Binding of aberrant glycoproteins recognizable by Helix pomatia agglutinin in adrenal cancers

Background. Aberrant glycosylation is a hallmark of cancer cells and plays an important role in oncogenesis and cancer progression including metastasis. This study aimed to assess alteration in cellular glycosylation, detected by lectin Helix pomatia agglutinin (HPA) binding, in adrenal cancers and to determine whether such altered glycosylation has prognostic significance. Methods. HPA binding lectin histochemistry was performed on archival paraffin wax‐embedded specimens of adrenocortical cancers excised from patients attending two tertiary referral centres. Benign tumours were used as controls. Demographic, histological and survival data were collected and compared between patients with HPA‐positive and HPA‐negative tumours. Results. Thirty‐two patients were treated for adrenal cancer between 2000 and 2016; their median age was 49 (range 23–79) years. Fifteen patients had functioning tumours (14 adrenal Cushing's tumours and 1 Conn's tumour). Mean(s.d.) tumour size was 127·71(49·70) mm. None of 10 control tumours expressed HPA‐binding glycoproteins. Invasion was associated with HPA‐binding glycoproteins (P = 0·018). Local recurrence or metastatic disease did not significantly differ between HPA‐positive and HPA‐negative adrenocortical cancers. Overall survival was significantly longer in patients with HPA‐negative tumours (median survival not reached versus 22 months in patients with HPA‐positive tumours; P = 0·002). Conclusion. Altered cellular glycosylation detected by lectin HPA is associated with poor survival in patients with adrenocortical cancer

Origin of strange metallic phase in cuprate superconductors

The origin of strange metallic phase is shown to exist due to these two conditions---(i) the electrons are strongly interacting such that there are no band and Mott-Hubbard gaps, and (ii) the electronic energy levels are crossed in such a way that there is an electronic energy gap between two energy levels associated to two different wave functions. The theory is also exploited to explain (i) the upward- and downward-shifts in the $T$-linear resistivity curves, and (ii) the spectral weight transfer observed in the soft X-ray absorption spectroscopic measurements of the La-Sr-Cu-O Mott insulator.Comment: To be published in J. Supercond. Nov. Mag

SUSY Breaking and Moduli Stabilization from Fluxes in Gauged 6D Supergravity

We construct the 4D N=1 supergravity which describes the low-energy limit of 6D supergravity compactified on a sphere with a monopole background a la Salam and Sezgin. This provides a simple setting sharing the main properties of realistic string compactifications such as flat 4D spacetime, chiral fermions and N=1 supersymmetry as well as Fayet-Iliopoulos terms induced by the Green-Schwarz mechanism. The matter content of the resulting theory is a supersymmetric SO(3)xU(1) gauge model with two chiral multiplets, S and T. The expectation value of T is fixed by the classical potential, and S describes a flat direction to all orders in perturbation theory. We consider possible perturbative corrections to the Kahler potential in inverse powers of $Re S$ and $Re T$, and find that under certain circumstances, and when taken together with low-energy gaugino condensation, these can lift the degeneracy of the flat direction for $Re S$. The resulting vacuum breaks supersymmetry at moderately low energies in comparison with the compactification scale, with positive cosmological constant. It is argued that the 6D model might itself be obtained from string compactifications, giving rise to realistic string compactifications on non Ricci flat manifolds. Possible phenomenological and cosmological applications are briefly discussed.Comment: 32 pages, 2 figures. Uses JHEP3.cls. References fixed and updated, some minor typos fixed. Corrected minor error concerning Kaluza-Klein scales. Results remain unchange

Wave Permanent Functions for Featureless Bosonic Mott Insulators on the 1/3-Filled Kagome Lattice

We study Bose-Hubbard models on tight-binding, non-Bravais lattices, with a filling of one boson per unit cell—and thus fractional site filling. We discuss situations where no classical bosonic insulator, which is a product state of particles on independent sites, is admitted. Nevertheless, we show that it is possible to construct a quantum Mott insulator of bosons if a trivial band insulator of fermions is possible at the same filling. The ground state wave function is simply a permanent of exponentially localized Wannier orbitals. Such a Wannier permanent wave function is featureless in that it respects all lattice symmetries and is the unique ground state of a parent Hamiltonian that we construct. Motivated by the recent experimental demonstration of a kagome optical lattice of bosons, we study this lattice at 1/3 site filling. Previous approaches to this problem have invariably produced either broken-symmetry states or topological order. Surprisingly, we demonstrate that a featureless insulator is a possible alternative and is the exact ground state of a local Hamiltonian. We briefly comment on the experimental relevance of our results to ultracold atoms as well as to 1/3 magnetization plateaus for kagome spin models in an applied field

Impact of Early Versus Delayed Atrial Fibrillation Catheter Ablation on Atrial Arrhythmia Recurrences

Online publish-ahead-of-print 16 April 2023Background: Catheter ablation is an effective strategy in atrial fibrillation (AF). However, its timing in the course of management remains unclear. The aim of this study was to determine if an early vs. delayed AF ablation strategy is associated with differences in arrhythmia outcomes during 12-month follow-up. Methods and results: One hundred patients with symptomatic AF referred to a tertiary centre for management were randomized in a 1:1 ratio to either an early ablation strategy (within 1 month of recruitment) or a delayed ablation strategy (optimized medical therapy followed by catheter ablation at 12 months post recruitment). The primary endpoint was atrial arrhythmia free survival at 12 months post-ablation. Secondary outcomes included: (i) AF burden, (ii) AF burden by AF phenotype, and (iii) antiarrhythmic drug (AAD) use at 12 months. Overall, 89 patients completed the study protocol (Early vs. Delayed: 48 vs. 41). Mean age was 59 ± 12.9 years (29% women). Pulmonary vein isolation was achieved in 100% of patients. At 12 months, 56.3% of patients in the early ablation group were free from recurrent arrhythmia, compared with 58.6% in the delayed ablation group (HR 1.12, 95% CI 0.59–2.13, P = 0.7). All secondary outcomes showed no significant difference including median AF burden (Early vs. Delayed: 0% [IQR 3.2] vs. 0% [5], P = 0.66), median AF burden amongst paroxysmal AF patients (0% [IQR 1.1] vs. 0% [4.5], P = 0.78), or persistent AF patients (0% [IQR 22.8] vs. 0% [5.6], P = 0.45) or AAD use (33% vs. 37%, P = 0.8). Conclusion: Compared with an early ablation strategy, delaying AF ablation by 12 months for AAD management did not result in reduced ablation efficacy.Jonathan M. Kalman, Ahmed M. Al-Kaisey, Ramanathan Parameswaran, Joshua Hawson, Robert D. Anderson, Michael Lim, David Chieng, Stephen A. Joseph, Alex McLellan, Joseph B. Morton, Paul B. Sparks, Geoffrey Lee, Prashanthan Sanders, and Peter M. Kistle

Impact of CPAP on the Atrial Fibrillation Substrate in Obstructive Sleep Apnea: The SLEEP-AF Study

BACKGROUND Observational studies report that obstructive sleep apnea (OSA) is associated with an increasingly remodeled atrial substrate in atrial fibrillation (AF). However, the impact of OSA management on the electrophysiologic substrate has not been evaluated. OBJECTIVES In this study, the authors sought to determine the impact of OSA management on the atrial substrate in AF. METHODS We recruited 24 consecutive patients referred for AF management with at least moderate OSA (apnea- hypopnea index [AHI] $15). Participants were randomized in a 1:1 ratio to commence continuous positive airway pressure (CPAP) or no therapy (n ¼ 12 CPAP; n ¼ 12 no CPAP). All participants underwent invasive electrophysiologic study (high- density right atrial mapping) at baseline and after a minimum of 6 months. Outcome variables were atrial voltage (mV), conduction velocity (m/s), atrial surface area <0.5 mV (%), proportion of complex points (%), and atrial effective re- fractory periods (ms). Change between groups over time was compared. RESULTS Clinical characteristics and electrophysiologic parameters were similar between groups at baseline. Compliance with CPAP therapy was high (device usage: 79% ± 19%; mean usage/day: 268 ± 91 min) and resulted in significant AHI reduction (mean reduction: 31 ± 23 events/h). There were no differences in blood pressure or body mass index between groups over time. At follow-up, the CPAP group had faster conduction velocity (0.86 0.16 m/s vs 0.69 0.12 m/s; P (time x group) ¼ 0.034), significantly higher voltages (2.30 0.57 mV vs 1.94 ± 0.72 mV; P < 0.05), and lower pro- portion of complex points (8.87% ± 3.61% vs 11.93% ± 4.94%; P ¼ 0.011) compared with the control group. CPAP therapy also resulted in a trend toward lower proportion of atrial surface area <0.5 mV (1.04% 1.41% vs 4.80% ± 5.12%; P ¼ 0.065). CONCLUSIONS CPAP therapy results in reversal of atrial remodeling in AF and provides mechanistic evidence advocating for management of OSA in AF. (J Am Coll Cardiol EP 2022;8:869–877)Chrishan J. Nalliah, BSC, LLB, MBBS, PHD, Geoffrey R. Wong, MBBS, PHD, Geoffrey Lee, MBBS, PHD, Aleksandr Voskoboinik, MBBS, PHD, Kirk Kee, MBBS, PHD, Jeremy Goldin, MBBS, Troy Watts, BSC, Dominik Linz, MD, PHD, e Ramanathan Parameswaran, MBBS, PHD, Hariharan Sugumar, MBBS, PHD, Sandeep Prabhu, MBBS, PHD, Alex McLellan, MBBS, PHD, Liang-Han Ling, MBBS, PHD, Stephen A. Joseph, MBBS, PHD, Joseph B. Morton, MBBS, PHD, Peter Kistler, MBBS, PHD, Prashanthan Sanders, MBBS, PHD, Jonathan M. Kalman, MBBS, PH

Impact of Catheter Ablation on Cognitive Function in Atrial Fibrillation: A Randomized Control Trial

BACKGROUND: Early postoperative cognitive dysfunction (POCD) has been reported following atrial fibrillation (AF) ablation. However, whether POCD is persistent long-term is unknown. OBJECTIVES: The purpose of this study was to determine if AF catheter ablation is associated with persistent cognitive dysfunction at 12-month follow-up. METHODS: This is a prospective study of 100 patients with symptomatic AF who failed at least 1 antiarrhythmic drug randomized to either ongoing medical therapy or AF catheter ablation and followed up for 12 months. Changes in cognitive performance were assessed using 6 cognitive tests administered at baseline and during follow-up (3, 6, and 12 months). RESULTS: A total of 96 participants completed the study protocol. Mean age was 59 ± 12 years (32% women, 46% with persistent AF). The prevalence of new cognitive dysfunction in the ablation arm compared with the medical arm was as follows: at 3 months: 14% vs 2%; P = 0.03; at 6 months: 4% vs 2%; P = NS; and at 12 months: 0% vs 2%; P = NS. Ablation time was an independent predictor of POCD (P = 0.03). A significant improvement in cognitive scores was seen in 14% of the ablation arm patients at 12 months compared with no patients in the medical arm (P = 0.007). CONCLUSIONS: POCD was observed following AF ablation. However, this was transient with complete recovery at 12-month follow-up.Ahmed M. Al-Kaisey, Ramanathan Parameswaran, Christina Bryant, Robert D. Anderson, Joshua Hawson, David Chieng, Aleksandr Voskoboinik, Hariharan Sugumar, Danielle West, Sonia Azzopardi, Sue Finch, Geoffrey Wong, Stephen A. Joseph, Alex McLellan, Liang-Han Ling, Prashanthan Sanders, Geoffrey Lee, Peter M. Kistler, Jonathan M. Kalma