Recovery of mobility function and life-space mobility after ischemic stroke: the MOBITEC-Stroke study protocol.

BACKGROUND: Stroke is a major cause of disability and stroke incidence increases with age. Stroke frequently results in permanent limitations of mobility, and, consequently, the need for the help of others in activities of daily living. In order to optimize rehabilitative efforts and their functional outcomes, detailed knowledge of the functional recovery process, regarding mobility, is needed. Objectives of the MOBITEC-Stroke study are: 1.) To characterize mobility, including lower extremity physical function (LEPF) and life space (the geospatial extent of all of a person's movements), and changes in mobility within the first year after stroke. 2.) To identify and characterize subgroups with different mobility trajectories. 3.) To evaluate whether changes in LEPF are associated with changes in life-space. 4.) To evaluate participants' reasons for going outdoors, transportation use, and assistance needed for outdoor movement. METHODS: Patients with incident first stroke who live in their own homes (target N = 59, based on sample size calculation) will be included in this cohort study. At 3, 6, 9, and 12 months after stroke a battery of mobility tests will be performed at the study centre, including laboratory-based tests of balance and strength, and quantitative gait analysis. Life-space assessment (including 1-week GPS measurements) will be performed in participants' real life. Semantic information on visited locations (reasons for going outdoors, transportation use, assistance needed) will be collected by using interactive digital maps. Linear mixed effects models will be used to model the trajectories of mobility measures for the total sample and for predefined subgroups. As an exploratory analysis, growth mixture models (GMMs) will be used to identify relevant subgroups with different trajectories. Linear mixed effect models will be used to test whether changes in LEPF parameters are associated with changes in life-space. Participants' motivation for going outdoors, transportation use, and assistance needed for outdoor mobility will be analysed descriptively. DISCUSSION: A comprehensive and detailed knowledge of recovery patterns will enable the planning of targeted and adaptively tailored rehabilitation measures. Information about patients' reasons for outdoor mobility will provide the opportunity to define individualized and patient-oriented rehabilitation goals. TRIAL REGISTRATION: ISRCTN85999967 (on 13 August 2020; retrospectively).

Risk factors for football injuries in young players aged 7 to 12 years.

Football (soccer) is very popular among children. Little is known about risk factors for football injuries in children. The aim was to analyze potential injury risk factors in 7- to 12-year-old players. We collected prospective data in Switzerland and the Czech Republic over two seasons. Coaches reported exposure of players (in hours), absence, and injury data via an Internet-based registration system. We analyzed time-to-injury data with extended Cox models accounting for correlations on team- and intra-person levels. We analyzed injury risk in relation to age, sex, playing position, preferred foot, and regarding age-independent body height, body mass, and BMI. Further, we analyzed injury risk in relation to playing surface. In total, 6038 player seasons with 395 295 hours of football exposure were recorded and 417 injuries occurred. Injury risk increased by 46% (Hazard Ratio 1.46 [1.35; 1.58]; P < .001) per year of life. Left-footed players had a higher injury risk (Hazard Ratio 1.53 [1.07; 2.19]; P = .02) for training injuries compared to right-footed players. Injury risk was increased in age-adjusted taller players (higher percentile rank). Higher match-training ratios were associated with a lower risk of match injuries. Injury risk was increased on artificial turf (Rate Ratio 1.39 [1.12; 1.73]; P < .001) and lower during indoor sessions (Rate Ratio 0.68 [0.52; 0.88]; P < .001) compared to natural grass. Age is known as a risk factor in older players and was confirmed to be a risk factor in children's football. Playing surface and leg dominance have also been discussed previously as risk factors. Differences in injury risks in relation to sex should be investigated in the future.

Head injuries in children's football-results from two prospective cohort studies in four European countries.

Head injuries are considered harmful in children. We analyzed head and neck injuries in organized football in 7- to 12-year-old children. Data for this analysis were obtained from a prospective cohort study over two consecutive football seasons in two European countries, and a randomized intervention trial over one season in four European countries. Football exposure and injuries were documented through an online database. Detailed information regarding injury characteristics and medical follow-up was retrieved from coaches, children and parents by phone. Thirty-nine head injuries and one neck injury (5% of all 791 injuries) were documented during 9933 player-seasons (total football exposure 688 045 hours). The incidence was 0.25 [95%CI 0.15, 0.35] head/neck injuries per 1000 match hours (N=23 match injuries) and 0.03 [95%CI 0.02, 0.03] per 1000 training hours. Eleven concussions (27.5%), nine head contusions (22.5%), eight lacerations or abrasions (20%), two nose fractures (2.5%), and two dental injuries (2.5%) occurred. The remaining eight injuries were nose bleeding or other minor injuries. Thirty injuries (75%) resulted from contact with another player, and ten injuries were due to collision with an object, falling or a hit by the ball. Whereas 70% of all head injuries (N=28) were due to frontal impacts, 73% of concussions (N=8) resulted from an impact to the occiput. The incidence and severity of head injuries in children's football are low. Coaches and parents, however, should be sensitized regarding the potential of concussions, particularly after an impact to the occiput.

A new injury prevention programme for children's football--FIFA 11+ Kids--can improve motor performance: a cluster-randomised controlled trial.

The present study evaluated the effects of a newly developed injury prevention programme for children's football ("FIFA 11+ Kids") on motor performance in 7-12-year-old children. We stratified 12 football teams (under-9/-11/-13 age categories) into intervention (INT, N = 56 players) and control groups (CON, N = 67). INT conducted the 15-min warm-up programme "FIFA 11+ Kids" twice a week for 10 weeks. CON followed a standard warm-up (sham treatment). Pre- and post-tests were conducted using: single leg stance; Y-balance test; drop and countermovement jump; standing long jump; 20-m sprint; agility run; slalom dribble; and wall volley test. We used magnitude-based inferences and linear mixed-effects models to analyse performance test results. We observed likely beneficial effects favouring INT in Y-balance (right leg; +3.2%; standardised mean difference (SMD) = 0.34; P = 0.58) and agility run (+3.6%; SMD = 0.45; P = 0.008). Possibly beneficial effects were found in Y-balance, drop jump reactive strength index, drop jump height, countermovement jump, standing long jump, slalom dribble and wall volley test. At least possibly beneficial improvements in favour of "FIFA 11+ Kids" were observed in nearly all parameters. Most effects were small, but slight improvements in motor performance may potentially contribute to a reduction of injury risk.

Fast in situ phase and stress analysis during laser surface treatment: a synchrotron x-ray diffraction approach.

An in situ stress analysis by means of synchrotron x-ray diffraction was carried out during laser surface hardening of steel. A single exposure set-up that based on a special arrangement of two fast silicon strip line detectors was established, allowing for fast stress analysis according to the sin(2)ψ x-ray analysis method. For the in situ experiments a process chamber was designed and manufactured, which is described in detail. First measurements were carried out at the HZG undulator imaging beamline (IBL, beamline P05) at the synchrotron storage ring PETRA III, DESY, Hamburg (Germany). The laser processing was carried out using a 6 kW high power diode laser system. Two different laser optics were compared, a Gaussian optic with a focus spot of ø 3 mm and a homogenizing optic with a rectangular spot dimension of 8 × 8 mm(2). The laser processing was carried out using spot hardening at a heating-/cooling rate of 1000 K/s and was controlled via pyrometric temperature measurement using a control temperature of 1150 °C. The set-up being established during the measuring campaign allowed for this first realization data collection rates of 10Hz. The data evaluation procedure applied enables the separation of thermal from elastic strains and gains unprecedented insight into the laser hardening process.

Quantitative determination of element concentrations in industrial oxide materials by laser-induced breakdown spectroscopy.

Calibration-free laser-induced breakdown spectroscopy (CF-LIBS) method is employed for quantitative determination of oxide concentrations in multi-component materials. Industrial oxide materials from steel industry are laser ablated in air, and the optical plasma emission is collected by spectrometers and gated detectors. The temperature and electron number density of laser-induced plasma are determined from measured LIBS spectra. Emission lines of aluminium (Al), calcium (Ca), iron (Fe), manganese (Mn), magnesium (Mg), silicon (Si), titanium (Ti), and chromium (Cr) of low self-absorption are selected, and the concentration of oxides CaO, Al(2)O(3), MgO, SiO(2), FeO, MnO, TiO(2), and Cr(2)O(3) is calculated by CF-LIBS analysis. For all sample materials investigated, we find good match of calculated concentration values (C(CF)) with nominal concentration values (C(N)). The relative error in oxide concentration, e(r) = |C(CF) - C(N)|/C(N), decreases with increasing concentration and it is e(r) ≤ 100% for concentration C(N) ≥ 1 wt.%. The CF-LIBS results are stable against fluctuations of experimental parameters. The variation of laser pulse energy over a large range changes the error by less than 10% for major oxides (C(N) ≥ 10 wt.%). The results indicate that CF-LIBS method can be employed for fast and stable quantitative compositional analysis of multi-component materials.

Differentiation of non-mesencephalic neural stem cells towards dopaminergic neurons.

Neural stem cells (NSCs), either isolated from fetal or adult human brain or derived from induced pluripotent stem cells, are now considered major candidates for in vitro generation of transplantable dopaminergic (DA) neurons and modeling of Parkinson's disease. It is generally thought that in vitro differentiation of neural stem cells into meso-diencephalic dopaminergic neurons, requires recapitulation of dopaminergic differentiation pathway normally occurring in the ventral mesencephalon during embryogenesis. This dopaminergic pathway is partially activated by a combination of the extracellular induction factors Sonic Hedgehog (Shh), Fibroblast Growth Factor 8 (FGF8) and Wnt1 that trigger specific intracellular transcription cascades. In vitro mimicking of these embryonic ventral mesencephalic conditions has been successful for dopaminergic differentiation of embryonic stem cells and ventral mesencephalic NSCs. Dopaminergic differentiation of non-mesencephalic NSCs (nmNSCs), however, is considered arduous. Here we examine whether Shh, FGF8 and Wnt1 can activate typical dopaminergic transcription factors, such as Lmx1a, Msx1 and Otx2 in nmNSCs. We found that Shh, FGF8 and Wnt1 induced the expression of Lmx1a and Otx2 in nmNSCs resulting in the differentiation of up to 39% of the nmNSCs into neurons expressing Pitx3. However, only a low number ( approximately 13%) of these cells became more DA-like neurons also expressing tyrosine hydroxylase (TH). The histone deacetylase (HDAC)-inhibitor trichostatin A combined with Shh, FGF8 and Wnt1 caused orchestrated induction of Lmx1a, Otx2, Msx1 plus the early DA transcription factor En1. Now significantly increased numbers of TH ( approximately 22%) and Pitx3 ( approximately 33%) neurons were observed. Most of these cells coexpressed the DA markers DAT and Vmat2. Taken together, we demonstrate that nmNSCs indeed can be differentiated towards DA-like neurons, but this differentiation is far from complete in comparison to ventral mesencephalic NSCs and embryonic stem cells; most likely, the nmNSCs lack the proper "primed" epigenetic state of these cells for DA differentiation facilitating the induction of DA specific transcription factors.

Diversity of exine structure in Upper Carboniferous (Westphalian) selaginellalean megaspores.

Studies of wall structure in Mesozoic and Recent selaginellalean megaspores have been well documented. However, Palaeozoic examples have received minimal attention. The principal Palaeozoic megaspore genus of likely selaginellalean affinity is Triangulatisporites, extending from the Upper Devonian to the Upper Carboniferous. The particulate wall ultrastructure of a previously published Carboniferous (Duckmantian) megaspore assigned to this genus suggested that this form of wall construction may have been the ancestral wall structure of the group, an observation which posed difficulties in relating selaginellalean ultrastructure to that of other contemporaneous lycopsid megaspores. Subsequent investigation showed that the genus also contains more laminate exines similar to those of other extinct lycopsids and extant Selaginella species. Our new examples of Triangulatisporites ultrastructure from the Langsettian, Duckmantian and Westphalian D yield more information regarding early variation of wall structure within Carboniferous selaginellalean megaspores and suggest that a more laminate wall composition is at least as old as the particulate form. However, without further investigation of Lower Carboniferous forms, we are unable to state which is indeed ancestral. The laminate structure reported here and elsewhere is, none the less, more easily related to comparable ultrastructure in other groups of Carboniferous lycopsid megaspores and could suggest a link with such genera as Zonalesporites and early Lagenicula. This would be in keeping with current concepts regarding the most primitive ultrastructural type within lycopsid megaspore walls.

The role of magnetic resonance imaging and scintigraphy in the diagnosis of pathologic changes of the mandible after radiation therapy.

A prospective study of 85 patients with oral cancer, treated with high-dose radiation therapy, was performed to assess the value of magnetic resonance imaging (MRI) and scintigraphy for diagnosis of pathologic changes in the mandible. During postradiotherapeutic monitoring, radiation osteomyelitis occurred in 12 cases, tumor recurrences infiltrating the mandible in five cases, and progressive periodontal disease in nine cases. MRI permitted early diagnosis of radiation osteomyelitis in 11 out of 12 cases; only two cases were false positive. In scintigraphy with 99mTc-HDP, all alterations of the mandible, such as osteoradionecrosis, tumor infiltration, and periodontitis, showed a high uptake, resulting in a sensitivity of up to 100%, but a low specificity of 57%. Scintigraphy permitted assessment of the extension and location of the lesions. Both methods were superior to conventional radiography and clinical examination and should be integrated into a comprehensive follow-up program after radiation therapy.

Slower aging in women: a proposed evolutionary explanation.

Differential female longevity is so far unexplained in evolutionary terms. The theory of evolutionarily necessary aging which goes back to Wallace appears to be up to the task. In this theory, aging minimizes competition between forebear and offspring. The aging equation which is implicit contains the well-known empirical Gompertz law as a special case. Moreover, its parameters are automatically sex-specific. It is shown that the slower aging of the female members of two species of mammals, humans and sperm whales, can be 'predicted' on the basis of this equation. A prediction of effective human monogamy under archaic conditions is obtained as a corollary. The analogous if opposite prediction for sperm whales (strong promiscuity) is empirically testable.

Chaos in physiology.

A bird's eye view of the role of nontrivial dynamical phenomena in physiological systems is presented. Many levels in the physiological hierarchy are affected. It appears that physiology has a particularly high affinity to chaos. The old central place of physiology in the circle of sciences can perhaps be regained if the two disciplines join resources. Even physics may turn out to be dependent on the chaotic micro dynamics of the brain.

Artificial life extension. The epigenetic approach.

An epigenetic approach starts out from the direct (rather than the underlying genetic) causes. An epigenetic approach to aging has little chance of succeeding before a minimum amount of knowledge has been accumulated on the "genetic programming" that is currently believed to underlie aging. Two recent advances, one empirical and one theoretical, jointly brighten the prospect. The empirical one is the discovery that melatonin functions as an aging-controlling hormone in mammals. In 1979, Dilman and co-workers isolated a biologically active pineal extract (epithalamin) in rats which, as they later showed, stimulates melatonin production. Pierpaoli and co-workers in 1987 directly administered melatonin to mice. Both groups observed a surprising 25-percent increase of life span in conjunction with a postponed senescence. A similar effect was also achieved with an engraftment of young pineal tissue into the thymus of old mice by Pierpaoli's group. Beneficial effects of epithalamin in humans were reported by Dilman's group. The second advance is a deductive evolution-theoretical approach to aging discovered in 1988. In populations living in a niche with a fixed carrying capacity, any individual is in the long run replaced by a single successor. It follows that, as the expected cumulative number of adult progeny of the same sex approaches unity as a function of life time of the progenitor, the latter's survivability must approach zero if the sum is to remain unity. A physiological prediction follows: a centralized physicochemical clock--like a sedimentation process--must exist somewhere in the organism controlling a secreted substance that reaches all cells. In this way, the pineal coacervates and the pineal's hormonal product melatonin were arrived at on an independent route again. While melatonin as a drug has been used on human volunteers for decades, its anti-aging effect has yet to be proved. Detailed hormone profiles in different age groups and under different life styles have to be performed. A modified Hayflick in vitro experiment is also needed to elucidate the mechanism by which melatonin works in cells.

[MRT in the diagnosis of mandibular osteomyelitis following radiotherapy]. / Die MRT in der Diagnose der Unterkieferosteomyelitis nach Strahlentherapie.

A prospective study was performed to assess the diagnostic potential of MRI in mandibular osteomyelitis after radiation therapy. A total of 60 MRI studies were performed in 39 patients with lymphoma and carcinoma of the head and neck. Clinically or histologically proven osteomyelitis of the mandible occurred in 10 patients depending on the radiation dose absorbed to bone; 9 of these were unequivocally diagnosed by typical MRI appearance, two cases were false positive. MRI is superior to other diagnostic methods such as conventional radiology and clinical examination. It should be performed routinely in an oncological follow-up after radiation therapy depending on the dental status and radiation dose.

Is the mind-body interface microscopic?

This paper puts forward the hypothesis that consciousness might be linked to matter in a way which is more sophisticated than the traditional macroscopic Cartesian hypothesis suggests. Advances in the biophysics of the nervous system, not only on the level of its macroscopic functioning but also on the level of individual ion channels, have made the question of 'how finely' consciousness is tied to matter and its dynamics more important. Quantum mechanics limits the attainable resolution and puts into doubt the idea of an infinitely fine-woven attachment. A recent approach to physics rekindles such a rationalist hope. 'Endophysics' focuses on the global implications of microscopic computer simulations of chemical and biophysical processes. A complete 'artificial universe' can be set up in the computer. It produces non-classical and nonlocal effects inside--on the 'interface' that exists between an internal observer ('fluid neuron') and the rest of the world. This interface is finer than any brain property to which the status of the mind-body interface has been attributed hitherto. A new class of experiments becomes possible in the artificial world and, by analogy, in the real world. Magnetic resonance imaging experiments, routinely performed under open-loop conditions, can be repeated under psychophysical (closed-loop) conditions--in search for microscopically induced changes in the perceived and measured structure of the world.

Timekeeping in genetically programmed aging.

Genetically programmed aging, with its cellular genetic switching implied by the in vitro Hayflick limit, requires additional timing devices to coordinate the switching processes within the different cells of a highly complex life form. Evolutionary arguments have been presented elsewhere to support the need for a centralized timing mechanism as against a localized mean-field alternative. Extensive evidence is now available for the role of the pineal gland and its secreted melatonin in the aging process. The nightly melatonin peak changes with age, thus providing a potential signal to inform all of the cells in the organism of its age. Here it is hypothesized that the decoding of this "durational signal" at the cellular level is carried out with the aid of the sleep induced pCO2 changes in the blood. To test this hypothesis, modifications of the in vitro Hayflick experiment and of the in vivo Pierpaoli longevity experiment involving rhythmic addition of melatonin and pH manipulations are proposed.

Does a centralized clock for ageing exist?

It is proposed that a centralized clock controlling ageing is located in the pineal gland with the calcification process occurring there providing a highly accurate bio-inorganic timing mechanism and the secreted melatonin carrying a signal to all cells in the organism. An explicit programme of data gathering and experiments suitable for the falsification of the proposal, which is consistent with presently known anatomical and physiological facts, is presented. The underlying motivation comes from evolutionary biology and the invariance, that is the allometry, of life expectancy curves.

A predictive model for life expectancy curves.

Life expectancy curves have a characteristic ominous shape that has fascinated scientists for centuries. Medawar was the first to explain this shape, specifically the steeply rising proneness of an average individual to die as a function of age, in evolutionary terms. The idea was that the "selective value" of the individual decreases as it has triggered other individuals taking its place (and carrying its genes) into existence. We demonstrate that this idea can be turned into a quantitative model. The resulting 4-parameter function reproduces well two well-known life expectancy curves from the first half of this century. Moreover, the easily interpretable parameters (3 of the 4) seem intuitively reasonable.

[Tono-pen versus manometer. Comparative measurements of intraocular pressure in human cadaver eyes]. / Tono-pen versus Manometer. Vergleichende Augeninnendruckmessungen an menschlichen Leichenaugen.

A new hand-held tonometer, the Tono-Pen (TP), was compared with a Statham membrane manometer (MAN). The TP is a pen-sized Mackay-Marg tonometer with electronic signal analysis and digital pressure display. Comparative measurements of intra-ocular pressure (IOP) were performed on six cadavers (12 eyes in situ), 3-6 hours after death. The IOP was changed in 5 to 10 mm Hg steps in a range between 0 and 60 mm Hg by an infusion system. As compared to the manometrically determined IOP, the TP gave small overestimation of IOP below 17 mm Hg and a small underestimation above 17 mm Hg (maximum deviation 2.5 mm Hg). The mean values of 29.9 (TP) and 30.4 mm Hg (MAN) were not significantly different (p greater than 0.05, analysis of variance). The correlation coefficient was 0.99. The relationship between TP (y axis) and MAN (x axis) pressure readings is characterized exactly by a slightly curvilinear graph (y = 0.82x + 0.0002x2 + 2.52; mm Hg). This may be approximated by a regression line with a slope of 0.94, a y intercept of 1.46 mm Hg and a standard deviation of the TP readings in relation to the regression line of 2.36 mm Hg. In conclusion, the good agreement between TP and MAN pressure readings is superior to the recently described agreement between TP and Goldmann tonometer readings.

Tono-Pen, a new tonometer.

UNLABELLED: The Tono-Pen is a miniaturized Mackay-Marg tonometer with electronic signal analysis and digital pressure display. In study 1, we compared the Tono-Pen with Goldmann tonometry in 108 healthy human subjects (216 eyes). In 33 of these subjects, the IOP was changed in a range between 0 and 50 mmHg by a scleral suction-cup system. In study 2, the Tono-Pen was compared with a Statham membrane manometer in 6 humans (12 eyes), 3-6h after death. The IOP was changed in a range between 0 and 60 mmHg by an infusion system. - RESULTS: Related to the Goldmann tonometer, the Tono-Pen gave a small overestimation of IOP below 16 mmHg (maximum deviation 1.5 mmHg at 0 mmHg Goldmann reading). Above 16 mmHg, however, the Tono-Pen increasingly underestimated the IOP determined by Goldmann tonometry (maximum deviation 8 mmHg at 50 mmHg Goldmann reading). Related to the manometer, the Tono-Pen gave a small overestimation of IOP below 17 mmHg and small underestimation above 17 mmHg (maximum deviation 2.5 mmHg at manometer readings of 0 and 60 mmHg, respectively). - CONCLUSIONS: Throughout the entire clinically relevant IOP range, an acceptable relationship between Tono-Pen and manometer readings was found in human cadaver eyes, whereas the relationship between Tono-Pen and Goldmann tonometric readings in the clinical study was found to be acceptable only in the low and physiological IOP range. The considerable deviation from the Goldmann readings in the high IOP range requires further modifications of the Tono-Pen.

[Tono-pen, a new position-independent tonometer. Comparison with the Goldmann tonometer by applanation measurement]. / Tono-Pen, ein neues lageunabhängiges Tonometer. Applanatorische Vergleichsmessungen mit dem Goldmann-Tonometer.

A new hand-held tonometer, Tono-Pen (TP), was compared with the Goldmann tonometer (GM). The TP utilizes the operating principle of the Mackay-Marg tonometer. However, the TP is battery-operated, only 18 cm long, weighs only 60 g, and features electronic signal analysis (single-chip microprocessor) and a digital pressure display (mm Hg). In 108 subjects (216 eyes) presenting no ocular abnormalities, comparative tonometric measurements were performed in randomized order by two investigators (A: TP; B: GM). In 33 of these subjects (66 eyes), the intraocular pressure (IOP) was changed by means of a scleral suction-cup system. A total of 457 pairs of values was obtained in an IOP range extending continuously from 0 to 50 mm Hg. The relationship between TP (y axis) and GM (x axis) pressure readings is described exactly by a slightly curvilinear graph (y = 0.96x - 0.003x2 + 1.48; mm Hg). This may be approximated by a regression line with a slope of 0.8, a y intercept of 2.76 mm Hg and a standard deviation of 2.5 mm Hg (y values) in relation to the regression line. The mean values were 17.6 (TP) and 18.6 mm Hg (GM), which were not significantly different (P less than 0.05). The correlation coefficient amounted to 0.97. Below an IOP (GM) of 16 mm Hg, the TP slightly overestimated the IOP by a maximum of 1.48 mm Hg at GM = 0). Above 16 mm Hg, the TP increasingly underestimated, the IOP by a maximum of 8 mm Hg at GM = 50). Summing up, the TP is unique among hand-held tonometers in its miniaturization. In the low and physiological pressure range, there is an acceptable relationship between TP and GM readings. In the high pressure range, however, its readings deviate considerably from those of the tonometer.