Suffix Trees Considered Harmful

The implications of adaptive theory have been far-reaching and pervasive. In this paper, au- thors demonstrate the evaluation of journaling file systems, which embodies the intuitive principles of programming languages. We prove that despite the fact that Scheme and Markov models are often incompatible, 802.11 mesh networks and Web services can agree to answer this grand challenge

Generation of high-frequency topographic Rossby waves in the Gulf of Mexico

The Loop Current Eddy (LCE) separation cycle energizes deep circulation in the eastern Gulf of Mexico, transferring energy from the surface intensified Loop Current (LC) to the typically quiescent lower layers. To document the generation and radiation of deep energy during this cycle, an array of 24 current and pressure recording inverted echo sounders (CPIES) is deployed in the region 89°W to 86°W, 25°N to 27.5°N with the intent to capture circulation near bathymetric features thought to be important for current-topographic interactions: Campeche Bank, Mississippi Fan, and West Florida Shelf. During the nearly two-year deployment, June 2019 to May 2021, three LCE separation events are observed, during which energy injected into the deep Gulf organizes into two distinct frequency bands (1/100 – 1/20 days–1 and 1/20 – 1/10 days–1). High-frequency variability dominates the array’s northwest corner in the vicinity of the Mississippi Fan. Wave properties are consistent with topographic Rossby Waves (TRWs) with wavelengths of 150 – 300 km. Their generation coincides with each LCE separation and is attributed to an upper-lower layer resonant coupling between surface meanders and the sloping topography of the Mississippi Fan. TRWs captured by the CPIES array will likely intensify as wavelengths shorten in steeper topography along propagation pathways towards the Sigsbee Escarpment, generating hazardous currents with the potential to disrupt oil and gas operations in the region

Evaluating models for lithospheric loss and intraplate volcanism beneath the Central Appalachian Mountains

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Long, M. D., Wagner, L. S., King, S. D., Evans, R. L., Mazza, S. E., Byrnes, J. S., Johnson, E. A., Kirby, E., Bezada, M. J., Gazel, E., Miller, S. R., Aragon, J. C., & Liu, S. Evaluating models for lithospheric loss and intraplate volcanism beneath the Central Appalachian Mountains. Journal of Geophysical Research: Solid Earth, 126(10), (2021): e2021JB022571, https://doi.org/10.1029/2021JB022571.The eastern margin of North America has been shaped by a series of tectonic events including the Paleozoic Appalachian Orogeny and the breakup of Pangea during the Mesozoic. For the past ∼200 Ma, eastern North America has been a passive continental margin; however, there is evidence in the Central Appalachian Mountains for post-rifting modification of lithospheric structure. This evidence includes two co-located pulses of magmatism that post-date the rifting event (at 152 and 47 Ma) along with low seismic velocities, high seismic attenuation, and high electrical conductivity in the upper mantle. Here, we synthesize and evaluate constraints on the lithospheric evolution of the Central Appalachian Mountains. These include tomographic imaging of seismic velocities, seismic and electrical conductivity imaging along the Mid-Atlantic Geophysical Integrative Collaboration array, gravity and heat flow measurements, geochemical and petrological examination of Jurassic and Eocene magmatic rocks, and estimates of erosion rates from geomorphological data. We discuss and evaluate a set of possible mechanisms for lithospheric loss and intraplate volcanism beneath the region. Taken together, recent observations provide compelling evidence for lithospheric loss beneath the Central Appalachians; while they cannot uniquely identify the processes associated with this loss, they narrow the range of plausible models, with important implications for our understanding of intraplate volcanism and the evolution of continental lithosphere. Our preferred models invoke a combination of (perhaps episodic) lithospheric loss via Rayleigh-Taylor instabilities and subsequent small-scale mantle flow in combination with shear-driven upwelling that maintains the region of thin lithosphere and causes partial melting in the asthenosphere.The authors acknowledge support from the U.S. National Science Foundation EarthScope and GeoPRISMS programs via grants EAR-1460257 (R. L. Evans), EAR-1249412 (E. Gazel), EAR-1249438 (E. A. Johnson), EAR-1250988 (S. D. King), EAR-1251538 (E. Kirby), and EAR-1251515 (M. D. Long). The collection and dissemination of most of the geophysical data and models discussed in this study were facilitated by the Incorporated Research Institutions for Seismology (IRIS). The facilities of the IRIS Consortium are supported by the United States National Science Foundation under Cooperative Agreement EAR-1261681

Evaluation of health care providers’ role transition and satisfaction in hospital-at-home for chronic obstructive pulmonary disease exacerbations: a survey study

__Abstract__ __Background__: Hospital-at-home is an accepted alternative for usual hospital treatment for patients with a Chronic Obstructive Pulmonary Disease (COPD) exacerbation. The introduction of hospital-at-home may lead to changes in health care providers’ roles and responsibilit

SMARCB1 loss induces druggable cyclin D1 deficiency via upregulation of MIR17HG in atypical teratoid rhabdoid tumors

Atypical teratoid rhabdoid tumor (ATRT) is a fatal pediatric malignancy of the central neural system lacking effective treatment options. It belongs to the rhabdoid tumor family and is usually caused by biallelic inactivation of SMARCB1, encoding a key subunit of SWI/SNF chromatin remodeling complexes. Previous studies proposed that SMARCB1 loss drives rhabdoid tumor by promoting cell cycle through activating transcription of cyclin D1 while suppressing p16. However, low cyclin D1 protein expression is observed in most ATRT patient tumors. The underlying mechanism and therapeutic implication of this molecular trait remain unknown. Here, we show that SMARCB1 loss in ATRT leads to the reduction of cyclin D1 expression by upregulating MIR17HG, a microRNA (miRNA) cluster known to generate multiple miRNAs targeting CCND1. Furthermore, we find that this cyclin D1 deficiency in ATRT results in marked in vitro and in vivo sensitivity to the CDK4/6 inhibitor palbociclib as a single agent. Our study identifies a novel genetic interaction between SMARCB1 and MIR17HG in regulating cyclin D1 in ATRT and suggests a rationale to treat ATRT patients with FDA- approved CDK4/6 inhibitors. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156416/2/path5493.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156416/1/path5493_am.pd

Examination of the association of sex and race/ethnicity with appearance concerns: A Scleroderma Patient-centered Intervention Network (SPIN) cohort study

Objective: Appearance concerns are common in systemic sclerosis (SSc) and have been linked to younger age and more severe disease. No study has examined their association with sex or race/ethnicity. Methods: SSc patients were sampled from the Scleroderma Patient-centered Intervention Network Cohort. Presence of appearance concerns was assessed with a single item, and medical and sociodemographic information were collected. Results: Of 644 patients, appearance concerns were present in 72%, including 421 of 565 women (75%), 42 of 79 men (53%), 392 of 550 patients who identified as White (71%), 35 of 41 who identified as Black (85%), and 36 of 53 who identified as another race/ethnicity (68%). In multivariate analysis, women had significantly greater odds of reporting appearance concerns than men (odds ratio (OR)=2.97, 95% confidence interval (CI)=1.78-4.95,

"It's just horrible": a qualitative study of patients' and carers' experiences of bowel dysfunction in Multiple Sclerosis

Background: Around 50% of people with multiple sclerosis (MS) experience neurogenic bowel dysfunction (constipation and / or faecal incontinence), reducing quality of life and increasing carer burden. No previous qualitative studies have explored the experiences of bowel problems in people with MS, or the views of their family carers. Objective: To understand 'what it is like' to live with bowel dysfunction and the impact this has on people with MS and carers. Methods: Using exploratory qualitative methods, 47 semi-structured interviews were conducted with participants recruited from specialist hospital clinics and community sources using purposive and chain-referral sampling. Data were analysed using a pragmatic inductive-deductive method. Results: Participants identified multiple psychological, physical and social impacts of bowel dysfunction. Health care professional support ranged from empathy and appropriate onward referral, to lack of interest or not referring to appropriate services. Participants want bowel issues to be discussed more openly, with clinicians instigating a discussion early after MS diagnosis and repeating enquiries regularly. Conclusions: Bowel dysfunction impacts on the lives of people with MS and their carers; their experience with care services is often unsatisfactory. Understanding patient and carer preferences about management of bowel dysfunction can inform clinical care and referral pathways

Estimation of minimally important differences in EQ-5D utility and VAS scores in cancer

<p>Abstract</p> <p>Background</p> <p>Understanding what constitutes an important difference on a HRQL measure is critical to its interpretation. The aim of this study was to provide a range of estimates of minimally important differences (MIDs) in EQ-5D scores in cancer and to determine if estimates are comparable in lung cancer.</p> <p>Methods</p> <p>A retrospective analysis was conducted on cross-sectional data collected from 534 cancer patients, 50 of whom were lung cancer patients. A range of minimally important differences (MIDs) in EQ-5D index-based utility (UK and US) scores and VAS scores were estimated using both anchor-based and distribution-based (1/2 standard deviation and standard error of the measure) approaches. Groups were anchored using Eastern Cooperative Oncology Group performance status (PS) ratings and FACT-G total score-based quintiles.</p> <p>Results</p> <p>For UK-utility scores, MID estimates based on PS ranged from 0.10 to 0.12 both for all cancers and for lung cancer subgroup. Using FACT-G quintiles, MIDs were 0.09 to 0.10 for all cancers, and 0.07 to 0.08 for lung cancer. For US-utility scores, MIDs ranged from 0.07 to 0.09 grouped by PS for all cancers and for lung cancer; when based on FACT-G quintiles, MIDs were 0.06 to 0.07 in all cancers and 0.05 to 0.06 in lung cancer. MIDs for VAS scores were similar for lung and all cancers, ranging from 8 to 12 (PS) and 7 to 10 (FACT-G quintiles).</p> <p>Discussion</p> <p>Important differences in EQ-5D utility and VAS scores were similar for all cancers and lung cancer, with the lower end of the range of estimates closer to the MID, i.e. 0.08 for UK-index scores, 0.06 for US-index scores, and 0.07 for VAS scores.</p

Quantitative Evidence for the Effects of Multiple Drivers on Continental-Scale Amphibian Declines

Since amphibian declines were first proposed as a global phenomenon over a quarter century ago, the conservation community has made little progress in halting or reversing these trends. The early search for a “smoking gun” was replaced with the expectation that declines are caused by multiple drivers. While field observations and experiments have identified factors leading to increased local extinction risk, evidence for effects of these drivers is lacking at large spatial scales. Here, we use observations of 389 time-series of 83 species and complexes from 61 study areas across North America to test the effects of 4 of the major hypothesized drivers of declines. While we find that local amphibian populations are being lost from metapopulations at an average rate of 3.79% per year, these declines are not related to any particular threat at the continental scale; likewise the effect of each stressor is variable at regional scales. This result - that exposure to threats varies spatially, and populations vary in their response - provides little generality in the development of conservation strategies. Greater emphasis on local solutions to this globally shared phenomenon is needed