Changes in hospital mortality for United States intensive care unit admissions from 1988 to 2012

Introduction A decrease in disease-specific mortality over the last twenty years has been reported for patients admitted to United States (US) hospitals, but data for intensive care patients are lacking. The aim of this study was to describe changes in hospital mortality and case-mix using clinical data for patients admitted to multiple US ICUs over the last 24 years. Methods We carried out a retrospective time series analysis of hospital mortality using clinical data collected from 1988 to 2012. We also examined the impact of ICU admission diagnosis and other clinical characteristics on mortality over time. The potential impact of hospital discharge destination on mortality was also assessed using data from 2001 to 2012. Results For 482,601 ICU admissions there was a 35% relative decrease in mortality from 1988 to 2012 despite an increase in age and severity of illness. This decrease varied greatly by diagnosis. Mortality fell by \u3e60% for patients with chronic obstructive pulmonary disease, seizures and surgery for aortic dissection and subarachnoid hemorrhage. Mortality fell by 51% to 59% for six diagnoses, 41% to 50% for seven diagnoses, and 10% to 40% for seven diagnoses. The decrease in mortality from 2001 to 2012 was accompanied by an increase in discharge to post-acute care facilities and a decrease in discharge to home. Conclusions Hospital mortality for patients admitted to US ICUs has decreased significantly over the past two decades despite an increase in the severity of illness. Decreases in mortality were diagnosis specific and appear attributable to improvements in the quality of care, but changes in discharge destination and other confounders may also be responsible

Quantification of the spatiotemporal microstructural organization of the human brain association, projection and commissural pathways across the lifespan using diffusion tensor tractography.

Using diffusion tensor tractography, we quantified the microstructural changes in the association, projection, and commissural compact white matter pathways of the human brain over the lifespan in a cohort of healthy right-handed children and adults aged 6-68 years. In both males and females, the diffusion tensor radial diffusivity of the bilateral arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, corticospinal, somatosensory tracts, and the corpus callosum followed a U-curve with advancing age; fractional anisotropy in the same pathways followed an inverted U-curve. Our study provides useful baseline data for the interpretation of data collected from patients

Towards Higgs boson production in gluon fusion to NNLO in the MSSM

We consider the Higgs boson production in the gluon-fusion channel to next-to-next-to-leading order within the Minimal Supersymmetric Standard Model. In particular, we present analytical results for the matching coefficient of the effective theory and study its influence on the total production cross section in the limit where the masses of all MSSM particles coincide. For supersymmetric masses below 500 GeV it is possible to find parameters leading to a significant enhancement of the Standard Model cross section, the $K$-factors, however, change only marginally.Comment: 20 pages; v2: modification of discussion of numerical effect, version to appear in EPJC; v3: eq.(18) corrected, minor correction

Weed Seed Bank Emergence across the Corn Belt

Field experiments, conducted from 1991 to 1994, generated information on weed seedbank emergence for 22 site-years from Ohio to Colorado and Minnesota to Missouri. Early spring seedbank densities were estimated through direct extraction of viable seeds from soil cores. Emerged seedlings were recorded periodically, as were daily values for air and soil temperature, and precipitation. Percentages of weed seedbanks that emerged as seedlings were calculated from seedbank and seedling data for each species, and relationships between seedbank emergence and microclimatic variables were sought. Fifteen species were found in 3 or more site-years. Average emergence percentages (and coefficients of variation) of these species were as follows: giant foxtail, 31.2 (84%); velvetleaf, 28.2 (66); kochia, 25.7 (79); Pennsylvania smartweed, 25.1 (65); common purslane, 15.4 (135); common ragweed, 15.0 (110); green foxtail, 8.5 (72); wild proso millet, 6.6 (104); hairy nightshade, 5.2 (62); common sunflower, 5.0 (26); yellow foxtail, 3.4 (67); pigweed species, 3.3 (103); common lambsquarters, 2.7 (111); wild buckwheat, 2.5 (63), and prostrate knotweed, 0.6 (79). Variation among site-years, for some species, could be attributed to microclimate variables thought to induce secondary dormancy in spring. For example, total seasonal emergence percentage of giant foxtail was related positively to the 1st date at which average daily soil temperature at 5 to 10 cm soil depth reached 16 C. Thus, if soil warmed before mid April, secondary dormancy was induced and few seedlings emerged, whereas many seedlings emerged if soil remained cool until June

Weed Seed Bank Emergence across the Corn Belt

Field experiments, conducted from 1991 to 1994, generated information on weed seedbank emergence for 22 site-years from Ohio to Colorado and Minnesota to Missouri. Early spring seedbank densities were estimated through direct extraction of viable seeds from soil cores. Emerged seedlings were recorded periodically, as were daily values for air and soil temperature, and precipitation. Percentages of weed seedbanks that emerged as seedlings were calculated from seedbank and seedling data for each species, and relationships between seedbank emergence and microclimatic variables were sought. Fifteen species were found in 3 or more site-years. Average emergence percentages (and coefficients of variation) of these species were as follows: giant foxtail, 31.2 (84%); velvetleaf, 28.2 (66); kochia, 25.7 (79); Pennsylvania smartweed, 25.1 (65); common purslane, 15.4 (135); common ragweed, 15.0 (110); green foxtail, 8.5 (72); wild proso millet, 6.6 (104); hairy nightshade, 5.2 (62); common sunflower, 5.0 (26); yellow foxtail, 3.4 (67); pigweed species, 3.3 (103); common lambsquarters, 2.7 (111); wild buckwheat, 2.5 (63), and prostrate knotweed, 0.6 (79). Variation among site-years, for some species, could be attributed to microclimate variables thought to induce secondary dormancy in spring. For example, total seasonal emergence percentage of giant foxtail was related positively to the 1st date at which average daily soil temperature at 5 to 10 cm soil depth reached 16 C. Thus, if soil warmed before mid April, secondary dormancy was induced and few seedlings emerged, whereas many seedlings emerged if soil remained cool until June

Functional Analysis of the Two Brassica AP3 Genes Involved in Apetalous and Stamen Carpelloid Phenotypes

The Arabidopsis homeotic genes APETALA3 (AP3) and PISTILLATA (PI) are B genes which encode MADS-box transcription factors and specify petal and stamen identities. In the current study, the stamen carpelloid (SC) mutants, HGMS and AMS, of B. rapa and B. napus were investigated and two types of AP3 genes, B.AP3.a and B.AP3.b, were functional characterized. B.AP3.a and B.AP3.b share high similarity in amino acid sequences except for 8 residues difference located at the C-terminus. Loss of this 8 residues in B.AP3.b led to the change of PI-derived motifs. Meanwhile, B.AP3.a specified petal and stamen development, whereas B.AP3.b only specified stamen development. In B. rapa, the mutations of both genes generated the SC mutant HGMS. In B. napus that contained two B.AP3.a and two B.AP3.b, loss of the two B.AP3.a functions was the key reason for the apetalous mutation, however, the loss-of-function in all four AP3 was related to the SC mutant AMS. We inferred that the 8 residues or the PI-derived motif in AP3 gene probably relates to petal formation

Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation