Slow conductance relaxation in insulating granular Al: evidence for screening effects.

It is shown that the conductance relaxations observed in electrical field effect measurements on granular Al films are the sum of two contributions. One is sensitive to gate voltage changes and gives the already reported anomalous electrical field effect. The other one is independent of the gate voltage history and starts when the films are cooled down to low temperature. Their relative amplitude is strongly thickness-dependent which demonstrates the existence of a finite screening length in our insulating films and allows its quantitative estimate (about 10 nm at 4 K). This metalliclike screening should be taken into account in the electron glass models of disordered insulators.

Hemianopia and neglect influence on straight-ahead perception.

In spatial neglect, the pathological ipsilesional deviation of the subjective straight ahead (SSA) received both 'translational' and 'rotational' interpretations. Furthermore, hemianopia per se could also influence straight-ahead (SA) perception. Here, we aimed at disentangling the relative effects of neglect and hemianopia on the SSA by using a method analyzing translation and rotation in parallel. We included patients with a right hemisphere stroke. Ten had neglect and hemianopia, 6 neglect only, 3 hemianopia only, and 12 neither one nor the other. 15 were controls. Participants had to adjust a bar, movable in translation and rotation, SA of the navel, in darkness. Patients with spatial neglect showed systematic rightward translation, greater when hemianoptic. The rotation component appeared more variable and was influenced by the presence of a visual field defect, as most of the patients with hemianopia showed an anticlockwise rotation and most of the patients without hemianopia a clockwise rotation. Non-neglect patients and control subjects demonstrated a fair performance level. In conclusion, both neglect and hemianopia resulted in a translation error of the SSA to the ipsilesional side. In neglect patients, additional hemianopia resulted in a counterclockwise rotation. Furthermore, rotation and translation errors appeared dissociated, suggesting a different coding of these dimensions by the right posterior hemisphere.

Chronic ethanol intake modulates vascular levels of endothelin-1 receptor and enhances the pressor response to endothelin-1 in anaesthetized rats.

BACKGROUND AND PURPOSE: The contribution of endothelin-1 (ET-1) to vascular hyper-reactivity associated with chronic ethanol intake, a major risk factor in several cardiovascular diseases, remains to be investigated. EXPERIMENTAL APPROACH: The biphasic haemodynamic responses to ET-1 (0.01-0.1 nmol kg(-1), i.v.) or to the selective ETB agonist, IRL1620 (0.001-1.0 nmol kg(-1), i.v.), with or without ETA or ETB antagonists (BQ123 (c(DTrp-Dasp-Pro-Dval-Leu)) at 1 and 2.5 mg kg(-1) and BQ788 (N-cis-2,6-dimethyl-piperidinocarbonyl-L-gamma-methylleucyl1-D-1methoxycarbonyltryptophanyl-D-norleucine) at 0.25 mg kg(-1), respectively) were tested in anaesthetized rats, after 2 weeks' chronic ethanol treatment. Hepatic parameters and ET receptor protein levels were also determined. KEY RESULTS: The initial hypotensive responses to ET-1 or IRL1620 were unaffected by chronic ethanol intake, whereas the subsequent pressor effects induced by ET-1, but not by IRL1620, were potentiated. BQ123 at 2.5 but not 1 mg kg(-1) reduced the pressor responses to ET-1 in ethanol-treated rats. Conversely, BQ788 (0.25 mg kg(-1)) potentiated ET-1-induced increases in mean arterial blood pressure in control as well as in ethanol-treated rats. Interestingly, in the latter group, increases in heart rate, induced by ET-1 at a dose of 0.025 mg kg(-1) were enhanced following ETB receptor blockade. Finally, we observed higher levels of ETA receptor in the heart and mesenteric artery and a reduction of ETB receptor protein levels in the aorta and kidney from rats chronically treated with ethanol. CONCLUSIONS AND IMPLICATIONS: Increased vascular reactivity to ET-1 and altered protein levels of ETA and ETB receptors could play a role in the pathogenesis of cardiovascular complications associated with chronic ethanol consumption.

Reducing rightward bias of subjective straight ahead in neglect patients by changes in body orientation.

BACKGROUND: The subjective straight ahead (SSA), a measure of the representation of body orientation, has been shown to be shifted to the lesion side in neglect patients, and to be influenced by stimulation of sensory systems involved in postural control. METHOD: This study investigates the influence of changing body orientation in the sagittal plane on the SSA in 21 patients with a right hemispheric lesion, of whom 12 had neglect, in comparison with six healthy control subjects. In order to quantify both horizontal components of SSA error (ie, yaw rotation and lateral shift), the study used a method requiring the alignment of a luminous rod with SSA. RESULTS: Neglect patients showed a significant rightward shift in the sitting position, which was greatly reduced in the supine position. No shift occurred in patients without neglect or in controls. Yaw rotation did not reach significance in any group. CONCLUSION: The data showed that the body centred frame of reference, mostly translated in neglect, is strongly improved in the supine position. Changing body orientation seems to be a convenient tool to correct the representation of body midline.

Success factors for implementing and sustaining a mature electronic medical record in a low-resource setting: a case study of iSanté in Haiti.

Electronic health information systems, including electronic medical records (EMRs), have the potential to improve access to information and quality of care, among other things. Success factors and challenges for novel EMR implementations in low-resource settings have increasingly been studied, although less is known about maturing systems and sustainability. One systematic review identified seven categories of implementation success factors: ethical, financial, functionality, organizational, political, technical and training. This case study applies this framework to iSanté, Haiti's national EMR in use in more than 100 sites and housing records for more than 750 000 patients. The author group, consisting of representatives of different agencies within the Haitian Ministry of Health (MSPP), funding partner the Centers for Disease Control and Prevention (CDC) Haiti, and implementing partner the International Training and Education Center for Health (I-TECH), identify successes and lessons learned according to the seven identified categories, and propose an additional cross-cutting category, sustainability. Factors important for long-term implementation success of complex information systems are balancing investments in hardware and software infrastructure upkeep, user capacity and data quality control; designing and building a system within the context of the greater eHealth ecosystem with a plan for interoperability and data exchange; establishing system governance and strong leadership to support local system ownership and planning for system financing to ensure sustainability. Lessons learned from 10 years of implementation of the iSanté EMR system are relevant to sustainability of a full range of increasingly interrelated information systems (e.g. for laboratory, supply chain, pharmacy and human resources) in the health sector in low-resource settings.

Perception of the vertical in patients with right hemispheric lesion: effect of galvanic vestibular stimulation.

Patients with right-brain injury present, more frequently in the acute phase, with a deviation of the subjective vertical (SV) contralateral to the lesion. The aim of this study was to investigate the influence of galvanic vestibular stimulation (GVS) on this disorder. Twelve patients presenting with a right hemispheric lesion, seven with neglect (N+) and five without (N-) were compared to eight control subjects. They had to orient vertically a luminous rod in darkness, in three galvanic stimulation (1.5 mA) conditions: cathode left, cathode right and no stimulation (baseline). Without stimulation, the patients' SV, and especially that of N+, showed an anticlockwise deviation. In comparison with baseline values, GVS induced a deviation toward the side opposite to the cathode in the three groups. In the patients, the deviation was of larger amplitude and appeared greater for left than for right cathodic stimulation. In conclusion, we showed an influence of vestibular stimulation on the SV of right brain-injured patients, especially when spatial neglect was present. As left cathodic stimulation can reduce the SV deviation associated with spatial neglect, such a tool could be introduced in rehabilitation.

An assessment of data quality in a multi-site electronic medical record system in Haiti.

OBJECTIVES: Strong data quality (DQ) is a precursor to strong data use. In resource limited settings, routine DQ assessment (DQA) within electronic medical record (EMR) systems can be resource-intensive using manual methods such as audit and chart review; automated queries offer an efficient alternative. This DQA focused on Haiti's national EMR - iSanté - and included longitudinal data for over 100,000 persons living with HIV (PLHIV) enrolled in HIV care and treatment services at 95 health care facilities (HCF). METHODS: This mixed-methods evaluation used a qualitative Delphi process to identify DQ priorities among local stakeholders, followed by a quantitative DQA on these priority areas. The quantitative DQA examined 13 indicators of completeness, accuracy, and timeliness of retrospective data collected from 2005 to 2013. We described levels of DQ for each indicator over time, and examined the consistency of within-HCF performance and associations between DQ and HCF and EMR system characteristics. RESULTS: Over all iSanté data, age was incomplete in <1% of cases, while height, pregnancy status, TB status, and ART eligibility were more incomplete (approximately 20-40%). Suspicious data flags were present for <3% of cases of male sex, ART dispenses, CD4 values, and visit dates, but for 26% of cases of age. Discontinuation forms were available for about half of all patients without visits for 180 or more days, and >60% of encounter forms were entered late. For most indicators, DQ tended to improve over time. DQ was highly variable across HCF, and within HCFs DQ was variable across indicators. In adjusted analyses, HCF and system factors with generally favorable and statistically significant associations with DQ were University hospital category, private sector governance, presence of local iSante server, greater HCF experience with the EMR, greater maturity of the EMR itself, and having more system users but fewer new users. In qualitative feedback, local stakeholders emphasized lack of stable power supply as a key challenge to data quality and use of the iSanté EMR. CONCLUSIONS: Variable performance on key DQ indicators across HCF suggests that excellent DQ is achievable in Haiti, but further effort is needed to systematize and routinize DQ approaches within HCFs. A dynamic, interactive "DQ dashboard" within iSanté could bring transparency and motivate improvement. While the results of the study are specific to Haiti's iSanté data system, the study's methods and thematic lessons learned holdgeneralized relevance for other large-scale EMR systems in resource-limited countries.

Function of the endothelin(B) receptor in cardiovascular physiology and pathophysiology.

One of the two receptors by which the potent vasoactive effects of endothelin (ET)-1 are mediated is the ET(B) receptor (ET(BR)), which is found in several tissues, but, more importantly from a cardiovascular point of view, on the endothelial cell. The endothelial cell also has the unique capability of releasing ET-1, as well as other factors, such as the endothelial-derived relaxing factors and prostacyclin, which counteract the myotropic effects of the peptide. The secretory and contractile responses to ET-1 rely on G-protein-coupled ET(BR)s, as well as ET(A)-G-protein-coupled receptor-like proteins. The mitogenic properties of ET-1 via ET(A) receptors (ET(AR)s) coupled to mitogen-activated protein kinases and tyrosine kinases on the vascular smooth muscle may occur in conjunction with the anti-apoptotic characteristics of the endothelial ET(BR)s. Interestingly, most of the relevant antagonists and agonists for both ET(AR)s and ET(BR)s have been developed by the pharmaceutical industry. This highlights the therapeutical potential of compounds that act on ET receptors. In normal as well as in physiopathological conditions, the ET(BR) plays an important role in the control of vascular tone, and must be taken into account when using ET receptor antagonists for the treatment of cardiovascular diseases. For the management of congestive heart failure, renal failure and primary pulmonary hypertension, the most recent literature supports the use of selective ET(AR) antagonists rather than mixed antagonists of ET(AR)s and ET(BR)s. Nonetheless, validation of this view will have to await the first clinical trials comparing the actions of ET(A) to mixed ET(A)/ET(B) receptor antagonists.

Reduction of cutaneous reaction time by directing eyes towards the source of stimulation.

Reaction time to expected lateral cutaneous stimulation was measured in Man when the eyes were directed (1) towards the stimulated area, (2) towards another point within the same hemispace and (3) towards the other hemispace. As performance was better in the first case, this suggests that compatible eye postural activity reinforces the effect of spatial attention.

Role of ETB and B2 receptors in the ex vivo platelet inhibitory properties of endothelin and bradykinin in the mouse.

1. We have developed a model to study the inhibitory properties of endogenous autacoids triggered by systemically-administered vasoactive peptides, on platelet aggregation ex vivo in the mouse. 2. Adenosine diphosphate (ADP) (0.5-10 microM) induces a concentration-dependent aggregation of platelet-rich plasma derived from C57BL/6 mice. Intravenously-administered endothelin-1 (0.01-1 nmolx kg(-1)), the selective ETB agonist, IRL-1620 (0.0 -1 nmol x kg(-1)) or bradykinin ( 1-100 nmol x kg(-1)) significantly reduced in a dose-dependent fashion the ADP-induced platelet aggregation. 3. The non-selective cyclo-oxygenase (COX) inhibitor, indomethacin, a selective COX-2 inhibitor NS-398 or the prostacyclin synthase inhibitor, tranylcypromine (10 mg x kg(-1)), markedly reduced the inhibitory properties of endothelin-1, whereas only a combination of both indomethacin, NS-398 or tranylcypromine and L-NAME (10 mg x kg(-1)) were required to abolish the response to bradykinin. 4. An ETB-selective antagonist (BQ-788) or knockout of the B2 receptor gene (in B2 knockout mice) abolishes the platelet inhibitory properties of endothelin-1 and bradykinin, respectively. 5. Our results suggest that intravenously-administered endothelin-1 and bradykinin, through ETB and B2 receptor activation, respectively, inhibit platelet aggregation ex vivo in the mouse. The inhibitory properties of endothelin-1 require the activation of COX-2 and the subsequent generation of prostacyclin. In addition to the two previously mentioned factors, nitric oxide is required for the anti-aggregatory effects of bradykinin.

Is there a distortion of body projection in extracorporeal space in neglect patients?

Neglect patients often present with a rightward shift of the direction straight-ahead of body midline. We investigated whether directions ahead of other body parts were similarly shifted or were differentially affected. Right brain-damaged patients, with and without neglect, and normal subjects had to indicate by manual pointings, the directions straight-ahead of the navel, the nose, the left and right shoulders. In neglect patients, constant errors varied across directions with a decrease in magnitude from left to right, suggesting a compression of body projection in extracorporeal space. Moreover, the projection of the left hemibody was smaller than the right in all subjects, with and without neglect. This unexpected finding is discussed with regard to other spatial asymmetries observed in normal subjects.

Plantar stimulation can affect subjective straight-ahead in neglect patients.

The rightward orientation bias of neglect patients has been shown to be decreased by postural changes, suggesting that afferences coding the posture relative to gravity might influence the body-centred spatial reference frame. In order to test this hypothesis, we evaluated the effects of plantar stimulations on the subjective straight-ahead (SSA) of two neglect patients presenting with a strong rightward shift, as well as two non-neglect patients and three normal subjects. Vibratory or electrical stimulations were applied to the left or right plantar sole. Data showed that these manipulations influenced the SSA position in neglect patients only. The observed improvement could be explained by a direction-specific effect of vibration, in addition to a non-specific activation induced by both stimulations.

Improvement of the motor deficit of neglect patients through vestibular stimulation: evidence for a motor neglect component.

The effect of vestibular stimulation on motor performance has been studied comparatively in 2 groups of hemiplegic patients, one including 9 right brain-damaged patients (RBD) with neglect, the other 9 left brain-damaged patients (LBD) without neglect. In the RBD group, a transient but significant improvement of motor performance was observed following stimulation, although motor scores remained unchanged in two cases. Moreover, a temporary remission of personal neglect and anosognosia was obtained in 8 out of 9 patients. In contrast to the RBD group, the motor performance of the LBD group was not improved through vestibular stimulation, although a moderate improvement of force was noticed in one ambidextrous patient who had shown transient signs of neglect at the acute stage. These results suggest the participation of a motor neglect component in the motor deficit of neglect patients. The motor neglect component may be considered as one of the many manifestations of the neglect syndrome and, as such, can be improved by the sensory manipulations which presumably restore a conscious representation of the left side of space.

[Endothelin receptors in benign human tumours of uterine muscle]. / Récepteurs des endothélines dans les tumeurs bénignes du muscle utérin humain.

The endothelins (ET1, ET2, ET3) are a family of peptides that exert vasoactive and mitogenic effects. ETs bind to at least two subtypes of receptors: the ETA subtype is ET1 selective whereas the ETB subtype binds ET1, ET2 and ET3. By RT-PCR, we detected ETA receptor mRNA and ETB receptor mRNA in leiomyoma and in homologous myometrium distal from the tumor. Despite the presence of four spliced variants of ETA receptors, we identified a single class of ETA-binding sites. The level of ETB receptor mRNA was found to be higher in myometrium versus leiomyomas. Using complementary pharmacologic approach, we demonstrated the predominance of ETA receptors in normal myometrium (75% of total receptors). Both ETA and ETB transcripts coexist in leiomyomas, but we have reported only ETA binding sites. Because of growth properties of ET1, we suggest a role for this peptide in the tumoral development of human uterine smooth muscle.

Cutaneous thresholds and anxiety: influence of eye orientation and lateral asymmetry.

This study investigated the combined influence of anxiety and eye orientation on cutaneous thresholds. The relationship between anxiety and the lateral differences was also examined. Right-handed subjects of low and high trait anxiety received weak electric shocks on either hand. Cutaneous thresholds were recorded when eyes were directed towards or away from the stimulated area. State anxiety was retrospectively assessed. As compared to a contralateral eye orientation, directing the eyes ipsilaterally to the stimulated area yielded lower thresholds for subjects low in trait anxiety. This effect was not observed for subjects high in trait anxiety. The benefit of the ipsilateral orientation was higher for subjects with lower state-anxiety scores as well. Besides, subjects low in trait anxiety presented a left-hand advantage which was not shown by those high in trait anxiety. The left-right difference in thresholds was also positively correlated with state anxiety. The eye-orientation results are discussed in terms of anxiety-induced modification of spatial attention and the differential hand sensitivity findings in terms of hemispheric specialization.

Body representations and brain damage.

We review changes in body representation in patients with brain hemisphere damage and discuss their relationship with impaired limb movements in peripersonal space, navigation between objects/obstacles and control of the body's general posture and balance. The egocentric representation of the body's median sagittal axis (considered as the main zone around which movements are anchored) has been studied in most detail. This reference is distorted in patients with spatial neglect and involves a combination of ipsilesional translation and contralesional tilt. There are clear links with the patients' difficulties in egocentric tasks, activities of daily living and postural control. In both healthy subjects and patients, this reference axis can be modulated by somaesthetic, vestibular and visual stimulations; these phenomena have been used in rehabilitation programmes to reduce disease-induced deviations. A few studies have analyzed other lateral body reference (at the shoulders, in particular). These references were found to be more severely affected than the body midline (notably on the contralesional side). The severity of the distortion was related to the presence of lesions that mainly affected the parietal, somatosensory and multimodal association cortex (notably around the intraparietal sulcus) and, to a lesser extent, the middle temporal and frontal dorsolateral premotor cortex. These convergent results suggested that patients (notably those with neglect) have a complex distortion of the body schema and the perceptive representations of the body, that does not simply correspond to poor awareness of the contralateral hemicorpus.

Integration of visual and haptic informations in the perception of the vertical in young and old healthy adults and right brain-damaged patients.

OBJECTIVE: Multimodal perception raises the issue of sensory integration. The aim of this study is to assess whether the visuo-haptic subjective vertical could be predicted from the visual and haptic unimodal performances, according to a Bayesian model, which optimizes the reliability of the multimodal estimate. The limits of the model were assessed by evaluating the impact of aging, cerebral damage and spatial deficits. METHOD: Young and older healthy participants, as well as patients with a right hemisphere lesion, suffering from spatial neglect or not, had to align a rod with the gravitational vertical in the visual, haptic and visuo-haptic modalities. RESULTS: Visuo-haptic subjective vertical was correctly predicted by the model in healthy participants, as well as in patients in spite of different performances. An anticlockwise deviation of the subjective vertical was observed in the neglect group whatever the experimental conditions. By contrast, no deviation was observed in both non-neglect and healthy groups, for the visual and the visuo-haptic modalities. Nevertheless, the haptic subjective vertical was deviated, anticlockwise in the non-neglect patients and older healthy adults, and clockwise in the young healthy adults. Moreover, the variance was the smallest in the bimodal condition. CONCLUSION: The integration of visual and haptic signals appeared to obey a Bayesian model optimizing the reliability of the multimodal estimate. This holds true despite of aging, brain damage or visuospatial disorders. Regarding the perception of the vertical, multisensory integration does not seem thus to depend only on right posterior cortical areas.

Functional neuro-anatomy of egocentric versus allocentric space representation.

INTRODUCTION: The functional neuroanatomy of the egocentric and allocentric representations of space remains poorly studied with neuroimaging. Here we aim to determine brain structures subserving two different kinds of spatial representations centred on the main axis of either the body or the external scene. METHOD: Sixteen healthy participants evaluated the alignment of a bar relative to the middle of their body (Ego) or relative to another stimulus (Allo) during functional MRI. In a control task (Ctrl), they had to judge the colour of the bar. RESULTS: Correct response rates and response times were similar in the three tasks. fMRI data revealed a predominant role of the right hemisphere in the egocentric task (Ego vs. Allo): selective activity was found in the occipital, superior parietal, and inferior frontal cortices, as well as in the precuneus and supplementary motor area. On the left side, the insula, thalamus, and cerebellum were also activated. Conversely, the allocentric task (Allo vs. Ctrl) showed selective activity centred on the left temporal gyrus. DISCUSSION: This study demonstrates a right hemisphere dominance for representations centred on the longitudinal body axis, but more left-sided activity for scene/object-centred representations of space. These new data shed light on the unique role of several regions involved in spatial perception and help better understand spatial deficits in patients with right hemispheric lesions.