Geophysical evidence for an enriched molten silicate layer above Mars's core.

The detection of deep reflected S waves on Mars inferred a core size of 1,830 ± 40 km (ref. 1), requiring light-element contents that are incompatible with experimental petrological constraints. This estimate assumes a compositionally homogeneous Martian mantle, at odds with recent measurements of anomalously slow propagating P waves diffracted along the core-mantle boundary2. An alternative hypothesis is that Mars's mantle is heterogeneous as a consequence of an early magma ocean that solidified to form a basal layer enriched in iron and heat-producing elements. Such enrichment results in the formation of a molten silicate layer above the core, overlain by a partially molten layer3. Here we show that this structure is compatible with all geophysical data, notably (1) deep reflected and diffracted mantle seismic phases, (2) weak shear attenuation at seismic frequency and (3) Mars's dissipative nature at Phobos tides. The core size in this scenario is 1,650 ± 20 km, implying a density of 6.5 g cm-3, 5-8% larger than previous seismic estimates, and can be explained by fewer, and less abundant, alloying light elements than previously required, in amounts compatible with experimental and cosmochemical constraints. Finally, the layered mantle structure requires external sources to generate the magnetic signatures recorded in Mars's crust.

First observations of core-transiting seismic phases on Mars.

We present the first observations of seismic waves propagating through the core of Mars. These observations, made using seismic data collected by the InSight geophysical mission, have allowed us to construct the first seismically constrained models for the elastic properties of Mars' core. We observe core-transiting seismic phase SKS from two farside seismic events detected on Mars and measure the travel times of SKS relative to mantle traversing body waves. SKS travels through the core as a compressional wave, providing information about bulk modulus and density. We perform probabilistic inversions using the core-sensitive relative travel times together with gross geophysical data and travel times from other, more proximal, seismic events to seek the equation of state parameters that best describe the liquid iron-alloy core. Our inversions provide constraints on the velocities in Mars' core and are used to develop the first seismically based estimates of its composition. We show that models informed by our SKS data favor a somewhat smaller (median core radius = 1,780 to 1,810 km) and denser (core density = 6.2 to 6.3 g/cm3) core compared to previous estimates, with a P-wave velocity of 4.9 to 5.0 km/s at the core-mantle boundary, with the composition and structure of the mantle as a dominant source of uncertainty. We infer from our models that Mars' core contains a median of 20 to 22 wt% light alloying elements when we consider sulfur, oxygen, carbon, and hydrogen. These data can be used to inform models of planetary accretion, composition, and evolution.

Laminar Organization of the Entorhinal Cortex in Macaque Monkeys Based on Cell-Type-Specific Markers and Connectivity.

The entorhinal cortex (EC) is a major gateway between the hippocampus and telencephalic structures, and plays a critical role in memory and navigation. Through the use of various molecular markers and genetic tools, neuron types constituting EC are well studied in rodents, and their layer-dependent distributions, connections, and functions have also been characterized. In primates, however, such cell-type-specific understandings are lagging. To bridge the gap between rodents and primates, here we provide the first cell-type-based global map of EC in macaque monkeys. The laminar organization of the monkey EC was systematically examined and compared with that of the rodent EC by using immunohistochemistry for molecular markers which have been well characterized in the rodent EC: reelin, calbindin, and Purkinje cell protein 4 (PCP4). We further employed retrograde neuron labeling from the nucleus accumbens and amygdala to identify the EC output layer. This cell-type-based approach enabled us to apply the latest laminar definition of rodent EC to monkeys. Based on the similarity of the laminar organization, the monkey EC can be divided into two subdivisions: rostral and caudal EC. These subdivisions likely correspond to the lateral and medial EC in rodents, respectively. In addition, we found an overall absence of a clear laminar arrangement of layer V neurons in the rostral EC, unlike rodents. The cell-type-based architectural map provided in this study will accelerate the application of genetic tools in monkeys for better understanding of the role of EC in memory and navigation.

Seismic detection of the martian core.

Clues to a planet's geologic history are contained in its interior structure, particularly its core. We detected reflections of seismic waves from the core-mantle boundary of Mars using InSight seismic data and inverted these together with geodetic data to constrain the radius of the liquid metal core to 1830 ± 40 kilometers. The large core implies a martian mantle mineralogically similar to the terrestrial upper mantle and transition zone but differing from Earth by not having a bridgmanite-dominated lower mantle. We inferred a mean core density of 5.7 to 6.3 grams per cubic centimeter, which requires a substantial complement of light elements dissolved in the iron-nickel core. The seismic core shadow as seen from InSight's location covers half the surface of Mars, including the majority of potentially active regions-e.g., Tharsis-possibly limiting the number of detectable marsquakes.

Scattering Attenuation of the Martian Interior through Coda Wave Analysis.

We investigate the scattering attenuation characteristics of the Martian crust and uppermost mantle to understand the structure of the Martian interior. We examine the energy decay of the spectral envelopes for 21 high-quality Martian seismic events from Sol 128 to Sol 500 of InSight operations. We use the model of Dainty et al. (1974b) to approximate the behavior of energy envelopes resulting from scattered wave propagation through a single diffusive layer over an elastic half-space. Using a grid search, we mapped the layer parameters that fit the observed InSight data envelopes. The single diffusive layer model provided better fits to the observed energy envelopes for High Frequency (HF) and Very High Frequency (VF) than for the Low Frequency (LF) and Broadband (BB) events. This result is consistent with the suggested source depths (Giardini et al., 2020) for these families of events and their expected interaction with a shallow scattering layer. The shapes of the observed data envelopes do not show a consistent pattern with event distance, suggesting that the diffusivity and scattering layer thickness is non-uniform in the vicinity of InSight at Mars. Given the consistency in the envelope shapes between HF and VF events across epicentral distances and the tradeoffs between the parameters that control scattering, the dimensions of the scattering layer remain unconstrained but require that scattering strength decreases with depth and that the rate of decay in scattering strength is fastest near the surface. This is generally consistent with the processes that would form scattering structures in planetary lithospheres.

Population-based incidence of diabetic ketoacidosis in type 2 diabetes: medical claims data analysis in Japan.

PURPOSE: Determination of the incidence rate of diabetic ketoacidosis (DKA) in type 2 diabetes mellitus (T2DM) is urgent, in response to the safety issue with use of the glucose lowering drugs, sodium-glucose cotransporter-2 inhibitors, and DKA. METHODS: We extracted data of adult patients with T2DM from a medical claims database in Japan, which included 1 million individuals. The study period was 2005-2013, before the era of sodium-glucose cotransporter-2 inhibitors. The inclusion criteria were patients with a diagnosis of T2DM who had at least 1 prescription for a glucose-lowering drug. We further examined the number of DKA-related admissions and medication use prior to admission. Calculation of DKA incidence was on a patient-years basis, with 95% confidence interval using a Poisson distribution. RESULTS: Of 36,674 adult patients with T2DM, we identified 74 cases admitted for DKA, with an estimated DKA incidence of 0.48/1000 (95% confidence interval, 0.38-0.60/1000) patient-years. Of these 74 cases, approximately two-thirds of patients had no past or recent history of glucose-lowering drug use before admission for DKA. CONCLUSIONS: This study estimated that the incidence of DKA was 0.48/1000 patient-years in Japan, similar to previous studies. We also found that underuse of glucose-lowering medication was common among patients hospitalized for DKA. KEY POINTS The population-based incidence of DKA in T2DM is largely unknown. In Japan, the estimated DKA incidence was 0.48/1000 (95% CI, 0.38-0.60/1000) patient-years. Drug-induced DKA is an emerging research area, and our results can be applied to evaluating the risk of DKA.

Influence of comorbidities on the implementation of the fundus examination in patients with newly diagnosed type 2 diabetes.

AIMS: To investigate the influence of comorbidities on undergoing a diabetic eye examination in patients with newly diagnosed type 2 diabetes mellitus (T2DM). DESIGN: Retrospective cohort study METHODS: This was a retrospective cohort study using data from health insurance claims made between January 2005 and March 2013 in Japan. The primary outcome was implementation of the fundus examination that includes fundus photography, ophthalmoscopy and optical coherence tomography by a doctor within one year of initial drug therapy for Type2 Diabetes Mellitus (T2DM). We used multivariable logistic regression models with adjustment for demographic parameters to investigate the influence of comorbidities (hypertension and/or hyperlipidemia) on patients with T2DM receiving fundus examinations. We conducted an additional analysis to investigate whether the site of treatment might influence the performance of fundus examinations in patients with T2DM. RESULTS: A total of 6,492 patients were eligible for this analysis, of which 1,044 (16.1%) had comorbidities and 2,212 (34.1%) received the fundus examination. In the multivariable analysis, there was a significant association between comorbidities and a lower proportion of examination implementation (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.48-0.68; P<0.001). The implementation proportion for patients treated for comorbidities and T2DM in the same facility was also low (OR, 0.52; 95% CI, 0.43-0.63; P<0.001). CONCLUSIONS: These results suggest that the proportion of taking fundus examination is low among patients with comorbidities, especially in patients treated at the same facility for comorbidities and T2DM. This may help to increase the proportion of T2DM patients receiving fundus examinations.

Factors Influencing the Placebo Effect in Patients with Primary Open-Angle Glaucoma or Ocular Hypertension: An Analysis of Two Randomized Clinical Trials.

OBJECTIVE: To explore factors related to the placebo effect in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OH). METHODS: This was a retrospective cohort study of patients with POAG and patients with OH who were treated with placebo. The patients' data were extracted from two randomized, double-masked, parallel, multicenter clinical trials (trial 1 and trial 2) in Japan. We explored the baseline factors that were associated with the intraocular pressure (IOP)-lowering effect of placebo ophthalmic solution after 4 weeks of instillation treatment at two time points by using multivariable models. The time points were Hour 0 (between 08:30 and 10:30 before instillation) and Hour 2 (within 1.5 to 2.5 h after instillation and by 12:30) at the baseline date and after 4 weeks. The changes in IOP from baseline to 4 weeks at the two time points were evaluated for the IOP-lowering effect induced by placebo instillation. RESULTS: Of the 330 patients included in the two trials, 89 patients were eligible for the analysis. The results of the multivariable analysis for Hour 0 indicated a high IOP at the baseline date (coefficient: 0.24, 95% confidence interval (CI): 0.02 to 0.46, P = 0.03), and the magnitude of the IOP fluctuation at the baseline date (coefficient: 0.57, 95% CI: 0.24 to 0.90, P = 0.001) was associated with the IOP-lowering effect after 4 weeks. With respect to Hour 2, the trial type was associated with the IOP-lowering effect (coefficient: -1.15, 95% CI: -2.14 to -0.16, P = 0.02). CONCLUSIONS: A large fluctuation in IOP during the day is associated with the IOP-lowering effect induced by placebo in patients with POAG or OH. This finding would be helpful to researchers when designing studies related to glaucoma in the early stages of clinical development of drugs.

Magnitude of serosal changes predicts peritoneal recurrence of gastric cancer.

BACKGROUND: Peritoneal dissemination is the most frequent mode of recurrence in patients with gastric cancer. We tried to identify factors that predict peritoneal recurrence with high sensitivity. STUDY DESIGN: Clinical and pathologic data from 587 consecutive patients with gastric cancer were reviewed retrospectively. The stepwise Cox proportional hazards regression model was used to assess the prognostic significance of the magnitude of serosal changes. Multiple stepwise logistic regression analysis was used to determine factors associated with peritoneal recurrence in 375 patients who underwent curative resection. RESULTS: The 5-year survival rate of patients with S2 disease (greatest dimension of macroscopic serosal changes >/= 2.5 cm) was 18%, which was worse than S0 (no serosal changes) and S1 disease (macroscopic serosal changes < 2.5 cm)(p < 0.001). Patients with S0 tumors who underwent curative resection had the best 5-year survival rate. Multivariate analyses indicated that the magnitude of serosal changes was an independent prognostic factor for survival both overall and after curative resection. Logistic regression analysis showed that peritoneal recurrence was more than four times as likely with S2 than with S0 or S1 tumors. The sensitivity for predicting peritoneal recurrence was 79%; the sensitivity of cytologic examination was 38%. CONCLUSIONS: Magnitude of serosal changes is easy to measure intraoperatively and predicts peritoneal recurrence of gastric cancer with greater sensitivity than conventional peritoneal lavage cytology.