Alpha-1 Antitrypsin is Markedly Decreased Following Pulmonary F. tularensis Challenge

Neutrophils form the first line of defense during infection and are indispensable in this function. The neutrophil elastase is a key effector molecule of the innate immune system with potent antimicrobial activity against Gram-negative bacteria, spirochaetes, and fungi. However, the release of neutrophil elastase during bacterial infection must be checked otherwise its release in the extracellular milieu will result in damage to surrounding tissues. Alpha-1 antitrypsin is a small glycoprotein clade A serpine serine protease inhibitor and has been shown to increase in humans following bacterial and viral infection. Francisella tularensis is a Gram-negative facultative intracellular bacterium and the causative agent of tularemia. Type A strains are the most virulent with an infectious dose as low as 10 colony forming units and a mortality rate of 30–60% among untreated cases of pneumonic tularemia. We report here significant reduction of this major inhibitor of the neutrophil elastase in plasma of F. tularensis LVS and F. tularensis (type A) SCHU S4 infected animals following pulmonary challenge. Associated with an imbalance of protease–antiprotease function at the alveolar level in lungs of infected animals, increased elastase activity was observed in lung lavage fluids accompanied by decrease lung function, i.e., loss of lung elastance with concomitant increase of pulmonary hysteresivity. Consistent with a competent acute phase response following F. tularensis LVS and F. tularensis (type A) SCHU S4 pulmonary challenge and proposed up-regulation of plasma haptoglobin during the course of the acute phase reaction, haptoglobin was observed significantly increased. These data suggest that unchecked neutrophil serine protease activity may arise from F. tularensis targeted reduction of plasma α(1)-antitrysin promoting lung tissue damage facilitating increased dissemination of this bacterium in infected animals

ABA Criminal Justice Section Task Force on College Due Process Rights and Victim Protections: Recommendations for Colleges and Universities in Resolving Allegations of Campus Sexual Misconduct

The Executive Committee of the ABA Criminal Justice Section commissioned the Task Force on College Due Process Rights and Victim Protections in November 2016. Immediately after, extensive efforts were made to find members that represented all interested parties: victims, the accused, universities, other stakeholders, and national experts. The Task Force was fully constituted in the winter of 2017, and it ended up including two voting members who were originally liaisons from the ABA Commission on Domestic and Sexual Violence and the ABA Section of Civil Rights and Social Justice. This elevation was made in recognition of their significant contributions

Black Hole Spectroscopy: Testing General Relativity through Gravitational Wave Observations

Assuming that general relativity is the correct theory of gravity in the strong field limit, can gravitational wave observations distinguish between black hole and other compact object sources? Alternatively, can gravitational wave observations provide a test of one of the fundamental predictions of general relativity? Here we describe a definitive test of the hypothesis that observations of damped, sinusoidal gravitational waves originated from a black hole or, alternatively, that nature respects the general relativistic no-hair theorem. For astrophysical black holes, which have a negligible charge-to-mass ratio, the black hole quasi-normal mode spectrum is characterized entirely by the black hole mass and angular momentum and is unique to black holes. In a different theory of gravity, or if the observed radiation arises from a different source (e.g., a neutron star, strange matter or boson star), the spectrum will be inconsistent with that predicted for general relativistic black holes. We give a statistical characterization of the consistency between the noisy observation and the theoretical predictions of general relativity, together with a numerical example.Comment: 19 pages, 7 figure

COrE (Cosmic Origins Explorer) A White Paper

COrE (Cosmic Origins Explorer) is a fourth-generation full-sky, microwave-band satellite recently proposed to ESA within Cosmic Vision 2015-2025. COrE will provide maps of the microwave sky in polarization and temperature in 15 frequency bands, ranging from 45 GHz to 795 GHz, with an angular resolution ranging from 23 arcmin (45 GHz) and 1.3 arcmin (795 GHz) and sensitivities roughly 10 to 30 times better than PLANCK (depending on the frequency channel). The COrE mission will lead to breakthrough science in a wide range of areas, ranging from primordial cosmology to galactic and extragalactic science. COrE is designed to detect the primordial gravitational waves generated during the epoch of cosmic inflation at more than $3\sigma$ for $r=(T/S)>=10^{-3}$. It will also measure the CMB gravitational lensing deflection power spectrum to the cosmic variance limit on all linear scales, allowing us to probe absolute neutrino masses better than laboratory experiments and down to plausible values suggested by the neutrino oscillation data. COrE will also search for primordial non-Gaussianity with significant improvements over Planck in its ability to constrain the shape (and amplitude) of non-Gaussianity. In the areas of galactic and extragalactic science, in its highest frequency channels COrE will provide maps of the galactic polarized dust emission allowing us to map the galactic magnetic field in areas of diffuse emission not otherwise accessible to probe the initial conditions for star formation. COrE will also map the galactic synchrotron emission thirty times better than PLANCK. This White Paper reviews the COrE science program, our simulations on foreground subtraction, and the proposed instrumental configuration.Comment: 90 pages Latex 15 figures (revised 28 April 2011, references added, minor errors corrected

The legal and ethical framework governing Body Donation in Europe-1st update on current practice

Previously, we have reported on the legal and ethical aspects and current practice of body donation in several European countries, reflecting cultural and religious variations as well as different legal and constitutional frameworks. We have also established good practice in body donation. Here we shall further extend the legal and ethical frameworks in place and also focus on novelties in the law and different directives. Of particular interest are points that address the commercialization of human bodies and body parts and weaknesses in the legal directives. Therefore, it is important to define what is ethical and what needs to be considered unethical in body donation and the subsequent utilisation of human bodies for teaching and research.peer-reviewe

Outbreak of Cyclosporiasis Associated with Imported Raspberries, Philadelphia, Pennsylvania, 2000

An outbreak of cyclosporiasis occurred in attendees of a wedding reception held in Philadelphia, Pennsylvania, on June 10, 2000. In a retrospective cohort study, 54 (68.4%) of the 79 interviewed guests and members of the wedding party met the case definition. The wedding cake, which had a cream filling that included raspberries, was the food item most strongly associated with illness (multivariate relative risk, 5.9; 95% confidence interval, 3.6 to 10.5). Leftover cake was positive for Cyclospora DNA by polymerase chain reaction analyses. Sequencing of the amplified fragments confirmed that the organism was Cyclospora cayetanensis. The year 2000 was the fifth year since 1995 that outbreaks of cyclosporiasis definitely or probably associated with Guatemalan raspberries have occurred in the spring in North America. Additionally, this is the second documented U.S. outbreak, and the first associated with raspberries, for which Cyclospora has been detected in the epidemiologically implicated food item

Planck intermediate results. XXIX. All-sky dust modelling with Planck, IRAS, and WISE observations

We present all-sky modelling of the high resolution Planck, IRAS, and WISE infrared (IR) observations using the physical dust model presented by Draine and Li in 2007 (DL). We study the performance and results of this model, and discuss implications for future dust modelling. The present work extends the DL dust modelling carried out on nearby galaxies using Herschel and Spitzer data to Galactic dust emission. We employ the DL dust model to generate maps of the dust mass surface density, the optical extinction Av, and the starlight intensity parametrized by Umin. The DL model reproduces the observed spectral energy distribution (SED) satisfactorily over most of the sky, with small deviations in the inner Galactic disk and in low ecliptic latitude areas. We compare the DL optical extinction Av for the diffuse interstellar medium with optical estimates for 2 10^5 quasi-stellar objects (QSOs) observed in the Sloan digital sky survey. The DL Av estimates are larger than those determined towards QSOs by a factor of about 2, which depends on Umin. The DL fitting parameter Umin, effectively determined by the wavelength where the SED peaks, appears to trace variations in the far-IR opacity of the dust grains per unit Av, and not only in the starlight intensity. To circumvent the model deficiency, we propose an empirical renormalization of the DL Av estimate, dependent of Umin, which compensates for the systematic differences found with QSO observations. This renormalization also brings into agreement the DL Av estimates with those derived for molecular clouds from the near-IR colours of stars in the 2 micron all sky survey. The DL model and the QSOs data are used to compress the spectral information in the Planck and IRAS observations for the diffuse ISM to a family of 20 SEDs normalized per Av, parameterized by Umin, which may be used to test and empirically calibrate dust models.Comment: Final version that has appeared in A&

Establishing a Primary Care Alliance for Conducting Cancer Prevention Clinical Research at Community Sites

In September 2020, the National Cancer Institute convened the first PARTNRS Workshop as an initiative to forge partnerships between oncologists, primary care professionals, and non-oncology specialists for promoting patient accrual into cancer prevention trials. This effort is aimed at bringing about more effective accrual methods to generate decisive outcomes in cancer prevention research. The workshop convened to inspire solutions to challenges encountered during the development and implementation of cancer prevention trials. Ultimately, strategies suggested for protocol development might enhance integration of these trials into community settings where a diversity of patients might be accrued. Research Bases (cancer research organizations that develop protocols) could encourage more involvement of primary care professionals, relevant prevention specialists, and patient representatives with protocol development beginning at the concept level to improve adoptability of the trials within community facilities, and consider various incentives to primary care professionals (i.e., remuneration). Principal investigators serving as liaisons for the NCORP affiliates and sub-affiliates, might produce and maintain Prevention Research Champions lists of PCPs and non-oncology specialists relevant in prevention research who can attract health professionals to consider incorporating prevention research into their practices. Finally, patient advocates and community health providers might convince patients of the benefits of trial-participation and encourage shared-decision making

Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging