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The Dependent Object Type (DOT) calculus was designed to put Scala on a sound basis, but while DOT relies on structural subtyping, Scala is a fundamentally class-based language. This impedance mismatch means that a proof of DOT soundness by itself is not enough to declare a particular subset of the language as sound. While a few examples of Scala snippets have been manually translated into DOT, no systematic compilation scheme has been presented so far. In this thesis we develop a series of calculi of increasing complexity to model Scala and present a type-preserving compilation scheme from each of these calculus into DOT. Along the way, we develop some necessary extensions to DOT., 153 pages, officially accepted doctoral thesis

Cilj rada je bio prokomentirati sigurnosne probleme u razmjeni DNS upita, proučiti načine zaštite (protokoli DoT i DoH), objasniti njihove prednosti i mane te na kraju demonstrirati korištenje protokola DoT u programu Imunes. The goal of this task was to comment on security related problems during DNS query exchanges, elaborate on different types of protection (protocols DoT and DoH), explain their pros and cons and demonstrate the use of protocol DoT in the program Imunes.

В статье определяется статус точки в системе графических средств английского языка, рассматриваются функционально-коммуникативные характеристики данного пунктуационного знака. На материале современной английской литературы анализируются примеры использования точки, определяется её роль в актуализации смысловых и эмоциональных коннотаций, а также рассматриваются случаи, когда точка, сохраняя высокую позиционно-содержательную значимость, служит выразителем авторского стиля автора. В статье приводится анализ использования точки в качестве внутреннего знака препинания, формирующего орфографический облик слова. В статье также устанавливается спектр функций и свойств точки как графического конвенционального знака, применяемого в формальных языках., The article defines the status of a full stop in the system of graphic means of the English language, considers the functional and communicative characteristics of this punctuation mark. Using the material of modern English literature, the examples of the use of the full stop are analyzed and its role in the actualization of semantic and emotional connotations is determined, as well as cases when the dot, having a high positional and content significance, is one of the means of manifesting the author’s individuality and originality of the writer’s style. The article provides an analysis of the use of the period as an internal punctuation mark that forms the spelling appearance of a word. The article also establishes the range of functions and properties of the dot as a graphic conventional sign used in formal languages.

U Teoriji prirodne filozofije Ruđera Boškovića, dinamika materije opisana je krivuljom sila, privlačnih ili odbojnih – ovisno o udaljenostima centara sila. Na velikim udaljenostima krivulja sila manifestira se slično Newtonovoj gravitaciji. Gravitacija je integrativna za vidljivi svemir, ali ne i za hipotetičko mnoštvo svemira za koje je moguće da paralelno postoje razdvojeni odbojnom silom, što je usporedivo sa suvremenim konceptom tamne energije. U konceptu kontinuiranih sila u diskontinuiranoj materiji, Faraday prepoznaje ideju o dinamičkom elektromagnetskom polju, koju je dovršio Maxwell, a kasnije Einstein predviđa postojanje gravitacijskih valova, nedavno i detektiranih (2015. – 2017., project LIGO). Valna priroda materije realnog prostor-vremena nalazi se u Boškovićevu modelu na maloj skali krivulje sila, a atomsko-korpuskularna dinamika klasične mehanike na velikoj skali., In Roger Boscovich’s Theory of Natural Philosophy, the dynamics of matter is described by the curve of forces, either attractive or repulsive – depending on the distances of the centres of forces. At great distances, the curve of forces is manifested similar to Newton’s gravitation. The gravitation is integrative for the visible universe, but not for the hypothetical multitude of universes that possibly parallelly exist separated by a repulsive force, comparable to the contemporary concept of the dark energy. In the concept of continuous forces in a discontinuous matter, Faraday recognises the idea of a dynamic electromagnetic field, completed by Maxwell, while Einstein later predicted the existence of gravitational waves recently detected (2015 – 2017, LIGO project). The wave-nature of real space-time matter is found in Boscovich’s model at the small scale of the curve of forces, while the atomic-corpuscular dynamics of classical mechanics is found at the large scale.

Red dot basal cell carcinoma is a distinctive clinical subtype of basal cell carcinoma. It has been reported in eight individuals with a male to female ratio of 1:1; and the patients’ ages ranged from 50 to 74 years. All patients had prior history of actinic keratoses and basal cell carcinoma. In addition, some patients also had prior squamous cell carcinoma, malignant melanoma, and/or dysplastic nevus. The tumor was usually of recent onset, asymptomatic, and on sun-exposed skin. It was most commonly located on the nose (five patients); other sites were the upper lip, the mid back, or thigh—each in one patient. The red dot basal cell carcinoma was solitary and small—usually 4 mm or less in diameter. It typically presented as a red macule or papule; however, it sometimes appeared as a flesh-colored or pink to light-red papule with a bright-red central area. Microscopic features showed basaloid tumor cells (arranged as either nodular aggregates or superficial buds or both). In the central portion of the lesion, there was a proliferation of erythrocyte-containing vascular spaces between the epidermis and the neoplasm. The basal cell carcinoma pathology subtype was either nodular and superficial (three patients), nodular (two patients), or superficial (one patient). The clinical differential diagnosis of red dot basal cell carcinoma included not only benign vascular lesions (such as hemangioma and telangiectasia) but also inflammatory conditions and adnexal tumors. Other basaloid cell neoplasms were in the pathologic differential diagnosis. The pathogenesis of red dot basal cell carcinoma is similar to that of other basal cell carcinoma clinical subtypes. Mohs surgery is the treatment of choice for red dot basal cell carcinomas. Red dot basal cell carcinoma has two categories of biologic behavior based on the ratio of the postoperative wound size as compared with the size of the preoperative tumor: nonaggressive (for which the ratio was 5:1 or less for three patients) and aggressive (for which the ratio was greater than 12:1 for three patients). There was no recurrence of the red dot basal cell carcinoma after treatment. In conclusion, the incidence of red dot basal cell carcinoma—a unique morphologic variant of basal cell carcinoma—may be higher than suggested by the number of reported patients with this basal cell carcinoma subtype.

International audience; Nanostructured organic templates originating from self-assembled block copolymers (BCPs) can be converted into inorganic nanostructures by sequential infiltration synthesis (SIS). This capability is particularly relevant within the framework of advanced lithographic applications because of the exploitation of the BCP-based nanostructures as hard masks. In this work, Al2O3 dot and antidot arrays were synthesized by sequential infiltration of trimethylaluminum and water precursors into perpendicularly oriented cylinder-forming poly(styrene-block-methyl methacrylate) (PS-b-PMMA) BCP thin films. The mechanism governing the effective incorporation of Al2O3 into the PMMA component of the BCP thin films was investigated evaluating the evolution of the lateral and vertical dimensions of Al2O3 dot and antidot arrays as a function of the SIS cycle number. The not-reactive PS component and the PS/PMMA interface in self-assembled PS-b-PMMA thin films result in additional paths for diffusion and supplementary surfaces for sorption of precursor molecules, respectively. Thus, the mass uptake of Al2O3 into the PMMA block of self-assembled PS-b-PMMA thin films is higher than that in pure PMMA thin films.

La pratique de la corbeille de mariage est une tradition ancienne dont les origines remontent à l’Antiquité. Composée, comme le trousseau, d’objets de parure ou aidant à se parer, elle était constituée par le mari et/ou sa famille, puis offerte à la future épouse, afin de rétablir le déséquilibre financier engendré par la dot. Son état d’obligation morale plus que d’obligation juridique a rendu sa pratique particulièrement mouvante et difficilement saisissable pour l’historien. L’étude de son évolution, notamment à partir des objets qui la composent, montre cependant un tournant au xviiie siècle, qu’illustre parfaitement la corbeille de mariage que Louis-Joseph de Bourbon Condé offrit à Charlotte Godefried de Rohan-Soubise en 1753. On la trouve décrite dans les registres de comptabilité de la famille Condé, et la nature des pièces qui la composent, leurs formes, leurs matériaux, leurs décors, leurs prix, l’identité de leurs fabricants ou fournisseurs soulignent le processus généralisé de normalisation de la pratique de cette tradition, reflet d’une société hiérarchisée à la recherche de codes. Il s’agira ainsi, au travers de l’étude des objets de cette corbeille princière et de leur inscription dans l’histoire de cette tradition, de mettre en exergue les mécanismes de normalisation qui se mettent en place dès la fin du xviie siècle, d’en comprendre les raisons mais également de percevoir le rôle d’indicateur social de ces objets de parure et leur fonction de support à une sémiologie symbolique conformiste. The practice of giving wedding presents to the bride is an old tradition that goes back to Antiquity. Composed, like the trousseau, of articles of finery or beauty accessories, it was composed by the husband and/or his family and then offered to the future wife in order to restore the financial imbalance induced by the dowry. More of a moral than a legal obligation, this practice is particularly unstable and, for historians, difficult to grasp. However, the study of its evolution, especially that of its constitutive objects, reveals the existence of a turning point during the eighteenth century, of which the wedding presents given by Louis-Joseph de Bourbon Condé to Charlotte Godefried de Rohan-Soubise in 1753 are a perfect illustration. The nature of the pieces, their shapes, materials, decorations, prices, the identity of their designers or suppliers are all detailed in the accounts registers of the Condé family. This description shows that the practice was becoming increasingly normalized, and reflects a hierarchical society searching for codes. On the one hand, this article will underline, through the study of these princely wedding presents and their link with the history of this tradition, the mechanism of normalization which appears at the end of the seventeenth century, and on the other hand it will explain the reasons for these changes, and bring out the role of social markers with which these objects were invested, and their function as reinforcements of a symbolic and conformist semiology.

La programmation modulaire est un principe de développement consistant à séparer une application en composants plus petits appelés modules. Le langage de programmation OCaml contient un langage de modules qui permet aux développeurs d'utiliser la programmation modulaire. Dans ce langage de modules, un module est un ensemble de types et de valeurs, les types des valeurs pouvant dépendre des types dénis dans le même module. OCaml étant un langage fortement typé, les modules possèdent également un type, appelé dans ce cas signature. Bien que les modules soient bien intégrés dans OCaml, une distinction est faite entre le langage de base, contenant les types dits primitifs, comme les entiers, les chaînes de caractères ou les fonctions, et le langage de modules. En par- ticulier, le terme foncteur est employé à la place de fonction pour parler des fonctions prenant un module en paramètre et en renvoyant un autre. D'un autre côté, dans les types de base d'OCaml se trouvent les enregistrements. Ces derniers peuvent être interprétés comme des listes de couples (label, valeur), et ressemblent aux modules. Cependant, les deux diérences majeures sont la possibilité de dénir des types dans un module ainsi que d'avoir des champs mutuellement dépendants. Ce mémoire vise à donner, dans un premier temps et après avoir déni les notions nécessaires, un calcul typé, DOT, dans lequel le langage de modules est confondu avec le langage de base grâce aux enregistrements. Cette unication implique que les modules (et, in ne, les foncteurs) sont des citoyens de première classe, c'est-à-dire que nous pouvons les manipuler comme tout autre terme, ce qui n'est pas le cas actuellement en OCaml. Dans un second temps, ce travail propose un algorithme de typage et de sous-typage, une implémentation OCaml de ces der- niers ainsi qu'un langage de surface qui nous permet d'écrire des programmes DOT.

Introduction: Updated international guidelines recommend the use of a two-step algorithm (glutamate dehydrogenase [GDH] or nucleic-acid amplification test [NAAT] plus toxin) rather than NAAT alone for the diagnosis of Clostridioides difficile (formerly Clostridium difficile) infections. The goal of our project was to evaluate the impact of a new bundle on the rate of hospital-acquired C. difficile infections (CDIs), hospital-acquired CDI standardized infection ratio (SIR), antibiotic days of therapy (DOT), and financial cost. Materials and Methods: The new bundle was implemented in April 2018. This bundle was implemented across five hospitals in Catholic Health Initiatives (CHI) Texas Division. The bundle included a switch from NAAT to a two-step process (GDH and toxin). We placed the new test in an order panel which included enteric isolation and required indications for C. difficile testing. We used quarterly data pre- and post-intervention to calculate SIR and DOT. Results: In the pre-intervention period, 15.5% of the total 3513 C. difficile NAAT was positive. In the post-intervention period, 5.7% of a total of 2845 GDH and toxin assays was positive for both GDH and toxin (P < 0.0001). SIR, which adjusts for denominator and change in testing methodology, also dropped from 1.02 to 0.43. The estimated cost associated with positive C. difficile cases dropped from 1,932,150 USD to 1,113,800 USD with an estimated yearly cost saving of 794,150 USD. Compliance with enteric isolation improved from 73.1% to 92.5% (P = 0.008). Conclusion: The new testing bundle led to a marked reduction in hospital-acquired CDI and unnecessary treatment, reduction in C. difficile testing, an increase in compliance with enteric isolation, and significant cost savings.

Cooper pair splitting (CPS) is a way to create spatially separated, entangled electron pairs. To this day, CPS is often identified in experiments as a spatial current correlation. However, such correlations can arise even in the absence of CPS, when a quantum dot is strongly coupled to the superconductor, and a subgap Shiba state is formed. Here, we present a detailed experimental characterization of those spatial current correlations, as the tunnel barrier strength between the quantum dot and the neighboring normal electrode is tuned. The correlation of the non-local signal and the barrier strength reveals a competition between CPS and the non-local probing of the Shiba state. We describe our experiment with a simple transport model, and obtain the tunnel couplings of our device by fitting the model's prediction to the measured conductance correlation curve. Furthermore, we use our theory to extract the contribution of CPS to the non-local signal., 12 pages, 3 figures

Polkadot, és un projecte de codi obert, desenvolupat per la Fundació Web3, llançat al Maig del 2020. És tracta d'un protocol compartit que busca la possibilitat que les blockchains puguin operar de manera conjunta, és a dir, busca crear una xarxa unificada, formada per l'agrupació de diferents blockchains. Es tracta d'una cadena multi-chain, escalable, col·laborativa i heterogènia. Està formada per dues components claus, el primer anomenat cadena de relleus, en anglès relay chain el qual la seva funció és interactuar amb cadenes fragmentades, que s'executen de forma paral·lela, conegudes com a parachains. Polkadot is an open source project, developed by the Web3 Foundation, launched in May 2020. It is a shared protocol that seeks the possibility that blockchains can operate together, that is, it seeks to create a unified network, formed by the grouping of different blockchains. It is a multi-chain chain, scalable, collaborative and heterogeneous. It consists of two key components, the first called relay chain, whose function is to interact with fragmented strings, which run parallelly, known as parachains. Polkadot, es un proyecto de código abierto, desarrollado por la Fundación Web3, lanzado en Mayo de 2020. Se trata de un protocolo compartido que busca la posibilidad de que las blockchains puedan operar de manera conjunta, es decir, busca crear una red unificada, formada por la agrupación de diferentes blockchains. Se trata de una cadena multi-chain, escalable, colaborativa y heterogénea. Está formada por dos componentes claves, el primero llamado cadena de relieves, en inglés relay chain el cual su función es interactuar con cadenas fragmentadas, que se ejecutan de forma paralela, conocidas como parachains.

In recent years, demand for scintillation detectors with high time resolution (better than 100 ps) has emerged in high-energy physics and medical imaging applications. In particular, time of flight positron emission tomography (TOF-PET) can greatly benefit from increasing time resolution of scintillators, which leads to the increase of signal-to-noise ratio, decrease of patient dose, and achievement of the superior spatial resolution of PET images. Currently, extensive research of various types of materials is carried out to achieve the best time resolution. In this review, the recent progress of various approaches is summarized and scintillation compounds with the best temporal characteristics are first reviewed. The review presents the physical processes causing fast luminescence in inorganic and organic materials. Special attention is paid to nanocomposites which belong to a new perspective class of scintillating materials, consisting of a plastic matrix, inorganic nanocrystalline fillers, and organic or inorganic luminescence activators and shifters. The main features and functions of all parts of existing and prospective nanocomposite scintillators are also discussed. A number of currently created and investigated nanocomposite materials with various compounds and structures are reviewed. © 2021 Elsevier B.V. Eesti Teadusagentuur, ETAg: PRG111, PRG629; European Regional Development Fund, ERDF: 2014-2020.4.01.15–0011, TK141 Authors thank Minobrnauki project FEUZ-2020-0059 and Estonian Research Council (grants PRG629 and PRG111 ) for financial support. Authors are also grateful for partial support from the European Regional Development Fund (DoRA Pluss program) and the ERDF funding in Estonia granted to the Center of Excellence TK141 “ Advanced materials and high-technology devices for sustainable energetics, sensorics and nanoelectronics ” (project No. 2014-2020.4.01.15–0011 ).

Highlights • The Legionella genus contains nine core effectors. • Three Legionella pneumophila core effectors are required for intracellular growth. • The Legionella genus core effectors display functional conservation among orthologs. • One Legionella core effector requires an accessory protein to perform its function., The intracellular pathogen Legionella pneumophila, as well as other Legionella species, utilize the Icm/Dot type-IV secretion system to translocate an exceptionally large and diverse repertoire of effectors into their host cells. However, only nine core effectors were found to be present in all analyzed Legionella species. In this study, we investigated the core effectors, and used intracellular growth complementation to determine whether orthologs of core effectors perform the same function in different Legionella species. We found that three out of the nine L. pneumophila core effectors are required for maximal intracellular growth. Examination of orthologous core effectors from four Legionella species spread over the Legionella phylogenetic tree revealed that most of them perform the same function. Nevertheless, some of the orthologs of the core effector LegA3 did not complement the L. pneumophila legA3 deletion mutant for intracellular growth. LegA3 is encoded as part of an operon together with another gene, which we named legA3C, encoding a non-translocated protein. We found that LegA3 and LegA3C physically interact with each other, are both required for maximal intracellular growth, and the LegA3-LegA3C orthologous pairs from all the Legionella species examined fully complement the L. pneumophila legA3 deletion mutant for intracellular growth. Our results indicate that the Legionella core effectors orthologs generally perform the same function and establish that LegA3 requires LegA3C to fulfill its conserved function., Graphical abstract Image, graphical abstract

Structures consisting of a single Si nanodot buried within an insulating nanometric SiO2 layer stacked between two Si layers show promising properties for room temperature operational single-electron transistors. Moreover, such structures are highly compatible with modern complementary metal-oxide semiconductor technologies. Metastable SiOx phase separates into a Si nanodot and insulating, homogeneous SiO2 during annealing, providing a solid path towards the desired structure. However, achieving the necessary amount of excessive Si, dissolved in the SiO2 for correct concentrations of SiOx, remains a technological challenge. In this work, we investigate ion-induced atom mixing in pre-built Si/SiO2/Si nanopillars, which is considered to be a technologically promising way to produce the necessary concentrations of spatially confined SiOx in a controlled manner. During the high-fluence ion irradiation, we notice a significant shortening of the nanopillar and preferential loss of O atoms. Both sputtering and nanoscale ion hammering are found to be the cause of the deformation. The ion-hammering effect on nanoscale is explained by multiple small displacements, strongly enhanced after the nanopillar was rendered completely amorphous. The methods presented here can be used to determine the ion-fluence threshold for sufficient atom mixing in spatially confined regions before the large structural deformations are formed.

Gui de Dampierre, Count of Flanders and Namur, had sixteen children from two different spouses, Mathilde de Béthune and later Isabelle de Luxembourg. Insofar as this important offspring fully served the diplomatic aims of Gui de Dampierre, the term “ matrimonial policy” takes on its full meaning. The one he implemented extended along three axes : from the outset, to fight against the influence of the Avesnes in Lotharingia and to ensure that the Prince-Bishopricof Liege was surrounded by allied princes ; later, to find allies in his desire to emancipate himself from the interventions of Philip iv ; and throughout his life, to find rich heirs, to comfortably settle his numerous descendants without squandering his own property., Gui de Dampierre, comte de Flandre et de Namur, eut seize enfants, issus de deux épouses différentes, Mathilde de Béthune, puis Isabelle de Luxembourg. Dans la mesure où cette importante progéniture servit pleinement les visées diplomatiques de Gui de Dampierre, le terme «politique matrimoniale » prend alors tout son sens. Celle qu’il mit en oeuvre s’étendit sur trois axes : d’emblée, lutter contre l’influence des Avesnes en Lotharingie et s’assurer de l’encerclement de la principauté épiscopale de Liège par des princes alliés ; plus tardivement, trouver des alliés dans sa volonté d’émancipation des interventions du roi de France Philippe IV ; et tout au long de sa vie, dénicher de riches héritières, pour installer confortablement sa nombreuse descendance, sans pour autant dilapider son propre patrimoine foncier., Gwijde van Dampierre, graaf van Vlaanderen en Namen, had zestien kinderen. Ze kwamen van twee verschillende echtgenoten, Mathilde van Béthune en later Isabella van Luxemburg. Dit belangrijke nageslacht ondersteunde de diplomatieke doelwitten van Gwijde van Dampierre. Daarom is de term ‘ huwelijksbeleid’ hier echt zinvol. Dat van Gwijde de Dampierre bestond uit drie hoofdlijnen : allereerst de invloed van de Avesnes in Lotharingen te verminderen en de omsluiting van het Prinsbisdom Luik door middel van geallieerde prinsen te verzekeren ; dan, verbonden te sluiten om zich van de interventies van Filips iv te emanciperen ; last but not least, rijke erfgenamen te vinden, om zijn talrijke nazaten een comfortabele financiële toekomst te bieden zodat zijn onroerend goed ongeschonden blijft., Wymmersch Guillaume. La politique matrimoniale de Gui de Dampierre, comte de Flandre (1252-1305) et de Namur (1263-1298). In: Revue belge de philologie et d'histoire, tome 98, fasc. 4, 2020. Histoire – Geschiedenis. pp. 957-1014.

India announced its first National Telecom Policy in 1994 and since then its telecommunications Industry has witnessed tremendous growth. At a teledensity of 89.92% (TRAI 2019), it is the second largest telecom market in the world. The policy maker, Department of Telecommunication (DoT) and the regulator, Telecom Regulatory Authority of India (TRAI) have taken several initiatives to ensure affordable services to telecom users. TRAI also drives initiatives to increase the level of awareness about telecom industry among users. To analyse impact of these initiatives by TRAI and DoT, this study presents an objective assessment of user's awareness and their assessment of affordability of telecom services. A structured questionnaire is used to collect data by surveying a sample of 408 telecom users. It was found that half of the respondents were aware of DoT; more than half were aware of the regulator TRAI and Indian governments vision for telecommunications and 85% of survey respondents found telecom services affordable. The level of affordability varied across gender, age group and education levels. Through regression analysis, the study found that awareness about telecom industry influences users' assessment of service affordability. Hence, TRAI and DoT should take actions to increase the level of awareness, which will improve users' perception of affordability and may lead to increased adoption of telecom services. In addition, it is suggested that affordability of female users can be addressed through customized tariff plan and schemes.

Cilj ovog diplomskog rada je opisati eksperimentalnu implementaciju te demonstraciju klijentske i poslužiteljske aplikacije za protokol DNS preko dedicirane QUIC veze. DoQ je novi protokol koji bi trebao posve zamijeniti dosadašnje sigurne verzije protokola DNS pritom pružajući bolje performanse. Razvijena programska podrška podržava pokretanje klijenta, stub (proxy) te rekurzivnog razlučitelja za protokol DoQ i DNS preko UDP-a. U radu se analizira učinkovitost DoQ-a u odnosu na istu funkcionalnost ostvarenu preko UDP-a te se razmatraju poboljšanja koja DoQ donosi u odnosu na druge protokole. The goal of this master thesis is to describe proof-of-concept code implementation and demonstration of client-server application for protocol DNS over dedicated QUIC connections. DoQ is a new protocol that aims to replace current secure versions of DNS protocol while offering better overall performance. Developed program supports running DoQ and DNS over UDP client, stub (proxy) and recursive resolver. In this thesis, efficiency of DoQ is analyzed in regard to DNS over UDP and improvements over other similar protocols are considered.

Background According to the Centers for Disease Control and Prevention, patients admitted to the hospital are commonly discharged on antibiotic therapy with prolonged courses of therapy, which contributes to excessive antibiotic exposure and adverse events. The purpose of this study was to evaluate total antibiotic duration of therapy at hospital discharge at Indiana University Health Arnett, White Memorial, and Frankfort hospitals. Methods A multicenter, retrospective electronic health record review was conducted from 1 January to 30 June 2019. Patients were included if they were at least 18 years of age, began antibiotic therapy while admitted, and continued antibiotic therapy at hospital discharge for 1 of the following indications: skin/soft tissue infection (SSTI), urinary tract infection (UTI), community-acquired pneumonia (CAP), or acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The number of days of therapy (DOT) of each inpatient and outpatient antibiotic prescribed was collected to calculate the total DOT, which was utilized to determine the appropriateness of the duration of therapy. Results Of the 547 patients included, 233 patients (42.6%) had CAP, 120 (21.9%) had UTI, 101 (18.5%) had SSTI, and 93 (17%) had AECOPD. The median duration of antibiotic therapy across all indications was 9 days (interquartile range [IQR], 7–11). Median duration for CAP was 9 days (IQR, 7–10), AECOPD was 7 days (IQR, 5–9), UTI was 8 days (IQR, 6–10), and SSTI was 12 days (IQR, 10–14). Conclusions Excess antimicrobial duration at hospital discharge represents an unmet need of antimicrobial stewardship programs., We reviewed the total duration of antibiotic therapy in 547 patients at the time of hospital discharge. When combining inpatient and outpatient days of therapy, antibiotic duration for common types of infection is excessive compared with recommendations from clinical practice guidelines.

Dans le présent article, nous avons insisté sur la dimension interprétative des données ethnographiques visuelles recueillies auprès des acteurs concernant leurs rôles dans le rite du mariage pour pouvoir sauvegarder et transmettre le contenu de ce patrimoine. Ces témoignages et observations filmés rendent compte des différents registres des savoirs locaux : gloses typologiques sur le comportement, sociabilité familiale, répertoires des usages immémoriaux en matière de gestion d’un rite de passage central de la vie sociale. Les lexiques spécialisés et la sagesse qui s’en dégagent, ainsi que les photos prises lors de l’évènement contribuent à mieux appréhender les particularités de ce savoir local sur une question éminemment anthropologique. Le système axiologique sous-jacent vise la reproduction de l’ordre rural dont une des caractéristiques principales est la relation verticale entre les aînés avec toutes les catégories des cadets sociaux. In this paper, the interpretative dimension of ethnographic visual data collected among actors regarding their roles in the rite of the wedding was privileged in order to safeguard and to hand the content of that heritage on. Those information and visual materials collected reflect different cultural contents of local knowledge: typological notes on the behaviour, from the perspective of family sociability, the register of immemorial usages regarding the management of a rite of passage central to social life. The specialised glossaries, wisdom that emerges and photos taken during the event also contribute to understanding the particularities of that local knowledge on a very anthropological issue. The underlying axiological system aims to the reproduction of rural order, one of the key aspects of which is the vertical relationship between elderly people and all the categories of people considered like socially younger. En este artículo, hemos hecho hincapié en la dimensión interpretativa de los datos etnográficos visuales recogidos sobre los actores en relación con su papel en el rito matrimonial para salvaguardar y transmitir el contenido de este patrimonio. Estos testimonios y observaciones filmadas dan cuenta de los diferentes registros del conocimiento local: glosas tipológicas sobre el comportamiento, la sociabilidad familiar y repertorios de prácticas inmemoriales en la gestión de un rito de paso central en la vida social. Los léxicos especializados y la sabiduría que se desprende de ellos, así como las fotos tomadas durante el evento, contribuyen a una mejor comprensión de las particularidades de este conocimiento local sobre una cuestión eminentemente antropológica. El sistema axiológico subyacente tiene como objetivo la reproducción del orden rural, una de cuyas características principales es la relación vertical entre los mayores y todas las categorías de cadetes sociales.

Background Drug resistant tuberculosis (DR-TB) infringes substantial burden in terms of longer treatment duration, morbidity and mortality. Timely identification of patients at risks of DR-TB will aid individualized treatment. Current study was aimed to ascertain several factors associated with DR-TB among patients attending a tertiary care hospital. Methods This retrospective study was conducted among patients with confirmed diagnosis of DR-TB and drug susceptible TB (DS-TB) seeking medical care from a tertiary care hospital during 2014–2019. The types of DR-TB included were rifampicin resistant tuberculosis (RR-TB), Multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). Appropriate statistical methods were implied to evaluate the factors associated with DR-TB. Results Out of 580 patients, DS-TB was diagnosed in 198 (34.1%) patients while DR-TB was present in 382 patients. Of resistance cases, RR-TB, MDR-TB and XDR-TB were diagnosed in 176 (30.3%), 195 (33.6%) and 11 (1.9%) patients, respectively. Significant differences (P < 0.05) in demographics and clinico-laboratory characteristics were observed between patients with DS-TB and DR-TB. Logistic regression analysis revealed age ≤38 years (OR: 2.5), single marital status (OR: 11.1), tobacco use (OR: 2.9), previous treatment (OR: 19.2), treatment failure (OR: 9.2) and cavity on chest X-ray (OR: 30.1) as independent risk factors for MDR-TB. However, XDR-TB was independently associated with age group of ≤38 years (OR: 13.6), students (OR: 13.0), previous treatment (OR: 12.5), cavity on chest X-ray (OR: 59.6). The independent risk factors associated with RR-TB are age ≤38 years (OR: 2.8), females (OR: 5.7), unemployed (OR: 41.5), treatment failure (OR: 4.9), previous treatment (OR: 38.2) and cavity on chest X-ray (OR: 4.3). ROC curve analysis accentuate the excellent predictive accuracy of all logistic regression models as shown by AUC (0.968, P < 0.001) for MDR-TB, AUC (0.941, P < 0.001) for XDR-TB and AUC (0.962, P < 0.001) for RR-TB. Conclusions Current study demonstrates a sizeable extent of resistant cases among pulmonary TB patients. This study presaged significant risk of DR-TB among females, young adults, unemployed, smokers, patients with previous treatment failure and cavitation on chest X-ray. Timely identification of high risk patients will give pronounced advantages regarding appropriate choices of prevention, treatment and disease control.

Thyroid cancer is usually diagnosed by ultrasound imaging and fine-needle aspiration biopsy. However, diagnosis of follicular thyroid carcinomas (FTC) is difficult because FTC lacks nuclear atypia and a consensus on histological interpretation. Diffuse optical tomography (DOT) offers the potential to diagnose FTC because it can measure tumor hypoxia, while image reconstruction of the thyroid is still challenging mainly due to the complex anatomical features of the neck. In this study, we attempted to solve this issue by creating a finite element model of the human neck excluding the trachea (a void region). By reconstruction of the absorption coefficients at three wavelengths, 3D tissue oxygen saturation maps of the human thyroid are obtained for the first time by DOT.

Surface nanopatterning induced by ion beam irradiation (IBI) has emerged as an effective nanostructuring technique since it induces patterns on large areas of a wide variety of materials, in short time, and at low cost. Nowadays, two main subfields can be distinguished within IBI nanopatterning depending on the irrelevant or relevant role played by the surface composition. In this review, we give an up-dated account of the progress reached when surface composition plays a relevant role, with a main focus on IBI surface patterning with simultaneous co-deposition of foreign atoms. In addition, we also review the advances in IBI of compound surfaces as well as IBI systems where the ion employed is not a noble gas species. In particular, for the IBI with concurrent metal co-deposition, we detail the chronological evolution of these studies because it helps us to clarify some contradictory early reports. We describe the main patterns obtained with this technique as a function of the foreign atom deposition pathway, also focusing in those systematic studies that have contributed to identify the main mechanisms leading to the surface pattern formation and development. Likewise, we explain the main theoretical models aimed at describing these nanopattern formation processes. Finally, we address two main special features of the patterns induced by this technique, namely, the enhanced pattern ordering and the possibility to produce both morphological and chemical patterns. This work was supported by Ministerio de Economía, Industria y Competitividad (MINECO, Spain), Agencia Estatal de Investigación (AEI, Spain), and Fondo Europeo de Desarrollo Regional (FEDER, EU) through Grant No. PGC2018-094763-B-I00, and by Comunidad de Madrid (Spain) under the Multiannual Agreement with UC3M in the line of Excellence of University Professors, No. EPUC3M23, in the context of the V Plan Regional de Investigación Científica e Innovación Tecnológica (PRICIT), as well as under the TRANSNANOAVANSENS program (S2018-NMT-4349).

En la documentació notarial del segle xiv trobem un tipus de contracte matrimonial minoritari a la Catalunya Vella, però prou freqüent i estès a les comarques gironines: l’agermanament entre esposos, pacte que estableix la societat de béns del matrimoni. Presentem les característiques principals d’aquest contracte, les seves possibilitats per a la història econòmica i algunes reflexions sobre el seu paper en la Catalunya del mas i l’hereu., In the 14th century public notarial archives, it appears a minority kind of marriage contract that is also common and widespread in the Northern area of Catalonia: the brotherhood between husband and wife, that sets partnership of possessions inside the marriage. Here we show the contract’s main characteristics, its possibilities for economic history and few reflections about the role it plays in the Catalonia of mas and unique heir (hereu).

Paule Payen épouse Hugues de Lionne en 1645 ; elle est la fille d’un riche financier parisien et apporte une immense dot de 500 000 livres tournois, il est d’extraction noble entame une prometteuse carrière dans le gouvernement de Louis XIV. Les fondations économiques et sociales du couple semblent donc solides. Cependant, l’année 1671 précipite le sort des deux époux : Paule Payen est publiquement accusée d’adultère par Hugues de Lionne. L’itinéraire qu’elle emprunte à partir de cette date est celui d’une déchéance globale, voire totale, au sens où tous les domaines de son existence sont attaqués. En effet, elle connaît un déclassement aux accents multiples : individuel, conjugal, familial, économique et social. Cet article vise à observer l’ampleur et les caractéristiques de cette déchéance, mais également à en comprendre les ressorts profonds. En effet, l’accusation d’adultère interroge puisqu’elle ne repose que sur la parole de l’époux et a pour conséquence directe de priver la dame de sa liberté et de ses droits sur sa dot, au profit de son mari. Or, plusieurs actions de Lionne ont fragilisé la position économique et sociale de sa famille : la lecture du contexte global qui entoure la chute de Paule Payen permet d’envisager l’existence d’une stratégie dont elle serait la victime. En effet, sa déchéance permet à ses héritiers de bâtir un rempart contre leur propre déclassement économique et social par la captation de la dot maternelle. Par conséquent, dans la société d’Ancien Régime, le poids du groupe, du corps, de la famille conjugale et de la lignée peut venir briser les destins individuels et un déclassement personnel peut masquer la crainte d’un déclassement lignager aux conséquences désastreuses. Paule Payen and Hugues de Lionne are married in 1645; she is the daughter of a wealthy financial expert, he is a nobleman engaged in the Louis XIV’s government. Therefore, the couple’s economic and social background is favorable. Nevertheless, in 1671 Hugues de Lionne accuses Paule Payen of adultery and her fate is sealed. From there, she knows a deep social decline: she’s no longer viewed as a good wife, a good mother, a respectable woman and she lose her liberty and her fortune. The purpose of this paper is to examine the reasons, the expansion and the implications of this social decline. The accusation of adultery is doubtful: it is a very practical way to keep the dowry away from the wife without additional explanations. The de Lionne family knows some financial troubles in the 1670’s, so the accusation of adultery looks like a strategy. Paule Payen as individual offers a too little counterweight to the family’s interests. In this way, the social decline of an individual seems to be used to prevent the total decline of the family line.

Extending nanostructures into the third dimension has become a major research avenue in modern magnetism, superconductivity and spintronics, because of geometry-, curvature- and topology-induced phenomena. Here, we introduce Co-Fe nanovolcanoes-nanodisks overlaid by nanorings-as purpose-engineered 3D architectures for nanomagnonics, fabricated by focused electron beam induced deposition. We use both perpendicular spin-wave resonance measurements and micromagnetic simulations to demonstrate that the rings encircling the volcano craters harbor the highest-frequency eigenmodes, while the lower-frequency eigenmodes are concentrated within the volcano crater, due to the non-uniformity of the internal magnetic field. By varying the crater diameter, we demonstrate the deliberate tuning of higher-frequency eigenmodes without affecting the lowest-frequency mode. Thereby, the extension of 2D nanodisks into the third dimension allows one to engineer their lowest eigenfrequency by using 3D nanovolcanoes with 30% smaller footprints. The presented nanovolcanoes can be viewed as multi-mode microwave resonators and 3D building blocks for nanomagnonics., Comment: 5 pages, 4 figures

Although the security benefits of domain name encryption technologies such as DNS over TLS (DoT), DNS over HTTPS (DoH), and Encrypted Client Hello (ECH) are clear, their positive impact on user privacy is weakened by--the still exposed--IP address information. However, content delivery networks, DNS-based load balancing, co-hosting of different websites on the same server, and IP address churn, all contribute towards making domain-IP mappings unstable, and prevent straightforward IP-based browsing tracking. In this paper, we show that this instability is not a roadblock (assuming a universal DoT/DoH and ECH deployment), by introducing an IP-based website fingerprinting technique that allows a network-level observer to identify at scale the website a user visits. Our technique exploits the complex structure of most websites, which load resources from several domains besides their primary one. Using the generated fingerprints of more than 200K websites studied, we could successfully identify 84% of them when observing solely destination IP addresses. The accuracy rate increases to 92% for popular websites, and 95% for popular and sensitive websites. We also evaluated the robustness of the generated fingerprints over time, and demonstrate that they are still effective at successfully identifying about 70% of the tested websites after two months. We conclude by discussing strategies for website owners and hosting providers towards hindering IP-based website fingerprinting and maximizing the privacy benefits offered by DoT/DoH and ECH., Comment: To appear in Proceedings of the 21st Privacy Enhancing Technologies Symposium (PETS 2021)

In magnetic resonance imaging, the application of a strong diffusion weighting suppresses the signal contributions from the less diffusion-restricted constituents of the brain's white matter, thus enabling the estimation of the transverse relaxation time T2 that arises from the more diffusion-restricted constituents such as the axons. However, the presence of cell nuclei and vacuoles can confound the estimation of the axonal T2, as diffusion within those structures is also restricted, causing the corresponding signal to survive the strong diffusion weighting. We devise an estimator of the axonal T2 based on the directional spherical variance of the strongly diffusion-weighted signal. The spherical variance T2 estimates are insensitive to the presence of isotropic contributions to the signal like those provided by cell nuclei and vacuoles. We show that with a strong diffusion weighting these estimates differ from those obtained using the directional spherical mean of the signal which contains both axonal and isotropically-restricted contributions. Our findings hint at the presence of an MRI-visible isotropically-restricted contribution to the signal in the white matter ex vivo fixed tissue (monkey) at 7T, and do not allow us to discard such a possibility also for in vivo human data collected with a clinical 3T system.

As quantum processors grow in complexity, attention is moving to the scaling prospects of the entire quantum computing system, including the classical support hardware. Recent results in high-fidelity control of individual spins in silicon, combined with demonstrations that these qubits can be manufactured in a similar fashion to field-effect transistors, create an opportunity to leverage the know-how of the complementary metal-oxide-semiconductor (CMOS) industry to address the scaling challenge at a system level. Here we review the prospects of scaling silicon-based quantum computing using CMOS technology. We consider the concept of a quantum computing system, which we decompose into three distinct layers-the quantum layer, the quantum-classical interface and the classical layer-and explore the challenges involved in their development, as well their assembly into an architecture. Silicon offers the enticing possibility that all layers can, in principle, be manufactured using CMOS technology, creating an opportunity to move from distributed quantum-classical systems to integrated quantum computing solutions., This Review examines the scaling prospects of quantum computing systems based on silicon spin technology and how the different layers of such a computer could benefit from using complementary metal-oxide-semiconductor (CMOS) technology.

Aquest treball presenta els dots com a font que permet escatir els nivells de riquesa i de desigualtats econòmiques entre l’artesanat barceloní d’època moderna. Partint de l’anàlisi de gairebé 160 capítols matrimonials (1501-1777), amb participació de diferents oficis, realitzem una proposta de categorització dels sectors socioproductius. Analitzem principalment el grup de terrissers, prenent-lo com a exemple per exposar l’evolució de les quantitats dotals i la seva categorització social. A través dels diferents oficis d’aquest sector professional, hom podrà evidenciar les desigualtats internes de riquesa i de poder adquisitiu., Wealth and inequality indicators in the craft world of Barcelona in the 16th and 17th centuries. Dowries and families in the pottery guildsThis paper presents dowries as a source for estimiting the levels of wealth and economic inequality among the Barcelona artisans of modern times. To do this, starting from the analysis of almost 160 prenuptial agreements (1501–1777), with the participation of different trades, a proposal is made for the categorization of unions. The main analysis looks at the potters’ guild, taking it as an example to explain the evolution of dowry amounts and their social categorization. Internal inequalities in terms of wealth and purchasing power can be shown through the different crafts of this guild., Indicadores de riqueza y de desigualdades en el mundo artesanal de Barcelona en los siglos XVI y XVII. Dotes y familias en los gremios de alfareríaEste trabajo presenta las dotes como la fuente que permite percibir los niveles de riqueza y de desigualdades económicas entre el artesanado barcelonés de época moderna. Partiendo del análisis de casi ciento sesenta capitulaciones matrimoniales (1501-1777), con la participación de diferentes oficios, realizamos una propuesta de categorización de los sectores productivos. Analizamos principalmente el grupo de alfareros, tomándolos como ejemplo para exponer la evolución de las cuantías dotales y su categorización social. A través de los diferentes oficios de este grupo productivo se podrán evidenciar las desigualdades internas en lo que se refiere a riqueza y a poder adquisitivo.

В статье сформулированы возможности систем обучения, основные проблемы при проектировании системы дистанционного обучения студентов: выбор платформы для создания системы; размещение учебного материала; контроль учебного процесса; администрирование ресурса; возможность расширения и модернизации системы. The article formulates the possibilities of learning systems, the main problems in the design of a distance learning system for students: choosing a platform for creating a system; placement of educational material; control of the educational process; resource administration; the possibility of expanding and upgrading the system.

Cette thèse analyse les causes profondes du sous-développement et des inégalités de genre en Afrique Sub-Saharienne. Le premier chapitre teste empiriquement l’hypothèse de Engels (1884) selon laquelle l’origine des inégalités de genre en Afrique serait la domestication historique des bovins. Pour résoudre les problèmes de biais d’endogenéités dans le choix de la domestication des bovins, j’adopte la stratégie des variables instrumentales en exploitant les facteurs géo-climatiques qui prédisent les terres les plus adaptées pour l’élevage des bovins. Les résultats des analyses montrent que les sociétés qui ont historiquement domestiquées les bovins ont eu plus d’inégalités de genre qui persistent jusqu’aujourd’hui. Le deuxième chapitre est co-écrit avec Raphael Godefroy et Joshua Lewis. Dans ce chapitre, nous analysons les effets de court et long termes de la grande peste bovine survenue en Afrique dans les années 1890. Nous utilisons la méthode des doubles différences combinant les différences entre les terres favorables pour l’élevage des bovins et les conditions climatiques contemporaines. Notre étude montre que les sociétés les plus touchées par la peste bovine sont moins peuplés et ont moins de bovins, de plus les descendants de ces sociétés sont aujourd’hui les plus pauvres. Le dernier chapitre analyse comment le genre des frères et sœurs influence l’âge au mariage des femmes. Les analyses basées sur le sexe du deuxième enfant révèlent que les femmes qui ont une petite sœur se marient plus tôt, ont plus d’enfants et sont moins éduquées. Les effets sont plus accentués dans les groupes ethniques qui utilisent la dot comme norme culturelle du mariage., This dissertation investigates the deep roots of differences in gender roles and development across societies in Sub-Saharan Africa. Chapter 1 examines the deep origins of differences in gender roles in Africa. I test empirically Engels (1884) hypothesis, that the origin of differences in gender roles in Africa was the historical domestication of cattle. To address potential endogeneity in historical cattle adoption, I adopt an instrumental variables approach that leverages geo-climatic factors affecting the suitability of lands for cattle-raising. I find empirical support for Engels (1884) hypothesis. Further, the results show that these differences in gender roles have persisted to present day. In chapter 2, which is co-authored with Raphael Godefroy and Joshua Lewis, we study the short- and long-run consequences of the 1890s African Rinderpest Epizoodic. We adopt a difference-in-differences strategy that combines differences across ethnic homelands in cattle-suitability with contemporaneous local drought conditions to identify ethnic groups that were more or less exposed to the outbreak. We find that the societies exposed to rinderpest experienced relative decreases in cattle-ownership in the decades after the outbreak. We uncover large relative long-run decreases in wealth among descendants of affected ethnic groups. These persistent economic losses appear to be partially driven by distressed migration. In chapter 3, I investigate how sibling gender composition affects women’s transition to first marriage in sub-Saharan Africa. To address potential endogeneity in the final sibling gender composition, I exploit the random assignment of the second child’s gender in household with at least two children. I find that female with a younger sister get married younger, with negative consequences for her education and literacy. The effects are stronger within countries that traditionally pay bride price at marriage.

Trois types de mariage (africain, civil, chrétien), trois célébrations (en famille, à la mairie, à l’Église), trois officiants différents (anciens des familles de futurs mariés, officier de l’État civil, prêtre), trois consentements (en famille, à la mairie, à l’Église), trois droits (coutumier, civil, canonique), deux registres (à la mairie, à l’Église), trois types de dépenses financières (en famille, à la mairie, à l’Église), trois enquêtes prénuptiales (en famille, à la mairie, à l’Église) pour une même personne baptisée catholique africaine pour être reconnue comme mariée par l’Église catholique. Cela semble trop demander pour une action réputée libre par excellence. La personne baptisée est exclue, temporairement ou définitivement, de l’accès aux autres sacrements ou de certains services paroissiaux, dès l’instant où elle célèbre le mariage africain, considéré comme un péché public et comme du concubinage, depuis le début de l’évangélisation de l’Afrique subsaharienne. Seule la célébration du mariage chrétien lui permet de se réconcilier avec Dieu et avec l’Église. Préoccupé par cette situation, l’épiscopat africain appela, au Synode de 1994, à des recherches approfondies, pouvant permettre d’éviter la superposition des trois types de mariage et émit le vœu d’en avoir qu’un. Jusqu’aujourd’hui, les solutions initiées n’y ont jamais remédié. Basées sur les conditions de fond et de forme, les célébrations du mariage religieux au Québec et du mariage africain en République démocratique du Congo produisent des effets civils. Notre étude s’en est inspirée pour proposer une compréhension du mariage fondée sur la théologie baptismale qui incorpore la personne à l’Église, la régénère en enfant de Dieu et la configure au Christ, par un caractère indélébile. Par ce caractère juridique baptismal, la célébration du mariage africain produirait des effets religieux, ce qui ne rendrait plus nécessaire la célébration du mariage dit « chrétien » pour des baptisés catholiques africains. Pour une mise en œuvre réussie de cette perspective, nous considérons indispensable la contribution du pouvoir civil., Three types of marriage (African, civil, Christian), three celebrations (in family, at the town hall, the Church), three different officiants (old of the families of future grooms, registrar, priest), three consents (in family, at the town hall, the Church), three rights (usual, civil, canonical), two registers (with the town hall, the Church), three types of financial expenditure (in family, with the town hall, the Church), three premarital investigations (in family, at the town hall, the Church) for the same African catholic person baptized to be recognized as married by Catholic church. That seems too much to require for an action considered free par excellence. The baptized person is excluded, temporarily or definitively, of the access to the other sacraments or certain parochial services, as of the moment when it celebrates the African marriage, considered a public sin and as cohabitation, since the beginning of the evangelization of sub-Saharan Africa. Only the celebration of the Christian marriage enables him to be reconciled with God and the Church. Worried by this situation, the African episcopate called, with the Synod of 1994, with deepened research, being able to allow to avoid the superposition of the three types of marriage and expressed the wish to have some that one. Until today, the initiated solutions never cured it. Based on the basic conditions and of form, the celebrations of the church wedding in Quebec and the African marriage in democratic Republic of Congo produce civil effects. Our study was inspired some to propose a comprehension of the marriage based on the baptismal theology which incorporates the person in the Church, regenerates it as a child of God and configures it with Christ, by an indelible character. By this baptismal character legal, the celebration of the African marriage would produce religious effects, which would not make necessary the celebration of the marriage says “Christian” for baptized catholic African. For an implementation successful of this prospect, we consider essential the contribution of the civil capacity.

Dissertação de Mestrado em Arquitetura com a especialização em Urbanismo, apresentada na Faculdade de Arquitetura da Universidade de Lisboa para obtenção do grau de Mestre Numa Sociedade em que as questões de Mobilidade Urbana Sustentável têm um papel importante para a qualidade de vida dos residentes de uma Cidade, este trabalho tem como visão, fomentar o ponto de situação atual sobre este tema e estudar o impacto que a relação entre o Ambiente Construído, Transportes e Mobilidade, tem numa cidade. Nesta dissertação será avaliada o impacto da acessibilidade multimodal das interfaces do Município de Setúbal, examinando a sua relação com o ambiente construído, o sistema de transportes e a Mobilidade. O trabalho é estruturado na revisão da literatura, que aborda as diferentes temáticas relacionadas com o tema principal; no estudo de casos de referência a nível internacional; na caracterização história e dos processos de planeamento que levaram até à situação atual do local de estudo escolhido; e por último nas análises que contribuem para a avaliação da Acessibilidade multimodal do local de estudo. A promoção de uma boa mobilidade multimodal proporciona melhores condições para alcançar mais oportunidades, nomeadamente a mais serviços, equipamentos e empregos, bem como para garantir uma boa interação entre o espaço público e a qualidade de vida na Cidade. ANSTRACT: In a society in which the issues of Sustainable Urban Mobility play an important role in the quality of life of the residents of a city, this work aims to promote the current situation on this topic and study the impact and the relationship between the Built Environment, Transport and Mobility, has in the city. In this dissertation, the impact of the multimodal accessibility of the interfaces of the city of Setúbal will be evaluated, examining its relationship with the built environment, the transport system and Mobility. The work is structured in the literature review, which addresses the different themes related to the main theme; in the study of reference cases at international level; in characterizing the history and planning processes that led to the current situation of the chosen study site; and lastly in the analyzes that contribute to the evaluation of the multimodal Accessibility of the place of study. The promotion of a good multimodal mobility provides better conditions to achieve more opportunities, more services, equipment and jobs, as well as to guarantee a good interaction between the public space and the quality of life in the City. N/A

The metatheory of Scala's core type system - the Dependent Object Types (DOT) calculus - is hard to extend, like the metatheory of other type systems combining subtyping and dependent types. Soundness of important Scala features therefore remains an open problem in theory and in practice. To address some of these problems, we use a semantics-first approach to develop a logical relations model for a new version of DOT, called guarded DOT (gDOT). Our logical relations model makes use of an abstract form of step-indexing, as supported by the Iris framework, to model various forms of recursion in gDOT. To demonstrate the expressiveness of gDOT, we show that it handles Scala examples that could not be handled by previous versions of DOT, and prove using our logical relations model that gDOT provides the desired data abstraction. The gDOT type system, its semantic model, its soundness proofs, and all examples in the paper have been mechanized in Coq.

Unmanned aircraft systems (UAS) are an excellent tool to remove bridge inspection workers from potential harm. Previous research has documented that UAS for bridge inspection is a strategic priority of a state&rsquo, s Department of Transportation (DOT), and this paper presents how they can increase safety and presents one methodology to quantify the economic benefit. Although previous studies have documented the potential benefits of using UAS for bridge inspection, these studies have primarily focused on efficiency and capabilities. This paper investigates in greater detail the potential to use UAS to increase the safety of bridge inspection, and includes the results of a survey of bridge inspectors, as well as a benefit cost methodology that utilizes worker compensation rates to quantify the safety benefits of UAS, the methodology is demonstrated using a case study for a DOT. The results of this research present evidence that UAS can increase the safety of bridge inspection, and the benefit&ndash, cost methodology and analysis suggest that using UAS to increase safety will provide benefits that are greater than agency costs.

Unmanned aircraft systems (UAS) are increasingly used for a variety of applications by state Departments of Transportation (DOT) and local transportation agencies due to technology advancements, lower costs, and regulatory changes that have simplified operations. There are numerous applications (e.g., bridge inspection, traffic management, incident response, construction and roadway mapping) and agencies find it challenging to prioritize which applications are most appropriate. Important factors to consider when prioritizing UAS applications include: 1) benefits, 2) ease of adoption, 3) stakeholder acceptance, and 4) technical feasibility. These factors can be evaluated utilizing various techniques such as the technology acceptance model, benefit analysis, and technology readiness level (TRL). This paper presents the methodology and results for the prioritization of UAS applications&rsquo, quality function deployment (QFD), which reflects both qualitative and quantitative components. The proposed framework can be used in the future as technologies mature, and the prioritization can be revised on a regular basis to identify future strategic implementation opportunities. Numerous transportation agencies have begun to use UAS, some have developed UAS operating policies and manuals, but there has been no documentation to support identification of the UAS applications that are most appropriate for deployment. This paper fills that gap and documents a method for identification of UAS applications for strategic deployment and illustrates the method with a case study.

Dans le tome deux de L’Histoire de la famille, Patrick Beillevaire écrivait que « de tout temps la notion de dot proprement dite est demeurée étrangère au système familial japonais ». Pourtant, certaines régions sont réputées pour l’effort financier que représente le mariage d’une fille à cause de ce que les parents devront lui donner. C’est le cas de Nagoya et de ses environs où l’on dit que « si tu as trois filles, le faîte du toit tombera ». L’importance de la dot n’aurait-elle pas été sous-estimée ? Cet article se propose de montrer dans quelle mesure on peut parler de dot au Japon et d’en apprécier l’importance à partir de l’analyse d’un travail de terrain réalisé dans le département d’Aichi et de la littérature ethnologique locale. L’article reviendra sur la notion de dot dans l’introduction, puis, dans une première partie, il détaillera la coutume des trousseaux dans la région pour en montrer ensuite l’importance économique en deuxième partie, ainsi que ses nouvelles formes dans un dernier volet. In the second volume of The History of the Family, Patrick Beillevaire wrote that “the notion of dowry itself has been a stranger to the Japanese family system from time immemorial”. However, some regions are famous for the great expense that parents bear when marrying their daughter. That is the case in Nagoya and its surroundings where it is said that “if you have three daughters, the ridge beam of the roof will fall”. Has the importance of the dowry thus been underestimated? The aim of this article is to understand to what extent it is possible to speak of dowry in Japan and to evaluate its scale, by analyzing the results of fieldwork conducted in Aichi prefecture as well as documents pertaining to the area. The notion of dowry is presented in the introduction. Secondly, I explain the main features of the custom of the trousseau (a form of dowry) in this area and discuss its economic aspect. Finally, the article considers the possible new forms that dowry might take in present-day Japan.

Heat treatment (HT) of a mixture of tannins and inorganic boron compounds showed effective results against wood decay organisms. Boron compounds play a critical role in the preservation of wood against wood decay organisms. The use of tannins and HT represents a relatively new environmentally friendly approach to the wood preservation industry. The aim of this study was to investigate the effect of tannin impregnation and HT on boron depletion, and termite and fungi resistance. Southern yellow pine (SYP) and yellow-poplar (YP) cube samples were used for this study. A mixture of condensed tannins from the Quebracho tree and disodium octaborate tetrahydrate (DOT) was injected into the specimens using a vacuum/pressure cycle, and the specimens were then heat-treated under N2 atmosphere for four hours at 190 &deg, C to investigate both the tannin&rsquo, s fixative ability to reduce boron leaching and the performance of the mixture against brown and white-rot fungi and termites. Tannins restricted boron leaching in 46% and 34% for SYP and YP, respectively, and also significantly increased the resistance against white-rot fungi for YP. Tannins and HT showed unpredictably good performance against termites. Tannins may be acting to denature proteins, in that case, fungal enzymes would be inhibited. This study revealed the importance of HT on a mixture of boron and tannins to decrease boron leaching and increase the durability of preservative systems.

Antimicrobial stewardship program aims to reduce antibiotic use. Periodic measurement and monitoring of antibiotic use and comparison within the institution as well as with other organizations are important indicators. We analyzed antibiotic usage in a general hospital in Saudi Arabia. Antibiotic data were collected retrospectively for 2011 and from 2013 to 2015, and only adult patients (>15 year of age) were included in the study. Data were presented as days of therapy (DOT) and defined daily dose (DDD). DDD was adjusted per 100 bed-days and according to the case mix index (CMI). The total DDD was 37,557 in 2013, 36,550 in 2014 and 38,738 in 2015. The DDD per 100 patient-days was 90.7–94.5. There was a discordant findings of antibiotic measurements based on the DDD compared to DOT, and DDD/100 bed-days compared to DOT/100 bed-days. There was a negative correlation between CMI and DDD per 100 bed days (r −0.696), but a positive correlation of CMI with DOT (r +0.93). Adjusted DDD/100 bed-days showed decrease in the usage of antibiotics, reflecting activities of the antibiotic stewardship program. The increase in DOT/100 bed-days may indicate the favorable utilization of combination therapy. Antibiotic usage needs to be adjusted per 100 bed-days and correlated with CMI for better reflection of optimal antibiotic utilization, activities of the antibiotic stewardship program, and to allow benchmarking. Keywords: DDD, Antibiotic stewardship, Benchmarking, Days of therapy, DOT

Program Pengendalian Resistensi Antibiotik (PPRA) merupakan program wajib rumah sakit Indonesia sesuai Permenkes No. 8 tahun 2015. Rumkital dr. Ramelan Surabaya termasuk salah satu rumah sakit yang telah menerapkan PPRA. Tujuan penelitian ini adalah untuk mengetahui deskripsi kuantitatif-kualitatif pemakaian antibiotik, serta luaran klinis dan mikrobiologis yang teramati pascapencanangan penerapan PPRA di ICU Rumkital dr. Ramelan Surabaya. Desain penelitian adalah studi observasi cross-sectional yang dilakukan selama 3 bulan (Februari–Mei 2016) di ICU Rumkital dr. Ramelan. Deskripsi kuantitatif diamati menggunakan Days of Therapy (DOT/100 hari-pasien), deskripsi kualitatif menggunakan alur Gyssens. Pengamatan luaran klinis dilakukan terhadap infeksi nosokomial, mortalitas terkait infeksi, dan lama tinggal di ICU ( Length of Stay /LOS). Pengamatan luaran mikrobiologis dilakukan terhadap pola penyebaran bakteri multiresisten. Hasil perhitungan jumlah konsumsi antibiotik didapatkan 151,63 DOT/100 hari-pasien. Penilaian kualitas antibiotik menunjukkan hasil 52,73% terapi tepat; 8,18% tidak tepat; 7,27% tanpa indikasi; 31,82% tidak tercapai kesepakatan antar penilai (κ=0,59; p

The intracellular pathogen Legionella pneumophila, as well as other Legionella species, utilize the Icm/Dot type-IV secretion system to translocate an exceptionally large and diverse repertoire of effectors into their host cells. However, only nine core effectors were found to be present in all analyzed Legionella species. In this study, we investigated the core effectors, and used intracellular growth complementation to determine whether orthologs of core effectors perform the same function in different Legionella species. We found that three out of the nine L. pneumophila core effectors are required for maximal intracellular growth. Examination of orthologous core effectors from four Legionella species spread over the Legionella phylogenetic tree revealed that most of them perform the same function. Nevertheless, some of the orthologs of the core effector LegA3 did not complement the L. pneumophila legA3 deletion mutant for intracellular growth. LegA3 is encoded as part of an operon together with another gene, which we named legA3C, encoding a non-translocated protein. We found that LegA3 and LegA3C physically interact with each other, are both required for maximal intracellular growth, and the LegA3-LegA3C orthologous pairs from all the Legionella species examined fully complement the L. pneumophila legA3 deletion mutant for intracellular growth. Our results indicate that the Legionella core effectors orthologs generally perform the same function and establish that LegA3 requires LegA3C to fulfill its conserved function.

Along with the technics that allows archaeology to adopt a precise knowledge about the composition of the materiality, also exists a critical thought that claims for take into account experience, perception and creativity. In the latter, we find Art-Archaeology approach. With this at background emerged the idea of the presence and the ontology of the ‘dot’ in archaeology, identified in the ongoing process of the attendance of a meeting at Kyoto, in the excavation of a simulated site, in the survey of an unidentified site and in a short research about Prehistoric tattoo. This idea, in its explicit simplicity, is part of a creative thought situated in the roots of the archaeological practice. In this paper I reflect about this through an artistic photo-essay that is at the same time an artistic and theoretical exercise, with the intention to identify the existence of the ‘dot’ in different dimensions of archaeology, and to make theory making art.

Background Mobile health (mHealth) interventions have the potential to improve health through patient education and provider engagement while increasing efficiency and lowering costs. This raises the question of whether disparities in access to mobile technology could accentuate disparities in mHealth mediated care. This study addresses whether programs planning to implement mHealth interventions risk creating or perpetuating health disparities based on inequalities in smartphone ownership. Methods Video Directly Observed Therapy (VDOT) is an mHealth intervention for monitoring tuberculosis (TB) treatment adherence through videos sent by patients to their healthcare provider using smartphones. We conducted secondary analyses of data from a single-arm trial of VDOT for TB treatment monitoring by San Diego, San Francisco, and New York City health departments. Baseline and follow-up treatment interviews were used to assess participant smartphone ownership, sociodemographics and TB treatment perceptions. Univariate and multivariable logistic regression analyses were used to identify correlates of smartphone ownership. Results Of the 151 participants enrolled, mean age was 41 years (range: 18–87 years) and 41.1% were female. Participants mostly identified as Asian (45.0%) or Hispanic/Latino (29.8%); 57.8% had at most a high school education. At baseline, 30.4% did not own a smartphone, which was similar across sites. Older participants (adjusted odds ratio [AOR] = 1.09 per year, 95% confidence interval [CI]: 1.05–1.12), males (AOR = 2.86, 95% CI: 1.04–7.86), participants having at most a high school education (AOR = 4.48, 95% CI: 1.57–12.80), and those with an annual income below $10,000 (AOR = 3.06, 95% CI: 1.19, 7.89) had higher odds of not owning a smartphone. Conclusions Approximately one-third of TB patients in three large United States of America (USA) cities lacked smartphones prior to the study. Patients who were older, male, less educated, or had lower annual income were less likely to own smartphones and could be denied access to mHealth interventions if personal smartphone ownership is required.

The economic relations between spouses in the Iberian Peninsula should be studied in their cultural context. A framework of analysis can be the Western and Eastern Christian Mediterranean. This work presents an overview of the economic regimes of marriage in the Italian Peninsula and the Byzantine Empire. Although these areas developed independently, they are historically related and share a similar economic and social reality. Based on this finding, the possible similarities between these regimes are raised. Finally, a common structure for this area is proposed and, at the same time, the way in which this structure is observed in the Iberian area Las relaciones económicas entre los cónyuges en la península ibérica deben estudiarse en su contexto cultural. Un marco de análisis puede ser el del Mediterráneo cristiano, occidental y oriental. En este trabajo se presenta una visión general de los regímenes económicos del matrimonio de la Península Itálica y del Imperio Bizantino, a continuación, a partir del caso ibérico, se platean las posibles similitudes entre estos regímenes que, si bien se desarrollan de forma independiente, están emparentados en origen y comparten una realidad económica y social similar. Finalmente se propone una estructura económica común para esta zona y se analiza el modo en que esa estructura se manifiesta en el ámbito ibérico

The metatheory of Scala’s core type system—the Dependent Object Types (DOT) calculus—is hard to extend, like the metatheory of other type systems combining subtyping and dependent types. Soundness of important Scala features therefore remains an open problem in theory and in practice. To address some of these problems, we use a semantics-first approach to develop a logical relations model for a new version of DOT, called guarded DOT (gDOT) . Our logical relations model makes use of an abstract form of step-indexing , as supported by the Iris framework, to model various forms of recursion in gDOT. To demonstrate the expressiveness of gDOT, we show that it handles Scala examples that could not be handled by previous versions of DOT, and prove using our logical relations model that gDOT provides the desired data abstraction. The gDOT type system, its semantic model, its soundness proofs, and all examples in the paper have been mechanized in Coq.

En aquest article es fa una aproximació al paper de les dones en les economies domèstiques de l’Alt Penedès del segle XVIII. Concretament, s’analitzen les tasques productives que portaven a terme i que eren fonamentals per al manteniment de les famílies, les seves relacions amb la propietat i l’explotació de la terra, la importància que tenien el dot i l’escreix al llarg de la seva vida, i l’evolució del dot durant la segona meitat del segle XVIII. En cada una d’aquestes qüestions es fa menció de les dones solteres, casades i vídues, atès que l’estat civil era la variable que més fortament condicionava el que les dones podien i no podien fer. També es para atenció, de manera transversal, al marc legal que constrenyia l’autonomia econòmica de les dones. Malgrat el silenci de les fonts, conseqüència directa de la baixa consideració que tenia el treball femení, del seu caràcter suposadament subsidiari i de la incapacitat legal a què les dones estaven sotmeses, l’examen de capítols matrimonials, inventaris post mortem, contractes de conreu i textos de testimonis de l’època, permet entreveure unes dones més actives i més autònomes que el que tradicionalment s’acostuma a pensar. El marc cultural i legal, així com la pobresa, eren obstacles importants que calia superar., This article examines the role of women in the domestic economies of the Alt Penedès during the eighteenth century. In particular, it analyses the productive tasks that women carried out, which were fundamental for the maintenance of the families, their relations with the ownership and the exploitation of land, the importance of the dowry and the escreix throughout their lives and how the former evolved during the second half of the eighteenth century. In exploring each of these aspects we distinguish among single women, married women and widows, since the marital status was the factor that most strongly conditioned what the women could and could not do. Attention is also paid, in a cross-cutting way, to the legal framework that constrained women's economic autonomy. Despite the silence of the sources, which is a direct consequence of the low regard for women's work, its presumed subsidiary nature and the legal incapacity to which women were subjected, the examination of marriage capitulations, post mortem inventories, agrarian contracts and texts written by testimonies of the time allows to see women being more active and more autonomous than what is usually thought. The cultural and legal framework, as well as poverty, were important obstacles to overcome.

L’étude du personnage de la jeune fille et du processus menant à son mariage dans le roman Flirt (1890) de Paul Hervieu met en lumière une opposition entre des jeux de séduction réputés américains et un système matrimonial traditionnel français. Cette dichotomie renvoie à des enjeux économiques, ce qui indique, plus largement, que la thématique du flirt pointe vers tout un appareil axiologique, celui de la modernité cosmopolite, paradigme nouveau dans le Paris de la Belle Époque.

During the modern era, the three Lorraine dioceses Metz, Toul and Verdun saw a very strong establishment of religious orders. This monastic force of Lorraine, inherited from the Middle Ages and the protection of the ducal family, concerns all the major European religious families and has enabled the emergence of reforms (such as that of the Benedictines of Saint-Vanne for example) or the creation of congregations that lasted well beyond the Revolution. We thought it was interesting to study this Monastic permanence of Lorraine from the perspective of novice and novitiate in order to try to understand if there is a specificity specific to these territories. Thanks to an impressive archival wealth, a database of more than 13,000 novices, both men and women, has been established for all religious orders where vows of religion are pronounced and established in the Lorraine dioceses. These data have opened the way to reflect on the birth of vocation, on the procedures for admission within the regulars, the recruitment rates and, more generally, the training of novices. So, our study develops on five themes following both the chronology of the novitiate and its major themes. The first is about the appearance of vocation and the contexts that allow it to flourish or not. Family impacts are very opposite. It is both an incentive factor that can go as far as forced vocation in specific contexts, and a factor of opposition, prompting candidates to seek parades to follow their life plan. In addition to the family, other actors are involved such as religious, books or significant events. The second theme develops the question of postulation with the choice of the religious order, the selection of candidates and the first teachings, a postulation that culminates in the ceremony of taking clothes with its symbolism. The third theme focuses on the influence of money with two issues. The first relates to the cost of the novitiate (pension, purchases of clothes, accessories necessary for engagement...) and the second on the socio-economic profile of the Lorraine candidates with the differences encountered from one order to order, from one sex to another. The fourth reflection questions the geography of the novitiate and the profiles of recruitment according to religious orders and centuries. Finally, the last is entirely devoted to the training of novices with their place within the monastic institution, learning according to gender and orders, the masters and mistresses of novices and the problems faced by novices until the ceremony of the profession that transforms the novice into a religious.This research has established, among other conclusions, that the novice is a character continually confronted with choices (enter or not in religion, choice of order, leave or stay ...) marked by contradictory influences of the family, of the order ... He is a complex and rich character because he allows us to understand the mechanisms that govern the voluntary or voluntary choice of a life devoted to God. This thesis helped to identify a recruitment profile marked by a chaotic 16th century followed by a spectacular upturn that was abruptly interrupted by the Thirty Years' Warbetween 1630 and 1650, before a slow ascent to the first third of the 18th century. century, followed by stabilization before a relative decline after 1770. We have also identified a trend towards Lorraine-centred recruitment, revealing a strong attachment to a nation, for most orders.Novices in Lorraine are therefore above all Lorraines faced, from their youth, with a dense monastic presence, with religious very involved in education and in family networks promoting the renewal of recruits., Les trois diocèses lorrains Metz, Toul et Verdun, ont vu durant l’époque moderne, une très forte implantation d’ordres religieux. Cette force monastique de la Lorraine, héritée du Moyen-Age et de la protection de la famille ducale, concerne toutes les grandes familles religieuses européennes et a permis l’émergence de réformes (comme celle des bénédictins de Saint-Vanne par exemple) ou encore la création de congrégations qui ont perduré bien au-delà de la Révolution. Il nous a semblé intéressant d’étudier cette permanence monastique lorraine sous l’angle du novice et du noviciat afin de chercher à comprendre s’il existe une spécificité propre à ces territoires. Grâce à une richesse archivistique impressionnante, une base de données de plus de 13 000 novices, tant hommes que femmes, a été établie pour l’ensemble des ordres religieux où sont prononcés des voeux de religion et implantés dans les diocèses lorrains. Ces données ont permis d’ouvrir la réflexion sur la naissance de la vocation, sur les procédures d’admission au sein des réguliers, les rythmes de recrutement et plus globalement, la formation des novices.Ainsi, notre étude se développe sur cinq thèmes suivant à la fois la chronologie du noviciat et ses grandes thématiques. La première porte sur l’apparition de la vocation et les contextes qui permettent ou non son épanouissement. Les impacts familiaux sont très opposés. La famille est, à la fois facteur d’encouragement pouvant aller jusqu’à la vocation forcée dans des contextes précis, et facteur d’opposition, poussant les candidats à chercher des parades pour suivre leur projet de vie. Outre la famille, d’autres acteurs interviennent comme des religieux, des livres ou des événements marquants. Le second thème développe la question de la postulation avec le choix de l’ordre religieux, la sélection des candidats et les premiers enseignements, postulation qui aboutit à la cérémonie de la prise d’habit avec sa symbolique. Le troisième thème est axé sur l’influence de l’argent avec deux problématiques. La première porte sur le coût du noviciat (pension, achats des vêtements, des accessoires nécessaires à l’engagement…) et la seconde sur le profil socio-économique des candidats lorrains avec les différences rencontrées d’un ordre à l’ordre, d’un sexe à l’autre. La quatrième réflexion interroge la géographie des noviciats et les profils du recrutement selon les ordres religieux et les siècles. Enfin, le dernier thème est entièrement consacré à la formation des novices avec leur place au sein de l’institution monastique, les apprentissages selon les sexes et les ordres, les maîtres et maîtresses des novices et les problèmes rencontrés par les novices jusqu’à la cérémonie de la profession qui transforme le novice en religieux.Cette recherche a permis d’établir, entre autres conclusions, que le novice est un personnage continuellement confronté à des choix (entrer ou non en religion, choix de l’ordre, partir ou rester…) marqué par des influences contradictoires de la famille, de l’ordre… C’est un personnage complexe et riche car il permet de comprendre les mécanismes qui régissent le choix volontaire ou non d’une vie consacrée à Dieu. Cette thèse a permis de cerner un profil de recrutement marqué par un XVIe siècle chaotique suivi d’une remontée spectaculaire qui est brutalement interrompue par la guerre de Trente Ans entre 1630 et 1650, avant une lente remontée jusqu’au premier tiers du XVIIIe siècle, suivi d’une stabilisation avant une relative décrue après 1770. Nous avons aussi dégagé une tendance à un recrutement centré sur la Lorraine, révélant un attachement très fort à une nation, pour la plupart des ordres. Les novices en Lorraine sont donc avant tout des lorrains confrontés, dès leur jeunesse, à une présence monastique dense, avec des religieux très impliqués dans l’éducation et dans des réseaux familiaux favorisant le renouvellement des recrues.

Critical glycemic events, such as hypo- or hyperglycemia, are extremely common during the first week post-partum in very preterm neonates. Both hypo- and hyperglycemic changes have been associated with poor neurological outcome. Continuous glucose monitoring (CGM) is a promising tool to reduce glycemic variability in the preterm population and whole-head Diffuse Optical Tomography (DOT) is a promising tool for continuous monitoring of brain hemodynamics in newborns. In this study, we performed a combined CGM-DOT acquisition in a very preterm newborn (28 weeks gestational age). The newborn was monitored for 7 days continuously. Twelve events were detected during this period: 8 mild hypoglycemic events, one severe hypoglycemic event, two mild hyperglycemic events and one event with a mild hypo- followed by a mild-hyperglycemia. DOT data were available for all the events but two. DOT data were reconstructed with a neonatal head model for the severe hypoglycemic event before the start of the hypoglycemic event and during the maximum peak of hypoglycemia. These preliminary results showed a regional specificity of the hemodynamic changes during hypoglycemia, with a predominant recruitment of the motor and parietal areas. This study highlights the importance of using whole-head DOT in this research field and the feasibility to perform combined CGM-DOT monitoring in very preterm neonates. Future clinical trials are required to investigate this clinical problem more thoroughly and shed light on the impact of tight glycemic control on the newborn brain.