Comparative dose-responses of recombinant human IL-2 and IL-7 on STAT5 phosphorylation in CD4+FOXP3- cells versus regulatory T cells: a whole blood perspective.

Interleukin(IL)-2 and IL-7 are cytokines with important functions related to CD4(+) lymphocyte proliferation, differentiation and survival. Depending on doses, they theoretically activate regulatory (Treg) and/or effector T cells (Teff) and thus may be indicated with different therapeutic objectives. In this study we assessed ex vivo the differential dose-responses of CD4(+) T cell subsets (Treg versus CD4(+)FOXP3(-) cells) to recombinant human (rh) IL-2 and rhIL-7. Fresh whole blood from healthy donors was stimulated with increasing doses of cytokines. By using a novel flow cytometry procedure of intracellular signaling pathway staining (e.g., detection of STAT5 phosphorylation; a pivotal marker of cytokine-induced activation; in combination with intracellular FOXP3 staining), we were able to specifically measure Treg and CD4(+)FOXP3(-) cell responses in the same tube. Half maximal effective concentrations (EC50) were calculated. We observed a dose-response effect on Treg and CD4(+)FOXP3(-) cells for both cytokines. Interestingly, low doses of hIL-2 preferentially activated Treg (EC50 Treg = 0.15 pg/ml versus CD4(+)FOXP3(-) cells = 750 pg/ml - p < 0.0001) whereas low doses of rhIL-7 preferentially induced CD4(+)FOXP3(-) cell activation (EC50 Treg = 25 pg/ml and CD4(+)FOXP3(-) cells = 2.5 pg/ml - p < 0.0001). To our knowledge, this work is the first to show differential dose-response effects on CD4(+)FOXP3(-) cells versus Treg of rhIL-7 and rhIL-2 in one ex vivo whole blood single tube assay including two intracellular stainings (i.e., pSTAT5 and FOXP3). Beyond the confirmation of the dose-dependent differential effects of IL-2 versus IL-7 on CD4(+)FOXP3(-) cells/Treg, our results illustrate the value of this approach for monitoring drugs' activities by flow cytometry in daily clinical practice.

Broadband cloaking and mirages with flying carpets.

This paper extends the proposal of Li and Pendry [Phys. Rev. Lett. 101, 203901-4 (2008)] to invisibility carpets for infinite conducting planes and cylinders (or rigid planes and cylinders in the context of acoustic waves propagating in a compressible fluid). Carpets under consideration here do not touch the ground: they levitate in mid-air (or float in mid-water), which leads to approximate cloaking for an object hidden underneath, or touch either sides of a square cylinder on, or over, the ground. The tentlike carpets attached to the sides of a square cylinder illustrate how the notion of a carpet on a wall naturally generalizes to sides of other small compact objects. We then extend the concept of flying carpets to circular cylinders and show that one can hide any type of defects under such circular carpets, and yet they still scatter waves just like a smaller cylinder on its own. Interestingly, all these carpets are described by non-singular parameters. To exemplify this important aspect, we propose a multi-layered carpet consisting of isotropic homogeneous dielectrics rings (or fluids with constant bulk modulus and varying density) which works over a finite range of wavelengths.

Hidden progress: broadband plasmonic invisibility.

One of the key challenges in current research into electromagnetic cloaking is to achieve invisibility at optical frequencies and over an extended bandwidth. There has been significant progress towards this using the idea of cloaking by sweeping under the carpet of Li and Pendry. Here, we show that we can harness surface plasmon polaritons at a metal surface structured with a dielectric material to obtain a unique control of their propagation. We exploit this control to demonstrate both theoretically and experimentally cloaking over an unprecedented bandwidth (650-900 nm). Our non-resonant plasmonic metamaterial is designed using transformational optics extended to plasmonics and allows a curved reflector to mimic a flat mirror. Our theoretical predictions are validated by experiments mapping the surface light intensity at a wavelength of 800 nm.

Analyzing Age-Related Macular Degeneration Progression in Patients with Geographic Atrophy Using Joint Autoencoders for Unsupervised Change Detection.

Age-Related Macular Degeneration (ARMD) is a progressive eye disease that slowly causes patients to go blind. For several years now, it has been an important research field to try to understand how the disease progresses and find effective medical treatments. Researchers have been mostly interested in studying the evolution of the lesions using different techniques ranging from manual annotation to mathematical models of the disease. However, artificial intelligence for ARMD image analysis has become one of the main research focuses to study the progression of the disease, as accurate manual annotation of its evolution has proved difficult using traditional methods even for experienced practicians. In this paper, we propose a deep learning architecture that can detect changes in the eye fundus images and assess the progression of the disease. Our method is based on joint autoencoders and is fully unsupervised. Our algorithm has been applied to pairs of images from different eye fundus images time series of 24 ARMD patients. Our method has been shown to be quite effective when compared with other methods from the literature, including non-neural network based algorithms that still are the current standard to follow the disease progression and change detection methods from other fields.

Revolution analysis of three-dimensional arbitrary cloaks.

We extend the design of radially symmetric three-dimensional invisibility cloaks through transformation optics to cloaks with a surface of revolution. We derive the expression of the transformation matrix and show that one of its eigenvalues vanishes on the inner boundary of the cloaks, while the other two remain strictly positive and bounded. The validity of our approach is confirmed by finite edge-elements computations for a non-convex cloak of varying thickness.

Effectiveness of Decompressive Hemicraniectomy to Treat a Life-Threatening Cerebral Fat Embolism.

BACKGROUND AND IMPORTANCE: Cerebral fat embolism (CFE) occurs mainly after long-bone fractures. Often reducing to minor neurological disorders as confusion, it can sometimes cause more severe consequences such as coma or even death. While CFE has been described for several years, there is no consensual treatment. CLINICAL PRESENTATION: We report the case of a 15-year-old girl with a severe cerebral fat embolism secondary to a longboard fall with a femur fracture. She developed in less than 4 hours a coma. On day 4, she lost her brainstem reflexes with a clinical condition close to brain death, with a very high intracranial pressure (ICP) value above 75 mmgH at worst. She was treated as having a trauma brain injury based on ICP control with a decompressive hemicraniectomy. She recovered in some weeks, allowing discharge to a post ICU rehabilitation center, one month after admission. CONCLUSION: We report a severe case of cerebral fat embolism with good outcome. It was managed as a trauma brain injury. We emphasize the neurological management based on ICP and discuss the position of hemicraniectomy.

Postoperative lymphopenia: An independent risk factor for postoperative pneumonia after lung cancer surgery, results of a case-control study.

OBJECTIVE: Postoperative lymphopenia has been proposed as a risk factor for postoperative infections but has never been identified as such in a multivariate analysis. Postoperative pneumonia (POP) is one of the most common complications after lung cancer surgery and is associated with a worse outcome. We aimed to evaluate the association between postoperative lymphopenia and POP after lung cancer surgery. METHODS: Patients admitted for lung cancer surgery (lobectomy, bilobectomy, or pneumonectomy) aged ≥ 18 years and with no history of an immunosuppressive state were eligible for inclusion. Lymphocyte counts were determined in blood drawn on the day before surgery and at postoperative days 1, 3 and 7. POP diagnosis was based on clinical, biological and radiological data. A logistic regression model adjusted on currently described risk factors for POP was used to explain the onset of this condition. RESULTS: Two hundred patients were included, of whom 43 (21.5%) developed POP. Preoperative lymphocyte count was 1.8±0.6x10(9) cells/L and 2.0±0.7x10(9) cells/L in patients with and without POP, respectively (P = .091). In both groups, the lymphocyte count nadir occurred at postoperative day 1. In multivariate analysis, lymphopenia at postoperative day 1 was significantly associated with increased risk of POP (odds ratio: 2.63, 95% CI [1.03-5.40]). POP rate at postoperative day 7 was higher in patients presenting low lymphocyte counts (≤1.19x10(9) cells/L) at postoperative day 1 (P = .003). CONCLUSIONS: Our study showed that lymphopenia following lung cancer surgery was maximal at postoperative day 1 and was associated with POP.

Flip-flop method: A new T1-weighted flow-MRI for plants studies.

The climate warming implies an increase of stress of plants (drought and torrential rainfall). The understanding of plant behavior, in this context, takes a major importance and sap flow measurement in plants remains a key issue for plant understanding. Magnetic Resonance Imaging (MRI) which is well known to be a powerful tool to access water quantity can be used to measure moving water. We describe a novel flow-MRI method which takes advantage of inflow slice sensitivity. The method involves the slice selectivity in the context of multi slice spin echo sequence. Two sequences such as a given slice is consecutively inflow and outflow sensitive are performed, offering the possiblility to perform slow flow sensitive imaging in a quite straigthforward way. The method potential is demonstrated by imaging both a slow flow measurement on a test bench (as low as 10 µm.s-1) and the Poiseuille's profile of xylemian sap flow velocity in the xylematic tissues of a tomato plant stem.

Transcranial Color Duplex Ultrasound: A Reliable Tool for Cerebral Hemodynamic Assessment in Brain Injuries.

BACKGROUND: Transcranial color duplex ultrasound (TCCD) is becoming an important tool for cerebral monitoring of brain-injured patients. To date, TCCD reproducibility has been studied in healthy volunteers or patients with subarachnoid hemorrhage and its efficiency in many brain injuries has not been proved. Our aim was to evaluate TCCD interobserver agreement in different brain injuries. PATIENTS AND METHODS: We performed a prospective monocentric trial conducted from January 2014 to September 2014 in intensive care unit (ICU) of Saint-Etienne university teaching hospital, France.Brain-damaged patients admitted in ICU were included, excluding those with decompressive craniectomy. Two randomized operators among the ICU medical staff consecutively performed measurements of cerebral blood flow velocities with TCCD. RESULTS: One hundred measurements were obtained from 42 patients. Hemodynamic and end-tidal CO2 pressure were similar between both measurement set. The results obtained with the Bland-Altman method showed bias at 0.52 (95% confidence interval [CI], -4.19 to 3.16), 0.53 (95% CI, -1.86 to 2.92), and 0.002 (95% CI, -0.06 to 0.06) for mean velocity, diastolic velocity, and pulsatility index, respectively. The limits of agreement were (-32.4; 31.4), (-20.4; 21.4), (-0.5; 0.5) for mean velocity, diastolic velocity, and pulsatility index, respectively. The Passing and Bablok regression have shown a quasilinear relationship between measurements. CONCLUSIONS: We reported the reliability of TCCD interobserver agreement in brain-damaged patients.

Numerical and experimental study of an invisibility carpet in a water channel.

We propose a numerical and an experimental study of an invisibility carpet for linear water waves. In the first part, we introduce the concept of an invisibility carpet in the case of linear water waves and apply this concept for a bounded problem: a wavetank. In the second part, we study a simpler case where we attempt to render invisible a vertical dihedral at the end of a wavetank. This is done by placing a structure consisting of 18 vertical poles with trapezoidal cross-sections in front of the dihedral. For these two configurations, with and without the carpet, we focus on the far-field reflected wave consisting of an inline mode and the first sloshing (plus progressive) mode. We show that our design achieves invisibility.

STAT5 phosphorylation in T cell subsets from septic patients in response to recombinant human interleukin-7: a pilot study.

Septic shock is characterized by lymphocyte alterations associated with increased risk of nosocomial infections and mortality. IL-7, a cytokine required for T cell survival, is thought as a novel therapy for septic patients with severe lymphopenia. We assessed CD4(+) lymphocyte responsiveness to rhIL-7 in septic shock patients ex vivo. Thirteen septic shock patients and 10 controls were included. The MFI of pSTAT5, a key signaling molecule for IL-7, was measured by flow cytometry in CD4(+)FOXP3- (Teffs) and CD4(+)FOXP3(+) (Tregs) lymphocytes after whole-blood incubation with increasing doses of rhIL-7. The basal level of pSTAT5 in nonstimulated T cells was higher in patients. However, the maximal activation level in response to the highest doses of rhIL-7 was similar in both groups. Importantly, low doses of rhIL-7 preferentially activated Teff versus Treg in patients and nonsurvivors tended to present with decreased pSTAT5 expression. This pilot study is the first to highlight, in septic patients, the interest of pSTAT5 measurement in whole blood for the monitoring of rhIL-7 therapy. Such a method could represent an innovative, biologic tool for monitoring leukocyte pharmacological responses to biotherapies in daily clinical practice in other clinical contexts.