt, abbr. MBC) in a B cell-specific manner. While the developing lesions display many features of human ABC DLBCL, their B220 -/CD138 + immunophenotype reflects plasmablastic characteristics. To refine this mouse model, we incorporated additional C5/MCD lesions by engineering a B cell-specific loss of Prmd1 or Spib overexpression generating Prdm1 fl/fl;Myd88 p.L252P/wt;R26 LSL.BCL2/wt;Cd19 Cre/wt (PPMBC) and Myd88 p.L252P/wt;R26 LSL.BCL2/LSL.Spib;Cd19 Cre/wt (SMBC) compound animals. Both, the B cell-specific loss of Prdm1 and Spib overexpression on the MBC background resulted in a marked reduction of CD138 + cells in the spleens of 10 weeks old animals compared to control (Fig. 1A), accompanied by a decrease in serum immunoglobulins, indicative of a plasma cell differentiation block and in agreement with the reported function of PRMD1 and SPIB as transcription factors regulating plasma cell differentiation. Both PPMBC and SMBC mice developed lymphoma significantly earlier than MBC animals. These tumors largely displayed a B220 +/CD138 - immunophenotype. As transcriptional profiling is the gold standard for differentiation between GCB and ABC DLBCL, we generated germinal center- and activated blood B cell gene sets from healthy donors. We then performed gene set enrichment analyses between SMBC/PPMBC tumors and either MBC or Kmt2d fl/fl;VavP-Bcl2;Cɣ1 Cre/wt (KBC) lymphomas, the latter being reminiscent of human GCB DLBCL. While both PPMBC and SMBC samples were enriched for GCB gene signatures when compared to MBC, they enriched for ABC gene sets in comparison to KBC, potentially suggesting a developmental stage between KBC and MBC lesions (Fig. 1B). We next aimed to employ our PPMBC model of C5 DLBCL as a pre-clinical tool, in order to derive therapeutic approaches for this disease. In this regard, we note BCL2 has emerged as a potential therapeutic target in DLBCL. The BCL2 inhibitor venetoclax produces response rates of ~18% in relapsed/refractory DLBCL (Davids et al., 2017). Similarly, in a phase I/II clinical trial involving 80 patients with relapsed/refractory DLBCL, ibrutinib induced complete or partial remissions in 37% of ABC-DLBCL patients, but in only 5% GCB-DLBCL patients (Wilson et al., 2015). Building on these observations, we asked whether single agent or combined venetoclax and ibrutinib treatment might display pre-clinical activity in the PPMBC setting. Indeed, combination treatment with ibrutinib and venetoclax resulted in a significant survival benefit compared to single compound or untreated animals (Fig. 1C). Given this preclinical activity, we treated 6 relapsed/refractory (r/r) non-GCB DLBCL patients (determined by Hans algorithm) in an off-label setting and observed tumor shrinkage in 5 of 6 patients (Fig. 1D). Thus, our clinical data corroborate our preclinical observations and suggest that combined venetoclax and ibrutinib may display clinical activity in a subset of r/r non-GCB DLBCL. Figure 1 Figure 1. Disclosures Hallek: Roche: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Mundipharma: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Speakers Bureau. Calado: Myricx Pharma: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company, Patents & Royalties: Cancer Treatments. WO patent WO 2020/128475 A1 (2020). Pasqualucci: Sanofi: Research Funding; Astra Zeneca: Research Funding. von Tresckow: Amgen: Consultancy, Honoraria; AbbVie: Other: congress and travel support; Pentixafarm: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: congress and travel support; MSD: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: congress and travel support, Research Funding; AstraZeneca: Honoraria, Other: congress and travel support; Kite-Gilead: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding. Chapuy: Gilead: Honoraria; BMS: Honoraria; Regeneron: Consultancy; Gilead Sciences: Research Funding; Astra Zeneca: Honoraria. Reinhardt: CDL Therapeutics: Current holder of individual stocks in a privately-held company; Gilead: Research Funding; Merck: Consultancy; Vertex: Consultancy; AstraZeneca: Consultancy; Abbvie: Consultancy. OffLabel Disclosure: Treatment of DLBCL patients with ibrutinib and venetoclax.

Abstract Coding region amino acid substitutions within the globin genes can cause thalassemia, any of a wide variety of pathologic variants or entirely harmless variant haemoglobin. Which occurs depends upon the nature and location of the mutation. Both structural and thalassemia-producing mutations can occur for a unique mutation depending on the mutant sequence produced. Homozygotes for frameshift β 41/42 and compound β 41/42 and beta0-thalassemia produced heterozygotes for frameshift severe symptoms and have a thalassemia major phenotype. Severe phenotype has not been reported in the β 41/42 frameshift heterozygosity and the resulting abnormal hemoglobin has never been studied. We report the β c.126–129del CTTT frameshift mutation (exon1) resulting in a truncated β chain (58 AA) in a heterozygous Vietnamese adult patient who was referred to the hospital for anemia and renal failure The haematological indices were as follows: Hb 9.0g/dL, RBC 4.38×1012L, MCH 19.8 pg, MCV 62 fL, and reticulocytes 100 000/mm3 (4.4%). Serum creatinine was 221 mmol/L and creatinine clearance was low (22 ml/mn/1.73m2). Both kidneys were small (L=64mm;l=22mm). Renal biopsy was not performed for this reason. Hemoglobin electrophoresis at alkaline pH did not show any abnormal band while electrophoresis at acidic pH on citrate agar plate demonstrated an abnormal band less cathodal than Hb F. Hb A2 was 5.7%. The elution profile obtained from VARIANT ™ HPLC system was normal when using the β-thalassemia short program (Bio-Rad Laboratories, Hercules, CA, USA), while an abnormal peak representing 10% of the total amount of Hb was identified in the D/E area when using the HbA1c elution program. Both the isopropanol precipitation and heat stability tests showed a relevant molecular instability of the variant Hb. Heinz body test was positive. The Hb variant was isolated from the unstable component. The seven common α-thalassemia deletion defects as well as triplication were excluded using gap-PCR. Except for Hb Indianapolis, no clear cases of renal failure have ever been reported in association with the heterozygous state for unstable β chain. We have studied the truncated β globin chain in order to understand the instability of the abnormal hemoglobin. We have built a 3D model of the abnormal variant. Using biochemistry techniques and molecular modelling we show that: the synthetic 58 amino acids truncated protein was unable to fold in physiological conditions, sequence from AA 41 to AA 53 is structured as a primary helix but fully buried and unable to be exposed to the solvent, the Phe42Ser substitution is responsible for the major structural defect, key residues in position β 42, 44, 45, 48, 49, 51, 54, 55 and 57 are very sensitive for stability of hemoglobin as most of the substitutions for these residues disturb subunit packing in flexible joint probably leading to dissociation at β globin gene with this 4 bp deletion encodes the α1-β1 interface. The a truncated translational product which is unstable in the erythrocyte β–globin chains. Our data leading to the unbalancing of the α and suggest that this thalassemic hemoglobinopathy may have a variable phenotypic pattern in heterozygotes and may sometimes be associated with haemolytic crisis responsible for late renal failure.

Introduction. The problem of dissemination and application of digital technologies in the fi eld of labour has been extremely relevant over the past decade. The development of the digital economy inevitably leads to a profound transformation of the labour market. Traditional labour relations, the content of which is mostly indefi nite, are replaced by non-standard forms of employment, short-term employment contracts, fl exible working hours and performance, employees remotely from the location of the employer are becoming common practice. The aim of the article is to clarify the features of the transformations taking place in the fi eld of labour under the infl uence of digital technologies, as well as to outline the main trends in Ukrainian labour legislation in the context of digitalization. Results. The aurhor focuses on the legal regulation of remote and home-based work, the introduction of electronic document management in labor relations, including personnel. The latest legislative changes that contributed to the introduction of electronic employment record books and electronic sick lists are analyzed. Particular focus has been placed on the study of a new model of non-standard employment on the basis of gig contracts within the digital platform “Diia City”, introduced by the Law of Ukraine «On Stimulating the Development of the Digital Economy in Ukraine». Conclusions. It has become clear today that the development of labour legislation in Ukraine is much slower than digital technologies capture both the labour market and our daily lives. The digitalization of the economy challenges modern labour legislation, which should not stand in the way of information technology progress and the introduction of new information technologies in labour relations, with the advent of which work becomes less tied to workplace and time, and gives greater autonomy to the employee. However, there are other problems, such as limiting the employer’s interference in the employee’s private life, especially in the context of the employee’s right to rest or so-called disconnection (the right not to be in touch during non-working hours). Thus, improving the mechanism of legal regulation of individual and collective labour relations, revision of their theoretical structures and characteristics, as well as the problem of providing all workers, regardless of employment, including informal employment, bogus self-employed, working on online platforms, the minimum of labour and social rights in the realities of the digital economy is of growing importance in the digital economy. Key words: digitalization, transformation of labour relations, remote work, electronic document management, electronic employment record book, electronic sick list, digital platforms, gig contract, gig specialist.

Abstract Background: Large deletions involving the beta globin complex are relatively rare. They can be categorized generally into five groups by deletion size and/or location: 1) beta zero thalassemia (BZT); 2) delta beta thalassemia (DBT); 3) hereditary persistence of fetal hemoglobin (HPFH); 4) gamma delta beta thalassemia (GDBT); and 5) epsilon gamma delta beta thalassemia (EGDBT). These deletions are not well understood but often have significant clinical impact, either when present alone or in combination with other hemoglobin mutations. In this study, we analyze phenotypic and molecular data on a large number of cases with deletions in the beta globin gene complex to better classify these five groups of deletions as they occur in isolation. Methods: A query of the routine clinical testing patient files from the Mayo Clinic Metabolic Hematology and Molecular Genetics Laboratories from 2010 to 2015 identified 179 patients with a deletion confirmed by a Multiplex Ligation-dependent Probe Amplification (MLPA) assay. Twenty-four probes sets were placed from the 5' locus control region (LCR) to the 3' hypersensitivity region, spanning the beta globin gene complex. Using a Luminex LX200 flow cytometer, a gene dosage ratio was calculated for each probe set using the median fluorescent intensity value collected. The size and location of the deletion and patient phenotype were compared. Results: Of the 179 total cases, the following large deletions were identified: beta gene (HBB) (n = 47), delta (HBD) through HBB (n = 105), A-gamma (HBG2) through HBB (n = 20), and locus control region (LCR) through HBB (n = 7). One case had a deletion involving the LCR epsilon with the rest of the complex left intact. A subset (n = 60) of cases had compound hemoglobin mutations that altered the phenotype. The BZT cases had relatively high Hb A2 levels and variable Hb F levels consistent with promotor region loss. The main differences between DBT and HPFH included Hb F and Hb A2 levels. GDBT cases presented with median Hb F levels higher than that observed in DBTs, normal Hb A2, and microcytic anemia. EGDBT cases had variable features according to age of the patient and Hb F level; severe microcytic anemia was observed in neonates, milder microcytic anemia in young children, and microcytosis without anemia in an adult case. The phenotypic features of 119 patients with isolated large deletions are compiled in table 1. Conclusion: In general, all five categories of large deletions in an isolated heterozygous state can present with microcytic anemia and are typically benign with the exception of transient severe microcytic anemia in neonatal EGDBT cases. Although phenotypes associated with large deletions involving the beta globin gene complex are frequently distinctive, significant phenotypic overlap can be seen in a subset of cases. These cases require molecular analysis due to their clinical importance when in combination with another beta globin gene complex mutation for an adequate diagnosis and treatment approach. Table 1. Deletion type Age n HbF (%) HbA2 (%) Hb (g/dL) MCV (fL) RBC (10^12/L) RDW (%) MCH (pg/cell) BZT 20 6.3 (0.6-94.4) 6.8 (3.4-11.6) 11.1 (8.3-14.5) 65.4 (60.8-77.2) 5.4 (4.2-6.2) 19.2 (16.6-21.2) 20.9 (18.3-25.7) DBT 56 10.6 (2.7-22.4) 2.7 (2.5-3.1) 11.7 (8.6-14.4) 68.9 (61.3-83.5) 5.3 (4.1-7.3) 21.4 (18.2-26.8) 21.6 (19.9-39.2) HPFH 23 25.9 (17.6-39.7) 2.0 (1.5-2.4) 11.6 (8.1-16.7) 78.4 (60.2-101.9) 4.4 (3.0-6.3) 17.5 (14.1-22.3) 25.4 (17.6-29.7) GDBT 14 13.3 (8.2-19.0) 2.6 (1.8-2.7) 11.0 (8.6-14.1) 72.5 (57.9-82.1) 5.1 (3.5-6.2) 20.6 (17.4-23.5) 22 (17.9-25.1) EGDBT* 28 Y 1 0.3 3 13.3 59.4 6.9 15.4 19.2 1-4 Y 3 0.9 (0-1.6) 3.2 (2.9-3.5) 9.5 (8.8-13.3) 57.8 (57.6-59.4) 5.2 (4.9-6.9) 16.6 (15.4-17.4) 18.5 (18.1-19.2) <6 month 2 21.4 (14.8-27.9) 2.6 (2.2-2.9) 6.3 (6.0-6.6) 61.3 (59.9-62.6) 3.4 (3.3-3.3) 21.5 (21.2-21.7) 18.4 (18.1-18.7) medians, (min, max); *stratified by age Disclosures No relevant conflicts of interest to declare.

Statement of the problem. There are a lot of works in the national musicology focusing on the study of vocal chamber music for voice and piano by Ukrainian composers of the 20th century. Researchers cover quite a wide range of issues regarding vocal pieces and touch upon the problems of cyclocreation, dramaturgy, features of musical and linguistic means, etc. However, they rarely pay attention to translation, though there are many vocal opuses, in which composers use foreign poetry. In this case, the specifi c choice of the translated sample helps to determine the principles of the composer’s approach to the embodiment of the poetic text, especially in comparison with other works based on the same sources. Hence separate songs from D. Klebanov’s vocal cycle on the poems of H. Heine did not become an exception, thereby confi rming the relevance of the proposed topic. The purpose of the article is to determine specifi c features of the embodiment of H. Heine’s poetry translations in the vocal cycle of D. Klebanov on the basis of two romances – “In a grove, on a wild path”, “My love, lay your hand on my heart”, as compared to the works of other composers of the twentieth century . To achieve the research objectives the following methods were used: historical, structural-functional, genre-style and comparative. Results. Under consideration are peculiarities of the embodiment of H. Heine’s poetry translations in the vocal cycle of D. Klebanov, one of the founders of Kharkiv composition school. For this work the author took eight verses from the fi rst two cycles of the “Book of Songs” by the German poet. They were based on the motives of love poems with vivid images of nature; sometimes the poems are full of sadness, a sense of loneliness. When D. Klebanov was choosing certain samples from different poetic cycles, he tried to stick to the plot of the “Book of Songs”, since he ordered the poems in the same way they were written in the collection. Another indicator of the composer’s relation to Heiner’s texts is the choice of poetic works which are given in the cycle in Ukrainian and Russian languages. The composer’s individual vision of Heine’s lyric poetry is clearly seen when compared to the vocal works of other composers of the twentieth century, M. Medtner and E. Denisov, written on the same poetic texts. In cross-romances, similar musical-linguistic means are used, including the metrical principle of vocalization of the poetic text, homophonic-harmonic structure, harmony of classical-romantic type. However, each of the composers renders the fi gurative and semantic implications of the poems in their own way. M. Medtner builds his romance “My love, lay your hand on my heart” according to the crescendo principle. Beginning with a quieter dynamics, the composer gradually increases the volume of the sound, which at the end leads to a general climax that moves from the point of the golden section. D. Klebanov chose a different way – to reinforce the dramatism of the poem. This was possible thanks to various musical and linguistic means: a strict, intense melody in the bass doubled in the sixth with a chromatic motion and semiquavers at the end of each bar in the last line of the fi rst stanza, designation Meno mosso, chromaticized vocal melody. The composers’ choice of poetic translations depends on the place and role of the romance in the general structure of the cycle. The eight-part composition of D. Klebanov is based on the wave principle of the plot development. The original four romances pave the way to the fi rst climax – unrequited love in the fi rst romance (“Every morning I awake and ask”), painful memories in the second one (“In a grove, on a wild path”), a tragic image in the third one (“My love, lay your hand on my heart “), and an attempt to overcome the pain in the fourth romance (“First I was afraid of darkness”). Further on, the development is based on contrast: the image of death in the fi fth romance (“Your lovely face, so fair and dear”), a subtle feeling of love in the sixth one (“Oh, let me plunge my heart”), worries because of the marriage of a loved one to another guy in the seventh romance (“I hear the fl ute and the fi ddle”) and disappointment in her spiritual values in the last one (“The violets blue”). Such a location of the third romance justifi es the choice of translation, where the colours are thickening and the content becomes even darker. Such kind of a fi gurative and semantic plot resembles the tradition of a romantic vocal cycle, in which the emotional state of the lyrical character, his emotional collisions сome to the fore. In this perspective, “ 3 Poems of H. Heine” by D. Medtner demonstrate another relationship between the romances of the cycle. All of them have feelings of sorrow, despair circle, a no-go. At the same time, distancing from the immediate events is felt, as if it is a look at someone else’s life, which is evidenced by the storytelling from the third person in the second and third romances. Therefore, the fi rst romance, based on the poem “My love, lay your hand on my heart”, is a kind of “preface” to the cycle, which involves some personal detachment. This leads to the selection of softened content in the translated version of the poem. The second romance, “In a grove, on a wild path”, has a similar function in the vocal cycle of D. Klebanov as it became the preparation for the climax of the third one. The semantic line of his poem is based on two storylines: the external one is the “theme of the journey” that is refl ected in the image of nature, and the internal one is the “theme of sadness”, which focuses on the feelings of the lyrical hero. The composer here, like Анна in the third romance, deepens the line of inner experiences. This became possible thanks to the Tranquillo tempo, fl at minor tonality, massive discordant accompaniment chords, variable measure, melody of the recitative-oratorial type. H. Heine’s poem, presented in the work of D. Klebanov, became the basis of the fi fth romance of E. Denisov’s vocal opus. Like the Ukrainian master, E. Denisov builds his cycle in the spirit of the romantic tradition, but in revealing the fi gurative structure of the poem he goes a different way. He makes a clear distinction between two fi gurativesemantic lines. This is refl ected in the form of a romance that has the features of binarity and variability, the embodiment of the metro-rhythmic structure of the verse based on two opposing principles - metric and cantilena, as well as other means of musical expression. Thus, choosing the same poem by H. Heine, D. Klebanov and E. Denisov represent their own vision of its content. Conclusions The comparative analysis of the embodiment of Heine’s texts by D. Klebanov and other composers of the twentieth century helps to highlight the individual approach of the Ukrainian artist. Despite the fact that the composer chooses similar means of musical expression, he fi nds his own way of refl ecting the semantics of the poetic source. In the above mentioned romances – “In a grove, on a wild path” and “My love, lay your hand on my heart” – the author focuses on the inner confl icts of the lyrical hero, his experiences. Attention paid to the sensory side of the poems also determined the selected translations, since the rejection of translators from the original results in a certain deformation of its meaning and fi gurative structure, which infl uences the musical embodiment of the poetic source.

In industry, software projects might span over decades and many engineers join or leave the company over time. For these reasons, no single engineer has all of the knowledge when maintenance tasks such as Traceability Link Recovery (TLR), Bug Localization (BL), and Feature Location (FL) are performed. Thus, collaboration has the potential to boost the quality of maintenance tasks since the solution of an engineer might be enhanced with contributions of solutions from other engineers. However, assembling a team of software engineers to collaborate may not be as intuitive as we might think. In the context of a worldwide industrial supplier of railway solutions, this work evaluates how the quality of TLR, BL, and FL is affected by the criteria for selecting engineers for collaboration. The criteria for collaboration are based on engineers’ profile information to select the set of search queries that are involved in the maintenance task. Collaboration is achieved by applying automatic query reformulation, and the location relies on an evolutionary algorithm. Our work uncovers how software engineers who might be seen as not being relevant in the collaboration can lead to significantly better results. A focus group confirmed the relevance of the findings.

Introduction Augustine House was one of the most important building programmes in Canterbury Christ Church University’s history. The purpose was to create and develop a large state of the art library and student support centre that offered innovative, technology-rich facilities for staff and students to use. An important feature of Augustine House was the creation of fl exible recreational and learning spaces that would allow students to learn, work and relax in a manner and place of their choosing. The iBorrow project was part of the second phase of the Joint Information Systems Committee’s institutional innovation programme. The aim of the project was to create a laptop loan service that was entirely self-service and that should be no more complicated than borrowing a book. Radio-frequency identifi cation (RFID) tags were placed inside iBorrow notebooks in the anticipation that the geo-location tracking data overlaid with additional information would provide a better understanding on how students use the digital and electronic resources available to them as individuals or within groups.

AbstractData-driven machine learning models, compared to numerical models, demonstrated promising improvements in detecting damage in structural health monitoring (SHM) applications. In such approaches, sensors’ data are used to train a model either in a centralized model (server) or locally inside each sensor unit node (client). The centralized learning model often leads to computing and privacy issues such as wireless transmission costs and data-sensitive vulnerability, especially in real-time settings. The decentralized model also poses different challenges such as feature correlations and relationships loss in decentralized learning settings. To handle the shortcomings of both models, we propose a new Personalized federated learning (FL) model augmented with tensor data fusion to learn and detect damage in SHM. Our approach employs FL which enables the central machine learning model to gain experience from diverse datasets located at different sensor locations. Furthermore, our proposed model addresses the problems associated non-i.i.d. data by employing the Moreau envelopes as a regularized loss function in the learning process of client’s models. Our methods help in decoupling the client models from the central one which improves personalized in FL. Our experimental evaluation on real structural datasets demonstrates promising damage detection accuracy without the need to transmit the actual data to the centralized learning model. The results also show that the data correlations and relationships from all participating sensors are preserved.

The nomenclatural type material of Rhizophagus intraradices (basionym Glomus intraradices) was originally described from a trap pot culture established with root fragments, subcultures of which later became registered in the INVAM culture collection as FL 208. Subcultures of FL 208 (designated as strain ATT 4) and a new strain, independently isolated from the type location (ATT 1102), were established as both pot cultures with soil-like substrate and in vitro root organ culture. Long-term sampling of these cultures shows spores of the species to have considerable morphological plasticity, not described in the original description. Size, shape and other features of the spores were much more variable than indicated in the protologue. Phylogenetic analyses confirmed earlier published evidence that sequences from all R. intraradices cultures formed a monophyletic clade, well separated from, and not representing a sister clade to, R. irregularis. Moreover, new phylogenetic analyses show that Rhizoglomus venetianum and R. irregularis are synonymous. The morphological characters used to separate these species exemplify the difficulties in species recognition due to the high phenotypic plasticity in the genus Rhizophagus. Rhizophagus intraradices is morphologically re-described, an epitype is designated from a single-spore isolate derived from ATT 4, and R. venetianum is synonymised with R. irregularis.

A convolution neural network (CNN) based deep learning method has been proposed for automatic classification and localization of nonlinear loads present in an interconnected power system. The identification of nonlinear loads has been previously dealt with the use of Nonlinear Auto Regression neural network with eXogenous inputs (NARX), Backpropagation Neural Network (BPNN), Probabilistic Neural Network (PNN), Artificial Neural Networks (ANN) and Fuzzy Logic (FL). However, these techniques had not explored the area of classification of industrial and domestic nonlinear loads in an interconnected power system. Also, a Deep learning-based solution for identification of the type of nonlinear load has not been reported in the literature to date. Hence, to address these shortcomings, an IEEE-9 Bus system with industrial nonlinear loads has been used to obtain various current waveforms with distortions. The recorded current waveforms are transformed into a time-frequency (TF) domain plane, and the obtained images are then fed to the deep learning algorithm. The colored images of the TF plots of each type of nonlinear load in Red-Green-Blue (RGB) index provide the best visual features for extraction. The TF domain signatures of individual events are scaled to a standard size before feeding to the algorithm. Through these TF signatures, unique features were extracted with the deep learning algorithm, and then passed on to different stages of convolution and max-pooling with fully connected layers. The softmax classifier at the end classifies the input data into the type of nonlinear present in the power system. The algorithm, when run at different buses, also identifies the location of the nonlinear load. The proposed methodology avoids the usage of any additional fusion layer for obtaining unique features, reduces the training time and maintains the highest accuracy of 100%.

ObjectiveAutomated syndromic surveillance using mobile devices is an emerging public health focus that has a high potential for enhanced disease tracking and prevention in areas with poor infrastructure. Pacific Northwest National Laboratory sought to develop an Android mobile application for syndromic biosurveillance that would i) use the phone camera to take images of human faces to detect individuals that are sick through a machine learning (ML) model and ii) collect image data to increase training data available for ML models. The initial prototype use case is for screening and tracking the health of soldiers for use by the Department of Defense’s Disease Threat Reduction Agency.IntroductionInfectious diseases present with multifarious factors requiring several efforts to detect, prevent, and break the chain of transmission. Recently, machine learning has shown to be promising for automated surveillance leading to rapid and early interventions, and extraction of phenotypic features of human faces [3, 5]. In addition, mobile devices have become a promising tool to provide on-the-ground surveillance, especially in remote areas and geolocation mapping [4].Pacific Northwest National Laboratory (PNNL) combines machine learning with mobile technology to provide a groundbreaking prototype of disease surveillance without the need for internet, just a camera. In this android application, VisionDx, a machine learning algorithm analyses human face images and within milliseconds notifies the user with confidence level whether or not the person is sick. VisionDx comes with two modes, photo and video, and additional features of history, map, and statistics. This application is the first of its kind and provides a new way to think about the future of syndromic surveillance.MethodsData. Human healthy (n = 1096) and non-healthy (n = 1269) facial images met the criteria for training the Machine Learning model after preprocessing them. The healthy images were obtained from the Chicago face database [6] and California Institute of Technology [2]. There are no known collections of disease facial images. Using open source image collection/curation services, images were identified by a variety of keywords, including specific infectious diseases. The criteria for image inclusion was 1. a frontal face was identified using OpenCV library [1], and 2. the image contained signs of disease through visual inspection (e.g., abnormal color, texture, swelling).Model. To identify a sick face from a healthy one, we used transfer machine learning and experimented with various pretrained Convolutional Neural Networks (CNN) from Google for mobile and embedded vision applications. Using MobileNet, we trained the final model with our data and deployed it to our prototype mobile app. Google Mobile Vision API and TensorFlow mobile were used to detect human faces and run predictions in the mobile app.Mobile Application. The Android app was built using Android Studio to provide an easily navigable interface that connects every action between tabbed features. The app features (i.e., Map, Camera, History, and Statistics) are in tab view format. The custom-made camera is the main feature of the app, and it contains face detection capability. A real-time health status detection function gives a level of confidence based the algorithm results found on detected faces in the camera image.ResultsPNNL's prototype Android application, VisionDx, was built with user-friendly tab views and functions to take camera images of human faces and classify them as sick or healthy through an inbuilt ML model. The major functions of the app are the camera, map, history, and statistics pages. The camera tab has a custom-made camera with face detection algorithm and classification model of sick or healthy. The camera has image or video mode and results of the algorithm are updated in milliseconds. The Statistics view provides a simple pie chart on sick/healthy images based on user selected time and location. The Map shows pins representing all labeled images stored, and the History displays all the labeled images. Clicking on an image in either view shows the image with metadata, i.e., model confidence levels, geolocation, and datetime.The CNN model prediction accuracy has ~98% validation accuracy and ~96% test accuracy. High model performance shows the possibility that deep learning could be a powerful tool to detect sickness. However, given the limited dataset, this high accuracy also means the model is most likely overfit to the data. The training set is limited: a. the number of training images is small compared to the variability in facial expressions and skin coloring, and b. the sick images only contained overt clinical signs. If trained on a larger, diverse set of data, this prototype app could prove extremely useful in surveillance efforts of individual to large groups of people in remote areas, e.g., to identify individuals in need of medical attention or get an overview of population health. In effort to improve the model, VisionDx was developed as a data collection tool to build a more comprehensive dataset. Within the tool, users can override the model prediction, i.e., false positive or false negative, with a simple toggle button. Lastly, the app was built to protect privacy so that other phone aps can't access the images unless shared by a user.ConclusionsDeveloped at PNNL for the Defense Threat Reduction Agency, VisionDx is a novel, camera-based mobile application for real-time biosurveillance and early warning in the field without internet dependency. The prototype mobile app takes pictures of faces and analyzes them using a state-of-the-art machine learning model to give two confidence levels of likelihood of being sick and healthy. With further development of a labeled dataset, such as by using the app as a data collection too, the results of the algorithm will quickly improve leading to a ground-breaking approach to public health surveillance.References1. Bradski G. (n.d.) The OpenCV Library. Retrieved Sept 30, 2018 at http://www.drdobbs.com/open-source/the-opencv-library/1844043192. Computational Vision: Archive. (1999). Retrieved Sept 22, 2018 at http://www.vision.caltech.edu/html-files/archive.html3. Ferry Q, Steinberg J, Webber C, et al (2014). Diagnostically relevant facial gestalt information from ordinary photos. ELife, 3, e02020.4. Fornace KM, Surendra H, Abidin TR, et al (2018). Use of mobile technology-based participatory mapping approaches to geolocate health facility attendees for disease surveillance in low resource settings. International Journal of Health Geographics, 17(1), 21. https://doi.org/10.1186/s12942-018-0141-05. Lopez DM, de Mello FL, G Dias, CM, et al (2017). Evaluating the Surveillance System for Spotted Fever in Brazil Using Machine-Learning Techniques. Frontiers in Public Health, 5. https://doi.org/10.3389/fpubh.2017.003236. Ma DS, Correll J, Wittenbrink B. (2015) The Chicago face database: A free stimulus set of faces and norming data. Behavior Research Methods, 47(4), 1122–1135. https://doi.org/10.3758/s13428-014-0532-5

Phlegmasia cerulea dolens (PCD) is a rare complication of acute deep vein thrombosis (DVT) characterized by fulminant venous thrombosis that compromises arterial blood flow, resulting in tissue ischemia, venous gangrene, and possible loss of limb. A high rate of morbidity and mortality associated with PCD requires prompt recognition and treatment. An accepted therapeutic algorithm for the management of PCD does not currently exist. Acute reduction in clot burden can be achieved through catheter-directed thrombolysis (CDT) with lower rates of post-thrombotic symptoms, and there has been a recent trend toward use of CDT. We report the case of a 26-year-old female who presented with PCD of her left leg and underwent successful CDT, highlighting the benefits of rapid recognition of a rare complication of acute DVT, and the role for a multidisciplinary endovascular approach to managing fulminant limb-threatening venous thrombosis.La phlegmatia caerulea dolens (PCD) est une complication rare de la thrombose veineuse profonde (TVP) aiguë caractérisée par une thrombose veineuse foudroyante qui compromet le débit sanguin et résulte en une ischémie tissulaire, une évolution vers la gangrène et le risque de perte de membre. La PCD est associée à un taux élevé de morbidité et de mortalité et requiert une reconnaissance et un traitement rapides. Il n’existe actuellement pas de modèle défini d’intervention pour la prise en charge de la PCD. Une réduction rapide du caillot peut être obtenue par thrombolyse guidée par cathéter (TGC), intervention associée à un taux plus faible de symptômes post-thrombotiques. Le recours à la TGC est d’ailleurs plus fréquent depuis peu. Nous décrivons ici le cas d’une patiente âgée de 26 ans qui présentait une PCD à la jambe gauche et qui a été traitée avec succès par TGC. Ce cas fait ressortir l’importance de savoir reconnaître rapidement une complication rare de la TVP aiguë, ainsi que d’appliquer une approche endovasculaire multidisciplinaire dans la prise en charge d’une thrombose veineuse fulminante susceptible de causer la perte d’un membre.Phlegmasia cerulea dolens (PCD) is a rare manifestation of acute proximal deep vein thrombosis (DVT) in which extensive clot causes arterial insufficiency and compartment compression.1 This can result in venous gangrene, threatening limb viability, and requires acute intervention. Catheter-directed thrombolysis (CDT) entails selective infusion of a thrombolytic agent at the site of thrombus via a penetrating catheter under radiographic guidance. This approach is a viable therapeutic option in the management of PCD as it can rapidly restore limb perfusion while minimizing systemic bleeding complications.Clinical practice guidelines directing the use of CDT for treatment of lower limb DVTs are varied. The most recent 2016 American College of Chest Physicians’ guidelines provide a weak recommendation for CDT in carefully selected patients,2 whereas the Society of Interventional Radiology strongly advises consideration of CDT in patients with extensive iliofemoral DVT.3 Limited trial data has highlighted the efficacy of CDT in optimizing venous patency and mitigating the incidence of chronic DVT complications, namely post-thrombotic syndrome (PTS) and venous ulceration, in acute iliofemoral DVT.4–7 The immediate thromboreduction afforded by CDT may minimize the chronic venous remodelling that results from the presence of residual clot which underlies the pathophysiology of PTS. A full appreciation of the immediate and long-term complications of CDT is lacking, thus creating controversy surrounding its use.8 We report a case of PCD that was successfully treated with CDT, highlighting the need for rapid recognition of a rare complication of an acute DVT and the benefit of CDT in carefully selected patients.CASE DESCRIPTIONA 26-year-old female presented to the Emergency Department (ED) at one of our tertiary care, academic hospitals with an 8-hour history of acute-onset, non-resolving left leg pain, swelling, and discoloration. The patient had also been experiencing exertional dyspnea and gradually worsening pleuritic chest pain for the past 1.5 weeks. Thromboembolic risk factors included obesity and use of the oral contraceptive pill. There was no history of previous venous thromboembolism, autoimmune disease, pregnancy loss, or malignancy. Family history was positive for postpartum pulmonary embolism in the patient’s mother.The patient was hemodynamically stable in the ED although with a slightly elevated heart rate of 93 bpm on arrival at triage. Her physical examination revealed a left leg that was markedly edematous from proximal thigh to foot, with accompanying blue discoloration, and significant pain to palpation of her limb. The range of motion was limited due to pain. Although the leg’s neurovascular status was intact, distal pulses were weak and the leg was cooler compared to the other. A computed tomography pulmonary angiogram confirmed the presence of multiple large, acute pulmonary emboli in the interlobar, lobar, and segmental arteries bilaterally with associated lung infarcts and leftward bowing of the interventricular septum, suggestive of right heart strain. Doppler ultrasound of the patient’s leg revealed extensive occlusive thrombus extending distally from the left external iliac vein to the trifurcation (Figure 1). Weight-based low molecular weight heparin was initiated; however, given the extensive burden of clot, consultations with both the Hematologist and Interventional Radiologist led to the decision of pursuing CDT. Prior to initiation of CDT, an IVC filter was inserted given the extent of the patient’s pulmonary emboli. Figure 1. Venogram of left femoral vein (white arrow) demonstrating extensive thrombus (A). Proximal view of thrombus in left external iliac vein (B). Using ultrasound guidance, the extensive thrombus was pulse sprayed with tissue plasminogen activator (TPA) using an AngioJet device (Figure 2), followed by mechanical thrombectomy and balloon angioplasty of the external iliac vein. TPA and heparin infusions were continued at the site of the thrombus in conjunction with systemic anticoagulation using a heparin infusion protocol. Follow-up venogram 24 hours later demonstrated patency of the left superficial and common femoral veins with residual non-occlusive thrombus in the left common iliac vein, at which time the selective infusions of tPA and heparin were discontinued. The patient tolerated the procedure well with no complications and was discharged home on rivaroxaban four days later.Figure 2. Venograms during and 24 hours post-CDT. Angio Jet device in situ, with inferior catheter site holes for TPA release (A). Balloon angioplasty of stenosis in left external iliac vein (B). Venogram post-CDT, demonstrating patency in the left femoral and external iliac veins (C). DISCUSSIONClinical features that have been shown to optimize the success of endovascular therapy for DVTs include acute onset of symptoms, often within 14 days, iliofemoral location of clot, and low risk bleeding profile, 2 all of which were present in our patient and likely contributed to her favourable outcome. Moreover, our patient had extensive, flow-limiting thrombus on Doppler ultrasound that was clinically manifest as widespread limb edema, acute ischemic pain, and discoloration, consistent with a diagnosis of PCD. Rapid recognition of PCD is required to institute venous recanalization and salvage limb viability. Guidelines for the management of this scenario are currently lacking but there has been a recent trend toward use of more aggressive techniques such as CDT. 8,9 Ongoing (ATTRACT, DUTCHCAVA) multicentre trials will help to inform future decision-making regarding the possibility of broadening the use of endovascular therapy for management of acute DVT,10 as it currently remains highly individualized and centre-specific.Ultimately, this case illustrates the role for a multidisciplinary approach to the management of a limb-threatening DVT. Recognition of PCD and rapid referral to a centre that is capable of performing an interventional radiological procedure may help to prevent significant morbidity. REFERENCES1. Chinsakchai K, Duis T, Moll FL, et al. Trends in management of phlegmasia cerulea dolens. Vasc Endovascular Surg 2011;45(1):5–14.2. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016;149(2):315–52.3. Vedantham S, Millward SF, Cardella JF, et al. Society of Interventional Radiology position statement: treatment of acute iliofemoral deep vein thrombosis with use of adjunctive catheter-directed intrathrombus thrombolysis. J Vasc Interv Radiol 2006;17:613–16.4. Elsharawy M and Elzayat E. Early results of thrombolysis vs. anticoagulation in iliofemoral venous thrombosis. A randomised clinical trial. Eur J Vasc Endovasc Surg 2002;24(3):209–14.5. Enden T, Klow NE, Sandvik L, et al. Catheter-directed thrombolysis vs. anticoagulant therapy alone in deep vein thrombosis: results of an open randomized, controlled trial reporting on short-term patency. J Thromb Haemost 2009;7(8):1268–75.6. Enden T, Haig Y, Klow NE, et al. Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial. Lancet 2012;379(9810):31–38.7. Haig Y, Enden T, Grotta O, et al. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol 2016;3(2):e64–71.8. Bashir R, Zack CJ, Zhao H, et al. Comparative outcomes of catheter-directed thrombolysis plus anticoagulation vs. anticoagulation alone to treat lower-extremity proximal deep vein thrombosis. JAMA Intern Med 2014;174(9):1494–501.9. Watson L, Broderick C, Armon MP. Thrombolysis for acute deep vein thrombosis. Cochrane Data Syst Rev 2014;1, Art. No.: CD002783.10. Liew A and Douketis J. Catheter-directed thrombolysis for extensive iliofemoral deep vein thrombosis: review of literature and ongoing trials. Expert Rev Cardiovasc Ther 2016;14(2):189–200.