Managerial and Organizational Challenges in the Age of AI.

This Viewpoint discusses the managerial and organizational challenges that could result from the use of artificial intelligence systems in psychiatric research and care.

Changes in orogenic style and surface environment recorded in Paleoproterozoic foreland successions.

The Earth's interior and surficial systems underwent dramatic changes during the Paleoproterozoic, but the interaction between them remains poorly understood. Rocks deposited in orogenic foreland basins retain a record of the near surface to deep crustal processes that operate during subduction to collision and provide information on the interaction between plate tectonics and surface responses through time. Here, we document the depositional-to-deformational life cycle of a Paleoproterozoic foreland succession from the North China Craton. The succession was deposited in a foreland basin following ca. 2.50-2.47 Ga Altaid-style arc-microcontinent collision, and then converted to a fold-and-thrust belt at ca. 2.0-1.8 Ga due to Himalayan-style continent-continent collision. These two periods correspond to the assembly of supercratons in the late Archean and of the Paleoproterozoic supercontinent Columbia, respectively, which suggests that similar basins may have been common at the periphery of other cratons. The multiple stages of orogenesis and accompanying tectonic denudation and silicate weathering, as recorded by orogenic foreland basins, likely contributed to substantial changes in the hydrosphere, atmosphere, and biosphere known to have occurred during the Paleoproterozoic.

Associations with age and glomerular filtration rate in a referred population with chronic kidney disease: methods and baseline data from a UK multicentre cohort study (NURTuRE-CKD).

BACKGROUND: Chronic kidney disease (CKD) is common but heterogenous and is associated with multiple adverse outcomes. The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD cohort was established to investigate risk factors for clinically important outcomes in persons with CKD referred to secondary care. METHODS: Eligible participants with CKD stages G3-4 or stages G1-2 plus albuminuria >30 mg/mmol were enrolled from 16 nephrology centres in England, Scotland and Wales from 2017 to 2019. Baseline assessment included demographic data, routine laboratory data and research samples. Clinical outcomes are being collected over 15 years by the UK Renal Registry using established data linkage. Baseline data are presented with subgroup analysis by age, sex and estimated glomerular filtration rate (eGFR). RESULTS: A total of 2996 participants was enrolled. Median (interquartile range) age was 66 (54-74) years, eGFR 33.8 (24.0-46.6) mL/min/1.73 m2 and urine albumin to creatinine ratio 209 (33-926) mg/g; 58.5% were male. Of these participants, 1883 (69.1%) were in high-risk CKD categories. Primary renal diagnosis was CKD of unknown cause in 32.3%, glomerular disease in 23.4% and diabetic kidney disease in 11.5%. Older participants and those with lower eGFR had higher systolic blood pressure and were less likely to be treated with renin-angiotensin system inhibitors (RASi) but were more likely to receive a statin. Female participants were less likely to receive a RASi or statin. CONCLUSIONS: NURTuRE-CKD is a prospective cohort of persons who are at relatively high risk of adverse outcomes. Long-term follow-up and a large biorepository create opportunities for research to improve risk prediction and to investigate underlying mechanisms to inform new treatment development.

Growth model for international academic medicine partnerships: Qualitative analysis of Ghana postgraduate Ob/Gyn training program.

This study aims to detail the capacity strengthening process of the Ghana Ob/Gyn postgraduate training program in order to inform a model by which international academic medicine partnerships can form, grow, and effectively tackle development challenges. A qualitative analysis with grounded theory methodological approach was utilized. Convenience and purposive sampling were used to select certified Ob/Gyn training program graduates. Interviews were conducted face-to-face in in Accra, Kumasi, Cape Coast, and Tamale, Ghana between June 21 to August 20, 2017. An additional data analysis of 48 semi-structured interviews previously collected for another study were examined for factors pertinent to graduate career development. Coded data were grouped according to themes and subthemes. Emerging themes demonstrated that graduates further complete the maternal care team and facilitate collaboration amongst healthcare workers. Themes also included graduates' pursuit of subspecialty training and research. Graduates cited the training program as key to their professional development. Graduates assume leadership roles in hospital management and operations, teaching, mentoring, interprofessional maternal care team, and knowledge-sharing. Graduates expressed eagerness to subspecialize and to advance their research training and skills. The results suggest a growth model of international academic medicine partnerships from basic obstetric training to advanced training. The model is developed for adaptability in other SSA countries and low-resource settings so that it may effectively strengthen health workforce capacity. We hope that this program can serve as a model for other partnerships in medical specialties.

Coexisting divergent and convergent plate boundary assemblages indicate plate tectonics in the Neoarchean.

The coexistence of divergent (spreading ridge) and convergent (subduction zone) plate boundaries at which lithosphere is respectively generated and destroyed is the hallmark of plate tectonics. Here, we document temporally- and spatially-associated Neoarchean (2.55-2.51 Ga) rock assemblages with mid-ocean ridge and supra-subduction-zone origins from the Angou Complex, southern North China Craton. These assemblages record seafloor spreading and contemporaneous subduction initiation and mature arc magmatism, respectively, analogous to modern divergent and convergent plate boundary processes. Our results provide direct evidence for lateral plate motions in the late Neoarchean, and arguably the operation of plate tectonics, albeit with warmer than average Phanerozoic subduction geotherms. Further, we surmise that plate tectonic processes played an important role in shaping Earth's surficial environments during the Neoarchean and Paleoproterozoic.

Giant impacts and the origin and evolution of continents.

Earth is the only planet known to have continents, although how they formed and evolved is unclear. Here using the oxygen isotope compositions of dated magmatic zircon, we show that the Pilbara Craton in Western Australia, Earth's best-preserved Archaean (4.0-2.5 billion years ago (Ga)) continental remnant, was built in three stages. Stage 1 zircons (3.6-3.4 Ga) form two age clusters with one-third recording submantle δ18O, indicating crystallization from evolved magmas derived from hydrothermally altered basaltic crust like that in modern-day Iceland1,2. Shallow melting is consistent with giant impacts that typified the first billion years of Earth history3-5. Giant impacts provide a mechanism for fracturing the crust and establishing prolonged hydrothermal alteration by interaction with the globally extensive ocean6-8. A giant impact at around 3.6 Ga, coeval with the oldest low-δ18O zircon, would have triggered massive mantle melting to produce a thick mafic-ultramafic nucleus9,10. A second low-δ18O zircon cluster at around 3.4 Ga is contemporaneous with spherule beds that provide the oldest material evidence for giant impacts on Earth11. Stage 2 (3.4-3.0 Ga) zircons mostly have mantle-like δ18O and crystallized from parental magmas formed near the base of the evolving continental nucleus12. Stage 3 (<3.0 Ga) zircons have above-mantle δ18O, indicating efficient recycling of supracrustal rocks. That the oldest felsic rocks formed at 3.9-3.5 Ga (ref. 13), towards the end of the so-called late heavy bombardment4, is not a coincidence.

Evidence supporting a cultural evolutionary theory of prosocial religions in contemporary workplace safety data.

A prominent line of cultural evolutionary theory hypothesizes that religiously inspired prosocial behavior enhances the fecundity of pious groups, causing them to outcompete non-religious communities and spread their prosocial values. We present evidence concerning contemporary workplace safety, in the United States, that unexpectedly tested implications of this cultural evolutionary hypothesis. Avoiding workplace injury requires cooperation and injury influences fitness, thus cultural evolutionary theory would anticipate that religious communities should exhibit fewer workplace injuries. Indeed, we find that the proportion of a community adhering to a religion correlates negatively with rates of workplace injury in its private-sector establishments. This correlation emerges primarily when secular workplace safety authorities are not prominent, thus echoing evidence that religiously inspired prosocial behavior mainly occurs absent "earthly" sanctioning authorities. Furthermore, the percent of religiously affiliated individuals in a community correlates with safety investments, suggesting that workplace injury reductions in religious communities result from individually costly, group-benefitting cooperation.

Post-remediation geophysical assessment: Investigating long-term electrical geophysical signatures resulting from bioremediation at a chlorinated solvent contaminated site.

There is a growing need to assess long-term impacts of active remediation strategies on treated aquifers. A variety of biogeochemical alterations can result from interactions of the amendment with the aquifer, conceivably leading to a geophysical signal associated with the long-term alteration of an aquifer. This concept of post-remediation geophysical assessment was investigated in a shallow, chlorinated solvent-contaminated aquifer six to eight years after amendment delivery. Surface resistivity imaging and cross-borehole resistivity and induced polarization (IP) imaging were performed on a transect that spanned treated and untreated zones of the aquifer. Established relationships between IP parameters and surface electrical conductivity were used to predict vertical profiles of electrolytic conductivity and surface conductivity from the inverted cross-borehole images. Aqueous geochemistry data, along with natural gamma and magnetic susceptibility logs, were used to constrain the interpretation. The electrical conductivity structure determined from surface and borehole imaging was foremost controlled by the electrolytic conductivity of the interconnected pore space, being linearly related to fluid specific conductance. The electrolytic conductivity (and thus the conductivity images alone) did not discriminate between treated and untreated zones of the aquifer. In contrast, inverted phase angles and surface conductivities did discriminate between treated and untreated zones of the aquifer, with the treated zone being up to an order of magnitude more polarizable in places. Supporting aqueous chemistry and borehole logging datasets indicate that this geophysical signal from the long-term impact of the remediation on the aquifer is most likely associated with the formation of polarizable, dispersed iron sulfide minerals.

GlomSpheres as a 3D co-culture spheroid model of the kidney glomerulus for rapid drug-screening.

The glomerulus is the filtration unit of the kidney. Injury to any component of this specialised structure leads to impaired filtration and eventually fibrosis and chronic kidney disease. Current two and three dimensional (2D and 3D) models that attempt to recreate structure and interplay between glomerular cells are imperfect. Most 2D models are simplistic and unrepresentative, and 3D organoid approaches are currently difficult to reproduce at scale and do not fit well with current industrial drug-screening approaches. Here we report a rapidly generated and highly reproducible 3D co-culture spheroid model (GlomSpheres), better demonstrating the specialised physical and molecular structure of a glomerulus. Co-cultured using a magnetic spheroid formation approach, conditionally immortalised (CI) human podocytes and glomerular endothelial cells (GEnCs) deposited mature, organized isoforms of collagen IV and Laminin. We demonstrate a dramatic upregulation of key podocyte (podocin, nephrin and podocalyxin) and GEnC (pecam-1) markers. Electron microscopy revealed podocyte foot process interdigitation and endothelial vessel formation. Incubation with pro-fibrotic agents (TGF-ß1, Adriamycin) induced extracellular matrix (ECM) dysregulation and podocyte loss, which were attenuated by the anti-fibrotic agent Nintedanib. Incubation with plasma from patients with kidney disease induced acute podocyte loss and ECM dysregulation relative to patient matched remission plasma, and Nintedanib reduced podocyte loss. Finally, we developed a rapid imaging approach to demonstrate the model's usefulness in higher throughput pharmaceutical screening. GlomSpheres therefore represent a robust, scalable, replacement for 2D in vitro glomerular disease models.

Temporal assortment of cooperators in the spatial prisoner's dilemma.

We study a spatial, one-shot prisoner's dilemma (PD) model in which selection operates on both an organism's behavioral strategy (cooperate or defect) and its decision of when to implement that strategy, which we depict as an organism's choice of one point in time, out of a set of discrete time slots, at which to carry out its PD strategy. Results indicate selection for cooperators across various time slots and parameter settings, including parameter settings in which cooperation would not evolve in an exclusively spatial model-as in work investigating exogenously imposed temporal networks. Moreover, in the presence of time slots, cooperators' portion of the population grows even under different combinations of spatial structure, transition rules, and update dynamics, though rates of cooperator fixation decline under pairwise comparison and synchronous updating. These findings indicate that, under certain evolutionary processes, merely existing in time and space promotes the evolution of cooperation.

Optical design and intensity interferometry simulations in support of the Kilometer Space Telescope.

Very large telescopes will be needed for the future of space science, space laser-com, and other interstellar or interplanetary applications. However, as telescopes' diameters increase, their weight and cost increase dramatically. An approximation for ground-based observatories is that their cost increases to the power of 2.7 of its diameter [SAO, Special Report #385 (1979), p. 9]. Large space-based telescopes become limited by the rocket size and power. Multiple telescopes are also needed for very long baseline interferometry (VLBI), which further increases cost. A solution to overcome these issues is the use of inflatable telescopes. A thin mirror material clearly has much lower mass; however, controlling its surface error or wavefront can be a challenge. Intensity interferometry is an imaging method that has a much looser sensitivity to wavefront error (WFE), and thus is an ideal match for very large inflatable telescopes. A spherical inflatable mirror is the most practical; however, it suffers from spherical aberration. This paper presents new optical designs and simulations for intensity interferometry in support of large inflatable spherical telescopes. The optical system design includes a novel five-mirror off-axis, free-form, spherical aberration corrector. The system design shown is a 10 m diameter f/1 spherical primary mirror with 1.2 arcmin (0.02°) field of view (FOV). MATLAB simulations of intensity interferometry combine signal with noise and WFE. Visibility-based VLBI image simulations are shown based on various telescope arrays. Simulations show that with a 1 GHz detector, a 1 cm RMS WFE is tolerable. So the challenge of the optical design is then more about gathering and concentrating the light down to a reasonable size detector. Further simulations of signal combined with noise indicate that the signal rate must be about 100 times higher than the noise rate for an adequate intensity interferometry measurement. Visibility-based image simulations reveal that many telescopes (5-20 per axis) are needed in a 2D array out to the first visibility minimum to adequately resolve unknown features of a distant object.

Oxygen isotopes trace the origins of Earth's earliest continental crust.

Much of the current volume of Earth's continental crust had formed by the end of the Archaean eon1 (2.5 billion years ago), through melting of hydrated basaltic rocks at depths of approximately 25-50 kilometres, forming sodic granites of the tonalite-trondhjemite-granodiorite (TTG) suite2-6. However, the geodynamic setting and processes involved are debated, with fundamental questions arising, such as how and from where the required water was added to deep-crustal TTG source regions7,8. In addition, there have been no reports of voluminous, homogeneous, basaltic sequences in preserved Archaean crust that are enriched enough in incompatible trace elements to be viable TTG sources5,9. Here we use variations in the oxygen isotope composition of zircon, coupled with whole-rock geochemistry, to identify two distinct groups of TTG. Strongly sodic TTGs represent the most-primitive magmas and contain zircon with oxygen isotope compositions that reflect source rocks that had been hydrated by primordial mantle-derived water. These primitive TTGs do not require a source highly enriched in incompatible trace elements, as 'average' TTG does. By contrast, less sodic 'evolved' TTGs require a source that is enriched in both water derived from the hydrosphere and also incompatible trace elements, which are linked to the introduction of hydrated magmas (sanukitoids) formed by melting of metasomatized mantle lithosphere. By concentrating on data from the Palaeoarchaean crust of the Pilbara Craton, we can discount a subduction setting6,10-13, and instead propose that hydrated and enriched near-surface basaltic rocks were introduced into the mantle through density-driven convective overturn of the crust. These results remove many of the paradoxical impediments to understanding early continental crust formation. Our work suggests that sufficient primordial water was already present in Earth's early mafic crust to produce the primitive nuclei of the continents, with additional hydrated sources created through dynamic processes that are unique to the early Earth.

Refining the unilateral ureteral obstruction mouse model: No sham, no shame.

Fibrosis, as a common final pathway in many renal diseases, contributes significantly to the decline of organ function and to progression to end-stage renal disease. To establish therapeutic interventions that target fibrosis, animal models are essential. The most widely used model of renal fibrosis is the unilateral ureteral obstruction (UUO) model. Typically, the control for this model is a sham-operated animal. Sham surgery causes pain and distress to these control animals, and here we aim to show that there is no difference in the main read-outs of this model between sham-operated animals and non-operated C57BL/6J mice. In five experiments, quantification of Picro Sirius Red stained collagen in the renal cortex did not show any difference between 15 sham and 25 non-operated individuals. A comparison of the regulation of genes involved with fibrosis did not show any difference between sham and non-operated groups at 21 days post surgery either. We conclude that there are no significant differences between non-operated controls and sham animals with respect to collagen deposition and fibrosis pathways in the UUO mouse model.

The internal structure and geodynamics of Mars inferred from a 4.2-Gyr zircon record.

Combining U-Pb ages with Lu-Hf data in zircon provides insights into the magmatic history of rocky planets. The Northwest Africa (NWA) 7034/7533 meteorites are samples of the southern highlands of Mars containing zircon with ages as old as 4476.3 ± 0.9 Ma, interpreted to reflect reworking of the primordial Martian crust by impacts. We extracted a statistically significant zircon population (n = 57) from NWA 7533 that defines a temporal record spanning 4.2 Gyr. Ancient zircons record ages from 4485.5 ± 2.2 Ma to 4331.0 ± 1.4 Ma, defining a bimodal distribution with groupings at 4474 ± 10 Ma and 4442 ± 17 Ma. We interpret these to represent intense bombardment episodes at the planet's surface, possibly triggered by the early migration of gas giant planets. The unradiogenic initial Hf-isotope composition of these zircons establishes that Mars's igneous activity prior to ∼4.3 Ga was limited to impact-related reworking of a chemically enriched, primordial crust. A group of younger detrital zircons record ages from 1548.0 ± 8.8 Ma to 299.5 ± 0.6 Ma. The only plausible sources for these grains are the temporally associated Elysium and Tharsis volcanic provinces that are the expressions of deep-seated mantle plumes. The chondritic-like Hf-isotope compositions of these zircons require the existence of a primitive and convecting mantle reservoir, indicating that Mars has been in a stagnant-lid tectonic regime for most of its history. Our results imply that zircon is ubiquitous on the Martian surface, providing a faithful record of the planet's magmatic history.

Long-term prognosis of patients treated by coronary sinus-based percutaneous annuloplasty: single centre experience.

AIMS: This study aims to report long-term mortality, echocardiographic, and clinical outcomes of patients receiving treatment for functional mitral regurgitation (FMR) with the Carillon device. METHODS AND RESULTS: This was a single centre analysis of prospectively collected data from patients treated with the Carillon Mitral Contour System for symptomatic congestive heart failure despite guideline-directed medical therapy, who were included from a single centre from the TITAN II study. All patients presented with New York Heart Association (NYHA) class 2 or greater symptoms, grade 2+ to 4+ FMR, left ventricular enlargement, and reduced ejection fraction. Surviving patients were evaluated for long-term follow-up post-procedure, averaging 6.9 years. Fifteen (15) patients (mean age 72 years, 60% male, 100% NYHA class III or IV, 50% MR grade 3+ or 4+) were treated with the Carillon device. The Kaplan-Meier mortality rate was 40% at 6 years of follow-up. Long-term survival through 6 years was associated with echocardiographic improvement in mitral regurgitation (change in effective regurgitant orifice area in survivors versus non-survivors from baseline to 1 year follow-up, -9.0 ± 5.6 vs. -1.7 ± 1.5, P = 0.02) and clinical status at 12 months (difference in NYHA at 1 year follow-up between survivors versus non-survivors, P = 0. 05) which was sustained throughout follow-up. All patients at 6 year follow-up had ≤2+ MR, with 6 of 7 having 0-1+ MR. Left ventricular end-diastolic volume was reduced from 154.0 ± 65.7 mL at baseline to 104.5 ± 59.2 mL at 6 year follow-up, P = 0.03 in survivors with both measurements. CONCLUSIONS: Among patients with congestive heart failure treated with the Carillon device, long-term survival is associated with favourable 1 year and sustained improvements in mitral regurgitation, left ventricular volume, ejection fraction, and clinical status.

Image distortion, pupil coma, and relative illumination.

Relative illumination is affected by image distortion, pupil coma, and pupil magnification. Image and pupil aberrations have a known relationship that also can be written in terms of pupil magnification. Pupil coma is the stretching or compression of the pupil along the field axis, which directly affects relative illumination. Front-stopped designs have pupil aberrations on the exit pupil while rear-stopped systems have pupil aberrations on the entrance pupil. Of the primary pupil aberrations, pupil coma can have the largest effect on the relative illumination in optical designs with significant image distortion (ex: fisheye lens). The Lagrange invariant holds for systems with image distortion using a paraxial approximation of pupil coma. Relative illumination can be written in terms of % distortion, pupil magnification, and object-space field angle.

Zernike monomials in wide field of view optical designs.

Zernike polynomials are universal in optical modeling and testing of wavefronts; however, their polynomial behavior can cause a misinterpretation of individual aberrations. Wavefront profiles described by Zernike polynomials contain multiple terms with different orders of pupil radius (ρ). Zernike polynomials are a sum of high and low orders of ρ to minimize the RMS wavefront error and to preserve orthogonality. Since the low-order polynomials are still contained in the net Zernike sum, there is redundancy in individual monomials. Monomial aberrations, also known as Seidel or primary aberrations, are useful in studying an optical design's complexity, alignment, and field behavior. Zernike polynomial aberrations reported by optical design software are not indicative of individual (monomial) aberrations in wide field of view designs since the low-order polynomials are contaminated by higher order terms. An aberration node is the field location where an individual (monomial) aberration is zero. In this paper, a matrix method is shown to calculate the individual monomial aberrations given the set of Zernike polynomials. Monomial aberrations plotted as a function of field angle (H) indicate the field order (Hn) and the location of true aberration nodes. Contrarily, Zernike polynomial versus field (ZvF) plots can indicate false aberration nodes, due to the polynomial mixing of high- and low-order terms. Accurate knowledge of the monomial aberration nodes, converted from Zernike polynomials, provides the link between a ray-trace model or lab wavefront measurement and nodal aberration theory (NAT). This method is applied to two different optical designs: (1) 120° circular FOV fish-eye lens and (2) 120∘×4∘ rectangular FOV, off-axis, freeform four-mirror design.