Primary Blast Traumatic Brain Injury in the Rat: Relating Diffusion Tensor Imaging and Behavior

The incidence of traumatic brain injury (TBI) among military personnel is at its highest point in U.S. history. Experimental animal models of blast have provided a wealth of insight into blast injury. The mechanisms of neurotrauma caused by blast, however, are still under debate. Specifically, it is unclear whether the blast shockwave in the absence of head motion is sufficient to induce brain trauma. In this study, the consequences of blast injury were investigated in a rat model of primary blast TBI. Animals were exposed to blast shockwaves with peak reflected overpressures of either 100 or 450 kPa (39 and 110 kPa incident pressure, respectively) and subsequently underwent a battery of behavioral tests. Diffusion tensor imaging (DTI), a promising method to detect blast injury in humans, was performed on fixed brains to detect and visualize the spatial dependence of blast injury. Blast TBI caused significant deficits in memory function as evidenced by the Morris Water Maze, but limited emotional deficits as evidenced by the Open Field Test and Elevated Plus Maze. Fractional anisotropy, a metric derived from DTI, revealed significant brain abnormalities in blast-exposed animals. A significant relationship between memory deficits and brain microstructure was evident in the hippocampus, consistent with its role in memory function. The results provide fundamental insight into the neurological consequences of blast TBI, including the evolution of injury during the sub-acute phase and the spatially dependent pattern of injury. The relationship between memory dysfunction and microstructural brain abnormalities may provide insight into the persistent cognitive difficulties experienced by soldiers exposed to blast neurotrauma and may be important to guide therapeutic and rehabilitative efforts

Biomechanical Tolerance of Whole Lumbar Spines in Straightened Posture Subjected to Axial Acceleration

Quantification of biomechanical tolerance is necessary for injury prediction and protection of vehicular occupants. This study experimentally quantified lumbar spine axial tolerance during accelerative environments simulating a variety of military and civilian scenarios. Intact human lumbar spines (T12‐L5) were dynamically loaded using a custom‐built drop tower. Twenty‐three specimens were tested at sub‐failure and failure levels consisting of peak axial forces between 2.6 and 7.9 kN and corresponding peak accelerations between 7 and 57 g. Military aircraft ejection and helicopter crashes fall within these high axial acceleration ranges. Testing was stopped following injury detection. Both peak force and acceleration were significant (p \u3c 0.0001) injury predictors. Injury probability curves using parametric survival analysis were created for peak acceleration and peak force. Fifty‐percent probability of injury (95%CI) for force and acceleration were 4.5 (3.9–5.2 kN), and 16 (13–19 g). A majority of injuries affected the L1 spinal level. Peak axial forces and accelerations were greater for specimens that sustained multiple injuries or injuries at L2–L5 spinal levels. In general, force‐based tolerance was consistent with previous shorter‐segment lumbar spine testing (3–5 vertebrae), although studies incorporating isolated vertebral bodies reported higher tolerance attributable to a different injury mechanism involving structural failure of the cortical shell. This study identified novel outcomes with regard to injury patterns, wherein more violent exposures produced more injuries in the caudal lumbar spine. This caudal migration was likely attributable to increased injury tolerance at lower lumbar spinal levels and a faster inertial mass recruitment process for high rate load application. Published 2017. This article is a U.S. Government work and is in the public domain in the USA

Integrated results from the COPERNICUS and GALILEO studies.

OBJECTIVES: To report on the efficacy and safety of intravitreal aflibercept in patients with macular edema secondary to central retinal vein occlusion (CRVO) in an integrated analysis of COPERNICUS and GALILEO. PATIENTS AND METHODS: Patients were randomized to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until week 24. From week 24 to week 52, all intravitreal aflibercept-treated patients in both studies and sham-treated patients in COPERNICUS were eligible to receive intravitreal aflibercept based on prespecified criteria. In GALILEO, sham-treated patients continued to receive sham treatment through week 52. RESULTS: At week 24, mean gain in best-corrected visual acuity and mean reduction in central retinal thickness were greater for intravitreal aflibercept-treated patients compared with sham, consistent with individual trial results. At week 52, after 6 months of intravitreal aflibercept as-needed treatment in COPERNICUS, patients originally randomized to sham group experienced visual and anatomic improvements but did not improve to the extent of those initially treated with intravitreal aflibercept, while the sham group in GALILEO did not improve over week 24 mean best-corrected visual acuity scores. Ocular serious adverse events occurred in CONCLUSION: This analysis of integrated data from COPERNICUS and GALILEO confirmed that intravitreal aflibercept is an effective treatment for macular edema following CRVO

Development of chiral phosphoric acids based on ferrocene-bridged paracyclophane frameworks

International audienceThis work deals with the development of a new family of planar chiral phosphoric acids, based on a ferrocenophane/paracyclophane scaffold. The synthetic approach has been improved by taking advantage of a chiral phosphorylating agent to access enantiomerically enriched acids via diastereomers separation. These phosphoric acids have been used as catalysts for the enantioselective H-transfer reduction of alpha-substituted quinolines with Hantzsch esters. Optimization of both the catalyst and the Hantzsch reductant allowed ee in the range 82-92% to be attained starting from alpha-arylquinolines

Partial pharmacologic blockade shows sympathetic connection between blood pressure and cerebral blood flow velocity fluctuations

Cerebral autoregulation (CA) dampens transfer of blood pressure (BP)-fluctuations onto cerebral blood flow velocity (CBFV). Thus, CBFV-oscillations precede BP-oscillations. The phase angle (PA) between sympathetically mediated low-frequency (LF: 0.03–0.15 Hz) BP- and CBFV-oscillations is a measure of CA quality. To evaluate whether PA depends on sympathetic modulation, we assessed PA-changes upon sympathetic stimulation with and without pharmacologic sympathetic blockade. In 10 healthy, young men, we monitored mean BP and CBFV before and during 120-second cold pressor stimulation (CPS) of one foot (0 °C ice-water). We calculated mean values, standard deviations and sympathetic LF-powers of all signals, and PAs between LF-BP- and LF–CBFV-oscillations. We repeated measurements after ingestion of the adrenoceptor-blocker carvedilol (25 mg). We compared parameters before and during CPS, without and after carvedilol (analysis of variance, post-hoc t-tests, significance: p < 0.05). Without carvedilol, CPS increased BP, CBFV, BP-LF- and CBFV-LF-powers, and shortened PA. Carvedilol decreased resting BP, CBFV, BP-LF- and CBFV-LF-powers, while PAs remained unchanged. During CPS, BPs, CBFVs, BP-LF- and CBFV-LF-powers were lower, while PAs were longer with than without carvedilol. With carvedilol, CPS no longer shortened resting PA. Sympathetic activation shortens PA. Partial adrenoceptor blockade abolishes this PA-shortening. Thus, PA-measurements provide a subtle marker of sympathetic influences on CA and might refine CA evaluation

On the single mode approximation in spinor-1 atomic condensate

We investigate the validity conditions of the single mode approximation (SMA) in spinor-1 atomic condensate when effects due to residual magnetic fields are negligible. For atomic interactions of the ferromagnetic type, the SMA is shown to be exact, with a mode function different from what is commonly used. However, the quantitative deviation is small under current experimental conditions (for $^{87}$Rb atoms). For anti-ferromagnetic interactions, we find that the SMA becomes invalid in general. The differences among the mean field mode functions for the three spin components are shown to depend strongly on the system magnetization. Our results can be important for studies of beyond mean field quantum correlations, such as fragmentation, spin squeezing, and multi-partite entanglement.Comment: Revised, newly found analytic proof adde