Impact of 3 different short-term chemotherapy regimens on lymphocyte-depletion and reconstitution in melanoma patients.

Recent immunotherapy trials have shown that lymphodepletion induced by short-term chemotherapy favors subsequent expansion of adoptively transferred T cells, by homeostatic mechanisms. To take advantage of this effect, novel regimens are being developed with the aim to enhance tumor immunity and reduce treatment toxicity. We have designed a clinical phase I trial combining chemotherapy, reinfusion of PBMC containing Melan-A(MART-1)-specific T cells, and vaccination with Melan-A peptide in Incomplete Freund's Adjuvant. Treatment with Busulfan plus Fludarabine depleted lymphocytes only weakly. Cyclophosphamide (CTX) plus Fludarabine depleted lymphocytes more profoundly, with a maximal effect using high doses of CTX. It is interesting to note that, the degree of homeostatic T-cell proliferation correlated tightly with the extent of lymphodepletion. As compared with CD4 T cells, CD8 T cells showed higher susceptibility to chemotherapy, followed by more rapid homeostatic proliferation and recovery, resulting in strong inversions of CD4/CD8 ratios. Despite efficient homeostatic proliferation of total CD4 and CD8 T cells, the frequency of CD8 T cells specific for Melan-A and cancer-testis antigens remained relatively low. In contrast, EBV-specific T cells expanded and reached high numbers. We conclude that short-term chemotherapy promoted homeostatic lymphocyte proliferation depending on the intensity of lymphocyte depletion, however without preferential expansion of tumor antigen-specific T cells.

Face Short-Term Memory-Related Electroencephalographic Patterns can Differentiate Multi- versus Single-Domain Amnestic Mild Cognitive Impairment.

Amnestic mild cognitive impairment (aMCI) is characterized by memory deficits alone (single-domain, sd-aMCI) or associated with other cognitive disabilities (multi-domain, md-aMCI). The present study assessed the patterns of electroencephalographic (EEG) activity during the encoding and retrieval phases of short-term memory in these two aMCI subtypes, to identify potential functional differences according to the neuropsychological profile. Continuous EEG was recorded in 43 aMCI patients, whose 16 sd-aMCI and 27 md-aMCI, and 36 age-matched controls (EC) during delayed match-to-sample tasks for face and letter stimuli. At encoding, attended stimuli elicited parietal alpha (8-12 Hz) power decrease (desynchronization), whereas distracting stimuli were associated with alpha power increase (synchronization) over right central sites. No difference was observed in parietal alpha desynchronization among the three groups. For attended faces, the alpha synchronization underlying suppression of distracting letters was reduced in both aMCI subgroups, but more severely in md-aMCI cases that differed significantly from EC. At retrieval, the early N250r recognition effect was significantly reduced for faces in md-aMCI as compared to both sd-aMCI and EC. The results suggest a differential alteration of working memory cerebral processes for faces in the two aMCI subtypes, face covert recognition processes being specifically altered in md-aMCI.

Reactive rise in blood pressure upon cuff inflation: cuff inflation at the arm causes a greater rise in pressure than at the wrist in hypertensive patients.

OBJECTIVE: Cuff inflation at the arm is known to cause an instantaneous rise in blood pressure, which might be due to the discomfort of the procedure and might interfere with the precision of the blood pressure measurement. In this study, we compared the reactive rise in blood pressure induced by cuff inflation when the cuff was placed at the upper arm level and at the wrist. PARTICIPANTS AND METHODS: The reactive rise in systolic and diastolic blood pressure to cuff inflation was measured in 34 normotensive participants and 34 hypertensive patients. Each participant was equipped with two cuffs, one around the right upper arm (OMRON HEM-CR19, 22-32 cm) and one around the right wrist (OMRON HEM-CS 19, 17-22 cm; Omron Health Care Europe BV, Hoofddorp, The Netherlands). The cuffs were inflated in a double random order (maximal cuff pressure and position of the cuff) with two maximal cuff pressures: 180 and 240 mmHg. The cuffs were linked to an oscillometric device (OMRON HEM 907; Omron Health Care). Simultaneously, blood pressure was measured continuously at the middle finger of the left hand using photoplethysmography. Three measurements were made at each level of blood pressure at the arm and at the wrist, and the sequence of measurements was randomized. RESULTS: In normotensive participants, no significant difference was observed in the reactive rise in blood pressure when the cuff was inflated either at the arm or at the wrist irrespective of the level of cuff inflation. Inflating a cuff at the arm, however, induced a significantly greater rise in blood pressure than inflating it at the wrist in hypertensive participants for both systolic and diastolic pressures (P<0.01), and at both levels of cuff inflation. The blood pressure response to cuff inflation was independent of baseline blood pressure. CONCLUSIONS: The results show that in hypertensive patients, cuff inflation at the wrist produces a smaller reactive rise in blood pressure. The difference between the arm and the wrist is independent of the patient's level of blood pressure.

Effects of prior short multiple-sprint exercises with different intersprint recoveries on the slow component of oxygen uptake during high-intensity exercise.

This study compares the effects of two short multiple-sprint exercise (MSE) (6 × 6 s) sessions with two different recovery durations (30 s or 180 s) on the slow component of oxygen uptake ([Formula: see text]O(2)) during subsequent high-intensity exercise. Ten male subjects performed a 6-min cycling test at 50% of the difference between the gas exchange threshold and [Formula: see text]O(2peak) (Δ50). Then, the subjects performed two MSEs of 6 × 6 s separated by two intersprint recoveries of 30 s (MSE(30)) and 180 s (MSE(180)), followed 10 min later by the Δ50 (Δ50(30) and Δ50(180), respectively). Electromyography (EMG) activities of the vastus medialis and lateralis were measured throughout each exercise bout. During MSE(30), muscle activity (root mean square) increased significantly (p ≤ 0.04), with a significant leftward-shifted median frequency of the power density spectrum (MDF; p ≤ 0.01), whereas MDF was significantly rightward-shifted during MSE(180) (p = 0.02). The mean [Formula: see text]O(2) value was significantly higher in MSE(30) than in MSE(180) (p < 0.001). During Δ50(30), [Formula: see text]O(2) and the deoxygenated hemoglobin ([HHb]) slow components were significantly reduced (-27%, p = 0.02, and -34%, p = 0.003, respectively) compared with Δ50. There were no significant modifications of the [Formula: see text]O(2) slow component in Δ50(180) compared with Δ50 (p = 0.32). The neuromuscular and metabolic adaptations during MSE(30) (preferential activation of type I muscle fibers evidenced by decreased MDF and a greater aerobic metabolism contribution to the required energy demands), but not during MSE(180), may lead to reduced [Formula: see text]O(2) and [HHb] slow components, suggesting an alteration in motor units recruitment profile (i.e., change in the type of muscle fibers recruited) and (or) an improved muscle O(2) delivery during subsequent exercise.

Short-term storage in vitro and large-scale propagation of grapevine genotypes

The objective of this work was to evaluate the large-scale propagation of grapevine genotypes after short-term storage in vitro. Microshoots from ten grapevine genotypes were used. The following storage temperatures were evaluated: 10, 20, and 25°C. After short-term storage, the shoots were propagated in up to five successive subcultures, to assess the large-scale propagation of the germplasm maintained under conditions of minimal growth. The propagated shoots were rooted in different concentrations of indolbutiric acid (IBA) and acclimatized in greenhouse. The best temperature for short-term storage in vitro and survival of the genotypes was 20°C. In the propagation phase, the highest number of shoots per explant was found in the subcultures 4 and 5, with averages of 4.9 and 4.8 shoots per explant, respectively. In the rooting phase, the best results for number of roots were obtained using a culture medium supplemented with 0.4 µmol L-1 of IBA, with an average of three roots per shoot. During the acclimation phase, a survival rate higher than 95% was achieved after 30 days in the greenhouse. Grapevine genotypes maintained for six months in vitro, at 20ºC, can be micropropagated in large scale.

Ego identity in adolescence: preliminary validation of a French short-form of the EIPQ

Following the seminal work on personal identity of Erikson, Marcia's identity status model has been one of the most enduring paradigms. The Ego Identity Process Questionnaire (EIPQ; Balistreri, Busch-Rossnagel, & Geissinger, 1995) is a widely used measure of identity status. The purpose of this study was to evaluate the factor structure and the reliability of a French version of the EIPQ. The hypothesized structures were not confirmed. In light of the failed attempts to validate the original version, an alternative short-form version of the EIPQ (EIPQ-SF), maintaining the integrity of the original model, was developed in one sample and cross-validated in another sample. Additionally, theoretically consistent associations between the EIPQ-SF dimensions and self-esteem confirmed convergent validity. Globally, the results indicated that the French short-version of the EIPQ might be a useful instrument for the assessment of the identity statuses in adolescence and emerging adulthood.

Is my hand connected to my body? The impact of body continuity and arm alignment on the virtual hand illusion

When a rubber hand is placed on a table top in a plausible position as if part of a person"s body, and is stroked synchronously with the person"s corresponding hidden real hand, an illusion of ownership over the rubber hand can occur (Botvinick and Cohen 1998). A similar result has been found with respect to a virtual hand portrayed in a virtual environment, a virtual hand illusion (Slater et al. 2008). The conditions under which these illusions occur have been the subject of considerable study. Here we exploited the flexibility of virtual reality to examine four contributory factors: visuo-tactile synchrony while stroking the virtual and the real arms, body continuity, alignment between the real and virtual arms, and the distance between them. We carried out three experiments on a total of 32 participants where these factors were varied. The results show that the subjective illusion of ownership over the virtual arm and the time to evoke this illusion are highly dependent on synchronous visuo-tactile stimulation and on connectivity of the virtual arm with the rest of the virtual body. The alignment between the real and virtual arms and the distance between these were less important. It was found that proprioceptive drift was not a sensitive measure of the illusion, but was only related to the distance between the real and virtual arms.

Effect of repetitive arm cycling following botulinum toxin injection for poststroke spasticity: evidence from FMRI.

BACKGROUND AND OBJECTIVE: Investigations were performed to establish if repetitive arm cycling training enhances the antispastic effect of intramuscular botulinum toxin (BTX) injections in postischemic spastic hemiparesis. Effects on cerebral activation were evaluated by functional magnetic resonance imaging (fMRI). METHODS: Eight chronic spastic hemisyndrome patients (49 ± 10 years) after middle cerebral artery infarction (5.5 ± 2.7 years) were investigated. BTX was injected into the affected arm twice, 6 months apart. Spasticity was assessed using the Ashworth Scale and range of motion before and 3 months after BTX injections. Images were analyzed using Brain Voyager QX 1.8, and fMRI signal changes were corrected for multiple comparisons. RESULTS: During passive movements of affected and nonaffected hands, fMRI activity was increased bilaterally in the sensorimotor cortex (MISI), secondary somatosensory areas (SII), and supplementary motor area predominantly in the contralesional hemisphere, compared with the rest. Following repetitive arm cycling, fMRI activity increased further in MISI of the lesioned hemisphere and SII of the contralesional hemisphere. For patients with residual motor activity, treatment-related fMRI activity increases were associated with reduced spasticity; in completely plegic patients, there was no fMRI activity change in SII but increased spasticity after training. CONCLUSION: Increased activity in SII of the contralesional hemisphere and in MISI of the lesioned hemisphere reflect a treatment-induced effect in the paretic arm. It is hypothesized that the increased BOLD activity results from increased afferent information related to the antispastic BTX effect reinforced by training.

The short-rooted phenotype of the brevis radix mutant partly reflects root abscisic acid hypersensitivity.

To gain further insight into abscisic acid (ABA) signaling and its role in growth regulation, we have screened for Arabidopsis (Arabidopsis thaliana) mutants hypersensitive to ABA-mediated root growth inhibition. As a result, we have identified a loss-of-function allele of BREVIS RADIX (BRX) in the Columbia background, named brx-2, which shows enhanced response to ABA-mediated inhibition of root growth. BRX encodes a key regulator of cell proliferation and elongation in the root, which has been implicated in the brassinosteroid (BR) pathway as well as in the regulation of auxin-responsive gene expression. Mutants affected in BR signaling that are not impaired in root growth, such as bes1-D, bzr1-D, and bsu1-D, also showed enhanced sensitivity to ABA-mediated inhibition of root growth. Triple loss-of-function mutants affected in PP2Cs, which act as negative regulators of ABA signaling, showed impaired root growth in the absence of exogenous ABA, indicating that disturbed regulation of ABA sensitivity impairs root growth. In agreement with this result, diminishing ABA sensitivity of brx-2 by crossing it with a 35S:HAB1 ABA-insensitive line allowed significantly higher recovery of root growth after brassinolide treatment. Finally, transcriptomic analysis revealed that ABA treatment negatively affects auxin signaling in wild-type and brx-2 roots and that ABA response is globally altered in brx-2. Taken together, our results reveal an interaction between BRs, auxin, and ABA in the control of root growth and indicate that altered sensitivity to ABA is partly responsible for the brx short-root phenotype.

Inheritance of late flowering in natural variants of soybean cultivars under short-day conditions

The objective of this work was to determine the inheritance of the long juvenile period trait in natural variants of the Doko, BR 9 (Savana), Davis, Embrapa 1 (IAS 5RC), and BR 16 soybean cultivars. Complete diallel crosses were made between the Doko and BR 16 cultivars and their variants. A 3:1 segregation ratio was observed in the F2 populations of the 'Doko' x Doko-18T, 'Doko' x Doko-Milionária, 'Davis' x São Carlos, and 'BR 9 (Savana)' x MABR92-836 (Savanão) crosses, indicating that the long juvenile period trait is controlled by a pair of recessive genes. The difference in late flowering between the Doko cultivar and both of its variants was caused by a recessive spontaneous mutation at the same genetic locus. However, the variants Doko-18T and Doko-Milionária are identical mutants that share a pair of genes that control the long juvenile period under short-day conditions. These mutants can be used in breeding programs to develop cultivars adapted to low-latitude tropical regions.

Measurement with an automated oscillometric wrist device with position sensor leads to lower values than measurements obtained with an automated oscillometric arm device from the same manufacturer in elderly persons.

OBJECTIVE: Home blood pressure (BP) monitoring is recommended by several clinical guidelines and has been shown to be feasible in elderly persons. Wrist manometers have recently been proposed for such home BP measurement, but their accuracy has not been previously assessed in elderly patients. METHODS: Forty-eight participants (33 women and 15 men, mean age 81.3±8.0 years) had their BP measured with a wrist device with position sensor and an arm device in random order in a sitting position. RESULTS: Average BP measurements were consistently lower with the wrist than arm device for systolic BP (120.1±2.2 vs. 130.5±2.2 mmHg, P<0.001, means±SD) and diastolic BP (66.0±1.3 vs. 69.7±1.3 mmHg, P<0.001). Moreover, a 10 mmHg or greater difference between the arm and wrist device was observed in 54.2 and 18.8% of systolic and diastolic measures, respectively. CONCLUSION: Compared with the arm device, the wrist device with position sensor systematically underestimated systolic as well as diastolic BP. The magnitude of the difference is clinically significant and questions the use of the wrist device to monitor BP in elderly persons. This study points to the need to validate BP measuring devices in all age groups, including in elderly persons.

Short-term Hydropower Planning System

The Thesis gives a decision support framework that has significant impact on the economic performance and viability of a hydropower company. The studyaddresses the short-term hydropower planning problem in the Nordic deregulated electricity market. The basics of the Nordic electricity market, trading mechanisms, hydropower system characteristics and production planning are presented in the Thesis. The related modelling theory and optimization methods are covered aswell. The Thesis provides a mixed integer linear programming model applied in asuccessive linearization method for optimal bidding and scheduling decisions inthe hydropower system operation within short-term horizon. A scenario based deterministic approach is exploited for modelling uncertainty in market price and inflow. The Thesis proposes a calibration framework to examine the physical accuracy and economic optimality of the decisions suggested by the model. A calibration example is provided with data from a real hydropower system using a commercial modelling application with the mixed integer linear programming solver CPLEX.

Short-term increase in particulate matter blunts nocturnal blood pressure dipping and daytime urinary sodium excretion

Short-term exposure to ambient particulate matter with aerodynamic diameters<10 µm were found to be positively associated with blood pressure. Yet, little information exists regarding the association between particles and circadian rhythm of blood pressure. Hence, we analyzed the association of exposure to particulate matter with aerodynamic diameters<10 µm on the day of examination and ≤7 days before with ambulatory blood pressure and with sodium excretion in 359 adults from the general population using multiple linear regression. After controlling for potential confounders, a 10-µg/m3 increase in particulate matter with aerodynamic diameters<10 µm levels was associated with nighttime systolic blood pressure (β=1.32 mm Hg 95% CI, 0.06-2.58 mm Hg at lag 0; P=0.04), nighttime diastolic blood pressure (0.72 mm Hg 95% CI, 0.03-1.42 mm Hg at lag 2; P=0.04), nocturnal systolic blood pressure dipping (-0.96 mm Hg 95% CI, -1.89 to -0.03 mm Hg at lag 0; P=0.044), and daytime urinary sodium excretion (-0.05 log-mmol/min 95% CI, -0.10 to -0.01 log-mmol/min at lag 0; P=0.027) but not with nighttime sodium excretion. The associations with blood pressure rapidly diminished with increasing lag days, and the associations with daytime sodium excretion were maximal with particulate matter with aerodynamic diameters<10 µm in exposures 2 to 5 days before. The associations of short-term increases in particulate matter with aerodynamic diameters<10 µm with higher nighttime blood pressure and blunted systolic blood pressure dipping were preceded by associations with reduced ability of the kidney to excrete sodium during daytime. The underlying mechanism linking air pollution to increased cardiovascular risk may include disturbed circadian rhythms of renal sodium handling and blood pressure.