Verification of Austroads concrete pavement design method using EverFE computer program

The current Austroads concrete pavement design procedure is based on the PCA’s empirical design method originally developed in 1960’s, which may only be applicable for certain loading and environmental conditions. With the increased utilisation of larger and heavier commercial vehicles, eventually future pavements cannot be designed using this method. While this method is still considered adequate at present, this paper attempts to investigate whether there is a need to revise the design procedure in the future. In the present study, pavement design was initially performed as per the Austroads procedure using the RMS pavement design spreadsheet for a comparison with the EverFE 3D Finite Element Analysis computer program. Traffic data from Pennant Hills Road in North Parramatta and the eastbound lanes of the M2 motorway in North Epping, Sydney were used. The results of this study reveals that the equivalent stress values of standard vehicles obtained from Austroads method are lower than the maximum tensile stress obtained from EverFE for unbonded boundary condition by as little as 5.7% (for TRDT) to a maximum of 15.7% (for SAST). However, for the selected traffic compositions, it has been found that the difference in equivalent stress values does not influence allowable axle repetitions and the resulting pavement thickness. EverFE was subsequently used to model the response of a rigid pavement configuration to hypothetical axle loadings for different wheel positions from pavement edge. It was found that under the assumed traffic loading the pavement stresses could increase threefold but temperature gradient in the pavement would still be the most significant factor in affecting pavement stresses. The overall results therefore suggest that the Austroads concrete pavement design method is presently adequate, but there may be a need to revise the current design method if the traffic loading increases significantly in the future

Gene expression profiling reveals consistent differences between clinical samples of human leukaemias and their model cell lines

Microarray gene expression profiles of fresh clinical samples of chronic myeloid leukaemia in chronic phase, acute promyelocytic leukaemia and acute monocytic leukaemia were compared with profiles from cell lines representing the corresponding types of leukaemia (K562, NB4, HL60). In a hierarchical clustering analysis, all clinical samples clustered separately from the cell lines, regardless of leukaemic subtype. Gene ontology analysis showed that cell lines chiefly overexpressed genes related to macromolecular metabolism, whereas in clinical samples genes related to the immune response were abundantly expressed. These findings must be taken into consideration when conclusions from cell line-based studies are extrapolated to patients

Impact of the COVID-19 Pandemic on Inpatient Antibiotic Consumption in Switzerland.

The aim of this study was to analyze inpatient antibiotic consumption during the first 16 months of the COVID-19 pandemic in Switzerland. The entire period (January 2018-June 2021) was divided into the prepandemic period, the first and second waves, and the intermediate period. In the first year of the pandemic, total overall inpatient antibiotic consumption measured in defined daily doses (DDD) per 100 bed-days remained stable (+1.7%), with a slight increase in ICUs of +4.2%. The increase in consumption of broad-spectrum antibiotics was +12.3% overall and 17.3% in ICUs. The segmented regression model of monthly data revealed an increase in overall antibiotic consumption during the first wave but not during the second wave. In the correlation analysis performed in a subset of the data, a significant positive association was found between broad-spectrum antibiotic consumption and an increasing number of hospitalized COVID-19 patients (p = 0.018). Restricting this dataset to ICUs, we found significant positive correlations between the number of hospitalized COVID-19 patients and total antibiotic consumption (p = 0.007) and broad-spectrum antibiotic consumption (p < 0.001). In conclusion, inpatient antibiotic use during the different periods of the COVID-19 pandemic varied greatly and was predominantly notable for broad-spectrum antibiotics

The cognitive and neural basis of option generation and subsequent choice

Decision-making research has thoroughly investigated how people choose from a set of externally provided options. However, in ill-structured real-world environments, possible options for action are not defined by the situation but have to be generated by the agent. Here, we apply behavioral analysis (Study 1) and functional magnetic resonance imaging (Study 2) to investigate option generation and subsequent choice. For this purpose, we employ a new experimental task that requires participants to generate options for simple real-world scenarios and to subsequently decide among the generated options. Correlational analysis with a cognitive test battery suggests that retrieval of options from long-term memory is a relevant process during option generation. The results of the fMRI study demonstrate that option generation in simple real-world scenarios recruits the anterior prefrontal cortex. Furthermore, we show that choice behavior and its neural correlates differ between self-generated and externally provided options. Specifically, choice between self-generated options is associated with stronger recruitment of the dorsal anterior cingulate cortex. This impact of option generation on subsequent choice underlines the need for an expanded model of decision making to accommodate choice between self-generated option

The cognitive and neural basis of option generation and subsequent choice

Decision-making research has thoroughly investigated how people choose from a set of externally provided options. However, in ill-structured real-world environments, possible options for action are not defined by the situation but have to be generated by the agent. Here, we apply behavioral analysis (Study 1) and functional magnetic resonance imaging (Study 2) to investigate option generation and subsequent choice. For this purpose, we employ a new experimental task that requires participants to generate options for simple real-world scenarios and to subsequently decide among the generated options. Correlational analysis with a cognitive test battery suggests that retrieval of options from long-term memory is a relevant process during option generation. The results of the fMRI study demonstrate that option generation in simple real-world scenarios recruits the anterior prefrontal cortex. Furthermore, we show that choice behavior and its neural correlates differ between self-generated and externally provided options. Specifically, choice between self-generated options is associated with stronger recruitment of the dorsal anterior cingulate cortex. This impact of option generation on subsequent choice underlines the need for an expanded model of decision making to accommodate choice between self-generated options

Cardiac outcomes in adults with supravalvar aortic stenosis

Aims Supravalvar aortic stenosis is a rare form of left ventricular outflow tract obstruction that is often progressive in childhood. Little data are available on outcomes in the adult population. Our aim was to define cardiac outcomes in adults with supravalvar aortic stenosis. Methods and results This is a multicentre retrospective study of cardiac outcomes in adults (≥18 years) with supravalvar aortic stenosis. We examined: (i) adverse cardiac events (cardiovascular death, myocardial infarction, stroke, heart failure, sustained arrhythmias, and infective endocarditis) and (ii) the need for cardiac surgery in adulthood. One hundred and thirteen adults (median age at first visit 19 years; 55% with Williams-Beuren syndrome; 67% with surgical repair in childhood) were identified. Adults without Williams-Beuren syndrome had more severe supravalvar aortic stenosis and more often associated left ventricular outflow tract obstructions (P < 0.001). In contrast, mitral valve regurgitation was more common in patients with Williams-Beuren syndrome. Eighty-five per cent of adults (96/113) had serial follow-up information (median follow-up 6.0 years). Of these patients, 13% (12/96) had an adverse cardiac event and 13% (12/96) had cardiac operations (7 valve repair or replacements, 4 supravalvar aortic stenosis repairs, 1 other). Cardiac surgery was more common in adults without Williams-Beuren syndrome (P = 0.007). Progression of supravalvar aortic stenosis during adulthood was rare. Conclusion Adults with supravalvar aortic stenosis remain at risk for cardiac complications and reoperations, while progression of supravalvar aortic stenosis in adulthood is rare. Valve surgery is the most common indication for cardiac surgery in adulthoo

NMDA Receptors on Non-Dopaminergic Neurons in the VTA Support Cocaine Sensitization

The initiation of behavioral sensitization to cocaine and other psychomotor stimulants is thought to reflect N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic plasticity in the mesolimbic dopamine (DA) circuitry. The importance of drug induced NMDAR mediated adaptations in ventral tegmental area (VTA) DA neurons, and its association with drug seeking behaviors, has recently been evaluated in Cre-loxp mice lacking functional NMDARs in DA neurons expressing Cre recombinase under the control of the endogenous dopamine transporter gene (NR1(DATCre) mice).Using an additional NR1(DATCre) mouse transgenic model, we demonstrate that while the selective inactivation of NMDARs in DA neurons eliminates the induction of molecular changes leading to synaptic strengthening, behavioral measures such as cocaine induced locomotor sensitization and conditioned place preference remain intact in NR1(DATCre) mice. Since VTA DA neurons projecting to the prefrontal cortex and amygdala express little or no detectable levels of the dopamine transporter, it has been speculated that NMDA receptors in DA neurons projecting to these brain areas may have been spared in NR1(DATCre) mice. Here we demonstrate that the NMDA receptor gene is ablated in the majority of VTA DA neurons, including those exhibiting undetectable DAT expression levels in our NR1(DATCre) transgenic model, and that application of an NMDAR antagonist within the VTA of NR1(DATCre) animals still blocks sensitization to cocaine.These results eliminate the possibility of NMDAR mediated neuroplasticity in the different DA neuronal subpopulations in our NR1(DATCre) mouse model and therefore suggest that NMDARs on non-DA neurons within the VTA must play a major role in cocaine-related addictive behavior