Spin-polarized superconductivity: order parameter topology, current dissipation, and multiple-period Josephson effect

We discuss transport properties of fully spin-polarized triplet superconductors, where only electrons of one spin component (along a certain axis) are paired. Due to the structure of the order parameter space, wherein phase and spin rotations are intertwined, a configuration where the superconducting phase winds by $4\pi$ in space is topologically equivalent to a configuration with no phase winding. This opens the possibility of supercurrent relaxation by a smooth deformation of the order parameter, where the order parameter remains non-zero at any point in space throughout the entire process. During the process, a spin texture is formed. We discuss the conditions for such processes to occur and their physical consequences. In particular, we show that when a voltage is applied, they lead to an unusual alternating-current Josephson effect whose period is an integer multiple of the usual Josephson period. These conclusions are substantiated in a simple time-dependent Ginzburg-Landau model for the dynamics of the order parameter. One of the potential applications of our analysis is for moir\'e systems, such as twisted bilayer and double bilayer graphene, where superconductivity is found in the vicinity of ferromagnetism.Comment: 12+7 pages, 6 figure

Space Solar Cell Research and Development Projects at Emcore Photovoltaics

The GaInP2/InGaAs/Ge triple junction device lattice matched to germanium has achieved the highest power conversion efficiency and the most commercial success for space applications [1]. What are the practical performance limits of this technology? In this paper we will describe what we consider to be the practical performance limits of the lattice matched GaInP2/InGaAs/Ge triple junction cell. In addition, we discuss the options for next generation space cell performance

New Cancer Immunotherapy Agents in Development: a report from an associated program of the 31

This report is a summary of \u27New Cancer Immunotherapy Agents in Development\u27 program, which took place in association with the 31st Annual Meeting of the Society for Immunotherapy of Cancer (SITC), on November 9, 2016 in National Harbor, Maryland. Presenters gave brief overviews of emerging clinical and pre-clinical immune-based agents and combinations, before participating in an extended panel discussion with multidisciplinary leaders, including members of the FDA, leading academic institutions and industrial drug developers, to consider topics relevant to the future of cancer immunotherapy

Blockade of interleukin-6 signalling with siltuximab enhances melphalan cytotoxicity in preclinical models of multiple myeloma

Signalling through the interleukin (IL)-6 pathway induces proliferation and drug resistance of multiple myeloma cells. We therefore sought to determine whether the IL-6-neutralizing monoclonal antibody siltuximab, formerly CNTO 328, could enhance the activity of melphalan, and to examine some of the mechanisms underlying this interaction. Siltuximab increased the cytotoxicity of melphalan in KAS-6/1, INA-6, ANBL-6, and RPMI 8226 human myeloma cell lines (HMCLs) in an additive-to-synergistic manner, and sensitized resistant RPMI 8226.LR5 cells to melphalan. These anti-proliferative effects were accompanied by enhanced activation of drug-specific apoptosis in HMCLs grown in suspension, and in HMCLs co-cultured with a human-derived stromal cell line. Siltuximab with melphalan enhanced activation of caspase-8, caspase-9, and the downstream effector caspase-3 compared with either of the single agents. This increased induction of cell death occurred in association with enhanced Bak activation. Neutralization of IL-6 also suppressed signalling through the phosphoinositide 3-kinase/Akt pathway, as evidenced by decreased phosphorylation of Akt, p70 S6 kinase and 4E-BP1. Importantly, the siltuximab/melphalan regimen demonstrated enhanced anti-proliferative effects against primary plasma cells derived from patients with myeloma, monoclonal gammopathy of undetermined significance, and amyloidosis. These studies provide a rationale for translation of siltuximab into the clinic in combination with melphalan-based therapies

Prognostic and functional implications of left atrial late gadolinium enhancement cardiovascular magnetic resonance

Abstract Background Left atrial (LA) late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging is indicative of fibrosis, and has been correlated with reduced LA function, increased LA volume, and poor procedural outcomes in cohorts with atrial fibrillation (AF). However, the role of LGE as a prognostic biomarker for arrhythmia in cardiac disease has not been examined. Methods In this study, we assessed LA LGE using a 3D LGE CMR sequence to examine its relationships with new onset atrial arrhythmia, and LA and left ventricular (LV) mechanical function. Results LA LGE images were acquired in 111 patients undergoing CMR imaging, including 66 patients with no prior history of an atrial arrhythmia. During the median follow-up of 2.7 years (interquartile range (IQR) 1.8–3.7 years), 15/66 (23%) of patients developed a new atrial arrhythmia. LA LGE ≥10% of LA myocardial volume was significantly associated with an increased rate of new-onset atrial arrhythmia, with a hazard ratio of 3.16 (95% CI 1.14–8.72), p = 0.026. There were significant relationships between LA LGE and both LA ejection fraction (r = − 0.39, p < 0.0005) and echocardiographic LV septal e’ (r = − 0.24, p = 0.04) and septal E/e’ (r = 0.31, p = 0.007). Conclusions Elevated LA LGE is associated with reduced LA function and reduced LV diastolic function. LA LGE is associated with new onset atrial arrhythmia during follow-up

Retifanlimab in patients with recurrent microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) endometrial cancer: Final results from the POD1UM-101 study (Cohort H)

peer reviewe

Phase 2 study of retifanlimab (INCMGA00012) in patients (pts) with selected solid tumors (POD1UM-203).

International audience2571 Background: Checkpoint inhibitors (CPIs) are an effective treatment (tx) for many tumor types. Retifanlimab, an investigational humanized anti–PD-1 monoclonal antibody, has shown safety, pharmacology, and clinical activity consistent with the class. POD1UM-203 (NCT03679767) assessed efficacy and safety of retifanlimab in pts with selected solid tumors where CPI monotherapy is highly active. Methods: Eligible pts (≥18 y) had tx-naïve metastatic non-small cell lung cancer (NSCLC) with high PD-L1 expression (tumor proportion score ≥50%), cisplatin ineligible locally-advanced/metastatic urothelial cancer (UC) with PD-L1 expression (combined positive score ≥10%), unresectable/metastatic melanoma, or tx-naïve locally advanced/metastatic clear-cell renal cell carcinoma (RCC). Measurable disease (RECIST v1.1) was required. ECOG PS >1 and prior PD-1/PD-L1 directed tx were exclusions. Retifanlimab was administered as an IV infusion at 500 mg every 4 wks over 30 min. Primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), progression-free survival, overall survival, safety, and pharmacokinetics. Results: A total of 121 pts (35 melanoma, 23 NSCLC, 29 UC, 34 RCC) received ≥1 dose of retifanlimab and were included in the analyses. Median duration of tx was 169 d (range, 1–442). The efficacy cut-off for the primary analysis occurred once all pts had been followed for at least 6 mo from the time of initial tx. Confirmed RECIST v1.1 responses were observed in all tumor types (Table) and were consistent with published ORR for other CPIs; median DOR was not reached for any tumor cohort and tx was ongoing at the time of data cutoff for 17, 11, 9, and 15 pts with melanoma, NSCLC, UC, and RCC, respectively. The most common tx-emergent AEs (TEAEs, >10% incidence) were asthenia (17.4%), arthralgia (14.9%), decreased appetite (14.0%), pruritus (12.4%), rash (10.7%), and urinary tract infection (10.7%); majority of TEAEs were low grade (≤ grade 2) and none led to tx discontinuation. Immune-related AEs occurred in 23 pts (19.0%), most common (>1% incidence) were hypothyroidism (7.4%), rash (4.1%), hyperthyroidism (2.5%), and pruritus (1.7%). Immune-related AEs led to dose delay in 5 pts (4.1%), but none led to tx discontinuation and/or dose interruption. Conclusions: Retifanlimab demonstrated antitumor activity and was generally well-tolerated in pts with melanoma, NSCLC, UC, or RCC comparable with approved CPIs for these tumor types. These results support ongoing further development of retifanlimab. Clinical trial information: NCT03679767. [Table: see text

Diagnosis of Delayed Post-Hypoxic Leukoencephalopathy (Grinker’s Myelinopathy) with MRI Using Divided Subtracted Inversion Recovery (dSIR) Sequences: Time for Reappraisal of the Syndrome?

Background: Delayed Post-Hypoxic Leukoencephalopathy (DPHL), or Grinker’s myelinopathy, is a syndrome in which extensive changes are seen in the white matter of the cerebral hemispheres with MRI weeks or months after a hypoxic episode. T2-weighted spin echo (T2-wSE) and/or T2-Fluid Attenuated Inversion Recovery (T2-FLAIR) images classically show diffuse hyperintensities in white matter which are thought to be near pathognomonic of the condition. The clinical features include Parkinsonism and akinetic mutism. DPHL is generally regarded as a rare condition. Methods and Results: Two cases of DPHL imaged with MRI nine months and two years after probable hypoxic episodes are described. No abnormalities were seen on the T2-FLAIR images with MRI, but very extensive changes were seen in the white matter of the cerebral and cerebellar hemisphere on divided Subtraction Inversion Recovery (dSIR) images. dSIR sequences may produce ten times the contrast of conventional inversion recovery (IR) sequences from small changes in T1. The clinical findings in both cases were of cognitive impairment without Parkinsonism or akinetic mutism. Conclusion: The classic features of DPHL may only represent the severe end of a spectrum of diseases in white matter following global hypoxic injury to the brain. The condition may be much more common than is generally thought but may not be recognized using conventional clinical and MRI criteria for diagnosis. Reappraisal of the syndrome of DPHL to include clinically less severe cases and to encompass recent advances in MRI is advocated