Car Groups Research Articles

Improvement of the method of time rationing for assembling car groups on one track

Purpose. To improve the method for standardizing the duration of the shunting operation of assembling cars on one track. This can be achieved as a result of solving the following research problems: development of a method for searching the optimal order of assembling cars on one track; distribution parameters estimation of the random value of the duration of shunting operation of assembling cars on one track based on calculation experiments. Methodology. During the research, the methods of theory of railway operation, dynamic programming and mathematical statistics were used. Findings. Research on the assembling process of car group to one track established the distribution parameters of the random variable of time spent for shunting. In the course of the research, the problem of choosing the optimal order of shunting operations during car assembling was formalized and solved as a problem of dynamic programming. The time spent for shunting work was chosen as the optimality criterion. The paper considers the possibility of approximating the data of calculation experiments by analytical dependencies. It was found out that the use of linear polynomials with interaction allows obtaining dependencies describing time standards with a relative accuracy of ±5 %. Originality. The method is improved for developing the time standards for shunting work, which, unlike the existing one, is based on the performance of a series of calculation experiments, each of which solves the optimization problem of finding such an order of assembling cars that ensures minimum time consumption for shunting. Practical value. The methods developed in the work and the dependencies obtained allow improving the quality of decisions made when developing technology and designing railway stations and sidings of industrial enterprises.

Impact of physician-staffed ground emergency medical services-administered pre-hospital trauma care on in-hospital survival outcomes in Japan

PurposeIn Japan, the vehicle used in pre-hospital trauma care systems with physician-staffed ground emergency medical services (GEMS) is referred to as a “doctor car”. Doctor cars are highly mobile physician-staffed GEMS that can provide complex pre-hospital trauma management using various treatment strategies. The number of doctor car operations for patients with severe trauma has increased. Considering facility factors, the association between doctor cars and patient outcomes remains unclear. Therefore, this study aimed to examine the relationship between doctor cars for patients with severe trauma and survival outcomes in Japan.MethodsA nationwide retrospective cohort study was conducted to compare the impact of the doctor car group with the non-physician-staffed GEMS group on in-hospital survival in adult patients with severe trauma. The data were analyzed using multivariable logistic regression models with generalized estimating equations.ResultsThis study included 372,365 patients registered in the Japan Trauma Data Bank between April 2009 and March 2019. Of the 49,144 eligible patients, 2361 and 46,783 were classified into the doctor car and non-physician staffed GEMS groups, respectively. The adjusted odds ratio (OR) for survival was significantly higher in the doctor car group than in the non-physician staffed GEMS group (adjusted OR = 1.228 [95% confidence interval 1.065–1.415]).ConclusionUsing nationwide data, this novel study suggests that doctor cars improve the in-hospital survival rate of patients with severe trauma in Japan. Therefore, doctor cars could be an option for trauma strategies.

Optimization of track distribution of industrial railway stations between car designations

Purpose. To improve the method for distributing the tracks of industrial railway stations for the accumulation of car groups between separate assignments. The optimization problem is to find such a distribution of classification work between the industrial marshalling yard and freight stations, as well as such a distribution of marshalling yard tracks between individual destinations, which ensures the minimum time expenditures on shunting work. Methodology. The studies were carried out using the methods of the theory of railway operation, simulation modeling and dynamic programming. Findings. The optimization problem of distribution of sorting work between the marshalling yard and freight stations of an industrial enterprise, as well as searching for such a distribution of marshalling yard tracks between individual destinations, which ensures the minimum time expenditures for shunting work, has been solved. Originality. The paper proposes a method for formalizing and solving the problem of distributing the tracks of industrial railway stations for the accumulation of car groups between individual destinations as a dynamic programming problem. Unlike the existing methods, where the number of tracks is considered as a constraint, in the proposed method, the number of tracks is an objective function argument of minimizing the duration of shunting operations, which improves the quality of the solutions obtained. Practical value. The method proposed in the paper, due to the rational distribution of the existing track arrangement of railway stations, makes it possible to reduce the time expenditures on the making- and breaking-up the trains and shunting transfers and, due to this, increase the carrying capacity of the stations, as well as reduce the cost of production of enterprises.

The Synergistic Effects of the Combination of L-Carnitine and Lycopene on the Lycopene Bioavailability and Duodenal Health of Roosters.

The objective of this study was to investigate the impact of Lycopene and L-Carnitine, individually or in combination, on various physiological and molecular factors related to intestinal health and absorption ability in Roosters, such as intestinal morphology, serum biochemical parameters, genes involved in Lycopene uptake, nutritional transport genes, and tight junction genes. The findings of the study revealed that the combination of L-Carnitine and Lycopene supplementation had been found to increase the serum concentration levels of TP and ALB. Interestingly, the relative mRNA expression of genes responsible for Lycopene uptakes, such as SR-BI and BCO2, was higher in the LC group compared to other groups. Additionally, the expression of specific nutritional transport genes in the duodenum was significantly affected by both CAR and LC supplementation groups. The tight junction gene OCLN showed a significant increase in expression in the combination group compared to using either Lycopene or L-Carnitine alone. This study concludes that using Lycopene and L-carnitine in combination in poultry feed can potentially improve intestinal morphology and serum biochemical parameters, increase Lycopene bioavailability, improve nutrients uptake, and enhance the integrity of duodenal tight junctions in Roosters.

The clinical impact of the ratio of C-reactive protein to albumin (CAR) in patients with acute- and lymphoma-type adult T-cell leukemia-lymphoma (ATL).

Recently, the ratio of C-reactive protein to albumin (CAR) is used as an inflammatory marker that has been demonstrated to be a simple and reliable prognostic factor in solid tumors and hematological malignancy. However, no studies of the CAR have been performed in patients with adult T-cell leukemia-lymphoma (ATL). We retrospectively analyzed the clinical features and outcomes in 68 newly diagnosed acute- and lymphoma-type ATL [(acute-(n=42) or lymphoma-type (n=26)] patients in Miyazaki Prefecture from 2013 to 2017. Furthermore, we investigated correlations between pretreatment CAR levels and clinical features. The median age was 67 years (range, 44 - 87). Patients were initially treated by either palliative therapy (n=14) or chemotherapy [n=54; CHOP therapy (n=37)/ VCAP-AMP-VECP therapy (n=17)], and showed median survival durations of 0.5 months and 7.4 months, respectively. The factors affecting OS by multivariate analysis were age, BUN, and CAR. Importantly, we revealed that the high CAR group (optimal cut-off point; 0.553) was a significant indicator of worse OS by multivariate analysis (p< 0.001, HR; 5.46). The median survival of patients with a CAR< 0.553 was 8.37 months, while patients with a CAR>0.553 had a median survival of 3.94 months. The different clinical features between high CAR and low CAR groups were hypoproteinemia and the implementation of chemotherapy. Furthermore, in the chemotherapy group, but not the palliative therapy group, CAR was a significant prognostic marker. Our study indicated that CAR may be a new simple and significant independent prognostic marker in acute- and lymphoma-type ATL patients.

1267. Efficacy and Safety of Switching to DTG/3TC in Virologically Suppressed PLWH by Age, Including Those Aged ≥65 Years: Pooled Results from the TANGO and SALSA Studies

Abstract Background The proportion of older adults living with HIV is growing, increasing the focus of managing age-related comorbidities and polypharmacy while maintaining virologic suppression. DTG/3TC is an international guidelines–recommended 2-drug regimen demonstrating high and durable efficacy, high barrier to resistance, and good safety and tolerability. We present pooled TANGO and SALSA efficacy and safety results analyzed by age (&amp;lt; 50, ≥ 50 to &amp;lt; 65, and ≥ 65 years). Methods Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily DTG/3TC fixed-dose combination or continuing current antiretroviral regimen (CAR; TANGO: TAF-based; SALSA: NNRTI-/bPI-/INSTI-based) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and &amp;lt; 50 c/mL (Snapshot, ITT-E) and safety were analyzed by age. Results Of 1234 participants (DTG/3TC, n=615; CAR, n=619), 71% were aged &amp;lt; 50 years, 26% aged 50 to &amp;lt; 65 years, and 3% aged ≥ 65 years. At Week 48, in participants aged 50 to &amp;lt; 65 years, 1 (&amp;lt; 1%) and 3 (2%) participants in the DTG/3TC and CAR groups, respectively, had HIV-1 RNA ≥ 50 c/mL, comparable to results in the overall population (Table 1). No participants aged ≥65 years had HIV-1 RNA ≥ 50 c/mL. Proportions with HIV-1 RNA &amp;lt; 50 c/mL were high regardless of age group. Adjusted mean change from baseline in CD4+ cell count and CD4+/CD8+ ratio was also consistent with overall results regardless of age (&amp;lt; 50 vs ≥ 50 years). No participants in the DTG/3TC group had confirmed virologic withdrawal (CVW); 1 participant in the CAR group had CVW (aged &amp;lt; 50 years; no resistance detected). Proportions of participants with baseline non-ART medication use and comorbidities increased with age in both treatment groups (Table 2). Across all age groups, proportions of any AEs were similar between the DTG/3TC and CAR groups, with few AEs leading to withdrawal and higher proportions of drug-related AEs with DTG/3TC vs CAR; similar results were observed in the overall population. Conclusion Among PLWH, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile across all age groups, including those aged ≥65 years. As non-ART medication use and comorbidities increased with age, a well-tolerated 2-drug regimen may help older PLWH avoid drug interactions. Disclosures Manyu Prakash, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Richard Grove, MSc, GlaxoSmithKline: Employee|GlaxoSmithKline: Stocks/Bonds Brian R. Wynne, M.D., ViiV Healthcare: I am an employee|ViiV Healthcare: Stocks/Bonds Choy Man, BSc, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Jean A. van Wyk, MBChB, MFPM, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Clifford B. Jones, BSc MSc MB ChB, GSK: Stocks/Bonds|viiv healthcare: Employee Chinyere Okoli, MSc, DIP, ViiV Healthcare: I am an employee of ViiV healthcare|ViiV Healthcare: Stocks/Bonds Emilio Letang, MD, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Mounir Ait-Khaled, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Andrew Clark, MD, ViiV Healthcare: Employee|ViiV Healthcare: Stocks/Bonds.

391 Young Scholar Award Talk: Supplementation of Oligosaccharide-Based Polymer Enhanced Growth and Disease Resistance of Weaned Pigs by Modulating Intestinal Integrity and Systemic Immunity

Abstract Oligosaccharides have been reported to possess ETEC receptor activity for bacterial adhesions; thus, additional supplementation may efficiently prevent enterotoxin-induced secretory diarrhea. Moreover, grafted polymers that combine multiple substances have been proposed for their potential synergistic effects on preventing human and animal diseases. Therefore, the objective of this experiment was to investigate dietary supplementation of oligosaccharide-based polymer on growth performance, diarrhea severity, intestinal health, and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli (ETEC) when compared with in-feed antibiotics. Forty-eight pigs (7.23 ± 1.11 kg BW) were individually housed in disease containment rooms and randomly allotted to one of four treatments with 12 replicate pigs per treatment. The four dietary treatments were a nursery basal diet (CON), and 3 additional diets supplemented with 50 mg/kg antibiotics (Carbadox; CAR), 10 or 20 mg/kg of oligosaccharide-based polymer (OBP). The experiment lasted 18 d [7 d before and 11 d after the first inoculation (d 0)]. All pigs were orally inoculated with 3mL of F18 ETEC for 3 consecutive days from d 0 post-inoculation (PI). Growth performance and diarrhea severity were measured throughout the experiment. Blood, lymph nodes, spleen, and intestinal mucosa samples were collected during the peak infection period (d 2 and d 5 PI) and recovery period (d 11 PI). Pigs in CAR or OBP treatment groups had greater (P&amp;lt;0.05) body weight on d 5 or d 11 PI than pigs in the CON group, respectively. Supplementation of CAR or OBP enhanced (P&amp;lt;0.05) feed efficiency from d 0 to 5 PI and reduced (P&amp;lt;0.05) frequency of diarrhea throughout the experiment, compared with pigs in the CON group. Pigs in CAR or OBP groups had reduced (P&amp;lt;0.05) neutrophil counts and serum haptoglobin concentration compared to pigs in the CON group on d 2 and 5 PI. Pigs in OBP reduced (P&amp;lt;0.05) total coliforms in mesenteric lymph nodes on d 5 and 11 PI, whereas pigs in CAR or OBP groups had reduced (P&amp;lt;0.05) total coliforms in the spleen on d 11 PI compared with pigs in the CON group. On d 5 PI, pigs in the OBP group had greater (P&amp;lt;0.05) gene expression of ZO1 in jejunal mucosa, but less (P&amp;lt;0.05) mRNA expression of IL1B, IL6, and TNF in ileal mucosa, in comparison with pigs in the CON group. On d 11 PI, supplementation of CAR or OBP up-regulated (P&amp;lt;0.05) gene expression of CLDN1 in jejunal mucosa, but OBP reduced (P&amp;lt;0.05) IL6 gene expression in ileal mucosa compared to pigs in the CON group. In conclusion, supplementation of oligosaccharide-based polymer improved growth performance, alleviated diarrhea severity, and enhanced gut health in weaned pigs infected with ETEC F18 in a manner similar to in-feed antibiotics.

Comparative Prevalence of Acute Kidney Injury in Chinese Patients Receiving Vancomycin with Concurrent β-Lactam Antibiotics: A Retrospective Cohort Study

PurposeThe combination of vancomycin and piperacillin/tazobactam (VAN + PTZ) provides a broad spectrum of activity against multiple pathogens. However, a major issue in previous research concerned significant nephrotoxicity associated with this drug combination, and most studies have been conducted in American and European countries, with no similar data available from China. Therefore, this study evaluated the nephrotoxic effects of VAN + PTZ in a large-scale Chinese cohort to determine the prevalence of acute kidney injury (AKI) in this population by comparing PTZ and vancomycin monotherapies and the combined use of vancomycin and β-lactam antibiotics. MethodsThis retrospective cohort study identified adult patients who received vancomycin either as monotherapy or in combination with PTZ or carbapenem (VAN + CAR) for at least 48 hours at Jiangsu Province Hospital from January 1, 2017, to December 31, 2018. Patients were also evaluated for the development of AKI, defined according to the Kidney Disease Improving Global Outcome criteria. Duration of vancomycin exposure, steady-state trough vancomycin concentrations, and other risk factors for AKI were assessed. A Bayesian network meta-analysis was conducted to validate our results and comparatively evaluate the nephrotoxicity of β-lactam antibiotics in combination with vancomycin. FindingsIn all, 752 patients were included in the present study. The prevalence of AKI was higher in the VAN + PTZ group than in the VAN and VAN + CAR groups (15.2% vs 4.0% and 6.0%, respectively). After adjustment for confounding factors, VAN + PTZ was still related to AKI (odds ratio [OR] = 4.37; 95% CI, 1.65–11.59; P = 0.003). The network meta-analysis indicated that VAN + PTZ was associated with a significantly higher risk for AKI than was VAN (OR = 3.23; 95% CI, 2.50–4.35), PTZ (OR = 2.86; 95% CI, 1.92–4.12), VAN + cefepime (FEP) (OR = 2.37; 95% CI, 1.80–3.19), or VAN + CAR (OR = 2.28; 95% CI, 1.64–3.21). However, there was no significant difference with respect to AKI prevalence among the VAN, PTZ, VAN + FEP, and VAN + CAR groups. ImplicationsThe prevalence of AKI was higher with VAN + PTZ therapy than with VAN or PTZ monotherapy or with the concurrent use of VAN and FEP or CAR in our study. Clinicians should adequately assess renal function and consider this differential risk for nephrotoxicity when choosing empiric antibiotics in hospitalized patients to minimize the rates of AKI.

The use of dipeptide supplementation as a means of mitigating the negative effects of dietary soybean meal on Zebrafish Danio rerio

Soybean meal (SBM) inclusion in aquaculture diets has been found to negatively affect growth and induce intestinal inflammation in fish. The objective of this study was to determine the effect of health-promoting dipeptide supplementation into SBM-based feeds on growth performance, intestinal health, and muscle free amino acid composition, an indicator of dietary amino acid availability, in a zebrafish model. There were five treatment groups in this study. The first group ((+) Control) received a fishmeal-based diet. The second group ((−) Control) received SBM-based diet. The last three groups (Ala-Glu, Car, and Ans) were fed SBM-based diets, supplemented with alanyl-glutamine, carnosine, and anserine respectively. The Ala-Glu and Car groups experienced a significantly higher weight gain than the (−) Control group, weighing 35.38% and 33.96% more, respectively at the conclusion of the study. There were no significant differences in gene expression among the groups, but Ala-Glu had the highest expression of both nutrient absorption genes measured, PepT1 and fabp2. Ala-Glu had significantly longer intestinal villi, and a significantly higher villus length-to-width ratio than the (−) Control group. The Car group had a significantly higher post-prandial tissue concentration of lysine, compared to the (−) Control group. The increase in villus surface area and expression of nutrient absorption genes represent an improvement in intestinal absorptive capacity in the Ala-Glu group. The results from this study provide support for the use of alanyl-glutamine and carnosine supplementation as a means of improving growth performance of zebrafish fed with a high level SBM-based diet.

Improvement of the method for standardizing the duration of rail cars shunting

Purpose. To improve the method for calculating the time standard for shunting cars from track to track in order to take into account the local operating conditions of railway stations and railway sidings. Methodology. During the research, the methods of theory of railway operation were used. The problem of calculating the time standard for shunting operation was solved as the problem of searching the optimal division of train set into the car groups to achieve minimal time consumption for shunting operation. Findings. In the course of the study, the methods for calculating the time standards for initial and final operations, as well as movements performed when shunting cars from track to track were improved. It was proved that the minimum time spent on shunting cars from track to track was achieved when the train set was divided into the minimum possible number of parts and the cars were shunted in the longest possible groups and one remaining group. It was also established that with sufficient accuracy for engineering problems the duration of shunting train set from track to track can be represented by the piecewise linear function of the car number in it. Originality. The work originality consists in improving the method for calculating the time standard for shunting cars from track to track, that, unlike the existing one, takes into account the length limitations of the car groups being shunted from track to track, as well as the actual composition of operations performed in the process of shunting. Practical value. The use of the developed method allows setting time standards for shunting cars from track to track, taking into account the local operating conditions of railway stations and sidings of industrial enterprises. The method also makes it possible to simplify solving problems of searching the optimal order of performing more complex shunting operations, such as sorting cars into several tracks, collecting cars on one track, train formation, and others.

МЕТОДИКА РАСЧЕТА ДОПОЛНИТЕЛЬНЫХ ЗАТРАТ ВРЕМЕНИ НА ФОРМИРОВАНИЕ «БАРЬЕРНЫХ ГРУПП» ВАГОНОВ

The paper proposes a method for calculation of additional time consumption on making-up of «barrier car groups» used as protecting facilities on classification tracks. The method allows selecting an optimal way of making-up of «barrier groups», assessing the expediency of their application as a protecting facility and comparing this technology with alternative means of preventing the overrun of rolling stock beyond the limits of the effective length of classification tracks. As a result, the author has studied interdependencies of classification work parameters and time consumption on making-up of «barrier car groups».

The cardioprotective effect persisting during recovery from cold acclimation is mediated by the β2-adrenoceptor pathway and Akt activation.

The infarct size-limiting effect elicited by cold acclimation (CA) is accompanied by increased mitochondrial resistance and unaltered β1-adrenergic receptor (AR) signaling persisting for 2 wk at room temperature. As the mechanism of CA-elicited cardioprotection is not fully understood, we examined the role of the salvage β2-AR/Gi/Akt pathway. Male Wistar rats were exposed to CA (8°C, 5 wk), whereas the recovery group (CAR) was kept at 24°C for additional 2 wk. We show that the total number of myocardial β-ARs in the left ventricular myocardium did not change after CA but decreased after CAR. We confirmed the infarct size-limiting effect in both CA and CAR groups. Acute administration of β2-AR inhibitor ICI-118551 abolished the protective effect in the CAR group but had no effect in the control and CA groups. The inhibitory Giα1/2 and Giα3 proteins increased in the membrane fraction of the CAR group, and the phospho-Akt (Ser473)-to-Akt ratio also increased. Expression, phosphorylation, and mitochondrial location of the Akt target glycogen synthase kinase (GSK-3β) were affected neither by CA nor by CAR. However, GSK-3β translocated from the Z-disk to the H-zone after CA, and acquired its original location after CAR. Our data indicate that the cardioprotection observed after CAR is mediated by the β2-AR/Gi pathway and Akt activation. Further studies are needed to unravel downstream targets of the central regulators of the CA process and the downstream targets of the Akt protein after CAR.NEW & NOTEWORTHY Cardioprotective effect of cold acclimation and that persisting for 2 wk after recovery engage in different mechanisms. The β2-adrenoceptor/Gi pathway and Akt are involved only in the mechanism of infarct size-limiting effect occurring during the recovery phase. GSK-3β translocated from the Z-line to the H-zone of sarcomeres by cold acclimation returns back to the original position after the recovery phase. The results provide new insights potentially useful for the development of cardiac therapies.

Optimizing storage location assignment in an automotive Ro-Ro terminal

Automotive roll-on/roll-off (Ro-Ro) transportation is an efficient and competitive method for the large-scale transshipment of commercial cars. However, the low-efficiency operations and insufficient storage resources of automotive Ro-Ro terminals have constrained the development of Ro-Ro transportation. This paper investigates the storage location assignment problem (SLAP) for the arrival of cars at the yard, and it aims to improve the ship-loading efficiency and contribute to efficient storage at Ro-Ro terminals. Two deadlock situations resulting from blocked routes are analyzed in detail. Based on the Ro-Ro ship stowage plan, a car group concept is proposed to reflect the loading sequence of cars into a Ro-Ro ship. The dispersion degree is defined to describe the centralized layout of every car group in the yard. A linear 0-1 integer programming model is formulated to minimize the total dispersion degrees of all car groups. Furthermore, an indicator called the attraction degree is presented to quantify the preferred degree of each location for storing different groups of cars. A hierarchical two-stage exchange strategy (HTSES) is designed to obtain the car layout with the minimum total dispersion degree. To reduce the scale of the solved problem, a rolling-horizon heuristic approach based on closed-loop (positive and negative) feedback is proposed. Positive feedback based on the guidance mechanism describes the guidance provided by the existing car layout to arriving cars, while negative feedback based on the reformulation mechanism represents the influence of arriving cars on the car layout. A series of numerical experiments show that the proposed method can effectively produce a satisfactory car assignment plan for the management of automotive Ro-Ro terminals.

Determination Reference of Concentration (RfC) Xylen Exposure Based on Xylen NOAEL in White Rats and Workers’ Body Weight and Height in Surabaya Car Painting Area, Indonesia

This study aims to calculate the value of RfC from xylen exposure around the car painting area of �Surabaya, Indonesia. This is an observational cross-sectional study with quantitative data analysis methods conducted manually. The population in this study was groups of car painting workers and groups of car repairer on Jalan Pengenal Kota Surabaya. The sampling technique was proportionate stratified random sampling to take 51 people. The measurement of xylen concentration around the car painting area was 635.98 mg/m3 (146.47 ppm). This value is above the threshold value according to Minister of Manpower and Transmigration Regulation Number 13 of 2011 and Minister of Manpower Regulation Number. 5 of 2018 is 434 mg/m3 (100 ppm). RfC of car painting workers with NOAEL 50 mg/kg was 7.76 mg/kg. © 2020, Indian Journal of Forensic Medicine and Toxicology. All rights reserved.

S898 CD19+ RELAPSE POST CD19 CHIMERIC ANTIGEN RECEPTOR (CAR) T CELLS IN CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) IS DETERMINED BY T CELL FITNESS

Background:Although exciting clinical data have been presented with the use of the two autologous CD19 CAR T cells approved for the treatment of ALL and refractory lymphomas, challenges remain and their use in CLL remains experimental. CD19 positive and negative relapses have been described for which different mechanisms of resistance have been proposed. CD19+ relapses could be related to the host immune microenvironment or due to inadequate T cell fitness due to exhaustion. Therefore, there is still a need for further pre‐clinical modelling using immunocompetent mice to explore CAR plus immunotherapy combinations to enhance efficacy. CLL is an ideal disease model to explore this as it is associated with a tumour supportive microenvironment and T cells exhibit multiple functional defects and features of exhaustion, features closely recapitulated in Em‐TCL1 (TCL1) mice, and induced in healthy mice by adoptive transfer (AT) of murine CLL splenocytes.Aims:To demonstrate the effect of CLL T cell dysfunction on CAR T cell efficacy and improve function using aPDL1 blocking antibodies.Methods:Immunocompetent C57BL/6 mice (WT) received AT of pooled 35 x106 syngeneic splenic TCL1 CLL cells. Syngeneic donor CAR T cells were generated from T cells from WT or WT mice given AT CLL with CLL load &gt;80% (AT CAR). CD3+ were magnetic bead enriched then activated with CD3/CD28 Dynabeads (Thermofisher) and r‐IL2 (Roche), transduced with retroviral supernatant from MSGV‐1D3–28Z‐1.3mut (CD19‐CD28) and cultured and expanded for 4 days before injection. Two groups received intraperitoneal (IP) aPDL1 10 mg/kg from D‐1 every 72 hours (with and without AT CAR T cells) and all groups (except aPDL1 alone) were given 100 mg/kg IP cyclophosphamide on D‐1. On D0 the CAR groups received 1.5–2x106 CAR T cells with aPDL1 continuing until W12. Mice were bled every two weeks starting D+7 from CAR T cells to assess CLL load, CAR/T cell subsets and groups were culled together when they got sick or peripheral blood (PB) CLL&gt;70%.Results:Compared to WT CAR T cells, AT CAR T cells proliferate less in culture, skew towards CD8 cells, exhibit significantly lower transduction efficiencies in CD8 cells and have higher expression of PD1+ in both CD4 and CD8 cells. All mice treated with CAR T cells cleared their CLL and normal B cells at D+7, and those mice treated with WT CAR T cells all remained in remission until W18, whereas 50–60% of mice treated with AT CAR T cells slowly relapsed from D+21. Spleen weights in WT CAR treated mice were equivalent to age matched controls whilst AT CAR treated mice had variable size by W18. The addition of aPDL1 to AT CAR T cells did not alter their performance from AT CAR T cells alone in any parameter examined. CAR T cell expansion in all groups was greatest at D+7 and the majority of CAR+ cells were CD8+ and PD1+. PD1+ expression was significantly higher in AT compared to WT CAR T cells at D+7.Summary/Conclusion:CD19+ relapse post CAR T cells is determined by T cell fitness as WT CAR T cells can prevent relapse and can normalise PD1+ expression and spleen size. CAR T cells derived from CLL T cells are less able to prevent CD19+ relapse and this is not improved using concurrent aPDL1, which also seems to have limited activity in treatment alone of AT TCL1 CLL. Ongoing studies using CAR plus immunotherapy and BTK inhibitor combinations are addressing which steps are necessary to optimize CAR T cell fitness.image

Effects of oral administration of various essential oils on blood metabolites, intestine development, microbial enumeration and meat quality in broilers

A total of eighty 21-day-olds (1.1±0.01kg) ROSS 308 broilers were randomly allocated into 4 groups, with 20 replicates per group and 1 chicken per replicate per cage. Three experimental groups (CAR, THY, ORE group) were given oral administration of 200ìL essential oils (carvacrol, thyme and oregano) at 18:00h every day. The results showed no significant differences on blood metabolites among each group (P&gt;0.05). The villus height of the small intestines in the CAR group increased significantly (P less than 0.05) from 1360.10 to 1552.54ìm as compared to the control group, the goblet cell counts in the THY and ORE groups significantly increased by 20.91% (P less than 0.05) and 31.82% (P less than 0.05), respectively, compared to the control group. The E.coli and Salmonella in ORE group significantly decreased by 11.16% (P less than 0.05) and 9.54% (P less than 0.05), respectively, compared to the control group. The Redness (a*) values of the muscles of the CAR and ORE groups were observed to increase significantly (P less than 0.05) from 3.58 to 7.95 and 6.86, respectively, compared to the control group. In conclusion, oral administration of the essential oils carvacrol, thyme, and oregano promoted intestinal development, improved the intestinal environment and the meat quality of broilers.

DNA Adduct Assessment During Antihormonal Treatment of Perianal Gland Tumors With Tamoxifen in Male Dogs.

Determination of DNA adduct count was performed in mononuclear cells during antihormonal treatment of perianal gland tumors. Eight- to fifteen-year-old dogs with carcinoma (CAR Group; N=5), epithelioma (EPI Group; N=16) or adenoma (ADE Group; N=24) were used. The control group suffered from perineal hernia or rectal diverticulum (CTR Group; N=25). Blood was collected at baseline, and at one and six months after the beginning of the anti-hormonal treatment with tamoxifen (1 mg/kg of body weight). DNA adduct count was determined using autoradiography. At baseline, DNA adduct count reached the highest value in the CTR Group, and the lowest in the EPI Group (p<0.05). Six-month-long therapy with tamoxifen resulted in a significant increase in the DNA adduct count by 78.7%, 221.5% and 198.3% in the ADE, EPI and CAR groups, respectively (p<0.05). Increased DNA adduct formation after long-term administration of tamoxifen shows its genotoxicity.

Transportation mode and timing of spinal cord decompression and stabilization in patients with traumatic spinal cord injury in Iran.

Cross-sectional retrospective study. To describe the transportation mode to hospital and timing of spinal cord decompression and stabilization (D&S), length of hospital stay, frequency of pressure injuries, and sepsis during hospitalization. Brain and Spinal Injury Research Center, Tehran, Iran. Eight hundred and thirty patients with traumatic spinal cord injury (TSCI) were enrolled. Mode of transportation and length of time to reach the first hospital, length of hospital stay (LOS), and the time span between hospital arrival and decompression and stabilization (D&S) were recorded. Fifty-nine percent of the enrolled individuals were transported to the first hospital by ambulance, while 41% were transferred by vehicles without medical equipment and personnel. Median length of time to reach the first hospital was 1 h for both ambulance and non-equipped car groups, with no statistically significant difference (p = 0.1). Median LOS, frequencies of pressure injuries, and sepsis based on the injury levels were not significantly different between two transportation modalities. One hundred and seventy-seven individuals had early surgery, and 254 had late surgery. Median LOS was 13 days in the early surgery group and 20 days in the late surgery group (p = 0.002). Frequencies of pressure injuries and sepsis were not significantly different between the late and early surgery groups for various injury levels. About 59% of our patients had been transported to a hospital by non-medical personnel. Those with late surgery had significantly longer LOS. Improving TSCI patients' transportation method and early surgical interventions, if possible, may be considered.

Natural variability in exposure to fine particles and their trace elements during typical workdays in an urban area

Studies on the natural human exposures to fine particulate matter (PM2.5) and their elements composition are practically non-existent in South America. In order to understand the natural exposure of the typical Brazilian population to PM2.5 and their trace element composition, we measured PM2.5 concentrations and collected mass on filters for nine continuous hours during a typical workday of volunteers. In addition, bus routes were performed at peak and non-peak periods, mimicking the routine activity of the population. Mean concentrations of PM2.5 in the bus and car groups were similar while the fraction of BCe was higher for the bus group. For all routes, mean PM2.5 concentrations were higher during peak than non-peak hours, with an average of 43.5 ± 33.1 μg m−3 and 14.3 ± 10.2 μg m−3, respectively. The trace elements S, K and Na originated mainly from vehicle emissions; Na was associated with the presence of biofuel in diesel. Toxic elements (Pb, Cr, Cu, Ni, Zn, Mn) were found at low levels as evident by the total hazard index that ranged from 2.15 × 10−03 to 1.38 for volunteers. For all routes, the hazard index ranged from 2.25 × 10−03 to 5.03. Average PM2.5 respiratory deposition dose was estimated to be 0.60 μg/kg-hour for peak hours. Potential health damages to people during their movements and at workplaces close to the traffic were identified. Improvements in the design of the building to reduce the entrance of air pollutants as well as the use of filters in the buses could help to limit population exposure.

An improved dynamic model of friction draft gear with a transitional characteristic accounting for housing deformation

ABSTRACTA white-box friction draft gear model has been developed. All components of the draft gear are considered. The distinctive feature of the model, as compared to its predecessor, is the transitional characteristic, which accounts for the effect of elastic deformations of the draft gear housing on the position of the friction wedge system components under loading. The adjustment of the model parameters for improved agreement with experimental data is discussed. The new model can be used in the simulation of shunting impacts for single cars and car groups represented by detailed finite-element models. An example of the simulation is presented and compared with experimental data obtained using a shunting hump test stand.