Capital Expenditure Decisions and the Role of the Not-for-Profit Hospital: An Application of a Social Goods Model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68370/2/10.1177_107755879004700404.pd

Supporting measurements or more averages? How to quantify cerebral blood flow most reliably in 5 minutes by arterial spin labeling

Purpose To determine whether sacrificing part of the scan time of pseudo-continuous arterial spin labeling (PCASL) for measurement of the labeling efficiency and blood T1 is beneficial in terms of CBF quantification reliability. Methods In a simulation framework, 5-minute scan protocols with different scan time divisions between PCASL data acquisition and supporting measurements were evaluated in terms of CBF estimation variability across both noise and ground truth parameter realizations taken from the general population distribution. The entire simulation experiment was repeated for a single-post-labeling delay (PLD), multi-PLD, and free-lunch time-encoded (te-FL) PCASL acquisition strategy. Furthermore, a real data study was designed for preliminary validation. Results For the considered population statistics, measuring the labeling efficiency and the blood T1 proved beneficial in terms of CBF estimation variability for any distribution of the 5-minute scan time compared to only acquiring ASL data. Compared to single-PLD PCASL without support measurements as recommended in the consensus statement, a 26%, 33%, and 42% reduction in relative CBF estimation variability was found for optimal combinations of supporting measurements with single-PLD, free-lunch, and multi-PLD PCASL data acquisition, respectively. The benefit of taking the individual variation of blood T1 into account was also demonstrated in the real data experiment. Conclusions Spending time to measure the labeling efficiency and the blood T1 instead of acquiring more averages of the PCASL data proves to be advisable for robust CBF quantification in the general population

More on Massive 3D Supergravity

Completing earlier work on three dimensional (3D) N=1 supergravity with curvature-squared terms, we construct the general supergravity extension of cosmological massive gravity theories. We expand about supersymmetric anti-de Sitter vacua, finding the conditions for bulk unitarity and the critical points in parameter space at which the spectrum changes. We discuss implications for the dual conformal field theory.Comment: v1 : 53 pages, 1 figure; v2 : significantly shortened, 42 p., version published in Class. Quant. Gra

The Short-term Car Flow Planning Model in Rail Freight Company – Case Study

AbstractWith the promotion of the environmentally friendly transportation modes (the European Commission supports the freight transport operations in the rail sector), an increase in the diversification of the demand is observed. While most rail freight companies tend to apply fixed schedules, this approach is not effective turns out to be ineffective due to the need to meet the customer's specific requirements.The purpose of this paper is to present a case study of empty wagon flow planning over a medium term horizon and to discuss the opportunities of improvement of this plans by discrete optimization. In order to increase the utilization and availability of wagons, the planning procedure with a rolling horizon has to be implemented. Unfortunately, since the plan has to be updated ca. every 4hours, this planning approach needs effective optimization tools. Our hybrid two-stage approach is designed to be implemented in such business environment. This formulation allows us to solve real life instances even for a 7-day time horizon

High-throughput CRISPRi phenotyping identifies new essential genes in Streptococcus pneumoniae.

Genome-wide screens have discovered a large set of essential genes in the opportunistic human pathogen <i>Streptococcus pneumoniae</i> However, the functions of many essential genes are still unknown, hampering vaccine development and drug discovery. Based on results from transposon sequencing (Tn-seq), we refined the list of essential genes in <i>S. pneumoniae</i> serotype 2 strain D39. Next, we created a knockdown library targeting 348 potentially essential genes by CRISPR interference (CRISPRi) and show a growth phenotype for 254 of them (73%). Using high-content microscopy screening, we searched for essential genes of unknown function with clear phenotypes in cell morphology upon CRISPRi-based depletion. We show that SPD_1416 and SPD_1417 (renamed to MurT and GatD, respectively) are essential for peptidoglycan synthesis, and that SPD_1198 and SPD_1197 (renamed to TarP and TarQ, respectively) are responsible for the polymerization of teichoic acid (TA) precursors. This knowledge enabled us to reconstruct the unique pneumococcal TA biosynthetic pathway. CRISPRi was also employed to unravel the role of the essential Clp-proteolytic system in regulation of competence development, and we show that ClpX is the essential ATPase responsible for ClpP-dependent repression of competence. The CRISPRi library provides a valuable tool for characterization of pneumococcal genes and pathways and revealed several promising antibiotic targets

Genetic polymorphisms and weight loss in obesity: A randomised trial of hypo-energetic high-versus low-fat diets

OBJECTIVES: To study if genes with common single nucleotide polymorphisms (SNPs) associated with obesity-related phenotypes influence weight loss (WL) in obese individuals treated by a hypo-energetic low-fat or high-fat diet. DESIGN: Randomised, parallel, two-arm, open-label multi-centre trial. SETTING: Eight clinical centres in seven European countries. PARTICIPANTS: 771 obese adult individuals. INTERVENTIONS: 10-wk dietary intervention to hypo-energetic (-600 kcal/d) diets with a targeted fat energy of 20%-25% or 40%-45%, completed in 648 participants. OUTCOME MEASURES: WL during the 10 wk in relation to genotypes of 42 SNPs in 26 candidate genes, probably associated with hypothalamic regulation of appetite, efficiency of energy expenditure, regulation of adipocyte differentiation and function, lipid and glucose metabolism, or production of adipocytokines, determined in 642 participants. RESULTS: Compared with the noncarriers of each of the SNPs, and after adjusting for gender, age, baseline weight and centre, heterozygotes showed WL differences that ranged from -0.6 to 0.8 kg, and homozygotes, from -0.7 to 3.1 kg. Genotype-dependent additional WL on low-fat diet ranged from 1.9 to -1.6 kg in heterozygotes, and from 3.8 kg to -2.1 kg in homozygotes relative to the noncarriers. Considering the multiple testing conducted, none of the associations was statistically significant. CONCLUSIONS: Polymorphisms in a panel of obesity-related candidate genes play a minor role, if any, in modulating weight changes induced by a moderate hypo-energetic low-fat or high-fat diet

The Anthropocene is functionally and stratigraphically distinct from the Holocene

Human activity is leaving a pervasive and persistent signature on Earth. Vigorous debate continues about whether this warrants recognition as a new geologic time unit known as the Anthropocene. We review anthropogenic markers of functional changes in the Earth system through the stratigraphic record. The appearance of manufactured materials in sediments − including aluminum, plastics and concrete − coincides with global spikes in fallout radionuclides and particulates from fossil-fuel combustion. Carbon, nitrogen, and phosphorus cycles have been substantially modified over the last century. Rates of sea-level rise, and the extent of human perturbation of the climate system, exceed Late Holocene changes. Biotic changes include species invasions worldwide and accelerating rates of extinction. These combined signals render the Anthropocene stratigraphically distinct from the Holocene and earlier epochs

Pattern of symptomatic congenital heart disease amongst Oriental neonates: a decade's experience

Between 1981 and 1990, 765 symptomatic neonates with major congenital heart malformations were admitted into the Grantham Hospital. This represented an incidence of 10 per 10,000 live births for Hong Kong. The figure was comparable to those reported for Caucasians. Among the 744 Oriental neonates, obstruction of the pulmonary outflow tract occurred most frequently (281, 37.8%), followed by left ventricular outflow tract obstruction (169, 22.7%), left-to-right shunting (115, 15.5%), complete transposition (92, 12.4%), common mixing situations (62, 8.3%), and miscellaneous causes (25,3.3%). When compared with the available reports from the West, Chinese neonates had a high preference for pulmonary outflow tract obstruction (p<0.005), especially the anomaly of pulmonary atresia and intact ventricular septum. This correlated well with cyanosis as the commonest neonatal presentation (64%). Contrary to previous reports that aortic coarctation was rare among Orientals, this abnormality was observed frequently in our study. The rare occurrence of critical aortic valvar stenosis among Chinese, however, was supported by our present analysis. Other lesions, such as left-to-right shunting and complete transposition, showed no significant racial difference in the frequency of occurrence. Such knowledge concerning the pattern of congenital heart disease amongst Oriental neonates can facilitate early diagnosis and timely referral of babies to the appropriate center for management.published_or_final_versio

Trawl fishing impacts on the status of seabed fauna in diverse regions of the globe

Bottom trawl fishing is a controversial activity. It yields about a quarter of the world's wild seafood, but also has impacts on the marine environment. Recent advances have quantified and improved understanding of large-scale impacts of trawling on the seabed. However, such information needs to be coupled with distributions of benthic invertebrates (benthos) to assess whether these populations are being sustained under current trawling regimes. This study collated data from 13 diverse regions of the globe spanning four continents. Within each region, we combined trawl intensity distributions and predicted abundance distributions of benthos groups with impact and recovery parameters for taxonomic classes in a risk assessment model to estimate benthos status. The exposure of 220 predicted benthos-group distributions to trawling intensity (as swept area ratio) ranged between 0% and 210% (mean = 37%) of abundance. However, benthos status, an indicator of the depleted abundance under chronic trawling pressure as a proportion of untrawled state, ranged between 0.86 and 1 (mean = 0.99), with 78% of benthos groups > 0.95. Mean benthos status was lowest in regions of Europe and Africa, and for taxonomic classes Bivalvia and Gastropoda. Our results demonstrate that while spatial overlap studies can help infer general patterns of potential risk, actual risks cannot be evaluated without using an assessment model that incorporates trawl impact and recovery metrics. These quantitative outputs are essential for sustainability assessments, and together with reference points and thresholds, can help managers ensure use of the marine environment is sustainable under the ecosystem approach to management

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology