High Q Hybrid Mie-Plasmonic Resonances in van der Waals Nanoantennas on Gold Substrate.

Dielectric nanoresonators have been shown to circumvent the heavy optical losses associated with plasmonic devices; however, they suffer from less confined resonances. By constructing a hybrid system of both dielectric and metallic materials, one can retain low losses, while achieving stronger mode confinement. Here, we use a high refractive index multilayer transition-metal dichalcogenide WS2 exfoliated on gold to fabricate and optically characterize a hybrid nanoantenna-on-gold system. We experimentally observe a hybridization of Mie resonances, Fabry-Perot modes, and surface plasmon-polaritons launched from the nanoantennas into the substrate. We measure the experimental quality factors of hybridized Mie-plasmonic (MP) modes to be up to 33 times that of standard Mie resonances in the nanoantennas on silica. We then tune the nanoantenna geometries to observe signatures of a supercavity mode with a further increased Q factor of over 260 in experiment. We show that this quasi-bound state in the continuum results from strong coupling between a Mie resonance and Fabry-Perot-plasmonic mode in the vicinity of the higher-order anapole condition. We further simulate WS2 nanoantennas on gold with a 5 nm thick hBN spacer in between. By placing a dipole within this spacer, we calculate the overall light extraction enhancement of over 107, resulting from the strong, subwavelength confinement of the incident light, a Purcell factor of over 700, and high directivity of the emitted light of up to 50%. We thus show that multilayer TMDs can be used to realize simple-to-fabricate, hybrid dielectric-on-metal nanophotonic devices granting access to high-Q, strongly confined, MP resonances, along with a large enhancement for emitters in the TMD-gold gap.

Prdx1 inhibits tumorigenesis via regulating PTEN/AKT activity.

It is widely accepted that reactive oxygen species (ROS) promote tumorigenesis. However, the exact mechanisms are still unclear. As mice lacking the peroxidase peroxiredoxin1 (Prdx1) produce more cellular ROS and die prematurely of cancer, they offer an ideal model system to study ROS-induced tumorigenesis. Prdx1 ablation increased the susceptibility to Ras-induced breast cancer. We, therefore, investigated the role of Prdx1 in regulating oncogenic Ras effector pathways. We found Akt hyperactive in fibroblasts and mammary epithelial cells lacking Prdx1. Investigating the nature of such elevated Akt activation established a novel role for Prdx1 as a safeguard for the lipid phosphatase activity of PTEN, which is essential for its tumour suppressive function. We found binding of the peroxidase Prdx1 to PTEN essential for protecting PTEN from oxidation-induced inactivation. Along those lines, Prdx1 tumour suppression of Ras- or ErbB-2-induced transformation was mediated mainly via PTEN.

Halide Segregation in Mixed-Halide Perovskites: Influence of A-Site Cations.

Mixed-halide perovskites offer bandgap tunability essential for multijunction solar cells; however, a detrimental halide segregation under light is often observed. Here we combine simultaneous in situ photoluminescence and X-ray diffraction measurements to demonstrate clear differences in compositional and optoelectronic changes associated with halide segregation in MAPb(Br0.5I0.5)3 and FA0.83Cs0.17Pb(Br0.4I0.6)3 films. We report evidence for low-barrier ionic pathways in MAPb(Br0.5I0.5)3, which allow for the rearrangement of halide ions in localized volumes of perovskite without significant compositional changes to the bulk material. In contrast, FA0.83Cs0.17Pb(Br0.4I0.6)3 lacks such low-barrier ionic pathways and is, consequently, more stable against halide segregation. However, under prolonged illumination, it exhibits a considerable ionic rearrangement throughout the bulk material, which may be triggered by an initial demixing of A-site cations, altering the composition of the bulk perovskite and reducing its stability against halide segregation. Our work elucidates links between composition, ionic pathways, and halide segregation, and it facilitates the future engineering of phase-stable mixed-halide perovskites.

Diagnostic yield of intravascular ultrasound in patients with clinical signs and symptoms of lower extremity venous disease.

BACKGROUND: Intravascular ultrasound (IVUS) examination has a higher sensitivity compared with venography in the assessment of obstructive venous disease. However, at most venous centers, both modalities continue to be used concomitantly. This study evaluated the diagnostic clinical yield of IVUS examination as a singular intraoperative investigative modality in patients in whom clinical signs and symptoms of venous disease were severe enough to merit such an examination and in whom a venogram was not performed simultaneously. METHODS: From January, 2013, to December, 2018, there were 31 limbs (29 patients) who only had IVUS planimetry without concomitant venogram. Clinical parameters such as pain, swelling and Venous Clinical Severity Score were measured preoperatively and postoperatively. The degree of stenosis noted on intraoperative IVUS was compared with the preoperative duplex. Incidence of complications, technical success, and clinical yield of IVUS examination were noted. RESULTS: The etiology of venous lesion was post thrombotic in the majority of patients (74%). All patients (100%) were either in Clinical, Etiologic, Anatomic, and Pathologic class C3 or higher. In all patients (100%) taken to the operating room, IVUS examination identified stenosis in at least one of the following three veins: common iliac vein, external iliac vein, and common femoral vein. Intervention was in the form of angioplasty with endovenous stenting. There was significant improvement in pain, swelling and Venous Clinical Severity Score after the intervention. CONCLUSIONS: IVUS is an effective diagnostic tool that displays high quality, real-time cross-sectional anatomy during venous interventions. When used as the sole intraoperative diagnostic modality, it seems to have a high clinical yield in patients in whom signs and symptoms of venous disease are severe enough to merit intervention.

Effect of iliofemoral-caval venous intervention on lower extremity compartment pressure in patients with chronic venous insufficiency.

BACKGROUND: Chronic compartment syndrome (CCS) secondary to venous hypertension from chronic venous insufficiency is an uncommonly described entity. The measurement of high resting compartment pressure is helpful in establishing the diagnosis of CCS. The effect of deep venous intervention on compartment pressures in patients with chronic venous insufficiency is not well described. This study evaluated a subset of patients with signs and symptoms of venous disease in whom intervention (hyperdilation or new endovenous stent placement) was performed on the iliofemoral-caval venous system. The effect of the specific intervention was objectively measured by documenting preoperative and postoperative compartment pressures in the posterior superficial compartment of the calf at rest in the supine position. METHODS: From January 2018 to January 2019, there were 80 limbs that underwent either hyperdilation (n = 34) or new endovenous stent placement (n = 46). All patients had measurement of compartment pressures before and after intervention with a simple needle manometer system. Values of 15 mm Hg or higher were considered indicative of CCS in the appropriate clinical context. Clinical parameters such as pain, swelling, and Venous Clinical Severity Score were measured preoperatively and postoperatively. RESULTS: Venous intervention in the form of hyperdilation or endovenous stent placement was associated with reduction in compartment pressure of the extremity undergoing the intervention. In the new stent subset, the compartment pressure was reduced from 17.4 (±4.9) mm Hg to 12.6 (±3.7) mm Hg (P < .0001). In the hyperdilation subset, the compartment pressure was reduced from 14.9 (±4.1) mm Hg to 10.3 (±2.7) mm Hg (P < .0001). There was also a significant improvement in pain, swelling, and Venous Clinical Severity Score after intervention. In patients undergoing hyperdilation, there was a significant improvement in the ejection fraction of the calf pump after intervention from 54.8% (±23.1%) to 52.1% (±18.7%; P = .009). CONCLUSIONS: Deep venous intervention in the form of hyperdilation or endovenous stent placement was associated with symptomatic improvement and reduction of compartment pressure of the extremity undergoing intervention.

Peripheral venous hypertension in chronic venous disease.

BACKGROUND: Microvascular venous hypertension has emerged as a central feature of chronic venous disease (CVD). Yet, the incidence and severity of peripheral venous hypertension in the clinical setting have not been reported. This is an observational study of venous hypertension in the lower limb of a large cohort of patients with suspected CVD referred to a single referral center during a 16-year period. METHODS: Clinical and venous laboratory test data for 8868 limbs of 5792 patients with CVD symptoms seen from 1999 to 2015 were analyzed. Subset A limbs had a mix of obstruction/reflux or neither (n = 4132). These are limbs in which duplex ultrasound reflux (yes/no) status is known. The incidence and severity of obstruction in these limbs are unknown as tests of obstruction were not routinely performed. Subset B limbs had central obstruction (n = 159). These are limbs with intravascular ultrasound-proven stenosis in the iliac veins that was corrected by stent placement. Reflux was assessed by duplex ultrasound and air plethysmography (venous filling index [VFI90]). Pressure measurements included supine venous pressure, erect venous pressure, and ambulatory venous pressure (AMVP). Pressure measurements are categorized according to Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) clinical class, reflux and obstruction with Venn distributions of prevalence. RESULTS: All pressures (supine, erect, and ambulatory) trended worse in higher CEAP clinical classes. Supine foot venous pressures were elevated in 70% and 76% of subsets A and B, respectively. A positive association between elevated supine pressures and reflux could not be shown in this study. Supine foot venous pressure did not worsen with increasing reflux in the two subsets, but erect foot venous pressure did. Elevated supine pressures were associated with obstruction in subset B. AMVP worsened in most higher reflux categories. Ambulatory venous hypertension was dominantly associated (Venn distribution) with reflux, less commonly with obstruction. CONCLUSIONS: Supine venous hypertension is associated with obstruction and does not worsen with reflux. In contrast, erect foot venous pressure worsens in severe reflux categories. Ambulatory venous hypertension worsens in higher CEAP clinical classes. It worsens with increasing reflux. AMVP is dominantly associated (Venn distribution) with reflux, not obstruction.

Caliber-targeted reinterventional overdilation of iliac vein Wallstents.

BACKGROUND: Wallstents (Boston Scientific, Marlborough, Mass) are most commonly used in iliac-caval stenting. Approximately 20% of stented limbs require reintervention to correct in-stent restenosis (ISR) or stent compression (SC). Corrective balloon dilation to rated stent caliber (isodilation) is not always successful. We investigated whether modest overdilation of the Wallstent by 2 to 4 mm (10%-20%) beyond the rated diameter would yield better mechanical clearance of ISR/SC, leading to a larger flow channel, improved conductance, reduction of peripheral venous pressure, and better clinical outcome. Outflow lumen caliber exponentially influences peripheral venous pressure, a key mechanism in chronic venous disease. Beyond the mechanical effects, the rationale for overdilation rests on the theory that an improvement in flow channel at the margins may yield an outsized pressure reduction and clinical improvement. METHODS: There were 274 previously stented limbs that underwent reinterventional balloon dilation for clearance of ISR/SC during a recent 3-year period. Isodilation to rated diameter of the stent was judged effective in 71 limbs (isodilated subset); 203 limbs (overdilated subset) for which initial isodilation was ineffective underwent overdilation of the resident Wallstent by 2 to 4 mm (10%-20%) beyond the original rated diameter. IVUS planimetry was used intraoperatively to calculate SC and ISR and their subsequent clearance in the two subsets. The dilated segments were observed by clinical and duplex ultrasound examination afterward. The two subsets were compared in the following outcome measures: intraprocedural efficacy in clearing ISR/SC and achieving target lumen caliber, subsequent clinical outcomes, duplex ultrasound caliber durability, and improvement in supine foot venous pressures. This is a single-center retrospective analysis of data contemporaneously entered into a time stamped electronic medical record system. RESULTS: The median follow-up was 18 months (range, 1-35 months). Overdilation of the stent resulted in significantly better intraoperative flow channel area improvement per intravascular ultrasound. This was reflected in significantly better clinical outcome and improvement in peripheral venous pressure in the overdilated subset. Overdilation appeared to be durable up to 20 months after intervention by duplex ultrasound monitoring. CONCLUSIONS: Overdilation appears to be a useful technique to correct ISR/SC and to restore target lumen caliber during reinterventional correction of a resident iliac vein Wallstent. More durable caliber improvement, superior clinical outcome, and reduction in peripheral venous hypertension were noticed in overdilated stents compared with isodilation.

Impact of degree of stenosis in May-Thurner syndrome on iliac vein stenting.

OBJECTIVE: May-Thurner syndrome (MTS) patients with lifestyle-limiting symptoms undergo stenting of the iliac vein for relief of compressive disease. The impact of degree of stenosis on clinical symptoms and outcomes after stenting is unknown and examined in our study. METHODS: Retrospective review of contemporaneously entered data of 202 patients who underwent stenting for MTS between 2005 and 2011 was performed. Classification into three groups based on luminal area obtained by intraoperative intravascular ultrasound interrogation of the involved femoroiliocaval segments was carried out. Normal luminal diameters and areas were defined as 12 mm and 125 mm2, 14 mm and 150 mm2, and 16 mm and 200 mm2 in the common femoral, external iliac, and common iliac veins, respectively. Mild (<60%), moderate (60%-89%), and severe (>90%) compression groups were defined using the normal values noted previously and observed after stenting to evaluate outcomes. Kaplan-Meier analysis was done to assess primary, primary assisted, and secondary patencies. Visual analog scale for pain scores, grade of swelling, and Venous Clinical Severity Score (VCSS) before and after stenting at 6, 24, and 48 months were analyzed using paired t-test and Tukey test. Logistic regression was used to gauge the impact of multiple variables including degree of stenosis on stent reintervention. RESULTS: There were 55 patients who had mild, 87 patients who had moderate, and 60 patients who had severe iliac vein compression. Baseline demographic characteristics and comorbidities were similar across all groups. In addition, there was no statistically significant difference in median baseline visual analog scale score, grade of swelling, and VCSS among the groups. Compression was treated with angioplasty and stenting encompassing all areas of disease as determined by intravascular ultrasound. Stent technique involved use of Wallstent (Boston Scientific, Marlborough, Mass) only in 183 patients and Wallstent-Z stent (Cook Medical, Bloomington, Ind) combination in the remainder. No difference in median stent patency was noted on follow-up. Clinically, at 48 months, a statistically significant recurrence of pain, swelling, and worsening of VCSS were noted in the severe stenosis group but not in the other two groups. No variable was noted to have an impact on stent reintervention. CONCLUSIONS: Severity of MTS stenosis is not a predictor of initial clinical symptoms. Long term, patients with ≥90% initial MTS stenosis experience recurrence of symptoms. The degree of iliac venous stenosis does not appear to affect stent patency. Such information will help counsel patients before intervention.

Characteristics and outcomes of stent occlusion after iliocaval stenting.

OBJECTIVE: With increasing use of iliocaval stenting, complications have become more noticeable. Stent occlusion is one such outcome that has not been studied in detail. Characteristics of stent occlusion in addition to outcomes after recanalization are presented. METHODS: An analysis of 3468 initial iliocaval stents placed during an 18-year period from 1997 to 2015 was performed. A total of 102 stent occlusions were identified, amounting to a 3% stent occlusion rate. Characteristics evaluated included onset after stent placement, techniques used for restoring patency, and their outcome. Kaplan-Meier analysis was used to assess stent patency. Regression analysis was used to evaluate risk factors for stent occlusion. RESULTS: Stent occlusions occurred at a median of 5.8 months after placement. The occluded stent could be reopened after a wide range of intervals, the longest being 14 years. The majority (69%) of occlusions were chronic (>30 days) and the remainder (31%) were acute; 77% of the occlusions occurred in post-thrombotic limbs. The most common technique used to recanalize the acutely occluded stent was pharmacomechanical thrombectomy, whereas wire recanalization with balloon angioplasty was the technique most used for chronic occlusions. Of the 102 occluded stents, patency was achieved in 75 of 88 (84%) attempts. After successful recanalization, the median primary patency was 7 ± 1.9 months, median primary assisted patency was 7.5 ± 3.5 months, and median secondary patency was 25 ± 8.3 months. Clinically, there was improvement in the visual analog scale pain scores from a median of 3.5 to 1 (P < .01), in the median grade of swelling from 2 to 1 (P < .01), and in the mean Venous Clinical Severity Score from 6.4 to 3.8 (P < .01) after recanalization. A 40% ulcer healing rate was noted after recanalization during a median follow-up period of 17 months. There were no significant adverse events or mortality. Regression analysis revealed stent placement for native vein occlusion as the only statistically significant predictor of stent occlusion. CONCLUSIONS: Stent occlusion after iliocaval stenting is a rare occurrence. Recanalization of occluded stents can be performed with minimal morbidity even months to years after occlusion with good outcomes. Long-term patency of occluded stents that were recanalized is poor compared with patency of the initially placed stent.

Ambulatory venous pressure, air plethysmography, and the role of calf venous pump in chronic venous disease.

BACKGROUND: Ambulatory venous pressure (AMVP) records pressure dynamics with calf exercise. Air plethysmography (APG) measures related volume detail. APG has been suggested as a noninvasive surrogate for AMVP. We examine the correlations between APG and AMVP parameters and the role of "calf pump failure" in chronic venous disease (CVD). METHODS: A total of 8456 limbs in 4610 patients investigated for CVD during a 20-year period were analyzed. APG and AMVP data were available in 4599 limbs for calculation of Pearson correlation coefficient; 1347 of these limbs had significant iliac vein stenosis, proven by intravascular ultrasound. Venn diagrams are used to explore overlapping incidence of APG and AMVP abnormalities. RESULTS: APG calf volume and reflux (venous volume, venous filling index) showed progressively significant deterioration with advancing Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) clinical class, anatomic extent of reflux (superficial, deep, perforator), and reflux severity (axial reflux, segmental score). Notably, calf ejection volume increased in a nearly linear fashion (R = 0.71) to venous volume such that residual volume fraction (RVF) remained normal even in the worst of these categories. AMVP too progressively deteriorated with clinical disease and reflux severity. Venous filling time was the key parameter as the pressure drop alone was abnormal in only 4% of the limbs analyzed. There was no correlation between RVF and AMVP (R = 0.22) or between AMVP and many other APG parameters. Venn distribution showed only minor overlap (30%) between AMVP and key APG abnormalities overall, but the overlap increases from 40% to 70% in advanced clinical and reflux categories. AMVP was rarely abnormal (7%) when APG was normal. Median AMVP was normal in calf pump failure categories, however defined (subnormal ejection fraction, RVF, or both). Median AMVP is normal in venous obstruction without reflux, while AMVP abnormalities are associated three to seven times more with reflux than with obstruction. CONCLUSIONS: APG (venous filling index) is a useful index of reflux. Calf pump ejection is a powerful and plastic compensatory mechanism, and calf pump failure is rare. Ambulatory venous hypertension is dominantly associated with reflux and less with obstruction. AMVP too worsens with clinical and reflux severity categories. However, there is little correlation between APG and AMVP parameters as APG measures volume and AMVP measures pressure, each in its own domain, and the volume-pressure curve is nonlinear. AMVP may be omitted in routine clinical testing if APG is normal, as the yield (7%) will be very low. AMVP reflects venous hypertension, the end stage in CVD. AMVP should be used to identify such cases when APG is abnormal.

Novel Single-Stranded DNA Virus Genomes Recovered from Chimpanzee Feces Sampled from the Mambilla Plateau in Nigeria.

Metagenomic approaches are rapidly expanding our knowledge of the diversity of viruses. In the fecal matter of Nigerian chimpanzees we recovered three gokushovirus genomes, one circular replication-associated protein encoding single-stranded DNA virus (CRESS), and a CRESS DNA molecule.