An economic analysis comparing health care resource use and cost of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin versus gemcitabine and cisplatin as neoadjuvant therapy for muscle invasive bladder cancer.

PURPOSE: To compare healthcare resource utilization (HRU) and costs associated with dose-dense methotrexate, vinblastine, doxorubicin, cisplatin (ddMVAC) and gemcitabine, cisplatin (GC) as neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). METHODS: Patient treated at Dana-Farber Cancer Institute from 2010 to 2019 were identified. HRU data on chemotherapy administered, supportive medications, patient monitoring, clinic, infusion, emergency department (ED) visits and hospitalization were collected retrospectively. Unit costs for HRU components were obtained from the Centers for Medicare and Medicaid Website and HRU was compared between groups using quantile regression analysis. RESULTS: 137 patients were included; 51 received ddMVAC and 86 GC. Baseline characteristics were similar, except lower mean age (P < 0.001) and higher proportion of ECOG-PS = 0 (P < 0.001) for ddMVAC. ddMVAC required more granulocyte-colony stimulating factor support (P < 0.001), central line placement (P = 0.017), cardiac imaging (P < 0.001), and infusion visits (P < 0.001), whereas GC required more clinic visits. ED visits were higher for ddMVAC (P = 0.048), while chemotherapy cycle delays and hospitalization days were higher for GC (P = 0.008). After adjusting for ECOG-PS and age, the cost per patient was approximately 41% lower (95%CI: 28% to 52%; P < 0.001) for GC vs. ddMVAC, which translated to a median adjusted cost savings of $7,410 (95%CI: $5,474-$9,347) per patient. CONCLUSIONS: Although excess HRU did not clearly favor one regimen, adjusting for PS and age indicated lower costs with GC vs. ddMVAC. Given the similar cumulative cisplatin delivery with both regimens, the associated values and costs supports the preferential selection of GC in the neoadjuvant setting of MIBC.

Digital Orthopaedics: A Glimpse Into the Future in the Midst of a Pandemic.

BACKGROUND: The response to COVID-19 catalyzed the adoption and integration of digital health tools into the health care delivery model for musculoskeletal patients. The change, suspension, or relaxation of Medicare and federal guidelines enabled the rapid implementation of these technologies. The expansion of payment models for virtual care facilitated its rapid adoption. The authors aim to provide several examples of digital health solutions utilized to manage orthopedic patients during the pandemic and discuss what features of these technologies are likely to continue to provide value to patients and clinicians following its resolution. CONCLUSION: The widespread adoption of new technologies enabling providers to care for patients remotely has the potential to permanently change the expectations of all stakeholders about the way care is provided in orthopedics. The new era of Digital Orthopaedics will see a gradual and nondisruptive integration of technologies that support the patient's journey through the successful management of their musculoskeletal disease.

Cavity electromechanics with parametric mechanical driving.

Microwave optomechanical circuits have been demonstrated to be powerful tools for both exploring fundamental physics of macroscopic mechanical oscillators, as well as being promising candidates for on-chip quantum-limited microwave devices. In most experiments so far, the mechanical oscillator is either used as a passive element and its displacement is detected using the superconducting cavity, or manipulated by intracavity fields. Here, we explore the possibility to directly and parametrically manipulate the mechanical nanobeam resonator of a cavity electromechanical system, which provides additional functionality to the toolbox of microwave optomechanics. In addition to using the cavity as an interferometer to detect parametrically modulated mechanical displacement and squeezed thermomechanical motion, we demonstrate that this approach can realize a phase-sensitive parametric amplifier for intracavity microwave photons. Future perspectives of optomechanical systems with a parametrically driven mechanical oscillator include exotic bath engineering with negative effective photon temperatures, or systems with enhanced optomechanical nonlinearities.

Coupling microwave photons to a mechanical resonator using quantum interference.

The field of optomechanics has emerged as leading platform for achieving quantum control of macroscopic mechanical objects. Implementations of microwave optomechanics to date have coupled microwave photons to mechanical resonators using a moving capacitance. While simple and effective, the capacitive scheme suffers from limitations on the maximum achievable coupling strength. Here, we experimentally implement a fundamentally different approach: flux-mediated optomechanical coupling. In this scheme, mechanical displacements modulate the flux in a superconducting quantum interference device (SQUID) that forms the inductor of a microwave resonant circuit. We demonstrate that this flux-mediated coupling can be tuned in situ by the magnetic flux in the SQUID, enabling nanosecond flux tuning of the optomechanical coupling. Furthermore, we observe linear scaling of the single-photon coupling rate with the in-plane magnetic transduction field, a trend with the potential to overcome the limits of capacitive optomechanics, opening the door for a new generation of groundbreaking optomechanical experiments.

Posterior Hip Precautions Do Not Impact Early Recovery in Total Hip Arthroplasty: A Multicenter, Randomized, Controlled Study.

BACKGROUND: Posterior hip precautions have been routinely prescribed to decrease dislocation rates. The purpose of this study was to determine whether the absence of hip precautions improved early recovery after total hip arthroplasty via the posterolateral approach. METHODS: Patients undergoing total hip arthroplasty via the posterolateral approach at 3 centers were enrolled. Patients meeting the selection criteria were randomized to standard hip precautions (SHP) or no hip precautions (NHP) for 6 weeks following surgery. HOOS Jr, Health State visual analog score, and rate of pain scores were recorded preoperatively and in subsequent postoperative visits; dislocation episodes were also noted. Standard statistical analysis was performed. RESULTS: From 2016 to 2017, 159 patients were randomized to SHP and 154 patients were randomized to NHP. Controlling for the center at which the surgery was performed, the only difference in outcome scores between the 2 groups was at 2 weeks; the NHP group had a lower HOOS Jr score when compared to the SHP group (P = .03). There was no difference in outcome scores at any other time points when compared to preoperative assessments. In the SHP group, there were 2 recorded dislocations (1.3%) and 1 in the NHP group (0.7%; P = .62). CONCLUSION: In this multicenter, randomized, controlled study, the absence of hip precautions in the postoperative period did not improve subjective outcomes which may be explained by the self-limiting behavior of NHP patients. Furthermore, with the numbers available for the study, there was no difference in the rate of dislocation between the 2 groups.

Modern theory of tuberculosis: culturomic analysis of its historical origin in Europe and North America.

INTRODUCTION: An historical account of the modern theory of tuberculosis (TB) using a culturomic analysis has not been studied. OBJECTIVE: To analyze, using culturomic methods, the history of our modern understanding of TB as a unitary disease. METHODS: A culturomic analysis of millions of digitized texts was undertaken to quantify 200-year trends in usage of the modern term tuberculosis and pre-modern terms consumptive, phthisis, and scrofula, and to correlate these trends with significant historical events. RESULTS: Our understanding of TB originated with Laënnec in Paris, who proposed that the seemingly disparate wasting conditions phthisis, scrofula, and consumption were each related to the same post-mortem anatomical sign: the tubercle. The term tuberculosis was coined by Schonlein in 1829, but the term's usage remained uncommon until Villemin's 1865 discovery that TB was a communicable disease, Koch's 1882 discovery of Mycobacterium tuberculosis, and Pasteur's 1884 discovery of a vaccine against another communicable disease, smallpox. CONCLUSION: Our modern understanding of TB as a unitary disease was embraced slowly. Acceptance required new terminology describing the idea, scientific confirmation that TB is an infectious disease, and evidence suggesting that it might be prevented. An innovative idea is not enough to induce widespread acceptance. The study illustrates how culturomic methods can be used to study the adoption and diffusion of an innovation, in this case the modern theory of TB.

Pick-up and drop transfer of diamond nanosheets.

Nanocrystalline diamond (NCD) is a promising material for electronic and mechanical micro- and nanodevices. Here we introduce a versatile pick-up and drop technique that makes it possible to investigate the electrical, optical and mechanical properties of as-grown NCD films. Using this technique, NCD nanosheets, as thin as 55 nm, can be picked-up from a growth substrate and positioned on another substrate. As a proof of concept, electronic devices and mechanical resonators are fabricated and their properties are characterized. In addition, the versatility of the method is further explored by transferring NCD nanosheets onto an optical fiber, which allows measuring its optical absorption. Finally, we show that NCD nanosheets can also be transferred onto two-dimensional crystals, such as MoS2, to fabricate heterostructures. Pick-up and drop transfer enables the fabrication of a variety of NCD-based devices without requiring lithography or wet processing.

Identifying [corrected] signatures of photothermal current in a double-gated semiconducting nanotube.

The remarkable electrical and optical properties of single-walled carbon nanotubes have allowed for engineering device prototypes showing great potential for applications such as photodectors and solar cells. However, any path towards industrial maturity requires a detailed understanding of the fundamental mechanisms governing the process of photocurrent generation. Here we present scanning photocurrent microscopy measurements on a double-gated suspended semiconducting single-walled carbon nanotube and show that both photovoltaic and photothermal mechanisms are relevant for the interpretation of the photocurrent. We find that the dominant or non-dominant character of one or the other processes depends on the doping profile, and that the magnitude of each contribution is strongly influenced by the series resistance from the band alignment with the metal contacts. These results provide new insight into the interpretation of features in scanning photocurrent microscopy and lay the foundation for the understanding of optoelectronic devices made from single-walled carbon nanotubes.

Optomechanical coupling between a multilayer graphene mechanical resonator and a superconducting microwave cavity.

The combination of low mass density, high frequency and high quality factor, Q, of mechanical resonators made of two-dimensional crystals such as graphene make them attractive for applications in force/mass sensing and exploring the quantum regime of mechanical motion. Microwave optomechanics with superconducting cavities offers exquisite position sensitivity and enables the preparation and detection of mechanical systems in the quantum ground state. Here, we demonstrate coupling between a multilayer graphene resonator with quality factors up to 220,000 and a high-Q superconducting cavity. Using thermomechanical noise as calibration, we achieve a displacement sensitivity of 17 fm Hz(-1/2). Optomechanical coupling is demonstrated by optomechanically induced reflection and absorption of microwave photons. We observe 17 dB of mechanical microwave amplification and signatures of strong optomechanical backaction. We quantitatively extract the cooperativity C, a characterization of coupling strength, from the measurement with no free parameters and find C = 8, which is promising for the quantum regime of graphene motion.

Solid organ transplant patients experience high rates of infection and other complications after total knee arthroplasty.

Survival after solid organ transplants in the United States is increasing, and there is a need to understand the complications in knee arthroplasty patients who underwent organ transplantation. A retrospective study was conducted from 1993-2008 on 19 patients (23 knee arthroplasties) with previous successful solid organ transplants. Eleven knee arthroplasties were performed after renal transplantation, and 12 after nonrenal solid organ transplant (seven liver, four heart, one lung). Complications occurred in 9/23 patients (39.1%) and infections occurred in 4/23 patients (17.3%). Of the infected knees, two had MRSA, one had MSSA, and one Escherichia coli. Noninfectious complications (5/24, 21.7%) include aseptic loosening, quadriceps rupture, femoral fracture, hemarthrosis, and arthrofibrosis. All patients with complications were on immunosuppressant medications at the time of arthroplasty. There was a significantly higher rate of infection in the renal group compared to the non-renal group (P = 0.022). There was also a higher overall complication rate in the renal group however this did not reach significance.

Large spin-orbit coupling in carbon nanotubes.

It has recently been recognised that the strong spin-orbit interaction present in solids can lead to new phenomena, such as materials with non-trivial topological order. Although the atomic spin-orbit coupling in carbon is weak, the spin-orbit coupling in carbon nanotubes can be significant due to their curved surface. Previous works have reported spin-orbit couplings in reasonable agreement with theory, and this coupling strength has formed the basis of a large number of theoretical proposals. Here we report a spin-orbit coupling in three carbon nanotube devices that is an order of magnitude larger than previously measured. We find a zero-field spin splitting of up to 3.4 meV, corresponding to a built-in effective magnetic field of 29 T aligned along the nanotube axis. Although the origin of the large spin-orbit coupling is not explained by existing theories, its strength is promising for applications of the spin-orbit interaction in carbon nanotubes devices.

Coupling carbon nanotube mechanics to a superconducting circuit.

The quantum behaviour of mechanical resonators is a new and emerging field driven by recent experiments reaching the quantum ground state. The high frequency, small mass, and large quality-factor of carbon nanotube resonators make them attractive for quantum nanomechanical applications. A common element in experiments achieving the resonator ground state is a second quantum system, such as coherent photons or a superconducting device, coupled to the resonators motion. For nanotubes, however, this is a challenge due to their small size. Here, we couple a carbon nanoelectromechanical (NEMS) device to a superconducting circuit. Suspended carbon nanotubes act as both superconducting junctions and moving elements in a Superconducting Quantum Interference Device (SQUID). We observe a strong modulation of the flux through the SQUID from displacements of the nanotube. Incorporating this SQUID into superconducting resonators and qubits should enable the detection and manipulation of nanotube mechanical quantum states at the single-phonon level.

Laser-thinning of MoS2: on demand generation of a single-layer semiconductor.

Single-layer MoS(2) is an attractive semiconducting analogue of graphene that combines high mechanical flexibility with a large direct bandgap of 1.8 eV. On the other hand, bulk MoS(2) is an indirect bandgap semiconductor similar to silicon, with a gap of 1.2 eV, and therefore deterministic preparation of single MoS(2) layers is a crucial step toward exploiting the large direct bandgap of monolayer MoS(2) in electronic, optoelectronic, and photovoltaic applications. Although mechanical and chemical exfoliation methods can be used to obtain high quality MoS(2) single layers, the lack of control in the thickness, shape, size, and position of the flakes limits their usefulness. Here we present a technique for controllably thinning multilayered MoS(2) down to a single-layer two-dimensional crystal using a laser. We generate single layers in arbitrary shapes and patterns with feature sizes down to 200 nm and show that the resulting two-dimensional crystals have optical and electronic properties comparable to that of pristine exfoliated MoS(2) single layers.

Predictors of positive retroperitoneal lymph nodes in patients with high risk testicular cancer.

PURPOSE: Percent of embryonal carcinoma and lymphovascular invasion in the primary tumor are risk factors for occult retroperitoneal metastatic disease. High risk patients with clinical stage I and IIA nonseminomatous germ cell tumor who underwent primary retroperitoneal lymph node dissection were identified to discern any other risk factors for metastatic disease. MATERIALS AND METHODS: Patients who had undergone retroperitoneal lymph node dissection at our institution from 1993 to 2009 were identified and clinical charts were reviewed. A total of 90 patients with orchiectomy specimens containing more than 30% embryonal carcinoma who underwent primary retroperitoneal lymph node dissection were identified and perioperative data were obtained. RESULTS: Of 353 patients 90 (25%) had greater than 30% embryonal carcinoma and underwent primary retroperitoneal lymph node dissection. Of these patients 45 (50%) had lymphovascular invasion. Median followup was 1.1 years. Positive lymph nodes identified at retroperitoneal lymph node dissection were noted in 30 (46%) and 15 (60%) patients with clinical stage I vs clinical stage II disease. On multivariate analysis embryonal carcinoma (OR 1.02, 95% CI 1.00-1.04) and lymphovascular invasion (OR 3.52, 95% CI 1.43-8.67) were associated with positive lymph nodes at retroperitoneal lymph node dissection. The positive predictive value for 100% embryonal carcinoma was 65.5%, although the negative predictive value for 30% embryonal carcinoma was 85.7%. CONCLUSIONS: Embryonal carcinoma and lymphovascular invasion were significantly and independently associated with the risk of occult retroperitoneal metastatic disease. These results should be considered when counseling patients about appropriate treatment options.

Strong coupling between single-electron tunneling and nanomechanical motion.

Nanoscale resonators that oscillate at high frequencies are useful in many measurement applications. We studied a high-quality mechanical resonator made from a suspended carbon nanotube driven into motion by applying a periodic radio frequency potential using a nearby antenna. Single-electron charge fluctuations created periodic modulations of the mechanical resonance frequency. A quality factor exceeding 10(5) allows the detection of a shift in resonance frequency caused by the addition of a single-electron charge on the nanotube. Additional evidence for the strong coupling of mechanical motion and electron tunneling is provided by an energy transfer to the electrons causing mechanical damping and unusual nonlinear behavior. We also discovered that a direct current through the nanotube spontaneously drives the mechanical resonator, exerting a force that is coherent with the high-frequency resonant mechanical motion.

Tunable few-electron double quantum dots and Klein tunnelling in ultraclean carbon nanotubes.

Quantum dots defined in carbon nanotubes are a platform for both basic scientific studies and research into new device applications. In particular, they have unique properties that make them attractive for studying the coherent properties of single-electron spins. To perform such experiments it is necessary to confine a single electron in a quantum dot with highly tunable barriers, but disorder has prevented tunable nanotube-based quantum-dot devices from reaching the single-electron regime. Here, we use local gate voltages applied to an ultraclean suspended nanotube to confine a single electron in both a single quantum dot and, for the first time, in a tunable double quantum dot. This tunability is limited by a novel type of tunnelling that is analogous to the tunnelling in the Klein paradox of relativistic quantum mechanics.

Reduced risk of cytomegalovirus infection in solid organ transplant recipients treated with sirolimus: a pooled analysis of clinical trials.

INTRODUCTION: Cytomegalovirus (CMV) is an opportunistic infection that causes substantial morbidity and mortality in transplant recipients. This pooled analysis of Wyeth clinical trials explored the incidence of CMV infection in solid organ transplant recipients treated with sirolimus versus comparator immunosuppressant drugs. METHODS: Wyeth-conducted, multicenter, randomized, comparative trials with at least one non-sirolimus-containing arm and at least 6 months' complete data were included. Cases of CMV were investigator-identified. The occurrence of CMV in sirolimus-treated patients was assessed versus all other comparator agents, versus antimetabolite agents, and versus calcineurin inhibitors. RESULTS: Nine trials in recipients of renal, liver, and cardiac transplants met the inclusion criteria; eight enrolled de novo allograft recipients, and one was a conversion trial. The primary pooled analysis revealed an odd ratio for CMV infection of 0.64 (95% confidence interval [CI] 0.42 to 1.0, P = .047) on sirolimus versus comparator immunosuppressant drugs. The subanalysis of sirolimus versus antimetabolites showed an odds ratio for CMV of 0.39 (95% CI 0.19 to 0.81, P = .012), and for sirolimus versus calcineurin inhibitors the odds ratio was 0.58 (95% CI 0.34 to 1.01, P = .054). CONCLUSION: This pooled analysis demonstrated a reduced risk of CMV infection among sirolimus-treated patients as compared to those receiving alternative forms of immunosuppression in Wyeth-sponsored clinical trials in solid organ transplantation. This risk reduction persisted in subgroup analyses stratified by class of comparator treatment.