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Background and ObjectivesThe goal of this work was to determine whether locally acting ACE-083 is safe and well tolerated and increases muscle volume, motor function, and quality of life (QoL) in adults with Charcot-Marie-Tooth disease (CMT) type 1.MethodsThis phase 2 study enrolled adults with CMT1 or CMTX (N = 63). Part 1 was open label and evaluated the safety and tolerability of different dose levels of ACE-083 for use in part 2. Part 2 was a randomized, placebo-controlled, 6-month study of 240 mg/muscle ACE-083 injected bilaterally into the tibialis anterior muscle, followed by a 6-month, open-label extension in which all patients received ACE-083. Pharmacodynamic endpoints included total muscle volume (TMV; primary endpoint), contractile muscle volume (CMV), and fat fraction. Additional secondary endpoints included 6-minute walk test, 10-m walk/run, muscle strength, and QoL. Safety was assessed with treatment-emergent adverse events (TEAEs) and clinical laboratory tests.ResultsIn part 1 (n = 18), ACE-083 was generally safe and well tolerated at all dose levels, with no serious adverse events, TEAEs of grade 3 or greater, or death reported. In part 2 (n = 45 enrolled, n = 44 treated), there was significantly greater change in TMV with ACE-083 compared with placebo (least-squares mean difference 13.5%;p= 0.0096). There was significant difference between ACE-083 and placebo for CMV and change in ankle dorsiflexion strength. Fat fraction and all other functional outcomes were not significantly improved by ACE-083. Moderate to mild injection-site reactions were the most common TEAEs.DiscussionDespite significantly increased TMV and CMV, patients with CMT receiving ACE-083 in tibialis anterior muscles did not demonstrate greater functional improvement compared with those receiving placebo.Trial Registration InformationClinical Trials Registration:NCT03124459.Classification of EvidenceThis study provides Class II evidence that intramuscular ACE-083 is safe and well tolerated and increases total muscle volume after 6 months of treatment in adults with CMT1 or CMTX.

INTRODUCTION/AIMS: Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive muscular dystrophy without approved therapies. In this study we evaluated whether locally acting ACE-083 could safely increase muscle volume and improve functional outcomes in adults with FSHD. METHODS: Participants were at least 18 years old and had FSHD1/FSHD2. Part 1 was open label, ascending dose, assessing safety and tolerability (primary objective). Part 2 was randomized, double-blind for 6 months, evaluating ACE-083240 mg/muscle vs placebo injected bilaterally every 3 weeks in the biceps brachii (BB) or tibialis anterior (TA) muscles, followed by 6 months of open label. Magnetic resonance imaging measures included total muscle volume (TMV; primary objective), fat fraction (FF), and contractile muscle volume (CMV). Functional measures included 6-minute walk test, 10-meter walk/run, and 4-stair climb (TA group), and performance of upper limb midlevel/elbow score (BB group). Strength, patient-reported outcomes (PROs), and safety were also evaluated. RESULTS: Parts 1 and 2 enrolled 37 and 58 participants, respectively. Among 55 participants evaluable in Part 2, the least-squares mean (90% confidence interval, analysis of covariance) treatment difference for TMV was 16.4% (9.8%-23.0%) in the BB group (P < .0001) and 9.5% (3.2%-15.9%) in the TA group (P = .01). CMV increased significantly in the BB and TA groups and FF decreased in the TA group. There were no consistent improvements in functional or PRO measures in either group. The most common adverse events were mild or moderate injection-site reactions. DISCUSSION: Significant increases in TMV with ACE-083 vs placebo did not result in consistent functional or PRO improvements with up to 12 months of treatment.

Introduction: PAH is characterized by pulmonary vascular remodeling and right ventricular dysfunction. Sotatercept acts as a reverse remodeling agent proposed to rebalance anti- and pro-proliferative signaling based on pre-clinical models of PAH. Clinical efficacy and safety of sotatercept are being studied in the Phase 2 PULSAR and SPECTRA studies. Sotatercept will be further investigated in a Phase 3 clinical program comprised of 4 studies to establish efficacy, safety, and its potential value on top of background therapy across the spectrum of PAH. Methods: Sotatercept will be administered at a starting dose of 0.3 mg/kg, with a target dose of 0.7 mg/kg, subcutaneously every 21 days. All participants will be on background PAH therapy. The efficacy/safety of sotatercept in patients with WHO FC II/III will be assessed in STELLAR (NCT04576988), a double-blind, placebo-controlled, randomized study. The primary endpoint is change in 6MWD from baseline to week 24. A secondary endpoint is multicomponent improvement (MCI), defined as meeting all the following at week 24 vs baseline: ≥30m increase in 6MWD, decrease in NT-proBNP ≥30% or maintenance/achievement of Results: HYPERION, ZENITH and SOTERIA are active, and STELLAR is recruiting, with a target enrollment of 284 participants. Conclusion: The robust Phase 3 clinical program has the potential to further characterize the efficacy and safety of sotatercept across a broad spectrum of patients with PAH and provide a novel treatment option.

Introduction ACE-083 is a locally acting follistatin-based therapeutic that binds myostatin and other muscle regulators and has been shown to increase muscle mass and force in neuromuscular disease mouse models. This first-in-human study examined these effects. Methods In this phase 1, randomized, double-blind, placebo-controlled, dose-ranging study in healthy postmenopausal women, ACE-083 (50-200 mg) or placebo was administered unilaterally into rectus femoris (RF) or tibialis anterior (TA) muscles as 1 or 2 doses 3 weeks apart. Results Fifty-eight postmenopausal women were enrolled, 42 ACE-083 and 16 placebo. No serious adverse events (AE), dose-limiting toxicities, or discontinuations resulting from AEs occurred. Maximum (mean ± SD) increases in RF and TA muscle volume were 14.5% ± 4.5% and 8.9% ± 4.7%, respectively. No significant changes in mean muscle strength were observed. Discussion ACE-083 was well tolerated and resulted in significant targeted muscle growth. ACE-083 may have the potential to increase muscle mass in a wide range of neuromuscular disorders. Muscle Nerve 57: 921-926, 2018.

Introduction Elevated interleukin (IL)-6 occurs in patients with active rheumatoid arthritis (RA), which has been shown to lead to a decrease in cytochrome P450 (CYP) enzyme activity and alterations in drug concentrations metabolized by CYP. IL-6 signaling blockade by IL-6 receptor (IL-6R) antagonists may reverse this effect of IL-6 and restore CYP activity. This study evaluated the pharmacokinetic profile of simvastatin (a CYP3A4 substrate) before and 1 week after a single dose of sarilumab (a human monoclonal antibody [mAb] blocking the IL-6Rα) in patients with RA, to assess potential interaction. Methods Nineteen patients with active RA received oral simvastatin 40 mg 1 day before and 7 days after subcutaneous injection of sarilumab 200 mg. The pharmacokinetic parameters of simvastatin and its primary metabolite, β-hydroxy-simvastatin acid, were calculated using noncompartmental analysis. Results Compared with simvastatin alone, single-dose simvastatin administration 7 days after single-dose sarilumab administration in patients with RA resulted in reduced simvastatin and β-hydroxy-simvastatin acid exposure in plasma. Mean effect ratios (90 % confidence interval) for simvastatin peak plasma concentration (C max) and area under the concentration–time curve extrapolated to infinity (AUC∞) were 54.1 % (42.2–69.4 %) and 54.7 % (47.2–63.3 %), respectively. No changes occurred in time to C max or half-life for either simvastatin or β-hydroxy-simvastatin acid after sarilumab administration. Conclusions Sarilumab treatment resulted in a reduction in exposure of simvastatin, consistent with reversal of IL-6-mediated CYP3A4 suppression in patients with active RA, as was reported for tocilizumab with simvastatin and for sirukumab with midazolam. Clinical trial registration number NCT02017639. Electronic supplementary material The online version of this article (doi:10.1007/s40262-016-0462-8) contains supplementary material, which is available to authorized users.

Introduction: ACE‐083 is a locally acting follistatin‐based therapeutic that binds myostatin and other muscle regulators and has been shown to increase muscle mass and force in neuromuscular disease mouse models. This first‐in‐human study examined these effects. Methods: In this phase 1, randomized, double‐blind, placebo‐controlled, dose‐ranging study in healthy postmenopausal women, ACE‐083 (50–200 mg) or placebo was administered unilaterally into rectus femoris (RF) or tibialis anterior (TA) muscles as 1 or 2 doses 3 weeks apart. Results: Fifty‐eight postmenopausal women were enrolled, 42 ACE‐083 and 16 placebo. No serious adverse events (AE), dose‐limiting toxicities, or discontinuations resulting from AEs occurred. Maximum (mean ± SD) increases in RF and TA muscle volume were 14.5% ± 4.5% and 8.9% ± 4.7%, respectively. No significant changes in mean muscle strength were observed. Discussion: ACE‐083 was well tolerated and resulted in significant targeted muscle growth. ACE‐083 may have the potential to increase muscle mass in a wide range of neuromuscular disorders. Muscle Nerve 57: 921–926, 2018

Recently, at a post-talk discussion about Kabbalah and the Chassidic communities, I found myself speaking about the work of deepening the psychological and spiritual space encountered in the field ...

The voltammetric determination of dopamine in the presence of ascorbic acid is strongly dependent on the local transport conditions because of the reduction of the product quinone with the ascorbate. Rotating ring-disk electrodes (RRDE) may be applied both to the kinetics of this system and to analytical advantage in detecting trace amounts of ascorbate. In the present work, RRDE techniques were used to determine the rate constant by which oxidized dopamine, generated at the disk, was reduced by ascorbate present in solution. This was accomplished by comparing the current generated at the ring by reduction of unreacted dopamine quinone to the amount predicted by theory for an infinitely fast reaction rate. Rate constants were obtained for ascorbate concentrations from 100 to 400 μM and dopamine concentrations from 2 to 10 mM using three different electrodes. A second-order rate constant of 1.5 × 106 M-1 s-1 was found.

Electrochemical studies of the products of C{sub 60} {gamma}-irradiated in cyclohexane were conducted using the frequency response of hydrodynamic modulation at rotating disk electrodes (HMRDE) to determine transport properties by a methodology independent of the concentration of the electroactive species. The diffusion coefficients of C{sub 60} and its {gamma}-irradiated product were separately determined to be 1.9 {times} 10{sup {minus}6} and 0.96 {times} 10{sup {minus}6} cm{sup 2}/s, respectively, at 50 C. The estimated Stokes radius of the radiolytic product of C{sub 60} approaches twice that of the fullerene itself. Such a result for {gamma}-radiolysis in cyclohexane solution is consistent with the formation of cyclohexane adducts and likely some C{sub 60} dimer.

Intraband modulation in semiconductor gain media has recently been shown to provide a wideband nonlinearity which is five orders of magnitude larger than the Kerr non-linearity in silica fiber. We discuss recent work on the application of this nonlinearity to the wavelength conversion function in all optical networks; specifically, carrier wavelength spectral translation by four-wave mixing. In addition to reviewing the current performance of these devices including conversion efficiency, signal-to-noise and a simple system demonstration, we will describe the underlying physics of the ultra-fast four-wave mixing mechanism and its application to TeraHertz spectroscopy of intraband scattering. An overview of wavelength conversion in the context of all-optical networks is provided and competing techniques to four-wave mixing wavelength conversion are also discussed.

Physical, spectral and chromatographic data for all 209 individual PCB congeners is presented. The individual congeners were synthesized and then isolated and purified.Recent emphasis on the source of the toxicity of commercial PCB formulations has increased the need for a complete set of the PCB congeners. Through the use of two capillary GC columns: 40% octadecyl/ 15% phenyl methyl siloxane and 50% phenyl methyl siloxane, it was possible to separate 201 PCB congeners with only four unresolved pairs. The data compiled in this study for all 209 congeners will aid in the identification of selected individual components of these environmental pollutants. The use of this data also presents the opportunity for the improved quantification of the commercial PCB formulations.

We discuss wavelength tuning and its corresponding quantum efficiency modulated by the standing wave effects in a resonant-cavity enhanced (RCE) photodetector. Specific design conditions are made for a thin In/sub 0.53/Ga/sub 0.47/As (900 /spl Aring/) photodetector wafer-fused to a GaAs-AlAs quarter wavelength stacks (QWS). Analytic expressions for the calculation of resonant wavelength and standing wave effects are derived, using a hard mirror concept of fixed phase upon reflection, and are found to agree reasonably well with the exact numerical approach, using a transmission matrix method. We then experimentally demonstrate that wavelength tuning as large as 140 nm and its corresponding quantum efficiency modulated by the standing wave effects are clearly observed in our wafer-fused photodetectors, consistent with the predictions. The external quantum efficiency at 1.3 /spl mu/m wavelength and absorption bandwidth for the wafer-fused RCE photodiodes integrated with an amorphous Si-SiO/sub 2/ dielectric mirror are measured to be 94% and 14 nm, respectively. This technique allows the formation of multichannel photodetectors with high quantum efficiency and small crosstalk, suitable for application to wavelength demultiplexing and high-speed, high-sensitivity optical communication systems. >

RATIONALE: The tachykinins substance P and neurokinin A (NKA) are implicated in the pathophysiology of asthma. Objective: We tested the safety, tolerability, and pharmacologic and biological efficacy of a tachykinin NK(1)/NK(2) receptor antagonist, AVE5883, in patients with asthma in two double-blind, placebo-controlled crossover studies. METHODS: The pharmacologic efficacy of a single inhaled dose (4.8 mg) of AVE5883 was tested against inhaled NKA in 20 patients with asthma. Subsequently, we studied the biological efficacy of the pharmacologically effective dose on inhaled allergen in a multiple-dose trial (4.8 mg three times per day, 9 d) in 12 patients with asthma with dual responses to inhaled house dust mite. On Day 8, an allergen challenge was conducted, and airway response was measured by FEV(1) until 9 hours postallergen. Exhaled NO, provocative concentration of methacholine bromide causing a 20% fall in FEV(1), and induced sputum were performed on Days 1, 7, and 9. RESULTS: AVE5883 had a bad taste, and transient bronchospasm occurred in some subjects. A single inhaled dose shifted the dose response to NKA by 1.2 doubling doses. Pretreatment with multiple doses of AVE5883 enhanced the allergen-induced early and late airway responses. There were no significant differences in the allergen-induced changes in exhaled NO, provocative concentration of methacholine bromide causing a 20% fall in FEV(1), and sputum cell differentials between placebo and AVE5883. CONCLUSIONS: Despite its demonstrated pharmacologic activity against inhaled NKA, multiple doses of AVE5883 increased the allergen-induced airway responses without affecting markers of airway hyperresponsiveness and airway inflammation. Our data question the prominent role of neurogenic inflammation in asthma and, consequently, the therapeutic potential of dual tachykinin antagonists

Objective: To evaluate immune responses to neoantigen and recall antigens in healthy subjects treated with teriflunomide. Methods: This was a randomized, double-blind, placebo-controlled study. Subjects received oral teriflunomide (70 mg once daily for 5 days followed by 14 mg once daily for 25 days) or placebo for 30 days. Antibody responses were evaluated following rabies vaccination (neoantigen) applied at days 5, 12, and 31 of the treatment period. Occurrence of delayed-type hypersensitivity (DTH) to Candida albicans, Trichophyton, and tuberculin (recall antigens) was assessed before and at the end of treatment to investigate cellular memory response. Safety and pharmacokinetics were evaluated. Results: Forty-six randomized subjects were treated (teriflunomide, n = 23; placebo, n = 23) and completed the rabies vaccination. Geometric mean titers for rabies antibodies were lower with teriflunomide at days 31 and 38 than with placebo. However, all subjects achieved sufficient seroprotection following rabies vaccination (titers well above the 0.5 IU/mL threshold). Overall, the DTH response to recall antigens in the teriflunomide group did not notably differ from responses in the placebo group. Conclusions: Following vaccination, geometric mean titers for rabies antibodies were lower with teriflunomide than with placebo. However, teriflunomide did not limit the ability to achieve seroprotective titers against this neoantigen. Evaluation of DTH showed that teriflunomide had no adverse impact on the cellular memory response to recall antigens. Classification of evidence: This study provides Class II evidence that in normal subjects treated with teriflunomide, antibody titer responses to rabies vaccination are lower than with placebo but sufficient for seroprotection.

The voltammetric characteristics of polycrystalline Au and W electrodes cleaned (thermal annealing at 1100 K) and characterized (Auger electron spectroscopy) in ultrahigh vacuum (UHV) have been examined in ultrapure AlCl 3 /1-ethyl-3-methylimidazolium chloride (EtMeImCl) melts in UHV. These experiments were performed using a custom-designed transfer system that allows for the all-Al electrochemical cell to be filled with EtMeImCl in an auxiliary UHV chamber and later transferred under UHV to the main UHV chamber that houses the Auger electron spectrometer. The results obtained for the underpotential (UPD) and bulk deposition of Al on Au were found to be very similar to those reported in the literature for measurements carried out under 1 atm of an inert gas in a glovebox. For the far more reactive W surfaces, voltammetric features ascribed to the stripping of underpotential-deposited Al could be observed following a single scan from 1.0 V vs Al 3 + /Al to a potential negative enough for bulk deposition of Al to ensue. This behavior is unlike that reported in the literature for experiments performed in a glovebox, which required either extensive potential cycling in the Al bulk deposition and stripping region or excursions to potentials positive enough for chlorine evolution to ensue for Al UPD features to be clearly discerned. These observations open new prospects for fundamental electrochemical studies of well-characterized, highly reactive metals, including single crystals, in a variety of low vapor pressure ionic liquids.

Wavelength conversion is recognized as an important function in future fiber networks employing wavelength division multiplexing. The authors have recently demonstrated broad-band wavelength conversion over spans as large as 27 nm. Their approach uses ultra-fast four-wave mixing dynamics associated with intraband relaxation mechanisms in semiconductor traveling-wave amplifiers (TWA's). In the paper the authors present new results showing conversion over wavelength spans as large as 65 nm. This surpasses the previous record by over a factor of two. Of equal importance, they also verify experimentally their previous theoretical prediction that wavelength conversion efficiency varies as the cube of TWA single pass gain. In the course of our previous work, we have shown that the theoretical efficiency, η, of this process can be expressed by the simple relation: η = 3G + 2P + R(Δ⋋) where η is the ratio in dB of the converted signal output power to the signal input power and G is the single pass TWA optical gain. A crucial point is the presence of 3G in this expression - essentially, the wavelength converter uses the available TWA optimal gain three times. We verified this expression using an experimental setup similar to that described in. Tunable, single-frequency, erbium fiber ring lasers were used as pump and signal sources and TWA devices used contained tensile-strained mutli-quantum well active layers described in. Figure 1 shows conversion efficiency data plotted versus single-pass saturated optical gain. The pump power was -5.2 dBm and the signal power was -11.3 dBm. The measured slope of 3.18 confirms the cubic dependence of efficiency on single pass gain.

Highly nondegenerate four-wave mixing was investigated in a 1.5 µm compressively strained multi-quantum-well semiconductor traveling-wave optical amplifier at detuning frequencies up to 600 GHz. A gain nonlinearity with a characteristic relaxation time of 650 fs was determined from the data, and the nonlinear gain coefficient was estimated to be 4.3×10^–23 m^3. Dynamic carrier heating is believed to be the major source of nonlinear gain in this device at the wavelengths investigated.

THE recent syntheses1,2 of macroscopic quantities of C60 have suggested possible applications in host–guest and organic chemistry, tribology, electrochemistry and semiconductor tech-nology. Here we report the preparation of alkali-metal-doped films of C60 and C70 which have electrical conductivities at room temperature that are comparable to those attained by n-type doped polyacetylene. The highest conductivities observed in the doped films are: 4Scm−1 (Cs/C60), 100 (Rb/C60), 500 (K/C60), 20 (Na/C60), 10 (Li/C60), 2 (K/C70). The doping process is reversed on exposure of the films to the atmosphere. At high doping levels, the films become more resistive. We attribute the conductivity induced in these films to the formation of energy bands from the π orbitals of C60 or C70, which become partially filled with carriers on doping. The smaller alkali metal ions should be able to fit into the interstices in the lattice without disrupting the network of contacts between the carbon spheroids. In the case of C60, this would allow the development of an isotropic band structure, and we therefore propose that these materials may constitute the first three-dimensional 'organic' conductors.

The use of strained layer multiple quantum well optical amplifiers for high frequency modulation and switching of a laser diode output is described. Modulation bandwidth of 1.8 GHz and digital modulation at 2 Gbit/s have been demonstrated.

Nondegenerate four-wave mixing in semiconductor optical amplifiers was studied both as a spectroscopic tool for probing semiconductor dynamics and as a wavelength conversion technique. Four-wave mixing spectra were measured at detuning frequencies ranging from GHz to THz rates and ultrasfast intraband mechanisms having relaxation time constants of 650 fs and less than 100 fs were revealed in the measurements. Cross-polarization four-wave mixing was also measured to study the inter quantum-well carrier transport process in quantum-well amplifiers. In addition, broadband wavelength conversion using four-wave mixing in semiconductor optical amplifiers was investigated. Results concerning the conversion efficiency over spans up to 65 nm, as well as a demonstration of wavelength conversion with gain are presented. The issue of converted signal-to-background noise in this process is also addressed.

Interwell carrier transport in a semiconductor optical amplifier having a structure of alternating tensile and compressively strained quantum wells was studied by four‐wave mixing at detuning frequencies up to 1 THz. A calculation of transbarrier transport efficiency is also presented to qualitatively explain the measured signal spectra.

The efficiency of broadband optical wavelength conversion by four-wave mixing in semiconductor traveling-wave amplifiers is measured for wavelength shifts up to 65 nm using a tandem amplifier geometry. A quantity we call the relative conversion efficiency function, which determines the strength of the four-wave mixing nonlinearity, was extracted from the data. Using this quantity, gain requirements for lossless four-wave mixing wavelength conversion are calculated and discussed. Signal to background noise ratio is also measured and discussed in this study. >

We present a theoretical analysis and experimental measurements of broadband optical wavelength conversion by four-wave mixing in semiconductor traveling-wave amplifiers. In the theoretical analysis, we obtain an analytical expression for the conversion efficiency. In the experiments, both up and down-conversion efficiencies are measured as a function of wavelength shift for shifts up to 27 nm. The experimental data are well explained by the theoretical calculation. The observed higher conversion efficiency for wavelength down-conversion is believed to be caused by phase interferences that exist between various mechanisms contributing to the four-wave mixing process. >

The underlying argument against obesity is that it predisposes to many conditions of significant morbidity and mortality, and the associations are very strong.1 But, just to put a small fly in this ointment, I am unclear why, as …

Ultrafast dynamics in a 1.5‐μm tensile‐strained quantum‐well optical amplifier has been studied by highly nondegenerate four‐wave mixing at detuning frequencies up to 1.7 THz. Frequency response data indicate the presence of two ultrafast physical processes with characteristic relaxation lifetimes of 650 fs and

I suspect that I am not alone in being concerned about the opinions of Dr Des Spence in his recent article revisiting pain and its treatment.1 2 I take issue with six of his most recent assertions.1 This figure is well recognised—for example, a recent report claimed 19% on the basis of interviews with 46 000 people across Europe.3 The standard definition is a pain occurring more than twice a week for more than 6 months and of a severity of more than 5/10. It is a point prevalence, and will include people whose duration of pain is limited, but it clearly describes an …

The authors demonstrate a polarisation insensitive tunable reflective filter, with an integrated in-line optical amplifier providing a net fibre coupled gain for the device. The filter has a spectral width of 10 A FWHM, with 1 A deviation between the TE and TM input polarisations. The filter can be tuned over a spectral range of 95 A. Tunable filter-amplifier devices can be useful for low noise WDM receivers, and for channel selection in WDM networks.

A six-wavelength laser array with an integrated amplifier and modulator designed for transmission of a single selectable wavelength is demonstrated. The lasers have thresholds of ~20 mA, and the single-step printed gratings yield an average channel spacing of 200 GHz. Output powers through the modulator of several milliwatts are obtained from all six lasers when 75 mA is applied to the amplifier.

A novel scheme for a digitally tunable laser requiring only P+Q+1 optical amplifiers for a device with in total P×Q wavelength channels is presented. A 32-channel InP/InGaAsP based device is fabricated. An optimised active layer and low on-chip losses result in a high optical output power.

An electroabsorption modulator integrated with a DBR laser and driven with a dual gate FET forms a transform-limited, wavelength-tunable soliton transmitter. Back-to-back bit error rate measurements at 2.5 Gbit/s are reported.

The authors demonstrate an electroabsorption modulator operating at 1.55 mu m wavelength, which is integrated with passive waveguide gradually tapered spotsize transformers allowing a low loss coupling to cleaved flat optical fibres. The modulator has 10.1 dB total fibre to fibre insertion loss with 15 dB extinction ratio and 300 AA spectral range. The modulator polarisation sensitivity is lower than 0.5 dB. >

Transmission over 192 km of conventional singlemode fibre is achieved using a packaged 1.56 mu m DBR laser-electroabsorption modulator transmitter operating at 5.0 Gbit/s. In an optically amplified system experiment, a dispersion penalty less than 0.5 dB at a bit error rate of 10/sup -9/ is measured. >

The authors have demonstrated a compact (70 µm free-space radiation length), potentially robust, broadband (1.53–1.56 µm), polarisation-insensitive 3 dB optical power splitter based on InP using free-space radiative input-output coupling. This passive, 3 dB splitter is compatible with photonic integrated circuits.

Broadly tunable, narrowband wavelength filters that can be integrated with other photonic devices are important elements for WDM multi/demultiplexing systems. Recently, we have demonstrated a broadly tunable, narrowband wavelength selective grating assisted vertical directional coupler with a 215 A tuning range. In the Letter, an improved version of the vertically stacked buried rib InGaAsP/InP integrable wavelength filter that has a tuning range greater than 370 A is reported.

Summary form only given. Electrically injected long-wavelength vertical cavity lasers (VCLs) employing InGaAsP (1.3 mu m) active regions fused to GaAs-AlAs mirrors on GaAs substrates are demonstrated. The lasers operate pulsed at room temperature (300 K) with a threshold current of 9 mA and a threshold current density of 9.5 kA/cm/sup 2/. These devices operate CW (continuous wave) at temperatures as high as 230 K; the CW threshold current at 230 K is 3.6 mA. The use of the GaAs-AlAs mirror makes the device more mechanically robust, improving the thermal conductivity and reducing problems with nonuniform injection. >

Editor—Taylor et al come to the conclusion that their study of homoeopathy versus placebo in perennial allergic rhinitis “has failed to confirm our original hypothesis that homeopathy is a placebo.”1 Unfortunately, the statistics do not prove that. The basis for the study was a prestudy power calculation that required 120 patients to prove the hypothesis with a 5% significance and an 80% power.2 In fact, the authors only recruited 51 patients but analysed the results as if they had the required number. Their only conclusion was that they did not have enough data to make a conclusion. If we accept the availability of only 51 patients at the outset, what are the relevant calculations? The power calculation is only 43%, and to maintain the power calculation at 80% the P value becomes 34%. The only conclusion is that the trial is not able to prove anything.

The authors report all-optical 100 Gbit/s wavelength conversion employing cross-phase modulation for the first time.