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

Development and application of sensitive genome-wide platforms to study the genetic and epigenetic (DNA methylation) makeup of gametes and early bovine embryos

Pour ce projet, nous avons développé une plateforme pour l’analyse pangénomique de la méthylation de l’ADN chez le bovin qui est compatible avec des échantillons de petites tailles. Cet outil est utilisé pour étudier les caractéristiques génétiques et épigénétiques (méthylation de l’ADN) des gamètes soumis aux procédures de procréation médicalement assisitée et des embryons précoces. Dans un premier temps, une plateforme d’analyse de biopuces spécifiques pour l’étude de la méthylation de l’ADN chez l’espèce bovine a été développée. Cette plateforme a ensuite été optimisée pour produire des analyses pangénomiques de méthylation de l’ADN fiables et reproductibles à partir d’échantillons de très petites tailles telle que les embryons précoces (≥ 10 ng d’ADN a été utilisé, ce qui correspond à 10 blastocystes en expansion). En outre, cet outil a permis d’évaluer de façon simultanée la méthylation de l’ADN et le transcriptome dans le même échantillon, fournissant ainsi une image complète des profils génétiques et épigénétiques (méthylation de l’ADN). Comme preuve de concept, les profils comparatifs de méthylation de l’ADN spermatique et de blastocystes bovins ont été analysés au niveau de l’ensemble du génome. Dans un deuxième temps, grâce à cette plateforme, les profils globaux de méthylation de l’ADN de taureaux jumeaux monozygotes (MZ) ont été analysés. Malgré qu’ils sont génétiquement identiques, les taureaux jumeaux MZ ont des descendants avec des performances différentes. Par conséquent, l’hypothèse que le profil de méthylation de l’ADN spermatique de taureaux jumeaux MZ est différent a été émise. Dans notre étude, des différences significatives entre les jumeaux MZ au niveau des caractéristiques de la semence ainsi que de la méthylation de l’ADN ont été trouvées, chacune pouvant contribuer à l’obtention de performances divergentes incongrues des filles engendrées par ces jumeaux MZ. Dans la troisième partie de ce projet, la même plateforme a été utilisée pour découvrir les impacts d’une supplémentation à forte concentration en donneur de méthyle universel sur les embryons précoces bovins. La supplémentation avec de grandes quantités d’acide folique (AF) a été largement utilisée et recommandée chez les femmes enceintes pour sa capacité bien établie à prévenir les malformations du tube neural chez les enfants. Cependant, plus récemment, plusieurs études ont rapporté des effets indésirables de l’AF utilisé à des concentrations élevées, non seulement sur le développement de l’embryon, mais aussi chez les adultes. Au niveau cellulaire, l’AF entre dans le métabolisme monocarboné, la seule voie de production de S-adénosyl méthionine (SAM), un donneur universel de groupements méthyles pour une grande variété de biomolécules, y compris l’ADN. Par conséquent, pour résoudre cette controverse, une forte dose de SAM a été utilisée pour traiter des embryons produits in vitro chez le bovin. Ceci a non seulement permis d’influencer le phénotype des embryons précoces, mais aussi d’avoir un impact sur le transcriptome et le méthylome de l’ADN. En somme, le projet en cours a permis le développement d’une plateforme d’analyse de la méthylation de l’ADN à l’échelle du génome entier chez le bovin à coût raisonnable et facile à utiliser qui est compatible avec les embryons précoces. De plus, puisque c’est l’une des premières études de ce genre en biologie de la reproduction bovine, ce projet avait trois objectifs qui a donné plusieurs nouveaux résultats, incluant les profils comparatifs de méthylation de l’ADN au niveau : i) blastocystes versus spermatozoïdes ; ii) semence de taureaux jumeaux MZ et iii) embryons précoces traités à de fortes doses de SAM versus des embryons précoces non traités.

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.

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.

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.

Early life history of larvae and early juvenile atlantic horse mackerel trachurus trachurus off the portuguese west coast

Early life history traits (ELHTs) are key to understand recruitment patterns in marine animals. However, for reef fishes, studies on ELHTs are mainly focused on tropical systems and little is known for temperate reefs. In this study we used SMURFs (Standard Monitoring Units for the Recruitment of Reef Fishes) to collect fish in a temperate rocky reef system (Arrábida Marine Park, Portugal) on a weekly basis for three months during the recruitment period. Six sub-surface SMURFs sampled 2490 Atlantic horse mackerel (Trachurus trachurus) postlarvae and juveniles. Sagittal and lapilli otoliths were extracted from a subsample of 296 fish and ELHTs, such as size and age at settlement, growth rate and age at first secondary growth formation were examined. Additionally, we tested three growth curves and selected the best suited to back-calculate the hatching pattern based on the lengths of all sampled fish. Standard length ranged from 6.13 mm to 48.56 mm and subsampled fish were aged between 19 days to 44 days. Age and size at settlement were estimated between 19 days and 36 days for individuals of 6.13 mm and 24.95 mm, respectively. Otolith shape changed clearly with increasing age and, on average, secondary growth started to form on day 33 (±3 days). Age/length relationship was well described by a Gompertz growth model which was used to back-calculate hatching dates. Four distinct hatching cohorts were identified with fish of the earliest cohort showing a faster body and otolith growth. This study indicates that the nearshore environment might have an important role in the early growth, development and hence recruitment of Atlantic horse mackerel. Information on the early life history of Atlantic horse mackerel is key to understand recruitment processes for this economically and biologically important species.

Nutrients limiting the Algal Growth Potential (AGP) in the Gulf of Riga, eastern Baltic Sea, in spring and early summer 1996

In May, June and July 1996, samples wcre collected along one transect greatly influenced by river discharge (eastern side of the gulf), along one transect slightly influence by river discharge (western side), at one station Iocated in the mouth of the main river (River Daugava), at one station located in the center of the Gulf and at several nearshore locations of the western side. Ratios of rnolecular concentrations of in situ dissolved ioorganic nitrogen, phosphorus and silicon, as weIl as enrichment bioassays were llsed to dctcrrnine which nutrient (s) lirnited the potential biomass of phytoplankton. Both comparison of (NO.d-N02+NJ.L): P04 (DIN: DIP) values with Redfic1d's ratio and bioassay inspection led to the sarne conclusions. Phosphorus was clearly the nutrient most limiting for the potcntial biornass of test species in nitrogen- rich waters, which occurred in mid spring, in the upper layer of the southern-eastern part of the Gulf which is greatly influenced by river discharge. In late spring, with the decrease of the total DIN reserve, nitrogen and phosphorus showed an equallimiting role. In deeper layers of this area and out of the river plume (western side and central part of the gulf), nitrogen was the limiting nutrient. In summer, whcn river discharge was the lowest, a11 DIN concentrations but one ranged between 1.6 and 2.6 µM, and the whole area was nitrogen-limited for both the cyanobacterial and the algal test strains. In 74% of the samples for which nitrogen was the limiting nutrient, phosphorus was recorded to be the second potentially limiting nutrient. In contrast, silicon never appeared as limiting the growth potential of either Microcystis aeruginosa or Phaeodactylum tricornutum; phosphorus was the limiting nutrient when DIN: Si03 values were >1 (in May), but DIN: Si03 was <1 when nitrogen was limiting (June and July). The authors conclude that the recently reported decrease of silicon loading in coastal waters and its subsequent enhanced importance in pushing the outcome of species competition towards harmful species may not yet be the most important factor for the Gulf of Riga. Iron appeared for 12% of the tests in the list of nutrients limiting the potential biomass. Tentative results also indicated that a significant fraction of the nitrogen (~,4 µg-atom N 1(-1) taken up by Microcystis aeruginosa may have been in the form of dissolved organic nitrogen (DON). It is thus also suggested tentatively that more attention be paid to these nitrients during further research in the Gulf of Riga.

Use of flucinolone acetonide for patients with diabetic macular oedema:patient selection criteria and early outcomes in real world setting

Introduction: Fluocinolone acetonide slow release implant (Iluvien®) was approved in December 2013 in UK for treatment of eyes which are pseudophakic with DMO that is unresponsive to other available therapies. This approval was based on evidence from FAME trials which were conducted at a time when ranibizumab was not available. There is a paucity of data on implementation of guidance on selecting patients for this treatment modality and also on the real world outcome of fluocinolone therapy especially in those patients that have been unresponsive to ranibizumab therapy. Method: Retrospective study of consecutive patients treated with fluocinolone between January and August 2014 at three sites were included to evaluate selection criteria used, baseline characteristics and clinical outcomes at 3-month time point. Results: Twenty two pseudophakic eyes of 22 consecutive patients were included. Majority of patients had prior therapy with multiple intravitreal anti-VEGF injections. Four eyes had controlled glaucoma. At baseline mean VA and CRT were 50.7 letters and 631 μm respectively. After 3 months, 18 patients had improved CRT of which 15 of them also had improved VA. No adverse effects were noted. One additional patient required IOP lowering medication. Despite being unresponsive to multiple prior therapies including laser and anti-VEGF injections, switching to fluocinolone achieved treatment benefit. Conclusion: The patient level selection criteria proposed by NICE guidance on fluocinolone appeared to be implemented. This data from this study provides new evidence on early outcomes following fluocinolone therapy in eyes with DMO which had not responded to laser and other intravitreal agents.

Spatial and Functional Organization of Pig Trade in Different European Production Systems: Implications for Disease Prevention and Control

Understanding the complexity of live pig trade organization is a key factor to predict and control major infectious diseases, such as classical swine fever (CSF) or African swine fever (ASF). Whereas the organization of pig trade has been described in several European countries with indoor commercial production systems, little information is available on this organization in other systems, such as outdoor or small-scale systems. The objective of this study was to describe and compare the spatial and functional organization of live pig trade in different European countries and different production systems. Data on premise characteristics and pig movements between premises were collected during 2011 from Bulgaria, France, Italy, and Spain, which swine industry is representative of most of the production systems in Europe (i.e., commercial vs. small-scale and outdoor vs. indoor). Trade communities were identified in each country using the Walktrap algorithm. Several descriptive and network metrics were generated at country and community levels. Pig trade organization showed heterogeneous spatial and functional organization. Trade communities mostly composed of indoor commercial premises were identified in western France, northern Italy, northern Spain, and north-western Bulgaria. They covered large distances, overlapped in space, demonstrated both scale-free and small-world properties, with a role of trade operators and multipliers as key premises. Trade communities involving outdoor commercial premises were identified in western Spain, south-western and central France. They were more spatially clustered, demonstrated scale-free properties, with multipliers as key premises. Small-scale communities involved the majority of premises in Bulgaria and in central and Southern Italy. They were spatially clustered and had scale-free properties, with key premises usually being commercial production premises. These results indicate that a disease might spread very differently according to the production system and that key premises could be targeted to more cost-effectively control diseases. This study provides useful epidemiological information and parameters that could be used to design risk-based surveillance strategies or to more accurately model the risk of introduction or spread of devastating swine diseases, such as ASF, CSF, or foot-and-mouth disease.