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Purpose: Demographic change will lead to an increase in age-associated cancers. The demand for primary treatment, especially oncologic therapies, is difficult to predict. This work is an attempt to project the demand for radiation therapy (RT) in 2030, taking into account demographic changes using prostate cancer (PC) as an example. Materials and methods: Using the GENESIS database of the Federal Statistical Office, we retrieved demographic population projections for 2030 and retrospective demographic surveys from 1999 to 2019. Additionally, we queried incidence rates for PC in the respective age groups of 50–54, 55–59, 60–64, 65–69, 70–74, 75–79, 80–84, and +85 years from 1999–2019 via the Federal Cancer Registry of the Robert Koch Institute. We used a regression method to determine the age-dependent correlation between the incidence of PC and the population size of the respective age group by combining the data from 1999 to 2019. This information was used to calculate the incidence rates in the age groups of the expected population for 2030 and the expected new cases of PC in 2030. Finally, we extrapolated the indications for the demand for RT based on data from the Report on Cancer Incidence in Germany from 2016. Results: Considering a population-dependent incidence rate, an increase in new cases of PC is expected. This increase is particularly evident in the age groups of 70–74 and 80–84 years. With regards to RT, the estimate indicates an overall increase of 27.4% in demand. There is also a shift in RT demands towards older patients, especially in the 80- to 84-year-old age group. Conclusion: We observe an age-associated increase in primary cases of PC. This is likely to result in an increased demand for RT. The exact demand cannot be predicted. However, trends can be estimated to plan for the demand. This, though, requires a good database from cancer registries. [ABSTRACT FROM AUTHOR]

During transcranial electric stimulation, increasing intracellular Ca2+ levels beyond those needed for inducing long term potentiation (LTP) may collapse aftereffects. State-dependent plastic aftereffects are reduced when applied during muscle activation as compared with rest. Cortical surround inhibition by antagonistic muscle activation inhibits the center-innervated agonist. The objective of this study is to determine the interaction of state dependency of transcranial alternating current stimulation (tACS) aftereffects at rest and under activation of agonist and antagonist muscles during stimulation with different intensities. In 13 healthy participants, we measured motor-evoked potential (MEP) amplitudes before and after applying tACS at 140 Hz over the motor cortex in nine single-blinded sessions using sham, 1 mA, and 2 mA stimulation intensities during rest and activation of agonist and antagonist muscles. During rest, only 1 mA tACS produced a significant MEP increase, whereas the 2 mA stimulation produced no significant MEP size shift. During agonist activation 1 mA did not induce MEP changes; after 2 mA, first a decrease and later an increase of MEPs were observed. Antagonist activation under sham tACS led to an inhibition, which was restored to baseline by 1 and 2 mA tACS. Increasing stimulation intensity beyond 1 mA does not increase excitability, compatible with too strong intracellular Ca2+ increase. Antagonist innervation leads to MEP inhibition, supporting the concept of surround inhibition, which can be overcome by tACS at both intensities. During agonist innervation, a tACS dose-dependent relationship exists. Our results integrate concepts of “leaky membranes” under activation, surround inhibition, intracellular Ca2+ increase, and their role in the aftereffects of tACS. NEW & NOTEWORTHY Stimulation intensity and activation of center versus surround muscles affect cortical excitability alterations generated by 140-Hz tACS. At rest, excitatory aftereffects were induced by tACS with 1 mA, but not 2 mA stimulation intensity. With agonistic muscle activation, excitability first decreases, and then increases with 2 mA. For antagonist activation, the MEP amplitude reduction observed in the sham condition is counteracted upon by 1 and 2 mA tACS. This reflects the relation of LTP-like aftereffects to Ca2+ concentration alterations. [ABSTRACT FROM AUTHOR]

Rationale: There is little clinical data available about seizure rates in psychiatric inpatients, and there are no studies with reference data to the frequencies of antidepressant (AD) use for this important clinical population. Objective: This study investigates seizure rates during AD treatment in psychiatric inpatient settings, drawn from the transnational pharmacovigilance programme Arzneimittelsicherheit in der Psychiatrie (AMSP) in relation to the known frequencies of ADs used in the participating clinics. Comparisons are made to former publications and their limitations. Results: Seventy-seven cases were identified with grand mal seizures (GMS) during AD treatment between 1993 and 2008, with a total number of 142,090 inpatients under surveillance treated with ADs in the participating hospitals. The calculated overall rate of reported seizures of patients during AD treatment in this collective is 0.05 % for ADs imputed alone or in combination with other psychotropic drug groups and 0.02 % when only ADs were given and held responsible for GMS. The patients receiving tri- or tetracyclic ADs (TCAs) had a 2-fold risk to develop a seizure as compared to the overall average rate in this sample. In 11 cases, there was only one AD imputed-the majority of these cases (9/11) were TCA. Monotherapy with selective serotonin reuptake inhibitors (SSRI) or dual serotonin and noradrenaline reuptake inhibitors (SNRI) were never imputed alone in this sample. Conclusions: The results of the study favour the assumption that SSRIs, noradrenergic and specific serotonergic antidepressants (NaSSA) and dual SNRI might be more appropriate than TCAs for the treatment of psychiatric patients with an enhanced seizure risk. [ABSTRACT FROM AUTHOR]

Rational: Activation of nicotinic acetylcholine receptors has a major neuromodulatory impact on central nervous system function. Beyond acute activation, chronic nicotine intake has long-lasting effects on cortical excitability in animal experiments, caused by receptor up- or down-regulation. Knowledge about the impact of nicotine on cortical excitability in humans, however, is limited. Objectives: We therefore aimed to explore the effect of nicotine intake on cortical excitability in healthy human smokers and non-smokers. Methods: The primary motor cortex served as model, and cortical excitability was monitored via transcranial magnetic stimulation (TMS). Corticospinal excitability and intracortical excitability were recorded before and after application of nicotine patch in both groups. Corticospinal excitability was explored by motor threshold and input/output curve (I/O curve), and intracortical excitability was explored by means of paired-pulse TMS techniques (intracortical facilitation (ICF), short-latency intracortical inhibition (SICI), I-wave facilitation and short-latency afferent inhibition (SAI)). Results: The results show that smokers during nicotine withdrawal display increased corticospinal excitability with regard to the I/O curve (TMS intensity 150 % of resting motor threshold) compared to non-smokers and furthermore enhanced SAI and diminished ICF at the intracortical circuit level. After administration of nicotine, intracortical facilitation in smokers increased, while in non-smokers, inhibition (SICI, SAI) was enhanced. Conclusion: Our results show that chronic nicotine consumption in smokers alters cortical excitability independent from acute nicotine consumption and that acute nicotine has different effects on motor cortical excitability in both groups. [ABSTRACT FROM AUTHOR]

Key points Application of 2 mA cathodal transcranial direct current stimulation for 20 min results in cortical excitability enhancement instead of inhibition., Longer or more intensive stimulation does not necessarily increase its efficacy., Short intracortical inhibition and facilitation are shifted towards excitability enhancement after both 2 mA anodal and cathodal stimulation., I-waves, input-output curves and cortical silent period are unaffected immediately after 2 mA stimulation., Abstract Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm2 has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition. No significant changes were observed in the other protocols. Sham tDCS did not induce significant MEP alterations. These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation, but might also shift the direction of excitability alterations. This should be taken into account for applications of the stimulation technique using different intensities and durations in order to achieve stronger or longer lasting after-effects. [ABSTRACT FROM AUTHOR]

The article presents a method for measuring flow velocity and several macroroughness parameters including boulder concentration, boulder diameter and protrusion in steep mountain streams. It explains the between-site variations in flow resistance by nondimensionalization of discharge and flow velocity using channel slope and a characteristic roughness length. It mentions that boulder concentration is best parameter used for measuring flow velocity through simple regression equation.

We investigate possible linear waves and nonlinear wave interactions in a bounded three-layer fluid system using both analysis and numerical simulations. For sharp interfaces, we obtain analytic solutions for the admissible linear mode-one parent/signature waves that exist in the system. For diffuse interfaces, we compute the overtaking interaction of nonlinear mode-two solitary waves. Mathematically, owing to a small loss of energy to dispersive tails during the interaction, the waves are not solitons. However, this energy loss is extremely minute, and because the dispersively coupled waves in the system exhibit the three types of Lax KdV interactions, we conclude that for all intents and purposes the solitary waves exhibit soliton behavior. [ABSTRACT FROM AUTHOR]

Sensors based on the nitrogen-vacancy defect in diamond are being developed to measure weak magnetic and electric fields at the nanoscale. However, such sensors rely on measurements of a shift in the Lamor frequency of the defect, so an accumulation of quantum phase causes the measurement signal to exhibit a periodic modulation. This means that the measurement time is either restricted to half of one oscillation period, which limits accuracy, or that the magnetic field range must be known in advance. Moreover, the precision increases only slowly (as T?0.5) with measurement time T (ref. 3). Here, we implement a quantum phase estimation algorithm on a single nuclear spin in diamond to combine both high sensitivity and high dynamic range. By achieving a scaling of the precision with time to T?0.85, we improve the sensitivity by a factor of 7.4 for an accessible field range of 16 mT, or, alternatively, we improve the dynamic range by a factor of 130 for a sensitivity of 2.5 µT Hz?1/2. Quantum phase estimation algorithms have also recently been implemented using a single electron spin in a nitrogen-vacancy centre. These methods are applicable to a variety of field detection schemes, and do not require quantum entanglement. [ABSTRACT FROM AUTHOR]

Several mechanisms have been proposed that control the amount of plasticity in neuronal circuits and guarantee dynamic stability of neuronal networks. Homeostatic plasticity suggests that the ease with which a synaptic connection is facilitated/suppressed depends on the previous amount of network activity. We describe how such homeostatic-like interactions depend on the time interval between two conditioning protocols and on the duration of the preconditioning protocol. We used transcranial direct current stimulation (tDCS) to produce short-lasting plasticity in the motor cortex of healthy humans. In the main experiment, we compared the aftereffect of a single 5-min session of anodal or cathodal tDCS with the effect of a 5-min tDCS session preceded by an identical 5-min conditioning session administered 30, 3, or 0 min beforehand. Five-minute anodal tDCS increases excitability for about 5 min. The same duration of cathodal tDCS reduces excitability. Increasing the duration of tDCS to 10 min prolongs the duration of the effects. If two 5-min periods of tDCS are applied with a 30-min break between them, the effect of the second period of tDCS is identical to that of 5-min stimulation alone. If the break is only 3 min, then the second session has the opposite effect to 5-min tDCS given alone. Control experiments show that these shifts in the direction of plasticity evolve during the 10 min after the first tDCS session and depend on the duration of the first tDCS but not on intracortical inhibition and facilitation. The results are compatible with a time-dependent “homeostatic-like" rule governing the response of the human motor cortex to plasticity probing protocols. [ABSTRACT FROM AUTHOR]

Over two decades ago, some numerical studies and laboratory experiments identified the phenomenon of leapfrogging internal solitary waves located on separated pycnoclines. We revisit this problem to explore the behaviour of the near resonance phenomenon. We have developed a numerical code to follow the long-time inviscid evolution of isolated mode-two disturbances on two separated pycnoclines in a three-layer stratified fluid bounded by rigid horizontal top and bottom walls. We study the dependence of the solution on input system parameters, namely the three fluid densities and the two interface thicknesses, for fixed initial conditions describing isolated mode-two disturbances on each pycnocline. For most parameter values, the initial disturbances separate immediately and evolve into solitary waves, each with a distinct speed. However, in a narrow region of parameter space, the waves pair up and oscillate for some time in leapfrog fashion with a nearly equal average speed. The motion is only quasi-periodic, as each wave loses energy into its respective dispersive tail, which causes the spatial oscillation magnitude and period to increase until the waves eventually separate. We record the separation time, oscillation period and magnitude, and the final amplitudes and celerity of the separated waves as a function of the input parameters, and give evidence that no perfect periodic solutions occur. A simple asymptotic model is developed to aid in interpretation of the numerical results. [ABSTRACT FROM AUTHOR]

Modulation of activity in the left temporoparietal area (LTA) by 10 Hz repetitive transcranial magnetic stimulation (rTMS) results in a transient reduction of tinnitus. We aimed to replicate these results and test whether transcranial direct current stimulation (tDCS) of LTA could yield similar effect. Patients with tinnitus underwent six different types of stimulation in a random order: 10-Hz rTMS of LTA, 10-Hz rTMS of mesial parietal cortex, sham rTMS, anodal tDCS of LTA, cathodal tDCS of LTA and sham tDCS. A non-parametric analysis of variance showed a significant main effect of type of stimulation ( P = 0.002) and post hoc tests showed that 10-Hz rTMS and anodal tDCS of LTA resulted in a significant reduction of tinnitus. These effects were short lasting. These results replicate the findings of the previous study and, in addition, show preliminary evidence that anodal tDCS of LTA induces a similar transient tinnitus reduction as high-frequency rTMS. [ABSTRACT FROM AUTHOR]

Weak transcranial direct current stimulation (tDCS) can induce long lasting changes in cortical excitability. In the present study we asked whether tDCS applied to the left primary motor cortex (M1) also produces aftereffects distant from the site of the stimulating electrodes. We therefore tested corticospinal excitability in the left and the right M1 and transcallosal excitability between the two cortices using transcranial magnetic stimulation (TMS) before and after applying tDCS. Eight healthy subjects received 10 min of anodal or cathodal tDCS (1 mA) to the left M1. We examined the amplitude of contralateral motor evoked potentials (MEPs) and the onset latency and duration of transcallosal inhibition with single pulse TMS. MEPs evoked from the tDCS stimulated (left) M1 were increased by 32% after anodal and decreased by 27% after cathodal tDCS, while transcallosal inhibition evoked from the left M1 remained unchanged. The effect on MEPs evoked from the left M1 lasted longer for cathodal than for anodal tDCS. MEPs evoked from the right M1 were unchanged whilst the duration of transcallosal inhibition evoked from the right M1 was shortened after cathodal tDCS and prolonged after anodal tDCS. The duration of transcallosal inhibition returned to control values before the effect on the MEPs from the left M1 had recovered. These findings are compatible with the idea that tDCS-induced aftereffects in the cortical motor system are limited to the stimulated hemisphere, and that tDCS not only affects corticospinal circuits involved in producing MEPs but also inhibitory interneurons mediating transcallosal inhibition from the contralateral hemisphere. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) of the human motor cortex results in polarityspecific shifts of cortical excitability during and after stimulation. Anodal tDCS enhances and cathodal stimulation reduces excitability. Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation, while cathodal tDCS hyperpolarises cortical neurones. However, not much is known about the ion channels and receptors involved in these effects. Thus, the impact of the sodium channel blocker carbamazepine, the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested, tDCS-protocols inducing excitability alterations (1) only during tDCS and (2) eliciting long-lasting after-effects were applied after drug administration. Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS. Flunarizine resulted in similar changes. Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation, which elicits no after-effects, but prevented the induction of long-lasting after-effects independent of their direction. These results suggest that, like in other animals, cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation, thus modulating the conductance of sodium and calcium channels. Moreover, they suggest that the after-effects may be NMDA receptor dependent. Since NMDA receptors are involved in neuroplastic changes, the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting. The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS, which may have important future clinical applications. [ABSTRACT FROM AUTHOR]

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Purpose: To analyse the relationship between radiation-induced clonogenic cell death, chromosome aberrations and markers of proliferative senescence or differentiation. Materials and methods: Plateau-phase human dermal fibroblasts from 18 donors were irradiated with graded doses of 1-6 Gy 200kV X-rays. Cell survival was determined by a colony-forming assay. Markers of differentiation or senescence were: spontaneous and radiation-induced clonal differentiation, which was determined morphologically and by the cellular potential to proliferate in clonal culture, also single-cell β-galactosidase (β-gal) staining at pH 6.0; and the secretion of transforming growth factor-β (TGF-β1) into the culture medium. Chromosome aberrations were determined as genomic yields of dicentric chromosomes and the excess acentric fragments, scored in Giemsa-stained metaphases, and as partial yields of reciprocal translocations for chromosomes 4, 7 and 9 using the FISH method. Results: A broad spread was found in the shapes of the survival curves, with SF2 ranging from 0.041±0.015 to 0.63±0.05. Radiation-induced clonal differentiation as well as the secretion of TGF-β1 was elevated in radiosensitive samples. With respect to chromosome aberrations, a significant correlation was found between clonogenic survival and radiation-induced excess acentric fragments. Conclusions: In the fibroblast cell system, in vitro radiosensitivity is determined not only by processes directly involved in DNA-damage recognition and repair, but also by intracellular signalling cascades, which will lead to differentiation processes. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Depression intervention in resource-poor regions" by K.A.L.A. Kuruppuarachchi and L.T. Wijeratne in the 2004 issue.

Purpose Severe dry eye is often observed in patients suffering from Sjögren's syndrome (SS) or chronic graft‐versus‐host‐disease (cGVHD). Although the underlying pathomechanisms differ, deficient tear production, as well as meibomian gland dysfunction (MGD) are present in both. Non‐contact Meibography can achieve a non‐invasive investigation of the meibomian glands inside the tarsal plates of the eyelids. The purpose of this study was to evaluate the correlation of non‐contact Meibography to dry eye symptoms in patients suffering from SS or cGVHD. Methods We examined 37 patients suffering from SS and 11 patients with cGVHD of our dry eye unit. Subjective dry eye symptoms were evaluated with a visual analogue scale and the Ocular Surface Disease Index© (OSDI). Clinical signs of MGD were graded from 0 to 3 according to the Report of the TFOS Workshop on MGD. Non‐contact Meibography was performed by a Heidelberg Retina Angiograph 1, featuring two infrared diode lasers. Partial or complete loss of the meibomian glands was scored according to the meiboscore of Arita and colleagues. Results The mean age of the study population was 55.3 ± 13.4 years and 91.7% were women. The Meiboscore correlated significantly with the subjective symptoms assessed by visual analogue scale. The grading of the lid margins correlated significantly with the Meiboscore. Conclusion Non‐contact Meibography is a valuable tool in the diagnosis of MGD. Standard ophthalmic angiography cameras equipped with infrared diodes can easily perform it. The meiboscore correlates with the intensity of subjective symptoms and lid margin changes in patients suffering from SS or cGVHD. [ABSTRACT FROM AUTHOR]

A response by F. Fregni and colleagues to a letter to the editor about their article "Transcranial direct current stimulation," in the 2005 issue, is presented.