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The PTOLEMY transverse drift filter is a new concept to enable precision analysis of the energy spectrum of electrons near the tritium beta-decay endpoint. This paper details the implementation and optimization methods for successful operation of the filter. We present the first demonstrator that produces the required magnetic field properties with an iron return-flux magnet. Two methods for the setting of filter electrode voltages are detailed. The challenges of low-energy electron transport in cases of low field are discussed, such as the growth of the cyclotron radius with decreasing magnetic field, which puts a ceiling on filter performance relative to fixed filter dimensions. Additionally, low pitch angle trajectories are dominated by motion parallel to the magnetic field lines and introduce non-adiabatic conditions and curvature drift. To minimize these effects and maximize electron acceptance into the filter, we present a three-potential-well design to simultaneously drain the parallel and transverse kinetic energies throughout the length of the filter. These optimizations are shown, in simulation, to achieve low-energy electron transport from a 1 T iron core (or 3 T superconducting) starting field with initial kinetic energy of 18.6 keV drained to, 29 pages, 25 figures

Clothing damage analysis is an important tool for forensic investigations and, even it is a niche field, it is gaining interest. Moreover, the attention is shifting from evaluating just the “biological” traces found on the clothes to the modifications that clothes themselves undergo in the context of a specific traumatic dynamic. The Authors analyze a case of the investigation on a hole in the jacket worn by the victim when he was attacked, performed through optical microscope and morphological and elemental SEM/EDX analysis, to determine the origin of this texture damage to verify a witness story.

Objective To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma. Clinicaltrials.gov Identifier NCT02250651. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-021-01624-9.

Strategies to enhance the induction of high magnitude T cell responses through vaccination are urgently needed. Major histocompatibility complex (MHC) class II–associated invariant chain (Ii) plays a critical role in antigen presentation, forming MHC class II peptide complexes for the generation of CD4+ T cell responses. Preclinical studies evaluating the fusion of Ii to antigens encoded in vector delivery systems have shown that this strategy may enhance T cell immune responses to the encoded antigen. We now assess this strategy in humans, using chimpanzee adenovirus 3 and modified vaccinia Ankara vectors encoding human Ii fused to the nonstructural (NS) antigens of hepatitis C virus (HCV) in a heterologous prime/boost regimen. Vaccination was well tolerated and enhanced the peak magnitude, breadth, and proliferative capacity of anti-HCV T cell responses compared to non-Ii vaccines in humans. Very high frequencies of HCV-specific T cells were elicited in humans. Polyfunctional HCV-specific CD8+ and CD4+ responses were induced with up to 30% of CD3+CD8+ cells targeting single HCV epitopes; these were mostly effector memory cells with a high proportion expressing T cell activation and cytolytic markers. No volunteers developed anti-Ii T cell or antibody responses. Using a mouse model and in vitro experiments, we show that Ii fused to NS increases HCV immune responses through enhanced ubiquitination and proteasomal degradation. This strategy could be used to develop more potent HCV vaccines that may contribute to the HCV elimination targets and paves the way for developing class II Ii vaccines against cancer and other infections.

The paper exemplifies the application of the methodology involving historic and architectural research complemented by HBIM and operational modal testing in the structural modelling of a heritage palace, the Galleria degli Antichi in the historic town of Sabbioneta (Italy), included in the UNESCO World Heritage list since 2008. This monumental building was built in the 16th century. Full details on the history of the building and the information obtained in the non destructive survey are given in the paper. The good knowledge of the structural geometry, along with the complete inspection carried out and the large number of identified vibration modes, allowed to establish a numerical model of the monumental building for a first quantitative assessment of its structural condition.

Selected results from the investigation program of a historic R.C. bridge are presented in the paper. The bridge, crossing the Adda river between the Municipalities of Brivio and Cisano Bergamasco, consists of three tied arch spans, about 44.0 m length each, and represents a crucial node for the vehicular traffic of the region. After a maintenance intervention performed on one pier, the local Authorities committed to Politecnico di Milano an extensive investigation including: (i) documentary research and review of the bridge history; (ii) visual inspection and geometric survey of each span; (iii) full-scale load tests and ambient vibration tests; (iv) FE modelling of each span and validation of the numerical models (through comparison with the available experimental results) and (v) structural assessment of the bridge in its present condition. After a concise review of the bridge history, the paper summarizes the complete results of the experimental tests performed on one span (visual inspection, geometric survey, full-scale load tests and dynamic tests) as well as the development of numerical models.

Introduction: The Patient-Centered Medical Home (PCMH) model aims to transform primary care by delivering high-quality, safe, comprehensive, patient-centered, and accessible care. Few evaluations of PCMH curricula for internal medicine residency programs have been published. The objective of this study was to develop and implement a PCMH curriculum, a new PCMH rotation, and to redesign the resident ambulatory care clinic and private primary care practices of the residency program. Effects were evaluated by examining: 1) residents’ attitudes towards primary care and PCMH, 2) residents’ skills in communicating and managing care and 3) patients’ assessments of practice accessibility. Methods: From 2010-2015, we implemented a multi-modal program combining practice redesign, a lecture series, a one-month PCMH rotation, clinical activities, a quality improvement project, and self-reflection at an academic community hospital, a Federally Qualified Health Center (FQHC) and faculty practice offices to internal medic ne residents. Evaluations were conducted through resident self-assessment, patient assessment of practice accessibility, and objective structured clinical examinations. Results: Twelve residents [41% (12/29)] completed all components of the curriculum. After the rotation, residents thought their PCMH skills improved in 13 components of PCMH (all domains: p

Multi-armed bandit problems are receiving a great deal of attention because they adequately formalize the exploration-exploitation trade-offs arising in several industrially relevant applications, such as online advertisement and, more generally, recommendation systems. In many cases, however, these applications have a strong social component, whose integration in the bandit algorithm could lead to a dramatic performance increase. For instance, we may want to serve content to a group of users by taking advantage of an underlying network of social relationships among them. In this paper, we introduce novel algorithmic approaches to the solution of such networked bandit problems. More specifically, we design and analyze a global strategy which allocates a bandit algorithm to each network node (user) and allows it to "share" signals (contexts and payoffs) with the neghboring nodes. We then derive two more scalable variants of this strategy based on different ways of clustering the graph nodes. We experimentally compare the algorithm and its variants to state-of-the-art methods for contextual bandits that do not use the relational information. Our experiments, carried out on synthetic and real-world datasets, show a marked increase in prediction performance obtained by exploiting the network structure., Comment: NIPS 2013

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We reduce ranking, as measured by the Area Under the Receiver Operating Characteristic Curve (AUC), to binary classification. The core theorem shows that a binary classification regret of r on the induced binary problem implies an AUC regret of at most 2r. This is a large improvement over approaches such as ordering according to regressed scores, which have a regret transform of $r \mapsto nr$ where n is the number of elements.