Retrorectus mesh reinforcement of ileostomy site fascial closure: stoma closure and reinforcement (SCAR) trial phase I/II results.

PURPOSE: Loop ileostomy (LI) is commonly employed during colorectal surgeries to reduce the consequences of anastomotic leak. Unfortunately, LI is associated with a 10-30% incisional hernia (IH) rate after closure. We hypothesized that prophylactic mesh reinforcement during LI takedown would safely prevent subsequent IH formation. METHODS: This single-center, phase I/II prospective study evaluated adult patients undergoing LI closure after left-sided colorectal cancer procedures. After LI closure, the posterior rectus sheath was mobilized and reapproximated with absorbable suture. A reduced-weight, macroporous, polypropylene mesh (Softmesh, BD) was placed in the retrorectus position to allow 3 cm of overlap and secured with fibrin sealant. The anterior fascia was closed with slowly absorbable suture. CT images obtained for cancer surveillance were reviewed by a radiologist blinded to the study intervention to evaluate for evidence of hernia or surgical site occurrence (SSO). RESULTS: Twenty patients were included with mean defect and mesh sizes of 11.2 cm2 and 64.2 cm2, respectively. Mean operative time for LI takedown and mesh augmented closure was 84 min with mesh implantation time being 16.4 min. Two patients were readmitted within 30 days for ileus, no patient required procedural intervention. Over a mean follow-up period of 20 ± 7 months, no SSO or hernias were observed clinically or on CT imaging. CONCLUSION: In our small series, retromuscular mesh reinforcement of LI closure appears feasible, safe and effective. This mesh reinforcement approach should be further investigated to evaluate its long-term effectiveness.

Tunable Photon Statistics Exploiting the Fano Effect in a Waveguide.

A strong optical nonlinearity arises when coherent light is scattered by a semiconductor quantum dot coupled to a nanophotonic waveguide. We exploit the Fano effect in such a waveguide to control the phase of the quantum interference underpinning the nonlinearity, experimentally demonstrating a tunable quantum optical filter which converts a coherent input state into either a bunched or an antibunched nonclassical output state. We show theoretically that the generation of nonclassical light is predicated on the formation of a two-photon bound state due to the interaction of the input coherent state with the quantum dot. Our model demonstrates that the tunable photon statistics arise from the dependence of the sign of two-photon interference (either constructive or destructive) on the detuning of the input relative to the Fano resonance.

Nonreciprocal Transmission and Reflection of a Chirally Coupled Quantum Dot.

We report strongly nonreciprocal behavior for quantum dot exciton spins coupled to nanophotonic waveguides under resonant laser excitation. A clear dependence of the transmission spectrum on the propagation direction is found for a chirally coupled quantum dot, with spin up and spin down exciton spins coupling to the left and right propagation directions, respectively. The reflection signal shows an opposite trend to the transmission, which a numerical model indicates is due to direction-selective saturation of the quantum dot. The chiral spin-photon interface we demonstrate breaks reciprocity of the system and opens the way to spin-based quantum optical components such as optical diodes and circulators in a chip-based solid-state environment.

Electro-mechanical control of an on-chip optical beam splitter containing an embedded quantum emitter.

We demonstrate electro-mechanical control of an on-chip GaAs optical beam splitter containing a quantum dot single-photon source. The beam splitter consists of two nanobeam waveguides, which form a directional coupler (DC). The splitting ratio of the DC is controlled by varying the out-of-plane separation of the two waveguides using electromechanical actuation. We reversibly tune the beam splitter between an initial state, with emission into both output arms, and a final state with photons emitted into a single output arm. The device represents a compact and scalable tuning approach for use in III-V semiconductor integrated quantum optical circuits.

Tuning Nonlinear Mechanical Mode Coupling in GaAs Nanowires Using Cross-Section Morphology Control.

We investigate the nonlinear mechanical properties of GaAs nanowires with anisotropic cross-section. Fundamental and second order flexural modes are studied using laser interferometry with good agreement found between experiment and theory describing the nonlinear response under mechanical excitation. In particular, we demonstrate that the sign of the nonlinear coupling between orthogonal modes is dependent on the cross-section aspect ratio. The findings are of interest for applications such as amplitude to frequency conversion and vectorial force sensing.

Homogeneous array of nanowire-embedded quantum light emitters.

The potential for scale-up coupled with minimized system size is likely to be a major determining factor in the realization of applicable quantum information systems. Nanofabrication technology utilizing the III-V semiconductor system provides a path to scalable quantum bit (qubit) integration and a materials platform with combined electronic/photonic functionality. Here, we address the key requirement of qubit-site and emission energy control for scale-up by demonstrating uniform arrays of III-V nanowires, where each nanowire contains a single quantum dot. Optical studies of single nanowire quantum dots reveal narrow linewidth exciton and biexciton emission and clear state-filling at higher powers. Individual nanowire quantum dots are shown to emit nonclassically with clear evidence of photon antibunching. A model is developed to explain unexpectedly large excited state separations as revealed by photoluminescence emission spectra. From measurements of more than 40 nanowire quantum dots, we find emission energies with an ensemble broadening of 15 meV. The combination of deterministic site control and the narrow distribution in ensemble emission energy results in a system readily capable of scaling for multiqubit quantum information applications.

Effect of a GaAsP shell on the optical properties of self-catalyzed GaAs nanowires grown on silicon.

We realize the growth of self-catalyzed core-shell GaAs/GaAsP nanowires (NWs) on Si substrates using molecular-beam epitaxy. Transmission electron microscopy of single GaAs/GaAsP NWs demonstrates their high crystal quality and shows domination of the GaAs zinc-blende phase. Using continuous-wave and time-resolved photoluminescence (PL), we make a detailed comparison with uncapped GaAs NWs to emphasize the effect of the GaAsP capping in suppressing the nonradiative surface states. Significant PL enhancement in the core-shell structures exceeding 3 orders of magnitude at 10 K is observed; in uncapped NWs PL is quenched at 60 K, whereas single core-shell GaAs/GaAsP structures exhibit bright emission even at room temperature. From analysis of the PL temperature dependence in both types of NW we are able to determine the main carrier escape mechanisms leading to the PL quench.

Long lifetimes of quantum-dot intersublevel transitions in the terahertz range.

Carrier relaxation is a key issue in determining the efficiency of semiconductor optoelectronic device operation. Devices incorporating semiconductor quantum dots have the potential to overcome many of the limitations of quantum-well-based devices because of the predicted long quantum-dot excited-state lifetimes. For example, the population inversion required for terahertz laser operation in quantum-well-based devices (quantum-cascade lasers) is fundamentally limited by efficient scattering between the laser levels, which form a continuum in the plane of the quantum well. In this context, semiconductor quantum dots are a highly attractive alternative for terahertz devices, because of their intrinsic discrete energy levels. Here, we present the first measurements, and theoretical description, of the intersublevel carrier relaxation in quantum dots for transition energies in the few terahertz range. Long intradot relaxation times (1.5 ns) are found for level separations of 14 meV (3.4 THz), decreasing very strongly to approximately 2 ps at 30 meV (7 THz), in very good agreement with our microscopic theory of the carrier relaxation process. Our studies pave the way for quantum-dot terahertz device development, providing the fundamental knowledge of carrier relaxation times required for optimum device design.

Measurement method for photoluminescent quantum yields of fluorescent organic dyes in polymethyl methacrylate for luminescent solar concentrators.

A method for measuring the photoluminescent quantum yields (PLQY) of luminescent organic dyes is presented. The self-absorption probability calculated at different dye concentrations is used to determine the absolute quantum yield from the observed values. The results for a range of commercially available dyes show high quantum yields, even at high concentrations, and an absence of quenching. The PLQY of several dye mixtures are also presented. The results indicate an absence of any reduction of PLQY in a dye mixture as compared with the individual PLQY of the dyes.

Demonstration of air-guided quantum cascade lasers without top claddings.

We report on quantum cascade lasers employing waveguides based on a predominant air confinement mechanism in which the active region is located immediately at the device top surface. The lasers employ ridge-waveguide resonators with narrow lateral electrical contacts only, with a large, central top region not covered by metallization layers. Devices based on this principle have been reported in the past; however, they employed a thick, doped top-cladding layer in order to allow for uniform current injection. We find that the in-plane conductivity of the active region - when the material used is of high quality - provides adequate electrical injection. As a consequence, the devices demonstrated in this work are thinner, and most importantly they can simultaneously support air-guided and surface-plasmon waveguide modes. When the lateral contacts are narrow, the optical mode is mostly located below the air-semiconductor interface. The mode is predominantly air-guided and it leaks from the top surface into the surrounding environment, suggesting that these lasers could be employed for surface-sensing applications. These laser modes are found to operate up to room temperature under pulsed injection, with an emission spectrum centered around l (1/4) 7:66 mum.

Effects of gasoline formulation on methyl tert-butyl ether (MTBE) contamination in private wells near gasoline stations.

UNLABELLED: The extent of methyl tert-butyl ether (MTBE) contamination in private wells near gasoline stations, which lack the relative protection afforded many public waters supplies through zoning and routine testing, was examined. Samples were collected from 74 private wells near 21 randomly selected gasoline stations and from 21 control wells, one per facility. Two hypotheses are tested: (1) private wells downgradient and close (<0.5 mi) to gasoline stations (case wells) are more likely to have MTBE contamination than private wells upgradient and distant (>1.5 mi) (control wells); and (2) private wells near gasoline stations selling oxygenated gasoline are more likely to have MTBE contamination than private wells near gasoline stations selling conventional gasoline. Data on the concurrence of MTBE and other gasoline constituents are presented. RESULTS: MTBE concentrations ranged from <1.0 micro/L (microg/L) to 61 microg/L, with a mean of 12.0 microg/L. MTBE contamination of > or =1 microg/L was detected more frequently in case wells (28%) than control wells (5%) (p = 0.015). MTBE contamination of > or =1 microg/L occurred more frequently in private wells near facilities selling oxygenated gasoline (38%) than private wells near facilities selling conventional gasoline (20%) (p = 0.11). Statistical significance may have been achieved with a larger sample size. Benzene (0.5 microg/L) was found concurrently with MTBE in only one well, which also had the highest concentration of MTBE.

Inactivation of O6-alkylguanine-DNA alkyltransferase by 8-substituted O6-benzylguanine analogs in mice.

PURPOSE: The purpose of this study was to determine the usefulness of various 8-substituted O6-benzylguanine (BG) analogs as modulators of the DNA repair protein. O6-alkylguanine-DNA alkyltransferase (AGT). More specifically, the degree of inactivation of AGT in mouse brain, liver, kidney and tumor by O6-benzyl-8-oxoguanine (8-oxoBG), 8-aza-O6-benzylguanine (8-azaBG), O6-benzyl-8-bromoguanine (8-bromoBG) and O6-benzyl-8-trifluoromethylguanine (8-tfmBG) was compared to inactivation by BG, a modulator in phase II clinical trials. BG is converted rapidly to 8-oxoBG in rodents, monkeys and humans. It was reasoned that 8-substituted analogs of BG would exhibit different pharmacological properties compared to BG which could influence tissue bioavailability and, thus, the extent of AGT inactivation in vivo. We compared the tissue distribution of these agents and AGT activity following administration of the 8-substituted analogs. MATERIALS AND METHODS: At various time points up to 24 h after i.p. administration of the BG analogs, tissues (i.e. brain, liver, kidney), A549 lung tumor xenografts (i.p.) or D456 brain tumor xenografts (i.c.) were harvested from athymic nude mice for AGT analysis. AGT activity was quantified in tissue extracts using a biochemical assay with [3H]methylated DNA as a substrate. In addition, concentrations of BG and 8-oxoBG were determined by HPLC with fluorescence detection in mouse tissues following administration of drug. RESULTS: Each of the 8-substituted analogs of BG demonstrated variable AGT inactivation capabilities that were comparable to or better than those of BG especially in kidney and brain tissues. There was a more pronounced depletion of AGT inactivation in brain and D456 brain tumor xenografts following administration of BG compared to 8-oxoBG that could be explained by a much greater concentration of AGT-inactivating drug (BG plus the metabolite 8-oxoBG for mice treated with BG versus 8-oxoBG for mice treated with 8-oxoBG) present in these tissues. The AUCs for brain, kidney and liver were 3.2, 6.9 and 1 1.8 times greater for BG than for 8-oxoBG. CONCLUSIONS: 8-substituted analogs of BG possess unique AGT-inactivation profiles in vivo that are different from that of BG. The AGT-inhibitory activities of BG and its major metabolite, 8-oxoBG, are related to tissue disposition of both drugs.

Effect of O6-benzylguanine on nitrogen mustard-induced toxicity, apoptosis, and mutagenicity in Chinese hamster ovary cells.

O6-Benzylguanine (BG) inactivates O6-alkylguanine-DNA alkyltransferase (AGT), resulting in an increase in the sensitivity of cells to the toxic effects of O6-alkylating agents. BG significantly enhances the cytotoxicity and decreases the mutagenicity of nitrogen mustards [i.e., phosphoramide mustard (PM), melphalan, and chlorambucil], a group of alkylating agents not known to produce O6-adducts in DNA. The enhancement is observed in cells irrespective of AGT activity. Exposure of Chinese hamster ovary cells to 100 microM BG results in enhancement in the cytotoxicity of PM (300 microM), chlorambucil (40 microM), and melphalan (10 microM) by 9-, 7-, and 18-fold, respectively. In contrast, mutation frequency after treatment with 300 microM PM is decreased from 259 mutants/10(6) cells to 22 mutants/10(6) cells when cells are pretreated with BG. The enhancement of toxicity of these bis-alkylating agents appears to involve cross-link formation, because neither cytotoxicity nor mutagenicity of a monoalkylating PM analogue is significantly altered when combined with BG. Enhanced cytotoxicity and decreased mutagenicity is concomitant with a dramatic increase in the number of cells undergoing apoptosis when BG is combined with PM, melphalan, or chlorambucil at 72-94 h after treatment. Cell cycle analysis demonstrates that BG alone or combined with nitrogen mustards arrests cells in G1 phase of the cell cycle. At 16 h after treatment, 11 and 57% of cells treated with PM alone or with BG plus PM are in G1 phase, respectively. Our data suggest that treatment with BG causes G1 arrest and drives noncycling cells treated with nitrogen mustards into apoptosis, thus protecting against mutagenic DNA damage introduced by nitrogen mustards.

Inverted electron-hole alignment in InAs-GaAs self-assembled quantum dots.

New information on the electron-hole wave functions in InAs-GaAs self-assembled quantum dots is deduced from Stark effect spectroscopy. Most unexpectedly it is shown that the hole is localized towards the top of the dot, above the electron, an alignment that is inverted relative to the predictions of all recent calculations. We are able to obtain new information on the structure and composition of buried quantum dots from modeling of the data. We also demonstrate that the excited state transitions arise from lateral quantization and that tuning through the inhomogeneous distribution of dot energies can be achieved by variation of electric field.

Phase I clinical and pharmacological study of O6-benzylguanine followed by carmustine in patients with advanced cancer.

O6-benzylguanine (BG) is a potent inactivator of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT) that enhances sensitivity to nitrosoureas in tumor cell lines and tumor-bearing animals. The major objectives of this study were to define the optimal modulatory dose and associated toxicities of benzylguanine administered alone and in combination with carmustine; to define the maximally tolerated dose and associated toxicities of carmustine administered with benzylguanine and to describe the pharmacokinetics of BG in humans and its effects on AGT depletion and recovery in peripheral blood mononuclear cells. Patients with histologically confirmed advanced solid tumors or lymphoma that had failed to respond to standard therapy or for which no standard therapy was available were eligible to participate in this study. Patients initially received BG as a 1-h i.v. infusion without carmustine. After a 14-day washout (ie., without therapy) period, patients received BG as a 1-h i.v. infusion followed, 1 h later, by a 15-min i.v. infusion of carmustine. Cycles of chemotherapy were repeated every 6 weeks. Cohorts of patients received BG doses ranging from 10 to 120 mg/m2 and carmustine doses ranging from 13 to 50 mg/m2. Plasma and urine samples were collected and analyzed for BG, and O6-benzyl-8-oxoguanine concentrations and AGT activity was determined in peripheral blood mononuclear cells. There was no toxicity attributable to BG alone at any dose tested. Bone marrow suppression was the primary and dose-limiting toxicity of BG combined with carmustine and was cumulative in some patients. The neutrophil nadir occurred at a median of day 27, with complete recovery in most patients by day 43. Nonhematological toxicity included fatigue, anorexia, increased bilirubin, and transaminase elevation. Recommended doses for Phase II testing are 120 mg/m2 BG given with carmustine at 40 mg/m2. BG rapidly disappeared from plasma and was converted to a major metabolite, O6-benzyl-8-oxoguanine, which has a 2.4-fold higher maximal concentration and 20-fold higher area under the concentration versus time curve than BG. AGT activity in peripheral blood mononuclear cells was rapidly and completely suppressed at all of the BG doses. The rate of AGT regeneration was more rapid for patients treated with the lowest dose of BG but was similar for BG doses ranging from 20-120 mg/m2. In conclusion, coadministration of BG and carmustine is feasible in cancer patients, but the maximal dose of carmustine that can be safely administered with BG is approximately one-third of the standard clinical dose. Bone marrow suppression, which may be cumulative, is the dose-limiting toxicity of the combination. Prolonged AGT suppression is likely attributable primarily to the effect of O6-benzyl-8-oxoguanine.

Muscle spindle activity in the affected upper limb after a unilateral stroke.

Weakness, loss of dexterity and exaggerated reflex responses to proprioceptive and cutaneous stimuli are typical features of hemiparetic stroke. Since the extent to which altered fusimotor drive contributes to these deficits has not been established, this study was designed to assess fusimotor function in stroke patients by comparing three aspects of muscle spindle afferent behaviour (background discharge rate, responses to reflex inputs and responses to voluntary contractions) in 11 subjects affected by recent cerebrovascular lesions, with those in 18 healthy volunteers. The mean background discharge rates of muscle spindle afferents in the radial nerve when subjects attempted to relax the recorded limb completely were 6.6 +/- 5.3 Hz (n = 26) in patients and 6.4 +/- 6.1 Hz (n = 76) in control subjects. The variability of discharge rate of active afferents was also similar (0.12 +/- 0.07 and 0.09 +/- 0. 10, respectively). Reflex activation of fusimotor neurons was assessed using trains of electrical stimuli to the superficial radial nerve or to the palm of the hand, and using natural skin stimuli. Neither type of cutaneous stimulation affected muscle spindle afferent discharge in the absence of an EMG response. During deliberate voluntary contractions muscle spindle discharge rates were enhanced similarly in both the control and patient groups, indicating that volitional drives could access fusimotor neurons in the patients. Qualitatively, spindle behaviour was similar in patients and control subjects. These findings suggest that fusimotor function is not disturbed any more or less than skeletomotor function in hemiparetic patients and it is concluded that fusimotor dysfunction probably contributes little to their deficit.

Evidence for fusimotor drive in stroke patients based on muscle spindle thixotropy.

To study fusimotor function in stroke patients, we compared the amplitude of stretch reflexes elicited in flexor carpi radialis (FCR) after contraction of FCR with the wrist held flexed ('hold-short') or extended ('hold-long'). Seven subjects with impaired hand function and spasticity due to stroke, and seven healthy subjects were investigated. Surface electrodes recorded electromyographic activity of wrist flexors and extensors while subjects performed isometric wrist flexions with the wrist alternately in 15 degrees of flexion or extension. After contractions the wrist was moved passively to the mid-position, and stretch reflexes were elicited via controlled mechanical taps delivered over the FCR tendon. For both groups, the amplitude of the stretch reflex was greater after 'hold-short' than 'hold-long' contractions. This finding is consistent with the 'after-effects' of intrafusal fibre activation, and suggests that fusimotor neurones are activated during voluntary contractions of the paretic limb, just as in the limb of a healthy subject.

Muscle sympathetic vasoconstrictor activity in hydrocortisone-induced hypertension in humans.

AIM: This study was undertaken to test the hypothesis that increased sympathetic vasomotor drive is responsible for cortisol-induced hypertension. METHODS: Ten healthy male subjects on a fixed sodium diet (150 mmol/day) were randomized to five days of treatment with cortisol (200 mg/day) or placebo in a double-blind crossover study. On day 5 of each treatment, multi-unit muscle sympathetic activity was recorded from the common peroneal nerve. Resting muscle sympathetic activity (MSA) was measured in the recumbent position and stimulated MSA was measured in the final 20 sec of end-inspiratory capacity apnoea and end-expiratory apnoea and in the second minute of a cold pressor stimulus. A subgroup of six subjects also underwent identical MSA measurements following 5 days treatment with dexamethasone (3 mg/day). MAJOR FINDINGS: Cortisol, but not placebo, significantly increased systolic (115+/-2 vs 129+/-3 mmHg precortisol vs cortisol day 5, p < 0.001) and diastolic blood pressure (53+/-3 vs 61+/-3, p < 0.05). Resting MSA was significantly reduced by cortisol (23.9+/-2.3 to 5.0+/-2.0 bursts/min, placebo vs cortisol, p < 0.01). Cortisol significantly attenuated the increase in MSA observed at end-inspiratory apnoea (56.3+/-3.9 vs 35.4+/-6.6, p < 0.05) and end-expiratory apnoea (50.5+/-3.5 vs 26.3+/-6.2 bursts/min, n = 8, p < 0.05), and during the cold pressor response (55.0+/-12.7 vs 21.4+/-7.6, n = 5, p < 0.05). Dexamethasone significantly increased systolic blood pressure and suppressed resting and stimulated MSA. No changes in body weight, haematocrit or angiotensin II concentrations occurred during dexamethasone treatment. CONCLUSION: MSA is significantly suppressed by cortisol treatment. As suppression of MSA is also observed during treatment with the pure glucocorticoid dexamethasone, suppressed MSA cannot be attributed to increased plasma volume or to changes in angiotensin II concentration. We conclude that cortisol-induced hypertension is not due to increased muscle sympathetic vasomotor drive.