Erratum:

This corrects the article DOI: 10.1103/PhysRevLett.123.033201.

Sympathetic Ground State Cooling and Time-Dilation Shifts in an

We report on Raman sideband cooling of ^{25}Mg^{+} to sympathetically cool the secular modes of motion in a ^{25}Mg^{+}-^{27}Al^{+} two-ion pair to near the three-dimensional (3D) ground state. The evolution of the Fock-state distribution during the cooling process is studied using a rate-equation simulation, and various heating sources that limit the efficiency of 3D sideband cooling in our system are discussed. We characterize the residual energy and heating rates of all of the secular modes of motion and estimate a secular motion time-dilation shift of -(1.9±0.1)×10^{-18} for an ^{27}Al^{+} clock at a typical clock probe duration of 150 ms. This is a 50-fold reduction in the secular motion time-dilation shift uncertainty in comparison with previous ^{27}Al^{+} clocks.

RpA, an extracellular protease similar to the metalloprotease of serralysin family, is required for pathogenicity of Ralstonia pickettii.

AIM: To investigate the biochemical and functional properties of an extracellular protease, RpA, in Ralstonia pickettii WP1 isolated from water supply systems. METHODS AND RESULTS: An extracellular protease was identified and characterized from R. pickettii WP1. A mutant strain WP1M2 was created from strain WP1 by mini-Tn5 transposition. The culture filtrates from WP1M2 had a lower cytotoxic effect than the parental WP1 on several mammalian cell lines. Cloning and sequence analysis revealed the Tn5 transposon inserted at a protease gene (rpA) which is 81% homologous to prtA and aprX genes of Pseudomonas fluorescens. The rpA gene encodes a 482-residue protein showing sequence similarity to metalloproteases of the serralysin family. The RpA protein was expressed in Escherichia coli using a pET expression vector and purified as a 55 kDa molecular weight protein. Furthermore, the protease activity of RpA was inhibited by protease inhibitor and heat treatment. CONCLUSIONS: The in vitro cytotoxic activity of R. pickettii culture filtrates was attributed to RpA protease. SIGNIFICANCE AND IMPACT OF THE STUDY: An extracellular protease, RpA, was identified from R. pickettii WP1 isolated from water supply system. The RpA metalloproteases is required for the pathogenicity of R. pickettii to mammalian cell lines.

Pneumocystis jiroveci pneumonia in patients with systemic lupus erythematosus after rituximab therapy.

Pneumocystis jiroveci pneumonia (PCP) is an uncommon but potentially life-threatening infection in immunocompromised patients with low blood T cells. Rituximab, a chimeric human/murine monoclonal antibody against the B cell-specific antigen CD20, has been increasingly used and appears to be effective in the treatment of autoimmune disorders, including systemic lupus erythematosus (SLE). PCP has been reported in some patients with autoimmune diseases or lymphoma subjected to rituximab treatment, but has not yet been reported in SLE patients. We report PCP in two patients with SLE after rituximab treatment. Fever and respiratory symptoms associated with diffuse pulmonary infiltrates developed within weeks after rituximab therapy. One patient died of respiratory failure. Another patient recovered uneventfully after treatment with clindamycin and primaquine.

Quantum coherence between two atoms beyond Q=10(15).

We place two atoms in quantum superposition states and observe coherent phase evolution for 3.4×10(15) cycles. Correlation signals from the two atoms yield information about their relative phase even after the probe radiation has decohered. This technique allowed a frequency comparison of two (27)Al(+) ions with fractional uncertainty 3.7(-0.8)(+1.0)×10(-16)/√[τ/s]. Two measures of the Q factor are reported: The Q factor derived from quantum coherence is 3.4(-1.1)(+2.4)×10(16), and the spectroscopic Q factor for a Ramsey time of 3 s is 6.7×10(15). We demonstrate a method to detect the individual quantum states of two Al(+) ions in a Mg(+)-Al(+)-Al(+) linear ion chain without spatially resolving the ions.

Trapped-ion state detection through coherent motion.

We demonstrate a general method for state detection of trapped ions that can be applied to a large class of atomic and molecular species. We couple a spectroscopy ion (27Al+) to a control ion (25Mg+) in the same trap and perform state detection through off-resonant laser excitation of the spectroscopy ion that induces coherent motion. The motional amplitude, dependent on the spectroscopy ion state, is measured either by time-resolved photon counting or by resolved sideband excitations on the control ion. The first method provides a simplified way to distinguish clock states in 27Al+, which avoids ground-state cooling and sideband transitions. The second method reduces spontaneous emission and optical pumping on the spectroscopy ion, which we demonstrate by nondestructively distinguishing Zeeman sublevels in the (1)S0 ground state of 27Al+.

Measurement-induced entanglement for excitation stored in remote atomic ensembles.

A critical requirement for diverse applications in quantum information science is the capability to disseminate quantum resources over complex quantum networks. For example, the coherent distribution of entangled quantum states together with quantum memory (for storing the states) can enable scalable architectures for quantum computation, communication and metrology. Here we report observations of entanglement between two atomic ensembles located in distinct, spatially separated set-ups. Quantum interference in the detection of a photon emitted by one of the samples projects the otherwise independent ensembles into an entangled state with one joint excitation stored remotely in 10(5) atoms at each site. After a programmable delay, we confirm entanglement by mapping the state of the atoms to optical fields and measuring mutual coherences and photon statistics for these fields. We thereby determine a quantitative lower bound for the entanglement of the joint state of the ensembles. Our observations represent significant progress in the ability to distribute and store entangled quantum states.

Frequency comparison of two high-accuracy Al+ optical clocks.

We have constructed an optical clock with a fractional frequency inaccuracy of 8.6x10{-18}, based on quantum logic spectroscopy of an Al+ ion. A simultaneously trapped Mg+ ion serves to sympathetically laser cool the Al+ ion and detect its quantum state. The frequency of the {1}S{0}<-->{3}P{0} clock transition is compared to that of a previously constructed Al+ optical clock with a statistical measurement uncertainty of 7.0x10{-18}. The two clocks exhibit a relative stability of 2.8x10{-15}tau{-1/2}, and a fractional frequency difference of -1.8x10{-17}, consistent with the accuracy limit of the older clock.

Frequency-comb spectroscopy on pure quantum states of a single molecular ion.

Spectroscopy is a powerful tool for studying molecules and is commonly performed on large thermal molecular ensembles that are perturbed by motional shifts and interactions with the environment and one another, resulting in convoluted spectra and limited resolution. Here, we use quantum-logic techniques to prepare a trapped molecular ion in a single quantum state, drive terahertz rotational transitions with an optical frequency comb, and read out the final state nondestructively, leaving the molecule ready for further manipulation. We can resolve rotational transitions to 11 significant digits and derive the rotational constant of 40CaH+ to be B R = 142 501 777.9(1.7) kilohertz. Our approach is suited for a wide range of molecular ions, including polyatomics and species relevant for tests of fundamental physics, chemistry, and astrophysics.

Systematic uncertainty due to background-gas collisions in trapped-ion optical clocks.

We describe a framework for calculating the frequency shift and uncertainty of trapped-ion optical atomic clocks caused by background-gas collisions, and apply this framework to an 27Al+ clock to enable a total fractional systematic uncertainty below 10-18. For this clock, with 38(19) nPa of room-temperature H2 background gas, we find that collisional heating generates a non-thermal distribution of motional states with a mean time-dilation shift of order 10-16 at the end of a 150 ms probe, which is not detected by sideband thermometry energy measurements. However, the contribution of collisional heating to the spectroscopy signal is highly suppressed and we calculate the BGC shift to be -0.6(2.4) × 10-19, where the shift is due to collisional heating time dilation and the uncertainty is dominated by the worst case ±π/2 bound used for collisional phase shift of the 27Al+ superposition state. We experimentally validate the framework and determine the background-gas pressure in situ using measurements of the rate of collisions that cause reordering of mixed-species ion pairs.

Long-Term Outcome of Liver Transplant Recipients After the Development of Renal Failure Requiring Dialysis: A Study Using the National Health Insurance Database in Taiwan.

BACKGROUND: The aims of this study were to identify the incidence of renal failure requiring dialysis and to investigate the long-term outcome after renal failure in liver transplantation (LT) patients. METHODS: The primary database used was the Taiwan National Health Insurance Research Database. Subjects with LT from 1997 to 2009 were included. Patients were grouped into the dialysis cohort if they once received hemodialysis owing to any pattern of renal failure during peri-transplantation periods or after LT. Otherwise, they were categorized into the nondialysis cohort. We conducted a retrospective observational study on the correlation of renal failure requiring dialysis and its effect on LT recipients. RESULTS: The analysis included data of 1,771 LT recipients with a mean follow-up time of 3.8 ± 2.9 years. The mean age was 43.2 ± 19.3 years, and 69.4% were male. Overall patient survival was 86.2% at 1 year, 82.2% at 3 years, and 80.5% at 5 years. Renal failure requiring dialysis had developed in the 323 patients (18.2%). Among them, 26 individuals (1.5%) had progressed to end-stage renal disease without renal recovery after perioperative hemodialysis. Individuals who developed renal failure requiring dialysis had a higher mortality compared with LT recipients never requiring dialysis (hazard ratio, 8.75; 95% confidence interval, 7.0-10.9). CONCLUSIONS: Renal failure requiring dialysis development after LT is common and carries high mortality in Chinese liver allograft recipients. Recognizing risk factors permits the timely institution of proper treatment, which is the key to reducing untoward outcomes.

Diagnosis of pulmonary alveolar proteinosis: usefulness of papanicolaou-stained smears of bronchoalveolar lavage fluid.

BACKGROUND: The globules (stained green, orange, or orange in the center coated with a green rim) seen in Papanicolaou-stained smears of bronchoalveolar lavage fluid are suggested to be characteristic of pulmonary alveolar proteinosis (PAP). OBJECTIVE: To evaluate the usefulness of Papanicolaou-stained smears of bronchoalveolar lavage fluid in aiding a diagnosis of PAP. METHODS: Papanicolaou-stained smears of bronchoalveolar lavage fluid obtained from 7 patients (5 idiopathic, 2 secondary) with PAP were evaluated. To serve as controls, the smears of 11 normal subjects and 128 patients with other pulmonary disorders were also examined. The findings on the presence and number of globules were recorded. To differentiate PAP from other pulmonary disorders, the highest globule value obtained from the control group was chosen as the cutoff point. RESULTS: The characteristic globules were not found in normal subjects and only found in 6 of 128 patients with other pulmonary disorders. Their clinical diagnoses were Sjögren syndrome in 2 cases; polymyositis, idiopathic pulmonary fibrosis, asbestosis, and hypersensitivity pneumonitis in 1 case each. The numbers of globules in these 6 patients were 1, 3, 17, 7, 3, and 2. In contrast, more than 100 globules were found in all patients with PAP. The number of globules was highly sensitive and specific in aiding a diagnosis of PAP when the cutoff value was set at 18. CONCLUSION: The globules seen in Papanicolaou-stained smears of bronchoalveolar lavage fluid may be valuable in aiding a diagnosis of PAP, especially when the number of globules is more than 18.

Three-dimensional analysis for radio-frequency ablation of liver tumor with blood perfusion effect.

Increase of temperature above 50 approximately 60 degrees C for few minutes by the emitted radio-frequency (RF) energy has been shown to be able to denaturate the intracellular proteins and destruct membranes of tumor cells. To improve the efficacy of this thermal therapy, it is important to investigate factors that may affect the RF heating characteristics for the hepatocellular carcinoma and metastatic liver tumors. In order to make sure the applied RF energy is adequate to ablate the target tumor, a 3D thermoelectric analysis for the system consisting of liver, liver arteries and 4 mm diameter tumor is conducted. The effect of blood perfusion is addressed in this study.

Adenocarcinoma in the middle third of the stomach--an evaluation for the prognostic significance of clinicopathological features.

BACKGROUND/AIMS: The prognosis of patients with gastric adenocarcinoma varies with the location of the tumor. Adenocarcinoma in the middle third of the stomach has been claimed to have a better outcome than those in other locations. However, there is still very limited information specifically regarding the prognostic factors which influence the survival time of patients with adenocarcinoma in the middle third of the stomach. This retrospective study was designed with the aim to evaluate and uncover the possible significant clinicopathological parameters for adenocarcinoma in the middle third of the stomach. METHODOLOGY: Between 1986 and 1992, 363 patients underwent gastric resection for primary gastric adenocarcinoma at this hospital. Fifty-two (14.3%) of these patients were included in this study and they all met the following criteria: 1) tumor primarily located in the middle third of the stomach without distant metastases or peritoneal seeding, 2) undergoing curative resection and 3) undergoing R2 nodal dissection, at least. The clinicopathological findings were obtained by detailed review of the medical records and the histologic slides. All surviving patients were also contacted and their current conditions were recorded. RESULTS: The overall 5-year survival rate (Kaplan-Meier method) was 42.5%. In univariate survival analysis by Kaplan-Meier method and long-rank test, serosal invasion (p < 0.01), lymph node metastasis (p < 0.01) and lymphatic involvement (p < 0.01) had an individual prognostic significance. When a multivariate analysis using Cox proportional hazards regression was performed, serosal invasion (P < 0.01) and lymphatic involvement (p < 0.05) appeared as the only two independent prognostic factors regarding long-term survival. When these 52 patients were categorized into patients with early gastric cancer (n = 10) and patients with advanced gastric cancer (n = 42), there was a significant difference (p < 0.01) between the survival rates (90.0% vs. 29.1%). When these tumors were further categorized into early gastric cancer (n = 10), early simulating advanced gastric cancer (n = 14) and Borrmann type advanced gastric cancer (n = 28), there were significant differences (P < 0.01 and P < 0.01, respectively) in 5-year overall survival rates between early gastric cancer (90.0%) and Borrmann type advanced gastric cancer (18.9%), also between early simulating advanced gastric cancer (52.5%) and Borrmann type advanced gastric cancer (18.9%). UICC stage also had significant influence (P < 0.01) on the survival rates. CONCLUSIONS: Serosal invasion and lymphatic involvement are the significant, independent prognostic factors in predicting the survival rate of patients with adenocarcinoma in the middle third of the stomach. Since more advanced stage tumors usually carry a poorer prognosis, early detection is of extreme importance for improving the survival rate.

Persistent mechanical allodynia positively correlates with an increase in activated microglia and increased P-p38 mitogen-activated protein kinase activation in streptozotocin-induced diabetic rats.

BACKGROUND: In experimental early painful diabetic neuropathy, persistent hyperglycaemia induces dys-regulated sodium channel (Navs) expression in the dorsal root ganglion (DRG) and activates microglia in the spinal dorsal horn (SDH). However, information on diabetes-induced chronic neuropathic pain is limited. Therefore, we investigated abnormal Navs in the DRG and activated glial cells in the SDH of diabetic rats with chronic neuropathic pain. METHODS: Sixty-six rats were divided into diabetic and control groups: control rats (n = 18; 1 mL of normal saline via the right femoral vein) and diabetic rats [n = 48; 60 mg/kg streptozotocin (STZ) via the right femoral vein]. Hindpaw behavioural tests, Navs expression in the DRG, activation of glial cells in the SDH and the number of neurons in the SDH were measured at 1 and 2 weeks, and 1, 2, 3 and 6 months following saline and STZ administration. RESULTS: All diabetic rats exhibited hyperglycaemia from day 7 to 6 months. The diabetic rats decreased withdrawal threshold to mechanical stimuli but had blunted responses to thermal stimuli. Consistent up-regulation of Nav1.3 and down-regulation of Nav1.8 was observed. Microglial cells were activated early in the SDH and lasted for 6 months. A positive correlation between mechanical allodynia, Nav1.3 and microglial activation was observed. In addition, microglia activation in the SDH of STZ-induced diabetes was mediated, in part, by phosphorylation of p-38 mitogen-activated protein kinase. CONCLUSIONS: Diabetic rats showed hindpaw mechanical allodynia for 6 months. Persistent mechanical allodynia was positively associated with sustained increased activation of Nav1.3 and increased p38 phosphorylation in activated microglia.

Hyperthyroidism and thyroid cancer risk: a population-based cohort study.

AIM: Thyroid hormones regulate the rate of metabolism and affect the differentiation and growth of many tissues in the body. We investigated the association between hyperthyroidism and cancer risk in Taiwan. PATIENTS AND METHODS: A random sample of 1 000 000 individuals from Taiwan's National Health Insurance database was enrolled. We found 17 033 patients to have newly diagnosed hyperthyroidism between 2000 and 2005. These patients were recruited along with a match cohort of 34 066 patients without hyperthyroidism. Starting from index date, we followed up all patients for 4 years to identify those who developed cancer. RESULTS: During the 4-year follow-up study, cancer was diagnosed in 1.23% of patients with hyperthyroidism and 1.02% of the member of the comparison cohort. Regression analysis showed that patients with hyperthyroidism were at greater risk of cancer incidence, especially thyroid cancer, compared the comparison cohort (HR: 1.213; 95% CI: 1.022-1.440; p<0.05 and HR: 7.355; 95% CI: 3.885-13.92; p<0.05, respectively). After adjusting for age, gender, diabetes mellitus, hypertension, hyperlipidemia, gout, geographic region, and income, patients with hyperthyroidism remained at increased risk of cancer incidence and thyroid cancer (Adjusted HR: 1.206; 95% CI: 1.015-1.433 and 6.803; 95% CI: 3.584-12.91, respectively) (both p<0.05). The longer the duration of hyperthyroidism, the greater the risk of thyroid cancer. CONCLUSIONS: This 4-year follow up study suggests that patients with hyperthyroidism are at increased risk of cancer, especially thyroid cancer.

Taiwan aneurysm registry: multivariate analysis of two-month, one-year, and two-year outcomes after endovascular and microsurgical treatment of ruptured aneurysms.

We compared the outcomes of endovascular coiling with microsurgical clipping of aneurysms in a Taiwanese population. In an ambi-directional cohort design, patient baseline characteristics and clinical course after treatment for ruptured subarachnoid aneurysm were abstracted from medical records from three hospitals to examine and compare differences in post-operative outcomes between those treated with endovascular coiling and those treated with microsurgical clipping. Outcomes were measured, using the modified Rankin scale, two months, one year and two years postoperatively. Of the 642 patients enrolled in the study, 281 underwent endovascular treatment and 361 underwent neurosurgery. The demographics and baseline characteristics of two groups were comparable except for a larger maximum target aneurysm lumen size (p=0.02) in the endovascular group. Patients who underwent the endovascular procedure tended to have a better quality of life than those who had neurosurgery (p<0.01). When the severity of symptom data was pooled into two groups (Rankin values 0-2 and 3-6) a statistically significant relationship was found between the severity of symptoms and age, Hunt and Hess grade, number of target aneurysms detected, and log of maximum target aneurysm lumen size (all p≤0.01). After controlling for potential confounding factors and using the lumped Rankin outcome data, no significant difference in outcome was found between the two procedures at either time point. Our study indicated that endovascular coiling achieves results comparable to surgical clipping for patients with ruptured subarachnoid aneurysms in a Taiwanese population.

Optical clocks and relativity.

Observers in relative motion or at different gravitational potentials measure disparate clock rates. These predictions of relativity have previously been observed with atomic clocks at high velocities and with large changes in elevation. We observed time dilation from relative speeds of less than 10 meters per second by comparing two optical atomic clocks connected by a 75-meter length of optical fiber. We can now also detect time dilation due to a change in height near Earth's surface of less than 1 meter. This technique may be extended to the field of geodesy, with applications in geophysics and hydrology as well as in space-based tests of fundamental physics.