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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.

Drones have been increasing in popularity and are able to cause skin injuries ranging from minor abrasions to severe lacerations. The objective of this study was to determine the aspects of drone blades that cause injuries, and to help manufacturers design safer drones by suggesting an injury threshold. The blade tip thickness, blade length, angular velocity, and blade tip speed of a variety of popular drones were measured. The injury caused by each drone blade contacting a fetal bovine skin surrogate at different speeds was recorded. Blade tip speed had the highest correlation to injury severity, while blade tip thickness, blade length, and rpm had little to no correlation with the resulting injury. Blade tip speeds above 25 m/s resulted in minor abrasions, and speeds above 60 m/s resulted in minor lacerations. To prevent severe injuries, drone manufacturers should design drones with blade tip speeds below the threshold of 60 m/s.

Drones have been increasing in popularity and are able to cause skin injuries ranging from minor abrasions to severe lacerations. The objective of this study was to determine the aspects of drone blades that cause injuries, and to help manufacturers design safer drones by suggesting an injury threshold. The blade tip thickness, blade length, angular velocity, and blade tip speed of a variety of popular drones were measured. The injury caused by each drone blade contacting a fetal bovine skin surrogate at different speeds was recorded. Blade tip speed had the highest correlation to injury severity, while blade tip thickness, blade length, and rpm had little to no correlation with the resulting injury. Blade tip speeds above 25 m/s resulted in minor abrasions, and speeds above 60 m/s resulted in minor lacerations. To prevent severe injuries, drone manufacturers should design drones with blade tip speeds below the threshold of 60 m/s.

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.

Our ideas of masculinity are in continuous evolution, devolution, and reformulation. Collectively we experience these shifts through the troubling, exciting, dangerous, and creative ways in which we encounter the “masculine” psyche. The reflections here are based on personal experience in the arena where masculinity is responding to itself: in the experience of primary contact when observing the bodies of other men. The observations focus on tendencies being manifest currently in the behaviors men are exhibiting in private space for men, exploring the ways men feel and do not feel comfortable being seen and seeing others. This very fundamental experience, observing and being observed, is (considered in the context of all male environments where nudity had been and might be implicit in the encounter. The men's locker room is the setting for these observations, spaces that historically have been arenas for open male association and are now increasingly becoming spaces of modesty and distancing between men. ...

As older age groups continue to account for an increasing portion of the US population, the burden of cancer and other age-associated disease becomes a larger public health concern. Due to limited population data, however, disease surveillance statistics are typically truncated at age 84 years and then grouped into a terminal age category of ≥85 years. We used more detailed older age data from the 2010 census in conjunction with Surveillance, Epidemiology, and End Results cancer registry records for 2008-2012 diagnoses to estimate 5-year age-specific incidence rates through ages 90-94 years and ≥95 years for major cancers. Overall cancer rates increased to a maximum in the 80-89-year ranges and subsequently declined. Incidence rates peaked in younger age groups for several specific cancers, including breast, cervix uteri, corpus uteri, and prostate. Whereas, rates for colon and rectum, leukemia, melanoma, pancreas, stomach, and urinary bladder continued to rise among men and women into their early 90s. Rates of liver and intrahepatic bile duct cancer showed an initial spike among men aged 60-64 years followed by a larger peak at ages 80-84. Since these age-specific incidence patterns were based on cross-sectional data, they may vary over time for some cancers (eg, lung and liver) as the prevalence of major risk factors change across birth cohorts. Future studies using new, publicly available databases with these additional older age groups can examine cancer subtypes defined by our emerging understanding of molecular biomarkers. There is a need for accurate annual post-census population estimates for older age categories to enable continuous monitoring of disease dynamics among these rapidly growing population groups.

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 ...

Cheating, as a psychological mechanism, is common to all, weaving through early family dynamics and evolving sexual identities. When it erupts in our love relationships, confusion, destruction, and de-integration of existing psychological states occur for all those affected by the cheating. The eruption of cheating can be viewed as a spontaneous response of the individual to disrupt a state of psychological stagnation and regression that may have no conscious path for dissolution. The transgressive actions bring up the possibility of a secret or separated consciousness, potentially breaking into states of existing merger in the established relationship system. This prior state of adaptation may have provided stability and security, while limiting the development of a separated consciousness with its urge toward acknowledgement. These essential, spontaneous elements in cheating can be found in Jung's later description of the psychology of the transference, where illicit impulses are seen at the foundation of the drive for individuation. The familiar psychological complex of the one betrayed is also explored, highlighting the potential for maturation in the one most wounded by the cheating. Clinical material is utilized here to amplify the relationship between cheating and the need for psychological evolution.

Homosexuality, as a description and category of human experience, has a long, complicated and problematic history. It has been utilized as a carrier of theological, political, and psychological ideologies of all sorts, with varying and contradictory influences into the lives of us all. Analytical psychology, emphasizing the purposiveness found in manifestations of the psyche, offers a unique approach to this subject. The focus moves from causation to the meanings embedded in erotic expressions, fantasies, and dreams. Consequently, homosexuality loses its predetermined meaning and finds its definition in the psychology of the individual. Categories of ‘sexual orientation’ may defend against personal analysis, deflecting the essential fluidity and mystery of Eros. This is illustrated with samples of the variety found in ‘homosexual’ material. Translations of Abstract L’homosexualite comme description et comme categorie de l’experience humaine a une histoire longue et problematique. Elle a ete le vehicule d’ideologies en tous genres, theologiques, politiques et psychologiques, avec des effets variables et contradictoires dans nos vies. La psychologie analytique, mettant l’accent sur la dimension teleologique presente dans les manifestations de la psyche, fournit un angle d’approche unique de cette question. L’accent se deplace de la causalitea la polysemie des expressions erotiques, des fantasmes et des reves. Par consequent, l’homosexualite se desencombre de ses significations predeterminees et trouve a se definir dans la psychologie de l’individu. Les categories d’« orientation sexuelle » peuvent constituer une defense contre l’analyse personnelle, empechant la fluidite essentielle et le mystere de l’Eros. Ceci est illustre par des vignettes temoignant de la diversite du materiel clinique dit « homosexuel ». Homosexualitat als Beschreibung und Kategorie menschlicher Erfahrung hat eine lange, komplizierte und problematische Geschichte. Sie ist als Trager benutzt worden fur theologische, politische und psychologische Ideologien aller Art mit wechselnden und widerspruchlichen Einflussen auf unser aller Leben. Die Analytische Psychologie, die die Intentionalitat in den seelischen Manifestationen betont, bietet einen einzigartigen Zugang zu diesem Thema. Der Fokus wechselt von der Verursachung zu den Bedeutungen, die erotischen Ausdrucksformen, Phantasien und Traumen zukommen. In der Konsequenz verliert die Homosexualitat ihre herkommliche Bedeutung und findet ihre Definition in der Psychologie des Einzelnen. Kategorien der ‘sexuellen Orientierung’ mogen sich gegen personliche Analyse stellen, mogen von der wesenhaften Fluiditat und dem Geheimnis des Eros ablenken. Dies wird durch Beispiele illustriert, die in der Vielfalt von ‘homosexuellem’ Material zu finden sind. L’omosessualita in quanto descrizione e categoria dell’esperienza umana ha una storia lunga, complicata e problematica. E’ stata utilizzata come contenitore di ideologie teologiche, politiche e psicologiche di ogni tipo con influenze varie e contraddittorie nella vita di noi tutti. La psicologia analitica, enfatizzando l’intenzionalita delle manifestazioni della psiche, offre un approccio unico a tale soggetto. L’attenzione si sposta dalla causa al significato nascosto nelle espressioni erotiche, nelle fantasie e nei sogni. Di conseguenza l’omosessualita perde il suo significato predeterminato e trova le sue definizioni nella psicologia dell’ individuo. Categorie quali ‘orientamento sessuale’ possono difenderci dall’analisi personale, deviando la nostra attenzione dalla fluidita essenziale e dal mistero di Eros. Cio verra illustrato con esempi vari tratti da materiali ‘omosessuali’. La homosexualidad, como una descripcion y categoria de la experiencia humana, tiene una larga, complicada y problematica historia. Ha sido utilizada como portadora de ideologias teologicas, politicas y psicologicas de todo tipo, con variadas y contradictorias influencias en las vidas de todos nosotros. La psicologia analitica, acentuando la busqueda de sentido en las manifestaciones de la psique, ofrece un enfoque extraordinario al respecto. El foco se motoriza de la causalidad de los significados enquistados en las expresiones eroticas, en las fantasias, y en los suenos, a la busqueda de su proposito. En consecuencia, la homosexualidad pierde su significado predeterminado y encuentra su definicion en la psicologia del individuo. Las categorias de ‘orientacion sexual’ pueden defendernos contra el analisis personal, desviando la fluidez y el misterio esenciales de Eros. Esto es ilustrado con muestras de la variedad encontrada en material ‘homosexual’.

Objective: To establish if there is a role for gabapentin or nortriptyline in the treatment of chronic orchialgia. Methods: Twenty-six consecutive patients with chronic orchialgia were seen in the chronic pain clinic by a multidisciplinary team. A pain questionnaire was completed prior to commencing either gabapentin or nortriptyline. They were reviewed at 3 months and a repeat questionnaire completed. A 50% improvement in pain was considered successful. Results: Complete data was available for 19 patients. Overall, 61.5% of patients commenced on gabapentin and 66.6% of patients commenced on nortriptyline had a greater than 50% improvement in pain. Patients with post-vasectomy testicular pain were considered as a subgroup. None of these patients had a greater than 50% improvement in pain. However, 80% of patients in the subgroup with idiopathic chronic orchialgia had a greater than 50% improvement in pain. Conclusion: Although this is a small study, it appears that gabapentin and nortriptyline are effective in the treatment of idiopathic chronic orchialgia but not post-vasectomy pain.

Recovery and the postoperative period are times of significant physiological change, and, as with induction, the risks of complications and the need for rapid responses are at their greatest. The importance of controlled management and monitoring is discussed in this article. Airway control and breathing remain the most important aspects, and these are principally affected by residual muscular blockade, changing inhalational gas mixtures and returning reflex and conscious activity. The issues surrounding the assessment and appropriate management of muscular block, and the importance of maintaining oxygenation and normocapnia are emphasized. The various groups of sedating agents and the difficulties in their reversal are reviewed. The recovery period on the general ward is also examined, with particular emphasis on the provision and value of oxygenation, fluid management and analgesia.

This paper explores the dynamic tension between an evolving collective phenomenon and the nature of analytic process. Specifically, the focus will be erotic experiences which acquire a meaning through the culture at large, a meaning that may not be supportable when that material is subjected to psychological analysis. This stimulates a conflict between the symbolic attitude and the cultural perspective of the time. While the struggle between the individual and collective consciousness always emerges in analysis, the subject of same-gender sexual relations has become such a controversial and divisive issue in the current political environment that views toward homosexuality demand powerful allegiances and identification with either historic or contemporary ideas. People now identify as ‘gay’ and tend to see themselves as something akin to a race or perhaps alternative gender. Sexuality and relationship between same gendered people tends to be viewed through the lens of civil rights and the undeniable need for social equality. In this far-reaching and expanding collective phenomenon, psychology, in its support of human rights and accommodation to emerging trends, may be diminished in its capacity to pursue the meaning inherent in these human experiences. The position developed in this paper is that psychological experience, whether in the imaginal realm, dreams or personal consciousness, must be available for full analysis. Clinical experience and dreams are used to amplify this challenge to dynamic analytic practice.

Background Very late antigen (VLA-4) antagonists have been proposed as potential therapies for diseases in which cell recruitment and accumulation are causative. Asthma, which is characterized by airway inflammation involving the accumulation of eosinophils and mononuclear cells, is one such disease. Objective We sought to assess the effect of IVL745, a VLA-4 antagonist, on the early and late asthmatic response (LAR) and on markers of airway inflammation after allergen inhalation. Methods The study was of a placebo-controlled, double-blind, randomized, 2-way crossover design. Sixteen subjects with mild-to-moderate asthma controlled with short-acting β 2 -agonists only and with a LAR to inhaled allergen participated in the study. At one treatment period they took 20 mg of IVL745 and one treatment period placebo. Both treatments were taken twice daily for 7 days, with a single dose on day 8. Treatments were separated by a washout period of at least 2 weeks. On day 7 of each treatment period, sputum was induced and collected, and exhaled nitric oxide (NO) was measured. On day 8, an inhaled bolus allergen challenge was performed, and blood was taken for pharmacokinetics. On day 9, exhaled NO was measured, and a methacholine challenge was done. On day 10, sputum was induced and collected. Adverse events, peak expiratory flow (PEF), use of short-acting β 2 -agonists, and asthma symptoms were recorded daily throughout the study. Results There was no statistically significant difference between IVL745 and placebo in the effect on the LAR after allergen challenge, as measured by the area under the curve of the percentage change in FEV 1 from the prechallenge baseline (mean [SEM], −81.99 [18.80] after IVL745 and −72.58 [21.29] after placebo; 95% CI of difference, −36 to 16.8; P = .46) or by the maximum percentage change from the prechallenge baseline (mean [SEM], −23.44 [4.73] after IVL745 and −21.30 [5.17] after placebo; 95% CI of difference, −11 to 6.29; P = .60). There was a statistically significant decrease in the percentage of eosinophils in sputum on day 7 of treatment with IVL745 (mean [SEM], 7.32 [1.46]) compared with placebo (mean [SEM], 15.00 [1.92]; 95% CI of difference, −13 to −1.2; P = .02). There was no statistically significant difference between IVL745 and placebo with respect to the early asthmatic response, methacholine hyperresponsiveness, exhaled NO, postallergen sputum, symptoms, inhaled β 2 -agonist use, or PEF. Conclusion In patients with mild-to-moderate atopic asthma, IVL745 did not affect the early and late response to inhaled allergen or markers of airway inflammation, except for a modest reduction in sputum eosinophils.

The stepwise electrochemical oxidation of p-methoxyphenol and hydroquinone at boron-doped diamond (BDD) electrodes was investigated in perchloric acid media using rotating ring–disk electrode (RRDE) and hydrodynamic modulation techniques. Initial oxidation of these compounds to p-benzoquinone at the disk may be confirmed by reduction of the quinone at the ring electrode. Further oxidation, ultimately to CO2, can be followed by the loss of redox active products at the ring. Comparison of BDD anodic activity to those of graphite, gold, and platinum electrodes, utilizing RRDE configurations, shows that the high oxygen evolution overpotential exhibited by BDD allows for more efficient anodic conversion of p-methoxyphenol and hydroquinone to products beyond the quinone stage. BDD, unlike the other electrode materials, showed no corrosion or fouling when used under these conditions. These results complement product analysis studies by other groups on BDD for organic contaminant remediation by exhaustive electrolysis.

A new reflective configuration for a monolithically integrated channel selector with power monitor is proposed. One star coupler, one arrayed waveguide grating, and a minimum number of semiconductor optical amplifier (SOA) gates are used to achieve loss-free transmission. A 32-channel device controlled by only 12 SOA gates is realized in InP. Low on-chip losses result in strongly reduced bias currents and an improved signal to noise ratio compared to previously demonstrated devices. The use of SOAs allows for switching on a nanosecond time scale.

Rotating and hydrodynamically modulated rotating disk electrodes of boron-doped diamond (BDD) and tetrahedral amorphous nitrogen incorporated carbon (taC : N) were employed to extend analytical sensitivity and linear current response of these materials for dopamine analysis at physiological pH to 200 nM. Hydrodynamically modulated rotating disk electrode (HMRDE) techniques discriminate against nonmass transfer limited components, allowing more complete implementation of the wider electrochemical window of these materials. Experiments performed in the presence of ascorbate showed typical catalytic enhancement of the dopamine oxidation current and a corresponding loss of response to dopamine quinone at the ring in a rotating ring-disk electrode (RRDE) configuration. Utilizing these phenomena, a RRDE method for simultaneous determination of both dopamine and ascorbate concentrations in solutions containing comparable levels of both species is presented.

A mode-adapted semiconductor optical amplifier (SOA) has been fabricated and packaged. At the gain peak, 1500 nm, the fiber to fiber gain was measured to be 32.5 dB. Statistics for eight packaged devices indicate that a fiber-to-fiber gain of 26.3 dB /spl plusmn/ 1.3 dB and a saturation output power of 12.4 dBm /spl plusmn/ 0.4 dBm are typical at a bias of 500 mA for /spl lambda/ = 1550 nm. Polarization sensitivity at 1550 nm was measured to be 1.1 dB /spl plusmn/ 0.4 dB and the transverse electric (TE) polarization state noise figure (NF) was determined to be 7.0 dB /spl plusmn/ 0.5 dB. The coupling loss was 1.3 dB /spl plusmn/ 0.1 dB per facet. This SOA, with a 1.3-nm filter, was used as an optical preamplifier in a 10-Gb/s return-to-zero (RZ) system testbed with a pseudorandom binary sequence (PRBS) of 2/sup 31/ -1. A 14.5-dB improvement in receiver sensitivity was observed at a bit error rate (BER) of 10/sup -11/.

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.

Self-assembly of C60 molecules on planar n- or p-type Si(100) has been accomplished by direct tethering onto the Si surface without using any intermediate functional hydrocarbon chain. Photoresponse has been observed on these monolayer modified electrodes in both aqueous and nonaqueous media. The p-type Si(100) surface with a bound C60 monolayer is also capable of mediating redox reactions. These C60 monolayer modified Si electrodes are very stable in both acidic aqueous and polar nonaqueous solvents. Characterization by fast atom bombardment mass spectroscopy (FAB−MS) suggests that simultaneous hydrosilylation and hydrogenation reactions account for the nature of the monolayer formation.

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.

The mechanisms of silver and mercury metal deposition on boron-doped diamond electrodes were investigated using a prior model of three-dimensional diffusion controlled nucleation/growth to interpret the data. The mechanism of nucleation depends upon the nucleation overpotential and metal ion concentration. At low overpotentials, instantaneous nucleation can be observed and, at high overpotentials or concentrations, the process becomes progressive. No underpotential phenomena are observed, consistent with exceptionally weak interaction between the deposited metal and the diamond surface. Active sites corresponding to a low density of surface sites on the electrode which act as critical nuclei during the electrodeposition. Anodic reactions of silver were also investigated. It was found that the resulting product depends on the silver concentration in the solution. Soluble Ag(II) forms only at low concentration (

Morphological, spectroscopic, and electrochemical aspects of boron-doped diamond (BDD) films grown on silicon surfaces originating from three different laboratories have been examined by atomic force microscopy (AF), Raman scattering, Auger electron spectroscopy, and cyclic voltammetry in polyethylene oxide LiClO{sub 4} electrolytes in ultrahigh vacuum. All specimens displayed AFM images characteristic of diamond and Raman spectra consistent with a wide range of boron concentrations (10{sup 19} to 10{sup 21} B atom/cm{sup 3}), with no evidence for the presence of gross graphitic impurities. The cyclic voltammetry of two of the specimens (denoted as GV2 and CWRU), however, showed features at potentials positive to lithium bulk deposition attributed to lithium-ion intercalation/deintercalation phenomena in non-diamond carbon present as a surface impurity, perhaps at the grain boundaries. This finding is consistent with earlier results for a specimen of type GV2 in aqueous electrolytes for which rates of heterogeneous electron transfer for certain redox couples were found higher than those for nominally clean BDD surfaces.

Postoperative nausea and vomiting (PONV) is a common and distressing event following surgery. About one in four patients are affected. It has an associated morbidity and mortality caused by both the direct effects of vomiting and the difficulties in managing other aspects of postoperative care. This article discusses the five principal areas to be considered when assessing and managing the risks of PONV: premorbid patient issues; the immediate preoperative situation; the nature of the proposed surgery; anaesthetic technique; and the postoperative circumstances. Advances in the understanding of normal physiology and the pathophysiological states induced by any surgical intervention have revealed that a multimodal approach is essential to manage this condition. Treatment must begin in the preoperative period and aim to reduce both physical and psychological risk factors. The anaesthetic technique must be tailored to the type and length of surgery, and a postoperative plan created to reduce the incidence of PONV and provide effective treatments. The importance of the role of polypharmacy is also discussed.

Electronic and structural aspects of a MnO{sub 2} electrode in a rechargeable MnO{sub 2}/Zn battery environment have been investigated by in situ Mn K-edge x-ray absorption fine structure (XAFS). The relative amplitudes of the three major Fourier transform shells of the extended XAFS function of the rechargeable MnO{sub 2} electrode in the undischarged state were similar to those found for ramsdellite, a MnO{sub 2} polymorph with substantial corner-sharing linkages among the basic MnO{sub 6} octahedral units. The analyses of the background-subtracted pre-edge peaks and absorption edge regions for the nominally 1-e{sup {minus}} discharged electrode were consistent with Mn{sup 3+} as being the predominant constituent species, rather than a mixture of Mn{sup 4+} and Mn{sup 2+} sites. Furthermore, careful inspection of both the x-ray absorption near edge structure and EXAFS indicated that the full recharge of MnO{sub 2}, which had been previously discharged either by one or two equivalent electrons, generates a material with decreased corner-sharing linkages compared to the original undischarged MnO{sub 2}.

We present a novel coupling scheme consisting of an integrated beam expander, a specifically tailored TiO/sub 2/ antireflection coating, optical index matching gel, and uncoated flat-end single-mode fiber (SMF). This scheme was used to package four-channel semiconductor optical amplifier arrays. Far-field profiles for each discrete amplifier in the array are typically 80 and 150 FWHM, perpendicular and parallel to the junction plane, respectively. The TiO/sub 2/ AR coating overcomes the indices mismatching of fiber glass and InP based device, and reduce optical reflection to 0.002% at 1.55 /spl mu/m. Misalignment tolerance in the l-dB excess loss range, for a discrete channel, is typically 5 /spl mu/m vertically and 8 /spl mu/m laterally. The average coupling loss is 4.3 dB per facet for the devices measured. Fiber coupled small signal gain for the amplifiers is typically 11.6 dB and a saturation output power of 3.0 dBm. The method of characterization and optimization of the TiO/sub 2/ coating is discussed.

Since the introduction of practical work in DNA technology to school science courses, there has been a need to expand on the limited set of available protocols to demonstrate further biological principles. The current paper sets out two additional practical exercises which can be used in schools. The first experiment involves restriction analysis of bacteriophage lambda DNA to map its cos sites, and in the second experiment the effect of methylation of lambda DNA on restriction enzyme digestion is examined. Based on practical exercises already widely available, these protocols extend analysis of actual molecular events and aid in their interpretation (Miller, 1993, 1994; Madden, 1993; Harrison, Sampson, and Harrison, 1992).

Following the introduction of practical work in DNA technology to school science courses using the inexpensive DNA kits produced by Science and Plants for Schools (SAPS) and the National Centre for Biotechnology Education (NCBE), there is a need to expand the limited set of available protocols. This paper describes a computer simulation for schools and colleges which complements the laboratory work with DNA kits. This enables a pupil to predict initial restriction maps which may later be checked by electrophoresis. It outlines the principles of construction of restriction maps from base (or nucleotide) sequence and gel electrophoresis data. Keywords: DNA, Restriction analysis, Mapping

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.

Near field holography is a method of using grating photomasks in which the m = -1 and m = 0 diffracted beams of a UV source interfere to form a standing wave pattern. This simple hologram can then be used to expose a grating pattern on a process wafer when held in near- contact. This technique is especially attractive for use in OEICs and PICs when fabrication of the grating masks is accomplished with e-beam lithography and dry etching, since the diffractive properties of the mask can be controlled by the physical parameters of the mask. The grating period on masks made in this way can be precisely controlled to produce arrays of lasers each separated by only a small change in frequency (order 100 GHz) as may be required for WDM applications. We review the phenomenology of fused silica phase grating masks and describe work toward establishing characterization criteria, implementing practical printing methods, improving e-beam precision, and demonstrating laser array performance. We discuss principle issues and progress in each of the technical areas.

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. >

The next generation of undersea lightwave systems is likely to take advantage of the nonlinear properties of the transmission fiber by employing optical solitons [1,2]. A critical component will be the transmitter which generates the solitons and encodes the data. Previously, we have reported a monolithic extended-cavity laser, which actively mode-locked, generates solitons [3], An extended-cavity laser integrated with a modulator exhibited multi-peaked pulses due to internal reflections and a corresponding time bandwidth product of 0.8, which would prohibit soliton applications [4], Here, we report the first monolithic semiconductor transmitter which has applications in soliton systems. An extended-cavity laser section generates 8-ps solitons by active mode-locking and data is encoded by means of the integrated modulator at a bit rate of 4.9 Gbit/s. The optical pulses exhibit a time-bandwidth product of 0.30 and the extinction ratio of the monolithically integrated electro-absorption modulator is 20 dB.

We present a new design for a digitally tunable laser using two waveguide grating routers with different free spectral range. For an N-channel device, both the number of required amplifiers and the number of required grating arms scale as the square root of N, resulting in a more compact device than previously demonstrated and better scaleability. Contrary to previously demonstrated devices with a reduced number of amplifiers, all wavelength channels are multiplexed together in one common channel, allowing for a higher output power. Tuning speeds below 10 ns are envisioned. Experimental results are presented.

The U.S. Department of Defense (DOD) is the largest single user of energy in the United States (U.S.) [2], representing 0.8% of the total U.S. energy consumed and 78% of the energy consumed by the Federal government. Approximately 25% of DOD energy use is consumed by its buildings and facilities. The DOD currently has 316,238 buildings across 5429 sites translating to a monetary value of $450B [3]. The Office of the Secretary of Defense (OSD) has published an energy policy to ensure the DOD infrastructure is secure, safe, reliable and efficient [4]. The realization of this OSD energy policy, within the DOD, is being guided by (1) the Energy Policy Act of 2005, (2) Executive Order (EO) 13423, and (3) the Energy Independence and Security Act of 2007, to ensure a 30% energy reduction by 2015. The Policy Act of 2005, as well as EO 13423, has set a minimum contribution of renewable energy from DOD s installations of 5% by fiscal year (FY)2012 and no less than 7.5% beginning FY2013 [5]. Under the Distributed Power Systems for Sustainable Energy project described in this report, United Technologies Research Center (UTRC) in collaboration with the University of Wisconsin Madison (UWM), has demonstrated the key technologies that will enable scalable deployment of distributed power sources and energy storage. These key technologies have been demonstrated in such a way that the distributed power sources would appear as a single stable entity to the electrical grid. The technologies demonstrated as part of this project, when adopted, will provide the infrastructure and controls required for efficient and reliable use of renewable energy sources. These microgrids will provide the largest opportunity for reducing external grid utilization, reducing the environmental impact associated with the use of non-renewable sources, and is an important step toward the required security of energy supply at DOD installations.

The introduction of practical work in DNA technology to school science courses is hampered by the current lack of suitable procedures, by the cost of the equipment, and by the fact that many of the reagents used in research in this field are toxic. The recent development of the science has meant that relatively few biology teachers have practical experience of DNA techniques during their training. The inclusion of theoretical work in genetic engineering in current syllabuses indicates the demand for accompanying practical work. This paper outlines an approach which is both innovative and sufficiently straightforward for immediate incorporation into school practical courses. In-service training would facilitate the introduction of such work.

A photonic circuit implementing ten frequency reference filters for narrow-channel wavelength division multiplexing (WDM) has been fabricated. A diluted multiquantum-well waveguide structure is shown to yield a very low TE/TM polarization dependence of 1 AA, as well as improved absolute frequency control and reproducibility. A standard deviation in absolute filter wavelength of 3.33 AA is measured on a random set of devices from a 2-in wafer. The ten channels are evenly spaced by 7.2 AA. Such filters can be used to lock tunable lasers to a set of reference frequencies for WDM applications. The demonstrated diluted multiquantum-well waveguide structure with low birefringence and improved absolute wavelength control could potentially be used in other WDM integrated circuits requiring tight wavelength tolerance and polarization insensitivity. >