7X multiplexed, optofluidic detection of nucleic acids for antibiotic-resistance bacterial screening.

Rapid and accurate diagnosis of bacterial infections resistant to multiple antibiotics requires development of new bio-sensors for differentiated detection of multiple targets. This work demonstrates 7x multiplexed detection for antibiotic-resistance bacterial screening on an optofluidic platform. We utilize spectrally multiplexed multi-spot excitation for simultaneous detection of nucleic acid strands corresponding to bacterial targets and resistance genes. This is enabled by multi-mode interference (MMI) waveguides integrated in an optofluidic device. We employ a combinatorial three-color labeling scheme for the nucleic acid assays to scale up their multiplexing capability to seven different nucleic acids, representing three species and four resistance genes.

Influence of perioperative anaesthetic and analgesic interventions on oncological outcomes: a narrative review.

Surgery is an important treatment modality for the majority of solid organ cancers. Unfortunately, cancer recurrence following surgery of curative intent is common, and typically results in refractory disease and patient death. Surgery and other perioperative interventions induce a biological state conducive to the survival and growth of residual cancer cells released from the primary tumour intraoperatively, which may influence the risk of a subsequent metastatic disease. Evidence is accumulating that anaesthetic and analgesic interventions could affect many of these pathophysiological processes, influencing risk of cancer recurrence in either a beneficial or detrimental way. Much of this evidence is from experimental in vitro and in vivo models, with clinical evidence largely limited to retrospective observational studies or post hoc analysis of RCTs originally designed to evaluate non-cancer outcomes. This narrative review summarises the current state of evidence regarding the potential effect of perioperative anaesthetic and analgesic interventions on cancer biology and clinical outcomes. Proving a causal link will require data from prospective RCTs with oncological outcomes as primary endpoints, a number of which will report in the coming years. Until then, there is insufficient evidence to recommend any particular anaesthetic or analgesic technique for patients undergoing tumour resection surgery on the basis that it might alter the risk of recurrence or metastasis.

Blue-Detuned Magneto-Optical Trap.

We present the properties and advantages of a new magneto-optical trap (MOT) where blue-detuned light drives "type-II" transitions that have dark ground states. Using ^{87}Rb, we reach a radiation-pressure-limited density exceeding 10^{11} cm^{-3} and a temperature below 30 µK. The phase-space density is higher than in normal atomic MOTs and a million times higher than comparable red-detuned type-II MOTs, making the blue-detuned MOT particularly attractive for molecular MOTs, which rely on type-II transitions. The loss of atoms from the trap is dominated by ultracold collisions between Rb atoms. For typical trapping conditions, we measure a loss rate of 1.8(4)×10^{-10} cm^{3} s^{-1}.

Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation.

Astrocytes possess many of the same signalling molecules as neurons. However, the role of astrocytes in information processing, if any, is unknown. Using electrophysiological and imaging methods, we report the first evidence that astrocytes modulate neuronal sensory inhibition in the rodent thalamus. We found that mGlu2 receptor activity reduces inhibitory transmission from the thalamic reticular nucleus to the somatosensory ventrobasal thalamus (VB): mIPSC frequencies in VB slices were reduced by the Group II mGlu receptor agonist LY354740, an effect potentiated by mGlu2 positive allosteric modulator (PAM) LY487379 co-application (30 nM LY354740: 10.0 ± 1.6% reduction; 30 nM LY354740 & 30 µM LY487379: 34.6 ± 5.2% reduction). We then showed activation of mGlu2 receptors on astrocytes: astrocytic intracellular calcium levels were elevated by the Group II agonist, which were further potentiated upon mGlu2 PAM co-application (300 nM LY354740: ratio amplitude 0.016 ± 0.002; 300 nM LY354740 & 30 µM LY487379: ratio amplitude 0.035 ± 0.003). We then demonstrated mGlu2-dependent astrocytic disinhibition of VB neurons in vivo: VB neuronal responses to vibrissae stimulation trains were disinhibited by the Group II agonist and the mGlu2 PAM (LY354740: 156 ± 12% of control; LY487379: 144 ± 10% of control). Presence of the glial inhibitor fluorocitrate abolished the mGlu2 PAM effect (91 ± 5% of control), suggesting the mGlu2 component to the Group II effect can be attributed to activation of mGlu2 receptors localised on astrocytic processes within the VB. Gating of thalamocortical function via astrocyte activation represents a novel sensory processing mechanism. As this thalamocortical circuitry is important in discriminative processes, this demonstrates the importance of astrocytes in synaptic processes underlying attention and cognition.

Multiplexed efficient on-chip sample preparation and sensitive amplification-free detection of Ebola virus.

An automated microfluidic sample preparation multiplexer (SPM) has been developed and evaluated for Ebola virus detection. Metered air bubbles controlled by microvalves are used to improve bead-solution mixing thereby enhancing the hybridization of the target Ebola virus RNA with capture probes bound to the beads. The method uses thermally stable 4-formyl benzamide functionalized (4FB) magnetic beads rather than streptavidin coated beads with a high density of capture probes to improve the target capture efficiency. Exploiting an on-chip concentration protocol in the SPM and the single molecule detection capability of the antiresonant reflecting optical waveguide (ARROW) biosensor chip, a detection limit of 0.021pfu/mL for clinical samples is achieved without target amplification. This RNA target capture efficiency is two orders of magnitude higher than previous results using streptavidin beads and the limit of detection (LOD) improves 10×. The wide dynamic range of this technique covers the whole clinically applicable concentration range. In addition, the current sample preparation time is ~1h which is eight times faster than previous work. This multiplexed, miniaturized sample preparation microdevice establishes a key technology that intended to develop next generation point-of-care (POC) detection system.

Enhancement of ARROW Photonic Device Performance via Thermal Annealing of PECVD-based SiO2 Waveguides.

Silicon-based optofluidic devices are very attractive for applications in biophotonics and chemical sensing. Understanding and controlling the properties of their dielectric waveguides is critical for the performance of these chips. We report that thermal annealing of PECVD-grown silicon dioxide (SiO2) ridge waveguides results in considerable improvements to optical transmission and particle detection. There are two fundamental changes that yield higher optical transmission: (1) propagation loss in solid-core waveguides is reduced by over 70%, and (2) coupling efficiencies between solid- and liquid-core waveguides are optimized. The combined effects result in improved optical chip transmission by a factor of 100-1000 times. These improvements are shown to arise from the elimination of a high-index layer at the surface of the SiO2 caused by water absorption into the porous oxide. The effects of this layer on optical transmission and mode confinement are shown to be reversible by alternating subjection of waveguides to water and subsequent low temperature annealing. Finally, we show that annealing improves detection of fluorescent analytes in optofluidic chips with a signal-to-noise ratio improvement of 166x and a particle detection efficiency improvement of 94%.

A trap-based pulsed positron beam optimised for positronium laser spectroscopy.

We describe a pulsed positron beam that is optimised for positronium (Ps) laser-spectroscopy experiments. The system is based on a two-stage Surko-type buffer gas trap that produces 4 ns wide pulses containing up to 5 × 10(5) positrons at a rate of 0.5-10 Hz. By implanting positrons from the trap into a suitable target material, a dilute positronium gas with an initial density of the order of 10(7) cm(-3) is created in vacuum. This is then probed with pulsed (ns) laser systems, where various Ps-laser interactions have been observed via changes in Ps annihilation rates using a fast gamma ray detector. We demonstrate the capabilities of the apparatus and detection methodology via the observation of Rydberg positronium atoms with principal quantum numbers ranging from 11 to 22 and the Stark broadening of the n = 2 → 11 transition in electric fields.

Optofluidic analysis system for amplification-free, direct detection of Ebola infection.

The massive outbreak of highly lethal Ebola hemorrhagic fever in West Africa illustrates the urgent need for diagnostic instruments that can identify and quantify infections rapidly, accurately, and with low complexity. Here, we report on-chip sample preparation, amplification-free detection and quantification of Ebola virus on clinical samples using hybrid optofluidic integration. Sample preparation and target preconcentration are implemented on a PDMS-based microfluidic chip (automaton), followed by single nucleic acid fluorescence detection in liquid-core optical waveguides on a silicon chip in under ten minutes. We demonstrate excellent specificity, a limit of detection of 0.2 pfu/mL and a dynamic range of thirteen orders of magnitude, far outperforming other amplification-free methods. This chip-scale approach and reduced complexity compared to gold standard RT-PCR methods is ideal for portable instruments that can provide immediate diagnosis and continued monitoring of infectious diseases at the point-of-care.

Selective production of Rydberg-stark states of positronium.

Rydberg positronium (Ps) atoms have been prepared in selected Stark states via two-step (1s→2p→nd/ns) optical excitation. Two methods have been used to achieve Stark-state selection: a field ionization filter that transmits the outermost states with positive Stark shifts, and state-selected photoexcitation in a strong electric field. The former is demonstrated for n=17 and 18 while the latter is performed for n=11 in a homogeneous electric field of 1.9 kV/cm. The observed spectral intensities and their dependence on the polarization of the laser radiation are in agreement with calculations that include the perturbations of the intermediate n=2 manifold. Our results pave the way for the generation of Rydberg Ps atoms with large electric dipole moments that are required for the realization of schemes to control their motion using inhomogeneous electric fields, an essential feature of some proposed Ps free-fall measurements requiring focused beams of long-lived atoms.

Wideband arrhythmia-Insensitive-rapid (AIR) pulse sequence for cardiac T1 mapping without image artifacts induced by an implantable-cardioverter-defibrillator.

PURPOSE: To develop and evaluate a wideband arrhythmia-insensitive-rapid (AIR) pulse sequence for cardiac T1 mapping without image artifacts induced by implantable-cardioverter-defibrillator (ICD). METHODS: We developed a wideband AIR pulse sequence by incorporating a saturation pulse with wide frequency bandwidth (8.9 kHz) to achieve uniform T1 weighting in the heart with ICD. We tested the performance of original and "wideband" AIR cardiac T1 mapping pulse sequences in phantom and human experiments at 1.5 Tesla. RESULTS: In five phantoms representing native myocardium and blood and postcontrast blood/tissue T1 values, compared with the control T1 values measured with an inversion-recovery pulse sequence without ICD, T1 values measured with original AIR with ICD were considerably lower (absolute percent error > 29%), whereas T1 values measured with wideband AIR with ICD were similar (absolute percent error < 5%). Similarly, in 11 human subjects, compared with the control T1 values measured with original AIR without ICD, T1 measured with original AIR with ICD was significantly lower (absolute percent error > 10.1%), whereas T1 measured with wideband AIR with ICD was similar (absolute percent error < 2.0%). CONCLUSION: This study demonstrates the feasibility of a wideband pulse sequence for cardiac T1 mapping without significant image artifacts induced by ICD.

"Vasovagal" response during ventricular fibrillation: incidence and implications.

BACKGROUND: The purpose of this study was to assess the relationship between changes in sinus node cycle length (SNCL) during ventricular fibrillation (VF) and the peripheral changes in blood pressure (BP) and sympathetic nerve activity (SNA) in human subjects. We hypothesized that patients with no SNCL shortening during VF have a vasovagal-like response with a greater decrease in BP and SNA when compared to patients with SNCL shortening. METHODS: SNCL, BP, and SNA recordings were attempted in 24 patients undergoing the implantation of a dual-chamber implantable defibrillator. Changes were measured during the first 5 seconds of VF and compared with the 5 seconds prior to VF induction. RESULTS: SNCL shortened during VF in nine patients (mean%∆SNCL = -12 ± 8%) and remained unchanged or lengthened in seven patients (mean%∆SNCL = 7 ± 7%). Eight patients had ventriculoatrial (VA) conduction prohibiting assessment of SNCL changes. In patients with SNCL shortening, the %∆MBP (mean BP) was -47 ± 6% compared to -58 ± 8% in patients with no SNCL shortening (P < 0.01). In patients with VA conduction, the %∆MBP was -54 ± 3%. SNA recordings were successfully obtained in four patients. When compared to baseline, SNA increased by 34 ± 30% in two patients with SNCL shortening, decreased by 25% in one patient with SNCL lengthening, and by 90% in the fourth patient with VA conduction. CONCLUSIONS: We have shown that patients with no SNCL shortening have a significantly greater decrease in MBP during VF when compared to patients with SNCL shortening. The underlying mechanism appears to be reflex mediated with a vasovagal-like response in patients with no SNCL shortening.

The role of L-arginine in the prevention and treatment of pre-eclampsia: a systematic review of randomised trials.

Pre-eclampsia is a significant health issue in pregnancy, complicating between 2-8% of pregnancies. L-arginine is an important mediator of vasodilation with a potential preventative role in pregnancy related hypertensive diseases. We aimed to systematically review randomised trials in the literature assessing the role of L-arginine in prevention and treatment of pre-eclampsia. We searched the Cochrane Controlled Trials Register, PUBMED, and the Australian and International Clinical Trials Registry, to identify randomised trials involving pregnant women where L-arginine was administered for pre-eclampsia to improve maternal and infant health outcomes. We identified eight randomised trials, seven of which were included. The methodological quality was fair, with a combined sample size of 884 women. For women at risk of pre-eclampsia, L-arginine was associated with a reduction in pre-eclampsia (RR: 0.34, 95% CI: 0.21-0.55), when compared with placebo and a reduction in risk of preterm birth (RR: 0.48 and 95% CI: 0.28 to 0.81). For women with established hypertensive disease, L-arginine was associated with a reduction in pre-eclampsia (RR: 0.21; 95% CI: 0.05-0.98). L-arginine may have a role in the prevention and/or treatment of pre-eclampsia. Further well-designed and adequately powered trials are warranted, both in women at risk of pre-eclampsia and in women with established disease.

Effect of maternal weight on postterm delivery.

OBJECTIVE: Examine the effect of prepregnancy weight and maternal gestational weight gain on postterm delivery rates. STUDY DESIGN: This was a retrospective cohort study of term, singleton births (N=375 003). We performed multivariable analyses of the association between postterm pregnancy and both prepregnancy body mass index (BMI) and maternal weight gain. RESULT: Prolonged or postterm delivery (41 or 42 weeks) was increasingly common with increasing prepregnancy weight (P<0.001) and increasing maternal weight gain (P<0.001). Underweight women were 10% less likely to deliver postterm than normal weight women who gain within the recommendations (adjusted odds ratio 0.90 (95% confidence interval 0.83, 0.97)). Overweight women who gain within or above recommendations were also at increased risk of a 41-week delivery. Finally, obese women were at increased risk of a 41-week delivery with increasing risk with increasing weight (below, within and above recommendations adjusted odds ratios 1.19, 1.21, and 1.27, respectively). CONCLUSION: Elevated prepregnancy weight and maternal weight gain both increase the risk of a postterm delivery. Although most women do not receive preconceptional care, restricting weight gain to the within the recommended range can reduce the risk of postterm pregnancy in normal, overweight and obese women.

Stark deceleration of CaF molecules in strong- and weak-field seeking states.

We report the Stark deceleration of CaF molecules in the strong-field seeking ground state and in a weak-field seeking component of a rotationally-excited state. We use two types of decelerator, a conventional Stark decelerator for the weak-field seekers and an alternating gradient decelerator for the strong-field seekers, and we compare their relative merits. We also consider the application of laser cooling to increase the phase-space density of decelerated molecules.

Implantation of cardiac rhythm devices during concomitant anticoagulation or antiplatelet therapy.

Cardiac rhythm devices are increasingly being utilized as the population ages and the incidence of chronic heart failure, bradyarrhythmias and the indications for pacing and prevention of sudden cardiac arrest expand. The number of patients receiving oral anticoagulants and dual antiplatelet therapy is similarly increasing. Implantation of cardiac rhythm devices during concomitant use of oral anticoagulants or antiplatelet regimens poses an increased risk of perioperative bleeding complications. Traditionally, heparin-based bridging protocols have been recommended for such patients to mitigate the bleeding risk while reducing the risk of thrombotic complications. Although the literature is limited, an appraisal of the literature reveals that bridging may not be the best strategy. We review the literature and propose strategies to promote successful perioperative outcomes, while reducing the risk of bleeding or thrombosis during the time of implantation for patients on chronic anticoagulation and antiplatelet therapies.

Cardiac resynchronization therapy device implantation in patients with therapeutic international normalized ratios.

BACKGROUND: Many patients who need cardiac resynchronization therapy (CRT) require chronic anticoagulation. Current guidelines recommend discontinuation of warfarin and the initiation of anticoagulant "bridging" therapy during these procedures. We evaluated the safety of CRT-device (CRT-D) implantation without interruption of warfarin therapy. METHODS: A total of 123 consecutive patients requiring CRT-D therapy were enrolled, 49 identified as high risk for thromboembolic events who received either intravenous heparin, low molecular weight heparin, or warfarin therapy. The control group comprised 74 patients with low risk of thromboembolic events who required only cessation of warfarin perioperatively. Patients were evaluated at discharge and 15 and 30 days postoperatively for pocket hematomas, thromboembolic events, and bleeding. Patients' length of stay was also catalogued. RESULTS: Patients in the bridging arm had a significant increase in the rate of pocket hematomas (4.1%[control] vs 5.0%[warfarin] vs 20.7%[bridging], P = 0.03) and subsequent longer length of stay (1.6 +/- 1.6 [control] vs 2.9 +/- 2.7 [warfarin] vs 3.7 +/- 3.2 [bridging], P < 0.001). Hematoma formation postoperatively was not different among patients undergoing an upgrade procedure versus those without preexisting cardiac rhythm devices (12% vs 6.2%, P = NS). Patients with a prosthetic mechanical mitral valve had a higher incidence of pocket hematoma formation (1.8% vs 20%, P = 0.03). CONCLUSIONS: Our findings suggest that implantation of CRT-Ds without interruption of warfarin therapy in patients at high risk of thromboembolic events is a safe alternative to routine bridging therapy. This strategy is associated with reduced risk of pocket hematomas and shorter length of hospital stay. (PACE 2010; 400-406).

Mechlorethamine, procarbazine and prednisone for the treatment of resistant lymphoma in dogs.

Forty-one dogs with resistant lymphoma were treated with a modified MOPP (mechlorethamine, vincristine, procarbazine and prednisone) protocol (MPP [mechlorethamine, procarbazine and prednisone] administered on a 21-day cycle, shortened from the 28-day MOPP cycle). The overall response rate to MPP was 34% for a median of 56 days (95% confidence interval 30-238). Seventeen percent of dogs had a complete response for a median duration of 238 days, 17% had a partial response for a median of 56 days and 32% had stable disease for a median of 24 days. Histological grade or cell morphology on cytology was associated with response. Minimal toxicity was observed with the MPP protocol, suggesting that further dose intensification or addition of another chemotherapeutic agent would be possible.

Scatter in repolarization timing predicts clinical events in post-myocardial infarction patients.

BACKGROUND: Increased spatial and temporal dispersion of repolarization contributes to ventricular arrhythmogenesis. Beat-to-beat fluctuations in T-wave timing are thought to represent such dispersion and may predict clinical events. OBJECTIVE: The purpose of this study was to assess whether a novel noninvasive measure of beat-to-beat instability in T-wave timing would provide additive prognostic information in post-myocardial infarction patients. METHODS: We studied 678 patients from 12 hospitals with 32-lead 5-minute electrocardiogram recordings 6-8 weeks after myocardial infarction. Custom software identified R wave-to-T wave intervals (RTIs) and diastolic intervals (DIs). Repolarization scatter (RTI:DI(StdErr)) was then calculated as the standard error about the RTI:DI regression line. In addition, left ventricular ejection fraction (LVEF), short-term heart rate variability (HRV) parameters, and QT variability index were measured. Patients were followed for the composite endpoint of death or life-threatening ventricular arrhythmia. RESULTS: After a mean follow-up of 63 months, 134 patients met the composite endpoint. An RTI:DI(StdErr) >5.50 ms was associated with a 210% increase in arrhythmias or deaths (P <.001). After adjusting for LVEF, RTI:DI(StdErr) remained an independent predictor (P <.001). RTI:DI(StdErr) was also independent of short-term HRV parameters and the QT variability index. CONCLUSIONS: Increased repolarization scatter, a measure of high-frequency, cycle-length-dependent repolarization instability, predicts poor outcomes in patients after myocardial infarction.