Hidden Communication Deficits in Children with Autism and Early Behavioral Interventions

Taking a behavioral systems approach to autism, early hidden communicative deficits are introduced as precursors of autistic development. This paper argues that early identification of communication (language and cognition) impairments followed by intensive behavioral interventions, as early as infancy, may have the most preventive effect on the development of autism.

The Expression of Rap6 in the Adult Mouse Brain and Early Mouse Embryonic Development

The previously identified RAP6 (Rab5 activating protein 6) was associated with plasma membrane mediated endocytosis and contains a Rab5 guanine nucleotide exchange factor (GEF) domain. RAP6 has been shown to act a Ras activating protein (GAP) domain. The identification of RAP6 and its crucial role in both receptors mediated endocytosis and fluid phase endocytosis presents the opportunity to investigate its role in murine embryonic development and in the adult brain. To confirm and characterize the presence of RAP6 during embryonic development and in the adult brain, the current study examined the expression of both the RGD and the Vps9 domains of RAP6 through in situ hybridization. We present an extensive evaluation of the expression for both RAP6 domains through in situ hybridization of 12.5 and 14.5 weeks old C67 mouse embryos and adult C67 mouse brain. The current study confirms the presence of both RAP6 domains and presents an extensive evaluation its expression in embryonic development and the adult brain. These data together support the role of RAP6 in receptor mediated endocytosis and fluid phase endocytosis relevant active during murine embryonic development and adult brain processes.

Effects of Prenatal and Early Postnatal Exposure to Aversive Stimuli on Fearfulness and Exploratory Behavior in Bobwhite Qauil Neonates (Colinus virginianus)

Neophobia, the fear of novelty, is a behavioral trait found across a number of animal species, including humans. Neophobic individuals perceive novel environments and stimuli to have aversive properties, and exhibit fearful behaviors when presented with non-familiar situations. The present study examined how early life exposure to aversive novel stimuli could reduce neophobia in bobwhite quail chicks. Experiment 1 exposed chicks to a novel auditory tone previously shown to be aversive to naïve chicks (Suarez, 2012) for 24 hours immediately after hatching, then subsequently tested them in the presence of the tone within a novel maze task. Postnatally exposed chicks demonstrated decreased fearfulness compared to naïve chicks, and behaved more similarly to chicks tested in the presence of a known attractive auditory stimulus (a bobwhite maternal assembly call vocalization). Experiment 2 exposed chicks to the novel auditory tone for 24 hours prenatally, then subsequently tested them within a novel maze task. Prenatally exposed chicks showed decreased fearfulness to a similar degree as those postnatally exposed, revealing that both prenatal and postnatal exposure methods are capable of decreasing fear of auditory stimuli. Experiment 3 exposed chicks to a novel visual stimulus for 24 hours postnatally, then subsequently tested them within a novel emergence box / T-maze apparatus. Chicks exposed to the visual stimulus showed decreased fearfulness compared to naïve chicks, thereby demonstrating the utility of this method across sense modalities. Experiment 4 assessed whether early postnatal exposure to one novel stimulus could generalize and serve to decrease fear of novelty when chicks were tested in the presence of markedly different stimuli. By combining the methods of Experiments 1 and 3, this experiment revealed that chicks exposed to one type of stimulus (auditory or visual) demonstrated decreased fear when subsequently tested in the presence of the opposite type of novel stimulus. These results suggest that experience with novel stimuli can moderate the extent to which neophobia will develop during early development.

Doctrine and Tradition in Benjamin's early Thought : A relegated Chapter in the Study of his Reception of Kant

En el presente trabajo indagamos el significado de los conceptos de "doctrina" y "tradición" en las reflexiones de Benjamin hacia 1917, íntimamente vinculados con su recepción de Kant. Los escasos análisis de tal recepción relegan este aspecto. Intentamos mostrar que estos conceptos expresan un interés por la idea kantiana de unidad sistemática del conocimiento, y sostenemos que Benjamin reinterpreta tal unidad en términos mesiánicos: ya no como un supuesto necesario, sino como una exigencia de redención. Finalmente, exhibimos de qué modo estas nociones se hallan implícitas en el escrito "Sobre el programa de una filosofía futura"

Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone

OBJECTIVES: This study was designed to evaluate the impact of eplerenone on collagen turnover in preserved systolic function heart failure (HFPSF).

BACKGROUND: Despite growing interest in abnormal collagen metabolism as a feature of HFPSF with diastolic dysfunction, the natural history of markers of collagen turnover and the impact of selective aldosterone antagonism on this natural history remains unknown.

METHODS: We evaluated 44 patients with HFPSF, randomly assigned to control (n = 20) or eplerenone 25 mg daily (n = 24) for 6 months, increased to 50 mg daily from 6 to 12 months. Serum markers of collagen turnover and inflammation were analyzed at baseline and at 6 and 12 months and included pro-collagen type-I and -III aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha. Doppler-echocardiographic assessment of diastolic filling indexes and tissue Doppler analyses were also obtained.

RESULTS: The mean age of the patients was 80 +/- 7.8 years; 46% were male; 64% were receiving an angiotensin-converting enzyme inhibitor, 34% an angiotensin-II receptor blocker, and 68% were receiving beta-blocker therapy. Pro-collagen type-III and -I aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha increased with time in the control group. Eplerenone treatment had no significant impact on any biomarker at 6 months but attenuated the increase in pro-collagen type-III aminoterminal peptide at 12 months (p = 0.006). Eplerenone therapy was associated with modest effects on diastolic function without any impact on clinical variables or brain natriuretic peptide.

CONCLUSIONS: This study demonstrates progressive increases in markers of collagen turnover and inflammation in HFPSF with diastolic dysfunction. Despite high background utilization of renin-angiotensin-aldosterone modulators, eplerenone therapy prevents a progressive increase in pro-collagen type-III aminoterminal peptide and may have a role in management of this disease. (The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure; NCT00505336).

The impact of childhood residential mobility on mental health outcomes in adolescence and early adulthood: a record linkage study.

Background Understanding the causes of poor mental health in early childhood and adolescence is important as this can be a significant determinant of mental well-being in later years. One potential and relatively unexplored factor is residential mobility in formative years. Previous studies have been relatively small and potentially limited due to methodological issues. The main aim of this study was to investigate the relationship between early residential instability and poor mental health among adolescents and young adults in Northern Ireland.

Methods A Census-based record linkage study of 28% of children aged 0–8 years in 2001 in Northern Ireland (n=49 762) was conducted, with six monthly address change assessments from health registration data and self-reported mental health status from the 2011 Census. Logistic regression models were built adjusting for socioeconomic status (SES), household composition and marital dissolution.

Results There was a graded relationship between the number of address changes and mental ill-health (adjusted OR 3.67, 95% CIs 2.11 to 6.39 for 5 or more moves). This relationship was not modified by SES or household composition. Marital dissolution was associated with poor mental health but did not modify the relationship between address change and mental health (p=0.206). There was some indication that movement after the age of five was associated with an increased likelihood of poor mental health.

Conclusions This large study clearly confirms the close relationship between address change in early years and later poor mental health. Residential mobility may be a useful marker for children at risk of poorer mental health in adolescence and early adulthood

Phylum-wide transcriptome analysis of oogenesis and early embryogenesis in selected nematode species

Oogenesis is a prerequisite for embryogenesis in Metazoa. During both biological processes important decisions must be made to form the embryo and hence ensure the next generation: (1) Maternal gene products (mRNAs, proteins and nutrients) must be supplied to the embryo. (2) Polarity must be established and axes must be specified. While incorporation of maternal gene products occurs during oogenesis, the time point of polarity establishment and axis specification varies among species, as it is accomplished either prior, during, or after fertilisation. But not only the time point when these events take place varies among species but also the underlying mechanisms by which they are triggered. For the nematode model Caenorhabditis elegans the underlying pathways and gene regulatory networks (GRNs) are well understood. It is known that there the sperm entry point initiates a primary polarity in the 1-celled egg and with it the establishment of the anteroposterior axis. However, studies of other nematodes demonstrated that polarity establishment can be independent of sperm entry (Goldstein et al., 1998; Lahl et al., 2006) and that cleavage patterns, symmetry formation and cell specification also differ from C. elegans. In contrast to the studied Chromadorea (more derived nematodes including C. elegans), embryos of some marine Enoplea (more basal representatives) even show no discernible early polarity and blastomeres can adopt variable cell fates (Voronov and Panchin 1998). The underlying pathways controlling the obviously variant embryonic processes in non-Caenorhabditis nematodes are essentially unknown. In this thesis I addressed this issue by performing a detailed unbiased comparative transcriptome analysis based on microarrays and RNA sequencing of selected developmental stages in a variety of nematodes from different phylogenetic branches with C. elegans as a reference system and a nematomorph as an outgroup representative. In addition, I made use of available genomic data to determine the presence or absence of genes for which no expression had been detected. In particular, I focussed on components of selected pathways or GRNs which are known to play essential roles during C. elegans development and/or other invertebrate or vertebrate model systems. Oogenesis must be regulated differently in non-Caenorhabditis nematodes, as crucial controlling components of Wnt and sex determination signaling are absent in these species. In this respect, I identified female-specific expression of potential polarity associated genes during gonad development and oogenesis in the Enoplean nematode Romanomermis culicivorax. I could show that known downstream components of the polarity complexes PAR-3/-6/PKC-3 and PAR-1/-2 are absent in non-Caenorhabditis species. Even PAR-2 as part of the polarity complex does not exist in these nematodes. Instead, transcriptomes of nematodes (including C. elegans), show expression of other polarity-associated complexes such as the Lgl (Lethal giant larvae) complex. This result could pose an alternative route for nematodes and nematomorphs to initiate polarity during early embryogenesis. I could show that crucial pathways of axis specification, such as Wnt and BMP are very different in C. elegans compared to other nematodes. In the former, Wnt signaling, for instance, is mediated by four paralogous beta-catenins, while other Chromadorea have fewer and Enoplea only one beta-catenin. The transcriptomes of R. culicivorax and the nematomorph show that regulators of BMP (e.g. Chordin), are specifically expressed during early embryogenesis only in Enoplea and the close outgroup of nematomorphs. In conclusion, my results demonstrate that the molecular machinery controlling oogenesis and embryogenesis in nematodes is unexpectedly variable and C. elegans cannot be taken as a general model for nematode development. Under this perspective, Enoplean nematodes show more similarities with outgroups than with C. elegans. It appears that certain pathway components were lost or gained during evolution and others adopted new functions. Based on my findings I can conjecture, which pathway components may be ancestral and which were newly acquired in the course of nematode evolution.

The Political and Social Dynamics of Poverty, Poor Relief and Health Care in Early-Modern Portugal

By the end of the fifteenth century most European countries had witnessed a profound reformation of their poor relief and health care policies. As this book demonstrates, Portugal was among them and actively participated in such reforms. Providing the first English language monograph on this topic, Laurinda Abreu examines the Portuguese experience and places it within the broader European context. She shows that, in line with much that was happening throughout the rest of Europe, Portugal had not only set up a systematic reform of the hospitals but had also developed new formal arrangements for charitable and welfare provision that responded to the changing socioeconomic framework, the nature of poverty and the concerns of political powers. The defining element of the Portuguese experience was the dominant role played by a new lay confraternity, the confraternity of the Misericórdia, created under the auspices of King D. Manuel I in 1498. By the time of the king's death in 1521 there were more than 70 Misericórdias in Portugal and its empire, and by 1640, more than 300. All of them were run according to a unified set of rules and principles with identical social objectives. Based upon a wealth of primary source documentation, this book reveals how the sixteenth-century Portuguese crown succeeded in implementing a national poor relief and health care structure, with the support of the Papacy and local elites, and funded principally through pious donations. This process strengthened the authority of the royal government at a time which coincided with the emergence of the early modern state. In so doing, the book establishes poor relief and public health alongside military, diplomatic and administrative authorities, as the pillars of centralisation of royal power.

Invented spelling activities in small groups and early spelling and reading

Our aim was to assess the impact of an invented spelling programme conducted in small groups on children’s written language acquisition in Portuguese. We expected the experimental group to have better post-test results than the control group in spelling and reading. Participants were 160 preschool-age children who were randomly divided into an experimental and a control group. Their age, cognitive ability, knowledge of letters and phonological abilities were controlled. Children’s spelling and reading were evaluated in a pre- and a post-test. Inbetween, experimental group participated in an invented spelling programme in small groups and the control group in story readings. The experimental group showed better results in spelling and reading in the post-test than the control one. Different dynamics occurred in the small groups which had different impacts on children’s acquisitions. These results provide empirical support for the proposal that invented spelling should be incorporated into early literacy instruction.

Platform management and early supplier involvement in NPD

Platform strategies reflect a firm’s technology policy towards its new product development (NPD) activities. Depending on the technological complexities embedded in the platform, certain degree of interdependence is created between the firm and its suppliers. Firms may decide to what extent the suppliers should be involved in its NPD activities. There has been an increasing interest with issues related to supplier involvement in NPD. Involving suppliers early in NPD can help firms reduce costs, reduce concept-to-customer development time, improve quality, and provide innovative technologies. However, it requires a great effort and many tradeoffs need to be considered. This paper discusses the implications of early supplier involvement in new product development, specifically regarding to sourcing decisions and NPD processes when new components are designed and incorporated into the new platform. We would like to understand to what extent the NPD collaborates with suppliers, and at which stage of the NPD process suppliers are invited to participate in platform designs. A case study of Oticon, a Danish manufacturer of hearing aids, is presented. We describe how the successful introduction of a new platform of hearing aids is realized as well as how and when Oticon’s suppliers were involved during this process.

Orthographic regularization in Early Modern English: Grapheme distribution and vowel length indication

The present study is an attempt at assessing the level of consistency in the orthographic systems of selected sixteenth and seventeenth-century printers and at tracing the influence that normative writings could have potentially exerted on them. The approach taken here draws upon the philological tradition of examining and comparing several texts written in the same language, but produced at different times. The study discusses the orthography of the editions of The Schoole of Vertue, a manual of good conduct for children, published between 1557 and 1687. The orthographic variables taken into account fall into two criteria: the distribution and functional load of the selected graphemes and the indication of vowel length.

CHRONOMETRY OF LATE ENEOLITHIC AND ‘EARLY BRONZE’ CULTURES IN THE MIDDLE DNIESTER AREA: INVESTIGATIONS OF THE YAMPIL BARROW COMPLEX

The paper discusses the 2010-2015 studies of the radiocarbon chronology of Podolia ‘barrow cultures’ on the left bank of the middle dniester . The studies have relied on series of 14 C dates for the Klembivka 1, Pidlisivka 1, Porohy 3a and Prydnistryanske 1 sites determined in Kyiv and Poznań laboratories . They are the first attempt to construct a regional (‘Yampil’) radiocarbon scale for ‘Early Bronze’ funerary rites (4th/3rd-2nd millennium BC) as practised by barrow builders – the communities of the Tripolye and Yamnaya cultures – and the secondary barrow users – the designers of necropolises located on barrows – belonging to the Catacomb, Babyno and Noua cultures.