Hereditary hepatic and systemic amyloidosis caused by a new deletion/insertion mutation in the apolipoprotein AI gene.

We report a Spanish family with autosomal-dominant non-neuropathic hereditary amyloidosis with a unique hepatic presentation and death from liver failure, usually by the sixth decade. The disease is caused by a previously unreported deletion/insertion mutation in exon 4 of the apolipoprotein AI (apoAI) gene encoding loss of residues 60-71 of normal mature apoAI and insertion at that position of two new residues, ValThr. Affected individuals are heterozygous for this mutation and have both normal apoAI and variant molecules bearing one extra positive charge, as predicted from the DNA sequence. The amyloid fibrils are composed exclusively of NH2-terminal fragments of the variant, ending mainly at positions corresponding to residues 83 and 92 in the mature wild-type sequence. Amyloid fibrils derived from the other three known amyloidogenic apoAI variants are also composed of similar NH2-terminal fragments. All known amyloidogenic apoAI variants carry one extra positive charge in this region, suggesting that it may be responsible for their enhanced amyloidogenicity. In addition to causing a new phenotype, this is the first deletion mutation to be described in association with hereditary amyloidosis and it significantly extends the value of the apoAI model for investigation of molecular mechanisms of amyloid fibrillogenesis.

Deletion of mu- and kappa-opioid receptors in mice changes epidermal hypertrophy, density of peripheral nerve endings, and itch behavior.

The mu- (MOR) and kappa- (KOR) opioid receptors have been implicated in the regulation of homeostasis of non-neuronal cells, such as keratinocytes, and sensations like pain and chronic pruritus. Therefore, we have studied the phenotype of skin after deletion of MOR and KOR. In addition, we applied a dry skin model in these knockout mice and compared the different mice before and after induction of the dermatitis in terms of epidermal thickness, epidermal peripheral nerve ending distribution, dermal inflammatory infiltrate (mast cells, CD4 positive lymphocytes), and scratching behavior. MOR knockout mice reveal as phenotype a significantly thinner epidermis and a higher density of epidermal fiber staining by protein gene product 9.5 than the wild-type counterparts. Epidermal hypertrophy, induced by the dry skin dermatitis, was significantly less developed in MOR knockout than in wild-type mice. Neither mast cells nor CD4 T(h)-lymphocytes are involved in the changes of epidermal nerve endings and epidermal homeostasis. Finally, behavior experiments revealed that MOR and KOR knockout mice scratch less after induction of dry skin dermatitis than wild-type mice. These results indicate that MOR and KOR are important in skin homeostasis, epidermal nerve fiber regulation, and pathophysiology of itching.

Extreme self-monitoring, fear of hypoglycemia and obsessive-compulsive disorder in type 1 diabetes mellitus: when less is better

Background: Pre-existing psychological factors can strongly influence coping with type 1 diabetes mellitus and interfere with self-monitoring. Psychiatric disorders seem to be positively associated with poor metabolic control. We present a case of extreme compulsive blood testing due to obsessive fear of hypoglycemia in an adolescent with type 1 diabetes mellitus. Case report: Type 1 diabetes mellitus (anti GAD-antibodies 2624 U/l, norm < 9.5) was diagnosed in a boy aged 14.3 years [170 cm (+ 0.93 SDS), weight 50.5 kg (+ 0.05 SDS)]. Laboratory work-up showed no evidence for other autoimmune disease. Family and past medical history were unremarkable. Growth and developmental milestones were normal. Insulin-analog based basal-bolus regime was initiated, associated to standard diabetic education. Routine psychological evaluation performed at the onset of diabetes revealed intermittent anxiety and obsessivecompulsive traits. Accordingly, a close psychiatric follow-up was initiated for the patient and his family. An adequate metabolic control (HbA1c drop from >14 to 8%) was achieved within 3 months, attributed to residual -cell function. In the following 6 months, HbA1c rose unexpectedly despite seemingly adequate adaptations of insulin doses. Obsessive fear of hypoglycemia leading to a severe compulsive behavior developed progressively with as many as 68 glycemia measurements per day (mean over 1 week). The patient reported that he could not bear leaving home with glycemia < 15 mmol/l, ending up with school eviction and severe intra-familial conflict. Despite intensive psychiatric outpatient support, HbA1c rose rapidly to >14% with glycemia-testing reaching peaks of 120 tests/day. The situation could only be discontinued through psychiatric hospitalization with intensive behavioral training. As a result, adequate metabolic balance was restored (HbA1c value: 7.1 %) with acceptable 10-15 daily glycemia measurements. Discussion: The association of overt psychiatric disorders to type 1 diabetes mellitus is very rare in the pediatric age group. It can lead to a pathological behavior with uncontrolled diabetes. Such exceptional situations require long-term admissions with specialized psychiatric care. Slow acceptation of a "less is better" principle in glycemia testing and amelioration of metabolic control are difficult to achieve.

Debating the centre : the theory of principal qualificand (mukhyavisesya) in classical Indian philosophy

The theory of language has occupied a special place in the history of Indian thought. Indian philosophers give particular attention to the analysis of the cognition obtained from language, known under the generic name of śābdabodha. This term is used to denote, among other things, the cognition episode of the hearer, the content of which is described in the form of a paraphrase of a sentence represented as a hierarchical structure. Philosophers submit the meaning of the component items of a sentence and their relationship to a thorough examination, and represent the content of the resulting cognition as a paraphrase centred on a meaning element, that is taken as principal qualificand (mukhyaviśesya) which is qualified by the other meaning elements. This analysis is the object of continuous debate over a period of more than a thousand years between the philosophers of the schools of Mimāmsā, Nyāya (mainly in its Navya form) and Vyākarana. While these philosophers are in complete agreement on the idea that the cognition of sentence meaning has a hierarchical structure and share the concept of a single principal qualificand (qualified by other meaning elements), they strongly disagree on the question which meaning element has this role and by which morphological item it is expressed. This disagreement is the central point of their debate and gives rise to competing versions of this theory. The Mïmāmsakas argue that the principal qualificand is what they call bhāvanā ̒bringing into being̒, ̒efficient force̒ or ̒productive operation̒, expressed by the verbal affix, and distinct from the specific procedures signified by the verbal root; the Naiyāyikas generally take it to be the meaning of the word with the first case ending, while the Vaiyākaranas take it to be the operation expressed by the verbal root. All the participants rely on the Pāninian grammar, insofar as the Mimāmsakas and Naiyāyikas do not compose a new grammar of Sanskrit, but use different interpretive strategies in order to justify their views, that are often in overt contradiction with the interpretation of the Pāninian rules accepted by the Vaiyākaranas. In each of the three positions, weakness in one area is compensated by strength in another, and the cumulative force of the total argumentation shows that no position can be declared as correct or overall superior to the others. This book is an attempt to understand this debate, and to show that, to make full sense of the irreconcilable positions of the three schools, one must go beyond linguistic factors and consider the very beginnings of each school's concern with the issue under scrutiny. The texts, and particularly the late texts of each school present very complex versions of the theory, yet the key to understanding why these positions remain irreconcilable seems to lie elsewhere, this in spite of extensive argumentation involving a great deal of linguistic and logical technicalities. Historically, this theory arises in Mimāmsā (with Sabara and Kumārila), then in Nyāya (with Udayana), in a doctrinal and theological context, as a byproduct of the debate over Vedic authority. The Navya-Vaiyākaranas enter this debate last (with Bhattoji Dïksita and Kaunda Bhatta), with the declared aim of refuting the arguments of the Mïmāmsakas and Naiyāyikas by bringing to light the shortcomings in their understanding of Pāninian grammar. The central argument has focused on the capacity of the initial contexts, with the network of issues to which the principal qualificand theory is connected, to render intelligible the presuppositions and aims behind the complex linguistic justification of the classical and late stages of this debate. Reading the debate in this light not only reveals the rationality and internal coherence of each position beyond the linguistic arguments, but makes it possible to understand why the thinkers of the three schools have continued to hold on to three mutually exclusive positions. They are defending not only their version of the principal qualificand theory, but (though not openly acknowledged) the entire network of arguments, linguistic and/or extra-linguistic, to which this theory is connected, as well as the presuppositions and aims underlying these arguments.

Time in e-Learning Research: A Qualitative Review of the Empirical Consideration of Time in Research into e-Learning

Peer-reviewed

Value Processingin Organizations - Individual Perceptions in Three Case Companies

Values and value processes are said to be needed in every organization nowadays, as the world is changing and companies have to have something to "keep it together". Organizational values, which are approvedand used by the personnel, could be the key. Every organization has values. But what is the real value of values? The greatest and most crucial challenge is the feasibility of the value process. The main point in this thesis is tostudy how organizational members at different hierarchical levels perceive values and value processes in their organizations. This includes themes such as how values are disseminated, the targets of value processing, factors that affect the process, problems that occur during the value implementation and improvements that could be made when organizational values are implemented. These subjects are studied from the perspective of organizational members (both managers and employees); individuals in the organizations. The aim is to get the insider-perspective on value processing, from multiple hierarchical levels. In this research I study three different organizations (forest industry, bank and retail cooperative) and their value processes. The data is gathered from companies interviewing personnel in the head office and at the local level. The individuals areseen as members of organizations, and the cultural aspect is topical throughout the whole study. Values and cultures are seen as the 'actuality of reality' of organizations, interpreted by organizational members. The three case companies were chosen because they represented different lines of business and they all implemented value processing differently. Sincethe emphasis in this study is at the local level, the similar size of the local units was also an important factor. Values are in 'fashion' -but what does the fashion tell us about the real corporate practices? In annual reports companies emphasize the importance and power of official values. But what is the real 'point' of values? Values are publicly respected and advertised, but still it seems that the words do not meet the deeds. There is a clear conflict between theoretical, official and substantive organizational values: in the value processing from words to real action. This contradiction in value processing is studied through individual perceptions in this study. I study the kinds of perceptions organizationalmembers have when values are processed from the head office to the local level: the official value process is studied from the individual's perspective. Value management has been studied more during the 1990's. The emphasis has usually been on managers: how they consider the values in organizations and what effects it has on the management. Recent literature has emphasized values as tools for improving company performance. The value implementation as a process has been studied through 'good' and 'bad' examples, as if one successful value process could be copied to all organizations. Each company is different with different cultures and personnel, so no all-powerful way of processing values exists. In this study, the organizational members' perceptions at different hierarchical levels are emphasized. Still, managers are also interviewed; this is done since managerial roles in value dissemination are crucial. Organizational values cannot be well disseminated without management; this has been proved in several earlier studies (e.g. Kunda 1992, Martin 1992, Parker 2000). Recent literature has not sufficiently emphasized the individual's (organizational member's) role in value processing. Organizations consist of differentindividuals with personal values, at all hierarchical levels. The aim in this study is to let the individual take the floor. Very often the value process is described starting from the value definition and ending at dissemination, and the real results are left without attention. I wish to contribute to this area. Values are published officially in annual reports etc. as a 'goal' just like profits. Still, the results/implementationof value processing is rarely followed, at least in official reports. This is a very interesting point: why do companies espouse values, if there is no real control or feedback after the processing? In this study, the personnel in three different companies is asked to give an answer. In the empirical findings, there are several results which bring new aspects to the research area of organizational values. The targets of value processing, factors effecting value processing, the management's roles and the problems in value implementation are presented through the individual's perspective. The individual's perceptions in value processing are a recurring theme throughout the whole study. A comparison between the three companies with diverse value processes makes the research complete

Let's share perspectives! Mentalistic skills involved in cooperation = ¿A tu Izquierda o a la Mía? Habilidades Mentalistas Implicadas en la Cooperación

Previous research has found a link between theory of mind and cooperation. The aim of this study is to deepen into this relationship, to identify which theory of mind skills are more related to the cooperative capacity on a referential communication task. A total of 50 children from first and fifth grade completed a battery of theory of mind tasks, and also a cooperative task where children worked in pairs to build block models. Each pair was composed by a builder and a guide, who gave instructions to his partner about how to build a replica of the model. The results show a significant relationship between the theory of mind skills and cooperation. Specifically, we found that the second-order false-belief task was the variable most related to cooperation after controlling the effect of age. In addition, we observed that the mentalist skills were more important for cooperation in the builders than in the guides. Finally, we discuss the findings of this study and make suggestions for the future

Duration and compliance with antidepressant treatment in immigrant and native-born populations in Spain: a four year follow-up descriptive study

Background: Non-compliance with antidepressant treatment continues to be a complex problem in mental health care. In immigrant populations non-compliance is one of several barriers to adequate management of mental illness; some data suggest greater difficulties in adhering to pharmacological treatment in these groups and an increased risk of therapeutic failure. The aim of this study is to assess differences in the duration and compliance with antidepressant treatment among immigrants and natives in a Spanish health region. Methods: Population-based (n = 206,603), retrospective cohort study including all subjects prescribed ADT between 2007 and 2009 and recorded in the national pharmacy claims database. Compliance was considered adequate when the duration was longer than 4 months and when patients withdrew more than 80% of the packs required. Results: 5334 subjects (8.5% of them being immigrants) initiated ADT. Half of the immigrants abandoned treatment during the second month (median for natives = 3 months). Of the immigrants who continued, only 29.5% presented good compliance (compared with 38.8% in natives). The estimated risk of abandoning/ending treatment in the immigrant group compared with the native group, adjusted for age and sex, was 1.28 (95%CI 1.16-1.42). Conclusions: In the region under study, immigrants of all origins present higher percentages of early discontinuation of ADT and lower median treatment durations than the native population. Although this is a complex, multifactor situation, the finding of differences between natives and immigrants in the same region suggests the need to investigate the causes in greater depth and to introduce new strategies and interventions in this population group.

Involuntary outpatient treatment for mental health problems in Switzerland: a literature review.

BACKGROUND: In 2008, the Swiss Civil Code was amended. From 1 January 2013, each Swiss canton may propose specific provisions for involuntary outpatient treatment (community treatment orders (CTOs)) for individuals with mental disorders. AIM: This review catalogues the legal provisions of the various Swiss cantons for CTOs and outlines the differences between them. It sets this in the context of variations in clinical provisions between the cantons. METHODS: Databases were searched to obtain relevant publications about CTOs in Switzerland. The Swiss Medical Association, Swiss Federal Statistical Office, Swiss Health Observatory and all the 26 Cantonal medical officers were contacted to complete the information. Conférence des cantons en matière de protection des mineurs et des adultes (COPMA), the authority which monitors guardianship legislation, and Pro Mente Sana, a patients' right association, were also approached. RESULTS: Three articles about CTOs in Switzerland were identified. Psychiatric provisions vary considerably between cantons and only a few could provide complete or even partial figures for rates of compulsion in previous years. Prior to 2013, only 6 of the 20 cantons, for which information was returned, had any provision for CTOs. Now, every canton has some form of legal basis but the level of detail is often limited. In eight cantons, the powers of the measure are not specified (for example, use of medication). In 12 cantons, the maximum duration of the CTO is not specified. German speaking cantons and rural cantons are more likely to specify the details of CTOs. CONCLUSION: Highly variable Swiss provision for CTOs is being introduced despite the absence of convincing international evidence for their effectiveness or good quality data on current coercive practice. Careful monitoring and assessment of these new cantonal provisions are essential.

Efeito da concentração de sacarose na germinação in vitro do pólen de cinco acessos de bacurizeiro (Platonia insignis MART.)

O bacurizeiro é uma das espécies fruteiras nativas de maior importância socioeconômica das regiões Norte e Meio-Norte do Brasil. No entanto, ainda há carência de conhecimentos científicos sobre a espécie, especialmente sobre sua biologia floral, mecanismos reprodutivos e viabilidade do pólen. O conhecimento sobre a viabilidade do pólen é fundamental para o melhoramento genético, especialmente quando se tem em mente a realização de hibridizações controladas. O objetivo deste trabalho foi avaliar o efeito da sacarose e de acessos na viabilidade do pólen de bacurizeiro por meio da germinação in vitro. Avaliaram-se cinco acessos (BGB 6, BGB 11, BGB 48, BGB 32 e BGB 16) de bacurizeiro combinados com um tratamento-controle, sem sacarose, e quatro concentrações de sacarose (5; 7,5; 10 e 20%), em delineamento inteiramente ao acaso, em arranjo fatorial 5 x 5, com oito repetições. Na maioria dos acessos, a germinação in vitro do pólen atingiu um máximo (71,1 e 63,0%) entre as concentrações de sacarose de 9,4 e 9,7% e, a partir daí, caiu de forma drástica até atingir um percentual inferior a 10% de germinação na concentração de 20% de sacarose. Foram encontrados bons percentuais de germinação (entre 63,0 e 77,1%) para todos os acessos, com exceção do acesso BGB 16, que não alcançou 50%.

Problems of the architecture design in the system integration

This thesis studies the problems and their reasons a software architect faces in his work. The purpose of the study is to search and identify potential factors causing problens in system integration and software engineering. Under a special interest are non-technical factors causing different kinds of problems. Thesis was executed by interviewing professionals that took part in e-commerce project in some corporation. Interviewed professionals consisted of architects from technical implementation projects, corporation's architect team leader, different kind of project managers and CRM manager. A specific theme list was used as an guidance of the interviews. Recorded interviews were transcribed and then classified using ATLAS.ti software. Basics of e-commerce, software engineering and system integration is described too. Differences between e-commerce and e-business as well as traditional business are represented as are basic types of e-commerce. Software's life span, general problems of software engineering and software design are covered concerning software engineering. In addition, general problems of the system integration and the special requirements set by e-commerce are described in the thesis. In the ending there is a part where the problems founded in study are described and some areas of software engineering where some development could be done so that same kind of problems could be avoided in the future.

Surgery Versus Radiotherapy for Early Oropharyngeal Tumors: a Never-Ending Debate.

OPINION STATEMENT: Therapeutic options for early stage oropharyngeal squamous cell carcinoma (OPSCC) include both surgery and radiotherapy as single treatment modality. Retrospective data reporting on locoregional control and survival rates in early stage OPSCC have shown equivalent efficacy, although no prospective randomized trials are available to confirm these results. Given the assumed comparable oncologic results in both groups, complication rates and functional outcomes associated with each modality play a major role when making treatment decisions. Radiotherapy is used preferentially in many centers because few trials have reported higher complication rates in surgical patients. However, these adverse effects were mainly due to traditional invasive open surgical approaches used for access to the oropharynx. In order to decrease the morbidity of these techniques, transoral surgical (TOS) approaches have been developed progressively. They include transoral laser microsurgery (TLM), transoral robotic surgery (TORS), and conventional transoral techniques. Meta-analysis comparing these new approaches with radiotherapy showed equivalent efficacy in terms of oncologic results. Furthermore, studies reporting on functional outcomes in patients undergoing TOS for OPSCC did not show major long-term functional impairment following treatment. Given the abovementioned statements, it is our practice to treat early stage OPSCC as follows: whenever a single modality treatment seems feasible (T1-2 and N0-1), we advocate TOS resection of the primary tumor associated with selective neck dissection, as indicated. In our opinion, the advantage of this approach relies on the possibility to stratify the risk of disease progression based on the pathological features of the tumor. Depending on the results, adjuvant radiation treatment or chemoradiotherapy can be chosen for high-risk patients. For tumors without adverse features, no adjuvant treatment is given. This approach also allows prevention of potential radiation-induced late complications while keeping radiotherapy as an option for any second primary lesions whenever needed. Definitive radiotherapy is generally reserved for selected patients with specific anatomical location associated with poor functional outcome following surgery, such as tumor of the soft palate, or for patients with severe comorbidities that do not allow surgical treatment.

Facilitar la teoría de la mente en niños con alteraciones del lenguaje

The ability to recognize mental states in oneself and others, or the theory of mind, has been a widely studied topic in last years. Traditionally, these studies have focused on the understanding of false belief, one of the most important milestones in its development. Studies conducted with children with language difficulties suggest that they have a delay in false belief acquisition. On the other hand, numerous studies have established a relationship between the understanding of false belief and language skills. In particular, it has been suggested that training based in labelling objects with double perspective facilitates the understanding of false belief. The aim of the present study is to test the effect of the structuration level of labelling training in a group of children with difficulties in language development. A total of 14 children, aged between 58 and 107 months, were trained in 3 sessions, and a pre-test and a post-test were administered to evaluate the effects of the training. The results confirm a delay in false belief understanding in children with developmental language difficulties, and suggest that the structured labelling training is effective to improve this understanding

La Relación del lenguaje con la teoría de la mente en edad escolar

In the past years a considerable amount of research has been carried out on the development of theory of mind (ToM) reporting that language and ToM performance are correlated. However it is less clear what aspect of language is related with ToM development. Some studies show a greater influence of semantics aspects, whereas others suggest that sentential complement sentences, a specific aspect of syntax, are crucial for false belief understanding (FB). Yet others argue that pragmatic abilities correlate with FB understanding. The aim of this study is investigate, on the one side, the development of ToM between the ages of 6 and 8 and on the other side, the relationship between some aspects of language and the ToM improvement. Several ToM tasks were administrated to evaluate children’s performance at two different ages (60 participants aged 6 and 8 years) and four tasks to assess language abilities. The results show a significant increase in the understanding of the mind between the ages of 6 and 8. Furthermore, results reveal a significant relationship between syntax and tasks that require FB understanding, while pragmatics is more strongly associated with tasks that involve more complex socio-cognitive understandings