A Neural Circuit Arbitrates between Persistence and Withdrawal in Hungry Drosophila

In pursuit of food, hungry animals mobilize significant energy resources and overcome exhaustion and fear. How need and motivation control the decision to continue or change behavior is not understood. Using a single fly treadmill, we show that hungry flies persistently track a food odor and increase their effort over repeated trials in the absence of reward suggesting that need dominates negative experience. We further show that odor tracking is regulated by two mushroom body output neurons (MBONs) connecting the MB to the lateral horn. These MBONs, together with dopaminergic neurons and Dop1R2 signaling, control behavioral persistence. Conversely, an octopaminergic neuron, VPM4, which directly innervates one of the MBONs, acts as a brake on odor tracking by connecting feeding and olfaction. Together, our data suggest a function for the MB in internal state-dependent expression of behavior that can be suppressed by external inputs conveying a competing behavioral drive

Pathogenesis and management of Buerger's disease

Buerger’s disease or thromboangiitis obliterans causes pain, ulceration, or gangrene in the lower or upper extremity. It is associated with chronic cigarette smoking and is believed to be an immune mediated vasculitis. The pathogenesis is still unknown but recent postulate of its association with odontal bacteria has generated much renewed interest. Despite its recognition more than a century ago, little progress has been made in its treatment. Until the pathogenesis is elucidated, abstinence from cigarette is the only effective therapy

Differential CD4+ T-Cell Cytokine and Cytotoxic Responses Between Reactivation and Latent Phases of Herpes Zoster Infection

BACKGROUND: CD4+ T cells are a critical component of effective immune responses to varicella zoster virus (VZV), but their functional properties during the reactivation acute vs latent phase of infection remain poorly defined. METHODS: Here we assessed the functional and transcriptomic properties of peripheral blood CD4+ T cells in persons with acute herpes zoster (HZ) compared to those with a prior history of HZ infection using multicolor flow cytometry and RNA sequencing. RESULTS: We found significant differences between the polyfunctionality of VZV-specific total memory, effector memory, and central memory CD4+ T cells in acute vs prior HZ. VZV-specific CD4+ memory T-cell responses in acute HZ reactivation had higher frequencies of IFN-γ and IL-2 producing cells compared to those with prior HZ. In addition, cytotoxic markers were higher in VZV-specific CD4+ T cells than non-VZV-specific cells. Transcriptomic analysis of CONCLUSIONS: In summary, VZV-specific CD4+ T cells from acute HZ individuals had unique functional and transcriptomic features, and VZV-specific CD4+ T cells as a group had a higher expression of cytotoxic molecules including Perforin, Granzyme-B, and CD107a

Computational investigation of diesel nozzle internal flow during the complete injection event

[EN] Currently, diesel engines are calibrated using more and more complex multiple injection strategies. Under these conditions, the characteristics of the flow exiting the fuel injector are strongly affected by the transient interaction between the needle, the sac volume and the orifices, which are not yet clear. In the current paper, a methodology combining a 1D injector model and 3D-CFD simulations is proposed. First, the characteristics of the nozzle flow have been experimentally assessed in transient conditions by means of injection rate and momentum flux measurements. Later, the 3D-CFD modeling approach has been validated at steady-state fixed lift conditions. Finally, a previously developed 1D injector model has been used to extract the needle lift profiles and transient pressure boundary conditions used for the full-transient 3D-CFD simulations, using adaptive mesh refinement (AMR) strategies to be able to simulate the complete injection rate starting from 1 mu m lift.This work was partly sponsored by "Ministerio de Economia y Competitividad'', of the Spanish Government, in the frame of the Project "Estudio de la interaccion chorro-pared en condiciones realistas de motor'', Reference TRA2015-67679-c2-1-R. The authors would like also to thank the computer resources, technical expertise and assistance provided by Universidad de Valencia in the use of the supercomputer "Tirant''. Mr. Jaramillo's Thesis is funded by "Conselleria d'Educacio, Cultura i Esports'' of Generalitat Valenciana in the frame of the program "Programa VALI + D para investigadores en formacion, Reference ACIF/2015/040.Salvador, FJ.; De La Morena, J.; Bracho Leon, G.; Jaramillo-Císcar, D. (2018). Computational investigation of diesel nozzle internal flow during the complete injection event. Journal of the Brazilian Society of Mechanical Sciences and Engineering. 40(3):153-167. https://doi.org/10.1007/s40430-018-1074-zS153167403Hall CAS, Lambert JG, Balogh SB (2014) EROI of different fuels and the implications for society. Energy Policy 64:141–152. https://doi.org/10.1016/j.enpol.2013.05.049Lujan JM, Tormos B, Salvador FJ, Gargar K (2009) Comparative analysis of a DI diesel engine fuelled with biodiesel blends during the European MVEG-A cycle: preliminary study (I). Biomass Bioenergy 33:941–947. https://doi.org/10.1016/j.biombioe.2009.02.004Pickett LM, Siebers DL (2004) Soot in diesel fuel jets: effects of ambient temperature, ambient density, and injection pressure. Combust Flame 138:114–135. https://doi.org/10.1016/j.combustflame.2004.04.006Dec JE (1997) A Conceptual Model of DI Diesel Combustion Based on Laser-Sheet Imaging. SAE Tech. Pap. 970873Wang X, Huang Z, Zhang W et al (2011) Effects of ultra-high injection pressure and micro-hole nozzle on flame structure and soot formation of impinging diesel spray. Appl Energy 88:1620–1628. https://doi.org/10.1016/j.apenergy.2010.11.035Sayin C, Gumus M, Canakci M (2013) Influence of injector hole number on the performance and emissions of a di diesel engine fueled with biodiesel-diesel fuel blends. Appl Therm Eng 61:121–128. https://doi.org/10.1016/j.applthermaleng.2013.07.038Mohan B, Yang W, Chou SK (2013) Fuel injection strategies for performance improvement and emissions reduction in compression ignition engines—A review. Renew Sustain Energy Rev 28:664–676. https://doi.org/10.1016/j.rser.2013.08.051Payri R, Salvador FJ, Gimeno J, De la Morena J (2011) Influence of injector technology on injection and combustion development, Part 1: hydraulic characterization. Appl Energy 88:1068–1074. https://doi.org/10.1016/j.apenergy.2010.10.012Park SW, Kim JW, Lee CS (2006) Effect of injector type on fuel-air mixture formation of high-speed diesel sprays. Proc Inst Mech Eng D 220:647–659. https://doi.org/10.1243/09544070D20304Moon S, Komada K, Sato K et al (2015) Ultrafast X-ray study of multi-hole GDI injector sprays: effects of nozzle hole length and number on initial spray formation. Exp Therm Fluid Sci 68:68–81. https://doi.org/10.1016/j.expthermflusci.2015.03.027Powell CF, Kastengren AL, Liu Z, Fezzaa K (2010) The effects of diesel injector needle motion on spray structure. J Eng Gas Turbines Power 133:12802. https://doi.org/10.1115/1.4001073Huang W, Moon S, Ohsawa K (2016) Near-nozzle dynamics of diesel spray under varied needle lifts and its prediction using analytical model. Fuel 180:292–300. https://doi.org/10.1016/j.fuel.2016.04.042Sun Z-Y, Li G-X, Chen C et al (2015) Numerical investigation on effects of nozzle’s geometric parameters on the flow and the cavitation characteristics within injector’s nozzle for a high-pressure common-rail DI diesel engine. Energy Convers Manag 89:843–861. https://doi.org/10.1016/j.enconman.2014.10.047Devassy BM, Habchi C, Daniel E (2015) Atomization modelling of liquid jets using a two-surface density approach. At Sprays 25:47–80Moon S, Gao Y, Park S et al (2015) Effect of the number and position of nozzle holes on in- and near-nozzle dynamic characteristics of diesel injection. Fuel 150:112–122. https://doi.org/10.1016/j.fuel.2015.01.097Payri R, Salvador FJ, Carreres M, De la Morena J (2016) Fuel temperature influence on the performance of a last generation common-rail diesel ballistic injector. Part II: 1D model development, validation and analysis. Energy Convers Manag 114:376–391. https://doi.org/10.1016/j.enconman.2016.02.043Plamondon E, Seers P (2014) Development of a simplified dynamic model for a piezoelectric injector using multiple injection strategies with biodiesel/diesel-fuel blends. Appl Energy 131:411–424. https://doi.org/10.1016/j.apenergy.2014.06.039Postrioti L, Malaguti S, Bosi M et al (2014) Experimental and numerical characterization of a direct solenoid actuation injector for diesel engine applications. Fuel 118:316–328. https://doi.org/10.1016/j.fuel.2013.11.001Desantes JM, Salvador FJ, Lopez JJ, De la Morena J (2011) Study of mass and momentum transfer in diesel sprays based on X-ray mass distribution measurements and on a theoretical derivation. Exp Fluids 50:233–246. https://doi.org/10.1007/s00348-010-0919-8De la Morena J, Neroorkar K, Plazas AH et al (2013) Numerical analysis of the influence of diesel nozzle design on internal flow characteristics for 2-valve diesel engine application. At Sprays 23:97–118. https://doi.org/10.1615/AtomizSpr.2013006361Duke DJ, Schmidt DP, Neroorkar K et al (2013) High-resolution large eddy simulations of cavitating gasoline-ethanol blends. Int J Engine Res 14:578–589. https://doi.org/10.1177/1468087413501824Mitroglou N, McLorn M, Gavaises M et al (2014) Instantaneous and ensemble average cavitation structures in diesel micro-channel flow orifices. Fuel 116:736–742. https://doi.org/10.1016/j.fuel.2013.08.060Wang X, Li K, Su W (2012) Experimental and numerical investigations on internal flow characteristics of diesel nozzle under real fuel injection conditions. Exp Therm Fluid Sci 42:204–211. https://doi.org/10.1016/j.expthermflusci.2012.04.022Sou A, Pratama RH (2016) Effects of asymmetric inflow on cavitation in fuel injector and discharged liquid jet. At Sprays 26:939–959. https://doi.org/10.1615/AtomizSpr.2015013501Xue Q, Battistoni M, Powell CF et al (2015) An Eulerian CFD model and X-ray radiography for coupled nozzle flow and spray in internal combustion engines. Int J Multiph Flow 70:77–88. https://doi.org/10.1016/j.ijmultiphaseflow.2014.11.012Castilla R, Gamez-Montero PJ, Ertrk N et al (2010) Numerical simulation of turbulent flow in the suction chamber of a gearpump using deforming mesh and mesh replacement. Int J Mech Sci 52:1334–1342. https://doi.org/10.1016/j.ijmecsci.2010.06.009Parlak Z, Engin T (2012) Time-dependent CFD and quasi-static analysis of magnetorheological fluid dampers with experimental validation. Int J Mech Sci 64:22–31. https://doi.org/10.1016/j.ijmecsci.2012.08.006Chiatti G, Chiavola O, Palmieri F (2009) Spray modeling for diesel engine performance analysis. SAE Tech Pap 2009-01-0835. https://doi.org/10.4271/2009-01-0835Marcer R, Audiffren C, Viel A, et al (2010) Coupling 1D system AMESim and 3D CFD EOLE models for diesel injection simulation Renault. In: ILASS—Eur. 2010, 23rd Annu. Conf. Liq. At. Spray Syst., pp 1–10Desantes JM, Salvador FJ, Carreres M, Martínez-López J (2014) Large-eddy simulation analysis of the influence of the needle lift on the cavitation in diesel injector nozzles. Proc Inst Mech Eng D 229:407–423. https://doi.org/10.1177/0954407014542627Battistoni M, Xue Q, Som S (2016) Large-eddy simulation (LES) of spray transients: start and end of injection phenomena. Oil Gas Sci Technol 71:24. https://doi.org/10.2516/ogst/2015024CONVERGE is a trade mark of convergent science. https://convergecfd.comMacian V, Bermúdez V, Payri R, Gimeno J (2003) New technique for determination of internal geometry of a diesel nozzle with the use of silicone methodology. Exp Tech 27:39–43. https://doi.org/10.1111/j.1747-1567.2003.tb00107.xDabiri S, Sirignano WA, Joseph DD (2007) Cavitation in an orifice flow. Phys Fluids 19:72112. https://doi.org/10.1063/1.2750655Mohan B, Yang W, Chou SK (2014) Cavitation in injector nozzle holes—a parametric study. Eng Appl Comput Fluid Mech 8:70–81Salvador FJ, Hoyas S, Novella R, Martinez-Lopez J (2011) Numerical simulation and extended validation of two-phase compressible flow in diesel injector nozzles. Proc Inst Mech Eng D 225:545–563. https://doi.org/10.1177/09544070JAUTO1569Som S, Longman DE, Ramirez AI, Aggarwal S (2012) Influence of nozzle orifice geometry and fuel properties on flow and cavitation characteristics of a diesel injector. In: Fuel Inject. Automot. Eng., pp 112–126Desantes JM, Salvador FJ, Carreres M, Jaramillo D (2015) Experimental characterization of the thermodynamic properties of diesel fuels over a wide range of pressures and temperatures. SAE Int J Fuels Lubr 8:2015-01-0951. https://doi.org/10.4271/2015-01-0951Bosch W (1966) The fuel rate indicator: a new measuring instrument for display of the characteristics of individual injection. SAE Pap. 660749Payri R, Salvador FJ, Gimeno J, Bracho G (2008) A new methodology for correcting the signal cumulative phenomenon on injection rate measurements. Exp Tech 32:46–49. https://doi.org/10.1111/j.1747-1567.2007.00188.xPayri F, Payri R, Salvador FJ, Martínez-López J (2011) A contribution to the understanding of cavitation effects in diesel injector nozzles through a combined experimental and computational investigation. Comput Fluids 58:88–101. https://doi.org/10.1016/j.compfluid.2012.01.005Lichtarowicz AK, Duggins RK, Markland E (1965) Discharge coefficients for incompressible non-cavitating flow through long orifices. J Mech Eng Sci 7:210–219. https://doi.org/10.1243/JMES_JOUR_1965_007_029_02Lopez JJ, Salvador FJ, De la Garza OA, Arrègle J (2012) Characterization of the pressure losses in a common rail diesel injector. Proc Inst Mech Eng D 226:1697–1706. https://doi.org/10.1177/0954407012447020Salvador FJ, Carreres M, Jaramillo D, Martínez-López J (2015) Comparison of microsac and VCO diesel injector nozzles in terms of internal nozzle flow characteristics. Energy Convers Manag 103:284–299. https://doi.org/10.1016/j.enconman.2015.05.062LMS (2010) Imagine.Lab AMESim v.10. User’s manualPayri R, Salvador FJ, Martí-Aldaraví P, Martínez-López J (2012) Using one-dimensional modeling to analyze the influence of the use of biodiesels on the dynamic behavior of solenoid-operated injectors in common rail systems: detailed injection system model. Energy Convers Manag 54:90–99. https://doi.org/10.1016/j.enconman.2011.10.00

Assessment of perinatal outcome after sustained tocolysis in early labour (APOSTEL-II trial)

Contains fulltext : 80242.pdf (publisher's version ) (Open Access)BACKGROUND: Preterm labour is the main cause of perinatal morbidity and mortality in the Western world. At present, there is evidence that tocolysis for 48 hours is useful in women with threatened preterm labour at least before 32 weeks. This allows transfer of the patient to a perinatal centre, and maximizes the effect of corticosteroids for improved neonatal survival. It is questionable whether treatment with tocolytics should be maintained after 48 hours. METHODS/DESIGN: The APOSTEL II trial is a multicentre placebo-controlled study. Pregnant women admitted for threatened preterm labour who have been treated with 48 hours corticosteroids and tocolysis will be eligible to participate in the trial between 26+0 and 32+2 weeks gestational age. They will be randomly allocated to nifedipine (intervention) or placebo (control) for twelve days or until delivery, whatever comes first.Primary outcome is a composite of perinatal death, and severe neonatal morbidity up to evaluation at 6 months after birth. Secondary outcomes are gestational age at delivery, number of days in neonatal intensive care and total days of the first 6 months out of hospital. In addition a cost-effectiveness analysis will be performed. Analysis will be by intention to treat. The power calculation is based on an expected 11% difference in adverse neonatal outcome. This implies that 406 women have to be randomised (two sided test, beta 0.2 at alpha 0.05). DISCUSSION: This trial will provide evidence as to whether maintenance tocolysis reduces severe perinatal morbidity and mortality in women with threatened preterm labour before 32 weeks. TRIAL REGISTRATION: Clinical trial registration: http://www.trialregister.nl, NTR 1336, date of registration: June 3rd 2008

Nutrition and lung cancer: a case control study in Iran

Background: Despite many prospective and retrospective studies about the association of dietary habit and lung cancer, the topic still remains controversial. So, this study aims to investigate the association of lung cancer with dietary factors. Method: In this study 242 lung cancer patients and their 484 matched controls on age, sex, and place of residence were enrolled between October 2002 to 2005. Trained physicians interviewed all participants with standardized questionnaires. The middle and upper third consumer groups were compared to the lower third according to the distribution in controls unless the linear trend was significant across exposure groups. Result: Conditional logistic regression was used to evaluate the association with lung cancer. In a multivariate analysis fruit (Ptrend < 0.0001), vegetable (P = 0.001) and sunflower oil (P = 0.006) remained as protective factors and rice (P = 0.008), bread (Ptrend = 0.04), liver (P = 0.004), butter (Ptrend = 0.04), white cheese (Ptrend < 0.0001), beef (Ptrend = 0.005), vegetable ghee (P < 0.0001) and, animal ghee (P = 0.015) remained as risk factors of lung cancer. Generally, we found positive trend between consumption of beef (P = 0.002), bread (P < 0.0001), and dairy products (P < 0.0001) with lung cancer. In contrast, only fruits were inversely related to lung cancer (P < 0.0001). Conclusion: It seems that vegetables, fruits, and sunflower oil could be protective factors and bread, rice, beef, liver, dairy products, vegetable ghee, and animal ghee found to be possible risk factors for the development of lung cancer in Iran

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

The relationship of systemic markers of renal function and vascular function with retinal blood vessel responses

Purpose: To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease.Methods: Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index.Results: Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p<0.05). Arterial reaction time was linked to serum creatinine (p=0.036) and eGFR (p=0.039), venous reaction time was linked to creatinine clearance (p=0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p<0.001 and p=0.003 respectively) and the dilatation amplitude (p=0.038 and p=0.048 respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p=0.004) and dilatation amplitude (p=0.017), vWf was linked to the maximum constriction response (p=0.016), and creatinine clearance to the baseline diameter fluctuation (p=0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p=0.022). Conclusions: Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses