OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.

Background: Brain metastases are frequently seen in neurosurgical practice. Standardised criteria are created to better classify these common pathologies in research studies. This study’s goal was to evaluate RANO-BM criteria’s current thresholds in a cohort of patients with brain metastases managed by SRS. Methods: We performed a retrospective metastasis-level analysis of patients treated with SRS for brain metastases. The data collected included cohort demographics, metastases characteristics, outcomes, and the rate of true positives, false negatives, true negatives and false positives as defined by RANO-BM criteria at last follow-up before second SRS. Results: 251 metastases in 50 patients were included in the analysis. RANO-BM criteria using current thresholds yielded a sensitivity of 38%, a specificity of 95%, a positive predictive value of 71% and a negative predictive value of 84%. Modified RANO-BM criteria using absolute diameter differences of 2.5 mm yielded a sensitivity of 83%, a specificity of 87%, a positive predictive value of 67% and a negative predictive value of 94%. Pseudoprogression occurred significantly earlier than tumor progression, with a median time of onset of 6.9 months and 12.1 months respectively. Conclusions: Current RANO-BM criteria unreliably identifies clinically relevant tumor progression, but are useful in assessing diameter increases caused by tumor progression and pseudoprogression.

We report here three clinical cases as exemples of our rich and frequent collaboration between the department of psychiatry and the department of medecine, nephrology and hemodialysis. This work can serve as a basis for further reflection in order to improve mutual demands. We based our description on three patients chosen for their homogeneity in demand, rapidity of evaluation, the same clinician who evaluated the demand. Either case: a 42-year-old woman, who was admitted for alteration of general state, severe headaches and chronic addiction to alcohool, 71-year-old woman sufferring from recurrent unipolar depression who came for somatic exploration and severe weight loss or 55-year-old man who was transferred from cardio-pulmonary intensive care unit after a volontary ingestion of neuroleptic- were reevaluated by the psychiatrist and the special follow-up was indicated as the patient was discharded from internal medecine department. We were interested in studying how important to the patient this indication turned to be on time.

Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: FIREFISH (NCT02913482) is an ongoing, multicenter, open-label operationally seamless study of risdiplam in infants aged 1–7 months with Type 1 SMA and two SMN2 gene copies. Exploratory Part 1 (n=21) assesses the safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Confirmatory Part 2 (n=40) is assessing the safety and efficacy of risdiplam. Results: In a Part 1 interim analysis (data-cut 09/07/18), 93% (13/14) of babies had ≥4-point improvement in CHOP-INTEND total score from baseline at Day 245, with a median change of 16 points. The number of infants meeting HINE-2 motor milestones (baseline to Day 245) increased. To date (data-cut 09/07/18), no drug-related safety findings have led to patient withdrawal. No significant ophthalmological findings have been observed. Conclusions: In FIREFISH Part 1, risdiplam improved motor function in infants with Type 1 SMA.

Introduction: Insufficient analgesia affects around 50% of emergency department patients. The use of a protocol helps to reduce the risk of oligoanalgesia in this context. Our objective was to describe the feasibility and efficacy of a multimodal analgesia protocol (combining paracetamol, oxycodone, and inhaled low-dose methoxyflurane) initiated by triage nurse. Methods: We performed a prospective, observational study in the emergency department at Grenoble Alpes University Hospital (Grenoble, France) between October 2017 and April 2018. Non severe adult trauma patients with a numerical pain rating scale (NRS) score ≥4 and receiving MEOF were included. The primary efficacy criterion was the proportion of patients with an NRS score ≤3 at 15min post-administration. Pain intensity was measured for 60 min as well as during radiography. Data on adverse events and satisfaction were also recorded. Data are presented as median [interquartile (IQR)] and were compared using non parametric tests. Results: A total of 200 adult patients were included (age: 32 [IQR: 23–49] years; 126 men (63%)). Patients presented at triage with a pain score of 7 [IQR: 6-8]. Sixty-six patients (33%) reported an NRS score ≤3 at 15 min post-administration. The time required to achieve a decrease of at least 2 points in the NRS score was 10 [IQR 5–20] min. The pain intensity was 4 [IQR: 2–5] before radiography and 4 [IQR: 2–6] during radiography. Adverse events were frequent (n = 128, 64%), mainly dizziness. No serious adverse events were reported and 89% of minor adverse events resolved at one hour. Both patients and health care providers reported good levels of satisfaction. Conclusion: The administration of a nurse-driven multimodal analgesia protocol combining paracetamol, oxycodone, and low-dose methoxyflurane was feasible on triage. It rapidly produced long-lasting analgesia in adult trauma patients.

The acoustics of a straight annular lined duct containing a swirling mean flow is considered. The classical Ingard–Myers impedance boundary condition is shown not to be correct for swirling flow. By considering behaviour within the thin boundary layers at the duct walls, the correct impedance boundary condition for an infinitely thin boundary layer with swirl is derived, which reduces to the Ingard–Myers condition when the swirl is set to zero. The correct boundary condition contains a spring-like term due to centrifugal acceleration at the walls, and consequently has a different sign at the inner (hub) and outer (tip) walls. Examples are given for mean flows relevant to the interstage region of aeroengines. Surface waves in swirling flows are also considered, and are shown to obey a more complicated dispersion relation than for non-swirling flows. The stability of the surface waves is also investigated, and as in the non-swirling case, one unstable surface wave per wall is found.

This paper gives a modified Myers boundary condition in swirling inviscid flow, which differs from the standard Myers boundary condition by assuming a small but non-zero boundary layer thickness. The new boundary condition is derived and is shown to have the correct quadratic error behaviour with boundary layer thickness and also to agree with previous results when the swirl is set to zero. The boundary condition is initially derived for swirling flow with constant azimuthal velocity, but easily extends to radially varying swirling flow, with terms depending on the boundary layer model. The modified Myers boundary condition is then given in the time domain rather than in the frequency domain. The effect of the boundary layer profile is then considered, and shown to be small compared to the boundary layer thickness. The boundary condition is then used to analyse the eigenmodes and Green’s function in a realistic flow. Modelling the thickness of the boundary layer properly is shown to be essential in order to get accurate results.

We consider a specific accumulation event that occurred in January 2002 in western Dronning Maud Land, Antarctica. Snow samples were obtained a few days after accumulation. We combine meteorological analyses and isotopic modelling to describe the isotopic composition of moisture during transport. Backward trajectories were calculated, based on European Centre for Medium-Range Weather Forecasts operational archive data so that the history of the air parcels transporting water vapour to the accumulation site could be reconstructed. This trajectory study showed that the air masses were not (super)saturated along most of the transport path, which is in contrast with assumptions in Lagrangian fractionation models and probably true for most precipitation events in Antarctica. The modelled fractionation along the trajectories was too limited to explain the measured isotopic content of the snow. It is shown that the observed isotopic composition of precipitation resulted from fractionation of initially more depleted water. This lower initial isotopic composition of water vapour might result from atmospheric mixing with more depleted air along the trajectory or from earlier condensation cycles, not captured by the trajectories. This is in accordance with isotope fields resulting from general circulation models, indicating a gradient in isotopic composition from the Equator to Antarctica.

Documenting past changes in the East Antarctic surface mass balance is important to improve ice core chronologies and to constrain the ice-sheet contribution to global mean sea-level change. Here we reconstruct past changes in the ratio of surface mass balance (SMB ratio) between the EPICA Dome C (EDC) and Dome Fuji (DF) East Antarctica ice core sites, based on a precise volcanic synchronization of the two ice cores and on corrections for the vertical thinning of layers. During the past 216 000 a, this SMB ratio, denoted SMBEDC/SMBDF, varied between 0.7 and 1.1, being small during cold periods and large during warm periods. Our results therefore reveal larger amplitudes of changes in SMB at EDC compared with DF, consistent with previous results showing larger amplitudes of changes in water stable isotopes and estimated surface temperature at EDC compared with DF. Within the last glacial inception (Marine Isotope Stages, MIS-5c and MIS-5d), the SMB ratio deviates by up to 0.2 from what is expected based on differences in water stable isotope records. Moreover, the SMB ratio is constant throughout the late parts of the current and last interglacial periods, despite contrasting isotopic trends.

Presented in this paper are the preliminary results from a blade-vortex interaction (BVI) test series conducted in the University of Glasgow's 1·61m x 2·13m closed-return, low-speed windtunnel, in which a single vortex interaction with a rigid, loaded rotor blade was studied. This work is an extension of that by Horner and Galbraith, which describes the flow phenomena present during single vortex interaction with an unloaded blade. The paper presents blade surface pressure data recorded by 72 pressure transducers located in the outer regions of the blade during these interactions. Integrated Cn and Cm1/4 data are also presented to provide a detailed history of a BVI event. In addition, a method of isolating the bound circulation and vortex induced effects is presented, from which it is concluded that for a BVI event the vortex-induced effects are (to a first approximation) independent of rotor pitch setting.

Thin GaAs photovoltaic heterostructures are grown by MOCVD with various p-GaAs base thicknesses. The total n/p absorbing thickness is varied systematically. Output voltages up to ∼1.155V were obtained for individual n/p junctions at an average illumination intensity of ∼8W/cm2. Novel phototransducer devices are then achieved with a vertical epitaxial heterostructure architecture, monolithically integrating 5 or more such thin n/p junctions. Around the design wavelength, the stacked heterostructure design is yielding an optimal external quantum efficiency approaching unity divided by the number of junctions. The modeled and measured conversion efficiencies are exceeding 60%. The photocarrier extraction properties are simulated for different junction thicknesses using a model based on a 3-dimensional (3D) radially-symmetric TCAD implementation of the heterostructures. The study clearly demonstrates that for such thin n/p junctions the photocarrier extraction can still be efficient due to the operation at reduced current densities and higher voltages in heterostructures enhancing electrical power extraction. With the supplementary add-on of a window layer with a reduced sheet resistance for the stacked structure, we demonstrate the possible efficient operation of phototransducers for optical inputs exceeding 150 W/cm2, even for the case of devices designed without gridlines.

The purpose of this paper is to give a rapid overview of the recent developments in the field of X-ray diffraction on polycrystalline materials from the viewpoint of the instruments. After a brief historical report, the main types of laboratory diffractometers are presented. At the end of the twentieth century the apparition of position sensitive detectors and artificial crystal monochromators have induced the conception of new diffractometer often based on old geometrical arrangements. Those modern diffractometers are described with respect to the more conventional ones. Among the experimental parameters which can characterize a given diffractometer, the instrumental resolution function and the acquisition time of the pattern are of primary importance. The different apparatus are compared with respect to those two parameters.

The origin of solar energetic particle (SEP) events is an issue for the understanding of particle acceleration and transport in astrophysics, as well as for space weather. We outline some recent studies addressing from the observational viewpoint the relationship between interacting and escaping particles, conditions for particle escape from the Sun, and the interplanetary magnetic field configurations where the particles propagate.

Neuronal abnormalities have been described in the intestine of helminth-infected rats. However, the physiological ramifications of these changes have not been determined. Here, we examined epithelial ion secretion, indicated by increases in short-circuit current (Isc), evoked by electrical transmural stimulation (TS) of enteric nerves in Ussing-chambered jejunal tissues from Nippostrongylus brasiliensis-infected rats. Rats were examined at 10 and 35 days post-infection (p.i.); non-infected rats served as controls. TS resulted in significantly reduced ion secretion in jejunum from 10 day p.i. rats compared to controls or jejunum from 35 day p.i. rats. The TS response in tissue from infected rats had, unlike controls, no cholinergic component. Tissues from both non-infected and infected rats were equally responsive to the muscarinic agonist bethanechol, suggesting that the cholinergic defect was neuronal and not an inability of the epithelium to respond to cholinergic stimulation. However, increases in Isc evoked by exogenous substance P (SP) in tissue from rats 10 day p.i. were reduced in magnitude to approximately 25% of control values. Concomitant with these physiological changes, tissue from infected rats contained increased amounts of substance P immunoreactivity and intestinal sections displayed increased numbers of substance P-immunoreactive nerve fibre profiles at both 10 and 35 days p.i. Thus, following N. brasiliensis infection there is a shift in the enteric nervous system away from cholinergic to non-cholinergic regulation, associated with increased amounts of the pro-inflammatory neuropeptide, substance P. We speculate that changes in neuronal structure and function are intimately involved in the co-ordinated multicellular response to intestinal parasitic infection and subsequent gut recovery.

Airborne 137Cs level in France is not decreasing significantly anymore (mean yearly value around 0,25 µ Bq.m-3 contrarily to what was noticed in the past decades. This observation points out the role of processes that delay the atmospheric cleaning and participate to the persistence of radionuclide in the air at ground-level after a deposit, in the frame of medium as well as long-dated post-accidental contexts. The current background level also yields to consider 137Cs in the atmosphere as a tracer of atmospheric processes like resuspension and re-emission from biomass burnings. This allows us to explain 2/3 of the peaks observed over the last six years. The remaining 1/3 is mainly noticed in winter when spreading of pollutants in the atmosphere is often weak due to temperature gradient inversion. On average, continental air masses are responsible for increases by a factor of 3 while oceanic air masses are characterised by levels 3 times lower, compared to the mean value. Feeding of 137Cs in air at ground-level is the result of both local resuspension that signs 137Cs activity levels in soils to which is added a remote contribution from time to time (resuspension of Saharan dust or re-emission from fires occurring in eastern territories with high 137Cs deposition level). Finally, 137Cs activity levels in air masses crossing over France can be described on average by a longitudinal gradient.