The spread and intensity of lumbar epidural anaesthesia are unpredictable. Moreover, segments L5 and S1 are frequently missed. In this study the effect of 30 degrees trunk elevation on the spread and intensity of lumbar epidural sensory and motor blockade and on the cardiovascular system were studied. METHODS. After oral premedication with 7.5 mg midazolam, 30 patients 20 to 40 years of age, ASA 1-2, were randomly allocated to one of two groups according to their body position during injection of 20 ml 2% lidocaine (3 + 8 + 9 ml) into a lumbar epidural catheter (L2/3 or L3/4) and during the following 30 min: supine horizontal position or supine 30 degrees trunk elevation with 30 degrees leg elevation (hammock position). The patients received 500 ml Ringer solution before the epidural injection, followed by more Ringer solution. Systolic and diastolic blood pressures and heart rate were monitored noninvasively every 5 min; 30 min after the epidural injection the spread of analgesia (dullness of pinprick) and anaesthesia (no sensation of pinprick) as well as motor block according to Bromage were tested. A spread of anaesthetic segments including T12 to L3 was considered adequate for hip surgery, L3 to L5 for knee surgery, and L3 to S2 for foot surgery. Student's t-test, ANOVA, chi-square (Wilcoxon), and Mann-Whitney tests were used for statistical analysis. P < 0.05 was considered statistically significant. RESULTS. The median cephalad level of analgesia was lower in patients with the hammock position than those with the horizontal position (L1 vs T10; P < 0.05). There was no significant difference in the cranial level of anaesthesia (L2 vs L1) (Table 2). No significant difference was seen in the number of patients having adequate anaesthesia for hip surgery. Anaesthesia in the segments L5 and S1 was seen in 2/15 patients in the horizontal position and 8/15 patients in the hammock position (P < 0.05). The hammock position resulted in a higher percentage of patients having adequate anaesthesia for knee surgery (60% vs 13%; P < 0.05) and foot surgery (53% vs 13%; P < 0.05) (Table 3). Motor block was more profound in patients in the hammock position (Table 4). Blood pressure and heart rate did not change significantly in patients in the horizontal position (Fig. 1); there was a decrease in both systolic (7 mmHg) and diastolic (5 mmHg) blood pressures in patients in the hammock position. Heart rate did not change significantly (Fig. 2). No patient needed vasopressor support; the body position could be maintained in all patients during the observation period. One or two epidural reinjections according to the spread of anaesthesia 30 min after the first injection and to the scheduled operation resulted in adequate anaesthesia in every patient. DISCUSSION. More patients in the hammock position developed adequate anaesthesia in the relevant segments for knee and foot operations than patients in the horizontal position. These included the frequently missed segments L5 and S1. Patients in the hammock position had a clinically insignificant drop in systolic and diastolic blood pressure. In contrast to the young and healthy patients in this study, more severe cardiovascular changes might result in geriatric and/or ill patients subjected to a hammock position. For this reason, use of the technique in geriatric and/or ill patients requires special attention.


OBJECTIVE
To study the release of free endotoxin from Escherichia coli exposed to varying concentrations of the penicillin-binding protein (PBP) 3-specific beta-lactam antibiotic cefuroxime, the aminoglycoside tobramycin, and a combination of the two, and to test the relationship between bacterial killing rate and endotoxin release.

METHODS
A clinical isolate of Escherichia coli in logarithmic phase was exposed to 0.1, 2, 10, and 50 x minimum inhibitory concentration (MIC) of cefuroxime, tobramycin, and a combination of the two. Samples for viable counts and endotoxin analysis were drawn immediately before and after the addition of the antibiotics and at 1, 2, 4, 6, and 24 h. All experiments were performed in triplicate. For the analysis of endotoxin, a chromogenic limulus amoebocyte lysate assay was used.

RESULTS
Endotoxin liberation was found to be proportional to the number of killed bacteria for each antibiotic regimen at each concentration level justifying the endotoxin-liberating potential to be expressed as release of endotoxin per killed bacterium, an expression that was independent of the inoculum size. At all concentration levels there was a statistically significant difference between the treatments, with the highest release of endotoxin per killed bacterium for cefuroxime, lower for tobramycin and the lowest for the combination of the two drugs (P < 0.001). With increasing doses, there was a significant reduction (P < 0.001) in the propensity to release endotoxin. When the bacterial killing rate was correlated to the propensity to release endotoxin in bacteria exposed to tobramycin or the combination of tobramycin and cefuroxime, a significant negative correlation was found (P < 0.01). This reduction in endotoxin release was not caused by an unspecific endotoxin binding of tobramycin.

CONCLUSIONS
Addition of tobramycin reduced the cefuroxime-induced endotoxin release per killed bacterium to a level which was even lower than that of tobramycin alone in spite of an increased killing rate. Increasing concentrations of tobramycin led to reduction in endotoxin release, which may be of benefit when dosing aminoglycosides once daily.


Purpose – The purpose of this paper is to find consumption-related similarities and differences between the three major dimensional models of national culture, to help researchers select specific models or dimensions for their cross-cultural studies. Design/methodology/approach – First, a review of the theoretical background of cultural values and three models of national culture is provided: those by Hofstede, Schwartz and GLOBE. Then these models are compared through partial correlation analysis, controlling for GNP/capita of a set of 25 relevant consumer behavior-related data with country scores of 21 dimensions of the three dimensional models. Findings – Of all models several dimensions explain differences in consumer behavior. Some dimensions explain values related to specific consumer behavior domains better than others. Only a few dimensions of different models do not show meaningful interesting relationships with consumer behavior issues. Dimensions with the same label do not explain similar differences. Practical implications – Cross-cultural researchers can choose from the several cultural models, but selecting a model only based on descriptions of the contents of dimensions is difficult. The relationships of dimensions with concrete consumer behavior data found in this study facilitate choice. This analysis may help researchers who consider conducting cross-cultural analysis of consumer behavior data to select a specific model, or specific dimensions of different models that apply best to their research question. Originality/value – This is the first study that compares the three major dimensional models with examples of consumer behavior-related items.


An outward travelling-wave current distribution can be produced on a centre-fed dipole, by loading it with nonreflecting loading at the ends of each element. The radiation resistance of such an aerial is evaluated in an isotropic, collisionless, warm plasma, using hydrodynamic theory. It is shown that this aerial is less affected by the presence of plasma than the usual unloaded dipole aerial, which has a sinusoidal current distribution, and that it can usefully be employed in satellite transmission.


A key challenge for people that are new to reviewing is pitching the review at the right level, and getting the tone and structure of a review right. This course aims to help participants understand a) the different expectations of different venues and submission types, b) the processes they use to make decisions, and c) good techniques for producing a review for these different circumstances. Combined with developing a good understanding of these different expectations, participants have a chance to critique anonymised proto-reviews, and try to guess the venue they are written for and the recommendation they make.


Shrinking microprocessor feature size and growing transistor density may increase the soft-error rates to unacceptable levels in the near future. While reliable systems typically employ hardware techniques to address soft-errors, software-based techniques can provide a less expensive and more flexible alternative. This paper presents a control-flow error classification and proposes two new software-based comprehensive control-flow error detection techniques. The new techniques are better than the previous ones in the sense that they detect errors in all the branch-error categories. We implemented the techniques in our dynamic binary translator so that the techniques can be applied to existing x86 binaries transparently. We compared our new techniques with the previous ones and we show that our methods cover more errors while has similar performance overhead.


The cancer risk of nondysplastic Barrett's esophagus is very low (0.33-0.5 per year). Therefore, any endoscopic ablation technique is an overtreatment. Patients with low-grade intraepithelial neoplasia confirmed by a specialized GI pathologist seem to have a significant risk for developing high-grade intraepithelial neoplasia (HGIN) or cancer. Therefore, endoscopic treatment in this case seems to be justified. However, up to now there has been no prospective study supporting this. In recent years, endoscopic treatment of HGIN and mucosal Barrett's cancer has become a widely accepted treatment approach and even the therapy of choice in many countries. Endoscopic resection (ER) is the best validated treatment method in patients with HGIN and mucosal Barrett's cancer, and is widely used all over the world. In contrast to ablative treatment methods like argon plasma coagulation and radiofrequency ablation, ER allows histological assessment of the resected specimen in order to assess the depth of infiltration of the tumor. However, ER of the neoplastic lesions should always be followed by ablation of the nondysplastic remaining Barrett's esophagus in order to reduce the risk of recurrence or metachronous neoplasia. The long-time complete remission rate with this two-step strategy is ≥95%. A matter of continuing debate is whether patients with Barrett's cancer infiltrating the upper third of the mucosal layer (pT1sm1) can be treated by ER. Data from our and other centers indicate that a subgroup of patients with pT1sm1 adenocarcinomas without the presence of risk factors (poor differentiation grade, lymph or blood vessel infiltration, size >20 mm, ulcerated lesion) have a very low risk for lymph node metastasis (<2%) and endoscopic therapy can be an alternative to radical surgery.


Fifty-nine postmyocardial infarction patients received combined therapy involving chemotherapy, physiotherapy, therapeutic exercises and yoga therapy. Thirty-seven controls received the same treatment without yoga exercise. The yoga complex implied elementary simple positions, relaxation exercise and respiratory exercise. A clinical response evident in both the groups appeared more pronounced in the test group as shown by marked improvement in external respiration and blood counts, in exercise tolerance and psychosomatic condition of the patients.


Burmese has two styles of speaking and writing: the colloquial style, which is used for talking to friends and for writing letters, and the literary style, which is used in more formal contexts, such as academic articles, newspaper reports, and narrative passages in fiction. This volume, the final book in a four-part Burmese language course, introduces learners to the literary style. It assumes a prior knowledge of Burmese script and a grounding in the colloquial style.Okell starts with simple sentences, and, over a series of short lessons, gradually increases the range of vocabulary and the level of complexity. The texts Okell uses for study are excerpts from Burmese children s schoolbooks highlighting themes of home- and school-life and Burmese nationalism and independence. Each passage is accompanied by a full translation and is followed by a set of exercises designed to familiarize the reader with the new vocabulary and sentence structures. Accompanying audio files allow students to hear the texts read aloud. Language professors, their students, or those learning Burmese on their own will appreciate the accessible approach and the manageablesize of the lessons of the very practical textbooks in this series."


A novel JPEG2000-based algorithm, termed quality pre-specifiable layered JPEG2000 (QPSL-JPEG2000), for realizing a layered image transmission (LIT) system is presented in this paper. In the QPSL-JPEG2000 algorithm, the resolution and rate associated with each layer of the LIT system can be pre-specified. It encodes an image one layer at a time using the modified JPEG2000 technique. The encoding process at each layer only covers the subbands having resolution level lower than the designated resolution at that layer subject to the pre-specified incremental rate budget. The encoding results at the previous layers will be used in the current layer to accelerate the encoding process. Numerical results show that the QPSL-JPEG2000 algorithm outperforms its counterparts for constructing the rate and resolution pre-specified LIT systems.


In the present experiment an attempt has been made to optimize the effect of different medium, levels of sucrose, pH, adenine sulphate and light intensity for culture establishment and shoot proliferation in guava using nodal segment explants. Culture establishment was greatly influenced by media types. Maximum establishment of explants (74.57%) was recorded on MS medium supplemented with 2.0 mg/l BAP + 0.2 mg/l IBA. In proliferation study, the maximum shoot proliferation was observed in MS + 1 mg/l BAP + 0.25 mg/l GA3. Sucrose 3% was found to be more favorable for maximum proliferation and growth of shoots moreover, it was reduced gradually as increased or decreased levels of sucrose from 30 g/l. among the various pH levels tested, pH 5.5 recorded maximum number of shoots (8.08) and maximum length of shoots (3.75 cm).In proliferation medium the length of shoot, numbers of shoots and growth rate were increased as increased the adenine sulphate level in the medium. Maximum proliferation was observed on 160 mg/l adenine sulphate in the medium. High light intensity 3000 lux was found to be most suitable for proper growth of regenerated shoots. Low light intensity (1000 lux) resulted in stunted growth. All the above factors significantly influenced shoot multiplication and growth. Thus, optimization of these factors showed significantly increased number of shoots and rapid multiplication. This could be useful for the in vitro production of cost effective healthy planting material of guava Keywards: Adenine sulphate, Light intensity, Multiplication, pH, Shoots


The effect of junction space-charge-layer thickness modulation is normally omitted in the conventional diffusion capacitance model. This note calculates the diffusion capacitance including such an effect and investigates the errors introduced by the conventional model under a wide range of bias conditions, as well as for different doping concentrations, different layer thicknesses, and different temperatures.


The widespread use of derivatives has created considerable new risks, especially of a systemic nature. To reduce risks regulators hare mandating the use of central counter-parties, of trade repositories and of regulated trading facilities. The paper gives a short overview of pending European proposals. It also deals with the court decisions that have been rendered in relating to derivatives, or structured products in several European jurisdictions, especially opposing local authorities and private investors to banks.


Gul-e-Shadab Mukhtar**, Mohammad Nawaz, Yasmin Nawaz and Asmathullah-Kakar Department of Zoology, University of Balochistan, Quetta, Pakistan  Abstract.During survey of grasshopper fauna (2005-2006) in various representative localities of Quetta division of Balochistan, 14 species were collected. Out of these, 11 species are recorded for the first time from this area. These are: Acrida exaltata (7.0%), Aiolopus thalassinus thalassinus (16.9 %), Heteracris illustris (0.22%), Locusta migratoria (4.3%), Oedaleus senegalensis (3.14%), Oedaleus abruptus (0.22%), Ochrilidia gracilis gracilis (2.7%), Schistocerca gregaria (1.6%), Scintharista notabilis (16.2%), Sphingonotus rubescens rubescens (8.31%) and Truxalis eximia eximia (3.0%), The species distributions and occurrence at the district level are also considered.


Relational index structures, as for instance the Relational Interval Tree, the Relational RTree, or the Linear Quadtree, support efficient processing of queries on top of existing object-relational database systems. Furthermore, there exist effective and efficient models to estimate the selectivity and the I/O cost in order to guide the cost-based optimizer whether and how to include these index structures into the execution plan. By design, the models immediately fit to common extensible indexing/optimization frameworks, and their implementations exploit the built-in statistics facilities of the database server. In this paper, we show how these statistics can also be used for accelerating the access methods themselves by reducing the number of generated join partners. The different join partners are grouped together according to a cost-based grouping algorithm. Our first experiments on an Oracle9i database yield a speed-up of up to 1,000% for the Relational Interval Tree, the Relational R-Tree and for the Linear Quadtree.


Node classification is a central task in graph data analysis. Scarce or even no labeled data of emerging classes is a big challenge for existing methods. A natural question arises: can we classify the nodes from those classes that have never been seen? In this paper, we study this zero-shot node classification (ZNC) problem which has a two-stage nature: (1) acquiring high-quality class semantic descriptions (CSDs) for knowledge transfer, and (2) designing a well generalized graph-based learning model. For the first stage, we give a novel quantitative CSDs evaluation strategy based on estimating the real class relationships, to get the "best" CSDs in a completely automatic way. For the second stage, we propose a novel Decomposed Graph Prototype Network (DGPN) method, following the principles of locality and compositionality for zero-shot model generalization. Finally, we conduct extensive experiments to demonstrate the effectiveness of our solutions.


A single intake of 200-250 ml of the mineral water "Naftusia" may lead to a negative balneological reaction manifested in an increase of pain and activity of the indicator enzyme alanine aminotransferase in the blood. On the contrary small amounts of this mineral water taken not long before meals prevents the above negative effects.


The paper is concerned with a description of the results of polyrheovasographical studies in 102 patients with late stages of vibrational disease. The authors distinguished 3 variants of vascular disturbances: hypertonic, hypotonic, dystonic. The cold test detected in most of the patients changes of the vascular reactivity in the form of increased, decreased and--less frequently--inverse reactions to this stimula. The conclusion is made that polyrheovazographical studies permit to clarify the character and degree of the expressiveness of vascular disorders in most of the patients with vibrational disease which is very important for defining the stage of the disease and the assessment of the working capacity in this contingent.


The rise in adoption of mobile cloud computing (MCC) has increased the security concerns and this fact has motivated security practitioners to consider novel lightweight authentication approaches in order to improve the authentication as a service (AaaS). Indeed, the authentication process has a direct e ect on client's perception of trust and therefore the authentication method is required to be robust and easy to use simultaneously. In this paper, we have proposed virtual port knocking authentication method which uses port knocking to authenticate users by using the closed port. Moreover, it employs the virtualization concept taken into account as a constructive concept in MCC to enhance the performance which is a ected by long length of knock sequence in the basic port knocking. The statistical results indicate that the proposed method o ers an acceptable level of security calculated based on the probability of hacking. The empirical results indicate that the imposed bu ering load to the cloud gateway is decreased around 4% for the short length knock sequence while, the enhancement is about 12% in case of using the long knock sequence.


Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder that causes congenital glaucoma. Previous experiences have shown that drainage procedures are often required to control associated glaucoma. The conventional surgical approach in trabeculectomy carries a significant risk of intraoperative expulsive hemorrhage. Here, we describe a modified approach of the conventional trabeculectomy technique, which may lower the risk of expulsive hemorrhage. A viscoelastic device was employed to maintain a steady intraocular pressure throughout the procedure. Details of the surgical technique and material used are described. One patient with congenital glaucoma associated with SWS underwent a successful trabeculectomy using the modified technique. Postoperative intraocular pressure was successfully reduced and no intraoperative complications occurred. We describe a successful case of trabeculectomy in a SWS case where a modified technique was applied.


In a group of 269 untreated hypertensive patients the effect of a single oral dose of captopril (25 mg) on blood pressure was studied for 90-120 minutes. The systolic blood pressure decreased by more than 20% in 9.5% and by more than 30% in 1.1% of the patients. In 22.6% the diastolic blood pressure decreased by more than 20%; in 4.5% it fell more than 30%. The calculated mean arterial pressure (MAP) was reduced by more than 20% in 12.3% of the patients and by more than 30% in 3%. Three patients showed transient neurological deficits. Factors related to a strong blood pressure drop were: renal artery disease and resistant hypertension. However, a potentially dangerous fall in blood pressure, i.e. an acute fall of MAP of over 30%, was also observed in the absence of these risk factors. Therefore not all patients at risk can be identified in advance, and treatment with ACE-inhibitors has to be started under well-controlled circumstances especially in elderly patients.


The study determined the effect of UNICEF promoted traditional communication patterns on the attitude of farmers towards malaria prevention and control in Imo State Nigeria. Two groups of respondents were selected from four Local Government Areas of the State. First was a group that participated in a UNICEF communication project (the community dialogue) and another was a group that never participated in the community dialogue. Two hundred (200) respondents were selected from each group. A set structured questionnaire was used to collect data from the respondents. Result of the t-test showed that UNICEF promoted health messages had positive effects on the attitude of the participants towards malaria prevention and control practices. Key Words : Attitude, Farmers, Community Dialogue, Malaria, Communication


—Human-robot interaction (HRI) and human-robot collaboration (HRC) has become more popular as the industries are taking initiative to idealize the era of automation and digitalization. Introduction of robots are often considered as a risk due to the fact that robots do not own the intelligent as human does. However, the literature that uses deep learning technologies as the base to improve HRI safety are limited, not to mention transfer learning approach. Hence, this study intended to empirically examine the efficacy of transfer learning approach in human detection task by fine-tuning the SSD models. A custom image dataset is developed by using the surveillance system in TT Vision Holdings Berhad and annotated accordingly. Thereafter, the dataset is partitioned into the train, validation, and test set by a ratio of 70:20:10. The learning behaviour of the models was monitored throughout the fine-tuning process via total loss graph. The result reveals that the SSD fine-tuned model with MobileNetV1 achieved 87.20% test AP, which is 6.1% higher than the SSD fine-tuned model with MobileNetV2. As a trade-off, the SSD fine-tuned model with MobileNetV1 attained 46.2 ms inference time on RTX 3070, which is 9.6 ms slower as compared to SSD fine-tuned model with MobileNetV2. Taking test AP as the key metric, SSD fine-tuned model with MobileNetV1 is considered as the best fine-tuned model in this study. In conclusion, it has shown that the transfer learning approach within the deep learning domain can help to protect human from the risk by detecting human at the first place.


The WEEL guide for dimethyl ether (DME) was originally established in 1996 and updated in 2010. Literature searches to identify new toxicity information were performed in November 2020 and evaluated by the WEEL Revisions Subcommittee. No new studies or data relevant to the WEEL guide were identified. DME has very low acute inhalation toxicity with a 4 h LC50 in rats of 164,000 ppm, and a cardiac sensitization threshold in dogs of >200,000 ppm. In repeated inhalation studies of up to 2 years in the rat, DME was not carcinogenic and produced minimal toxicity at 25,000 and 10,000 ppm: the NOAEC was 2000 ppm. DME was not teratogenic in pregnant rats up to 40,000 ppm; slight maternal and fetal toxicity were observed at >5000 ppm. DME was not mutagenic in vitro or in vivo. The primary finding with inhalation exposure was a reversible CNS depression. Based on a clear NOAEC of 2000 ppm for all effects in a lifetime inhalation study in rats, and the general low level of toxicity found in acute and subchronic toxicity studies, a WEEL of 1000 ppm (v/v; 8-h time-weighted average) was reaffirmed in 2021 and should provide an adequate margin of safety.


Residues of the insect growth regulator diflubenzuron were quantified on horse chestnut (Aesculus hippocastanum L.) leaves treated with a diflubenzuron 480 g litre(-1) SC, Dimilin. To analyse the samples, an analytical procedure was developed involving a simple extraction step followed by high-performance liquid chromatography on an octadecyl-modified silica column with methanol + 0.01 M ammonium acetate mobile phase. The results showed diflubenzuron to be highly stable on horse chestnut leaves; more than 4 months (127 days) after application, 38% (on average) of the insecticide still remained on/in the leaves. The data confirmed biological observations showing diflubenzuron's long-term efficacy against the horse chestnut leafminer, Cameraria ohridella Deschka and Dimić, which is the most important pest of the horse chestnut in Europe. The hypothesis of possible penetration of diflubenzuron into the leaf mass is explored and discussed.


Through the utilization of the "Magnus effect" on the Flettner rotor ship, the attention of the public has been directed to the underlying physical principle. It has been found that the Prandtl boundary-layer theory furnishes a satisfactory explanation of the observed phenomena. The present article deals with the prevention of this separation or detachment of the flow by drawing the boundary layer into the inside of a body through a slot or slots in its surface.


As a special case of symmetric game in which the players share a common payoff matrix, evolutionary game provides a suitable approach to model and explore the emergence of cooperative behavior in natural and social systems. The evolutionary spatial game (ESG) further specifies the payoff for each individual by both the payoff matrix M and the spatial dependence structure of the population on a geophysical domain. Two players game serves as a foundation of modeling various biological/social interactive systems and provides a great amount of interesting game theoretical models such as prisoner's dilemma game, snow drift game etc. We formulate a two players evolutionary spatial game under the framework of initialization, effective local payoff, and the Markov chain for strategy update. The spatial dependence structure is modeled by a probability distribution parameterized by the dependence geometry and strength in the neighborhood of each location. Particularly, we study the structure based on Gaussian process. Computational methods are proposed and applied to study the convergence of simulations. In addition, limiting non-local differential equation is introduced and analysed in terms of spreading speeds and traveling waves.


The aim of bachelor thesis was to develop a literature search for the potential creation of oftrihalomethanes (THMs FP) as indicators of water quality in surface water treatment. The THM FP test was monitorated to evaluate the effectiveness of current technological methods of treatment of natural water with special consideration of water with increased content of humic substances. The attention was focused on comparison of the THM FP values with the normally applicable water quality parameters; it means the concentration of dissoluble organic carbon (DOC), UV254, CODMn, CODCr. The obtained evidence suggests that THM FP test allows sensitively assess water quality in term of content of chemically and biologically easily biodegradable organic substances. The potential of THM formation has been proved as a valuable tool for quantify non-specific organic contaminants in treated water, which can usefully complete previously used criteria for assessing quality of treated water. KLICOVA SLOVA: potencial tvorby trihalogenmethanů (THM FP), huminove latky, ucinnost upravy vody, jakost pitne vody


Abstract Herein we describe a unique case of previously healthy child in Greece who developed septic arthritis of hip due to Salmonella enteritidis. To the best of our knowledge, this is the first report in the literature of septic arthritis of hip in a child with no preexisting disease caused by S. enteritidis. The case was documented by culture of the aspirated joint fluid and blood cultures. The isolated microorganism was identified on species level in the National Reference Centre for Salmonella and Shigella. Antimicrobial therapy and arthrotomy were performed. The patient developed sequalae (complete disruption of the femoral cap) and she is still followed.


Background Early identification of RA and early treatment is associated with a better disease outcome. Achieving early identification of RA requires that patients seek medical advice in time. Thus far motivations of patients with RA to seek medical help have been studied in relative small studies (around 30 patients per study, min 3, max 120 patients)1and have not been compared to the motivations of persons with joint complaints for other reasons. Objectives We aimed to increase the comprehension of patients' motivations & perceptions determining the urgency in which persons with joint complaints seek medical advice. Methods We studied 612 patients with joint complaints that visited recently initiated Early Arthritis Recognition Clinics (EARC) in Leiden and Groningen; these screening clinics aim to identify arthritis very early by reducing the delay with which general practitioners send patients to rheumatologists (GP delay). At this clinic patients filled out a questionnaire with questions on their symptoms and their motivations to seek medical advice. The period between the first symptom and the first visit to the EARC was called the total delay and the period between the first symptom and the first visit to a general practitioner patient delay. Motivations were compared between patients with a short or prolonged patient delay, between patients with and without arthritis, and between men and women. Results The median total delay was 10.5 (IQR 3.6-40.5) weeks, the median patient delay was 3.0 (IQR 0.7-12.9) weeks. 44.4% of the patients visiting the EARC had arthritis, in this subgroup the median patient delay was 2.1 (IQR 0.7-7.0) weeks. In all 612 patients frequently mentioned concerns to seek help were worsening of complaints (66%) and because of impairments in daily functioning (35%). The most frequent reason to postpone seeking medical help was the thought that complaints would pass (39%). Both in all patients and in arthritis patients, persons that sought help within 3 weeks after symptom onset had more often a sudden onset of complaints (P<0.001), experienced more often absentness of work (P<0.001), and had more impairments in daily functioning (P=0.004). In contrast, a longer patient delay (>3 weeks) was associated with a waxing and waning pattern of symptoms (P=0.011), the conception that the complaints would pass (P<0.001) and the belief that the symptoms were not serious (P=0.003). The patient delay was not significantly different between men and women (median 2.6 and 3.4 weeks resp.). Nevertheless, female patients reported more frequently progression of complaints as motivation to seek help (P=0.013), whereas men mentioned more often to be concerned about the cause of the complaints (P=0.03). Conclusions This large-scale study observed several motivations and symptom characteristics influencing the urgency of persons with joint complaints to seek medical help. Especially arthritis patients with a gradual course of complaints did not consider their symptoms as ominous. These data can be helpful in order to define strategies aiming at early identification of arthritis. References Stack R.J, Shaw K, Mallen C et al. Ann Rheum Dis 2011 epub ahead of print. Disclosure of Interest None Declared


The stocks of the Atlantic salmon (Salmo salar) in many rivers in North America and Europe have declined in recent years and are experiencing a crisis. Despite their high degree of legal protection, the quality of their aquatic environments within rivers and in the sea, including local coastal waters, appears to be deteriorating. Salmon survival, has declined both within the sea and within rivers. The status of the Atlantic salmon stocks is considered here, together with the adverse effects of different sources, and those steps that may need to be taken to improve the condition of the salmon. This paper is intended to assist management bodies in taking steps to resolve the problems that exist for salmon, both within rivers and in the sea. It makes particular use of information available on the River Dee in Scotland.


The purpose of this study is to develop an
optimized ANN model to determine the optimal
start time for HVAC systems For this,programs for
predicting room air temperature and ANN model using
generalized delta rule were developed, and learning
data for 27 spaces using systems of experimental
design were collected through simulation for predicting
room air temperature. Then,ANN was trained and the
optimized ANN model was presented.


Students' reading of the course materials had never been measured because no data was available. It was assumed that students who performed better in their learning would have read their course materials more compared to those who performed poorly. The Singapore University of Social Sciences (SUSS) provided course materials in electronic forms in textbooks and study guides. The purpose of this study, based on data from the Academic Year 2020, was to find out was there a correlation between students' reading of the course materials and their performance in 10 online courses. A quantitative approach was used in the study. It was found that a very weak positive relationship, r (0.151), existed for students who read the e-textbooks while there was almost no relationship, r (0.084), for students who read the study guides when correlated with their performance. Furthermore, a statistical significance existed in the medians of e-textbook and study guide usages between those students who passed the online courses compared to those who failed. This significance could also be found in students' grade-bands. This study will be of interest to institutions with data available on students' readership behaviour. It is relevant to the sub-theme of "inspiring innovations" as it involves data analytics for online learning.


Background: Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGf) family, a group of angiogenic growth factors important in cancer development. Over-expression of PlGF is known to be associated with pathological angiogenesis. Recently, PlGF has been shown to have 4 isoforms, -1, -2, -3 and -4. This current study examined the expression of PlGF-1 and -2 in human breast cancer and how changes in expression of these isoforms may be linked to prognosis of the disease.Materials and Methods: Breast cancer primary tumours (n=114) and matched background tissue (n=30) were processed for RNA extraction. RNA was reversed transcribed and quantified before analysis by Q-PCR. The results were expressed as copy number of transcript/50ng RNA and standardised using β-actin. Statistical analysis was carried out using student t test (mean±SD) and Mann-Whitney U test (median/IQR) where appropriate. Immunohistochemistry was also carried out on a number of matched background and tumour sections.Results: Analysis of patients with a 10 year follow-up showed that transcript levels of PlGF-1 were increased in node positive tumours when compared to node negative (104.2±52.2 versus 52.5±13.6, respectively, but this did not reach significance(p=0.34). Prognostic indicators (NPI status, TNM status and grade of tumour) were not associated with significant changes in levels of PlGF-1. Moreover, there was no difference in expression with overall ER status of tumours; however, PlGF-1 was significantly increased in ERβ positive tumours (median values ERβ-ive and ERβ+ive (14.10 vs 68.75 respectively, p=0.014). Most interestingly, there was a significant increase in PlGF-1 expression in patients with poor outcome (median values patients remaining disease-free 16.5, patients who died from breast cancer 78.2, p=0.03). In comparison, the PGF-2 isoform showed little change in expression between tumour and background samples. However, Immunohistochemistry demonstrated a marked increased in PGF-2 expression in tumour sections (staining intensity (mean±SD): Background 102.05± 46.65 vs Tumour 172.85±40.33, n=20, p=0.0001).Conclusions: We can conclude from this data that there is a differential expression of the PlGF isoforms in human breast cancer. Inappropriate expression of PlGF isoforms may play a role in human breast cancer progression. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3041.


The changes in the global balance of power that emerged following the Cold War have had far-reaching implications for the conduct, management and resolution of local conflicts. They have necessitated a fresh examination of the rules and norms of international crisis management and conflict resolution at a global level. This book provides analyses of international intervention in local conflicts including those in Cambodia, Somalia, Yugoslavia, the Western Balkans and Northern Ireland. Special attention is devoted to American and European involvement in Middle East conflicts, as well as the unique role of regional and local actors in determining their course. This will be an invaluable resource for students and scholars of international relations and conflict resolution.


In this study, we primarily aimed to investigate coaches' roles and their considerations in shifting coaching roles they perform. Employing a qualitative descriptive research, we conducted semi-structured interview sessions with ten instructional coaches to determine their roles and considerations in shifting roles during coaching English teachers in primary schools. Utilizing Braun and Clarke's (2006) six-phase approach, we employed thematic analysis to analyse the desired data collected in the study. The findings suggested that there were three roles instructional coaches enacted, namely, the role of the implementer, advocate, and educator. The roles were influenced by coaches' considerations of teacher readiness, coaching style and coaches' qualities. The findings also showed that the coaches performed a non-authoritative approach in their coaching and constantly role-shifted between the roles according to the demand of different situations. Influencing their decision in role-shifting, the coaches' roles and their considerations provide insights into instructional coaching. As such, practitioners and stake holders can reflect and enhance the implementation of the coaching programme to encourage supportive coaching activities. Because there is a need to conduct adequate research on instructional coaching specifically in the context of Malaysia, this study offers an insight into coaches' specific roles in Malaysia. Future research can take a closer look at the "in-the-moment" coaching process to determine the professional development programmes designed based on coaches' understanding of role-shifting.


Background: The composition and function of intestinal microbial communities are important for human health. However, these intestinal floras are sensitive to changes in the environment. Adverse changes to intestinal flora can affect the health of astronauts in complex space environments, resulting in difficulties of implementing space missions.Results: Under the influence of different space environmental factors, the species composition at the phylum and genus level were significantly affected by the combined effects environment. Furthermore, screening was conducted to identify biomarkers that could be regarded as environmental markers. And there have also been some noticeable changes in the function of intestinal floras. Moreover, the antibiotic resistance genes (ARGs) were also found to be differently expressed under different environmental conditions.Conclusion: The combined effects environment could significantly affect the species composition, function and the expression of ARGs of intestinal flora which may provide a theoretical basis for space medical supervision and healthcare. Meanwhile, these changes require more attention because they may induce diseases that may further affect performance during space missions.


Low-lying and high-spin states of 124Cs are studied through the 116 Sn(11 B,3n)124 Cs reaction at a beam energy of 45 MeV. Several new linking transitions are observed, including three transitions between the yrast and πh11/2 ⊗ νd3/2 bands and two transitions between the yrast and πh11/2 ⊗ ν(d5/2, g7/2) bands. These transitions fix the excitation energy of the yrast band and its decay path, and confirm the existence of eight E1 linking transitions between the yrast and πh11/2 ⊗ ν(d5/2, g7/2) bands observed before. These E1 linking transitions infer the octupole correlation in Cs. The decay paths of the yrast band are investigated, and discrepancies in the level scheme of 124Cs in the latest two studies are clarified. The reason for the discrepancies is discussed. A new decoupled band is established and temporarily assigned as the unfavored signature partner of πh11/2 ⊗ νd3/2 configuration.


In this paper we discuss tests for residual cross section dependence in nonlinear panel data models. The tests are based on average pair-wise residual correlation coefficients. In nonlinear models, the definition of the residual is ambiguous and we consider two approaches: deviations of the observed dependent variable from its expected value and generalized residuals. We show the asymptotic consistency of the cross section dependence (CD) test of Pesaran (2004). In Monte Carlo experiments it emerges that the CD test has the correct size for any combination of N and T whereas the LM test relies on T large relative to N. We then analyze the roll-call votes of the 104th U.S. Congress and find considerable dependence between the votes of the members of Congress.


. The projected climate change and increase in thermal conditions in northern latitudes over the next 60 yr has the potential to alter the metabolic scope and potential fi tness of aquatic ectotherms. Here, we experimentally tested if elevated egg incubation temperature affected metabolic scope in juvenile brown trout ( Salmo trutta ) as a phenotypically plastic response. Cohorts of brown trout from anadromous and resident crosses were raised through embryogenesis in either natural river temperatures (cold) or elevated ( + 3 ° C, warm) temperatures until they could feed exogenously. The standard metabolic rate (SMR), maximum metabolic rate (MMR), and aerobic scope (AS = MMR − SMR) of juveniles from four anadro-mous-resident crosses and from both incubation temperatures were tested at 13 ° C. We found that metabolic measures (SMR, MMR, AS) were lower in warm than cold-incubated fi sh. There was no difference in the metabolic rates of fi sh from different anadromous-resident crosses. The results of this experiment are consistent with the countergradient variation hypothesis (CGV) in which phenotypic variation, in this case variation in metabolic rates, is inversely related to thermal conditions, originally proposed in relation to altitudinal or latitudinal gradients. While previous studies have related CGV to genetic differences between populations, our study shows that thermal differences encountered at the embryonic stage can produce a phenotypic pattern consistent with CGV. It is dif fi cult to predict the consequences of these metabolic changes in a future warmer climate, as lower metabolic rates indicate that brown trout will probably expend less energy, but a reduced aerobic scope may counteract this affect, limiting their ability as a top predator and in escaping predators. Our results suggest that there are mechanisms used to adjust to elevated water temperature that can be initiated during embryogenesis. Given that there were no differences among crosses, it is likely that temperature-induced differences are the result of plastic responses. but no was found. The only effect on growth was temperature prior to hatching.


A torque ripple optimization scheme for SRM drive, based on exhaustive search method and 2-phase excitation model of SRM has been presented in this paper. The 2-phase excitation model of SRM used here takes into account the nonlinear effects because of saturation and mutual flux linkages caused by multi-phase excitation. In the proposed scheme the incoming and outgoing phase currents are modulated to minimize the torque ripple. Because of the highly nonlinear nature of torque, exhaustive search method is used for optimizing the torque ripple, by simulating the model multiple times. Modulation of phase current is done by addition, subtraction and multiplication of constants and variables. This can be very easily achieved in DSP micro-controllers and FPGAs. It has been shown by simulations, that the proposed optimization scheme reduces the torque ripple by more than 50% as compared to constant current scheme. The proposed optimization scheme has been experimentally validated


AIMS
The purpose of the present study was to define the dose-response relationship between exogenous dopamine and systemic haemodynamics, renal haemodynamics, and renal excretory function at infusion rates in the range 0 to 12.5 microg kg(-1) min(-1) in normal volunteers.

METHODS
While undergoing water diuresis, eight subjects were infused with 0, 1, 2, 3, 5, 7.5, 10 or 12.5 microg of dopamine kg(-1) min(-1) over 2 h in a randomized and double-blind fashion. On each study day, renal clearance studies were performed during a 1 h baseline period and subsequently during the second 1 h infusion period. Lithium clearance (CL(Li)) was used to estimate proximal tubular outflow.

RESULTS
Cardiac output increased with the four highest doses. Mean arterial pressure followed a biphasic pattern with a decrease during the two lowest doses and a dose-dependent increase from the 7.5 microg kg(-1) min(-1) dose onwards. Effective renal plasma flow increased with all doses of dopamine, but peaked with the 3 microg kg(-1) min(-1) infusion rate [from 617 (585-649) ml min(-1) with placebo to 915 (824-1006) ml min(-1) (means with 95% CI, P<0.001)]. None of the doses changed glomerular filtration rate (GFR). Sodium clearance (CL(Na)) and CL(Li) were elevated with the four lowest doses but increased further from 7.5 microg kg(-1) min(-1) onwards. Compared with placebo, the percentage increase in CL(Na) with increasing dose was 77 (5-159), 93 (13-172), 107 (24-190), 121 (60-181), 253 (65-441), 284 (74-494), and 212 (111-312) %, respectively. There were only small, inconsistent decreases in absolute proximal reabsorption rate (APR = GFR-CL(Li)). Fractional distal reabsorption of sodium (FDR(Na) = (CL(Li)-CL(Na))/CL(Li)) decreased with all doses, reaching its nadir with 7.5 microg kg(-1) min(-1) [from 95.9 (94.6-97.2) % with placebo to 91.5 (90.0-93.0) % (P<0.01)] whereafter a flat dose-response curve was observed.

CONCLUSIONS
In conclusion, the renal vasodilating effect of dopamine was maximal with 3 microg kg(-1) min(-1). The dose-dependent attenuation seen with higher doses is consistent with an increased alpha-adrenergic stimulation opposing the effect on dopaminergic receptors. The present CL(Li) studies confirm that dopamine increases proximal tubular outflow. The results suggest that the natriuretic effect of depressor doses of dopamine was primarily caused by attenuation of the increase in distal sodium reabsorption normally seen after an increase in proximal tubular outflow. Pressor doses further increased sodium excretion, indicating the presence of pressure natriuresis at these high doses.


The purpose of the current work is to investigate how country-level and region-specific characteristics influence the adoption of a major financial telecommunication innovation and standard (SWIFT) in the banking sector. Using annual data on the diffusion and usage intensity of SWIFT between more than 100 countries, this study finds that, along other characteristics, economies with higher GPDs and closer to the innovation source have on average a faster adoption rate than smaller, distant economies, all else equal. The analysis also shows that even though financial institutions differ considerably, network effects persist and dominate firm heterogeneity. The results are overall consistent with other findings using similar estimation techniques, and provide a stronger test by focusing on one specific innovation in the financial services industry rather then aggregate IT measures.


Federalism is a power-sharing political system, which designates power through various layers of government. Powers are delegated and decentralized by the constitution over the different layers of government. In federalism, intergovernmental or inter-province relations are very crucial for better delivery of the federal system. The provinces in Nepal are at loggerheads and as they are facing internal conflicts, and the inter-governmental relations are not so smooth. The provinces are attempting to make their internal cooperation better but this is not achieved due to political transition. Given this complex context, poor intergovernmental relations and conflicts between the three layers of government in Nepal have become one of the key challenges for the successful implementation of federalism. Limited knowledge, short experience with federalism and lack of legal and policy issues have created these gaps. The contexts have further jeopardized inter-governmental relations. Weak intergovernmental relations in federalism would ultimately pose a challenge to federalism and result in political instability in Nepal.


Strontium concentration and isotopic data for subsurface flowing groundwaters of the Ganges-Brahmaputra (G-B) delta in the Bengal Basin demonstrate that this is a potentially significant source of strontium to the oceans, equal in magnitude to the dissolved strontium concentration carried to the oceans by the G-B river waters. The strontium concentrations of groundwaters are higher by a factor of about 10 than typical G-B river waters and they have similar87Sr/86Sr ratio to the river waters. These new data suggest that the present contribution of the G-B system to the rise in 87Sr/86Sr ratio in seawater is higher by at least a factor of 2 to 5 than the average over the past 40 million years.


Leafy greens are responsible for nearly half of the produce-related Shiga toxin-producing Escherichia coli (STEC) outbreaks in the United States and recent investigations have implicated agricultural water as a potential source. Current FDA detection protocols require extensive analysis time. We aimed to use Oxford Nanopore rapid sequencing kits for an in-field determination of agricultural water microbiome and possible detection and characterization of STECs strain(s) in these samples. We tested the performance of the nanopore rapid sequencing kit (RAD004) for fast microbiome determination using the well characterized ZymoBIOMICS mock microbial community and the number of reads for each identified species was present in the expected proportion. Rapid sequencing kit (LRK001 and RAD004) library preparation of DNA extracted from agricultural water resulted in poor nanopore sequencing reactions, with low output (0.3–1.7 M reads), a high proportion of failed reads (50–60%), and highly sheared DNA before and after a magnetic bead clean up. To improve performance, we prepared a DNA library with the ligation kit (LSK109), which includes multiple cleaning steps, reducing inherent inhibitors and producing a better outcome (2.2 M reads, 15% failed reads). No definitive presence of STEC could be confirmed in any of the sites. Approximately 100 reads from each site (0.02% of total reads) were identified as Escherichia coli, but the specific strain or their virulence genes could not be detected. Sites 9, 10, and 12 were found to be positive for STEC presence by microbiological techniques after enrichment. The rapid sequencing kits can be appropriate for genus or species level microbial identification, but we recommend the use of the ligation kit for increased sequencing depth and removal of contaminants in agricultural water. However, we were not able to identify any STEC strains in these nanopore microbiome samples, due to low initial concentrations. The results from this pilot study provide preliminary evidence that MinION sequencing of agricultural water using the ligation kit has the potential to be used for rapid microbiome determination in the field with optimal results for water quality surveillance.


Engineering cost budgeting is crucial to the healthy development of the engineering and construction industry. To solve the problem of large deviations in budget results from using traditional methods of cost budgeting based on evaluation results or drawing conversions, the BIM engineering cost budgeting method based on social network analysis method is studied in this paper. On the basis of analyzing cost budgeting requirements and determining modeling economic criteria, the social network analysis method is used to analyze the project cost risks. According to the project quantity list, professional BIM software is used to budget the project cost. Case verification proves the feasibility of this budgeting method as the budget deviation is reduced by about 78% compared with the traditional method. The result of the paper has a more ideal practical application effect and positive significance for optimizing the traditional cost budgeting methods


Purpose: The subject geography is taught with the objective that learners will acquire basic foundation skills so as to propel them towards making valuable contributions to the society. The overall objective of this study was to examine influence of teachers' attitude on students' geography performance in public schools. A critical literature review
Methodology: The paper used a desk study review methodology where relevant empirical literature was reviewed to identify main themes and to extract knowledge gaps.
Findings: The findings of the study concluded that learners choose the subject of geography because they love and understand it. The learners have in mind the careers that they intend to pursue in future when they choose geography. Geography's diversity and scope also appealed to learners as a reason for choosing geography Friends have little influence in career aspiration choice. The teacher has an influence on the learner's choice for geography.
Unique Contribution to Theory, Policy and Practice: Geography subject is relevant in understanding the major problems that face the society today. The subject also contributes in better understanding of the environment. Geography should be made compulsory among all the secondary school students because its importance in attaining a clean environment and sustainable development cannot be underestimated. The teacher should relate the problems faced in the society to the content that is being taught so that learners can have a real life experience on the aspects that they learn in class. This will boost the subject's importance in understanding the various problems faced in the society.


Distant supervision (DS) is a promising approach for relation extraction but often suffers from the noisy label problem. Traditional DS methods usually represent an entity pair as a bag of sentences and denoise labels using multi-instance learning techniques. The bag-based paradigm, however, fails to leverage the inter-sentence-level and the entity-level evidence for relation extraction, and their denoising algorithms are often specialized and complicated. In this paper, we propose a new DS paradigm--document-based distant supervision, which models relation extraction as a document-based machine reading comprehension (MRC) task. By re-organizing all sentences about an entity as a document and extracting relations via querying the document with relation-specific questions, the document-based DS paradigm can simultaneously encode and exploit all sentence-level, inter-sentence-level, and entity-level evidence. Furthermore, we design a new loss function--DSLoss (distant supervision loss), which can effectively train MRC models using only $\langle$document, question, answer$\rangle$ tuples, therefore noisy label problem can be inherently resolved. Experiments show that our method achieves new state-of-the-art DS performance.


Infectious diseases are important causes of morbidity and mortality in immunocompromised patients with hematological malignancies, severe aplastic anemia (SAA), and myelodysplasia. Major advances in infectious diseases supportive care have been critical to improving the outcome of patients suffering from these life-threatening diseases. Advances in diagnosis, treatment, and prevention of life-threatening infections have reduced morbidity and mortality, improved quality of life, and enabled the use of potentially curative chemotherapy, radiation, hematopoietic stem cell transplantation (HSCT), and immunosuppressive therapy to patients battling these devastating diseases. Despite these advances, the continued development of antimicrobial resistance, emergence of new pathogens, and the evolution of host factors present evolving challenges to the successful management of infectious complications in this expanding patient population.


Reflective x-Si backplanes allow projection displays to evolve toward higher pixel count and greater miniaturization, extending the range of competitive application. As light valve area A is reduced, projector output into solid angle S equalsV (pi) NA2 can in many cases be considered to decrease roughly as approximately (A*S)0.5, with the 0.5 exponent representing typical microdisplay operating in a regime that is neither purely brightness-limited nor purely power-limited. Polarization modulation entails a modified scaling approximately (A*S/2)0.5; color sequential operation, approximately (1/3)*(A*S)0.5; spatially divided single-light-valve RGB projection, approximately (A*S/3)0.5. Projection lenses for three-light-valve system must provide an increased working distance to accommodate a color recombiner. Zoom lens are often required in front projectors, and rear projection usually entails a short lens-to-screen distance. It has become cost-effective to use plastic aspherical elements to meet these requirements. Periodic strip-PBS arrays have been widely adopted for polarization recycling, but aperiodic homogenizers are sometimes used to correct the uneven magnification and symmetry limitations of conic reflectors. Bright-state and dark-state beams must occupy distinct etendues in the half space above a reflective light valve, creating a vulnerability to crosstalk. Crosstalk from a polarizing beamsplitter gives rise to a residual background intensity approximately 0.3*NA2, unless a quarterwave corrector is used. Crosstalk can also arise from stress birefringence in prism substrates. Stray light makes an indirect contribution to background, but can sometimes be corrected by filtering.


Introduction: Nowadays, non-contagious diseases have been extended due to the renovation of societies, technology promotion, and density of population on urban zones and tendency of population to unsuitable habits. Cardiovascular diseases are from these failures and are the most widespread cause of death and disability in the most countries as well as in Iran. The purpose of this study was to evaluate the effect of family-centered empowerment model (FCEM) on the quality of life of the myocardial infarction patients. Method: This clinical trial conducted on all of myocardial infarction patients hospitalized in Coronary Care Unit of the selected Hospital (72 persons in intervention and control groups). Sampling was conducted by convenience sampling and then random allocation. For intervention group FCEM was implemented with four dimensions of perceived threat with group discussion method, self-efficacy with problem solving methods, self-esteem with educational partnership and outcome and process evaluations and usual care was done for control group members. In this study the instruments used were demographic variables, specialty instruments of FCEM, and SF-36 quality of life instrument. To analysis the data, Chi square, independent and dependent t, U man Whitney, Wilcoxon signed rank tests and Pearson correlation coefficient were used. Results: 8 dimensions of quality of life were similar in both groups before the intervention (P>0.05), but after the intervention both groups had significant differences (P<0.05). But, paired t-test showed significant differences only in the intervention group (P<0.05). Conclusion: FCEM for myocardial infarction patients was feasible and associated with improvement or modification of patients' quality of life. © 2015, Slack Incorporated. All rights reserved.


This paper deals with trajectory tracking for omnidirectional vehicles, and collision avoidance problems with non-cooperative vehicles. To achieve the two purposes, Switching between controls for those objectives is expected to be effective. We employ the minimal collision time as a criterion of switching. The switching control law depending on the minimal collision time is proposed.


OBJECTIVE
There are positive correlations between subjective health reports and episodic memory performance in older adults. However, previous studies have not evaluated the scope of such complex relationships, nor the potentially nonlinear magnitude of these correlations across age and time. We employed multiple subjective heath indices to evaluate the scope and nonlinearity of such relationships with memory performance.

METHOD
We utilized a cross-sectional (N = 2,783 at baseline) and longitudinal sample (N = 311) of healthy older adults aged 65 and older from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study. We used time-varying effects modeling (TVEM) to assess potential differences in relationship magnitudes between memory and three subjective health subscales (general health, role physical function, and physical function, from the Short Form Health Survey; SF-36) across five years.

RESULTS
Episodic memory positively predicted all subjective health measures cross-sectionally and longitudinally in our sample. TVEM revealed the relationships between all subjective health measures and episodic memory were stable across age. While role physical function and physical function maintained stable relationships with episodic memory across time, general health became increasingly coupled with memory five years following baseline.

DISCUSSION
Together, our findings highlight stable and varying relationships between episodic memory and multiple subjective health indicators across metrics of time in older adults.


Abstract The initial and cumulative efficacy of two antiseptic handwash preparations in eliminating Serratia marcescens from hands was evaluated on volunteers. Two antiseptics with persistent skin antibacterial activity, 4% chlorhexidine gluconate in detergent and 1.5% triclosan in natural soap, were studied in a new protocol designed according to Food and Drug Administration guidelines. After a single handwash, both preparations exhibited a degerming action statistically superior to the mechanical elimination of the marker organism that was achieved by the nonmedicated controls. Following a further nine hand recontamination sequence with 109 colony-forming units (cfu)/mL S marcescens (mean pre-disinfection baseline, log10 6.6), the efficacy of chlorhexidine and triclosan was significantly augmented: the mean log10 reduction factors were 4.15 and 3.78, respectively. In the absence of internationally accepted testing standards for antiseptic handwash products, the significance of protocol variables is discussed. The advantages to preventative microbiology of antiseptics with persistent skin antibacterial activity are highlighted.


The aim of this research is to understand the mechanism(s) of RVR formation during the changes in operating condition from the Best Efficiency Point (BEP) to Part Load (PL). A Computational Fluid Dynamic (CFD) methodology by the means of ANSYS-CFX is applied on a reduced high head Francis turbine model. The reduced model consists of one stay vane, two guide vanes, one runner blade, one splitter and a full draft tube. Numerical simulation is first performed at BEP as well as PL to ensure the appropriate employment of turbulence models and boundary conditions. In the second step, the inlet boundary conditions are changed linearly from BEP to PL in order to achieve the transient conditions inside the draft tube. The initial condition of the second step is the converged BEP result. The transient simulation is continued until the RVR is fully developed in the draft tube at part load condition. The numerical results for BEP, PL and BEP to PL are in a good agreement with the experimental data. The effect of the RVR is considered from two aspects. The first one is the frequency, and the amplitude of the pressure pulsations induced by the RVR in the draft tube. The second one is the velocity field in the draft tube which is investigated over time during load rejection. Moreover, the flow structure is visualized using the λ2 criterion. The mechanism(s) of RVR formation and damping is accurately investigated by the presented approach. Furthermore, the results provide a better understanding of the physics behind the RVR formation. The obtained results aim to design an effective RVR controlling approach.


Deoxygenation of glycerol in aqueous medium catalyzed by Pt/WO3/ZrO2 at relatively low temperatures (110–140 °C) under hydrogen pressure range from 2 to 5 MPa in a fixed-bed continuous-flow reactor gives 1,3-propanediol (1,3-PDO) and n-propanol (n-PrOH) as the predominant products, indicating high selectivity for deoxygenation of the secondary hydroxyl group over the primary hydroxyl groups of the glycerol. The optimum catalyst was prepared by calcination of WO3/ZrO2 at 700 °C and loading of 3.0 wt% Pt with W content of 10 wt%. The effect of reaction temperature, hydrogen pressure and initial water content were evaluated to find the optimum reaction conditions. The glycerol conversion and the yield of 1,3-PDO greatly depended on these factors. At 130 °C, 4 MPa and 70.2% conversion, the yield of 1,3-PDO was up to 32.0% (1,3-PDO/1,2-PDO = 17.7). The proposed mechanism for glycerol deoxygenation in aqueous medium over Pt/WO3/ZrO2 is an ionic pathway involving proton and hydride ion transfer steps.


The aim of this work was to improve the in vitro dissolution of simvastatin through development of self-nanoemulsifying tablets. Various modified oils, surfactant and co-surfactant mixtures were used to prepare different self-nanoemulsifying drug delivery systems (SNEDDS) whose composition was optimized using drug-solubility, ternary phase diagram, system stability and droplet size distribution studies. Optimized SNEDDSs, with acceptable surfactant ratio, stability and particle size (nano-range) upon dilution with simulated gastric fluid (SGF, pH 1.2) under gentle agitation conditions, were loaded onto microcrystalline cellulose and nano-size colloidal silicon dioxide powders using loading factor (Lf) = 0.2 and excipient ratio (R) = 20. Prepared powders were compressed into tablets and the in vitroperformance of the prepared self-nanoemulsifying tablets was investigated. Results revealed that systems with 10% relatively polar oils (C8), 60% Cremophore® RH 40 (surfactant), and 30% Transcutol® HP (co-surfactant), acquired good self-nanoemulsification properties either in liquid or tableted forms. Prepared self-nanoemulsifying tablets demonstrated significantly higher dissolution rates, compared to direct compression tablets (DCT) and marketed tablet (Zocor®). In conclusion, self-nanoemulsifying tablets were able to introduce simvastatin successfully in a unique immediate-release solid dosage form.

 Key words: Simvastatin, self-nanoemulsifying tablets, self-nanoemulsifying drug delivery systems (SNEDDS), droplet size.


In vitro gamma-radiation-induced chromatid breaks per cell (b/c) in lymphocytes may be associated with risk of papillary thyroid cancer (PTC). This pilot case-control study involved 106 patients with thyroid disease (57 with PTC and 49 with benign thyroid disease) and 105 cancer-free matched controls. Multivariate logistic regression analyses identified that an elevated gamma-radiation-induced b/c value was a risk factor for PTC (adjusted odds ratio = 4.54; 95% CI, 2.07-9.95), and a dose-response relationship was evident when the b/c values were categorized into tertiles. High levels of chromatid breaks induced by gamma-radiation may constitute an independent risk factor for PTC, but further study is needed.


The aging of population is accompanied by simultaneous increasing of rate of age-associated ophthalmic diseases resulting in vision decreasing. However, visual impairment in elderly and senile age is rarely considered in the epidemiology of falls in these groups. The purpose of the study is to investigate medical social aspects of falls in older age groups with visual impairment. The retrospective methodology was applied to study falls in 4832 elderly and senile patients with visual impairment due to cataract glaucoma, diabetic retinopathy and age-related macular degeneration. The high incidence of falls in men and women aged 80 and older, amounting to 82.6 and 125.7 cases per 1000 of population of corresponding age respectively was established. The falls in elderly patients with low vision is more often registered in case of diabetic retinopathy than of glaucoma, cataract and age-related macular degeneration without significant differences at the age 50-59 years and 60-69 years. The diabetic retinopathy is the most common cause of falls requiring hospitalization in all age groups. To In reducing prevalence of falls and resulted hospitalization, to optimize traumatological care of patients of older age groups, the priority is for early identification and treatment of people with diabetic retinopathy.


This review provides detailed information on perovskite solar cell device background and monitors stepwise scientific efforts applied to improve device performance with time. The work reviews previous studies and the latest developments in the perovskite crystal structure, electronic structure, device architecture, fabrication methods, and challenges. Advantages, such as easy bandgap tunability, low charge recombination rates, and low fabrication cost, are among the topics discussed. Some of the most important elements highlighted in this review are concerns regarding commercialization and prototyping. Perovskite solar cells are generally still lab-based devices suffering from drawbacks such as device intrinsic and extrinsic instabilities and rising environmental concerns due to the use of the toxic inorganic lead (Pb) element in the perovskite (ABX3) light-active material. Some interesting recommendations and possible future perspectives are well articulated.


The authors study the dynamical behaviour of a multi-holes system in partial wetting. Applying the method recently developed by us to the problem the authors derive for the first time the equation of motion of the contact lines, where the free surface of the wetting liquid meets the solid surface, in the presence of multi-holes. The equation obtained is found to take into account the cooperative effects generated by the spatial interactions among holes.


Purpose: To observe and compare enamel fluoride uptake in enamel by three fluoride varnishes, a fluoride foam, and a fluoride gel. Methods: Bovine incisors were ground and cut into six groups (n=10) of cubic samples, set in resin cement such that a single square surface of facial enamel was exposed in each sample. These enamel surfaces were polished and treated, with a group assigned to each of three 5% sodium fluoride varnishes (BISCO, 3M ESPE, GC America), a fluoride foam (Dentsply Sirona), a fluoride gel (Crosstex International, Inc), as well as a water control group. After application of product, the samples were agitated at 37°C before removal of product by potassium hydroxide solution (10mL, 1.0M, saturated with calcium phosphate). A layer of exposed enamel was dissolved in each sample with perchloric acid (2.5mL, 1.0M) which was then neutralized with sodium hydroxide. The resulting solution was buffered in TISAB II and measured for fluoride content by ion selective electrode (ISE), which was adjusted for sample surface area. Results: Enamel each group the following mean values and standard error: 8.32±0.44 μg/cm 2 , 2 , and 4.04±0.20 μg/cm 2 in the BISCO, 3M ESPE, and GC America varnishes, 6.52±0.64 μg/cm 2 in the fluoride foam, 7.03 ± 0.51 μg/ cm 2 in the fluoride gel, and 1.59 ± 0.11 μg/cm 2 in the control group. When in contact with tooth enamel, topical fluoride treatments including varnishes, gels and foams can induce fluorapatite by chemically incorporating fluoride in the tooth structure. This enamel fluoride uptake can be measured and compared to guide clinicians on the relative efficacy of different fluoride treatments. Results demonstrated here show that the BISCO varnish has a statistically higher EFU compared to other tested products.


The CB1 cannabinoid receptor in brain is a G-protein-coupled receptor that exists as a protein possessing seven transmembrane helices that span the membrane. The intracellular surface is able to interact with f1p4oteins of the Gi/o family to regulate effector proteins, including adenylate cyclase, Ca2+ channels, and K+ channels, and to stimulate the mitogen-activated protein kinase pathway. The CB1 cannabinoid receptor recognizes three classes of agonist ligands: cannabinoid, eicosanoid, and aminoalkylindole. These agonist subtypes may interact with the CB1 cannabinoid receptor by some common points of association, yet may have subtle differences in the way that they interact with the receptor protein. This may be evident in the allosteric regulation by monovalent cations and individual agonists. The juxtamembrane region of the C-terminal is able to activate G-proteins. It is proposed that conformational changes in the receptor induced by agonist ligands may alter the conformation or exposure of the juxtamembrane C-terminal region extending from helix VII.


Personality disorder rigidity and extremity can be geometrically defined and operationalized within the 5-factor model (FFM) of personality. A series of geometric and substantive assumptions were derived and then tested in samples of college students (N = 1,323) and psychiatric patients (N = 86). Normal and disordered personalities were found to coexist in a variety of regions of the FFM multivariate space. Within regions, the profiles of normal and disordered personalities were very similar in characteristic configuration but notably different in profile variability. Personality-disordered individuals tended to be located in the perimeters or outer regions of the FFM space, as indicated by their longer vector lengths. These findings generalized across 2 measures of personality disorders and across 2 measures of normal personality traits.


On the basis of precious few facts from the artist's lifetime, nineteenth-century authors with varying agendas wove stories around Juan de Pareja, the seventeenth-century Afro-Hispanic painter who was enslaved by Diego Velázquez for some two decades. Before the opening of Paris's Galerie espagnole in 1838, writers hewed closely to Pareja's first biography, published in Antonio Palomino's El museo pictórico y escala óptica (1715–24). Thereafter, however, fanciful plot twists and cameo appearances by other historical characters, notably Peter Paul Rubens, became part of tales relayed in the popular press, from newspapers and magazines to children's books, language primers, and plays. This essay focuses on the origins of particularly persistent threads in this extensive body of previously unexamined narratives and considers how such dynamic fabulation intersected with abolitionist agendas, popular illustrations of Pareja's life, and seventeenth-century works of art.


To improve user experience and profits of corporations, modern industrial recommender systems usually aim to select the items that are most likely to be interacted with (e.g., clicks and purchases). However, they overlook the fact that users may purchase the items even without recommendations. The real effective items are the ones that can contribute to purchase probability uplift. To select these effective items, it is essential to estimate the causal effect of recommendations. Nevertheless, it is difficult to obtain the real causal effect since we can only recommend or not recommend an item to a user at one time. Furthermore, previous works usually rely on the randomized controlled trial (RCT) experiment to evaluate their performance. However, it is usually not practicable in the recommendation scenario due to its expensive experimental cost. To tackle these problems, in this paper, we propose a causal collaborative filtering (CausCF) method inspired by the widely adopted collaborative filtering (CF) technique. It is based on the idea that similar users not only have a similar taste on items but also have similar treatment effects under recommendations. CausCF extends the classical matrix factorization to the tensor factorization with three dimensions---user, item, and treatment. Furthermore, we also employ regression discontinuity design (RDD) to evaluate the precision of the estimated causal effects from different models. With the testable assumptions, RDD analysis can provide an unbiased causal conclusion without RCT experiments. Through dedicated experiments on both offline and online experiments, we demonstrate the effectiveness of our proposed CausCF on the causal effect estimation and ranking performance improvement.


FUSARIUM HEAD BLIGHT IN CANADIAN WINTER WHEAT: UTILIZING ASSOCIATION MAPPING AND GENOMIC SELECTION FOR RESISTANCE BREEDING Harwinder Singh Sidhu University of Guelph, 2020 Advisor(s): Istvan Rajcan Alireza Navabi Fusarium Head Blight (FHB) is a devastating disease of Wheat (Triticum aestivum L.) caused primarily by Fusarium graminearum Schwabe in Canada. Wheat FHB results in yield and produce quality losses. The clearest symptoms of FHB are premature bleaching of spikelets in the field, and fusarium damaged kernels in the harvested seed. Insufficient and costly disease control strategies make breeding for FHB resistance in wheat an ideal choice. There is a lack of FHB resistance sources in the Canadian wheat germplasm and Genome Wide Association Studies (GWAS) can be utilized to identify such sources. Furthermore, as no Quantitative Trait Loci (QTL) provides absolute resistance to FHB, identification of novel sources of resistance is desired. Genomic Selection (GS) has great potential in crop improvement, specifically for quantitative traits. A diversity panel that represents the genetic diversity of the Canadian, i.e., high latitude North American winter wheat was assembled for this thesis and the genetic diversity, population structure, and linkage disequilibrium of the germplasm was studied. To identify QTL associated with FHB, a GWAS study was conducted using the phenotypic data collected at three locations over two years. For understanding the role of number of genotypic markers, population structure, and choice of model in trait prediction modelling, a GS study was conducted. The Canadian Winter Wheat Diversity Panel is a diverse collection of winter wheat capturing diversity both in time and geography from Canada. The panel comprises of seven subpopulations with different LD, allele frequencies, and genetic diversity parameters. Multiple QTL associated with FHB related traits were identified on 13 chromosomes which may harbor genes involved in plant defense and stress response mechanisms. For FHB resistance improvement, the GS study demonstrated that the modelling parameters can be determined based upon the genotypic information available. Deoxynivalenol contamination was one of the traits with the highest prediction accuracy. GS can account for minor effect QTL, which is beneficial when breeding for quantitative traits. FHB resistant varieties are needed for an effective and economical disease control strategy in wheat and GS can complement current breeding efforts to develop FHB resistant wheat varieties.


We demonstrated previously that high physiological concentrations of free fatty acids (FFA) rapidly decrease insulin binding, degradation, and action in isolated rat hepatocytes. In this study, hepatocytes from lean and obese Sprague-Dawley rats (Alab, Stockholm) were preincubated with or without 0.4 mM oleic acid, and the effect on insulin binding and tyrosine kinase activity was measured. In the absence of exogenous FFA, insulin binding was reduced in hepatocytes from obese compared with lean rats (mean ± SE reduction 44 ±7%, n = 8, P < 0.01). Furthermore, the inhibitory effect of oleic acid added to hepatocytes from lean rats (n = 8; 40 ± 9%, P < 0.01) was not seen in cells from obese rats. Treating obese rats with Etomoxir, a carnitine palmitoyl transferase I inhibitor, increased insulin binding to isolated hepatocytes by 41 ± 13% (n = 5, P < 0.05). There was no difference in total binding to partially purified insulin receptors from solubilized hepatocytes from lean and obese rats, whether cells were or were not preincubated with oleic acid. Tyrosine kinase activity of partially purified receptors from basal or insulin-stimulated cells was not affected by either obesity, treatment with Etomoxir, or preincubating the cells with oleic acid. Thus, both obesity and elevated ambient FFA levels are associated with impaired insulin cell surface binding to isolated hepatocytes, possibly through an effect of lipid oxidation on the internalization/recycling of the insulin-receptor complex without any perturbation of the receptor tyrosine kinase activity. The data suggest that the reduced insulin binding to hepatocytes from obese rats is due to elevated ambient FFA levels.


A novel RSSI-based localization algorithm is proposed for wireless sensor networks. The proposed distributed range-free localization scheme is implemented by a mobile anchor node equipped with a GPS. The mobile anchor node moves in sensor area and broadcasts its current position periodically. A stationary sensor node computes its location using two positions of the mobile anchor node. After first round localization is done, the un-located sensor nodes can compute their locations with the help of localized stationary sensor nodes. Our localization algorithm is simulated in Opnet10.0. Simulation results show that our proposed localization scheme outperforms the other localization algorithms using mobile anchor nodes.


We present optical long-slit spectra and complementary broad and narrow band images of the bipolar protoplanetary nebula OH231.8+4.2. Absolute J2000 coordinates have been calculated for our maps from the position of nearby stars. Our maps of the optical continuum show the spatial distribution of the starlight scattered by dust grains. This component is found to be highly elongated along the nebular axis, with a structure very similar to that of the molecular emission. Flux variations with time of the red continuum emission are detected. Our long-slit spectroscopy of H_α and other atomic lines reveals wide spectral profiles and, in general, a complex spatial and spectral emission distribution. The emission arises from two broad lobes and is shifted toward shorter (north lobe) and longer wavelengths (south lobe), indicating that the gas is flowing outwards at high velocity. The clumpiness of the emission nebula is remarkable. A simple model has been used to describe the complex structure and kinematics of this source. Our model suggests that, in addition to the two extended, hollow lobes identified in the H_α images, a smaller, bubble-like expanding structure should lie inside the south lobe. A comparison of the emission line spectrum with predictions of theoretical shock models confirms that the optical lines have been shock excited. We have estimated the electron density of the lobes and deduced the total ionized mass of the nebula, obtaining a low value of ∼5 x 10^-4 M_⨀. We interpret the shaping and evolution of OH231.8+4.2 in the wind interaction scenario for planetary nebulae formation. The peculiar structure and kinematics of the molecular outflow and the ionized envelope are explained in terms of a shock regime transition: the well collimated molecular outflow and the different components of the optical nebula would consist of circumstellar material swept-up by a unique shock in a radiative, and non-radiative regime, respectively. Finally, we briefly discuss the controversial evolutionary status of OH 231.8+4.2.


Great disparities exist in women's health outcomes in rural indigenous communities in Guatemala; indigenous women are less likely to utilize family planning and cervical cancer screening services. This pilot study assessed baseline women's health knowledge and the effects of a comprehensive women's health course on women's health knowledge and behaviors. From February to November 2013, 61 participants in a seven-week language-appropriate women's health curriculum were evaluated before and after the course using a 10-item knowledge assessment. Cervical cancer screening and contraceptive utilization rates were assessed by self-report before and after the course. Several women's health knowledge deficits were noted: belief that contraception causes cancer, inability to name symptoms of STIs, lack of understanding of pap smears, and lack of familiarity with condoms. The average pre-test score was 54.6%; increasing to 83.7% on the post-test (p<0.0001). 79% had received a pap smear prior to the course; this increased to 92% at the post-test (p=0.013). 53% had utilized contraception prior to the course; at the time of the post-test the percentage was 54% (p=1). This study reveals important patterns in women's health beliefs in rural Guatemala, and shows that a seven-week curriculum was effective in improving scores on a knowledge assessment.


In this paper, we introduce a new method for ellipse detection. This method takes the advantages of major axis of an ellipse to find ellipse parameter fast and efficiently. It only needs a one-dimensional accumulator array to accumulate the length information for minor axis of the ellipse. This method does not require the evaluation of the tangents or curvatures of the edge contours, which are generally very sensitive to noisy working conditions. No complicated mathematical computation is involved in the implementation and the required computational storage space is much cheaper compared to the current methods. Experiments with both synthetic and real images indicate the effectiveness of the proposed method.


The program SJ-10 is one of the scientific satellite programs in the Strategic Priority Research Program on Space Science, the Chinese Academy of Sciences, and was launched in April 6, 2016. There are totally 19 scientific payloads. Among them, there are two multitask payloads, one is a multi-function furnace for 8 materials research missions, the other is a payload of three-dimensional cell culture for researches on neural stem cell and hematopoietic stem cell. The recoverable satellite consists mainly of two capsules: a recoverable capsule was recovered on April 18, 2016 with all payloads of life science in addition of the payload of the multi-function furnace and the payload for measurements of Soret Coefficients of Crude Oil (SCCO), and an un-recoverable capsule persisted to work in additional 8 days of all other physical payloads. The experiments were operated via tele-operations, and all experimental data were received by the ground station in near real time. The data and recoverable samples are analyzed by the teams of experimental program. The development of the recoverable satellite SJ-10, the performance during the space mission, and the recovery procedure were presented in this paper.


Abstract We consider functional responses with network dependence observed for each individual at irregular time points. To model both the interindividual dependence and within-individual dynamic correlation, we propose a network functional varying coefficient (NFVC) model. The response of each individual is characterized by a linear combination of responses from its connected nodes and its exogenous covariates. All the model coefficients are allowed to be time dependent. The NFVC model adds to the richness of both the classical network autoregression model and the functional regression models. To overcome the complexity caused by the network interdependence, we devise a special nonparametric least-squares-type estimator, which is feasible when the responses are observed at irregular time points for different individuals. The estimator takes advantage of the sparsity of the network structure to reduce the computational burden. To further conduct the functional principal component analysis, a novel within-individual covariance function estimation method is proposed and studied. Theoretical properties of our estimators, which involve techniques related to empirical processes, nonparametrics, functional data analysis and various concentration inequalities, are analyzed. We analyze a social network dataset to illustrate the powerfulness of the proposed procedure.


Myelodysplastic syndromes (MDS) comprise a clinically and pathologically diverse collection of hematopoietic neoplasms, most commonly presenting with peripheral cytopenias typically in the context of bone marrow hypercellularity. Mechanistically, at least in the early phases of the disease, this apparently paradoxical picture is primarily due to ineffective hematopoiesis, which is accompanied by a variety of morphologic abnormalities in hematopoietic cells. The identification of recurrent, clinically relevant cytogenetic defects in MDS has spurred the research of molecular mechanisms that contribute to its inception as well as to the development of heterogeneous subtypes. Although conventional cytogenetic analyses remain a diagnostic mainstay in MDS, the application of contemporary techniques including molecular cytogenetics, microarray technologies and multiparametric flow cytometry may ultimately reveal new diagnostic parameters that are theoretically more objective and sensitive than current morphologic approaches. This review aims to outline the role of genetic and immunophenotypic studies in the evaluation of MDS, including findings that may potentially influence future diagnostic classifications, which could refine prognostication and ultimately facilitate the growth of targeted therapies.


Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

Chronic graft versus host disease (cGVHD) is a life threatening impediment to the otherwise curative potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Intensive study has unveiled the lymphoid subsets that drive multifaceted autoimmune and fibrotic cascades which disrupt healthy tissues. Clinical and in-vivo data implicate B-cells and certain subsets of CD4 helper T-cells in the development and progression of cGVHD. These specific immune subsets are unique in their singular dependence upon the TEC-family kinases BTK or ITK for receptor driven activation. Ibrutinib is an irreversible inhibitor of BTK and ITK that has produced durable remissions in B-cell malignancies with minimal toxicity. We sought to examine ibrutinib's potential to attenuate B-cell and CD4 T-cell driven anti-host immunity in the setting of cGVHD. We utilized two complementary murine models independently focused on interrogating sclerodermatous T-cell driven cGVHD (LPJ→C57BL/6) or alloantibody driven bronchiolar obliterans (BO) and multi-organ system disease without skin involvement (C57BL/6→B10.BR). We examined therapeutic administration of 25mg/kg/day ibrutinib initiated when mice first develop signs of cGVHD (25-28 days after allo-HSCT). In the minor-MHC mismatch LPJ→C57BL/6 model, ibrutinib significantly extended median time to cGVHD progression by 14 days and 33% (6 of 18) of ibrutinib treated mice remained progression free as compared to 12% (2 of 18) of mice receiving vehicle and 10% (1 of 11) of mice receiving cyclosporine 10mg/kg/day (p<0.02). Overall survival was also highest in the ibrutinib treatment cohort. Mice receiving ibrutinib showed restoration of external cGVHD criterion including body weight, posture, skin lesions, hair loss, and mobility. There was significant ablation of lymphohistiocytic T- and B-cell pulmonary and renal infiltration in ibrutinib treated animals. Data from the C57BL/6→B10.BR model confirmed the efficacy of ibrutinib in significantly restoring pulmonary compliance, elastance, and resistance to levels indistinguishable from that of a healthy animal and significantly better than cGVHD vehicle treated controls (n=12/group)(p<0.01). These results were associated with significantly decreased alloantibody deposition and decreased fibrosis in the lungs of ibrutinib treated mice. Germinal center (GC) reactions, required for multi-organ system pathology in this model, were also significantly reduced within the spleens of mice receiving therapeutic ibrutinib (p<0.05). Using in-vivo genetic ablation models, we demonstrate the critical nature of BTK and ITK respectively in the development of cGVHD pathognomonic BO. Our data support ibrutinib as a promising therapeutic direction for the treatment of cGVHD by virtue of its ability to suppress BTK and ITK signaling.

Citation Format: Jason A. Dubovsky, Ryan Flynn, Jing Du, Bonnie K. Harrington, Yiming Zhong, Carrie Yang, William Towns, Amy Lehman, Amy Johnson, Steven Devine, Samantha Jaglowski, Jonathan S. Serody, William J. Murphy, David H. Munn, Leo Luznik, Geoffrey Hill, Kelli K.P. MacDonald, Ivan Maillard, John Koreth, Corey Cutler, Robert J. Soiffer, Joseph H. Antin, Jerome Ritz, Angela Panoskaltsis-Mortari, John C. Byrd, Bruce R. Blazar. Ibrutinib can reverse established chronic graft-versus-host disease, which is dependent upon IL-2 inducible T-cell kinase (ITK) and Bruton's tyrosine kinase (BTK)-driven lymphocyte activation. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2591. doi:10.1158/1538-7445.AM2014-2591


OBJECTIVE
To explore the effects of posterolateral lumbar fusion (PLF) and posterior lumbar interbody fusion (PLIF) on the stability of postoperative unstable single lumbar segment and the biomechanical alterations of the adjacent segments.

METHODS
A finite element model of L3-S1 segments with a single segmental degeneration at the L4-5 level was established, and the model of L4-5 segmental instability after posterior laminectomy and facetectomy was also established, in which laminar and interior 2/3 area of bilateral facet joints were resected. Physical loads were applied to the models and the changes of the range of motion (ROM) at L4-5 level in different models were recorded at the condition of flexion, extension, lateral bending and rotation. PLF and PLIF were performed on postoperative unstable model respectively, the changes of the ROM at L4-5 level, the ROM and the stress on the adjacent discs in different models were recorded.

RESULTS
Compared to the unstable model, the L4-5 segmental stability was restored after PLF or PLIF. The ROMs of L3-4 and L5-S1 levels were similar to the preoperative unstable model. The stress on adjacent discs (L3-4 and L5-S1) was increased significantly, and maximum stress distribution changed and concentrated in the anterior annulus fiber in the two fusion models. There was no significant difference of the maximum stress on adjacent discs between PLF and PLIF models [(1.056 ± 0.061) mPa vs (1.070 ± 0.075) mPa; (1.147 ± 0.055) mPa vs (1.162 ± 0.075)mPa, P>0.05].

CONCLUSIONS
Lumbar segmental stability after posterior laminectomy and facetectomy can be recovered by both PLF and PLIF. Both PLF and PLIF may increase the possibility of adjacent segment degeneration because of the augmentation of maximum stress on adjacent discs.