Additional file 4: of Dendritic cells change IL-27 production pattern during childhood

Figure S4. Age related frequencies of IL-27-positive mDCs (top row) and pDCs (lower row)

Additional file 3: of Dendritic cells change IL-27 production pattern during childhood

Figure S3. Age-related cell frequency

DataSheet1_Phenylalanine hydroxylase mRNA rescues the phenylketonuria phenotype in mice.docx

Phenylketonuria (PKU) is an inborn error of metabolism caused by a deficiency in functional phenylalanine hydroxylase (PAH), resulting in accumulation of phenylalanine (Phe) in patients’ blood and organs. Affected patients encounter severe developmental delay, neurological deficits, and behavioral abnormalities when not treated. Early diagnosis and treatment are extremely important; newborn screening programs have been implemented in most countries to ensure early identification of patients with PKU. Despite available treatment options, several challenges remain: life-long adherence to a strict diet, approval of some medications for adults only, and lack of response to these therapies in a subpopulation of patients. Therefore, there is an urgent need for treatment alternatives. An mRNA-based approach tested in PKU mice showed a fast reduction in the accumulation of Phe in serum, liver and brain, the most significant organ affected. Repeated injections of LNP-formulated mouse PAH mRNA rescued PKU mice from the disease phenotype for a prolonged period of time. An mRNA-based approach could improve the quality of life tremendously in PKU patients of all ages by replacing standard-of-care treatments.</p

Comparison of study characteristics.

<p>Comparison of study characteristics.</p

Questionnaire items used for scoring.

<p>Numbers in brackets (%) are frequencies of parents' answers, denominator of n = 1226 in Leicester subsample used for generating the tool, and of n = 140 in MAS-90 subsample. * before/after imputation with values from prior follow-up assessments and baseline.</p><p>Questionnaire items used for scoring.</p

Questionnaire items used as inclusion criteria and outcome definition, comparing original and validation cohort.

<p>Questionnaire items used as inclusion criteria and outcome definition, comparing original and validation cohort.</p

Characteristics of families in sample used for external validation, by follow-up status.

<p>ISCED, International Standard classification of Education; BMI, Body mass index; IgE, Immunoglobulin E; 95%-CI, bootstrapped 95% confidence intervals; kU/l, kilo Units per litre.</p><p>Characteristics of families in sample used for external validation, by follow-up status.</p

Score distribution (relative frequency) from model building sample.

<p>(n = 1226, left side, from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0115852#pone.0115852-Pescatore1" target="_blank">[13]</a>) and external validation sample (n = 140, right side). Primary inclusion, scoring and outcome definitions. * no child with age 1 year in external validation sample (score 0 not possible).</p

Predicted probability of developing asthma 5 years later, for a single particular score value.

<p>Performance measures by score in table above. Primary inclusion, scoring, and outcome definitions. Probabilities from original paper (dotted line). * Values not meaningful and/or no accurate estimate possible. PPV/NPV, positive/negative predictive value; LR+/-, positive/negative likelihood ratio.</p

Discrimination and Performance of the asthma prediction score in the MAS-90 birth cohort used for external validation.

<p>* rescaled to its maximum value; # 100 imputations, accounted for calculating confidence intervals; $ according to the corresponding outcome definition; § primary inclusion: cough or wheeze at 3 years – primary scoring: available items at 3 years – primary outcome: wheeze and asthma medication at 8 years; Odds Ratio per 1-point increase in asthma prediction score; Secondary outcome definition details up to age 20 years in methods section; CI, confidence interval.</p><p>Discrimination and Performance of the asthma prediction score in the MAS-90 birth cohort used for external validation.</p