Bridging Inferences and Reference Management: Evidence from an Experimental Investigation in Catalan and Russian.

This article focuses on the choice of nominal forms in a language with articles (Catalan) in comparison to a language without articles (Russian). An experimental study (consisting of various naturalness judgment tasks) was run with speakers of these two languages which allowed to show that in bridging contexts native speakers' preferences vary when reference is made to one single individual or to two disjoint referents. In the former case, Catalan speakers chose (in)definite NPs depending on their accessibility to contextual information that guarantees a unique interpretation (or the lack of it) for the entity referred to. Russian speakers chose bare nominals as a default form. When reference is made to two disjoint referents (as encoded by the presence of an additional altre/drugoj "other" NP), speakers prefer an optimal combination of two indefinite NPs (i.e., un NP followed by un altre NP in Catalan; odin "some/a" NP followed by drugoj NP in Russian). This study shows how speakers of the two languages manage to combine grammatical knowledge (related to the meaning of the definite and the indefinite articles and altre in Catalan; and the meaning of bare nominals, odin and drugoj in Russian) with world knowledge activation and accessibility to discourse information.

Arritmias en pacientes con miopatía miotubular ligada al cromosoma X / Arrhythmias in patients with X-linked myotubular myopathy

Introducción: La miopatía miotubular es una enfermedad muscular congénita causada por una mutación en el gen de la miotubularina (MTM1). La miopatía miotubular ligada al cromosoma X (XLMTM) afecta a los hombres con síntomas de aparición temprana como debilidad muscular, hipotonía y dificultad respiratoria. Hasta donde sabemos, la afectación cardíaca en estos pacientes no se ha descrito previamente, a diferencia de otros tipos de miopatías congénitas, como la miopatía nemalínica o la miopatía con cores. Casos clínicos: Presentamos dos casos clínicos de XLMTM que comenzaron con bradicardia sinusal grave o bloqueo auriculoventricular desde los primeros días de vida, con Holter patológico en ambos casos. Se descartó una afectación cardíaca primaria por estudios electrofisiológicos y se recuperó la frecuencia cardíaca normal con soporte respiratorio adecuado. Conclusión: Estos casos con bradicardia grave en una patología bien conocida, como la XLMTM, suponen un matiz en el diagnóstico diferencial habitual de las miopatías congénitas.(AU)

Introduction: Myotubular myopathy is a congenital muscle disease caused by a mutation in the myotubularin (MTM1) gene. The X-linked myotubular myopathy (XLMTM) affects males with early-onset symptoms such as muscle weakness, hypotonia, and respiratory distress. To our knowledge, cardiac involvement has not been previously described in this condition, in contrast to other types of congenital myopathies such as nemaline myopathy or core myopathy. Case reports: We report two clinical cases of XLMTM that started with severe sinus bradycardia or auriculoventricular block from the first days of life, with pathologic 24-hours Holter monitoring in both cases. A primary cardiac affection was excluded by electrophysiological studies and normal heart rate was recovered with proper respiratory support. Discussion: These cases with sever bradyarrhythmia in a well know pathology such the XLMTM represents a nuance on the usual differential diagnostics of congenital myopathies.(AU)

[Acute cerebellar ataxia in Griscelli syndrome type 2]. / Ataxia cerebelosa aguda en el síndrome de Griscelli de tipo 2.

TITLE: Ataxia cerebelosa aguda en el síndrome de Griscelli de tipo 2.

Arrhythmias in patients with X-linked myotubular myopathy. / Arritmias en pacientes con miopatía miotubular ligada al cromosoma X.

INTRODUCTION: Myotubular myopathy is a congenital muscle disease caused by a mutation in the myotubularin (MTM1) gene. The X-linked myotubular myopathy (XLMTM) affects males with early-onset symptoms such as muscle weakness, hypotonia, and respiratory distress. To our knowledge, cardiac involvement has not been previously described in this condition, in contrast to other types of congenital myopathies such as nemaline myopathy or core myopathy. CASE REPORTS: We report two clinical cases of XLMTM that started with severe sinus bradycardia or auriculoventricular block from the first days of life, with pathologic 24-hours Holter monitoring in both cases. A primary cardiac affection was excluded by electrophysiological studies and normal heart rate was recovered with proper respiratory support. DISCUSSION: These cases with sever bradyarrhythmia in a well know pathology such the XLMTM represents a nuance on the usual differential diagnostics of congenital myopathies.

TITLE: Arritmias en pacientes con miopatía miotubular ligada al cromosoma X.Introducción. La miopatía miotubular es una enfermedad muscular congénita causada por una mutación en el gen de la miotubularina (MTM1). La miopatía miotubular ligada al cromosoma X (XLMTM) afecta a los hombres con síntomas de aparición temprana como debilidad muscular, hipotonía y dificultad respiratoria. Hasta donde sabemos, la afectación cardíaca en estos pacientes no se ha descrito previamente, a diferencia de otros tipos de miopatías congénitas, como la miopatía nemalínica o la miopatía con cores. Casos clínicos. Presentamos dos casos clínicos de XLMTM que comenzaron con bradicardia sinusal grave o bloqueo auriculoventricular desde los primeros días de vida, con Holter patológico en ambos casos. Se descartó una afectación cardíaca primaria por estudios electrofisiológicos y se recuperó la frecuencia cardíaca normal con soporte respiratorio adecuado. Conclusión. Estos casos con bradicardia grave en una patología bien conocida, como la XLMTM, suponen un matiz en el diagnóstico diferencial habitual de las miopatías congénitas.

On the distribution and interpretation of voice in Greek anticausatives.

This paper provides experimental evidence in support of the view that Greek does not have three productive morphological classes of anticausative verbs, but only two: the class of verbs that bear non-active voice morphology and the class of verbs that are morphologically active. Across two experiments, native Greek speakers are found to prefer for each anticausative verb either non-active or active voice morphological marking, in the presence or absence of explicit contextual information. It is also shown experimentally that native speakers prefer an interpretation that involves a specific cause for all anticausatives, especially when the existence of such a cause is favored by the contextual setting. Our empirical findings are consistent with the view that the Voice Phrase that is realized as non-active voice morphology in Greek anticausatives is expletive. From a theoretical perspective, we analyze the expletiveness of this Voice projection as the result of semantic redundancy: the Voice head of Greek anticausatives combines with a v head that encodes a redundant cause meaning component and is, therefore, interpreted merely as introducing an identity function.

Parkinson's disease patient-specific neuronal networks carrying the LRRK2 G2019S mutation unveil early functional alterations that predate neurodegeneration.

A deeper understanding of early disease mechanisms occurring in Parkinson's disease (PD) is needed to reveal restorative targets. Here we report that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) obtained from healthy individuals or patients harboring LRRK2 PD-causing mutation can create highly complex networks with evident signs of functional maturation over time. Compared to control neuronal networks, LRRK2 PD patients' networks displayed an elevated bursting behavior, in the absence of neurodegeneration. By combining functional calcium imaging, biophysical modeling, and DAn-lineage tracing, we found a decrease in DAn neurite density that triggered overall functional alterations in PD neuronal networks. Our data implicate early dysfunction as a prime focus that may contribute to the initiation of downstream degenerative pathways preceding DAn loss in PD, highlighting a potential window of opportunity for pre-symptomatic assessment of chronic degenerative diseases.

Circadian glucocorticoid oscillations preserve a population of adult hippocampal neural stem cells in the aging brain.

A decrease in adult hippocampal neurogenesis has been linked to age-related cognitive impairment. However, the mechanisms involved in this age-related reduction remain elusive. Glucocorticoid hormones (GC) are important regulators of neural stem/precursor cells (NSPC) proliferation. GC are released from the adrenal glands in ultradian secretory pulses that generate characteristic circadian oscillations. Here, we investigated the hypothesis that GC oscillations prevent NSPC activation and preserve a quiescent NSPC pool in the aging hippocampus. We found that hippocampal NSPC populations lacking expression of the glucocorticoid receptor (GR) decayed exponentially with age, while GR-positive populations decayed linearly and predominated in the hippocampus from middle age onwards. Importantly, GC oscillations controlled NSPC activation and GR knockdown reactivated NSPC proliferation in aged mice. When modeled in primary hippocampal NSPC cultures, GC oscillations control cell cycle progression and induce specific genome-wide DNA methylation profiles. GC oscillations induced lasting changes in the methylation state of a group of gene promoters associated with cell cycle regulation and the canonical Wnt signaling pathway. Finally, in a mouse model of accelerated aging, we show that disruption of GC oscillations induces lasting changes in dendritic complexity, spine numbers and morphology of newborn granule neurons. Together, these results indicate that GC oscillations preserve a population of GR-expressing NSPC during aging, preventing their activation possibly by epigenetic programming through methylation of specific gene promoters. Our observations suggest a novel mechanism mediated by GC that controls NSPC proliferation and preserves a dormant NSPC pool, possibly contributing to a neuroplasticity reserve in the aging brain.

Relating (Un)acceptability to Interpretation. Experimental Investigations on Negation.

Although contemporary linguistic studies routinely use unacceptable sentences to determine the boundary of what falls outside the scope of grammar, investigations far more rarely take into consideration the possible interpretations of such sentences, perhaps because these interpretations are commonly prejudged as irrelevant or unreliable across speakers. In this paper we provide the results of two experiments in which participants had to make parallel acceptability and interpretation judgments of sentences presenting various types of negative dependencies in Basque and in two varieties of Spanish (Castilian Spanish and Basque Country Spanish). Our results show that acceptable sentences are uniformly assigned a single negation reading in the two languages. However, while unacceptable sentences consistently convey single negation in Basque, they are interpreted at chance in both varieties of Spanish. These results confirm that judgment data that distinguish between acceptable and unacceptable negative utterances can inform us not only about an adult's grammar of his/her particular language but also about interesting cross-linguistic differences. We conclude that the acceptability and interpretation of (un)grammatical negative sentences can serve linguistic theory construction by helping to disentangle basic assumptions about the nature of various negative dependencies.

Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns.

Different neurodegenerative disorders often show similar lesions, such as the presence of amyloid plaques, TAU-neurotangles and synuclein inclusions. The genetically inherited forms are rare, so we wondered whether shared epigenetic aberrations, such as those affecting DNA methylation, might also exist. The studied samples were gray matter samples from the prefrontal cortex of control and neurodegenerative disease-associated cases. We performed the DNA methylation analyses of Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Alzheimer-like neurodegenerative profile associated with Down's syndrome samples. The DNA methylation landscapes obtained show that neurodegenerative diseases share similar aberrant CpG methylation shifts targeting a defined gene set. Our findings suggest that neurodegenerative disorders might have similar pathogenetic mechanisms that subsequently evolve into different clinical entities. The identified aberrant DNA methylation changes can be used as biomarkers of the disorders and as potential new targets for the development of new therapies.

Is Mandarin Chinese a Truth-Based Language? Rejecting Responses to Negative Assertions and Questions.

This paper addresses the central question of whether Mandarin Chinese (MC) is a canonical truth-based language, a language that is expected to express the speaker's disagreement to a negative proposition by means of a negative particle followed by a positive sentence. Eight native speakers of MC participated in an oral Discourse Completion Task that elicited rejecting responses to negative assertions/questions and broad focus statements (control condition). Results show that MC speakers convey reject by relying on a combination of lexico-syntactic strategies (e.g., negative particles such as bù, méi(yǒu), and positive sentences) together with prosodic (e.g., mean pitch) and gestural strategies (mainly, the use of head nods). Importantly, the use of a negative particle, which was the expected outcome in truth-based languages, only appeared in 52% of the rejecting answers. This system puts into question the macroparametric division between truth-based and polarity-based languages and calls for a more general view of the instantiation of a reject speech act that integrates lexical and syntactic strategies with prosodic and gestural strategies.

Is there a universal answering strategy for rejecting negative propositions? Typological evidence on the use of prosody and gesture.

Previous research has proposed that languages diverge with respect to how their speakers confirm and contradict negative questions. Taking into account the classification between truth-based and polarity-based languages, this paper is mainly concerned with the expression of REJECT (a semantic operation that signals a contradiction move with respect to the common ground, along Krifka's lines) in two languages belonging to two typologically distinct answering systems, namely Catalan (polarity-based) and Russian (a mixed system using polarity-based, truth-based, and echoic strategies). This investigation has two goals. First, to assess empirically the relevance of prosodic and gestural patterns in the interpretation of confirming and rejecting responses to negative polar questions. Second, to test the claim that in fact speakers resort to strikingly similar universal strategies at the time of expressing rejecting answers to discourse accessible negative assertions and negative polar questions, namely the use of linguistic units that encode REJECT in combination with ASSERT. The results of our investigation support the existence of a universal answering system for rejecting negative polar questions that integrates lexical and syntactic strategies with prosodic and gestural patterns, and instantiate the REJECT and ASSERT operators. We will also discuss the implications these results have for the truth-based vs. polarity-based taxonomy.

Grados de depresión en padres de niños con cáncer / Depression grades in parents which have cancer children

Es bien conocido que las enfermedades somáticas padecidas por los pacientes, afectan el estado psicológico de las personas con quienes estos guardan un vínculo cercano. Intentamos corroborar este hecho aplicándoles test de Hamilton a 58 padres de pacientes, hospitalizados en las alas de oncología pediátrica de diversos centros de salud de Caracas. Se observó una prevalencia de depresión en el 90% de los padres y además pudimos ver que los grados de depresión variaban de acuerdo a ciertos determinantes como el tiempo de desarrollo de la enfermedad y el ambiente del centro hospitalario. Siendo por ende necesario brindar atención psicológica especializada a los acompañantes de los pacientes en los distintos centros de salud

It is well known that the suffering of an illness can affect not only the patient, but also every person that relates intimately to him. We attempted the verification of this statement by applying Hamilton tests to 58 parents of patients which were hospitalized in the several pediatric oncology-specialized health care centers in Caracas. The outcome was a predominance of depression in 90% of the parents; in addition, observed how the different degrees of depression could fluctuate according to certain factors like: Development time of the illness and the hospital’s environment. It is necessary to provide specialized psychological care to the relatives or any companions of the patients hospitalized in health care centers

Determination of critical concentrations of second-line anti-tuberculosis drugs with clinical and microbiological relevance.

BACKGROUND: Reliable DST against second-line anti-tuberculosis drugs (SLDs) is crucial for the management of the increasing burden of patients affected by multidrug- and extensively drug-resistant TB. METHODS: This study utilizes 252 clinical isolates of Mycobacterium tuberculosis from five countries (Hong Kong Special Administrative Region, Korea, Latvia, Peru, Philippines) with documented treatment histories to establish clinically and microbiologically relevant critical concentrations (CCs) of six SLDs for three routine testing methods: the absolute concentration method using Löwenstein-Jensen (LJ) medium, the 1% proportion method using Middlebrook 7H10 agar medium, and the radiometric BACTEC 460 system. FINDINGS: In LJ medium, CCs of capreomycin, ethionamide, kanamycin, ofloxacin, rho-aminosalicylic acid and cycloserine (CS) were respectively 40.0, 40.0, 30.0, 3.0, 1.0 and 30.0 mg/l. In 7H10 agar medium, the respective CCs for the first five antibiotics (except CS) were 8.0, 2.0-3.0, 3.0-5.0, 1.0-1.5 and 0.5-1.0 mg/l. In BACTEC 460 broth, the respective CCs were 1.5-2.0, 1.0-1.5, 2.0-3.0, 0.5-1.0 and 0.5-1.0 mg/l. Precautions in DST interpretation was also discussed. INTERPRETATION: By adopting this set of CCs as a global standard to define second-line drug susceptibility and resistance, as well as precautions in result interpretation, the screening, diagnosis and management of patients with drug-resistant TB can be greatly improved.

[Molecular characterization of extended-spectrum ss-lactamases-producing Escherichia coli and Klebsiella pneumoniae in hospitals of the Caribean Region, Colombia]. / Caracterización molecular de Escherichia coli y Klebsiella pneumoniae productores de ss-lactamasas de espectro extendido en hospitales de la Región Caribe, Colombia.

ESBL-producing in Enterobacteriaceae, is the main resistance mechanism to extended spectrum cephalosporin and monobactams. Seventy isolates collected of hospitals in four cities of the Colombian Caribean, were characterized to ESBL production and metalo-beta-lactamases by microbiological test. The ss-lactamases characterization were performed by IEF and RPC; genotyping by PFGE. Results evidenced the ESBL production at four cities with more frequency in Klebsiella pneumoniae isolated from UCI. The ss-lactamases present in Escherichia coli and in K. pneumoniae contributed co-resistance to different antibiotic families. Enzymes were detected with resistance to cephalosporin and carbapenems, suggesting presence of carbapenemases. Polyclonal isolates noticed, neither demonstrated presence of endemic strains nor association with epidemic outbreak. It is evident the importance to combine clinical, microbiological and molecular information to surveillance the prevalence and evolution of these enzymes in these hospitals.

Caracterización molecular de Escherichia coli y Klebsiella pneumoniae productores de ß-lactamasas de espectro extendido en hospitales de la Región Caribe, Colombia / Molecular characterization of extended-spectrum ß-lactamases-producing Escherichia coliand Klebsiella pneumoniae in hospitals of the Caribean Region, Colombia

ESBL-producing in Enterobacteriaceae, is the main resistance mechanism to extended spectrum cephalosporin and monobactams. Seventy isolates collected of hospitals in four cities of the Colombian Caribean, were characterized to ESBL production and metalo-ß-lactamases by microbiological test. The ß-lactamases characterization were performed by IEF and RPC; genotyping by PFGE. Results evidenced the ESBL production at four cities with more frequency in Klebsiella pneumoniae isolated from UCI. The ß-lactamases present in Escherichia coli and in K. pneumoniae contributed co-resistance to different antibiotic families. Enzymes were detected with resistance to cephalosporin and carbapenems, suggesting presence of carbapenemases. Polyclonal isolates noticed, neither demonstrated presence of endemic strains nor association with epidemic outbreak. It is evident the importance to combine clinical, microbiological and molecular information to surveillance the prevalence and evolution of these enzymes in these hospitals.

La producción de BLEE en Enterobacteriaceae, es el principal mecanismo de resistencia a cefalosporinas de espectro extendido y monobactámicos. Setenta aislados recuperados de hospitales de cuatro ciudades del Caribe colombiano, fueron caracterizados micro-biológicamente para la producción de BLEE y metalo-ß-lactamasas. La caracterización de las ß-lactamasas se realizó por IEF y RPC; la genotipificación por PFGE. Los resultados evidenciaron la producción de BLEE en las cuatro ciudades con mayor frecuencia en Klebsiella pneumoniae aislada de UCI. Las ß-lactamasas presentes en Escherichia coli y en K. pneumoniae aportaron co-resistencia a diferentes familias de antimicrobianos. Se detectaron enzimas con resistencia a cefalosporinas y carbapenems, sugiriendo presencia de carbapenemasas. La policlonalidad observada no demostró presencia de cepas endémicas ni asociación con brotes epidémicos. Se evidencia la importancia de combinar datos clínicos, microbiológicos y moleculares para vigilar la prevalencia y evolución de ß-lactamasas en estos hospitales.

Targets for global tuberculosis control.

The United Nations Millennium Development Goals (MDGs) have added to the suite of targets and indicators used to evaluate progress in tuberculosis (TB) control. This paper reviews the history of target setting for TB control and lays out the complete set of indicators and targets that will guide TB control through to 2015, the target year for all MDGs.

Speaking the same language: treatment outcome definitions for multidrug-resistant tuberculosis.

SETTING: Globally it is estimated that 273000 new cases of multidrug-resistant tuberculosis (MDR-TB, resistance to isoniazid and rifampicin) occurred in 2000. To address MDR-TB management in the context of the DOTS strategy, the World Health Organization and partners have been promoting an expanded treatment strategy called DOTS-Plus. However, standard definitions for MDR-TB patient registration and treatment outcomes do not exist. OBJECTIVE: To propose a standardized set of case registration groups and treatment outcome definitions for MDR-TB and procedures for conducting cohort analyses under the DOTS-Plus strategy. DESIGN: Using published definitions for drug-susceptible TB as a guide, a 2-year-long series of meetings, conferences, and correspondence was undertaken to review published literature and country-specific program experience, and to develop international agreement. RESULTS: Definitions were designed for MDR-TB patient categorization, smear and culture conversion, and treatment outcomes (cure, treatment completion, death, default, failure, transfer out). Standards for conducting outcome analyses were developed to ensure comparability between programs. CONCLUSION: Optimal management strategies for MDR-TB have not been evaluated in controlled clinical trials. Standardized definitions and cohort analyses will facilitate assessment and comparison of program performance. These data will contribute to the evidence base to inform decision makers on approaches to MDR-TB control.

Adverse events in the treatment of multidrug-resistant tuberculosis: results from the DOTS-Plus initiative.

Adverse events associated with second-line drugs have been mentioned as obstacles in the management of multidrug-resistant tuberculosis (MDR-TB). Data on adverse events were collected from five DOTS-Plus sites in Estonia, Latvia, Peru (Lima), the Philippines (Manila) and the Russian Federation (Tomsk Oblast). The results show that among 818 patients enrolled on MDR-TB treatment only 2% of patients stopped treatment, but 30% required removal of the suspected drug(s) from the regimen due to adverse events. The study shows that adverse events are manageable in the treatment of MDR-TB in resource-limited settings provided that standard management strategies are applied.