Observation of the Nernst signal generated by fluctuating Cooper pairs

Long-range order is destroyed in a superconductor warmed above its critical temperature (Tc). However, amplitude fluctuations of the superconducting order parameter survive and lead to a number of well established phenomena such as paraconductivity : an excess of charge conductivity due to the presence of short-lived Cooper pairs in the normal state. According to an untested theory, these pairs generate a transverse thermoelectric (Nernst) signal. In amorphous superconducting films, the lifetime of Cooper pairs exceeds the elastic lifetime of quasi-particles in a wide temperature range above Tc; consequently, the Cooper pairs Nernst signal dominate the response of the normal electrons well above Tc. In two dimensions, the magnitude of the expected signal depends only on universal constants and the superconducting coherence length, so the theory can be unambiguously tested. Here, we report on the observation of a Nernst signal in such a superconductor traced deep into the normal state. Since the amplitude of this signal is in excellent agreement with the theoretical prediction, the result provides the first unambiguous case for a Nernst effect produced by short-lived Cooper pairs

Platelet Activating Factor Blocks Interkinetic Nuclear Migration in Retinal Progenitors through an Arrest of the Cell Cycle at the S/G2 Transition

Nuclear migration is regulated by the LIS1 protein, which is the regulatory subunit of platelet activating factor (PAF) acetyl-hydrolase, an enzyme complex that inactivates the lipid mediator PAF. Among other functions, PAF modulates cell proliferation, but its effects upon mechanisms of the cell cycle are unknown. Here we show that PAF inhibited interkinetic nuclear migration (IKNM) in retinal proliferating progenitors. The lipid did not, however, affect the velocity of nuclear migration in cells that escaped IKNM blockade. The effect depended on the PAF receptor, Erk and p38 pathways and Chk1. PAF induced no cell death, nor a reduction in nucleotide incorporation, which rules out an intra-S checkpoint. Notwithstanding, the expected increase in cyclin B1 content during G2-phase was prevented in the proliferating cells. We conclude that PAF blocks interkinetic nuclear migration in retinal progenitor cells through an unusual arrest of the cell cycle at the transition from S to G2 phases. These data suggest the operation, in the developing retina, of a checkpoint that monitors the transition from S to G2 phases of the cell cycle

Patterns and predictors of long-term retention of inflammatory bowel or rheumatoid disease patients on innovator infliximab: an analysis of a Canadian prescriptions claims database [Erratum]

Baer PA, Aumais G, Ewara EM, et al. Patient Prefer Adherence. 2018;12:1805–1814. On page 1805, the affiliations were incorrectly listed. Read the original articl

Patterns and predictors of long-term retention of inflammatory bowel or rheumatoid disease patients on innovator infliximab: an analysis of a Canadian prescriptions claims database

Philip A Baer,1 Guy Aumais,2 Emmanuel M Ewara,3 Majed Khraishi,4 A Marilise Marrache,5 Remo Panaccione,6 John P Wade,7 John K Marshall8 1Baer Weinberg MPC, Scarborough, ON, 2Department of Medicine, Université de Montréal, Gastro-enterology Unit, Hôpital Maisonneuve-Rosemont, Montréal, QC, 3Government Affairs and Market Access, Janssen Inc., Toronto, ON, 4Medical Affairs, Janssen Inc., Toronto, ON, 5Faculty of Medicine, Division of Rheumatology, Memorial University of Newfoundland and Nexus Clinical Research, St John’s, NL, 6Inflammatory Bowel Disease Unit, Department of Medicine, University of Calgary, Calgary, AB, 7Department of Medicine, Division of Rheumatology, University of British Columbia, Vancouver, BC, 8Department of Medicine, Division of Gastroenterology, McMaster University and Farncombe Family Digestive Health Research Institute, Hamilton, ON, Canada Background: Long-term effectiveness is an important factor when considering treatment decisions. Objective: To determine the long-term retention patterns of Canadian inflammatory bowel disease (IBD) and rheumatologic disease (RD) patients, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with innovator infliximab (IFX) and to assess the impact of year-over-year cumulative IFX exposure on retention in both patient populations. Patients and methods: This analysis used a Canadian longitudinal prescription claims database to measure retention on IFX over a period of 5 years. Twelve-month unadjusted odds ratios of retention by time on IFX were calculated for the overall cohort, and within-group comparisons evaluated differences according to age, sex, region, insurance coverage, use of concomitant immunosuppressant therapy, indication (RD cohort only), and previous biologic experience. Between-group analyses compared unadjusted 5-year retention among the same variables. Variables that were independently associated with longer retention on IFX were identified using multivariable regression. Results: Seven thousand eight hundred and six IBD patients and 2,935 RD patients on stable treatment with IFX were included in the analysis. Sixty-nine percent of IBD patients and 66% of RD patients were retained on IFX after 1 year and 33% and 29%, respectively, were retained after 5 years. Moreover, the probability of being retained on IFX significantly increased with cumulative time on IFX. Independent predictors of 5-year retention included sex, region, and type of insurance coverage among IBD patients and region, type of insurance, prior biologic therapy, and specific indication among RD patients. Patients with IBD were 17% more likely to be retained on IFX over 5 years compared to patients with RD. Conclusion: Real-world Canadian IBD and RD patients on IFX have good overall long-term treatment retention. Previous duration of IFX treatment predicts better future retention, and this knowledge could help inform treatment decisions when patients have been stable on IFX treatment for varying periods of time. Keywords: administrative database, inflammation, anti-TNF drugs, biologicals, retentio

Safety of guselkumab with and without prior TNF-α inhibitor treatment: pooled results across four studies in patients with psoriatic arthritis

Objective: Assess pooled safety results through the end of the Phase 2/3 studies of guselkumab (≤2 years) in tumor necrosis factor-α inhibitor (TNFi) -naïve and -experienced patients with psoriatic arthritis (PsA). Methods: Data were pooled from the Phase 2 and DISCOVER-1 (TNFi-naïve/experienced), DISCOVER-2 (TNFi-naïve), and COSMOS (TNFi-experienced) studies. Patients with active PsA were randomized to guselkumab 100 mg every 4 or 8 weeks (Q4W+Q8W=Combined Guselkumab) or placebo with crossover to guselkumab Q4W or Q8W at Week 24. Time-adjusted adverse event (AE) rates (events/100 patient-years [PY]) and clinical laboratory findings were assessed during the placebo-controlled period and through end of study. Results: Of 1554 randomized patients (n=373 [guselkumab Q4W], 664 [guselkumab Q8W], and 517 [placebo]), 1138 (73.23%) were TNFi-naive and 416 (26.76%) were TNFi-experienced. Respective AE rates through Week 24 were 220.8/100PY (TNFi-naïve) and 251.6/100PY (TNFi-experienced) in the Combined Guselkumab group and 196.1/100PY (TNFi-naïve) and 303.0/100PY (TNFi-experienced) in the Placebo group. Among all guselkumab-treated patients (including those who crossed over from placebo), low AE rates were maintained during long-term evaluation in both TNFi-naïve (139.69/100PY) and TNFi-experienced (174.0/100PY) patients. Rates/100PY of AEs leading to treatment discontinuation, serious AEs, and other AEs of interest as well as occurrence of elevated hepatic transaminase levels and decreased neutrophil counts were consistent between placebo and guselkumab-treated patients through Week 24 treatment regardless of prior TNFi use and remained low through the end of the studies. Conclusion: The safety profile of guselkumab in TNFi-experienced patients was consistent with that in TNFi-naïve patients, which remained favorable for up to 2 years.</p

Multiple quantum criticality in a two-dimensional superconductor

The diverse phenomena associated with the two-dimensional electron gas (2DEG) that occurs at oxide interfaces include, among others, exceptional carrier mobilities, magnetism and superconductivity. Although these have mostly been the focus of interest for potential future applications, they also offer an opportunity for studying more fundamental quantum many-body effects. Here, we examine the magnetic-field-driven quantum phase transition that occurs in electrostatically gated superconducting LaTiO3/SrTiO3 interfaces. Through a finite-size scaling analysis, we show that it belongs to the (2 + 1)D XY model universality class. The system can be described as a disordered array of superconducting puddles coupled by a 2DEG and, depending on its conductance, the observed critical behaviour is single (corresponding to the long-range phase coherence in the whole array) or double (one related to local phase coherence, the other one to the array). A phase diagram illustrating the dependence of the critical field on the 2DEG conductance is constructed, and shown to agree with theoretical proposals. Moreover, by retrieving the coherence-length critical exponent nu, we show that the quantum critical behaviour can be clean or dirty according to the Harris criterion, depending on whether the phase-coherence length is smaller or larger than the size of the puddles