[Postoperative treatment and rehabilitation following flexor tendon injuries]. / Weiterbehandlung und Rehabilitation nach Beugesehnenverletzungen.

BACKGROUND: The ideal surgical and postoperative treatment for flexor tendon injuries, especially in zone 2, is still subject to continuous modifications and professional discussions. OBJECTIVE: Presentation of established rehabilitation concepts, specific problems and new treatment approaches with practical recommendations for application. MATERIAL AND METHODS: Comparison of commonly used treatment concepts by assessing surgical flexor tendon repair, splint choice and clinical application in patients. Discussion of new surgical approaches and standards and their influence on postoperative therapy after flexor tendon injuries. RESULTS: The Washington regimen has retained its status as the standard in the current follow-up treatment of flexor tendon injuries. New suture materials and techniques enable early active rehabilitation of sutured flexor tendons with good clinical results, such as increased range of motion for interphalangeal joint extension and improved distal interphalangeal joint flexion with overall acceptable frequencies of suture rupture. CONCLUSION: A stable tendon repair with smooth gliding is the foundation for treatment after flexor tendon injuries. After intraoperative active digital extension-flexion testing of the sutured tendon an early active rehabilitation approach should follow. New splint designs in combination with primary stable tendon suture techniques have the potential to improve the postoperative outcome, presupposing a reliable cooperation of the patient.

Heartbeat Dynamics Analysis under Cold-Pressure Test using Wavelet p-Leader Non-Gaussian Multiscale Expansions.

Multiscale and multifractal (MF) analyses have been proven an effective tool for the characterisation of heartbeat dynamics in physiological and pathological conditions. However, pre-processing methods for the unevenly sampled heartbeat interval series are known to affect the estimation of MF properties. In this study, we employ a recently proposed method based on wavelet p-leaders MF spectra to estimate MF properties from cardiovascular variability series, which are also pre-processed through an inhomogeneous point-process modelling. Particularly, we exploit a non-Gaussian multiscale expansion to study changes in heartbeat dynamics as a response to a sympathetic elicitation given by the cold-pressor test. By comparing MF estimates from raw heartbeat series and the point-process model, results suggest that the proposed modelling provides features statistically discerning between stress and resting condition at different time scales. These findings contribute to a comprehensive characterization of autonomic nervous system activity on cardiovascular control during cold-pressor elicitation.

Wavelet p-Leader Non-Gaussian Multiscale Expansions for EEG series: an Exploratory Study on Cold-Pressor Test.

Brain dynamics recorded through electroencephalography (EEG) have been proven to be the output of a nonstationary and nonlinear system. Thus, multifractality of EEG series has been exploited as a useful tool for a neurophysiological characterization in health and disease. However, the role of EEG multifractality under peripheral stress is unknown. In this study, we propose to make use of a novel tool, the recently defined non-Gaussian multiscale analysis, to investigate brain dynamics in the range of 4-8Hz following a cold-pressor test versus a resting state. The method builds on the wavelet p-leader multifractal spectrum to quantify different types of departure from Gaussian and linear properties, and is compared here to standard linear descriptive indices. Results suggest that the proposed non-Gaussian multiscale indices were able to detect expected changes over the somatosensory and premotor cortices, over regions different from those detected by linear analyses. They further indicate that preferred responses for the contralateral somatosensory cortex occur at scales 2.5s and 5s. These findings contribute to the characterization of the so-called central autonomic network, linking dynamical changes at a peripheral and a central nervous system levels.

Multiscale properties of instantaneous parasympathetic activity in severe congestive heart failure: A survivor vs non-survivor study.

Multifractal analysis of cardiovascular variability series is an effective tool for the characterization of pathological states associated with congestive heart failure (CHF). Consequently, variations of heartbeat scaling properties have been associated with the dynamical balancing of nonlinear sympathetic/vagal activity. Nevertheless, whether vagal dynamics has multifractal properties yet alone is currently unknown. In this study, we answer this question by conducting multifractal analysis through wavelet leader-based multiscale representations of instantaneous series of vagal activity as estimated from inhomogeneous point process models. Experimental tests were performed on data gathered from 57 CHF patients, aiming to investigate the automatic recognition accuracy in predicting survivor and non-survivor patients after a 4 years follow up. Results clearly indicate that, on both CHF groups, the instantaneous vagal activity displays power-law scaling for a large range of scales, from ≃ 0.5s to ≃ 100s. Using standard SVM algorithms, this information also allows for a prediction of mortality at a single-subject level with an accuracy of 72.72%.

Symptoms, functioning and coping strategies in individuals with schizophrenia spectrum disorders who do not take antipsychotic medication: a comparative interview study.

BACKGROUND: A considerable proportion of people with schizophrenia spectrum disorders do not take antipsychotic medication but seem to be functioning well. However, little is known about this group. To test the assumption that absence of medication is compensated for by more effective coping and increased social support, this study compared symptoms, functioning, coping strategies and social support in non-medicated and medicated individuals with schizophrenia spectrum disorders. METHOD: In all, 48 participants with a DSM-IV schizophrenia spectrum disorder who were taking (n = 25) or not taking antipsychotic medication (n = 23) were included. Assessment consisted of self-ratings of symptoms, symptom-related distress and social support combined with a semi-structured interview that assessed general and social functioning, subjective evaluation of symptoms and coping strategies. RESULTS: Symptom severity and distress did not differ between the groups. However, the non-medicated participants had significantly higher levels of general functioning than medicated participants and a longer duration of being non-medicated was significantly associated with a higher level of general functioning. In contrast to the hypotheses, not taking medication was not associated with more effective coping strategies or with higher levels of social support. Medicated participants more frequently reported the use of professional help as a coping strategy. CONCLUSIONS: Our results corroborate previous studies finding improved functioning in individuals with schizophrenia spectrum disorders who do not take medication compared with those who take medication, but do not support the notion that this difference is explicable by better coping or higher levels of social support. Alternative explanations and avenues for research are discussed.

Point-process high-resolution representations of heartbeat dynamics for multiscale analysis: A CHF survivor prediction study.

Multiscale analysis of human heartbeat dynamics has been proved effective in characterizeing cardiovascular control physiology in health and disease. However, estimation of multiscale properties can be affected by the interpolation procedure used to preprocess the unevenly sampled R-R intervals derived from the ECG. To this extent, in this study we propose the estimation of wavelet coefficients and wavelet leaders on the output of inhomogeneous point process models of heartbeat dynamics. The RR interval series is modeled using probability density functions (pdfs) characterizing and predicting the time until the next heartbeat event occurs, as a linear function of the past history. Multiscale analysis is then applied to the pdfs' instantaneous first order moment. The proposed approach is tested on experimental data gathered from 57 congestive heart failure (CHF) patients by evaluating the recognition accuracy in predicting survivor and non-survivor patients, and by comparing performances from the informative point-process based interpolation and non-informative spline-based interpolation. Results demonstrate that multiscale analysis of point-process high-resolution representations achieves the highest prediction accuracy of 65.45%, proving our method as a promising tool to assess risk prediction in CHF patients.

P-leader multifractal analysis and sparse SVM for intrapartum fetal acidosis detection.

Interpretation and analysis of intrapartum fetal heart rate, enabling early detection of fetal acidosis, remains a challenging signal processing task. Among the many strategies that were used to tackle this problem, scale-invariance and multifractal analysis stand out. Recently, a new and promising variant of multifractal analysis, based on p-leaders, has been proposed. In this contribution, we use sparse support vector machines applied to p-leader multifractal features with a double aim: Assessment of the features actually contributing to classification; Assessment of the contribution of non linear features (as opposed to linear ones) to classification performance. We observe and interpret that the classification rate improves when small values of the tunable parameter p are used.

Multiscale wavelet p-leader based heart rate variability analysis for survival probability assessment in CHF patients.

A priori discrimination of high mortality risk amongst congestive heart failure patients constitutes an important clinical stake in cardiology and involves challenging analyses of the temporal dynamics of heart rate variability (HRV). The present contribution investigates the potential of a new multifractal formalism, constructed on wavelet p-leader coefficients, to help discrimination between survivor and non survivor patients. The formalism, applied to a high quality database of 108 patients collected in a Japanese hospital, enables to assess the existence of multifractal properties amongst congestive heart failure patients and to reveal significant differences in the multiscale properties of HRV between survivor and non survivor patients, for scales ranging from approximately 60 to 250 beats.

Impact of Theiler's virus infection on hippocampal neuronal progenitor cells: differential effects in two mouse strains.

AIMS: Disease-associated alterations in hippocampal neurogenesis are discussed as an important factor contributing to long-term consequences of central nervous system diseases. Therefore, the study aimed to determine the impact of Theiler's murine encephalomyelitis virus infection on hippocampal cell proliferation, neuronal progenitor cells and neurogenesis as well as the influence of microglia on respective disease-associated alterations. METHODS: The impact of the infection was evaluated in two mouse strains which differ in the disease course, with an acute polioencephalitis followed by virus elimination in C57BL/6 mice and a chronic demyelinating disease in SJL/J mice. RESULTS: Infection with the low neurovirulent BeAn strain did not exert significant acute effects regardless of the mouse strain. In the chronic phase, the number of neuronal progenitor cells and early postmitotic neurones was significantly reduced in infected SJL/J mice, whereas no long-term alterations were observed in C57BL/6 mice. A contrasting course of microglia activation was observed in the two mouse strains, with an early increase in the number of activated microglia cells in SJL/J mice and a delayed increase in C57BL/6 mice. Quantitative analysis did not confirm a correlation between the number of activated microglia and the number of neuronal progenitor cells and early postmitotic neurones. However, flow cytometric analyses revealed alterations in the functional state of microglial cells which might have affected the generation of neuronal progenitor cells. CONCLUSIONS: Theiler's murine encephalomyelitis virus infection can exert delayed effects on the hippocampal neuronal progenitor population with long-term alterations evident 3 months following infection. These alterations proved to depend on strain susceptibility and might contribute to detrimental consequences of virus encephalitis such as cognitive impairment.

Methodology for multifractal analysis of heart rate variability: from LF/HF ratio to wavelet leaders.

The present contribution aims at proposing a comprehensive and tutorial introduction to the practical use of wavelet Leader based multifractal analysis to study heart rate variability. First, the theoretical background is recalled. Second, practical issues and pitfalls related to the selection of the scaling range or statistical orders, minimal regularity, parabolic approximation of spectrum and parameter estimation, are discussed. Third, multifractal analysis is connected explicitly to other standard characterizations of heart rate variability: (mono)fractal analysis, Hurst exponent, spectral analysis and the HF/LF ratio. This review is illustrated on real per partum fetal ECG data, collected at an academic French public hospital, for both healthy fetuses and fetuses suffering from acidosis.

Incidence of sudden cardiac death, myocardial infarction and far- and near-transyears.

We analyzed cycles with periods, tau, in the range of 0.8-2.0 years, characterizing, mostly during 1999-2003, the incidence of sudden cardiac death (SCD), according to the International Classification of Diseases, 10th revision (ICD10), code I46.1. In the tau range examined, only yearly components could be documented in time series from North Carolina, USA; Tbilisi, Georgia; and Hong Kong, in the latter two locations based on relatively short time series. By contrast, in Minnesota, USA, we found only a component with a longer than (= trans) yearly (transyearly) tau of 1.39 years; the 95% confidence interval (CI) of the tau extended from 1.17 to 1.61 years, falling into the category of transyears (defined as a tau and a 95% CI between 1.0 and 2.0 years, with the limits of the 95% CI of the spectral component's tau overlapping neither of these lengths). During the same span from 1999 to 2003 in Arkansas, USA, a component of about 1-year in length was present, and in addition, one with a tau of 1.69 year with a CI extending from 1.29 to 2.07 years, a far-transyear candidate, far-transyears being defined as having a tau with a CI between 1.20 and 2.0 year, with the CI overlapping neither of these lengths. In the Czech Republic, there was also a calendar-yearly tau and one of 1.76 years. In the latter two geographic/geomagnetic areas, the about-yearly and the longer cycles' amplitudes were of similar prominence. The taus are only candidate transyears; the 95% CIs of their taus overlap the 2-year length. When a series on SCD from 1994 to 2003 from the Czech Republic was analyzed, the 95% CI of the transyear's tau no longer overlapped the 2-year length. Transyears were also found in the Czech Republic for myocardial infarctions (MI), meeting the original transyear definition in both a shorter and a longer series. Moreover, in the 1994-2003 series on MI from the Czech Republic, a near-transyear was also found, meeting the definition of a period with a 95% CI overlapping neither precisely 1.0 year nor 1.2 years, along with a far-transyear, defined as a tau between 1.2 and 2.0 years, again with the 95% CI covering neither of these lengths. Herein, we discuss near- and far-transyears more generally in the light of their background in physics and the concept of reciprocal cyclicities.

Chronomics, neuroendocrine feedsidewards and the recording and consulting of nowcasts--forecasts of geomagnetics.

A multi-center four-hourly sampling of many tissues for 7 days (00:00 on April 5-20:00 to April 11, 2004), on rats standardized for 1 month in two rooms on antiphasic lighting regimens happened to start on the day after the second extremum of a moderate double magnetic storm gauged by the planetary geomagnetic Kp index (which at each extremum reached 6.3 international [arbitrary] units) and by an equatorial index Dst falling to -112 and -81 nT, respectively, the latter on the first day of the sampling. Neuroendocrine chronomes (specifically circadian time structures) differed during magnetically affected and quiet days. The circadian melatonin rhythm had a lower MESOR and lower circadian amplitude and tended to advance in acrophase, while the MESOR and amplitude of the hypothalamic circadian melatonin rhythm were higher during the days with the storm. The circadian parameters of circulating corticosterone were more labile during the days including the storm than during the last three quiet days. Feedsidewards within the pineal-hypothalamic-adrenocortical network constitute a mechanism underlying physiological and probably also pathological associations of the brain and heart with magnetic storms. Investigators in many fields can gain from at least recording calendar dates in any publication so that freely available information on geomagnetic, solar and other physical environmental activity can be looked up. In planning studies and before starting, one may gain from consulting forecasts and the highly reliable nowcasts, respectively.

Multiple resonances among time structures, chronomes, around and in US. Is an about 1.3-year periodicity in solar wind built into the human cardiovascular chronome?

AIMS: Velocity changes in the solar wind, recorded by satellite (IMP8 and Wind) are characterized by a solar cycle dependent approximately 1.3-year component. The presence of any approximately 1.3-year component in human blood pressure (BP) and heart rate (HR) and in mortality from myocardial infarction (MI) is tested and its relative prominence compared to the 1.0-year variation. MATERIALS AND METHODS: Around the clock manual or automatic BP and HR measurements from four subjects recorded over 5 to 35 years and a 29-year record of mortality from MI in Minnesota were analyzed by linear-nonlinear rhythmometry. Point and 95% confidence interval (CI) estimates were obtained for the approximately 1.3-year period and amplitude. The latter is compared with the 1.0-year amplitude for BP and HR records concurrent to the solar data provided by one of us (JDR). RESULTS: An approximately 1.3-year component is resolved nonlinearly for MI, with a period of 1.23 (95% CI: 1.21; 1.26) year. This component was invariably validated with statistical significance for BP and HR by linear rhythmometry. Nonlinearly, the 95% CI for the 1.3-year amplitude did not overlap zero in 11 of the 12 BP and HR series. Given the usually strong synchronizing role of light and temperature, it is surprising that 5 of the 12 cardiovascular series had a numerically larger amplitude of the 1.3-year versus the precise 1.0-year component. The beating of the approximately 1.3-year and 1.0-year components was shown by gliding spectra on actual and simulated data. DISCUSSION AND CONCLUSION: The shortest 5-year record (1998-2003) revealed an approximately 1.3-year component closer to the solar wind speed period characterizing the entire available record (1994-2003) than that for the concurrent 5-year span. Physiological variables may resonate with non-photic environmental cycles that may have entered the genetic code during evolution.

Celecoxib versus diclofenac in the management of osteoarthritis of the knee.

OBJECTIVE: A clinical trial was conducted in 600 patients with OA of the knee to test the hypothesis that the specific COX-2 inhibitor, celecoxib, has equivalent efficacy and a superior tolerability/safety profile when compared to diclofenac, the current worldwide standard of care. METHODS: Patients were administered celecoxib 100 mg BID, diclofenac 50 mg TID or placebo for 6 weeks in a multicentre, double-blind. placebo-controlled trial. RESULTS: Primary efficacy measures (index joint pain by VAS, WOMAC index) indicated statistically significant improvement versus placebo for both celecoxib and diclofenac and no statistically significant differences between celecoxib and diclofenac. American Pain Society (APS) measures to assess the rapidity of onset of action showed statistically significant and comparable pain relief versus placebo within 24 h for both celecoxib and diclofenac. More diclofenac patients reported GI side effects than patients treated with either placebo or celecoxib. Diclofenac-treated patients experienced statistically significant elevations in mean hepatic transaminases and serum creatinine and reductions in haemoglobin concentration when compared to placebo, events not observed with celecoxib. CONCLUSION: Celecoxib 200 mg daily is as effective as diclofenac 150 mg daily for relieving signs and symptoms of OA of the knee, including pain, and has a rapid onset of action. However, celecoxib appears to have a superior safety and tolerability profile.

Heterogeneous relaxation patterns in supercooled liquids studied by solvation dynamics

We have measured the solvation dynamics of a dipolar supercooled liquid near its glass transition in a temperature range in which the average structural relaxation time varies more than four orders of magnitude. The analysis of the time dependent average emission energy and the inhomogeneous linewidth of the S0<--T1(0-0) transition reveals that the orientation correlation decay pattern intrinsic in each relaxing unit is associated with a stretching exponent beta(intr)=1.00+/-0.08 in the entire range T(g)(KWW) the individual time constants remain correlated to their initial values at t=0.

Changing leaders: the board's role in CEO succession ... roundtable discussion.

The selection of a CEO is one of the most important- and risky-events in the life of any company. Yet the way CEOs are chosen remains little discussed and little understood. The succession process has traditionally unfolded behind closed doors--some observers have even likened it to the election of a pope. To shed light on what works and what doesn't in CEO succession, the authors lead a roundtable discussion with five distinguished corporate directors: Philip Caldwell, George D. Kennedy, G. G. Michelson, Henry Wendt, and Alfred M. Zeien. Collectively, the five directors have participated in dozens of successions, either as board members or as CEOs. In a lively and frank exchange of views and experiences, the roundtable participants explore a broad range of questions: What can a company do to ensure a successful succession? How should management-development and succession processes be managed? How should the board work with the sitting chief executive during the process? What makes for a strong CEO candidate? When should outside candidates be considered? How much competition should be encouraged among potential CEO candidates? What role should executive search firms play? What role should former CEOs play after they are succeeded? Their conversation illuminates a corporate challenge that is as difficult as it is important.

[The origin of the biological week from data on the rhythm of cardiac contractions in people during the solar activity cycle]. / O probleme proiskhozhdeniia biologicheskoi nedeli po dannym o variatsiiakh ritma chastoty serdechnykh sokrashchenii u liudei v tsikle solnechnoi aktivnosti.

A human biologic week in the heart rate variations was compared with the variations of the sunspot area and geomagnetic activity over the solar cycle. The low ratio of amplitude of circaseptan rhythm to that of circadian rhythm in the heart rate of several clinically healthy men who did around-the-clock self-measurements in a number of years coincides with the period of anomalously low amplitude of circaseptan rhythm of the solar activity. Results herein suggest that physiologic circaseptan rhythms are built into the genome being adapted evolutionary to the original heliogeomagnetic environmental circaseptans.

DNA-mediated folding and assembly of MyoD-E47 heterodimers.

Basic region helix-loop-helix (bHLH) transcription factors regulate key steps in early development by binding to regulatory DNA sites as heterodimers consisting of a tissue-specific factor and a widely expressed factor. We have examined the folding, dimerization, and DNA binding properties of the muscle-specific bHLH protein MyoD and its partner E47, to understand why these proteins preferentially associate in heterodimeric complexes with DNA. In the absence of DNA, the E47 bHLH domain forms a very stable homodimer, whereas MyoD is unfolded and monomeric. Fluorescence quenching experiments show that MyoD does not dimerize with E47 under dilute conditions in the absence of DNA. Residues in and around the loop of the E47 bHLH domain contribute to its markedly greater stability. An altered MyoD bHLH substituted with the loop segment from E47 folds in the absence of DNA, and it readily dimerizes with E47. In the presence of a specific DNA binding site, MyoD and E47 both form homodimeric complexes with DNA that have similar dissociation constants, despite the very different stabilities of these protein dimers off DNA. A 1:1 mixture of these bHLH domains forms almost exclusively heterodimeric complexes on DNA. Assembly of these bHLH-DNA complexes is apparently governed by the strength of each subunit's interaction with the DNA and not by the strength of protein-protein interactions at the dimer interface. These findings suggest that preferential association of MyoD with E47 in DNA complexes results from more favorable DNA contacts made by one or both subunits of the heterodimer in comparison with either homodimeric complex.

Very rapid, ionic strength-dependent association and folding of a heterodimeric leucine zipper.

Leucine zippers (coiled coils) are dimerization motifs found in several DNA-binding transcription factors. A parallel leucine zipper composed of the acidic chain X1-EYQALEKEVAQLEAENX2-ALEKEVAQLEHEG-amide and the basic chain X1-EYQALKKKVAQLKAKNX2ALKKKVAQLKHKG-amide was designed to study the kinetics of folding of a heterodimeric leucine zipper and to investigate the role of electrostatic attraction between oppositely charged peptide chains to the folding reaction. Each peptide alone did not form a leucine zipper at ionic strength (mu) < 1 M because of electrostatic repulsion between like charges in a homodimer. Therefore, the formation of the heterodimeric leucine zipper could be investigated by simple mixing of acidic and basic chains. To monitor folding, a fluorescent label was located either at the N-terminus (X1 = fluorescein-GGG, X2 = Q) or in the center of the coiled coil (X1 = acetyl, X2 = W). Folding could be described by a simple two-state reaction involving the disordered monomers and the folded heterodimer. The same bimolecular rate constant (k(on)) was observed independent of the location of the fluorescent label, indicating that both fluorescence probes monitored the same reaction. Lowering of the ionic strength increased k(on) from 4 x 10(6) M-1 s-1 (mu = 525 mM) to about 5 x 10(7) M-1 s-1 (mu = 74 mM). When extrapolated to mu = O, k(on) was approximately 10(9) M-1 s-1, which is near the diffusion limit. In contrast, the rate of dissociation depended very weakly on ionic strength; k(off) decreased only by about 2-fold when mu was lowered from 525 to 74 mM. Equilibrium association constants (Ka) of the heterodimeric zippers measured directly and calculated from kinetic constants (Ka = k(on)/k(off) were in good agreement. The observed two-state mechanism, the strong dependence on ionic strength of k(on) but not of k(off), and the nearly diffusion-limited association rate at very low ionic strength point to a folding pathway in which the formation of an electrostatically stabilized dimeric intermediate may be rate-limiting and the subsequent folding to the final dimer is very rapid and follows a "down-hill" free energy landscape. The small increase of k(off) at increasing ionic strength indicates a minor contribution of electrostatics to the stability of the folded leucine zipper.