Evidence-Based Assessment of Congenital Heart Disease Genes to Enable Returning Results in a Genomic Study

Background: Congenital heart disease (CHD) is the most common major congenital anomaly and causes significant morbidity and mortality. Epidemiologic evidence supports a role of genetics in the development of CHD. Genetic diagnoses can inform prognosis and clinical management. However, genetic testing is not standardized among individuals with CHD. We sought to develop a list of validated CHD genes using established methods and to evaluate the process of returning genetic results to research participants in a large genomic study. Methods: Two-hundred ninety-five candidate CHD genes were evaluated using a ClinGen framework. Sequence and copy number variants involving genes in the CHD gene list were analyzed in Pediatric Cardiac Genomics Consortium participants. Pathogenic/likely pathogenic results were confirmed on a new sample in a clinical laboratory improvement amendments-certified laboratory and disclosed to eligible participants. Adult probands and parents of probands who received results were asked to complete a post-disclosure survey. Results: A total of 99 genes had a strong or definitive clinical validity classification. Diagnostic yields for copy number variants and exome sequencing were 1.8% and 3.8%, respectively. Thirty-one probands completed clinical laboratory improvement amendments-confirmation and received results. Participants who completed postdisclosure surveys reported high personal utility and no decision regret after receiving genetic results. Conclusions: The application of ClinGen criteria to CHD candidate genes yielded a list that can be used to interpret clinical genetic testing for CHD. Applying this gene list to one of the largest research cohorts of CHD participants provides a lower bound for the yield of genetic testing in CHD

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Seismic stratigraphy of the central South China Sea basin and implications for neotectonics

Coring/logging data and physical property measurements from International Ocean Discovery Program Expedition 349 are integrated with, and correlated to, reflection seismic data to map seismic sequence boundaries and facies of the central basin and neighboring regions of the South China Sea. First-order sequence boundaries are interpreted, which are Oligocene/Miocene, middle Miocene/late Miocene, Miocene/Pliocene, and Pliocene/Pleistocene boundaries. A characteristic early Pleistocene strong reflector is also identified, which marks the top of extensive carbonate-rich deposition in the southern East and Southwest Subbasins. The fossil spreading ridge and the boundary between the East and Southwest Subbasins acted as major sedimentary barriers, across which seismic facies changes sharply and cannot be easily correlated. The sharp seismic facies change along the Miocene-Pliocene boundary indicates that a dramatic regional tectonostratigraphic event occurred at about 5 Ma, coeval with the onsets of uplift of Taiwan and accelerated subsidence and transgression in the northern margin. The depocenter or the area of the highest sedimentation rate switched from the northern East Subbasin during the Miocene to the Southwest Subbasin and the area close to the fossil ridge in the southern East Subbasin in the Pleistocene. The most active faulting and vertical uplifting now occur in the southern East Subbasin, caused most likely by the active and fastest subduction/obduction in the southern segment of the Manila Trench and the collision between the northeast Palawan and the Luzon arc. Timing of magmatic intrusions and seamounts constrained by seismic stratigraphy in the central basin varies and does not show temporal pulsing in their activities.Keywords: South China Sea, Neotectonism, Core-well-seismic integration, Seismic facies, Seismic stratigraphy, IODP Expedition 34

Ages and magnetic structures of the South China Sea constrained by deep tow magnetic surveys and IODP Expedition 349

Combined analyses of deep tow magnetic anomalies and International Ocean Discovery Program Expedition 349 cores show that initial seafloor spreading started around 33 Ma in the northeastern South China Sea (SCS), but varied slightly by 1-2 Myr along the northern continent-ocean boundary (COB). A southward ridge jump of ∼20 km occurred around 23.6 Ma in the East Subbasin; this timing also slightly varied along the ridge and was coeval to the onset of seafloor spreading in the Southwest Subbasin, which propagated for about 400 km southwestward from ∼23.6 to ∼21.5 Ma. The terminal age of seafloor spreading is ∼15 Ma in the East Subbasin and ∼16 Ma in the Southwest Subbasin. The full spreading rate in the East Subbasin varied largely from ∼20 to ∼80 km/Myr, but mostly decreased with time except for the period between ∼26.0 Ma and the ridge jump (∼23.6 Ma), within which the rate was the fastest at ∼70 km/Myr on average. The spreading rates are not correlated, in most cases, to magnetic anomaly amplitudes that reflect basement magnetization contrasts. Shipboard magnetic measurements reveal at least one magnetic reversal in the top 100 m of basaltic layers, in addition to large vertical intensity variations. These complexities are caused by late-stage lava flows that are magnetized in a different polarity from the primary basaltic layer emplaced during the main phase of crustal accretion. Deep tow magnetic modeling also reveals this smearing in basement magnetizations by incorporating a contamination coefficient of 0.5, which partly alleviates the problem of assuming a magnetic blocking model of constant thickness and uniform magnetization. The primary contribution to magnetic anomalies of the SCS is not in the top 100 m of the igneous basement.Keywords: Crustal evolution, Deep tow magnetic survey, South China Sea tectonics, International Ocean Discovery Program Expedition 349, Magnetic anomaly, ModelingKeywords: Crustal evolution, Deep tow magnetic survey, South China Sea tectonics, International Ocean Discovery Program Expedition 349, Magnetic anomaly, Modelin

The US Program in Ground-Based Gravitational Wave Science: Contribution from the LIGO Laboratory

Recent gravitational-wave observations from the LIGO and Virgo observatories have brought a sense of great excitement to scientists and citizens the world over. Since September 2015,10 binary black hole coalescences and one binary neutron star coalescence have been observed. They have provided remarkable, revolutionary insight into the "gravitational Universe" and have greatly extended the field of multi-messenger astronomy. At present, Advanced LIGO can see binary black hole coalescences out to redshift 0.6 and binary neutron star coalescences to redshift 0.05. This probes only a very small fraction of the volume of the observable Universe. However, current technologies can be extended to construct "3rd Generation" (3G) gravitational-wave observatories that would extend our reach to the very edge of the observable Universe. The event rates over such a large volume would be in the hundreds of thousands per year (i.e. tens per hour). Such 3G detectors would have a 10-fold improvement in strain sensitivity over the current generation of instruments, yielding signal-to-noise ratios of 1000 for events like those already seen. Several concepts are being studied for which engineering studies and reliable cost estimates will be developed in the next 5 years

EVALITA Evaluation of NLP and Speech Tools for Italian - December 17th, 2020

Welcome to EVALITA 2020! EVALITA is the evaluation campaign of Natural Language Processing and Speech Tools for Italian. EVALITA is an initiative of the Italian Association for Computational Linguistics (AILC, http://www.ai-lc.it) and it is endorsed by the Italian Association for Artificial Intelligence (AIxIA, http://www.aixia.it) and the Italian Association for Speech Sciences (AISV, http://www.aisv.it)

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia