Sensitivity and performance of the Advanced LIGO detectors in the third observing run

On April 1st, 2019, the Advanced Laser Interferometer Gravitational-Wave Observatory (aLIGO), joined by the Advanced Virgo detector, began the third observing run, a year-long dedicated search for gravitational radiation. The LIGO detectors have achieved a higher duty cycle and greater sensitivity to gravitational waves than ever before, with LIGO Hanford achieving angle-averaged sensitivity to binary neutron star coalescences to a distance of 111 Mpc, and LIGO Livingston to 134 Mpc with duty factors of 74.6% and 77.0% respectively. The improvement in sensitivity and stability is a result of several upgrades to the detectors, including doubled intracavity power, the addition of an in-vacuum optical parametric oscillator for squeezed-light injection, replacement of core optics and end reaction masses, and installation of acoustic mode dampers. This paper explores the purposes behind these upgrades, and explains to the best of our knowledge the noise currently limiting the sensitivity of each detector. © 2020 authors. Published by the American Physical Society

Omanicotyle heterospina n. gen. et n. comb. (Monogenea: Microcotylidae) from the gills of Argyrops spinifer (Forsskal) (Teleostei: Sparidae) from the Sea of Oman

Background: The Sultanate of Oman's aquaculture industry is expanding with an on-going assessment of potential new fish species for culture. The king soldier bream, Argyrops spinifer (Forsskål) (Sparidae), is one such species that is under consideration. During a routine health assessment of specimens caught in the Sea of Oman throughout the period November 2009 to March 2011, a number of gill polyopisthocotylean monogeneans were recovered. Methods: A subsequent study of the monogeneans using a range of morphology-based approaches indicated that these were Bivagina heterospina Mamaev et Parukhin, 1974. In the absence of pre-existing molecular data, an expanded description of this species is provided, including a differential diagnosis with other species and genera belonging to the subfamily Microcotylinae Monticelli, 1892 with the subsequent movement of this species to a new genus to accommodate it. Results: The polyopisthocotyleans collected from the gills of A. spinifer appear to be unique within the family Microcotylidae Taschenberg, 1879 in that, morphologically, they possess a pair of large, muscular vaginae each armed with a full crown of 16-18 robust spines and a unique dorsal region of folded tegument, which permits their discrimination from species of Bivagina Yamaguti, 1963. Sequencing of the SSU rDNA (complete 1968 bp) and LSU rDNA (partial 949 bp) places the specimens collected during this study within the subfamily Microcotylinae, but the LSU rDNA sequence differs from Bivagina and also from other microcotylid genera. Morphological features of B. heterospina sensu Mamaev et Parukhin, 1974 and the specimens collected from the current study are consistent with one another and represent a single species. The vaginal armature of these worms is unique and differs from all other genera within the Microcotylinae, including Bivagina, and its movement to Omanicotyle n. gen. to accommodate this species is proposed. Conclusions: A new genus, Omanicotyle n. gen., is erected to accommodate Omanicotyle [Bivagina] heterospina n. comb. which represents the first monogenean to be described from Omani marine waters. Given the pathogenic potential of microcotylids on captive held fish stocks, a full assessment of Omanicotyle heterospina n. gen. et n. comb. is now required before large-scale production commences

Effect of garlic on blood pressure: A systematic review and meta-analysis

The electronic version of this article is the complete one and can be found online at the publisher's website.Background: Non-pharmacological treatment options for hypertension have the potential to reduce the risk of cardiovascular disease at a population level. Animal studies have suggested that garlic reduces blood pressure, but primary studies in humans and non-systematic reviews have reported mixed results. With interest in complementary medicine for hypertension increasing, it is timely to update a systematic review and meta-analysis from 1994 of studies investigating the effect of garlic preparations on blood pressure. Methods: We searched the Medline and Embase databases for studies published between 1955 and October 2007. Randomised controlled trials with true placebo groups, using garlic-only preparations, and reporting mean systolic and/or diastolic blood pressure (SBP/DBP) and standard deviations were included in the meta-analysis. We also conducted subgroup meta-analysis by baseline blood pressure (hypertensive/normotensive), for the first time. Meta-regression analysis was performed to test the associations between blood pressure outcomes and duration of treatment, dosage, and blood pressure at start of treatment. Results: Eleven of 25 studies included in the systematic review were suitable for meta-analysis. Meta-analysis of all studies showed a mean decrease of 4.6 ± 2.8 mm Hg for SBP in the garlic group compared to placebo (n = 10; p = 0.001), while the mean decrease in the hypertensive subgroup was 8.4 ± 2.8 mm Hg for SBP (n = 4; p < 0.001), and 7.3 ± 1.5 mm Hg for DBP (n = 3; p < 0.001). Regression analysis revealed a significant association between blood pressure at the start of the intervention and the level of blood pressure reduction (SBP: R = 0.057; p = 0.03; DBP: R = -0.315; p = 0.02). Conclusion: Our meta-analysis suggests that garlic preparations are superior to placebo in reducing blood pressure in individuals with hypertension.Karin Ried, Oliver R. Frank, Nigel P. Stocks, Peter Fakler and Thomas Sulliva

DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia

We performed a systematic analysis of blood DNA methylation profiles from 4,483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1,048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia

Oral tolerance inhibits pulmonary eosinophilia in a cockroach allergen induced model of asthma: a randomized laboratory study

<p>Abstract</p> <p>Background</p> <p>Antigen desensitization through oral tolerance is becoming an increasingly attractive treatment option for allergic diseases. However, the mechanism(s) by which tolerization is achieved remain poorly defined. In this study we endeavored to induce oral tolerance to cockroach allergen (CRA: a complex mixture of insect components) in order to ameliorate asthma-like, allergic pulmonary inflammation.</p> <p>Methods</p> <p>We compared the pulmonary inflammation of mice which had received four CRA feedings prior to intratracheal allergen sensitization and challenge to mice fed PBS on the same time course. Respiratory parameters were assessed by whole body unrestrained plethysmography and mechanical ventilation with forced oscillation. Bronchoalveolar lavage fluid (BAL) and lung homogenate (LH) were assessed for cytokines and chemokines by ELISA. BAL inflammatory cells were also collected and examined by light microscopy.</p> <p>Results</p> <p>CRA feeding prior to allergen sensitization and challenge led to a significant improvement in respiratory health. Airways hyperreactivity measured indirectly via enhanced pause (Penh) was meaningfully reduced in the CRA-fed mice compared to the PBS fed mice (2.3 ± 0.4 vs 3.9 ± 0.6; p = 0.03). Directly measured airways resistance confirmed this trend when comparing the CRA-fed to the PBS-fed animals (2.97 ± 0.98 vs 4.95 ± 1.41). This effect was not due to reduced traditional inflammatory cell chemotactic factors, Th2 or other cytokines and chemokines. The mechanism of improved respiratory health in the tolerized mice was due to significantly reduced eosinophil numbers in the bronchoalveolar lavage fluid (43300 ± 11445 vs 158786 ± 38908; p = 0.007) and eosinophil specific peroxidase activity in the lung homogenate (0.59 ± 0.13 vs 1.19 ± 0.19; p = 0.017). The decreased eosinophilia was likely the result of increased IL-10 in the lung homogenate of the tolerized mice (6320 ± 354 ng/mL vs 5190 ± 404 ng/mL, p = 0.02).</p> <p>Conclusion</p> <p>Our results show that oral tolerization to CRA can improve the respiratory health of experimental mice in a CRA-induced model of asthma-like pulmonary inflammation by reducing pulmonary eosinophilia.</p

Sensitivity and performance of the Advanced LIGO detectors in the third observing run

On April 1st, 2019, the Advanced Laser Interferometer Gravitational-Wave Observatory (aLIGO), joined by the Advanced Virgo detector, began the third observing run, a year-long dedicated search for gravitational radiation. The LIGO detectors have achieved a higher duty cycle and greater sensitivity to gravitational waves than ever before, with LIGO Hanford achieving angle-averaged sensitivity to binary neutron star coalescences to a distance of 111 Mpc, and LIGO Livingston to 134 Mpc with duty factors of 74.6% and 77.0% respectively. The improvement in sensitivity and stability is a result of several upgrades to the detectors, including doubled intracavity power, the addition of an in-vacuum optical parametric oscillator for squeezed-light injection, replacement of core optics and end reaction masses, and installation of acoustic mode dampers. This paper explores the purposes behind these upgrades, and explains to the best of our knowledge the noise currently limiting the sensitivity of each detector.A Buikema … D.D. Brown … A.A. Ciobanu … D.J. Ottaway … P.J. Veitch … et al

Btk regulates macrophage polarization in response to lipopolysaccharide

Bacterial Lipopolysaccharide (LPS) is a strong inducer of inflammation and does so by inducing polarization of macrophages to the classic inflammatory M1 population. Given the role of Btk as a critical signal transducer downstream of TLR4, we investigated its role in M1/M2 induction. In Btk deficient (Btk (−\−)) mice we observed markedly reduced recruitment of M1 macrophages following intraperitoneal administration of LPS. Ex vivo analysis demonstrated an impaired ability of Btk(−/−) macrophages to polarize into M1 macrophages, instead showing enhanced induction of immunosuppressive M2-associated markers in response to M1 polarizing stimuli, a finding accompanied by reduced phosphorylation of STAT1 and enhanced STAT6 phosphorylation. In addition to STAT activation, M1 and M2 polarizing signals modulate the expression of inflammatory genes via differential activation of transcription factors and regulatory proteins, including NF-κB and SHIP1. In keeping with a critical role for Btk in macrophage polarization, we observed reduced levels of NF-κB p65 and Akt phosphorylation, as well as reduced induction of the M1 associated marker iNOS in Btk(−/−) macrophages in response to M1 polarizing stimuli. Additionally enhanced expression of SHIP1, a key negative regulator of macrophage polarisation, was observed in Btk(−/−) macrophages in response to M2 polarizing stimuli. Employing classic models of allergic M2 inflammation, treatment of Btk (−/−) mice with either Schistosoma mansoni eggs or chitin resulted in increased recruitment of M2 macrophages and induction of M2-associated genes. This demonstrates an enhanced M2 skew in the absence of Btk, thus promoting the development of allergic inflammation

Differences between the non-steroidal aromatase inhibitors anastrozole and letrozole – of clinical importance?

Aromatase inhibition is the gold standard for treatment of early and advanced breast cancer in postmenopausal women suffering from an estrogen receptor-positive disease. The currently established group of anti-aromatase compounds comprises two reversible aromatase inhibitors (anastrozole and letrozole) and on the other hand, the irreversible aromatase inactivator exemestane. Although exemestane is the only widely used aromatase inactivator at this stage, physicians very often have to choose between either anastrozole or letrozole in general practice. These third-generation aromatase inhibitors (letrozole/Femara (Novartis Pharmaceuticals, Basel, Switzerland) and anastrozole/Arimidex (AstraZeneca, Pharmaceuticals, Macclesfield, Cheshire, UK)), have recently demonstrated superior efficacy compared with tamoxifen as initial therapy for early breast cancer improving disease-free survival. However, although anastrozole and letrozole belong to the same pharmacological class of agents (triazoles), an increasing body of evidence suggests that these aromatase inhibitors are not equipotent when given in the clinically established doses. Preclinical and clinical evidence indicates distinct pharmacological profiles. Thus, this review focuses on the differences between the non-steroidal aromatase inhibitors allowing physicians to choose between these compounds based on scientific evidence. Although we are waiting for the important results of a still ongoing head-to-head comparison in patients with early breast cancer at high risk for relapse (Femara Anastrozole Clinical Evaluation trial; ‘FACE-trial'), clinicians have to make their choices today. On the basis of available evidence summarised here and until FACE-data become available, letrozole seems to be the best choice for the majority of breast cancer patients whenever a non-steroidal aromatase inhibitor has to be chosen in a clinical setting. The background for this recommendation is discussed in the following chapters

Airway sizes and proportions in children quantified by a video-bronchoscopic technique

Background: A quantitative understanding of airway sizes and proportions and a reference point for comparisons are important to a bronchoscopist. The aims of this study were to measure large airway areas, and define proportions and predictors of airway size in children. Methods: A validated videobronchoscope technique was used to measure in-vivo airway cross-sectional areas (cricoid, right (RMS) and left (LMS) main stem and major lobar bronchi) of 125 children. Airway proportions were calculated as ratios of airways to cricoid areas and to endotracheal tube (ETT) areas. Mann Whitney U, T-tests, and one-way ANOVA were used for comparisons and standard univariate and backwards, stepwise multivariate regression analyses were used to define airway size predictors. Results: Airways size increased progressively with increasing age but proportions remained constant. The LMS was 21% smaller than the RMS. Gender differences in airways' size were not significant in any age group or airway site. Cricoid area related best to body length (BL): cricoid area (mm2) = 26.782 + 0.254*BL (cm) while the RMS and LMS area related best to weight: RMS area (mm2) = 23.938 + 0.394*Wt (kg) and LMS area (mm2) = 20.055 + 0.263*Wt (kg) respectively. Airways to cricoid ratios were larger than airway to ETT ratios (p=0.0001). Conclusions: The cricoid and large airways progressively increase in size but maintain constant proportional relationships to the cricoid across childhood. The cricoid area correlates with body length while the RMS and LMS are best predicted by weight. These data provide for quantitative comparisons of airway lesions