High-performance cavity-dumped Q-switched Alexandrite laser CW diode-pumped in double-pass configuration.

We present a high-performance Alexandrite laser for LIDAR applications with repetition rates up to 20 kHz in cavity-dumped Q-switched operation continuous-wave diode-pumped in the red spectral region. With a double-pass pump configuration, short pulses with 2.8 ns duration at repetition frequencies ranging from 1 kHz to 20 kHz could be demonstrated. At 5 kHz a - to our knowledge - record pulse energy of over 500 µJ could be achieved at 755 nm in TEM00. Furthermore, a stability measurement at an energy of around 350 µJ with 5 kHz showed no degradation over 150 Mega-shots. The influence of the crystal temperature on the laser performance is also investigated, first in continuous-wave and secondly in cavity-dumped Q-switched operation.

Experimental and numerical study of interlock requirements for high-power EYDFAs.

In this work, we studied the interlock requirements in a seed failure scenario for Er3+:Yb3+ doped fiber amplifiers (EYDFAs) pumped with high intensities in the MWcm-2 range at 9XX nm. We fed a time-dependent FEM-tool with the data from backwards directed amplified spontaneous emission (ASE) transients of different commercially available core-pumped single-mode fibers. In the FEM-tool, the Er3+:Yb3+ system is defined as a bi-directional energy transfer process and described by the corresponding rate equations. The power evolution of the pump, seed, and ASE signal is computed by differential equations taking into account the transient population densities of the relevant energy levels. With the model, we computed the temporal evolution of the corresponding energy levels after a seeder failure to take place within tens to hundreds of µs and calculated the associated gain. The fibers under test provide a critical total gain of 30 dB after ∼ 80 µs within the Yb3+ band and after ∼300 µs within the Er3+ band. This time decreases with increasing pump power and doping concentration. The results can be extrapolated to high-power cladding-pumped EYDFAs to meet the challenging requirements of engineering-level systems.

Gain dynamics in Er(3+):Yb(+) co-doped fiber amplifiers.

Understanding the gain dynamics of fiber amplifiers is essential for the implementation and active stabilization of low noise amplifiers or for coherent beam combining schemes. The gain dynamics of purely Er3+ or Yb3+ doped fiber amplifiers are well studied, whereas no analysis for co-doped systems, especially for Er3+:Yb3+ co-doped fiber amplifiers has been performed, so far. Here, we analyze for the first time the gain dynamics of Er3+:Yb3+ co-doped fiber amplifiers theoretically and experimentally. It is shown that due to the energy transfer between the Yb3+ and Er3+ ions a full analytical solution is not possible. Thus, we used numerical simulations to gain further insights. Comparison of experimental and numerical results shows good qualitative agreement. In addition, we were able to determine the Yb3+-Er3+ transfer function of the energy transfer experimentally.

Gain dynamics in Raman fiber lasers and passive pump-to-Stokes RIN suppression.

We report on theoretical and experimental investigations of gain dynamics in Raman fiber lasers in the frequency range of 1 Hz-1 MHz. An analytical solution of the problem is due to the nonlinear nature of the Raman effect not feasible. Thus, we used a numerical simulation to gain general insights. Experimentally and numerically obtained results for a Raman fiber laser emitting at 1180 nm show good qualitative agreement. We also present a potential physical interpretation of the observed dynamical properties. In addition, we report on an experimental proof-of-principle of a passive pump-to-Stokes RIN suppression scheme for the main Stokes order in cascaded Raman fiber lasers utilizing an additional parasitic Stokes order. Again, results from numerical and experimental studies of a cascaded Raman fiber laser at 1180 nm and 1240 nm show good agreement and confirm the passive pump-to-Stokes RIN suppression at 1180 nm. The dependencies between the resonator design and the parameters of the noise suppression are investigated. In addition, it is shown that the scheme can also be applied to cascaded Raman fiber lasers with more then two Stokes shifts. This opens the possibility to design for example low-noise Raman fiber lasers at 1480 nm to pump low-noise Er(3+) doped fiber amplifiers.

Co-seeded Er3+:Yb3+ single frequency fiber amplifier with 60 W output power and over 90% TEM(00) content.

We report on the design and fabrication of an Er(3+):Yb(3+) triple clad fiber and on the power scaling of a single frequency fiber amplifier at 1.5 µm based on that fiber. In addition, we report on mode content measurements in order to reveal the overlap of the amplifier output with the TEM(00) mode. The triple clad design was used to enable high output power levels, a good slope efficiency and an excellent beam quality. A maximum single frequency output power of 61 W at 1.5 µm could be achieved with the aid of the co-seeding method, which was used to suppress parasitic processes at 1.0 µm. With a scanning ring cavity the mode content of the amplifier output was analyzed with respect to the TEM modes. For all output power levels the TEM(00) content was above 90%.

Stabilized high-power laser system for the gravitational wave detector advanced LIGO.

An ultra-stable, high-power cw Nd:YAG laser system, developed for the ground-based gravitational wave detector Advanced LIGO (Laser Interferometer Gravitational-Wave Observatory), was comprehensively characterized. Laser power, frequency, beam pointing and beam quality were simultaneously stabilized using different active and passive schemes. The output beam, the performance of the stabilization, and the cross-coupling between different stabilization feedback control loops were characterized and found to fulfill most design requirements. The employed stabilization schemes and the achieved performance are of relevance to many high-precision optical experiments.

[Migraine with typical aura without headache; first presentation at older age]. / Visuele verschijnselen bij migraine met typisch aura.

Transient visual phenomena in later life due to a visual aura in migraine are not uncommon and can also occur without headache. This migraine with aura is not always recognized as such. Since visual phenomena can also have a variety of other causes, they can present a diagnostic dilemma in both primary and secondary care. Visual aura phenomena have various and often complex manifestations and are usually observed binocularly. In case of transient visual phenomena, the patient's history is of utmost importance to determine whether there is a mono- or binocular cause of the complaints. Timely recognition of visual phenomena in the context of migraine can prevent unnecessary diagnostics and treatments.

Heparin-induced thrombocytopenia: An update for the COVID-19 era.

The increased use of heparin during the current COVID-19 pandemic has highlighted the risk of a rare but potentially serious complication of heparin therapy, viz. heparin-induced thrombocytopenia (HIT). This is a short review on the pharmacology of heparin and its derivatives, and the pathophysiology of HIT. Guidance on laboratory testing for and clinical management of HIT is presented in accordance with international guidelines. There are important similarities and differences between HIT and the new entity of vaccine-induced immune thrombotic thrombocytopenia, also known as thrombosis with thrombocytopenia syndrome, which clinicians need to be aware of.

Recommendations for the diagnosis and management of vaccine-induced immune thrombotic thrombocytopenia.

There have recently been safety concerns regarding an increased risk of vaccine-induced immune thrombotic thrombocytopenia (VITT) following administration of SARS-CoV-2 adenoviral vector vaccines. The Southern African Society of Thrombosis and Haemostasis reviewed the emerging literature on this idiosyncratic complication. A draft document was produced and revised by consensus agreement by a panel of professionals from various specialties. The recommendations were adjudicated by independent international experts to avoid local bias. We present concise, practical guidelines for the clinical management of VITT.

Patient blood management: A solution for South Africa.

For more than 70 years the default therapy for anaemia and blood loss was mostly transfusion. Accumulating evidence demonstrates a significant dose-dependent relationship between transfusion and adverse outcomes. This and other transfusion-related challenges led the way to a new paradigm. Patient blood management (PBM) is the application of evidence-based practices to optimise patient outcomes by managing and preserving the patient's own blood. 'Real-world' studies have shown that PBM improves patient outcomes and saves money. The prevalence of anaemia in adult South Africans is 31% in females and 17% in males. Improving the management of anaemia will firstly improve public health, secondly relieve the pressure on the blood supply, and thirdly improve the productivity of the nation's workforce. While high-income countries are increasingly implementing PBM, many middle- and low-income countries are still trying to upscale their transfusion services. The implementation of PBM will improve South Africa's health status while saving costs.

[Summary of the practice guideline 'Thyroid disorders' (first revision) from the Dutch College of General Practitioners]. / Samenvatting van de standaard 'Schildklieraandoeningen' (eerste herziening) van het Nederlands Huisartsen Genootschap.

--The practice guideline 'Thyroid disorders' developed by the Dutch College of General Practitioners replaces the practice guideline 'Functional thyroid disorders' from 1996. Recommendations for palpable thyroid disorders have been added. --Hypothyroidism can often be treated by the general practitioner. The guideline offers specific recommendations for substitution therapy based on the 'start low, go slow'-principle. --Pharmacological treatment of hyperthyroidism is described as an optional activity for general practitioners. --A conservative approach is taken to the treatment of subclinical thyroid dysfunction. The development of symptoms may justify treatment initiation. --Cooperation has improved harmonisation of this practice guideline with the Netherlands Association for Internal Medicine's practice guideline 'Functional thyroid disorders' and the Dutch Institute for Healthcare Improvement's practice guideline 'Thyroid carcinomas'.

[Cerebral infarction due to polycythaemia as the initial manifestation of renal cell carcinoma]. / Herseninfarct door polycytemie als eerste uiting van een niercelcarcinoom.

A 65-year-old man with known diabetes mellitus and hypertension (cardiovascular risk factors) presented to the Emergency Clinic with a transient language disorder and motor- and cognitive-function disorders that had been present for the past half a year. Brain imaging revealed multiple white-matter lesions and a recent infarction. Routine blood tests revealed polycythaemia. Further tests revealed an elevated erythropoietin level and bilateral renal tumours. The cognitive functions improved after repeated phlebotomies and surgical resection of the renal-cell carcinomas. Before surgery, transcranial ultrasound had shown very low cerebral flow velocities, which became normal after correction of the haematocrit. This case emphasises the importance of routine blood tests in patients with suspected cerebral infarction. To our knowledge, this is the first case of cerebral infarction as the first manifestation ofa renal-cell carcinoma.

A model to detect interactions between roxithromycin and oral contraceptives.

Twenty-two healthy women participated in a study to determine whether roxithromycin (a new macrolide antibiotic agent) obtunds the activity of a triphasic oral contraceptive. The duration of the study was four menstrual cycles. Medication was given as follows: (1) cycle 1, no medication to demonstrate ovulation; (2) cycle 2, triphasic oral contraceptive daily to suppress ovulation; (3) cycle 3, triphasic oral contraceptive daily plus roxithromycin, 150 mg b.i.d.; and (4) cycle 4, triphasic oral contraceptive daily plus rifampin, 300 mg daily. Sonography of the ovaries was performed on day 13, and serum progesterone was measured on day 21 of each cycle. Elevated progesterone indicated ovulation. The presence of a maturing follicle supported this finding. All volunteers ovulated in the first cycle and no volunteers ovulated in the second and third cycles. However, 11 women ovulated when rifampin and the triphasic oral contraceptive were given concomitantly. The findings suggest there is no reason to believe that roxithromycin interferes with the efficacy of oral contraceptives.

Differentiation between reactive gliosis and diffuse astrocytoma by in situ hybridization.

The authors examined the use of chromosomal analysis by in situ hybridization to differentiate between nonneoplastic reactive gliosis and astrocytomas in cases in which routine histology was inconclusive. Numerical chromosomal aberrations were found in 80% of low-grade astrocytoma specimens and in none of the reactive gliosis specimens. Aneusomic tumor cells were detected in four of 13 stereotactic samples with an initially inconclusive tissue diagnosis, three of which were later diagnosed as astrocytoma. The in situ hybridization procedure may have additional value in the differential diagnosis of reactive gliosis versus low-grade astrocytoma.

Evaluation of mathematic models to assess platelet kinetics.

Twelve mathematic methods used to calculate the mean platelet survival time were compared by determining the "goodness of fit" of the models to the platelet survival curves of 15 reference subjects and 54 patients. Platelets were labeled with [111In]oxine. The linear (LN), exponential, weighted mean, multiple hit (MH), Dornhorst (DH), Meuleman (ML), alpha order (AO), and polynomial (PO) mathematic models were investigated. The goodness of fit for the exponential model was determined by the nonlinear least squares method (EP), and also by the linear least squares method on logarithmically transformed data (EX) as is recommended. The modified weighted mean (MWM) and the usual weighted mean method (WM) obtained with these exponential models were tested. The Dornhorst (DH10) and Meuleman (ML10) models, where the potential age-dependent platelet survival times were kept constant at 10 days, were also evaluated. The goodness of fit results, expressed as % s.d. indicated that the LN (5.2%), EX (5.0%), EP (4.4%), WM (3.7%), DH10 (3.7%), and ML10 (3.7%) models all fitted the data significantly worse than the MWM, MH, DH, ML, AO, and PO models (range 3.2-3.3%). The mean platelet survival time determined with the MH model differed significantly from the results with the DH, ML, and AO models. The results of mean platelet survival time calculated with different mathematic models cannot, therefore, be compared directly. The models that fitted the platelet survival curve well varied slightly in sensitivity to noise as is indicated by the coefficient of variation of the mean platelet survival time estimates for the reference subjects (range 7.9-12.0%). Fitting data to at least two mathematic models has definite advantages. Data on which the calculations are based are probably invalid if the following are true: (a) if the mean platelet survival time estimated with the alpha order model is shorter than that estimated with the EP, MWM, or MH models, or (b) the mean platelet survival time estimated with either the DH, ML, AO, or PO models, is longer than the LN, MWM, or MH estimate of the mean platelet survival time. We conclude that the mean platelet survival time can be reliably estimated by fitting the data to either the MWM method (if limited computing facilities are available) or the MH model. Confidence in the result will be increased if considered in conjunction with the finding obtained with one other model; in those cases where the platelet survival time is very short, the alpha order model is recommended.(ABSTRACT TRUNCATED AT 400 WORDS)

Kinetics and in vivo distribution of in-111-labelled platelets and platelet function in familial hypercholesterolaemia.

The kinetics, in vivo distribution and sites of sequestration of autologous In-111-labelled platelets and other platelet function parameters were studied in ten patients with type IIa or IIb familial hypercholesterolaemia and thrombotic complications of atherosclerosis. The in vitro platelet aggregation response to ADP (P = 0.50) and collagen (P = 0.46); binding of fibrinogen to platelets (P = 0.61); and plasma beta-thromboglobulin levels (P = 0.42) of the patients and normal reference subjects did not differ significantly. The in vivo distribution of In-111-labelled platelets at equilibrium was within normal limits, and at the end of platelet life-span the sequestration pattern of labelled platelets in the reticuloendothelial system was also normal (spleen P = 0.31; liver P = 0.54). There was minimal evidence of in vivo platelet activation: only mean platelet lifespan (MPLS), 195 +/- 57 hours (difference between mean MPLS of patients and controls was 25 hours, with a 95% confidence interval from 23 to 31 hours; P = 0.02); mean platelet platelet turnover, 2298 +/- 824 platelets/microliter/hour (P = 0.005); plasma platelet factor 4 (P = 0.02); and the mean circulating platelet aggregate ratio, 0.8 +/- 0.1 (P = 0.02); differed significantly from normal. These results suggest that abnormalities of platelet function and kinetics observed in type II hyperlipoproteinaemia cannot be ascribed wholly to the hyperlipidaemia, but may be induced by the associated atherosclerosis.

Indium-111-labelled human platelets: a method for use in severe thrombocytopenia.

We describe and evaluate a simple method for labelling autologous human platelets with Indium-111-oxine in patients with severe thrombocytopenia. Twenty patients with immune thrombocytopenia and platelet counts ranging from 5 to 119 X 10(9)/1 were investigated. Platelets were isolated from blood by differential centrifugation, residual platelets were repeatedly washed from the red cell layer and buffy coat and labelled with In 111 in saline. A mean of 55% +/- 21 of platelets were harvested from the blood, labelled with 49% +/- 24 efficiency and 15.8 X 10(8) labelled platelets reinjected to the patients. Contamination of the platelets with red cells and plasma was low. The labelled platelets were viable as assessed by in vitro aggregation, recovery in the circulation and mean survival time. This method permits quantitative platelet imaging with autologous labelled platelets in patients with severe thrombocytopenia.

Polarization dependent gain in neodymium and ytterbium doped fiber amplifiers.

We present comparative measurements of polarization dependent gain in neodymium and ytterbium doped fiber amplifiers. It is demonstrated, that this effect is always present in neodymium doped fiber amplifiers while under appropriate operation conditions it can be suppressed in ytterbium doped fiber amplifiers.

Novel suppression scheme for Brillouin scattering.

We demonstrate a new scheme for the efficient suppression of Brillouin scattering of a single-frequency laser source in a 72 m-long Neodymium-doped fiber amplifier by simultaneous amplification of two seed lasers separated in wavelength by two times the Brillouin-shift. This scheme can be independently employed in addition to conventional methods of suppressing stimulated Brillouin scattering enabling further power scaling of existing systems.

Kinetics, distribution, and sites of destruction of indium-111 oxine labelled red cells in haemolytic anaemia.

The survival of red cells labelled with indium-111 oxine in the circulation was determined. In vivo distribution at equilibrium and sites of deposition at the T50In--that is, the half life of labelled red cells--were quantitated with a scintillation camera and computer assisted image analysis. Although the rate of elution. Of 111In from the red cells was higher than that of chromium-51-disodium chromate, estimates of T50In and T50Cr corresponded reasonably well and were shortened in haemolytic anaemia. In normal subjects red cells were sequestered mainly in the liver and spleen. In five patients with different types of haemolytic anaemia two distinct patterns of red cell sequestration could be recognised: mainly splenic sequestration, and destruction of red cells in the liver, spleen, and the bone marrow. These patterns were expected for the particular disease studied.