Repetitive TMS over the human oculomotor cortex: comparison of 1-Hz and theta burst stimulation

The aim of the study was to compare the effect duration of two different protocols of repetitive transcranial magnetic stimulation (rTMS) on saccade triggering. In four experiments, two regions (right frontal eye field (FEF) and vertex) were stimulated using a 1-Hz and a theta burst protocol (three 30Hz pulses repeated at intervals of 100ms). The same number of TMS pulses (600 pulses) was applied with stimulation strength of 80% of the resting motor threshold for hand muscles. Following stimulation the subjects repeatedly performed an oculomotor task using a modified overlap paradigm, and saccade latencies were measured over a period of 60min. The results show that both 1-Hz and theta burst stimulation had inhibitory effects on saccade triggering when applied over the FEF, but not over the vertex. One-hertz rTMS significantly increased saccade latencies over a period of about 8min. After theta burst rTMS, this effect lasted up to 30min. Furthermore, the decay of rTMS effects was protocol-specific: After 1-Hz stimulation, saccade latencies returned to a baseline level much faster than after theta burst stimulation. We speculate that these time course differences represent distinct physiological mechanisms of how TMS interacts with brain function.

Single-pulse transcranial magnetic stimulation over the frontal eye field can facilitate and inhibit saccade triggering

The aim of this study was to investigate the effect of single-pulse transcranial magnetic stimulation on the triggering of saccades. The right frontal eye field was stimulated during modified gap and overlap paradigms with flashed presentation of the lateral visual target of 80 ms. In order to examine possible facilitating or inhibitory effects on saccade triggering, three different time intervals of stimulation were chosen, i.e. simultaneously with onset of the target, during the presentation and after target end. Stimulation applied simultaneously with target onset significantly decreased the latency of contralateral saccades in the gap but not in the overlap paradigm. Stimulation after target end significantly increased saccade latency for both sides in the gap paradigm and for the contralateral side in the overlap paradigm. Stimulation during presentation had no effect in either paradigm. The results show that, depending on the time interval and the paradigm tested, a facilitation or inhibition of saccade triggering can be achieved. The results are discussed in a context of two probable transcranial magnetic stimulation effects, a direct interference with the frontal eye field on the one hand and a remote interference with the superior colliculus on the other hand.

Early over-expression of GRP receptors in prostatic carcinogenesis

BACKGROUND The GRP receptor shows high over-expression in prostatic adenocarcinoma and high grade PIN, but low expression in normal prostate glands. This represents the molecular basis for GRP receptor imaging of prostate cancer with radioactive compounds. However, a focal, high density GRP receptor expression can be observed in hitherto uncharacterized prostate glands. METHODS GRP receptors were quantitatively measured with in vitro receptor autoradiography using ¹²⁵I-Tyr⁴ -bombesin in samples from 115 prostates. On successive tissue sections, ¹²⁵I-Tyr⁴ -bombesin autoradiography was compared with H&E staining and MIB-1 and 34βE12 immunohistochemistry. RESULTS On one hand, it was confirmed that GRP receptors were expressed in adenocarcinoma and high grade PIN in high density and high incidence (77% and 73%, respectively), but in normal prostate glands in low density and low frequency (18%). On the other hand, a novel and intriguing observation was the existence of focal non-invasive prostate glands with high GRP receptor density, characterized by low grade nuclear atypia and increased proliferation, compatible with lower grade PIN. There was a significant GRP receptor density gradient (P ≤ 0.005), increasing from normal prostate glands (mean relative optical density, ROD, of ¹²⁵I-Tyr⁴ -bombesin binding: 0.17) over atypical glands without increased MIB-1 labeling (0.28) and atypical glands with increased MIB-1 expression (0.44) to high grade PIN and adenocarcinoma (0.64 and 0.58, respectively). CONCLUSIONS GRP receptor over-expression may be a novel, specific marker of early prostatic neoplastic transformation, arising in low grade PIN, and progressively increasing during malignant progression. This should be considered when interpreting in vivo GRP receptor imaging in males.

Improvements in Implant Dentistry over the Last Decade: Comparison of Survival and Complication Rates in Older and Newer Publications

Purpose: The objective of this systematic review was to assess and compare the survival and complication rates of implant-supported prostheses reported in studies published in the year 2000 and before, to those reported in studies published after the year 2000. Materials and Methods: Three electronic searches complemented by manual searching were conducted to identify 139 prospective and retrospective studies on implant-supported prostheses. The included studies were divided in two groups: a group of 31 older studies published in the year 2000 or before, and a group of 108 newer studies published after the year 2000. Survival and complication rates were calculated using Poisson regression models, and multivariable robust Poisson regression was used to formally compare the outcomes of older and newer studies. Results: The 5-year survival rate of implant-supported prostheses was significantly increased in newer studies compared with older studies. The overall survival rate increased from 93.5% to 97.1%. The survival rate for cemented prostheses increased from 95.2% to 97.9%; for screw-retained reconstruction, from 77.6% to 96.8%; for implant-supported single crowns, from 92.6% to 97.2%; and for implant-supported fixed dental prostheses (FDPs), from 93.5% to 96.4%. The incidence of esthetic complications decreased in more recent studies compared with older ones, but the incidence of biologic complications was similar. The results for technical complications were inconsistent. There was a significant reduction in abutment or screw loosening by implant-supported FDPs. On the other hand, the total number of technical complications and the incidence of fracture of the veneering material was significantly increased in the newer studies. To explain the increased rate of complications, minor complications are probably reported in more detail in the newer publications. Conclusions: The results of the present systematic review demonstrated a positive learning curve in implant dentistry, represented in higher survival rates and lower complication rates reported in more recent clinical studies. The incidence of esthetic, biologic, and technical complications, however, is still high. Hence, it is important to identify these complications and their etiology to make implant treatment even more predictable in the future.

Interhemispheric cerebral blood flow balance during recovery of motor hand function after ischemic stroke - a longitudinal MRI study using arterial spin labeling perfusion

BACKGROUND Unilateral ischemic stroke disrupts the well balanced interactions within bilateral cortical networks. Restitution of interhemispheric balance is thought to contribute to post-stroke recovery. Longitudinal measurements of cerebral blood flow (CBF) changes might act as surrogate marker for this process. OBJECTIVE To quantify longitudinal CBF changes using arterial spin labeling MRI (ASL) and interhemispheric balance within the cortical sensorimotor network and to assess their relationship with motor hand function recovery. METHODS Longitudinal CBF data were acquired in 23 patients at 3 and 9 months after cortical sensorimotor stroke and in 20 healthy controls using pulsed ASL. Recovery of grip force and manual dexterity was assessed with tasks requiring power and precision grips. Voxel-based analysis was performed to identify areas of significant CBF change. Region-of-interest analyses were used to quantify the interhemispheric balance across nodes of the cortical sensorimotor network. RESULTS Dexterity was more affected, and recovered at a slower pace than grip force. In patients with successful recovery of dexterous hand function, CBF decreased over time in the contralesional supplementary motor area, paralimbic anterior cingulate cortex and superior precuneus, and interhemispheric balance returned to healthy control levels. In contrast, patients with poor recovery presented with sustained hypoperfusion in the sensorimotor cortices encompassing the ischemic tissue, and CBF remained lateralized to the contralesional hemisphere. CONCLUSIONS Sustained perfusion imbalance within the cortical sensorimotor network, as measured with task-unrelated ASL, is associated with poor recovery of dexterous hand function after stroke. CBF at rest might be used to monitor recovery and gain prognostic information.

Analysis of hand kinematics reveals inter-individual differences in intertemporal decision dynamics

During intertemporal decisions, the preference for smaller, sooner reward over larger-delayed rewards (temporal discounting, TD) exhibits substantial inter-subject variability; however, it is currently unclear what are the mechanisms underlying this apparently idiosyncratic behavior. To answer this question, here we recorded and analyzed mouse movement kinematics during intertemporal choices in a large sample of participants (N = 86). Results revealed a specific pattern of decision dynamics associated with the selection of “immediate” versus “delayed” response alternatives, which well discriminated between a “discounter” versus a “farsighted” behavior—thus representing a reliable behavioral marker of TD preferences. By fitting the Drift Diffusion Model to the data, we showed that differences between discounter and farsighted subjects could be explained in terms of different model parameterizations, corresponding to the use of different choice mechanisms in the two groups. While farsighted subjects were biased toward the “delayed” option, discounter subjects were not correspondingly biased toward the “immediate” option. Rather, as shown by the dynamics of evidence accumulation over time, their behavior was characterized by high choice uncertainty.

Medical, psychological and socio-economic implications of chronic hand eczema: a cross-sectional study.

BACKGROUND Hand eczema (HE) is a common skin disease with major medical psychological and socio-economic implications. Onset and prognosis of HE are determined by individual as well as environmental factors. So far, most epidemiological data on HE have been reported from Scandinavian and recently German studies. OBJECTIVE To investigate the characteristics and medical care of patients with chronic HE (CHE) in Switzerland, and identify risk factors. METHODS In this cross-sectional study, data from patients with chronic HE were obtained by means of medical history, dermatological examination and patient questionnaires. Multiple logistic regression analysis was applied to identify risk factors for high severity and dermatology life quality index (DLQI). RESULTS In seven dermatology departments, 199 patients (mean age 40.4 years, 50.8% female) with CHE (mean duration 6.6 years) were enrolled. Moderate to severe HE was reported by 70.9% of patients, and was associated with age <30 or >50 years, localization of lesions and pruritus. Because of the CHE, 37.3% of patients were on sick leave over the past 12 months, 14.8% had changed or lost their job. Practically all patients applied topical therapy, 21% were treated with alitretinoin, and 21% with psoralen plus UVA light (PUVA). The effects on the health-related quality of life was moderate to large in 33.7% and 39.4% of CHE patients, respectively. Factors associated with a high impact on DLQI (mean 9.7 ± 5.8) were female sex, lesions on back of the hands and pruritus as well as mechanical skin irritation and wearing gloves. CONCLUSION In agreement with recent studies, the Swiss data demonstrate the high impact of CHE on medical well-being, patient quality of life and work ability. As it is associated with an intense use of health care services, high rate of sick leave, job loss and change, CHE may cause a high socio-economic burden.

Flow separation and roughness lengths over large bedforms in a tidal environment

This study characterises the shape of the flow separation zone (FSZ) and wake region over large asymmetric bedforms under tidal flow conditions. High resolution bathymetry, flow velocity and turbulence data were measured along two parallel transects in a tidal channel covered with bedforms. The field data are used to verify the applicability of a numerical model for a systematic study using the Delft3D modelling system and test the model sensitivity to roughness length. Three experiments are then conducted to investigate how the FSZ size and wake extent vary depending on tidally-varying flow conditions, water levels and bathymetry. During the ebb, a large FSZ occurs over the steep lee side of each bedform. During the flood, no flow separation develops over the bedforms having a flat crest; however, a small FSZ is observed over the steepest part of the crest of some bedforms, where the slope is locally up to 15°. Over a given bedform morphology and constant water levels, no FSZ occurs for velocity magnitudes smaller than 0.1 m s**-1; as the flow accelerates, the FSZ reaches a stable size for velocity magnitudes greater than 0.4 m s**-1. The shape of the FSZ is not influenced by changes in water levels. On the other hand, variations in bed morphology, as recorded from the high-resolution bathymetry collected during the tidal cycle, influence the size and position of the FSZ: a FSZ develops only when the maximum lee side slope over a horizontal distance of 5 m is greater than 10°. The height and length of the wake region are related to the length of the FSZ. The total roughness along the transect lines is an order of magnitude larger during the ebb than during the flood due to flow direction in relation to bedform asymmetry: during the ebb, roughness is created by the large bedforms because a FSZ and wake develops over the steep lee side. The results add to the understanding of hydrodynamics of natural bedforms in a tidal environment and may be used to better parameterise small-scale processes in large-scale studies.

Authentication in mobile devices through hand gesture recognition

This article proposes an innovative biometric technique based on the idea of authenticating a person on a mobile device by gesture recognition. To accomplish this aim, a user is prompted to be recognized by a gesture he/she performs moving his/her hand while holding a mobile device with an accelerometer embedded. As users are not able to repeat a gesture exactly in the air, an algorithm based on sequence alignment is developed to correct slight differences between repetitions of the same gesture. The robustness of this biometric technique has been studied within 2 different tests analyzing a database of 100 users with real falsifications. Equal Error Rates of 2.01 and 4.82% have been obtained in a zero-effort and an active impostor attack, respectively. A permanence evaluation is also presented from the analysis of the repetition of the gestures of 25 users in 10 sessions over a month. Furthermore, two different gesture databases have been developed: one made up of 100 genuine identifying 3-D hand gestures and 3 impostors trying to falsify each of them and another with 25 volunteers repeating their identifying 3- D hand gesture in 10 sessions over a month. These databases are the most extensive in published studies, to the best of our knowledge.

Mechanisms of Human Mitochondrial DNA Maintenance: The Determining Role of Primary Sequence and Length over Function

Although the regulation of mitochondrial DNA (mtDNA) copy number is performed by nuclear-coded factors, very little is known about the mechanisms controlling this process. We attempted to introduce nonhuman ape mtDNA into human cells harboring either no mtDNA or mutated mtDNAs (partial deletion and tRNA gene point mutation). Unexpectedly, only cells containing no mtDNA could be repopulated with nonhuman ape mtDNA. Cells containing a defective human mtDNA did not incorporate or maintain ape mtDNA and therefore died under selection for oxidative phosphorylation function. On the other hand, foreign human mtDNA was readily incorporated and maintained in these cells. The suicidal preference for self-mtDNA showed that functional parameters associated with oxidative phosphorylation are less relevant to mtDNA maintenance and copy number control than recognition of mtDNA self-determinants. Non–self-mtDNA could not be maintained into cells with mtDNA even if no selection for oxidative phosphorylation was applied. The repopulation kinetics of several mtDNA forms after severe depletion by ethidium bromide treatment showed that replication and maintenance of mtDNA in human cells are highly dependent on molecular features, because partially deleted mtDNA molecules repopulated cells significantly faster than full-length mtDNA. Taken together, our results suggest that mtDNA copy number may be controlled by competition for limiting levels of trans-acting factors that recognize primarily mtDNA molecular features. In agreement with this hypothesis, marked variations in mtDNA levels did not affect the transcription of nuclear-coded factors involved in mtDNA replication.

Patriarch Kirill's game over Ukraine. OSW Commentary No. 144, 14.08.2014

The protests on Kyiv’s Maidan which commenced in November 2013, followed by the conflict in Ukraine’s eastern regions, have redefined the political and social relations between Russia and Ukraine, and have added complexity to the dependences between the Orthodox Churches operating in the two countries. The Kremlin’s policy has put the Russian Orthodox Church–Moscow Patriarchate (ROC) in an awkward position. The ROC is Russia’s largest religious organisation, which also exercises symbolic sovereignty over Ukraine’s most numerous Orthodox community, the Ukrainian Orthodox Church–Moscow Patriarchate (UOC–MP), which since 13 August has had a new leader, Metropolitan Onufry. The head of the ROC, the Patriarch of Moscow and All-Russia, Kirill, has been facing a dilemma as to how he should respond to the Russian government’s aggressive policy towards Ukraine. His firm support of the Kremlin’s moves in Ukraine, may lose the Russian Church its social influence in this country. This might also catalyse a process within which Ukraine’s largest Orthodox Church would gradually become independent of Moscow. On the other hand, if he condemns the Kremlin’s policy, this would adversely affect the co-operation between ‘the altar and the throne’ which has been rapidly developing over the past few years in Russia, and which has offered multiple benefits to the Russian Church. As a result, Patriarch Kirill has distanced the ROC from the recent developments in Ukraine and has adopted a neutral stance. However, Kirill’s choice has aggravated the negative perception of the ROC among the Orthodox community in Ukraine. Given its close relations with the Kremlin, the ROC is increasingly viewed there as an instrument of political struggle and an exponent of the Russian government’s interests. The ROC’s stance has cast the UOC–MP, which has links with the Russian Church, in an unfavourable light, and has fostered its efforts to become more independent from the Moscow Patriarchate. Regardless of how the situation evolves, the recent developments in Ukraine have made it clear that the interests of the Russian Church and the Kremlin, which have coincided for years, now come into conflict, mainly due to the disagreement over the methods used. Despite this, the Russian Church is not withdrawing from the cooperation of ‘the altar and the throne’, and submits itself to the Kremlin’s decisions.

Right hand road to Laramie. Road all right

Photo album title: Detroit to San Francisco over Lincoln Highway. May 27-June 18, 1915. Henry B. Joy; A.F. Bement, E. Eisenhut

Common variants in left/right asymmetry genes and pathways are associated with relative hand skill

Humans display structural and functional asymmetries in brain organization, strikingly with respect to language and handedness. The molecular basis of these asymmetries is unknown. We report a genome-wide association study meta-analysis for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)] (n = 728). The most strongly associated variant, rs7182874 (P = 8.68×10-9), is located in PCSK6, further supporting an association we previously reported. We also confirmed the specificity of this association in individuals with RD; the same locus was not associated with relative hand skill in a general population cohort (n = 2,666). As PCSK6 is known to regulate NODAL in the development of left/right (LR) asymmetry in mice, we developed a novel approach to GWAS pathway analysis, using gene-set enrichment to test for an over-representation of highly associated variants within the orthologs of genes whose disruption in mice yields LR asymmetry phenotypes. Four out of 15 LR asymmetry phenotypes showed an over-representation (FDR≤5%). We replicated three of these phenotypes; situs inversus, heterotaxia, and double outlet right ventricle, in the general population cohort (FDR≤5%). Our findings lead us to propose that handedness is a polygenic trait controlled in part by the molecular mechanisms that establish LR body asymmetry early in development. © 2013 Brandler et al.

Fluorescence-enhanced optical imaging on three-dimensional phantoms using a hand-held probe based frequency-domain intensified charge coupled device (ICCD) optical imager

Fluorescence-enhanced optical imaging is an emerging non-invasive and non-ionizing modality towards breast cancer diagnosis. Various optical imaging systems are currently available, although most of them are limited by bulky instrumentation, or their inability to flexibly image different tissue volumes and shapes. Hand-held based optical imaging systems are a recent development for its improved portability, but are currently limited only to surface mapping. Herein, a novel optical imager, consisting primarily of a hand-held probe and a gain-modulated intensified charge coupled device (ICCD) detector, is developed towards both surface and tomographic breast imaging. The unique features of this hand-held probe based optical imager are its ability to; (i) image large tissue areas (5×10 sq. cm) in a single scan, (ii) reduce overall imaging time using a unique measurement geometry, and (iii) perform tomographic imaging for tumor three-dimensional (3-D) localization. Frequency-domain based experimental phantom studies have been performed on slab geometries (650 ml) under different target depths (1-2.5 cm), target volumes (0.45, 0.23 and 0.10 cc), fluorescence absorption contrast ratios (1:0, 1000:1 to 5:1), and number of targets (up to 3), using Indocyanine Green (ICG) as fluorescence contrast agents. An approximate extended Kalman filter based inverse algorithm has been adapted towards 3-D tomographic reconstructions. Single fluorescence target(s) was reconstructed when located: (i) up to 2.5 cm deep (at 1:0 contrast ratio) and 1.5 cm deep (up to 10:1 contrast ratio) for 0.45 cc-target; and (ii) 1.5 cm deep for target as small as 0.10 cc at 1:0 contrast ratio. In the case of multiple targets, two targets as close as 0.7 cm were tomographically resolved when located 1.5 cm deep. It was observed that performing multi-projection (here dual) based tomographic imaging using a priori target information from surface images, improved the target depth recovery over using single projection based imaging. From a total of 98 experimental phantom studies, the sensitivity and specificity of the imager was estimated as 81-86% and 43-50%, respectively. With 3-D tomographic imaging successfully demonstrated for the first time using a hand-held based optical imager, the clinical translation of this technology is promising upon further experimental validation from in-vitro and in-vivo studies.