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Oxidative stress and redox imbalance adversely affect embryonic development. We developed two oxidative balance scores (OBS) that include dietary and nondietary exposures. We hypothesized that higher scores (i.e., lower oxidative stress) would be associated with lower risk of neural tube defects, orofacial clefts, conotruncal heart defects, and limb deficiencies. We used data from the National Birth Defects Prevention Study to create a dietary OBS based on intake of 13 nutrients and an overall OBS that included the 13 nutrients and eight additional nondietary factors related to oxidative balance (e.g., smoking). We used logistic regression to examine odds ratios associated with having low or high scores (i.e., <10th or >90th percentiles). Continuous models indicated reduced odds associated with high versus low scores (i.e., comparing odds at the 90th versus 10th percentile values of the distribution) on the overall OBS for cleft lip with or without cleft palate [adjusted odds ratio (aOR) 0.72, 95% confidence interval (CI) 0.63–0.82], longitudinal limb deficiency (aOR 0.73, CI 0.54–0.99), and transverse limb deficiency (aOR 0.74, CI 0.58–0.95); increased odds for anencephaly (aOR 1.40, CI 1.07–1.84); and primarily nonsignificant associations with conotruncal heart defects. Results for the dietary OBS were similar. This study provides some evidence that oxidative stress contributes to congenital anomalies related to neural crest cell development. [ABSTRACT FROM AUTHOR]

Objective: We examined the social network support, composition, and structure of pediatric cancer caregivers. Methods: We used a self‐report survey to collect egocentric social network data from 107 caregivers of pediatric cancer patients and calculated descriptive statistics to examine cancer‐related support network composition, function, and structure. We then ran logistic regressions to examine the relationships between network characteristics and overall satisfaction with social support. Results: Family members were the most common source of emotional support and logistical support, and health care providers were the most common source of informational support. Participants perceived the "most helpful" forms of support as being: (1) emotional support from family and health care providers; (2) informational support from health care providers and other cancer caregivers; and (3) logistical support from family. Overall, caregivers wished that 9.8% of their network ties had provided more support, with family members being the most common alter type to disappoint caregivers and offer less support than needed/expected. Caregivers who reported higher network disappointment (having network members who offered less support than needed/expected) were significantly less satisfied with emotional support than those with lower network disappointment (Odds Ratio = 0.18, p = 0.02), and caregivers with higher network disappointment were significantly less satisfied with logistical support compared to those with lower network disappointment (Odds Ratio = 0.14, p = 0.01). Conclusion: Our results show differences in the nature of social support provided by different types of network members. These findings have implications for tailoring social network interventions to improve caregiver and family outcomes. [ABSTRACT FROM AUTHOR]

Background: There is emerging evidence that children with complex congenital heart defects (CHDs) are at increased risk for childhood lymphoma, but the mechanisms underlying this association are unclear. Thus, we sought to evaluate the role of DNA methylation patterns on "CHD‐lymphoma" associations. Methods: From >3 million live births (1988–2004) in California registry linkages, we obtained newborn dried bloodspots from eight children with CHD‐lymphoma through the California BioBank. We performed case–control epigenome‐wide association analyses (EWAS) using two comparison groups with reciprocal discovery and validation to identify differential methylation associated with CHD‐lymphoma. Results: After correction for multiple testing at the discovery and validation stages, individuals with CHD‐lymphoma had differential newborn methylation at six sites relative to two comparison groups. Our top finding was significant in both EWAS and indicates PPFIA1 cg25574765 was hypomethylated among individuals with CHD‐lymphoma (mean beta = 0.04) relative to both unaffected individuals (mean beta = 0.93, p = 1.5 × 10−12) and individuals with complex CHD (mean beta = 0.95, p = 3.8 × 10−8). PPFIA1 encodes a ubiquitously expressed liprin protein in one of the most commonly amplified regions in many cancers (11q13). Further, cg25574765 is a proposed marker of pre‐eclampsia, a maternal CHD risk factor that has not been fully evaluated for lymphoma risk in offspring, and the tumor microenvironment that may drive immune cell malignancies. Conclusions: We identified associations between molecular changes present in the genome at birth and risk of childhood lymphoma among those with CHD. Our findings also highlight novel perinatal exposures that may underlie methylation changes in CHD predisposing to lymphoma. [ABSTRACT FROM AUTHOR]

Congenital heart disease is exceedingly prevalent in trisomy 13 and 18. Improved survival following congenital heart surgery has been reported, however, mortality remains significantly elevated. Utilizing inpatient data on trisomy 13 and 18 from the 2003–2016 Pediatric Health Information System database, a survival model was developed and validated using data from the California Perinatal Quality Care Collaborative and the California Office of Statewide Health Planning and Development. The study cohort included 1,761 infants with trisomy 13 and 18. Two models predicting survival to 6 months of age were developed and tested. The initial model performed excellently, with a c‐statistic of 0.87 and a c‐statistic of 0.76 in the validation cohort. After excluding procedures performed on the day of death, the revised model's c‐statistic was 0.76. Certain variables, including cardiac surgery, gastrostomy, parenteral nutrition, and mechanical ventilation, are predictive of survival to 6 months of age. This study presents a model, which potentially can inform decision‐making regarding congenital heart surgery. [ABSTRACT FROM AUTHOR]

Intimate relationship functioning depends upon the ability to accommodate one's partner and to inhibit retaliatory and aggressive impulses when disagreements arise. However, accommodation and inhibition may be difficult when self-control strength is weak or depleted by prior exertion of self-control. The present study considered whether state self-control depletion prospectively predicts male and female self-reports of anger with partner and arguing with partner. Consistent with the I3 Model (Finkel, 2014, Adv Exp Soc Psychol, 49, 1-104), we also considered whether the association between elevated anger and arguing (i.e., instigation) and partner aggression was stronger when state self-control (i.e., inhibition) was depleted or among people high in negative urgency. In this ecological momentary assessment (EMA) study, heavy drinking married and cohabiting heterosexual couples (N = 191) responded to three randomly signaled reports each day for 30 days. Depletion predicted anger and arguing with partners both cross-sectionally and prospectively for men and women. However, after controlling for prior levels of anger and arguing, these effects were diminished, and supplemental analyses revealed that anger and arguing with partner predicted subsequent depletion. Anger and arguing were strongly associated with concurrent reports of partner aggression perpetration and victimization (verbal and/or physical). However, neither state self-control depletion nor negative urgency moderated these effects. Overall, results suggest a modest impact of depletion on daily couple functioning as well as a potential cyclical effect of arguing on depletion. [ABSTRACT FROM AUTHOR]

Patients with refractory or relapsed (r/r) disease have limited treatment options and poor outcomes. SALVAGE TREATMENTS FOR RELAPSED/REFRACTORY SECONDARY CNS LYMPHOMA IN THE CAR T ERA: A REAL-WORLD COMPARISON B Introduction: b Secondary central nervous system lymphoma (SCNSL) is a rare and aggressive subtype of non-Hodgkin lymphoma that involves the neuraxis. [Extracted from the article]

B Introduction: b HIV-associated lymphomas affect a uniquely disadvantaged group of patients, who were often denied insurance based on preexisting conditions until the Affordable Care Act (ACA) was signed in 2010. Impact of the Affordable Care Act and Medicaid Expansion on Insurance Coverage and Outcomes in Patients with HIV-associated Aggressive B-cell Non-Hodgkin Lymphomas We investigated the impact of ACA and its Medicaid expansion in 2014 which covered the low-income strata, on outcomes among patients with HIV-associated aggressive B-cell non-Hodgkin lymphomas (HIV-aB-NHL). [Extracted from the article]

Humans are exposed to potentially harmful amounts of the neurotoxin monomethylmercury (MMHg) through consumption of marine fish and mammals. However, the pathways of MMHg production and bioaccumulation in the ocean remain elusive. In anaerobic environments, inorganic mercury (Hg) can be methylated to MMHg through an enzymatic pathway involving the hgcAB gene cluster. Recently, hgcA‐like genes have been discovered in oxygenated marine water, suggesting the hgcAB methylation pathway, or a close analog, may also be relevant in the ocean. Using polymerase chain reaction amplification and shotgun metagenomics, we searched for but did not find the hgcAB gene cluster in Arctic Ocean seawater. However, we detected Hg‐cycling genes from the mer operon (including organomercury lyase, merB), and hgcA‐like paralogs (i.e., cdhD) in Arctic Ocean metagenomes. Our analysis of Hg biogeochemistry and marine microbial genomics suggests that various microorganisms and metabolisms, and not just the hgcAB pathway, are important for Hg methylation in the ocean. [ABSTRACT FROM AUTHOR]

Ready access to health research studies is becoming more important as researchers, and their funders, seek to maximize the opportunities for scientific innovation and health improvements. Large-scale population-based prospective studies are particularly useful for multidisciplinary research into the causes, treatment and prevention of many different diseases. UK Biobank has been established as an open-access resource for public health research, with the intention of making the data as widely available as possible in an equitable and transparent manner. Access to UK Biobank's unique breadth of phenotypic and genetic data has attracted researchers worldwide from across academia and industry. As a consequence, it has enabled scientists to perform world-leading collaborative research. Moreover, open access to an already deeply characterized cohort has encouraged both public and private sector investment in further enhancements to make UK Biobank an unparalleled resource for public health research and an exemplar for the development of open-access approaches for other studies. [ABSTRACT FROM AUTHOR]

Background: With their unique history of exposure to extensive nuclear testing between 1946 and 1958, descendants of Marshall Island residents may have underappreciated genetic abnormalities, increasing their risk of birth defects. Methods: We conducted a retrospective cohort study of resident women with at least one singleton live birth between 1997 and 2013 in northwest Arkansas using state birth certificate data linked to data from the Arkansas Reproductive Health Monitoring System, a statewide birth defects registry. We calculated unadjusted and adjusted prevalence ratios (PR) and 95% confidence intervals (CI) from modified Poisson regression analyses for non‐Hispanic (NH) whites, NH‐blacks, Hispanics and Marshallese, using NH‐whites as the reference group. Results: Of the 91,662 singleton births during the study period, 2,488 were to Marshallese women. Due to the relatively small number of Marshallese births, we could not calculate prevalence estimates for some defects. Marshallese infants had higher rates of congenital cataracts (PR = 9.3; 95% CI: 3.1, 27.9). Although the number of defects was low, Marshallese infants also had higher rates of truncus arteriosus (PR = 44.0; 95% CI: 2.2, 896.1). Conclusions: Marshallese infants may have increased risk of specific birth defects, but estimates are unstable because of small sample size so results are inconclusive. Larger population‐based studies would allow for further investigation of this potential risk among Marshallese infants. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer is increased in those with birth defects, including those with congenital heart disease (CHD). Lymphoma risk is increased in children with CHD. This study analyzes the effect of CHD and CHD severity on childhood cancer risk. Methods: We analyzed cancer risk in a population‐based cohort of children with and without CHD born between 1988 and 2004 by linking data from the California Birth Defects Monitoring Program with data from the California Cancer Registry. We compared cancer risk in children with and without CHD, excluding children with chromosomal anomalies. Results: Of >3 million children in the birth cohort, 65,585 had birth defects (2%), 25,981 with CHD. Cancer occurred in 4,781 (0.15%) children, 43 (0.17%) with CHD. Cancer risk in CHD was increased (hazard ratio [HR]) 2.63, 95% CI: 1.95, 3.55). Leukemia was the most common cancer in those without CHD (1,722/4,738, 36%), central nervous system tumors were second (1,073/4,738, 23%), and lymphoma third (410/4,738, 9%). Among children with CHD, lymphoma and leukemia occurred with the same frequency (12/43, 28% for each). HR for lymphoma was 8.37 (CI: 4.71, 14.86) with CHD versus without. HR for leukemia was 2.05 (CI: 1.16, 3.61) with CHD versus without. CHD complexity was higher in lymphoma (3, interquartile range [IQR]: 2–3) than those with leukemia (1, IQR, 1–2; p < .02). Conclusion: Cancer risk is increased in children with CHD. Lymphoma risk is increased in CHD and is correlated with more complex CHD. These results suggest a shared developmental origin for CHD and lymphoma may be present. [ABSTRACT FROM AUTHOR]

COMBINED MODALITY ULTRA-LOW-DOSE ADAPTIVE RADIOTHERAPY AND RITUXIMAB AS TREATMENT STRATEGY FOR INDOLENT NON-HODGKIN LYMPHOMAS: THE UT SOUTHWESTERN EXPERIENCE B Methods: b We conducted an IRB approved retrospective review of patients with iNHL who were treated with both ULDRT and rituximab (4 weekly doses of 375 mg/m SP 2 sp ) as frontline therapy, either concurrently, or within a short interval (median 13 days), at our institution from 2017-2023. B Introduction: b For indolent non-Hodgkin lymphomas (iNHL), ultra-low-dose radiation therapy (ULDRT) with 4 Gy (2 Gy × 2 or "boom-boom") has demonstrated durable local control (70%), though distal relapses may occur. [Extracted from the article]

B Introduction: b Chimeric antigen receptor (CAR)-T cell therapy use has increased exponentially following its approval for multiple indications in non-Hodgkin lymphomas, multiple myeloma, and acute lymphoblastic leukemia. Patients who experienced MACE versus no MACE had a significantly higher age at CAR-T cell therapy (74.5 years vs. 64.9 years, I p i =.009), higher peak C-reactive protein (CRP) with a median of 116.7 mg/dL versus 73.85 mg/dL, I p i = 0.006 respectively. [Extracted from the article]

Abstract: Background: Malnutrition is a problem within hospitals, which impacts upon clinical outcomes. The present audit assesses whether a hospital menu meets the energy and protein standards recommended by the British Dietetic Association's (BDA) Nutrition and Hydration Digest and determines the contribution of oral nutrition supplements (ONS) and additional snacks. Methods: Patients in a UK South West hospital were categorised as ‘nutritionally well’ or ‘nutritionally vulnerable’ in accordance with their Malnutrition Universal Screening Tool score. Energy and protein content of food selected from the menu (‘menu choice’), menu food consumed (‘hospital intake’) and total food consumed including snacks (‘overall intake’) were calculated and compared with the standards. Results: In total, 93 patients were included. For ‘nutritionally well’ patients (n = 81), energy and protein standards were met by 11.1% and 33.3% (‘menu choice’); 7.4% and 22.2% (‘hospital intake’); and 14.8% and 28.4% (‘overall intake’). For ‘nutritionally vulnerable’ patients (n = 12), energy and protein standards were met by 0% and 8.3% (‘menu choice’); 0% and 8.3% (‘hospital intake’); and 8.3% and 16.7% (‘overall intake’). Ten percent of patients consumed ONS. Patients who consumed hospital snacks (34%) were more likely to meet the nutrient standards (P ≤ 0.001). Conclusions: The present audit demonstrated that most patients are not meeting the nutrient standards recommended by the BDA Nutrition and Hydration Digest. Recommendations include the provision of energy/protein‐dense snacks, as well as menu, offering ONS where clinically indicated, in addition to training for staff. A food services dietitian is ideally placed to lead this, forming a vital link between patients, caterers and clinical teams. [ABSTRACT FROM AUTHOR]

Mixtures and pure stands of perennial ryegrass, tall fescue, white clover and red clover were grown in a three-cut and a five-cut system in southern Norway, at a low fertilization rate (100 kg N ha−1 year−1). The nutritional quality (annual weighted averages) of the dried forage from the two-first harvesting years was analysed. There was no significant effect of species diversity on crude protein ( CP) concentration. In the three-cut system, we found a significant species diversity effect leading to 10% higher concentrations of acid detergent fibre ( ADF), 20-22% lower concentrations of water-soluble carbohydrate ( WSC) and 4% lower net energy for lactation ( NEL) concentrations in mixtures compared with pure stands (averaged across the two-first years). In the five-cut system, similar effects were seen in the first year only. This diversity effect was associated with a reduction in WSC and NEL concentrations and an increase in ADF, NDF and CP concentrations in the grass species, and not in red clover, when grown in mixtures. This is thought to be a combined result of better N availability and more shading in the mixtures. Species diversity reduced the intra-annual variability in nutritional quality in both cutting systems. [ABSTRACT FROM AUTHOR]

SUMMARY The concept of whole blood ( WB) as a treatment modality for trauma patients requiring transfusion therapy is not new. Successfully employed in the early 20 century, WB was the product of choice for military trauma resuscitation until the advent of component therapy changed the landscape of transfusion medicine. However, the recognition of the success of WB in the military operational setting has provided some enthusiasm to explore its revival as a cold-stored option in the civilian trauma resuscitation sector. Concerns continue to exist over potential limitations for its application in regards to the efficacy of platelets after cold storage, the risk of haemolytic transfusion reactions following the transfusion of un-cross-matched WB and the logistical issues for civilian blood banks in providing WB. This review aims to reconcile these concerns with data available in the literature, with a view to establishing that there is in vitro evidence supporting the haemostatic effects of cold-stored WB as a potential therapeutic option in both the pre-hospital and in-hospital civilian trauma resuscitation settings. [ABSTRACT FROM AUTHOR]

Four-species mixtures and pure stands of perennial ryegrass, tall fescue, white clover and red clover were grown in three-cut and five-cut systems at Ås, southern Norway, at a low fertilization rate (100 kg N ha−1 year−1). Over a three-year experiment, we found strong positive effects of species diversity on annual dry-matter yield and yield stability under both cutting frequencies. The overyielding in mixtures relative to pure stands was highest in the five-cut system and in the second year. Among the possible pairwise species interaction effects contributing to the diversity effect, the grass-grass interaction was the strongest, being significant in both cutting systems and in all years. The grass-legume interactions were sometimes significant, but no significant legume-legume interaction could be detected. Competitive relationships between species varied from year to year and also between cutting systems. Estimations based on species identity effects and pair-specific interactions suggested that the optimal proportions of red clover, white clover, perennial ryegrass and tall fescue in seed mixtures would have been around 0·1, 0·2, 0·4 and 0·3 in the three-cut system, and 0·1, 0·3, 0·3 and 0·3 in the five-cut system. [ABSTRACT FROM AUTHOR]

It is unclear the amount of time spent or the effectiveness with which the cardiologist was able to provide family reassurance prior to the echocardiogram. Our group reported primary care providers and trainees have had limited exposure to the 2014 AUC document and incorrectly identified many "rarely appropriate" echocardiogram indications as "appropriate" (specifically innocent heart murmurs).[4] If a parent arrives to a cardiology evaluation expecting an echocardiogram, then an unexplained deviation from this expected plan is likely to produce anxiety. In conclusion, Ip I et al i . should be commended for highlighting the significant issues paediatric cardiologists must recognise regarding parental anxiety and referring provider expectations in patients presenting with innocent heart murmurs. [Extracted from the article]

SUMMARY Objectives To determine what percentage of red blood cell ( RBC) units that were issued to the operating room ( OR) were returned unused, and to determine how often all of the RBCs that were issued for a patient were returned unused using the institution's maximum surgical blood ordering schedule ( MSBOS) as a guide. Background The MSBOS provides guidelines for blood ordering, but is merely a suggestion for the ordering clinicians. This study examined how closely ordering practices followed the MSBOS, and how often ordered RBCs were actually transfused. Methods For a 4-week period, RBC issue and utilization data were collected on elective surgery patients who were eligible for electronic cross-match at a tertiary care hospital. These data were compared to the MSBOS. Results There were 1350 surgical procedures performed. Of these cases, 439 patients had a type and screen (T&S) performed, and 215/439 (49%) patients had at least 1 RBC issued during their case. To these 215 patients, 742 RBC units were issued and 537/742 (72%) of these units were returned to the blood bank unused. In 152/215 (71%) cases with issued RBCs, all of the RBCs were returned to the blood bank unused. Amongst the surgical categories in this study, the percentage of cases where none of the issued RBCs were transfused ranged from 38 to 93%. Conclusions Significant numbers of RBC units are issued but not transfused during surgery. Involving the surgical team in the blood issuing process and using a data-driven MSBOS may reduce the number of unused units. [ABSTRACT FROM AUTHOR]

Frosty pod rot ( FPR), caused by Moniliophthora roreri, is responsible for significant losses in Theobroma cacao. Due to limited options for FPR management, biological control methods using Trichoderma are being studied. Combinations of three formulations and two Trichoderma isolates were studied between May 2009 and April 2011. The formulations were 0·3 mL L−1 of the surfactant BreakThru 100 SL ( BT), a mixture of 1% w/v Sure-Jell (source of pectin) and 1% w/v potato dextrose broth ( PDB) ( PP), and an invert oil emulsion of 50% v/v corn oil/2·5% w/v lecithin/0·5% w/v PDB ( COP). Water and fungicide, copper oxychloride, were included as controls. Humidity chamber studies indicated that Trichoderma conidia germinated in all formulations if free water was maintained, while only the COP formulation supported germination under drying conditions. In the field, Trichoderma ovalisporum DIS-70a and Trichoderma harzianum DIS-219f were applied monthly in each of the three formulations at a rate of 180 mL per tree, 2·46 × 107 conidia per mL. The COP/ DIS-70a formulation provided the largest yield increase compared to all other treatments, including the fungicide control. Averaged over the 2 years, the COP formulation increased yield to 30·7% healthy pods compared to 9·7% healthy pods in the water control. Although the formulation/isolate combinations did not consistently increase endophytic colonization, the PP/ DIS-219f, COP/ DIS-219f and COP/ DIS-70a combinations increased total endophytic/epiphytic colonization by Trichoderma. The invert corn oil formulation of DIS-70a significantly enhanced yield of healthy cacao pods over 2 years providing a promising model for optimizing Trichoderma-based biocontrol strategies. [ABSTRACT FROM AUTHOR]

Background: This study sought to examine how exerting self-control to inhibit stereotype use affects alcohol consumption. In addition, we sought to expand previous findings via examination of how individual differences in motivations to approach or avoid alcohol consumption interact with self-control depletion to determine the regulation of ad-lib drinking behavior. Methods: Sixty-one social drinkers (31 female) were recruited to participate in a socially relevant self-control depletion task in which they were randomly assigned to 1 of 2 creative writing conditions: (i) the self-control depletion condition with explicit instructions to refrain from using stereotypes, or (ii) the nondepletion condition in which no instructions were given regarding the use of stereotypes. Participants then completed an ad-lib drinking task and self-report questionnaires pertaining to their motivation to consume alcohol. Results: As predicted, results indicated a significant 3-way interaction between depletion condition, approach inclinations, and avoidance inclinations. Specifically, self-control depletion predicted greater drinking disinhibition (i.e., mean sip size, total alcohol consumption) only among participants high in both approach and avoidance. Conclusions: Taken together, results from this study highlight the importance of both approach and avoidance inclinations in the failure to regulate alcohol consumption following a routine, socially relevant form of self-control depletion. Our results also suggest that the high approach/high avoidance motivational profile may predict the greatest risk among those actively trying to regulate their drinking. [ABSTRACT FROM AUTHOR]

Background Congenital heart defects (CHDs) are common birth defects and are associated with high hospital costs. The objectives of this study were to assess hospitalization costs, across the lifespan, of patients with CHDs in Arkansas. Methods Data from the 2006 to 2011 Healthcare Cost and Utilization Project Arkansas State Inpatient Databases were used. We included hospitalizations of patients whose admission occurred between January 1, 2006, and December 31, 2011, and included a principal or secondary CHD ICD-9-CM diagnosis code (745.0-747.49, except 747.0 and 745.5 for preterm infants). Hospitalizations were excluded if they involved out-of-state residents, normal newborn births, or if missing data included age at admission, state of residence, or hospital charges. Children were defined as those < 18 years-old at time of admission. Results Between 2006 and 2011, there were 2,242,484 inpatient hospitalizations in Arkansas. There were 9071 (0.4%) hospitalizations with a CHD, including 5,158 hospitalizations of children (2.2% of hospitalizations among children) and 3,913 hospitalizations of adults (0.2% of hospitalizations of adults). Hospital costs for these CHD hospitalizations totaled $355,543,696. The average annual cost of CHD hospitalizations in Arkansas was $59,257,283 during this time period. Infants accounted for 72% of all CHD-related hospital costs; total costs of CHD hospitalizations for children were almost five times those of hospitalization costs for adults with CHD. Conclusion Hospitalizations with CHDs account for a disproportionate share of hospital costs in Arkansas. Hospitalizations of children with CHD accounted for a higher proportion of total hospitalizations than did hospitalizations of adults with CHD. Birth Defects Research (Part A) 103:814-820, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aortopathy can be defined as aortic dilation, aneurysm, dissection, and tortuosity. Familial aortopathy may occur secondary to fibrillin-1 ( FBN1) mutations in the setting of Marfan syndrome, or may occur as a result of other genetic defects with different, but occasionally overlapping, phenotypes. Because of the phenotypic overlap and genetic heterogeneity of disorders featuring aortopathy, we developed a next generation sequencing (NGS) assay and comparative genomic hybridization (CGH) array to detect mutations in 10 genes that cause thoracic aortic aneurysms (TAAs). Here, we report on the clinical and molecular findings in 175 individuals submitted for aortopathy panel testing at ARUP laboratories. Ten genes associated with heritable aortopathies were targeted using hybridization capture prior to sequencing. NGS results were analyzed, and variants were confirmed using Sanger sequencing. Array CGH was used to detect copy-number variation. Of 175 individuals, 18 had a pathogenic mutation and 32 had a variant of uncertain significance (VUS). Most pathogenic mutations (72%) were identified in FBN1. A novel large SMAD3 duplication and FBN1 deletion were identified. Over half who had TAAs or other aortic involvement tested negative for a mutation, suggesting that additional aortopathy genes exist. We anticipate that the clinical sensitivity of at least 10.3% will rise with VUS reclassification and as additional genes are identified and included in the panel. The aortopathy NGS panel aids in the timely molecular diagnosis of individuals with disorders featuring aortopathy and guides proper treatment. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Individuals with congenital heart defects (CHDs) have high hospital resource use. We sought to identify factors associated with hospital costs and multiple hospitalizations among individuals with CHDs. Methods Data from the 2006 to 2011 Healthcare Cost and Utilization Project Arkansas State Inpatient Databases were linked across encrypted patient identifiers to develop a cohort of Arkansas residents aged 1 to 64 years who were hospitalized at least once with a CHD during this time period. Infants were excluded because patient identifiers were missing for 18 to 52% each year. CHDs were identified using principal and secondary International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses codes. All hospitalizations of individuals ever admitted with a CHD were included. Mean and median patient-level costs were estimated; the association of hospital costs and patient readmissions were examined with linear and logistic regression. Results There were 1,185,868 inpatient hospitalizations of Arkansas residents aged 1 to 64 years between 2006 and 2011; these were accrued by 603,925 patients. Of those, 2542 patients (0.42%) had at least one hospitalization with a CHD diagnosis. Total costs for these 2542 patients were $126,999,837 and they accumulated 7898 hospitalizations. Factors associated with increased costs included patient age, CHD type, cardiac procedures, and comorbidities. Factors associated with hospital readmission within 1 year included age, CHD type, expected payer, and comorbidities. Conclusion Individuals with CHDs in Arkansas experience variation in hospital use and costs by patient characteristics. Future research should investigate factors associated with readmissions, cardiac procedures, and comorbidities, as these are strongly associated with hospital costs. Birth Defects Research (Part A) 103:589-596, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

In the United States, fractions are an important part of the middle school curriculum, yet many middle school students struggle with fraction concepts. Teachers also have difficulty with the conceptual understanding needed to teach fractions and rely on textbooks when making instructional decisions. This reliance on textbooks, the idea that teaching and learning of fractions is a complex process, and that fraction understanding is the foundation for later topics such as proportionality, algebra, and probability, makes it important to examine the variation in presentation of fraction concepts in U. S. textbooks, especially the difference between traditional and standards-based curricula. The purpose of this study is to determine if differences exist in the presentation of fractions in conventional and standards-based textbooks and how these differences align with the recommendations of National Council of Teachers of Mathematics, Common Core State Standards, and the research on the teaching and learning of fractions. [ABSTRACT FROM AUTHOR]

Background Kleefstra syndrome arises from haploinsufficiency of EHMT1 caused by either microdeletions at 9q34.3 or intragenic mutations. Patients with Kleefstra syndrome have multisystem involvement including intellectual disability, hypotonia, and characteristic facial features. Methods We report on the severe neonatal presentation of the first case of Kleefstra syndrome associated with hypoplastic left heart syndrome and multicystic renal disease in a patient with a 9q34.3 microdeletion. Results Array-CGH analysis revealed a 2.1 Mb deletion at 9q34.3, including EHMT1 and NOTCH1. Conclusion Kleefstra syndrome is a multisystem disorder with a high frequency of congenital heart disease and less frequently, renal defects. Mortality has rarely been documented, particularly in infancy. Based on the present case and the extant literature, a routine echocardiogram and renal ultrasound should be ordered in all cases of Kleefstra syndrome. The cardiac changes seen in this patient could be the result of the haploinsufficiency of EHMT1, NOTCH1, or their combined effect. Birth Defects Research (Part A), 2014. © 2014 Wiley Periodicals, Inc. Birth Defects Research (Part A) 100:985-990, 2014. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Objectives Observational and genetic studies have shown that lipoprotein(a) [ Lp(a)] levels and apolipoprotein(a) [apo(a)] isoform size are both associated with coronary heart disease ( CHD) risk, but the relative independence of these risk factors remains unclear. Clarification of this uncertainty is relevant to the potential of future Lp(a)-lowering therapies for the prevention of CHD. Methods Plasma Lp(a) levels and apo(a) isoform size, estimated by the number of kringle IV ( KIV) repeats, were measured in 995 patients with CHD and 998 control subjects. The associations between CHD risk and fifths of Lp(a) levels were assessed before and after adjustment for KIV repeats and, conversely, the associations between CHD risk and fifths of KIV repeats were assessed before and after adjustment for Lp(a) levels. Results Individuals in the top fifth of Lp(a) levels had more than a twofold higher risk of CHD compared with those in the bottom fifth, and this association was materially unaltered after adjustment for KIV repeats [odds ratio ( OR) 2.05, 95% confidence interval ( CI) 1.38-3.04, P < 0.001]. Furthermore, almost all of the excess risk was restricted to the two-fifths of the population with the highest Lp(a) levels. Individuals in the bottom fifth of KIV repeats had about a twofold higher risk of CHD compared with those in the top fifth, but this association was no longer significant after adjustment for Lp(a) levels ( OR 1.13, 95% CI 0.77-1.66, P = 0.94). Conclusions The effect of KIV repeats on CHD risk is mediated through their impact on Lp(a) levels, suggesting that absolute levels of Lp(a), rather than apo(a) isoform size, are the main determinant of CHD risk. [ABSTRACT FROM AUTHOR]

Williams syndrome results from a microdeletion of approximately 1.5 Mb of chromosome 7q11.23. Several patients have been reported with the reciprocal microduplication in association with a variety of phenotypic features including cognitive impairment and typical facial features, though only a few have had birth defects. We report on three probands with duplications within 7q11.23 of variable sizes; two with cardiovascular involvement including aortic dilation and the other with unilateral renal and gonadal agenesis. We offer a comparison with previously reported cases of duplications of 7q11.23. In light of the present cases, we recommend undertaking echocardiographic and renal ultrasound evaluation of patients with documented 7q11.23 duplications. Further, this cytogenetic abnormality should be part of the differential diagnosis for patients with aortic dilation, as well as those with unilateral renal and gonadal agenesis. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background and purpose von Willebrand factor propeptide ( VWF: Ag II) is potentially a more sensitive marker of acute endothelial activation than von Willebrand factor antigen ( VWF:Ag). These biomarkers have not been simultaneously assessed in asymptomatic versus symptomatic carotid stenosis patients. The relationship between endothelial activation and cerebral microembolic signals ( MESs) detected on transcranial Doppler ultrasound is unknown. Methods In this multicentre observational analytical study, plasma VWF:Ag and VWF: Ag II levels in patients with ≥50% asymptomatic carotid stenosis were compared with those from patients with ≥50% symptomatic carotid stenosis in the 'early' (≤4 weeks) and 'late' (≥3 months) phases after transient ischaemic attack or ischaemic stroke. Endothelial activation was also longitudinally assessed in symptomatic patients during follow-up. Transcranial Doppler ultrasound monitoring classified patients as MES-positive or MES-negative. Results Data from 31 asymptomatic patients were compared with those from 46 early symptomatic and 35 late phase symptomatic carotid stenosis patients, 23 of whom had undergone carotid intervention. VWF: Ag II levels were higher in early (12.8 μg/ml; P < 0.001), late (10.6 μg/ml; P = 0.01) and late post-intervention (10.6 μg/ml; P = 0.038) symptomatic patients than asymptomatic patients (8.9 μg/ml). VWF:Ag levels decreased in symptomatic patients followed up from the early to late phase after symptom onset ( P = 0.048). Early symptomatic MES-negative patients had higher VWF: Ag II levels (13.3 vs. 9.0 μg/ml; P < 0.001) than asymptomatic MES-negative patients. Conclusions Endothelial activation is enhanced in symptomatic versus asymptomatic carotid stenosis patients, in early symptomatic versus asymptomatic MES-negative patients, and decreases over time in symptomatic patients. VWF: Ag II levels are a more sensitive marker of endothelial activation than VWF:Ag levels in carotid stenosis. The potential value of endothelial biomarkers and concurrent cerebral MES detection at predicting stroke risk in carotid stenosis warrants further study. [ABSTRACT FROM AUTHOR]

Lotus corniculatus (bird's-foot trefoil) and L. pedunculatus (greater bird's-foot trefoil) have the potential to contribute nutritional benefits to grass-legume swards in temperate regions, but there is a lack of information on their competitive ability in such mixtures. This experiment compared the sward contribution and condensed tannin ( CT) content of nine Lotus varieties established in plots on a low-fertility upland site in Wales, UK, containing mixtures of meadow fescue ( Festuca pratensis) and white clover ( Trifolium repens) varieties of different leaf size, or without white clover (control). Total dry-matter ( DM) yields and Lotus DM were evaluated in two cuts in each of three harvest years, with CT content of Lotus measured at Cut 1 in each year. Lotus corniculatus varieties were significantly higher yielding than those of L. pedunculatus, except in Year 3. In all cuts, except Cut 1 in Year 1 and Year 3, the presence of white clover increased total DM yield compared with the zero-clover treatment. Total DM yields were higher with large-leaved cv. Katrina than with small-leaved cv. AberAce except for Cut 1 in Year 1. Annual Lotus DM yields were significantly higher in the presence of white clover, except in Year 3, but were not significantly affected by white clover leaf size. The highest concentration of sward CT (17 mg g−1 of sward DM) was insufficient to bring about measurable environmental benefits. A Lotus breeding programme aimed at increasing the leaf/stem ratio within persistent germplasm could be pursued to ensure delivery of appropriate levels of sward CT. [ABSTRACT FROM AUTHOR]

Aims To examine the relationship of self-reported diabetes, and of random blood glucose levels among individuals without known diabetes, with the prevalence of cardiovascular disease in Chinese adults. Methods We examined cross-sectional data from the China Kadoorie Biobank of 0.5 million people aged 30-79 years recruited from 10 diverse regions of China in the period 2004-2008. Logistic regression was used to estimate the odds ratios of prevalent cardiovascular disease associated with self-reported diabetes, and with measured random blood glucose levels among participants with no history of diabetes, adjusting simultaneously for age, sex, area, education, smoking, alcohol, blood pressure and physical activity. Results A total of 3.2% of participants had self-reported diabetes (men 2.9%; women 3.3%) and 2.8% had screen-detected diabetes (men 2.6%; women 2.8%), i.e. they had no self-reported history of diabetes but a blood glucose level suggestive of a diagnosis of diabetes. Compared with individuals without a history of diabetes, the odds ratios associated with self-reported diabetes were 2.18 (95% CI 2.06-2.30) and 1.88 (95% CI 1.75-2.01) for prevalent ischaemic heart disease and stroke/transient ischaemic attack, respectively. Among participants without self-reported diabetes there was a positive association between random blood glucose and ischaemic heart disease and stroke/transient ischaemic attack prevalence ( P for trend <0.0001). Below the diabetic threshold (<11.1 mmol/l) each additional 1 mmol/l of random blood glucose was associated with 4% (95% CI 2-5%) and 5% (95% CI 3-7%) higher odds of prevalent ischaemic heart disease and stroke/transient ischaemic attack, respectively. Conclusions In this adult Chinese population, self-reported diabetes was associated with a doubling of the odds of prevalent cardiovascular disease. Below the threshold for diabetes there was still a modest, positive association between random blood glucose and prevalent cardiovascular disease. [ABSTRACT FROM AUTHOR]

Arrhythmia in Adults with Single Ventricles Objectives The study sought to identify the impact of cardiac arrhythmias on hospitalizations in adults with single ventricle (SV) congenital heart disease (CHD). Background Surgical advances have dramatically improved survival in patients with CHD. Cardiac arrhythmias and sudden cardiac death are common in adults with CHD. Methods and Results Data from 43 pediatric hospitals in the 2004 to 2011 Pediatric Health Information System database were used to identify patients ≥18 years of age admitted with International Classification of Diseases-9th Revision codes for a diagnosis of either hypoplastic left heart syndrome (HLHS), tricuspid atresia (TA) or common ventricle (CV), and a cardiac arrhythmia. Primary and secondary diagnoses, length of stay (LOS), hospital charges, and interventional procedures were determined. Multilevel models were used to evaluate differences in demographics, diagnoses, and clinical outcomes among the 3 subgroups (HLHS, TA, and CV). Interactions of charges with arrhythmia and admission year were examined using ANOVA. There were 642 admissions in 424 patients with SV CHD and an arrhythmia diagnosis. A single arrhythmia diagnosis was present in 454 admissions (71%). Total hospital charges were $80.7 million with mean charge per admission of $127,296 ± 243,094. The mean charge per hospital day was $16,653 ± 17,516 and increased across the study period (P < 0.01). Arrhythmia distributions were impacted by SV anatomic subtype (P < 0.001). Hospital resource utilization was significantly different among arrhythmia groups (P < 0.001). Conclusions In adults with SV CHD, arrhythmias are affected by SV anatomic subtype and impact adversely upon hospital resource utilization. [ABSTRACT FROM AUTHOR]

HLA-specific antibodies bind discrete clusters of amino acids called epitopes, but serological assignment of antibody specificities makes no reference to this. As HLA typing for solid organ transplantation is provided at only medium (serologically equivalent) resolution, this means that recipient HLA antibodies to donor HLA epitopes may not be identified. We have designed a novel and rapid HLA-A epitope typing method (epityping) using a two-stage PCR- SSP-based method to detect the HLA-A locus epitopes described by El Awar et al. 2007, Transplantation, 84, 532. The initial PCR step utilizes HLA-A locus-specific primers; the product is cleaned using the QIAquick Spin Purification procedure. The purified product is tested using our in-house epitope-specific primer panel, the results being visualized using gel electrophoresis. Twenty two UCLA DNA Exchange samples were epityped, blinded to the HLA type. Of the 75 primer pairs, the mean correlation coefficient was 0.95 with each sample giving 67 or more correct primer results. In all cases, it was possible to derive the first field classic HLA type from the epityping results. These results indicate that a method for identification of HLA epitopes which is comparable in time, cost and technical expertise to current HLA typing methods is achievable. Redesigning HLA typing to correlate with what the antibody binds should minimize inappropriate organ allocation. We suggest that epityping provides a more effective method than standard HLA typing for solid organ transplantation. [ABSTRACT FROM AUTHOR]

Despite the broad benefits that DNA barcoding can bring to a diverse range of biological disciplines, a number of shortcomings still exist in terms of the experimental design of studies incorporating this approach. One underlying reason for this lies in the confusion that often exists between species discovery and specimen identification, and this is reflected in the way that hypotheses are generated and tested. Although these aims can be associated, they are quite distinct and require different methodological approaches, but their conflation has led to the frequently inappropriate use of commonly used analytical methods such as neighbour-joining trees, bootstrap resampling and fixed distance thresholds. Furthermore, the misidentification of voucher specimens can also have serious implications for end users of reference libraries such as the Barcode of Life Data Systems, and in this regard we advocate increased diligence in the a priori identification of specimens to be used for this purpose. This commentary provides an assessment of seven deficiencies that we identify as common in the DNA barcoding literature, and outline some potential improvements for its adaptation and adoption towards more reliable and accurate outcomes. [ABSTRACT FROM AUTHOR]

The structure of bacterial communities in first-year spring and summer sea ice differs from that in source seawaters, suggesting selection during ice formation in autumn or taxon-specific mortality in the ice during winter. We tested these hypotheses by weekly sampling (January–March 2004) of first-year winter sea ice (Franklin Bay, Western Arctic) that experienced temperatures from −9°C to −26°C, generating community fingerprints and clone libraries for Bacteria and Archaea. Despite severe conditions and significant decreases in microbial abundance, no significant changes in richness or community structure were detected in the ice. Communities of Bacteria and Archaea in the ice, as in under-ice seawater, were dominated by SAR11 clade Alphaproteobacteria and Marine Group I Crenarchaeota, neither of which is known from later season sea ice. The bacterial ice library contained clones of Gammaproteobacteria from oligotrophic seawater clades (e.g. OM60, OM182) but no clones from gammaproteobacterial genera commonly detected in later season sea ice by similar methods (e.g. Colwellia, Psychrobacter). The only common sea ice bacterial genus detected in winter ice was Polaribacter. Overall, selection during ice formation and mortality during winter appear to play minor roles in the process of microbial succession that leads to distinctive spring and summer sea ice communities. [ABSTRACT FROM AUTHOR]

The collective impact of several environmental factors on the biocontrol activity of Trichoderma stromaticum ( Ts) against Moniliophthora perniciosa ( Mp), the cause of cacao witches’ broom disease, was assessed under field conditions of shaded cacao ( Theobroma cacao) in south-eastern Bahia, Brazil. Biocontrol experiments were performed adjacent to an automated weather station, with sensors and Ts-treated brooms placed at different canopy heights. Sporulation occurred at the same dates for all Ts isolates, but in different quantities. Broom moisture >30%, air temperature of approximately 23 ± 3°C, relative humidity >90%, solar radiation intensities <0·12 KW m−² and wind speed near zero were the key environmental parameters that preceded Ts sporulation events. A multiple logistic regression indicated that these weather variables combined were capable of distinguishing sporulation from non-sporulation events, with a significant effect of wind speed. Analyses of environmental factors at ground level indicated similar pre-sporulation conditions, with a soil moisture content above a threshold of 0·34 m3 m−3 preceding all sporulation events. The sporulation of five selected Ts isolates was compared at four different canopy heights. Isolates responded differently to weather variation in terms of sporulation and antagonism to Mp at different canopy levels, indicating that different microclimates are established along the vertical profile of a shaded cacao plantation. The potential of these findings for development of predictive mathematical models and disease-management approaches is discussed. [ABSTRACT FROM AUTHOR]