Association Between Pain Sensitization and Disease Activity in Patients With Rheumatoid Arthritis: A Cross‐Sectional Study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141868/1/acr23266.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141868/2/acr23266_am.pd

Lithium and Halpha in stars and brown dwarfs of sigma Orionis

We present intermediate- and low-resolution optical spectra around Halpha and LiI 6708 A for a sample of 25 low mass stars and 2 brown dwarfs with confirmed membership in the pre-main sequence stellar sigma Orionis cluster. Our observations are intended to investigate the age of the cluster. The spectral types derived for our target sample are found to be in the range K6-M8.5, which corresponds to a mass interval of roughly 1.2-0.02 Msun on the basis of state-of-the-art evolutionary models. Radial velocities (except for one object) are found to be consistent with membership in the Orion complex. All cluster members show considerable Halpha emission and LiI in absorption, which is typical of very young ages. We find that our pseudo-equivalent widths appear rather dispersed (and intense in the case of Halpha) for objects cooler than M3.5 spectral class, occurring at the approximate mass where low mass stars are expected to become fully convective. The least massive brown dwarf in our sample, SOri 45 (M8.5, ~0.02 Msun), displays variable Halpha emission and a radial velocity that differs from the cluster mean velocity. Tentative detection of forbidden lines in emission indicates that this brown dwarf may be accreting mass from a surrounding disk. We also present recent computations of LiI curves of growth for low gravities and for the temperature interval (about 4000-2600 K) of our sample. The comparison of our observations to these computations allows us to infer that no lithium depletion has yet taken place in sigma Orionis, and that the observed pseudo-equivalent widths are consistent with a cluster initial lithium abundance close to the cosmic value. Hence, the upper limit to the sigma Orionis cluster age can be set at 8 Myr, with a most likely value around 2-4 Myr.Comment: 17 pages (figures included). Accepted for publication in A&

Horizontal transport affecting trace gas seasonality in the Tropical Tropopause Layer (TTL)

We analyze horizontal transport from midlatitudes into the tropics (in-mixing) and its impact on seasonal variations of ozone, carbon monoxide and water vapor in the Tropical Tropopause Layer (TTL). For this purpose, we use three-dimensional backward trajectories, driven by ECMWF ERA-Interim winds, and a conceptual one-dimensional model of the chemical composition of the TTL. We find that the fraction of in-mixed midlatitude air shows an annual cycle with maximum during NH summer, resulting from the superposition of two inversely phased annual cycles for in-mixing from the NH and SH, respectively. In-mixing is driven by the monsoonal upper-level anticyclonic circulations. This circulation pattern is dominated by the Southeast Asian summer monsoon and, correspondingly, in-mixing shows an annual cycle. The impact of in-mixing on TTL mixing ratios depends on the in-mixed fraction of midlatitude air and on the meridional gradient of the particular species. For CO the meridional gradient and consequently the effect of in-mixing is weak. For water vapor, in-mixing effects are negligible. For ozone, the meridional gradient is large and the contribution of in-mixing to the ozone maximum during NH summer is about 50%. This in-mixing contribution is not sensitive to the tropical ascent velocity, which is about 40% too fast in ERA-Interim. As photochemically produced ozone in the TTL shows no distinct summer maximum, the ozone annual anomaly in the upper TTL turns out to be mainly forced by in-mixing of ozone-rich extratropical air during NH summer

Single Cell Genome Amplification Accelerates Identification of the Apratoxin Biosynthetic Pathway from a Complex Microbial Assemblage

Filamentous marine cyanobacteria are extraordinarily rich sources of structurally novel, biomedically relevant natural products. To understand their biosynthetic origins as well as produce increased supplies and analog molecules, access to the clustered biosynthetic genes that encode for the assembly enzymes is necessary. Complicating these efforts is the universal presence of heterotrophic bacteria in the cell wall and sheath material of cyanobacteria obtained from the environment and those grown in uni-cyanobacterial culture. Moreover, the high similarity in genetic elements across disparate secondary metabolite biosynthetic pathways renders imprecise current gene cluster targeting strategies and contributes sequence complexity resulting in partial genome coverage. Thus, it was necessary to use a dual-method approach of single-cell genomic sequencing based on multiple displacement amplification (MDA) and metagenomic library screening. Here, we report the identification of the putative apratoxin. A biosynthetic gene cluster, a potent cancer cell cytotoxin with promise for medicinal applications. The roughly 58 kb biosynthetic gene cluster is composed of 12 open reading frames and has a type I modular mixed polyketide synthase/nonribosomal peptide synthetase (PKS/NRPS) organization and features loading and off-loading domain architecture never previously described. Moreover, this work represents the first successful isolation of a complete biosynthetic gene cluster from Lyngbya bouillonii, a tropical marine cyanobacterium renowned for its production of diverse bioactive secondary metabolites

Archaeological sites as Distributed Long-term Observing Networks of the Past (DONOP)

The authors would also like to acknowledge the support of the National Science Foundation, specifically the Arctic Social Sciences Program, and RANNIS (The Icelandic Center for Research).Archaeological records provide a unique source of direct data on long-term human-environment interactions and samples of ecosystems affected by differing degrees of human impact. Distributed long-term datasets from archaeological sites provide a significant contribution to establish local, regional, and continental-scale environmental baselines and can be used to understand the implications of human decision-making and its impacts on the environment and the resources it provides for human use. Deeper temporal environmental baselines are essential for resource and environmental managers to restore biodiversity and build resilience in depleted ecosystems. Human actions are likely to have impacts that reorganize ecosystem structures by reducing diversity through processes such as niche construction. This makes data from archaeological sites key assets for the management of contemporary and future climate change scenarios because they combine information about human behavior, environmental baselines, and biological systems. Sites of this kind collectively form Distributed Long-term Observing Networks of the Past (DONOP), allowing human behavior and environmental impacts to be assessed over space and time. Behavioral perspectives are gained from direct evidence of human actions in response to environmental opportunities and change. Baseline perspectives are gained from data on species, landforms, and ecology over timescales that long predate our typically recent datasets that only record systems already disturbed by people. And biological perspectives can provide essential data for modern managers wanting to understand and utilize past diversity (i.e., trophic and/or genetic) as a way of revealing, and potentially correcting, weaknesses in our contemporary wild and domestic animal populations.PostprintPeer reviewe

Deep Sequencing of the Oral Microbiome Reveals Signatures of Periodontal Disease

The oral microbiome, the complex ecosystem of microbes inhabiting the human mouth, harbors several thousands of bacterial types. The proliferation of pathogenic bacteria within the mouth gives rise to periodontitis, an inflammatory disease known to also constitute a risk factor for cardiovascular disease. While much is known about individual species associated with pathogenesis, the system-level mechanisms underlying the transition from health to disease are still poorly understood. Through the sequencing of the 16S rRNA gene and of whole community DNA we provide a glimpse at the global genetic, metabolic, and ecological changes associated with periodontitis in 15 subgingival plaque samples, four from each of two periodontitis patients, and the remaining samples from three healthy individuals. We also demonstrate the power of whole-metagenome sequencing approaches in characterizing the genomes of key players in the oral microbiome, including an unculturable TM7 organism. We reveal the disease microbiome to be enriched in virulence factors, and adapted to a parasitic lifestyle that takes advantage of the disrupted host homeostasis. Furthermore, diseased samples share a common structure that was not found in completely healthy samples, suggesting that the disease state may occupy a narrow region within the space of possible configurations of the oral microbiome. Our pilot study demonstrates the power of high-throughput sequencing as a tool for understanding the role of the oral microbiome in periodontal disease. Despite a modest level of sequencing (∼2 lanes Illumina 76 bp PE) and high human DNA contamination (up to ∼90%) we were able to partially reconstruct several oral microbes and to preliminarily characterize some systems-level differences between the healthy and diseased oral microbiomes

Exome sequencing of individuals with Huntington’s disease implicates FAN1 nuclease activity in slowing CAG expansion and disease onset

The age at onset of motor symptoms in Huntington’s disease (HD) is driven by HTT CAG repeat length but modified by other genes. In this study, we used exome sequencing of 683 patients with HD with extremes of onset or phenotype relative to CAG length to identify rare variants associated with clinical effect. We discovered damaging coding variants in candidate modifier genes identified in previous genome-wide association studies associated with altered HD onset or severity. Variants in FAN1 clustered in its DNA-binding and nuclease domains and were associated predominantly with earlier-onset HD. Nuclease activities of purified variants in vitro correlated with residual age at motor onset of HD. Mutating endogenous FAN1 to a nuclease-inactive form in an induced pluripotent stem cell model of HD led to rates of CAG expansion similar to those observed with complete FAN1 knockout. Together, these data implicate FAN1 nuclease activity in slowing somatic repeat expansion and hence onset of HD

Microfluidics: reframing biological enquiry

The underlying physical properties of microfluidic tools have led to new biological insights through the development of microsystems that can manipulate, mimic and measure biology at a resolution that has not been possible with macroscale tools. Microsystems readily handle sub-microlitre volumes, precisely route predictable laminar fluid flows and match both perturbations and measurements to the length scales and timescales of biological systems. The advent of fabrication techniques that do not require highly specialized engineering facilities is fuelling the broad dissemination of microfluidic systems and their adaptation to specific biological questions. We describe how our understanding of molecular and cell biology is being and will continue to be advanced by precision microfluidic approaches and posit that microfluidic tools - in conjunction with advanced imaging, bioinformatics and molecular biology approaches - will transform biology into a precision science

Engaging at a Garden Vignette: The Effect on Neuropsychiatric Behaviour in Moderate to Severe Dementia

Neuropsychiatric behaviour is common in all those with dementia (1). Approaches to behaviour management have been both pharmacologic and nonpharmacologic. This study explored a nonpharmacologic intervention designed to reflect the understanding of behaviour as guided by: Need-driven Dementia-compromised Behaviour, Self-determination, Biophilia and Attention Restoration Theories. It was hypothesized that engaging at a garden vignette would reduce both neuropsychiatric behaviour and psychoactive medication given. A quasi-experimental within-subject repeated measures design was used. The five-phase design included baseline and two-week intervention and washout phases that were repeated. The study was set in a long-term care facility specializing in ‘difficult to manage’ behaviour. Participant admission criteria were limited to proxy consent, and moderate to severe dementia severity with no pain limitations. The garden vignettes included all materials required to ‘garden’ and create a feeling of a ‘garden’. Each vignette was easily accessed, centrally located, open to self-determined visits and available twenty-four hours per day during the intervention phases. The Mini-Mental State Exam and the Geriatric Dementia Scale were used to determine dementia severity. Measurement of neuropsychiatric behaviour was completed during the last week of each phase using the Neuropsychiatric Inventory –Nursing Home (NPI-NH), Cornell Scale for Depression in Dementia (CSDD), Single Question Depression Test (SQDT), Apathy Inventory (AI) and the Ryden Aggression Scale 2 (modified)(RAS2). Chart review recorded psychoactive PRN medication use. Activity at the garden vignette was video recorded twenty-four hours per day, seven days per week for the two weeks of each intervention phase. Significant neuropsychiatric behaviour changes were primarily between baseline and all other phases for the NPI-NH, NPI-NH-OD, CSDD and the RAS2. Greater neuropsychiatric behaviour and caregiver distress at baseline was associated with spending more time at the vignette. Spending significantly more time at the vignette in phase 2 was associated with spending more time in phase 4. Removal of the vignette created greater neuropsychiatric behaviour and caregiver distress in phase 3. A greater level of depression in phase 4 was associated with spending more time at the vignette and being self-determined was associated with less depression. There was no evidence of effect on apathy, self-assessed depression or psychoactive PRN medication administration

California’s ECE Workforce: What We Know Now and the Data Deficit That Remains

In 2006, to provide an in-depth portrait of the center-based and licensed family child care workforce across the state and regionally, the Center for the Study of Child Care Employment (CSCCE) and the California Child Care Resource and Referral Network conducted the California Early Care and Education Workforce Study. This study built on California’s long history of leadership in early childhood workforce research, which reaches back to the late 1970s. Yet, 12 years after this study, California lags behind a majority of other states when it comes to the status of its workforce data.The absence of an updated statewide survey or a statewide workforce registry creates numerous challenges to the implementation of evidence-based decision making. Too often, determinations about the workforce are made with scant information, which can lead to deciding that a policy does not work and moving on to developing new initiatives without sufficient or accurate information to assess impact and effectiveness or guide new approaches. Without better data, there is a risk of replicating the very same undetected or undocumented problems that led a previous approach to be deemed ineffective or failing. Additionally, numerous changes in the political, economic, and cultural environment in the past 12 years render the 2006 study severely out of date and underscore the urgency for current and ongoing data to accurately assess the consequences of policy approaches and interventions.This brief directs stakeholders to three more recent, though not comprehensive, sources of information about the California early childhood workforce: 1) local workforce data sources from three counties; 2) annual federal data collected by the U.S. Bureau of Labor Statistics; and 3) California-specific data drawn from the 2012 National Survey of Early Care and Education. Findings from the latter two sources are detailed below.We caution readers that moving among various datasets on the early childhood workforce can be challenging due to differences in how the population is determined, terminology used to describe members of the workforce, and phrasing of questions. A common challenge that arises is divergent numbers in the estimated size of the early childhood workforce, as we detail in Box 1