Ultrafast intraoperative parathyroid hormone monitoring system: prospective, multicentre, clinical validity study.

BACKGROUND: Intraoperative parathyroid hormone (PTH) monitoring is a proven and reliable adjunct to parathyroid surgery, able to improve the outcomes and efficiency of the diagnostic and therapeutic pathway for patients with primary hyperparathyroidism. This study evaluated the innovative, compact, fully automated NBCL CONNECT Analyzer, which can measure whole-blood PTH in 5 min. METHODS: A prospective multicentre study was conducted in stages: results reviews, recommendations, and implementation of improvements to the mechanical design, components of cartridges, calibration, and sampling protocols. Patients undergoing parathyroidectomy had PTH levels measured on the Analyzer and main laboratory platforms, either Roche or Abbott. The Miami criterion of a 50% drop in PTH concentration was used to define biochemical cure during surgery, and normal postoperative calcium level as cure of primary hyperparathyroidism. Measurements on the Analyzer were done by laboratory staff in London and nurses in Stuttgart. The Pearson coefficient (R) and Wilcoxon test were used for statistical analysis. RESULTS: Some 234 patients (55 male, 179 female) with a median age of 58.5 (age full range 15-88) years underwent parathyroidectomy (195 minimally invasive, 38 bilateral neck exploration, 1 thoracoscopic; 12 conversions) for primary hyperparathyroidism between November 2021 and July 2022. Primary hyperparathyroidism was cured in 225 patients (96.2%). The sensitivity, specificity, and overall accuracy of the Analyzer assay in predicting biochemical cure were 83.9, 100, and 84.8% in phase 1; 91.2, 100, and 91.3% in phase 2; and 98.6, 100, and 98.6% in phase 3. There were no false-positive results (positive predictive value 100%). Correlations between Analyzer measurements and those obtained using the Roche device were very strong (R = 0.98, P < 0.001 in phase 1; R = 0.92, P < 0.001 in phase 2; R = 0.94, P < 0.001 in phase 3), and correlations for Analyzer readings versus those from the Abbott platform were strong (R = 0.82, P < 0.001; R = 0.89, P < 0.001; R = 0.91, P < 0.001). The Analyzer showed continued good mechanical performance, with stable and repeatable operations (calibrations, quality controls). Introducing a stricter sampling protocol and improvements in the clot-detecting system led to a decrease in the number of clotted samples and false-negative results. Outcomes were not affected by measurements performed either by nurses or laboratory staff. CONCLUSION: Intraoperative PTH monitoring during parathyroid surgery can be done accurately, simply, and quickly in whole blood using the Analyzer.

Structure and short-time diffusion of concentrated suspensions consisting of silicone-stabilised PMMA particles: a quantitative analysis taking polydispersity effects into account.

We characterise structure and dynamics of concentrated suspensions of silicone-stabilised PMMA particles immersed in index-matching decalin-tetralin mixtures by means of static and quasielastic light scattering experiments. These particles can reproducibly be prepared via a comparatively easy route and are thus promising model systems with hard-sphere interaction. We demonstrate the hard-sphere behaviour of dense suspensions of these systems rigorously taking polydispersity effects into account. Structure factors S(Q) can in the entire range of volume fractions with liquid-like structure quantitatively be modelled using a multi-component Percus-Yevick ansatz regarding the particle size distribution and the form factor assuming a core-shell model with a scattering length density gradient in the PMMA core. Herewith, hydrodynamic functions H(Q) are in the whole accessible Q-range beyond the second maximum of H(Q) quantitatively modelled using a rescaled δγ-approach for all investigated volume fractions. With these data, previously provided characterisation of dilute systems is extended: the excellent agreement of structural and dynamic properties with theoretical predictions for hard spheres demonstrates the suitability of these particles as a model system for hard spheres.

Pediatric computed tomography doses in Germany from 2016 to 2018 based on large-scale data collection.

PURPOSE: Accumulating evidence from epidemiological studies that pediatric computed tomography (CT) examinations can be associated with a small but non-zero excess risk for developing leukemia or brain tumor highlights the need to optimize doses of pediatric CT procedures. Mandatory dose reference levels (DRL) can support reduction of collective dose from CT imaging. Regular surveys of applied dose-related parameters are instrumental to decide when technological advances and optimized protocol design allow lower doses without sacrificing image quality. Our aim was to collect dosimetric data to support adapting current DRL to changing clinical practice. METHOD: Dosimetric data and technical scan parameters from common pediatric CT examinations were retrospectively collected directly from Picture Archiving and Communication Systems (PACS), Dose Management Systems (DMS), and Radiological Information Systems (RIS). RESULTS: We collected data from 17 institutions on 7746 CT series from the years 2016 to 2018 from examinations of the head, thorax, abdomen, cervical spine, temporal bone, paranasal sinuses and knee in patients below 18 years of age. Most of the age-stratified parameter distributions were lower than distributions from previously-analyzed data from before 2010. Most of the third quartiles were lower than German DRL at the time of the survey. CONCLUSIONS: Directly interfacing PACS, DMS, and RIS installations allows large-scale data collection but relies on high data-quality at the documentation stage. Data should be validated by expert knowledge or guided questionnaires. Observed clinical practice in pediatric CT imaging suggests lowering some DRL in Germany is reasonable.

Virial coefficients of hard, homonuclear dumbbells in two- to four-dimensional Euclidean spaces.

We calculated virial coefficients up to the eighth order for hard dumbbells in two-, three-, and four-dimensional Euclidean spaces employing Mayer-sampling Monte Carlo simulations. We improved and extended available data in two dimensions, provide virial coefficients in R^{4} in dependence on their aspect ratio, and recalculated virial coefficients for three-dimensional dumbbells. Highly accurate, semianalytical values for the second virial coefficient of homonuclear, four-dimensional dumbbells are provided. We compare the influence of the aspect ratio and the dimensionality to the virial series for this concave geometry. Lower-order reduced virial coefficients B[over ̃]_{i}=B_{i}/B_{2}^{i-1} depend in first approximation linearly from the inverse excess part of their mutual excluded volume.

Viscoelastic properties of pNIPAM-hydrogels: A mode-coupling theory study.

We investigate the viscoelastic properties of poly(N-isopropylacrylamide) (pNIPAM) hydrogels cross-linked with glutaraldehyde by means of small amplitude oscillatory and steady shear experiments in dependence on the frequency and shear rate. These properties are strongly influenced by the ratio of monomer and glutaraldehyde as a cross-linker. Due to the thermosensitivity of pNIPAM, the rheological properties of these hydrogels can be tuned by the temperature as an external stimulus. The experimentally obtained viscosities and linear viscoelastic moduli are analyzed by a schematic mode-coupling ansatz employing a rescaled F12-model.

Equation of state of hard lenses: A combined virial series and simulation approach.

We provide highly accurate equation-of-state data for the isotropic phase of hard lenses obtained by means of cluster Monte Carlo simulations. This data is analyzed using a virial approach considering coefficients up to the order eight and Carnahan-Starling type closure relations for the virial series. The comparison with previously investigated systems consisting of hard, oblate ellipsoids of revolution allows insights into the detailed influence of the particle geometry. We propose a generalized Carnahan-Starling approach as a heuristic equation of state for the isotropic phase of hard lenses that in first approximation shows the same dependence on the excess part of the excluded volume as identified for oblate, hard lenses of revolution.

Virial coefficients of hard hyperspherocylinders in R

We provide second- to sixth-order virial coefficients of hard hyperspherocylinders in dependence on their aspect ratio ν. Virial coefficients of an anisotropic geometry in four dimensions are calculated employing an optimized Mayer-sampling algorithm. As the second virial coefficient of a hard particle is identical to its excluded hypervolume, the numerically obtained second virial coefficients can be compared to analytical relations for the excluded hypervolume based on geometric measures of the respective, convex geometry in dependence on its aspect ratio ν.

How Long Does It Take to Regain Normocalcaemia in the Event of Postsurgical Hypoparathyroidism? A Detailed Time Course Analysis.

Background: Postsurgical hypoparathyroidism (PH) is the most common side effect of bilateral thyroid resections. Data regarding the time course of recovery from PH are currently unavailable. Therefore, a detailed analysis of the time course of PH recovery and conditions associated with rapid recovery was conducted. Methods: This is a retrospective analysis of prospectively documented data. Patients with biochemical signs of PH or need for calcium supplementation were followed-up for 12 months. Logistic regression analyses were used to identify covariates of early as opposed to late recovery from PH. Results: There were 1097 thyroid resections performed from 06/2015 to 07/2016 with n = 143 PH. Median recovery time was 8 weeks and six patients (1.1% of total thyroid resections) required calcium supplementation > 12 months. Recovery of PH within 4 and 12 weeks was characterized by high PTH levels on the first postoperative day (4 weeks: OR 1.13, 95% CI 1.06−1.20; 12 weeks: OR 1.08, 95%CI 1.01−1.16). Visualization of all PTGs emerged as an independent predictor of recovery within 12 months (OR 2.32, 95% CI 1.01−4.93) and 24 weeks (OR 2.69, 95% CI 1.08−6.69). Conclusion: In the setting of specialized high-volume endocrine surgery, permanent PH is rare. However, every second patient will require more than 2 months of continued medical surveillance. Early recovery was associated with only moderately decreased postsurgical PTH-levels. Successful late recovery appeared to be associated with the number of parathyroid glands visualized during surgery.

Reexamining equations of state of oblate hard ellipsoids of revolution: Numerical simulation utilizing a cluster Monte Carlo algorithm and comparison to virial theory.

We provide highly accurate equation-of-state data determined by means of cluster Monte Carlo simulations for the isotropic phase of oblate hard ellipsoids of revolution. Both equation-of-state data and phase boundaries of the isotropic phase are obtained from relatively large ensembles with typically 1000 particles. The comparison of simulation data with a virial approach gives evidence for the importance of high-order so-far-unknown virial coefficients and therewith many-particle interactions in dense, isotropic systems of anisotropic particles. While a virial approach with a rescaled Carnahan-Starling correction for the unknown, higher-order virial coefficients reproduces the simulation data of moderately anisotropic particles with high accuracy, we suggest for highly anisotropic shapes a simple, heuristic equation of state as a suitable approach.

A review of the state-of-the-art in automatic post-editing.

This article presents a review of the evolution of automatic post-editing, a term that describes methods to improve the output of machine translation systems, based on knowledge extracted from datasets that include post-edited content. The article describes the specificity of automatic post-editing in comparison with other tasks in machine translation, and it discusses how it may function as a complement to them. Particular detail is given in the article to the five-year period that covers the shared tasks presented in WMT conferences (2015-2019). In this period, discussion of automatic post-editing evolved from the definition of its main parameters to an announced demise, associated with the difficulties in improving output obtained by neural methods, which was then followed by renewed interest. The article debates the role and relevance of automatic post-editing, both as an academic endeavour and as a useful application in commercial workflows.

Calculation of third to eighth virial coefficients of hard lenses and hard, oblate ellipsoids of revolution employing an efficient algorithm.

We provide third to eighth virial coefficients of oblate, hard ellipsoids of revolution and hard lenses in dependence on their aspect ratio ν. Employing an algorithm optimized for hard anisotropic shapes, highly accurate data are accessible with comparatively small numerical effort. For both geometries, reduced virial coefficients B[over ̃]_{i}(ν)=B_{i}(ν)/B_{2}^{i-1}(ν) are in first approximation proportional to the inverse excess contribution α^{-1} of their excluded volume. The latter quantity is directly accessible from second virial coefficients and analytically known for convex bodies.

[18F]fluoro-ethylcholine-PET Plus 4D-CT (FEC-PET-CT): A Break-Through Tool to Localize the "Negative" Parathyroid Adenoma. One Year Follow Up Results Involving 170 Patients.

BACKGROUND: The diagnostic performance of [18F]fluoro-ethylcholine-PET-CT&4D-CT (FEC-PET&4D-CT) to identify parathyroid adenomas (PA) was analyzed when ultrasound (US) or MIBI-Scan (MS) failed to localize. Postsurgical one year follow-up data are presented. METHODS: Patients in whom US and MS delivered either incongruent or entirely negative findings were subjected to FEC-PET&4D-CT and cases from July 2017 to June 2020 were analyzed, retrospectively. Cervical exploration with intraoperative PTH-monitoring (IO-PTH) was performed. Imaging results were correlated to intraoperative findings, and short term and one year postoperative follow-up data. RESULTS: From July 2017 to June 2020 in 171 FEC-PET&4D-CTs 159 (92.9%) PAs were suggested. 147 patients already had surgery, FEC-PET&4D-CT accurately localized in 141; false neg. 4, false pos. 2, global sensitivity 0.97; accuracy 0.96, PPV 0.99. All of the 117 patients that already have completed their 12-month postoperative follow up had normal biochemical parameter, i.e., no signs of persisting disease. However, two cases may have a potential for recurrent disease, for a cure rate of at least 98.3%. CONCLUSION: FEC-PET&4D-CT shows unprecedented results regarding the accuracy localizing PAs. The one-year-follow-up data demonstrate a high cure rate. We, therefore, suggest FEC-PET-CT as the relevant diagnostic tool for the localization of PAs when US fails to localize PA, especially after previous surgery to the neck.

Neuromonitoring of the Recurrent Laryngeal Nerve Reduces the Rate of Bilateral Vocal Cord Dysfunction in Planned Bilateral Thyroid Procedures.

PURPOSE: Bilateral vocal cord dysfunction (bVCD) is a rare but feared complication of thyroid surgery. This long term retrospective study determined the effect of intraoperative neuromonitoring (IONM) of the recurrent laryngeal nerve (RLN) during thyroid surgeries with regard to the rate of bVCD and evaluated the frequency as well as the outcome of staged operations. METHODS: Retrospective analysis of prospectively documented data (2000-2019) of a tertiary referral centers' database. IONM started in 2000 and, since 2010, discontinuation of surgery was encouraged in planned bilateral surgeries to prevent bVCD, if non-transient loss of signal (ntLOS) occurred on the first side. Datasets of the most recent 40-month-period were assessed in detail to determine the clinical outcome of unilateral ntLOS in planned bilateral thyroid procedures. RESULTS: Of 22,573 patients, 65 had bVCD (0.288%). The rate of bVCD decreased from 0.44 prior to 2010 to 0.09% after 2010 (p < 0.001, Chi2). Case reviews of the most recent 40 months period identified ntLOS in 113/3115 patients (3.6%, 2.2% NAR), of which 40 ntLOS were recorded during a planned bilateral procedure (n = 952, 2.1% NAR). Of 21 ntLOS occurring on the first side of the bilateral procedure, 15 procedures were stopped, subtotal contralateral resections were performed, and thyroidectomy was continued in 3 patients respectively, with the use of continuous vagal IONM. Eighteen cases of VCD were documented postop, and all but one patient had a full recovery. Seven patients had staged resections after 1 to 18 months (median 4) after the first procedure. CONCLUSION: IONM facilitates reduced postoperative bVCD rates. IONM is, therefore, recommendable in planned bilateral procedures. The rate of non-complete bilateral surgery after intraoperative non-transient LOS was 2%.

A roadmap to neural automatic post-editing: an empirical approach.

In a translation workflow, machine translation (MT) is almost always followed by a human post-editing step, where the raw MT output is corrected to meet required quality standards. To reduce the number of errors human translators need to correct, automatic post-editing (APE) methods have been developed and deployed in such workflows. With the advances in deep learning, neural APE (NPE) systems have outranked more traditional, statistical, ones. However, the plethora of options, variables and settings, as well as the relation between NPE performance and train/test data makes it difficult to select the most suitable approach for a given use case. In this article, we systematically analyse these different parameters with respect to NPE performance. We build an NPE "roadmap" to trace the different decision points and train a set of systems selecting different options through the roadmap. We also propose a novel approach for APE with data augmentation. We then analyse the performance of 15 of these systems and identify the best ones. In fact, the best systems are the ones that follow the newly-proposed method. The work presented in this article follows from a collaborative project between Microsoft and the ADAPT centre. The data provided by Microsoft originates from phrase-based statistical MT (PBSMT) systems employed in production. All tested NPE systems significantly increase the translation quality, proving the effectiveness of neural post-editing in the context of a commercial translation workflow that leverages PBSMT.

Strong bonding of corneal incisions using a noncontact fiber-optic laser soldering method.

Suturing of corneal incisions requires significant skill. We demonstrate a noncontact method that will simplify the bonding process. 5-mm-long penetrating vertical and slanted incisions were made in corneas of eyes, extracted from dead piglets. A fiber-optic laser system was used for laser soldering of the incisions, under close temperature control, using albumin solder. The burst-pressure PB immediately after the soldering was found to be PB ≈ 92 and 875 mmHg, for vertical and slanted incisions, respectively. PB = 875 mmHg is an exceptionally high figure, ≈10 times the clinically acceptable value for sutured incisions. Laser soldering was then performed on penetrating incisions made in the corneas of live healthy piglets, of weight ≈10 Kg. After a healing period, the eyes were extracted, and the corneas were examined by histopathology and by optical coherence tomography. Our method immediately generated watertight and strong bonding without noticeable corneal shape distortion. These results would be beneficial for cataract surgery and for corneal transplantations. The fiber-optic system makes it much easier to bond corneal incisions. In the future, laser soldering could be automated and efficiently used by less experienced surgeons, thereby reducing the workload on the experienced ones.

Robot-assisted laser tissue soldering system.

Fast and reliable incision closure is critical in any surgical intervention. Common solutions are sutures and clips or adhesives, but they all present difficulties. These difficulties are especially pronounced in classical and robot-assisted minimally-invasive interventions. Laser soldering methods present a promising alternative, but their reproducibility is limited. We present a system that combines a previously reported laser soldering system with a robotic system, and demonstrate its feasibility on the incision-closure of ex-vivo mice skins. In this demonstration, we measured tearing forces of ~2.5N, 73% of the tearing force of a mouse skin without an incision. This robot-assisted laser soldering technique has the potential to make laser tissue soldering more reproducible and revolutionize surgical tissue bonding.

Virial coefficients of anisotropic hard solids of revolution: The detailed influence of the particle geometry.

We provide analytical expressions for the second virial coefficients of differently shaped hard solids of revolution in dependence on their aspect ratio. The second virial coefficients of convex hard solids, which are the orientational averages of the mutual excluded volume, are derived from volume, surface, and mean radii of curvature employing the Isihara-Hadwiger theorem. Virial coefficients of both prolate and oblate hard solids of revolution are investigated in dependence on their aspect ratio. The influence of one- and two-dimensional removable singularities of the surface curvature to the mutual excluded volume is analyzed. The virial coefficients of infinitely thin oblate and infinitely long prolate particles are compared, and analytical expressions for their ratios are derived. Beyond their dependence on the aspect ratio, the second virial coefficients are influenced by the detailed geometry of the particles.

140 W peak power laser system tunable in the LWIR.

We present a high peak power rapidly tunable laser system in the long-wave infrared comprising an external-cavity quantum cascade laser (EC-QCL) broadly tunable from 8 to 10 µm and an optical parametric amplifier (OPA) based on quasi phase-matching in orientation-patterned gallium arsenide (OP-GaAs) of fixed grating period. The nonlinear crystal is pumped by a pulsed fiber laser system to achieve efficient amplification in the OPA. Quasi phase-matching remains satisfied when the EC-QCL wavelength is swept from 8 to 10 µm with a crystal of fixed grating period through tuning the pump laser source around 2 µm. The OPA demonstrates parametric amplification from 8 µm to 10 µm and achieves output peak powers up to 140 W with spectral linewidths below 3.5 cm-1. The beam profile quality (M2) remains below 3.4 in both horizontal and vertical directions. Compared to the EC-QCL, the linewidth broadening is attributed to a coupling with the OPA.

Depolarized light scattering from prolate anisotropic particles: The influence of the particle shape on the field autocorrelation function.

We provide a theoretical analysis for the intermediate scattering function typically measured in depolarized dynamic light scattering experiments. We calculate the field autocorrelation function g1(VH)(Q,t) in dependence on the wave vector Q and the time t explicitly in a vertical-horizontal scattering geometry for differently shaped solids of revolution. The shape of prolate cylinders, spherocylinders, spindles, and double cones with variable aspect ratio is expanded in rotational invariants flm(r). By Fourier transform of these expansion coefficients, a formal multipole expansion of the scattering function is obtained, which is used to calculate the weighting coefficients appearing in the depolarized scattering function. In addition to translational and rotational diffusion, especially the translational-rotational coupling of shape-anisotropic objects is considered. From the short-time behavior of the intermediate scattering function, the first cumulants Γ(Q) are calculated. In a depolarized scattering experiment, they deviate from the simple proportionality to Q(2). The coefficients flm(Q) strongly depend on the geometry and aspect ratio of the particles. The time dependence, in addition, is governed by the translational and rotational diffusion tensors, which are calculated by means of bead models for differently shaped particles in dependence on their aspect ratio. Therefore, our analysis shows how details of the particle shape--beyond their aspect ratio--can be determined by a precise scattering experiment. This is of high relevance in understanding smart materials which involve suspensions of anisotropic colloidal particles.