Inventory of current EU paediatric vision and hearing screening programmes

Background: We examined the diversity in paediatric vision and hearing screening programmes in Europe. Methods: Themes relevant for comparison of screening programmes were derived from literature and used to compile three questionnaires on vision, hearing and public-health screening. Tests used, professions involved, age and frequency of testing seem to influence sensitivity, specificity and costs most. Questionnaires were sent to ophthalmologists, orthoptists, otolaryngologists and audiologists involved in paediatric screening in all EU fullmember, candidate and associate states. Answers were cross-checked. Results: Thirty-nine countries participated; 35 have a vision screening programme, 33 a nation-wide neonatal hearing screening programme. Visual acuity (VA) is measured in 35 countries, in 71% more than once. First measurement of VA varies from three to seven years of age, but is usually before the age of five. At age three and four picture charts, including Lea Hyvarinen are used most, in children over four Tumbling-E and Snellen. As first hearing screening test otoacoustic emission (OAE) is used most in healthy neonates, and auditory brainstem response (ABR) in premature newborns. The majority of hearing testing programmes are staged; children are referred after one to four abnormal tests. Vision screening is performed mostly by paediatricians, ophthalmologists or nurses. Funding is mostly by health insurance or state. Coverage was reported as >95% in half of countries, but reporting was often not first-hand. Conclusion: Largest differences were found in VA charts used (12), professions involved in vision screening (10), number of hearing screening tests before referral (1-4) and funding sources (8)

Transnational Corporation Mergers and its Impact on Development

Globalizācijas ietekmē, pieaugot korporāciju iespējām veikt darbību starptautiskā mērogā, ir izveidojies ļoti dinamisks un konkurentu bagāts tirgus teju visās industrijās un nozarēs. Lai saglabātu savu konkurētspēju un spētu pielāgoties straujajām pārmaiņām, korporācijām ir bijis jāattīstās un jāaug ļoti straujā tempā. Līdz ar to, ir aktualizējušās apvienošanas un pārņemšanas stratēģijas, ko korporācijas izmanto kā ātrākas izaugsmes un attīstības rīkus, lai nodrošinātu savu konkurētspēju un ieņemtu stabilu vietu savas nozares tirgū. Līdz ar to, pētījuma mērķis ir identificēt transnacionālo korporāciju apvienošanās darījumu ietekmi uz uzņēmumu attīstību. Analizējot divus apvienošanās darījumus, tiek identificēti darījumus motivējošie faktori un noteikta darījumu ietekme uz korporāciju finanšu rādītājiem un šo korporāciju turpmāko darbību.Due to globalization, the increasing possibilities for corporations to operate internationally have created a very dynamic and competitive market within virtually all industries and branches. In order to remain competitive and adapt to rapid change, corporations have had to develop and grow at a very fast pace. As a result, merger and acquisition strategies have become more topical by corporations using them as tools for faster growth and development to secure their competitiveness and gain a stable position in their market. Therefore, the aim of the research is to identify transnational corporation merger impact on business development. By analyzing two merger transactions, deal motivating factors are identified and the impact of transactions on the financial ratios of corporations and their future performance is determined

Structural Basis for the Specificity of Human NUDT16 and Its Regulation by Inosine Monophosphate.

Human NUDT16 is a member of the NUDIX hydrolase superfamily. After having been initially described as an mRNA decapping enzyme, recent studies conferred it a role as an "housecleaning" enzyme specialized in the removal of hazardous (deoxy)inosine diphosphate from the nucleotide pool. Here we present the crystal structure of human NUDT16 both in its apo-form and in complex with its product inosine monophosphate (IMP). NUDT16 appears as a dimer whose formation generates a positively charged trench to accommodate substrate-binding. Complementation of the structural data with detailed enzymatic and biophysical studies revealed the determinants of substrate recognition and particularly the importance of the substituents in position 2 and 6 on the purine ring. The affinity for the IMP product, harboring a carbonyl in position 6 on the base, compared to purine monophosphates lacking a H-bond acceptor in this position, implies a catalytic cycle whose rate is primarily regulated by the product-release step. Finally, we have also characterized a phenomenon of inhibition by the product of the reaction, IMP, which might exclude non-deleterious nucleotides from NUDT16-mediated hydrolysis regardless of their cellular concentration. Taken together, this study details structural and regulatory mechanisms explaining how substrates are selected for hydrolysis by human NUDT16

Binding constants of product binding to NUDT16.

<p>All values were determined by Origin from MicroCal Software, Inc., after fitting the experimental data to a one binding-site model, allowing all parameters to evolve freely in the course of the fit.</p

Interactions between NUDT16 and IMP.

<p>(A) Overview of the IMP molecules bound to NUDT16 dimer. Both the view and the color codes correspond to the ones used in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131507#pone.0131507.g001" target="_blank">Fig 1A</a>. IMP and Mg²⁺ ions are shown as sticks and van der Waals spheres, respectively. (B) Electrostatic surface representation of NUDT16 bound to IMP. Molecular surface of NUDT16 is colored according to its electrostatic potential as calculated by the APBS program [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131507#pone.0131507.ref024" target="_blank">24</a>]. The color ramp varies from blue to red corresponding to +5<i>k</i>T/e and to -5<i>k</i>T/e, respectively. (C) Interactions between NUDT16, IMP and Mg²⁺ around the ribose and the base. NUDT16 is shown in the cartoon representation and colored either in violet (NUDIX motifs) or blue-grey (other region of the protein). IMP, IMP-interacting residues and Val22 are shown as sticks with their carbon atoms colored either in violet (residues belonging to the NUDIX motif), blue-grey (other NUDT16 residues) or green (IMP). NUDT16 residues are labeled using the single-letter code. Mg²⁺ ions are displayed as orange van der Waals spheres. Water molecules involved in hydrogen-bond network between NUDT16 and IMP are represented as small red spheres and labeled in red according to their numbering in the PDB file. H-bonds are symbolized by dashed lines. (D) Interactions between NUDT16, IMP and Mg²⁺ around the phosphate. Same color code as in (C) except that H-bonds and salt-bridges are represented by purple and yellow dashed lines respectively. (E) Ligplot [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131507#pone.0131507.ref025" target="_blank">25</a>] diagram of the interactions between NUDT16, IMP and Mg²⁺. Water molecules and Mg²⁺ ions are show as cyan and green spheres respectively. Covalent bonds in the IMP molecule are colored in violet and in orange when they belong to NUDT16. Hydrogen bonds and salt-bridges are represented by green dashed lines, hydrophobic interactions by red dashed lines. NUDT16 residues are labeled in black and red when they are involved in hydrophobic and polar interactions, respectively. Heteroatoms on the hypoxanthine ring of IMP are labelled in violet. Bonds between the Mg²⁺ ions and other atoms are depicted by violet plain lines. Water molecules (when they are shown in Fig 3C) are labeled in cyan according to their numbering in the PDB file.</p