ALL_demographics and baseline_Dryad

Demographics and baseline data of all recruited participant

ANALYSED_RCT_Whole group_Dryad

Baseline (ii) and follow up (fu) data for participants followed up

Lower respiratory tract infections in early childhood – authors' reply

Authors' reply to correspondence regarding their article.</p

Loss of specific subpopulations of interneurons seen within various regions of the hippocampus.

<p>Loss of interneurons is a characteristic often seen in the hippocampus of the NCLs. We divided the hippocampus into defined regions and stained sections for specific subpopulations of interneurons and subsequently counted the subpopulations within the sections. (<b>A</b>) PV+ interneurons decreased in the dentate gyrus (DG) at 9 months but remain unchanged in other areas where PV+ interneurons were present. (<b>B</b>) SOM+ interneurons were first decreased at 5 months in the hilus and stratum oriens with further decline observed at 9 months. Decline of SOM+ interneurons was also seen at 9 months in the stratum radiatum as well as the combined CA fields of the hippocampus. (<b>C–D</b>) A significant reduction in the number of CB+ interneurons was observed within the stratum oriens at 9 months when compared to WT. [Mean +/− SEM, <i>n</i> = 3 (*<i>p</i>≤0.05, **<i>p</i>≤0.01, ***p≤0.001, ****<i>p</i>≤0.0001)].</p

Additional file 3: Table S1. of Non-invasive molecular imaging of inflammatory macrophages in allograft rejection

Timecourse biodistribution of 99mTc-SER-4 in wild-type mice. Biodistribution of 99mTc-SER-4 in wild-type mice at 1, 3 and 6 h post injection. Data expressed as percentage injected dose per gram of tissue (%ID/g). (PDF 63 kb

Additional file 4: Table S2. of Non-invasive molecular imaging of inflammatory macrophages in allograft rejection

Biodistribution of 99mTc-IgG and 99mTc-SER-4 in C57Bl/6 wild-type (WT) and Sn-/- (KO) mice. Biodistribution of 99mTc-IgG isotype control in C57Bl/6 wild-type mice (WT × Isotype) 99mTc-SER-4 in C57Bl/6 wild-type (WT × 99mTc-SER4) and Sn-/- mice (Sn KO × 99mTcSER4) were expressed as percentage injected dose per gram of tissue (%ID/g). (PDF 70 kb

Decreased dendritic spine density in the mature cortex of <i>Cln6^nclf</i> mice.

<p>Golgi impregnation was used to label dendritic spines on the primary dendrite of excitatory cortical projection neurons in age-matched 2 month controls (<b>A</b>) and <i>Cln6^nclf</i> (<b>B</b>) mice. <b>(C)</b> The <i>Cln6^nclf</i> mutant mouse excitatory pyramidal neurons have reduced spine density. [Mean spine density +/− SEM, <i>n</i> = 40 neurons counted per genotype (***<i>p</i>≤0.0001)].</p

Learning and memory deficits are associated with mutation in <i>Cln6</i>.

<p>Following a period of habituation and training, memory and learning performance were tested in a radial arm maze task. <b>(A–B)</b> In an assay of memory, <i>Cln6^nclf</i> mice displayed a significant increase in the latency (time in seconds) to complete an 8-arm radial maze task during a 5-trial session. <b>(C–D)</b> Deficits in the mean amount of time required to complete the task <b>(C)</b> and the mean total distance traveled (in meters) to complete the correct maze sequence <b>(D)</b> occurred in <i>Cln6^nclfmice</i> when the maze task was altered 24-hours later to assay learning. [Mean +/− SEM, <i>n</i> = 6–9 (**<i>p</i>≤0.01, ***<i>p</i>≤0.0001)].</p

Upregulation of microglial marker CD68 in the thalamus and cerebral cortex of <i>Cln6^nclf</i> mice.

<p>Quantitative thresholding analysis in <i>Cln6^nclf</i> mice was compared to age matched WT, revealing a significant increase in the expression of the microglia marker CD68 in the VPM/VPL (<b>A</b>), M1 (<b>C</b>), S1BF (<b>B</b>), and V1 (<b>D</b>) regions in the <i>Cln6^nclf</i> mouse over WT. [Mean% immunoreactivity +/− SEM, <i>n</i> = 3 (*<i>p</i>≤0.05, **<i>p</i>≤0.01, ***p≤0.001, ****<i>p</i>≤0.0001)].</p

Early childhood lower respiratory tract infection and premature adult death from respiratory disease in Great Britain: a national birth cohort study

Background: Lower respiratory tract infections (LRTIs) in early childhood are known to influence lung development and lifelong lung health, but their link to premature adult death from respiratory disease is unclear. We aimed to estimate the association between early childhood LRTI and the risk and burden of premature adult mortality from respiratory disease. Methods: This longitudinal observational cohort study used data collected prospectively by the Medical Research Council National Survey of Health and Development in a nationally representative cohort recruited at birth in March, 1946, in England, Scotland, and Wales. We evaluated the association between LRTI during early childhood (age Findings: 5362 participants were enrolled in March, 1946, and 4032 (75%) continued participating in the study at age 20–25 years. 443 participants with incomplete data on early childhood (368 [9%] of 4032), smoking (57 [1%]), or mortality (18 [ Interpretation: In this prospective, life-spanning, nationally representative cohort study, LRTI during early childhood was associated with almost a two times increased risk of premature adult death from respiratory disease, and accounted for one-fifth of these deaths.</p