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Crater counting is a widely applied methodology for dating large areas of planetary surfaces, but is difficult to apply the method to constrain the durations of stratigraphic unconformities. Unconformities with exhumed craters are thought to indicate long hiatuses that can only be indirectly dated through stratigraphic relationships with other surfaces with uniform exposure ages. On Mars, sedimentary deposits with prominent unconformities with exhumed craters are found in layered deposits in the Arabia Terra region as well as Gale crater within Mount Sharp. In this work, we present a Linear Crater Counting methodology and apply it to constrain these unconformities observed in Arabia Terra and in Mount Sharp. The method applies a linear sampling domain correction to conventional two‐dimensional crater size frequency distributions and Bayesian Poisson process statistics in order to constrain the likely durations of these unconformities. We found that unconformities in Arabia Terra were on the order of 0.1–1 Gyr in length and that the unconformity preserved at Mount Sharp is at least 0.2 Gyr in length given estimates of the ages of the host craters. Hiatuses of these lengths constrain the age of the overlying deposits to be Late Hesperian or Amazonian in age. Two utility plots are also provided, along with the derivation, for researchers to apply this method to dating arbitrary geologic contacts on Mars and to adapt it to other bodies. Plain Language Summary: The crater counting method is a widely used method to date planetary surfaces. Crater counting works by comparing the number of craters in an area to the expected number of craters that should be observed for that area using a model of how many craters form and their expected size through time. On Mars, geologic contacts of sedimentary deposits with exhumed craters are seen in Arabia Terra and in Gale crater in Mount Sharp. Craters exhumed in these geologic contacts are thought to indicate long gaps in time between the formation dates of the upper and lower rock layers. However, dating these time gaps directly is not possible with conventional crater counting. To solve this problem, we developed a new linear crater counting method which describes the likely number of craters for a given age that could be found along a line on the surface of Mars. We apply this method to the geologic contacts seen in Arabia Terra and in Gale crater, and find that the time gaps are hundreds of millions of years in length to over a billion years in length. Our results confirm predictions that these deposits are geologically younger than previously thought. Key Points: We describe a novel linear crater counting method to date stratigraphic unconformities using partially exhumed craters along unit boundariesWe found that layered deposits in Arabia Terra and the Upper mound unit in Gale crater could be Amazonian in Age from applying our methodOur methodology can be applied broadly to better understand chronostratigraphy across the solar system [ABSTRACT FROM AUTHOR]

Our understanding of the paleoclimate of Mars and the dominant forcing functions that drive large‐scale changes largely remains a mystery. However, the Martian Polar Layered Deposits (PLD) offer a promising avenue for unraveling the planet's recent paleoclimate history. Despite recent progress to detect a climate signal in the PLD, definitive evidence of a correlation between the stratigraphic record and Mars' recent orbital history remains elusive. We utilized new and updated techniques, including high‐resolution stratigraphic reconstruction from High Resolution Imagine Science Experiment stereo imagery and digital terrain models, combined with a technique of variable dip correction to account for three dimensional bedding orientations. Signal processing methods, such as wavelet and Fourier analysis, were applied to perform detailed time‐series analysis. These analyses revealed a quasi‐periodic signal indicative of fine bedding at a scale of approximately 2 m. Based on previously proposed deposition rates, these fine layers appear to correspond to timescales centering around 4,000 years. This suggests that the meter‐scale layers may not be the result of orbital forcing and hint at an unknown sub‐Milankovitch climate forcing mechanism. We discuss potential exogenic causal mechanisms, such as cyclic variations in solar activity, and endogenic factors, including large‐scale changes in dust distribution. Understanding the formation processes of these fine layers may significantly enhance our knowledge of Martian climate history and its driving forces. Plain Language Summary: In this paper, we investigate the presence, distribution, and significance of small‐scale layers in the northern polar layered deposits (PLD) of Mars. Solar radiation is a key variable in determining the long‐term evolution and stability of the polar caps, and it is closely linked to changes in the planet's orbit, such as precession, eccentricity, and obliquity. We argue that the thickness and periodicity of these fine layers reflect a causal mechanism that cannot be attributed solely to climate changes resulting from the long‐term evolution of Mars' orbit. Based on proposed accumulation rates of the polar ice, we suggest that the quasi‐periodic bedding may represent a climate signal occurring on timescales several orders of magnitude shorter than those of the orbit changes in Mars, centering around 4,000 years. These observations help to characterize and better understand the PLD and their formation. Key Points: Meter‐scale bedding is widespread throughout Mars northern polar layered depositsUsing image and topographic data, we show that the fine bedding is quasi‐periodic within a confined range of wavelengths from 1.5 to 3 mUnder previous deposition rate estimates, meter‐scale bedding corresponds to ∼ ${\sim} $4,000‐year, sub‐Milankovitch timescales [ABSTRACT FROM AUTHOR]

Objective: To compare efficacy and safety of tacrine hydrochloride with placebo in patients with probable Alzheimer's disease.Design: A 12-week, double-blind, placebo-controlled, parallel-group study.Setting: Outpatients at 23 centers.Patients: Men and women with probable Alzheimer's disease, at least 50 years old, mildly to moderately impaired, without other significant medical conditions.Interventions: In the initial 6 weeks, patients received placebo, 20 mg/d of tacrine, or 40 mg/d of tacrine. In the second 6 weeks, half received the same treatment and half increased tacrine dose: those receiving placebo increased to 20 mg/d, those receiving 20 mg/d increased to 40 mg/d, and those receiving 40 mg/d increased to 80 mg/d.Primary Outcome Measures: Alzheimer's Disease Assessment Scale (ADAS) cognitive component and clinician-rated Clinical Global Impression of Change (CGIC).Results: Four hundred sixty-eight patients entered. After 12 weeks, dose-related improvement was significant on the ADAS cognitive (P = .014), clinician-rated CGIC (P = .014), and caregiver-rated CGIC (P = .006). Comparison of 80 mg/d with placebo showed significant improvement on the ADAS cognitive (P = .015), clinician-rated CGIC (P = .016), and caregiver-rated CGIC (P = .028). Significant effects appeared as early as 6 weeks on the ADAS cognitive and caregiver-rated CGIC. Among patients receiving 80 mg/d of tacrine, 51% achieved a four-point or greater improvement of the ADAS cognitive component after 12 weeks of treatment. Reversible asymptomatic transaminase elevations greater than three times normal occurred in 25% of patients. Other treatment-related events included nausea and/or vomiting (8%), diarrhea (5%), abdominal pain (4%), dyspepsia (3%), and rash (3%).Conclusions: These results confirm the efficacy and safety of tacrine in some patients with Alzheimer's disease. After 12 weeks, the magnitude of the treatment effect is clinically important and recognized by the physician and caregiver. Liver toxicity is reversible and easily detected by weekly alanine aminotransferase determinations. [ABSTRACT FROM AUTHOR]

Objective: To determine whether fetal exposure to cigarette smoke impairs postnatal chemoreceptor control of ventilation and hypercapnic and hypoxic awakening responses., Study Design: Smoking (n = 13) and nonsmoking (n = 34) women were recruited during pregnancy. Serum cotinine levels were measured to assess level of nicotine exposure. The infants were studied at 2 to 3 months of age for ventilatory and awakening responses to hypoxia (17%, 15% and 13% inspired O2) and hypercapnia 4%, 6%, and 8% inspired CO2). Continuous measures were analyzed with unpaired t tests and analysis of variance for repeated measures. Proportions of awakening and periodic breathing were analyzed by means of a comparison of proportions., Results: The infants of smokers had lower birth weights (3022 +/- 566 vs 3518 +/- 491 gm; p < or = 0.005) and were older at the time of study (10.4 +/- 2.8 vs 8.7 +/- 1.3 weeks; p < 0.01) than the control infants. Maternal cotinine levels were higher in smokers (97.8 +/- 107 ng/ml vs no cotinine; p < 0.0001). More infants of smokers failed to awaken with hypoxia than did control infants (54% vs 15%; p = 0.006). The ventilatory responses to hypoxia and hypercapnia were similar in the two groups. All infants awakened with hypercapnia, and there was no difference in the awakening threshold for carbon dioxide (50.3 +/- 4.5 vs 48.3 +/- 5.4 mm Hg; p = 0.28)., Conclusion: Infants of mothers who smoked during pregnancy have deficient hypoxic awakening responses, which may contribute to the increased risk of sudden infant death syndrome in infants of smoking mothers.

Objective: To characterize the hepatic effects of tacrine treatment in patients with Alzheimer's disease., Design: Controlled trials of tacrine therapy consisting of two blinded, parallel-group trials; three blinded, enrichment-design trials; and their respective open-label extensions., Setting: Multicenter clinical trials in the United States, France, and Canada., Patients: A total of 2446 men and women at least 50 years of age with a diagnosis of probable Alzheimer's disease of mild to moderate severity and in good health without significant hepatic, cardiovascular, or renal disease., Intervention: Administration of tacrine vs placebo, with weekly measurement of serum hepatic enzymes., Main Outcome Measures: Incidence, maximum severity, and timing of event for serum alanine aminotransferase (ALT) elevation., Results: Among the 2446 patients who received tacrine in clinical trials, ALT levels greater than the upper limit of normal (ULN) occurred on at least one occasion in 1203 patients (49%), ALT levels greater than three times the ULN occurred in 621 patients (25%), and ALT levels greater than 20 times the ULN occurred in 40 patients (2%). The elevated ALT levels were generally asymptomatic and occurred more frequently in women than men. The mean time from initiation of tacrine treatment to first ALT level greater than three times the ULN was 50 days, and 90% of all initial ALT levels greater than three times the ULN occurred during the first 12 weeks of treatment. Of 145 patients who discontinued tacrine treatment because of an ALT level greater than three times the ULN and were rechallenged, 127 (88%) were able to resume long-term therapy with the drug. In all instances, discontinuing tacrine completely reversed elevations in ALT levels, and no deaths related to hepatotoxicity occurred., Conclusions: These data suggest that the potential for serious hepatic toxicity can be reduced through careful monitoring of ALT levels in patients who may benefit from tacrine therapy.