Quantum cascade laser-based mid-IR frequency metrology system with ultra-narrow linewidth and 1 × 10⁻¹³-level frequency instability.

We demonstrate a powerful tool for high-resolution mid-IR spectroscopy and frequency metrology with quantum cascade lasers (QCLs). We have implemented frequency stabilization of a QCL to an ultra-low expansion (ULE) reference cavity, via upconversion to the near-IR spectral range, at a level of 1×10(-13). The absolute frequency of the QCL is measured relative to a hydrogen maser, with instability <1×10(-13) and inaccuracy 5×10(-13), using a frequency comb phase stabilized to an independent ultra-stable laser. The QCL linewidth is determined to be 60 Hz, dominated by fiber noise. Active suppression of fiber noise could result in sub-10 Hz linewidth.

Mutations in Danish patients with long QT syndrome and the identification of a large founder family with p.F29L in KCNH2.

BACKGROUND: Long QT syndrome (LQTS) is a cardiac ion channelopathy which presents clinically with palpitations, syncope or sudden death. More than 700 LQTS-causing mutations have been identified in 13 genes, all of which encode proteins involved in the execution of the cardiac action potential. The most frequently affected genes, covering > 90% of cases, are KCNQ1, KCNH2 and SCN5A. METHODS: We describe 64 different mutations in 70 unrelated Danish families using a routine five-gene screen, comprising KCNQ1, KCNH2 and SCN5A as well as KCNE1 and KCNE2. RESULTS: Twenty-two mutations were found in KCNQ1, 28 in KCNH2, 9 in SCN5A, 3 in KCNE1 and 2 in KCNE2. Twenty-six of these have only been described in the Danish population and 18 are novel. One double heterozygote (1.4% of families) was found. A founder mutation, p.F29L in KCNH2, was identified in 5 "unrelated" families. Disease association, in 31.2% of cases, was based on the type of mutation identified (nonsense, insertion/deletion, frameshift or splice-site). Functional data was available for 22.7% of the missense mutations. None of the mutations were found in 364 Danish alleles and only three, all functionally characterised, were recorded in the Exome Variation Server, albeit at a frequency of < 1:1000. CONCLUSION: The genetic etiology of LQTS in Denmark is similar to that found in other populations. A large founder family with p.F29L in KCNH2 was identified. In 48.4% of the mutations disease causation was based on mutation type or functional analysis.

Robust, frequency-stable and accurate mid-IR laser spectrometer based on frequency comb metrology of quantum cascade lasers up-converted in orientation-patterned GaAs.

We demonstrate a robust and simple method for measurement, stabilization and tuning of the frequency of cw mid-infrared (MIR) lasers, in particular of quantum cascade lasers. The proof of principle is performed with a quantum cascade laser at 5.4 µm, which is upconverted to 1.2 µm by sum-frequency generation in orientation-patterned GaAs with the output of a standard high-power cw 1.5 µm fiber laser. Both the 1.2 µm and the 1.5 µm waves are measured by a standard Er:fiber frequency comb. Frequency measurement at the 100 kHz-level, stabilization to sub-10 kHz level, controlled frequency tuning and long-term stability are demonstrated.

Detection of Subclinical Atrial Fibrillation in High-Risk Patients Using an Insertable Cardiac Monitor.

OBJECTIVES: The study sought to determine the incidence of subclinical atrial fibrillation (AF) in high-risk patients and to compare the effect of continuous versus intermittent monitoring. BACKGROUND: AF often occurs in a subclinical form, which makes it difficult to detect. The authors do not know the incidence of subclinical AF among patients ≥65 years of age with hypertension and diabetes mellitus. This group of patients has increased risk of developing AF and in addition a high thromboembolic risk, if AF is present. METHODS: A total of 82 outpatients ≥65 years of age (median age 71.3 years [interquartile range [IQR]: 67.4 to 75.1 years]) with hypertension and diabetes mellitus, and no history of AF or any other cardiovascular disease, were consecutively included. All patients received an insertable cardiac monitor (ICM) and were followed for a median of 588 days (IQR: 453 to 712 days). We compared continuous monitoring with 72-h Holter monitoring 1 month after ICM insertion. The primary endpoint was AF ≥2 min for the ICM and AF ≥30 s for the Holter monitoring. RESULTS: During follow-up 17 (20.7%) patients were found to have subclinical AF detected by ICM with a median time to first detected episode of 91 days (IQR: 41 to 251 days) from inclusion. Only 2 (2.4%) patients also had AF episodes on the 72-h Holter monitoring. All detected episodes were completely asymptomatic. CONCLUSIONS: The incidence of subclinical AF in this group of patients was surprisingly high. Continuous monitoring with ICM detected significantly more AF episodes than 72-h Holter monitoring. (Detection of Subclinical Atrial Fibrillation in High Risk Patients Using Implantable Loop Recorder; NCT02041832).

Invasively Measured Aortic Systolic Blood Pressure and Office Systolic Blood Pressure in Cardiovascular Risk Assessment: A Prospective Cohort Study.

Aortic systolic blood pressure (BP) represents the hemodynamic cardiac and cerebral burden more directly than office systolic BP. Whether invasively measured aortic systolic BP confers additional prognostic value beyond office BP remains debated. In this study, office systolic BP and invasively measured aortic systolic BP were recorded in 21 908 patients (mean age: 63 years; 58% men; 14% with diabetes mellitus) with stable angina pectoris undergoing elective coronary angiography during January 2001 to December 2012. Multivariate Cox models were used to assess the association with incident myocardial infarction, stroke, and death. Discrimination and reclassification were assessed using Harrell's C and the Continuous Net Reclassification Index. Data were analyzed with and without stratification by diabetes mellitus status. During a median follow-up period of 3.7 years (range: 0.1-10.8 years), 422 strokes, 511 myocardial infarctions, and 1530 deaths occurred. Both office and aortic systolic BP were associated with stroke in patients with diabetes mellitus (hazard ratio per 10 mm Hg, 1.18 [95% confidence interval, 1.07-1.30] and 1.14 [95% confidence interval, 1.05-1.24], respectively) and with myocardial infarction in patients without diabetes mellitus (hazard ratio, 1.07 [95% confidence interval, 1.02-1.12] and 1.05 [95% confidence interval, 1.01-1.10], respectively). In models including both BP measurements, aortic BP lost statistical significance and aortic BP did not confer improvement in either C-statistics or net reclassification analysis. In conclusion, invasively measured aortic systolic BP does not add prognostic information about cardiovascular outcomes and all-cause mortality compared with office BP in patients with stable angina pectoris, either with or without diabetes mellitus.