Ultrafast IR spectroscopy of photo-induced electron transfer in self-assembled donor-acceptor coordination cages.

Photo-induced processes in self-assembled coordination cages were studied by femtosecond infrared pump-probe spectroscopy. Densely packed, interpenetrated double cages were constructed from eight bis-monodentate redoxactive ligands bound to four Pd(ii) nodes. Two types of ligands consisting of electron rich phenothiazine (PTZ) or electron deficient anthraquinone (ANQ) chromophores were used to assemble either homo-octameric or mixed-ligand cages. Upon photoexcitation the homo-octameric acceptor cage undergoes intersystem crossing to a long-lived triplet state, similar to the free acceptor ligand. Excitation of the free donor ligand leads to a fluorescent state with intramolecular charge transfer character. This fluorescence is completely quenched in the homo-octameric donor double cage due to a ligand-to-metal charge transfer followed by back electron transfer on a ps timescale. Only for the mixed-ligand cage irradiation produces a charge separated state with an oxidized PTZ radical cation and a reduced ANQ radical anion as proven by their vibrational fingerprints in the transient IR spectra. In dichloromethane the lifetime of this charge separated state extends from tens of ps to >1.5 ns which is attributed to the broad distribution of mixed-ligand cages with different stoichiometry and/or stereo configurations.

Multipass OPCPA system at 100 kHz pumped by a CPA-free solid-state amplifier.

We present a compact few-cycle 100 kHz OPCPA system pumped by a CPA-free picosecond Nd:YVO4 solid-state amplifier with all-optical synchronization to an ultra-broadband Ti:sapphire oscillator. This pump approach shows an exceptional conversion rate into the second harmonic of almost 78%. Efficient parametric amplification was realized by a two stage double-pass scheme with following chirped mirror compressor. The amount of superfluorescence was measured by an optical cross-correlation. Pulses with a duration of 8.7 fs at energies of 18 µJ are demonstrated. Due to the peak power of 1.26 GW, this simple OPCPA approach forms an ideal high repetition rate driving source for high-order harmonic generation.

Developing mental health research in sub-Saharan Africa: capacity building in the AFFIRM project.

BACKGROUND: There remains a large disparity in the quantity, quality and impact of mental health research carried out in sub-Saharan Africa, relative to both the burden and the amount of research carried out in other regions. We lack evidence on the capacity-building activities that are effective in achieving desired aims and appropriate methodologies for evaluating success. METHODS: AFFIRM was an NIMH-funded hub project including a capacity-building program with three components open to participants across six countries: (a) fellowships for an M.Phil. program; (b) funding for Ph.D. students conducting research nested within AFFIRM trials; (c) short courses in specialist research skills. We present findings on progression and outputs from the M.Phil. and Ph.D. programs, self-perceived impact of short courses, qualitative data on student experience, and reflections on experiences and lessons learnt from AFFIRM consortium members. RESULTS: AFFIRM delivered funded research training opportunities to 25 mental health professionals, 90 researchers and five Ph.D. students across 6 countries over a period of 5 years. A number of challenges were identified and suggestions for improving the capacity-building activities explored. CONCLUSIONS: Having protected time for research is a barrier to carrying out research activities for busy clinicians. Funders could support sustainability of capacity-building initiatives through funds for travel and study leave. Adoption of a train-the-trainers model for specialist skills training and strategies for improving the rigor of evaluation of capacity-building activities should be considered.

Generating evidence to narrow the treatment gap for mental disorders in sub-Saharan Africa: rationale, overview and methods of AFFIRM.

There is limited evidence on the acceptability, feasibility and cost-effectiveness of task-sharing interventions to narrow the treatment gap for mental disorders in sub-Saharan Africa. The purpose of this article is to describe the rationale, aims and methods of the Africa Focus on Intervention Research for Mental health (AFFIRM) collaborative research hub. AFFIRM is investigating strategies for narrowing the treatment gap for mental disorders in sub-Saharan Africa in four areas. First, it is assessing the feasibility, acceptability and cost-effectiveness of task-sharing interventions by conducting randomised controlled trials in Ethiopia and South Africa. The AFFIRM Task-sharing for the Care of Severe mental disorders (TaSCS) trial in Ethiopia aims to determine the acceptability, affordability, effectiveness and sustainability of mental health care for people with severe mental disorder delivered by trained and supervised non-specialist, primary health care workers compared with an existing psychiatric nurse-led service. The AFFIRM trial in South Africa aims to determine the cost-effectiveness of a task-sharing counselling intervention for maternal depression, delivered by non-specialist community health workers, and to examine factors influencing the implementation of the intervention and future scale up. Second, AFFIRM is building individual and institutional capacity for intervention research in sub-Saharan Africa by providing fellowship and mentorship programmes for candidates in Ethiopia, Ghana, Malawi, Uganda and Zimbabwe. Each year five Fellowships are awarded (one to each country) to attend the MPhil in Public Mental Health, a joint postgraduate programme at the University of Cape Town and Stellenbosch University. AFFIRM also offers short courses in intervention research, and supports PhD students attached to the trials in Ethiopia and South Africa. Third, AFFIRM is collaborating with other regional National Institute of Mental Health funded hubs in Latin America, sub-Saharan Africa and south Asia, by designing and executing shared research projects related to task-sharing and narrowing the treatment gap. Finally, it is establishing a network of collaboration between researchers, non-governmental organisations and government agencies that facilitates the translation of research knowledge into policy and practice. This article describes the developmental process of this multi-site approach, and provides a narrative of challenges and opportunities that have arisen during the early phases. Crucial to the long-term sustainability of this work is the nurturing and sustaining of partnerships between African mental health researchers, policy makers, practitioners and international collaborators.

Measurements of double-polarized compton scattering asymmetries and extraction of the proton spin polarizabilities.

The spin polarizabilities of the nucleon describe how the spin of the nucleon responds to an incident polarized photon. The most model-independent way to extract the nucleon spin polarizabilities is through polarized Compton scattering. Double-polarized Compton scattering asymmetries on the proton were measured in the Δ(1232) region using circularly polarized incident photons and a transversely polarized proton target at the Mainz Microtron. Fits to asymmetry data were performed using a dispersion model calculation and a baryon chiral perturbation theory calculation, and a separation of all four proton spin polarizabilities in the multipole basis was achieved. The analysis based on a dispersion model calculation yields γ(E1E1)=-3.5±1.2, γ(M1M1)=3.16±0.85, γ(E1M2)=-0.7±1.2, and γ(M1E2)=1.99±0.29, in units of 10(-4) fm(4).

Methadone is a local anaesthetic-like inhibitor of neuronal Na+ channels and blocks excitability of mouse peripheral nerves.

BACKGROUND: Opioids enhance and prolong analgesia when applied as adjuvants to local anaesthetics (LAs). A possible molecular mechanism for this property is a direct inhibition of voltage-gated Na(+) channels which was reported for some opioids. Methadone is an effective adjuvant to LA and was recently reported to inhibit cardiac Na(+) channels. Here, we explore and compare LA properties of methadone and bupivacaine on neuronal Na(+) channels, excitability of peripheral nerves, and cell viability. METHODS: Effects of methadone were explored on compound action potentials (CAP) of isolated mouse saphenous nerves. Patch clamp recordings were performed on Na(+) channels in ND7/23 cells, the α-subunits Nav1.2, Nav1.3, Nav1.7, and Nav1.8, and the hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2). Cytotoxicity was determined using flow cytometry. RESULTS: Methadone (IC50 86-119 µM) is a state-dependent and unselective blocker on Nav1.2, Nav1.3, Nav1.7, and Nav1.8 with a potency comparable with that of bupivacaine (IC50 177 µM). Both bupivacaine and methadone also inhibit C- and A-fibre CAPs in saphenous nerves in a concentration-dependent manner. Tonic block of Nav1.7 revealed a discrete stereo-selectivity with a higher potency for levomethadone than for dextromethadone. Methadone is also a weak blocker of HCN2 channels. Both methadone and bupivacaine induce a pronounced cytotoxicity at concentrations required for LA effects. CONCLUSIONS: Methadone induces typical LA effects by inhibiting Na(+) channels with a potency similar to that of bupivacaine. This hitherto unknown property of methadone might contribute to its high efficacy when applied as an adjuvant to LA.

Neutron skin of (208)pb from coherent pion photoproduction.

Information on the size and shape of the neutron skin on (208)Pb is extracted from coherent pion photoproduction cross sections measured using the Crystal Ball detector together with the Glasgow tagger at the MAMI electron beam facility. On exploitation of an interpolated fit of a theoretical model to the measured cross sections, the half-height radius and diffuseness of the neutron distribution are found to be c(n)=6.70±0.03(stat.) fm and a(n)=0.55±0.01(stat.)(-0.03)(+0.02)(sys.) fm, respectively, corresponding to a neutron skin thickness Δr(np)=0.15±0.03(stat.)(-0.03)(+0.01)(sys.) fm. The results give the first successful extraction of a neutron skin thickness with an electromagnetic probe and indicate that the skin of (208)Pb has a halo character. The measurement provides valuable new constraints on both the structure of nuclei and the equation of state for neutron-rich matter.

[Update on the pharmacology and effects of local anesthetics]. / Update zu Pharmakologie und Wirkung von Lokalanästhetika.

Local anesthetics (LA) are broadly used in all disciplines and it could be considered that relatively little is reflected on the mechanisms of action of this old substance group. However, several molecular mechanisms of LAs mediating wanted and unwanted effects remain to be explored. Furthermore, the number of indications for application of LAs seems to be expanding. The local anesthetic effect of LAs is primarily mediated by a potent inhibition of voltage-gated sodium channels. However, this effect is due to much more than the interaction of LAs with one single molecule. Most recent studies indicated that the development of selective local anesthetics might be possible and LAs also interact with several other membrane molecules. Although the relevance of these effects is still unclear, they might play a role in systemic analgesia, tissue protection and anti-inflammatory effects of LA. The therapeutic index of systemically applied LA is very narrow. Systemic application is formally not permitted because the impending systemic toxicity is still a life-threatening complication. Although the cardiac and central nervous toxicity at least partly result from an unselective block of neuronal and cardiac sodium channels, preclinical studies suggest the involvement of several mechanisms. A local LA toxicity is less clinically impressive; however, all LAs induce a significant tissue toxicity for which the underlying mechanisms have been partly identified. This review reports on recent findings on mechanisms and on the clinical relevance of some LA-induced effects which are of relevance for anesthesiological activities.

Photoproduction of π0 mesons off neutrons in the nucleon resonance region.

Precise angular distributions have been measured for the first time for the photoproduction of π0 mesons off neutrons bound in the deuteron. The effects from nuclear Fermi motion have been eliminated by a complete kinematic reconstruction of the final state. The influence of final-state-interaction effects has been estimated by a comparison of the reaction cross section for quasifree protons bound in the deuteron to the results for free protons and then applied as a correction to the quasifree neutron data. The experiment was performed at the tagged photon facility of the Mainz Microtron MAMI with the Crystal Ball and TAPS detector setup for incident photon energies between 0.45 and 1.4 GeV. The results are compared to the predictions from reaction models and partial-wave analyses based on data from other isospin channels. The model predictions show large discrepancies among each other and the present data will provide much tighter constraints. This is demonstrated by the results of a new analysis in the framework of the Bonn-Gatchina coupled-channel analysis which included the present data.

The opioid methadone induces a local anaesthetic-like inhibition of the cardiac Na⁺ channel, Na(v)1.5.

BACKGROUND AND PURPOSE: Treatment with methadone is associated with severe cardiac arrhythmias, a side effect that seems to result from an inhibition of cardiac hERG K⁺ channels. However, several other opioids are inhibitors of voltage-gated Na⁺ channels. Considering the common assumption that an inhibition of the cardiac Na⁺ channel Na(v)1.5, is the primary mechanism for local anaesthetic (LA)-induced cardiotoxicity, we hypothesized that methadone has LA-like properties leading to a modulation of Na(v)1.5 channels. EXPERIMENTAL APPROACH: The whole-cell patch clamp technique was applied to investigate the effects of methadone on wild-type and mutant human Na(v)1.5 channels expressed in HEK293 cells. A homology model of human Na(v)1.5 channels was used to perform automated ligand-docking studies. KEY RESULTS: Methadone inhibited Na(v)1.5 channels in a state-dependent manner, that is, tonic block was stronger with inactivated channels than with resting channels and a use-dependent block at 10 Hz. Methadone induced a concentration-dependent shift of the voltage dependency of both fast and slow inactivation towards more hyperpolarized potentials, and impaired recovery from fast and slow inactivation. The LA-insensitive mutants N406K and F1760A exhibited reduced tonic and use-dependent block by methadone, and docking predictions positioned methadone in a cavity that was delimited by the residue F1760. Dextromethadone and levomethadone induced discrete stereo-selective effects on Na(v)1.5 channels. CONCLUSIONS AND IMPLICATIONS: Methadone interacted with the LA-binding site to inhibit Na(v)1.5 channels. Our data suggest that these channels are a hitherto unrecognized molecular component contributing to cardiac arrhythmias induced by methadone.

Narrow structure in the excitation function of η photoproduction off the neutron.

The photoproduction of η mesons off nucleons bound in 2H and 3He has been measured in coincidence with recoil protons and recoil neutrons for incident photon energies from threshold up to 1.4 GeV. The experiments were performed at the Mainz MAMI accelerator, using the Glasgow tagged photon facility. Decay photons from the η→2γ and η→3π0 decays and the recoil nucleons were detected with an almost 4π electromagnetic calorimeter combining the Crystal Ball and TAPS detectors. The data from both targets are of excellent statistical quality and show a narrow structure in the excitation function of γn→nη. The results from the two measurements are consistent, taking into account the expected effects from nuclear Fermi motion. The best estimates for position and intrinsic width of the structure are W=(1670±5) MeV and Γ=(30±15) MeV. For the first time precise results for the angular dependence of this structure have been extracted.

[The bipolar cup Avantage in hip revision surgery]. / Die bipolare Pfanne Avantage in der Hüftrevisionschirurgie.

BACKGROUND: Luxations in revision arthroplasty are a serious complication with an incidence of up to 30 percent. In particular in patients with previous operation and resection of bone and soft tissue, the instability increases significantly. The use of the bipolar revision cup Avantage has to be proven valuable to avoid recurrent luxation. METHODS AND PATIENTS: 27 consecutive revisions of the bipolar acetabular component were performed. The mean age at the time of revision was 67 years (range 40-91 years). The mean rate of previous operations was 5.1 cases (range 1-14). In 11 hips (40.7%) the acetabular cup was revised, in 16 hips (59.3%) an additional stem revision was performed. In 10 cases the revision was performed by a proximal femur reconstruction, in one patient by a total femur reconstruction. The follow-up was short-term, at a mean of 20 months (range 13-29 months). The clinical results were evaluated prospectively by the Harris hip score (HHS) and the activity score according to Sutherland (aSL). The migration of the cup and the change of the inclination angle were calculated radiographically. RESULTS: There has been one dislocation of the polyethylene liner in the recent follow-up, which could be treated conservatively by closed reduction. No patients required reoperation because of technical errors or loosening of the bipolar acetabular implant. The HHS improved from a mean of 40.5 (range 7-77.4) to 66.8 points (range 17.4-89.9). The modified Sutherland score improved to 5.9 (range 3-9) of 10 possible points. Radiographic follow-up revealed neither evidence of component loosening nor migration or polyethylene wear. CONCLUSION: Use of this bipolar unconstrained component was successful in restoring stability in hip revision arthroplasty, e.g., in patients with severely unstable hips. It has to be observed carefully if there are any disadvantages of these devices because of higher polyethylene wear in the mid- or long-term follow-up. The possible disadvantages of dissociations between the inner liner from the outer liner or damage of the polyethylene liner limits the indication of this device to serious revision cases.

Beam-helicity asymmetries in double-pion photoproduction off the proton.

Beam-helicity asymmetries have been measured at the MAMI accelerator in Mainz in the three isospin channels gamma[over -->]p-->pi(+)pi(0)n, gamma[over -->]p-->pi(0)pi(0)p, and gamma[over -->]p-->pi(+)pi(-)p. The circularly polarized photons, produced from bremsstrahlung of longitudinally polarized electrons, were tagged with the Glasgow magnetic spectrometer. Charged pions and the decay photons of pi(0) mesons were detected in a 4pi electromagnetic calorimeter which combined the Crystal Ball detector with the TAPS detector. The precisely measured asymmetries are very sensitive to details of the production processes and are thus key observables in the modeling of the reaction dynamics.

Incoherent neutral pion photoproduction on 12C.

We present the first detailed measurement of incoherent photoproduction of neutral pions to a discrete state of a residual nucleus. The 12C(gamma,pi(0))(12)C*(4.4 MeV) reaction has been studied with the Glasgow photon tagger at MAMI employing a new technique which uses the large solid angle Crystal Ball detector both as a pi(0) spectrometer and to detect decay photons from the excited residual nucleus. The technique has potential applications to a broad range of future nuclear measurements with the Crystal Ball and similar detector systems elsewhere. Such data are sensitive to the propagation of the Delta in the nuclear medium and will give the first information on matter transition form factors from measurements with an electromagnetic probe. The incoherent cross sections are compared to two theoretical predictions including a Delta-hole model.

Measurement of the Gerasimov-Drell-Hearn Integrand for 2H from 200 to 800 MeV.

A measurement of the helicity dependence of the total inclusive photoabsorption cross section on the deuteron was carried out at MAMI (Mainz) in the energy range 200

Limits on the high-energy gamma and neutrino fluxes from the SGR 1806-20 giant flare of 27 December 2004 with the AMANDA-II detector.

On 27 December 2004, a giant gamma flare from the Soft Gamma-Ray Repeater 1806-20 saturated many satellite gamma-ray detectors, being the brightest transient event ever observed in the Galaxy. AMANDA-II was used to search for down-going muons indicative of high-energy gammas and/or neutrinos from this object. The data revealed no significant signal, so upper limits (at 90% C.L.) on the normalization constant were set: 0.05(0.5) TeV-1 m;{-2} s;{-1} for gamma=-1.47 (-2) in the gamma flux and 0.4(6.1) TeV-1 m;{-2} s;{-1} for gamma=-1.47 (-2) in the high-energy neutrino flux.

Measurement of helicity-dependent photoabsorption cross sections on the neutron from 815 to 1825 MeV.

Helicity-dependent total photoabsorption cross sections on the deuteron have been measured for the first time at ELSA (Bonn) in the photon energy range from 815 to 1825 MeV. Circularly polarized tagged photons impinging on a longitudinally polarized LiD target have been used together with a highly efficient 4pi detector system. The data around 1 GeV are not compatible with predictions from existing multipole analyses. From the measured energy range an experimental contribution to the GDH integral on the neutron of [33.9 +/- 5.5(stat) +/- 4.5(syst)] microb is extracted.

Experimental check of the Gerasimov-Drell-Hearn sum rule for 1H.

For the first time we checked the fundamental Gerasimov-Drell-Hearn (GDH) sum rule for the proton experimentally in the photon energy range from 0.2-2.9 GeV with the tagged photon facilities at MAMI (Mainz) and ELSA (Bonn). New data of the doubly polarized total cross section difference are presented in the energy range from 1.6 to 2.9 GeV. The contribution to the GDH integral from 0.2-2.9 GeV yields [254+/-5(stat)+/-12(syst)] microb with negative contributions in the Regge regime at photon energies above 2.1 GeV. This trend supports the validity of the GDH sum rule.

Photoproduction of eta-mesic 3He.

The photoproduction of eta-mesic 3He has been investigated using the TAPS calorimeter at the Mainz Microtron accelerator facility MAMI. The total inclusive cross section for the reaction gamma3He-->etaX has been measured for photon energies from threshold to 820 MeV. The total and angular differential coherent eta cross sections have been extracted up to energies of 745 MeV. A resonancelike structure just above the eta production threshold with an isotropic angular distribution suggests the existence of a resonant quasibound state. This is supported by studies of a competing decay channel of such a quasibound eta-mesic nucleus into pi(0)pX. A binding energy of (-4.4+/-4.2) MeV and a width of (25.6+/-6.1) MeV is deduced for the quasibound eta-mesic state in 3He.

Search for extraterrestrial point sources of neutrinos with AMANDA-II.

We present the results of a search for point sources of high-energy neutrinos in the northern hemisphere using AMANDA-II data collected in the year 2000. Included are flux limits on several active-galactic-nuclei blazars, microquasars, magnetars, and other candidate neutrino sources. A search for excesses above a random background of cosmic-ray-induced atmospheric neutrinos and misreconstructed downgoing cosmic-ray muons reveals no statistically significant neutrino point sources. We show that AMANDA-II has achieved the sensitivity required to probe known TeV gamma-ray sources such as the blazar Markarian 501 in its 1997 flaring state at a level where neutrino and gamma-ray fluxes are equal.