Therapeutic options for patients with multiple myeloma whose disease has relapsed after a prior auto-SCT include novel biologic therapies, traditional chemotherapy or a second transplant, with no ...clear standard of care. Few published studies address the safety and efficacy of a second auto-SCT for relapsed disease. We reviewed the Abramson Cancer Center experience with salvage auto-SCT for relapsed multiple myeloma. Forty-one patients had received a salvage auto-SCT at our institution; the median time between transplants was 37 months (range 3-91). The overall response rate in assessable patients was 55%, and treatment-related mortality was 7%. With a median follow-up time of 15 months, the median PFS was 8.5 months and the median overall survival (OS) was 20.7 months. In a multivariate analysis of OS, independent prognostic factors were >or=5 prior lines of therapy and time to progression after initial auto-SCT of <or=12 months. We conclude that in well-selected patients, salvage auto-SCT is safe and effective for relapsed myeloma.
We present the Dark Energy Camera (DECam) discovery of the optical counterpart of the first binary neutron star merger detected through gravitational-wave emission, GW170817. Our observations ...commenced 10.5 hr post-merger, as soon as the localization region became accessible from Chile. We imaged 70 deg2 in the i and z bands, covering 93% of the initial integrated localization probability, to a depth necessary to identify likely optical counterparts (e.g., a kilonova). At 11.4 hr post-merger we detected a bright optical transient located from the nucleus of NGC 4993 at redshift z = 0.0098, consistent (for km s−1 Mpc−1) with the distance of 40 8 Mpc reported by the LIGO Scientific Collaboration and the Virgo Collaboration (LVC). At detection the transient had magnitudes of and , and thus an absolute magnitude of , in the luminosity range expected for a kilonova. We identified 1500 potential transient candidates. Applying simple selection criteria aimed at rejecting background events such as supernovae, we find the transient associated with NGC 4993 as the only remaining plausible counterpart, and reject chance coincidence at the 99.5% confidence level. We therefore conclude that the optical counterpart we have identified near NGC 4993 is associated with GW170817. This discovery ushers in the era of multi-messenger astronomy with gravitational waves and demonstrates the power of DECam to identify the optical counterparts of gravitational-wave sources.
We present UV, optical, and near-infrared (NIR) photometry of the first electromagnetic counterpart to a gravitational wave source from Advanced Laser Interferometer Gravitational-wave Observatory ...(LIGO)/Virgo, the binary neutron star merger GW170817. Our data set extends from the discovery of the optical counterpart at 0.47-18.5 days post-merger, and includes observations with the Dark Energy Camera (DECam), Gemini-South/FLAMINGOS-2 (GS/F2), and the Hubble Space Telescope (HST). The spectral energy distribution (SED) inferred from this photometry at 0.6 days is well described by a blackbody model with T 8300 K, a radius of R 4.5 × 10 14 cm (corresponding to an expansion velocity of v 0.3 c ), and a bolometric luminosity of L bol 5 × 10 41 erg s−1. At 1.5 days we find a multi-component SED across the optical and NIR, and subsequently we observe rapid fading in the UV and blue optical bands and significant reddening of the optical/NIR colors. Modeling the entire data set, we find that models with heating from radioactive decay of 56Ni, or those with only a single component of opacity from r-process elements, fail to capture the rapid optical decline and red optical/NIR colors. Instead, models with two components consistent with lanthanide-poor and lanthanide-rich ejecta provide a good fit to the data; the resulting "blue" component has M ej blue 0.01 M and v ej blue 0.3 c , and the "red" component has M ej red 0.04 M and v ej red 0.1 c . These ejecta masses are broadly consistent with the estimated r-process production rate required to explain the Milky Way r-process abundances, providing the first evidence that binary neutron star (BNS) mergers can be a dominant site of r-process enrichment.
Both receptor-interacting protein kinase 1 (RIPK1) and RIPK3 can signal cell death following death receptor ligation. To study the requirements for RIPK-triggered cell death in the absence of death ...receptor signaling, we engineered inducible versions of RIPK1 and RIPK3 that can be activated by dimerization with the antibiotic coumermycin. In the absence of TNF or other death ligands, expression and dimerization of RIPK1 was sufficient to cause cell death by caspase- or RIPK3-dependent mechanisms. Dimerized RIPK3 induced cell death by an MLKL-dependent mechanism but, surprisingly, also induced death mediated by FADD, caspase 8 and RIPK1. Catalytically active RIPK3 kinase domains were essential for MLKL-dependent but not for caspase 8-dependent death. When RIPK1 or RIPK3 proteins were dimerized, the mode of cell death was determined by the availability of downstream molecules such as FADD, caspase 8 and MLKL. These observations imply that rather than a 'switch' operating between the two modes of cell death, the final mechanism depends on levels of the respective signaling and effector proteins.
•This IFCN guideline assesses the categories of evidence for clinical utility of EEG in adults with epilepsy.•EEG is useful for epilepsy diagnosis, classification and characterization before epilepsy ...surgery.•EEG monitoring is helpful to detect and quantify nonconvulsive seizures, especially in critically ill patients.
Electroencephalography (EEG) remains an essential diagnostic tool for people with epilepsy (PWE). The International Federation of Clinical Neurophysiology produces new guidelines as an educational service for clinicians to address gaps in knowledge in clinical neurophysiology. The current guideline was prepared in response to gaps present in epilepsy-related neurophysiological assessment and is not intended to replace sound clinical judgement in the care of PWE. Furthermore, addressing specific pathophysiological conditions of the brain that produce epilepsy is of primary importance though is beyond the scope of this guideline. Instead, our goal is to summarize the scientific evidence for the utility of EEG when diagnosing and monitoring PWE.
Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a ...multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.
Summary
Microbial photoautotrophs on glaciers engineer the formation of granular microbial‐mineral aggregates termed cryoconite which accelerate ice melt, creating quasi‐cylindrical pits called ...‘cryoconite holes’. These act as biogeochemical reactors on the ice surface and provide habitats for remarkably active and diverse microbiota. Evolution of cryoconite holes towards an equilibrium depth is well known, yet interactions between microbial activity and hole morphology are currently weakly addressed. Here, we experimentally perturbed the depths and diameters of cryoconite holes on the Greenland Ice Sheet. Cryoconite holes responded by sensitively adjusting their shapes in three dimensions (‘biocryomorphic evolution’) thus maintaining favourable conditions for net autotrophy at the hole floors. Non‐targeted metabolomics reveals concomitant shifts in cyclic AMP and fucose metabolism consistent with phototaxis and extracellular polymer synthesis indicating metabolomic‐level granular changes in response to perturbation. We present a conceptual model explaining this process and suggest that it results in remarkably robust net autotrophy on the Greenland Ice Sheet. We also describe observations of cryoconite migrating away from shade, implying a degree of self‐regulation of carbon budgets over mesoscales. Since cryoconite is a microbe‐mineral aggregate, it appears that microbial processes themselves form and maintain stable autotrophic habitats on the surface of the Greenland ice sheet.
Highlights • Individuals with HIV onantiretroviral treatment (ART) experience mortality at lower levels of alcohol use. • Individuals with HIV experience physiologic frailty at lower levels of ...alcohol use. • Alcohol consumption limits should be lower among HIV+ individuals.
Abstract
The Greenland Ice Sheet harbours a wealth of microbial life, yet the total biomass stored or exported from its surface to downstream environments is unconstrained. Here, we quantify ...microbial abundance and cellular biomass flux within the near-surface weathering crust photic zone of the western sector of the ice sheet. Using groundwater techniques, we demonstrate that interstitial water flow is slow (~10
−2
m d
−1
), while flow cytometry enumeration reveals this pathway delivers 5 × 10
8
cells m
−2
d
−1
to supraglacial streams, equivalent to a carbon flux up to 250 g km
−2
d
−1
. We infer that cellular carbon accumulation in the weathering crust exceeds fluvial export, promoting biomass sequestration, enhanced carbon cycling, and biological albedo reduction. We estimate that up to 37 kg km
−2
of cellular carbon is flushed from the weathering crust environment of the western Greenland Ice Sheet each summer, providing an appreciable flux to support heterotrophs and methanogenesis at the bed.
Clinical inertia Phillips, L S; Branch, W T; Cook, C B ...
Annals of internal medicine,
11/2001, Letnik:
135, Številka:
9
Journal Article
Recenzirano
Medicine has traditionally focused on relieving patient symptoms. However, in developed countries, maintaining good health increasingly involves management of such problems as hypertension, ...dyslipidemia, and diabetes, which often have no symptoms. Moreover, abnormal blood pressure, lipid, and glucose values are generally sufficient to warrant treatment without further diagnostic maneuvers. Limitations in managing such problems are often due to clinical inertia-failure of health care providers to initiate or intensify therapy when indicated. Clinical inertia is due to at least three problems: overestimation of care provided; use of "soft" reasons to avoid intensification of therapy; and lack of education, training, and practice organization aimed at achieving therapeutic goals. Strategies to overcome clinical inertia must focus on medical students, residents, and practicing physicians. Revised education programs should lead to assimilation of three concepts: the benefits of treating to therapeutic targets, the practical complexity of treating to target for different disorders, and the need to structure routine practice to facilitate effective management of disorders for which resolution of patient symptoms is not sufficient to guide care. Physicians will need to build into their practice a system of reminders and performance feedback to ensure necessary care.
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