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Multituberculates were among the most taxonomically diverse mammals of the early Paleocene, having survived the catastrophic Cretaceous-Paleogene mass extinction and radiating soon thereafter. Although their evolution during the early Paleocene saw the advent of increasingly specialized dentitions, multituberculates generally remained small, rarely exceeding body sizes greater than those of extant rabbits. A conspicuous exception is the Taeniolabidoidea, a primarily North American clade whose members include the largest multituberculates yet discovered. Taeniolabidoidea includes several genera, with one of these, Catopsalis, being speciose and geographically wide ranging. Until recently, the chronological succession of Catopsalis appeared to document a trend of increasing body size. We report here on a new species of Catopsalis from the early Paleocene of Alberta that violates this trend and suggests that the evolutionary history of Catopsalis is considerably more complex. Catopsalis kakwa new species is not only the smallest species of Catopsalis, but is the smallest taeniolabidoid so far discovered, with an estimated body mass between 400 g and 660 g. In contrast to previous studies, we used recently proposed regressions based on lower cheek tooth row length to estimate body masses for North American taeniolabidoids. Our results propose more modest body mass estimates, particularly for the largest taeniolabidoids. The occurrence of C. kakwa n. sp. in the late early Paleocene implies either a significant ghost lineage, or reversal of several characters, including body size, during the latter part of the early Paleocene; the more likely of these scenarios must await a better understanding of the phylogenetic position of C. kakwa n. sp.
Objectives: Glioblastoma is a lethal disease in the elderly population. We aimed to evaluate disease and treatment outcomes in the oldest-old patients. Methods: Patients >80 years old with histologically confirmed glioblastoma treated between 2004 and 2009 were identified. We included patients managed with best supportive care (BSC), temozolomide (TMZ) alone, radiotherapy (RT) alone, or concomitantly with TMZ (CRT). Survival outcomes were analyzed using the Kaplan–Meier method. Results: Ultimately, 48 patients were analyzed. Median age and Eastern Cooperative Oncology Group (ECOG) Performance Status were 82 years and 2, respectively. The median Age-Adjusted Charlson Index (AAC) was 6. Gross total and subtotal resections were performed in 16.7% and 18.8% of patients, respectively. Biopsy followed by RT alone was the treatment modality for 23/48 (47.9%), while 17/48 (35.4%) received surgery followed by RT alone or CRT. A total of 8 (16.7%) were managed with BSC after biopsy. Median overall survival (OS) and progression-free survival (PFS) were 4.1 (95% confidence interval [95% CI] 3.3-4.9) and 2.7 (95% CI 1.5-3.9) months, respectively. Improved median OS was observed in those treated with surgical resection followed by RT alone or CRT (7.1 months), compared to biopsy followed by RT alone (4.2 months) or BSC (2.0 months; p=0.002). Surgical resection, age≤85, and AAC<6 were associated with better OS (p=0.032, p=0.031, and p=0.02, respectively). Cause of death was neurological progression in 56% of cases. RT was well-tolerated. Conclusions: PFS and OS outcomes remain poor in the oldest-old patients (>80 years old). Younger age, lower AAC, surgical resection, and adjuvant treatment were associated with improved OS.
Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity.
To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.
The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT.
In the replication cohorts, we observed a significant interaction between FTO, BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10−4) and with the Han/Eskin random effects method (P = 1.4 × 10−7) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model (P = 6.9 × 10−8). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO.
This meta-analysis provides additional support for a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
In 1471, King Henry VI of England died in the Tower of London amid disputed circumstances. Between his death and Henry VIII’s break with Rome in the 1530s, he was venerated as a saint and martyr. Modern historians have generally dismissed this cult as a political phenomenon, created and used by the Tudors as they sought legitimacy. While there is some truth in that assessment, political allegiance was only a part of the impetus for the participation of Henry’s devotees in the cult. Alongside carefully crafted (and perhaps, artificial) portrayals of Henry’s virtues lay something else his former subjects found compelling: his very real political failures, and more importantly the adversity that they engendered. Henry’s devotees used these royal adversities as the basis from which to imagine a sympathetic relationship between themselves and “good King Herre” in which he had great concern for their fatal and near-fatal emergencies. These neglected devotional aspects of Henry VI’s cult are the subject of this article.
The fertility and soil health of organic agroecosystems are determined in part by the size and turnover rate of soil carbon (C) and nitrogen (N) pools. Our research contrasts the effects of best management practices (BMP) (reduction in soil disturbance, addition of organic amendments) on C and N cycling in soils from two field sites representing five organic agroecosystems. Total soil organic C (SOC), a standard measure of soil health, contains equal amounts of biologically and non-biologically active C that is not associated with release of mineral N. A three-pool first-order model can be used to estimate the size and turnover rates of C pools but requires data from a long-term incubation. Our research highlights the use of two rapid C fractions, hydrolysable and permanganate (0.02 M) oxidizable C, to assess shifts in biologically active C. Adoption of BMP in organic management systems reduced the partitioning of C to the active pool while augmenting the slow pool C. These pools are associated with potentially mineralizable N supplied by residues, amendments and soil organic matter affecting the concentration and release of mineral N to crops. Our data show that minimizing disturbance (no tillage, pasture) and mixed compost additions have the potential to reduce carbon dioxide emissions while enhancing slow pool C and or its turnover, a reservoir of nutrients available to the soil biota. Use of these rapid, sensitive indicators of biological C activity will aid growers in determining whether a BMP fosters nutrient loss or retention prior to shifts in total SOC.
To determine the effect of graft choice (allograft, bone-patellar tendon-bone autograft, or hamstring autograft) on deep tissue infections following anterior cruciate ligament (ACL) reconstructions.
Retrospective cohort study.
SETTING AND POPULATION
Patients from 6 US health plans who underwent ACL reconstruction from January 1, 2000, through December 31, 2008.
We identified ACL reconstructions and potential postoperative infections using claims data. A hierarchical stratified sampling strategy was used to identify patients for medical record review to confirm ACL reconstructions and to determine allograft vs autograft tissue implanted, clinical characteristics, and infection status. We estimated infection rates overall and by graft type. We used logistic regression to assess the association between infections and patients’ demographic characteristics, comorbidities, and choice of graft.
On review of 1,452 medical records, we found 55 deep wound infections. With correction for sampling weights, infection rates varied by graft type: 0.5% (95% CI, 0.3%-0.8%) with allografts, 0.6% (0.1%–1.5%) with bone-patellar tendon-bone autografts, and 2.5% (1.9%–3.1%) with hamstring autograft. After adjusting for potential confounders, we found an increased infection risk with hamstring autografts compared with allografts (odds ratio, 5.9; 95% CI, 2.8–12.8). However, there was no difference in infection risk among bone-patellar tendon-bone autografts vs allografts (odds ratio, 1.2; 95% CI, 0.3–4.8).
The overall risk for deep wound infections following ACL reconstruction is low but it does vary by graft type. Infection risk was highest in hamstring autograft recipients compared with allograft recipients and bone-patellar tendon-bone autograft recipients.
The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body composition, including muscle and bone measures of monozygotic (MZ) female twin pairs discordant for HRT. We identified 7,855 nominally significant differentially methylated regions (DMRs) associated with 4,044 genes. Of the genes with DMRs, five (ACBA1, CCL5, FASLG, PPP2R2B, and UHRF1) were also differentially expressed. All have been previously associated with HRT or estrogenic regulation, but not with HRT-associated DNA methylation. All five genes were associated with bone mineral content (BMC), and ABCA1, FASLG, and UHRF1 were also associated with body adiposity. Our study is the first to show that HRT associates with genome-wide DNA methylation alterations in WBCs. Moreover, we show that five differentially expressed genes with DMRs associate with clinical measures, including body fat percentage, lean body mass, bone mass, and blood lipids. Our results indicate that at least part of the known beneficial HRT effects on body composition and bone mass may be regulated by DNA methylation associated alterations in gene expression in circulating WBCs.
To explore the feasibility of identifying anterior cruciate ligament (ACL) allograft implantations and infections using claims.
Retrospective cohort study.
We identified ACL reconstructions using procedure codes at 6 health plans from 2000 to 2008. We then identified potential infections using claims-based indicators of infection, including diagnoses, procedures, antibiotic dispensings, specialty consultations, emergency department visits, and hospitalizations. Patients’ medical records were reviewed to determine graft type, validate infection status, and calculate sensitivity and positive predictive value (PPV) for indicators of ACL allografts and infections.
A total of 11,778 patients with codes for ACL reconstruction were identified. After chart review, PPV for ACL reconstruction was 96% (95% confidence interval [CI], 94%–97%). Of the confirmed ACL reconstructions, 39% (95% CI, 35%–42%) used allograft tissues. The deep infection rate after ACL reconstruction was 1.0% (95% CI, 0.7%–1.4%). The odds ratio of infection for allografts versus autografts was 0.41 (95% CI, 0.19–0.78). Sensitivity of individual claims-based indicators for deep infection after ACL reconstruction ranged from 0% to 75% and PPV from 0% to 100%. Claims-based infection indicators could be combined to enhance sensitivity or PPV but not both.
While claims data accurately identify ACL reconstructions, they poorly distinguish between allografts and autografts and identify infections with variable accuracy. Claims data could be useful to monitor infection trends after ACL reconstruction, with different algorithms optimized for different surveillance goals.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
Over 90% of Canadian kochia populations are resistant to acetolactate
synthase (ALS)– inhibiting herbicides. We questioned whether the target
site–based resistance could affect plant growth and competitiveness.
Homozygous F2 herbicide-resistant (HR) kochia plants with an
amino acid substitution at Trp574 (sources: Alberta [AB],
Saskatchewan [SK], and Manitoba [MB]), or Pro197 (MB, AB with two
populations) were grown in replacement series with homozygous F2
herbicide-susceptible (HS) plants from the corresponding heterogeneous
population (total: six populations). In pure stands, growth of HR plants
from AB and SK was similar to that of HS plants, regardless of mutation;
conversely, MB2-HR plants (Trp574Leu) developed more slowly and
were taller than MB2-HS plants. Final dry weight of HR plants in pure stands
was similar across all six populations, whereas that for HS plants in pure
stands and HR–HS plants in mixed stands (50–50%) varied with population.
Results for AB and SK populations suggest little impact of either ALS
mutation on kochia growth, whereas those for MB lines would suggest an
unidentified factor (or factors) affecting the HS, HR, or both biotypes. The
variable response within and between lines, and across HS biotypes
highlights the importance of including populations of various origins and
multiple susceptible controls in HR biotype studies.