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Introduction A neutrophilic infiltrate characterizes bacterial pneumonia. Macrophage infiltration is similarly characteristic of the viral pneumonia caused by SARS‐CoV‐2. These infiltrating macrophages, while phagocytic and capable of engulfing virus laden alveolar cells, are also rich in tissue factor—a thromboplastin. This prothrombotic aspect likely explains how a respiratory virus whose malign effects should be confined to the oropharynx, bronchi and lungs, can cause a panoply of extra‐pulmonary organ disorders. Elevated ferritin levels in ICU Covid 19 patients, and elevated acute phase proteins suggest immune overreaction. Elevated d‐dimers implicate clotting as well. This evidence links hyperactive innate immunity (macrophage lung infiltrates) with the elevated levels of oligomeric fibrin present in the bloodstream of these patients. Methods An in‐house assay measuring oligomeric (soluble) fibrin (also referred to as soluble fibrin monomer complexes or SFMC) in whole blood, previously developed for monitoring incipient disseminated intravascular coagulation (DIC) during liver transplantation, was made available to COVID ICU attendings. Since SFMC constitutes the input to intravascular fibrin clots and d‐dimer reflects fibrin clot dissolution, it was thought that the two tests, run in tandem along with assays of immune activation, might clarify the frequency and possibly the cause of DIC in patients with severe COVID‐19 pneumonia. Results Classical DIC with intravascular clotting and thrombocytopenia was documented only rarely. However, early in the pandemic shortly after the assay was made available, it identified three patients undergoing acute defibrination. In each patient virtually all of the body's fibrinogen was transformed into SFMC over 3–4 days and deposited somewhere in the vasculature without any gross clots being detected. Conclusions Three COVID‐19 patients with evidence of a hyperactive immune response (elevated ferritin and acute phase proteins) defibrinated while blood levels of SFMC were being monitored. SFMC levels that were five times higher than normal appeared in the circulation during the defibrination process. SFMC at these levels may precipitate as showers of microclots, damaging heart, kidney, brain, and so forth.

Background Physical inactivity is associated with an increased risk of cardiovascular disease. High intensity interval training (HIIT) has been shown to improve important health parameters, including aerobic capacity, arterial blood pressure, cardiac autonomic modulation and left ventricular mechanics. However, adaptations in left atrial (LA) mechanics and aortic stiffness remain unclear. Therefore, the aim of the present study was to assess any left atrial and aortic adaptations to HIIT. Methods Forty-one physically inactive males and females (aged 23 ± 2.7 years) volunteered for the study. Participants were randomised to either a 4-week HIIT intervention (n = 21) or 4-week control period (n = 20). The HIIT protocol consisted of 3 x 30-second maximal cycle ergometer sprints with a resistance of 7.5% body weight, interspersed with 2-minutes of active unloaded recovery. Speckle tracking imaging of the left atrium and M-Mode tracing of the aorta was performed pre and post HIIT and control period using commercially available software (EchoPac; GE Medical Systems). Analysis of covariance, with baseline measures as the covariate, was used to explore any differences in left atrial mechanics and aortic stiffness between the intervention and control groups. Stepwise linear regression analysis using LA stiffness as the dependent variable was conducted. Results Following 4-weeks of HIIT, there was significant improvement in LA mechanics, including LA reservoir (13.9 ± 13.4%, p = 0.033) and LA stiffness (-0.05 ± 0.04%-1, p = 0.032) compared to the control condition. In addition, improvements were observed in aortic distensibility (2.1 ± 2.7 cm2 × dyn×-1 × 103, p = 0.031) and aortic stiffness index (-2.6 ± 4.6, p = 0.041) compared to the control condition. In stepwise linear regression analysis, aortic distensibility change was significantly associated with LA stiffness change (p = 0.002), with an R2 of 0.613. Conclusion A short-term programme of HIIT was associated with a significant improvement in LA mechanics and aortic stiffness. These adaptations may have important health implications and contribute to the improved left ventricular diastolic and systolic mechanics, aerobic capacity and reduced arterial blood pressure previously documented following HIIT.

Background Outcome of Mitral Valve Prolapse (MVP) was controversial for long time. Many studies reported great differences in the incidence of cardiovascular events due, above all, to heterogeneous and small studied populations. Most of theme were also published to late '80 of the last century till early '00. Purpose To make a contemporary survey on the incidence of cardiovascular events in a selected population of patients affected by primary MVP referred to a tertiary cardiovascular center for the medical and surgical care of valvular heart disease. Methods We reviewed our MVP database; patients with at least 2 cardiologic evaluations inclusive of echocardiographic examination and at least 6 months follow up were enrolled. A total of 250 patients (126 F) were selected. Their mean age was 52.1 years (ranging from 13 to 88 yo). The average follow-up time was 100 months (8,33 yrs). Results At the first medical and echocardiographic examination 8 patients (3,2%) had no mitral regurgitation (MR), 104 (41.6%) have a trace/mild MR, 93 (37,2%) a moderate MR and 46 (18,4%) a severe MR. They were widely asymptomatic (NYHA I 205-82%, NYHA II 44-17.60%, NYHA III 1- 0.40%). Most of theme presented a bileaflet (140-55.8%) or a posterior MVP (94 - 37.6%); an isolated anterior MVP was rare (16 - 6,4%). Flail leaflet was present in 8 (3,2%) and 25 (10%) had a chordal rupture. Respectively 165 (65,6%) and 115 (46,1%) patients had thick and redundant leaflets. Mean antero-posterior mitral annulus diameter was 37 mm. During the follow up 7 patients died of non-cardiac cause and 5 (2%) of suspected cardiac cause (2 because of acute coronary syndrome and 3 died suddenly). MR progresses in 43 (17,2%) patients and finally we observed 81 (32,4%) moderate/severe and severe MR. 12 new chordal rupture occurred during the follow up in most cases concerning mitral chordae linked to posterior mitral leaflet (10 cases-83,3%). The worsening of MR provoked an evolution of the clinical condition of 48 patients (19.2%) which developed Dyspnea On Excertion (DOE) with 42 new NYHA II and 6 new NYHA III. At the end of the follow up the amount of patients symptomatic for DOE was 93 (37.2% vs 18% at the initial evaluation). A total of 45 patients (18%) underwent mitral valve surgery. 40 needed in-hospital treatment in most cases due to the development of atrial fibrillation (19 -7.6%) or heart failure ( 8- 3,2%). Endocarditis occurred in 4 patients (1.6%) and cerebrovascular accidents/cardioembolic event in 6 (2.4%). The overall cardiovascular event rate was 4,33/100 patients-year, significantly higher than reported in community based studies. Conclusions The prognosis of a MVP population referred to a tertiary cardiovascular center is not benign. The most frequent complications are progression of MR and MV surgery. Sudden death is also more frequent than in general population. More studies are needed to identify what patients with MVP are at risk for it.

Background Hyperglycemia leading to increased oxidative stress is implicated in the increased risk for the development of macrovascular and microvascular complications in patients with type 1 diabetes mellitus. Methods and Results A random subcohort of 349 participants was selected from the DCCT / EDIC (Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications) cohort. This included 320 controls and 29 cardiovascular disease cases that were augmented with 98 additional known cases to yield a case cohort of 447 participants (320 controls, 127 cases). Biosamples from DCCT baseline, year 1, and closeout of DCCT , and 1 to 2 years post‐ DCCT ( EDIC years 1 and 2) were measured for markers of oxidative stress, including plasma myeloperoxidase, paraoxonase activity, urinary F 2α isoprostanes, and its metabolite, 2,3 dinor‐8 iso prostaglandin F 2α . Following adjustment for glycated hemoblobin and weighting the observations inversely proportional to the sampling selection probabilities, higher paraoxonase activity, reflective of antioxidant activity, and 2,3 dinor‐8 iso prostaglandin F 2α , an oxidative marker, were significantly associated with lower risk of cardiovascular disease (−4.5% risk for 10% higher paraoxonase, P iso prostaglandin F 2α , P =0.0092). In contrast, the oxidative markers myeloperoxidase and F 2α isoprostanes were not significantly associated with cardiovascular disease after adjustment for glycated hemoblobin. There were no significant differences between DCCT intensive and conventional treatment groups in the change in all biomarkers across time segments. Conclusions Heightened antioxidant activity (rather than diminished oxidative stress markers) is associated with lower cardiovascular disease risk in type 1 diabetes mellitus, but these biomarkers did not change over time with intensification of glycemic control. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 00360815 and NCT 00360893.

We report on the mechanisms leading to beam quality degradation in conventional and DBR tapered lasers at high operating powers. The simulations were performed on ELoD2 975nm DBR tapered lasers using an in-house laser simulation tool, Speclase. We show how light propagating outside the ridge waveguide leads to beam quality degradation, showing both how the absorption in this region is bleached and where the forward propagating light comes from — even when the rear facet is anti-reflection coated.

In this work, we demonstrate how our external cavity modelling tool can be used to study and analyze how intentional feedback can be exploited to enhance the spectral performance of high-brightness lasers. As an example, Littrow cavity with a DBR tapered laser is modelled.

This work presents results of modeling the impact of unintentional optical feedback on the performance of high-brightness DBR tapered laser. The simulations are performed with our external cavity laser modelling tool consisting of a 2.5D laser simulation tool coherently coupled to commercial ray tracing software. We consider the impact of the unintentional feedback on the output power, efficiency and beam quality.

Background Online technology has revolutionised the way in which people connect and share their experiences. It also brings new opportunities to engage patients in health and social care research through the use of an online research community platform (ORCP). For example, it can improve the accuracy and usefulness of information gathered about research priorities, and it can be used to understand behaviours and preferences. Given an increasing prevalence of long-term conditions including rheumatoid arthritis, online technology represents a novel route for participation and engagement in research. Objectives To explore the benefits and limitations of an ORCP through understanding lived experiences of adults with rheumatoid arthritis. Methods We used a purposive sampling approach to ensure variation of key attributes amongst people with rheumatoid arthritis. A total of eight individuals used the ORCP during the pilot study. Qualitative data were collected through online focus groups, conducted as semi-structured interviews and asynchronous threaded discussions. The study was conducted in line with fieldwork guidelines, and written informed consent was obtained. Results The closed ORCP enabled a physically disconnected group to share their experiences of living with rheumatoid arthritis, describing the symptoms, diagnostic experience and support they received. In addition, participants shared their experiences and opinions about treatment delivery and adherence, the impact of rheumatoid arthritis, and the experiences of transitional care from paediatric to adult health services, where appropriate. Reasons and feeling about research participants and drug development processes were also discussed. Conclusions Our pilot study provided important accounts from people living with rheumatoid arthritis, highlighting the substantial impact of the disease on their daily lives. The ORCP removed physical contact between the researcher and participants, the absence of which may enable a richer data collection. However, it also has its limitations, primarily because the researcher is less able to gauge participants9 attitudes and concerns. ORCPs represent a novel route of data collection, enabling researchers to immerse themselves into a community of individuals, whether they be patients, carers or professionals. Acknowledgements The authors would like to thank the individuals who contributed their thoughts and experiences to the pilot study. Disclosure of Interest S. Stones Employee of: McCann Complete Medical., S. Bull Employee of: McCann Complete Medical., S. Becerra Employee of: McCann Complete Medical.

The primary focus of cardiopulmonary bypass management in Jehovah's Witness patients is the need to conserve blood. A consequence of these strategies inevitably results in hemodilution that is frequently extreme enough to dilute clotting factors and potentially impair coagulation. The purpose of this case report is to demonstrate that a hemodiluted patient requires less heparin to sustain anticoagulation and less protamine to reverse heparin at cardiopulmonary bypass termination. Patient harm may ensue unless the effects of extreme hemodilution are recognized.

Perioperative bleeding is a potentially devastating complication in neurosurgical patients, and plasma fibrinogen concentration has been identified as a potential modifiable risk factor for perioperative bleeding. The aim of this study was to evaluate preconditioning with Crotalus atrox venom (Cv-PC) as potential preventive therapy for reducing perioperative hemorrhage in the rodent model of surgical brain injury (SBI). C. atrox venom contains snake venom metalloproteinases that cleave fibrinogen into fibrin split products without inducing clotting. Separately, fibrinogen split products induce fibrinogen production, thereby elevating plasma fibrinogen levels. Thus, the hypothesis was that preconditioning with C. atrox venom will produce fibrinogen spilt products, thereby upregulating fibrinogen levels, ultimately improving perioperative hemostasis during SBI. We observed that Cv-PC SBI animals had significantly reduced intraoperative hemorrhage and postoperative hematoma volumes compared to those of vehicle preconditioned SBI animals. Cv-PC animals were also found to have higher levels of plasma fibrinogen at the time of surgery, with unchanged prothrombin time. Cv-PC studies with fractions of C. atrox venom suggest that snake venom metalloproteinases are largely responsible for the improved hemostasis by Cv-PC. Our findings indicate that Cv-PC increases plasma fibrinogen levels and may provide a promising therapy for reducing perioperative hemorrhage in elective surgeries.

Objectives Crystalloid administered during cardiopulmonary bypass may significantly dilute clotting factor concentrations, particularly in low blood volume patients. Should the administered fluid (pump prime plus IVs) drop the clotting factor concentrations below approximately 38%, almost all patients will bleed, heparin levels will be overestimated and excessive neutralizing protamine will be administered. This combination can render blood virtually unclottable. This paper describes algorithms that quantify dilution risk and the maximum fluid that can be safely administered. A confirmatory calculation to prevent excessive protamine administration is also described.

Summary Reasons for performing study: The importance of osteoarthritis (OA) in the horse and the difficulty in its early diagnosis have led to a search for potential biomarkers of joint disease. If the levels of such markers are to be interpreted accurately, clinicians and researchers need to know whether they are influenced by environmental factors and/or interventions such as exercise and repeated arthrocentesis. Objective: To investigate the influence of repeated arthrocentesis and exercise on nitric oxide (NO), prostaglandin E2 (PGE2) and glycosaminoglycan (GAG) concentrations in synovial fluid (SF) from normal equine joints. Methods: SF was collected from the left metacarpophalangeal (MCP), radiocarpal and tarsocrural joints of 16 horses. Half of the horses were exercised and arthrocentesis was repeated 14, 14.5, 17 and 24 days after the start of the exercise programme, in both exercised and control horses. Nitric oxide was determined in SF from the MCP joint only and PGE2 and GAG concentrations were determined in SF from all joints. Results: Repeated arthrocentesis caused an increase in NO concentration in the MCP joint on Day 14.5, in PGE2 concentrations in the radiocarpal and tarsocrural joints on Day 14.5 and the release of GAGs into SF of the MCP and radiocarpal joints on Day 17. Exercise resulted in an increase in PGE2 levels in all joints but did not influence the other parameters measured. Potential relevance: Repeated arthrocentesis is a potential confounding factor for the use of synovial NO, PGE2 and GAG concentrations as markers of joint disease. Based on this study, such a confounding effect can be avoided if one week or more separates arthrocentesis procedures. Moderate exercise causes a transient rise in PGE2 in SF.

This paper examines the mission success of a federally funded research center by using bibliometric methods that include quantitative, descriptive, and citation analyses. We developed a methodology to facilitate examination of patterns in research, publishing, and collaborations, quantification and categorization of research partners, classification of topics, historical and emerging areas of research, and publishing venues. These patterns over a 12-yr period are used to assess whether the institute is achieving its mission goals of 1) fostering collaborative research, 2) becoming a center of excellence, and 3) educating scientists and students. Our findings indicate that a self-study of publishing activities yields useful results about programmatic strengths and weaknesses. This could be a first step of a larger study of federal government research and programmatic evaluation

Administration of activated protein C (APC) protects from renal dysfunction, but the underlying mechanism is unknown. APC exerts both antithrombotic and cytoprotective properties, the latter via modulation of protease-activated receptor-1 (PAR-1) signaling. We generated APC variants to study the relative importance of the two functions of APC in a model of LPS-induced renal microvascular dysfunction. Compared with wild-type APC, the K193E variant exhibited impaired anticoagulant activity but retained the ability to mediate PAR-1-dependent signaling. In contrast, the L8W variant retained anticoagulant activity but lost its ability to modulate PAR-1. By administering wild-type APC or these mutants in a rat model of LPS-induced injury, we found that the PAR-1 agonism, but not the anticoagulant function of APC, reversed LPS-induced systemic hypotension. In contrast, both functions of APC played a role in reversing LPS-induced decreases in renal blood flow and volume, although the effects on PAR-1-dependent signaling were more potent. Regarding potential mechanisms for these findings, APC-mediated PAR-1 agonism suppressed LPS-induced increases in the vasoactive peptide adrenomedullin and infiltration of iNOS-positive leukocytes into renal tissue. However, the anticoagulant function of APC was responsible for suppressing LPS-induced stimulation of the proinflammatory mediators ACE-1, IL-6, and IL-18, perhaps accounting for its ability to modulate renal hemodynamics. Both variants reduced active caspase-3 and abrogated LPS-induced renal dysfunction and pathology. We conclude that although PAR-1 agonism is solely responsible for APC-mediated improvement in systemic hemodynamics, both functions of APC play distinct roles in attenuating the response to injury in the kidney.

A state-of-the-art laser diode simulation tool has been used to investigate how phonon reflection at epitaxial interfaces impacts upon the performance of high-power 980 nm ridge waveguide lasers. Due to the inclusion of phonon reflection, a 0.5 K increase in quantum well temperature and a reduction in front facet output power of up to 0.6 mW is observed. The results demonstrate that whilst this effect is relatively small, a first order correction should be made to obtain accurate simulation results.

An investigation into the degradation of an 808 nm AlGaAs/GaAs compressively strained high-power laser bar is performed using a range of experimental techniques that focus on understanding the performance of the individual emitters that make up the laser bar—a so-called by-emitter analysis. We find that thermally induced current runaway, beginning in the edge emitters, is an important factor in the degradation of this bar and its eventual failure. Facet temperature measurements reveal that temperature distributions where the emitters are hotter at the bar edges as compared to those in the bar centre can occur in aged laser bars. This is in contrast to the facet temperature distributions observed in new devices and also in measurements of the bulk temperature.

A systematic study of the dependence of the optical gain on the injection current and temperature in InGaAsN/GaAs lasers has been performed. The amplified spontaneous emission has been measured from a series of both facet-coated and uncoated 1.3 μm edge-emitting double quantum well lasers. The net gain, modal gain, cavity loss, quasi-Fermi level separation and width of the gain spectra have been extracted using Cassidy's method. The peak gain was found to shift 0.41 nm/K between 300 K and 340 K and 0.60 nm/K between 340 K and 380 K. The value of the peak gain was found to decrease with temperature at a rate of 0.26 cm−1/K. The increase in the full at width half maxima of the gain spectra was determined to be 0.35 nm/K. These values are all comparable to those found for the more traditional 1.3 μm InP-based devices, suggesting that InGaAsN/GaAs lasers are a viable alternative to replace such InP-based devices, in particular for uncooled access network applications. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Photoluminescence microscopy (PLM) and photoluminescence (PL) spectroscopy have been used to investigate the influences of the number of quantum wells (QWs) and nitrogen concentration [N] on the quality of InGaAsN multiple QWs (MQWs). No misfit dislocations and/or carrier localization were observed in as-grown InGaAsN MQWs. PL measurement results suggest that the PL efficiency and interfaces in the InGaAsN/GaAs QWs do not deteriorate with increasing number of QWs. In an InGaAsN 7 QW structure, even after annealing at temperatures as high as 850 °C, misfit dislocations were still not observed. This is contrary to the lattice relaxation behaviour of annealed InGaAs MQWs and is attributed to the impurity pinning of dislocations by nitrogen. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

A theoretical investigation into the impact of the thermal boundary resistance on the performance of uncooled edge-emitting 1.3μm InGaAsN/GaAs quantum well lasers has been performed. A state-of-the-art 2D laser diode simulation tool has been extended to accurately model the thermal resistance due to the acoustic material mismatch and defect scattering at epitaxial interfaces. A small, but noticeable, increase in quantum well temperature is observed. The results clearly highlight the need for the inclusion of thermal boundary resistance in device simulation tools. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

We demonstrate a rear-side phase-locking architecture with two high-brightness diode lasers. This technique is based on the passive phase-locking of emitters in an external cavity on their rear facet, and their coherent combination on the front facet. Two high-brightness high-power tapered laser diodes are coherently combined using a Michelson-based cavity. The combining efficiency is above 80% and results in an output power of 6.7 W in a nearly diffraction-limited beam. The rear-side architecture is then used with a laser bar of 5 tapered emitters using an interferometric extended cavity, based on a diffractive optical element. We describe the experimental evaluation of the diffractive optical element, and the phase-locked operation of the laser bar.

The net modal gain, effective group index and linewidth enhancement factor (LWEF) in edge-emitting InGaAsN/GaAs lasers have been determined as a function of both temperature and injection current from experimentally amplified spontaneous emission spectra. The shift of the peak gain with temperature was found to be 0.49 nm/K. Values of effective group index between 3.52 and 3.59 were measured, suggesting a relatively high refractive index of 3.75 for a dilute nitride quantum well. LWEF values between 1.87 and 2.84 were measured.

This paper presents a model for simulating the impact of external optical feedback on large-optical cavity high-brightness diode lasers. The simulations are performed with our 2.5D simulation tool for high-brightness laser diodes. The external cavity is modelled using commercial coherent ray tracing software. We consider the impact of the optical feedback on the excitation of amplified spontaneous emission in the parasitic vertical modes.

Advanced optical traps can probe single molecules with Angstrom-scale precision, but drift limits the utility of these instruments. To achieve A-scale stability, a differential measurement scheme between a pair of laser foci was introduced that substantially exceeds the inherent mechanical stability of various types of microscopes at room temperature. By using lock-in detection to measure both lasers with a single quadrant photodiode, we enhanced the differential stability of this optical reference frame and thereby stabilized an optical-trapping microscope to 0.2 A laterally over 100 s based on the Allan deviation. In three dimensions, we achieved stabilities of 1 A over 1,000 s and 1 nm over 15 h. This stability was complemented by high measurement bandwidth (100 kHz). Overall, our compact back-scattered detection enables an ultrastable measurement platform compatible with optical traps, atomic force microscopy, and optical microscopy, including super-resolution techniques.

BACKGROUND: Glutathione S-transferases (GSTs) facilitate detoxification of drugs by catalysing the conjugation of the reduced glutathione (GSH) to electrophilic xenobiotic substrates and therefore have a function in multi-drug resistance. As a result, knowledge of GSTs can inform both drug resistance in, and novel interventions for, the control of endo- and ectoparasite species. Acaricide resistance and the need for novel control methods are both pressing needs for Dermanyssus gallinae, a highly economically important haematophagous ectoparasite of poultry.METHODS: A transcriptomic database representing D. gallinae was examined and 11 contig sequences were identified with GST BlastX identities. The transcripts represented by 3 contigs, designated Deg-GST-1, -2 and -3, were fully sequenced and further characterized by phylogenetic analysis. Recombinant versions of Deg-GST-1, -2 and -3 (rDeg-GST) were enzymically active and acaricide-binding properties of the rDeg-GSTs were established by evaluating the ability of selected acaricides to inhibit the enzymatic activity of rDeg-GSTs.RESULTS: 6 of the identified GSTs belonged to the mu class, followed by 3 kappa, 1 omega and 1 delta class molecules. Deg-GST-1 and -3 clearly partitioned with orthologous mu class GSTs and Deg-GST-2 partitioned with delta class GSTs. Phoxim, permethrin and abamectin significantly inhibited rDeg-GST-1 activity by 56, 35 and 17 % respectively. Phoxim also inhibited rDeg-2-GST (14.8 %) and rDeg-GST-3 (20.6 %) activities.CONCLUSIONS: Deg-GSTs may have important roles in the detoxification of pesticides and, with the increased occurrence of acaricide resistance in this species worldwide, Deg-GSTs are attractive targets for novel interventions.

We present results from an efficient, self-consistent spectral laser model, which incorporates nonequilibrium gain and is suitable for the routine simulation of quantum well laser diodes. Nonequilibrium gain is calculated using a dynamic gain model, which simulates the dynamic relaxation of the quantum well carrier energy distributions under the influence of continuous-wave electrical and optical excitation. The spectral laser model employs a 2D bipolar electrical model solved in the lateral and epitaxial directions. The optical field is solved in the lateral and longitudinal directions using the 2D wide-angle beam propagation method. Steady state nonequilibrium gain is included in the laser model via parameterized look up tables. Results show that the inclusion of nonequilibrium gain is essential for the prediction of device operating characteristics, even when the device is operated in continuous-wave mode.

Using a quantitatively calibrated imaging system and specially fabricated tapered lasers with windowed n-contacts, the authors image the spontaneous emission distribution inside two different laser cavities as a function of injection current. In the first device, an array of narrow-angle index-guided tapered lasers, significant thermal and electrical coupling between the emitters was observed. In the second device, a wide-angle gain-guided tapered laser, significant spatial hole burning was observed above threshold. The spontaneous emission distributions of this wide-angle device have been compared with simulation results from a 2.5D laser simulator and show good quantitative agreement in the quantum well carrier density.

A novel and advanced characterization technique is described for performing optical studies of the luminescence properties of materials. It was developed for the investigation of semiconductor materials, including semiconductor laser diodes and photonic integrated circuits. A quantitatively calibrated, spatially and spectrally resolved imaging technique is described, which is based upon the technologies of photoluminescence microscopy and photoluminescence spectroscopy. The principles of the spectroscopically resolved photo- and electroluminescence microscopy techniques are outlined in this paper, and the developed instrument is described in detail. Design calculations used to select and set up the experimental apparatus are presented, and results are found to compare well with this analysis. Various experimental measurements are used to demonstrate the performance of the new instrument. The study of strain and defects in high-power laser diodes is presented as one of the more challenging applications of the new technique. The results presented demonstrate the ability of this technique to image photoluminescence shifts occurring in the substrate of packaged laser bars, enabling the investigation of strain, defects and their evolution with aging. Other applications of the technique include the spectroscopic measurement of near- and far-field patterns and virtual sources of laser diodes, investigations of spectral hole burning and optical scattering processes in lasers and photonic integrated circuits, and studies of organic LEDs. In the future, applications are also envisaged in medicine and the biological sciences.

Experimental measurements of the spatial distribution of the spontaneous emission produced inside the cavity of a 4° 980 nm tapered laser are presented and compared with the results of a 2.5 D half-space, hot-cavity simulation. A custom device with a windowed n-contact was designed and fabricated for this work. The effectiveness of this windowed contact was investigated and appears to be satisfactory. The measurement system for photo- and electroluminescence microscopy imaging was quantitatively calibrated with an error of < ±15%. Good agreement between the experimental and simulated results are presented, with an error of ~ 6% in the carrier density at the output facet.

A spectroscopically-resolved photoluminescence microscopy technique for the optical study of semiconductor laser diodes is described. The system has been developed by incorporating a twin etalon tuneable filter with a spectral width of 0.6 nm into an existing photoluminescence microscopy imaging system. The design calculations used to make the experimental apparatus are compared with results from the developed system and show reasonable agreement. The study of packaging-induced strain and defects in high-power laser diodes is used to illustrate this technique. Initial results are presented and compare well with an existing technique, micro-photoluminescence spectroscopy. The results show that shifts (< 1 nm) in the peak photoluminescence wavelength can be observed in regions with defects and/or different soldering-induced strain. Luminescence shifts as large as 15 nm in the region around a dark line defect are observed and these cause a significant disturbance in the strain field in the adjacent regions, where luminescence shifts as large as 5 nm are observed.

The degradation behaviour of AlGaAs high power laser bars has been investigated using micro-electroluminescence (μ-EL) spectroscopy, electroluminescence microscopy (ELM) and micro-photocurrent (μ-PC) spectroscopy. The emitters in each bar have been individually studied in detail. A significant blue shift of the EL spectra was observed for certain emitters. Inspection of these blue-shifted emitters with ELM also showed the presence of extended defects. The EL spectral shifts correlate with the blue shift of the quantum well (QW) absorption edge observed by photocurrent (PC) spectroscopy and is caused by a mounting induced strain. This correlation suggests that μ-EL spectroscopy is a reliable and sensitive technology for the recognition of defective emitters and thus for the reliability assessment of high power laser bars.

International audience; We describe a new coherent beam combining architecture based on passive phase-locking of two laser diodes in a Michelson external cavity on their rear facet, and their coherent combination on the front facet. As a proof-of-principle, two ridge lasers have been coherently combined with >90 % efficiency. The phase-locking range, and the resistance of the external cavity to perturbations have been thoroughly investigated. The combined power has been stabilized over more than 15 min with an optical feedback as well as with an automatic adjustment of the driving currents. Furthermore, two high-brightness high-power tapered laser diodes have been coherently combined in a similar arrangement; the combining efficiency is 70% and results in an output power of 4 W. We believe that this new configuration combines the simplicity of passive self-organizing architectures with the optical efficiency of master-oscillator power-amplifier ones.

Five multichannel hematology analyzers (four different models) were evaluated to determine the ability of analyzers to correctly measure packed cell volume (PCV) values across the clinically relevant range. A sixth analyzer (fifth model) was subsequently included using archival data. Twenty-two different blood samples with PCVs ranging from 0.2 to 0.6 L/L were run in duplicate on each analyzer. Duplicate reference PCV determinations were also done using the recently described ICSH-recommended reference method. Simultaneously, a simpler "surrogate reference" procedure was performed in duplicate. Analyzer values were compared to ICSH reference and to surrogate reference PCV values using Deming regression analysis. Compared to either reference, all analyzers showed a slope of less than 1.0, thereby overestimating the PCV at 0.2 L/L and underestimating the PCV at 0.6 L/L to some extent. This outcome was surprising. Deming regression slopes would be expected to average at 1.0. Instruments whose slopes are significantly less than 1.0 will show decreased sensitivity to both anemic and polycythemic patients. We know of no inherent reason why multichannel analyzers should behave in this fashion.

SummaryThrombosis accounts for a high proportion of disability and death in the West. Although soluble fibrin (SF) assays have been shown to be good predictors of thrombosis, current quantitative assays are too complex or lengthy to provide timely results, while simpler methods are qualitative and lack sensitivity. We here describe a rapid, new, protamine-based whole-blood screening method for SF which is quantitative and suitable for point-of-care use. Citrated whole blood is mixed with reagent under controlled conditions and the time until development of an SF precipitate is measured. Negative samples remain precipitate-free for 300 seconds. Strongly positive samples develop precipitate in as little as 10 seconds. SF times are mathematically converted to arbitrary SF units (SFU). This Rapid-SF test provides a simple and reliable means of detecting the presence of SF, and is well-suited for whole-blood rapid screening in the emergency department, operating room or clinic.

We report on the design aspects of high performance diode lasers for application in high-brightness spectral beam combining and coherent beam combining modules. Key performance trade-offs are identified and potential solutions are explored.

In this work, an ultracompact electro-optic modulator based on refractive index modulation by plasma dispersion effect in PhC all-optical gate (AOG) is proposed. The index modulation is achieved by applying a time-varying bias voltage across the electrical contacts of the AOG. The proposed modulator has potential for high-speed operation, with bandwidths in excess of 30GHz achievable.

In this study, the authors examine some of the factors affecting the brightness and the beam quality of high-power tapered lasers. The large volume resonators required to achieve a high-power, high-brightness operation make the beam quality sensitive to carrier lensing and a multimode operation. These cause bleaching of the regions outside the ridge waveguide. The beam quality in the conventional and the distributed Bragg reflector tapered lasers is examined in the absence of the self-heating effects to investigate the effect of the carrier lensing effects. The influence of the front facet reflectivity and the taper angle on the beam quality is investigated. The beam quality was found to degrade with an increase in the front facet reflectivity and for the larger taper angles in the conventional tapered lasers, especially at low ridge waveguide currents. Finally, the performance of the conventional tapered lasers employing a beamspoiler was assessed. The beam quality was found to be comparable with that achieved in the DBR tapered lasers.

Prior research reveals that differential grading patterns exist among the academic disciplines. One explanation may lie in discipline-related differences in teaching goals and beliefs about the meaning grades should convey. This study examined the effects of academic discipline and teaching goals on grading beliefs. A national sample (n = 442) of undergraduate teaching faculty provided responded to a survey measuring the importance of various teaching goals and orientations toward norm-referenced or criterion-referenced grading (Frame of Reference), and beliefs about using grades to sort and select students on the basis of achievement (Gatekeeping). Both teaching goals and academic discipline were significantly related to gatekeeping beliefs, but not to beliefs about frames of reference for grading. Higher gatekeeping scores were associated with faculty in the paradigmatic fields and those who emphasized analytic skills and time management. Lower gatekeeping scores were associated with the preparadigmatic disciplines and teaching goals of synthesis and integration and developing respect for others. Faculty who identified their primary teaching role as subject matter oriented were more gatekeeping than those who identified themselves primarily as being student/personal development oriented.

Disease activity in rheumatoid arthritis (RA) is difficult to measure objectively. Both clinical and laboratory measures were evaluated by the statistical method of consensus analysis. In the literature, laboratory tests as a group have proved more effective; however, studies did not include self-assessment questionnaires. We evaluated the effectiveness of a Modified Health Assessment Questionnaire (MHAQ) relative to other clinical and laboratory tests measuring disease activity in 100 patients with RA. Hemoglobin, hematocrit, mean corpuscular volume, fibrinogen level, Wes-tergren erythrocyte sedimentation rate and C-reactive protein tests, along with tests of morning stiffness, visual analog pain scale, Ritchie index, total joint count, and MHAQ, were evaluated simultaneously. The erythrocyte sedimentation rate was confirmed as a highly effective test to follow disease activity. The MHAQ was the best clinical test; in the methotrexate-treated subgroup it ranked as highly as the most effective laboratory assays. MHAQ is a more effective tool than many laboratory tests currently ordered for monitoring RA disease activity and should be a part of the record of each visit of an arthritis patient.

As examples of what Walker Percy calls "diagnostic fiction," both Headhunter and The Thanatos Syndrome trace contemporary discontents back to a growing disconnection from purpose and justice. Both books use the interactions of psychiatrists and their patients to illustrate how modern civilization's sickness can be spread or fought, and both authors prophesy against those who promote this sickness through their longing for power. While "addicts of desire" such as Findley's Dr Kurtz and Percy's Dr Comeaux are finally defeated by true "physician[s] of the soul" such as Dr Marlow and Dr More, both novels end by reminding readers that anomie and nihilism still afflict this civilization. En tant qu'exem-ples de ce que Walker Percy qualifie de "fiction diagnostique," Le chasseur de tetes tout comme he syndrome de Thanatos font remonter l'origine des m6contentements actuels A la disjonction croissante entre intention et justice. Ces deux livres font appel h l'interaction entre les psychiatres et leurs patient/es pour illustrer la fagon dont la maladie de la civilisation moderne peut s' etendre ou etre combattue, et la faton dont les auteurs prophetisent contre ceux et celles qui cherchent a activer cette maladie afin d'obtenir plus de pouvoir. Tandis que les "accros du desir," le Dr Kurtz de Findley et le Dr. Comeaux de Percy, sont finalement mis en echec par de vrais "phsysicien[s] de ]me" tels que Dr. Marlow et Dr. More, les deux romans concluent en rappelant aux lecteurs et lectrices que I'anomie et le nihilisme continuent a affliger cette civilisation. As Kenneth Radu has noted, Headhunter (1993) is Timothy Findley's indictment of a world in which "limits have disappeared" and "perversion and insanity have changed places with humanity and reason" (40) - that is, it is Findley's indictment of much of the modern world. Although he has set his story in a dystopian Toronto of the near future, Findley clearly wants his readers to recognize that this unreal city embodies ideas and truths that can be found in all the "civilized" places of the earth. Playing his ideas out against the existing geography and culture of Toronto, Findley attempts to expose and explain what he sees as a latent strain of nihilism in modern culture, a strain that has emerged because this civilization (in his words) "has ceased to be in the hands of those of us who call ourselves civilized" (Slopen 41). In this novel, plagues afflict both the body and the spirit. "Sturnusemia," the latest pandemic illness (said to be spread by starlings and other animals), claims victims throughout the city, but so do madness and despair. Many citizens show signs of an immitigable acedia; their diminished ability to feel and pursue healthy desires leads them to seek pleasure in mastery and murder. Believing themselves free of responsibilities for others, inhabitants of a world in which values and limits are rare while lies and self-deception are common, they act as if everything that is, anything - is permitted. In fact, everything is permitted: "their" doctor, Rupert Kurtz, director of the Parkin Institute of Psychiatric Research and epitome of establishment values, grants them permission to pursue their worst impulses.' Such permissions are the basis of his successful career (Headhunter 434). Amidst the abolition of all restraint, Kurtz's eventual antagonist, the psychiatrist Charles Marlow, realizes that "Sturnusemia and AIDS were [now] not the only plagues. Civilization - sickened - had itself become a plague. And its course, in [this] world, could be followed by tracing the patterns of mental breakdown" (271). Signs and symptoms everywhere point not to contingent difficulties but to a coming end. As Marlow notes that "Psychiatric case loads, everywhere, carried alarming numbers," he finds that only one diagnosis is possible: a death-urge is winning. "Broken dreamers, their minds in ruins. This was the human race" (271). Findley's image of civilization mutating into a plague carries an echo of that "unknown and terrible plague" dreamt of by Raskolnikov at the end of Dostoevsky's Crime and Punishment (555). …

The political novel, says Irving Howe, is a work of fiction alive with the “internal tensions” born of abstract ideologies colliding with “representations of human behavior and feeling” (20) and since World War II, by his estimation, such fiction has only been produced outside the West (254). In his 1986 epilogue to Politics and the Novel Howe describes authors such as V. S. Naipaul, Nadine Gordimer, and Milan Kundera among others as creators of “a literature of blockage, a literature of impasse” (252) that offers “no way out of the political dilemmas with which they end their books.” He praises their ability to document “utterly intractable” circumstances while pointedly refusing to accept the totalist stances propounded by the subjects of so many of their novels (253-54).

MCNP6 is simply and accurately described as the merger of MCNP5 and MCNPX capabilities, but it is much more than the sum of these two computer codes. MCNP6 is the result of six years of effort by the MCNP5 and MCNPX code development teams. These groups of people, residing in Los Alamos National Laboratory’s X Computational Physics Division, Monte Carlo Codes Group (XCP-3) and Nuclear Engineering and Nonproliferation Division, Radiation Transport Modeling Team (NEN-5) respectively, have combined their code development efforts to produce the next evolution of MCNP. While maintenance and major bug fixes will continue for MCNP5 1.60 and MCNPX 2.7.0 for upcoming years, new code development capabilities only will be developed and released in MCNP6. In fact, the initial release of MCNP6 contains numerous new features not previously found in either code. These new features are summarized in this document. Packaged with MCNP6 is also the new production release of the ENDF/B-VII.1 nuclear data files usable by MCNP. The high quality of the overall merged code, usefulness of these new features, along with the desire in the user community to start using the merged code, have led us to make the first MCNP6 production release: MCNP6 version 1. High confidence in the MCNP6 code is based on its performance with the verification and validation test suites, comparisons to its predecessor codes, our automated nightly software debugger tests, the underlying high quality nuclear and atomic databases, and significant testing by many beta testers.

We report on the EC BRIDLE project, which aims to develop a direct diode laser source (with more than 2kW of output power from a 100μm diameter optical fibre and an efficiency of 40%) for industrial sheet metal cutting applications. The project concepts are explored, from novel tailored diode laser mini-bars to advanced beam combining architectures.

Super large optical cavities can give the desired wide vertical near-field (and narrow vertical far-field), which simplify the optics and feedback in an external cavity laser. However, vertical structures support many higher order modes and may suffer from poor modal discrimination. We examine important additional considerations for the design of external cavity diode lasers. An optical trap can reduce the waveguide width and improve modal discrimination, but some higher order modes are still unavoidable. Thus, the laser materials and growth must be carefully optimised to ensure that light coupled back into the laser cannot propagate in these unwanted modes.