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Statistically and clinically significant cognitive declines are observed in a small subset of individuals with Parkinson's Disease (PD) following treatment with Deep Brain Stimulation (DBS).We examine the association between multi-domain cognitive decline (MCD) and demographic and baseline clinical variables and the incidence of serious adverse events (SAE) arising within a six-month interval following DBS for PD.Study participants with PD who displayed MCD at 6-month follow-up evaluation after DBS (n = 18) were contrasted with individuals with PD from the same study who did not show cognitive decline after DBS (n = 146). Logistic regression analyses were employed to assess relationship between predictors, including age (70 years old), pre-DBS cognitive screening test performance, SAE, and MCD. MCD+ and MCD-groups were also compared on other baseline clinical and demographic variables.MCD showed modest association with older age and lower baseline neurocognitive screening performance, whereas the groups did not differ on most other baseline clinical and demographic variables. SAEs during the study interval were the most robust predictor of MCD in the DBS group. A variety of SAEs were documented in study participants experiencing MCD after DBS surgery, including, but not limited to, infections and small intracranial hemorrhages.Older age and lower baseline cognition measured prior to treatment are associated with MCD measured at six-months after DBS. SAE occurring following DBS surgery are also predictive of MCD. These predictors may reflect aspects of "frailty" in advanced PD. Risk factors for SAE warrant careful consideration in clinical trials.

The development of ultra-thin flat liquid sheets capable of running in vacuum has provided an exciting new target for X-ray absorption spectroscopy in the liquid and solution phases. Several methods have become available for delivering in-vacuum sheet jets using different nozzle designs. We compare the sheets produced by two different types of nozzle; a commercially available borosillicate glass chip using microfluidic channels to deliver colliding jets, and an in-house fabricated fan spray nozzle which compresses the liquid on an axis out of a slit to achieve collision conditions. We find in our tests that both nozzles are suitable for use in X-ray absorption spectroscopy with the fan spray nozzle producing thicker but more stable jets than the commercial nozzle. We also provide practical details of how to run these nozzles in vacuum.

We report the first demonstration of time-resolved X-ray absorption spectroscopy to track previously undetected photoinduced dynamics of a paradigmatic crystalline conjugated polymer: poly(3-hexylthiophene) (P3HT) commonly used in solar cell devices. The pi to pi* transition, the first step of solar energy conversion, is pumped with a 15 fs optical pulse and the dynamics are probed by an attosecond soft X-ray pulse at the carbon K-edge. We observe direct spectroscopic signatures of the initially hot excitonic state, which is delocalized over multiple polymer chains, undergoing a rapid evolution on a sub 50 fs timescale which can be directly associated with cooling and localization to form the lowest excitonic state on a single polymer chain. This sensitivity of time-resolved X-ray spectroscopy to the primary electron dynamics occurring directly after excitation paves the way for new insights in a wide range of organic optoelectronic materials.

π -conjugated semiconducting polymers have the potential to provide low cost, flexible and thin optoelectronic devices such as light-emitting diodes, field effect transistors and solar cells. The ultrafast dynamics of tightly bound, Frenkel excitons in these materials are crucial for the performance of these devices [1] , [2] . In this work we demonstrate the first application of soft X-ray transient absorption spectroscopy to study exciton dynamics in an organic semiconducting polymer, poly(3-hexylthiophene) (P3HT). The samples are pumped with a ∼ 15 fs optical pulse resonant with the π → π * transition at 2.25 eV, relevant to solar energy conversion. The probe is a soft X-ray supercontinuum extending to 350 eV with attosecond pulse duration generated via high harmonic generation [3] . Figure 1a shows the transient absorption spectrum of P3HT in the vicinity of the carbon K edge. At all positive time delays a blue shift in the absorption edge is observed giving rise to the strong increase in absorption at 286.25 eV. At short time delays this is accompanied by a weaker positive differential absorption feature 1.2 eV below the edge. The low energy feature is highly transient and decays with a lifetime of 16 8 fs. With the support of TDDFT simulations ( Fig. 1b ), we associate the spectral blue shift with the localised ± singlet exciton and the low energy transient feature as a direct spectroscopic signature of delocalisation of the exciton between polymer chains. Our results suggest that the photoexcited H-aggregate type state undergoes rapid localisation on a sub 50 fs timescale consistent with theoretical predictions for this polymer [4] .

Science, 355 (6322), ISSN:0036-8075, ISSN:1095-9203

In this paper we examine the spectral changes in a white light laser filament due to different pulse shapes generated by a pulse shaping setup. We particularly explore how the properties of the filament spectra can be controlled by parametrically tailored white light pulses. The experiments are carried out in a gas cell with up to 9 bar of argon. Plasma generation and self-phase modulation strongly affect the pulse in the spectral and temporal domain. By exploiting these effects we show that the pulse spectrum can be modified in a desired way by either using second order parametric chirp functions to shift the filament spectrum to higher or lower wavelengths, or by optimizing pulse shapes with a genetic algorithm to generate more complex filament spectra. This paper is one of the first examples of the application of complex, parametrically shaped white light pulses., 14 pages, 7 figures

Light can be used to modify and control properties of media, as in the case of electromagnetically induced transparency or, more recently, for the generation of slow light or bright coherent XUV and X-ray radiation. Particularly unusual states of matter can be created by light fields with strengths comparable to the Coulomb field that binds valence electrons in atoms, leading to nearly-free electrons oscillating in the laser field and yet still loosely bound to the core [1,2]. These are known as Kramers-Henneberger states [3], a specific example of laser-dressed states [2]. Here, we demonstrate that these states arise not only in isolated atoms [4,5], but also in rare gases, at and above atmospheric pressure, where they can act as a gain medium during laser filamentation. Using shaped laser pulses, gain in these states is achieved within just a few cycles of the guided field. The corresponding lasing emission is a signature of population inversion in these states and of their stability against ionization. Our work demonstrates that these unusual states of neutral atoms can be exploited to create a general ultrafast gain mechanism during laser filamentation., Comment: 9 pages, 4 figures, 10 pages supplementary material, 8 supplementary figures

We present laser-induced condensation as a method for detecting of ultra-low concentrations of volatile organic compounds featuring a detection threshold well below 1 ppb. The method was tested in lab scale experiments and compared with quantitative photo-ionization detection measurements. The method was shown to be sensitive to the laser excitation wavelength between 1.6’2.0 um range.

Light is used to modify or control properties in many quantum systems, leading to phenomena such as electromagnetically induced transparency, the generation of slow light or bright coherent XUV radiation. Using light fields, with strengths comparable to the Coulomb field which binds valence electrons in atoms, particularly unusual quantum states can be created which describe a nearly free electron oscillating in the laser field yet still loosely bound to the core1, 2. We demonstrate that such states can arise not only in isolated atoms3, but also in gases at a few atmospheric pressures, guiding intense laser pulses, where they can act as a gain medium. This gain is created within just a few cycles of the guided field. Using shaped pulses4 with 5–10 fs risetimes, we create pulse conditions, within a laser filament, where these states can persist, and we observe in the corresponding emission, the signatures of these states. This work demonstrates a general, new, ultrafast gain mechanism during filamentation, in which any driven atom can achieve inversion intra-pulse, using pulse shaping techniques.

Time-resolved spectroscopy at element-specific absorption edges provides a powerful tool to study ultrafast phenomena of matter on the atomic scale in the gas, solid or liquid phase. Combining element sensitivity of core-to-valence transitions due to the very localized initial core state and femtosecond/attosecond time resolution of new soft X-ray sources based on high-harmonic generation from long-wavelength drivers, accurate electronic and structural information is now accessible.

We characterized the white-light supercontinuum emission by a sub-petawatt laser system in the atmosphere via light detection and ranging measurements. As much as 1 J of supercontinuum is generated in the atmosphere, corresponding to a conversion efficiency of 30 %. This generation occurs at altitudes below 100 m. The high initial beam intensity results in the saturation of the number of self-guided filaments. Therefore, the “photon bath” surrounding the filaments strongly contributes to the white-light generation. These finding is well reproduced by numerical simulations based on the experimental parameters.

We investigate the pulse partitioning of a 6.3 mJ, 450 fs pulse at 1030 nm to produce plasma channels. At such moderate energies, splitting the energy into several sub-pulses reduces the ionization efficiency and thus does not extend the plasma lifetime. We numerically show that when sufficient energy to produce multifilamentation is available, splitting the pulse temporally in a pulse train increases the gas temperature compared to a filament bundle of the same energy. This could improve the mean free path of the free electrons, therefore enhancing the efficiency of discharge triggering., Correcting typo in Eq. (12) and unit of $\beta_{ep}$ in Table I

Background and purpose To ascertain whether freezing of gait (FOG) and stride reduction (SR) may be relieved by the use of an attachable, adjustable laser (the Mobilaser). Methods Seven parkinsonian patients with FOG and SR were randomized in an open-label, randomized, cross-over clinical study at a tertiary referral center. The Mobilaser was attached to a 4-wheeled walker by Velcro and switched on, producing an adjustable red line, which the subjects stepped on or over while ambulating a standardized course. The length of time each subject took, and the number of freezes they experienced traversing the course, using a 4-wheeled walker with the device turned on and off, were compared. Results A total of 7 patients were investigated; however, one was excluded from the study due to severe deconditioning, prohibiting completion of the testing. Of the 6 enrolled, all subjects took less time to ambulate the course using the attachable, adjustable laser than without it (Wilcoxon signed-rank test, P=0.03). In addition, the total number of freezes was less in all 6 subjects when using the device than without it. No adverse events occurred during the trial. Discussion and conclusions The Mobilaser is potentially an effective and safe device for alleviating parkinsonian FOG and SR.

Mid-infrared (mid-IR) spectroscopy provides a unique chemical fingerprint of biomaterials, including DNA and proteins, from single molecules to highly organised structures and, ultimately, to live cells and tissues. However, acquiring good signal–to–noise mid-IR spectroscopic images, at the cellular level, typically involves a synchrotron, with imaging times of order of minutes. Here we use a new laser-based table-top IR spectroscopic micro-imaging system, to obtain vibrational fingerprint signatures of living human ovarian cancer cells at a diffraction limited spatial resolution, and at a spectral resolution (< 20 cm−1) sufficient to map out the spatial distributions of chemical moieties inside the cell itself. The bright laser pulses give very high signal–to–noise images, and ∼100 psec image acquisition times that are roughly 1011 times faster than current mid-IR spectroscopic imaging techniques. The imaging method is quantitative, non-phototoxic, marker-free and easily fast enough to “freeze” moving, living specimens. It can be applied to a range of cell-level biochemical processes, and we believe it could impact on the fields of drug action, cell physiology, pathology and disease as a whole.

In the version of this Letter originally published, the units of the bottom three values in the Fig. 1d legend were incorrect; they should have been W cm–2. This has now been corrected.

An increasing number of women fail to achieve pregnancy due to either failed fertilization or embryo arrest during preimplantation development. This often results from decreased oocyte quality. Indeed, reduced mitochondrial DNA copy number (mitochondrial DNA deficiency) may disrupt oocyte quality in some women. To overcome mitochondrial DNA deficiency, whilst maintaining genetic identity, we supplemented pig oocytes selected for mitochondrial DNA deficiency, reduced cytoplasmic maturation and lower developmental competence, with autologous populations of mitochondrial isolate at fertilization. Supplementation increased development to blastocyst, the final stage of preimplantation development, and promoted mitochondrial DNA replication prior to embryonic genome activation in mitochondrial DNA deficient oocytes but not in oocytes with normal levels of mitochondrial DNA. Blastocysts exhibited transcriptome profiles more closely resembling those of blastocysts from developmentally competent oocytes. Furthermore, mitochondrial supplementation reduced gene expression patterns associated with metabolic disorders that were identified in blastocysts from mitochondrial DNA deficient oocytes. These results demonstrate the importance of the oocyte’s mitochondrial DNA investment in fertilization outcome and subsequent embryo development to mitochondrial DNA deficient oocytes.

The filamentation of ultrashort laser pulses [1] attracts considerable interest due to its potential applications in remote sensing technologies, free space communications as well as weather diagnostics and modulation systems. They generate a plasma wake that modifies the physico-chemical properties of the air, allowing the condensation of aerosol particles in sub-saturated air. [2,3] This phenomenon is promising as a technique for analyzing and possibly modifying the behavior of clouds. [4]

This study examines cross-national differences in relation to software piracy between a Zambian and a South Africa student sample on components of Bandura’s Social Cognitive Theory. The sample was selected based on the vastly different software piracy rates between Zambia (82%) and South Africa (35%) and the fact that software piracy rates are higher amongst student groups. The questionnaire was composed of previously developed scales measuring attitudes, social norms, intentions, incen- tives, deterrents, self-efficacy, and moral disengagement within the context of software piracy. The sample was gathered from one University in Zambia (N = 69) and one in South Africa (N = 71) in the students’ final and penultimate years of study. Statistical differences were found between the two samples on the attitudes and social norms scales, with the South African sample having more posi- tive attitudes and more favourable social norms towards software piracy than the Zambian sample. In terms of the theoretical model, attitudes, social norms and self-efficacy predicted software piracy intentions in both samples.

Background Deep brain stimulation (DBS) improves motor symptoms in Parkinson9s disease (PD), but questions remain regarding neuropsychological decrements sometimes associated with this treatment, including rates of statistically and clinically meaningful change, and whether there are differences in outcome related to surgical target. Methods Neuropsychological functioning was assessed in patients with Parkinson9s disease (PD) at baseline and after 6 months in a prospective, randomised, controlled study comparing best medical therapy (BMT, n=116) and bilateral deep brain stimulation (DBS, n=164) at either the subthalamic nucleus (STN, n=84) or globus pallidus interna (GPi, n=80), using standardised neuropsychological tests. Measures of functional outcomes were also administered. Results Comparison of the two DBS targets revealed few significant group differences. STN DBS was associated with greater mean reductions on some measures of processing speed, only one of which was statistically significant in comparison with stimulation of GPi. GPi DBS was associated with lower mean performance on one measure of learning and memory that requires mental control and cognitive flexibility. Compared to the group receiving BMT, the combined DBS group had significantly greater mean reductions at 6-month follow-up in performance on multiple measures of processing speed and working memory. After calculating thresholds for statistically reliable change from data obtained from the BMT group, the combined DBS group also displayed higher rates of decline in neuropsychological test performance. Among study completers, 18 (11%) study participants receiving DBS displayed reliable decline by multiple indicators in two or more cognitive domains, a significantly higher rate than in the BMT group (3%). This multi-domain cognitive decline was associated with less beneficial change in subjective ratings of everyday functioning and quality of life (QOL). The multi-domain cognitive decline group continued to function at a lower level at 24-month follow-up. Conclusions In those with PD, the likelihood of significant decline in neuropsychological functioning increases with DBS, affecting a small minority of patients who also appear to respond less optimally to DBS by other indicators of QOL. Trial registration number NCT00056563 and NCT01076452.

Objective: To measure the prevalence of cobalamin (vitamin B12) deficiency in geriatric outpatients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment. Objective: Prospective study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays. In patients with serum cobalamin levels ≤300 pg/mL, the response to cobalamin treatment in the group with levels of methylmalonic acid and/or homocysteine >3 standard deviations (SD) above the mean for normals was compared with that of those without such elevations. Setting: Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center, Denver, CO. Patients: One-hundred and fifty-two consecutive outpatients, ages 65 to 99, were screened. Twenty-nine subjects with serum cobalamin levels ≤300 pg/mL were prospectively evaluated and treated with cobalamin. Main Outcome Measures: Cobalamin, methylmalonic acid, homocysteine, complete blood counts, neurologic examination, and neuropsychological testing. Results: The prevalence of cobalamin deficiency as defined by a serum cobalamin level ≤300 pg/mL and levels of serum methylmalonic acid and/or homocysteine elevated to >3 SD was 14.5% of the screened outpatients. A similar proportion of patients with low normal serum cobalamin levels (between 201 and 300 pg/mL) demonstrated elevated metabolites >3 SD (56%) compared with patients with low serum cobalamin levels (≤200 pg/mL) (62%). Cobalamin therapy caused a marked fall or complete correction of the elevated methylmalonic acid and homocysteine levels in each patient who was treated prospectively. Results for complete blood count, lactate dehydrogenase, bilirubin, baseline neurologic score, and baseline neuropsychologic scores did not differ in the group of patients with elevated metabolites compared with those with normal metabolites. The mean red cell volume fell significantly in the patients with elevated metabolites after 6 months of cobalamin treatment. One patient with elevated metabolites had marked improvement in his neurologic abnormalities after 6 months of cobalamin treatment. Conclusion: There was a high (14.5%) prevalence of cobalamin deficiency as demonstrated by elevations in serum methylmalonic acid and homocysteine in addition to low or low normal serum cobalamin levels in elderly outpatients. The serum cobalamin level was insensitive for screening since similar numbers of patients with low normal serum cobalamin levels of 201–300 pg/mL compared with patients with low cobalamin levels (≤200 pg/mL) had markedly elevated metabolites which fell with cobalamin treatment. Additional studies will be required to define the full clinical benefit from treatment with Cbl in elderly subjects. J Am Geriatr Soc 40:1197–1204, 1992

A bonded rhomb sample geometry is used to study the spin-dependent absorption characteristics of an intersubband transition in the conduction band of a GaAs/AlGaAs quantum well. Optical saturation experiments, using linearly and circularly polarized beams, were compared to measure the population relaxation time of the upper subband and the degree to which spin polarization is occurring in the electron population. In sharp contrast to previous interband absorption studies, the intersubband data are consistent with a picture in which the angular momentum of the incident photons appears to bypass the electron system completely and instead exerts a direct torque on the crystal lattice.

Intersubband transitions within the conduction band in semiconductor quantum wells have been widely explored, which eventually led to their application in quantum well infrared photodetectors and quantum cascade lasers (QCLs). There have been considerably fewer studies of hole intersubband transitions, which are more complicated than their electronic counterparts. They are very interesting, however, because of optical activity for both TM and TE light polarization, offering the possibility of both edge and surface-normal emission or absorption. Earlier studies have mostly focused on bound- continuum transitions in GaAs/AlGaAs and Si/SiGe systems for infrared detection.

Little is known regarding the effects of antiparkinsonian drugs in US racial or ethnic minorities.: To evaluate the safety, tolerability, and efficacy of adjunctive pramipexole in Parkinson disease (PD) patients of African, Asian, or Hispanic heritage stably treated with levodopa.Multicenter, parallel-group, double-blind, randomized, placebo-controlled trial.: Seventeen Parkinson Study Group sites in the United States and Puerto Rico.One hundred forty-four PD patients of African, Asian, or Hispanic heritage enrolled from January 1997 to August 1998 and observed until October 1998.Subjects received pramipexole or placebo (3:1 ratio), 0.375 mg/d to a maximum tolerated dose (or=4.5 mg/d) over a 6-week period, achieving optimum levels (0.375, 1.5, 3.0, or 4.5 mg/d) in the 4-week maintenance period.Change in the sum of the Unified Parkinson's Disease Rating Scale parts 2 (activities of daily living) and 3 (motor) from baseline to week 10.Parkinsonism improved (mean [SD] reduction in Unified Parkinson's Disease Rating Scale activities of daily living + motor score at 10 weeks, 10.27 [11.96] pramipexole vs 6.54 [13.58] placebo, P = 0.012) and was similar in each group. Adverse events occurred in 85.3% on pramipexole and 68.6% on placebo. Hallucinations and insomnia were more common on pramipexole than placebo (18 vs 0, P = 0.023, and 15 vs 0, P = 0.045, respectively).Pramipexole is an effective adjunctive antiparkinsonian therapy in PD patients of African, Asian, and Hispanic heritage. Tolerability and safety overall were similar among the groups, but differences in profiles of adverse effects and tolerability were suggested.

Optical saturation experiments have been performed on hh1-hh2 intersubband transitions in two samples of p-doped GaAs∕AlGaAs quantum wells. The transitions had energies of 183 and 160meV and the measured population relaxation times were 2±1.5 and 0.3±0.1ps, respectively. Modeling of the quantum wells with a 6×6 k⋅p method shows that intersubband scattering by LO phonons can account for these relaxation times. The valence bandstructure is typically more complicated than the conduction bandstructure in a quantum well but these measurements show that LO phonons are the dominant intersubband scattering mechanism in both cases.

A pulsed midinfrared photoconductivity study of electron recapture in dot-in-a-well infrared photodetectors yields bias-dependent electron-capture lifetimes in the range of 3–600ns and photoconductive gain factors of ∼104–105. The dependence of the lifetimes on temperature and electric field argues for these surprisingly long values being due to electron intervalley transfer. Under normal device operating conditions, photoexcited electrons transfer efficiently out of the central GaAs Γ minimum into the high energy L and X valleys, where they couple only weakly to the Γ-like confined states in the InAs dots.

Laser filaments interacting with cirrus like ice crystals produce a large number of small secondary ice particles by re-condensation of the released water vapor. This new phenomenon drastically modifies its radiative forcing