Innovations in research and clinical care using patient-generated health data.

Patient-generated health data (PGHD), or health-related data gathered from patients to help address a health concern, are used increasingly in oncology to make regulatory decisions and evaluate quality of care. PGHD include self-reported health and treatment histories, patient-reported outcomes (PROs), and biometric sensor data. Advances in wireless technology, smartphones, and the Internet of Things have facilitated new ways to collect PGHD during clinic visits and in daily life. The goal of the current review was to provide an overview of the current clinical, regulatory, technological, and analytic landscape as it relates to PGHD in oncology research and care. The review begins with a rationale for PGHD as described by the US Food and Drug Administration, the Institute of Medicine, and other regulatory and scientific organizations. The evidence base for clinic-based and remote symptom monitoring using PGHD is described, with an emphasis on PROs. An overview is presented of current approaches to digital phenotyping or device-based, real-time assessment of biometric, behavioral, self-report, and performance data. Analytic opportunities regarding PGHD are envisioned in the context of big data and artificial intelligence in medicine. Finally, challenges and solutions for the integration of PGHD into clinical care are presented. The challenges include electronic medical record integration of PROs and biometric data, analysis of large and complex biometric data sets, and potential clinic workflow redesign. In addition, there is currently more limited evidence for the use of biometric data relative to PROs. Despite these challenges, the potential benefits of PGHD make them increasingly likely to be integrated into oncology research and clinical care.

Neoproterozoic glacial origin of the Great Unconformity.

The Great Unconformity, a profound gap in Earth's stratigraphic record often evident below the base of the Cambrian system, has remained among the most enigmatic field observations in Earth science for over a century. While long associated directly or indirectly with the occurrence of the earliest complex animal fossils, a conclusive explanation for the formation and global extent of the Great Unconformity has remained elusive. Here we show that the Great Unconformity is associated with a set of large global oxygen and hafnium isotope excursions in magmatic zircon that suggest a late Neoproterozoic crustal erosion and sediment subduction event of unprecedented scale. These excursions, the Great Unconformity, preservational irregularities in the terrestrial bolide impact record, and the first-order pattern of Phanerozoic sedimentation can together be explained by spatially heterogeneous Neoproterozoic glacial erosion totaling a global average of 3-5 vertical kilometers, along with the subsequent thermal and isostatic consequences of this erosion for global continental freeboard.

How Many People Use Sign Language? A National Health Survey-Based Estimate.

An empirical estimate of how many deaf and hard-of-hearing persons use sign language in the USA was obtained a half-century ago, but no study has measured how many people sign regardless of deafness. This study estimated the number of deaf, hard-of-hearing, and hearing adult signers. Concatenation of the 2010-2018 National Health Interview Surveys was required to provide sufficient sample size. Unadjusted and age-by-sex-adjusted sign language use prevalence across the range of hearing acuity was estimated. Adult sign language use was substantial (2.80%), with its rate of use greater for women than men and younger adults than older adults. As a group, deaf respondents had a far higher rate of sign language use than any other hearing acuity group. This study provides the first empirical estimate of adult sign language use generally, and the first update of any sign language use estimate in a half-century.

Patient-reported outcomes: using ESAS to screen for anemia.

PURPOSE: Patient perspectives of their symptom burden provide valuable data to clinicians. We have investigated the Edmonton Symptom Assessment Scale (ESAS) extensively in our radiation oncology and supportive care clinics. We were interested in examining whether ESAS data could correlate with anemia. METHODS: Our clinics have used a modified ESAS since 2015; patients now input data directly into the electronic medical record using a tablet interface. Of 9813 patients providing ESAS reports, we retrieved hemoglobin (Hb) data from 8304. Of these, 1351 patients had both performed on the same day. Anemia existed if Hb was < 13.0 g/L (man) or < 12 g/L (woman). RESULTS: When self-reported scores for both tiredness and shortness of breath were 7 and above, the positive predictive value (PPV) for anemia was 80%, and specificity was 97.6%. Corresponding sensitivity was 8.2% and accuracy was 48.9%. This 2-item model could be a valuable screening tool for lack of anemia in cancer patients in the outpatient setting: if patients rate both these ESAS items < 7, there exists < 3% false positive risk. An expanded 5-item model adding lack of appetite, pain, and bone marrow primary site increased sensitivity and accuracy at the expense of specificity and PPV. We consider this less clinically functional than the two-item screen. CONCLUSION: This is one of the first reports of PRO data screening for a clinical sign, in this case, anemia. Predicting freedom from anemia is feasible using 2 ESAS survey questions: tiredness and shortness of breath.

Supercontinent cycles and the calculation of absolute palaeolongitude in deep time.

Traditional models of the supercontinent cycle predict that the next supercontinent--'Amasia'--will form either where Pangaea rifted (the 'introversion' model) or on the opposite side of the world (the 'extroversion' models). Here, by contrast, we develop an 'orthoversion' model whereby a succeeding supercontinent forms 90° away, within the great circle of subduction encircling its relict predecessor. A supercontinent aggregates over a mantle downwelling but then influences global-scale mantle convection to create an upwelling under the landmass. We calculate the minimum moment of inertia about which oscillatory true polar wander occurs owing to the prolate shape of the non-hydrostatic Earth. By fitting great circles to each supercontinent's true polar wander legacy, we determine that the arc distances between successive supercontinent centres (the axes of the respective minimum moments of inertia) are 88° for Nuna to Rodinia and 87° for Rodinia to Pangaea--as predicted by the orthoversion model. Supercontinent centres can be located back into Precambrian time, providing fixed points for the calculation of absolute palaeolongitude over billion-year timescales. Palaeogeographic reconstructions additionally constrained in palaeolongitude will provide increasingly accurate estimates of ancient plate motions and palaeobiogeographic affinities.

Completing the loop of the Late Jurassic-Early Cretaceous true polar wander event.

The reorientation of Earth through rotation of its solid shell relative to its spin axis is known as True polar wander (TPW). It is well-documented at present, but the occurrence of TPW in the geologic past remains controversial. This is especially so for Late Jurassic TPW, where the veracity and dynamics of a particularly large shift remain debated. Here, we report three palaeomagnetic poles at 153, 147, and 141 million years (Myr) ago from the North China craton that document an ~ 12° southward shift in palaeolatitude from 155-147 Myr ago (~1.5° Myr-1), immediately followed by an ~ 10° northward displacement between 147-141 Myr ago (~1.6° Myr-1). Our data support a large round-trip TPW oscillation in the past 200 Myr and we suggest that the shifting back-and-forth of the continents may contribute to the biota evolution in East Asia and the global Jurassic-Cretaceous extinction and endemism.

A Great late Ediacaran ice age.

The emergence of the Ediacara biota soon after the Gaskiers glaciation ca. 580 million years ago (Ma) implies a possible glacial fuse for the evolution of animals. However, the timing of Ediacaran glaciation remains controversial because of poor age constraints on the ∼30 Ediacaran glacial deposits known worldwide. In addition, paleomagnetic constraints and a lack of convincing Snowball-like cap carbonates indicate that Ediacaran glaciations likely did not occur at low latitudes. Thus, reconciling the global occurrences without global glaciation remains a paradox. Here, we report that the large amplitude, globally synchronous ca. 571-562 Ma Shuram carbon isotope excursion occurs below the Ediacaran Hankalchough glacial deposit in Tarim, confirming a post-Shuram glaciation. Leveraging paleomagnetic evidence for a ∼90° reorientation of all continents due to true polar wander, and a non-Snowball condition that rules out low-latitude glaciations, we use paleogeographic reconstructions to further constrain glacial ages. Our results depict a 'Great Ediacaran Glaciation' occurring diachronously but continuously from ca. 580-560 Ma as different continents migrated through polar-temperate latitudes. The succession of radiation, turnover and extinction of the Ediacara biota strongly reflects glacial-deglacial dynamics.

Volcanic phosphorus supply boosted Mesozoic terrestrial biotas in northern China.

The Mesozoic terrestrial Jehol Biota of northern China exceeds the biomass and biodiversity of contemporaneous Lagerstätten. From 135 to 120 Ma, biotic radiation may have responded to the peak destruction of the North China Craton. However, the direct mechanistic link between geological and biological evolution is unclear. Phosphorus (P), a bio-essential nutrient, can be supplied by weathering of volcanics in terrestrial ecosystems. The middle-late Mesozoic volcanic-sedimentary sequences of northern China are amazingly rich in terrestrial organisms. Here we demonstrate episodic increases in P delivery, biological productivity, and species abundance in these strata to reveal the coevolution of volcanism and terrestrial biotas. A massive P supply from the weathering of voluminous volcanic products of craton destruction thus supported a terrestrial environment conducive to the high prosperity of the Jehol Biota. During the nascent stage of craton destruction, such volcanic-biotic coupling can also account for the preceding Yanliao Biota with relatively fewer fossils.

No evidence of supracrustal recycling in Si-O isotopes of Earth's oldest rocks 4 Ga ago.

Identifying the oldest evidence for the recycling of hydrated crust into magma on Earth is important because it is most effectively achieved by subduction. However, given the sparse geological record of early Earth, the timing of first supracrustal recycling is controversial. Silicon and oxygen isotopes have been used as indicators of crustal evolution on Archean igneous rocks and minerals to trace supracrustal recycling but with variable results. We present Si-O isotopes of Earth's oldest rocks [4.0 billion years ago (Ga)] from the Acasta Gneiss Complex, northwest Canada, obtained using multiple techniques applied to zircon, quartz, and whole rock samples. Undisturbed zircon is considered the most reliable recorder of primary Si signatures. By combining reliable Si isotope data from the Acasta samples with filtered data from Archean rocks globally, we observe that widespread evidence for a heavy Si signature is recorded since 3.8 Ga, marking the earliest record of surface silicon recycling.

Surges in volcanic activity on the Moon about two billion years ago.

The history of mare volcanism critically informs the thermal evolution of the Moon. However, young volcanic eruptions are poorly constrained by remote observations and limited samples, hindering an understanding of mare eruption flux over time. The Chang'e-5 mission returned the youngest lunar basalts thus far, offering a window into the Moon's late-stage evolution. Here, we investigate the mineralogy and geochemistry of 42 olivine and pyroxene crystals from the Chang'e-5 basalts. We find that almost all of them are normally zoned, suggesting limited magma recharge or shallow-level assimilation. Most olivine grains record a short timescale of cooling. Thermal modeling used to estimate the thickness and volume of the volcanism sampled by Chang'e-5 reveals enhanced magmatic flux ~2 billion years ago, suggesting that while overall lunar volcanic activity may decrease over time, episodic eruptions at the final stage could exhibit above average eruptive fluxes, thus revising models of lunar thermal evolution.

Large-scale academic achievement testing of deaf and hard-of-hearing students: past, present, and future.

The first large-scale, nationwide academic achievement testing program using Stanford Achievement Test (Stanford) for deaf and hard-of-hearing children in the United States started in 1969. Over the past three decades, the Stanford has served as a benchmark in the field of deaf education for assessing student academic achievement. However, the validity and reliability of using the Stanford for this special student population still require extensive scrutiny. Recent shifts in educational policy environment, which require that schools enable all children to achieve proficiency through accountability testing, warrants a close examination of the adequacy and relevance of the current large-scale testing of deaf and hard-of-hearing students. This study has three objectives: (a) it will summarize the historical data over the last three decades to indicate trends in academic achievement for this special population, (b) it will analyze the current federal laws and regulations related to educational testing and special education, thereby identifying gaps between policy and practice in the field, especially identifying the limitations of current testing programs in assessing what deaf and hard-of-hearing students know, and (c) it will offer some insights and suggestions for future testing programs for deaf and hard-of-hearing students.

Dichotomy in crustal melting on early Mars inferred from antipodal effect.

The Martian crustal dichotomy (MCD) between the southern highlands and the northern lowlands is the planet's most ancient crustal structure, but its origins and evolution remain enigmatic. Understanding of the MCD comes largely from present-day and shallow crustal constraints. Lacking ancient and deeper constraints, hypotheses for the origin of the MCD range from an early giant impact, partial melting from sustained mantle convection, or some combination. We investigate with seismological modeling the best-preserved case of the "antipodal effect"-energy from an impact that concentrates and induces uplift and fracturing promoting volcanism at its antipode-the Hellas crater and the Alba Patera volcano on Mars. The volcano is latitudinally offset âˆ¼2° (∼119 km) from the expected antipode, and we explore whether the MCD can explain this deflection. Variations across the MCD in topography, thickness, and composition have only minor effects. Simulations capable of sufficiently decelerating southern surface waves require the presence of 2%-5% more partial melt in the southern highlands. As the age of impact ca. 4 billion years ago post-dates the formation of the MCD, our partial melting results thus imply that, with or without an early giant impact, the MCD was modified by mantle convection in order to supply enough heat for crustal melts for several hundreds of millions of years after Mars formation.

Evolving mantle convection from bottom up to top down.

When it comes to convection, what goes up must come down. Or is it, what goes down must come up? The truth is it depends. Although convection must be mass balanced, there is no reason that it must be force balanced: the positive and negative buoyancy forces driving convection up and down, respectively, do not necessarily need to be balanced. The balance, or imbalance, all depends on the top and bottom boundary layers. Thus, convection in Earth's mantle depends on the temperature differences across the core-mantle boundary below and the lithosphere-asthenosphere boundary above. Convective asymmetry predominated by positive buoyancy, or bottom-up convection, would be driven by plume ascent, whereas if it were predominated by negative buoyancy, or top-down convection, it would be driven by plate subduction. Symmetric convection would balance plume ascent and plate subduction. Is mantle convection on Earth balanced, dominantly top down or bottom up, or time dependent?

Barium content of Archaean continental crust reveals the onset of subduction was not global.

Earth's earliest continental crust is dominated by tonalite-trondhjemite-granodiorite (TTG) suites, making these rocks key to unlocking the global geodynamic regime operating during the Archaean (4.0-2.5 billion years ago [Ga]). The tectonic setting of TTG magmatism is controversial, with hypotheses arguing both for and against subduction. Here we conduct petrological modeling over a range of pressure-temperature conditions relevant to the Archaean geothermal gradient. Using an average enriched Archaean basaltic source composition, we predict Ba concentrations in TTG suites, which is difficult to increase after magma generated in the source. The results indicate only low geothermal gradients corresponding to hot subduction zones produce Ba-rich TTG, thus Ba represents a proxy for the onset of subduction. We then identify statistically significant increases in the Ba contents of TTG suites worldwide as recording the diachronous onset of subduction from regional at 4 Ga to globally complete sometime after 2.7 Ga.

Ordovician-Silurian true polar wander as a mechanism for severe glaciation and mass extinction.

The Ordovician-Silurian transition experienced severe, but enigmatic, glaciation, as well as a paradoxical combination of mass extinction and species origination. Here we report a large and fast true polar wander (TPW) event that occurred 450-440 million years ago based on palaeomagnetic data from South China and compiled reliable palaeopoles from all major continents. Collectively, a ~50˚ wholesale rotation with maximum continental speeds of ~55 cm yr-1 is demonstrated. Multiple isolated continents moving rapidly, synchronously, and unidirectionally is less consistent with and plausible for relative plate motions than TPW. Palaeogeographic reconstructions constrained by TPW controlling for palaeolongitude explain the timing and migration of glacial centers across Gondwana, as well as the protracted end-Ordovician mass extinction. The global quadrature pattern of latitude change during TPW further explains why the extinction was accompanied by elevated levels of origination as some continents migrated into or remained in the amenable tropics.

Archean cratonic mantle recycled at a mid-ocean ridge.

Basalts and mantle peridotites of mid-ocean ridges are thought to sample Earth's upper mantle. Osmium isotopes of abyssal peridotites uniquely preserve melt extraction events throughout Earth history, but existing records only indicate ages up to ~2 billion years (Ga) ago. Thus, the memory of the suspected large volumes of mantle lithosphere that existed in Archean time (>2.5 Ga) has apparently been lost somehow. We report abyssal peridotites with melt-depletion ages up to 2.8 Ga, documented by extremely unradiogenic 187Os/188Os ratios (to as low as 0.1095) and refractory major elements that compositionally resemble the deep keels of Archean cratons. These oceanic rocks were thus derived from the once-extensive Archean continental keels that have been dislodged and recycled back into the mantle, the feasibility of which we confirm with numerical modeling. This unexpected connection between young oceanic and ancient continental lithosphere indicates an underappreciated degree of compositional recycling over time.

Fusible mantle cumulates trigger young mare volcanism on the cooling Moon.

The Chang'E-5 (CE5) mission has demonstrated that lunar volcanism was still active until two billion years ago, much younger than the previous isotopically dated lunar basalts. How the small Moon retained enough heat to drive such late volcanism is unknown, particularly as the CE5 mantle source was anhydrous and depleted in heat-producing elements. We conduct fractional crystallization and mantle melting simulations that show that mantle melting point depression by the presence of fusible, easily melted components could trigger young volcanism. Enriched in calcium oxide and titanium dioxide compared to older Apollo magmas, the young CE5 magma was, thus, sourced from the overturn of the late-stage fusible cumulates of the lunar magma ocean. Mantle melting point depression is the first mechanism to account for young volcanism on the Moon that is consistent with the newly returned CE5 basalts.

Requirements and reliability of AI in the medical context.

The digital information age has been a catalyst in creating a renewed interest in Artificial Intelligence (AI) approaches, especially the subclass of computer algorithms that are popularly grouped into Machine Learning (ML). These methods have allowed one to go beyond limited human cognitive ability into understanding the complexity in the high dimensional data. Medical sciences have seen a steady use of these methods but have been slow in adoption to improve patient care. There are some significant impediments that have diluted this effort, which include availability of curated diverse data sets for model building, reliable human-level interpretation of these models, and reliable reproducibility of these methods for routine clinical use. Each of these aspects has several limiting conditions that need to be balanced out, considering the data/model building efforts, clinical implementation, integration cost to translational effort with minimal patient level harm, which may directly impact future clinical adoption. In this review paper, we will assess each aspect of the problem in the context of reliable use of the ML methods in oncology, as a representative study case, with the goal to safeguard utility and improve patient care in medicine in general.

Orbital forcing of ice sheets during snowball Earth.

The snowball Earth hypothesis-that a runaway ice-albedo feedback can cause global glaciation-seeks to explain low-latitude glacial deposits, as well as geological anomalies including the re-emergence of banded iron formation and "cap" carbonates. One of the most significant challenges to snowball Earth has been sedimentological cyclicity that has been taken to imply more climate dynamics than expected when the ocean is completely covered in ice. However, recent climate models suggest that as atmospheric CO2 accumulates, the snowball climate system becomes sensitive to orbital forcing. Here we show the presence of nearly all Milankovitch (orbital) cycles preserved in stratified banded iron formation deposited during the Sturtian snowball Earth. These results provide evidence for orbitally forced cyclicity of global ice sheets that resulted in periodic oxidation of ferrous iron. Orbital glacial advance and retreat cycles provide a simple mechanism to reconcile both the sedimentary dynamics and the enigmatic survival of multicellular life during snowball Earth.