Tracking the Ionization Site in Neutral Molecules.

When a diatomic molecule is exposed to intense light, the valence electron may tunnel from a higher potential (corresponding to an upfield atom) due to the suppressed internuclear barrier. This process is known as ionization enhancement and is a key mechanism in strong field ionization of molecules. Alternatively, the bound electron wave function can evolve adiabatically in the laser field, resulting in ionization from the downfield atom. Here, we introduce a method to quantify the relative contribution of these two processes. Applying this method to experimentally measured electron momenta distributions following strong field ionization of N_{2} with infrared laser light, we find approximately a 2∶1 ratio of electrons ionized from a downfield atom, relative to upfield. This suggests that the bound state wave function largely adapts adiabatically to the changing laser field, although the nonadiabatic process of ionization enhancement still contributes even in neutral molecules. Our method can be applied to any diatomic neutral molecule to better understand the evolution of the initially bound electron wave packet and hence the nature of the molecular ionization process.

Orientation-dependent stereo Wigner time delay and electron localization in a small molecule.

Attosecond metrology of atoms has accessed the time scale of the most fundamental processes in quantum mechanics. Transferring the time-resolved photoelectric effect from atoms to molecules considerably increases experimental and theoretical challenges. Here we show that orientation- and energy-resolved measurements characterize the molecular stereo Wigner time delay. This observable provides direct information on the localization of the excited electron wave packet within the molecular potential. Furthermore, we demonstrate that photoelectrons resulting from the dissociative ionization process of the CO molecule are preferentially emitted from the carbon end for dissociative 2Σ states and from the center and oxygen end for the 2Π states of the molecular ion. Supported by comprehensive theoretical calculations, this work constitutes a complete spatially and temporally resolved reconstruction of the molecular photoelectric effect.

Emergence of a Higher Energy Structure in Strong Field Ionization with Inhomogeneous Electric Fields.

Studies of strong field ionization have historically relied on the strong field approximation, which neglects all spatial dependence in the forces experienced by the electron after ionization. More recently, the small spatial inhomogeneity introduced by the long-range Coulomb potential has been linked to a number of important features in the photoelectron spectrum, such as Coulomb asymmetry, Coulomb focusing, and the low energy structure. Here, we demonstrate using midinfrared laser wavelength that a time-varying spatial dependence in the laser electric field, such as that produced in the vicinity of a nanostructure, creates a prominent higher energy peak. This higher energy structure (HES) originates from direct electrons ionized near the peak of a single half-cycle of the laser pulse. The HES is separated from all other ionization events, with its location and width highly dependent on the strength of spatial inhomogeneity. Hence, the HES can be used as a sensitive tool for near-field characterization in the "intermediate regime," where the electron's quiver amplitude is comparable to the field decay length. Moreover, the large accumulation of electrons with tuneable energy suggests a promising method for creating a localized source of electron pulses of attosecond duration using tabletop laser technology.

Attosecond physics at the nanoscale.

Recently two emerging areas of research, attosecond and nanoscale physics, have started to come together. Attosecond physics deals with phenomena occurring when ultrashort laser pulses, with duration on the femto- and sub-femtosecond time scales, interact with atoms, molecules or solids. The laser-induced electron dynamics occurs natively on a timescale down to a few hundred or even tens of attoseconds (1 attosecond = 1 as = 10-18 s), which is comparable with the optical field. For comparison, the revolution of an electron on a 1s orbital of a hydrogen atom is ∼152 as. On the other hand, the second branch involves the manipulation and engineering of mesoscopic systems, such as solids, metals and dielectrics, with nanometric precision. Although nano-engineering is a vast and well-established research field on its own, the merger with intense laser physics is relatively recent. In this report on progress we present a comprehensive experimental and theoretical overview of physics that takes place when short and intense laser pulses interact with nanosystems, such as metallic and dielectric nanostructures. In particular we elucidate how the spatially inhomogeneous laser induced fields at a nanometer scale modify the laser-driven electron dynamics. Consequently, this has important impact on pivotal processes such as above-threshold ionization and high-order harmonic generation. The deep understanding of the coupled dynamics between these spatially inhomogeneous fields and matter configures a promising way to new avenues of research and applications. Thanks to the maturity that attosecond physics has reached, together with the tremendous advance in material engineering and manipulation techniques, the age of atto-nanophysics has begun, but it is in the initial stage. We present thus some of the open questions, challenges and prospects for experimental confirmation of theoretical predictions, as well as experiments aimed at characterizing the induced fields and the unique electron dynamics initiated by them with high temporal and spatial resolution.

Carrier-wave Rabi-flopping signatures in high-order harmonic generation for alkali atoms.

We present a theoretical investigation of carrier-wave Rabi flopping in real atoms by employing numerical simulations of high-order harmonic generation (HHG) in alkali species. Given the short HHG cutoff, related to the low saturation intensity, we concentrate on the features of the third harmonic of sodium (Na) and potassium (K) atoms. For pulse areas of 2π and Na atoms, a characteristic unique peak appears, which, after analyzing the ground state population, we correlate with the conventional Rabi flopping. On the other hand, for larger pulse areas, carrier-wave Rabi flopping occurs, and is associated with a more complex structure in the third harmonic. These characteristics observed in K atoms indicate the breakdown of the area theorem, as was already demonstrated under similar circumstances in narrow band gap semiconductors.

Wound closure in patients with DFU: a cost-effectiveness analysis of two cellular/tissue-derived products.

OBJECTIVE: Determine the cost-effectiveness of extracellular matrix (ECM) relative to human fibroblast-derived dermal substitute (HFDS) on diabetic foot ulcer (DFU) wound closure. METHOD: Outcomes data were obtained from a 12-week, randomised, clinical trial of adults aged 18 years or older diagnosed with type 1 or type 2 diabetes with a DFU. Patients were treated with either ECM or HFDS treatment. A two-state Markov model (healed and unhealed) with a 1-week cycle length was developed using wound-closure rates from the trial to estimate the number of closed-wound weeks and the expected DFU cost per patient. Results were recorded over 12 weeks to estimate the number of closed-wound weeks per treatment and the average cost to achieve epithelialisation (primary outcome). The perspective of the analysis was that of the payer, specifically the Centers for Medicare and Medicaid Services. No cost discounting was performed because of the short duration of the study. RESULTS: The study consisted of 26 patients, with 13 in each group. In the ECM group, 10 wounds closed (77%), with an average closure time of 36 days; 11 wounds closed in the HFDS group (85%), with an average closure time of 41 days. There was no significant difference between these results (p=0.73). Over 12 weeks, the expected cost per DFU was $2522 (£1634) for ECM and $3889 (£2524) for HFDS. Patients treated with HFDS incurred total treatment costs that were approximately 54% higher than those treated with ECM. Sensitivity analyses revealed that the total cost of care for two applications of HFDS was more costly than eight applications of ECM by approximately $500 (£325). CONCLUSION: In patients with DFU, ECM yielded similar clinical outcomes to HFDS but at a lower cost. Health-care providers should consider ECM as a cost-saving alternative to HFDS. DECLARATION OF INTEREST: A.M. Gilligan, and C.R. Waycaster, are employees of Smith & Nephew Inc.. This study was funded by Smith & Nephew Inc.. A.L. Landsman, reports no conflicts of interest.

Unified approach to probing Coulomb effects in tunnel ionization for any ellipticity of laser light.

We present experimental data that show significant deviations from theoretical predictions for the location of the center of the electron momenta distribution at low values of ellipticity ε of laser light. We show that these deviations are caused by significant Coulomb focusing along the minor axis of polarization, something that is normally neglected in the analysis of electron dynamics, even in cases where the Coulomb correction is otherwise taken into account. By investigating ellipticity-resolved electron momenta distributions in the plane of polarization, we show that Coulomb focusing predominates at lower values of ellipticity of laser light, while Coulomb asymmetry becomes important at higher values, showing that these two complementary phenomena can be used to probe long-range Coulomb interaction at all polarizations of laser light. Our results suggest that both the breakdown of Coulomb focusing and the onset of Coulomb asymmetry are linked to the disappearance of Rydberg states with increasing ellipticity.

Probing nonadiabatic effects in strong-field tunnel ionization.

We investigate experimentally the validity of proposed theories extending the tunneling approximation towards the multiphoton regime in strong-field ionization of helium. We employ elliptically polarized laser pulses and demonstrate how the influence of the ion potential on the released electron encoded in the measured observable provides the desired sensitivity to detect nonadiabatic effects in tunnel ionization. Our results show that for a large intensity range the proposed nonadiabatic theories contradict the experimental trends of the data, while adiabatic assumptions are confirmed.

Probing the longitudinal momentum spread of the electron wave packet at the tunnel exit.

We present an ellipticity-resolved study of momentum distributions arising from strong-field ionization of helium. The influence of the ion potential on the departing electron is considered within a semiclassical model consisting of an initial tunneling step and subsequent classical propagation. We find that the momentum distribution can be explained by including the longitudinal momentum spread of the electron at the exit from the tunnel. Our combined experimental and theoretical study provides an estimate of this momentum spread.

Unstable acute and chronic Charcot's deformity: staged skeletal and soft-tissue reconstruction.

Acute and chronic Charcot's foot deformity is a progressive, disabling and disfiguring condition that is prone to ulceration and infection. If conservative treatment is ineffective, bone and soft-tissue reconstruction is a viable option.

Onset and saturation of ion heating by odd-parity rotating magnetic fields in a field-reversed configuration.

Heating of figure-8 orbit ions by odd-parity rotating magnetic fields (RMF(O)) applied to an elongated field-reversed configuration (FRC) is investigated. The largest energy gain occurs at resonances (s congruent to omega(R)/omega) of the RMF(O) frequency, omega(R), with the figure-8 orbital frequency, omega, and is proportional to s2 for s-even resonances and to s for s-odd resonances. The threshold for the transition from regular to stochastic orbits explains both the onset and saturation of heating. The FRC magnetic geometry lowers the threshold for heating below that in the tokamak by an order of magnitude.

Fibrin microbeads (FMB) as a 3D platform for kidney gene and cell therapy.

Cell and gene therapy may alter the outcome of renal diseases, such as hereditary nephropathies, acute and chronic glomerulonephritis and allograft nephropathy. However, owing to blockade of many viral and cellular vehicles by the complex glomerular architecture, the exact nature of gene and cell delivery into specific renal compartments remains currently unknown. To study the interaction of viral vectors with a variety of renal cells and mesenchymal stem cells (MSCs), we employed a novel biological three-dimensional (3D) matrix comprised of fibrin microbeads (FMB) in comparison to monolayer cell culture. Our studies showed that renal cells of both established and primary lines can grow efficiently on FMB and differentiate into epithelial structures, as shown by electron microscopy. Gene delivery into renal cells in 3D was observed for several viral vectors and growth in 3D on FMB conferred resistance to renal cancer cells in the context of oncolytic adenoviruses. Finally, MSCs from various rodent species attached to FMB, grew robustly, survived for several weeks and could efficiently be transduced on FMB. Thus, on the basis of growth, differentiation and transduction of renal cells in 3D, FMB emerge as a novel 3D cellular microenvironment that differs substantially from monolayer cell cultures.

Dietary phosphate-dependent growth is not mediated by changes in plasma phosphate concentration.

The present study was undertaken in order to assess the role of dietary phosphate in growth. A diet deficient in phosphate led to a suppression of growth in juvenile rats. The phenomenon is similar to that described for diets deficient in other essential single components such as Mg, Zn or K. However, unlike the other constituents, dietary phosphate restriction affected the growth rate much more than it altered the serum phosphate concentration; addition of phosphate to the drinking water of rats fed a low-phosphate diet restored the growth rate without a concomitant change in serum phosphate concentration. The suppression of growth rate by the deletion of phosphate was associated with a delayed decrease in food intake. This finding implies that the variation in appetite was secondary to the change in growth. The increase in body weight following phosphate supplementation was associated with a concomitant increment in food intake. The phosphate-dependent growth was, however, evident also in rats that were pair-fed with those that were not supplied with phosphate. It is concluded that dietary phosphate-dependent growth is not mediated by changes in phosphate concentrations in the extracellular fluid. It is plausible that signals arising from receptors for phosphate in the digestive system constitute part of the growth control apparatus in rats.

The effects of a moderate and high dose of vitamin C on wound healing in a controlled guinea pig model.

The purpose of this pilot study was to investigate the effect of vitamin C on wound healing in a controlled animal study. Twenty male guinea pigs were divided into two groups and were maintained on one of two commercially prepared diets: 1) supplemented with a moderate dose of vitamin C, or 2) supplemented with a high dose of vitamin C. After 6 weeks, a dorsal incision was made on the back of each of the animals. The incision was closed by primary intention as the animals continued on their respective diets until they were sacrificed. At the time of testing, either 10 days or 21 days postoperatively, the animals' skin was excised around the original incision using a metal template. A second skin sample was excised from each animal from an area adjacent to the original skin incision. This was done in order to determine the breaking force of the intact unaffected skin. Tension studies were performed to measure and compare the integrity and strength of the healing incisions. Biopsies were also sent for histopathologic analysis. The study presented here focused on whether or not increases in dietary vitamin C may improve the strength of a skin wound postoperatively. Although the sample size was small, the data suggest that a trend may exist in which increased vitamin C intake prior to and after surgery may result in faster recovery of skin integrity and strength across the wound. Although the difference between the groups is not statistically significant, the data clearly indicate that the animals receiving the higher dose of vitamin C demonstrated greater wound integrity than those receiving the moderate dose of the vitamin.

Can synthetic bone models approximate the mechanical properties of cadaveric first metatarsal bone?

The authors evaluated the value of plastic foam models for approximating the mechanical properties of cadaveric bone. Three mechanical tests (3-point bending, cantilevered load to failure, screw push-out) were performed to evaluate the performance of fresh (nonpreserved) human metatarsals, plastic solid foam anatomic models, and modified anatomic models. The test results indicate that plastic models may simulate the mechanical properties of natural bone in tests in which only elastic deformation is achieved. However, under circumstances where load is applied until material failure, the mechanical properties vary dramatically. These tests indicate that specific goals should be established with these results in mind, when planning mechanical testing studies with either plastic or cadaveric models.

The role of combined magnetic field bone growth stimulation as an adjunct in the treatment of neuroarthropathy/Charcot joint: an expanded pilot study.

This study was designed to assess the value of combined magnetic field (CMF) bone growth stimulation in the treatment of acute, phase 1, Charcot neuroarthopathy. Thirty-one subjects were studied. Initially 10 controls and 11 study patients were examined. When the initial results were analyzed, 10 additional study patients were added. The result was a statistically significant reduction in time to consolidation, 23.8 weeks for the control versus 11 weeks for the study group. Additionally, less destruction of the bony architecture was noted in the study group as compared to the control. Thus the results of this expanded pilot study demonstrate the efficacy of CMF in accelerating the consolidation process of acute, phase 1, Charcot joint, and decreasing the amount of residual deformity.

Off-loading neuropathic wounds associated with diabetes using an ankle-foot orthosis.

Patients with chronic diabetes have a broad spectrum of associated peripheral neurologic deficits that culminate in an increased susceptibility to ulcer formation. The authors focus on the use of the ankle-foot orthosis as both a treatment and a definitive solution for achieving ulcer closure and for minimizing the chance of ulcer recurrence in the ambulatory patient. An analysis of the pathologic forces encountered, and the solution achieved with the ankle-foot orthosis is presented. In addition, the results from a clinical pilot study in subjects with recalcitrant ulcers secondary to Charcot's neuroarthropathy are presented.

The biochemical pathway mediating the proliferative response of bone cells to a mechanical stimulus.

Calvarial bone cells of rats were subjected to either a cyclic biaxial strain of 0.17 per cent (1700 microstrain) or a hydrostatic pressure of 2.5, five, or ten pounds per square inch (17.2, 34.5, or sixty-nine kilopascals). The frequency was held constant at one hertz for both types of mechanical stimulation. When cultured bone cells that had been subjected to a cyclic biaxial strain for two hours were harvested twenty-two hours later, it was found that the level of prostaglandin E2 had increased significantly (p < 0.01) as had cellular proliferation (p < 0.01), as indicated by the incorporation of [3H]-thymidine. The addition to the medium of indomethacin, an inhibitor of prostaglandin synthesis, at a ten-micromolar concentration significantly inhibited (p < 0.01) the increase in prostaglandin E2 synthesis but had no effect on the strain-induced increase in cellular proliferation, as indicated by the incorporation of [3H]-thymidine. Twenty-four hours after exposure to the same cyclic biaxial strain for thirty seconds, other cultured bone cells showed a significant increase in the level of cytoskeletal calmodulin (p < 0.05) and in the DNA content (p < 0.05). N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7), a calmodulin antagonist, was added to the medium at a one-micromolar concentration, which had been shown to have no effect on the increase in the DNA content of control cells; W-7 completely blocked the increase in the level of cytoskeletal calmodulin and in the DNA content in the cells that were subjected to a cyclic biaxial strain. The bone cells subjected to a hydrostatic pressure showed a dose-dependent increase in the concentration of cytosolic Ca2+, as measured with Fura 2-AM, a fluorescent indicator of intracellular calcium. With a pressure of ten pounds per square inch (sixty-nine kilopascals), the increase in the concentration of cytosolic Ca2+ was nearly eight times greater than that at 2.5 pounds per square inch (17.2 kilopascals) (126 +/- 15.2 compared with 16 +/- 8.0 nanomolar, mean and standard deviation). The addition to the medium of neomycin, an inhibitor of the inositol phosphate cascade, at a ten-millimolar concentration completely blocked the increase in the concentration of cytosolic Ca2+ in these cells; this concentration of neomycin had been shown to have no effect on proliferation in control bone cells. There was also a dose-dependent relationship between the duration of the stimulus and the cellular proliferation. Remarkably, one cycle of pressure at ten pounds per square inch (sixty-nine kilopascals) and a frequency of approximately one hertz produced a 57 per cent increase in the incorporation of [3H]-thymidine at twenty-four hours (p < 0.001). From these findings, we hypothesized that the inositol phosphate cascade-cytosolic Ca(2+)-cytoskeletal calmodulin system plays a dominant role in the signal transduction of a mechanical stimulus into increased proliferation of bone cells, at least under the conditions reported here.

Research perspectives in first metatarsal osteotomy and fixation stability.

Well-designated research is required to provide clinical guidance by validation of old and new methods. Variables, including technologic advancement in surgical techniques, diagnosis, shoe design, and immobilization all contribute to the challenge of investigating surgical procedures of the foot. This article highlights some of the relevant research pertaining to first metatarsal osteotomies and internal fixation and provides direction for potential, future research. Numerous aspects about the research techniques involved are discussed.