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The notion of synthetic dimensions has expanded the realm of topological physics to four dimensional (4D) space lately. In this work, non-Hermiticity is used as a synthetic parameter in PT-symmetric photonic crystals to study the topological physics in 4D non-Hermitian synthetic parameter space. We realize a 3D exceptional hypersurface (EHS) in such 4D parameter space, and the degeneracy points emerge due to the symmetry of synthetic parameters. We further demonstrate the existence of exceptional degenerate points (EDPs) on the EHS that originates from the chirality of exceptional points (EPs), and the exceptional surface near EDPs behaves like a Dirac cone. We further show that a very narrow reflection plateau can be found near these EDPs, and their sensitivity towards the PT-symmetry breaking environmental perturbation can make these degeneracy points useful in optical sensing and many other nonlinear and quantum optical applications.

An exceptional point occurring in a tailor-made lossy optical system has been recently found to alter optical properties in counter-intuitive ways. In the context of tunable plasmonic devices, exceptional points can be useful as a driving mechanism to enhance tunability. Here, we experimentally demonstrate how a plasmonic exceptional point can be incorporated in metasurface Q-plates to have the generated vortex beam tuned through a change of structural parameter. We have observed an orbital rotation in the far-field by 45 degrees in crossing the exceptional point. We expect a new generation of tunable plasmonic devices in polarization control, beam structuring and holograms, which can take advantage of the huge sensitivity from exceptional points.

Background: Scrub typhus causes up to 35% mortality if left untreated. One billion people living in the endemic regions are at risk. In spite of its heavy disease burden in some of the most populated areas in the world, there is no vaccine available. Although the disease can be effectively treated by proper antibiotics, timely and accurate diagnosis remains a challenge. Orientia tsutsugamushi infects a variety of mammalian cells in vitro and replicates in the cytoplasm of the infected cells. Microarray analysis has been used extensively to study host-pathogen interactions in in vitro models to understand pathogenesis. However there is a lack of in vivo studies., Results: In this study, C3HeB/FeJ (C3H) mice were infected by O. tsutsugamushi via the intraperitoneal route and monitored gene expression at 10 different time points post infection. We observed two distinct types of expression profiles in the genes that we analyzed. There are two valleys (4-18 h and 2-4 days) with low number of differentially expressed genes (DEG) with three peaks with high number of DEG at 2 h, 1-day and 7-day post infection. Further analysis revealed that pathways like complement and coagulation cascade, and blood clotting cascade pathways showed significant global changes throughout entire time course. Real time quantitative Polymerase Chain Reaction (RT-qPCR) confirmed the change of expression for genes involved in complement and coagulation cascade. These results suggested dynamic regulation of the complement and coagulation cascades throughout most of the time post infection while some other specific pathways, such as fatty acid metabolism and tryptophan metabolism, are turned on or off at certain times post infection., Conclusions: The findings highlight the complex interconnection among all different biological pathways. It is conceivable that specific pathways such as cell growth control and cell development in the host are affected by Orientia in the initial phase of infection for Orientia to grow intracellularly. Once Orientia is replicating successfully inside the host as infection progresses, the infection could activate pathways involved in cellular immune responses to defend for host cell survival and try to eliminate the pathogen.

Rationale: End-stage renal disease (ESRD) patients have high annual mortality mainly due to cardiovascular causes. The acute effects of obstructive and central sleep apnea on cardiac function in ESRD patients have not been determined. We therefore tested, in patients with ESRD, the hypotheses that (1) sleep apnea induces deterioration in cardiac function overnight and (2) attenuation of sleep apnea severity by ultrafiltration (UF) attenuates this deterioration., Methods: At baseline, ESRD patients, on conventional hemodialysis, with left ventricular ejection fraction (LVEF) >45% had polysomnography (PSG) performed on a non-dialysis day to determine the apnea-hypopnea index (AHI). Echocardiography was performed at the bedside, before and after sleep. Isovolumetric contraction time divided by left ventricular ejection time (IVCT/ET) and isovolumetric relaxation time divided by ET (IVRT/ET) were measured by tissue doppler imaging. The myocardial performance index (MPI), a composite of systolic and diastolic function was also calculated. One week later, subjects with sleep apnea (AHI ≥15) had fluid removed by UF, followed by repeat PSG and echocardiography. -Results: Fifteen subjects had baseline measurements, of which 7 had an AHI <15 (no-sleep-apnea group) and 8 had an AHI ≥15 (sleep-apnea group). At baseline, there was no overnight change in the LVEF in either the no-sleep-apnea group or the sleep-apnea group. In the no-sleep-apnea group, there was also no overnight change in MPI, IVCT/ET and IVRT/ET. However, in the sleep-apnea group there were overnight increases in MPI, IVCT/ET and IVRT/ET (p = 0.008, 0.007 and 0.031, respectively), indicating deterioration in systolic and diastolic function. Following fluid removal by UF in the sleep-apnea group, the AHI decreased by 48.7% (p = 0.012) and overnight increases in MPI, IVCT/ET and IVRT/ET observed at baseline were abolished., Conclusions: In ESRD, cardiac function deteriorates overnight in those with sleep apnea, but not in those without sleep apnea. This overnight deterioration in the sleep-apnea group may be at least partially due to sleep apnea, since attenuation of sleep apnea by UF was accompanied by elimination of this deleterious overnight effect., (© 2020 S. Karger AG, Basel.)

The programmed death-ligand 1 (PD-L1) is a major checkpoint protein that helps cancer cells evade the immune system. A non-invasive imaging agent with rapid clearance rate would be an ideal tool to predict and monitor the efficacy of anti-PD-L1 therapy. The aim of this research was to engineer a subnanomolar, high-affinity fibronectin type 3 domain (FN3)-based small binder targeted against human PD-L1 (hPD-L1) present on tumor cells. A naive yeast G4 library containing the FN3 gene with three binding loop sequences was used to isolate high-affinity binders targeted to purified full-length hPD-L1. The selected binder clones displayed several mutations in the loop regions of the FN3 domain. One unique clone (FN3hPD-L1-01) with a 6x His-tag at the C-terminus had a protein yield of >5 mg/L and a protein mass of 12 kDa. In vitro binding assays on six different human cancer cell lines (MDA-MB-231, DLD1, U87, 293 T, Raji and Jurkat) and murine CT26 colon carcinoma cells stably expressing hPD-L1 showed that CT26/hPD-L1 cells had the highest expression of hPD-L1 in both basal and IFN-γ-induced states, with a binding affinity of 2.38 ± 0.26 nM for FN3hPD-L1-01. The binding ability of FN3hPD-L1-01 was further confirmed by immunofluorescence staining on ex vivo CT26/hPD-L1 tumors sections. The FN3hPD-L1-01 binder represents a novel, small, high-affinity binder for imaging hPD-L1 expression on tumor cells and would aid in earlier imaging of tumors. Future clinical validation studies of the labeled FN3hPD-L1 binder(s) have the potential to monitor immune checkpoint inhibitors therapy and predict responders., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Guanine(G)-rich human telomeric (HT) DNA repeats, crucial to maintenance of genome stability, readily form G-quadruplexes (GQs) with various folding topologies. Research on excitation dynamics of HT-GQs is, however, scarce. Herein, we report a femtosecond time-resolved fluorescence coupled with transient absorption investigation on HT-GQ with the basket-type structure in Na + solution. The result unveils an unusual multichannel nonradiative mechanism dominated by states with varying character of charge transfer lasting ten and hundreds of picoseconds, accounting altogether for an overwhelming ∼85% of the overall deactivation involving proton transfer. Our comparative study shows that encapsulating the GQ in nanocavity water pool or changing it into hydrid-type topologies with the presence of K + ions alter differently energies and lifetimes of these states, yet without affecting the nature of the electronic excitation involved. The finding of this work underscores a leading role of structural rigidity in regulating the interplay with the microenvironment of photoexcited monomolecularly folded HT-GQs.

We analyze the photonic topological phases in bianisotropic metamaterials characterized by a chirality tensor with zero trace. We found that the strength of chirality component determines the topological character of the metamaterial. The underlying medium can be considered as a topological semimetal with the nontrivial band gap in the momentum space. The topological properties are described by the spin-orbit Hamiltonians with spin 1 and characterized by the nonzero topological invariants. In particular, photonic quantum Hall states exist when the longitudinal chirality component exceeds the permittivity, whereas photonic quantum spin Hall states are present when the chiral nihility occurs. Considering the dispersion in the frequency domain, the bianisotropic metamaterial is regarded as a photonic Weyl system that supports the Weyl points and Fermi arcs. The topological features are further illustrated with the robust transport of edge states at an irregular boundary of the metamaterial.

Background: High discontinuation rates remain a challenge for home hemodialysis (HHD) and peritoneal dialysis (PD). We compared technique failure risks among Canadian patients receiving HHD and PD., Methods: Using the Canadian Organ Replacement Register, we studied adult patients who initiated HHD or PD within 1 year of beginning dialysis between 2000 and 2012, with follow-up until 31 December 2013. Technique failure was defined as a transfer to any alternative modality for a period of ≥60 days. Technique survival between HHD and PD was compared using a Fine and Gray competing risk model. We also examined the time dependence of technique survival, the association of patient characteristics with technique failure and causes of technique failure., Results: Between 2000 and 2012, 15 314 patients were treated with a home dialysis modality within 1 year of dialysis initiation: 14 461 on PD and 853 on HHD. Crude technique failure rates were highest during the first year of therapy for both home modalities. During the entire period of follow-up, technique failure was lower with HHD compared with PD (adjusted hazard ratio = 0.79; 95% confidence interval 0.69-0.90). However, the relative technique failure risk was not proportional over time and the beneficial association with HHD was only apparent after the first year of dialysis. Comparisons also varied among subgroups and the superior technique survival associated with HHD relative to PD was less pronounced in more recent years and among older patients. Predictors of technique failure also differed between modalities. While obesity, smoking and small facility size were associated with higher technique failure in both PD and HHD, the association with age and gender differed. Furthermore, the majority of discontinuation occurred for medical reasons in PD (38%), while the majority of HHD patients experienced technique failure due to social reasons or inadequate resources (50%)., Conclusions: In this Canadian study of home dialysis patients, HHD was associated with better technique survival compared with PD. However, patterns of technique failure differed significantly among these modalities. Strategies to improve patient retention across all home dialysis modalities are needed., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Current particle sorting methods such as microfluidics, acoustics, and optics focus on exploiting the differences in the mass, size, refractive index, or fluorescence staining. However, there exist formidable challenges for them to sort label-free submicron particles with similar volume and refractive index yet distinct shapes. In this work, we report an optofluidic nanophotonic sawtooth array (ONSA) that generates sawtooth-like light fields through light coupling, paving the physical foundation for shape-selective sieving. Submicron particles interact with the coupled hotspots which impose different optical torques on the particles according to their shapes. Unstained S. aureus and E. coli are used as a model system to demonstrate this shape-selective sorting mechanism based on the torque-induced body dynamics, which was previously unattainable by other particle sorting technologies. More than 95% of S. aureus is retained within ONSA, while more than 97% of E. coli is removed. This nanophotonic chip offers a paradigm shift in shape-selective sorting of submicron particles and expands the boundary of optofluidics-based particle manipulation.

Dynamically encircling an exceptional point (EP) in parity-time ( PT ) symmetric waveguide systems exhibits interesting chiral dynamics that can be applied to asymmetric mode switching for symmetric and anti-symmetric modes. The counterpart symmetry-broken modes (i.e., each eigenmode is localized in one waveguide only), which are more useful for applications such as on-chip optical signal processing, exhibit only non-chiral dynamics and therefore cannot be used for asymmetric mode switching. Here, we solve this problem by resorting to anti-parity-time (anti- PT ) symmetric systems and utilizing their unique topological structure, which is very different from that of PT -symmetric systems. We find that the dynamical encircling of an EP in anti- PT -symmetric systems with the starting point in the PT -broken phase results in chiral dynamics. As a result, symmetry-broken modes can be used for asymmetric mode switching, which is a phenomenon and application unique to anti- PT -symmetric systems. We perform experiments to demonstrate the new wave-manipulation scheme, which may pave the way towards designing on-chip optical systems with novel functionalities., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2019.)

Metamaterials have enabled the design of electromagnetic wave absorbers with unprecedented performance. Conventional metamaterial absorbers usually employ multiple structure components in one unit cell to achieve broadband absorption. Here, a simple metasurface microwave absorber is proposed that has one metal-backed logarithmic spiral resonator as the unit cell. It can absorb >95% of normally incident microwave energy within the frequency range of 6 GHz-37 GHz as a result of the scale invariant geometry and the Fabry-Perot-type resonances of the resonator. The thickness of the metasurface is 5 mm and approaches the Rozanov limit of an optimal absorber. The physics underlying the broadband absorption is discussed. A comparison with Archimedean spiral metasurface is conducted to uncover the crucial role of scale invariance. The study opens a new direction of electromagnetic wave absorption by employing the scale invariance of Maxwell equations and may also be applied to the absorption of other classical waves such as sound.

Elderly patients who receive home dialysis (peritoneal dialysis or home hemodialysis) may have reduced survival compared to younger patients. Therefore, it is important to ascertain the goals of home dialysis in the elderly rather than simply fixate on standard metrics such as technique survival. As Canada's population continues to age, the prevalence of end-stage kidney disease among the elderly population is increasing. Patients with multiple comorbidities are now surviving long enough to be started on dialysis. Although home dialysis has been associated with better survival and improved quality of life, its impact on the frail and elderly populations require further elucidation. Home dialysis patients can either independently perform tasks or have support in the home to safely conduct dialysis. Moreover, patients burdened with frailty and multiple comorbidities who lack support in the home may not be able to perform home dialysis safely. Innovative strategies to improve accessibility to home-based therapies need further exploration. In addition, the concept of goal-directed dialysis promotes more individualized treatment. Future continuous quality improvement initiatives must examine if goal-directed dialysis leads to better quality of life outcomes in the elderly., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chronic kidney disease (CKD) is associated with premature cardiovascular morbidity and mortality. Traditional Framingham risk factors contribute partially to the malignant form of cardiovascular disease in CKD. Uremic-specific risk factors including chronic inflammation, retention of uremic toxins, and abnormal bone mineral metabolism have independently been linked to the pathogenesis of premature vascular aging, atherosclerosis, and cardiovascular disease. In this review we explore the mechanisms by which premature aging occurs in CKD through its pathologic effects on cardiovascular health, and the determinants of cardiac disease in patients with CKD. We outline strategies for prevention and therapeutic interventions in this vulnerable population., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The interior space of large-scale buildings, such as hospitals, with a variety of departments, is so complicated that people may easily lose their way while visiting. Difficulties in wayfinding can cause stress, anxiety, frustration and safety issues to patients and families. An indoor navigation system including route planning and localization is utilized to guide people from one place to another. The localization of moving subjects is a critical-function component in an indoor navigation system. Pedestrian dead reckoning (PDR) is a technology that is widely employed for localization due to the advantage of being independent of infrastructure. To improve the accuracy of the localization system, combining different technologies is one of the solutions. In this study, a multi-sensor fusion approach is proposed to improve the accuracy of the PDR system by utilizing a light sensor, Bluetooth and map information. These simple mechanisms are applied to deal with the issue of accumulative error by identifying edge and sub-edge information from both Bluetooth and the light sensor. Overall, the accumulative error of the proposed multi-sensor fusion approach is below 65 cm in different cases of light arrangement. Compared to inertial sensor-based PDR system, the proposed multi-sensor fusion approach can improve 90% of the localization accuracy in an environment with an appropriate density of ceiling-mounted lamps. The results demonstrate that the proposed approach can improve the localization accuracy by utilizing multi-sensor data and fulfill the feasibility requirements of localization in an indoor navigation system., Competing Interests: The authors declare no conflict of interest.

There is a resurgence in clinical adoption of home hemodialysis globally driven by several demonstrated clinical and economic advantages. Yet, the overall adoption of home hemodialysis remains under-represented in most countries. The practicality of managing ESKD with home hemodialysis is a common concern among practicing nephrologists in the United States. The primary objective of this invited feature is to deliver a practical guide to managing ESKD with home hemodialysis. We have included common clinical scenarios, clinical and infrastructure management problems, and approaches to the day-to-day management of patients undergoing home hemodialysis., (Copyright © 2019 by the American Society of Nephrology.)

The concept of gauge field is a cornerstone of modern physics and the synthetic gauge field has emerged as a new way to manipulate particles in many disciplines. In optics, several schemes of Abelian synthetic gauge fields have been proposed. Here, we introduce a new platform for realizing synthetic SU(2) non-Abelian gauge fields acting on two-dimensional optical waves in a wide class of anisotropic materials and discover novel phenomena. We show that a virtual non-Abelian Lorentz force arising from material anisotropy can induce light beams to travel along Zitterbewegung trajectories even in homogeneous media. We further design an optical non-Abelian Aharonov-Bohm system which results in the exotic spin density interference effect. We can extract the Wilson loop of an arbitrary closed optical path from a series of gauge fixed points in the interference fringes. Our scheme offers a new route to study SU(2) gauge field related physics using optics.

Background: Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) is a significant cause of morbidity among haemodialysis patients and is associated with pathological changes in phosphate, calcium and parathyroid hormone (PTH). In the ACTIVE Dialysis study, extended hours dialysis reduced serum phosphate but did not cause important changes in PTH or serum calcium. This secondary analysis aimed to determine if changes in associated therapies may have influenced these findings and to identify differences between patient subgroups., Methods: The ACTIVE Dialysis study randomised 200 participants to extended hours haemodialysis (≥24 h/week) or conventional haemodialysis (≤18 h/week) for 12 months. Mean differences between treatment arms in serum phosphate, calcium and PTH; and among key subgroups (high vs. low baseline phosphate/PTH, region, time on dialysis, dialysis setting and frequency) were examined using mixed linear regression., Results: Phosphate binder use was reduced with extended hours (- 0.83 tablets per day [95% CI -1.61, - 0.04; p = 0.04]), but no differences in type of phosphate binder, use of vitamin D, dose of cinacalcet or dialysate calcium were observed. In adjusted analysis, extended hours were associated with lower phosphate (- 0.219 mmol/L [- 0.314, - 0.124; P < 0.001]), higher calcium (0.046 mmol/L [0.007, 0.086; P = 0.021]) and no change in PTH (0.025 pmol/L [- 0.107, 0.157; P = 0.713]). The reduction in phosphate with extended hours was greater in those with higher baseline PTH and dialysing at home., Conclusion: Extended hours haemodialysis independently reduced serum phosphate levels with minimal change in serum calcium and PTH levels. With a few exceptions, these results were consistent across patient subgroups., Trial Registration: Clinicaltrials.gov NCT00649298 . Registered 1 April 2008.

Background: Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer treatment., Methods: We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007-2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence., Results: We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios [aHR] = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014., Conclusion: Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Globally, the number of patients undergoing maintenance dialysis is increasing, yet throughout the world there is significant variability in the practice of initiating dialysis. Factors such as availability of resources, reasons for starting dialysis, timing of dialysis initiation, patient education and preparedness, dialysis modality and access, as well as varied "country-specific" factors significantly affect patient experiences and outcomes. As the burden of end-stage kidney disease (ESKD) has increased globally, there has also been a growing recognition of the importance of patient involvement in determining the goals of care and decisions regarding treatment. In January 2018, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference focused on dialysis initiation, including modality choice, access, and prescription. Here we present a summary of the conference discussions, including identified knowledge gaps, areas of controversy, and priorities for research. A major novel theme represented during the conference was the need to move away from a "one-size-fits-all" approach to dialysis and provide more individualized care that incorporates patient goals and preferences while still maintaining best practices for quality and safety. Identifying and including patient-centered goals that can be validated as quality indicators in the context of diverse health care systems to achieve equity of outcomes will require alignment of goals and incentives between patients, providers, regulators, and payers that will vary across health care jurisdictions., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Phase gradient metagratings (PGMs) have provided unprecedented opportunities for wavefront manipulation. However, this approach suffers from fundamental limits on conversion efficiency; in some cases, higher order diffraction caused by the periodicity can be observed distinctly, while the working mechanism still is not fully understood, especially in refractive-type metagratings. Here we show, analytically and experimentally, a refractive-type metagrating which can enable anomalous reflection and refraction with almost unity efficiency over a wide incident range. A simple physical picture is presented to reveal the underlying diffraction mechanism. Interestingly, it is found that the anomalous transmission and reflection through higher order diffraction can be completely reversed by changing the integer parity of the PGM design, and such phenomenon is very robust. Two refractive acoustic metagratings are designed and fabricated based on this principle and the experimental results verify the theory.

Three-dimensional (3D) Dirac points inheriting relativistic effects from high-energy physics appear as gapless excitations in the topological band theory. Hosting fourfold linear dispersion, they play the central role among various topological phases, such as representing the degeneracy of paired Weyl nodes carrying opposite chiralities. While they have been extensively investigated in solid state systems for electrons, 3D Dirac points have not yet been observed in any classical systems. Here, we experimentally demonstrate 3D photonic Dirac points in the microwave region with an elaborately designed metamaterial, where two symmetrically placed Dirac points are stabilized by electromagnetic duality symmetry. Furthermore, spin-polarized surface arcs (counterparts of Fermi arcs in electronic systems) are demonstrated, which opens the gate toward implementing spin-multiplexed topological surface wave propagation. Closely linked to other exotic states through topological phase transitions, our system offers an effective medium platform for topological photonics.

We develop a metric-torsion theory for chiral structures by using a generalized framework of transformation optics. We show that the chirality is uniquely determined by a metric with the local rotational degree of freedom. In analogy to the dislocation continuum, the chirality can be alternatively interpreted as the torsion tensor of a Riemann-Cartan space, which is mimicked by the anholonomy of the orthonormal basis. As a demonstration, we reveal the equivalence of typical three-dimensional chiral metamaterials in the continuum limit. Our theory provides an analytical recipe to design optical chirality.

Background and Aims: Intensive hemodialysis is associated with more frequent arteriovenous (AV) access complications. We performed a retrospective cohort study to ascertain potential risk factors associated with access dysfunction in a cohort of nocturnal home hemodialysis (HHD) patients., Material and Methods: Consecutive patients undergoing HHD from October 1999 to November 2015 using an AV access were included. Patient demographics and clinical variables were collected. Primary outcome was defined as any access dysfunction including thrombosis, stenosis, or intervention. Frequent dysfunction was defined as > 2 events per access year. Factors associated with access dysfunction and abandonment were studied using logistic regression and Cox regression analysis, respectively., Results: 189 patients were included. 62.4% were male, and 77.2% had an AV fistula. The median duration of follow-up was 60.3 months. 105 patients (56%) had access dysfunction, resulting in an incidence of 66.2 events per 100 access years. History of renal transplant (OR 0.44, 95% CI 0.22 - 0.91), the use of AV graft (OR 9.23, 95% CI 3.41 - 25.00), and vintage of AV access (OR 1.01 per month, 95% CI 1.00 - 1.02) were significant predictors of access dysfunction. Patients with AV grafts (OR 7.11, 95% CI 2.71 - 18.69) and history of access dysfunction prior to HHD (OR 4.51, 95% CI 1.65 - 12.34) had more frequent dysfunction., Conclusion: AV accesses appear to have a finite duration of functionality, with history of renal transplant being a protective factor, and more dysfunction was found in AV grafts. Access-related factors account for frequent dysfunction rather than patient or HHD factors. The role of access surveillance, especially in patients having high risk of dysfunction, remains to be investigated.
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We review some recent progress in the exploration of pseudospin-1 physics using dielectric photonic crystals (PCs). We show some physical implications of the PCs exhibiting an accidental degeneracy induced conical dispersion at the Γ point, such as the realization of zero refractive index medium and the zero Berry phase of a loop around the nodal point. The photonic states of such PCs near the Dirac-like point can be described by an effective spin-orbit Hamiltonian of pseudospin-1. The wave propagation in the positive, negative, and zero index media can be unified within a framework of pseudospin-1 description. A scale change in PCs results in a rigid band shift of the Dirac-like cone, allowing for the manipulation of waves in pseudospin-1 systems in much the same way as applying a gate voltage in pseudospin-1/2 graphene. The transport of waves in pseudospin-1 systems exhibits many interesting phenomena, including super Klein tunneling, robust supercollimation, and unconventional Anderson localization. The transport properties of pseudospin-1 systems are distinct from their counterparts in pseudospin-1/2 systems, which will also be presented for comparison., Competing Interests: The authors declare that they have no conflicts of interest.

Introduction: Vascular access complications are associated with increased morbidity and mortality in home hemodialysis (HHD). Nurse-administered vascular access checklist is a feasible quality improvement strategy aimed to lower HHD access errors., Methods: We conducted a prospective quality improvement initiative for consecutive HHD patients between April 2013 and December 2016 at the Toronto General Hospital. Vascular access audits were administered every 6 months during clinic visits and during retraining sessions after an infection. We aimed to (1) determine whether prospective serial administration of vascular audit will decrease in the number of errors performed by the patient and (2) to determine whether there is an association between the number of errors and vascular access related infection., Findings: A total of 370 audits were performed on 122 patients with a mean HHD vintage of 6.7 (0.8-19.5) years. The mean number of errors per patient decreased from 1.24 ± 1.75 (baseline) to 0.33 ± 0.49 (last follow-up), P < 0.001. Among patients who had serial vascular access audits performed, there was a significant decrease in median number of errors (baseline median 1, [0-2] end of study median 0, [0-1] P = 0.01). Patients performing buttonhole cannulation made most proportion of errors as compared to CVC, 54% vs. 40% (P = 0.01) respectively; and as compared to rope ladder cannulation 54% vs. 37% (P = 0.008). We were unable to demonstrate an association between the change in patient reported errors and vascular access related infection., Discussion: Vascular access audit is a feasible quality initiative, which leads to a decrease in the number of patient reported errors in vascular access. The longitudinal clinical sequelae of this strategy warrants further examination., (© 2019 International Society for Hemodialysis.)

Introduction: Venous needle dislodgement (or venous port disconnection) during hemodialysis (HD) may lead to catastrophic blood loss, particularly during unsupervised home HD. A prototype venous line clamp was developed for use in conjunction with the Redsense blood loss sensor. We hypothesize that this prototype device will provide additional safety to dialysis without excessive burden., Methods: This was a single-center, prospective cohort study. Participants kept a log of bleeding, troubleshooting and clamp deployment events, and completed questionnaires before device first use and after device final use. The primary outcome was appropriate device function, evaluated by review of bleeding and clamp deployment events. The secondary outcomes were patient/nursing staff expectations and experience of the device., Findings: Fourteen patients used the device during a combined total of 214 HD treatments. Five participants (36%) had experienced a bleeding or disconnection event prior to study recruitment. All vascular access types were represented. The device was tested during incenter HD (n = 7 patients) and home HD (n = 7 patients). There were eight clamp deployment events, three of which were in the setting of minor bleeding at the venous access site. No other bleeding events were reported. The main troubleshooting issues were related to cumbersome device connections. Participants perceived additional safety with the device (median score 4.25 out of 5; range 1-5). However, the amount of additional work created was variable, and large in some cases (median score 2 out of 5; range 0-4.5). There was no association between HD vintage and device burden (P = 0.55)., Discussion: This "proof of concept" study confirmed that a clamp on the venous line, operating in conjunction with a venous access blood detector, is feasible regardless of HD location or vascular access type. The device improved patient safety perception during HD but was burdensome. Design modifications could improve future device iterations., (© 2019 International Society for Hemodialysis.)

Aim: Poor sleep quality is common in haemodialysis patients and associated with worse outcomes. In this pre-specified analysis, we examined the impact of extended hours haemodialysis on sleep quality., Methods: The ACTIVE Dialysis trial randomized 200 participants to extended (≥24 h/week) or standard (target 12-15 h) hours haemodialysis over 12 months. Sleep quality was measured in the Kidney Disease Quality of Life Short Form 1.3 (KDQOL-SF) by overall sleep quality score (0-10, 10 = 'very good') and the sleep subscale (0-100, 100 = 'best possible sleep') every 3 months via blinded telephone interview. The average intervention effect was calculated by mixed linear regression adjusted by time point and baseline score. Factors predicting sleep quality were assessed by multivariate regression analysis., Results: Overall sleep quality score and sleep subscale at baseline were similar in both groups (5.9 [95%CI 5.4-6.4] vs. 6.3 [5.9-6.8]; 65.0 [60.9-69.1] vs. 63.2 [59.1-67.3]; extended and standard hours, respectively). Extended hours haemodialysis led to a non-significant improvement in overall sleep quality score (average intervention effect 0.44 (-0.01 to 0.89), P = 0.053) and sleep subscale (average intervention effect 3.58 (-0.02 to 7.18), P = 0.051). Poor sleep quality was associated with being female and with current smoking. Sleep quality was positively associated with EuroQol-5D (EQ5D) and the SF-36 Physical Component and Mental Component Summary Scores but not with hospitalizations., Conclusion: Sleep quality was not significantly improved by extended hours dialysis in this study. Sleep quality is positively correlated with quality of life in haemodialysis patients and is poorer in women and current smokers., (© 2018 Asian Pacific Society of Nephrology.)

Pulmonary hypertension (PH) defined as a mean pulmonary arterial pressure ≥25 mmHg is a common complication in hemodialysis occurring in up to 58% of patients. PH is classified according to its etiology. We report in a patient with severe PH of mixed etiology (connective tissue disease and left-sided heart failure) who improved after initiation of intensive home hemodialysis. We postulated that the use of a frequent mode of hemodialysis may ameliorate PH via enhanced volume control. Thereby, an intensive hemodialysis schedule may be preferred renal replacement modality in this patient population., (© 2019 International Society for Hemodialysis.)

Aims: Renal inflammation, leading to fibrosis and impaired function is a major contributor to the development of hypertension. The NLRP3 inflammasome mediates inflammation in several chronic diseases by processing the cytokines pro-interleukin (IL)-1β and pro-IL-18. In this study, we investigated whether MCC950, a recently-identified inhibitor of NLRP3 activity, reduces blood pressure (BP), renal inflammation, fibrosis and dysfunction in mice with established hypertension., Methods and Results: C57BL6/J mice were made hypertensive by uninephrectomy and treatment with deoxycorticosterone acetate (2.4 mg/day, s.c.) and 0.9% NaCl in the drinking water (1K/DOCA/salt). Normotensive controls were uninephrectomized and received normal drinking water. Ten days later, mice were treated with MCC950 (10 mg/kg/day, s.c.) or vehicle (saline, s.c.) for up to 25 days. BP was monitored by tail-cuff or radiotelemetry; renal function by biochemical analysis of 24-h urine collections; and kidney inflammation/pathology was assessed by real-time PCR for inflammatory gene expression, flow cytometry for leucocyte influx, and Picrosirius red histology for collagen. Over the 10 days post-surgery, 1K/DOCA/salt-treated mice became hypertensive, developed impaired renal function, and displayed elevated renal levels of inflammatory markers, collagen and immune cells. MCC950 treatment from day 10 attenuated 1K/DOCA/salt-induced increases in renal expression of inflammasome subunits (NLRP3, ASC, pro-caspase-1) and inflammatory/injury markers (pro-IL-18, pro-IL-1β, IL-17A, TNF-α, osteopontin, ICAM-1, VCAM-1, CCL2, vimentin), each by 25-40%. MCC950 reduced interstitial collagen and accumulation of certain leucocyte subsets in kidneys of 1K/DOCA/salt-treated mice, including CD206+ (M2-like) macrophages and interferon-gamma-producing T cells. Finally, MCC950 partially reversed 1K/DOCA/salt-induced elevations in BP, urine output, osmolality, [Na+], and albuminuria (each by 20-25%). None of the above parameters were altered by MCC950 in normotensive mice., Conclusion: MCC950 was effective at reducing BP and limiting renal inflammation, fibrosis and dysfunction in mice with established hypertension. This study provides proof-of-concept that pharmacological inhibition of the NLRP3 inflammasome is a viable anti-hypertensive strategy., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Objectives: Canadian home hemodialysis guidelines highlight the potential differences in complications associated with arteriovenous fistula (AVF) cannulation technique as a research priority. Our primary objective was to determine the feasibility of randomizing patients with ESKD training for home hemodialysis to buttonhole versus stepladder cannulation of the AVF. Secondary objectives included training time, pain with needling, complications, and cost by cannulation technique., Design, Setting, Participants, & Measurements: All patients training for home hemodialysis at seven Canadian hospitals were assessed for eligibility, and demographic information and access type was collected on everyone. Patients who consented to participate were randomized to buttonhole or stepladder cannulation technique. Time to train for home hemodialysis, pain scores on cannulation, and complications over 12 months was recorded. For eligible but not randomized patients, reasons for not participating in the trial were documented., Results: Patient recruitment was November 2013 to November 2015. During this time, 158 patients began training for home hemodialysis, and 108 were ineligible for the trial. Diabetes mellitus as a cause of ESKD (31% versus 12%) and central venous catheter use (74% versus 6%) were more common in ineligible patients. Of the 50 eligible patients, 14 patients from four out of seven sites consented to participate in the study (28%). The most common reason for declining to participate was a strong preference for a particular cannulation technique (33%). Patients randomized to buttonhole versus stepladder cannulation required a shorter time to complete home hemodialysis training. We did not observe a reduction in cannulation pain or complications with the buttonhole method. Data linkages for a formal cost analysis were not conducted., Conclusions: We were unable to demonstrate the feasibility of conducting a randomized, controlled trial of buttonhole versus stepladder cannulation in Canada with a sufficient number of patients on home hemodialysis to be able to draw meaningful conclusions., (Copyright © 2019 by the American Society of Nephrology.)

Home dialysis therapy, including home hemodialysis and peritoneal dialysis, is underused as a modality for the treatment of chronic kidney failure. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative sponsored a home dialysis conference in late 2017 that was designed to identify the barriers to starting and maintaining patients on home dialysis therapy. Clinical, operational, policy, and societal barriers were identified that need to be overcome to ensure that dialysis patients have the freedom to choose their treatment modality. Education of patients and patient partners, as well as health care providers, about home dialysis therapy, if offered at all, is often provided in a cursory manner. Lack of exposure to home dialysis therapies perpetuates a lack of familiarity and thus a hesitancy to refer patients to home dialysis therapies. Patient and care partner support, both psychosocial and financial, is also critical to minimize the risk for burnout leading to dropout from a home dialysis modality. Thus, the facilitation of home dialysis therapy will require a systematic change in chronic kidney disease education and the approach to dialysis therapy initiation, the creation of additional incentives for performing home dialysis, and breakthroughs to simplify the performance of home dialysis modalities. The home dialysis work group plans to develop strategies to overcome these barriers to home dialysis therapy, which will be presented at a follow-up home dialysis conference., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Many novel properties of non-Hermitian systems are found at or near the exceptional points-branch points of complex energy surfaces at which eigenvalues and eigenvectors coalesce. In particular, higher-order exceptional points can result in optical structures that are ultrasensitive to external perturbations. Here we show that an arbitrary order exceptional point can be achieved in a simple system consisting of identical resonators placed near a waveguide. Unidirectional coupling between any two chiral dipolar states of the resonators mediated by the waveguide mode leads to the exceptional point, which is protected by the transverse spin-momentum locking of the guided wave and is independent of the positions of the resonators. Various analytic response functions of the resonators at the exceptional points are experimentally manifested in the microwave regime. The enhancement of sensitivity to external perturbations near the exceptional point is also numerically and analytically demonstrated.

Acquisition of self-reactive effector CD4 + T cells is a major component of the autoimmune response that can occur during myocarditis, an inflammatory form of cardiomyopathy. Although the processes by which self-reactive T cells gain effector function have received considerable attention, how these T cells contribute to effector organ inflammation and damage is less clear. Here, we identified an IL-3-dependent amplification loop that exacerbates autoimmune inflammation. In experimental myocarditis, we show that effector organ-accumulating autoreactive IL-3 + CD4 + T cells stimulate IL-3R + tissue macrophages to produce monocyte-attracting chemokines. The newly recruited monocytes differentiate into antigen-presenting cells that stimulate local IL-3 + CD4 + T cell proliferation, thereby amplifying organ inflammation. Consequently, Il3 -/- mice resist developing robust autoimmune inflammation and myocardial dysfunction, whereas therapeutic IL-3 targeting ameliorates disease. This study defines a mechanism that orchestrates inflammation in myocarditis, describes a previously unknown function for IL-3, and identifies IL-3 as a potential therapeutic target in patients with myocarditis., (© 2019 Anzai et al.)

Sleep is integral to life 1 . Although insufficient or disrupted sleep increases the risk of multiple pathological conditions, including cardiovascular disease 2 , we know little about the cellular and molecular mechanisms by which sleep maintains cardiovascular health. Here we report that sleep regulates haematopoiesis and protects against atherosclerosis in mice. We show that mice subjected to sleep fragmentation produce more Ly-6C high monocytes, develop larger atherosclerotic lesions and produce less hypocretin-a stimulatory and wake-promoting neuropeptide-in the lateral hypothalamus. Hypocretin controls myelopoiesis by restricting the production of CSF1 by hypocretin-receptor-expressing pre-neutrophils in the bone marrow. Whereas hypocretin-null and haematopoietic hypocretin-receptor-null mice develop monocytosis and accelerated atherosclerosis, sleep-fragmented mice with either haematopoietic CSF1 deficiency or hypocretin supplementation have reduced numbers of circulating monocytes and smaller atherosclerotic lesions. Together, these results identify a neuro-immune axis that links sleep to haematopoiesis and atherosclerosis.

Rationale & Objective: Increasing uptake of home hemodialysis (HD) has led to interest in characteristics that predict discontinuation of home HD therapy for reasons other than death or transplantation. Recent reports of practice pattern variability led to the hypothesis that there are patient- and center-specific factors that influence these discontinuations., Study Design: Retrospective cohort study., Setting & Participants: Incident home HD patients at 7 centers in Canada between 2000 and 2010., Predictor: Treatment center, case-mix, and process-of-care variables., Outcomes: Technique failure (defined as discontinuation of home HD therapy for any reason other than training failure, death, or transplantation) and mortality., Analytical Approach: Regression modeling of technique failure using Cox proportional hazard models adjusting for treatment center and modifiable and nonmodifiable patient-level variables, censored for death and transplantation., Results: The cohort consisted of 579 patients. Mean age was 49.9±14.1 years, 74% were of European ancestry, median dialysis vintage was 1.9 (IQR, 0.6-5.2) years, and 68% used an arteriovenous access. Mean duration of dialysis was 31.2±12.6 hours per week. Unadjusted 1- and 2-year technique survival and overall survival were 90% and 83% and 94% and 87%, respectively. Treating center was a strong predictor of technique failure and mortality, with HRs ranging from 0.37 to 5.11 for technique failure (1 of 6 centers with P<0.05 relative to the reference) and 0.17 to 8.73 for mortality (3 of 6 centers with P<0.05 relative to the reference). With baseline adjustment for center, only older age and more than 3 treatments per week remained significant predictors of technique failure, while no individual-level variables remained as significant predictors of survival., Limitations: Limited statistical power., Conclusions: Home HD treating centers may influence technique failure and patient mortality independent of case-mix. The relationship between processes of care and patient outcomes requires further investigation., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways 1 , how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metabolism. Here we describe a subset of immune cells-integrin β7 + natural gut intraepithelial T lymphocytes (natural IELs)-that is dispersed throughout the enterocyte layer of the small intestine and that modulates systemic metabolism. Integrin β7 - mice that lack natural IELs are metabolically hyperactive and, when fed a high-fat and high-sugar diet, are resistant to obesity, hypercholesterolaemia, hypertension, diabetes and atherosclerosis. Furthermore, we show that protection from cardiovascular disease in the absence of natural IELs depends on the enteroendocrine-derived incretin GLP-1 2 , which is normally controlled by IELs through expression of the GLP-1 receptor. In this metabolic control system, IELs modulate enteroendocrine activity by acting as gatekeepers that limit the bioavailability of GLP-1. Although the function of IELs may prove advantageous when food is scarce, present-day overabundance of diets high in fat and sugar renders this metabolic checkpoint detrimental to health.

Novel classical wave phenomenon analogs of the quantum spin Hall effect are mostly based on the construction of pseudo-spins. Here we show that the non-trivial topology of a system can also be realized using orbital angular momentum through a coupling between the angular momentum and the wave vector. The idea is illustrated with a tight-binding model and experimentally demonstrated with a transmission line network. We show experimentally that even a very small network cluster exhibits angular momentum-dependent one-way topological edge states, and their properties can be described in terms of local Chern numbers. Our work provides a new mechanism to realize counterparts of the quantum spin Hall effect in classical waves and may offer insights for other systems.

Background: To determine the 2-year clinical and functional outcomes of an Asian cohort at ultra-high risk (UHR) of psychosis. Method: This was a longitudinal study with a follow-up period of 2 years on 255 help-seeking adolescents and young adults at UHR of psychosis managed by a multi-disciplinary mental health team in Singapore. Clients received case management, psychosocial, and pharmacological treatment as appropriate. Data comprising symptom and functional outcomes were collected over the observation period by trained clinicians and psychiatrists. Results: The 2-year psychosis transition rate was 16.9%, with a median time to transition of 168 days. After 2 years, 14.5% of the subjects had persistent at-risk symptoms while 7.5% developed other non-psychotic psychiatric disorders. 38.4% of the cohort had recovered and was discharged from mental health services. The entire cohort's functioning improved as reflected by an increase in the score of the Social and Occupational Functioning Assessment Scale during the follow-up period. Predictors to psychosis transition included low education level, baseline unemployment, a history of violence, and brief limited intermittent psychotic symptoms, while male gender predicted the persistence of UHR state, or the development of non-psychotic disorders. Conclusion: Use of the current UHR criteria allows us to identify individuals who are at imminent risk of developing not just psychosis, but also those who may develop other mental health disorders. Future research should include identifying the needs of those who do not transition to psychosis, while continuing to refine on ways to improve the UHR prediction algorithm for psychosis.

Background: Home dialysis patients may be at an increased risk of adverse events after transitional states. The home dialysis virtual ward (HDVW) trial was conducted in Canadian dialysis centers and aimed to evaluate potential care gaps and patient satisfaction during the HDVW., Methods: The HDVW was a multicenter single-arm trial including peritoneal dialysis and home hemodialysis patients after 4 different events (hospital discharge, medical procedure, antibiotics, completion of training). Telephone-led interviews using a standardized assessment tool were performed over a 2-week period to assess a patient's care and adjust treatment as required. Upon completion, patients were surveyed to evaluate their perceived impact on domains of care using a rating scale; 1 not satisfied to 10 completely satisfied., Results: The HDVW trial included 193 patients with a median number of potential care gaps/interventions of 1 (0-2) per patient. Patients admitted to the HDVW after hospital discharge were at a higher risk of potential gaps in care (OR 2.16, 95% CI 1.29-3.62), while longer dialysis vintage was -associated with a lower number of gaps/interventions (OR 0.97 per year, 95% CI 0.95-0.98). A total of 105/193 (54%) patients completed satisfaction surveys. Patients were highly satisfied with the HDVW (median rating scale score 8, IQR 2) and felt it had a positive impact (rating scale score ≥7) on their overall health, understanding of treatment and access to a nephrologist., Conclusion: The HDVW was effective at identifying several potential care gaps, and patients were satisfied across several domains of care. This intervention may be valuable in supporting home dialysis patients during care transitions., (© 2019 S. Karger AG, Basel.)

Background: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple provider teams. Siloed care contributes to limited access between physicians, resulting in delays in the diagnosis and treatment of kidney disease and inappropriate use of healthcare resources. These gaps contribute to dissatisfied and disempowered providers and patients. Digital systems such as eConsult can support collaborative management and address these gaps, thereby streamlining the consultation and referral process between primary care physicians (PCPs) and nephrologists. In this study, we evaluated an established eConsult platform integrated with a central triage process for a network of PCPs and nephrologists. The study aimed to assess the acceptability, feasibility, and impact on access to nephrology when using eConsult integrated into the management of kidney disease between PCPs and nephrologists., Methods: We conducted a 1-year pilot study and used mixed methods to measure the acceptability and feasibility of using eConsult for the management of kidney disease. We compared eConsult and traditional referrals with respect to types of consultation, referrals, and times to response to determine impact on access to kidney care. We conducted semi-structured interviews of PCPs and nephrologists to assess physician experience., Results: From January 8, 2018, to January 11, 2019, 52 PCPs and 23 nephrologists participated in the study, with 250 traditional referrals and 106 eConsults submitted during that period. The median response time for eConsult was 15 (3-64) h, with 25% originating outside the central Toronto region. The median time to first clinic appointment from a traditional referral was 4 months (111 [61-163] days). PCP and nephrologist interviews revealed high user satisfaction, citing efficiency and timely response as key facilitators., Conclusion: The eConsult platform was acceptable, feasible, and facilitated access to nephrology care compared to traditional referrals. Physicians report improvements in physician care delivery, nephrology care gaps, patient experience, and healthcare utilization., (© 2019 S. Karger AG, Basel.)

i-Motifs are tetraplex DNAs known to be stable at acidic pH. The structure of i-motifs is important in DNA nanotechnology; i-motif-forming sequences with consecutive cytosine (C) molecules are abundant throughout the human genome. There is, however, little information on the structure of C-rich DNAs under physiologically relevant neutral conditions. The electron dynamics of i-motifs, crucial to both biology and materials applications, also remains largely unexplored. In this work, we report a combined femtosecond and nanosecond broadband time-resolved fluorescence (TRF) and steady-state fluorescence investigation on homo-oligomer dC 20 , a human telomeric sequence (HTS) 5'-dC 3 (TA 2 C 3 ) 3 , and its analogue performed with different excitation at both acidic and neutral pH. Our study provides direct observation of intrinsic fluorescence and the first full probe of the real-time dynamics of the intrinsic fluorescence from i-motifs formed from varied sequences and pH conditions. The results obtained demonstrate concrete evidence for the existence at neutral pH of i-motifs from both dC 20 and the HTS. It also identifies that, under neutral conditions, the i-motif from dC 20 adopting the bimolecular folding structure is significantly more stable than the HTS i-motif featuring the unimolecular topology. Our femtosecond and nanosecond TRF study unveils excitation dynamics distinctive of the interdigitated architecture of i-motifs with the excited states involved exhibiting deactivation over a remarkably broad timescale through multiple channels involving proton-coupled electron transfer lasting tens of picoseconds, as signified by the solvent kinetic isotope effect, and structure-dependent charge recombination in the hundreds of picoseconds to tens of nanoseconds time regime., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Since the inception of hemodialysis (HD) for patients with chronic kidney disease, the "perfect" dialysis prescription has remained elusive. Part of this may relate to the heterogeneity among populations, individual patients, and differences in access to health provision. The optimal balance between dialysis frequency and duration to achieve reductions in patient morbidity and mortality continues to be debated. The concept of dialysis adequacy originated from a post hoc mathematical analysis of the National Cooperative Study and has evolved to become a way of calculating dialysis dose and standardizing the dialysis prescription. In contrast, in its originally conceived sense, dialysis adequacy referred to the effective clearance of small solutes. Given the evolution of dialysis practice, we now aim to consider dialysis adequacy in a broader and more holistic manner particularly in view of our aging population and focus toward important patient-centered outcomes. While the traditional thrice weekly, HD regimen remains the default renal replacement modality, alternative strategies including short daily HD, long conventional HD, and long nocturnal HD are being widely implemented. We aim for optimal solute clearance, effective ultrafiltration to achieve normotension (while avoiding intradialytic symptoms) and maintenance of nutritional parameters all within the caveat that quality of life and autonomy are preserved., (© 2018 Wiley Periodicals, Inc.)

Apart from being an analogue of the prototype for photoinduced intramolecular charge transfer (ICT), 2-ethylhexyl 4-dimethylaminobenzoate (EHDMABA) is also one of the earliest patented and most commonly used sunscreen components. There is, however, little documented information about the photophysics and factors affecting the photophysics of this molecule. Such information is of importance for both the understanding of the ICT reaction and assessing the underlying process of photoprotection, especially in view of the "sunscreen controversy" that has arisen from the contrasting in vivo vs. in vitro photobiological results on this and related UV filters. We report herein a femtosecond broadband time-resolved fluorescence (fs-TRF), complemented by transient absorption (fs-TA) to allow a full probe of the excited state cascades for EHDMABA and two of its derivatives in solvents of varied properties. The results provide direct evidence for a nearly solvent independent inner sphere ICT reaction occurring on the sub-picosecond time scale, and an ensuing solvent dictated deactivation of the ICT state. The ICT state in the aprotic solvent acetonitrile decayed solely through the intrinsic intersystem crossing (ISC) to produce a potentially harmful triplet excited state. In the protic solvent, the solvation and formation of ICT-induced solute-solvent hydrogen (H)-bonding opened the originally inaccessible internal conversion (IC) channel of the ICT state, leading to the rapid reformation of the ground state molecule with a unitary efficiency in the aqueous solution. This H-bonding-mediated IC restrained or eliminated the intrinsic ISC, providing a mechanism at the molecular level for the benign dissipation of the electronic excitation. The precise rate of IC was observed to vary with the alkoxy substituent and its efficiency was affected by the H-bonding capacity of the solvent. The findings of this work demonstrate the pivotal role of the microenvironment and the direct participation of solvent molecules through H-bonding in drastically altering the nonradiative dynamics and promoting or inhibiting photostability and photoprotection. This may assist in developing next-generation UV filters and help in improving formulation design for the optimal efficacy of sunscreen products. The pronounced H-bonding-induced fluorescence quenching and variation in the fluorescence wavelength imply that these molecules may also serve as a sensitive fluorescence probe for the H-bonding properties of the microenvironment.

Exceptional points (EPs) associated with a square-root singularity have been found in many non-Hermitian systems. In most of the studies, the EPs found are isotropic, meaning that the same singular behavior is obtained independent of the direction from which they are approached in the parameter space. In this Letter, we demonstrate both theoretically and experimentally the existence of an anisotropic EP in an acoustic system that shows different singular behaviors when the anisotropic EP is approached from different directions in the parameter space. Such an anisotropic EP arises from the coalescence of two square-root EPs having the same chirality.

We measured the electromagnetic stress-induced local strain distribution on a centimeter-sized parallel-plate metallic resonant unit illuminated with microwave radiation. Using a fiber interferometer, we found that the strain changes sign across the resonant unit, in agreement with theoretical predictions that the attractive electric and repulsive magnetic forces act at different locations. The enhancement of the corresponding maximum local electromagnetic stress is stronger than the enhancement of the net force, reaching a factor of >600 compared to the ordinary radiation pressure.

Topological characteristics of energy bands, such as Dirac and Weyl nodes, have attracted substantial interest in condensed matter systems as well as in classical wave systems. Among these energy bands, the type-II Dirac point is a nodal degeneracy with tilted conical dispersion, leading to a peculiar crossing dispersion in the constant-energy plane. Such nodal points have recently been found in electronic materials. The analogous topological feature in photonic systems remains a theoretical curiosity, with experimental realization expected to be challenging. Here, we experimentally realize the type-II Dirac point using a planar metasurface architecture, where the band degeneracy point is protected by the underlying mirror symmetry of the metasurface. Gapless edge modes are found and measured at the boundary between the different domains of the symmetry-broken metasurface. Our Letter shows that metasurfaces are simple and practical platforms for realizing electromagnetic type-II Dirac points, and their planar structure is a distinct advantage that facilitates applications in two-dimensional topological photonics.

The debate surrounding whether peritoneal dialysis or hemodialysis is associated with differential survival continues as the numerous comparative studies over the past 3 decades have yielded conflicting results. Findings have also evolved over time in the setting of changing patient characteristics, advances in dialytic technologies, and the use of more robust statistical and epidemiologic approaches. Here, we will critically review the body of evidence, both historical and contemporary, comparing survival across dialysis modalities. Significant limitations of the observational nature of the current literature will be highlighted given that no adequately powered randomized controlled trials exist. Given the lack of consistency and limitations of current studies, coupled with the poor survival across both modalities, we can likely conclude that survival comparisons between both modalities do not appreciably differ. Hence, the choice of dialysis modality should not be dictated by survival comparisons, but rather be based on an individualized and informed decision making that places patient preference and lifestyle considerations at the forefront, while integrating medical factors and availability of resources and support. The emphasis of future research should move beyond survival outcomes when comparing dialysis modalities, and instead be redirected to patient-endorsed and patient-reported outcomes., (© 2018 Wiley Periodicals, Inc.)

Purpose: Stem cell transplants are an effective approach to repair large bone defects. However, comprehensive techniques to monitor the fate of transplanted stem cells in vivo are lacking. Such strategies would enable corrective interventions at an early stage and greatly benefit the development of more successful tissue regeneration approaches. In this study, we designed and synthesized a dual-modality imaging probe (Feru-AFC) that can simultaneously localize transplanted stem cells and diagnose immune rejection-induced apoptosis at an early stage in vivo . Methods: We used a customized caspase-3 cleavable peptide-dye conjugate to modify the surface of clinically approved ferumoxytol nanoparticles (NPs) to generate the dual-modality imaging probe with fluorescence "light-up" feature. We labeled both mouse mesenchymal stem cells (mMSCs, matched) and pig mesenchymal stem cells (pMSCs, mismatched) with the probe and transplanted the labeled cells with biocompatible scaffold at the calvarial defects in mice. We then employed intravital microscopy (IVM) and magnetic resonance imaging (MRI) to investigate the localization, engraftment, and viability of matched and mismatched stem cells, followed by histological analyses to evaluate the results obtained from in vivo studies. Results: The Feru-AFC NPs showed good cellular uptake efficiency in the presence of lipofectin without cytotoxicity to mMSCs and pMSCs. The fluorescence of Feru-AFC NPs was turned on inside apoptotic cells due to the cleavage of peptide by activated caspase-3 and subsequent release of fluorescence dye molecules. Upon transplantation at the calvarial defects in mice, the intense fluorescence from the cleaved Feru-AFC NPs in apoptotic pMSCs was observed with a concomitant decrease in the overall cell number from days 1 to 6. In contrast, the Feru-AFC NP-treated mMSCs exhibited minimum fluorescence and the cell number also remained similar. Furthermore, in vivo MRI of the Feru-AFC NP-treated mMSC and pMSCs transplants could clearly indicate the localization of matched and mismatched cells, respectively. Conclusions: We successfully developed a dual-modality imaging probe for evaluation of the localization and viability of transplanted stem cells in mouse calvarial defects. Using ferumoxytol NPs as the platform, our Feru-AFC NPs are superparamagnetic and display a fluorescence "light-up" signature upon exposure to activated caspase-3. The results show that the probe is a promising tool for long-term stem cell tracking through MRI and early diagnosis of immune rejection-induced apoptosis through longitudinal fluorescence imaging., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.