Fast, High-Fidelity Conditional-Phase Gate Exploiting Leakage Interference in Weakly Anharmonic Superconducting Qubits.

Conditional-phase (cz) gates in transmons can be realized by flux pulsing computational states towards resonance with noncomputational ones. We present a 40 ns cz gate based on a bipolar flux pulse suppressing leakage (0.1%) by interference and approaching the speed limit set by exchange coupling. This pulse harnesses a built-in echo to enhance fidelity (99.1%) and is robust to long-timescale distortion in the flux-control line, ensuring repeatability. Numerical simulations matching experiment show that fidelity is limited by high-frequency dephasing and leakage by short-timescale distortion.

KIT mutations and CD117 overexpression are markers of better progression-free survival in vulvar melanomas.

BACKGROUND: Few studies have addressed prognostic markers and none has correlated molecular status and prognosis in vulvar melanomas. OBJECTIVES: To evaluate the clinicopathological features of 95 cases of vulvar melanoma. METHODS: p53, CD117, Ki-67, neurofibromin, brafv600e and nrasq61r immunostains, and molecular analyses by either targeted next-generation or direct sequencing, were performed on available archival materials. RESULTS: Molecular testing detected mutations in KIT (44%), BRAF (25%), NF1 (22%), TP53 (17%), NRAS (9%) and TERT promoter (9%). Co-mutation of KIT and NF1 and of KIT and NRAS were identified in two and one cases, respectively. KIT mutations were significantly associated with better progression-free survival in univariate analyses. In multivariate analyses CD117 expression was significantly associated with better progression-free survival. Tumour thickness was significantly associated with worse progression-free and overall survival, and perineural invasion significantly correlated with reduced melanoma-specific survival and reduced overall survival. Cases were from multiple centres and only a subset of samples was available for molecular testing. CONCLUSIONS: KIT mutations and CD117 overexpression are markers of better progression-free survival. In addition to its prognostic value, molecular testing may identify cases that might respond to targeted agents or immunotherapeutic approaches.

The Potato Cryobank at The International Potato Center (Cip): A Model for Long Term Conservation of Clonal Plant Genetic Resources Collections of the Future.

BACKGROUND: Cryobanks are a secure, efficient and low cost method for the long-term conservation of plant genetic resources for theoretically centuries or millennia with minimal maintenance. OBJECTIVE: The present manuscript describes CIP's modified protocol for potato cryopreservation, its large-scale application, and the establishment of quality and operational standards, which included a viability reassessment of material entering the cryobank. MATERIALS AND METHODS: In 2013, CIP established stricter quality and operational standards under which 1,028 potato accessions were cryopreserved with an improved PVS2-droplet protocol. In 2014 the viability of 114 accessions cryopreserved in 2013 accessions were reassessed. RESULTS: The average recovery rate (full plant recovery after LN exposure) of 1028 cryopreserved Solanum species ranged from 34 to 59%, and 70% of the processed accessions showed a minimum recovery rate of ≥20% and were considered as successfully cryopreserved. CONCLUSION: CIP has established a new high quality management system for cryobanking. Periodic viability reassessment, strict and clear recovery criteria and the monitoring of the percent of successful accessions meeting the criteria as well as contamination rates are metrics that need to be considered in cryobanks.

Use of modifying phrases in surgical pathology reports: is there a different understanding between pathologists and treating physicians?

When not all the histopathologic and clinical features necessary for a pathology diagnosis are present in a particular specimen, pathologists may use modifying phrases to convey various degrees of certainty, e.g., "consistent with…" and "suggestive of…." However, it is unclear whether pathologists use such phrases consistently or whether treating physicians fully understand their intended meaning. A questionnaire concerning six common modifying phrases ("consistent with, suggestive of, suspicious for, highly consistent with, highly suggestive of, some features of") was sent to all physicians from a single institution who either issued or routinely received surgical pathology reports. Physicians were asked to rank their understanding of each phrase on a printed scale between 1 ("no evidence of") and 10 ("diagnostic of"). One hundred sixty physicians (74.3%) responded. Despite wide variation, there was a hierarchy (from more to less diagnostic): highly consistent > highly suspicious > consistent > suspicious > suggestive > some features (p < 1 × 10-7). There were no significant differences between pathologists and treating physicians (p = 0.72) or attendings and residents (p = 0.9). Pathologists and treating physicians share an overall common understanding of their hierarchical relationship, albeit with wide ranges. Based upon our results, we propose to use only three qualifying phrases to convey the degree of certainty for a particular diagnosis: "suggestive of" (> 25 ≤ 50% certainty), "suspicious for" (> 50 ≤ 75%), and "consistent with" (> 75%). The phrase "no evidence of" should probably be used only when there is ≤ 5% confidence in a diagnosis, and conversely, "diagnostic of" should probably be used only when there is ≥ 95% confidence in a diagnosis.

Protecting quantum entanglement from leakage and qubit errors via repetitive parity measurements.

Protecting quantum information from errors is essential for large-scale quantum computation. Quantum error correction (QEC) encodes information in entangled states of many qubits and performs parity measurements to identify errors without destroying the encoded information. However, traditional QEC cannot handle leakage from the qubit computational space. Leakage affects leading experimental platforms, based on trapped ions and superconducting circuits, which use effective qubits within many-level physical systems. We investigate how two-transmon entangled states evolve under repeated parity measurements and demonstrate the use of hidden Markov models to detect leakage using only the record of parity measurement outcomes required for QEC. We show the stabilization of Bell states over up to 26 parity measurements by mitigating leakage using postselection and correcting qubit errors using Pauli-frame transformations. Our leakage identification method is computationally efficient and thus compatible with real-time leakage tracking and correction in larger quantum processors.

Prognostic value of various morphometric measurements of tumour extent in prostate needle core tissue.

AIMS: Predicting prostatic cancer patients' outcome is a major objective for clinicians and patients. Several nomograms are currently implemented prior to treatment to help predict clinical and pathological outcome. The aim of this study was to investigate the prognostic significance of morphometric measurements of cancer on the needle biopsy specimen in relation to the final pathological stage or the biochemical failure status following radical prostatectomy, and to determine which measurement of tumour length in cases with discontinuous foci of cancer (DFC) is most reliably reflective of the pathological stage. METHODS AND RESULTS: Of the 100 patients included in this study, 34% had high-stage disease (pT >or= 3 and/or pN1) and 16% experienced biochemical recurrence. The analysis showed that fraction of positive cores, total percentage of cancer and both total and greatest millimetric cancer lengths were the variables most closely associated with pathological stage and biochemical failure status. CONCLUSIONS: This study confirms the prognostic value of recording tumour extent in prostatic needle biopsy reporting. However, the results are inconclusive in determining the best method to record tumour length in cores with DFC and larger studies are needed to answer this question fully.

Loss of heterozygosity for genes on 11p and the clinical course of patients with lung carcinoma.

Forty-five primary human lung carcinomas were evaluated for the loss of heterozygosity for genes on the short end of chromosome 11. Of 40 evaluable heterozygous cases, loss of the 11p genes c-H-ras and insulin was documented in nine cases (22%). The clinical parameters investigated for each patient included the disease stage at presentation, the presence of metastatic disease in either bronchial or mediastinal lymph nodes, and the presence of positive parietal pleural margins in the surgically resected specimen. There were no differences found with respect to these indicators when patients exhibiting the loss of heterozygosity were compared with those who did not have such genetic loss. In addition, when the clinical courses of the two patient groups were compared, there was no difference in survival. We conclude that the loss of heterozygosity for c-H-ras and insulin on 11p is a common finding in primary non-small cell human lung carcinomas but does not confer a more aggressive phenotype on these tumors. Although this genetic lesion may be important in the initial transformation of the cells to carcinoma, the available data for lung carcinoma are insufficient to prove causality.

Frequent microsatellite instability in primary small cell lung cancer.

Alterations in microsatellite sequences characterize hereditary nonpolyposis colorectal cancer. This microsatellite instability is due in some kindreds to a germline mutation of the mismatch repair gene hMSH2 on chromosome 2p. Although microsatellite alterations have been reported in other hereditary nonpolyposis colorectal cancer-associated tumors including endometrial and gastric cancers, such changes were not detected in most other major neoplasms. We found that 15 of 33 (45%) primary small cell lung cancers, tumors not found in the hereditary nonpolyposis colorectal cancer syndrome, displayed alterations of microsatellite loci which consisted of deletions or expansions of (CA)n dinucleotide repeats. In 8 of these 15 neoplasms, microsatellite instability was detected in more than 10% of all tested alleles. However, small cell lung cancers that revealed instability contained widespread allelic loss and had a uniformly poor prognosis. These results expand considerably the known spectrum of tumors with microsatellite instability.

Homozygous deletion on chromosome 9p and loss of heterozygosity on 9q, 6p, and 6q in primary human small cell lung cancer.

We analyzed the pattern of allelic loss in 33 primary human small cell lung cancers (SCLCs) using highly informative microsatellite markers on chromosomes 2p, 3p, 5q, 6, 9, 13q, and 17p. Nineteen of these tumors (58%) displayed loss of heterozygosity on chromosome 9. Fourteen SCLCs demonstrated loss of heterozygosity for all informative markers on both chromosomal arms; two tumors demonstrated partial loss on chromosome 9p. In one tumor, a multiplex polymerase chain reaction assay disclosed a homozygous deletion at 9p21-22 including the markers IFN-alpha, D9S126, and D9S171. Two SCLCs retained all informative markers on 9p but showed allelic loss of the entire 9q arm, while one case had a partial loss of proximal 9q extending into all of 9p. Analysis of other chromosomal arms showed loss of heterozygosity on 3p (93%), 5q (75%), 6p (46%), 6q (47%), 13q (75%), and 17p (93%). It was necessary to test multiple markers at several loci because of the frequent expression of microsatellite instability that confounded our mapping efforts in SCLCs with replication errors. This study demonstrates the frequent loss of a suppressor gene locus on chromosome 9p21-22 and identifies novel suppressor loci on 6p, 6q, and 9q in primary SCLC.

Heterotransplantation of a human prostatic adenocarcinoma cell line in nude mice.

Nude mice of NIH/Swiss background were utilized for the heterotransplantation of a tissue culture cell line derived from a human prostate adenocarcinoma metastatic to the brain. These cells, which had been grown in vitro for 13 passages, formed solid tumors when injected s.c. into nude mice. The cell line DU 145 has been passaged 60 times in vitro over a period of 18 months. Tumors removed from the mice were serially transplanted to additional mice and reestablished in vitro. Light-microscopic analysis of the tumor grown in nude mice revealed a strong similarity to the patient's metastatic tumor. The ultrastructure of the tumor cells propagated in nude mice was compared to that of the original human tumor cells and to the tissue culture cells, both before and after passage in nude mouse. No major differences were detected. Karyotypic analysis of the tumor cells grown in vitro before mouse passage, grown in nude mouse, and grown in vitro after mouse passage indicated chromosomal identity and consistent marker chromosomes: three large acrocentric chromosomes and metacentric minute chromosomes.

Evaluation of an epithelial plasticity biomarker panel in men with localized prostate cancer.

BACKGROUND: Given the potential importance of epithelial plasticity (EP) to cancer metastasis, we sought to investigate biomarkers related to EP in men with localized prostate cancer (PC) for the association with time to PSA recurrence and other clinical outcomes after surgery. METHODS: Men with localized PC treated with radical prostatectomy at the Durham VA Medical Center and whose prostatectomy tissues were included in a tissue microarray (TMA) linked to long-term outcomes. We performed immunohistochemical studies using validated antibodies against E-cadherin and Ki-67 and mesenchymal biomarkers including N-cadherin, vimentin, SNAIL, ZEB1 and TWIST. Association studies were conducted for each biomarker with baseline clinical/pathologic characteristics an risk of PSA recurrence over time. RESULTS: Two hundred and five men contributed TMA tissue and had long-term follow-up (median 11 years). Forty-three percent had PSA recurrence; three died of PC. The majority had high E-cadherin expression (86%); 14% had low/absent E-cadherin expression. N-cadherin was rarely expressed (<4%) and we were unable to identify an E-to-N-cadherin switch as independently prognostic. No associations with clinical risk group, PSA recurrence or Gleason sum were noted for SNAIL, ZEB1, vimentin or TWIST, despite heterogeneous expression between patients. We observed an association of higher Ki-67 expression with Gleason sum (P=0.043), National Comprehensive Cancer Network risk (P=0.013) and PSA recurrence (hazard ratio 1.07, P=0.016). CONCLUSIONS: The expression of EP biomarkers in this cohort of men with a low risk of PC-specific mortality was not associated with aggressive features or PSA relapse after surgery.

A randomized comparison of high-dose versus conventional-dose cyclophosphamide, doxorubicin, and vincristine for extensive-stage small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group.

To assess the effect of dose escalation in the treatment of small-cell lung cancer (SCLC), 298 patients with extensive-stage disease were treated with either conventional-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1 mg/m2), (CDCAV); or high-dose cyclophosphamide (1,200 mg/m2), doxorubicin (70 mg/m2), and vincristine (1 mg/m2) (HDCAV). No dose attenuation was allowed during the initial three cycles of therapy in either treatment arm. All patients received CDCAV in cycles 4 through 6, during which time dosages were adjusted according to granulocyte and platelet nadirs. No additional chemotherapy was administered until disease progression or relapse was documented. Complete responses were more frequent with HDCAV (22% v 12%; P = .045). However, overall response rate (63% v 53%) and median survival (29.3 v 34.7 weeks) were not significantly different (P greater than .05). HDCAV was substantially more toxic than CDCAV, causing more episodes of life-threatening leukopenia (ie, granulocytes less than 500/microL; 79% v 40%; P less than .05) and infections (15% v 4%; P less than .05). Dose intensification of cyclophosphamide and doxorubicin during induction chemotherapy did not produce any survival benefit compared with conventional dosages of these agents in SCLC patients with extensive-stage disease.

The dynamics of prostate-specific antigen after definitive radiation therapy for prostate cancer.

We report the use of an exponential model for capturing the dynamics of serial measurements of prostate-specific antigen (PSA) made just before and after definitive radiation therapy of localized prostate cancer. Our study patients consisted of 164 men treated at a community hospital and without use of adjuvant hormonal therapy, and we had a mean of 5 years follow-up. We found that the model fits allowed us to condense PSA dynamic information into four parameters, including the initial pretreatment value of PSA, and three of these related significantly to subsequent outcome. The model also provided greater understanding of the prognosis of men with rising PSA after radiation therapy. Specifically, two of the model's parameters allowed us to compare the PSA status of these men to those with hormone-refractory disease, and we discovered that at the time of "biochemical relapse," there is a broad spectrum in expected probability of imminent death as well as in time to an adverse outcome. Thus, the model provides information that allows one to stratify men with rising PSA into a continuous spectrum from low to high risk for an adverse outcome. We believe these results show that exponential models have the potential for providing useful clinical information about men with rising PSA after definitive radiation therapy and that they could help us decide when further therapy is needed. Therefore, we recommend further study and development of these models as part of clinical research protocols involving radiation therapy of localized prostate cancer.

Predicting tumor failure in prostate carcinoma after definitive radiation therapy: limitations of models based on prostate-specific antigen, clinical stage, and Gleason score.

In this report, we use new patient data to test three popular models developed to predict the outcome of definitive radiation therapy. The data come from 240 men with localized prostate cancer and who were treated with definitive radiation therapy at a community hospital. All three models tested were based on the three commonly available variables of pretreatment prostate-specific antigen (PSA), Gleason score, and tumor stage, and we used the Cox proportional hazards model and the logistic regression model to relate these variables to outcome. We discovered that in our data, the optimal way to use pretreatment PSA was as natural log(PSA), the optimal way to use T stage was in three categories: T1 and T2, T3, and T4, and that the optimal use of Gleason score was as <7 versus > or =7. Nevertheless, models confined to the optimal use of these three variables leave much uncertainty about important outcomes, such as the probability of relapse within 5 years.

A prognostic score for hormone-refractory prostate cancer: analysis of two cancer and leukemia group B studies.

Previously, we have shown that serial measurements of prostate-specific antigen (PSA) in hormone-refractory prostate cancer (HRPC) can be used to calculate an average relative velocity (rva) of PSA. Together, the level of PSA and the rva formed a two-variable model for survival time that worked at any time during the course of HRPC. Here, we have added serial measurements of hemoglobin and weight to test whether they improve the prior model based on PSA alone. Data from two Cancer and Leukemia Group B studies (9181 and 9182) on HRPC were combined to study the relationship between survival and serial measurements of PSA, serum hemoglobin, and patient weight. Altogether, there were 348 patients who could be evaluated. We used the Cox proportional hazard model for survival time with the interval censored method to accommodate time-dependent covariates, and tests for significance were two sided. Log (PSA), rva, log (hemoglobin), and log [weight (in kg)] were all significantly related to survival time during the course of HRPC (P < 3.0 x 10(-5)). Together, they formed a prognostic score based upon the relative hazard. Higher values of this score implied higher probability of death as the next observed event. Serial measurements of PSA, hemoglobin, and weight provide a prognostic score that can be applied continuously during the course of HRPC. Changes in the score may provide a reproducible measure of treatment effect.

Disparate results between proliferation rates of surgically excised prostate tumors and an in vitro bioassay using sera from a positive randomized controlled trial.

In vitro bioassay has been used extensively to test the effects of culturing cancer cells in sera from humans participating in dietary interventions, i.e, studies of modified intake of nutrients for the purpose of reducing cancer risk or progression. It has been hypothesized that cell proliferation rates determined by the in vitro bioassay indicate whether modification of dietary intake could decrease cancer cell growth in vivo. It has been suggested, however, that the in vitro bioassay may not correlate with tumor cell proliferation rates in prostate cancer. We investigated the concordance of cell proliferation rates from surgically excised prostate tumor tissue with the in vitro bioassay using sera from matched patients. We used samples from an earlier randomized clinical trial that showed that supplementation with flaxseed significantly inhibited prostate cancer cell proliferation rates in vivo as indicated by Ki67 staining in tumor specimens. Proliferation rates of LNCaP, DU145 and PC3 cell lines cultured in 10% human sera from participants in the flaxseed trial were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Spearman's Rho correlation coefficients (ρ) indicated no association between Ki67 staining in prostate tumors and the in vitro bioassay for the three cell lines. These disparate findings suggest that the in vitro bioassay may not provide an accurate assessment of the environment in vivo.

Vitamin D and prostate cancer: a prediagnostic study with stored sera.

This study evaluates the risk of prostate cancer in relation to serum levels of the major vitamin D metabolites, 25-hydroxyvitamin D (25-D3) and 1,25-dihydroxyvitamin D (1,25-D). Between 1964 and 1971, more than 250,000 serum samples were collected from members of the Kaiser Permanente Medical Care Plan in Oakland and San Francisco and stored for future use. Levels of 25-D and 1,25-D were measured in samples from 90 black and 91 white men diagnosed with prostate cancer before December 31, 1987 and controls individually matched on age, race, and day of serum storage. Mean serum 1,25-D was 1.81 pg/ml lower in cases than in matched controls (P = 0.002). Risk of prostate cancer decreased with higher levels of 1,25-D especially in men with low levels of 25-D. However, mean 25-D was not significantly different in cases and controls. The association of lower 1,25-D with prostate cancer was found in men above the median age of 57 years at serum storage but not younger men and was similar in black and white men. In men > or = 57 years of age, 1,25-D was an important predictor of risk for palpable and anaplastic tumors but not for tumors incidentally discovered during surgery to treat the symptoms of benign prostatic hyperplasia or well differentiated tumors.

Extramedullary hematopoiesis in the prostate.

A case of bone marrow myelofibrosis with extramedullary hematopoiesis in the prostate gland is described. This 75-year-old man had an 8-year history of myelofibrosis, massive hepatosplenomegaly, and progressive anemia and a 5-year history of bladder outlet obstruction symptomatology. Transurethral resection of prostate was performed, and light microscopic examination of the prostatic chips revealed a diffuse distribution of atypical megakaryocytes, immature granulocytes, and normoblasts in the prostatic stroma. The prostatic glandular epithelium was uninvolved. Immunostaining for hemoglobin in erythroid precursors and a chloroacetate esterase stain for granulocytic precursors were useful in confirming the diagnosis and in defining the extent of prostatic involvement. Extramedullary hematopoiesis is a rare process in the prostate gland, but it should be included in the differential diagnosis of cellular prostatic stromal lesions, particularly when atypical giant cells are observed.

Systemic kappa light-chain deposition. An ultrastructural and immunohistochemical study.

This report describes the pathology of kappa light-chain deposition in a 55-year-old patient who presented with respiratory insufficiency and hepatomegaly. Biopsies of lung and liver showed PAS-positive deposits which did not stain with congo red, crystal violet, or thioflavin-T. By indirect immunoperoxidase techniques, the deposits were composed of kappa light-chain immunoglobin. Electron microscopy revealed granular and fibrillar electron-dense material which lacked the characteristics of amyloid. Subsequent clinical studies showed this patient had a plasma cell dyscrasia. These data show that kappa light-chain deposition is not limited to the kidney, and that the first manifestation of a plasma cell dyscrasia may be systemic deposits of light chain. These deposits can be distinguished from amyloid by their immunochemical, tinctorial, and ultrastructural appearance.

Histologic grade, DNA ploidy, and intraglandular tumor extent as indicators of tumor progression of clinical stage B prostatic carcinoma. A direct comparison.

Histologic grade, DNA ploidy, and percentage tumor area were assessed in prostatectomy specimens from 73 patients with clinical stage B adenocarcinoma of the prostate and analyzed for their value as predictors of tumor progression. Further, the relationship between percentage tumor area and DNA ploidy was studied. Percentage tumor area was the indicator most strongly associated with the likelihood of tumor extension beyond the capsule of the prostate and of tumor progression as assessed in a logistic regression model. Grade was slightly superior to percentage area in predicting time to progression in a Cox model analysis. Increasing percentage tumor area was associated with an increased likelihood of aneuploidy. Little additional predictive ability was obtained with the concurrent use of two indicators in multivariate analysis, suggesting a high degree of interrelatedness of percentage tumor area, histologic grade, and DNA ploidy. DNA ploidy was not an independent predictive factor, and from a practical standpoint histologic grade and percentage tumor area were more important predictors of tumor progression than DNA ploidy.