Quantum microwave parametric interferometer

Classical interferometers are indispensable tools for the precise determination of various physical quantities. Their accuracy is bound by the standard quantum limit. This limit can be overcome by using quantum states or nonlinear quantum elements. Here, we present the experimental study of a nonlinear Josephson interferometer operating in the microwave regime. Our quantum microwave parametric interferometer (QUMPI) is based on superconducting flux-driven Josephson parametric amplifiers combined with linear microwave elements. We perform a systematic analysis of the implemented QUMPI. We find that its Gaussian interferometric power exceeds the shot-noise limit and observe sub-Poissonian photon statistics in the output modes. Furthermore, we identify a low-gain operation regime of the QUMPI which is essential for optimal quantum measurements in quantum illumination protocols.Comment: 6 pages, 5 figure

Cryogenic microwave link for quantum local area networks

Scalable quantum information processing with superconducting circuits is about to advance from individual processors in single dilution refrigerators to more powerful distributed quantum computing systems located in separate cooling units in order to achieve a practical quantum advantage. Hence, realization of hardware platforms for quantum local area networks (QLANs) compatible with superconducting technology is of high importance. Here, we demonstrate a basic prototype for a microwave QLAN based on a cryogenic link connecting two individual dilution cryostats over a distance of 6.6m with a base temperature of 52mK in the center. We provide details about the system design, installation, and performance. We employ superconducting coaxial microwave transmission lines to form a quantum communication channel and characterize its potential by demonstrating robust entanglement distribution in the form of two-mode squeezing between remote parties. By preserving entanglement distribution at link temperatures up to 1K, we experimentally verify the fluctuation-dissipation theorem. Consequently, we demonstrate that our system can form the backbone for future distributed quantum computing applications

Noncollinear electric dipoles in a polar, chiral phase of CsSnBr3_3 perovskite

Polar and chiral crystal symmetries confer a variety of potentially useful functionalities upon solids by coupling otherwise noninteracting mechanical, electronic, optical, and magnetic degrees of freedom. We describe two unstudied phases of the 3D perovskite, CsSnBr$_3$, which emerge below 85 K due to the formation of Sn(II) lone pairs and their interaction with extant octahedral tilts. Phase II (77 K<$T$<85 K, space group $P2_1/m$) exhibits ferroaxial order driven by a noncollinear pattern of lone pair-driven distortions within the plane normal to the unique octahedral tilt axis, preserving the inversion symmetry observed at higher temperatures. Phase I ($T$<77 K, space group $P2_1$) additionally exhibits ferroelectric order due to distortions along the unique tilt axis, breaking both inversion and mirror symmetries. This polar and chiral phase exhibits second harmonic generation from the bulk and a large, intrinsic polarization$-$electrostriction coefficient along the polar axis ($Q_{22}\approx$1.1 m$^4$ C$^{-2}$), resulting in acute negative thermal expansion ($\alpha_V=-9\times10^{-5}$ K$^{-1}$) through the onset of spontaneous polarization. The unprecedented structures of phases I and II were predicted by recursively following harmonic phonon instabilities to generate a tree of candidate structures and subsequently corroborated by synchrotron X-ray powder diffraction and polarized Raman and $^{81}$Br nuclear quadrupole resonance spectroscopies. Relativistic electronic structure scenarios compatible with reported photoluminescence measurements are discussed. Together, the polar symmetry, small bandgap, large spin-orbit splitting of Sn 5$p$ orbitals, and predicted strain sensitivity of the symmetry-breaking distortions suggest bulk samples and epitaxial films of CsSnBr$_3$ or its neighboring solid solutions as strong candidates for bulk Rashba effects

Prediction of disability-free survival in healthy older people

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6–77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people. Trial registration Clinicaltrials.gov (NCT01038583

Refractory hypothyroidism due to enteral malabsorption of levothyroxine after cholecystectomy

Management of hypothyroidism may be challenging due to malabsorption or non-adherence. Replacement of enteral dose is 1.6-1.8mcg/kg with intestinal absorption of 70-80%. Some patients require higher doses of levothyroxine (LT4 \u3e 1.9mcg/kg). Various gastrointestinal disorders that lead to malabsorption or loss of intestinal secretions may result in higher requirement. We present a case of refractory hypothyroidism despite large doses of oral levothyroxine due to malabsorption of oral LT4. A 60-year old, 130 kg female presented with fatigue and intermittent diarrhea, with TSH 206 uIU/ml (0.45-5.33 uIU/ml) and FT4 \u3c 0.25 ng/dl (0.61-1.44 ng/dl). She had had total thyroidectomy and radioiodine treatment at outside institution for papillary thyroid microcarcinoma and had normal thyroid function tests on standard doses of LT4 until she underwent cholecystectomy. She reported intermittent diarrhea and abnormal thyroid function tests (TSH 206 uIU/ml) following cholecystectomy. Her doses were increased gradually and she was taking LT4 1200 mcg and lliothyronine 25mcg orally daily on an empty stomach without missed doses when she presented. Extensive gastrointestinal evaluation failed to reveal any evidence of malabsorption. She was hospitalized multiple times for severe symptomatic hypothyroidism. LT4 absorption tests revealed poor enteral absorption. Subcutaneously administered LT4 did not result in a rise in FT4 or TT4. She responded to twice weekly intravenous 300mcg LT4 and daily 600 mcg LT4 soft gel capsules, with TSH improving to 18uIU/ml and FT4 0.68ng/dl. Hypothyroidism in our patient was refractory to large doses of oral LT4 and responded to intravenous but not subcutaneous LT4. Studies indicate possible hypotheses including intestinal malabsorption of LT4 due reduction in bile salts after cholecystectomy, type 3-deiodinase overexpression and altered intestinal microbiota. About 10-20% of hypothyroid patients require greater than weight based amounts of LT4 for unknown reasons. We recommend early initiation of parenteral LT4 therapy to reduce morbidity. More studies are needed to evaluate mechanism of enteral LT4 malabsorption in such refractory cases

Low molecular weight heparin as a risk factor for pregnancy-and lactation-associated osteoporosis

Introduction: Pregnancy-and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, that can cause several vertebral fractures with disabling back pain. Young women on low molecular weight heparin (LMWH) during pregnancy are at an increased risk for PLO. Data is very limited on the association LMWH and postpartum osteoporosis. We report a case of a young woman on long term LMWH use who presented with multiple vertebral fractures Case: A 26 y/o woman who was 2 months postpartum presented with sudden onset of severe back pain. Past medical history significant for recurrent deep vein thrombosis, factor V Leiden disease and use of low molecular weight heparin during pregnancy. MRI of lumbosacral spine showed compression deformities involving superior endplate of L2-L5 vertebral bodies. Bone density showed Z score of -2.4 in lumbar spine,-1.6 in total hip and -1.3 in femoral neck. No family history of osteoporosis, and work up for secondary osteoporosis negative. Bone scan showed superior endplate fractures of T9, T11, T12 and L1. Lactation was stopped and she was started on treatment with Teriparatide. Her back pain improved. A repeat MRI was done after 4 months of treatment as she complained of back spasms, that showed well healed fracture. Discussion: Pregnancy and lactation are known risk factors for osteoporosis. Hormonal changes during lactation cause 5-10% loss of trabecular mineral content in order to provide calcium in milk. Women with risk factors for secondary bone loss and fragility are at increased risk of fracture. Long term use of heparin can cause bone loss by decreased formation and increased resorption. Bone loss can be seen after 6 months of therapy with heparin. With increasing use of LMWH during pregnancy for various indications this can be considered as a new risk factor for PLO. This case illustrates the fact that clinicians should have a high suspicion for PLO in young women with LMWH use

Adult atypical sellar teratoid tumor presenting as diabetes insipidus

Objective: Atypical teratoid /rhabdoid tumor (ATRT) is a rare and aggressive central nervous system tumor that usually occurs in childhood but has rarely been reported in adults. We were able to identify 50 reported adult cases, 12 of which were sellar. We report a case of adult sellar ATRT who died within 2 months of presentation with headaches, visual deficits, polyuria, and polydipsia. Our case aims to highlight the importance of considering ATRT in the differential of sellar masses especially in adults presenting with rapid progression of symptoms. Case Presentation: A 62-year-old female was transferred to our institution for management of a pituitary mass. Her symptoms developed over 2 months, starting with daily headaches, nausea, followed by polyuria, polydipsia and finally double vision. She had left 6th nerve palsy on admission. She was diagnosed with central hypothyroidism and diabetes insipidus (DI). Magnetic resonance imaging (MRI) revealed a sellar mass with extension into superior sellar margin, an adjacent mass within the anterior third ventricle, with minimal connection between these adjacent masses with intraventricular and subarachnoid hemorrhage. She rapidly deteriorated, developed seizures, head CT demonstrated pituitary apoplexy and worsening intraventricular hemorrhage. She underwent emergent craniotomy, a large pituitary mass was found and decompressed, and third ventricular clot was removed. Histopathological study revealed malignant epithelioid neoplasm, consistent with ATRT infiltrating the pituitary gland and fibrocollagenous stroma. The neoplastic cells showed divergent phenotypes based on immunophenotypes - cytokeratin+, EMA +, SMA+, CD 34+ and loss of SMARCB1/ INI1 protein. Radiation therapy was started but her condition continued to deteriorate. She underwent left frontal ventriculoperitoneal shunt with external ventricular drain placement for progressive hydrocephalus, without significant improvement. MRI brain demonstrated leptomeningeal spread. She expired within 2 months of diagnosis. Conclusion: ATRT is very rare in adults and has a very poor prognosis. The more common presenting symptoms of sellar ATRT are headaches and visual symptoms. DI has not been previously reported and increased the suspicion for a non-adenoma etiology in our patient. Definite diagnosis is based on immunohistochemical features. Treatment modalities in adults include surgery, chemotherapy and radiotherapy. ATRT should be considered in the differential for patients with sellar masses presenting with atypical features or rapid progression. Early recognition and aggressive combination therapy is reported to be associated with improved outcomes

Hepatocellular carcinoma presenting as hypercalcemia

Objective: Humoral hypercalcemia is commonly seen associated with squamous cell cancers and breast cancers, but is also reported in other cancers. This is usually mediated through parathyroid hormone-related peptide (PTH-rP). PTH-rP interacts with the PTH/PTH-rP receptor that activates renal calcium reabsorption and promotes resorption of calcium from the bone. Hepatocellular carcinoma (HCC) may present with paraneoplastic syndromes and hypercalcemia was reported in 4-7% of patients. HCC presenting with hypercalcemia without bone metastasis is uncommon. We present one such case along with the discussion of mechanism of hypercalcemia. Case Presentation: 67 year old woman with a history of intravenous drug abuse and alcohol abuse presented with confusion, epigastric pain and generalized weakness of 2 week duration. Her vital signs were normal. She appeared drowsy and was oriented to person only. A magnetic resonance imaging of the brain ruled out a cerebrovascular event. Her labs showed ionized calcium 1.50 (1.0 - 1.35 mmol/L), intact parathyroid hormone 14 (15 - 65 pg/ mL), PTH-rP 39 (14 - 27 pg/mL), 25 hydroxy vitamin D 10 (\u3e 20 ng/mL), 1, 25 dihydroxy vitamin D 24 (20 - 74 pg/mL), alkaline phosphatase 153 (0 - 140 IU/L), creatinine 0.53 (\u3c 1.16 mg/dL) and GFR 110 (\u3e 60 ml/ min/1.73m2). Liver function tests were abnormal and hepatitis C antibody was positive. Computed tomography of the abdomen revealed nodular cirrhotic liver with a 10 x 10 cm right hepatic mass compatible with HCC. She had elevated alpha fetoprotein and cancer antigen 19-9 levels. Due to hepatic cirrhosis, initially she was treated with gentle intravenous hydration with no improvement in calcium levels. Ionized calcium worsened to 1.90 mmol/L. She received intravenous zoledronic acid without significant improvement in her calcium levels and mental status. She is planned for further cancer directed therapy. Conclusion: 80% of hypercalcemia in cancer patients is estimated to be PTH-rP mediated. However, additional mechanisms that cause bone resorption or decreased renal excretion may be responsible. Bisphosphonates inhibit osteoclast bone resorption, and are used for paraneoplastic hypercalcemia associated with malignancy because of their favorable efficacy and lower toxicity. Refractory hypercalcemia has been reported in patients with HCC as noted in our patient. The PTH-rP level in our case was not very high in contrast with the expected direct association between severity of hypercalcemia and degree of PTH-rP elevation suggesting other contributing factors. We believe immobilization and volume contraction were the other driving mechanisms for her refractory hypercalcemia