Journal articles: 'FC-centre' – Grafiati (2024)

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The complexes FcNHC (O)CCo3(CO)9 ( Fc = ferrocenyl ) (3) and Fc ( alaOMe )C(O)CCo3(CO)9 (ala = alanine ) (5) have been synthesized from the +C(O)CCo3(CO)9 cation and FcNH2 or Fc ( alaOMe )H respectively. Derivatives FcNHC (O)CCo3(CO)6[P( OPh )3]3 (4) and Fc ( alaOMe )C(O)CCo3(CO)6[P( OPh )3]3 (6) are also described. Analysis of the spectroscopic and redox behaviour shows that the amide linkage acts as a -I, -M substituent group to Fc and the Co3C unit acts as a-I, +M group. Unlike complexes where these redox centres are directly linked, electronic effects are not transmitted between Co3C and Fc . Oxidation at the ferrocene centre and reduction at the Co3C centre in (3) and (5) is chemically reversible whereas oxidation of the amino acid moiety is irreversible; oxidation of the cluster takes place in (4) and (6) but no intervalence charge transfer is observed.

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Let S be a cancellative semigroup. This paper is motivated by the problem of finding a description of semigroup rings K[S] over a field K that are semiprime or prime. Results of this type are well-known in the case of a group ring K[G], cf. [8]. The description, as well as the proofs, involve the FC-centre of G defined as the subset of all elements with finitely many conjugates in G. In [4], [5] Krempa extended the FC-centre techniques to the case of an arbitrary cancellative semigroup S. He defined a subsemigroup Δ(S) of S which coincides with the FC-centre in the case of groups, and can be used to describe the centre and to study special elements of K[S]. His results were strengthened by the author in [7], where Δ(S) was also applied in the context of prime and semiprime algebras K[S]. However, Δ(S) itself is not sufficient to characterize semigroup rings of this type. We note that in [2], [3] Dauns developed a similar idea for a study of the centre of semigroup rings and certain of their generalizations.

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Two rotaxanes containing [60]fullerene (C60) as pendants on a crown-ether necklace, to which ferrocene (Fc) as axle stoppers were added, have been synthesized. One rotaxane has an ammonium cation in the centre of the axle (C60;Fc)Rot+ and the other has a neutral axle (C60;Fc)Rot. Optimized structures, calculated using a molecular orbital method, suggest that in the ground states (C60;Fc)Rot+ has a shorter distance between C60 and Fc than that of (C60;Fc)Rot. In both rotaxanes, efficient intra-rotaxane photoinduced electron-transfer processes have been observed by the selective excitation of C60 which acts as a photosensitized electron acceptor. The rates and efficiencies of the charge-separation and charge-recombination processes were evaluated by time-resolved fluorescence and transient absorption measurements with changing solvent polarity. From the different kinetic parameters between (C60;Fc)Rot+ and (C60;Fc)Rot, the light-induced molecular motions of these rotaxanes in the excited states and charge-separated states were separately revealed.

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ObjectiveData remain divergent regarding the activational effects of endogenous hormones on adult cognitive function. We examined the association between cognition, hormones and androgen receptor (AR) CAG repeat length in a large cohort of men.DesignCommunity-based, cross-sectional study of 3369 men aged 40–79 years.MethodsCognition tests were the Rey-Osterrieth Complex Figure, Camden Topographical Recognition Memory and Digit-Symbol Substitution. A fluid cognition (FC) z-score was computed from the individual tests. Testosterone, oestradiol (OE2) and 5α-dihydrotestosterone were measured by gas chromatography–mass spectrometry; DHEAS, LH, FSH and sex hormone-binding globulin (SHBG) by electrochemiluminescence. Free testosterone and OE2 were calculated from total hormone, SHBG and albumin. CAG repeat lengths were assayed by PCR genotyping.ResultsTotal testosterone and free testosterone were associated with higher FC z-scores, LH and FSH with lower FC z-scores in age-adjusted linear regressions. After adjusting for health, lifestyle and centre, a modest association was only observed between DHEAS and a lower FC z-score (β=−0.011, P=0.02), although this was driven by subjects with DHEAS levels >10 μmol/l. Locally weighted plots revealed no threshold effects between hormones and FC. There was no association between CAG repeat length and FC z-score after adjustment for age and centre (β=−0.007, P=0.06), nor any interaction effect between CAG repeat length and hormones.ConclusionOur results suggest that endogenous hormones are not associated with a vision-based measure of FC among healthy, community-dwelling men. Further studies are warranted to determine whether ‘high’ DHEAS levels are associated with poorer performance on a broader range of neuropsychological tests.

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Abstract Background Fecal Calprotectin (FC) is helpful in distinguishing functional from organic bowel disease. Also, it has proven useful in monitoring disease activity in inflammatory bowel disease (IBD). The uptake of its use in clinical practice has increased considerably, though access varies significantly. Studies exploring current practice patterns among GI specialists and how to optimize its use are limited. In 2017, Kingston Health Sciences Centre (KHSC) began funding FC testing at no cost to patients. Aims We aimed to better understand practice patterns of gastroenterologists in IBD patients where there is in house access to FC assays, and to generate hypotheses regarding its optimal use in IBD monitoring. We hypothesize that FC is not being used in a regular manner for monitoring of IBD patients. Methods A retrospective chart audit study was done on all KHSC patients who had FC testing completed from 2017–2018. Qualitative data was gathered from dictated reports using rigorous set definitions regarding indication for the test, change in clinical decision making, and frequency patterns of testing. Specifically, change in use for colonoscopy or in medical therapy was coded only if the dictated note was clear that a decision hinged largely on the FC result. Frequency of testing was based on test order date. Reactive testing was coded as tests ordered to confirm a clinical flare. Variable testing was coded where monitoring tests that varied in intervals greater than 3 months and crossed over the other set frequency codes. Quantitative data regarding FC test values, and dates were also collected. This data was then analyzed using descriptive statistics. Results Of the 834 patients in our study, 7 were under 18 years old and excluded. 562(67.34%) of these patients had a pre-existing diagnosis of IBD; 193 (34%) with Ulcerative Colitis (UC), 369 (66%) with Crohn’s Disease (CD). FC testing changed the clinician’s decision for medical therapy in 12.82% of cases and use for colonoscopy 13.06% of the time for all comers. Of the FC tests, 79.8% were sent in a variable frequency pattern and 2.68% with reactive intent. The remaining 17.5% were monitored with a regular pattern, with 8.57% patients having their FC monitored at regular intervals greater than 6 months, 7.68% every 6 months, and 1.25% less than 6 months. The average FC level of patients with UC was 356.2ug/ml and 330.6 ug/ml for CD. The mean time interval from 1st to 2nd test was 189.6 days. Conclusions FC testing changed clinical decisions regarding medical therapy and use for colonoscopy about 13% of the time. FC testing was done variably 79.8% of the time, where as 17.5% of patients had a regular FC monitoring schedule. An optimal monitoring interval for IBD flares using FC for maximal clinical benefit has yet to be determined. Large scale studies will be required to answer this question. Funding Agencies None

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Abstract Background/Objectives The paediatric reference range of fecal calprotectin (FC) has not been decisively established and previous studies show a wide within-age variability, suggesting that other factors like anthropometric data or type of feeding can influence FC. Our aims were to establish the normal levels of FC in healthy children grouped by age and analyze whether sex, gestational age, birth weight, type of delivery, type of feeding, or anthropometric data influence FC values. Methods This multicentre, cross-sectional, and observational study enrolled healthy donors under 18 years of age who attended their Primary Health Care Centre for their routine Healthy Child Program visits. The exclusion criteria were: (i) immunodeficiency, (ii) autoimmune or (iii) gastrointestinal disease; (iv) medication usage; (v) gastrointestinal symptoms; or (vi) positive finding in the microbiological study. Results We enrolled 395 subjects, mean age was 4.2 years (range 3 days to 16.9 years), and 204 were male. The median FC was 77.0 mcg/g (interquartile range 246). A negative correlation between age and FC was observed (Spearman’s rho = −0.603, P<0.01), and none of the other factors analyzed were found to influence FC levels. Conclusions Normal FC values in healthy children (particularly in infants) are higher than those considered to be altered in adults and show a negative correlation with age. It is necessary to reconsider the upper limits of FC levels for paediatric patients according to age, with further studies required to determine other factors that influence FC during infancy.

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Abstract Background Faecal calprotectin (FC) is a non-invasive marker of gastrointestinal inflammation. Aim To determine whether higher FC levels in individuals with quiescent Crohn's disease are associated with clinical relapse over the ensuing 12 months. Methods A single centre prospective study was undertaken in Crohn's disease patients in clinical remission. The receiver operating characteristic (ROC) curve for the primary endpoint of clinical relapse by 12 months, based on FC at baseline, was calculated. Kaplan–Meier curves of time to relapse were based on the resulting optimal FC cutoff for predicting relapse. Results Of 97 patients recruited, 92 were either followed up for 12 months without relapsing, or reached the primary endpoint within that period. Of these, 10 (11%) relapsed by 12 months. Median FC was lower for non-relapsers, 96 μg/g (IQR 39–237), than for relapsers, 414 μg/g (IQR 259–590), (p = 0.005). The area under the ROC curve to predict relapse using FC was 77.4%. An optimal cutoff FC value of 240 μg/g to predict relapse had sensitivity of 80.0% and specificity of 74.4%. Negative predictive value was 96.8% and positive predictive value was 27.6%, FC ≥ 240 μg/g was associated with likelihood of relapse by 12-months 12.18 (95%CI 2.55–58.2) times higher than lower values (p = 0.002). Conclusions In this prospective dataset, FC is a useful tool to help identify quiescent Crohn's disease patients at a low risk of relapse over the ensuing 12 months. FC of 240 μg/g was the optimal cutoff in this cohort.

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AbstractLet U(KλG) be the group of units of the infinite twisted group algebra KλG over a field K. We describe the FC-centre ΔU of U(KλG) and give a characterization of the groups G and fields K for which U(KλG) = ΔU. In the case of group algebras we obtain the Cliff-Sehgal-Zassenhaus theorem.

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Glucose oxidase is immobilized on a ZnO-Fc nanoparticle modified electrode. The new architecture of ZnO supported electron mediators to shuttle electrons from the redox centre of the enzyme to the surface of the working electrode can bring about successful glucose oxidation.

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AbstractBackground and AimsSeveral factors have been reported to affect faecal calprotectin [FC] values, and significant variation in FC concentrations has been observed in inflammatory bowel disease [IBD] patients. We aimed to evaluate FC variability in IBD patients, and to assess the robustness of a single stool punch.MethodsThis is a single-centre observational case-control study. Disease activity was assessed using endoscopic and clinical activity scores, as well as C-reactive protein levels. Stool samples were collected twice within a 1 to 6 days interval, and FC was measured on punches and hom*ogenates by fluorometric enzyme immunocapture assay.ResultsIn all, 260 stool samples were collected from 120 patients. Intrastool variability was low, with an intraclass correlation coefficient for single measures between three punches from a single stool sample of 0.91, and median coefficient of variation [CV] of 17%. CV of two stool samples a few days apart [intra-individual variability] were significantly higher [p <0.01] with median CV of 36%. FC standard deviations correlated with mean FC levels either for intrastool or for intra-individual variability, with a Spearman’s coefficient of rank correlation of 0.85 and 0.78, respectively [p <0.01]. Disease type, location, activity, and FC levels did not influence variability.ConclusionsA single stool punch is reliable for FC measurement, considering that intrastool variability is low. Intra-individual variability a few days apart is significantly higher. Therefore, decision-making strategies based on single measurements should consider this variability, to determine the minimum optimal variation to be achieved, rather than a cut-off, especially in high FC levels.

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Abstract Background Faecal calprotectin (FC) is a biomarker elevated in active inflammatory bowel disease (IBD). FC is more sensitive in colonic than small bowel IBD. Ileo-colonoscopy is usually performed to confirm a diagnosis of IBD. Isolated non-specific terminal ileitis is often inconclusive despite biopsy. We aimed to assess the factors that predict terminal ileal Crohn’s disease after ileitis is seen at colonoscopy. Methods A single centre retrospective study of all endoscopic cases of isolated terminal ileitis diagnosed at colonoscopy over a 4 year period (January 2015 – December 2018) was performed. Data was obtained from the Unisoft Endoscopy reporting software. Statistical analyses included chi-square, student t-test and binary logistic regression. Faecal calprotectin, CRP and histology were noted. &gt;150μg/mg was used as a cut off for elevated FC. Results 139 cases were identified and exclusion criteria were applied (known Crohn’s disease, colonic disease). 74 cases were included for analysis. The mean age was 43.9. 44 (59.5%) of the cases were women. 38 (51.4%) had FC performed of which 27 (71.1%) had a FC &gt;150μg/mg. 60 (81.1%) cases had macroscopic terminal ileum ulcers, 9 (15%) of these had histological evidence of ulceration. Subsequent diagnoses of Crohn’s disease were made in 15 (20.3%) patients. Odds ratio of 1.28 (p = 0.016, Cl 0.45-0.047) in the TI ulcers + FC &gt;150μg/mg vs. no TI ulcers + FC &lt;150μg/mg. Conclusion 1 in 5 patients with isolated terminal ileitis were subsequently diagnosed with Crohn’s disease. Almost 90% of these new cases had a faecal calprotectin &gt;150μg/mg. There is poor correlation between endoscopic and histological terminal ileum ulceration. We conclude that terminal ileal ulceration in combination with faecal calprotectin &gt;150μg/mg increases the likelihood of a new diagnosis of Crohn’s disease.

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The study was conducted at the experimental field of Horticulture Research Centre, BARI, Gazipur during Rabi seasons in three years (2012 to 2015) to investigate the response of broccoli (cv. Premium crop) under different irrigation regimes. The experiment was conducted in RCBD with five replications. There were four treatments: I1=Irrigation up to FC at 5 days interval after plant establishment (PE), I2= Irrigation up to FC at 10 days interval after PE, I3 = Irrigation up to FC at 15 days interval after PE and I4= Irrigation up to FC at 20 days interval after PE. A significant response of broccoli to different irrigation levels was observed. Among the different treatments, I2 (irrigation at 10 days interval) was significantly better yielding (19.98 t/ha, 20.63 t/ha and 16.24 t/ha in 1st, 2nd and 3rd year, respectively). The lowest yields were observed from the treatment I4 each in all 3 years. The highest seasonal water (382.30 mm, 296.58 mm and 305.00 mm in 1st, 2nd and 3rd year) were used in treatment I1 and the lowest (204.60 mm, 185.66 mm and 179.77mm in the 1st, 2nd and 3rd year) were used in treatment I4, I3 and I3, respectively. The results suggest that irrigation at 10 days interval (I2) might be optimum irrigation schedule for broccoli production on the basis of gross return. But in respect of economic profitability, the highest marginal rate of return is obtained from treatment I3.The Agriculturists 2016; 14(1) 98-106

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Abstract Background Faecal calprotectin (FC) demonstrates an excellent correlation with endoscopic inflammation. In addition, a treatment-decision algorithm for Crohn’s disease (CD) incorporating FC outperforms and improves 12-month mucosal healing compared with a strategy based on symptoms alone. The aim of this study was to determine whether normalisation of FC (&lt;250 μg/g) within 12-months of diagnosis is associated with a reduction in disease progression in CD. Methods This was a retrospective cohort study performed at a tertiary IBD centre. All incident cases of CD diagnosed between 2005 and 2017 were identified. Patients with an FC measurement of &gt;250 μg/g at diagnosis who also had at least 1 follow-up FC measured within the first 12-months of diagnosis and &gt;12 months of follow-up were included. The primary endpoint was a composite of progression in Montreal disease behaviour (B1 to B2/3 or B2 to B3 or new perianal disease), surgery or hospitalisation. Results A total of 375 patients were included with a median follow-up of 5.3 years (IQR 3.1–7.4). Normalisation of FC (&lt;250 μg/g) within 12 months of diagnosis was confirmed in 43.5% (n = 163/375) of the cohort. On multivariable Cox-proportional hazards regression analysis, individuals who normalised their FC within 12 months of diagnosis had a significantly lower risk of composite disease progression (HR 0.351, 95% CI 0.235–0.523, p &lt; 0.001) (Figure 1). Cumulative rates of composite disease progression were 7.8%, 21.4% and 29.9% in those that normalised their FC vs. 22.8%, 50.7% and 60.5% in those that did not at 2, 5 and 7 years after diagnosis, respectively. In addition, normalisation of FC was the only predictor that remained significant for all the separate progression end-points (progression in Montreal behaviour / new perianal disease: HR 0.250, 95% CI 0.122–0.512, p &lt; 0.001; hospitalisation: HR 0.346, 95% CI 0.217–0.553, p &lt; 0.001; surgery: HR 0.370. 95% CI 0.181–0.755, p = 0.006). The strongest predictor of whether an individual normalised their FC within 12 months was the commencement of a biologic within 3 months of diagnosis (OR 4.288, 95% CI 1.585–11.0601, p = 0.004). Conclusion Normalisation of FC by 12-months of diagnosis is associated with a reduced risk of disease progression in CD. Our data provide strong support for implementation of treat-to-target strategies earlier than previously tested in Crohn’s disease. The immediate implication for healthcare providers and patients is that by ensuring resolution of mucosal inflammation - measured by proxy with faecal calprotectin, and regardless of other variables - within 1 year of diagnosis has a dramatic effect on disease course.

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The bovine IgG1 and IgG2 isotypes exhibit large differences in effector functions. To examine the structural basis for this, the 12-domain structures of IgG1 and IgG2 were investigated by pulsed neutron scattering using a recently developed camera LOQ. This method reports on the average relative disposition in solution of the Fab and Fc fragments in IgG. The radii of gyration (RG) were found to be similar at 5.64 and 5.71 nm for IgG1 and IgG2 respectively in 100% 2H2O buffers. The two cross-sectional radii of gyration (RXS) were also similar at 2.38-2.41 and 0.98-1.02 nm. Similar values were obtained for porcine IgG. Both bovine IgG1 and IgG2 possess similar overall solution structures, despite sequence differences at the hinge region at the centre of their structures. An automated computer survey of possible IgG structures was developed, in which coordinates for the two Fab fragments were displaced in a two-dimensional plane relative to those of the Fc fragment in 0.25 nm steps. The scattering curves calculated from these structures were found to be sensitive to relative displacements of the three fragments, but not on their rotational orientation about their longest axes. Good agreement with the solution scattering data was obtained with a planar IgG model in which the C-terminus of the CH1 domain of Fab was 3.6 nm from the N-terminus of Fc in both IgG1 and IgG2, with a precision of 0.7 nm. Energy refinement showed that this spatial separation is compatible with the hinge sequences of bovine IgG1 and IgG2. The results show that multidomain protein structures can be modelled using LOQ data, and that a long hinge sequence does not necessarily reflect a large distance between Fab and Fc. The steric accessibility of Fc sites for interactions with cell-surface Fc receptors and C1q of complement is shown to be generally similar for IgG1 and IgG2, and the difference in effector function between IgG1 and IgG2 is probably based on deletions in the IgG2 hinge sequence.

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Technologies such as seed priming have been reported to result in early and uniform crop germination, enhancing optimum crop stand and establishment, eventually leading to optimal crop yields in the Arid and Semi-Arid Lands (ASALs). This study, therefore, was initiated to evaluate the dry matter production of chickpea under different priming methods, varying priming durations and different initial soil moisture levels. Field experiments were carried out at Mwea Irrigation Agricultural Development Centre (MIAD) farm Kirinyaga County, Kenya during 2012/2013 seasons. A split plot experimental design was used to test effects of no priming, hydro priming and halo priming at 0.1, 0.2 and 0.3 % NaCl2 concentration) and at 8, 10 and 12 hours priming duration on germination and growth of desi chickpea ICCV 95107. Altogether, the trial comprised 13 treatment combinations replicated three times with pre-sowing irrigation to soils at field capacity (FC) (100%), 75 %, 50 % and 25 %. Data was collected at growth stages of 25,50,75,90 and 105 days after sowing (DAS). The highest dry matter (DM) yields of 5001.1 and 3973.0 kg/ha was realized under 100 % FC at 105 DAS in season I and II, respectively. Dry matter accumulation (kg/ha) increased from 25 DAS to 105 DAS in both season under all pre sowing irrigation conditions, which correlates to growth stages. Dry matter also increased with increased pre sowing irrigation from 25% FC to 100% FC, and at every stage of growth. Halo priming for 8 hours with 0.2% NaCl2 distilled water solution gave the highest DM at all stages of growth (P ≤ 0.05). Significantly higher DM yields (P ≤ 0.05) were produced at 25% FC pre sowing irrigation with no priming (6500.0 kg/ha) and 0.2% NaCl2 for 12 hours (5900.0 kg/ha) by 90 DAS D during the wet season (SI). Dry matter ranged from 6440.0kg/ha at 50% FC- 0.2% NaCl2 for 8 hours to 6713.0kg/ha at 75% FC- 0.1% NaCl2 for 10 hours 6970.0 kg/ha at 0.2% NaCl2 for 8 hours. During the drier season (SII), the highest DM yields of 5017.0 and 4285.0 kg/ha were realized from 100% FC pre-sowing irrigation and priming of 0.2% NaCl2 for 12 hours and 0.2% NaCl2 for 10 hours, respectively. Therefore, adequate soil moisture of over 75% FC is necessary if effectiveness of priming 0.1 to 0.2% NaCl2 for 8 to 12 hours is to be realized under clay ASALs sandy loam soils of Mwea where droughts lead to prolonged seed emergence period, leading to deterioration of the seedbed and increased soil compaction, that eventually result in poor crop emergence, establishment and poor crop yields.

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Introduction: Haemodialysis requires recirculation, and it happens when dialysed blood returningthrough the venous needle re-enters the extracorporeal circuit through the arterial needle, ratherthan returning to the systemic circulation. Significant recirculation should be expected, when there isan inadequate reduction in the values of urea. During End-Stage Renal Disease (ESRD), adequatedialysis is of utmost importance because it influences the morbidity and mortality of the patients.Methods and materials: The study was carried out in 200 patients who underwent haemodialysisat the dialysis unit in Kalyani kidney care centre, Erode. Patients were actively evaluated fromFebruary 2018 till November 2018. Patients were randomized and accordingly 64 patients wereenrolled in category I Arteriovenous fistula (AVF), 63 Patients in category II Internal JugularCatheter (IJC) and category III Femoral Catheter (FC) each and 10 patients in category IV PermCatheter (PC). Success recirculation was estimated and adequacy of haemodialysis was donevirtually. Calculated Kt/V was done in almost all patients. Results: The mean access recirculationrate was 6.3+5.1% in those with AVF, while in IJC and FC groups were 6.7+4.5% and 24.4+11.7%respectively. When the two groups were compared, AVF vs FC groups, the difference was statisticallysignificant (p value<0.001) and in IJC vs FC groups, the difference was statistically less significant(p-value <0.001) in both AR% and online Kt/V. Conclusion: An arteriovenous2QQ2 fistula has lessaccess recirculation, when compared to temporary catheters. On the other hand, the femoralcatheter has more access recirculation, when compared to the internal jugular catheter. Thedifference in calculated Kt/V with the three types of vascular access has no statistical significance.

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There is an increasing interest in non-invasive methods to assess gut inflammation. The data regarding the correlations between inflammatory markers and activity of inflammatory bowel disease (IBD) are still controversial. In the last years faecal calprotectin became the most widely used biomarker in diagnosis and monitoring the IBD activity. We prospectively studied the correlation between the serological inflammatory markers (platelets, erythrocyte sedimentation rate - ESR, fibrinogen, C Reactive Protein -CRP, ferritin, albumin), faecal calprotectin and severity of IBD in a tertiary referral centre in North-East Romania. Our study demonstrated that is a good correlation between serologic inflammatory markers (platelets, fibrinogen and ferritin, not ESR and albumin) and severity of IBD. CRP is a good marker in Crohn�s disease (CD) but not in ulcerative colitis (UC). Faecal calprotectin (FC) is the best inflammatory biomarker which correlates with activity both in UC and CD. Inflammatory biomarkers, especially FC are an important tool to evaluate patients with IBD.

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Underfilling is the vital process to reduce the impact of the thermal stress that results from the mismatch in the co-efficient of thermal expansion (CTE) between the silicon chip and the substrate in Flip Chip Packaging. This paper reported the pattern of underfill’s hardness during curing process for large die Ceramic Flip Chip Ball Grid Array (FC-CBGA). A commercial amine based underfill epoxy was dispensed into HiCTE FC-CBGA and cured in curing oven under a new method of two-step curing profile. Nano-identation test was employed to investigate the hardness of underfill epoxy during curing steps. The result has shown the almost similar hardness of fillet area and centre of the package after cured which presented uniformity of curing states. The total curing time/cycle in production was potentially reduced due to no significant different of hardness after 60 min and 120 min during the period of second hold temperature.

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Abstract Abstract 1600 Background: It is well known that Fc gamma receptors expressed on monocytes and macrophages enhance the presentation of antibody-bound antigens. Human Fc gamma receptors are coded by genes located on chromosome 1q23. Fc gamma RIIA (CD32) is a transmembrane protein expressed on neutrophils. Efficacy of phagocytosis by polymorphonuclear neutrophils is known to vary between allotypes of Fc gamma RIIa. Polymorphisms of Fc gamma RIIA have been linked to susceptibility to infections by encapsulated bacteria (N. meningitides, H. influenzae) and severe sepsis by several authors. Moreover, susceptibility to perinatal HIV-1 infection has been attributed to polymorphisms of Fc gamma RIIA, and this is the only association of FC gamma RIIA with viral diseases in the literature. FcγRIIA gene has two condominantly expressed alleles the 131-Arg (R131) and the 131-His (H131) allele. R131 binds IgG2 much less avidly than H131. Aim of the study: To propose Fc gamma RIIA polymorphisms as a genetic risk factor for acquisition and latency of EBV infection in patients with lymphoproliferative diseases. Patients and Methods: Forty Greek patients with EBV-unrelated low grade B-cell leukemic lymphomas (chronic lymphocytic leukemia: 23, marginal zone lymphoma: 11, mantle cell lymphoma: 3, hairy cell leukemia: 2, follicular lymphoma: 1), were included in the study. Patients' sera were tested with ELISA for the presence of EBV-VCA IgG antibodies. DNA from peripheral blood was studied by quantitative real time - PCR for the EBV-R gene, while RNA from peripheral blood was studied by RT-PCR for the EBV-LMP1 oncoprotein. Genomic DNA from peripheral blood was tested for Fc gamma RIIA 131Histidin(H)/arginine(R) SNP, by PCR, followed by restriction fragment length polymprphim (RFLP) using the appropriate enzyme (BstUI, Fermentas, Vilnius, Lithuania). We used Pearson Chi-square for the statistical analysis of the results. Results: All but 2 patients were positive for EBV-VCA IgG antibodies. Nineteen patients (47.5%) were EBV-positive. LMP1 was expressed in 13/19 (68.4%) EBV-positive patients. The vast majority (16/19, 84.2%) of EBV positive patients carried the R131 allele (13 were heterozygous and 3 hom*ozygous), while only 3 were hom*ozygous for the H131 allele. Among 21 EBV-negative patients, only 6 (28.5%) carried the R131 allele (4 heterozygous and 2 hom*ozygous) (2-sided p=0001). R131 allele was present in 11/13 (84.6%) LMP1-positive patients in comparison to 6/21 (28.0%) EBV-negative patients (2-sided p=0.002). Discussion: The high prevalence of FC gamma RIIA polymorphisms among EBV-positive patients indicates a possible pathogenetic role of the FC gamma RIIA in acquisition and chronicity of EBV infection. LMP1 is the major oncoprotein of EBV. The correlation of this polymorphism to LMP1 expression is an indication that it may play a major role in the expression of latency phase proteins, a fact that may further be implicated in the pathogenesis of lymphoproliferative diseases in these patients. We continue the study in our centre, increasing the number of patients enrolled. Disclosures: No relevant conflicts of interest to declare.

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Abstract Background Balloon pulmonary angioplasty (BPA) is an emerging treatment in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic disease (CTED). We describe the first safety and efficacy results of BPA in the Netherlands. Methods We selected all consecutive patients with inoperable CTEPH and CTED accepted for BPA treatment who had a six-month follow-up in the St. Antonius Hospital in Nieuwegein and the Amsterdam University Medical Center (UMC) in Amsterdam. Functional class (FC), N‑terminal pro-brain natriuretic peptide (NT-proBNP), 6‑minute walking test distance (6MWD) and right-sided heart catheterisation were performed at baseline and six months after last BPA. Complications for each BPA procedure were noted. Results A hundred and seventy-two BPA procedures were performed in 38 patients (61% female, mean age 65 ± 15 years). Significant improvements six months after BPA treatment were observed for functional class (63% FC I/II to 90% FC I/II, p = 0.014), mean pulmonary artery pressure (−8.9 mm Hg, p = 0.0001), pulmonary vascular resistance (−2.8 Woods Units (WU), p = 0.0001), right atrial pressure (−2.0 mm Hg, p = 0.006), stroke volume index (+5.7 ml/m2, p = 0.009) and 6MWD (+48m, p = 0.007). Non-severe complications occurred in 20 (12%) procedures. Conclusions BPA performed in a CTEPH expert centre is an effective and safe treatment in patients with inoperable CTEPH.

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BackgroundLong-term treatment with riociguat has been shown to enhance exercise capacity in patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH). This study sought to evaluate the long-term haemodynamic effects of riociguat in patients with PAH and inoperable CTEPH.MethodsDuring this single-centre long-term observational study, riociguat was administered at a three-times-daily dose of up to 2.5 mg. The primary outcome was pulmonary vascular resistance (PVR). The secondary outcomes included mean pulmonary arterial pressure (PAP), cardiac index, mortality, clinical worsening events, 6-min walk distance (6MWD) and World Health Organization functional class (WHO FC).Results37 patients (CTEPH n=19; PAH n=18) were included. The median follow-up period was 96 months. The survival estimates for all the patients at 1/3/5/8 years were 0.97/0.86/0.72/0.61, without significant differences between patients with CTEPH and PAH. At the final data cut-off, PVR decreased (1232±462 dyn·s·cm–5versus 835±348 dyn·s·cm–5, p<0.001), cardiac index increased (1.7±0.4 L·min−1·m−2versus 2.4±0.5 L·min−1·m−2, p<0.001), 6MWD increased by 43.1±59.6 m, and WHO FC improved/stabilised/worsened in 40%/35%/25% of patients versus baseline. Improvement in PAP was not shown. Compared with patients in WHO FC I/II and III/IV at baseline, the 8-year clinical worsening-free survival estimates were 0.51 versus 0.19 (p=0.026).ConclusionsRiociguat improved PVR and cardiac index for up to 8 years, but not PAP. WHO FC may have certain predictive value for the long-term prognosis.

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Abstract A novel method is introduced to generate climatological frequency distributions of meteorological features from gridded datasets. The method is used here to derive a climatology of extratropical cyclones from sea level pressure (SLP) fields. A simple and classical conception of cyclones is adopted where a cyclone is identified as the finite area that surrounds a local SLP minimum and is enclosed by the outermost closed SLP contour. This cyclone identification procedure can be applied to individual time instants, and climatologies of cyclone frequency, fc, are obtained by simple time averaging. Therefore, unlike most other climatologies, the method is not based on the application of a tracking algorithm and considers the size of cyclones. In combination with a conventional cyclone center tracking algorithm that allows the determination of cyclone life times and the location of cyclogenesis and cyclolysis, additional frequency fields can be obtained for special categories of cyclones that are generated in, move through, or decay in a specified geographical area. The method is applied to the global SLP dataset for the time period 1958–2001 from the latest 40-yr European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40). In the Northern Hemisphere and during winter, the cyclone frequency field has three maxima in the Pacific storm track (with fc up to 35%), the Atlantic storm track (with fc up to 32%), and the Mediterranean (with fc up to 15%). During the other seasons the fc values are generally reduced in midlatitudes and the subtropical monsoon areas appear as regions with enhanced fc. In the Southern Hemisphere, the seasonal variations are smaller with year-round maxima of fc in the belt from 50° to 70°S (along the coast of Antarctica, with maximum values of almost 40%) and to the east of the Andes (with fc up to 35% during summer). Application of a lifetime threshold value significantly reduces fc, in particular over and close to the continents. Subsets of cyclone frequency fields are calculated for several subjectively chosen regions of cyclone genesis, passage, and lysis. They show some interesting aspects of the behavior of extratropical cyclones; cyclones that decay along the U.S. West Coast, for instance, have a short lifetime and originate almost exclusively from the eastern North Pacific, whereas long-lived and long-distance Pacific cyclones terminate farther north in the Gulf of Alaska. The approach to calculate frequency distributions of atmospheric flow structures as introduced in this study can be easily applied to gridded data from global atmospheric models and assimilation systems. It combines the counts of atmospheric features with their area of influence, and hence provides a robust and easily interpretable measure of key meteorological structures when comparing and evaluating different analysis datasets and climate model integrations. Further work is required to comprehensively exploit the presented global ERA-40 cyclone climatology, in particular, aspects of its interannual variability.

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Background and ObjectiveDouble J (JJ) ureteric stenting represents one of the most significant causes of patient discomfort and dissat-isfaction following endourological procedures. At our institution, a large tertiary referral centre for complex stones, standard JJ stent removal was previously undertaken with a flexible cystoscope (FC) in the endoscopy department by a doctor. The pathway was prone to delays through capacity constraints and prioritization being given to cancer investigations. The Isiris® is a single-use stent removal system consisting of a ‘camera on chip’ disposable FC with an integrated grasper. We examine the feasibility of a nurse-led stent removal service using Isiris®, performed as an office-based procedure, and its effect on waiting times. Material and MethodsA specialist stone nurse undertook training in FC approved by the British Association of Urological Surgeons (BAUS) and the British Association of Urological Nurses (BAUN). Once competency was reached, a nurse-led service was offered to patients in the outpatient setting. A prospective database from April 2018 to March 2020 was maintained to include patient data for stent removals in the nurse-led clinic using Isiris®. This was compared to a retrospective dataset of FC and stent removal between July 2016 and December 2016, per-formed by a doctor in the endoscopy department. The delays in stent removal compared to the ‘ideal’ stent removal date (planned date plus or minus 3 days tolerance allowed) were compared between the two pathways. ResultsThe specialist nurse undertook BAUS theory training and competency was reached using an approved BAUS/BAUN competency package. 414 stent removals were booked in the nurse group, of which 395 were undertaken. 291 of 395 (74%) patients in the nurse removal Isiris® group had their stent removed on time, whereas only 16 of 54 (30%) patients had their stents removed on time in the FC stent removal group. A delay of more than 21 days was seen in 22% of FC group vs only 2% in the nurse-led Isiris® group. Both planned removal and actual stent dwell time were longer in the FC group compared to Isiris® group (p < 0.0001). There were no major complications with the use of Isiris® for stent removal in the nurse-led clinic. ConclusionThis study has demonstrated that it is feasible to introduce a nurse-led stent removal service. The introduction of this service using the Isiris® system has led to a reduction in delays of stent removal, which is likely to trans-late into significant quality of life improvement for patients and economic benefits for the healthcare system.

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Aim. As a clinical part of the Russian multi-centre randomised study, to assess the clinical benefits and safety of adding Trimetazidine MB to the standard treatment scheme in patients with stable angina (SA), in order to optimise their ambulatory therapy and improve their compliance. Material and methods. The study included 981 patients with Functional Class (FC) II-III SA and various concomitant diseases and syndromes, such as chronic heart failure (CHF), Type 2 diabetes mellitus (DM-2), or chronic obstructive pulmonary disease (COPD) in smokers. All participants were divided into two groups: Group I (n=838) received standard therapy plus trimetazidine MB (70 mg/d, twice a day), while Group II (n=143) received standard therapy only. The treatment and follow-up phases lasted for 12 months. Results. In Group I, the weekly number of angina attacks decreased by 42 % from the baseline at one month (р<0,0001), and by 70 % at 12 months (р<0,0001). The number of nitroglycerin (NTG) tablets taken decreased, respectively, by 41 % (р<0,0001) and 68 % (р<0,0001). In Group II, the decrease in angina attack number and NTG tablet number was significant only at 6 months and was less pronounced than in Group I. Therefore, in Group I, the number of patients with FC I increased by 7 times, while the number of FC III patients decreased by 1,8 times. No marked FC dynamics was observed in Group II. In Group I, left ventricular ejection fraction (LVEF) increased by 2,4 % (р<0,001), while interventricular septum and LV posterior wall thickness decreased, respectively, by 4,2 % (р<0,01) and 3,5 % (р<0,01). These parameters, however, did not change substantially in Group II patients. At 12 months, the number of patients hospitalised due to clinical decompensation, or becoming disable, was twice as high in Group II as in Group I. Conclusion. The Russian “PERSPECTIVE” Study results demonstrated high clinical effectiveness and safety ofTrimetazidineMB therapy, combined with standard treatment, in SA patients with CHF, DM-2, and COPD. Therefore, metabolic therapy could be more widely used in the real-world clinical settings.

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Wide span building is kind of building that need large space without any poles in the centre. Roof building construction is wide span structure that overshadow footsal, basketball and volley field in Bangka Belitung University. Arc structure become one of construction structures that often used in wide span buildings. In this planning, steel constructions using LRFD method. The result from this planning is dimention of gording using canal profil type 150.75.6.5.10 with quality of steel is BJ41. For trekstang/sargod using plain steel with diameter mm. Portal rafter using round profil PSB 10 inch diameter and coloumn using WF profil 458.417.30.50 with quality of steel is BJ41. Base plate dimentions is (600x600) mm with 32 mm thick for 16 bolts with inch diameter and 10 mm endplate for 6 high quality bolts type A490 with mm diameter. Dimentions of pedestal coloumn is (1400x1400) mm, 1400 mm high with 40 25-100 main reincforcement and 13-400 crossbar with fc’ 25 Mpa, fy 400 MPa. Dimentions of footplate pondations is (2100x2100)mm with 600 mm thick, pondations reinforcement using plain steel diameter and stek reinforcement using 16D29 with fc’=25 Mpa, fy=400 Mpa.

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Abstract The main objective of the project is to develop and validate the use of a fuel cell based power system for the propulsion of more/all electric aircraft. The Rapid 200-FC two-seater electric-motor-driven aeroplane which is powered by fuel cells is at present being completed and will be validated during a flight test in Autumn 2009. Several configurations have been evaluated in order to install the new energy and propulsion system on board while maintaining the centre of gravity within allowable limits. The fuel cell system and the electric motor are being integrated on board. The FC stack will be able to deliver a maximum continuous power of 20kW. A battery pack has to guarantee another 20kW of maximum continuous power for a limited time period (15 minutes), during take-off, climbing and, in the case of emergency, during landing. The main goal of the project is to validate the overall high performance of an all electric aircraft system which is capable of remaining aloft for one hour. A parametric analysis has also been carried out to evaluate which key technologies influence the performance of future aircraft to the greatest extent.

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Abstract Introduction Diagnostic delay &gt;12 months is frequent in Crohn’s disease [CD]. Recently, the International Organization for Inflammatory Bowel Disease [IO-IBD] developed a tool to identify early CD and reduce diagnostic delay. Subjects with an index ≥8 are more likely to have suspected CD (odds ratio [OR] 205, p &lt;0.0001). We aimed to validate this questionnaire at the community level in patients seen by the general practitioners [GPs] in two large areas of Lombardy, Italy. Methods Consecutive adult patients referring to the GP were screened. The GPs administered the Red Flags [RF] questionnaire to the eligible patients. All patients were referred to the nearest participating centre to confirm or exclude the diagnosis of CD. Sensitivity, specificity, and positive and negative predictive values [PPV, NPV] of the RF index [RFI] were calculated. Patients lost to follow-up after the first gastroenterological visit were analysed using a non-responder imputation, assuming they were negative for CD diagnosis. Results From November 2016 to November 2019, 112 patients were included. A total of 66 subjects [59%] completed the study after the first gastroenterological visit. The prevalence of CD was 3.6% in the study population [4/112]. The RF index had 50% sensitivity, 58% specificity, 4% PPV, and 97% NPV. A combined diagnostic strategy with faecal calprotectin [FC] [RFI ≥8 and/or FC &gt;250 ng/g] resulted in significantly improved accuracy: sensitivity 100% [29–100%], specificity 72% [55–85%], PPV = 21% [5–51%], NPV = 100% [88–100%]. Conclusions The RF Index combined with FC is a valid tool to identify patients with high probability of having CD at early stage.

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Abstract Rainfall is a driving factor of climate in the tropics and needs to be properly represented within a climate model. This study customizes the precipitation processes over the tropical regions of eastern Africa and the Indian Ocean using the International Centre for Theoretical Physics (ICTP) Regional Climate Model (RegCM3). The convective schemes of Grell with closures Arakawa–Schubert (Grell–AS)/Fritch–Chappel (Grell–FC) and Massachusetts Institute of Technology–Emanuel (MIT–EMAN) were compared to determine the most realistic spatial distribution of rainfall and partitioning of convective/stratiform rainfall when compared to observations from the Tropical Rainfall Measuring Mission (TRMM). Both Grell–AS and Grell–FC underpredicted convective rainfall rates over land, while over the ocean Grell–FC (Grell–AS) over- (under-) estimates convective rainfall. MIT–EMAN provides the most realistic pardoning and spatial distribution of convective rainfall despite the tendency for overestimating total rainfall. MIT–EMAN was used to further customize the subgrid explicit moisture scheme (SUBEX). Sensitivity tests were performed on the gridbox relative humidity threshold for cloudiness (RHmin) and the autoconversion scale factor (Cacs). An RHmin value of 60% (RHmin-60) reduced the amount of total rainfall over five heterogeneous rainfall regions in eastern Africa, with most of the reduction coming from the convective rainfall. Then, Cacs sensitivity tests improved upon the total rainfall amounts and convective stratiform partitioning compared to RHmin-60. Based upon all sensitivity simulations performed, the combination of the MIT–EMAN convective scheme, RHmin-60, and halving the model default value (0.4) of Cacs provided the most realistic simulation in terms of spatial distribution, convective partition, rainfall totals, and temperature bias when compared to observations.

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Coping skills provide a resource for tackling stress in everyday situations, including those relating to parenting. The aim of this article is to establish whether parents who experienced a 10-hour universal social emotional parenting program — Families Coping (FC) — benefit through increased productive coping strategies, decreased nonproductive coping strategies, and increased parent wellbeing, within a positive parenting framework. It is also of interest to see whether gender and/or partner attendance makes a difference in program outcomes such as coping styles and wellbeing. The data set combined two groups of parents (N = 23) of preschool-aged children from an early learning centre in inner-metropolitan Melbourne in 2013 and 2014 who undertook the FC parenting program. A mixed methods design was employed, where parents completed pre- and post-program questionnaires on coping and wellbeing. Results were considered with respect to gender and partner attendance. A one-way repeated-measures multiple analysis of variance (RM-MANOVA) showed a significant increase in one productive parenting style (Dealing with the Problem), a significant decrease in nonproductive parent coping, and a significant increase in parent wellbeing. Comparison of results between gender and partner attendance groups showed minimal differences in program effectiveness. Qualitative data mostly confirmed the key findings.

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Introduction: Flow cytometric (FC) immunophenotyping is an essential tool for the diagnosis of mature B cell lympho-proliferative disorders (B-LPDs). The most common CD5-negative/CD10-negative B-LPDs are hairy cell leukemia, lymphoplasmacytic lymphoma and marginal zone lymphoma. Although HCL has unique clinicopathologic characteristics, LPL and MZL are often difficult to distinguish by standard diagnostic methods. MYD88 L265P mutations are found in 90% of LPL and 8-10% of MZL, although the finding of this mutation may increase the suspicion of LPL, it is by no means definitive since they are also found in MZL. The distinction between LPL and MZL is of increasing clinical importance given treatment options and prognosis may differ. The Euroflow eight color B-LPD panel provides detailed information on the phenotype of clonal B-cells and has not previously been evaluated as a tool to distinguish these subtypes of B-LPD. Methods: A retrospective study of patients who were diagnosed with CD5-negative/CD10-negative B-LPD from January 2011 to October 2017 was conducted. Patients with HCL and diffuse large B cell lymphoma were excluded. Data collected included the FC immunophenotype, clinical findings, MYD88 mutational status, treatment and outcome. Data were obtained from the FC lab database at the National University Health System (NUHS) Hematology laboratory. Clinical data were obtained from the electronic patient medical records. A clinicopathologic diagnosis of either LPL, MZL or "indeterminate between LPL/MZL" was assigned to the patients based on consensus at the multidisciplinary tumor board. The FC phenotype (based on raw median fluorescence intensity values) of patients assigned to each diagnostic category were then compared. Hierarchical clustering using Gower's distance of variables and Ward's D linkage method were used to determine if the FC immunophenotyping patterns can distinguish LPL and MZL. Results: A total of 22 patients' data was included in the analysis. We found that the LPL cases formed a discrete cluster, while MZL cases were more widely dispersed (figure 1). LPL cases showed negative expression of CD 39, CD 43 and CD 95, while these markers are expressed in a significant proportion of MZL cases. In contrast, CD31 was expressed in the majority of LPL but not the MZL cases. CD 200 and CD38 were found to be variably expressed in both LPL and MZL cases. It is noteworthy that CD 27 was also not consistently expressed across all the cases in our study. There were also no significant differences in terms of surface IgM expression. Conclusions: Our study showed that the eight color flow cytometry has potential as a tool to differentiate LPL and MZL. The lack of a discrete clustering of the MZL cases in our analysis may be explained by the fact that MZL is a more heterogeneous entity compared to LPL. Positivity for CD31 and negativity for CD39, CD95 and CD43 appear to be features of LPL. MZL in contrast show positive expression of CD39, CD95 and CD43 and are negative for CD31. Earlier studies using four color FC suggested that CD200 may have value as a discriminative marker between LPL and MZL. Our data using eight color FC does not show the same discriminative power for CD200. The absence of consistent CD39 and CD27 expression is unusual as LPL and MZL are both post germinal centre B cell neoplasms in which the expression of these antigens is expected. We propose that FC immunophenotyping should be evaluated prospectively as an adjunct to standard clinicopathologic evaluation to distinguish LPL and MZL. Figure 1 Disclosures No relevant conflicts of interest to declare.

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The article presents the results of ongoing co-research at the fulfilment centre of Amazon in Leipzig. It demonstrates exemplarily that despotic forms of labour are a central feature also of digital capitalism. Amazon is implementing various strategies of real subsumption to get the workers functioning as a senso-motoric part of the digital machinery in order to exploit their labour power. It is monopolizing the knowledge about the production process, setting up the FC as a panoptic factory and producing an internal public. This however encounters moments of insubordination resulting in daily micro-conflicts over working conditions and capitalist commands. Workers try to withdraw themselves from the despotism of the factory, use primitive forms of sabotage and develop a counter-public.

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Abstract The trace element analysis system is presented using Proton Induced X-ray Emission (PIXE) analysis at a new Ion Beam Centre in Trnava. Standard PIXE system dedicated to the measurement of thick solid samples was extended by a new application for trace element analysis in aerosol samples. The sample holder was modified with respect to the dimensions of the aerosol filters, and a new sample holder and a Faraday cup (FC) were made. The first results of the PIXE aerosol analysis are presented in this paper. Furthermore, the geometric efficiency of the detection system was verified using 55Fe radioactive source emitting monoenergetic Mn X-ray lines. The measured data were compared with the Monte Carlo simulations regarding/disregarding the X-ray attenuation.

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OBJECTIVE: To compare three sampling methods and to pretest methods for the determination of fecal coliform (FC) counts andToxocaraspecies from sand in the day care outdoor environment.DESIGN: The sand samples were obtained from the play area and the sandbox of a day care centre and examined for the presence of FC andToxocaraspecies, the common roundworm of dogs and cats. The sampling methods included random selection and two types of judgement methods. The latter included one method where domestic animals were judged to be likely to defecate and the other where children would be likely to be playing. In addition, to obtain a global estimate of contamination, the entire areas of both the sandbox and the play area were sampled on the last day.SETTING: Outdoor day care environment.MAIN RESULTS: The most representative levels of bacterial contamination andToxocaraspecies originated from the combined sample of the entire surface areas rather than from any separate random or judgement method of sampling. FCs were found in all sampled areas of the sandbox (median 910 FCs/g of sand) and of the play area (median 350 FCs/g of sand).Toxocaraspecies were recovered from a number of areas in both the sandbox and the play area.CONCLUSIONS: Research on environmental microbial contamination of outdoor day care settings would benefit from the application of standardized and validated sampling and laboratory methods.

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ABSTRACT We estimate the rate of inspiral for a population of stellar mass black holes in the star cluster around the supermassive black hole (SMBHs) at the centre of Milky Way mass galaxies. Our approach is based on an orbit averaged Fokker Planck approach. This is then followed by a post-processing approach, which incorporates the impact of the angular momentum diffusion and the GW dissipation in the evolution of system. We make a sample of 104 BHs with different initial semimajor and eccentricities with the distribution of fc(a)/a and e, respectively, where fc(a) refers to the phase–space distribution function for cth species. Angular momentum diffusion leads to an enhancement in the eccentricity of every system in the above sample and so increases the rate of inspiral. We compute the fraction of time that every system spends in the LISA band with the signal-to-noise ratio $\rm {S/N} \ge 8$. Every system eventually approaches the loss-cone with a replenishment rate given by the diffusion rate of the cluster, $\mu / \rm {Gyr}^{-1} \lesssim 1$. This small rate reduces the total rate of the inspiral for individual MW mass galaxies with an estimate Robs ≲ 10−6−10−5 yr−1. A large collection of galaxies (Ngal &gt; 104 MW) may lead to an observable GW signal in the LISA band.

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Abstract INTRODUCTION: Cyclophosphamide (CTX) is an alkylating agent of the nitrogen mustard type, regarded as one of the most potent immunosuppressive drugs available. An activated form of this drug, phosphoramide mustard, alkylates, or binds, to DNA. Its cytotoxic effect is mainly due to cross-linking of strands of DNA and RNA, and to inhibition of protein synthesis. Its has been shown that CTX suppress T-helper cell functions with prolonged reduction of B cells due to the slower rate of recovery of B lymphocytes from an alkylating agent. As in many chemotherapeutic drugs, a major hindrance to the effectiveness of cyclophosphamide in long term leukemic therapy is the target cells subsequent development of resistance against the drug. OBJECTIVE: The main objective of the research was to implement the determinations of the ex vivo resistance to cyclophosphamide profile and to identify the genetic profile for pediatric patients with acute leukemias. METHODS: In order to determine the ex vivo drug resistance profile, MTT cytotoxicity assay was performed on mononuclear cells. Gene expression profiles were prepared on the basis of cRNA hybridization to oligonucleotide arrays of the human genome (Affymetrix) for 51 patients with ALL and 16 patients with AML. Hierarchical clustering, assignment location and biological function were performed during the correlation analysis for identified probe sets. Verification of the relative expression level of selected genes was carried out by real time PCR. In order to gain new insights into the molecular mechanisms involved in cyclophosphamide resistance, we performed array-based comparative genomic hybridization (aCGH) on a series of 24 primary acute leukemias, using a SurePrint G3 Human CGH Microarray, 8x60K (Agilent). Data was analyzed by bioinformatics tools: Partek Genomics Suite, PANTHER tools, KEGG Pathway, Agilent Feature Extraction & CytoGenomics. RESULTS: Based on the global expression profile and LC50 values we found, that cyclophosphamide and bortezomid are demonstrating the most different resistances profile, in relation to 20 antileukemic drugs analyzed in the entire research. We observed a multitude of differentially expressed genes, e.g., AKR1C3 (Fold Change=2,81, p-value=0,049), ANXA1 (FC=3,04, p=0,011), BCL2A1 (FC=2.69, p=0,019), SERPINA1 (FC=2.12, p=0.014), DHRS7 (FC=2.13, p=0.005), PCDH9 (FC=-4.58, p=0.015), TTC28 (FC=-2.25, p=0.033) and DUSP1; (FC=-2.91, p=0,002). We assigned the differentially expressed genes to functional pathways (Table 1). Table 2 shows consistently amplified and deleted regions in acute leukemias samples. A 0.29-Mb stable deleted region involving 10 genes was detected at 10q23.31. Among the affected genes are copy number variants in the IFIT3 gene (interferon-induced protein with tetratricopeptide repeats 3), which regulates cell migration, proliferation and signaling. IFIT3 exhibit an antiproliferative activity via the up-regulation of cell cycle negative regulators CDKN1A/p21 and CDKN1B/p27. Simultaneously we have found for this gene, a significant decrease of mRNA expression of in resistant cells (FC=-2.15, p=0.023). Table 1. Panther pathway analysis of differentially expressed genes (cutoff = 2 relative expression change). Table 1. Panther pathway analysis of differentially expressed genes (cutoff = 2 relative expression change). Table 2. Overview of aCGH findings in resistant acute leukemias samples. Table 2. Overview of aCGH findings in resistant acute leukemias samples. CONCLUSION: Our work delineated genes with diferentiated expression, recurrent copy number changes and revealed novel amplified loci and frequent deletions in resistant to cyclophosphamide in children leukemias, which may guide future work aimed at identifying the relevant target genes. In particular, deletion seems to be a frequent mechanism of inactivation of the IFIT3 gene. Among the candidate genes of resistance may also be included: ANXA1, SERPINA1, TCF7 and BCL2A1. This study was supported by Grant from the National Science Centre No. DEC-2011/03/D/NZ5/05749. Disclosures No relevant conflicts of interest to declare.

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Background: The evidence on the efficacy and safety of biosimilar infliximab (IFX) in patients with inflammatory bowel diseases (IBD) is sparse. Methods: Consecutive IBD patients visiting our centre were included. One cohort composed of prospectively followed patients who were switched from original to biosimilar IFX between January and March 2015. The second cohort included retrospectively assessed anti-tumor necrosis factor α-naïve patients who started therapy between January 2015 and January 2016. Disease activity was assessed using standard clinical indices, endoscopic evaluation, and laboratory parameters (blood count, C-reactive protein (CRP) and fecal calprotectin (FC)). Trough levels and anti-drug antibodies (ATIs) were also measured. Patients were evaluated 56 weeks (W56) after switch and at week 14 (W14) and week 46 (W46) in the naïve cohort. Results: Seventy-four IBD patients were switched to biosimilar IFX and 119 naïve patients newly initiated therapy with the preparation. Disease activity remained stable in a majority of switched patients (remission at week 0 (W0) vs. W56: 72.2 vs. 77.8%; median difference of both Harvey-Bradshaw index and Simple Clinical Colitis Activity Index between W0 and W56 was 0). When W0 and W56 were compared, no significant difference in CRP (4.3 ± 8.0 vs. 3.3 ± 3.8 mg/l; p = 0.89) and FC (135 ± 153 vs. 199 ± 225 µg/g; p = 0.17) was observed. In total, 92% of Crohn's disease (CD) and 83% of ulcerative colitis (UC) patients responded to induction therapy (W14) with biosimilar IFX. At W46, the response rate was 86% in CD and 64% in UC. Moreover, half of UC patients experienced mucosal healing at W14 and improvement of perianal disease occurred in 95% of CD at W46. In this cohort, clear steroid-sparing effect was observed. No increase in immunogenicity was found in switched patients (ATI positivity: 9.5 vs. 6.0%, p = 0.54) and the type and frequency of adverse events were comparable to the original preparation in both cohorts. Conclusion: Switching of IBD patients from original to biosimilar IFX is effective and safe.

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Components of the fleece and wool quality traits were measured or assessed on Merino hogget ewes in an unselected multiple-bloodline flock over a 7-year period at Trangie Agricultural Research Centre, N.S.W. The traits recorded were face cover score (FC), leg cover score (LC), neck fold score (NF), body fold score (BF), wax content (W), suint content (S), vegetable matter content (VM), dust penetration (D), follicle density (N) and follicle ratio (RA). Genetic differences within and between flocks of Merino sheep were examined for the traits, and estimates of heritability and within-flock genetic and phenotypic correlations and between-flock genetic correlations among the traits were obtained. Genetic and phenotypic correlations were also estimated between these traits and the major wool production traits: greasy fleece weight (GFW), clean fleece weight (CFW), fibre diameter (FD), body weight (BWT) and staple length (SL). Significant strain. flock within strain and flock effects were wresent for all traits. The influence of environmental effects (birth-rearing type, age at measurement and age of dam) on the traits was estimated, with the birth-rearing type being significant and the largest effect for most traits. Paternal half-sib heritability estimates were 0.44� 0.06 for FC, 0.35� 0.06 for LC, 0.24�0.05 for NF, 0.23�0.05 for BF, 0.38�0.07 for W, 0.42�0.07 for S, 0.06�0.04 for VM, 0.22�0.06 for D, 0.20� 0.07 for N and 0.21�0.07 for RA. Estimates of within-flock phenotypic and genetic correlations were in broad agreement with available published estimates. The implications of the results for Merino breeding programs are discussed.

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Background: Minimal Residual Disease (MRD) is a powerful predictor of event-free survival in acute lymphoblastic leukemia (ALL). However, as T-ALL is less common, MRD studies are limited, often with small cohorts, and even fewer have been done by flowcytometry-based MRD (FC-MRD). There have also been different time-points such as Post-Induction (PI-MRD), and late or Post-Consolidation (PC-MRD) that have shown significant correlation with overall, event, and relapse-free survival (OS, EFS & RFS). As the available literature is still not conclusive, we investigated the impact of FC-MRD on survival in childhood T-ALL at a large tertiary cancer care centre in India. Methods: Children less than 15-years age diagnosed with T-ALL from Jan-2014 to May 2018 were treated uniformly on a modified MCP-841 protocol that included a 4-drug induction (vincristine, prednisolone, l-asparaginase, daunomycin), and consolidation with high-dose cytarabine (24gm/m2 in 3 equal legs for children below 3-years, and 16gm/m2 in two equal legs, for 3 or more years age). Post-consolidation therapy followed the pattern of Interim Maintenance, two Delayed Intensification cycles, and 18 months of Maintenance. Central Nervous System (CNS)-directed therapy consisted of intrathecal methotrexate in all cycles, and those with CNS involvement received additional Cranial Radiation of 18Gy. In early-thymic-precursor (ETP-ALL) immunophenotype patients, dexamethasone replaced prednisolone in Induction. The protocol did not include High-Dose Methotrexate. FC-MRD was estimated by 10-color FC-MRD assay on Navios flow-cytometer (Beckman Coulter, Inc.) at Post-Induction(day-35), and Post-Consolidation(day-78) for those PI-MRD positive(+ve). FC-MRD was analyzed on Kaluza® software v-1.3. Any detectable value was taken as positive. Statistical analysis was performed using MedCalc Statistical Software®. Results: Of 368 eligible patients diagnosed at our centre in the study period, 81 did not undergo PI-MRD (14- Induction deaths, 13- treatment abandonment, 54- referral to other institute/ time-point missed/ did not consent/ other reasons). Another 18 abandoned treatment within 100 days of diagnosis and were also excluded. In the remaining 269, median age was 10-years (range:1-15), M:F-3.8:1. Median presenting WBC was 96.7 x 103/cmm (range:1.14-849), and thirteen patients had ETP. PI-MRD was positive in 125(46%) patients (median MRD -0.3%, range:0.0007-43.6%) of which 58(46.4%) developed medullary relapse, compared to 17 of 144(11.6%) for PI-MRD negative(-ve) patients, with Hazard Ratio (HR) for risk of medullary-relapse for PI-MRD+ve being 5.02(95% CI:3.16-7.96; p<0.0001). Median RFS was 20.5 months (95% CI:16.2-34.7) for PI-MRD+ve patients, while median was not-reached for PI-MRD-ve. PI-MRD+ve patients were at high risk for all events (medullary relapse, extramedullary relapse and death) with an incidence of 53.6% versus 27.8%; p<0.0001, and HR of 2.36 (95% CI:1.6-3.47; p<0.0001). Probability of EFS at 30 months was 68.9% for PI-MRD+ve and 41.1% for PI-MRD-ve patients(Fig-1), while there was no significant difference in 30-month OS, which were 78.7% and 77.9% respectively. Most relapsed/ refractory patients were unable to undergo intensive salvage regimens and/ or hematopoietic stem cell transplants due to socio-economic constraints. When their disease progressed, they were mostly sent home on palliative care on an oral metronomic chemotherapy protocol, on which they survived for varying periods of times. PC-MRD was available in 90 PI-MRD+ patients, and was positive in 28(31%), with median MRD level of 0.055% (range:0.0008-27.6%). PC-MRD+ve patients had significantly shorter RFS (median-14.3 months, 95% CI:7.1-49.7 months), with risk of relapse HR of 2.36 (95% CI:1.6-3.47; p<0.0001). Univariate and multivariate analysis using Cox-hazard model for age, hyperleukocytosis and ETP-immunophenotype showed that PI-MRD was the most significant and an independent high-risk factor for relapse with HR for multivariate analysis being 5.5(95% CI:2.85-11.45; p<0.0001). Conclusion: We conclude that 10-color FC-MRD done Post-Induction and Post-Consolidation detecting any residual disease reliably identifies those at highest risk of relapse and any other event. PI-MRD+ is an independent, and also the most important risk-factor for any event, and if PC-MRD is also positive, relapse occurs early. Figure 1 Disclosures No relevant conflicts of interest to declare.

Abstract:

Abstract Background There is an unmet need for blood-based biomarkers that help predict disease and its course at inception to allow tailoring of treatments, achieve early mucosal healing and improve clinical outcomes. In our study, we explore the clinical utility of miRNAs in Inflammatory bowel disease (IBD). Methods A 2-stage prospective multi-centre case–control study was performed. Small RNA sequencing was performed on a discovery cohort of immunomagnetically separated leucocytes (90 CD4+ and CD8+ T-lymphocytes and CD14+ monocytes) from 32 patients (9 CD, 14 UC, 8 healthy controls) to identify differentially expressed cell-specific miRNAs.Top miRNAs were then validated in whole blood in 294 treatment naïve newly diagnosed IBD and non-IBD patients (97 UC, 98 CD, 98 non-IBD) using RT-qPCR, recruited across 5 centres in UK and Europe. Phenotype and outcome data were collected and Cox proportional hazards were derived to assess the contribution of each miRNA to outcomes; defined as the need for 2 or more immunosuppressants and/or surgery after initial disease remission. RT-qPCR target miRNA relative quantification was calculated using 2−ΔΔCq method. Results Each leucocyte subset (30 CD4+ T cells, 28 CD8+ T cells and 32 CD14+ monocytes) was analysed between disease and controls, adjusting for age, gender and batch effects. A total of three miRNAs differentiated IBD from controls in CD4+ T cells including miR-1307-3p (FDR p = 0.01), miR-3615 (p = 0.02) and miR-4792 (p = 0.01); these signals being UC specific. In CD8 T cells, miR-200b-3p was the only differentially expressed miRNA and no CD14+ signals were seen.Three miRNAs were validated in whole blood in an independent multi-centre cohort of 294 patients using RT-qPCR. miR-1307-3p predicted IBD (1.55 fold change (fc),IQR: 1.00–1.87; p = 2.77 × 10–5),in particular UC (1.69 fc, IQR: 1.01–2.00; p = 1.56 × 10–6). Similarly, miR-3615 and miR-4792 were up-regulated in UC compared with controls (1.21fc, IQR:0.91–1.48; p = 8.26 × 10−4and 1.91 fc, IQR: 0.81–2.56; p = 9.21 × 10–3, respectively).There was no correlation with conventional inflammatory markers. Follow-up data were available on 195 IBD patients of which 80 patients required treatment escalation over a median time of 371 days (IQR: 140–711). miR-1307-3p was able to predict disease course in IBD (HR 1.98, IQR: 1.20–3.27; log-rank p = 1.80 × 10−3), in particular CD (HR 2.81; IQR: 1.11–3.53, p = 6.50 × 10–4). In UC, both miR-3615 (HR 3.34, CI: 1.43–7.78, p = 0.01) and miR-4792 (HR 3.96, CI: 1.65–9.52; p = 2.11 × 10–3) predicted treatment escalation. Conclusion We have identified unique CD4+ T-cell miRNAs that are differentially regulated in IBD. These blood-based miRNAs are able to predict treatment escalation at disease inception and have the potential for clinical translation.

Abstract:

Abstract. Meteorological conditions may drive relationships between aerosol and cloud-related properties. It is important to account for the meteorological contribution to observed cloud–aerosol relationships in order to improve understanding of aerosol–cloud–climate interactions. A new method of investigating the contribution of meteorological covariation to observed cloud–aerosol relationships is introduced. Other studies have investigated the contribution of local meteorology to cloud–aerosol relationships. In this paper, a complimentary large-scale view is presented. Extratropical cyclones have been previously shown to affect satellite-retrieved aerosol optical depth (τ), due to enhanced emission of sea salt and sea surface brightness artefacts in regions of higher wind speed. Extratropical cyclones have also been shown to affect cloud-related properties such as cloud fraction (fc) and cloud top temperature (Ttop). Therefore, it seems plausible to hypothesise that extratropical cyclones may drive relationships between cloud-related properties and τ. In this paper, this hypothesis is investigated for extratropical cyclones, henceforth referred to as storms, over the Atlantic Ocean. MODerate resolution Imaging Spectroradiometer (MODIS) retrieved τ, fc and Ttop data are analysed using a storm-centric coordinate system centred on extratropical cyclones which have been tracked using European Centre for Medium Range Weather Forecasts (ECMWF) reanalysis 850 hPa relative vorticity data. The tracked relative vorticity (ω) is used as a measure of storm strength, while position in the storm-centric domain is used to account for storm structure. Relationships between the cloud-related properties and τ are measured by calculating regression slopes and correlations. The fc–τ relationships are positive, while the Ttop–τ relationships are negative. By shuffling the pairing of the cloud and τ data at each location in the storm-centric domain and within narrow ω bins, the contribution of storm strength and storm structure to the observed relationships can be investigated. It is found that storm strength and storm structure can explain only a small component of the relationships observed in the MODIS data. The primary causes for observed cloud–aerosol relationships are likely to be other factors such as retrieval errors, local meteorology or aerosol–cloud interactions.

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Abstract Abstract 4406 We have found only one study aimed to find prognostic significance of abdominal lymph nodes in CLL (E. Montserrat et al, 2007). It was shown that Rai O CLL patients with enlarged abdominal lymph nodes had inferior survival. It merely means that CT scan could early reveal patients with enlarged lymph nodes. This cohort of patients is included in stage 0 only due to the fact of unavailability of CT scan at the times Rai and Binet staging were described (1975, 1977). The aim of the study was to evaluate prognostic significance of abdominal lymph nodes enlargement for the response to FC and FCR Patients and methods 71 untreated CLL patients were included according to the intent to treatment by fludarabine containing regimens (FC and FCR). Staging was performed according to Binet system. Stage B and C patients were included. Lymph nodes were revealed by CT and ultrasound before therapy (Lymph nodes more than 10mm in diameter were considered as abnormal and more than 100 mm in diameter were considered as bulky). CD38 was performed by CytoFlow (cut off 30%). Mutation analysis was done with PCR and sequencing (E.Nikitin, Hematological centre, Moscow), (cut off 98%). CR was defined according to NCI criteria. The patients were treated and followed-up by the single team of physicians, there were no losses of follow-us. SPSS - 17 statistical program was used for analysis. Results Overall response (OR) was 86% (61 pts), the rate of CR was 55% (39 pts), the rate of PR 31% (22 pts). In the whole group, FC: OR 81%, CR 46%, PR 35%. FCR: OR 91%, CR 67%, PR 24%), median of PFS was 26 mons (21 mons for FC and 35 for FCR, p=0.006). CD38 positivity, unmutated type and stage C had adverse prognostic significance in the whole group (p= 0,04; p=0,05; p=0,02), in FCR subgroups, mutation status and CD38 had marginal significance in FCR(p=0.9, p=0.75). Abdominal lymph nodes were enlarged in 41 pts (58%), 16 pts had bulky EAL(23%). PFS was lower in the group of patients with EAL in comparison to patients without EAL(18 and 48 mons, p 0.001). Difference in PFS has been also revealed in FC and FCR subgroups: 16 and 25 mons, p=0,003 for FC; 22 and 56 mons, p=0,01 for FCR (Fig.1) All fludarabine containing regimens resistant patients appeared to have EAL (10 pts). The duration of CR and PR were longer in patients without EAL(resp.p = 0.03 and 0.06, Fig. 2). The differences of PFS were also studied inside the groups defined by standard prognostic markers. CD38-, EAL+ patients had median PFS of 23mons, CD38-, EAL- patients-median not achieved (p= 0.01) CD 38+EAL+patients had median PFS of 12 mons, CD38+EAL- patients – 30 mons (p=0,04) Thus, CD38+ patients without EAL had even better PFS than CD38- patients with EAL. VH-mut+ EAL+ patients had median PFS of 18 mons, VH-mut+ EAL- patients – 58 mons (p=0,06) VH-mut- EAL+ patients had median PFS of 11 mons, VH-mut- EAL- patients – 18 mons (p=0,06) Thus, unmutated patients wit EAL had similar PFS with mutated patients without EAL. Stage B EAL+ patients had median PFS of 20 mons, Stage B EAL- patients – 58 mons (p=0,004) Stage C EAL+ patients had median PFS of 15 mons, Stage C EAL- patients – 21 mons (p=0,05) Thus, patients with stage B without EAL had PFS four times better, than patients with stage C, EAL+. Median PFS is similar in patients stage B EAL+ and stage C EAL-. The response equal to PR and more than PR after three cycles of chemotherapy was more frequent in patients without EAL (65% vs 18%, p < 0,001) Conclusion Enlarged abdominal lymph nodes(EAL) is an adverse prognostic marker for response both to FC and FCR. Differences in PFS according to EAL were also revealed inside standard prognostics subgroups (mutation status and CD38,stage). Even more, PFS of patients with standard adverse prognostic factors without EAL were similar to patients without standard adverse prognostic with EAL. CLL with EAL is a separate entity of CLL. Disclosures: No relevant conflicts of interest to declare.

Abstract:

AbstractThe Corrida de tores, as an important component of Spanish culture, has also been the subject of a dispute between the aficionados (supporters of the corrida) and the antitaurinos (opponents of the corrida) for centuries. Naturally, the spectacle has become an object of interest for researchers not only in the socio-cultural context, where it is becoming a spectacle full of artistry, accompanied by great emotions, or a tradition in some aspects resembling the Fiesta Nacional, but also becoming increasingly important on the political, moral and ethical level. The latter is related to the issue of animal protection and their humane treatment, while in the political dimension the links between the taurammatic tradition and the actions of political decision-makers are mainly analysed. Importantly, in the Catalan and Spanish public spaces, the corrida has become a national sporting role, with similar links to politics. In the light of the Catalan-Spanish antagonisms, this perspective is gaining particular importance, as evidenced, for example, by the flashback of football competition (Real Madrid FC vs. FC Barcelona) in the country under Francisco Franco’s regime, where sporting competition became an exemplary political game.The aim of the article is to analyze the dispute between politicians in Madrid and Catalanists and independents in the region in the context of the banning of the de toros corrida in Catalonia in 2010 and the reaction of the centre’s decision making centre to these actions. Moreover, the motives for this ban are sought, whether they are of an autotelic nature - in this case, the protection of animal rights -or whether they show the traits of instrumental use of tradition, de facto considered to be a “foreign”, because Spanish, part of the rhetoric and real policy pursued by Catalan nationalists and independents in the era of radicalisation of the independence movement in Catalonia.

Abstract:

The article presents the results of the analysis of the dynamics of the investment flows in fixed capital (FC) in the East of Russia and their economic efficiency for the period 2011–2018. Special attention is paid to the sectoral structure of FC investments in the regional economy, their importance for creating conditions for the accelerated socio-economic development of the Eastern border regions of Russia – the subjects of the Far Eastern Federal District and the Baikal Region. The purpose of this study is to assess the economic effects generated by the investments in the economy of the Eastern border regions of the Russian Federation. As a hypothesis, we consider the assumption that attracting investment to the region is a key factor of not only accelerated, but also sustainable development of the regions under consideration. The factors hindering the sustainable development of the economies of these regions are considered. It is shown that there are multidirectional trends in the socio-economic development of the considered regions. Analysis of investment flows and indicators of socio-economic development of the Eastern regions of the Russian Federation for the period 2011–2018 allows to confirm the conclusion that the existing institutional environment does not yet ensure sustainable economic development of the East of Russia. The integration processes here are hampered by excessively strong dependence on the federal centre and a focus on specific investors. Therefore, the Eastern Russian regions are forced to build their economic policy, focusing on creating attractive conditions for large investors. The stability of economic growth can be ensured only through stable growth of the region population and an improvement of the human capital quality. For the successful implementation of large-scale development plans for the East of Russia, it is necessary to stop the processes of depopulation of the territory and maintain optimal proportions between the economic and demographic reproduction

Abstract:

AbstractLetGbe a compactp-adic analytic group. We recall the well-understood finite radical{\Delta^{+}}and FC-centre Δ, and introduce ap-adic analogue of Roseblade’s subgroup{\mathrm{nio}(G)}, the unique largest orbitally sound open normal subgroup ofG. Further, whenGis nilpotent-by-finite, we introduce the finite-by-(nilpotentp-valuable) radical{\mathbf{FN}_{p}(G)}, an open characteristic subgroup ofGcontained in{\mathrm{nio}(G)}. By relating the already well-known theory of isolators with Lazard’s notion ofp-saturations, we introduce the isolated lower central (resp. isolated derived) series of a nilpotent (resp. soluble)p-valuable group, and use this to study the conjugation action of{\mathrm{nio}(G)}on{\mathbf{FN}_{p}(G)}. We emerge with a structure theorem forG,1\leq\Delta^{+}\leq\Delta\leq\mathbf{FN}_{p}(G)\leq\mathrm{nio}(G)\leq G,in which the various quotients of this series of groups are well understood. This sheds light on the ideal structure of the Iwasawa algebras (i.e. the completed group ringskG) of such groups, and will be used in future work to study the prime ideals of these rings.

Abstract:

Accurate identification of the hip joint centre (HJC) is crucial for the correct estimation of knee and hip joint loads and kinematics, which is particularly relevant in orthopaedic surgery and musculoskeletal modelling. Several methods have been described for calculation of the HJC in humans, however, no studies have used these methods in the horse despite a similar need for improved evaluation of hip joint biomechanics in rehabilitation and musculoskeletal modelling. This preliminary study uses the commonly used functional method (least-squares sphere fit) to determine the HJC in three equid cadavers. Bone pins with reflective markers attached were drilled into the tuber coxae (TC), tuber ischium (TI), tuber sacrale (TS), greater trochanter (GT), third trochanter (TT) and lateral femoral condyle (FC) of the uppermost limb of the cadavers positioned in lateral recumbency. Three repetitions of passive movements consisting of pro-and retraction, ab- and adduction and circumduction were performed. The HJC was calculated using a least-squares sphere fitting method and presented as a distance from the TC based on a percentage of the TC to TI vector magnitude. Mean (± standard deviation) of the HJC is located 52.4% (± 3.9) caudally, 0.2% (± 6.5) dorsally, and 19.8% (± 4.2) medially from the TC. This study is the first to quantify the HJC in horses ex vivo using a functional method. Further work (in vivo and imaging) is required to validate the findings of the present study.

Abstract:

Background and aims: Originator-adalimumab, an established treatment for patients with Crohn‘s disease (CD) showed no difference in efficacy or adverse events vs the adalimumab biosimilar SB5 (SB5-adalimumab) over 10 weeks of treatment. To understand the long-term efficacy of SB5-adalimumab in CD, patients who switched from originator-adalimumab to SB5-adalimumab were compared to a cohort who remained on originator-adalimumab over a follow up of 104 weeks. Methods: In this analysis, data on patients ≥18 years and diagnosed with CD treated at the IBD ISCARE centre were collected prospectively between July 2018 and January 2021. Clinical disease activity as measured by Harvey-Bradshaw index (HBI) at Week 52 was the primary outcome, while C-reactive protein (CRP), faecal calprotectin (FC), adalimumab trough levels in Weeks 10, 26, 52, 78, and 104, adverse events leading to therapy withdrawal, and persistence on treatment were secondary outcomes. To ensure comparable treatment cohorts, patients were propensity score matched (PSM) for age, gender, diagnosis, and disease activity. Results: A total of 54 patients were matched according to the given criteria in each group. At Week 52, the mean [SD] HBI score was 3.2 (2.5) in the originator-adalimumab group and 4.0 (3.6) in SB5-adalimumab patients (difference [95% CI] –0.78 [–2.8, 1.3]). Similarly, no clinically significant differences in CRP, FC, or trough levels were noted between originator-adalimumab and SB5-adalimumab cohorts through Week 52. The Kaplan-Meier estimates (95% CI) of patients remaining on treatment for the originator-adalimumab vs SB5-adalimumab cohorts were 0.870 (0.785–0.965) vs 0.648 (0.533–0.789) at Week 52. Conclusions: These long-term study results in CD patients after a non-medical switch from originator-adalimumab to SB5-adalimumab showed that the biosimilar SB5 had similar therapeutic effects as originator-adalimumab in terms of clinical disease activity, biological parameters, and pharmaco*kinetics profile at the primary endpoint of 52 weeks, as well as 104 weeks. Differences in persistence were not clinically driven. Persistence on treatment was lower in patients treated with biosimilar adalimumab SB-5.

Abstract:

Background:The biologic drug Rituximab (anti-CD20) is used therapeutically in SLE, however the clinical response to the therapy, which is expensive, is quite variable. Factors influencing the efficacy have been challenging to determine. The MRC funded MASTERPLANS consortium has investigated prognostic factors that determine the therapeutic response to biologic therapy in SLE. Genetics has not been studied on a large scale in this context. SLE is a complex clinical phenotype, it is likewise a complex genetic trait, although it has recently been shown that polygenic risk scores do have a relationship to the severity of the disease (1). In addition, genetic risk factors for SLE, coded at the IgG Fc gamma receptor locus, have the potential to influence antibody-dependent cell-mediated cytotoxicity.Objectives:To determine whether the genetics influences the clinical outcome of therapy with Rituximab. The study used both genome-wide data in the form of genetic risk scores as well as specific genetic data at a candidate locus, namely the IgG Fc gamma receptor locusMethods:Samples from the BILAG Biologics Register (BILAG BR) of individuals treated with Rituximab were subject to genome-wide genotyping with Illumina GSA V2 chip. Genetic risk scores (GRS) were calculated through a weighted risk sum. Genetic variation at the IgG Fc gamma receptor locus is not captured well on genotyping chips and hence common coding and copy number variation was studied using Multiplex Ligation-dependent Probe Amplification (MLPA) and sequencing.Results:BILAG-BR samples for SLE part of receiving Rituximab therapy were genotyped on GSA chip, 573 samples passed QC and were used in principal components analysis (PCA), among them, 310 samples both have RTX treatment information and GRS calculated. Examining the population using PCA in the informative samples revealed that the largest distinction, European versus African ancestry did not correlate with Rituximab response. When GRS was determined in the Responders versus the Non-responders there was a weak correlation with those with a higher risk score showing a tendency to be in the responder group (Fig. 1). We also examined variation at the IgG Fc gamma receptor locus, polymorphisms of which are associated with SLE and have been correlated with therapeutic outcome in lymphoma (2). In a subset of the BILAG-BR cohort, we show that carriage of the SLE risk allele atFCGR3A(158F) was enriched in the ‘responder at some point’ group compared to the non-responder group (P=0.03, Chi-square).Conclusion:We present preliminary data indicating that genetics at both the genome wide level and at theFCGRlocus show some influence on the outcome of therapy with Rituximab in SLE; more data are required in order to draw firm conclusions.References:[1]Reid S et al. High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus.Ann Rheum Dis.2019 Dec 11. [Epub ahead of print][2]Weng WK, Levy R. Two immunoglobulin G fragment C receptor polymorphisms independently predict response to rituximab in patients with follicular lymphoma. J Clin Oncol. 2003;21(21):3940–3947.Acknowledgments:King’s and GSTT Biomedical Research Centre and M01665X/1MRC Stratified Medicine grantDisclosure of Interests:Lu Liu: None declared, Ariella Amar: None declared, James Robinson: None declared, Ian N. Bruce Grant/research support from: Genzyme Sanofi, GSK, and UCB, Consultant of: Eli Lilly, AstraZeneca, UCB, Iltoo, and Merck Serono, Speakers bureau: UCB, David Morris: None declared, Tim Vyse: None declared

Abstract:

Abstract Background Anti-TNF agents, infliximab (IFX) and adalimumab (ADL) are first line treatment for moderate-to-severe Crohn’s disease (CD) and for preventing post-operative recurrence of CD (CD-POR) following right hemicolectomy (RH). However, a considerable proportion of patients develop allergic reactions and/or paradoxical inflammation to anti-TNFs necessitating switching to out of class biologic despite deep remission. We aimed to assess whether ustekinumab (UST), an IL12/IL23 inhibitor, can maintain deep remission in these patients. Methods This prospective, single centre study enrolled CD patients with B1 phenotype or on POR preventive therapy who were in prolonged deep remission when became intolerable of anti-TNFs. Deep remission was defined as clinical (HBI&lt;4), biomarker (normal CRP and faecal calprotectin [FC&lt;150μg/dl]), and endoscopic remission (SES-CD≤2 or Rutgeerts’ score [RS]≤1). Patients received UST (6mg/kg iv followed by 90mg sc q8 weeks) and were followed every 2 months with HBI score calculation and routine laboratory tests. Ileocolonoscopy was performed at 1y after UST initiation and the SES-CD or the RS were calculated. Absence of deep remission was defined as clinical (HBI&gt;5), or biomarker relapse or endoscopic recurrence (SES-CD&gt;2 or RS≥2, respectively). Results Twenty five patients (15 males), median age(range) 42(20-65)y were included. Seven patients had undergone RH, 6 had colitis and 12 had ileitis or ileocolitis; 13 patients had received ADL, 8 IFX and 4 both. Patients were in deep remission for 3.8 (2-10)y [median (range)]. Reasons for switching were severe psoriasis/proriasiform lesions (11), persistent arthralgias (10), infusion/injection reactions (2), anti-TNF-induced lupus erythematosus (2), sweet syndrome (1), and vasculitis (1). Two patients had more than one paradoxical inflammation. At baseline the median (range) CRP was 0.21mg/dl (0.10-0.40), FC 52μg/g (20-114). Trough levels for anti-TNFs in 15/25 patients were normal without antibodies. At 1-year post-switching endoscopic CD-POR was seen in 3/7 patients (RS≥2b) associated with biomarker relapse in 2 and clinical relapse in 1 patient. Of 18 patients with B1 phenotype deep remission was maintained in 15: two patients with infusion reactions to IFX relapsed and 1 patient developed endoscopic lesions in view of normal CRP but abnormal FC (SES-CD 6, 5 and 3, respectively). Paradoxical inflammation resolved in all 23 patients but de novo arthralgias developed in 2 patients. Thus, one year after switching to UST, 19/25 CD patients maintained deep remission. Conclusion UST seems to be a reliable therapeutic alternative for anti-TNF-dependent patients who have who cannot tolerate anti-TNFs.

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An ion exchange dialysis (IED) is used in the recovery of aluminium from residue. In this paper, the face-centred central composite design (FC-CCD) of the response surface methodology (RSM) and desirability approach is used for experimental design, modelling and process optimization of a counter flow IED system. The feed concentration, feed flowrate, sweep flowrate and sweep concentration were selected as the process variables, with the Al transport across a Nafion 117 membrane as the target response. A total of 30 experimental runs were conducted with six centre points. The response obtained was analysed by analysis of variance (ANOVA) and fitted to a second-order polynomial model using multiple regression analysis. The actual R2 and standard deviation of the model are 0.9548 and 0.2932, respectively. Depending on the time zone of reference (24 h or 32 h), the highest enrichment of >1.50 was achieved. The designed variables were numerically optimized by applying the desirability function to achieve the maximum Al transport. The optimised condition values were found to be a feed concentration of 1600 ppm, feed flowrate of 61.76%, sweep flowrate of 37.50% and sweep concentration of 0.75 N for the 80% target response at 32 h. Overall, the model can be used to effectively predict Al recovery using the designed system.