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The opportunistic pathogen Pseudomonas aeruginosa (Pa) causes severe nosocomial infections, especially in immunocompromised individuals and the elderly. Increasing drug resistance, the absence of a licensed vaccine and increased hospitalizations due to SARS-CoV-2 have made Pa a major healthcare risk. To address this, we formulated a candidate subunit vaccine against Pa (L-PaF), by fusing the type III secretion system tip and translocator proteins with LTA1 in an oil-in-water emulsion (ME). This was mixed with the TLR4 agonist (BECC438b). Lung mRNA sequencing showed that the formulation activates genes from multiple immunological pathways eliciting a protective Th1-Th17 response following IN immunization. Following infection, however, the immunized mice showed an adaptive response while the PBS-vaccinated mice experienced rapid onset of an inflammatory response. The latter displayed a hypoxic lung environment with high bacterial burden. Finally, the importance of IL-17 and immunoglobulins were demonstrated using knockout mice. These findings suggest a need for a balanced humoral and cellular response to prevent the onset of Pa infection and that our formulation could elicit such a response.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of infections in humans. In addition to its innate antibiotic resistance, P. aeruginosa is very effective in acquiring resistance resulting in the emergence of multi-drug resistance strains and a licensed vaccine is not yet available. We have previously demonstrated the protective efficacy of a novel antigen PaF (Pa Fusion), a fusion of the type III secretion system (T3SS) needle tip protein, PcrV, and the first of two translocator proteins, PopB. PaF was modified to provide a self-adjuvanting activity by fusing the A1 subunit of the heat-labile enterotoxin from Enterotoxigenic E. coli to its N-terminus to give L-PaF. In addition to providing protection against 04 and 06 serotypes of P. aeruginosa, L-PaF elicited opsonophagocytic killing and stimulated IL-17A secretion, which have been predicted to be required for a successful vaccine. While monomeric recombinant subunit vaccines can be protective in mice, this protection often does not transfer to humans where multimeric formulations perform better. Here, we use two unique formulations, an oil-in-water (o/w) emulsion and a chitosan particle, as well as the addition of a unique TLR4 agonist, BECC438 (a detoxified lipid A analogue designated Bacterial Enzymatic Combinatorial Chemistry 438), as an initial step in optimizing L-PaF for use in humans. The o/w emulsion together with BECC438 provided the best protective efficacy, which correlated with high levels of opsonophagocytic killing and IL-17A secretion, thereby reducing the lung burden among all the vaccinated groups tested.

Pseudomonas aeruginosa is an opportunistic pathogen responsible for a wide range of infections in humans. In addition to its innate antibiotic resistance, P. aeruginosa is very effective in acquiring resistance resulting in the emergence of multi-drug resistance strains and a licensed vaccine is not yet available. We have previously demonstrated the protective efficacy of a novel antigen PaF (Pa Fusion), a fusion of the type III secretion system (T3SS) needle tip protein, PcrV, and the first of two translocator proteins, PopB. PaF was modified to provide a self-adjuvanting activity by fusing the A1 subunit of the heat-labile enterotoxin from Enterotoxigenic E. coli to its N-terminus to give L-PaF. In addition to providing protection against 04 and 06 serotypes of P. aeruginosa, L-PaF elicited opsonophagocytic killing and stimulated IL-17A secretion, which have been predicted to be required for a successful vaccine. While monomeric recombinant subunit vaccines can be protective in mice, this protection often does not transfer to humans where multimeric formulations perform better. Here, we use two unique formulations, an oil-in-water (o/w) emulsion and a chitosan particle, as well as the addition of a unique TLR4 agonist, BECC438 (a detoxified lipid A analogue designated Bacterial Enzymatic Combinatorial Chemistry 438), as an initial step in optimizing L-PaF for use in humans. The o/w emulsion together with BECC438 provided the best protective efficacy, which correlated with high levels of opsonophagocytic killing and IL-17A secretion, thereby reducing the lung burden among all the vaccinated groups tested.

While the etiology of multiple sclerosis (MS) remains unclear, research from the clinic and preclinical models identified the essential role of inflammation and demyelination in the pathogenesis of MS. Current treatments focused on anti-inflammatory processes are effective against acute episodes and relapsing-remitting MS, but patients still move on to develop secondary progressive MS. MS progression is associated with activation of microglia and astrocytes, and importantly, metabolic dysfunction leading to neuronal death. Neuronal death also contributes to chronic neuropathic pain. Metabolic support of neurons by glia may play central roles in preventing progression of MS and chronic neuropathic pain. Here, we review mechanisms of metabolic cooperation between glia and neurons and outline future perspectives exploring metabolic support of neurons by glia.

Background Idiopathic recurrent acute pleuro-pericarditis (IRAP) is an increasingly recognised autoinflammatory disease comprising post-pericardiotomy-syndrome, recurrent pericarditis and post-myocardial-infarction-syndrome. Different autoimmune mechanisms were discussed in the past. Recently, IRAP is considered as an autoinflammatory disease. Therapeutic options comprise colchicine, prednisolone and interleukin (IL)−1beta blockingagents. Objectives to investigate whether idiopathic and post-interventional pleuro-pericarditis represent a clinical spectrum and to identify treatment options. Methods This study analyses demographic, clinical and laboratory features of post-interventional and idiopathic pleuro-pericarditis and adult onset Still’s disease (AOSD) as a reference. Patients with infectious disease, connective tissue disease, chronic heart failure, renal failure and other non-exsudative effusions were excluded from this analysis. Patients with IRAP were treated with colchicine, prednisolone and IL1β blocking agents. Results Between 2005 and 2017 66 cases of idiopathic and post-interventional pleuro-pericarditis were identified and compared to 83 cases of AOSD. Clinical and laboratory features suggest that idiopathic and post-interventional pleuro-pericarditis represent a clinical spectrum which is identical with IRAP. Prednisolone was started with 25 mg to 125 mg and tapered to less than 7 mg or discontinued if not effective. 47 of 66 patients (71%) were treated with prednisolone and 10/47 (21%) were in remission with no need of any further therapeutically escalation. Colchicine was given to 44/66 patients (67%) and 29/44 (66%) were in complete remission. Four of 66 patients (6%) did not respond or had contraindications against colchicine or prednisolone and were treated with anakinra. Of these patients 4/4 (100%) were in remission. During the follow-up period of 20 patient*months 2 of 4 patients maintained the remission with anakinra every 2nd day and two patients discontinued anakinra and remained in remission. Conclusions 1. post-pericardectomy-syndrome, post-myocardial-infarction-syndrome and idiopa-thic recurrent pericarditis represent a clinical spectrum of autoinflammatory diseases. 2. treatment options comprise colchicine as a first-line therapy, prednisolone and anti-IL1 blocking agents. Acknowledgements none. Disclosure of Interest None declared

Equipping teachers to use data is a critical piece of the school improvement puzzle. To help early career teachers (ECT) develop data-use acumen, some districts utilize mentoring supports. While research on mentoring in general is well-developed, research on how mentoring can or does support data-informed practice is not. To address this gap, we examined perceptions about data use in a small Texas district; anticipated differences among comparison groups (i.e., mentors and non-mentors; mentors and ECT) did not emerge. We conclude that without careful selection and supports, mentors may not be able to support data-informed practice to the degree assumed.

Die Wertigkeit der radikalen transurethralen Resektion der Prostata beim lokal begrenzten Prostatakarzinom (TURPC) als alternative Therapie wird in einer prospektiven Studie untersucht. Von Januar 1995 bis Juli 2008 wurden 533 Patienten mit einem medianen Alter von 67 (40–89) Jahren mit klinisch lokalisiertem Prostatakarzinom mit kurativer Intention vom Erstautor reseziert. Die Verteilung des Stadiums war (in %): pT1: 8, pT2: 61, pT3: 31, und G1: 2, G2: 80, G3: 18. Die TURPC erfordert die Niederdruckdauerspulung mit einem Flussigkeitsniveau im Irrigationsgefas auf einer Hohe von

AIM The present clinical trial was performed to assess the clinical and radiological outcome after operative treatment of proximal humeral fractures using the T-plate. METHODS All patients who were treated with the T-plate were included into the study. Patient satisfaction,complications and radiological findings were assessed. The clinical results were evaluated using the Constant-Murley score, the UCLA score, and the DASH score. Between December 1996 and October 2003, 74 patients (with 76 fractures)were treated with the T-plate. Surgically treated complications were 2 hematomas and 3 failures of the osteosynthesis under functional physiotherapy. In 19 patients the implants were removed because of persisting complaints. RESULTS After an average follow-up period of 67 months 52 patients (54 fractures) were examined. According to the Neer classification there were 34 2-part, 15 3-part and 5 4-part fractures.80% of the patients were satisfied with the result. According to the evaluated scores, 74 to 89% of the patients had an excellent to satisfactory outcome. CONCLUSION The T-plate enables the stable fixation of complex proximal humeral fractures and permits even in the elderly patient an early functional treatment. Anatomical reconstruction and stable fixation followed by early rehabilitation are most important to achieve a good functional outcome in the patient.

Evidence suggests that differential rearing influences the function of a receptor subtype critical for maintaining glutamate homeostasis. Maintaining homeostatic glutamatergic function may be an important protector against drug abuse.This study sought to determine if differential rearing influences the function of a receptor critical for glutamate homeostasis, which could in turn affect rates of amphetamine self-administration.Rats were assigned to enriched (EC), isolated (IC), or standard (SC) conditions. After rearing for 30 days, rats were trained to lever press for sucrose reinforcement before the implantation of indwelling jugular catheters. After reaching stable responding for amphetamine (0.03 or 0.1 mg/kg/infusion), rats were injected with five doses (0, 0.3, 1.0, 3.0, and 5.0 mg/kg) of the mGluR5 antagonist, 3-((2-methyl-1,3-thiazol-4-yl)ethynyl) pyridine hydrochloride (MTEP), 30 min before self-administration sessions. Following fixed-ratio (FR-1) testing, rats were administered identical doses of MTEP on a progressive-ratio (PR) reinforcement schedule.MTEP (3.0 mg/kg) attenuated FR-1 self-administration (0.03 mg/kg/infusion) in IC rats. MTEP also dose-dependently attenuated amphetamine self-administration (0.1 mg/kg/infusion) during FR-1 and PR sessions, with 5.0 mg/kg MTEP attenuating amphetamine self-administration in IC and SC rats and 3.0 mg/kg MTEP attenuating amphetamine self-administration in EC and SC rats. PR results also revealed that IC rats not treated with MTEP were more motivated to self-administer the higher dose of amphetamine.These results suggest that the mGlu5 receptor mediates differences in drug-taking behavior among differentially reared rats. Isolation also decreased sensitivity to MTEP, suggesting that environmental factors alter glutamate homeostasis which subsequently affects sensitivity and motivation to self-administer amphetamine.

The structure of the Lindblad equation of motion of quantum states is discussed. General specifications for this motion to lead asymptotically into equilibrium states are given. Incomplete 'thermalization', i.e. the Lindblad motion of only a selected subset of quantum states leads to a reduced quantum system whose observables are explicitly constructed and seen to incorporate memory terms. It is shown that under rather general conditions the absolute value of Lindblad operators is given by the (inverse square root of the) grand-canonical probability distribution.

Ziel: Die Altersbestimmung ist eine immer grosere Herausforderung in der forensischen Odontologie geworden, einerseits in Bezug auf die Anzahl der zu untersuchenden Probanden, andererseits bedingt durch die weltweite Migration und den dazu notwendigen Qualitatsanspruch hinsichtlich der odontologischen Beurteilung bei Strafverfahren. Ziele der vorliegenden Untersuchung waren die Bestimmung der Durchbruchszeiten von bleibenden Zahnen bei Kindern und Jugendlichen anhand einer Longitudinalstudie und der Vergleich dieser Ergebnisse mit der deutschen und internationalen Literatur.

Fifty-three men and 56 women viewed brief video segments of 32 male targets and rated them on three personality traits: extraversion, neuroticism, and masculinity-femininity (M-F). Judges were assessed on general intelligence, Big Five traits, and gender-related traits. Two measures of accuracy were computed: 1) consensus accuracy, which measured the correlation between judges' ratings and corresponding ratings made by previous judges, and 2) trait accuracy, which measured the correlation between judges' ratings and targets' assessed personality. There was no gender difference in overall accuracy. However, women showed higher trait accuracy than men in judging neuroticism. Consensus accuracy exceeded trait accuracy, and extraversion and M-F were judged more accurately than neuroticism. M-F judgments showed the highest level of consensus accuracy. Judges' intelligence correlated positively with accuracy. Except for openness, personality traits were generally unrelated to accuracy.

A theoretical framework for the description of the pulse‐induced reaction dynamics of molecules interacting with short, intense laser pulses is derived. Born–Oppenheimer adiabaticity is formulated in terms of quasistationary Floquet states; its violation and the structure of the potential mixing electronic levels, and thus effecting this violation, is discussed; it is shown that, on the basis of quasistationary states, this potential is (to a very good approximation) nonvanishing only around near degeneracies in the quasienergy spectrum where it has a simple two‐level structure. Ab initio calculations showing the effectivity of this scheme are performed for the H2 molecule. Particular emphasis is put on bond‐softening reactions; a new mechanism is described.

1. [1,2]-14C-Ethylene glycol (EG) was given to female CD (Sprague-Dawley) rats and CD-1 mice in order to determine tissue distribution and metabolic fate after intravenous (iv), peroral (po), and percutaneous (pc) doses. Rats were given doses of 10 or 1000 mg/kg by each route, and additional pc doses of 400, 600 or 800 mg/kg. Mice were also given iv and po doses of 10 or 1000 mg/kg, and intermediate po doses of 100, 200 or 400 mg/kg. Mice were given po doses of 100 or 1000 mg/kg, and both species were given a 50% (w/w) aqueous po dose to simulate antifreeze exposure. 2. For both species, EG is very rapidly and almost completely adsorbed after po doses. Perorally administered EG doses produced similar dose-dependent relationships described in prior studies for the disposition and excretion of iv doses. 3. The tissue distribution of EG following either iv or po routes was essentially the same, with similar percentages recovered for each dose by both routes and for either species. 4. Cutaneously-applied EG was slowly and rather poorly adsorbed in both species, in comparison with po-dose administration, and urinalysis after undiluted po doses indicated that EG probably penetrates rat skin in the parent form. There was an absence in both species of dose-dependent changes in disposition and elimination following the pc application of EG. 5. 14C-labelled EG, glycolic acid and/or oxalic acid accounted for the majority of the detectable radioactivity in the urine samples from all dose routes in the rat, while glycoaldehyde and glyoxylic acid were not detected in any of the urine fractions evaluated. Similar increases in glycolate production with increasing dose were also observed in mouse urine samples from iv and po dosing. Also, glyoxylate and oxalate were absent from mouse urine. 6. Oxidative metabolic pathways appeared to be saturated at high po doses in both species, resulting in a shift from principally 14CO2 exhalation to urinary 14C excretion, while the onset of capacity-limited metabolic changes appears to occur at lower doses for mice than for rats. 7. In summary, rats and mice displayed several similarities in the manner in which low doses of EG by several routes are distributed, metabolized, and excreted, but the onset of capacity-limited changes in metabolism occurs at lower doses for mice than for rats. Such differences in the disposition of EG may provide important interpretive information to help explain differences observed in developmental toxicity and nephrotoxic responses between these two rodent species.

It is shown that the shape dependence of final state probability distributions in pulsed laser–atom or molecule interactions has a simple explanation in the theory of quantum transport of Floquet states. More precisely, the predictions of a quasienergy resonance model—complex poles in the quasienergy plane produced by quantum transport and populated by state‐mixing at near‐degeneracies—are successfully compared with numerical solutions of the initial value problem of the Schrodinger equation for a Morse‐potential model.

The time evolution of atoms or molecules under the influence of a pulse of a single mode laser is most effectively described in the space of quasistationary Floquet states. Separating in this way the fast and slow time scales involved one finds that the time evolution is determined by the singularities in the quasienergy complex plane in strict analogy to the stationary case. Employing the Λ transformation we calculate quasienergies and the corresponding Floquet states perturbatively. We show, for the case of an H2 molecule, that Λ‐transformed many body perturbation theory is an excellent tool for the calculation of quasienergies and quasistationary states even for very intense laser fields. We then show that the evolution of the system in an effective two‐level subsystem allows for a quantitative calculation of transition probabilities.

In recent years, novel techniques have been developed to achieve high laser field intensities by shortening the duration of the pulses after several stages of amplification (by first stretching and subsequently compressing mode-locked laser pulses). A laser system built according to these principles at Imperial College is described. It is capable of reaching powers of ~ 1018 W cm−2 in pulse lengths of about 1 ps. The availability of field strengths 10 to 100 times as strong as the field experienced by the electron of the hydrogen atom in the first Bohr orbit opens up a new regime in the study of the interaction between light and matter. In particular, several effects, characteristic of very strong AC fields such as "above threshold ionisation" (ATI) high harmonic generation, etc are observed. Examples are given and their implications for atomic physics are discussed. Although such effects are novel and interesting in their own right, an important question which arises is the extent to which they may reveal new characteristics specific to the atom under study. Alternative possibilities are that most of the atomic features (correlations, shell structure, etc) are swamped by the effects of the strong field, or else that the atom is ionised before the strong field regime can even be reached. Some account of the controversies surrounding this question is given, and the importance of the dynamics is stressed. A theory is described which accounts for multiphoton excitation and ionisation by pulses of intense laser light in a generalised Landau-Zener model within a dressed atom basis of Floquet states. Different regimes of the interaction are classified, and a semi-classical limit is illustrated using action-angle plots of the Poincare section. These reveal how excitation takes place across a separatrix between two modes of motion, and how the growth of chaotic trajectories near such a separatrix provides new paths leading to ionization. Our approach stresses the significance of the match between pulse rise time and the magnitude of the avoided crossings between dressed atom states for the atom or molecule concerned.

Hypophosphatasia (HPP) is a heterogeneous rare, inherited disorder of bone and mineral metabolism caused by different mutations in the ALPL gene encoding the isoenzyme, tissue-nonspecific alkaline phosphatase (TNAP). Prognosis is very poor in severe perinatal forms with most patients dying from pulmonary complications of their skeletal disease. TNAP deficiency, however, may also result in neurological symptoms such as neonatal seizures. The exact biological role of TNAP in the human brain is still not known and the pathophysiology of neurological symptoms due to TNAP deficiency in HPP is not understood in detail. In this report, we describe the clinical features and functional studies of a patient with severe perinatal HPP which presented with rapidly progressive encephalopathy caused by new compound heterozygous mutations in the ALPL gene which result in a functional ALPL "knock out", demonstrated in vitro. In contrast, an in vitro simulation of the genetic status of his currently asymptomatic parents who are both heterozygous for one mutation, showed a residual in vitro AP activity of above 50%. Interestingly, in our patient, the fatal outcome was due to progressive encephalopathy which was refractory to antiepileptic therapy including pyridoxine, rather than hypomineralization and respiratory insufficiency often seen in HPP patients. The patient's cranial MRI showed progressive cystic degradation of the cortex and peripheral white matter with nearly complete destruction of the cerebrum. To our knowledge, this is the first MRI-based report of a deleterious neurological clinical outcome due to a progressive encephalopathy in an infant harboring a functional human ALPL "knock out". This clinical course of disease suggests that TNAP is involved in development and may be responsible for multiple functions of the human brain. According to our data, a certain amount of residual TNAP activity might be mandatory for normal CNS function in newborns and early childhood.

We present a theory of harmonic generation by a strongly driven atom within the framework of non-relativistic QED. The atom is assumed to possess a finite number N of levels and ionization is neglected. This atom is dressed by the driving field using a unitary time-dependent transformation. Within the quasistatic approximation this transformation is shown to lead from the bare to the Floquet atom. The interaction of the Floquet atom with the vacuum modes is derived and it is shown to give rise both to the high-order harmonic and to the hyper-Raman spectrum. In the case N=2 the spectrum of the light scattered into the vacuum modes can be evaluated analytically and it is shown to consist of two parts. Neglecting interference between these two parts, the first of them is the high-order harmonic spectrum displaying peaks at the odd harmonics of the driving field. The second part is the hyper-Raman spectrum which has finite bandwidth and which displays peaks at the even harmonics of the laser frequency, centred at the Stark-shifted natural atomic frequency. These two spectra partially overlap and they are discussed in various ranges of intensity of the driving field, both in the minimal coupling and in the multipolar scheme. The results support recent suggestions that the presence of the plateau is related to interference between the two spectra. The dependence of the high-order harmonic spectrum from the driving field intensity is found to be related to that of the hyper-Raman spectrum in such a way that when the former increases the latter decreases and vice versa. It is argued that this might help to explain the non-visibility of the hyper-Raman lines when the high-order harmonics are visible.

We explicitly construct a convergent perturbation series for intrinsically divergent Moller—Plesset cases. The means to accomplish this goal is an explicit reduction of the size of the perturbation. This is achieved by means of a Λ transformation and an unlinked-graph shift. Generic multi-reference cases are treated by single-reference methods after a simple and feasible transformation of the Hamiltonian matrix to a basis comprising a suitable reference zero-order vector. This effectively solves the intruder-state problem. We present the 1Δ state of C2 and the H2 ground state at large bond distance as typical examples.

We develop a method that allows the investigation of adiabatic evolution in periodically driven quantum systems. It is shown how Berry's geometrical phase emerges in quantum optics. We analyse microwave experiments performed on Rydberg atoms and suggest a new, non-perturbative mechanism to produce excited atomic states.

A new procedure for the splitting of many‐body Hamiltonians into ‘‘free’’ and ‘‘interaction’’ parts is proposed which leads to a rapidly converging perturbation expansion. The efficiency of this method is shown for the case of small molecules: Already first and second order perturbations turn out to produce very reasonable results even for excited states; higher terms rapidly converge to zero. An important point to notice is that our method allows for a priori estimates of the convergence (or divergence) behavior.

We show that discontinuities in the vacuum polarisation give rise to charge screening effects which are large and result in a lower bound Δ with − m < Δ < m for the energy levels of an electron bound in a supercritical field.

For pt.II see ibid., vol.26, no.13, p.1885-96 (1993). The authors employ the method developed in a previous paper for small systems-Be, LiH, H2-where full CI calculations are available for monitoring convergence of many-body perturbation theory. It is shown that divergent series, in particular for excited states, can be transformed into fast converging ones. In essence their method consists in performing infinite subsummations of perturbation series in order to improve convergence: coupling constants are redefined such that singularities are incorporated in a non-perturbative manner and remaining correlations can be expanded in a larger domain of the complex coupling constant plane. It is in this way that the notion of 'improved convergence' has a well defined meaning.

The theoretical background of schemes for accelerating convergence of Moller-Plesset-Goldstone perturbation theory is discussed. Aiming at practical applications the authors consider approximate formulations of the many-body theory of atoms and molecules in finite-dimensional Hilbert spaces. A key role is played by nearby singularities of energy levels and eigenfunctions considered as functions of a suitably chosen coupling parameter. Infinite subsummations in the perturbation series are performed such that the influence of these singularities is eliminated or, at least, sufficiently attenuated. The danger of double counting of diagrammatic contributions already included in these infinite subsummations is avoided by the very construction of the authors' scheme.

We recently proposed (parts I and II of this series of publications) a new method of infinite subsummation in the Moller-Plesset perturbation series with the objective of “effecting convergence of otherwise divergent series”. In the present work we undertake to study the importance of a shift of unlinked graphs in the Moller-Plesset renormalization term. We demonstrate that this modification of many-body perturbation theory presents a viable starting point for new approximations devised to obtain a substantial fraction of the correlation energy at low order. We present an explicit investigation of the excited states of LiH in a suitable full-CI model space, using our method to calculate the correlation energy and monitoring convergence up to tenth order.

Deleted in colorectal cancer (DCC) and its ligand netrin-1 are known as axonal guidance factors, being involved in angiogenesis, migration and survival of precursor cells in the embryonic mammalian central nervous system (CNS). So far, little is known about the distribution of those molecules in human CNS development.We investigated 22 human foetal brain specimens (12th and 28th week of gestation) for DCC and netrin-1 expression by means of immunohistochemistry, immunofluorescence and confocal laser microscopy. Statistical analysis was performed by applying a semi-quantitative score, including staining intensity and frequency and correlation with foetal age.DCC and netrin-1 were differentially expressed throughout the developing human foetal telencephalic and cerebellar cortical layers. Netrin-1 exhibited the highest levels in telencephalic germinal layers, whereas the strongest DCC immunoreactivity was seen in the developing cortical plate. Netrin-1 and DCC were predominantly present on cerebellar external granule layer cells. Distinct co-expression was seen in maturing foetal brainstem nuclei, cerebellar external granular layer and the choroid plexus. In contrast, endothelial cells showed strong netrin-1 expression with subsidiary DCC immunoreactivity. Pontine and telencephalic axonal fibre tracts also demonstrated strong netrin-1 expression.We show that DCC and netrin-1 are ubiquitously expressed in the human foetal brain; however, both exhibit a distinct spatio-temporal expression pattern. Together with the data from animal experiments, our findings might indicate also an important role for DCC and netrin-1 in human foetal CNS development.

A non-perturbative scheme for the interaction of strong laser pulses with atoms and molecules is discussed and model calculations are presented. A semiclassical analysis leads to a clear-cut distinction of four categories of reactions. Separatrix crossing mechanisms, the dissolution of initial tori and classical adiabatic motion are seen to play a central role in a non-perturbative picture of interactions with strong laser fields.

It is demonstrated that the Kramers-Henneberger transformation is the first step in a systematic construction of Floquet states. For a harmonic oscillator which interacts with a classical monochromatic radiation field, all steps of this construction can be performed explicitly and expressed as a simple renormalization scheme. The particular importance of zero-modes for the calculation of quasienergies becomes obvious already in this explicitly solvable model. The general structure of a Kramers-Henneberger expansion is briefly sketched.

Many-body perturbation theory (MBPT) based on Hartree-Fock and non-standard mean fields is employed to calculate the energy, the first and the second moments of Be and LiH. The results are compared with the 'exact' energy, etc obtained in a finite-dimensional model Hilbert space (full configuration interaction taken into account). The authors test the idea that part of the correlations calculated in a Hartree-Fock MBPT scheme can be simulated as mean field or low-order effects when non-standard mean fields derived in non-relativistic or relativistic quantum electrodynamics with non-standard gauges are employed to set up a systematic perturbation theory.

A basic mean-field theory for the interaction between several bound electrons of an atom and an intense electromagnetic field is presented. From it, the authors infer that simultaneous ejection of several electrons is to be seen as a zero-order process, i.e. as an independent quasi-particle reaction of dressed single-electron states and that the shell structure of the atom does not dominate the process. Indeed, even inner shell electrons can be ejected in this way, with comparable probability. Their conclusions contrast with those of other authors who have argued that complete shells tend to be blown off or that, as is the case in very low electromagnetic fields where single photon processes dominate, multiple ionization depends for its existence on the magnitude of electron-electron correlations. The authors estimate the turn-on time of the laser pulse required to observe simultaneous, multiple ionization.

For reasons of their outdoor work, mountain guides (MG) are heavily exposed to ultraviolet radiation during their work.A standardized interview and examination were performed on 283 male MG (median 41 years) from Germany, Switzerland and Austria and 309 age-matched controls. The median occupation time as MG was 17 years; 39.9% were working full-time.The incidence of skin cancer and precancerous lesions was obtained. Precancerous lesions as solar keratosis (SK) were significantly more frequent in MG (25.4% vs. 7.4%). There was no skin cancer [BCC, SSC, melanoma (MEL)] in the control subjects. Basal cell carcinoma (BCC) was diagnosed in 20 MG (7.1%) and SSC in four MG (1.4%). There were 10 highly suspicious melanocytic lesions; one MG had a histologically confirmed malignant MEL. Risk factors for SK in the multivariate analysis included occupation (P0.0001), age (P0.0001) and skin type (P = 0.0002). Within the MG group, age (P0.0001) and hair colour (P = 0.0058) were independent risk factors for SK. Severe lifetime sunburns (P = 0.0007) and skin type (P = 0.041) were the significant risk factors for BCC, within the MG group in addition to the number of guiding days (P = 0.010). The risk factor for skin cancer (BCC, SCC and MEL) was the number of heavy sunburns during lifetime (P = 0.0014).The present study demonstrates an association between high occupational ultraviolet-exposure and an increased prevalence of precancerous skin lesions and skin cancer. MG may be considered as an example for other outdoor professionals. Skin cancer of outdoor workers is likely to be an occupational disease. Primary and secondary prevention should be enforced.

The value of radical transurethral resection of prostate cancer (TURPC) as an alternative therapy was investigated in this prospective study. From January 1995 to July 2008, 533 patients with a median age of 67 years (range 40-89 years) and with clinically localized prostate cancer were resected by the corresponding author with curative intention. The tumor stages were as follows: pT1 8%; pT2 61%; pT3 31%; G1 2%; G2 80%; G3 18%. TURPC requires continuous low-pressure irrigation with the irrigator liquid level at 10 cm water above the pubic region. It also requires a suprapubic trocar, a resectoscope with a 28F sheath, an autoregulated electrosurgical unit, and video monitoring. The prostate is resected completely with peripheral capsule and seminal vesicles. The specimen is retrieved in fractions for correct histopathological staging. If indicated, laparoscopic staging lymphadenectomy is performed. A secondary session for control of positive margins follows after 8 weeks. The transfusion rate was 1.5%, revision for hemorrhage 2.4%, lung embolism 0.2%, bladder neck incision 14%, grade 2 incontinence 0.6% out of 314, and impotence 30% out of 136. The prostate-specific antigen (PSA) nadir wasor =0.2 ng/ml in 95% of 444 cases. PSA recurrence at 5 years was 6% for pT1, 18% for pT2, and 31% for pT3. Postoperative survival at 10 years was 96% for pT1, 91% for pT2, and 85% for pT3 patients. Prostate cancer can be resected transurethrally with reasonable oncological results. The outcome with respect to survival and PSA recurrence is comparable with the results of other published procedures. Low-pressure irrigation with a suprapubic trocar is mandatory for safe performance.

The Epo-EpoR pathway plays a role in tumour growth, metastasis and treatment resistance and is a potential target in oncological treatment. As the EpoR status in human meningiomas is unknown, our aim was to characterize EpoR expression in these tumours.We examined 131 meningioma samples of all WHO grades from 116 patients by immunohistochemistry for EpoR. Among these, 25 meningiomas showed brain invasion and 29 patients had a further tumour recurrence. A group of 20 patients without tumour recurrence served as controls. In 12 cases we were able to compare both the primary and the following recurrent tumours. The presence of EpoR in meningiomas was confirmed by RT-PCR and Western blot.EpoR was expressed in all meningiomas. Statistical analysis revealed that the mean expression levels of EpoR were significantly lower in primary tumours with known recurrence compared with a recurrence-free control group. Additional matched pair analysis in individual cases showed no significant differences between primary and recurrent tumours. No significant correlation between EpoR expression and WHO grade, age, sex or brain invasion was detected. Using specific primer pairs for RT-PCR, we were able to detect all three known isoforms of EpoR: the full-length isoform EpoR-F, the truncated isoform EpoR-T and the soluble isoform EpoR-S.Our results demonstrate the expression of EpoR in meningiomas. Lower EpoR mean levels might be a useful marker for a higher recurrence risk, but further studies are needed to clarify the influence of EpoR on recurrences and the role of the different isoforms.

Employing a (1+1)-dimensional model, we discuss non-perturbative methods for the description of the ionization of highly excited hydrogen atoms by a pulsed strong microwave field. We restrict our attention to high scaled frequenciesn3ω≧1 and show that the recently developed picture of Landau-Zener dynamics leads to a transparent explanation of prominent structures in the 10% ionization curve measured by Koch et al. in experiments using microwave cavities; these structures are predicted to depend on fringe field parameters in a systematic manner. Waveguide experiments are expected to yield qualitatively different results.

Relativistic mean-field equations are obtained by minimizing the effective energy obtained from the gauge-invariant energy density by eliminating electromagnetic degrees of freedom in certain characteristic nonlinear gauges. It is shown that by an appropriate choice of gauge many-body correlations, e.g. screening and three-body 'forces', can be included at the mean-field level. The many-body perturbation theory built on the latter is then expected to show improved 'convergence'.

The authors develop a mechanism for the selective excitation of molecular vibrational states by short strong laser pulses. This mechanism is based on constructive interference of Floquet states. A phase functional is constructed which allows the theoretical prediction of the parameters of optimal pulses. The role of anharmonicities of the molecular binding potential and their effect on the structure of the instantaneous Floquet states is clarified.

Objetivo: Desde el comienzo de la resección transuretral RTU en 1931 el reseccionista siempre tuvo en mente resecar el cáncer de próstata. Sin embargo, su práctica no tuvo éxito por deficiencias instrumentales y técnicas. La primera resección transuretral por cáncer de próstata RTUPC se llevó a cabo en nuestra Institución en 1957 por Hans J. Reuter. La irrigación a baja presión permitió una resección segura de la próstata incluyendo la cápsula. De esta forma iniciamos en 1985 un estudio prospectivo para verificar si la RTUPC era un procedimiento radical. Métodos: La RTUPC requiere una irrigación continua a baja presión con el reservorio de líquido anclado a la mesa de operaciones. El nivel de líquido debe mantenerse por debajo de 20 centímetros respecto a la región púbica en posición de litotomía. El flujo continuo con un trocar suprapúbico y un resectoscopio con vaina de calibre 28 Ch. Es indispensable una unidad de electro-bisturí autorregulada para adecuar la corriente de alta frecuencia a la resistencia al corte de los tejidos a resecar para que este sea preciso. El video monitoreo es obligado. La próstata se reseca completamente con su cápsula y algo de la grasa periprostática así como las vesículas seminales. Las muestras de tejido son etiquetadas por grupos para garantizar un correcto estadiaje histopatológico. Si la linfadenectomía laparoscópica está indicada, esta se llevará a cabo. A las 12 semanas se practica una segunda sesión de control de márgenes positivos. Resultados: Desde 1985 al 2004, 1017 pacientes con una media de edad de 68,9 años y cáncer de próstata localizado fueron resecados por 5 cirujanos diferentes con intención curativa. El porcentaje de estadios cancerosos fue de T1: 12, T2: 43, T3: 41, T4: 4. El grado de G1: 8, G2: 72, G3:20. La mortalidad fue de 1 sobre 1017. Precisaron de incisión de cuello vesical el 8,9%. Incontinencia grado 3: Ninguno. La supervivencia postoperatoria a los 10 años fue del 82% en los T1, 87% en los T2, 81% en los T3 y del 34% en los T4. La recidiva bioquímica definida como el aumento de tres valores consecutivos del PSA sin limite inferior, fue en 5 años del 15% en los T1, 19% en los T2 y 27% en los T3. Conclusiones: Considerando nuestros resultados, concluimos que la Resección Transuretral del Cáncer de Próstata (RTUPC) es tan radical como la cirugía abierta. Los resultados de supervivencia y la recidiva del PSA son comparables, la tasa de incontinencia es mas baja que con la cirugía abierta. Es obligatoria la irrigación a baja presión utilizando el trocar suprapúbico, vaina del 28 Ch. y un electrobisturí autorregulado, la videomonitorización y un reseccionista con experiencia.

Objective: Deep sternal wound infection (DSWI) leading to postoperative mediastinitis is a devastating complication of cardiac surgery, especially after usage of internal mammarian arteries. Standard wire-circlage may result in complex sequestrated sternal edge bone fragments in some cases. Definite stable chest closure remains a demanding challenge. Methods: Grade IV mediastinitis developping after routine open-heart surgery was treated by applying vacuum assisted closure therapy and surgical debridement initially, followed by rigid osseous plate fixation and soft tissue coverage using bilateral horizontal sliding flap if standard therapy was unsuccessful. Results: The proposed method achieved complete healing in all patients with failure of standard therapy (n=14, mean age 72±8.9 years, 5 male) which had led to unstable, infected and reinforced sternum. There was no mortality, low morbidity (1/14 patient with procedure-related pneumothorax). The median postoperative ventilation time and ICU stay were 1 hour and 2 days, respectively. The median hospital stay after sternal fixation was 15.8±6.9 days. Postoperative pain assessment with visual analog scale showed a median value of 0.5. Conclusion: This innovative concept of chest stabilization and closure represents a highly effective treatment modality of patients with complicated DSWI. Prospective studies are required to validate our first encouraging results of no mortality, low morbidity, short hospital stay and aesthetic outcome.

We investigate the dynamics of periodically driven anharmonic oscillators. In particular, we consider values of the coupling strength which are orders of magnitude higher than those required for the overlap of primary resonances. We observe a division of phase space into a regular and a stochastic region. Both regions are separated by a sharp chaos border which sets an upper limit to the stochastic heating of particles; its dependence on the coupling strength is studied. We construct perpetual adiabatic invariants governing regular motion. A bifurcation mechanism leading to the annihilation of resonances is explained.

General repercussions of the extraordinarily rich avoidedcrossing structure in the parametric dependence of quasi-energies are discussed. A coarse-graining procedure leading to smooth effective quasienergy surfaces is introduced. New features and their experimental consequences encountered in the attempt of attaining an adiabatic limit are elucidated.

We discuss the transport of quantum states on quasi-energy surfaces of periodically driven systems and establish their non-trivial structure. The latter is shown to be caused by diabatic transitions at lines of narrow avoided crossings. Some experimental consequences pertaining to adiabatic transport and Landau-Zener transitions among Floquet states are briefly sketched On traite des holonomies quantiques sur des surfaces de quasi-energie de systemes soumis a une excitation periodique, et on etablit leur topologie globale non triviale. On montre que cette derniere est causee par des transitions diabatiques entre niveaux au passage d'anti-croisements serres. On donne brievement quelques consequences experimentales concernant le transport adiabatique et les transitions de Landau-Zener entre etats de Floquet

At the moment autologous nerve grafting remains the only reasonable technique for reconstruction of peripheral nerve defects. Unfortunately, this technique has a lot of complications and disadvantages. These problems are related to the autologous nerve that is harvested for this procedure. Donor site morbidity with loss of sensitivity, painful neuroma formation and of course the restricted availability of autologous nerves stimulates the idea for alternative techniques on that field. In this paper we describe our experience with different graft materials for reconstruction of a 2 cm nerve gap in a median nerve model in rats. After implantation of various materials (biological/synthetic) the main experiments were conducted with a synthetic, biodegradable nerve conduit seeded with autologous Schwann cells. With this material we were able to reconstruct successfully a 2 cm gap in the rat median nerve. Regeneration with this material was found to be equally to an autologous nerve graft.