Detection of dimethyl methylphosphonate (DMMP) with an interband cascade laser sensor.

We demonstrate the sensitive detection of dimethyl methylphosphonate (DMMP, a hydrogen-bond (HB) basic phosphonate ester) using additional optical loss induced in an interband cascade laser with top optical cladding layer replaced by an exposed sensing window coated by a HB acidic sorbent layer. Thin coatings of the sorbents HCSFA2 and oapBPAF were deposited on the sensing window to allow reversible capture and concentration of DMMP for optical interrogation. Analyte levels down to 0.1 mg/m3 (∼20 ppb) were tested and successfully detected by monitoring the laser's threshold or its output power at a fixed bias as a function of DMMP delivery concentration.

Effect of pneumatic leg compression on post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy: a double-blind randomised controlled trial.

Post-induction hypotension is common and associated with postoperative complications. We hypothesised that pneumatic leg compression reduces post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy. In this double-blind randomised study, patients were allocated randomly to the pneumatic leg compression group (n = 50) or control (n = 50). In the intervention group, pneumatic leg compression was initiated before induction of anaesthesia. In the control group, pneumatic leg compression was initiated 20 min after anaesthesia induction. The primary outcome was the incidence of post-induction hypotension in these groups. Post-induction hypotension was defined as systolic blood pressure < 90 mmHg during the first 20 min after induction. Haemodynamic variables and area under the curve of post-induction systolic blood pressure over time were assessed. Complications associated with pneumatic leg compression were recorded, including: peripheral neuropathy; compartment syndrome; extensive bullae beneath the leg sleeves; and pulmonary thromboembolism. The incidence of post-induction hypotension decreased in the pneumatic leg compression group compared with that in the control group; 5 (10%) vs. 29 (58%), respectively, p < 0.001. In the pneumatic leg compression group, the lowest systolic, diastolic and mean blood pressures 20 min after induction of anaesthesia were significantly greater than the control group. Pneumatic leg compression resulted in an increased area under the curve of systolic blood pressure in the first 20 min after induction, p = 0.001. There were no pneumatic leg compression-related complications. Pneumatic leg compression reduced post-induction hypotension in elderly patients undergoing robot-assisted laparoscopic prostatectomy, suggesting that it is an effective and safe intervention to prevent post-induction hypotension among elderly patients undergoing general anaesthesia.

Suppression-Replacement KCNQ1 Gene Therapy for Type 1 Long QT Syndrome.

BACKGROUND: Type 1 long QT syndrome (LQT1) is caused by loss-of-function variants in the KCNQ1-encoded Kv7.1 potassium channel α-subunit that is essential for cardiac repolarization, providing the slow delayed rectifier current. No current therapies target the molecular cause of LQT1. METHODS: A dual-component suppression-and-replacement (SupRep) KCNQ1 gene therapy was created by cloning a KCNQ1 short hairpin RNA and a short hairpin RNA-immune KCNQ1 cDNA modified with synonymous variants in the short hairpin RNA target site, into a single construct. The ability of KCNQ1-SupRep gene therapy to suppress and replace LQT1-causative variants in KCNQ1 was evaluated by means of heterologous expression in TSA201 cells. For a human in vitro cardiac model, induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were generated from 4 patients with LQT1 (KCNQ1-Y171X, -V254M, -I567S, and -A344A/spl) and an unrelated healthy control. CRISPR-Cas9 corrected isogenic control iPSC-CMs were made for 2 LQT1 lines (correction of KCNQ1-V254M and KCNQ1-A344A/spl). FluoVolt voltage dye was used to measure the cardiac action potential duration (APD) in iPSC-CMs treated with KCNQ1-SupRep. RESULTS: In TSA201 cells, KCNQ1-SupRep achieved mutation-independent suppression of wild-type KCNQ1 and 3 LQT1-causative variants (KCNQ1-Y171X, -V254M, and -I567S) with simultaneous replacement of short hairpin RNA-immune KCNQ1 as measured by allele-specific quantitative reverse transcription polymerase chain reaction and Western blot. Using FluoVolt voltage dye to measure the cardiac APD in the 4 LQT1 patient-derived iPSC-CMs, treatment with KCNQ1-SupRep resulted in shortening of the pathologically prolonged APD at both 90% and 50% repolarization, resulting in APD values similar to those of the 2 isogenic controls. CONCLUSIONS: This study provides the first proof-of-principle gene therapy for complete correction of long QT syndrome. As a dual-component gene therapy vector, KCNQ1-SupRep successfully suppressed and replaced KCNQ1 to normal wild-type levels. In TSA201 cells, cotransfection of LQT1-causative variants and KCNQ1-SupRep caused mutation-independent suppression and replacement of KCNQ1. In LQT1 iPSC-CMs, KCNQ1-SupRep gene therapy shortened the APD, thereby eliminating the pathognomonic feature of LQT1.

Perisomatic changes in h-channels regulate depressive behaviors following chronic unpredictable stress.

Chronic stress can be a precipitating factor in the onset of depression. Lentiviral-mediated knockdown of HCN1 protein expression and reduction of functional Ih produce antidepressant behavior. However, whether h-channels are altered in an animal model of depression is not known. We found that perisomatic HCN1 protein expression and Ih-sensitive physiological measurements were significantly increased in dorsal but not in ventral CA1 region/neurons following chronic unpredictable stress (CUS), a widely accepted model for major depressive disorder. Cell-attached patch clamp recordings confirmed that perisomatic Ih was increased in dorsal CA1 neurons following CUS. Furthermore, when dorsal CA1 Ih was reduced by shRNA-HCN1, the CUS-induced behavioral deficits were prevented. Finally, rats infused in the dorsal CA1 region with thapsigargin, an irreversible inhibitor of the SERCA pump, exhibited anxiogenic-like behaviors and increased Ih, similar to that observed following CUS. Our results suggest that CUS, but not acute stress, leads to an increase in perisomatic Ih in dorsal CA1 neurons and that HCN channels represent a potential target for the treatment of major depressive disorder.

Systemic lupus erythematosus is a risk factor for cancer: a nationwide population-based study in Korea.

OBJECTIVE: Specific differences in cancer risk have been observed between systemic lupus erythematosus patients and the general population. Although meta-analyses have estimated cancer incidence in systemic lupus erythematosus patients, results have been inconclusive. Hence, we aimed to assess malignancy risk in systemic lupus erythematosus patients, compared to the risk in the general population. METHODS: Systemic lupus erythematosus patients ( n = 21,016; mean age 41.67 ± 13.14 years; female 90.22%) were selected from the Korean National Health Insurance Service database between 2008 and 2014. Age- and sex-matched controls were randomly sampled in a 5:1 ratio ( n = 105,080). RESULTS: During the 7 years of follow up, malignancy was detected in 763 (3.63%) systemic lupus erythematosus patients and 2667 (2.54%) controls. Systemic lupus erythematosus patients had a higher risk of malignancy than controls (odds ratio 1.44; 95% confidence interval 1.327-1.559), after multivariate adjustment. Systemic lupus erythematosus patients had a higher odds ratio for developing cervical, thyroid, ovarian, and oral cancer, as well as lymphoma, leukemia, and multiple myeloma than controls. Based on subgroup analysis, male systemic lupus erythematosus patients and patients younger than 40 years showed the highest lymphoma risk. CONCLUSIONS: Systemic lupus erythematosus might be an independent risk factor for cancer. Therefore, the importance of cancer screening programs should be emphasized in systemic lupus erythematosus patients. Our study is the first large nationwide cohort study for evaluating the risk of cancer in systemic lupus erythematosus patients.

Two-dimensional plasmonic grating for increased quantum efficiency in midwave infrared nBn detectors with thin absorbers.

We demonstrate a strategy for increasing the operating temperatures of nBn midwave infrared (MWIR) focal plane arrays, based on the use of two-dimensional plasmonic gratings to enhance the quantum efficiency (QE) of structures with very thin absorbers. Reducing the absorber volume correspondingly reduces the dark current in a diffusion-limited photodiode, while light trapping mediated by the plasmonic grating increases the net absorbance to maintain high QE. The plasmonically enhanced nBn MWIR sensors with absorber thicknesses of only 0.5 µm exhibit peak internal QEs as high as 57%, which enables a 5-fold reduction in dark current. Numerical simulations indicate the potential for further improvement.

Spin-Mechanical Coupling of an InAs Quantum Dot Embedded in a Mechanical Resonator.

We demonstrate strain-induced coupling between a hole spin in a quantum dot and mechanical motion of a cantilever. The optical transitions of quantum dots integrated into GaAs mechanical resonators are measured synchronously with the motion of the driven resonators. In a Voigt magnetic field, both electron and hole spin splittings are measured, showing negligible change for the electron spin but a large change for the hole spin of up to 36%. This large effect is attributed to the stronger spin orbit interaction of holes compared to electrons.

Systemic lupus erythematosus is a risk factor for cardiovascular disease: a nationwide, population-based study in Korea.

OBJECTIVE: To investigate the incidence and clinical significance of cardiovascular disease in systemic lupus erythematosus patients. METHODS: We included systemic lupus erythematosus patients ( n = 18,575) without previous cardiovascular disease and age- and sex-matched individuals without systemic lupus erythematosus (controls; n = 92,875) from the Korean National Health Insurance Service database (2008-2014). Both cohorts were followed up for incident cardiovascular disease and death until 2015. RESULTS: During follow up, myocardial infarction occurred in 203 systemic lupus erythematosus patients and 325 controls (incidence rate: 1.76 and 0.56 per 1000 person-years, respectively), stroke occurred in 289 patients and 403 controls (incidence rate: 2.51 and 0.70 per 1000 person-years, respectively), heart failure occurred in 358 patients and 354 controls (incidence rate 3.11 and 0.61 per 1000 person-years, respectively), and death occurred in 744 patients and 948 controls (incidence rate 6.54 and 1.64 per 1000 person-years, respectively). Patients with systemic lupus erythematosus had higher risks for myocardial infarction (hazard ratio: 2.74, 95% confidence interval: 2.28-3.37), stroke (hazard ratio: 3.31, 95% confidence interval: 2.84-3.86), heart failure (hazard ratio: 4.60, 95% confidence interval: 3.96-5.35), and cardiac death (hazard ratio: 3.98, 95% confidence interval: 3.61-4.39). CONCLUSIONS: Here, systemic lupus erythematosus was an independent risk factor for cardiovascular disease, thus cardiac assessment and management are critical in systemic lupus erythematosus patients.

Gemigliptin, a novel dipeptidyl peptidase-IV inhibitor, exerts a synergistic cytotoxicity with the histone deacetylase inhibitor PXD101 in thyroid carcinoma cells.

PURPOSE: The influence of the dipeptidyl peptidase-IV inhibitor gemigliptin alone or in combination with the histone deacetylase inhibitor PXD101 on survival of thyroid carcinoma cells was investigated. METHODS: SW1736, TPC-1, 8505C and BCPAP human thyroid carcinoma cells were used. To assess cell survival, cell viability, the percentage of viable cells and dead cells, cytotoxic activity, ATP levels and FACS analysis were measured. To validate the impact of gemigliptin combined with PXD101, the interactions were estimated by obtaining combination index in cells treated with two agents. RESULTS: In cells treated with gemigliptin or PXD101, cell viability, the percentage of viable cells and ATP levels were reduced, and the percentage of dead cells and cytotoxic activity were elevated. In cells treated with both gemigliptin and PXD101, compared with PXD101 alone, cell death was augmented, and all of the combination index values were lower than 1.0, suggesting the synergism between gemigliptin and PXD101. The percentage of apoptotic cells, and the protein levels of Bcl2 and cleaved poly (ADP-ribose) polymerase were elevated, and the protein levels of xIAP and survivin were reduced. The protein levels of phospho-Akt and phospho-AMPK were elevated, and cell migration was reduced. CONCLUSIONS: Our results demonstrate that gemigliptin induces cytotoxicity in thyroid carcinoma cells. Moreover, gemigliptin has a synergistic activity with PXD101 in the induction of cell death through involvement of Bcl2 family proteins, xIAP and survivin as well as mediation of Akt and AMPK in thyroid carcinoma cells.

Predictor of fluid responsiveness in the 'grey zone': augmented pulse pressure variation through a temporary increase in tidal volume.

BACKGROUND: Pulse pressure variation (PPV) is widely used as a predictor of fluid responsiveness. However, a previous study has suggested a 'grey zone' between 9 and 13% in which PPV would be inconclusive to predict fluid responsiveness. Considering PPV is based on cardiopulmonary interactions, we evaluated whether an augmented PPV using a temporary increase in tidal volume (V T ) from 8 to 12 ml kg -1 has the predictability for fluid responsiveness in patients within the grey zone. METHODS: Adult patients requiring general anaesthesia were enrolled. During the period when PPV was within the range of 9-13%, haemodynamic variables such as stroke volume index (SVI) and PPV with an 8 ml kg -1 tidal volume ventilation (PPV8) were obtained before and after volume expansion (6 ml kg -1 ) under mechanical ventilation. Augmented PPV induced by 2-min ventilation with a V T of 12 ml kg -1 (PPV12) was also recorded immediately before volume loading. The patients whose SVI increased ≥10% after volume expansion were considered responders. RESULTS: In 38 enrolled patients, 20 were responders. Receiver operating characteristic curve analysis showed PPV12 had an excellent predictability for fluid responsiveness {area under the curve [AUC]=0.935 [95% confidence interval (CI) 0.805-0.989]; sensitivity 95%; specificity 72%; P <0.0001}. The optimal threshold for PPV12 was >17%. However, PPV8 failed to show significant predictability [AUC=0.668 (95% CI 0.497-0.812); sensitivity 65%; specificity 61%; P =0.06]. CONCLUSION: In mechanically ventilated patients, our augmented PPV successfully predicted fluid responsiveness in the previously suggested grey zone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02653469.

Modeling impacts of climate change on the potential distribution of the carcinogenic liver fluke, Opisthorchis viverrini, in Thailand.

Global climate change is now regarded as imposing a significant threat of enhancing transmission of parasitic diseases. Maximum entropy species distribution modeling (MaxEnt) was used to explore how projected climate change could affect the potential distribution of the carcinogenic liver fluke, Opisthorchis viverrini, in Thailand. A range of climate variables was used: the Hadley Global Environment Model 2-Earth System (HadGEM2-ES) climate change model and also the IPCC scenarios A2a for 2050 and 2070. Occurrence data from surveys conducted in 2009 and 2014 were obtained from the Department of Disease Control, Ministry of Public Health, Thailand. The MaxEnt model performed better than random for O. viverrini with training AUC values greater than 0.8 under current and future climatic conditions. The current distribution of O. viverrini is significantly affected by precipitation and minimum temperature. According to current conditions, parts of Thailand climatically suitable for O. viverrini are mostly in the northeast and north, but the parasite is largely absent from southern Thailand. Under future climate change scenarios, the distribution of O. viverrini in 2050 should be significantly affected by precipitation, maximum temperature, and mean temperature of the wettest quarter, whereas in 2070, significant factors are likely to be precipitation during the coldest quarter, maximum, and minimum temperatures. Maps of predicted future distribution revealed a drastic decrease in presence of O. viverrini in the northeast region. The information gained from this study should be a useful reference for implementing long-term prevention and control strategies for O. viverrini in Thailand.

Multi-species sensing using multi-mode absorption spectroscopy with mid-infrared interband cascade lasers.

The application of an interband cascade laser, ICL, to multi-mode absorption spectroscopy, MUMAS, in the mid-infrared region is reported. Measurements of individual mode linewidths of the ICL, derived from the pressure dependence of lineshapes in MUMAS signatures of single, isolated, lines in the spectrum of HCl, were found to be in the range 10-80 MHz. Multi-line spectra of methane were recorded using spectrally limited bandwidths, of approximate width 27 cm-1, defined by an interference filter, and consist of approximately 80 modes at spectral locations spanning the 100 cm-1 bandwidth of the ICL output. Calibration of the methane pressures derived from MUMAS data using a capacitance manometer provided measurements with an uncertainty of 1.1 %. Multi-species sensing is demonstrated by the simultaneous detection of methane, acetylene and formaldehyde in a gas mixture. Individual partial pressures of the three gases are derived from best fits of model MUMAS signatures to the data with an experimental error of 10 %. Using an ICL, with an inter-mode interval of ~10 GHz, MUMAS spectra were recorded at pressures in the range 1-10 mbar, and, based on the data, a potential minimum detection limit of the order of 100 ppmv is estimated for MUMAS at atmospheric pressure using an inter-mode interval of 80 GHz.

Effect of early vs. late tracheostomy on clinical outcomes in critically ill pediatric patients.

BACKGROUND: Few studies investigated the optimal timing for tracheostomy and its influence on the clinical outcomes in critically ill pediatric patients. This study evaluated the differences in clinical outcomes between early and late tracheostomy in pediatric intensive care unit (ICU) patients. METHODS: We assessed 111 pediatric patients. Patients who underwent a tracheostomy within 14 days of mechanical ventilation (MV) were assigned to the early tracheostomy group, whereas those who underwent tracheostomy after 14 days of MV were included in the late tracheostomy group. Clinical outcomes, including mortality, duration of MV, length of ICU and hospital stays, and incidence of ventilator-associated pneumonia (VAP) were compared between the groups. RESULTS: Of the 111 pediatric patients, 61 and 50 were included in the early and late tracheostomy groups, respectively. Total MV duration and the length of ICU and hospital stay were significantly longer in the late tracheostomy group than in the early tracheostomy group (all P < 0.01). The VAP rate per 1000 ventilator days before tracheostomy was 2.6 and 3.8 in the early and late tracheostomy groups, respectively. There were no significant differences in mortality rate between the groups. No severe complications were associated with tracheostomy itself. CONCLUSIONS: Tracheostomy performed within 14 days after the initiation of MV was associated with reduced duration of MV and length of ICU and hospital stay. Although there was no effect on mortality rate, children may benefit from early tracheostomy without severe complications.

Development of Nested PCR-Based Specific Markers for Detection of Peach Rosette Mosaic Virus in Plant Quarantine.

The Peach rosette mosaic virus (PRMV) is a plant pathogen of the genus Nepovirus, and has been designated as a controlled quarantine virus in Korea. In this study, a specific reverse transcription (RT)-PCR marker set, nested PCR marker set, and modified-plasmid positive control were developed to promptly and accurately diagnose PRMV at plant-quarantine sites. The final selected PRMV-specific RT-PCR marker was PRMV-N10/C70 (967 bp), and the nested PCR product of 419 bp was finally amplified. The modified-plasmid positive control, in which the SalI restriction-enzyme region (GTCGAC) was inserted, verified PRMV contamination in a comparison with the control, enabling a more accurate diagnosis. It is expected that the developed method will continuously contribute to the plant-quarantine process in Korea.

Mid-infrared multi-mode absorption spectroscopy using interband cascade lasers for multi-species sensing.

An interband cascade laser (ICL) operating at 3.7 µm has been used to perform multimode absorption spectroscopy, MUMAS, at scan rates up to 10 kHz. Line widths of individual modes in the range 10-80 MHz were derived from isolated lines in the MUMAS signatures of HCl. MUMAS data for methane covering a spectral range of 30 nm yielded a detection level of 30 µbar·m for 1 s measurement time at 100 Hz. Simultaneous detection of methane, acetylene, and formaldehyde in a gas mixture containing all three species is reported.

Prediction of fluid responsiveness using a non-invasive cardiac output monitor in children undergoing cardiac surgery.

BACKGROUND: This study evaluated the ability of a non-invasive cardiac output monitoring device (NICOM) to predict fluid responsiveness in paediatric patients undergoing cardiac surgery. METHODS: Children aged <5 yr undergoing congenital heart surgery were included. Once the sternum had been closed after repair of the congenital heart defect, 10 ml kg(-1) colloid solution was administered for volume expansion. Transoesophageal echocardiography (TOE) was performed to measure stroke volume (SV) and respiratory variation in aortic blood flow peak velocity (ΔV(peak)) before and after volume expansion. Haemodynamic and NICOM variables, including SV(NICOM), stroke volume variance (SVV(NICOM)), cardiac index (CI(NICOM)), and percentage change in thoracic fluid content compared with baseline (TFCd0%), were also recorded. Patients in whom the stroke volume index (SVI), measured using TOE, increased by >15% were defined as fluid responders. RESULTS: Twenty-nine patients were included (13 responders and 16 non-responders). Before volume expansion, only ΔV(peak) differed between groups (P=0.036). The SVV(NICOM), HR, and central venous pressure did not predict fluid responsiveness, but ΔV(peak) did. The CI(NICOM) was not correlated with CI(TOE) (r=0.107, P=0.43). Using Bland-Altman analysis, the mean bias between CI(TOE) and CI(NICOM) was 0.89 litre min(-1) m(-2), with a precision of 1.14 litre min(-1) m(-2). Trending ability of NICOM for SVI and CI was poor when TOE was a reference method. CONCLUSIONS: The SVV(NICOM) did not predict fluid responsiveness in paediatric patients during cardiac surgery. In addition, there was no correlation between CI(TOE) and CI(NICOM). Fluid management guided by NICOM should be performed carefully. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01996956.

Gain and loss as a function of current density and temperature in interband cascade lasers.

We characterize the internal efficiency, internal loss, and optical gain versus current density in 7-stage interband cascade lasers operating at λ=3.1 and 3.45 µm using a cavity-length study of the external differential quantum efficiency (EDQE) and threshold current density at temperatures between 300 and 345 K. We find that the pronounced efficiency droop of the EDQE at high current densities is primarily due to an increase in the internal loss rather than a reduction in the internal efficiency. On the other hand, if the current density J is fixed, the temperature variation of the EDQE at that J is due primarily to a decrease of the internal efficiency. The gain versus current density is fit well by a logarithmic relationship, although the magnitude of the experimental gain is >20% below the theoretical estimate.

Interband cascade lasers with long lifetimes.

Narrow-ridge interband cascade lasers were subjected to accelerated aging. The aging curves were statistically evaluated by a log-normal distribution of the failure time, and by the mixed effects of the degradation parameters. Based on 10,000 h of output power trend data for lasers operating at 90°C and the maximum cw power, an unexpectedly long lifetime is predicted. The projected lifetimes range from about 500,000 h (57 years) for the linear degradation model to 183,000 h (21 years) for the exponential one.

Effects of the jaw-thrust manoeuvre in the semi-sitting position on securing a clear airway during fibreoptic intubation.

Securing a clear airway is important for successful fibreoptic intubation. We investigated whether the jaw-thrust manoeuvre in the 25° semi-sitting position improves airway clearance compared with the supine position in 88 anaesthetised patients randomly assigned to the two positions. After induction of anaesthesia, the fibreoptic bronchoscope was advanced into the mouth along the dorsum of the tongue during the jaw-thrust manoeuvre. Airway clearance was assessed at the level of the soft palate and epiglottis. Patients in the 25° semi-sitting position had clearer airways (judged subjectively by a three-level scale) than those in the supine position at the soft palate level (p = 0.012). At the level of the epiglottis, airway clearance was equally good in both positions. The mean (SD) times to view the vocal cord and carina were shorter in the 25° semi-sitting position (4 (1) s and 8 (1) s, respectively) compared with the supine position (6 (3) s and 11 (3) s; p < 0.001, respectively). The time to achieve intubation was also shorter in the 25° semi-sitting position (21 (5) s) than in the supine position (25 (7) s; p = 0.018).