Observation of topological frequency combs.

On-chip generation of optical frequency combs using nonlinear ring resonators has enabled numerous applications of combs that were otherwise limited to mode-locked lasers. Nevertheless, on-chip frequency combs have relied predominantly on single-ring resonators. In this study, we experimentally demonstrate the generation of a novel class of frequency combs, the topological frequency combs, in a two-dimensional lattice of hundreds of ring resonators that hosts fabrication-robust topological edge states with linear dispersion. By pumping these edge states, we demonstrate the generation of a nested frequency comb that shows oscillation of multiple edge state resonances across ≈40 longitudinal modes and is spatially confined at the lattice edge. Our results provide an opportunity to explore the interplay between topological physics and nonlinear frequency comb generation in a commercially available nanophotonic platform.

Late Toxicity of Prostate Ultrahypofractionated Radiation Therapy Compared With Moderate Hypofractionation in a Randomized Trial.

PURPOSE: We report late toxicity, quality of life (QOL), and urinary symptom score with prostate cancer radiation therapy in a randomized trial comparing moderate hypofractionation and ultrahypofrationation. METHODS AND MATERIALS: Patients with intermediate and high-risk prostate cancer were randomized to either Arm 1 (70 Gy/28 fractions) or Arm 2 (36.25 Gy/5 weekly fractions). Late toxicity was evaluated using the Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group/Subjective, Objective, Management, Analytical scales. QOL was assessed with the Expanded Prostate Inventory Composite-26 Short Form and urinary function with the International Prostate Symptom Score. RESULTS: Eighty participants were randomized. Two from Arm 1 withdrew, leaving 36 patients in Arm 1 and 42 in Arm 2. There were no significant differences in baseline characteristics, except for worse International Prostate Symptom Score in Arm 2. No difference was observed in freedom from grade 3 or worse toxicity between treatments (P = .921), with only a single grade 3 event in each arm. There was no significant difference in freedom from grade 2 or worse toxicity (P = .280). No difference was observed in freedom from grade 2 or worse genitorurinary toxicity, with cumulative probabilities of 69.0% and 87.0% at 5 years for Arms 1 and 2, respectively (0.132). No difference was observed in freedom from grade 2 or worse gastrointestinal toxicity, with cumulative probabilities of 74.0% in Arm 1 and 80.0% in Arm 2 (P = .430). There were no significant differences in Expanded Prostate Inventory Composite-26 Short Form QOL between arms. CONCLUSIONS: Ultrahypofrationation, delivered weekly, is well tolerated with no significant differences in freedom from late toxicity compared with moderate hypofractionation.

Higher rank chirality and non-Hermitian skin effect in a topolectrical circuit.

While chirality imbalances are forbidden in conventional lattice systems, non-Hermiticity can effectively avoid the chiral-doubling theorem to facilitate 1D chiral dynamics. Indeed, such systems support unbalanced unidirectional flows that can lead to the localization of an extensive number of states at the boundary, known as the non-Hermitian skin effect (NHSE). Recently, a generalized (rank-2) chirality describing a 2D robust gapless mode with dispersion ω = kxky has been introduced in crystalline systems. Here we demonstrate that rank-2 chirality imbalances can be established in a non-Hermitian (NH) lattice system leading to momentum-resolved chiral dynamics, and a rank-2 NHSE where there are both edge- and corner-localized skin modes. We then experimentally test this phenomenology in a 2-dimensional topolectric circuit that implements a NH Hamiltonian with a long-lived rank-2 chiral mode. Using impedance measurements, we confirm the rank-2 NHSE in this system, and its manifestation in the predicted skin modes and a highly unusual momentum-position locking response. Our investigation demonstrates a circuit-based path to exploring higher-rank chiral physics, with potential applications in systems where momentum resolution is necessary, e.g., in beamformers and non-reciprocal devices.

Photonic quadrupole topological insulator using orbital-induced synthetic flux.

The rich physical properties of multiatomic crystals are determined, to a significant extent, by the underlying geometry and connectivity of atomic orbitals. The mixing of orbitals with distinct parity representations, such as s and p orbitals, has been shown to be useful for generating systems that require alternating phase patterns, as with the sign of couplings within a lattice. Here we show that by breaking the symmetries of such mixed-orbital lattices, it is possible to generate synthetic magnetic flux threading the lattice. We use this insight to experimentally demonstrate quadrupole topological insulators in two-dimensional photonic lattices, leveraging both s and p orbital-type modes. We confirm the nontrivial quadrupole topology by observing the presence of protected zero-dimensional states, which are spatially confined to the corners, and by confirming that these states sit at mid-gap. Our approach is also applicable to a broader range of time-reversal-invariant synthetic materials that do not allow for tailored connectivity, and in which synthetic fluxes are essential.

Self-Induced Dirac Boundary State and Digitization in a Nonlinear Resonator Chain.

The low-energy excitations in many condensed matter and metamaterial systems can be well described by the Dirac equation. The mass term associated with these collective excitations, also known as the Dirac mass, can take any value and is directly responsible for determining whether the resultant band structure exhibits a band gap or a Dirac point with linear dispersion. Manipulation of this Dirac mass has inspired new methods of band structure engineering and electron confinement. Notably, it has been shown that a massless state necessarily localizes at any domain wall that divides regions with Dirac masses of different signs. These localized states are known as Jackiw-Rebbi-type Dirac boundary modes and their tunability and localization features have valuable technological potential. In this study, we experimentally demonstrate that nonlinearity within a 1D Dirac material can result in a self-induced domain boundary for the Dirac mass. Our experiments are performed in a dimerized magnetomechanical metamaterial that allows complete control of both the magnitude and sign of the local material nonlinearity, as well as the sign of the Dirac mass. We find that the massless bound state that emerges at the self-induced domain boundary acts similarly to a dopant site within an insulator, causing the material to exhibit a dramatic binary switch in its conductivity when driven above an excitation threshold.

Bound states at partial dislocation defects in multipole higher-order topological insulators.

The bulk-boundary correspondence, which links a bulk topological property of a material to the existence of robust boundary states, is a hallmark of topological insulators. However, in crystalline topological materials the presence of boundary states in the insulating gap is not always necessary since they can be hidden in the bulk energy bands, obscured by boundary artifacts of non-topological origin, or, in the case of higher-order topology, they can be gapped altogether. Recently, exotic defects of translation symmetry called partial dislocations have been proposed to trap gapless topological modes in some materials. Here we present experimental observations of partial-dislocation-induced topological modes in 2D and 3D insulators. We particularly focus on multipole higher-order topological insulators built from circuit-based resonator arrays, since crucially they are not sensitive to full dislocation defects, and they have a sublattice structure allowing for stacking faults and partial dislocations.

Acute Toxicity of Ultrahypofractionation Compared With Moderate Hypofractionation in Prostate Cancer Treatment: A Randomized Trial.

PURPOSE: We report on the early toxic effects and quality of life of localized prostate cancer radiation therapy in a randomized trial comparing moderate hypofractionation (MHF) with ultrahypofractionation (UHF). METHODS AND MATERIALS: We randomized patients with intermediate- to high-risk localized prostate cancer to radiation therapy with MHF (70 Gy in 28 daily fractions) or UHF (36.25 Gy in 5 weekly fractions). We analyzed early toxic effects (using Common Terminology Criteria for Adverse Events and Radiation Therapy Oncology Group/Subjective, Objective, Management, Analytic scales) and patient-reported quality of life (using the Expanded Prostate Inventory Composite questionnaire) when all patients had at least 6 months of follow-up. RESULTS: We randomized 80 participants. Two patients withdrew from radiation therapy. We ran analysis on results for 78 patients. The 2 arms were balanced in key patient and disease characteristics, except for a statistically worse baseline urinary function in the UHF arm (International Prostate Symptom Score >7: 68% vs 36%, P = .004). There were no statistically significant differences between the 2 arms in grade 3 or grade 2 toxic effects: grade ≥3 MHF 8%, UHF 2% (P = .235); grade ≥2 MHF 36%, UHF 24% (P = .235). There were also no significant differences in percentages of patients with a "minimal important change" of quality of life in the Incontinence (MHF 36%, UHF 33%; P = .746), Irritative/Obstructive (MHF 56%, UHF 74%; P = .074), or Bowel domains (MHF 58%, UHF 52%; P = .508) on the Expanded Prostate Inventory Composite questionnaire. CONCLUSIONS: UHF radiation therapy for prostate cancer is well tolerated, and there were no significant differences in toxic effects and quality of life changes between UHF and MHF up to 6 months after treatment in the current trial.

Trapped fractional charges at bulk defects in topological insulators.

Topological crystalline insulators (TCIs) can exhibit unusual, quantized electric phenomena such as fractional electric polarization and boundary-localized fractional charge1-6. This quantized fractional charge is the generic observable for identification of TCIs that lack clear spectral features5-7, including ones with higher-order topology8-11. It has been predicted that fractional charges can also manifest where crystallographic defects disrupt the lattice structure of TCIs, potentially providing a bulk probe of crystalline topology10,12-14. However, this capability has not yet been confirmed in experiments, given that measurements of charge distributions in TCIs have not been accessible until recently11. Here we experimentally demonstrate that disclination defects can robustly trap fractional charges in TCI metamaterials, and show that this trapped charge can indicate non-trivial, higher-order crystalline topology even in the absence of any spectral signatures. Furthermore, we uncover a connection between the trapped charge and the existence of topological bound states localized at these defects. We test the robustness of these topological features when the protective crystalline symmetry is broken, and find that a single robust bound state can be localized at each disclination alongside the fractional charge. Our results conclusively show that disclination defects in TCIs can strongly trap fractional charges as well as topological bound states, and demonstrate the primacy of fractional charge as a probe of crystalline topology.

Adjuvant Treatment of Early Ovarian Clear Cell Carcinoma: A Population-Based Study of Whole Abdominal Versus Pelvic Nodal Radiotherapy.

BACKGROUND: Adjuvant treatment in early ovarian clear cell carcinoma (OCCC) is not yet standardized. The objective of this population-based study was to compare the outcome of patients with early OCCC treated with adjuvant chemotherapy versus chemoradiotherapy (chemoRT) and evaluate the association of adjuvant radiotherapy regimens (whole abdominal radiotherapy [WART] versus pelvic nodal radiotherapy [PRT]) with outcome. PATIENTS AND METHODS: Chart review was conducted to identify patients with stage I and II OCCC with complete information on staging. Patients with stage IA, IB, or IC OCCC purely resulting from capsular rupture were excluded because the provincial protocol does not recommend adjuvant treatment. RESULTS: Overall, 403 patients were identified and 343 received adjuvant treatment, of whom 255 had stage IC or II OCCC and 153 were eligible for final analysis. On Cox multivariable regression, receipt of chemoRT (n=90) was associated with an improvement in failure-free survival (FFS) (hazard ratio [HR], 0.57; 95% CI, 0.34-0.94) compared with chemotherapy alone (n=63). Use of chemoRT also resulted in 54% reduction in the cumulative incidence of cancer-specific mortality (subdistribution HR, 0.46; 95% CI, 0.24-0.89). However, there was no significant difference in the HR for overall survival (OS) between the chemoRT (HR, 0.70; 95% CI, 0.43-1.13) and chemotherapy group. Relative to chemotherapy + WART (chemo-WART), chemotherapy + PRT (chemo-PRT) was not associated with any significant difference in HR for FFS (HR, 1.34; 95% CI, 0.40-4.44) or OS (HR, 1.13; 95% CI, 0.37-3.46). CONCLUSIONS: Adjuvant chemoRT was associated with a lower risk of failure compared with chemotherapy alone. However, there was no difference in OS between the adjuvant chemotherapy and chemoRT regimens. Additionally, no significant difference in terms of FFS or OS was found between the chemo-WART and chemo-PRT groups.

A fractional corner anomaly reveals higher-order topology.

Spectral measurements of boundary-localized topological modes are commonly used to identify topological insulators. For high-order insulators, these modes appear at boundaries of higher codimension, such as the corners of a two-dimensional material. Unfortunately, this spectroscopic approach is only viable if the energies of the topological modes lie within the bulk bandgap, which is not required for many topological crystalline insulators. The key topological feature in these insulators is instead fractional charge density arising from filled bulk bands, but measurements of such charge distributions have not been accessible to date. We experimentally measure boundary-localized fractional charge density in rotationally symmetric two-dimensional metamaterials and find one-fourth and one-third fractionalization. We then introduce a topological indicator that allows for the unambiguous identification of higher-order topology, even without in-gap states, and we demonstrate the associated higher-order bulk-boundary correspondence.

Robust temporal pumping in a magneto-mechanical topological insulator.

The transport of energy through 1-dimensional (1D) waveguiding channels can be affected by sub-wavelength disorder, resulting in undesirable localization and backscattering phenomena. However, quantized disorder-resilient transport is observable in the edge currents of 2-dimensional (2D) topological band insulators with broken time-reversal symmetry. Topological pumps are able to reduce this higher-dimensional topological insulator phenomena to lower dimensionality by utilizing a pumping parameter (either space or time) as an artificial dimension. Here we demonstrate a temporal topological pump that produces on-demand, robust transport of mechanical energy using a 1D magneto-mechanical metamaterial. We experimentally demonstrate that the system is uniquely resilient to defects occurring in both space and time. Our findings open a path towards exploration of higher-dimensional topological physics with time as a synthetic dimension.

Strong Nonreciprocity in Modulated Resonator Chains through Synthetic Electric and Magnetic Fields.

We study nonreciprocity in spatiotemporally modulated 1D resonator chains from the perspective of equivalent 2D resonator arrays with a synthetic dimension and transverse synthetic electric and magnetic fields. The synthetic fields are respectively related to temporal and spatial modulation of the resonator chain, and we show that their combination can induce strong transmission nonreciprocity, i.e., complete isolation with only a weak perturbative modulation. This nonreciprocal effect is analogous to the Hall effect for charged particles. We experimentally implement chains of two and three spatiotemporally modulated resonators and measure over 58 dB of isolation contrast.

High Dose Rate 192-Ir-Brachytherapy for Basal Cell Carcinoma of the Skin using a 3D Printed Surface Mold.

We report on the treatment of a Basal Cell Carcinoma of the skin with high-dose-rate (HDR) brachytherapy using a 3D-printed surface mold. The lesion was treated with 40 Gy in 10 fractions, administered every second day. The treatment was well tolerated and there were no significant toxicities. The patient had a complete response to radiation therapy. So it can concluded that 3D printed surface molds can be effectively used in the context of HDR skin brachytherapy.

Small cell carcinoma of cervix: A population-based study evaluating standardized provincial treatment protocols.

OBJECTIVES: To describe the patient characteristics, patterns of treatment, and outcome of patients with small cell carcinoma of Cervix (SmCC) treated with radical radiotherapy from a provincial cancer registry database. METHODS: Overall 25 patients with SmCC were treated with radical radiotherapy (with or without chemotherapy) from January 1, 1994 to December 31, 2013. Nineteen patients had pure SmCC while 6 had additional neuroendocrine component. Patients were treated with combined chemo-radiotherapy using multi-agent chemotherapy with pelvic or combined pelvic and para-aortic radiotherapy. All patients received brachytherapy. Use of prophylactic cranial irradiation was dependent on physician discretion. Survival was estimated using Kaplan-Meier method and compared using log-rank test. RESULTS: We report a median overall survival of 53.8 months for our cohort. After a median follow-up of 54 months for surviving patients, the overall survival (OS) and progression free survival (PFS) at 5-years were 48% and 46.4% respectively. Patients with stage I-IIA disease had superior 5-year PFS (67.3% vs. 11.1%; p = .004) and 5-year OS (62.5% vs. 22.2%; p = .006). Patients with node-negative disease had a trend towards better 5-year PFS (55.7% vs. 19%; p = .07) and OS (61.1% vs. 14.3% at 5-years; p = .06) Distant metastasis was the predominant site of disease progression (n = 12; 48%). CONCLUSION: Distant metastasis is the predominant pattern of failure for patients with SmCC treated with radical chemo-radiotherapy. With modern chemo-radiotherapy protocols we can expect a 5 year survival of around 50%. Early stage and node-negative status appear to be favorable prognostic factors with survival rates at 5-year over 60%.

Surface Mould Brachytherapy for Skin Cancers: The British Columbia Cancer Experience.

Purpose To report on skin tumor treatment with surface mould brachytherapy at our institution. Methods This was a retrospective review for all patients with skin tumors treated using Ir-192 high dose rate (HDR) surface mould brachytherapy from January 1, 2010 to December 31, 2017 in British Columbia. We identified 65 lesions (59 patients). Median age at diagnosis was 83 (range = 45-97). The majority were basal cell (54%, n = 35) or squamous cell carcinomas (31%, n = 20). Most lesions were located in the head and neck region. The most commonly used RT dose was 40 Gy/10 fractions; all patients had individualized CT-based planning. Results The two-year overall survival (OS) was 77.6% and two-year progression-free survival (PFS) was 71.5%. Most deaths were from unrelated causes. Response was assessed in clinic 2-4 months post-treatment. Our complete response (CR) rate was 96.8%, with partial response in two patients; two patients could not be assessed for response. We report a two-year local control (LC) rate of 84.9%, and local recurrence in five patients. The procedure was well tolerated, with no grade 3-5 acute or late toxicities. There was one case of grade 2 radionecrosis (Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03). The 100% isodose line median depth was 0.5 cm, and median surface dose = 126.5%. The median V90 = 92.3%. Conclusion Surface mould brachytherapy for skin tumors is a safe and effective modality, with excellent response rates. It is well-tolerated and a non-invasive option for elderly patients with comorbidities.

Synthetic phonons enable nonreciprocal coupling to arbitrary resonator networks.

Inducing nonreciprocal wave propagation is a fundamental challenge across a wide range of physical systems in electromagnetics, optics, and acoustics. Recent efforts to create nonreciprocal devices have departed from established magneto-optic methods and instead exploited momentum-based techniques such as coherent spatiotemporal modulation of resonators and waveguides. However, to date, the nonreciprocal frequency responses that these devices can achieve have been limited, mainly to either broadband or Lorentzian-shaped transfer functions. We show that nonreciprocal coupling between waveguides and resonator networks enables the creation of devices with customizable nonreciprocal frequency responses. We create nonreciprocal coupling through the action of synthetic phonons, which emulate propagating phonons and can scatter light between guided and resonant modes that differ in both frequency and momentum. We implement nonreciprocal coupling in microstrip circuits and experimentally demonstrate both elementary nonreciprocal functions such as isolation and gyration, as well as reconfigurable, higher-order nonreciprocal filters. Our results suggest nonreciprocal coupling as a platform for a broad class of customizable nonreciprocal systems, adaptable to all wave phenomena.

Integration of radiobiological modeling and indices in comparative plan evaluation: A study comparing VMAT and 3D-CRT in patients with NSCLC.

PURPOSE: The purpose of this article was to generate an algorithm to calculate radiobiological endpoints and composite indices and use them to compare volumetric modulated arc therapy (VMAT) and 3-dimensional conformal radiation therapy (3D-CRT) techniques in patients with locally advanced non-small cell lung cancer. METHODS AND MATERIALS: The study included 25 patients with locally advanced non-small cell lung cancer treated with 3D-CRT at our center between January 1, 2010, and December 31, 2014. The planner generated VMAT plans using clones of the original computed tomography scans and regions of interest volumes, which did not include the original 3D plans. Both 3D-CRT and VMAT plans were generated using the same dose-volume constraint worksheet. The dose-volume histogram parameters for planning target volume and relevant organs at risk (OAR) were reviewed. The calculation engine was written in the R programming language; the user interface was developed with the "shiny" R Web library. Dose-volume histogram data were imported into the calculation engine and tumor control probability (TCP), normal tissue complication probability (NTCP), composite cardiopulmonary toxicity index (CPTI), morbidity index: MI = ∑j = 1#ofrelevantOARs(wj ∗ NTCPj), uncomplicated TCP (UTCP=TCP∗∏k=1#ofOARs1-NTCPK100, and therapeutic gain (TG): ie, TG = TCP ∗ (100 - MI) were calculated. RESULTS: TCP was better with 3D-CRT (12.62% vs 11.71%, P < .001), whereas VMAT demonstrated superior NTCP esophagus (4.45% vs 7.39%, P = .02). NTCP spinal cord (0.001% vs 0.009%, P = .001), and NTCP heart/perfusion defect (44.57% vs 56.42%, P = .016). There was no difference in NTCP lung (6.27% vs 7.62%, P = .221) and NTCP heart/pericarditis (0.001% vs 0.15%, P = .129) between 2 techniques. VMAT showed substantial improvement in morbidity index (11.06% vs. 14.31%, P = 0.01), CPTI (47.59% vs 59.41%, P = .03), TG (P = .035), and trend toward superiority in UTCP (5.89 vs 4.75, P=.057). CONCLUSION: The study highlights the utility of the radiobiological algorithm and summary indices in comparative plan evaluation and demonstrates benefits of VMAT over 3D-CRT.

A quantized microwave quadrupole insulator with topologically protected corner states.

The theory of electric polarization in crystals defines the dipole moment of an insulator in terms of a Berry phase (geometric phase) associated with its electronic ground state. This concept not only solves the long-standing puzzle of how to calculate dipole moments in crystals, but also explains topological band structures in insulators and superconductors, including the quantum anomalous Hall insulator and the quantum spin Hall insulator, as well as quantized adiabatic pumping processes. A recent theoretical study has extended the Berry phase framework to also account for higher electric multipole moments, revealing the existence of higher-order topological phases that have not previously been observed. Here we demonstrate experimentally a member of this predicted class of materials-a quantized quadrupole topological insulator-produced using a gigahertz-frequency reconfigurable microwave circuit. We confirm the non-trivial topological phase using spectroscopic measurements and by identifying corner states that result from the bulk topology. In addition, we test the critical prediction that these corner states are protected by the topology of the bulk, and are not due to surface artefacts, by deforming the edges of the crystal lattice from the topological to the trivial regime. Our results provide conclusive evidence of a unique form of robustness against disorder and deformation, which is characteristic of higher-order topological insulators.

Optomechanical non-contact measurement of microparticle compressibility in liquids.

High-throughput label-free measurements of the optical and mechanical properties of single microparticles play an important role in biological research, drug development, and related large population assays. However, mechanical detection techniques that rely on the density contrast of a particle with respect to its environment cannot sense neutrally bouyant particles. On the other hand, neutrally buoyant particles may still have a high compressibility contrast with respect to their environment, opening a new window to their detection and analysis. Here we present a label-free high-throughput approach for measuring the compressibility (bulk modulus) of freely flowing microparticles by means of resonant measurements in an opto-mechano-fluidic resonator.

Dynamically induced robust phonon transport and chiral cooling in an optomechanical system.

The transport of sound and heat, in the form of phonons, can be limited by disorder-induced scattering. In electronic and optical settings the introduction of chiral transport, in which carrier propagation exhibits parity asymmetry, can remove elastic backscattering and provides robustness against disorder. However, suppression of disorder-induced scattering has never been demonstrated in non-topological phononic systems. Here we experimentally demonstrate a path for achieving robust phonon transport in the presence of material disorder, by explicitly inducing chirality through parity-selective optomechanical coupling. We show that asymmetric optical pumping of a symmetric resonator enables a dramatic chiral cooling of clockwise and counterclockwise phonons, while simultaneously suppressing the hidden action of disorder. Surprisingly, this passive mechanism is also accompanied by a chiral reduction in heat load leading to optical cooling of the mechanics without added damping, an effect that has no optical analog. This technique can potentially improve upon the fundamental thermal limits of resonant mechanical sensors, which cannot be attained through sideband cooling.Chiral transport can provide robustness against disorder, resulting in improved resonant modes for sensing and metrology. Here, Kim et al. demonstrate chiral phonon transport, disorder suppression and anomalous cooling without damping in an asymmetrically-pumped optomechanical system.