ScatterJ: An ImageJ plugin for the evaluation of analytical microscopy datasets.

We present ScatterJ, an ImageJ plugin that allows for extracting qualitative as well as quantitative information from analytical microscopy datasets. A large variety of analytical microscopy methods are used to obtain spatially resolved chemical information. The resulting datasets are often large and complex, and can contain information that is not obvious or directly accessible. ScatterJ extends and complements existing methods to extract information on correlation and colocalization from pairs of species-specific or element-specific maps. We demonstrate the possibilities to extract information using example datasets from biogeochemical studies, although the plugin is not restricted to this type of research. The information that we could extract from our existing data helped to further our understanding of biogeochemical processes such as mineral formation or heavy metal sorption. ScatterJ can be used for a variety of different two-dimensional (2D) and three-dimensional (3D) datasets such as energy-dispersive X-ray spectroscopy maps, 3D confocal laser scanning microscopy maps, and 2D scanning transmission X-ray microscopy maps.

Electron rearrangement dynamics in dissociating I(2)

The charge rearrangement in dissociating I_{2}^{n+} molecules is measured as a function of the internuclear distance R using extreme ultraviolet pulses delivered by the free-electron laser in Hamburg. Within an extreme ultraviolet pump-probe scheme, the first pulse initiates dissociation by multiply ionizing I_{2}, and the delayed probe pulse further ionizes one of the two fragments at a given time, thus triggering charge rearrangement at a well-defined R. The electron transfer between the fragments is monitored by analyzing the delay-dependent ion kinetic energies and charge states. The experimental results are in very good agreement with predictions of the classical over-the-barrier model demonstrating its validity in a thus far unexplored quasimolecular regime relevant for free-electron laser, plasma, and chemistry applications.

Optimizing the performance of the entropic splitter for particle separation.

Recently, it has been shown that entropy can be used to sort Brownian particles according to their size. In particular, a combination of a static and a time-dependent force applied on differently sized particles which are confined in an asymmetric periodic structure can be used to separate them efficiently, by forcing them to move in opposite directions. In this paper, we investigate the optimization of the performance of the "entropic splitter." Specifically, the splitting mechanism and how it depends on the geometry of the channel, and the frequency and strength of the periodic forcing is analyzed. Using numerical simulations, we demonstrate that a very efficient and fast separation with a practically 100% purity can be achieved by a proper optimization of the control variables. The results of this work could be useful for a more efficient separation of dispersed phases such as DNA fragments or colloids dependent on their size.

Hydrodynamically enforced entropic trapping of Brownian particles.

We study the transport of Brownian particles through a corrugated channel caused by a force field containing curl-free (scalar potential) and divergence-free (vector potential) parts. We develop a generalized Fick-Jacobs approach leading to an effective one-dimensional description involving the potential of mean force. As an application, the interplay of a pressure-driven flow and an oppositely oriented constant bias is considered. We show that for certain parameters, the particle diffusion is significantly suppressed via the property of hydrodynamically enforced entropic particle trapping.

Time-resolved measurement of interatomic coulombic decay in Ne2.

The lifetime of interatomic Coulombic decay (ICD) [L. S. Cederbaum et al., Phys. Rev. Lett. 79, 4778 (1997)] in Ne2 is determined via an extreme ultraviolet pump-probe experiment at the Free-Electron Laser in Hamburg. The pump pulse creates a 2s inner-shell vacancy in one of the two Ne atoms, whereupon the ionized dimer undergoes ICD resulting in a repulsive Ne+(2p(-1))-Ne+(2p(-1)) state, which is probed with a second pulse, removing a further electron. The yield of coincident Ne+-Ne2+ pairs is recorded as a function of the pump-probe delay, allowing us to deduce the ICD lifetime of the Ne2(+)(2s(-1)) state to be (150±50) fs, in agreement with quantum calculations.

Experimental and computational analysis of the secretome of the hyperthermophilic archaeon Pyrococcus furiosus.

Although Pyrococcus furiosus is one of the best studied hyperthermophilic archaea, to date no experimental investigation of the extent of protein secretion has been performed. We describe experimental verification of the extracellular proteome of P. furiosus grown on starch. LC-MS/MS-based analysis of culture supernatants led to the identification of 58 proteins. Fifteen of these proteins had a putative N-terminal signal peptide (SP), tagging the proteins for translocation across the membrane. The detected proteins with predicted SPs and known function were almost exclusively involved in important extracellular functions, like substrate degradation or transport. Most of the 43 proteins without predicted N-terminal signal sequences are known to have intracellular functions, mainly (70 %) related to intracellular metabolism. In silico analyses indicated that the genome of P. furiosus encodes 145 proteins with N-terminal SPs, including 21 putative lipoproteins and 17 with a class III peptide. From these we identified 15 (10 %; 7 SPI, 3 SPIII and 5 lipoproteins) under the specific growth conditions of this study. The putative lipoprotein signal peptides have a unique sequence motif, distinct from the motifs in bacteria and other archaeal orders.

Entropic splitter for particle separation.

We present a particle separation mechanism which induces the motion of particles of different sizes in opposite directions. The mechanism is based on the combined action of a driving force and an entropic rectification of the Brownian fluctuations caused by the asymmetric form of the channel along which particles proceed. The entropic splitting effect shown could be controlled upon variation of the geometrical parameters of the channel and could be implemented in narrow channels and microfluidic devices.

Psychotherapy in dizziness: a systematic review.

BACKGROUND: About 30-50% of complex dizziness disorders are organically not sufficiently explained or related to a psychiatric disorder. Of patients with such dizziness disorders, 80% are severely impaired by dizziness in their daily and working lives; nevertheless, they are often not diagnosed or treated adequately. OBJECTIVES: This review aims to give a systematic overview of psychotherapeutic approaches and their efficacy regarding the treatment of dizziness that is medically not sufficiently explained or related to a psychiatric disorder. METHODS: A systematic literature search was conducted in Medline, PSYNDEX and PsycINFO. Included in this systematic review were (randomised) controlled trials ((R)CTs) concerning psychotherapy in patients with dizziness, medically not sufficiently explained or associated with a psychiatric disorder. If possible, Hedges' g was used to express the effect sizes (ES) of the treatment. Heterogeneity was assessed using the Q statistic. In addition, the quality of the studies was rated. RESULTS: Three (R)CTs were included. All studies used cognitive-behavioural treatment methods in combination with relaxation techniques or vestibular rehabilitation. All studies suggested that psychotherapy may provide improvement. The mean ES in the treatment groups was 0.46 (95% CI 0.05 to 0.88) for dizziness related outcome, 0.10 (-0.44 to 0.64) for anxiety and 0.17 (-0.24 to 0.58) for depression whereas in the control groups the mean dizziness related ES was -0.04 (-0.44 to 0.37), anxiety related ES was -0.03 (-0.43 to 0.38) and depression related ES was -0.02 (-0.42 to 0.38). The quality of the studies was average. Sample sizes were small, however, and there was a lack of long term studies. CONCLUSION: This systematic review provides some preliminary evidence that psychotherapy may be effective in patients with dizziness that is medically not sufficiently explained or due to a psychiatric disorder. The results should be replicated in larger samples and follow-up RCTs.

Human neutrophil peptides sputum levels in symptomatic smokers and COPD patients.

BACKGROUND AND OBJECTIVES: Human Neutrophil Peptides (HNP) are major neutrophils' products which may contribute to the airway inflammation and lung remodelling during chronic obstructive pulmonary disease (COPD). We aimed to assess whether HNP sputum concentrations could be used as indicators of airway inflammation and progression towards pulmonary functional impairment, and correlate with the degree of airways obstruction. MATERIALS AND METHODS: We measured, by ELISA tests, HNP concentrations from 37 symptomatic smokers and 34 COPD patients. All participants underwent pulmonary function tests. Sputum samples were collected at the enrolment, and 6 months after smoking cessation. Differences between groups and correlation coefficients between variables were determined using non parametric tests. RESULTS: Sputum HNP concentrations were higher in COPD patients as compared to symptomatic smokers (14 +/- 1.5 microg/ml vs 1.6 +/- 0.4 microg/ml; p < 0.0001). Among COPD patients HNP concentrations were higher in individuals with severe obstruction than in patients with mild to moderate COPD (19.9 +/- 2.3 microg/ml vs 10.3 +/- 0.8 microg/ml, p = 0.003). A negative correlation was observed between HNP levels and FEV1 (rho = -0.38, p = 0.02), and FEV1/FVC (rho = -0.42, p = 0.01). No differences were found in HNP levels before and after 6 months of smoking withdrawal (1.1 microg/ml +/- 0.3 vs 1.1 microg/ml +/- 0.3 for symptomatic smokers, p = 0.9, and 14.4 microg/ml +/- 1 vs 16 microg/ml +/- 1.1 for COPD, p = 0.6). DISCUSSION: Sputum levels of HNP may represent a marker of severity of functional impairment in COPD. Our data support the hypothesis that HNP may have a role in smoking- and COPD-related lung inflammation.

Biased Brownian motion in extremely corrugated tubes.

Biased Brownian motion of point-size particles in a three-dimensional tube with varying cross-section is investigated. In the fashion of our recent work, Martens et al. [Phys. Rev. E 83, 051135 (2011)] we employ an asymptotic analysis to the stationary probability density in a geometric parameter of the tube geometry. We demonstrate that the leading order term is equivalent to the Fick-Jacobs approximation. Expression for the higher order corrections to the probability density is derived. Using this expansion orders, we obtain that in the diffusion dominated regime the average particle current equals the zeroth order Fick-Jacobs result corrected by a factor including the corrugation of the tube geometry. In particular, we demonstrate that this estimate is more accurate for extremely corrugated geometries compared with the common applied method using a spatially-dependent diffusion coefficient D(x, f) which substitutes the constant diffusion coefficient in the common Fick-Jacobs equation. The analytic findings are corroborated with the finite element calculation of a sinusoidal-shaped tube.

Predictors of crying, feeding and sleeping problems: a prospective study.

BACKGROUND: Infant regulatory problems, that is, excessive crying, feeding and/or sleeping difficulties, are precursors of adverse development. However, the aetiology of regulatory problems is still unclear. The aim of this study was to investigate pre-, peri- and post-natal neurophysiological and psychosocial predictors of single and multiple regulatory problems at 5 months of age. METHODS: This prospective longitudinal study included all children born at neonatal risk in a geographically defined area in southern Germany. The data of n = 5093 singleton infants (83.6%) were analysed using crude and multivariate logistic regression analyses. As outcome measures we used single and multiple regulatory problems, that is, crying, feeding and/or sleeping difficulties at 5 months of age, which were assessed via a standardized interview with the parents by study paediatricians as part of a neurodevelopmental examination. RESULTS: In total, 30.7% of the sample suffered from single or multiple regulatory problems at 5 months. Breastfeeding increased the odds of single sleeping problems 5.12-fold, but decreased the odds of single feeding problems [odds ratio (OR) 0.51; 95% confidence interval (CI) 0.35-0.74]. Very preterm birth was predictive of single feeding (OR 1.79; 95% CI 1.25-2.55) and multiple regulatory problems (OR 2.03; 95% CI 1.19-3.46), and foetal abnormalities increased the odds of single feeding and multiple regulatory problems from 1.53- to 1.64-fold. Family adversity and psychosocial stress factors were associated with single crying and multiple regulatory problems. CONCLUSIONS: Pre-, peri- and post-natal neurophysiological and psychosocial factors are predictive of single and multiple regulatory problems. The results may be useful in terms of early recognition of at risk groups for regulatory problems.

[Cognitive reserve and its relevance for the prevention and diagnosis of dementia]. / Kognitive Reservekapazität und ihre Bedeutung für Auftreten und Verlauf der Demenz.

Progressive brain damage is undoubtedly the main cause of clinical symptoms of dementia in neurodegenerative disorders such as Alzheimer's disease. However, the association between brain damage and cognitive symptoms is not linear. Certain interindividual differences such as a good school education or a greater brain volume are associated with a higher resilience against brain damage that is usually referred to as cognitive reserve (CR). Individuals with high CR have a diminished risk for dementia and both active and passive concepts for this phenomenon are discussed. In the concept of passive CR, peculiarities of brain structure such as higher synapse or neuron counts are regarded as buffers against brain damage. Symptoms of dementia do not occur until a certain threshold of damage is passed. In addition to the passive concepts, active mechanisms are also discussed that are associated with the ability to maintain a certain level of cognitive performance in the face of progressive neurodegeneration for a longer period. In subjects with healthy cognitive function, these active mechanisms contribute to the adaptation of brain activity when task difficulty level is increased. Confronted with progressive neurodegeneration, these active mechanisms help to compensate for brain damage. Individuals with higher CR show more efficient activation for solving the same task, which helps them to preserve normal levels of cognitive performance for a longer period.

A prospective study on the persistence of infant crying, sleeping and feeding problems and preschool behaviour.

AIM: To determine the persistence of regulatory problems (RP), i.e. excessive crying (>3 months of age), feeding and sleeping difficulties from infancy to preschool age, and to evaluate whether RP at 5 months are predictive of preschool adaptive behaviour and social skills. METHOD: A prospective population study of newborns admitted to neonatal care. RP at 5, 20 and 56 months of age were obtained via parent interviews and neurological examination and preschool adaptive behaviour and social skills by parent ratings. Logistic and linear regression analyses were conducted and controlled for psychosocial and neurological factors. RESULTS: More than half of the sample had RP at least at one measurement point. In about 8% of infants, RP persisted across the preschool years. Multiple RP and feeding problems increased the odds of eating problems at 20 and 56 months. Persistent RP and feeding problems were predictive of deficits in preschool adaptive behaviour and social skills. In addition, sex differences were found. CONCLUSIONS: Multiple RP and feeding problems had the highest stability. Persistent RP were predictive of adverse social and adaptive behaviour. Understanding of the aetiology may help to prevent persistent RP.

Living donor liver transplantation and its effect on the donor-recipient relationship--a qualitative interview study with donors.

An important aspect in the preoperative evaluation and a legal precondition for an living donor liver transplantation (LDLT) is a family or emotionally close relationship between donor and recipient. We investigated the development of the donor-recipient relationship after LDLT. We conducted semi-structured clinical interviews with 18 donors as part of a regular postoperative follow-up and analyzed them using the method of Grounded Theory. The donation does not lead to any major changes in the donor-recipient relationship, probably due to careful pre-selection. It does however enhance the existing positive or conflicting character of the relationship. Donors sometimes downplay negative aspects in the relationship and emphasize the improvement as a way of dealing with a major life event. A donation cannot fulfill expectations linked to it and it is unfavorable to be used to improve the relationship. Potential misuse or instrumentalization of the donation by the donor are possible. Postoperative feelings of gratitude are an issue after surgery. A good relationship enhances a better management of the postoperative course. The preoperative donor-recipient relationship should be as free of conflict as possible. A thorough preoperative evaluation of the donor-recipient relationship is particularly important to assess the donors' suitability and clarify conflicts and unrealistic expectations.

[The omega connector--a module for jointed coupling of titanium total prostheses in the middle ear]. / Der Omega-Connector: ein Modul zur gelenkigen Ankopplung von Titantotalprothesen im Mittelohr.

BACKGROUND: Hearing improvement after reconstruction of a defect ossicular chain depends on material, design and - crucially - coupling of the prosthesis. Coupling a total ossicular replacement prosthesis to the stapes footplate can be problematic and lead to prosthesis instability. In order to solve this problem, the Omega Connector was developed, a module allowing the middle ear surgeon to couple a titanium total prosthesis to the stapes footplate in a flexible, angle-variable manner. MATERIAL AND METHOD: The Omega Connector is made of pure titanium and consists of three compenents: head, neck and base plate. The head allows a jointed coupling to the stem of a titanium total prosthesis. Positioned between the remnants of the stapes crura, the bas plate proves for a stable connection with the stapes footplate. RESULTS: The Omega Connector was implanted during 14 revisions surgeries. In 10 of these surgeries a total ossicular replacement prosthesis was removed which was implanted at an earlier date and which was fixed and no longer functioning. In all 14 cases it was possible intraoperatively to position the Omega Connector correctly and to couple it to a titanium total prosthesis. The postoperative hearing gain was between 10 to 25 dB, with an average of 18 dB. CONCLUSION: For the first time, the Omega Connector offers to the surgeon the option to couple a titanium total prosthesis via a micro ball joint. Hearing results achieved so far are satisfying. The results confirm the advantages of the Omega Connector during implantation of a titanium total prosthesis. For a final evaluation, long-term studies have yet to be made.

Rectification in synthetic conical nanopores: a one-dimensional Poisson-Nernst-Planck model.

Ion transport in biological and synthetic nanochannels is characterized by phenomena such as ion current fluctuations and rectification. Recently, it has been demonstrated that nanofabricated synthetic pores can mimic transport properties of biological ion channels [P. Yu. Apel, Nucl. Instrum Methods Phys. Res. B 184, 337 (2001); Z. Siwy, Europhys. Lett. 60, 349 (2002)]. Here, the ion current rectification is studied within a reduced one-dimensional (1D) Poisson-Nernst-Planck (PNP) model of synthetic nanopores. A conical channel of a few nm to a few hundred nm in diameter, and of a few mum long is considered in the limit where the channel length considerably exceeds the Debye screening length. The rigid channel wall is assumed to be weakly charged. A one-dimensional reduction of the three-dimensional problem in terms of corresponding entropic effects is put forward. The ion transport is described by the nonequilibrium steady-state solution of the 1D Poisson-Nernst-Planck system within a singular perturbation treatment. An analytic formula for the approximate rectification current in the lowest order perturbation theory is derived. A detailed comparison between numerical results and the singular perturbation theory is presented. The crucial importance of the asymmetry in the potential jumps at the pore ends on the rectification effect is demonstrated. This so constructed 1D theory is shown to describe well the experimental data in the regime of small-to-moderate electric currents.

Entropic particle transport in periodic channels.

The dynamics of Brownian motion has widespread applications extending from transport in designed micro-channels up to its prominent role for inducing transport in molecular motors and Brownian motors. Here, Brownian transport is studied in micro-sized, two-dimensional periodic channels, exhibiting periodically varying cross-sections. The particles in addition are subjected to an external force acting alongside the direction of the longitudinal channel axis. For a fixed channel geometry, the dynamics of the two-dimensional problem is characterized by a single dimensionless parameter which is proportional to the ratio of the applied force and the temperature of the particle environment. In such structures entropic effects may play a dominant role. Under certain conditions the two-dimensional dynamics can be approximated by an effective one-dimensional motion of the particle in the longitudinal direction. The Langevin equation describing this reduced, one-dimensional process is of the type of the Fick-Jacobs equation. It contains an entropic potential determined by the varying extension of the eliminated channel direction, and a correction to the diffusion constant that introduces a space dependent diffusion. Different forms of this correction term have been suggested before, which we here compare for a particular class of models. We analyze the regime of validity of the Fick-Jacobs equation, both by means of analytical estimates and the comparisons with numerical results for the full two-dimensional stochastic dynamics. For the nonlinear mobility we find a temperature dependence which is opposite to that known for particle transport in periodic potentials. The influence of entropic effects is discussed for both, the nonlinear mobility and the effective diffusion constant.

Colchicine, cyclophosphamide and prednisone in the treatment of mild-moderate idiopathic pulmonary fibrosis: comparison of three currently available therapeutic regimens.

STUDY OBJECTIVES: In this study we evaluated the role of three currently available therapeutic regimens in the treatment of early stages of idiopathic pulmonary fibrosis (IPF). PATIENTS: The study population consisted of 57 consecutive suspected individuals with IPF. Patients with interstitial pneumonias other than IPF and subjects with advanced disease or contraindication to therapy were excluded. We evaluated 30 subjects with mild-moderate IPF, homogeneous baseline characteristics and prognostic parameters that were assigned to 3 treatment regimens: group 1 (n = 11): prednisone 1 mg/kg/ day; group 2 (n = 9): prednisone 0.5 mg/kg/day plus cyclophosphamide 100 mg/day; group 3 (n = 10): prednisone 0.5 mg/kg/day plus colchicine 1 mg/day. We analysed response to therapy by analysis of a clinical-radiographic-physiologic (CRP) score before treatment and at 6 months intervals for 18 months. Side effects and three years survival rate were also investigated. RESULTS: Although our study was performed in a subset of patients with early disease's stages, these data showed that none of the regimens was able to interfere with IPF's course. However treatment with colchicine plus prednisone resulted in fewer side effects and re-evaluation parameters showed a significant decrease of dyspnoea (p < 0.01). No significant differences were observed in survival rate among the three groups. CONCLUSIONS: None of the regimens analyzed was effective even in the treatment of the early stages of IPF. The association colchicine/corticosteroids could be considered a safe and not expensive regimen that may be used in the treatment of IPF, especially in patients who have experienced adverse effects from immunosuppressive agents, while waiting for newer therapeutic strategies.

Biased diffusion in confined media: test of the Fick-Jacobs approximation and validity criteria.

We study biased, diffusive transport of Brownian particles through narrow, spatially periodic structures in which the motion is constrained in lateral directions. The problem is analyzed under the perspective of the Fick-Jacobs equation, which accounts for the effect of the lateral confinement by introducing an entropic barrier in a one-dimensional diffusion. The validity of this approximation, based on the assumption of an instantaneous equilibration of the particle distribution in the cross section of the structure, is analyzed by comparing the different time scales that characterize the problem. A validity criterion is established in terms of the shape of the structure and of the applied force. It is analytically corroborated and verified by numerical simulations that the critical value of the force up to which this description holds true scales as the square of the periodicity of the structure. The criterion can be visualized by means of a diagram representing the regions where the Fick-Jacobs description becomes inaccurate in terms of the scaled force versus the periodicity of the structure.

Neutron production from feedback controlled thermal cycling of a pyroelectric crystal.

The LLNL Crystal Driven Neutron Source is operational and has produced record ion currents of approximately 10 nA and neutron output of 1.9(+/-0.3)x10(5) per thermal cycle using a crystal heating rate of 0.2 degrees C/s from 10 to 110 degrees C. A 3 cm diameter by 1 cm thick LiTaO(3) crystal with a socket secured field emitter tip is thermally cycled with feedback control for ionization and acceleration of deuterons onto a deuterated target to produce D-D fusion neutrons. The entire crystal and temperature system is mounted on a bellows which allows movement of the crystal along the beam axis and is completely contained on a single small vacuum flange. The modular crystal assembly permitted experimental flexibility. Operationally, flashover breakdowns along the side of the crystal and poor emitter tip characteristics can limit the neutron source. The experimental neutron results extend earlier published work by increasing the ion current and pulse length significantly to achieve a factor-of-two higher neutron output per thermal cycle. These findings are reviewed along with details of the instrument.