Germline mutations in the tumor suppressor gene PTEN cause PTEN Hamartoma Tumor Syndrome (PHTS). Pediatric patients with PHTS frequently develop lipomas. Treatment attempts with the mTORC1 inhibitor rapamycin were unable to reverse lipoma growth. Recently, lipomas associated with PIK3CA-related overgrowth syndrome were successfully treated with the novel PI3K inhibitor alpelisib. Here, we tested whether alpelisib has growth-restrictive effects and induces cell death in lipoma cells. We used PTEN-haploinsufficient lipoma cells from three patients and treated them with alpelisib alone or in combination with rapamycin. We tested the effect of alpelisib on viability, proliferation, cell death, induction of senescence, adipocyte differentiation, and signaling at 1–100 M alpelisib. Alpelisib alone or in combination with rapamycin reduced proliferation in a concentrationand time-dependent manner. No cell death but an induction of senescence was detected after alpelisib incubation for 72 h. Alpelisib treatment led to a reduced phosphorylation of AKT, mTOR, and ribosomal protein S6. Rapamycin treatment alone led to increased AKT phosphorylation. This effect could be reversed by combining rapamycin with alpelisib. Alpelisib reduced the size of lipoma spheroids by attenuating adipocyte differentiation. Since alpelisib was well tolerated in first clinical trials, this drug alone or in combination with rapamycin is a potential new treatment option for PHTS-related adipose tissue overgrowth.

BACKGROUND:Available measures of patient-reported outcomes for complementary and alternative medicine (CAM) inadequately capture the range of patient-reported treatment effects. The Self-Assessment of Change questionnaire was developed to measure multi-dimensional shifts in well-being for CAM users. With content derived from patient narratives, items were subsequently focused through interviews on a new cohort of participants. Here we present the development of the final version in which the content and format is refined through cognitive interviews.METHODS:We conducted cognitive interviews across five iterations of questionnaire refinement with a culturally diverse sample of 28 CAM users. In each iteration, participant critiques were used to revise the questionnaire, which was then re-tested in subsequent rounds of cognitive interviews. Following all five iterations, transcripts of cognitive interviews were systematically coded and analyzed to examine participants' understanding of the format and content of the final questionnaire. Based on this data, we established summary descriptions and selected exemplar quotations for each word pair on the final questionnaire.RESULTS:The final version of the Self-Assessment of Change questionnaire (SAC) includes 16 word pairs, nine of which remained unchanged from the original draft. Participants consistently said that these stable word pairs represented opposite ends of the same domain of experience and the meanings of these terms were stable across the participant pool. Five pairs underwent revision and two word pairs were added. Four word pairs were eliminated for redundancy or because participants did not agree on the meaning of the terms. Cognitive interviews indicate that participants understood the format of the questionnaire and considered each word pair to represent opposite poles of a shared domain of experience.CONCLUSIONS:We have placed lay language and direct experience at the center of questionnaire revision and refinement. In so doing, we provide an innovative model for the development of truly patient-centered outcome measures. Although this instrument was designed and tested in a CAM-specific population, it may be useful in assessing multi-dimensional shifts in well-being across a broader patient population.

Indlæggelsestiden i forbindelse med kirurgi er blevet kortere. Der er meget lidt viden om, hvordan den umiddelbare postoperative periode forløber. Formålet med undersøgelsen har været at vurdere om korte hospitalsforløb hos patienter, der er opereret for forstørret prostata, bevirker at de pårørende overtager en del af plejen, at undersøge om der kommer en øget belastning på andre dele af sundhedsvæsenet, samt at få en viden om hvordan patienterne har det i de første uger efter operationen. Der er foretaget kvalitative interviews med ti hustruer. Til analyse af interviewene er brugt den fænomenologiske metode, beskrevet af Giorgi og Karlsson. På baggrund af disse interviews er der udarbejdet et spørgeskema, som er udsendt til alle hustruer, hvis ægtefælle i perioden november 2004 til maj 2005 er blevet prostataopereret. Resultaterne fra spørgeskemaundersøgelsen blev sat ind i en access database. Resultatet viser at den første postoperative periode er præget af mange vandladningsgener så som inkontinens, hyppige vandladninger, blødning og urinstop. Gener som også belaster hustruerne. Hustruerne følte sig usikre på om efterforløbet var normalt, og de manglede viden om, hvor de kunne henvende sig med problemer. / The length of stay at hospital after surgery has shortened. Little is known about the immediate post-surgery period. The aim of this study is to assess whether spouses have to take active care of their husbands and to assess if the burden of other part of the health service increases as a result of early discharge after prostatic surgery. Furthermore, the study intends to increase the knowledge about how patients experience the first postoperative weeks. Initially qualitative interviews were conducted with ten spouses. The Phenomological method described by Giorgi and Karlsson was used for analysing the interviews. Based on the experience of this, a questionnaire was prepared and sent to all spouses of patients who had undergone prostatic surgery between November 2004 and May 2005. The results of the questionnaires were put into an access database. The principal finding is that many patients during the first postoperative period experience various urinary problems such as incontinence, frequency, haematuria, and urinary retention. Problems which negatively impacted on the spouses. Furthermore, the spouses were uncertain whether it was common to experience these problems, and they did not know whom to contact when in need of support / <p>ISBN 91-7997-152-0</p>

Linha de pesquisa: Curr?culos, avalia??o, pr?ticas pedag?gicas e forma??o de professores. / Submitted by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-05-03T14:25:28Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) maressa_carneiro_melo.pdf: 3083173 bytes, checksum: 1d3d359317036112df43c3c8e4876ea5 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-05-03T14:25:38Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) maressa_carneiro_melo.pdf: 3083173 bytes, checksum: 1d3d359317036112df43c3c8e4876ea5 (MD5) / Made available in DSpace on 2018-05-03T14:25:38Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) maressa_carneiro_melo.pdf: 3083173 bytes, checksum: 1d3d359317036112df43c3c8e4876ea5 (MD5) Previous issue date: 2017 / Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM) / Esta pesquisa tem como objetivo analisar a abordagem do ensino de pros?dia e, principalmente, dos atos diretivos de ordem e de pedido em Portugu?s Brasileiro nas atividades de quatro materiais did?ticos de Portugu?s Brasileiro como L?ngua Estrangeira utilizados em cursos de Portugu?s como L?ngua Estrangeira no N?cleo de L?nguas da Universidade Federal dos Vales do Jequitinhonha e Mucuri at? o ano de 2016. O ensino da pros?dia e dos atos de ordem e de pedido se fazem relevantes para falantes estrangeiros visto que s?o recursos que integram o sistema lingu?stico (SEARLE, 1981) e neles est?o impressos tra?os culturais do Portugu?s Brasileiro (BODOLAY, 2009). Para que o alocut?rio diferencie um ato diretivo de ordem do de pedido ? preciso que ele esteja atento ?s pistas pros?dicas utilizadas pelo locutor, aos pap?is sociais que ocupam no contexto de comunica??o e outros recursos extralingu?sticos que interferem na interpreta??o do enunciado. Assim sendo, tais recursos s?o totalmente exclusivos de uma l?ngua, segundo Marcuschi (2001) e Cruz-Ferreira (2003), tornando essenciais para a comunica??o de um falante estrangeiro. Para atender o objetivo central deste estudo, utilizamos como instrumento de coleta e an?lise a t?cnica de an?lise de conte?do de Bardin (2011). Como resultado principal, verificamos que tanto a pros?dia quanto os atos de ordem e de pedido s?o pouco explorados ou at? ignorados. Quando h? abordagem desses aspectos da l?ngua falada, os estilos de atividades dos materiais n?o utilizam os recursos orais, fazendo o uso da escrita para ensinar oralidade. / Disserta??o (Mestrado Profissional) ? Programa de P?s-Gradua??o em Educa??o, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / The aim of this research is to analyse the approach of teaching prosody and, mainly, of order and request acts in Brazilian Portuguese in the activities of four didactic materials of Brazilian Portuguese as a foreign language used in courses of Portuguese as a foreign Language at N?cleo de L?nguas of Federal University of Jequitinhonha and Mucuri Valleys up to the year 2016. The teaching of prosody and the acts of order and request becomes relevant for foreign speakers since they are resources that integrate the linguistic system (SEARLE, 1981) and in them are printed cultural traits of Brazilian Portuguese (BODOLAY, 2009). In order for the speaker to differentiate a directive act from an order to a request, he/she must be aware of the prosodic clues used by the speaker, the social roles they occupy in the context of communication and other extralinguistic resources that interfere in the interpretation of the utterance. Thus, these resources are totally unique to a language, according to Marcuschi (2001) and Cruz-Ferreira (2003), making it essential for the communication of a foreign speaker. In order to achieve the central objective of this study, we used, as a collection of data and analysis instrument, the content an analysis technique of Bardin (2011). As a main result we find that both prosody and order and request acts are little explored or even ignored. When there is an approach with deals with these aspects of spoken language, the styles of the materials activities do not use oral resources, making use of writing to teach orality.

Linha de pesquisa: Curr?culos, avalia??o, pr?ticas pedag?gicas e forma??o de professores. / Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2018-04-26T18:17:38Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) maressa_carneiro_melo.pdf: 3083173 bytes, checksum: 1d3d359317036112df43c3c8e4876ea5 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2018-04-27T14:59:32Z (GMT) No. of bitstreams: 2 license_rdf: 9 bytes, checksum: 42dd12a06de379d3ffa39b67dc9c7aff (MD5) maressa_carneiro_melo.pdf: 3083173 bytes, checksum: 1d3d359317036112df43c3c8e4876ea5 (MD5) / Made available in DSpace on 2018-04-27T14:59:32Z (GMT). No. of bitstreams: 2 license_rdf: 9 bytes, checksum: 42dd12a06de379d3ffa39b67dc9c7aff (MD5) maressa_carneiro_melo.pdf: 3083173 bytes, checksum: 1d3d359317036112df43c3c8e4876ea5 (MD5) Previous issue date: 2017 / Universidade Federal dos Vales do Jequitinhonha e Mucuri (UFVJM) / Esta pesquisa tem como objetivo analisar a abordagem do ensino de pros?dia e, principalmente, dos atos diretivos de ordem e de pedido em Portugu?s Brasileiro nas atividades de quatro materiais did?ticos de Portugu?s Brasileiro como L?ngua Estrangeira utilizados em cursos de Portugu?s como L?ngua Estrangeira no N?cleo de L?nguas da Universidade Federal dos Vales do Jequitinhonha e Mucuri at? o ano de 2016. O ensino da pros?dia e dos atos de ordem e de pedido se fazem relevantes para falantes estrangeiros visto que s?o recursos que integram o sistema lingu?stico (SEARLE, 1981) e neles est?o impressos tra?os culturais do Portugu?s Brasileiro (BODOLAY, 2009). Para que o alocut?rio diferencie um ato diretivo de ordem do de pedido ? preciso que ele esteja atento ?s pistas pros?dicas utilizadas pelo locutor, aos pap?is sociais que ocupam no contexto de comunica??o e outros recursos extralingu?sticos que interferem na interpreta??o do enunciado. Assim sendo, tais recursos s?o totalmente exclusivos de uma l?ngua, segundo Marcuschi (2001) e Cruz-Ferreira (2003), tornando essenciais para a comunica??o de um falante estrangeiro. Para atender o objetivo central deste estudo, utilizamos como instrumento de coleta e an?lise a t?cnica de an?lise de conte?do de Bardin (2011). Como resultado principal, verificamos que tanto a pros?dia quanto os atos de ordem e de pedido s?o pouco explorados ou at? ignorados. Quando h? abordagem desses aspectos da l?ngua falada, os estilos de atividades dos materiais n?o utilizam os recursos orais, fazendo o uso da escrita para ensinar oralidade. / Disserta??o (Mestrado Profissional) ? Programa de P?s-Gradua??o em Educa??o, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / The aim of this research is to analyse the approach of teaching prosody and, mainly, of order and request acts in Brazilian Portuguese in the activities of four didactic materials of Brazilian Portuguese as a foreign language used in courses of Portuguese as a foreign Language at N?cleo de L?nguas of Federal University of Jequitinhonha and Mucuri Valleys up to the year 2016. The teaching of prosody and the acts of order and request becomes relevant for foreign speakers since they are resources that integrate the linguistic system (SEARLE, 1981) and in them are printed cultural traits of Brazilian Portuguese (BODOLAY, 2009). In order for the speaker to differentiate a directive act from an order to a request, he/she must be aware of the prosodic clues used by the speaker, the social roles they occupy in the context of communication and other extralinguistic resources that interfere in the interpretation of the utterance. Thus, these resources are totally unique to a language, according to Marcuschi (2001) and Cruz-Ferreira (2003), making it essential for the communication of a foreign speaker. In order to achieve the central objective of this study, we used, as a collection of data and analysis instrument, the content an analysis technique of Bardin (2011). As a main result we find that both prosody and order and request acts are little explored or even ignored. When there is an approach with deals with these aspects of spoken language, the styles of the materials activities do not use oral resources, making use of writing to teach orality.

Personalen är i många fall den viktigaste resursen för olika företag. Likaså är den rekryteringsprocess som leder fram till anställning av rätt personal. Rekryteringsprocesser består av olika moment där företag kompletterar sina arbetsprofilsbedömningar medtestverktyg för att hitta de bäst lämpade kandidaterna för de vakanta tjänsterna. Två av dessa verktyg är de personlighet och begåvningstester som sökande kandidater genomför, där resultatet påverkar möjligheten till anställning. Användningen och påverkan av användningen berör företag på olika sätt, men det finns flera gemensamma nämnare vad gäller testernas roll i rekryteringen. Vi kommer i uppsatsen att ta reda på hur testerna som verktyg påverkar rekryteringen i företag genom att utreda både de positiva och negativa effekterna. Vi kommer även undersöka hur tilliten till testernas resultat och till testerna generellt ser ut. Tillvägagångssättet för att ta reda på detta kommer att ske genom intervjuer. 15 respondenter som är högst insatta i ämnet och på något sätt är eller har varit aktiva användare av testerna som verktyg, ligger till grunden för vårt underlag till empirin. Testerna som verktyg bidrar till en av oss upplevd motsägelsefullhet hos användarna. Det finns vitt skilda meningar kring validiteten i testresultaten. Det finns en sida som är positivt inställd till testerna och belyser fördelarna med användningen. Det finns en annan sida som pekar på att testerna som verktyg istället ger motsatt effekt och kan skada både rekryteringen och kandidaten som genomför testet. / In many cases, the staff is the most important resource for different companies, and the recruitment process should lead to the hiring of the most suitable staff. The recruitment process consists of different events where the company expands its job profiles with different types of test tools to find the best candidates. Two of these tools are the personality and ability tests that many applicants need to do when applying for a new job. Companies have different strategies and execution regarding the tests but there are several common denominators regarding the test rolls in recruitment. In the thesis, we will investigate test tools used in companies' recruitment processes, by calling out both the positive and negative effects. We will also examine how much trust the companies have in the results of the tests and how the tests generally contribute to recruitment. The research approach to finding out will be through interviews. All 15respondents are highly proficient in the subject and they are or have in some way been active users of the tests. The tests as tool support to a contradiction among the users. There are widely differing opinions on the validity of the test results. There is one group that is positively tuned to the tests and sees several benefits with its use. There is another group that points to the test as a tool instead gives the opposite effect and can damage both the recruitment and the person doing the test.

Syftet med arbetet är att undersöka vad det är som hindrar företag i dagsläget från att använda intermodala godstransporter med järnvägen, där frågeställningar som arbetet kommer att besvara är: Överväger fördelarna de nackdelar som finns med användningen av intermodala godstransporter på järnvägen? Samt hur ser framtiden ut för intermodala godstransporter på järnväg? För att besvara syftet har vi använt oss av kvalitativa metoder i form av intervjuer, där intervjufrågorna utformades utifrån semistrukturerade intervjuer. Det teoretiska ramverket är uppbyggt med hjälp av vetenskapliga artiklar och indelat i fyra aspekter som anses vara viktiga för kunder och deras val av transportslag vid transport av gods. Det empiriska materialet är utformat efter intervjuer med intervjupersoner som arbetar med intermodala godstransporter och där dessa arbetar på olika företag. Det empiriska materialet har sedan ställts mot det teoretiska ramverket för att ta fram en analys, där materialet analyserades genom en tematisk analysmetod. Arbetet kom fram till resultatet att hållbarhet alltid varit en av järnvägens starkaste fördelar, men järnvägens nackdelar är de som påverkar kundernas val mest. Nackdelarna är tid och leveranssäkerhet, för att motverka dessa nackdelar krävs det att man gör investeringar i järnvägsinfrastrukturen. Dessa investeringar kan vara att bygga ut eller förbättra den nuvarande järnvägsinfrastrukturen i hopp om att få fler spår och ett starkare nätverk kommer att minimera nackdelarna så att transporterna kan utföras snabbare och effektivare. Framtiden för järnvägen är lovande om investeringar och projekt planeras rätt. Förbättringar kommer leda till att godstransporter på järnväg ökar, dock överväger fördelarna i dagsläget inte nackdelarna om man är ett företag som har tidskänsliga transporter. / The purpose of this work is to investigate what prevents companies from currently using intermodal rail transportation, where the research questions to be answered are: Do the benefits outweigh the disadvantages of using intermodal rail transportation? What does the future hold for intermodal freight transportation by rail? To address the purpose, we have utilized qualitative methods in the form of interviews, where the interview questions were designed based on semi-structured interviews. The theoretical framework is built using scientific articles and divided into four aspects considered important for customers and their choice of transport mode for the transportation of goods. The empirical material is based on interviews with interviewees working with intermodal rail freight, representing different companies. The empirical material was then compared to the theoretical framework to conduct an analysis, where the material was analyzed using thematic analysis method. The study concluded that sustainability has always been one of the strongest advantages of rail transportation, but it is the disadvantages of rail transportation that have the greatest impact on customers' choices. The disadvantages include time and delivery reliability, and to counteract these disadvantages, investments in rail infrastructure are required. These investments can involve expanding or improving the current rail infrastructure, with the hope that more tracks and a stronger network will minimize the disadvantages, allowing for faster and more efficient transportation. The future of rail transportation is promising if investments and projects are planned correctly. Improvements will lead to an increase in rail freight, but currently, if a company has time-sensitive shipments, the disadvantages outweigh the benefits.

A partir da leitura de Ernesto Guerra da Cal em Língua e Estilo de Eça de Queiroz, um estudo completo dos procedimentos estilísticos de Eça, há citação sobre a leitura e a influência queirosiana no \"Modernismo\" espanhol, passagem esta que nos desafiou à procura da real importância da recepção da obra do autor lusitano na Espanha; definindo esta pesquisa como seu objeto de estudo uma série de artigos que haviam sido publicados em castelhano, acerca dessa temática, a partir de 1883 a 1903. Veremos a leitura \"versus\" da obra de Eça de Queirós e a leitura \"com\" a obra de Eça de Queirós na Espanha, alcançando a Geração de 98; e as traduções queirosianas editadas em castelhano, entre 1882 e 1915. / The starting point for the present essay is Guerra da Cal, Língua e Estilo de Eça de Queirós, a complet reading of Eça de Queirós stylistics, in which there are various references to the influence the Portuguese author in the Spanish \"Modernismo\". Following such point of view, this study focusses on a series of articles published between 1883 and 1903.Thus, we analyse here the \"pros\" and \"cons\" of the reception of Eça de Queirós\' oeuvre in Spain, including the reactions of the \"Generación del 98\" and an overview of the translations of the Portuguese novelist into Spanish between the years 1882 to 1915.

A partir da leitura de Ernesto Guerra da Cal em Língua e Estilo de Eça de Queiroz, um estudo completo dos procedimentos estilísticos de Eça, há citação sobre a leitura e a influência queirosiana no \"Modernismo\" espanhol, passagem esta que nos desafiou à procura da real importância da recepção da obra do autor lusitano na Espanha; definindo esta pesquisa como seu objeto de estudo uma série de artigos que haviam sido publicados em castelhano, acerca dessa temática, a partir de 1883 a 1903. Veremos a leitura \"versus\" da obra de Eça de Queirós e a leitura \"com\" a obra de Eça de Queirós na Espanha, alcançando a Geração de 98; e as traduções queirosianas editadas em castelhano, entre 1882 e 1915. / The starting point for the present essay is Guerra da Cal, Língua e Estilo de Eça de Queirós, a complet reading of Eça de Queirós stylistics, in which there are various references to the influence the Portuguese author in the Spanish \"Modernismo\". Following such point of view, this study focusses on a series of articles published between 1883 and 1903.Thus, we analyse here the \"pros\" and \"cons\" of the reception of Eça de Queirós\' oeuvre in Spain, including the reactions of the \"Generación del 98\" and an overview of the translations of the Portuguese novelist into Spanish between the years 1882 to 1915.

(in English): The goal of this thesis is to analyze mainly advantages of iPad use during lectures at special primary schools. In addition, the thesis takes a look at disadvantages of this style of education. The theoretical part includes the first four chapters. The main information source for this part is expert literature. The first step presents the basic terms from the field of education. The next step presents important information about mental retardation and autistic spectrum disorders, including the specific aspects of education of children with such mental disorders. Following are the characteristics of the iPad devices and the history of the device and its manufacturer, the Apple company. This part also includes other information and communication technology used for educational purposes at regular as well as special schools. Last chapter of this part excerpts advantages and disadvantages of iPad listed in used expert literature. The practical part uses the method of qualitative analysis, in the form of semi-structured interview to find out which positive and negative effects can iPad usage have for both parties involved - children and teachers. The analysis builds on the foundation laid in the theoretical part, checking how the answeres of the interviewees correspond to the contemporary...