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The efficacy and safety of rivipansel, a predominantly E-selectin antagonist, were studied in a phase 3, randomized, controlled trial for vaso-occlusive crisis (VOC) requiring hospitalization (RESET). A total of 345 subjects (204 adults and 141 children) were randomized and 320 were treated (162 with rivipansel, 158 with placebo) with an IV loading dose, followed by up to 14 additional 12-hourly maintenance doses of rivipansel or placebo, in addition to standard care. Rivipansel was similarly administered during subsequent VOCs in the Open-label Extension (OLE) study. In the full analysis population, the median time to readiness for discharge (TTRFD), the primary end point, was not different between rivipansel and placebo (−5.7 hours, P = .79; hazard ratio, 0.97), nor were differences seen in secondary end points of time to discharge (TTD), time to discontinuation of IV opioids (TTDIVO), and cumulative IV opioid use. Mean soluble E-selectin decreased 61% from baseline after the loading dose in the rivipansel group, while remaining unchanged in the placebo group. In a post hoc analysis, early rivipansel treatment within 26.4 hours of VOC pain onset (earliest quartile of time from VOC onset to treatment) reduced median TTRFD by 56.3 hours, reduced median TTD by 41.5 hours, and reduced median TTDIVO by 50.5 hours, compared with placebo (all P < .05). A similar subgroup analysis comparing OLE early-treatment with early-treatment RESET placebo showed a reduction in TTD of 23.1 hours (P = .062) and in TTDIVO of 30.1 hours (P = .087). Timing of rivipansel administration after pain onset may be critical to achieving accelerated resolution of acute VOC. Trial Registration: Clinicaltrials.gov, NCT02187003 (RESET), NCT02433158 (OLE).

Given the commercial and personnel assets involved as well as the unpredictable nature of the gains switching limbs, stock systems are among absolute highly exciting areas for net worth progress and GDP expansion. Forecasting the future and performances of every stock industry could help investors accumulate wealth during prosperous periods and reduce liabilities during turbulent moments. "Stock industry forecasting" is the process of estimating the eventual worth of transfer business shares and comparable monetary assets. Stock price forecasting has long been a popular area of study. Nevertheless, the widely adopted auto - regressive integrative movement averaged (ARIMA) approach has its inherent benefits and drawbacks. Longer short-term memory (LSTM) systems paradigm consumption towards forecasting additionally demonstrates intriguing potential. By comparing the concepts of such different approaches and the outcomes of predictions, this paper particularly contrasts such two concepts. The LSTM framework is thought to have the strongest forecasting power inside the end; however, data manipulation has a significant impact on it.

Self-modulation is a beam-plasma instability that is useful to drive large-amplitude wakefields with bunches much longer than the plasma skin depth. We present experimental results showing that, when increasing the ratio between the initial transverse size of the bunch and the plasma skin depth, the instability occurs later along the bunch, or not at all, over a fixed plasma length, because the amplitude of the initial wakefields decreases. We show cases for which self-modulation does not develop and we introduce a simple model discussing the conditions for which it would not occur after any plasma length. Changing bunch size and plasma electron density also changes the growth rate of the instability. We discuss the impact of these results on the design of a particle accelerator based on the self-modulation instability seeded by a relativistic ionization front, such as the future upgrade of the AWAKE experiment.

Background: Adhesive capsulitis is one of the most common problems of the arm. It is a painful and disabling condition and the etiology is unclear. Adhesive capsulitis is caused by tightening of the joint capsule and results in stiffness and pain. Adhesive capsulitis occurs in three distinct stages. Freezing stage, Frozen stage & Thawing stage. Till date, adhesive capsulitis remains to be more of a clinical diagnosis rather than radiological. Cyriax’s proposed shoulder capsular pattern was external rotation most limited followed by abduction followed by internal rotation. It remains unclear whether this pattern is exists in all the phases of adhesive capsulitis or not. Aim: To identify pattern of restriction of ROM in subjects with adhesive capsulitis in three phases of adhesive capsulitis. Methodology: The study included 60 subjects with idiopathic adhesive capsulitis. Passive ROM for shoulder Abduction, internal and external rotation was measured with universal Goniometer. Results & Conclusion: Findings suggest that various patterns of restrictions were found in different phase of Adhesive capsulitis. Key words: Adhesive capsulitis, Shoulder passive ROM, Pattern of restriction.

Background: Sciatica is the most common problem affecting the adult population annually. Mulligan TSLR is used to Increase the SLR range. The NFT is a gentle exercise that stretches irritated nerves. This study aimed to nd out the combined effect of NFT with mulligan traction SLR to reduce pain and improve function in participants with sciatica to get the best results. Methods: Participants with Sciatica were randomized into 2 groups by simple random sampling into Group A (Experimental Group) and Group B (Control group). Pre and post-treatment data were collected and analyzed using SPSS 22.0. Results: A greater statistically signicant improvement in pain & disability (p‹0.05) were found in Group A as compared to Group B. Conclusion: The study concluded that the combined effect of NFT with Mulligan TSLR is more effective in sciatica

Plantar fasciitis is an inammatory condition which causes pain and stiffness in the heel and medial arch of the plantar surface of the foot. There is hardly any study that has investigated the effectiveness of Muscle Energy technique with phonophoresis in Plantar Fasciitis along with physiotherapy intervention. The study aimed to nd the effectiveness of the phonophoresis with the MET in participants with plantar fasciitis to determine the benet of participants. So, a Quasi-Experimental study was conducted with 30 participants featured of plantar fasciitis. They were studied for a 4-weeks intervention. They were divided into 2 groups by convenience sampling: - Group A: MET and Group B: phonophoresis with the MET. Pre- and post-treatment data were collected and analysed using SPSS 22.0. Paired and unpaired t-test was used to nd out the signicance of the treatment. A signicant improvement in pain and functions (p

Cervical radiculopathy is marked by nerve compression of a herniated disk. McKenzie and ICT are more used in participants with Cervical Radiculopathy. There are no studies that combine the McKenzie with ICT and Conventional Exercise with ICT in participants with Cervical Radiculopathy. The study aimed to nd the effects of the McKenzie Technique with ICT and Conventional Exercise program with ICT in participants with Cervical Radiculopathy to determine the better of these for benet of participants. So, a Quasi-Experimental study was conducted with 30 participants that featured Cervical Radiculopathy. They were studied for a 4-weeks intervention. They were divided into 2 groups by convenience sampling: - Group A: McKenzie Technique with ICT and Group B: Conventional Exercise with ICT. Pre- and post-treatment data were collected and analyzed using SPSS 22.0. Paired and unpaired t-test was used to nd out the signicance of the treatment. A signicant improvement in pain, disability, muscle strength, and endurance (p

The relationship between communication and cognition which has been explored since mid-1900s is a highly contentious topic. Hypotheses from various researchers have experienced a gradual shift from cognitive/innate bases to social perspective of acquisition and development of speech and language skills in individuals with intellectual disability. This acquisition tends to be delayed or deviant (qualitative and /or quantitative). In the recent years, research in this area is experiencing a paradigm shift evolving from ‘incapacity' to ‘functioning' which is obvious in the clinical practice of assessment and intervention of speech and language skills in these individuals. Further, the rehabilitation process is experiencing a transition from clinician directed to child-oriented or hybrid approaches of intervention. This chapter will be a comprehensive document of recent trends in research and practice related to acquisition of language, assessment and intervention of communication difficulties for professionals working with intellectual disability.

The spread of multidrug-resistant (MDR) bacteria is an emerging threat to the environment and public wellness. Inappropriate use and indiscriminate release of antibiotics in the environment through un-metabolized form create a scenario for the emergence of virulent pathogens and MDR bugs in the surroundings. Mechanisms underlying the spread of resistance include horizontal and vertical gene transfers causing the transmittance of MDR genes packed in different host, which pass across different food webs. Several controlling agents have been used for combating pathogens; however, the use of lytic bacteriophages proves to be one of the most eco-friendly due to their specificity, killing only target bacteria without damaging the indigenous beneficial flora of the habitat. Phages are part of the natural microflora present in different environmental niches and are remarkably stable in the environment. Diverse range of phage products, such as phage enzymes, phage peptides having antimicrobial properties, and phage cocktails also have been used to eradicate pathogens along with whole phages. Recently, the ability of phages to control pathogens has extended from the different areas of medicine, agriculture, aquaculture, food industry, and into the environment. To avoid the arrival of pre-antibiotic epoch, phage intervention proves to be a potential option to eradicate harmful pathogens generated by the MDR gene flow which are uneasy to cure by conventional treatments.

In 2017, AWAKE demonstrated the seeded self-modulation (SSM) of a 400 GeV proton beam from the Super Proton Synchrotron (SPS) at CERN. The angular distribution of the protons deflected due to SSM is a quantitative measure of the process, which agrees with simulations by the two-dimensional (axisymmetric) particle-in-cell code LCODE. Agreement is achieved for beam populations between $10^{11}$ and $3 \times 10^{11}$ particles, various plasma density gradients ($-20 \div 20\%$) and two plasma densities ($2\times 10^{14} \text{cm}^{-3}$ and $7 \times 10^{14} \text{cm}^{-3}$). The agreement is reached only in the case of a wide enough simulation box (at least five plasma wavelengths)., Comment: 8 pages, 9 figures, 1 table

Combating bacterial pathogens has become a global concern especially when the antibiotics and chemical agents are failing to control the spread due to its resistance. Bacteriophages act as a safe biocontrol agent by selectively lysing the bacterial pathogens without affecting the natural beneficial microflora. The present study describes the screening of prominent enteric pathogens NDK1, NDK2, NDK3, and NDK4 (Escherichia, Klebsiella, Enterobacter, and Serratia) mostly observed in domestic wastewater; against which KNP1, KNP2, KNP3, and KNP4 phages were isolated. To analyze their potential role in eradicating enteric pathogens and toxicity issue, these bacteriophages were sequenced using next-generation sequencing and characterized based on its genomic content. The isolated bacteriophages were homologous to Escherichia phage (KNP1), Klebsiella phage (KNP2), Enterobacter phage (KNP3), Serratia phage (KNP4), and belonged to Myoviridae family of Caudovirales except for the unclassified KNP4 phage. Draft genome analysis revealed the presence of lytic enzymes such as holing and lysozyme in KNP1 phage, endolysin in KNP2 phage, and endopeptidase with holin in KNP3 phage. The absence of any lysogenic and virulent genes makes this bacteriophage suitable candidate for preparation of phage cocktail to combat the pathogens present in wastewater. However, KNP4 contained a virulent gene rendering it unsuitable to be used as a biocontrol agent. These findings make the phages (KNP1–KNP3) as a promising alternative for the biocontrol of pathogens in wastewater which is the main culprit to spread these dominated pathogens in different natural water bodies. This study also necessitates for genomic screening of bacteriophages for lysogenic and virulence genes prior to its use as a biocontrol agent.

Bacteriophages play significant role in driving microbial diversity; however, little is known about the diversity of phages in different ecosystems. A dynamic predator-prey mechanism called "kill the winner" suggests the elimination of most active bacterial populations through phages. Thus, interaction between phage and host has an effect on the composition of microbial communities in ecosystems. In this study, secondary phage metagenome data from aquatic habitats: wastewater treatment plant (WWTP), fresh, marine, and hot water spring habitat were analyzed using MG-RAST and STAMP tools to explore the diversity of the viruses. Differential relative abundance of phage families-Siphoviridae (34%) and Myoviridae (26%) in WWTP, Myoviridae (30%) and Podoviridae (23%) in fresh water, and Myoviridae (41%) and Podoviridae (8%) in marine-was found to be a discriminating factor among four habitats while Rudiviridae (9%), Globuloviridae (8%), and Lipothrixviridae (1%) were exclusively observed in hot water spring. Subsequently, at genera level, Bpp-1-like virus, Chlorovirus, and T4-like virus were found abundant in WWTP, fresh, and marine habitat, respectively. PCA analysis revealed completely disparate composition of phage in hot water spring from other three ecosystems. Similar analysis of relative abundance of functional features corroborated observations from taxa analysis. Functional features corresponding to phage packaging machinery, replication, integration and excision, and gene transfer discriminated among four habitats. The comparative metagenomics approach exhibited genetically distinct phage communities among four habitats. Results revealed that selective distribution of phage communities would help in understanding the role of phages in food chains, nutrient cycling, and microbial ecology. Study of specific phages would also help in controlling environmental pathogens including MDR bacterial populations using phage therapy approach by selective mining and isolation of phages against specific pathogens persisting in a given environment.

Relation between BLR and accretion disk

The objective of this present work was to develop and validate analytical method for quantitative determination of Levofloxacin and Ambroxol hydrochloride in a new tablet formulation. Chromatographic separation of the two drugs were analyzed on a Hypersil BDS C18 column (25cm X 4.6mm, 5 m m). The mobile phase constituted of Buffer: Acetonitirile: Methanol (650:250:100) with triethylamine and pH adjusted to 5.2 with dilute orthophosphoric acid was delivered at the flow rate 1.0 mL min -1 . Detection was performed at 220 nm. Separation was completed within 10 min. Calibration curves were linear with coefficient correlation between 0.99 to 1.0 over a concentration range of 7 to 22 m g mL -1 of Levofloxacin and 50 to 150 m g/mL for Ambroxol hydrochloride respectively. The relative standard deviation (R.S.D) was found 2.0%.

Rationale : Vaso-occlusive crisis (VOC) is a recurring complication of sickle cell disease (SCD) and a common reason for emergency department visits and hospitalizations among SCD patients. Few qualitative studies on the symptoms and impacts of SCD have been published. Specifically, while the duration of hospitalization for VOC is well-documented, little is known about the patient experience of recovery from a VOC. The purpose of this research was to understand the experience of recovery from VOC from the patient's perspective and to develop a brief measure to assess recovery to be administered across age groups in future clinical trial programs. Methods : A concept elicitation (CE) study consisted of face-to-face, one-on-one interviews with SCD patients, and caregivers of patients hospitalized for a VOC within 90 days prior to their interview. The semi-structured interview guide focused on the symptoms and impacts of VOC and the activities important to recovery following a VOC. A thematic analysis in MAXQDA qualitative software was conducted to identify key concepts. Results informed the development of a draft measure which was refined in two cognitive debriefing (CD) studies, one using interviewer administration format, and one using an electronic self-administration format. Interviews focused on the meaning and interpretation of the questionnaire instructions, items and responses, and feasibility of administration. Results: The CE sample included 16 participants; 5 adults and adolescents, 6 children ages 8-11, and 5 caregivers of younger children. Patients/caregivers reported that pain is not completely eliminated at time of actual discharge but gradually resolves over the week following hospitalization. In addition to pain, fatigue and the effects of pain medication also affect functional status in the immediate post-hospitalization period. The types of activities impaired during recovery were physical activities, social activities, daily activities such as work or school, and self-care activities. This conceptual framework resulted in a draft "Return to Normal Activity Questionnaire" (RNAQ), with equivalent versions for each age group, including caregiver report. Although the precise item wording and activity examples differed slightly by age group, all three versions shared the same four domains and the same response scale; an 11-point NRS with anchors 0 = "Cannot do at all" to 10 = "Can do completely as usual." The first CD study included 9 patients (3 per age group) with the interviewer administering the RNAQ verbally. Based on these interviews, self-report was determined infeasible for children 8-11. Thus, caregiver report was recommended for all children under 12. The self-administered version of the RNAQ was debriefed in a sample of adult and adolescent patients (N=17). Based on participant feedback, the NRS scale was reversed so that 0 indicates best functioning, to be consistent with a familiar pain rating question frequently used in clinical practice to evaluate VOC severity. Most patients reported that the typical time to complete recovery ranged from 2 days to one week; thus daily administration for 7 days following VOC hospitalization was recommended. Conclusions: The RNAQ was developed according to FDA PRO Guidance and appears to be appropriate for assessing recovery in SCD patients following a VOC hospitalization. Due to the small sample size in the first CD study, additional debriefing on the caregiver-reported version is recommended. In addition, psychometric validation is required to obtain full evidence of validity and to understand how to interpret RNAQ scores. Disclosures Vendetti: Pfizer, Inc.: Employment. Sivamurthy:Pfizer: Employment. Pleil:Pfizer Inc: Employment.

Hemophilia A and B are rare, X-linked bleeding disorders resulting from a partial or total deficiency of functionally active coagulation factor VIII or factor IX, respectively. Endogenous factor levels have traditionally been used to characterize the severity of the disorder, with severe hemophilia considered as circulating levels of factor less than 1% of normal. Identifying patients with severe hemophilia is essential to effective treatment, since these patients are at highest risk of spontaneous life or limb-threatening bleeding and disability resulting from repeated joint bleeding and are most likely to benefit from prophylaxis. However, there is variability in bleeding tendency, even among patients with severe hemophilia. This article will review potential modifiers of hemophilia-associated bleeding other than endogenous factor activity, which may influence bleeding tendencies and complications in hemophilic patients considered to have severe hemophilia. These potential modifiers include physiologic factors, such as elements of the hemostatic system; pathophysiologic factors, such as hemophilic arthropathy, associated inflammation, and angiogenesis; and others, such as seasonal variation, body weight, and physical activity.

In this computational study, we investigated (i) the functional importance of correlated basal ganglia (BG) activity associated with Parkinson's disease (PD) motor symptoms by analysing the effects of globus pallidus internum (GPi) bursting frequency and synchrony on a thalamocortical (TC) relay neuron, which received GABAergic projections from this nucleus; (ii) the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on the response of the TC relay neuron to synchronized GPi oscillations; and (iii) the functional basis of the inverse relationship that has been reported between DBS frequency and stimulus amplitude, required to alleviate PD motor symptoms [A. L. Benabid et al. (1991)Lancet, 337, 403–406]. The TC relay neuron selectively responded to and relayed synchronized GPi inputs bursting at a frequency located in the range 2–25 Hz. Input selectivity of the TC relay neuron is dictated by low-threshold calcium current dynamics and passive membrane properties of the neuron. STN-DBS prevented the TC relay neuron from relaying synchronized GPi oscillations to cortex. Our model indicates that DBS alters BG output and input selectivity of the TC relay neuron, providing an explanation for the clinically observed inverse relationship between DBS frequency and stimulus amplitude.

We examine a simple, fuel-air, model of combustion in spark ignition (si) engine with indirect injection. In our two fluid model, variations of fuel mass burned in cycle sequences appear due to stochastic fluctuations of a fuel feed amount. We have shown that a small amplitude of these fluctuations affects considerably the stability of a combustion process strongly depending on the quality of air-fulel mixture. The largest influence was found in the limit of a lean combustion. The possible effect of nonlinearities in the combustion process were also discussed., Comment: 9 pages, 3 figures, submitted to Journal of Vibration and Control

Abstract 4710 BACKGROUND Health outcomes often serve as a measure of treatment efficacy in clinical studies. Although self-reported, observational, & clinical techniques exist for assessing treatment efficacy in Vaso Occlusive Crisis (VOC) of Sickle Cell Disease (SCD) for both pediatric & adult populations; it is necessary to evaluate quality of evidence available in support of these techniques before they can be used with confidence. OBJECTIVES I. To assess quality of evidence available in support of clinical, humanistic & economic outcomes & clinical endpoints of VOC of SCD. II. To identify & characterize clinical, humanistic & economic outcomes & clinical endpoints for assessment of treatment efficacy of VOC of SCD from literature. METHOD Potentially relevant articles were searched electronically using terms related to VOC & pain crisis in SCD, across PubMed, COCHRANE & CINAHL databases. Dissertations, guidelines, abstracts, conference proceedings & case reports were excluded for lack of sufficient information. Reference lists of prior literature reviews, as well as reference lists of studies included in this review, served to identify additional articles. Only blinded randomized studies with a control group in treating VOC of SCD were included for further analyses. Qualified studies were searched for relevant clinical, humanistic, economic outcomes & clinical endpoints, which have previously been defined elsewhere. Qualified studies were assessed utilizing AHRQ's recommended Evidence based Practice Center- Strength of Evidence (EPC-SOE) methodology. EPC-SOE grades evidence across four primary domains: risk of bias, consistency, precision & directness. Evidence was also assessed for publication bias. Consequently, an overall grade of evidence for each outcome category was assigned. RESULT 1,917 potentially relevant study abstracts were identified & reviewed. Of these, 39 studies qualified for analyses. On assessment of the quality of evidence employing EPC-SOE methodology (Table 1), Humanistic outcomes were found to have the highest overall strength of evidence, whereas, clinical outcomes & clinical endpoints were found to have moderate overall strength of evidence. Economic outcomes were graded ‘insufficient’ due to lack of published studies. Studies were observed to use more than one outcome measure (25 studies) for assessing treatment efficacy, compared to a single measure (14 studies). 23 humanistic outcomes, 7 clinical outcomes, 6 clinical endpoints & 3 economic outcomes are available to assess treatment efficacy in VOC of SCD. Majority of the studies utilize Visual Analogue Scale (VAS) (14 studies) & Facial contours-based pain scales (5 studies) as humanistic outcome measures. Time to resolution (15 studies) & length of stay (13 studies) are preferred clinical outcome measures whereas amount of analgesics required during a VOC event (14 studies) are preferred clinical endpoints. CONCLUSION Evidence suggests that humanistic outcomes reflect true treatment effect & further research is very unlikely to change our confidence in using these measures as possible treatment efficacy endpoints. Whereas, assessment of our evidence reflects moderate confidence in using clinical outcomes & clinical endpoints as treatment efficacy endpoints & further research may suggest otherwise. A combination of humanistic & clinical outcomes & clinical endpoints rather than a single outcome measure, is a method of choice to assess treatment efficacies. Evidence however, is inconclusive towards using Economic outcomes as a possible endpoint. Disclosures: Thomas: Pfizer: Consultancy, Research Funding. Shafer:Pfizer: Employment. Sivamurthy:Pfizer: Employment. Kollmer:Pfizer: Employment, Equity Ownership. Vendetti:Pfizer: Employment.

Abstract 4699 Background Retrospective data analysis is relatively inexpensive & allows evaluation of rare conditions such as Vaso Occlusive Crisis (VOC) of Sickle Cell Disease (SCD) with ease, as compared to conducting actual prospective studies. A particularly useful application of a retrospective data analysis is to act as a pilot study that can be completed in anticipation of a prospective study. The analysis can help to identify feasibility issues & factors which affect study outcomes that need to be adjusted for in prospective studies. Objective To identify health outcome measures employed in retrospective database analysis of individuals suffering from VOC of SCD, from reviewed literature. Method Potentially relevant articles were searched electronically using terms related to VOC & pain crisis in SCD, across PubMed, COCHRANE & CINAHL databases. Dissertations, guidelines to management of VOC, abstracts, conference proceedings & case reports were excluded for lack of sufficient information. Reference lists of prior literature reviews, as well as reference lists of studies included in this review, served to identify additional articles. However, review articles were not included for further analyses. Studies analyzing retrospective databases such as chart reviews, hospital records, electronic medical records (EMR), claims data, health care cost & utilization project database (HCUP) were included for further analyses. Studies qualifying for full review were searched for relevant clinical, humanistic, economic outcomes & clinical endpoints, which have previously been defined elsewhere. Result 1,917 potentially relevant study abstracts were reviewed. Of which, 13 studies qualified for further analyses. 8 clinical outcomes, 6 humanistic outcomes, 3 economic outcomes & 1 clinical endpoint were found. Codes used to identify patients with VOC of SCD in claims databases were (282.42), (282.60), (282.62), (282.64) & (282.69). Four studies used HCUP database, 3 studies used EMRs, & 2 studies each used Medicaid claims data, chart reviews & hospital records for retrospective assessment of a VOC event. Majority of the studies captured length of stay (LOS) (8 studies) & readmission rates (5 studies) as clinical outcomes measure while Wong-Baker Faces scale in children (2 studies) & Numeric Rating scale (2 studies) in adults, were most common measures recorded. Type of hospital admission, type of SCD admission, severity of pain, age, hemoglobin count & polymorphonuclear leukocyte count, associated significantly with length of stay in patients with VOC of SCD (Table 1). Disease severity, severity of pain, use of steroids, age, type of visits & having co-morbid history of asthma associated significantly with 14- & 30-day readmission rates. Number of pain episodes, intensity of pain, LOS, presence of Human Platelet Alloantigen polymorph (HPA-3), amount of analgesic administered, cost of healthcare & 14- & 30-day readmission rates were found to be significant predictors of severity of a VOC (Table 2). Conclusion Research evidence available, while scarce, is applicable, in population of all ages with VOC of SCD. Findings suggest using LOS & readmission rates for assessment of a VOC event in a retrospective database as well as prospective studies aimed to assess treatment efficacies. Care should be taken during design of pilot & retrospective studies to ensure collection & adjustment for variables known to associate significantly with LOS & readmission rate before reaching a clinical conclusion. Further research is necessary to support the use of suggested retrospective indicators of a VOC event. Disclosures: Shafer: Pfizer: Employment. Sivamurthy:Pfizer: Employment. Kollmer:Pfizer: Employment, Equity Ownership. Vendetti:Pfizer: Employment.

Background : There has been growing interest in the vasculopathy occurring in sickle cell disease (SCD), which includes blunted nitric oxide (NO) responsiveness and low nitric oxide bioavailability due to ongoing hemolysis. Historical methods for measuring endothelial dysfunction like measurement of forearm blood flow or brachial artery flow-mediated dilation have either been cumbersome or invasive. Peripheral arterial tonometry (PAT) is a relatively new and simple technology for non-invasively measuring vascular tone changes related to endothelial dysfunction in peripheral arterial beds through a finger plethysmographic probe (a modification of measurement of brachial artery flow-mediated dilatation). Its use has been well researched in coronary artery disease and other cardiovascular disorders, where PAT has been found to provide early detection of endothelial dysfunction. However, use of PAT technology in SCD is still being examined and there are no studies focusing exclusively on pediatric SCD. Hypotheses: The SCD patients with more frequent symptoms will have lower PAT scores, correlating with more endothelial damage. The SCD patients with greater hemolysis will have lower PAT scores due to lower NO bioavailability. Conversely, therapeutic interventions like hydroxyurea therapy or a regular transfusion protocol would have higher PAT scores. Design/Methods : A convenience sample of pediatric SCD patients at baseline is being examined with the FDA-approved Endo-PAT2000 device (Itamar Medical). Plethysmographic probes were placed on corresponding fingers of both hands, and tracings were recorded. The dominant arm served as a control to correct for any baseline sympathetic overlay. The non-dominant arm was occluded with a blood pressure cuff for a period of five minutes and then released. A ratio of the post-occlusion dilatation compared to the baseline was automatically generated by the instrument (>1.67 signifying normal endothelial function). Medical records were abstracted for frequency of symptoms, baseline hemoglobin/reticulocyte count, hydroxyurea therapy, or chronic transfusions. Statistical analysis was done using the Mann-Whitney test due to the skewed distribution of the data. Results : A total of 31 subjects have been studied to date (age 7–20 yrs, mean 15.5, SD 3.4) : 24 with SCD-SS, 5 with SCD-SC, and 2 with SCD-Sbeta+ thalassemia. Mean EndoPAT score was 1.53 for subjects with frequent SCD symptoms, which was significantly lower than those who were not as symptomatic (mean EndoPAT score 1.71; p-value 0.032). Analysis by hemoglobin genotype trended towards a lower mean EndoPAT score for the SCD-SS group (1.61) compared to 1.71 for the combined [SCD-S Beta+Thalassemia and SCD-SC] subset. Within the SCD-SS group, addition of treatment modalities such as a regular chronic transfusion protocol (5 subjects) and hydroxyurea therapy (10 subjects) did not show any difference in the EndoPAT score (1.53 and 1.52 respectively). EndoPAT scores did not show significant correlation with hemoglobin and reticulocyte count as indirect measures of hemolysis. However, there was wide variability in EndoPAT scores noted within each group. Conclusions: EndoPAT scores of the subjects who were frequently symptomatic were significantly lower than those who were not as symptomatic, possibly explained by increased endothelial damage caused by repeated insults. Exploratory statistical analysis to tease out other factors which could affect the endothelial function like hemoglobin genotype and effect of treatment modalities were inconclusive in this cohort. EndoPAT values did not significantly correlate with baseline hemoglobin level or reticulocytosis. These data are consistent with the preliminary data of other groups examining endothelial dysfunction in adults with SCD, which also seem to indicate that forearm blood flow, rather than PAT, may have better correlation with NO scavenging & low NO bioavailability due to hemolysis. Findings of other studies also suggest that EndoPAT may correlate better with NO resistance. However, a wide range of the EndoPAT values was observed within each group of this cohort. A larger sample size may capture these differences in a condition like SCD which is known to be phenotypically heterogeneous.

In the present paper, results of the research on application of residual fine-grained, carbon-bearing materials as coke substitutes in the shaft process of copper matter smelting are discussed. The addition was introduced into the charge as a component of concentrate-made briquettes, then, its effects on properties of the obtained briquettes were analysed for their compressive and drop strengths. The results of investigations confirmed the potential use of proposed alternative fuels (as briquette components) in the process of copper matte smelting.

Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-β) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-β treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-β-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 10-6) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10-5) and near ZNF697 (combined P-value 8.15 × 10-5). Refereed/Peer-reviewed