The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy

The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.Portuguese Foundation for Science and Technology (FCT), the strategic funding of UID/BIO/04469/2013-CEB and UID/EQU/00511/2013-LEPABE units. This study was also supported by FCT and the European Community fund FEDER, through Program COMPETE, under the scope of the Projects “DNA mimics” PIC/IC/82815/2007, RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), “BioHealth—Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027 and NORTE-07-0124-FEDER-000025—RL2_ Environment and Health, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. The authors also acknowledge the grant of Susana P. Lopes (SFRH/BPD/95616/2013) and of the COST-Action TD1004: Theragnostics for imaging and therapy

Northern Eurasia Future Initiative (NEFI): facing the challenges and pathways of global change in the 21st century

During the past several decades, the Earth system has changed significantly, especially across Northern Eurasia. Changes in the socio-economic conditions of the larger countries in the region have also resulted in a variety of regional environmental changes that can have global consequences. The Northern Eurasia Future Initiative (NEFI) has been designed as an essential continuation of the Northern Eurasia Earth Science Partnership Initiative (NEESPI), which was launched in 2004. NEESPI sought to elucidate all aspects of ongoing environmental change, to inform societies and, thus, to better prepare societies for future developments. A key principle of NEFI is that these developments must now be secured through science-based strategies co-designed with regional decision makers to lead their societies to prosperity in the face of environmental and institutional challenges. NEESPI scientific research, data, and models have created a solid knowledge base to support the NEFI program. This paper presents the NEFI research vision consensus based on that knowledge. It provides the reader with samples of recent accomplishments in regional studies and formulates new NEFI science questions. To address these questions, nine research foci are identified and their selections are briefly justified. These foci include: warming of the Arctic; changing frequency, pattern, and intensity of extreme and inclement environmental conditions; retreat of the cryosphere; changes in terrestrial water cycles; changes in the biosphere; pressures on land-use; changes in infrastructure; societal actions in response to environmental change; and quantification of Northern Eurasia's role in the global Earth system. Powerful feedbacks between the Earth and human systems in Northern Eurasia (e.g., mega-fires, droughts, depletion of the cryosphere essential for water supply, retreat of sea ice) result from past and current human activities (e.g., large scale water withdrawals, land use and governance change) and potentially restrict or provide new opportunities for future human activities. Therefore, we propose that Integrated Assessment Models are needed as the final stage of global change assessment. The overarching goal of this NEFI modeling effort will enable evaluation of economic decisions in response to changing environmental conditions and justification of mitigation and adaptation efforts

Are mild head injuries as mild as we think? Neurobehavioral concomitants of chronic post-concussion syndrome

BACKGROUND: Mild traumatic brain injury (MTBI) can sometimes lead to persistent postconcussion symptoms. One well accepted hypothesis claims that chronic PCS has a neural origin, and is related to neurobehavioral deficits. But the evidence is not conclusive. In the attempt to characterise chronic MTBI consequences, the present experiment used a group comparison design, which contrasted persons (a) with MTBI and PCS, (b) MTBI without PCS, and (c) matched controls. We predicted that participants who have experienced MTBI but show no signs of PCS would perform similar to controls. At the same time, a subgroup of MTBI participants would show PCS symptoms and only these volunteers would have poorer cognitive performance. Thereby, the performance deficits should be most noticeable in participants with highest PCS severity. METHOD: 38 patients with a single MTBI that had occurred at least 12 month prior to testing, and 38 matched controls, participated in the experiment. A combination of questionnaires and neuropsychological test batteries were used to assess the extent of PCS and related deficits in neurobehavioral performance. RESULTS: 11 out of 38 MTBI participants (29%) were found to suffer from PCS. This subgroup of MTBI patients performed poorly on neuropsychological test batteries. Thereby, a correlation was found between PCS symptom severity and test performance suggesting that participants with more pronounced PCS symptoms performed worse in cognitive tasks. In contrast, MTBI patients with no PCS showed performed similar to matched control. We further found that loss of consciousness, a key criterion for PCS diagnosis, was not predictive of sustained PCS. CONCLUSION: The results support the idea that MTBI can have sustained consequences, and that the subjectively experienced symptoms and difficulties in everyday situations are related to objectively measurable parameters in neurocognitive function

Search for subsolar-mass binaries in the first half of Advanced LIGO's and Advanced Virgo's third observing run

We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2 M⊙ and 1.0 M⊙ in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q ≥ 0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14 yr-1. This implies an upper limit on the merger rate of subsolar binaries in the range [220-24200] Gpc-3 yr-1, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2 M &lt; mPBH &lt; 1.0 M⊙ is fPBH ≡ ΩPBH/ΩDM ≤ 6%. This improves existing constraints on primordial black hole abundance by a factor of ∼3. The other is a dissipative dark matter model, in which fermionic dark matter can collapse and form black holes. The upper limit on the fraction of dark matter black holes depends on the minimum mass of the black holes that can be formed: the most constraining result is obtained at Mmin = 1 M⊙, where fDBH ≡ ΩDBH/ΩDM ≤ 0.003%. These are the first constraints placed on dissipative dark models by subsolar-mass analyses.<br/

Search for gravitational-wave transients associated with magnetar bursts in Advanced LIGO and Advanced Virgo data from the third observing run

Gravitational waves are expected to be produced from neutron staroscillations associated with magnetar giant flares and short bursts. We presentthe results of a search for short-duration (milliseconds to seconds) andlong-duration ($\sim$ 100 s) transient gravitational waves from 13 magnetarshort bursts observed during Advanced LIGO, Advanced Virgo and KAGRA's thirdobservation run. These 13 bursts come from two magnetars, SGR 1935$+$2154 andSwift J1818.0$-$1607. We also include three other electromagnetic burst eventsdetected by Fermi GBM which were identified as likely coming from one or moremagnetars, but they have no association with a known magnetar. No magnetargiant flares were detected during the analysis period. We find no evidence ofgravitational waves associated with any of these 16 bursts. We place upperbounds on the root-sum-square of the integrated gravitational-wave strain thatreach $2.2 \times 10^{-23}$ $/\sqrt{\text{Hz}}$ at 100 Hz for theshort-duration search and $8.7 \times 10^{-23}$ $/\sqrt{\text{Hz}}$ at $450$ Hzfor the long-duration search, given a detection efficiency of 50%. For aringdown signal at 1590 Hz targeted by the short-duration search the limit isset to $1.8 \times 10^{-22}$ $/\sqrt{\text{Hz}}$. Using the estimated distanceto each magnetar, we derive upper bounds on the emitted gravitational-waveenergy of $3.2 \times 10^{43}$ erg ($7.3 \times 10^{43}$ erg) for SGR1935$+$2154 and $8.2 \times 10^{42}$ erg ($2.8 \times 10^{43}$ erg) for SwiftJ1818.0$-$1607, for the short-duration (long-duration) search. Assumingisotropic emission of electromagnetic radiation of the burst fluences, weconstrain the ratio of gravitational-wave energy to electromagnetic energy forbursts from SGR 1935$+$2154 with available fluence information. The lowest ofthese ratios is $3 \times 10^3$.<br

Search for gravitational waves from Scorpius X-1 with a hidden Markov model in O3 LIGO data

Results are presented for a semi-coherent search for continuous gravitational waves from the low-mass X-ray binary Scorpius X-1, using a hidden Markov model (HMM) to allow for spin wandering. This search improves on previous HMM-based searches of Laser Interferometer Gravitational-wave Observatory (LIGO) data by including the orbital period in the search template grid, and by analyzing data from the latest (third) observing run (O3). In the frequency range searched, from 60 to 500 Hz, we find no evidence of gravitational radiation. This is the most sensitive search for Scorpius X-1 using a HMM to date. For the most sensitive sub-band, starting at $256.06$Hz, we report an upper limit on gravitational wave strain (at $95 \%$ confidence) of $h_{0}^{95\%}=6.16\times10^{-26}$, assuming the orbital inclination angle takes its electromagnetically restricted value $\iota=44^{\circ}$. The upper limits on gravitational wave strain reported here are on average a factor of $\sim 3$ lower than in the O2 HMM search. This is the first Scorpius X-1 HMM search with upper limits that reach below the indirect torque-balance limit for certain sub-bands, assuming $\iota=44^{\circ}$

Search for subsolar-mass black hole binaries in the second part of Advanced LIGO's and Advanced Virgo's third observing run

We describe a search for gravitational waves from compact binaries with at least one component with mass 0.2 $M_\odot$ -- $1.0 M_\odot$ and mass ratio $q \geq 0.1$ in Advanced LIGO and Advanced Virgo data collected between 1 November 2019, 15:00 UTC and 27 March 2020, 17:00 UTC. No signals were detected. The most significant candidate has a false alarm rate of 0.2 $\mathrm{yr}^{-1}$. We estimate the sensitivity of our search over the entirety of Advanced LIGO's and Advanced Virgo's third observing run, and present the most stringent limits to date on the merger rate of binary black holes with at least one subsolar-mass component. We use the upper limits to constrain two fiducial scenarios that could produce subsolar-mass black holes: primordial black holes (PBH) and a model of dissipative dark matter. The PBH model uses recent prescriptions for the merger rate of PBH binaries that include a rate suppression factor to effectively account for PBH early binary disruptions. If the PBHs are monochromatically distributed, we can exclude a dark matter fraction in PBHs $f_\mathrm{PBH} \gtrsim 0.6$ (at 90% confidence) in the probed subsolar-mass range. However, if we allow for broad PBH mass distributions we are unable to rule out $f_\mathrm{PBH} = 1$. For the dissipative model, where the dark matter has chemistry that allows a small fraction to cool and collapse into black holes, we find an upper bound $f_{\mathrm{DBH}} < 10^{-5}$ on the fraction of atomic dark matter collapsed into black holes.Comment: https://dcc.ligo.org/P220013

GWTC-3: Compact Binary Coalescences Observed by LIGO and Virgo During the Second Part of the Third Observing Run

The third Gravitational-wave Transient Catalog (GWTC-3) describes signals detected with Advanced LIGO and Advanced Virgo up to the end of their third observing run. Updating the previous GWTC-2.1, we present candidate gravitational waves from compact binary coalescences during the second half of the third observing run (O3b) between 1 November 2019, 15:00 UTC and 27 March 2020, 17:00 UTC. There are 35 compact binary coalescence candidates identified by at least one of our search algorithms with a probability of astrophysical origin $p_\mathrm{astro} > 0.5$. Of these, 18 were previously reported as low-latency public alerts, and 17 are reported here for the first time. Based upon estimates for the component masses, our O3b candidates with $p_\mathrm{astro} > 0.5$ are consistent with gravitational-wave signals from binary black holes or neutron star-black hole binaries, and we identify none from binary neutron stars. However, from the gravitational-wave data alone, we are not able to measure matter effects that distinguish whether the binary components are neutron stars or black holes. The range of inferred component masses is similar to that found with previous catalogs, but the O3b candidates include the first confident observations of neutron star-black hole binaries. Including the 35 candidates from O3b in addition to those from GWTC-2.1, GWTC-3 contains 90 candidates found by our analysis with $p_\mathrm{astro} > 0.5$ across the first three observing runs. These observations of compact binary coalescences present an unprecedented view of the properties of black holes and neutron stars