Global optimization of multilayer dielectric coatings for precision measurements.

We describe the design of optimized multilayer dielectric coatings for precision laser interferometry. By setting up an appropriate cost function and then using a global optimizer to find a minimum in the parameter space, we were able to realize coating designs that meet the design requirements for spectral reflectivity, thermal noise, absorption, and tolerances to coating fabrication errors. We also present application of a Markov-Chain Monte Carlo (MCMC) based parameter estimation algorithm that can infer thicknesses of dielectric layers in a coating, given a measurement of the spectral reflectivity. This technique can be a powerful diagnostic tool for both commercial coating manufacturers, and the community using dielectric mirrors for precision metrology experiments.

Interlaboratory evaluation of LC-MS-based biomarker assays.

Validation of biomarker assays is crucial for effective drug development and clinical applications. Interlaboratory reproducibility is vital for reliable comparison and combination of data from different centers. This review summarizes interlaboratory studies of quantitative LC-MS-based biomarker assays using reference standards for calibration curves. The following points are discussed: trends in reports, reference and internal standards, evaluation of analytical validation parameters, study sample analysis and normalization of biomarker assay data. Full evaluation of these parameters in interlaboratory studies is limited, necessitating further research. Some reports suggest methods to address variations in biomarker assay data among laboratories, facilitating organized studies and data combination. Method validation across laboratories is crucial for reducing interlaboratory differences and reflecting target biomarker responses.

Aneurysm appearing at the anastomosis site 11 years after superficial temporal artery-middle cerebral artery bypass surgery: moyamoya disease with a rapidly growing aneurysm. Illustrative case.

BACKGROUND: Superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery is performed to prevent ischemia and hemorrhage in patients with moyamoya disease. Only a few reports have described aneurysms appearing around the anastomosis site after bypass surgery, and the underlying mechanism remains unknown. OBSERVATIONS: The present case involved a 62-year-old woman who underwent STA-MCA bypass surgery for ischemic quasi-moyamoya disease at 46 years of age. Postoperatively, she underwent annual magnetic resonance imaging examinations. At 11 years after STA-MCA bypass surgery, a 3-mm aneurysm appeared at the anastomosis site. Four years later, headache developed and the aneurysm had grown to 5 mm. Craniotomy clipping was performed to prevent rupture. The patient was discharged home 2 weeks after surgery without any apparent complications. LESSONS: Long-term observation is crucial after direct bypass surgery for moyamoya disease. Measures to prevent rupture should be considered for cases involving aneurysm complications.

Multi-laboratory evaluation of immunoaffinity LC-MS-based glucagon-like peptide-1 assay.

Background: Although the fit-for-purpose approach has been proposed for biomarker assay validation, practical data should be compiled to facilitate the predetermination of acceptance criteria. Methods: Immunoaffinity LC-MS was used to analyze glucagon-like peptide-1 as a model biomarker in six laboratories. Calibration curve, carryover, parallelism, precision, relative accuracy and processed sample stability were evaluated, and their robustness among laboratories was assessed. The rat glucagon-like peptide-1 concentrations in four blinded samples were also compared. Results: The obtained results and determined concentrations in the blinded samples at all laboratories were similar, with a few exceptions, and robust, despite the difference in optimization techniques among laboratories. Conclusion: The results provide insights into the predefinition of the acceptance criteria of immunoaffinity LC-MS-based biomarker assays.

Scattering loss in precision metrology due to mirror roughness.

Optical losses degrade the sensitivity of laser interferometric instruments. They reduce the number of signal photons and introduce technical noise associated with diffuse light. In quantum-enhanced metrology, they break the entanglement between correlated photons. Such decoherence is one of the primary obstacles in achieving high levels of quantum noise reduction in precision metrology. In this work, we compare direct measurements of cavity and mirror losses in the Caltech 40 m gravitational-wave detector prototype interferometer with numerical estimates obtained from semi-analytic intra-cavity wavefront simulations using mirror surface profile maps. We show a unified approach to estimating the total loss in optical cavities (such as the LIGO gravitational detectors) that will lead towards the engineering of systems with minimum decoherence for quantum-enhanced precision metrology.

Evaluation of the Influence of a History of Childhood Nocturnal Enuresis on Nighttime Urinary Frequency and the Causes of Nocturia in Adults.

OBJECTIVE: To examine whether a history of nocturnal enuresis affects nighttime urinary frequency and to evaluate nocturia etiologies in adults. MATERIALS AND METHODS: A total of 143 participants with at least one episode of nocturia per night were included in this study. The self-reported questionnaire collected data on demographic characteristics, medical history, history of nocturnal enuresis in elementary school, lower urinary tract symptoms, and frequency-volume charts. RESULTS: A history of nocturnal enuresis was observed in 52.4% of participants. However, night-time urinary frequency was significantly lower in participants with a history of nocturnal enuresis in elementary school than in those without such history. On multivariate analysis, a history of nocturnal enuresis was also negatively associated with nighttime urinary frequency (P <.01). There was a collinearity effect between age and nighttime urinary frequency. A history of nocturnal enuresis did not affect the presence of nocturnal polyuria or overactive bladder in participants. However, sleep disturbances were fewer in participants with a history of nocturnal enuresis (odds ratio 0.404). CONCLUSION: A history of nocturnal enuresis might be negatively associated with nighttime urinary frequency due to fewer sleep disturbances. Further, progression of nocturia may depend on conditions, such as age and acquired diseases.

Highlights of the 12th Japan Bioanalysis Forum Symposium.

Approximately 300 people associated with pharmaceutical industries, contractors, academic institutions and regulatory authorities attended the 12th Japan Bioanalysis Forum Symposium. The webinar was conducted from 9 to 11 March 2021. The theme of the symposium was 'for the next generation', and the event provided 'an opportunity for young researchers in bioanalysis (including students)' and 'an opportunity to discuss new frontiers of bioanalysis'. The speakers focused on hot topics of bioanalysis, including biomarker analysis, patient centric sampling, virtual clinical trials, gene therapy, cancer genome medicine and therapeutic middle molecules. The symposium presented a platform for the discussion of the prospects and challenges facing bioanalysts working in the field of pharmacokinetics. This report presents the key issues discussed.

A multilaboratory validation study of LC/MS biomarker assays for three lysophosphatidylcholines.

Aim: Although the fit-for-purpose approach has been proposed for validation procedures and acceptance criteria for biomarker assays, practical biomarker assays to facilitate clinical application and regulatory documents on biomarker assays remain limited. Materials & methods: We assigned six independent laboratories and selected three lysophosphatidylcholines (LPCs): LPC(16:0), LPC(18:0) and LPC(18:1) as model biomarkers. Using LC-MS, the following key validation parameters were evaluated: calibration curve, carryover, parallelism, precision and relative accuracy and these values were similar among all laboratories. Further, we determined LPC levels in six lots of rat plasma at unknown concentrations and compared them among the laboratories. Conclusion: Our multilaboratory validation and reproducibility data are useful for the development of future biomarker assay validation procedures, as well as regulatory documents.

Constraints on Cosmic Strings Using Data from the Third Advanced LIGO-Virgo Observing Run.

We search for gravitational-wave signals produced by cosmic strings in the Advanced LIGO and Virgo full O3 dataset. Search results are presented for gravitational waves produced by cosmic string loop features such as cusps, kinks, and, for the first time, kink-kink collisions. A template-based search for short-duration transient signals does not yield a detection. We also use the stochastic gravitational-wave background energy density upper limits derived from the O3 data to constrain the cosmic string tension Gµ as a function of the number of kinks, or the number of cusps, for two cosmic string loop distribution models. Additionally, we develop and test a third model that interpolates between these two models. Our results improve upon the previous LIGO-Virgo constraints on Gµ by 1 to 2 orders of magnitude depending on the model that is tested. In particular, for the one-loop distribution model, we set the most competitive constraints to date: Gµâ‰²4×10^{-15}. In the case of cosmic strings formed at the end of inflation in the context of grand unified theories, these results challenge simple inflationary models.

Point absorbers in Advanced LIGO.

Small, highly absorbing points are randomly present on the surfaces of the main interferometer optics in Advanced LIGO. The resulting nanometer scale thermo-elastic deformations and substrate lenses from these micron-scale absorbers significantly reduce the sensitivity of the interferometer directly though a reduction in the power-recycling gain and indirect interactions with the feedback control system. We review the expected surface deformation from point absorbers and provide a pedagogical description of the impact on power buildup in second generation gravitational wave detectors (dual-recycled Fabry-Perot Michelson interferometers). This analysis predicts that the power-dependent reduction in interferometer performance will significantly degrade maximum stored power by up to 50% and, hence, limit GW sensitivity, but it suggests system wide corrections that can be implemented in current and future GW detectors. This is particularly pressing given that future GW detectors call for an order of magnitude more stored power than currently used in Advanced LIGO in Observing Run 3. We briefly review strategies to mitigate the effects of point absorbers in current and future GW wave detectors to maximize the success of these enterprises.

Bioanalysis of therapeutic monoclonal antibody by peptide adsorption-controlled LC-MS.

Aim: We aimed to develop an easy, low-cost and versatile mass spectrometric method for the bioanalysis of a therapeutic monoclonal antibody (mAb) in human serum that employs peptide adsorption-controlled (PAC)-LC/MS using selected reaction monitoring mode (LC-MS/MS-SRM). Materials & methods: Rituximab was used as a model mAb. To apply the method to human serum samples, a peptide of the complementarity-determining region was selected as the surrogate peptide. The usefulness of PAC-LC-MS/MS-SRM was evaluated by a collaborative study. Results: The calibration curve ranged from 0.5 (or 1.0) to 1000.0 µg/ml. The selectivity, linearity, accuracy and precision met the predefined acceptance criteria. Conclusion: Our method could be a useful bioanalytical method for the quantification of mAbs in clinical samples.

Intradiploic Epidermoid Cyst Causing Otitis Media with Effusion: Case Report and Review of the Literature.

BACKGROUND: Epidermoid cysts are rare, slow-growing, benign tumors. They commonly occur at the cerebellopontine angle or the suprasellar region, and they can also occur in the skull. Intradiploic epidermoid cysts are often detected incidentally, but their progression can cause various symptoms. CASE DESCRIPTION: The patient was a 49-year-old woman who was diagnosed with otitis media with effusion based on a reported sensation of left ear blockage. Thorough examination revealed a mass lesion in the left occipital bone. Computed tomography depicted a mass lesion on the left occipital bone, part of which reached the inner table of the skull and eroded the mastoid air cell. On magnetic resonance imaging, T1-weighted signal was low but T2-weighted signal and diffusion-weighted signal were high. An intradiploic epidermoid cyst was suspected on the basis of imaging results, and it was surmised that mastoid cellulitis by the mass lesion accompanied by bone destruction had progressed to otitis media with effusion. The pathologic diagnosis was epidermoid cysts. Six months after the operation the otitis media with effusion had improved, and there had been no recurrence of epidermoid cysts. CONCLUSIONS: We experienced a case of occipital bone intradiploic epidermoid cysts diagnosed in conjunction with otitis media with effusion.

Frequency-Dependent Squeezed Vacuum Source for Broadband Quantum Noise Reduction in Advanced Gravitational-Wave Detectors.

The astrophysical reach of current and future ground-based gravitational-wave detectors is mostly limited by quantum noise, induced by vacuum fluctuations entering the detector output port. The replacement of this ordinary vacuum field with a squeezed vacuum field has proven to be an effective strategy to mitigate such quantum noise and it is currently used in advanced detectors. However, current squeezing cannot improve the noise across the whole spectrum because of the Heisenberg uncertainty principle: when shot noise at high frequencies is reduced, radiation pressure at low frequencies is increased. A broadband quantum noise reduction is possible by using a more complex squeezing source, obtained by reflecting the squeezed vacuum off a Fabry-Perot cavity, known as filter cavity. Here we report the first demonstration of a frequency-dependent squeezed vacuum source able to reduce quantum noise of advanced gravitational-wave detectors in their whole observation bandwidth. The experiment uses a suspended 300-m-long filter cavity, similar to the one planned for KAGRA, Advanced Virgo, and Advanced LIGO, and capable of inducing a rotation of the squeezing ellipse below 100 Hz.

Treatment of a Scalp Arteriovenous Malformation by a Combination of Embolization and Surgical Removal.

BACKGROUND: Scalp arteriovenous malformation is a rare disease. In terms of treatment, surgical removal is often effective and performed. With the development of endovascular treatments, a combination of surgical removal and embolization is now often performed. CASE DESCRIPTION: A 44-year-old man presented with a mass in his left occipital region. Cerebral angiography led to a diagnosis of scalp arteriovenous malformation. Although he had no neurologic deficits, perfusion computed tomography (CT) scan showed a slight decrease in blood flow in the left cerebral hemisphere, which was presumed to have been caused by the scalp arteriovenous malformation. He suffered from a sleep disorder caused by tinnitus, and a discomfort with the lesion itself; therefore, we decided to surgically remove the lesion. To suppress intraoperative bleeding and safely perform the surgery, preoperative embolization was also planned. After treatment, he had no neurologic deficits and the sleep disorder improved. Perfusion CT scan performed after the surgery showed an improvement in cerebral blood flow in the left cerebral hemisphere. CONCLUSIONS: Because cerebral blood flow may decrease depending on the progression of the lesion, the cerebral blood flow should be evaluated. Considering the treatment modalities depending on the lesion can provide treatment with less recurrence and higher patient satisfaction.

Generic MS-based method for the bioanalysis of therapeutic monoclonal antibodies in nonclinical studies.

Aim: A generic bioanalytical method was developed to quantify therapeutic IgG1 monoclonal antibodies (mAbs) in mouse sera by combining an easy sample preparation method with LC/MS using selected reaction monitoring. Materials & methods: Rituximab and trastuzumab were used as model mAbs. A synthetic stable isotope-labeled peptide or a stable isotope-labeled mAb was used as an internal standard. The method feasibility was evaluated by a collaborative study involving six laboratories. Results: The calibration curve ranged from 1.0 to 1000.0 µg/ml (correlation coefficient >0.99). The validation parameters including selectivity, linearity of calibration curve, accuracy and precision met the predefined acceptance criteria. Conclusion: Our method is a useful bioanalytical method for the quantification of therapeutic IgG mAbs in nonclinical animal studies.

A Case of Infratentorial Meningioma Causing Spontaneous Downbeat Nystagmus: Case Report and Review of the Literature.

BACKGROUND: Spontaneous downbeat nystagmus is a finding that raises suspicions of a central nervous system disorder. Vermis and lower brainstem lesions are considered to be responsible, but the exact mechanism is still controversial. We observed a rare case of spontaneous downbeat nystagmus caused by an infratentorial meningioma. CASE DESCRIPTION: A 50-year-old woman was incidentally diagnosed with infratentorial tumor. Later, she suffered from oscillopsia and the symptom disturbed her daily life especially while driving. Magnetic resonance imaging showed a tumor of approximately 30 mm in diameter at the dorsal midline of the posterior fossa. The tumor was compressing the cerebellar vermis and was apparently responsible for the symptoms that affected her daily life; therefore, we decided to perform tumor removal. The postoperative course was uneventful, and the spontaneous downbeat nystagmus completely disappeared. CONCLUSIONS: Vertical nystagmus is a finding that raises suspicion of a central nervous system disorder, and requires detailed examination. In addition, in case of vertical nystagmus because of tumor compression of the vermis, removal of the tumor can be an effective treatment.

Overall Similarities and a Possible Factor Affecting Plasma Metabolome Profiles Between Venous and Capillary Blood Samples From 20 Healthy Human Males.

Amino acids and lipids are biomarkers used to assess the presence and severity of disease, as well as the toxicological response to drugs. Although upper-extremity venipuncture is a well-used standard technique, fingertip capillary sampling is a more convenient procedure. Delineating the global differences in amino acid and lipid levels in capillary and venous blood samples is paramount for expanding the application of capillary blood tests in biomarker assays. We recruited 20 healthy male subjects and collected plasma obtained from both fingertip capillary and antecubital venous blood. The samples were analyzed to determine the overall profiles of amino acids and lipids and to test for differences in their levels between both vessel types. The results demonstrated that the differences between capillary and venous blood had a lower impact than interindividual variations; however, trends of separation between them were observed for amino acids. The levels of 5 out of 28 amino acids scored fold changes over 30%, while 9 out of 498 lipids had a fold change over 30%. The time required for fingertip blood collection could be a factor for the differences in 3 metabolites. These findings provide useful information for the application of fingertip capillary blood sampling in biomarker assays.

External quantum efficiency enhancement by photon recycling with backscatter evasion.

The nonunity quantum efficiency (QE) in photodiodes (PD) causes deterioration of signal quality in quantum optical experiments due to photocurrent loss as well as the introduction of vacuum fluctuations into the measurement. In this paper, we report that the external QE enhancement of a PD was demonstrated by recycling the reflected photons. The external QE for an InGaAs PD was increased by 0.01-0.06 from 0.86-0.92 over a wide range of incident angles. Moreover, we confirmed that this technique does not increase backscattered light when the recycled beam is properly misaligned.

Type IV collagen aggregates promote keratinocyte proliferation and formation of epidermal layer in human skin equivalents.

Type IV collagen isolated from lens capsule without enzymatic treatment is known to form a gel under physiological condition and influences cellular activities. In case of human keratinocytes, the suppression of proliferation on reconstituted type IV collagen gels was reported in monolayer culture. In this study, we examined effects of type IV collagen isolated from porcine lens capsule on epidermal formation in human skin equivalents (HSEs). Type IV collagen aggregates were prepared under the culture condition and the aggregates suppressed keratinocyte proliferation in monolayer culture as well as the culture on the gels. In HSEs, type IV collagen aggregates were reconstituted on the surface of contracted collagen gels containing human dermal fibroblasts and the keratinocytes were then cultured on the aggregates for 14 days. Interestingly, in HSEs with type IV collagen aggregates, the BrdU-positive keratinocytes were increased and the thickness of the epidermal layer was around twice than that of control culture. Epidermal differentiation markers were expressed in the upper layer of the epidermis and the defined deposition of human basement membrane components were increased at the dermal-epidermal junction. These results indicate that the type IV collagen aggregates stimulate the proliferation of basal keratinocytes and improve the stratification of epidermal layers in HSEs.

Guided lock of a suspended optical cavity enhanced by a higher-order extrapolation.

Lock acquisition of a suspended optical cavity can be a highly stochastic process and is therefore nontrivial. Guided lock is a method to make lock acquisition less stochastic by decelerating the motion of the cavity length based on an extrapolation of the motion from an instantaneous velocity measurement. We propose an improved scheme that is less susceptible to seismic disturbances by incorporating the acceleration as a higher-order correction in the extrapolation. We implemented the new scheme in a 300-m suspended Fabry-Perot cavity and improved the success rate of lock acquisition by a factor of 30.