175 GHz, 400-fs-pulse harmonically mode-locked surface emitting semiconductor laser

We report a harmonically mode-locked vertical external cavity surface emitting laser (VECSEL) producing 400 fs pulses at a repetition frequency of 175 GHz with an average output power of 300 mW. Harmonic mode-locking was established using a 300 µm thick intracavity single crystal diamond heat spreader in thermal contact with the front surface of the gain sample using liquid capillary bonding. The repetition frequency was set by the diamond microcavity and stable harmonic mode locking was achieved when the laser cavity length was tuned so that the laser operated on the 117th harmonic of the fundamental cavity. When an etalon placed intracavity next to the gain sample, but not in thermal contact was used pulse groups were observed. These contained 300 fs pulses with a spacing of 5.9 ps. We conclude that to achieve stable harmonic mode locking at repetition frequencies in the 100s of GHz range in a VECSEL there is a threshold pulse energy above which harmonic mode locking is achieved and below which groups of pulses are observed

Appropriateness of Upper Gastrointestinal Endoscopy: Comparison of American and Swiss Criteria

Objective: Examine the reproducibility of the RAND method for developing criteria for the appropriateness of medical procedures. Design: Comparison of two sets of explicit criteria for appropriateness of upper gastrointestinal (UGI) endoscopy, developed by separate expert panels from two countries.Setting: United States, Switzerland. Study participants: National experts from different medical specialties involved in the referral or application of UGI endoscopy.Interventions: Each panel was presented with about 500clinical scenarios (indications)that were rated on a nine-point scale as to the appropriateness of performing UGI endoscopy for a patient with that clinical presentation. Main outcome measurer: (1) distribution of appropriateness ratings and intrapanel agreement categories between the two panels, (2)between-panel agreement of assigning appropriateness for comparable indications and, (3) percentage of indications with major between-panel differences. Results: Ratings for 2/3 of indications could be compared. The Swiss panel showed higher intrapanel agreement (54.6% versus 46.2% p=0.002). Seventy-eight percent of comparable Indications were assigned to indentical categories of appropriateness by both panels (kappa=0.76,P <0.001). For 93% of the 376 comparable indications, there were no major interpanel differences. Conclusion: Separate expert panels in different countries, using a standardized methodology, produce criteria for appropriatenesof medical procedures that are similar. Given the resources being invested throught the world in devilping criteria and guidelines, international collaboration in seeking optimal use of limited health care resources should be intensifled. © 1997 Elsevier Science Ltd. All rights reserve

Pre-hospital management protocols and perceived difficulty in diagnosing acute heart failure

Aim To illustrate the pre-hospital management arsenals and protocols in different EMS units, and to estimate the perceived difficulty of diagnosing suspected acute heart failure (AHF) compared with other common pre-hospital conditions. Methods and results A multinational survey included 104 emergency medical service (EMS) regions from 18 countries. Diagnostic and therapeutic arsenals related to AHF management were reported for each type of EMS unit. The prevalence and contents of management protocols for common medical conditions treated pre-hospitally was collected. The perceived difficulty of diagnosing AHF and other medical conditions by emergency medical dispatchers and EMS personnel was interrogated. Ultrasound devices and point-of-care testing were available in advanced life support and helicopter EMS units in fewer than 25% of EMS regions. AHF protocols were present in 80.8% of regions. Protocols for ST-elevation myocardial infarction, chest pain, and dyspnoea were present in 95.2, 80.8, and 76.0% of EMS regions, respectively. Protocolized diagnostic actions for AHF management included 12-lead electrocardiogram (92.1% of regions), ultrasound examination (16.0%), and point-of-care testings for troponin and BNP (6.0 and 3.5%). Therapeutic actions included supplementary oxygen (93.2%), non-invasive ventilation (80.7%), intravenous furosemide, opiates, nitroglycerine (69.0, 68.6, and 57.0%), and intubation 71.5%. Diagnosing suspected AHF was considered easy to moderate by EMS personnel and moderate to difficult by emergency medical dispatchers (without significant differences between de novo and decompensated heart failure). In both settings, diagnosis of suspected AHF was considered easier than pulmonary embolism and more difficult than ST-elevation myocardial infarction, asthma, and stroke. Conclusions The prevalence of AHF protocols is rather high but the contents seem to vary. Difficulty of diagnosing suspected AHF seems to be moderate compared with other pre-hospital conditions

Figuring Rhetoric: From Antistrophe to Apostrophe through Catastrophe

This essay explores rhetoric tropologically through various strophes: antistrophe, catastrophe, and apostrophe. Our purpose is to delineate problems and possibilities that these tropes pose for rhetoric in an effort to create new rhetorics. We seek to display the antistrophic and catastrophic figurations of rhetoric and then use visual lenses of photography and cinema to disrupt the figurations. Following the disruption, we seek to heighten sensibilities to other figurations, in particular an apostrophic figuration. We cast apostrophe as a figure for change because it marks a deeply felt turn toward difference and otherness. Turned as such, rhetoric becomes erotic

Blast phase myeloproliferative neoplasm: Mayo-AGIMM study of 410 patients from two separate cohorts

A total of 410 patients with blast phase myeloproliferative neoplasm (MPN-BP) were retrospectively reviewed: 248 from the Mayo Clinic and 162 from Italy. Median survival was 3.6 months, with no improvement over the last 15 years. Multivariable analysis performed on the Mayo cohort identified high risk karyotype, platelet count < 100 × 109 /L, age > 65 years and transfusion need as independent risk factors for survival. Also in the Mayo cohort, intensive chemotherapy resulted in complete remission (CR) or CR with incomplete count recovery (CRi) rates of 35 and 24%, respectively; treatment-specified 3-year/5-year survival rates were 32/10% for patients receiving allogeneic stem cell transplant (AlloSCT) (n = 24), 19/13% for patients achieving CR/CRi but were not transplanted (n = 24), and 1/1% in the absence of both AlloSCT and CR/CRi (n = 200) (p < 0.01). The survival impact of AlloSCT (HR 0.2, 95% CI 0.1–0.3), CR/CRi without AlloSCT (HR 0.3, 95% CI 0.2–0.5), high risk karyotype (HR 1.6, 95% CI 1.1–2.2) and platelet count < 100 × 109 /L (HR 1.6, 95% CI 1.1–2.2) were confirmed to be interindependent. Similar observations were made in the Italian cohort. The current study identifies the setting for improved short-term survival in MPN-BP, but also highlights the limited value of current therapy, including AlloSCT, in securing long-term survival

Establishment of a New Cell-Based Assay To Measure the Activity of Sweeteners in Fluorescent Food Extracts

Taste receptors have been defined at the molecular level in the past decade, and cell-based assays have been developed using cultured cells heterologously expressing these receptors. The most popular approach to detecting the cellular response to a tastant is to measure changes in intracellular Ca2+ concentration using Ca2+-sensitive fluorescent dyes. However, this method cannot be applied to food-derived samples that contain fluorescent substances. To establish an assay system that would be applicable to fluorescent samples, we tested the use of Ca2+-sensitive photoproteins, such as aequorin and mitochondrial clytin-II, as Ca2+ indicators in a human sweet taste receptor assay. Using these systems, we successfully detected receptor activation in response to sweetener, even when fluorescent compounds coexisted. This luminescence-based assay will be a powerful tool to objectively evaluate the sweetness of food-derived samples even at an industry level

How to manage the transplant question in myelofibrosis

Allogeneic stem cell transplantation remains the only curative therapy for myelofibrosis. Despite advances in transplant, the morbidity and the mortality of the procedure necessitate careful patient selection. In this manuscript, we describe the new prognostic scoring system to help select appropriate patients for transplant and less aggressive therapies. We explore the advances in non-transplant therapy, such as with investigational agents. We review the blossoming literature on results of myeloablative, reduced intensity and alternative donor transplantation. Finally, we make recommendations for which patients are most likely to benefit from transplantation

Epigenetic abnormalities in myeloproliferative neoplasms: a target for novel therapeutic strategies

The myeloproliferative neoplasms (MPNs) are a group of clonal hematological malignancies characterized by a hypercellular bone marrow and a tendency to develop thrombotic complications and to evolve to myelofibrosis and acute leukemia. Unlike chronic myelogenous leukemia, where a single disease-initiating genetic event has been identified, a more complicated series of genetic mutations appear to be responsible for the BCR-ABL1-negative MPNs which include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Recent studies have revealed a number of epigenetic alterations that also likely contribute to disease pathogenesis and determine clinical outcome. Increasing evidence indicates that alterations in DNA methylation, histone modification, and microRNA expression patterns can collectively influence gene expression and potentially contribute to MPN pathogenesis. Examples include mutations in genes encoding proteins that modify chromatin structure (EZH2, ASXL1, IDH1/2, JAK2V617F, and IKZF1) as well as epigenetic modification of genes critical for cell proliferation and survival (suppressors of cytokine signaling, polycythemia rubra vera-1, CXC chemokine receptor 4, and histone deacetylase (HDAC)). These epigenetic lesions serve as novel targets for experimental therapeutic interventions. Clinical trials are currently underway evaluating HDAC inhibitors and DNA methyltransferase inhibitors for the treatment of patients with MPNs