(C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Objective: Open total arch procedures have been associated with significant morbidity and mortality in patients with multiple comorbidities. Aortic arch debranching with endovascular graft placement, the hybrid arch procedure, has emerged as a surgical option in this patient

population. This study evaluates the outcomes of a contemporary comparative series from one institution of open total arch and hybrid arch procedures for extensive aortic arch pathology.

Methods: From July 2000 to March 2009, 1196 open arch procedures were performed, including 45 elective and 7 emergency open total arch procedures. From 2005 to 2009, 64 hybrid arch procedures were performed: 37 emergency type A dissections and 27 elective open arch debranchings. Hemiarch procedures were excluded.

Results: The hybrid arch cohort was significantly older (P = .008) and had greater predominance of this website atherosclerotic selleck inhibitor pathophysiology (P < .001). The incidence of permanent cerebral neurologic deficit was similar at 4% (1/27) for the hybrid arch cohort and 9% (4/45) for the open aortic

arch cohort. In-hospital mortality was similar at 11% (3/27) for the hybrid arch cohort and 16% (7/45) for the open aortic arch cohort. However, in the open arch group, there was a significant difference in mortality between patients aged less than 75 years at 9% (3/34) and patients aged more than 75 years at 36% (4/11) (P = .05).

Conclusions: Hybrid arch procedures provide a safe alternative to open repair. This study suggests the hybrid arch approach has a lower mortality for high-risk patients aged more than 75 years. This extends the indication for the hybrid arch approach in patients with complex aortic arch pathology previously considered prohibitively high selleck products risk for conventional open total arch repair. (J Thorac Cardiovasc Surg 2010; 140: 590-7)”
“Lead (Pb) is an environmental factor suspected of contributing to neurodegenerative diseases such as Alzheimer’s disease (AD). In AD, it has been postulated

that increased production and/or decreased metabolism/clearance of beta-amyloid (A beta) may lead to amyloid plaque deposition as well as a cascade of other neuropathological changes. It has been suggested that Pb exposure may be associated with AD-like pathology and severe memory deficits in humans. Therefore, we investigated whether Pb exposure could induce A beta accumulation in the brain. In this study, we demonstrated that acute Pb treatments lead to increased levels of A beta in the cerebrospinal fluid (CSF) and brain tissues. Interestingly, Pb treatments did not affect A beta production in brain neurons. Furthermore, Pb treatments significantly decreased LRP1 protein expression in the choroid plexus (CP). Our results suggest disrupted LRP1-mediated transport of A beta in this region may be responsible for the A beta accumulation in brain. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Results: We have successfully constructed recombinant baculoviruses carrying NIS and GFP under the control of the cytomegalovirus IE-1 promoter. We found that transduced efficiency of baculovirus in 8505C, SW1116, A549 cells are low in absence

of sodium butyrate. Yet Bac-GFP infects FTC-133 cells at a high efficiency, 77.67%, 85.57% and 93.23% with MOI of 100, 200 and 400, respectively. The fluorescence intensity of the Bac-GFP infected tumor cells correlated positively with the MOI of the virus. Sodium butyrate induction increased both the infection efficiency and the fluorescence intensity, but increase of infection efficiency was insignificant in FTC-133 cells. Reporter gene (GFP) expression in FTC-133 is stable within 7 days after infection. BV-6 in vitro buy DihydrotestosteroneDHT The radioactivity incorporated by the tumor cells infected with Bac-NIS correlated positively with the MOI of Bac-NIS as well. In tumor cells co-infected with Bac-NIS and Bac-GFP, the amount of radioactivity incorporated significantly correlated with the GFP fluorescence intensity (r=0.922).

Conclusion: Baculovirus vectors are powerful vehicles for studying FTC-133 tumor cells in gene delivery. It is feasible to use a baculovirus vector to deliver NIS as a reporter gene to monitor the expression of target genes. This is therefore an effective approach for the detection of target

gene expression in gene therapy. (C) 2010 Elsevier Inc. All rights reserved.”
“A 4-tube multiplex RT-PCR (mRT-PCR), which showed higher sensitivity over conventional methods, was previously developed for the diagnosis of 14 viral pathogens of the respiratory tract. Herein the mRT-PCR was compared to the commercial Luminex mPCR-microsphere flow cytometry assay (Resplex II) which allows the detection of 12 different viruses. Eleven different viruses were identified in 91 nasopharyngeal swabs of children with acute respiratory infection,

influenza A (IAV) and B, respiratory syncytial virus (RSV), human rhinovirus (hRhV), human echovirus, parainfluenza viruses (PIV) 1, 2, 3 and 4, human metapneumovirus (hMPV), and human coronavirus NL63. The results of the two techniques showed 53 and 40 positive patients by the Resplex 11 assay and mRT-PCR, respectively, with a concordance in 35 positive and 33 negative patients (74.7%). Individual RT-PCR tests were performed AZD5582 mw to control viruses not simultaneously detected by the two multiplex assays. The major virus misdiagnosed by mRT-PCR was IAV whereas the major viruses misdiagnosed by Resplex II were PIV1, 3 and 4. The mRT-PCR remains a simple, rapid, and specific assay for the specific detection of respiratory viruses, and can be easily implemented with standards in clinical laboratories at a low cost. (C) 2009 Elsevier B.V. All rights reserved.”
“[F-18]-labelled choline analogues, such as 2-[F-18]fluoroethylcholine ((FECH)-F-18), have suggested to be a new class of choline derivatives highly useful for the imaging of prostate and brain tumours.

Compared with surgery

alone, surgery + OncoGel resulted in superior median BBB scores on posttreatment days 9 (21 versus 19, P < 0.001) through 14 (11 versus 8, P < 0.005). In experiment 2, both treatment groups had delayed onset of paresis compared with control. Compared with surgery + XRT, surgery + XRT + OncoGel resulted in superior median BBB scores on posttreatment days 13 (21 versus 19, P < 0.001) through 17 (12 versus 8, P < 0.005). Median time to loss of ambulation (BBB scale score :57) was maximized by the addition RepSox nmr of OncoGel to surgery plus XRT: control (8.5 days), surgery alone (13.5 days), surgery + OncoGel (16 days), surgery + XRT (17 days), and surgery + XRT + OncoGel (19 days). In experiment 3, both treatment

groups had delayed onset of paresis compared with control. Compared with XRT alone, XRT + OncoGel resulted in superior median BBB scores on posttreatment see more days 6 (21 versus 19, P < 0.001) through I 1 (13 versus 8, P < 0.005). However, compared with surgery + XRT + OncoGel, XRT + OncoGel resulted in worse median BBB scores on posttreatment days 8 (20 versus 2 1, P < 0.01) through 13 (7 versus 19, P < 0.005).

CONCLUSION: In a rat model of spinal metastatic disease, local delivery of OncoGel increased the efficacy of surgery and radiotherapy and delayed the onset of neurological decline. These results suggest that OncoGel may be an effective adjuvant therapy in the operative management of metastatic spinal column tumors and that combining local chemotherapy with surgery and adjuvant radiotherapy may improve outcomes of this disease.”
“We performed genome-wide analysis of copy-number changes and loss of heterozygosity (LOH) in Barrett’s esophageal adenocarcinoma by single nucleotide polymorphism

(SNP) microarrays to identify associated genomic alterations. DNA from 27 esophageal adenocarcinomas and 14 matching normal tissues was subjected to SNP microarrays. The data were analyzed using dChipSNP software. Copy-number changes occurring in at least 25% of the cases XAV-939 solubility dmso and LOH occurring in at least 19% were regarded as relevant changes. As a validation, fluorescence in situ hybridization (FISH) of 8q24.21 (CMYC) and 8p23.1 (SOX7) was performed. Previously described genomic alterations in esophageal adenocarcinomas could be confirmed by SNP microarrays, such as amplification on 8q (CMYC, confirmed by FISH) and 20q13 or deletion/LOH on 3p (FHIT) and 9p (CDKN2A). Moreover, frequent gains were detected on 2p23.3, 7q11.22, 13q31.1, 14q32.31, 17q23.2 and 20q13.2 harboring several novel candidate genes. The highest copy numbers were seen on 8p23.1, the location of SOX7, which could be demonstrated to be involved in amplification by FISH. A nuclear overexpression of the transcription factor SOX7 could be detected by immunohistochemistry in two amplified tumors. Copy-number losses were seen on 18q21.32 and 20p11.21, harboring interesting candidate genes, such as CDH20 and CST4.

Based on these observations, we hypothesized that thrombin may promote the development

of mature functional blood vessels.

Methods: Seventy-four (n=74) rabbits underwent bilateral femoral artery surgical excision. On the 20th postsurgical day increasing doses of VEGF or bFGF or thrombin were injected in one ischemic limb per rabbit and an equal volume of normal saline to the contralateral control limbs. Quantification of newly developed collateral vessels (diameter > 500 mu m) was performed by transauricular intra-arterial subtraction angiography. Computerized quantitative analysis of collateral vessels in angiography images was based on the concept of multiscale structural tensor. Perfusion LB-100 research buy analysis of an in vivo dynamic computed tomography study was performed to investigate hemodynamic recovery of the distal ischemic limbs. Tissue perfusion analysis was performed with the semiquantitative slope methodology, which focuses on the first-pass arterial phase.

Results: A single administration of thrombin exhibited a dose-dependent increase of arteriogenic outcome. Thrombin at 5000 IU induced a 30.2 +/- 7.4% (P < 0.05) increase of total collateral area and length. Both VEGF and bFGF were without any

significant effect at the concentrations used. Functional estimation of limb perfusion showed a statistically significant increase of blood flow recovery only for thrombin. The semiquantitative slope method perfusion score differed significantly in the 5000 IU thrombin treated limbs LY2874455 price (5.7 +/- 0.3 vs 5.0 +/- 0.3 in control ischemic limbs; P < .05), and was not significantly inferior from the score of normal nonoperated limbs (6.5 +/- 0.3) suggesting a trend towards

hemodynamic recovery of distal limb perfusion.

Conclusions: In a rabbit hindlimb ischemia model, thrombin promoted the formation of large collateral vessels and improved the perfusion of distal ischemic tissue. These results provide new insights in understanding the involvement buy Stattic of thrombin in vascular formation and point to a novel role of thrombin in arteriogenesis. (J Vase Surg 2009;49:1000-12.)

Clinical Relevance: Interplay between angiogenic growth factors and vascular maturation mechanisms are essential for the cascade of reactions involved in arteriogenesis, i.e. development of large conductance collateral vessels that may adequately compensate for atherosclerotic arterial occlusions. We have shown that thrombin stimulated robust collateral networks in the ischemic limbs, which was associated with a significant recovery of ischemic tissue perfusion as assessed by in-vivo perfusion studies. This may provide the basis for applications of thrombin and its nonthrombogenic analogs in therapeutic angiogenesis.”
“Objective: Elevated inflammatory cytokine levels have been implicated in the pathogenesis of non-healing chronic venous insufficiency (CVI) ulcers.

When DF devices were used in 6 mm lumen PTFE, the percent of fragments trapped was poor (13.7% to 27.8%). There were no statistically significant differences between the devices. The capture of fragments improved (22% vs 51.4%, P < .001) when devices appropriate for a 6 mm lumen were used in a 5 mm PTFE “”ICA”", functionally over-sizing the devices. POFR efficiency improved with increasing back-pressures and with repeated aspirations. Postprocedure, successive flushes of pressurized forward flow yielded additional plaque fragments and

CH5183284 concentration when the efficiency of POFR was assessed with forward flushing volumes similar to those used for DF, the efficiencies were similar, although larger fragments were more efficiently removed with POFR.

Conclusion: In our model, both protection strategies were less than ideal. For POFF, high back pressures or multiple aspirations improve Aurora Kinase inhibitor the efficiency of cerebral protection but additional fragments were released by pressurized flow even after aspiration of 150 mL of saline. DF devices create a pressure gradient and fragments apparently went around the device

with pressurized flow in our PTFE lumen. Over-sizing of DF devices partially corrected this problem and increased over all DF efficiency to be comparable to POFR for smaller fragments but not for larger fragments. (J Vase Surg 2009; 49:1181-8.)”
“Objectives: Functional popliteal artery entrapment syndrome (FPAES) is an uncommon overuse injury in young physically active adults manifest by neuromuscular symptoms (gastroc/soleus cramping, plantar paresthesias). It is commonly confused with chronic recurrent exertional compartment syndrome

(CRECS). This study evaluated the diagnostic testing, mechanism of injury, and treatment differences between FPAES and CRECS.

Methods. Between 1987 and 2007, 854 patients (557 women, 297 men; mean age, 28.5 years) were surgically treated for the diagnosis of CRECS or FPAES, or both. Compartment pressures were measured in all patients who had anterior lateral or posterior superficial calf symptoms (normal pressure <= 15 mm Hg). Noninvasive stress positional plethysmography was routine. Stress positional magnetic resonance imaging (MRI) or angiography (MRA) was performed on patients with positive plethysmography result and symptoms consistent with FPAES.

Results: VX-661 Of the 854 patients, 757 (95%) had elevated compartment pressures (2 :25 mm Hg), and fasciectomy was performed for CRECS under local anesthesia (anterior lateral, 508; posterior superficial, 191; distal deep posterior, 101). The result of stress plethysmography was positive in 139 (18%), but they were asymptomatic. Forty-three patients (27 women, 16 men; mean age, 26.6 years) had positive stress plethysmography, appropriate FPAES symptoms, and normal compartment pressures. MRA/MRI in all 43 demonstrated normal musculotendinous anatomy and lateral neurovascular compression with plantar flexion.

The detection

thresholds varied between the three brain areas, and between MD and FA images. Although spatial smoothing often improved the sensitivity, it also markedly enlarged the estimated lesion sizes.

Since conventional VBA preprocessing significantly affected the outcome and sensitivity of the method itself, the impact of analysis steps should be verified and considered before interpreting the findings. Our results provide insight into the sizes and intensity changes of lesions that can be detected with VBA applied to diffusion tensor imaging (DTI) data. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.”
“The URMC-099 in vivo current study evidenced hypothesis that mitochondrial dysfunction-oxidative stress-dependent

apoptotic pathways play a critical role in degeneration of dopaminergic neurons in Parkinson’s disease. Model of rotenone-induced parkinsonism in rats produced decrease in striatal complex I activity and reduced glutathione with increase in nitrites concentration and caspase-3 activity. This was confirmed by significant correlation of catalepsy score with neurochemical parameters. Moreover, electron microscopic examination of striatal neurons displayed ultrastructure affection as hyperchromatic nuclei and disrupted mitochondria that are typical features of undergoing apoptosis. Administration of L-dopa as replacement therapy, although Cl-amidine concentration caused symptomatic improvement in catalepsy score, but further worsening in neurochemical parameters. Therefore, efforts are not only to improve effect of L-dopa, but also to introduce drugs provide antiparkinsonian and neuroprotective effects. In this study, alpha-lipoic acid exhibited noticeable neuroprotective effects by a mechanism via intervention of mitochondrial dysfunction-oxidative stress-dependent apoptotic pathways. Combination of alpha-lipoic acid efficiently halting deleterious toxic effects of L-dopa, revealed normalization of catalepsy score in addition

to amelioration of neurochemical parameters and apparent preservation of striatal ultrastructure integrity, indicating benefit of both symptomatic and neuroprotective therapy. In conclusion, alpha-lipoic acid could be recommended as a disease-modifying therapy when given with L-dopa early in course of Parkinson’s disease. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Silmitasertib purchase Society. All rights reserved.”
“The P2 family of receptors for adenosine 5′-triphosphate (ATP) is involved in several neuronal and glial cell functions in the central nervous system (CNS), and impaired function of these receptors is associated with both neuronal and glial dysfunction. Using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemical analysis, we examined the expression profiles of P2 subtype receptors in the rat hippocampus following treatment with the neurotoxicant trimethyltin (TMT).

The inability of the mutant Pol proteins to incorporate into nucleocapsid particles, together with other evidence, argued that the four conserved cysteine residues are critical for RNA binding. One implication is that these four cysteine residues might form a putative zinc finger motif. Based on these findings, we speculate that the RNA binding activity of HBV Pol may be mediated by this newly identified putative zinc finger motif.”
“Background: The direct oral thrombin inhibitor dabigatran has a predictable anticoagulant effect and may be an alternative therapy to warfarin for patients who have acute venous thromboembolism.

Methods:

In a randomized, double-blind, noninferiority trial involving patients with acute venous thromboembolism who were initially Fulvestrant given parenteral anticoagulation therapy for a median of 9 days (interquartile range, 8 to

11), we compared oral dabigatran, Quizartinib chemical structure administered at a dose of 150 mg twice daily, with warfarin that was dose-adjusted to achieve an international normalized ratio of 2.0 to 3.0. The primary outcome was the 6-month incidence of recurrent symptomatic, objectively confirmed venous thromboembolism and related deaths. Safety end points included bleeding events, acute coronary syndromes, other adverse events, and results of liver-function tests.

Results: A total of 30 of the 1274 patients randomly assigned to receive dabigatran (2.4%), as compared with 27 of the 1265 patients randomly assigned to warfarin (2.1%),

had recurrent venous thromboembolism; the difference in risk was 0.4 percentage points (95% confidence interval [CI], -0.8 to 1.5; P<0.001 for the prespecified noninferiority margin). The hazard ratio with dabigatran was 1.10 (95% CI, 0.65 to 1.84). Major bleeding episodes occurred in 20 patients assigned to dabigatran (1.6%) and in 24 patients assigned to warfarin (1.9%) (hazard ratio with dabigatran, 0.82; 95% CI, 0.45 to 1.48), and episodes of any bleeding were observed in 205 patients assigned to dabigatran (16.1%) and 277 patients assigned to warfarin (21.9%; hazard ratio with dabigatran, 0.71; 95% CI, 0.59 to 0.85). The numbers of deaths, acute coronary syndromes, and abnormal liver-function tests were similar in the find more two groups. Adverse events leading to discontinuation of the study drug occurred in 9.0% of patients assigned to dabigatran and in 6.8% of patients assigned to warfarin (P=0.05).

Conclusions: For the treatment of acute venous thromboembolism, a fixed dose of dabigatran is as effective as warfarin, has a safety profile that is similar to that of warfarin, and does not require laboratory monitoring. (ClinicalTrials.gov number, NCT00291330.)

N Engl J Med 2009;361:2342-52.”
“The Epstein-Barr virus (EBV) SM protein is essential for lytic EBV DNA replication and virion production.

The consideration of how material properties change in diseases could lead to a new paradigm that may expand beyond the focus on biochemical readings alone and include a characterization of material properties in diagnosis and treatment, an effort referred to as materiomics.”
“To survive in a complex world, it is important that unattended, but salient, input can still draw one’s attention. In this article, we suggest that posterior alpha oscillations LDK378 (8-13 Hz) provide a mechanism for prioritizing and ordering unattended visual input according to ‘relevance’. Gamma oscillations (30-100 Hz) that are phase-locked to the alpha

oscillations keep competing unattended representations apart in time, thus creating a sequence of perceptual cycles. As inhibition gradually lowers within an alpha cycle, the ordered sequence of competing input is activated, producing a temporal phase code for saliency. The proposed mechanism is based on recent experiments indicating that the phase of alpha activity modulates perception and that alpha oscillations are produced by periodic pulses of inhibition.”
“The influenza virus

transcribes and replicates its genome inside the nucleus of infected cells. Both activities are performed by the viral RNA-dependent RNA polymerase that is composed of the three subunits PA, PB1, and PB2, and recent studies have shown that it DAPT price requires host cell factors to transcribe and replicate the viral genome. To identify these cellular partners, we generated a comprehensive physical interaction map between each polymerase subunit and the host cellular proteome. A total of 109 human interactors were identified by yeast two-hybrid screens, whereas 90 were retrieved by literature mining. We built the FluPol interactome network composed of the influenza virus polymerase (PA, PB1, and PB2) and the nucleoprotein NP and 234 human proteins that are connected through 279 viral-cellular protein interactions. Analysis of this interactome map revealed enriched cellular functions associated with the influenza virus polymerase, including

host factors involved in RNA polymerase II-dependent transcription and for mRNA processing. We confirmed that eight influenza virus polymerase-interacting proteins are required for virus replication and transcriptional activity of the viral polymerase. These are involved in cellular transcription (C14orf166, COPS5, MNAT1, NMI, and POLR2A), translation (EIF3S6IP), nuclear transport (NUP54), and DNA repair (FANCG). Conversely, we identified PRKRA, which acts as an inhibitor of the viral polymerase transcriptional activity and thus is required for the cellular antiviral response.”
“To determine the possible neurotoxic impact of prenatal exposure to polychlorinated biphenyls (PCBs), we analyzed banked cord blood from a Faroese birth cohort for PCBs.

Demographic information, angiographic variables, and types of endovascular interventions were recorded. The mean transit time and cerebral blood volumes

were recorded for the ipsilateral and contralateral middle cerebral artery territories. A binary logistic regression model was constructed see more to determine the independent predictors of developing intracranial hemorrhage.

RESULTS: A total of 57 patients (33 from the University of Pittsburgh and 24 from Michigan State University) with a mean age of 66 +/- 13 years and mean National Institutes of Health Stroke Scale scores of 16 +/- 5 were studied. The overall recanalization (Thrombolysis in Myocardial Infarction Trial scale 2 or 3 flow) was 72% for the cohort, and the overall rate of parenchymal hemorrhage was 5 of 57 (9%) patients. The overall hemorrhage rate was 19 of 57 (33%) patients. The only variable found to be predictive of the development of hemorrhage after intervention was reduced pretreatment cerebral blood volume (odds ratio, 0.49; 95% confidence interval, 0.35-0.91; P

< 0.022).

CONCLUSION: A reduced pretreatment ipsilateral cerebral LY2835219 blood volume value before endovascular revascularization of an acute middle cerebral artery or internal carotid artery occlusion significantly increases the risk of an intracranial hemorrhage.”
“Aims: Proton motive force (PMF) inhibition enhances the intracellular accumulation of autoinducers possibly find more interfering with biofilm formation. We evaluated the effect of the PMF

inhibitor carbonyl cyanide-m-chlorophenylhydrazone (CCCP) on Pseudomonas aeruginosa biofilm development.

Methods and Results: Four epidemiologically unrelated P. aeruginosa isolates were studied. A MexAB-oprM overproducing strain was used as control. Expression of gene mexB was examined and biofilm formation after incubation with 0, 12.5 and 25 mu mol l(-1) of CCCP was investigated. Mean values of optical density were analysed with one-way analysis of variance and t-test. Two isolates subexpressed mexB gene and only 25 mu mol l(-1) of CCCP affected biofilm formation. Biofilms of the other two isolates and control strain PA140 exhibited significantly lower absorbance (P ranging from < 0.01 to < 0.05) with either 12.5 or 25 mu mol l(-1) of CCCP.

Conclusions: The PMF inhibitor CCCP effect was correlated with the expression of MexAB-OprM efflux system and found to compromise biofilm formation in P. aeruginosa.

Significance and Impact of the Study: These data suggest that inhibition of PMF-dependent trasporters might decrease biofilm formation in P. aeruginosa.”
“OBJECTIVE: Barbiturate-induced coma can be used in patients to treat intractable intracranial hypertension when other therapies, such as osmotic therapy and sedation, have failed.

The US pathway involves activation of the inferior olive (dorsal accessory olive for eye blink) and its climbing fiber projections to the cerebellar cortex and nuclei. The conditioned response (CR) pathway involves the cerebellar interpositus nucleus, the superior cerebellar peduncle pathway to the magnocellular red nucleus and rubral projections to premotor and motor nuclei generating the behavioral response. Anatomical data, neuronal unit recordings, electrical stimulation, lesions and methods of reversible inactivation all strongly support the

hypothesis that the essential memory trace for the learning of these discrete conditioned responses is formed and stored CX-6258 mw in the cerebellar interpositus nucleus. Neuronal/synaptic plasticity

is also established in the cerebellar cortex in this form of learning but the role of the cortex is less clear. We argue that the cortex plays a key role in normal acquisition and adaptive timing of the conditioned response, under certain circumstances, but it remains unclear exactly https://www.selleckchem.com/products/ly2109761.html what features of conditioning are being encoded in the cerebellar cortex in this basic form of associative learning and memory. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Background Vaccinations are often delayed until well after the recommended ages, leaving many children exposed for longer than they should be. We estimated vaccination coverage at different ages, and delays in administration, in 45 low-income and Q-VD-Oph purchase middle-income countries.

Methods We used data for 217706 children from Demographic and Health Surveys between 1996 and 2005 (median 2002), which provided data for vaccination of children on the basis of events

recorded on vaccination cards and interviews with mothers, with imputation of missing values and survival analysis. We devised an index combining coverage and delay.

Findings For vaccinated children, the median of the median delays in the 45 countries was 2.3 weeks (IQR 1.4-4.6) for bacille Calmette-Guerin (BCG); 2.4 weeks (1.2-3.3) for diphtheria, tetanus, and pertussis (DTP1); 2.7 weeks (1.7-3.1) for measles-containing vaccine (MCV1); and 6.2 weeks (3.5-8.5) for DTP3. However, in the 12 countries with the longest delays for each vaccination, at least 25% of the children vaccinated were more than 10 weeks late for BCG, 8 weeks for DTP1, 11 weeks for MCV1, and 19 weeks for DTP3. Variation within countries was substantial: the median of the IQRs in the 45 countries for delay in DTP3 was 10.9 weeks, 7.9 weeks for MCV1, 5.4 weeks for BCG, and 5.3 weeks for DTP1. The median of the national coverage rates for DTP1 increased from 57% in children aged 12 weeks to 88% at 12 months, and for DTP3 from 65% at 12 months to 76% at 3 years.

Interpretation The timeliness of children’s vaccination varies widely between and particularly within countries, and published yearly estimates of national coverage do not capture these variations.