Blood pressure management in ischemic stroke patients undergoing mechanical thrombectomy

The relationship between presenting blood pressure in acute ischemic stroke patients and outcome is complex. Several studies have demonstrated a U-shaped curve with worse outcomes when blood pressure is high or low. The American Heart Association/American Stroke Association guidelines recommend values of blood pressure \u3c 185/110 mmHg in patients treated with intravenous t-PA and permissive hypertension up to 220/120 mmHg in those not treated with intravenous t-PA. The optimal blood pressure target is less clear in patients undergoing mechanical thrombectomy. Before thrombectomy, the guidelines recommend a blood pressure \u3c 185/110 mmHg though patients with even lower systolic blood pressures may have better outcomes. During and after thrombectomy, the guidelines recommend a blood pressure \u3c 180/105 mmHg. However, several studies have suggested that during thrombectomy the primary goal should be to prevent significant low blood pressure (e.g., target systolic blood pressure \u3e 140 mmHg or MAP \u3e 70 mmHg). After thrombectomy, the primary goal should be to prevent high blood pressure (e.g., target systolic blood pressure \u3c 160 mmHg or MAP \u3c 90 mmHg). To make more specific recommendations, large, randomized-control studies are needed that address factors such as the baseline blood pressure, timing and degree of revascularization, status of collaterals, and estimated risk of reperfusion injury

BurstCube: A CubeSat for Gravitational Wave Counterparts

BurstCube will detect long GRBs, attributed to the collapse of massive stars, short GRBs (sGRBs), resulting from binary neutron star mergers, as well as other gamma-ray transients in the energy range 10-1000 keV. sGRBs are of particular interest because they are predicted to be the counterparts of gravitational wave (GW) sources soon to be detectable by LIGO/Virgo. BurstCube contains 4 CsI scintillators coupled with arrays of compact low-power Silicon photomultipliers (SiPMs) on a 6U Dellingr bus, a flagship modular platform that is easily modifiable for a variety of 6U CubeSat architectures. BurstCube will complement existing facilities such as Swift and Fermi in the short term, and provide a means for GRB detection, localization, and characterization in the interim time before the next generation future gamma-ray mission flies, as well as space-qualify SiPMs and test technologies for future use on larger gamma-ray missions. The ultimate configuration of BurstCube is to have a set of $\sim10$ BurstCubes to provide all-sky coverage to GRBs for substantially lower cost than a full-scale mission.Comment: In the 35th International Cosmic Ray Conference, Busan, Kore

An exploratory investigation of endotoxin levels in novice long distance triathletes, and the effects of a multi-strain probiotic/prebiotic, antioxidant intervention.

Abstract: Gastrointestinal (GI) ischemia during exercise is associated with luminal permeability and increased systemic lipopolysaccharides (LPS). This study aimed to assess the impact of a multistrain pro/prebiotic/ antioxidant intervention on endotoxin unit levels and GI permeability in recreational athletes. Thirty healthy participants (25 males, 5 females) were randomly assigned either a multistrain pro/prebiotic/ antioxidant (LAB4ANTI; 30 billion CFU.d-1 containing 10 billion CFU.d-1 Lactobacillus acidophilus CUL-60 [NCIMB 30157], 10 billion CFU.d-1 Lactobacillus acidophillus CUL-21 [NCIMB 30156], 9.5 billion CFU.d-1 Bifidobacterium bifidum CUL-20 [NCIMB 30172] and 0.5 billion CFU.d-1 Bifidobacterium animalis subspecies lactis CUL-34 [NCIMB 30153]/ 55.8 mg.d-1 fructooligosaccharides/ 400 mg.d-1 α-lipoic acid, 600 mg.d-1 N-acetyl-carnitine); matched pro/prebiotic (LAB4) or placebo (PL) for 12 weeks preceding a long-distance triathlon. Plasma endotoxin units (via Limulus amebocyte lysate chromogenic quantification) and GI permeability (via 5 hour urinary lactulose (L): mannitol (M) recovery) were assessed at baseline, pre-race and 6 days post-race. Endotoxin unit levels were not significantly different between groups at baseline (LAB4ANTI: 8.20±1.60 pg.ml-1; LAB4: 8.92±1.20 pg.ml-1; PL: 9.72± 2.42 pg.ml-1). The use of a 12 week LAB4ANTI intervention significantly reduced endotoxin units both pre-race (4.37± 0.51 pg.ml-1) and 6 days post-race (5.18±0.57 pg.ml-1; p=0.03, ηp2 = 0.35), but only 6 days post-race with LAB4 (5.01± 0.28 pg.ml-1; p=0.01, ηp2 = 0.43). In contrast, endotoxin units remained unchanged with PL. L:M significantly increased from 0.01±0.01 at baseline to 0.06± 0.01 with PL only (p=0.004, ηp2 = 0.51). Mean race times (hr:min:sec) were not statistically different between groups despite faster times with both pro/prebiotoic groups (LAB4ANTI:13:17:07±34:48; LAB4: 12:47:13±25:06; PL: 14:12:51±29:54; p>0.05). Combined multistrain pro/prebiotic use may reduce endotoxin unit levels, with LAB4ANTI potentially conferring an additive effect via combined GI modulation and antioxidant protection

Cosmic-Ray Positrons: Are There Primary Sources?

Cosmic rays at the Earth include a secondary component originating in collisions of primary particles with the diffuse interstellar gas. The secondary cosmic rays are relatively rare but carry important information on the Galactic propagation of the primary particles. The secondary component includes a small fraction of antimatter particles, positrons and antiprotons. In addition, positrons and antiprotons may also come from unusual sources and possibly provide insight into new physics. For instance, the annihilation of heavy supersymmetric dark matter particles within the Galactic halo could lead to positrons or antiprotons with distinctive energy signatures. With the High-Energy Antimatter Telescope (HEAT) balloon-borne instrument, we have measured the abundances of positrons and electrons at energies between 1 and 50 GeV. The data suggest that indeed a small additional antimatter component may be present that cannot be explained by a purely secondary production mechanism. Here we describe the signature of the effect and discuss its possible origin.Comment: 15 pages, Latex, epsfig and aasms4 macros required, to appear in Astroparticle Physics (1999

Site-Specific Gene Editing of Human Hematopoietic Stem Cells for X-Linked Hyper-IgM Syndrome

X-linked hyper-immunoglobulin M (hyper-IgM) syndrome (XHIM) is a primary immunodeficiency due to mutations in CD40 ligand that affect immunoglobulin class-switch recombination and somatic hypermutation. The disease is amenable to gene therapy using retroviral vectors, but dysregulated gene expression results in abnormal lymphoproliferation in mouse models, highlighting the need for alternative strategies. Here, we demonstrate the ability of both the transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) platforms to efficiently drive integration of a normal copy of the CD40L cDNA delivered by Adeno-Associated Virus. Site-specific insertion of the donor sequence downstream of the endogenous CD40L promoter maintained physiologic expression of CD40L while overriding all reported downstream mutations. High levels of gene modification were achieved in primary human hematopoietic stem cells (HSCs), as well as in cell lines and XHIM-patient-derived T cells. Notably, gene-corrected HSCs engrafted in immunodeficient mice at clinically relevant frequencies. These studies provide the foundation for a permanent curative therapy in XHIM

Triticum timopheevii s.l. (‘new glume wheat’) finds in regions of southern and eastern Europe across space and time

Triticum timopheevii sensu lato (‘new glume wheat’, NGW) was first recognised as a distinct prehistoric cereal crop through work on archaeobotanical finds from Neolithic and Bronze Age sites in northern Greece. This was later followed by its identification in archaeobotanical assemblages from other parts of Europe. This paper provides an overview of the currently known archaeobotanical finds of Timopheev’s wheat in southeastern and eastern Europe and observes their temporal span and spatial distribution. To date, there are 89 prehistoric sites with these finds, located in different parts of the study region and dated from the Neolithic to the very late Iron Age. Their latest recorded presence in the region is in the last centuries BCE. For assemblages from the site as a whole containing at least 30 grain and/or chaff remains of Timopheev’s wheat, we take a brief look at the overall relative proportions of Triticum monococcum (einkorn), T. dicoccum (emmer) and T. timopheevii s.l. (Timopheev’s wheat), the three most common glume wheats in our study region in prehistory. We highlight several sites where the overall proportions of Timopheev’s wheat might be taken to suggest it was a minor component of a mixed crop (maslin), or an unmonitored inclusion in einkorn or emmer fields. At the same sites, however, there are also discrete contexts where this wheat is strongly predominant, pointing to its cultivation as a pure crop. We therefore emphasise the need to evaluate the relative representation of Timopheev’s wheat at the level of individual samples or contexts before making inferences on its cultivation status. We also encourage re-examination of prehistoric and historic cereal assemblages for its remains

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management