Clinical characteristics and outcomes of patients operated for primary hyperparathyroidism at Tampere University Hospital in 2017-2018.

BACKGROUND AND OBJECTIVE: Studies on the outcomes of parathyroid surgery are scarce. The aim was to report the outcomes and to study the association between pre- and peri-operative information with the outcomes of patients operated for primary hyperparathyroidism. METHODS: This was a retrospective, descriptive study with unselected patients treated surgically for primary hyperparathyroidism from a catchment population of 704,500 in Finland. Data were acquired from the electronic hospital registers based on parathyroid surgery procedure codes between 1 January 2017 and 31 December 2018. Preoperative data, surgical data, preoperative and postoperative laboratory values, histopathological findings, and postoperative clinical data were recorded. RESULTS: During the 2-year study period, 149 patients with primary hyperparathyroidism were treated surgically with a 97% remission rate. Surgical complications included postoperative bleeding in two patients (1%) and vocal cord paralysis in one patient (0.6%). No postoperative infections were reported. Three patients (2%) developed postoperative hypoparathyroidism necessitating the use of alfacalcidol more than 1 month after surgery. Ionized calcium measured 0-1 days after surgery was not statistically significantly associated with remission or postoperative hypoparathyroidism. Serum parathyroid hormone (PTH) assessed 0-1 days postoperatively was associated with persistent disease, but not with postoperative hypoparathyroidism. The histopathological diagnosis was adenoma or hyperplasia in 112 patients (75%), atypical adenoma in 28 patients (19%), and carcinoma in five patients (3%). Patients with parathyroid carcinoma had higher preoperative ionized calcium and PTH values than those with adenoma or hyperplasia. CONCLUSIONS: Most patients who were operated due to primary hyperparathyroidism achieved normocalcemia after surgery, and the frequency of complications was low. Ionized calcium taken 0-1 days after surgery was not associated with remission of hyperparathyroidism or postoperative hypoparathyroidism. High postoperative serum PTH predicted persistent disease.

Patients' Persistent Symptoms, Clinician Demographics, and Geo-Economic Factors Are Associated with Choice of Therapy for Hypothyroidism by European Thyroid Specialists: The "THESIS" Collaboration.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation.

Characteristics of specialists treating hypothyroid patients: the "THESIS" collaborative.

Introduction: Thyroid specialists influence how hypothyroid patients are treated, including patients managed in primary care. Given that physician characteristics influence patient care, this study aimed to explore thyroid specialist profiles and associations with geo-economic factors. Methods: Thyroid specialists from 28 countries were invited to respond to a questionnaire, Treatment of Hypothyroidism in Europe by Specialists: an International Survey (THESIS). Geographic regions were defined according to the United Nations Statistics Division. The national economic status was estimated using World Bank data on the gross national income per capita (GNI per capita). Results: 5,695 valid responses were received (response rate 33·0%). The mean age was 49 years, and 65·0% were female. The proportion of female respondents was lowest in Northern (45·6%) and highest in Eastern Europe (77·2%) (p <0·001). Respondent work volume, university affiliation and private practice differed significantly between countries (p<0·001). Age and GNI per capita were correlated inversely with the proportion of female respondents (p<0·01). GNI per capita was inversely related to the proportion of respondents working exclusively in private practice (p<0·011) and the proportion of respondents who treated >100 patients annually (p<0·01). Discussion: THESIS has demonstrated differences in characteristics of thyroid specialists at national and regional levels, strongly associated with GNI per capita. Hypothyroid patients in middle-income countries are more likely to encounter female thyroid specialists working in private practice, with a high workload, compared to high-income countries. Whether these differences influence the quality of care and patient satisfaction is unknown, but merits further study.

Raman enhancement in bowtie-shaped aperture-particle hybrid nanostructures fabricated with DNA-assisted lithography.

We report on efficient surface-enhanced Raman spectroscopy (SERS) supporting substrates, which are based on deoxyribonucleic acid (DNA)-assisted lithography (DALI) and a layered configuration of materials. In detail, we used nanoscopic DNA origami bowtie templates to form hybrid nanostructures consisting of aligned silver bowtie-shaped particles and apertures of similar shape in a silver film. We hypothesized that this particular geometry could facilitate a four-fold advantage in Raman enhancement compared to common particle-based SERS substrates, and further, we verified these hypotheses experimentally and by finite difference time domain simulations. In summary, our DALI-fabricated hybrid structures suppress the background emission, allow emission predominantly from the areas of high field enhancement, and support additional resonances associated with the nanoscopic apertures. Finally, these nanoapertures also enhance the fields associated with the resonances of the underlying bowtie particles. The versatility and parallel nature of our DNA origami-based nanofabrication scheme and all of the above-mentioned features of the hybrid structures therefore make our optically resonant substrates attractive for various SERS-based applications.

Optical characterization of DNA origami-shaped silver nanoparticles created through biotemplated lithography.

Here, we study optically resonant substrates fabricated using the previously reported BLIN (biotemplated lithography of inorganic nanostructures) technique with single triangle and bowtie DNA origami as templates. We present the first optical characterization of BLIN-fabricated origami-shaped silver nanoparticle patterns on glass surfaces, comprising optical transmission measurements and surface-enhanced Raman spectroscopy. The formed nanoparticle patterns are examined by optical transmission measurements and used for surface enhanced Raman spectroscopy (SERS) of Rhodamine 6G (R6G) dye molecules. Polarization-resolved simulations reveal that the higher SERS enhancement observed for the bowties is primarily due to spectral overlap of the optical resonances with the Raman transitions of R6G. The results manifest the applicability of the BLIN method and substantiate its potential in parallel and high-throughput substrate manufacturing with engineered optical properties. While the results demonstrate the crucial role of the formed nanogaps for SERS, the DNA origami may enable even more complex nanopatterns for various optical applications.

Thermal Control of Plasmonic Surface Lattice Resonances.

Plasmonic metasurfaces exhibiting collective responses known as surface lattice resonances (SLRs) show potential for realizing flat photonic components for wavelength-selective processes, including lasing and optical nonlinearities. However, postfabrication tuning of SLRs remains challenging, limiting the applicability of SLR-based components. Here, we demonstrate how the properties of high quality factor SLRs are easily modified by breaking the symmetry of the nanoparticle surroundings. We break the symmetry by changing the refractive index of the overlying immersion oil by controlling the ambient temperature of the device. We show that a modest temperature change of 10 °C can increase the quality factor of the SLR from 400 to 750. Our results demonstrate accurate and reversible modification of the properties of the investigated SLRs, paving the way toward tunable SLR-based photonic devices. More generally, we show how symmetry breaking of the environment can be utilized for efficient and potentially ultrafast modification of the SLR properties.

Multiply-resonant second-harmonic generation using surface lattice resonances in aluminum metasurfaces.

Nonlinear metamaterials show potential for realizing flat nonlinear optical devices but are generally lacking in terms of achievable conversion efficiencies. Recent work has focused on enhancing nonlinear processes by utilizing high quality factor resonances, such as collective responses known as surface lattice resonances (SLRs) taking place in periodic metal nanoparticle arrays. Here, we investigate how the dispersive nature of SLRs affects the nonlinear responses of SLR-supporting metasurfaces. Particularly, we measure second-harmonic generation from aluminum nanoparticle arrays and demonstrate that by tilting the sample along two orthogonal directions, the sample can be made multiply-resonant for several pump and second-harmonic signal wavelength combinations. Characterized metasurfaces are estimated to exhibit a second-order susceptibility value of 0.40 pm/V, demonstrating aluminum as a potential material for nonlinear metasurfaces.

Quasi-BIC Mode Lasing in a Quadrumer Plasmonic Lattice.

Plasmonic lattices of metal nanoparticles have emerged as an effective platform for strong light-matter coupling, lasing, and Bose-Einstein condensation. However, the full potential of complex unit cell structures has not been exploited. On the other hand, bound states in continuum (BICs) have attracted attention, as they provide topologically protected optical modes with diverging quality factors. Here, we show that quadrumer nanoparticle lattices enable lasing in a quasi-BIC mode with a highly out-of-plane character. By combining theory with polarization-resolved measurements of the emission, we show that the lasing mode has a topological charge. Our analysis reveals that the mode is primarily polarized out-of-plane as a result of the quadrumer structure. The quality factors of the out-of-plane BIC modes of the quadrumer array can be exceedingly high. Our results unveil the power of complex multiparticle unit cells in creating topologically protected high-Q modes in periodic nanostructures.

Coherence Switching with Metamaterials.

We demonstrate, theoretically, how the insertion of an enhanced epsilon-near-zero (EENZ) mirror in a laser cavity grants exceptional control over the coherence properties of the emitted light beam. By exploiting the peculiar sensitivity to polarization of EENZ materials, we achieve superior control over the spatial coherence of the emitted laser light, which can be switched at will between nearly incoherent and fully coherent, solely by means of polarization optics. Our EENZ cavity design is expected to be an efficient, compact, reconfigurable, and easily scalable source of light for illumination and speckle contrast imaging, as well as any other application that benefits from controlled spatial coherence.

Double resonant plasmonic lattices for Raman studies.

We demonstrate radiation induced enhancement of both the in coupling of Raman excitation wavelength and Raman signal in plasmonic nanoparticle lattices. Rectangular nanoparticle lattices show two independently controllable lattice resonances, which we tune to be resonant with both the Raman excitation wavelength and the Raman transitions of rhodamine 6G molecules. We demonstrate that these narrow and intense resonances produced by the nanoparticle lattices allow for Raman transition specific enhancements. The system allows for independent tuning of both resonance conditions, enabling an efficient and versatile platform for Raman studies of various molecules.

Optically induced crossover from weak to strong coupling regime between surface plasmon polaritons and photochromic molecules.

We demonstrate optically induced crossover from a weak to a strong coupling regime in a single photonic system consisting of propagating surface plasmon polaritons (SPPs) on a planar silver film and ultraviolet (UV)-switchable photochromic molecules. A gradual increase is observed in the vacuum Rabi splitting upon increasing UV exposure, along with intriguing behavior, where the reflectivity initially decreases due to increased losses at the weak coupling regime, and then increases due to the emergence of strongly coupled modes and the associated band gap formation at the resonance frequency of the uncoupled states. This work explicitly demonstrates the optical tunability of the degree of hybridization of the SPP and exciton modes, spanning the range from weak to intermediate and finally to the strong coupling regime.

Mirror-based scanning wavefront-folding interferometer for coherence measurements.

We demonstrate a modification to the traditional prism-based wavefront-folding interferometer that allows the measurement of spatial and temporal coherence, free of distortions and diffraction caused by the prism corners. In our modified system, the two prisms of the conventional system are replaced with six mirrors. The whole system is mounted on a linear XY-translation stage, with an additional linear stage in the horizontal arm. This system enables rapid and exact measurement of the full four-dimensional degree of coherence, even for relatively weak signals. The capabilities of our system are demonstrated by measuring the spatial coherence of two inhomogeneous and non-Schell model light sources with distinct characteristics.

Sub-picosecond thermalization dynamics in condensation of strongly coupled lattice plasmons.

Bosonic condensates offer exciting prospects for studies of non-equilibrium quantum dynamics. Understanding the dynamics is particularly challenging in the sub-picosecond timescales typical for room temperature luminous driven-dissipative condensates. Here we combine a lattice of plasmonic nanoparticles with dye molecule solution at the strong coupling regime, and pump the molecules optically. The emitted light reveals three distinct regimes: one-dimensional lasing, incomplete stimulated thermalization, and two-dimensional multimode condensation. The condensate is achieved by matching the thermalization rate with the lattice size and occurs only for pump pulse durations below a critical value. Our results give access to control and monitoring of thermalization processes and condensate formation at sub-picosecond timescale.

Lasing in Ni Nanodisk Arrays.

We report on lasing at visible wavelengths in arrays of ferromagnetic Ni nanodisks overlaid with an organic gain medium. We demonstrate that by placing an organic gain material within the mode volume of the plasmonic nanoparticles both the radiative and, in particular, the high ohmic losses of Ni nanodisk resonances can be compensated. Under increasing pump fluence, the systems exhibit a transition from lattice-modified spontaneous emission to lasing, the latter being characterized by highly directional and sub-nanometer line width emission. By breaking the symmetry of the array, we observe tunable multimode lasing at two wavelengths corresponding to the particle periodicity along the two principal directions of the lattice. Our results are relevant for loss-compensated magnetoplasmonic devices and topological photonics.

Ultrafast Pulse Generation in an Organic Nanoparticle-Array Laser.

Nanoscale coherent light sources offer potentially ultrafast modulation speeds, which could be utilized for novel sensors and optical switches. Plasmonic periodic structures combined with organic gain materials have emerged as promising candidates for such nanolasers. Their plasmonic component provides high intensity and ultrafast nanoscale-confined electric fields, while organic gain materials offer fabrication flexibility and a low acquisition cost. Despite reports on lasing in plasmonic arrays, lasing dynamics in these structures have not been experimentally studied yet. Here we demonstrate, for the first time, an organic dye nanoparticle-array laser with more than a 100 GHz modulation bandwidth. We show that the lasing modulation speed can be tuned by the array parameters. Accelerated dynamics is observed for plasmonic lasing modes at the blue side of the dye emission.

Long-term cardiovascular morbidity and mortality in patients treated for differentiated thyroid cancer.

OBJECTIVES: Thyroid hormone suppression therapy has been widely used in the treatment of thyroid cancer, but concerns have been raised about the cardiovascular risks of this treatment. The objective of this study was to evaluate long-term cardiovascular morbidity and mortality in patients treated for differentiated thyroid cancer (DTC) and to assess the effect of TSH suppression and radioiodine (RAI) treatment on the cardiovascular outcome. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: Patients (n = 901) treated for DTC between 1981 and 2002 at 2 Finnish University hospitals were compared with a randomly chosen reference group (n = 4485) matched for age, gender and the place of residence. Kaplan-Meier and Cox regression analyses were used to estimate the risk of morbidity or death due to different cardiovascular diseases (CVD) after the diagnosis of DTC. RESULTS: Morbidity due to any CVD (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.05-1.28) and due to all arrhythmias (HR 1.25, CI 1.06-1.48) and atrial fibrillation (AF) (HR 1.29, CI 1.06-1.57) was more frequent in the DTC patients than in the controls. The increased cardiovascular morbidity was confined to patients with a mean TSH level below 0.1 mU/L (HR 1.27, CI 1.03-1.58) and to those treated with RAI (HR 1.18, CI 1.05-1.31). Cardiovascular mortality, however, was lower among the patients than the controls (HR 0.73, CI 0.58-0.92), due to a lower mortality from coronary artery disease. CONCLUSIONS: Differentiated thyroid cancer patients have an increased CVD morbidity, which is mostly accountable to AF and to TSH suppression below 0.1 mU/L.

Hybrid plasmonic lattices with tunable magneto-optical activity.

We report on the optical and magneto-optical response of hybrid plasmonic lattices that consist of pure nickel and gold nanoparticles in a checkerboard arrangement. Diffractive far-field coupling between the individual emitters of the lattices results in the excitation of two orthogonal surface lattice resonance modes. Local analyses of the radiation fields indicate that both the nickel and gold nanoparticles contribute to these collective resonances and, thereby, to the magneto-optical activity of the hybrid arrays. The strong effect of noble metal nanoparticles on the magneto-optical response of hybrid lattices opens up new avenues for the realization of sensitive and tunable magneto-plasmonic nanostructures.

Increased risk of certain second primary malignancies in patients treated for well-differentiated thyroid cancer.

BACKGROUND: The objective was to evaluate the incidence of second primary malignancies (SPMs) in thyroid cancer patients compared to age- and gender-matched controls without thyroid cancer from the general population of the same region. METHODS: Tampere and Oulu University Hospitals treated 910 patients with well-differentiated thyroid cancer during 1981-2002. The Finnish cancer registry provided follow-up data for patients and controls (n = 4542) for an average of 16 years. The incidence of invasive malignancies per 10 000 person-years was calculated and compared between patients and controls. The follow-up period ended December 31st, 2011. RESULTS: Young patients <40 years [Rate Ratio (RR) 1.73, p = 0.037] and patients diagnosed since 1996 (RR 1.51, p = 0.029) had an increased incidence of SPMs. Patients had an increased risk of sarcomas and soft tissue tumours (RR 4.37, p = 0.004) and haematological and lymphatic malignancies (RR 1.87, p = 0.035), especially non-Hodgkin lymphomas (RR 2.78, p = 0.035). The overall incidence of SPMs was not statistically higher in patients (109 SPMs/910 patients vs. 500 SPMs/4542 controls, RR 1.12, p = 0.269). Most patients were radioiodine-treated (81 %). The risk of SPMs with low cumulative radioiodine doses was RR 0.94 (≤ 3.7 GBq, p = 0.650) and with high doses RR 1.37 (>3.7 GBq, p = 0.143). Cumulative radioiodine dose increased during the study period. CONCLUSIONS: The overall incidence of SPMs was not higher in patients than in controls. The incidence of SPMs in thyroid carcinoma patients was higher in patients <40 years old and patients diagnosed since 1996. The incidence of sarcomas and lymphomas was higher in patients than in controls.