Rain impacts on CO2 exchange in the western equatorial Pacific Ocean

The ocean plays a major role in the global carbon cycle through the atmosphere-ocean partitioning of atmospheric carbon dioxide. Rain alters the physics and carbon chemistry at the ocean surface to increase the amount of CO2 taken up by the ocean. This paper presents the results of a preliminary study wherein rain measurements in the western equatorial Pacific are used to determine the enhanced transfer, chemical dilution and deposition effects of rain on air-sea CO2 exchange. Including these processes, the western equatorial Pacific CO2 flux is modified from an ocean source of +0.019 mol CO2 m−2 yr−1 to an ocean sink of −0.078 mol CO2 m−2 yr−1. This new understanding of rain effects changes the ocean's role in the global carbon budget, particularly in regions with low winds and high precipitation

Inter-Observer Variation in the Pathologic Identification of Minimal Extrathyroidal Extension in Papillary Thyroid Carcinoma

Background: Extrathyroidal extension (ETE) is a significant prognostic factor in papillary thyroid carcinoma (PTC). Minimal extrathyroidal extension (mETE) is characterized by involvement of the sternothyroid muscle or perithyroid soft tissue, and is generally identified by light microscope examination. Patients with mETE, identified pathologically, are automatically upstaged to pT3. However, the prognostic implications of mETE have been a source of controversy in the literature. Moreover, there is also controversy surrounding the identification of mETE on pathological specimens. The objective of this study was to determine the level of agreement among expert pathologists in the identification of mETE in PTC cases. Methods: Eleven expert pathologists from the United States, Italy, and Canada were asked to perform a review of 69 scanned slides of representative permanent sections of PTC specimens. Each slide was evaluated for the presence of mETE. The pathologists were also asked to list the criteria they use to identify mETE. Results: The overall strength of agreement for identifying mETE was slight (??=?0.14). Inter-pathologist agreement was best for perithyroidal skeletal muscle involvement (??=?0.46, moderate agreement) and worst for invasion around thick-walled vascular structures (??=?0.02, slight agreement). In addition, there was disagreement over the constellation of histologic features that are diagnostic for mETE, which affected overall agreement for diagnosing mETE. Conclusions: Overall agreement for the identification of mETE is poor. Disagreement is a result of both variation in individual pathologists' interpretations of specimens and disagreement on the histologic criteria for mETE. Thus, the utility of mETE in staging and treatment of PTC is brought into question. The lack of concordance may explain the apparent lack of agreement regarding the prognostic significance of this pathologic feature.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140271/1/thy.2015.0508.pd

Inter-Observer Variation in the Pathologic Identification of Extranodal Extension in Nodal Metastasis from Papillary Thyroid Carcinoma

Background: Extranodal extension (ENE) in lymph node metastases has been shown to worsen the prognosis of papillary thyroid cancer (PTC). Despite the clinical significance of ENE, there are no stringent criteria for its microscopic diagnosis, and its identification is subject to inter-observer variability. The objective of this study was to determine the level of agreement among expert pathologists in the identification of ENE in PTC cases. Methods: Eleven expert pathologists from the United States, Italy, and Canada were asked to review 61 scanned slides of representative permanent sections of PTC specimens from Mount Sinai Beth Israel Medical Center in New York. Each slide was evaluated for the presence of ENE. The pathologists were also asked to report the criteria they use to identify ENE. Results: The overall strength of agreement in identifying ENE was only fair (??=?0.35), and the proportion of observed agreement was 0.68. The proportions of observed agreement for the identification of perinodal structures (fat, nerve, skeletal, and thick-walled vessel involvement) ranged from 0.61 to 0.997. Conclusions: Overall agreement for the identification of ENE is poor. The lack of agreement results from both variation in pathologists' identification of features and disagreement on the histologic criteria for ENE. This lack of concordance may help explain some of the discordant information regarding prognosis in clinical studies when this feature is identified.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140272/1/thy.2015.0551.pd

Metallicity and the Universality of the IMF

The stellar initial mass function (IMF), along with the star formation rate, is one of the fundamental properties that any theory of star formation must explain. An interesting feature of the IMF is that it appears to be remarkably universal across a wide range of environments. Particularly, there appears to be little variation in either the characteristic mass of the IMF or its high-mass tail between clusters with different metallicities. Previous attempts to understand this apparent independence of metallicity have not accounted for radiation feedback from high-mass protostars, which can dominate the energy balance of the gas in star-forming regions. We extend this work, showing that the fragmentation of molecular gas should depend only weakly on the amount of dust present, even when the primary heating source is radiation from massive protostars. First, we report a series of core collapse simulations using the ORION AMR code that systematically vary the dust opacity and show explicitly that this has little effect on the temperature or fragmentation of the gas. Then, we provide an analytic argument for why the IMF varies so little in observed star clusters, even as the metallicity varies by a factor of 100.Comment: 11 pages, 6 figures, emulateapj format, accepted to ApJ. Typos removed, references added, and discussion revised in section 3.2. Conclusions unchange

Negative beliefs about low back pain are associated with high pain intensity and high level disability in community-based women

Background Although previous studies have investigated beliefs about back pain in clinical and employed populations, there is a paucity of data examining the beliefs of the broader community. We aimed to characterize the beliefs that community-dwelling women have about back pain and its consequences, and to determine whether those with varying levels of pain intensity and disability differ in their beliefs. Methods 542 community-dwelling women, aged 24 to 80 years, were recruited from a research database. Participants completed a self-administered questionnaire that included detailed demographic information, the Chronic Pain Grade Questionnaire (CPG) and the Back Beliefs Questionnaire (BBQ). The CPG examined individuals\u27 levels of pain intensity and disability, and the BBQ investigated their beliefs about back pain and its consequences. Results 506 (93.4%) women returned the study questionnaire. The mean (SD) BBQ score for the cohort was 30.7 (6.0), indicating generally positive beliefs about back pain. However, those women with high intensity pain and high level disability had a mean (SD) score of 28.5 (5.7) and 24.8 (5.7) respectively, which reflects greater negativity about back pain and its consequences. There was an association between negative beliefs and high pain intensity (OR = 0.94 (95% CI: 0.90, 0.99), p = 0.01) and high level disability (OR = 0.93 (95% CI: 0.89, 0.97), p = 0.001), after adjusting for confounders. Conclusion This study highlights that although women living in the community were generally positive about back pain, subgroups of women with high pain intensity and high level disability were identified who had more pessimistic views. While a causal relationship cannot be inferred from these cross-sectional data, the results suggest that negative beliefs individuals have about back pain may be predictive of chronic, disabling spinal pain.<br /

Patient engagement in designing, conducting, and disseminating clinical pain research : IMMPACT recommended considerations

The consensus recommendations are based on the views of IMMPACT meeting participants and do not necessarily represent the views of the organizations with which the authors are affiliated. The following individuals made important contributions to the IMMPACT meeting but were not able to participate in the preparation of this article: David Atkins, MD (Department of Veterans Affairs), Rebecca Baker, PhD (National Institutes of Health), Allan Basbaum, PhD (University of California San Francisco), Robyn Bent, RN, MS (Food and Drug Administration), Nathalie Bere, MPH (European Medicines Agency), Alysha Croker, PhD (Health Canada), Stephen Bruehl, PhD (Vanderbilt University), Michael Cobas Meyer, MD, MBS (Eli Lilly), Scott Evans, PhD (George Washington University), Gail Graham (University of Maryland), Jennifer Haythornthwaite, PhD (Johns Hopkins University), Sharon Hertz, MD (Hertz and Fields Consulting), Jonathan Jackson, PhD (Harvard Medical School), Mark Jensen, PhD (University of Washington), Francis Keefe, PhD (Duke University), Karim Khan, MD, PhD, MBA (Canadian Institutes of Health Research), Lynn Laidlaw (University of Aberdeen), Steven Lane (Patient-Centered Outcomes Research Institute), Karen Morales, BS (University of Maryland), David Leventhal, MBA (Pfizer), Jeremy Taylor, OBE (National Institute for Health Research), and Lena Sun, MD (Columbia University). The manuscript has not been submitted, presented, or published elsewhere. Parts of the manuscript have been presented in a topical workshop at IASP World Congress on Pain in Toronto, in 2022.Peer reviewedPublisher PD

The Atypical Calpains: Evolutionary Analyses and Roles in Caenorhabditis elegans Cellular Degeneration

The calpains are physiologically important Ca2+-activated regulatory proteases, which are divided into typical or atypical sub-families based on constituent domains. Both sub-families are present in mammals, but our understanding of calpain function is based primarily on typical sub-family members. Here, we take advantage of the model organism Caenorhabditis elegans, which expresses only atypical calpains, to extend our knowledge of the phylogenetic evolution and function of calpains. We provide evidence that a typical human calpain protein with a penta EF hand, detected using custom profile hidden Markov models, is conserved in ancient metazoans and a divergent clade. These analyses also provide evidence for the lineage-specific loss of typical calpain genes in C. elegans and Ciona, and they reveal that many calpain-like genes lack an intact catalytic triad. Given the association between the dysregulation of typical calpains and human degenerative pathologies, we explored the phenotypes, expression profiles, and consequences of inappropriate reduction or activation of C. elegans atypical calpains. These studies show that the atypical calpain gene, clp-1, contributes to muscle degeneration and reveal that clp-1 activity is sensitive to genetic manipulation of [Ca2+]i. We show that CLP-1 localizes to sarcomeric sub-structures, but is excluded from dense bodies (Z-disks). We find that the muscle degeneration observed in a C. elegans model of dystrophin-based muscular dystrophy can be suppressed by clp-1 inactivation and that nemadipine-A inhibition of the EGL-19 calcium channel reveals that Ca2+ dysfunction underlies the C. elegans MyoD model of myopathy. Taken together, our analyses highlight the roles of calcium dysregulation and CLP-1 in muscle myopathies and suggest that the atypical calpains could retain conserved roles in myofilament turnover

Identification and Characterization of a Leucine-Rich Repeat Kinase 2 (LRRK2) Consensus Phosphorylation Motif

Mutations in LRRK2 (leucine-rich repeat kinase 2) have been identified as major genetic determinants of Parkinson's disease (PD). The most prevalent mutation, G2019S, increases LRRK2's kinase activity, therefore understanding the sites and substrates that LRRK2 phosphorylates is critical to understanding its role in disease aetiology. Since the physiological substrates of this kinase are unknown, we set out to reveal potential targets of LRRK2 G2019S by identifying its favored phosphorylation motif. A non-biased screen of an oriented peptide library elucidated F/Y-x-T-x-R/K as the core dependent substrate sequence. Bioinformatic analysis of the consensus phosphorylation motif identified several novel candidate substrates that potentially function in neuronal pathophysiology. Peptides corresponding to the most PD relevant proteins were efficiently phosphorylated by LRRK2 in vitro. Interestingly, the phosphomotif was also identified within LRRK2 itself. Autophosphorylation was detected by mass spectrometry and biochemical means at the only F-x-T-x-R site (Thr 1410) within LRRK2. The relevance of this site was assessed by measuring effects of mutations on autophosphorylation, kinase activity, GTP binding, GTP hydrolysis, and LRRK2 multimerization. These studies indicate that modification of Thr1410 subtly regulates GTP hydrolysis by LRRK2, but with minimal effects on other parameters measured. Together the identification of LRRK2's phosphorylation consensus motif, and the functional consequences of its phosphorylation, provide insights into downstream LRRK2-signaling pathways

Consumers’ experiences of back pain in rural Western Australia: Access to information and services, and self-management behaviours.

Background: Coordinated, interdisciplinary services, supported by self-management underpin effective management for chronic low back pain (CLBP). However, a combination of system, provider and consumer-based barriers exist which limit the implementation of such models into practice, particularly in rural areas where unique access issues exist. In order to improve health service delivery for consumers with CLBP, policymakers and service providers require a more in depth understanding of these issues. The objective of this qualitative study was to explore barriers experienced by consumers in rural settings in Western Australia (WA) to accessing information and services and implementing effective self-management behaviours for CLBP. Methods: Fourteen consumers with a history of CLBP from three rural sites in WA participated. Maximum variation sampling was employed to ensure a range of experiences were captured. An interviewer, blinded to quantitative pain history data, conducted semi-structured telephone interviews using a standardised schedule to explore individuals’ access to information and services for CLBP, and self-management behaviours. Interviews were digitally recorded and transcribed verbatim. Inductive analysis techniques were used to derive and refine key themes. Results: Five key themes were identified that affected individuals’ experiences of managing CLBP in a rural setting, including: 1) poor access to information and services in rural settings; 2) inadequate knowledge and skills among local practitioners; 3) feelings of isolation and frustration; 4) psychological burden associated with CLBP; and 5) competing lifestyle demands hindering effective self-management for CLBP.Conclusions: Consumers in rural WA experienced difficulties in knowing where to access relevant information for CLBP and expressed frustration with the lack of service delivery options to access interdisciplinary and specialist services for CLBP. Competing lifestyle demands such as work and family commitments were cited as key barriers to adopting regular self-management practices. Consumer expectations for improved health service coordination and a workforce skilled in pain management are relevant to future service planning, particularly in the contexts of workforce capacity, community health services, and enablers to effective service delivery in primary care