Integer-locking condition for stable dual-comb interferometry in situations with fluctuating frequency-comb repetition rates.

To make dual-comb interferometry usable in a wide range of applications, it is important to achieve reproducible measurement results even in non-ideal environments that affect the repetition-rate stability. Here, we consider dual-comb interferometry based on a pair of fully referenced optical frequency combs (OFCs) and investigate the impact of fluctuations in the OFC repetition frequencies on the peak position of the center burst in the interferogram. We identify a phase-locking scheme that minimizes the impact of these fluctuations through choosing a special combination of phase-locked frequencies, and the resulting type of operating condition is termed integer-locking condition. Under the integer-locking condition, the number of sampling points in each interferogram remains constant regardless of repetition-rate variations, and this enables more stable phase-resolved measurements in non-ideal environments. We demonstrate the application of this approach using absolute path-length measurements and discuss the accuracy limit imposed by the integer-locking condition. Our findings offer a strategy for robust dual-comb interferometry outside metrology laboratories.

Pharmacological Investigation of Hypoalbuminemia on the Prolonged and Potentiated Action of Midazolam in Rats.

Midazolam (MDZ) is clinically used for its sedative and anticonvulsant properties. However, its prolonged or potentiated effects are sometimes concerning. The main binding protein of MDZ is albumin, and reduced serum albumin levels could lead to MDZ accumulation, thereby potentiating or prolonging its effects. Previous investigations have not thoroughly examined these phenomena from a behavioral pharmacology standpoint. Consequently, this study aimed to evaluate both the prolonged and potentiated effects of MDZ, as well as the effects of serum albumin levels on the action of MDZ in low-albumin rats. Male Wistar rats were classified into control (20% protein diet), low-protein (5% protein), and non-protein groups (0% protein diet) and were fed the protein-controlled diets for 30 d to obtain low-albumin rats. The locomotor activity and muscle relaxant effects of MDZ were evaluated using the rotarod, grip strength, and open-field tests conducted 10, 60, and 120 min after MDZ administration. Serum albumin levels decreased significantly in the low-protein and non-protein diet groups compared with those in the control group. Compared with the control rats, low-albumin rats demonstrated a significantly shorter time to fall, decreased muscle strength, and a significant decrease in the distance traveled after MDZ administration in the rotarod, grip strength, and open-field tests, respectively. Decreased serum albumin levels potentiated and prolonged the effects of MDZ. Hence, serum albumin level is a critical parameter associated with MDZ administration, which should be monitored, and any side effects related to decreased albumin levels should be investigated.

The inter-laboratory validation study of EpiSensA for predicting skin sensitization potential.

The Epidermal Sensitization Assay (EpiSensA) is a reconstructed human epidermis (RhE)-based gene expression assay for predicting the skin sensitization potential of chemicals. Since the RhE model is covered by a stratified stratum corneum, various kinds of test chemicals, including lipophilic ones and pre-/pro-haptens, can be tested with a route of exposure akin to an in vivo assay and human exposure. This article presents the results of a formally managed validation study of the EpiSensA that was carried out by three participating laboratories. The purpose of this validation study was to assess transferability of the EpiSensA to new laboratories along with its within- (WLR) and between-laboratory reproducibility (BLR). The validation study was organized into two independent stages. As demonstrated during the first stage, where three sensitizers and one non-sensitizer were correctly predicted by all participating laboratories, the EpiSensA was successfully transferred to all three participating laboratories. For Phase I of the second stage, each participating laboratory performed three experiments with an identical set of 15 coded test chemicals resulting in WLR of 93.3%, 93.3%, and 86.7%, respectively. Furthermore, when the results from the 15 test chemicals were combined with those of the additional 12 chemicals tested in Phase II of the second stage, the BLR for 27 test chemicals was 88.9%. Moreover, the predictive capacity among the three laboratories showed 92.6% sensitivity, 63.0% specificity, 82.7% accuracy, and 77.8% balanced accuracy based on murine local lymph node assay (LLNA) results. Overall, this validation study concluded that EpiSensA is easily transferable and sufficiently robust for assessing the skin sensitization potential of chemicals.

Dysphagia Rehabilitation in Dysphagic Patients with Acute or Critical Illness: A Systematic Review and Meta-Analysis.

Dysphagia or swallowing dysfunction is common in patients with acute or critical illness, and diverse methods of dysphagia rehabilitation are provided worldwide. We aimed to examine the efficacy of rehabilitation to treat dysphagia in patients with acute or critical illness. We searched PubMed, ICHUSHI, and Cochrane Central Register of Controlled Trials databases from inception to November 22, 2023 for relevant randomized controlled trials. We focused on dysphagic patients with acute or critical illness who were not orotracheally intubated. Our target intervention included conventional rehabilitation and nerve stimulation/neuromodulation techniques as dysphagia rehabilitation. Comparators were conventional or standard care or no dysphagia interventions. Primary outcomes included mortality, incidence of pneumonia during the study period, and health-related quality of life (HRQoL) scores within 90 days of hospital discharge. We pooled the data using a random-effects model, and classified the certainty of evidence based on the Grading of Recommendations, Assessment, Development, and Evaluation system. Nineteen randomized controlled trials involving 1,096 participants were included. Dysphagia rehabilitation was associated with a reduced incidence of pneumonia (risk ratio [RR], 0.66; 95% confidence interval [CI], 0.54-0.81; moderate certainty), but not with reduced mortality (RR, 0.92; 95% CI, 0.61-1.39; very low certainty) or improved HRQoL scores (mean difference, -0.20; 95% CI, -20.34 to 19.94; very low certainty). Based on the available moderate- or very low- quality evidence, while dysphagia rehabilitation had no impact on mortality or HRQoL, they might reduce the incidence of pneumonia in dysphagic patients with acute or critical illness.

Effect of Neuromuscular Electrical Stimulation in Patients With Critical Illness: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Neuromuscular electrical stimulation (NMES) is used in the rehabilitation of patients with critical illness. However, it is unclear whether NMES prevents ICU-acquired weakness (ICU-AW). For this purpose, we conducted an updated systematic review and meta-analysis. DATA SOURCES: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases from April 2019 to November 2022 to identify new randomized controlled trials to the previous meta-analysis. STUDY SELECTION: We systematically searched the literature for all randomized controlled trials on the effect of NMES in patients with critical illness. DATA EXTRACTION: Two authors independently selected the studies and extracted data. They calculated the pooled effect estimates associated with the occurrence of ICU-AW and adverse events as primary outcomes and muscle mass change, muscle strength, length of ICU stay, mortality, and quality of life as secondary outcomes. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. DATA SYNTHESIS: Overall, eight studies were added to the previous 10 studies. Evidence suggests that the use of NMES reduces the occurrence of ICU-AW (six trials; risk ratio [RR], 0.48; 95% CI, 0.32-0.72); however, NMES may have little to no effect on pricking sensation in patients (eight trials; RR, 6.87; 95% CI, 0.84-56.50). NMES is likely to reduce the change in muscle mass (four trials; mean difference, -10.01; 95% CI, -15.54 to -4.48) and may increase muscle strength (six trials; standardized mean difference, 0.43; 95% CI, 0.19-0.68). Further, NMES may result in little to no difference in the length of ICU stay, and the evidence is uncertain about the effect on mortality and quality of life. CONCLUSIONS: This updated meta-analysis revealed that the use of NMES may result in a lower occurrence of ICU-AW in patients with critical illness, but its use may have little to no effect on pricking sensation in patients.

Hospital pharmacist interventions for the management of oral mucositis in patients with head and neck cancer receiving chemoradiotherapy: a multicenter, prospective cohort study.

PURPOSE: Oral mucositis is a severe adverse event in patients with head and neck cancer (HNC) receiving chemotherapy and radiotherapy that may cause the termination of cancer treatment. In this study, we aimed to reveal the benefits of pharmacist interventions in oral health care for patients with HNC receiving concurrent chemoradiotherapy (CCRT). METHODS: We conducted a multicenter, prospective cohort study on 173 patients from September 2019 to August 2022. We evaluated the association between the occurrence of oral mucositis during CCRT and various factors in the absence or presence of direct medication instructions from hospital pharmacists. RESULTS: Sixty-eight patients received medication instructions from pharmacists (the pharmacist intervention group), whereas 105 patients did not receive instructions (the control group). Logistic regression analysis showed that grade 2 (Gr 2) oral mucositis was significantly lower in patients receiving pharmacist interventions than in patients in the control group (adjusted odds ratio [aOR], 0.42; 95% confidence interval [CI], 0.18-0.96; P = 0.04). The time to onset of Gr 2 oral mucositis was significantly longer in the pharmacist intervention group than in the control group (hazard ratio, 0.53; 95% CI, 0.29-0.97; P = 0.04). CONCLUSION: Direct intervention, especially when provided by hospital pharmacists, can have a real effect in supporting patients with HNC experiencing severe side effects of treatments. Moreover, the integration of pharmacists into the oral healthcare team is becoming even more essential to reduce the severity of side effects.

The second nationwide surveillance of antibacterial susceptibility patterns of pathogens isolated from skin and soft-tissue infections in dermatology departments in Japan.

The present study compared trends in antimicrobial resistance patterns in pathogens isolated from skin and soft-tissue infections (SSTIs) in Japan with those of a nationwide survey conducted in 2013. Three organisms that caused most of the SSTIs were collected from 12 dermatology departments in medical centers and 12 dermatology clinics across Japan between April 2019 and August 2020. A total of 390 strains, including 267 Staphylococcus aureus, 109 coagulase-negative staphylococci (CNS), and 14 Streptococcus pyogenes strains were submitted to a central laboratory for antimicrobial susceptibility testing. Patient demographic and clinical information was collated. Methicillin-resistant S. aureus (MRSA) was detected in 25.8% (69/267) of the S. aureus strains. The prevalence of MRSA between the present study and the 2013 survey did not differ significantly. Furthermore, there were no significant differences in MIC values and susceptibility patterns of the MRSA strains to other agents, regardless of a history of hospitalization within 1 year or invasive medical procedures. Methicillin-resistant CNS (MRCNS) was detected in 48.6% (53/109) of CNS isolates, higher than the 35.4% prevalence in the 2013 survey. This difference could be attributed to the heterogeneity in the members of the MRCNS, which comprises multiple staphylococci species, between the 2013 and 2019 surveys. However, it was noted that the susceptibility profiles of the MRCNS to each antibiotic were not significantly different from those identified in the 2013 survey. Most strains of S. pyogenes were susceptible to each antibiotic, similar to the 2013 survey. Continuous monitoring of trends in pathogen and susceptibility profiles is important to advise local public health efforts regarding the appropriate treatment of SSTIs.

Triggerless data acquisition in asynchronous optical-sampling terahertz time-domain spectroscopy based on a dual-comb system.

By using two mutually phase-locked optical frequency combs with slightly different repetition rates, we demonstrate asynchronous optical-sampling terahertz time-domain spectroscopy (ASOPS THz-TDS) without using any trigger signals or optical delay lines. Due to a tight stabilization of the repetition frequencies, it was possible to accumulate the data over 48 minutes in a triggerless manner without signal degradation. The fractional frequency stability of the measured terahertz signal is evaluated to be ∼8.0 × 10-17 after 730 s. The frequency accuracy of the obtained terahertz spectrum is ensured by phase-locking the two frequency combs to a frequency standard. To clarify the performance of our system, we characterized the absorption line of water vapor around 0.557 THz. The good agreement of the measured center frequency and linewidth with the values predicted from the HITRAN database verifies the suitability of our ASOPS THz-TDS system for precise measurements.

Polarization-sensitive terahertz time-domain spectroscopy system without mechanical moving parts.

We report on the measurement of terahertz electric-field vector waveforms by using a system that contains no mechanical moving parts. It is known that two phase-locked femtosecond lasers with different repetition rates can be used to perform time-domain spectroscopy without using a mechanical delay stage. Furthermore, an electro-optic modulator can be used to perform polarization measurements without rotating any polarizers or waveplates. We experimentally demonstrate the combination of these two methods and explain the analysis of data obtained by such a system. Such a system provides a robust platform that can promote the usage of polarization-sensitive terahertz time-domain spectroscopy in basic science and practical applications. For the experimental demonstration, we alter the polarization of a terahertz wave with a polarizer.

Ultra-precise determination of thicknesses and refractive indices of optically thick dispersive materials by dual-comb spectroscopy.

Precise measurements of the geometrical thickness of a sample and its refractive index are important for materials science, engineering, and medical diagnosis. Among the possible non-contact evaluation methods, optical interferometric techniques possess the potential of providing superior resolution. However, in the optical frequency region, the ambiguity in the absolute phase-shift makes it difficult to measure these parameters of optically thick dispersive materials with sufficient resolution. Here, we demonstrate that dual frequency-comb spectroscopy can be used to precisely determine the absolute sample-induced phase-shift by analyzing the data smoothness. This method enables simultaneous determination of the geometrical thickness and the refractive index of a planar sample with a precision of five and a half digits. The thickness and the refractive index at 193.414 THz (λ = 1550 nm) of a silicon wafer determined by this method are 0.5204737(19) mm and 3.475625(58), respectively, without any prior knowledge of the refractive index.