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Achalasia is a chronic idiopathic disease characterized by the absence of esophageal body peristalsis and by defective lower esophageal sphincter (LES) relaxation. The incidence rate ranges from 1.07 to up to 2.8 new cases per year per 100,000 population. Presenting symptoms include dysphagia, regurgitation, vomiting, and weight loss. The diagnosis of achalasia has undergone a revolution in the last decade due to the advent of high-resolution manometry (HRM) and the consequent development of the Chicago Classification. Recent progress has allowed achalasia to be more precisely diagnosed and to be categorized into three subtypes, based on the prevalent manometric features of the esophageal peristalsis. Treatment options are pharmacotherapy, endoscopic management (Botox injection or pneumatic dilation), and surgery, e.g. laparoscopic Heller myotomy (LHM). More recently, a new endoscopic technique, per oral endoscopic myotomy (POEM), has developed as a less invasive approach alternative to the traditional LHM. Since the first POEM procedure was performed in 2008, increasing evidence is accumulating regarding its efficacy and safety profiles. Currently, POEM is being introduced as a reasonable therapeutic option, though randomized controlled trails are still lacking. The current review sheds light onto the diagnosis and management of achalasia, with special focus on the recent advances of HRM and POEM.

Optical mitigation of interchannel interference (ICI) for multiple spectrally overlapped data channels is experimentally demonstrated without multichannel detection and channel spacing estimation. The ICI mitigation takes place in three stages of periodically poled lithium niobate (PPLN) waveguides. In the first PPLN stage, the conjugate copies of channels are generated. In the second stage, the overlapped signals are coherently multiplexed with different complex taps. In the third stage, the concurrent nonlinear processes and the coherent multiplexing of the signals with their delayed copies compensate the ICI. The bit error rate and the constellation diagrams of wavelength division multiplexed (WDM) channels carrying quadrature phase-shift keying (QPSK) or 16 quadrature amplitude modulation (16-QAM) formats demonstrate the potential capability of the proposed method to reduce the ICI and its possible modulation format transparency. The effect of channel spacing on the performance of the method is also demonstrated. After optical ICI mitigation, a reduction of almost 4 dB is achieved for the value of optical signal-to-noise ratio at BER of 10–3 for 20-GBd QPSK signals with a channel spacing of 17.5 GHz. The overlapped WDM system of 20-GBd 16-QAM signals with channel spacing of 17.5 GHz is also ICI mitigated and error vector magnitudes are reduced by almost 28%.

Laser-induced hydrogen plasma in the density and temperature range of $(0.1--5)\ifmmode\times\else\texttimes\fi{}{10}^{23}\phantom{\rule{0.16em}{0ex}}{\mathrm{m}}^{\ensuremath{-}3}$ and $(6000--20000)\phantom{\rule{0.16em}{0ex}}\mathrm{K}$, respectively, was precisely diagnosed using two-color Thomson scattering technique, inferring the electron number density, electron temperature as well as ion temperature. Simultaneously, spectra of the Balmer series of spectral lines from H-$\ensuremath{\beta}$ to H-$\ensuremath{\zeta}$ were measured and plasma emission coefficient calculated within the quasicontiguous frequency-fluctuation model. The theoretical spectra are found to be in good agreement with experimental ones, including higher-density data where discrete lines were observed to merge forming a continuum.

Active galactic nuclei (AGN) are prominent environments for stellar capture, growth and formation. These environments may catalyze stellar mergers and explosive transients, such as thermonuclear and core-collapse supernovae (SNe). SN explosions in AGN discs generate strong shocks, leading to unique observable signatures. We develop an analytical model which follows the evolution of the shock propagating in the disc until it eventually breaks out. We derive the peak luminosity, bolometric lightcurve, and breakout time. The peak luminosities may exceed $10^{45}$ erg s$^{-1}$ and last from hours to days. The brightest explosions occur in regions of reduced density; either off-plane, or in discs around low-mass central black holes ($\sim 10^6\ M_\odot$), or in starved subluminous AGNs. Explosions in the latter two sites are easier to observe due to a reduced AGN background luminosity. We perform suites of 1D Lagrangian radiative hydrodynamics SNEC code simulations to validate our results and obtain the luminosity in different bands, and 2D axisymmetric Eulerian hydrodynamics code HORMONE simulations to study the morphology of the ejecta and its deviation from spherical symmetry. The observed signature is expected to be a bright blue, UV, or X-ray flare on top of the AGN luminosity from the initial shock breakout, while the subsequent red part of the lightcurve will largely be unobservable. We estimate the upper limit for the total event rate to be $\mathcal{R}\lesssim 100\ \rm yr^{-1}\ Gpc^{-3}$ for optimal conditions and discuss the large uncertainties in this estimate. Future high-cadence transient searches may reveal these events. Some existing tidal disruption event candidates may originate from AGN supernovae. Accepted to MNRAS

Utilizing self-assembled DNA structures in the development of nanoelectronic circuits requires transforming the DNA strands into highly conducting wires. Toward this end, we investigate the use of DNA self-assembled nanowires as templates for the deposition of a superconducting material. Nanowires formed by the deposition of superconducting NbN exhibit thermally activated and quantum phase slips as well as exceptionally large negative magnetoresistance. The latter effect can be utilized to suppress a significant part of the low temperature resistance caused by the quantum phase slips.

Summary ZUMA‐1 (NCT02348216) examined the safety and efficacy of axicabtagene ciloleucel (axi‐cel), an autologous CD19‐directed chimaeric antigen receptor (CAR)‐T cell therapy, in refractory large B‐cell lymphoma. To reduce treatment‐related toxicity, several exploratory safety management cohorts were added to ZUMA‐1. Specifically, cohort 6 investigated management of cytokine release syndrome (CRS) and neurologic events (NEs) with prophylactic corticosteroids and earlier corticosteroid and tocilizumab intervention. CRS and NE incidence and severity were primary end‐points. Following leukapheresis, patients could receive optional bridging therapy per investigator discretion. All patients received conditioning chemotherapy (days −5 through −3), 2 × 106 CAR‐T cells/kg (day 0) and once‐daily oral dexamethasone [10 mg, day 0 (before axi‐cel) through day 2]. Forty patients received axi‐cel. CRS occurred in 80% of patients (all grade ≤2). Any grade and grade 3 or higher NEs occurred in 58% and 13% of patients respectively. Sixty‐eight per cent of patients did not experience CRS or NEs within 72 h of axi‐cel. With a median follow‐up of 8·9 months, objective and complete response rates were 95% and 80% respectively. Overall, prophylactic corticosteroids and earlier corticosteroid and/or tocilizumab intervention resulted in no grade 3 or higher CRS, a low rate of grade 3 or higher NEs and high response rates in this study population.

In this paper, we propose a state-dependent switching controller for multiple-input multiple-output (MIMO) bilinear systems with constant delays in both the state and the input. The control input is assumed to be restricted to take only a finite number of values. The stability analysis of the closed loop is based on a Lyapunov–Krasovskii functional, and the design is reduced to solve a system of linear matrix inequalities. The controller can be designed by considering (state) delay-dependent or delay-independent conditions.

As the devastating impacts of global climate change and local anthropogenic stressors on shallow-water coral reefs are expected to rise, mesophotic coral ecosystems have increasingly been regarded as potential lifeboats for coral survival, providing a source of propagules to replenish shallower reefs. Yet, there is still limited knowledge of the capacity for coral larvae to adjust to light intensities that change with depth. This study elucidates the mechanisms underlying plasticity during early life stages of the coral Porites astreoides that enable survival across broad depth gradients. We examined physiological and morphological variations in larvae from shallow (8–10 m) and mesophotic (45 m) reefs in Bermuda, and evaluated differences in survival, settlement patterns and size among recruits depending on light conditions using a reciprocal ex situ transplantation experiment. Larvae released from mesophotic adults were found to have significantly lower respiration rates and were significantly larger than those derived from shallow adults, indicating higher content of energetic resources and suggesting a greater dispersal potential for mesophotic larvae compared to their shallow counterparts. Additionally, larvae released from mesophotic adults experienced higher settlement success and larger initial spat size compared to larvae from shallow adults, demonstrating a potential connection between parental origin, offspring quality, and recruitment success. Although both shallow and mesophotic larvae exhibited the capacity to survive and settle under reciprocal light conditions, all larvae had higher survival under mesophotic light conditions regardless of parental origin, suggesting that conditions experienced under low light may enable longer larval life, further extending the dispersal period. These results indicate that larvae from mesophotic Porites astreoides colonies are likely capable of reseeding shallow reefs in Bermuda, thereby supporting the Deep Reef Refugia Hypothesis.

Purpose To review the level of evidence of the psychometric properties of outcome measures for motor or functional skills for children with cerebral palsy classified across I to V levels of the Gross Motor Function Classification System. Methods A systematic search was completed in PubMed/MEDLINE, ISI Web of Science, CINAHL, and 4 complementary databases. The COSMIN Risk of Bias checklist and the updated criteria for good measurement properties were applied to assess the quality. Results Four outcome measures were identified from 12 articles: Gross Motor Function Measure, Gross Motor Performance Measure, Pediatric Evaluation of Disability Inventory, and Functional Independence Measure for Children. Evidence levels for validity, reliability, and responsiveness varied among measures. Conclusions Gross Motor Function Measure in all versions was the most investigated measure providing the best results, with the strongest evidence for validity and responsiveness properties. Reliability evidence should be improved to determine stability.

AbstractThe number and distribution of recessive alleles in the population for various diseases are not known at genome-wide-scale. Based on 6447 exome-sequences of healthy, genetically-unrelated Europeans of two distinct ancestries, we estimate that every individual is a carrier of at least 2 pathogenic variants in currently known autosomal recessive (AR) genes, and that 0.8-1% of European couples are at-risk of having a child affected with a severe AR genetic disorder. This risk is 16.5-fold higher for first cousins, but is significantly more increased for skeletal disorders and intellectual disabilities due to their distinct genetic architecture.