Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets

Although tissue factor (TF), the principial initiator of physiological coagulation and pathological thrombosis, has recently been proposed to be present in human blood, the functional significance and location of the intravascular TF is unknown. In the plasma portion of blood, we found TF to be mainly associated with circulating microvesicles. By cell sorting with the specific marker CD42b, platelet-derived microvesicles were identified as a major location of the plasma TF. This was confirmed by the presence of full-length TF in microvesicles acutely shedded from the activated platelets. TF was observed to be stored in the α-granules and the open canalicular system of resting platelets and to be exposed on the cell surface after platelet activation. Functional competence of the blood-based TF was enabled when the microvesicles and platelets adhered to neutrophils, as mediated by P-selectin and neutrophil counterreceptor (PSGL-1, CD18 integrins) interactions. Moreover, neutrophil-secreted oxygen radical species supported the intravascular TF activity. The pools of platelet and microvesicle TF contributed additively and to a comparable extent to the overall blood TF activity, indicating a substantial participation of the microvesicle TF. Our results introduce a new concept of TF-mediated coagulation crucially dependent on TF associated with microvesicles and activated platelets, which principally enables the entire coagulation system to proceed on a restricted cell surface

Category fluency in psychometric schizotypy: How altering emotional valence and cognitive load affects performance

Introduction. In clinical high-risk populations, category fluency deficits are associated with conversion to psychosis. However, their utility as clinical risk markers is unclear in psychometric schizotypy, a group experiencing schizophrenia-like traits that is at putative high risk for psychosis. Methods. We examined whether introducing affective or cognitive load, two important stress vulnerability markers, altered category fluency performance in schizotypy (n = 42) and non-schizotypy (n = 38) groups. To investigate this question, we developed an experimental paradigm where all participants were administered category fluency tests across baseline, pleasant valence, unpleasant valence, and cognitive load conditions. Results. Compared to the non-schizotypy group, those with schizotypy performed significantly worse in pleasant and unpleasant valence conditions, but not cognitive load or baseline fluency tests. Conclusions. This study demonstrated the role of affect – but not cognitive load – on category fluency in psychometric schizotypy, as group differences only emerged once affective load was introduced. One explanation for this finding is that semantic memory may be unimpaired under normal conditions in psychometric schizotypy, but may be compromised once affective load is presented. Future studies should examine whether fluency deficits – particularly when affect is induced – predict future conversion to psychosis in psychometric schizotypy cohorts

Salvage Fractionated Stereotactic Radiotherapy with or without Chemotherapy and Immunotherapy for Recurrent Glioblastoma Multiforme: A Single Institution Experience

BACKGROUND: The current standard of care for salvage treatment of glioblastoma multiforme (GBM) is gross total resection and adjuvant chemoradiation for operable patients. Limited evidence exists to suggest that any particular treatment modality improves survival for recurrent GBM, especially if inoperable. We report our experience with fractionated stereotactic radiotherapy (fSRT) with and without chemo/immunotherapy, identifying prognostic factors associated with prolonged survival. METHODS: From 2007 to 2014, 19 patients between 29 and 78 years old (median 55) with recurrent GBM following resection and chemoradiation for their initial tumor, received 18–35 Gy (median 25) in three to five fractions via CyberKnife fSRT. Clinical target volume (CTV) ranged from 0.9 to 152 cc. Sixteen patients received adjuvant systemic therapy with bevacizumab (BEV), temozolomide (TMZ), anti-epidermal growth factor receptor (125)I-mAb 425, or some combination thereof. RESULTS: The median overall survival (OS) from date of recurrence was 8 months (2.5–61) and 5.3 months (0.6–58) from the end of fSRT. The OS at 6 and 12 months was 47 and 32%, respectively. Three of 19 patients were alive at the time of this review at 20, 49, and 58 months from completion of fSRT. Hazard ratios for survival indicated that patients with a frontal lobe tumor, adjuvant treatment with either BEV or TMZ, time to first recurrence >16 months, CTV <36 cc, recursive partitioning analysis <5, and Eastern Cooperative Oncology Group performance status <2 were all associated with improved survival (P < 0.05). There was no evidence of radionecrosis for any patient. CONCLUSION: Radiation Therapy Oncology Group (RTOG) 1205 will establish the role of re-irradiation for recurrent GBM, however our study suggests that CyberKnife with chemotherapy can be safely delivered, and is most effective in patients with smaller frontal lobe tumors, good performance status, or long interval from diagnosis

Low Raman-noise correlated photon-pair generation in a dispersion-engineered chalcogenide As2S3 planar waveguide

We demonstrate low Raman-noise correlated photon-pair generation in a dispersion-engineered 10 mm As2S3 chalcogenide waveguide at room temperature. We show a coincidence-to-accidental ratio (CAR) of 16.8, a 250 times increase compared with previously published results in a chalcogenide waveguide, with a corresponding brightness of 3×105  pairs·s−1·nm−1 generated at the chip. Dispersion engineering of our waveguide enables photon passbands to be placed in the low spontaneous Raman scattering (SpRS) window at 7.4 THz detuning from the pump. This Letter shows the potential for As2S3 chalcogenide to be used for nonlinear quantum photonic devices.This work was supported by the Centre of Excellence, Federation Fellowship, and Discovery Early Career Researcher Award (DECRA) programs of the Australian Research Council (ARC). The Centre for Ultrahigh bandwidth Devices for Optical Systems (CUDOS) is an ARC Centre of Excellence (project number CE110001018)

0.85 PW laser operation at 3.3 Hz and high-contrast ultrahigh-intensity λ = 400 nm second-harmonic beamline

Includes bibliographical references (page 3831).We demonstrate the generation of 0.85 PW, 30 fs laser pulses at a repetition rate of 3.3 Hz with a record average power of 85 W from a Ti:sapphire laser. The system is pumped by high-energy Nd:glass slab amplifiers frequency doubled in LiB3O5 (LBO). Ultrahigh-contrast λ = 400 nm femtosecond pulses were generated in KH2PO4 (KDP) with>40% efficiency. An intensity of 6.5 × 1021 W∕cm2 was obtained by frequency doubling 80% of the available Ti:sapphire energy and focusing the doubled light with an f∕2 parabola. This laser will enable highly relativistic plasma experiments to be conducted at high repetition rate