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The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.
Hepatitis E virus (HEV) is an emerging cause of viral hepatitis worldwide. Recently, HEV-7 has been shown to infect camels and humans. We studied HEV seroprevalence in dromedary camels and among Bedouins, Arabs (Muslims, none-Bedouins) and Jews and assessed factors associated with anti-HEV seropositivity. Serum samples from dromedary camels (n = 86) were used to determine camel anti-HEV IgG and HEV RNA positivity. Human samples collected between 2009 and 2016 from >20 years old Bedouins (n = 305), non-Bedouin Arabs (n = 320) and Jews (n = 195), were randomly selected using an age-stratified sampling design. Human HEV IgG levels were determined using Wantai IgG ELISA assay. Of the samples obtained from camels, 68.6% were anti-HEV positive. Among the human populations, Bedouins and non-Bedouin Arabs had a significantly higher prevalence of HEV antibodies (21.6% and 15.0%, respectively) compared with the Jewish population (3.1%). Seropositivity increased significantly with age in all human populations, reaching 47.6% and 34.8% among ⩾40 years old, in Bedouins and non-Bedouin Arabs, respectively. The high seropositivity in camels and in ⩾40 years old Bedouins and non-Bedouin Arabs suggests that HEV is endemic in Israel. The low HEV seroprevalence in Jews could be attributed to higher socio-economic status.
This study aimed to investigate the prevalence of and risk factors for Eustachian tube dysfunction leading to middle-ear pathology in patients on chronic mechanical ventilation via tracheostomy tube.
A total of 40 patients on chronic ventilation were included in a prospective cohort study. Middle-ear status was determined by tympanometry. Tympanograms were categorised as types A, B or C; types B and C were defined as middle-ear pathology.
In all, 57 ears of 40 patients were examined. Disease was found in at least 1 ear in 26 out of 40 patients. Middle-ear pathology was found in 25 out of 34 patients who were tube fed (via nasogastric tube or percutaneous endoscopic gastrostomy) vs 1 patient out of the 6 fed orally (p = 0.014), and in 23 out of 31 with conscious or cognitive impairment vs 3 out of 9 cognitively intact patients (p = 0.044).
Middle-ear pathology is common in patients on chronic mechanical ventilation via tracheostomy tube. The highest prevalence was in those with impaired consciousness or cognition, and oral feeding appeared protective.
One view of major Solar Energetic Particle (SEP) events is that these (proton-dominated) fluxes are accelerated in heliospheric shock sources created by Interplanetary Coronal Mass Ejections (ICMEs), and then travel mainly along interplanetary magnetic field lines connecting the shock(s) to the observer(s). This places a particular emphasis on the role of the heliospheric conditions during the event, requiring a realistic description of the latter to interpret and/or model SEP events. The well-known ENLIL heliospheric simulation with cone model generated ICME shocks is used together with the SEPMOD particle event modeling scheme to demonstrate the value of applying these concepts at multiple inner heliosphere sites.
To use VRI systems, a field is divided into irrigation management zones (IMZs). While IMZs are dynamic in nature, most of IMZs prescription maps are static. High-resolution thermal images (TI) coupled with measured atmospheric conditions have been utilized to map the within-field water status variability and to delineate in-season IMZs. Unfortunately, spaceborne TIs have coarse spatial resolution and aerial platforms require substantial financial investments, which may inhibit their large-scale adoption. Three approaches are proposed to facilitate large-scale adoption of TI-based IMZs: 1) increase of the capacity of aerial TI by enhancing their spatial resolution; 2) sharpening the spatial resolution of satellite TI by fusing satellite multi-spectral images in the visible-near-infrared (VIS-NIR) range; 3) increase the capacity of aerial TI by fusing satellite multi-spectral images in the VIS-NIR range. The scientific and engineering basis of each of the approaches is described together with initial results.
The radiological detection of BMs is essential for optimizing a patient’s treatment. This statement is even more valid when stereotactic radiosurgery (SRS), a non-invasive image guided treatment that can target BM as small as 1-2 mm, is delivered as part of that care. The timing of image acquisition after contrast administration can influence the diagnostic sensitivity of contrast enhanced MRI for BM. Objective: Investigate the effect of time delayed acquisition after administration of intravenous Atavist® (Gadobutrol 1mmol/ml) on the detection of BM. Methods: This is a prospective IRB approved study of 50 patients with BM who underwent post-contrast MRI sequences immediately after injection of 0.1 mmol/kg Gadavist® as part of clinical care (t0), followed by axial T1 sequences after a 10 minutes (t1) and 20 minute delay (t2). MRI studies were blindly compared by 3 neuro-radiologists. Results: Single measure intraclass correlation coefficients were very high (0.914, 0.904 and 0.905 for t0, t1 and t2 respectively), corresponding to a reliable inter-observer correlation. The t2 delayed sequences showed a significant and consistently higher diagnostic sensitivity for BM by every participating neuroradiologist as well as for the entire cohort (p=0.016, p=0.035 and 0.034 respectively). A disproportionately high representation of BM detected on the delayed studies was located within posterior circulation territories (compared to predictions based on tissue volume and blood-flow volumes). Conclusion: Considering the safe and potentially high yield nature of delayed MRI sequences, it should supplement the basic MRI sequences in all patients in need of precise delineation of their intracranial disease.
Hemangiopericytomas (HPC) are widely recognized for their aggressive clinical behavior. We report a large multicenter study, through the International Gamma Knife Research Foundation reviewing management and outcome following stereotactic radiosurgery (SRS) for recurrent or newly-discovered HPC’s. Methods: Eight centers participated, reviewing a total of 90 patients harboring 133 tumors. Prior treatments included embolization (n = 8), chemotherapy (n=2), and fractionated radiotherapy (n=34). The median tumor volume at the time of SRS was 4.9 ml (range 0.2-42.4 ml). WHO-grade II (typical) HPC’s formed 78.9% (n=71) of the cohort. The median margin and maximal doses delivered were 15 Gy (2.8-24) and 32 Gy (8-51), respectively. The median clinical and radiographic follow-up period was 59 months (6-190) and 59 months (6-183), respectively. Results: At last follow-up, 55% of tumors and 62.2% of patients demonstrated local tumor control. New remote intracranial tumors were found in 27.8%. 24.4% of patients developed extra-cranial metastases. Adverse radiation effects were noted in 6.7%. The overall survival was 91.5%, 82.1%, 73.9%, 56.7%, and 53.7% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. Local progression free survival was 81.7%, 66.3%, 54.5%, 37.2%, and 25.5% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. In our cohort, 32 patients underwent 48 repeat SRS procedures for 76 lesions. Margin dose greater than 16 Gy (p=0.037) and tumor histology (p=0.006) were shown to influence PFS. Conclusions: SRS provides a reasonable rate of local tumor control and a low risk of adverse effects
Glioblastoma Multiforme is the most common malignant primary brain tumor, having a mean overall survival <2 years. The lack of an efficient immune response against the tumor have been attributed to its immunosuppressive capabilities and an immunosuppressing local environment. Aim: We set out to design a chimeric molecule that recognizes and binds tissue inducible metalloproteinase known to be induced in GBM cells (MMP-2) on one end. Its other end, the effector domain, mobilizes and recruits cytotoxic T-cells to mount an effective anti-tumor reaction. Methods: The targeting moiety is the small 36-amino acids Chlorotoxin, derived from the venom of the Israeli Yellow scorpion. The effector end is a single chain HLA-A2 (Human leukocyte antigen subtype A2) covalently bound to phosphoprotein-65 derived from the cytomegalovirus, to which most of the human population has developed a specific immune response. Results: The molecular construct was cloned and expressed in E.coli. The protein product was isolated, purified, and then folded in vitro. Various activity assays employed demonstrated retained activity of each domain, including flow-cytometry, intracellular staining, fluorescence immunohistochemistry, radiolabeled toxicity assays etc. Initial in-vivo studies show great promise. Conclusions: We present a proof of concept study for a new immunotherapy approach to battle GBM. A molecular construct which contains a non-antibody compact and highly specific targeting domain, combined with the ability to recruit anti-CMV T-cell lymphocyte population. The recruitment of potent memory CTL’s to the tumor’s milieu may prove resistant to the previously described local immunosuppressive environment brought about by the tumor.
For patient with a recurrent or residual acromegaly or Cushing’s disease (CD) after resection, Gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow up has hampered understanding of the latent risks of hypopituitarism in patients with a Acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for Acromegaly or CD. Methods: From a prospectively created, IRB approved database, we identified all patients with a Acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow up of 60 months were included. The median follow-up is 159.5 months (60.1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Results: 60 patients with either Acromegaly or CD were included. Median tumor volume at time of GKRS was 1.3 cm3 (0.3-13.4), median margin dose was 25 Gy (6-30). GKRS induced new pituitary deficiency occurred in 58.3% (n=35) of patients. Growth Hormone deficiency was most common (28.3%, n=17). The actuarial overall rates of hypopituitarism at 3, 5, and 10 years were 10%, 21.7%, and 53.3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumor was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (p=0.018). Conclusions: Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.
Meningiomas are the most common primary benign brain tumor. Radiosurgery (primary or adjuvant) allows excellent local control. The Geriatric scoring system (GSS) for pre-operative risk stratification and outcome prediction of patients with meningiomas has been previously reported. The GSS incorporates eight tumor and patient parameters on admission. A GSS score higher than 16 was previously reported to be associated with a more favorable outcome. We assessed the validity of the GSS score and its influence on outcome in patients treated with gamma-knife radiosurgery (GKRS). Methods: Patients treated with single session GKRS for WHO-1 meningioma during 1989-2013 at the University of Virginia were reviewed. A cohort of 323 patients, 50.2% (n=162) males. Median age was 56 (29-84), and median follow-up was 53.6 (6-235) months. Median tumor volume was 4.5 cm3 (0.2-23). Median margin and maximal doses were 15 Gy (8-36) and 32.3 Gy (20-65), respectively. Results: Tumor volume control was achieved in 87% (n=281), and post-GKRS clinical neurological improvement reported in 66.3% (n=214). The median change in KPS was +10 (range -30 to +40). The most common complication was intermittent headaches (34.1%, n=110) and cranial nerve deficits (14.2%, n=46). The GSS (calculated and grouped as GSS>16 and GSS<=16) was found to correlate with different Post-GKRS functional status (p<0.0001) and tumor control (p=0.028). Conclusion: The GSS, used for risk stratification and outcome prediction in patients with meningiomas seems valid for patients undergoing single session GRKS. GSS score greater than 16 is associated with a better long-term functional status and tumor control.
Gamma knife radiosurgery (GKRS) is well-established in the management of inaccessible, recurrent, or residual benign skull base meningiomas. Most series report clinical outcome parameters and complications in the short -intermediate period after radiosurgery. Reports of long-term tumor control and neurological status are still lacking. Objective: We report the presentation, treatment, and long-term outcome of skull base meningiomas after GKRS. Methods: From a prospectively collected IRB approved database, we selected patients with a WHO grade I skull base meningioma treated with a single-session GKRS and a minimum of 60 months follow up. 135 patients, 54.1% males (n=73) form the cohort. Median age was 54 years (19-80). Median tumor volume was 4.7 cm3 (0.5-23). Median margin dose was 15 Gy (7.5-36). Median follow up was 102.5 months (60.1-235.4). Patient and tumor characteristics were assessed to determine predictors of neurological function and tumor progression. Results: At last follow up, tumor volume control was achieved in 88.1% (n=119). Post-GKRS clinical improvement or stability was reported in 61.5%. The 5, 10, and 15 years actuarial progression free survival rates are 100%, 95.4%, and 68.8%, respectively. Favorable outcome (both tumor control and clinical preservation/improvement) was attained in 60.8% (n=79). Pre-GKRS performance status (KPS) was shown to influence tumor progression (p=0.0001) and post-GKRS clinical improvement / preservation (p=0.003). Conclusion: GKRS offers a highly durable rate of tumor control for WHO-I skull base meningiomas, with an acceptably low incidence of neurological deficits. KPS at the time of radiosurgery serves as a reliable long-term predictor of overall outcome.
Melanoma represents the third most common cause of CNS metastases. Immunotherapy has evolved as a treatment option for patients with stage-IV melanoma. Stereotactic radiosurgery (SRS) also elicits an immune response within the brain and may interact with immunotherapy. We report a cohort of patients treated for brain metastasis with immunotherapy and evaluate the effect of SRS timing on the intracranial response. Methods: All consecutively treated melanoma patients receiving Ipilimumab and SRS for their brain metastasis were included in the retrospective analysis. 46 patients harboring 232 brain metastases were reviewed. The median clinical follow-up was 7.9 months (3-42.6). Median age was 63 years (24.3-83.6). 32 patients received SRS before or during ipilimumab cycles (Group-A) whereas 14 patients received SRS after the ipilimumab treatment (Group-B). Radiographic and clinical responses were assessed at approximately 3 months intervals after SRS. Results: The two cohorts were comparable in pertinent pre-treatment aspects with the exception of SRS timing relative to ipilimumab. Local recurrence free duration (LRFD) was significantly longer in Group-A patients (19.6 months, range 1.1-34.7 months) as compared to group-B patients (3 months, range 0.4-20.4 months), respectively (p=0.002). Post-SRS perilesional edema was more significant in Group-A. Conclusions: The effect of SRS and ipilimumab in attaining LRFD seems greater when SRS is performed before or during ipilimumab treatments. The timing of immunotherapy and SRS may effect LRFD and post-radiosurgical edema. The interactions between immunotherapy and SRS warrant further investigation so as to optimize the therapeutic benefits and mitigate the risks associated with multimodality, targeted therapy.
Chemical and structural similarities between poorly preserved charcoal and its contaminants, as well as low radiocarbon concentrations in old samples, complicate 14C age determinations. Here, we characterize 4 fossil charcoal samples from the late Middle Paleolithic and early Upper Paleolithic strata of Kebara Cave, Israel, with respect to the structural and chemical changes that occur when they are subjected to the acid-base-acid (ABA) treatment. Differential thermal analysis and TEM show that acid treatment disrupts the structure, whereas alkali treatment results in the reformation of molecular aggregates. The major changes are ascribed to the formation of salt bridges at high pH and the disruption of the graphite-like crystallites at low pH. Weight losses during the treatments are consistently greater for older samples, implying that they are less well preserved. Based on the changes observed in vitro due to pH fluctuations, various methods for removing contamination, as well as a mechanism for preferential preservation of charcoal in nature, are proposed.
There are striking global inequities in our knowledge of the incidence, aetiology, and outcome of psychotic disorders. For example, only around 10% of research on incidence of psychotic disorders originates in low- and middle-income countries. We established INTREPID I to develop, implement, and evaluate, in sites in India (Chengalpet), Nigeria (Ibadan), and Trinidad (Tunapuna-Piarco), methods for identifying and recruiting untreated cases of psychosis, as a basis for investigating incidence and, subsequently, risk factors, phenomenology, and outcome. In this paper, we compare case characteristics and incidence rates across the sites.
In each site, to identify untreated cases of psychoses in defined catchment areas, we established case detection systems comprising mental health services, traditional and spiritual healers, and key informants.
Rates of all untreated psychoses were 45.9 (per 1 00 000 person-years) in Chengalpet, 31.2 in Ibadan, and 36.9 in Tunapuna-Piarco. Duration of psychosis prior to detection was substantially longer in Chengalpet (median 232 weeks) than in Ibadan (median 13 weeks) and Tunapuna-Piarco (median 38 weeks). When analyses were restricted to cases with a short duration (i.e. onset within preceding 2 years) only, rates were 15.5 in Chengalpet, 29.1 in Ibadan, and 26.5 in Tunapuna-Piarco. Further, there was evidence of age and sex differences across sites, with an older average age of onset in Chengalpet and higher rates among women in Ibadan.
Our findings suggest there may be differences in rates of psychoses and in the clinical and demographic profiles of cases across economically and socially distinct settings.
Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography–tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P < 0·05) and the incidence of POAF increased significantly with each higher quartile of preoperative plasma levels of 25(OH)D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P < 0·05) on the third postoperative day compared with preoperatively. Our findings demonstrate that higher plasma levels of 25(OH)D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study.
Differences in the seroprevalence and unique pattern of parvovirus B19 (B19V) acute infections have been documented around the world. This study was conducted to estimate the seroprevalence of anti-parvovirus B19V IgG antibodies in the Israeli population and to assess the pattern of acute infection based on data from two laboratories in Israel. The overall IgG prevalence in the 1008 representative sera samples was 61·4% and the age-adjusted prevalence rate was 58·2%. Seropositivity was significantly associated with age, ranging from 25·7% in children aged <10 years to 70% in people aged >20 years. While no significant differences in seropositivity were detected between sexes and population groups, significantly lower seroprevalence was observed in older Jews born in Africa or Asia. Acute infection rates of 4·1% (234 cases) were found based on the positive IgM results identified in samples from 5663 individuals collected between 2008 and 2013. Annual peaks of infection were observed in 2008 and 2011–2012 and major seasonal peak of B19V IgM positivity was identified in June each year. The number of requests for B19V serology was significantly higher for women aged 20–39 years while the majority IgM-positive cases were identified in young children. With more than 30% of the adult population being susceptible to B19V infection, monitoring B19V status should be considered in specific risk groups such as pregnant women.
We present the results of a numerical simulation of the corona and wind structure of the Sun-like exoplanet-host GJ 3021 using a global magnetohydrodynamic (MHD) model. The simulation is driven by the radial component of the surface magnetic field recovered with the Zeeman Doppler Imaging (ZDI) technique. We consider two different ZDI input maps, which have similar large-scale structures but different spatial resolutions and field strengths. These maps arise from different but comparable models used to fit the observed circularly polarised spectra of the star. Our simulations show that the structure of the inner corona is consistent among the considered cases. Larger discrepancies are found in the wind structure, in particular in the radial wind speed and the Alfvén surface topology. These elements can have a significant impact on the mass loss and angular momentum loss predicted for this system and in other studies based on this numerical data-driven approach.