The plant Arabidopsis thaliana (Arabidopsis) has become an important model species for the study of many aspects of plant biology. The relatively small size of the nuclear genome and the availability of extensive physical maps of the five chromosomes provide a feasible basis for initiating sequencing of the five chromosomes. The YAC (yeast artificial chromosome)-based physical map of chromosome 4 was used to construct a sequence-ready map of cosmid and BAC (bacterial artificial chromosome) clones covering a 1.9-megabase (Mb) contiguous region, and the sequence of this region is reported here. Analysis of the sequence revealed an average gene density of one gene every 4.8 kilobases (kb), and 54% of the predicted genes had significant similarity to known genes. Other interesting features were found, such as the sequence of a disease-resistance gene locus, the distribution of retroelements, the frequent occurrence of clustered gene families, and the sequence of several classes of genes not previously encountered in plants.

Background Extended half‐life (EHL) factor VIII (FVIII) and IX (FIX) products are intended to decrease the burden of prophylaxis for patients with haemophilia A or B. Whether these newer concentrates have led to meaningful clinical practice change remains vague. Aim To characterize the longitudinal use of standard (SHL) and EHL factor concentrates at haemophilia treatment centres (HTCs), using the ATHNdataset, a US database of 138 ATHN‐affiliated HTCs. Methods Factor concentrate use among moderate and severe haemophilia A and B patients without inhibitors was analysed at three time points over 18 months. Results Use of EHL concentrates rose from 10% of patients to 22% during this study. EHL FVIII prophylaxis is prescribed to the minority of patients, 28%; EHL FIX now predominates for prophylaxis, 52%. Rates of prescribed EHL products varied significantly by age group and HTC region. Median prescribed prophylaxis for SHL compared to EHL products was FVIII 6240 and 5200 and FIX 6968 and FIX 3900 IU/kg/y, respectively. On‐demand EHL use has grown but has minimal contribution to overall usage (2%). Conclusion Haemophilia treatment centre region and patient age impact the rate of adoption of EHL products; however, EHL prescribing continues to rise nationally, particularly for EHL FIX. Careful attention to annual cost of prophylaxis is imperative as the decrease in median EHL prophylaxis consumption is not offset by the higher unit cost of these products. It is unclear how further growth in use of EHLs will be impacted by emerging non‐factor replacement and gene therapies.

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Summary Subcutaneous (SQ) vs. intramuscular (IM) vaccination may cause fewer injection site complications in children with bleeding disorders, but little is known about comparative immunogenicity. To compare immunogenicity of hepatitis B virus (HBV) vaccination administered SQ or IM to individuals <2 years old with bleeding disorders, we performed a retrospective analysis of HBV surface antibody titres among patients enrolled in the universal data collection database who had received three doses of HBV vaccine solely by one route (SQ or IM). Data reviewed were from an initial visit before 24 months of age, until time of hepatitis antibody titre testing. The SQ and IM study groups did not differ in demographics, haemophilia type or severity or bleeding history. The mean age at the time of HBV surface antibody (anti-HBs) testing was 56.9 ± 20.3 months. Eighty-five of 92 subjects (92.4%) who received vaccine SQ developed a positive antibody titre (>12 IU/L), compared to 101/114 (88.6%) who received IM (P = 0.30). There was no statistically significant difference in distribution of titre values. The average age of the subjects at time of testing was 53 ± 20 months in the SQ group vs. 60 ± 20 months in the IM group (P = 0.02). The average time between the last dose of vaccine and anti-HBs testing was 47.6 ± 18.5 months among SQ vaccinated subjects vs. 51.6 ± 20.5 months in the IM group (P = 0.2). Immunogenicity to hepatitis B vaccination by the SQ and IM routes is similar.

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Congenital heart disease (CHD) is a common condition in the pediatric population, affecting up to 1% of all live births (i.e., around 40,000 newborns/year in the United States). Although CHD does have a wide range of severity, by the age of 5 years approximately 80% of patients will require at least one surgical intervention to achieve a complete/palliative cardiac repair. Today, in light of their much-improved surgical survival, the care of these patients focuses on morbidity prevention and/or treatment. One such morbidity has been the increased frequency of thrombotic occlusions [e.g., cardioembolic arterial ischemic strokes; arterial, cardiac, and/or newly created shunt thrombosis; venous thromboembolism (VTE)]. Patients with CHD are at high risk of developing thrombosis due to the disruption of blood flow, CHD-related coagulopathy, inflammation, and/or platelet activation secondary to extracorporeal circulation support required during open-heart surgery or as a bridge to recovery, which can increase thrombus formation. In this article, we will discuss how the coagulation system is altered in patients with CHD in regard to the patient’s anatomy, procedures they undergo to correct their congenital heart defect, and other risk factors that may increase their thrombotic risk, focusing on VTE. We will also discuss the most recently published reports pertaining to guidelines on prophylaxis and treatment of VTE in this population. Finally, we will briefly address the long-term VTE outcomes for patients with CHD.

To create a risk model for hospital-acquired venous thromboembolism in critically ill children upon admission to an ICU. DESIGN:Case-control study. SETTING:ICUs from eight children's hospitals throughout the United States. SUBJECTS:Critically ill children with hospital-acquired venous thromboembolism (cases) 0-21 years old and similar children without hospital-acquired venous thromboembolism (controls) from January 2012 to December 2016. Children with a recent cardiac surgery, asymptomatic venous thromboembolism, or a venous thromboembolism diagnosed before ICU admission were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:The multi-institutional Children's Hospital-Acquired Thrombosis registry was used to identify cases and controls. Multivariable logistic regression was used to determine the association between hospital-acquired venous thromboembolism and putative risk factors present at or within 24 hours of ICU admission to develop the final model. A total of 548 hospital-acquired venous thromboembolism cases (median age, 0.8 yr; interquartile range, 0.1-10.2) and 187 controls (median age, 2.4 yr; interquartile range, 0.2-8.3) were analyzed. In the multivariable model, recent central venous catheter placement (odds ratio, 4.4; 95% CI, 2.7-7.1), immobility (odds ratio 3.6, 95% CI, 2.1-6.2), congenital heart disease (odds ratio 2.9, 95% CI, 1.7-4.7), length of hospital stay prior to ICU admission greater than or equal to 3 days (odds ratio, 2.5; 95% CI, 1.1-5.6), and history of autoimmune/inflammatory condition or current infection (odds ratio, 2.1; 95% CI, 1.2-3.4) were each independently associated with hospital-acquired venous thromboembolism. The risk model had an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.73-0.84). CONCLUSIONS:Using the multicenter Children's Hospital-Acquired Thrombosis registry, we identified five independent risk factors for hospitalacquired venous thromboembolism in critically ill children, deriving a new hospital-acquired venous thromboembolism risk assessment model. A prospective validation study is underway to define a high-risk group for risk-stratified interventional trials investigating the efficacy and safety of prophylactic anticoagulation in critically ill children.

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