Metabolic profiling predicts response to anti-tumor necrosis factor α therapy in patients with rheumatoid arthritis

<p>Objective: Anti–tumor necrosis factor (anti-TNF) therapies are highly effective in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), but a significant number of patients exhibit only a partial or no therapeutic response. Inflammation alters local and systemic metabolism, and TNF plays a role in this. We undertook this study to determine if the patient's metabolic fingerprint prior to therapy could predict responses to anti-TNF agents.</p> <p>Methods: Urine was collected from 16 RA patients and 20 PsA patients before and during therapy with infliximab or etanercept. Urine metabolic profiles were assessed using nuclear magnetic resonance spectroscopy. Discriminating metabolites were identified, and the relationship between metabolic profiles and clinical outcomes was assessed.</p> <p>Results: Baseline urine metabolic profiles discriminated between RA patients who did or did not have a good response to anti-TNF therapy according to European League Against Rheumatism criteria, with a sensitivity of 88.9% and a specificity of 85.7%, with several metabolites contributing (in particular histamine, glutamine, xanthurenic acid, and ethanolamine). There was a correlation between baseline metabolic profiles and the magnitude of change in the Disease Activity Score in 28 joints from baseline to 12 months in RA patients (P = 0.04). In both RA and PsA, urinary metabolic profiles changed between baseline and 12 weeks of anti-TNF therapy. Within the responders, urinary metabolite changes distinguished between etanercept and infliximab treatment.</p> <p>Conclusion: The clear relationship between urine metabolic profiles of RA patients at baseline and their response to anti-TNF therapy may allow development of novel approaches to the optimization of therapy. Differences in metabolic profiles during treatment with infliximab and etanercept in RA and PsA may reflect distinct mechanisms of action.</p&gt

Racial and ethnic differences in incident myocardial infarction in end-stage renal disease patients: The USRDS

African Americans have a greater risk of cardiovascular disease (CVD) than Caucasians in early chronic kidney disease; however, limited data describe racial and ethnic differences in the risk of incident myocardial infarction (MI) among patients with end-stage renal disease (ESRD). We conducted a prospective, observational cohort study among 271 102 incident dialysis patients receiving renal replacement therapy enrolled in the United States Renal Data System (USRDS) for whom Medicare was the primary insurer between 1995 and 2000. The incidence and risk of any MI (non-fatal or fatal) estimated by Cox proportional hazards models was the primary outcome of interest. Of those with prevalent CVD at baseline (118 708), 14 849 had an incident non-fatal MI compared with 9926 events for those without prevalent CVD (152 394). Patients with prevalent CVD had higher crude rates of combined fatal and non-fatal MI (99.3/1000 person-years vs 42.9/1000 person-years) compared with those without prevalent CVD. Among those with prevalent CVD, African Americans (adjusted relative risk (aRR)=0.65, 95% confidence interval (CI):0.62–0.68), Asian Americans (aRR=0.74, 95% CI: 0.66–0.83), and Hispanics (aRR=0.72, 95% CI: 0.68–0.77) were 26–35% less likely to have an incident MI compared to Caucasians. Similarly, among those without prevalent CVD, racial/ethnic minorities were 26–42% less likely to have an incident MI compared to Caucasians. We conclude that in a national setting where comparable access to dialysis and associated medical care, exist, racial/ethnic minorities were found to have a lower risk of non-fatal and fatal MI than Caucasians

Lattice-switch Monte Carlo

We present a Monte Carlo method for the direct evaluation of the difference between the free energies of two crystal structures. The method is built on a lattice-switch transformation that maps a configuration of one structure onto a candidate configuration of the other by `switching' one set of lattice vectors for the other, while keeping the displacements with respect to the lattice sites constant. The sampling of the displacement configurations is biased, multicanonically, to favor paths leading to `gateway' arrangements for which the Monte Carlo switch to the candidate configuration will be accepted. The configurations of both structures can then be efficiently sampled in a single process, and the difference between their free energies evaluated from their measured probabilities. We explore and exploit the method in the context of extensive studies of systems of hard spheres. We show that the efficiency of the method is controlled by the extent to which the switch conserves correlated microstructure. We also show how, microscopically, the procedure works: the system finds gateway arrangements which fulfill the sampling bias intelligently. We establish, with high precision, the differences between the free energies of the two close packed structures (fcc and hcp) in both the constant density and the constant pressure ensembles.Comment: 34 pages, 9 figures, RevTeX. To appear in Phys. Rev.

A conflict management tool for conservation agencies

1. Growing pressure on natural resources is leading to more conservation conflicts. Governments and their statutory agencies devote increasing financial and human resources to this subject, but tend to adopt reactive, ad hoc approaches to management. 2. We combined theory and empirical data about five conservation conflicts in a transdisciplinary collaboration to co-develop a novel decision-making tool. 3. This tool uses a systematic stepwise approach with six distinct decision stages: (i) establishing whether there is a conflict or an impact; (ii) understanding the context of the conflict, including the stakeholders affected; (iii) developing shared understanding of the conflict and goals; (iv) building a consensus on how to reach the goals; (v) implementing measures; and (vi) monitoring the outcomes. 4. Policy implications. We argue this new tool has wide applicability and democratic legitimacy and offers an exciting and practical approach to improve the management of conservation conflicts

Theory of High \tc Ferromagnetism in SrB6SrB_6 family: A case of Doped Spin-1 Mott insulator in a Valence Bond Solid Phase

Doped divalent hexaborides such as $Sr_{1-x}La_xB_6$ exhibit high \tc ferromagnetism. We isolate a degenerate pair of $2p$-orbitals of boron with two valence electrons, invoke electron correlation and Hund coupling, to suggest that the undoped state is better viewed as a spin-1 Mott insulator; it is predicted to be a type of 3d Haldane gap phase with a spin gap $\sim 0.1 eV$, much smaller than the charge gap of $> 1.0 eV$ seen in ARPES. The experimentally seen high \tc `ferromagnetism' is argued to be a complex magnetic order in disguise - either a canted 6-sublattice AFM ($\approx 120^0$) order or its quantum melted version, a chiral spin liquid state, arising from a type of double exchange mechanism.Comment: 4 pages, 2 figures; minor corrections, references adde

A transdisciplinary approach to a conservation crisis: a case study of the Eurasian curlew (Numenius arquata) in Ireland

In this article, we build on a growing literature of examples of transdisciplinary approaches to illustrate the catalysts and outcomes of a stakeholder‐driven process to conservation practice. We illustrate this using the case of one of Europe's most rapidly declining bird species, the Eurasian curlew (Numenius arquata ). As part of the response to its continuing decline, a stakeholder‐driven workshop was held in Ireland in November 2016, bringing together over 80 stakeholders from a range of governmental, non‐governmental, and private organizations responsible for or interested in curlew conservation and management. This innovative workshop sought to formulate ideas and support the implementation of actions from stakeholders themselves on how to halt further losses of curlews, within the current legislative framework. Four years on, many of the short‐ and medium‐term actions identified during the workshop have been implemented jointly by stakeholders. However, curlew recovery will require continued communication and meaningful engagement with all relevant stakeholders together with increased government support underpinned by increased public awareness and ownership of the curlew's plight. Ultimately, many stakeholders will measure the success of curlew conservation in Ireland by the long‐term viability of the breeding population

Postsurgical Opioid Prescriptions and Risk of Long-term Use: An Observational Cohort Study Across the United States

Objective: The aim of this study was to evaluate differences in risk of longterm opioid therapy after surgery among an opioid-naive population using varying cutoffs based on days supplied (DS), total morphine milligram equivalents (MME) dispensed, and quantity of pills (QTY) dispensed. Background: In response to the US opioid crisis, opioid prescription (Rx) limits have been implemented on a state-by-state basis beginning in 2016. However, there is limited evidence informing appropriate prescribing limits, and the effect of these policies on long-term opioid therapy. Methods: Using the MarketScan claims databases, we identified all opioidnaive patients undergoing outpatient surgery between July 1, 2006 and June 30, 2015. We identified the initial postsurgical opioid prescribed, examining the DS, total MME, and QTY dispensed.We used Poisson to estimate adjusted risk differences and risk ratios of long-term opioid use comparing those receiving larger versus smaller volume of opioids. Results: We identified 5,148,485 opioid-naive surgical patients. Overall, 55.5% received an opioid for postoperative pain, with median days supply =5 and median total MME = 240. The proportion of patients receiving prescriptions above 7 DS increased from 11% in 2006 to 19% in 2015. Among those receiving postoperative opioids, 8% had long-term opioid use, and risk of long-term use was 1.16 times [95% confidence interval (CI), 1.10-1.25] higher among those receiving >7 days compared with those receiving ≤7 days. Those receiving >400 total MME (15% of patients) were at 1.17 times (95% CI, 1.10-1.25) the risk of long-term use compared with those receiving ≤400 MME. Conclusions: Between 2005 and 2015, the amounts of opioids prescribed for postoperative pain increased dramatically, and receipt of larger volume of opioids was associated with increased risk of long-term opioid therapy

Effects of deformation in the three-body structure of 11Li

11Li is studied within a three-body model 9Li+n+n where the core is allowed to be deformed and/or excite. In particular, we include reorientation couplings and couplings between the two bound states of 9Li. Contrary to the other examples studied within this model, we find that core excitation does not affect the structure of 11Li significantly. Reorientation couplings of the deformed 9Li can change the ground state of 11Li from a predominantly two neutron s1/2^2 configuration into a p1/2^2. In addition, we see no evidence for the existence of significant d-wave strength in its ground state, as opposed to the prediction by shell model. A comparison with shell model is presented.Comment: 13 pages, 9 figure

Nonuniform symmetry breaking in noncommutative λΦ4\lambda \Phi^4 theory

The spontaneous symmetry breaking in noncommutative $\lambda\Phi^4$ theory has been analyzed by using the formalism of the effective action for composite operators in the Hartree-Fock approximation. It turns out that there is no phase transition to a constant vacuum expectation of the field and the broken phase corresponds to a nonuniform background. By considering $=A \cos(\vec Q \cdot \vec x)$ the generated mass gap depends on the angles among the momenta $\vec k$ and $\vec Q$ and the noncommutativity parameter $\vec\theta$. The order of the transition is not easily determinable in our approximation.Comment: 18 pages, 4 figures, added reference