In July 1994, the Shoemaker–Levy 9 (SL9) impacts introduced hydrogen cyanide (HCN) to Jupiter at a well confined latitude band around −44°, over a range of specific longitudes corresponding to each ...of the 21 fragments (Bézard et al. 1997, Icarus 125, 94–120). This newcomer to Jupiter's stratosphere traces jovian dynamics. HCN rapidly mixed with longitude, so that observations recorded later than several months after impact witnessed primarily the meridional transport of HCN north and south of the impact latitude band. We report spatially resolved spectroscopy of HCN emission 10 months and 6 years following the impacts. We detect a total mass of HCN in Jupiter's stratosphere of 1.5±0.7×10
13 g in 1995 and 1.7±0.4×10
13 g in 2000, comparable to that observed several days following the impacts (Bézard et al. 1997, Icarus 125, 94–120). In 1995, 10 months after impact, HCN spread to −30° and −65° latitude (half column masses), consistent with a horizontal eddy diffusion coefficient of
K
yy
=2–3×10
10 cm
2
s
−1. Six years following impact HCN is observed in the northern hemisphere, while still being concentrated at 44° south latitude. Our meridional distribution of HCN suggests that mixing occurred rapidly north of the equator, with
K
yy
=2–5×10
11 cm
2
s
−1, consistent with the findings of Moreno et al. (2003, Planet. Space Sci. 51, 591–611) and Lellouch et al. (2002, Icarus 159, 112–131). These inferred eddy diffusion coefficients for Jupiter's stratosphere at 0.1–0.5 mbar generally exceed those that characterize transport on Earth. The low abundance of HCN detected at high latitudes suggests that, like on Earth, polar regions are dynamically isolated from lower latitudes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Introduction: Advances in the understanding of disease biology, the introduction of new drugs, and better supportive care have improved outcomes in multiple myeloma (MM). Most improvements have been ...observed in clinical trial and tertiary referral center populations but questions remain about the generalizability of these findings to patients treated in the community.
Methods: We studied all patients diagnosed with MM between 01/01/2001 and 12/31/2015 who had complete demographic and overall survival (OS) data available and were seen at Mayo Clinic (MAYO) or followed in the Surveillance, Epidemiology, and End Results Program (SEER, 18 registry data 2000 - 2016, 11/2018 submission). We retrieved age at diagnosis, sex, date of diagnosis, date of last follow-up, and OS for all patients. OS was defined as the time from diagnosis to death from any cause. Patients who were alive at the end of follow-up (12/31/ 2016) were censored. OS estimates were calculated using the Kaplan-Meier method. Age- and sex-adjusted Cox models were used to assess the association between the 5-year interval of diagnosis and OS. Expected OS estimates were calculated based on United States general population rate tables (Human Mortality Database) using a conditional approach. Standardized mortality ratios (SMR) were calculated by dividing the number of observed deaths by the number of expected deaths in age- and sex-matched general United States population controls. Linear regression models were fit to test for linear trends in early mortality and SMR over time (per 5-year interval). P-values below 0.05 were considered statistically significant.
Results: The median age at diagnosis was 3 years lower in patients at MAYO (64 years, 15% ≥ 75 years, 60% male, n = 3293) compared to SEER (67 years, 29% ≥ 75 years, 55% male, n = 61779). After a median follow-up of 2.8 years the median OS was longer in MAYO compared to SEER (5.4 versus 4.0 years, HR 0.82, 95% CI 0.78 - 0.86, p < 0.001) and remained statistically significant after adjusting for age and sex (HR 0.91, 95% CI 0.86 - 0.95, p < 0.001). Early mortality (1-year mortality) decreased between 2001-2005 and 2011-2015: From 20% to 11% at MAYO and from 26% to 19% in SEER. When grouping OS by year of diagnosis (in 5-year-intervals) improvements were seen in both populations (A) and remained statistically significant after adjusting for age and sex. The relative improvements were similar comparing the 5-year period after the introduction of the novel therapies (2006 - 2010) to 2001 - 2005 and more pronounced in MAYO for the most recent 5-year interval (2011 - 2015, A). This trend was reflected in a steady temporal improvement in 5-year OS estimates in MAYO including the most recent 5-year interval (2011 - 2015, B bottom left). In SEER there was a comparable increase between the first two 5-year intervals but a lesser improvement in more recently (2011 - 2015, B bottom left). A diagnosis of MM remained associated with significant excess mortality in all age groups over time in both populations (B top). There was a decrease in excess mortality over time at MAYO (SMR decline per 5-year interval 1.3, 95% CI 0.9 - 1.8, p < 0.001) while there was little change in SEER (SMR decline 0.0, 95% CI -0.3 - 0.3, p = 0.917, B bottom right). Further stratifying by age at diagnosis, the decrease in excess mortality was observed mostly in patients < 75 years at MAYO (SMR decline per 5-year interval 1.7, 95% CI 1.5 - 2.0, p < 0.001, C bottom left) and to a lesser extent in older patients (SMR decline 0.4, 95% CI 0.2 - 0.6, p < 0.001, C bottom right). No such trends towards improvement were observed in either age group in SEER (C bottom). In older patients, early mortality remained approximately 30% in both populations despite continued improvements, while the 5-year OS estimates for the most recent 5-year interval (2011 - 2015) were 37% at MAYO and 26% in SEER (C top).
Conclusions: Both early mortality and long-term survival have improved over time. Reductions in excess mortality were largely confined to younger patients with access to specialized care. Patients ≥ 75 years represent more than a quarter of all patients in the community, a third of them died within one year of the diagnosis, and only one in four was alive five years later. Older patients with MM remain a vulnerable population and have derived only limited benefit from recent advances in the field. Safe and effective therapies for older patients with MM remain an unmet need.
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Gertz:Ionis/Akcea: Consultancy; International Waldenstrom Foundation: Research Funding; Alnylam: Consultancy; Prothena Biosciences Inc: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Spectrum: Consultancy, Research Funding; Annexon: Consultancy; Appellis: Consultancy; Amgen: Consultancy; Medscape: Consultancy, Speakers Bureau; Physicians Education Resource: Consultancy; Abbvie: Other: personal fees for Data Safety Monitoring board; Research to Practice: Consultancy; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Proclara: Membership on an entity's Board of Directors or advisory committees; i3Health: Other: Development of educational programs and materials; Springer Publishing: Patents & Royalties; Amyloidosis Foundation: Research Funding. Dispenzieri:Alnylam: Research Funding; Akcea: Consultancy; Takeda: Research Funding; Pfizer: Research Funding; Janssen: Consultancy; Intellia: Consultancy; Celgene: Research Funding. Lacy:Celgene: Research Funding. Maurer:Nanostring: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Dingli:alexion: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Rigel: Consultancy; Karyopharm: Research Funding. Kapoor:Takeda: Honoraria, Research Funding; Celgene: Honoraria; Janssen: Research Funding; Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Glaxo Smith Kline: Research Funding; Cellectar: Consultancy. Leung:Takeda: Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; Aduro: Membership on an entity's Board of Directors or advisory committees; Omeros: Research Funding. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This is a series reviewing 14 cases of giant saccular aneurysms diagnosed at the Office of the Chief Medical Examiner of New York City collected over an 11-year period. Data collected on all 14 cases ...included neuropathological findings, comorbidities, and toxicological findings. Of these 14 cases, 8 were in women, and the ages ranged from 3 to 79 years, with a mean and a median of 50 years. Women were overrepresented in the sixth through eighth decades. Of the 14 cases described, 11 presented with a subarachnoid hemorrhage; 3, no hemorrhage; 2, subdural hemorrhage; 8, intraventricular hemorrhage; 2, intracerebral hemorrhage; and 8, more than 1 hemorrhage type. Location of the aneurysms varied with 6 in the left side of the brain, 6 present in the right side of the brain, and 2 at the midline. We described the clinical, pathological, and toxicological findings associated with these giant aneurysms.
Pomalidomide is a distinct immunomodulatory agent with significant activity in relapsed/refractory multiple myeloma (RRMM). The optimal treatment schedule in patients with RRMM who have received ...multiple lines of treatment, including bortezomib and lenalidomide, is 4 mg/day on days 1–21 of a 28-day cycle in combination with weekly low-dose dexamethasone. Improved responses and outcomes relative to traditional therapies continue to be confirmed in recently completed and ongoing trials. Pomalidomide exhibits direct tumoricidal, immunomodulatory, anti-angiogenic and anti-inflammatory activities, which facilitate combination therapy with agents with complementary mechanisms of action, resulting in greater anti-myeloma effects than single-agent therapy or previous combination therapies. For example, in combination with proteasome inhibitors and traditional chemotherapeutic agents in doublet or triplet regimens, pomalidomide provides high rates of durable response, and represents an important new treatment option for patients with RRMM requiring effective new therapies. Additionally, pomalidomide maintains its efficacy and tolerability profile in difficult-to-treat patients, including the elderly, patients with poor cytogenetics and those with renal impairment. This review summarises the clinical development of pomalidomide and discusses this effective agent for the treatment of patients with RRMM in the context of current myeloma treatment options, as well as potential future directions to further improve patient outcomes.
Delayed posthypoxic demyelination may rarely complicate an episode of severe hypoxia, with or without exposure to carbon monoxide. Following recovery from initial coma, progressive neurologic ...deterioration ensues with outcomes ranging from death to full recovery. Delayed posthypoxic demyelination is hypothesized to be immunemediated, with support coming from recent animal experiments.
We report a 46-year-old man who developed progressive cognitive deficits with abulia approximately 3 weeks after recovering from coma related to alcohol and morphine intoxication.
Despite treatment with high-dose steroids and plasmapheresis, he continued to deteriorate and remained in a vegetative state until his death under hospice care more than 2 months after his initial hypoxic insult. Serial brain imaging and postmortem examination showed bilateral necrosis of the globi pallidi and extensive demyelination in the centrum semiovale and corona radiata.
Based on an immune-mediated model of disease and given a lack of effective treatments, future use of immunomodulatory therapy may still be worth considering early in the course of this rare and potentially devastating condition.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
High-resolution infrared imaging spectroscopy of Mars has been achieved at the NASA Infrared Telescope Facility (IRTF) on June 19-21, 2003, using the Texas Echelon Cross Echelle Spectrograph (TEXES). ...The areocentric longitude was 206'. Following the detection and mapping of hydrogen peroxide H2O2 Encrenaz et al., 2004. Icarus 170, 424-429, we have derived, using the same data set, a map of the water vapor abundance. The results appear in good overall agreement with the TES results and with the predictions of the Global Circulation Model (GCM) developed at the Laboratory of Dynamical Meteorology (LMD), with a maximum abundance of water vapor of 3+/-1.5x10-4 (17+/-9 pr-D*mm). We have searched for CH4 over the martian disk, but were unable to detect it. Our upper limits are consistent with earlier reports on the methane abundance on Mars. Finally, we have obtained new measurements of CO2 isotopic ratios in Mars. As compared to the terrestrial values, these values are: (18O/17O)M/E = 1.03 +/- 0.09; (13C/12C)M/E = 1.00 +/- 0.11. In conclusion, in contrast with the analysis of Krasnopolsky et al. 1996. Icarus 124, 553-568, we conclude that the derived martian isotopic ratios do not show evidence for a departure from their terrestrial values.
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