Miracle-dz/UniFAR-FTUs huggingface dataset:
Microcavity Enhanced Beaming and Magneto-Optical Switching of Light

In this dissertation, we show numerically that a compact structure, consisting of multiple optical microcavities at both the entrance and exit sides of a subwavelength plasmonic slit, can lead to greatly enhanced directional transmission through the slit. The microcavities increase the resonant enhancement of the emission in the normal direction and/or the coupling between free space waves and the slit mode. An optimized structure with two microcavities on both the entrance and exit sides of the slit leads to ∼16 times larger transmission cross section per unit angle in the normal direction compared to the optimized reference slit without microcavities. We then introduce highly-compact resonant-cavity-enhanced magneto-optical switches for metaldielectric-metal (MDM) plasmonic waveguides. The static magnetic field induced asymmetry, which enhances or reduces the coupling between the waveguide and a side-coupled resonator, and the relatively large induced wave vector modulation are used to design a Fabry-Perot cavity magneto-optical switch, consisting of a MDM waveguide side-coupled to two MDM stub resonators. The on and off states correspond to either the presence or the absence of the externally applied static magnetic field. We then investigate the influence of Rabi splitting tuning on the dynamics of strongly coupled J-aggregate/surface plasmon polariton systems. In particular, the Rabi splitting is tuned by modifying the J-aggregate molecule concentration while a polaritonic system is provided by a nanostructure formed by holes array in a golden layer. From the periodic and concentration changes we identify, through numerical and experimental steady-state analyses, the best geometrical configuration for maximizing Rabi splitting, which is then used for transient absorption measurements. We finally study the combination of scanning probe technology with photonic nanojets. Here, by using advanced 3D fabrication techniques we integrate a microbead on an AFM cantilever thus realizing a system to efficiently position nanojets. This fabrication approach is robust and can be exploited in a myriad of applications, ranging from microscopy to Raman spectroscopy. We demonstrate the potential of portable nanojets by imaging different sub-wavelength structures.
SLN124, a GalNAc conjugated 19‐mer siRNA targeting tmprss6, reduces plasma iron and increases hepcidin levels of healthy volunteers

SLN124, an N‐acetylgalactosamine conjugated 19‐mer short interfering RNA, is being developed to treat iron‐loading anemias (including beta‐thalassemia and myelodysplastic syndromes) and myeloproliferative neoplasms (polycythemia vera). Through hepatic targeting and silencing of the TMPRSS6 gene, SLN124 increases endogenous hepcidin synthesis. This is the first clinical report of an siRNA targeting a component of iron homeostasis. This first‐in‐human, phase 1 study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of SLN124 (1.0, 3.0, and 4.5 mg/kg) in healthy volunteers. Twenty‐four participants were randomized in three sequential cohorts of eight subjects, each to receive a single dose of either SLN124 or placebo (6:2 randomization), administered subcutaneously. There were no serious or severe adverse events, or discontinuations due to adverse events, and most treatment‐emergent adverse events were mild, including transient mild injection site reactions, resolving without intervention. SLN124 was rapidly absorbed, with a median tmax of 4–5 h across all treatment groups, and largely eliminated from plasma by 48 h. Plasma concentrations increased in a greater than dose proportional fashion between treatment groups. In all SLN124 groups, a dose‐related effect was observed across iron metabolism markers, and across erythroid markers, SLN124 resulted in increased plasma hepcidin levels, peaking around Day 29, and consequent dose‐related sustained reductions in plasma iron and transferrin saturation with decreased reticulocyte production, MCHC, and MCV. Results suggest duration of action lasting up to 56 days after a single SLN124 dose, on hepcidin and hematological parameters of iron metabolism (serum iron and TSAT).
Necessary optimality conditions for a special class of bilevel programming problems with unique lower level solution

Abstract We consider a bilevel programming problem in Banach spaces whose lower level solution is unique for any choice of the upper level variable. A condition is presented which ensures that the lower level solution mapping is directionally differentiable, and a formula is constructed which can be used to compute this directional derivative. Afterwards, we apply these results in order to obtain first-order necessary optimality conditions for the bilevel programming problem. It is shown that these optimality conditions imply that a certain mathematical program with complementarity constraints in Banach spaces has the optimal solution zero. We state the weak and strong stationarity conditions of this problem as well as corresponding constraint qualifications in order to derive applicable necessary optimality conditions for the original bilevel programming problem. Finally, we use the theory to state new necessary optimality conditions for certain classes of semidefinite bilevel programming problems and present an example in terms of bilevel optimal control.
The mass of the Galactic dark matter halo from ∼9000 LAMOST DR5 K giants

We constrain the mass of the Milky Wayʼs dark matter halo, based on the kinematics of 9627 K giants at Galactocentric distances ranging over 5 kpc < r < 120 kpc drawn from LAMOST DR5. The substructure in this sample has been identified and removed carefully to enable construction of the underlying line-of-sight velocity dispersion at different radii from the Galactic center. We interpret the radial profile of the line-of-sight velocity dispersion using a spherical Jeans equation under the assumptions of anisotropy/isotropy and that radial velocity dispersion is approximately equal to line-of-sight velocity dispersion σ r ( r ) ≈ σ los ( r ) . If we assume that the dark matter halo follows an NFW profile and the stellar halo is isotropic (β = 0), then σ los ( r ) can be directly used to estimate the virial mass of the Galactic dark matter halo, M vir = 1.08 − 0.14 + 0.17 × 10 12 M ⊙ , and concentration parameter c = 18.5 − 2.9 + 3.6 . In case that the stellar halo is anisotropic, we cannot avoid differentiation of sparse velocity dispersions according to the Jeans equation, which may cause overestimation of the mass. We use an isotropic case to test and find that d ln ( σ los 2 ( r ) ) / d ln r overestimates the virial mass by 15% but within 1-σ error. We use d ln ( σ los 2 ( r ) ) / d ln r to fit the NFW profile and get M vir = 1.11 − 0.20 + 0.24 × 10 12 M ⊙ and c = 13.8 − 2.2 + 3.0 in case of β = 0.3.
Short and Long-Term Outcomes in Hirschsprung Disease: Are the Syndrome-Associated Patients Really Doing Worse?

Introduction: Given the lack of data to help caregivers in the follow-up of Hirschsprung disease (HD), this study aimed to compare the functional outcomes of isolated Hirschsprung disease (I-HD) to syndrome-associated Hirschsprung disease (SA-HD) at 1, 3, 5, and 10 years. Methods: A retrospective chart review of patients diagnosed with HD between January 1990 and May 2021 at our pediatric center was performed to collect data on patient characteristics, investigations, and treatments. Ninety-five patients were identified, of whom 76 were included in the study. SA-HD is defined as a syndrome known to be associated with HD or cognitive impairment. Results: Patient characteristics were comparable between groups (P > 0.05). There were 52 patients with I-HD and 24 with SA-HD. The patients median age was 9 days at diagnosis and 1.5 month at surgery. SA-HD patients became bowel continent at a significantly older age (mean age 8.43 vs 4.94 years, P = 0.0471) and received more bowel continence medications. At 5 years, SA-HD patients requiring ≥2 medications for bowel continence represented 54.5% versus 11.1% of I-HD patients (P = 0.009). Lastly, SA-HD patients had urinary incontinence at a significantly older age (P = 0.0136, 5 years). Conclusion: Clinicians should be aware that SA-HD patients are more prone to bladder dysfunction and became bowel continent at an older age than I-HD patients. They need more and prolonged bowel management medications, and other important complications need to be addressed in patient care. These results should prompt a longer follow-up period for these patients, especially in SA-HD.
Major Increase in Incidence of Pediatric ACL Reconstructions From 2005 to 2021: A Study From the Norwegian Knee Ligament Register

Background: The incidence of pediatric and adolescent anterior cruciate ligament reconstruction (ACLR) is increasing in several countries. It is uncertain whether this trend applies to countries that traditionally prefer an initial nonoperative treatment approach whenever possible, like Norway. Nationwide, long-term patient-reported outcomes and revision rates after ACLR in the pediatric population are also lacking. Purpose: To determine the incidence of pediatric ACLR in Norway since 2005, as well as to detect trends in surgical details and describe patient-reported outcomes up to 10 years after ACLR. Study Design: Descriptive cohort study. Methods: This study is based on prospectively collected data on girls ≤14 years and boys ≤16 years, registered in the Norwegian Knee Ligament Register at the time of their primary ACLR, between 2005 and 2021. The main outcome was the incidence of ACLR, adjusted to the corresponding population numbers for each year. The time trend was analyzed by comparing the mean of the first and last 3-year period (2005-2007 and 2019-2021). Patient-reported outcomes were assessed using the Knee injury and Osteoarthritis Outcome Score preoperatively and at 2, 5, and 10 years postoperatively. Results: A total of 1476 patients (1484 cases) were included, with a mean follow-up of 8.1 years (range, 1-17). The incidence of pediatric ACLRs per 100,000 population increased from 18 to 26, which corresponds to an increase of 40% for boys and 55% for girls. Concurrent meniscal procedures increased significantly from 45% to 62%, and the proportion of meniscal repairs increased from 19% to 43% when comparing the first and last time period. The mean Knee injury and Osteoarthritis Outcome Score values for the Sport and Recreation and Quality of Life subscales were between 72 and 75 at the 2-, 5- and 10-year follow-up. The 5-year revision rate was 9.9%. Conclusion: There was a major increase in incidence of pediatric ACLR in Norway during the study period. There was a shift in the approach to concomitant meniscal procedures from resection to repair, with more than a doubling of the proportion of meniscal repairs. Patient-reported outcomes revealed long-lasting reduced knee function.
Statistical inference for highly non-linear dynamical models in ecology and epidemiology

In this work we illustrate some of the challenges posed by highly non-linear stochastic models to statistical inference. In particular, we demonstrate how the likelihood function, which is not directly available when hidden states are present, can become highly multimodal under near-chaotic dynamics and low process noise. We identify two classes of methods that are relevant in this context: the first includes Particle Markov Chain Monte Carlo, Iterated Filtering and Parameters Cascading, the second Approximate Bayesian Computation and Synthetic Likelihood. After showing that the two groups are differently affected by the issue of multimodality, we compare their performance on a group of simple stochastic maps. We then select Particle Marginal Metropolis Hastings and Synthetic likelihood as representatives of each class, and we compare them on two complex models, using both real and simulated datasets. The result of the comparison is a cautionary tale, suggesting the joint use of both approaches in order to achieve robust conclusions.
Investigation of flame behavior and dynamics prior to lean blowout in a combustor with varying mixedness of reactants for the early detection of lean blowout

Lean blowout is one of the major challenges faced when the gas turbine combustors are operated with lean fuel–air mixture to meet the emission norm. We experimentally study the flame behavior and the dynamics of heat release rate fluctuations during a transition to lean blowout. The study comprising flame visualization and estimating several measures to predict lean blowout for both premixed and partially premixed flames (using fuel ports F1 to F5) in a swirl stabilized dump combustor. To that end, we acquire unsteady heat release rate in terms of CH* chemiluminescence obtained through a photomultiplier tube with a narrow band-pass filter. For evaluating different statistical measures, we use National Instrument Labview software while acquiring the heat release rate oscillations. For premixed and partially premixed flames, such measures and the flame behavior show a different and, in some cases, even opposite trends as lean blowout is approached. However, in both premixed and partially premixed flames, the mean and root mean square values of the heat release rate fluctuation decrease as we decrease the equivalence ratio. Further, we show that the value of mean frequency calculated using Hilbert transform of the heat release rate fluctuations is a good indicator of lean blowout. Apart from the early prediction of lean blowout, different statistics of heat release rate oscillations, such as kurtosis and skewness, are shown to identify only the occurrence of lean blowout for premixed (F1 and F2) and flames with lower level of premixing (F3). They are not useful for the flames with high levels of unmixedness like F4 and F5. On the other side, probability density function is seen useful for both premixed and partially premixed flames. In short, we present the relative importance of different measures stated earlier for the identification and early prediction of lean blowout for both premixed and partially premixed flames.
Feasibility of Using the Global Tales Protocol to Elicit Personal Narratives in 10-year-Old Children in Ireland

Introduction: This small-scale study explored the feasibility of the Global TALES protocol in eliciting personal narratives in typically developing monolingual Irish children, using the online Zoom platform. We investigated children’s performance on measures of productivity (total number of utterances; total number of words) and syntactic complexity (MLU in words). We also documented the topics children talked about in response to the six emotion-based prompts contained in the Global TALES protocol. Methods: Nineteen typically developing children (6 male, 13 female), aged between 10.0 and 10.11 years produced personal narratives in response to the Global TALES protocol. Given COVID-19 pandemic-related public health restrictions, the language samples were elicited using Zoom. All stories were transcribed and analysed using Systematic Analysis of Language Transcripts software. Qualitative content analysis was used to code the topics of the children’s stories. Results: Sixteen participants responded to all prompts. One participant only responded to three of the six prompts. The prompt that was least successful in eliciting a response was the “problem” prompt; 15.7% (n = 3) of the children did not provide a response to this prompt. On average, children produced 40 utterances, although individual variability was high. On average, MLU was 8.7, ranging from 6 to 11. Children’s topics closely resembled those reported in the Global TALES feasibility study despite the fact, the current study took place during the COVID-19 pandemic. The most frequent topics were related to family (events, illnesses, relationships, siblings) and finding or fixing something. Conclusion: The Global TALES protocol was successful in eliciting personal narratives from 10-year-old Irish English-speaking children. Future larger scale studies are now needed to investigate if the results generalise to the wider Irish population with a view to create local benchmarks of personal narrative performance.
Contribution of active commuting to and from school to device‐measured physical activity levels in young people: A systematic review and meta‐analysis

To analyze the contribution of active commuting to and from school (ACS) to device‐measured light physical activity (LPA) and moderate‐to‐vigorous physical activity (MVPA) levels in young people aged 6 to 18 years old, as well as, in both trip directions (i.e., home‐school, school‐home).
3D Tibial Acceleration and Consideration of 3D Angular Motion Using IMUs on Peak Tibial Acceleration and Impulse in Running

ABSTRACT Purpose Peak tibial acceleration (PTA) is defined as the peak acceleration occurring shortly after initial contact, often used as an indirect measure of tibial load. As the tibia is a rotating segment around the ankle, angular velocity and angular acceleration should be included in PTA. This study aimed to quantify three-dimensional tibial acceleration components over two different sensor locations and three running speeds, to get a better understanding of the influence of centripetal and tangential accelerations on PTA typically measured in running. Furthermore, it explores tibial impulse as an alternative surrogate measure for tibial load. Methods Fifteen participants ran 90 s on a treadmill at 2.8, 3.3, and 3.9 m·s−1, with inertial measurement units (IMUs) located distally and proximally on the tibia. Results Without the inclusion of rotational accelerations and gravity, no significant difference was found between axial PTA between both IMU locations, whereas in the tangential sagittal plane axis, there was a significant difference. Inclusion of rotational accelerations and gravity resulted in similar PTA estimates at the ankle for both IMU locations and caused a significant difference between PTA based on the distal IMU and PTA at the ankle. The impulse showed more consistent results between the proximal and distal IMU locations compared with axial PTA. Conclusions Rotational acceleration of the tibia during stance differently impacted PTA measured proximally and distally at the tibia, indicating that rotational acceleration and gravity should be included in PTA estimates. Furthermore, peak acceleration values (such as PTA) are not always reliable when using IMUs because of inconsistent PTA proximally compared with distally on an individual level. Instead, impulse seems to be a more consistent surrogate measure for the tibial load.
Immunoglobulin G4 in eosinophilic esophagitis: Immune complex formation and correlation with disease activity

Recent studies have shown deposition of immunoglobulin G4 (IgG4) and food proteins in the esophageal mucosa of eosinophilic esophagitis (EoE) patients. Our aims were to assess whether co‐localization of IgG4 and major cow's milk proteins (CMPs) was associated with EoE disease activity and to investigate the proteins enriched in proximity to IgG4 deposits.
Clinical and dopaminergic imaging characteristics of the FARPRESTO cohort of trial‐ready idiopathic rapid eye movement sleep behavior patients

Idiopathic/isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is considered the prodromal stage of alpha‐synucleinopathies. Thus, iRBD patients are the ideal target for disease‐modifying therapy. The risk FActoRs PREdictive of phenoconversion in iRBD Italian STudy (FARPRESTO) is an ongoing Italian database aimed at identifying risk factors of phenoconversion, and eventually to ease clinical trial enrollment of well‐characterized subjects.
Speech and language markers of neurodegeneration: a call for global equity.

In the field of neurodegeneration, speech and language assessments are useful for diagnosing aphasic syndromes and for characterizing other disorders. As a complement to classic tests, scalable and low-cost digital tools can capture relevant anomalies automatically, potentially supporting the quest for globally equitable markers of brain health. However, this promise remains unfulfilled due to limited linguistic diversity in scientific works and clinical instruments. Here we argue for cross-linguistic research as a core strategy to counter this problem. First, we survey the contributions of linguistic assessments in the study of primary progressive aphasia and the three most prevalent neurodegenerative disorders worldwide -Alzheimer's disease, Parkinson's disease, and behavioral variant frontotemporal dementia. Second, we address two forms of linguistic unfairness in the literature: the neglect of most of the world's 7,000 languages and the preponderance of English-speaking cohorts. Third, we review studies showing that linguistic dysfunctions in a given disorder may vary depending on the patient's language and that English speakers offer a suboptimal benchmark for other language groups. Finally, we highlight different approaches, tools, and initiatives for cross-linguistic research, identifying core challenges for their deployment. Overall, we seek to inspire timely actions to counter a looming source of inequity in behavioral neurology.
Simulation-based Value-at-Risk for nonlinear portfolios

Value-at-risk (VaR) has been playing the role of a standard risk measure since its introduction. In practice, the delta-normal approach is usually adopted to approximate the VaR of portfolios with option positions. Its effectiveness, however, substantially diminishes when the portfolios concerned involve a high dimension of derivative positions with nonlinear payoffs; lack of closed form pricing solution for these potentially highly correlated, American-style derivatives further complicate the problem. This paper proposes a generic simulation-based algorithm for VaR estimation that can be easily applied to any existing procedures. Our proposal leverages cross-sectional information and applies variable selection techniques to simplify the existing simulation framework. Asymptotic properties of the new approach demonstrate faster convergence due to the additional model selection component introduced. We have also performed sets of numerical results that verify the effectiveness of our approach in comparison with some existing strategies.
Nonlinear multilevel joint model for individual lesion kinetics and survival to characterize intra‐individual heterogeneity in patients with advanced cancer

In advanced cancer patients, tumor burden is calculated using the sum of the longest diameters (SLD) of the target lesions, a measure that lumps all lesions together and ignores intra‐patient heterogeneity. Here, we used a rich dataset of 342 metastatic bladder cancer patients treated with a novel immunotherapy agent to develop a Bayesian multilevel joint model that can quantify heterogeneity in lesion dynamics and measure their impact on survival. Using a nonlinear model of tumor growth inhibition, we estimated that dynamics differed greatly among lesions, and inter‐lesion variability accounted for 21% and 28% of the total variance in tumor shrinkage and treatment effect duration, respectively. Next, we investigated the impact of individual lesion dynamics on survival. Lesions located in the liver and in the bladder had twice as much impact on the instantaneous risk of death compared to those located in the lung or the lymph nodes. Finally, we evaluated the utility of individual lesion follow‐up for dynamic predictions. Consistent with results at the population level, the individual lesion model outperformed a model relying only on SLD, especially at early landmark times and in patients with liver or bladder target lesions. Our results show that an individual lesion model can characterize the heterogeneity in tumor dynamics and its impact on survival in advanced cancer patients.