Divergence of late Miocene Caribbean and tropical Eastern Pacific shallow-water benthic foraminifera

Abstrac

Relationship of benthic foraminiferal diversity to paleoproductivity in the Neogene of the Caribbean deep-sea

Abstrac

Neotectonic uplift of the Pacific Coast of Panama and Costa Rica, based on benthic foraminifera

Abstrac

Effects of the KCNQ channel opener ezogabine on functional connectivity of the ventral striatum and clinical symptoms in patients with major depressive disorder

Major depressive disorder (MDD) is a leading cause of disability worldwide, yet current treatment strategies remain limited in their mechanistic diversity. Recent evidence has highlighted a promising novel pharmaceutical target—the KCNQ-type potassium channel—for the treatment of depressive disorders, which may exert a therapeutic effect via functional changes within the brain reward system, including the ventral striatum. The current study assessed the effects of the KCNQ channel opener ezogabine (also known as retigabine) on reward circuitry and clinical symptoms in patients with MDD. Eighteen medication-free individuals with MDD currently in a major depressive episode were enrolled in an open-label study and received ezogabine up to 900 mg/day orally over the course of ten weeks. Resting state functional magnetic resonance imaging data were collected at baseline and post-treatment to examine brain reward circuitry. Reward learning was measured using a computerized probabilistic reward task. After treatment with ezogabine, subjects exhibited a significant reduction of depressive symptoms (Montgomery-Asberg Depression Rating Scale score change: −13.7±9.7,

Budesonide Oral Suspension Improves Symptomatic, Endoscopic, and Histologic Parameters Compared With Placebo in Patients With Eosinophilic Esophagitis

BACKGROUND & AIMS: Pharmacologic treatment of eosinophilic esophagitis (EoE) is limited to off-label use of corticosteroids not optimized for esophageal delivery. We performed a randomized, controlled phase 2 trial to assess the ability of budesonide oral suspension (BOS), a novel muco-adherent topical steroid formulation, to reduce symptoms and esophageal eosinophilia in adolescents and adults with EoE. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group trial, 93 EoE patients between the ages of 11 and 40 years with dysphagia and active esophageal eosinophilia were randomized to receive either BOS 2 mg or placebo twice daily for 12 weeks. Co-primary outcomes were change in Dysphagia Symptom Questionnaire (DSQ) score from baseline, and proportion of patients with a histologic response (≤6 eosinophils/high-power field) after treatment. Endoscopic severity scores and safety parameters were assessed. RESULTS: At baseline, mean DSQ scores were 29.3 and 29.0, and mean peak eosinophil counts were 156 and 130 per hpf in the BOS and placebo groups, respectively. After treatment, DSQ scores were 15.0 and 21.5, and mean peak eosinophil counts were 39 and 113 per high-power field, respectively (P < .05 for all). For BOS vs placebo, change in DSQ score was -14.3 vs -7.5 (P = .0096), histologic response rates were 39% vs 3% (P < .0001), and change in endoscopic severity score was -3.8 vs 0.4 (P < .0001). Adverse events were similar between groups. CONCLUSIONS: Treatment with BOS was well tolerated in adolescent and young adult patients with EoE and resulted in improvement in symptomatic, endoscopic, and histologic parameters using validated outcome instruments. ClinicalTrials.gov ID NCT01642212

Transit timings variations in the three-planet system: TOI-270

We present ground- and space-based photometric observations of TOI-270 (L231-32), a system of three transiting planets consisting of one super-Earth and two sub-Neptunes discovered by TESS around a bright (K-mag = 8.25) M3V dwarf. The planets orbit near low-order mean-motion resonances (5:3 and 2:1) and are thus expected to exhibit large transit timing variations (TTVs). Following an extensive observing campaign using eight different observatories between 2018 and 2020, we now report a clear detection of TTVs for planets c and d, with amplitudes of ∼10 min and a super-period of ∼3 yr, as well as significantly refined estimates of the radii and mean orbital periods of all three planets. Dynamical modelling of the TTVs alone puts strong constraints on the mass ratio of planets c and d and on their eccentricities. When incorporating recently published constraints from radial velocity observations, we obtain masses of Mb=1.48± 0.18, M⊕, Mc=6.20± 0.31, M⊕, and Md=4.20± 0.16, M⊕ for planets b, c, and d, respectively. We also detect small but significant eccentricities for all three planets: eb = 0.0167 ± 0.0084, ec = 0.0044 ± 0.0006, and ed = 0.0066 ± 0.0020. Our findings imply an Earth-like rocky composition for the inner planet, and Earth-like cores with an additional He/H2O atmosphere for the outer two. TOI-270 is now one of the best constrained systems of small transiting planets, and it remains an excellent target for atmospheric characterization

Formation of the Isthmus of Panama

The formation of the Isthmus of Panama stands as one of the greatest natural events of the Cenozoic, driving profound biotic transformations on land and in the oceans. Some recent studies suggest that the Isthmus formed manymillions of years earlier than the widely recognized age of approximately 3 million years ago (Ma), a result that if true would revolutionize our understanding of environmental, ecological, and evolutionary change across the Americas. To bring clarity to the question of when the Isthmus of Panama formed, we provide an exhaustive review and reanalysis of geological, paleontological, and molecular records. These independent lines of evidence converge upon a cohesive narrative of gradually emerging land and constricting seaways,withformationof theIsthmus of Panama sensustricto around 2.8 Ma. The evidence used to support an older isthmus is inconclusive, and we caution against the uncritical acceptance of an isthmus before the Pliocene.Facultad de Ciencias Naturales y Muse

Declining recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery in the community setting

Introduction: Randomized trials indicate that adjuvant radiotherapy plus tamoxifen decrease the five-year risk of recurrence among ductal carcinoma in situ patients treated with breast-conserving surgery from about 20% to 8%. The aims of this study were to examine the use and impact of these therapies on risk of recurrence among ductal carcinoma in situ patients diagnosed and treated in the community setting. Methods: We identified 2,995 patients diagnosed with ductal carcinoma in situ between 1990 and 2001 and treated with breast-conserving surgery at three large health plans. Medical charts were reviewed to confirm diagnosis and treatment and to obtain information on subsequent breast cancers. On a subset of patients, slides from the index ductal carcinoma in situ were reviewed for histopathologic features. Cumulative incidence curves were generated and Cox regression was used to examine changes in five-year risk of recurrence across diagnosis years, with and without adjusting for trends in use of adjuvant therapies. Results: Use of radiotherapy increased from 25.8% in 1990-1991 to 61.3% in 2000-2001; tamoxifen increased from 2.3% to 34.4%. A total of 245 patients had a local recurrence within five years of their index ductal carcinoma in situ. The five-year risk of any local recurrence decreased from 14.3% (95% confidence interval 9.8 to 18.7) for patients diagnosed in 1990-1991 to 7.7% (95% confidence interval 5.5 to 9.9) for patients diagnosed in 1998-1999; invasive recurrence decreased from 7.0% (95% confidence interval 3.8 to 10.3) to 3.1% (95% confidence interval 1.7 to 4.6). In Cox models, the association between diagnosis year and risk of recurrence was modestly attenuated after accounting for use of adjuvant therapy. Between 1990-1991 and 2000-2001, the proportion of patients with tumors with high nuclear grade decreased from 46% to 32% (P = 0.03) and those with involved surgical margins dropped from 15% to 0% (P = 0.03). Conclusions: The marked increase in the 1990s in the use of adjuvant therapy for ductal carcinoma in situ patients treated with breast-conserving surgery in the community setting only partially explains the 50% decline in risk of recurrence. Changes in pathology factors have likely also contributed to this decline

Cross-cutting principles for planetary health education

Since the 2015 launch of the Rockefeller Foundation Lancet Commission on planetary health,1 an enormous groundswell of interest in planetary health education has emerged across many disciplines, institutions, and geographical regions. Advancing these global efforts in planetary health education will equip the next generation of scholars to address crucial questions in this emerging field and support the development of a community of practice. To provide a foundation for the growing interest and efforts in this field, the Planetary Health Alliance has facilitated the first attempt to create a set of principles for planetary health education that intersect education at all levels, across all scales, and in all regions of the world—ie, a set of cross-cutting principles

Transit timings variations in the three-planet system : TOI-270

We present ground- and space-based photometric observations of TOI-270 (L231-32), a system of three transiting planets consisting of one super-Earth and two sub-Neptunes discovered by TESS around a bright (K-mag = 8.25) M3V dwarf. The planets orbit near low-order mean-motion resonances (5:3 and 2:1) and are thus expected to exhibit large transit timing variations (TTVs). Following an extensive observing campaign using eight different observatories between 2018 and 2020, we now report a clear detection of TTVs for planets c and d, with amplitudes of ∼10 min and a super-period of ∼3 yr, as well as significantly refined estimates of the radii and mean orbital periods of all three planets. Dynamical modelling of the TTVs alone puts strong constraints on the mass ratio of planets c and d and on their eccentricities. When incorporating recently published constraints from radial velocity observations, we obtain masses of Mb=1.48±0.18M⊕⁠, Mc=6.20±0.31M⊕⁠, and Md=4.20±0.16M⊕ for planets b, c, and d, respectively. We also detect small but significant eccentricities for all three planets : eb = 0.0167 ± 0.0084, ec = 0.0044 ± 0.0006, and ed = 0.0066 ± 0.0020. Our findings imply an Earth-like rocky composition for the inner planet, and Earth-like cores with an additional He/H2O atmosphere for the outer two. TOI-270 is now one of the best constrained systems of small transiting planets, and it remains an excellent target for atmospheric characterization