Photon Pressure with an Effective Negative Mass Microwave Mode.

Harmonic oscillators belong to the most fundamental concepts in physics and are central to many current research fields such as circuit QED, cavity optomechanics, and photon pressure systems. Here, we engineer a microwave mode in a superconducting LC circuit that mimics the dynamics of a negative mass oscillator, and couple it via photon pressure to a second low-frequency circuit. We demonstrate that the effective negative mass dynamics lead to an inversion of dynamical backaction and to sideband cooling of the low-frequency circuit by a blue-detuned pump field, which can be intuitively understood by the inverted energy ladder of a negative mass oscillator.

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.

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.

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.

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.

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.

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.

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.

The integrin alpha 6 beta 4 is a laminin receptor.

In this study, the putative laminin receptor function of the alpha 6 beta 4 integrin was assessed. For this purpose, we used a human cell line, referred to as clone A, that was derived from a highly invasive, colon adenocarcinoma. This cell line, which expresses the alpha 6 beta 4 integrin, adheres to the E8 and not to the P1 fragment of laminin. The adhesion of clone A cells to laminin is extremely rapid with half-maximal adhesion observed at 5 min after plating. Adhesion to laminin is blocked by GoH3, and alpha 6 specific antibody (60% inhibition), as well as by A9, a beta 4 specific antibody (30% inhibition). Most importantly, we demonstrate that alpha 6 beta 4 binds specifically to laminin-Sepharose columns in the presence of either Mg2+ or Mn2+ and it is eluted from these columns with EDTA but not with NaCl. The alpha 6 beta 4 integrin does not bind to collagen-Sepharose, but the alpha 2 beta 1 integrin does bind. Clone A cells do not express alpha 6 beta 1 as evidenced by the following observations: (a) no beta 1 integrin is detected in beta 1 immunoblots of GoH3 immunoprecipitates; and (b) no alpha 6 beta 1 integrin is seen in GoH3 immunoprecipitates of clone A extracts that had been immunodepleted of all beta 4 containing integrin using the A9 antibody. These data establish that laminin is a ligand for the alpha 6 beta 4 integrin and that this integrin can function as a laminin receptor independently of alpha 6 beta 1.

Rat model for carcinogenesis in ureterosigmoidostomy.

A rat model is used to study the carcinogenesis that occurs when urine is surgically diverted into the fecal stream, as in ureterosigmoidostomy. Adenocarcinoma of the colon occurs adjacent to the urine inlet. It is completely prevented by proximal diversion of the feces, implying that fecal carcinogens are activated locally by the urine or the urothelium.

A novel mode of arbovirus transmission involving a nonviremic host.

In nature, infected and uninfected arthropod vectors often feed together on an animal. In mimicking this scenario in the laboratory, uninfected vectors were found to acquire virus while cofeeding on the same host as infected vectors. However, the vertebrate host on which they fed did not develop detectable levels of virus in its blood. These observations were made with Thogoto virus, an influenza-like virus of medical and veterinary significance. Rhipicephalus appendiculatus ticks were used as the vector and guinea pigs as the vertebrate host. The results demonstrate that a vertebrate that is apparently refractory to infection by an arthropod-borne virus can still play an important role in the epidemiology of the virus, and they suggest a novel mode of arthropod-borne virus transmission.

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.

Intracellular signaling in the gonads.

The regulation of steroidogenesis in both the ovary and testis involves a complex interaction of a diversity of hormones and intracellular signaling pathways. The recent cloning of LH and FSH receptors has paved the way for an increased understanding of the mechanisms of receptor conformation, ligand-receptor interaction, and facilitation of post-receptor activity. The dominant role played by LH in the regulation of steroid production appears to be mediated by more than one intracellular signaling pathway. In addition to the stimulation of the adenylate cyclase-cAMP pathway, also known to be stimulated by FSH, the actions of LH may be additionally mediated by other intracellular messengers, such as those derived from the PLC pathway. Steroidogenesis in the gonads appears to be modulated by a variety of factors in addition to the gonadotropins. In this review, those factors of intracellular signaling mechanisms of which we have some understanding have been discussed. These include GnRH, PGF2 alpha, Ang II, VIP, GHRH, TNF alpha, CRF, EGF, and TGF alpha. Many of these factors have been shown to be locally synthesized, and specific receptors have been identified in the gonads. Many gonadal factors have the capacity to exert effects on steroidogenesis independent of the gonadotropins. Alternately, they have been demonstrated to alter the gonadal response to the gonadotropins via autocrine, paracrine, and intracrine mechanisms. As yet, our understanding of the intracellular signaling mechanisms used by novel gonadal regulators is limited. The involvement of the PLC, PLA2, and PLD pathways in this regard has been reviewed. It is becoming apparent that multiple signaling pathways may be stimulated by a single hormone, as in the case of GnRH, PGF2 alpha, and LH. The complexity of intracellular signal transduction in the gonads is enhanced by the potential cross-talk at numerous steps in the signaling cascades.

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.

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.

Differential pp60c-src activity in well and poorly differentiated human colon carcinomas and cell lines.

The results presented in this report demonstrate increased pp60c-src kinase activity associated with moderate to well differentiated colon tumors, corroborating previous observations by other groups. Extension of this analysis to include a small number of poorly differentiated colon carcinomas revealed src kinase activity comparable to that observed in normal colonic mucosa, considerably less than that observed in moderate/well differentiated lesions. Correlations of src kinase activity with differentiation was confirmed within a panel of colon cell lines where increased activity, associated with moderate/well differentiated lines, was accompanied by increased expression of pp60c-src protein. Use of an antiphosphotyrosine antibody in immunoprecipitation revealed the presence of novel phosphotyrosyl cellular substrates in human colon cell lines displaying elevated pp60c-src kinase activity. These observations suggest a role for the src protooncogene in colonic differentiation pathways.

Sequential studies of serum blocking activity in rats bearing chemically induced primary bowel tumors.

Colon and small-bowel tumors were induced in WF rats by treatment with one of three chemical carcinogens. Tumor occurrence and growth were monitored by multiple double-contrast examinations. Roentgenologic diagnoses and histologic examination of tumors were verified at tumor resection or autopsy. Serial serum samples from each of 11 rats were tested in microcytotoxicity assays for their ability to block the cytotoxicity of lymph node cells from rats with isografts of colon carcinoma NG-W1 against NG-W1 target cells. Sera from all tumor-bearing rats demonstrated specific blocking activity. With two exceptions, serum blocking activity preceded roentgenologic evidence of tumor. Sera of the 2 exceptional rats lacked blocking 2 and 8 weeks before tumor detection, respectively. The sera of only one animal specifically inhibited lymphocyte cytotoxicity despite consistently negative double-contrast examinations. At autopsy this rat was found to have an adenocarcinoma of the distal rectum, impossible to visualize by the roentgenologic technique used. In serum samples obtained from animals after successful tumor excision and with no radiologic evidence of recurrence, blocking activity could no longer be demonstrated. Rats that had received carcinogen but developed no tumor and had no abnormalities on double-contrast examination demonstrated no serum blocking activity.

Interleukin generation in experimental colon cancer of rats: effects of tumor growth and tumor therapy.

The capacity of inbred W/Fu rats bearing syngeneic colon carcinomas to generate interleukin(s) (IL) was studied during primary tumor growth, after tumor resection, and during postresection immunotherapy. During local tumor growth, there was a significant decrease in the capacity of the host's adherent mononuclear cells to generate IL-1 and of peripheral blood mononuclear cells to generate IL-2 (16.6 and 23%, respectively, when compared to control animals; P less than .01). The presence of regional metastases or large primary tumor burden resulted in a further sharp fall in IL generation (0.9 and 10% for IL-1 and IL-2, respectively, when compared to control animals; P less than .01). With the use of three different doses of tumor inoculum, inhibition of IL generation was shown to occur when tumors were barely palpable. Decrease in IL correlated with tumor growth and not with the initial number of tumor cells injected. Tumor resection resulted in a rise in IL-2 generation from 36 to 64% of control animals' levels. Postresection immunotherapy with the use of an active specific immunization protocol successfully modulated IL-2 production to normal in animals protected from tumor recurrence. Animals that developed recurrent tumors despite immunization exhibited a continued inability to generate IL (mean values of IL-2 production compared to controls: 184% in animals free of recurrence after immunotherapy, 1% in animals developing recurrent tumors after immunotherapy; P less than .01). These results suggested that alterations in IL generation may lead to immune unresponsiveness during tumor growth. Active specific immunotherapy protecting animals from recurrence after primary tumor resection may be predicated on the successful modulation of IL level generation by host immunocytes.