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Measures of urban productivity are typically positively associated with city population. But is this relationship causal? We discuss the main sources of bias in the proper identification of agglomeration effects. We also assess a variety of solutions that have been proposed in the literature to deal with them.

We compared the powers of the likelihood ratio test (LRT) and the Pearson correlation test (CT) from empirical Bayes estimates (EBEs) for various designs and shrinkages in the context of nonlinear mixed‐effect modeling. Clinical trial simulation was performed with a simple pharmacokinetic model with various weight (WT) effects on volume (V). Data sets were analyzed with NONMEM 7.2 using first‐order conditional estimation with interaction and stochastic approximation expectation maximization algorithms. The powers of LRT and CT in detecting the link between individual WT and V or clearance were computed to explore hidden or induced correlations, respectively. Although the different designs and variabilities could be related to the large shrinkage of the EBEs, type 1 errors and powers were similar in LRT and CT in all cases. Power was mostly influenced by covariate effect size and, to a lesser extent, by the informativeness of the design. Further studies with more models are needed. CPT Pharmacometrics Syst. Pharmacol. (2014) 4, e109; doi:10.1038/psp.2014.5; published online 9 April 2014

To compare the ventilator-associated pneumonia (VAP) incidence rates in mechanically ventilated patients according to the type of endotracheal suctioning (closed versus open). The Neurosurgery Intensive Care Unit of the Grenoble University Hospital, France. A prospective randomised study performed after a 6-month period of nursing personnel training. One hundred four consecutive patients needing mechanical ventilation for more than 48 h were randomised into two groups. To be eligible, patients had to have no active infection or respiratory affection in their passes. In the Stericath group (S+, n = 54), patients were not disconnected from the ventilator during suctioning. The others were routinely managed (S-, n = 50). In both groups patterns of frequency and duration of suctioning were performed according to a standardised protocol. The non-adjusted incidence rate of VAP was lower for S+ than for S- (7.32 versus 15.89 per 1000 patient-days, p = 0.07). Multivariate analysis performed using the Cox model showed an adjusted risk of VAP 3.5 times higher in S- (95% CI: 11.00-12.33). The risk being 4.3 higher in patients receiving gastric acid secretion inhibitors (1.08-16.82). In non-censored cases (n = 76) length of ICU stay increased by an average of 16.8 days when VAP was present (p = 0.0008). No adverse effect due to Stericath use was noted and volume of tracheal aspirate was similar between groups (p = 0.178). The use of Stericath reduced the incidence rate of VAP without demonstrating any adverse effect.

We develop a methodology to accurately compute transport costs. Based on the real transport network, our measure encompasses the characteristics of infrastructure, vehicle and energy used, as well as labor, insurance, tax and general charges borne by transport carriers. Computed for the 341 French employment areas, road transport shipments and the period 1978–1998, this new measure is compared to alternative ones such as great circle distance, real distance, or real time. We conclude that these proxies do a very good job in capturing transport costs in cross-section analysis. However, important discrepancies limit the possibility of using them in time series analysis. Moreover, our measure allows us to identify the policies that most impact transport costs. We show that transport technology and market structure are responsible for most of the transport cost decrease. Infrastructure improvements only condition the spatial distribution of the gains. Finally, some implications for researchers and regional policy makers are derived.

Mutations in each of the five eucaryotic initiation factor 2B (eIF2B) subunits have been found in leukodystrophies of various severity: Cree leukoencephalopathy, childhood ataxia with central hypomyelination/leukodystrophy with vanishing white matter and ovarioleukodystrophy. A continuum was observed from fatal infantile forms to adult forms without neurological deterioration. Disease severity was found to correlate with the age at disease onset and the specific amino-acid substitution. In order to analyze the functional consequences of eIF2B mutations, we measured the guanine nucleotide exchange factor (GEF) activity of eIF2B in transformed lymphocytes from 30 affected patients carrying mutations in eIF2B compared to 10 unaffected heterozygotes and 22 controls without eIF2B mutations. A significant decrease of 20–70% in GEF activity was observed in all mutated cells. The severity of this decrement of GEF activity correlated with age at onset of the disease. These results suggest that a deficiency in GEF activity underlies the encephalopathy associated eIF2B-related disease. Our study demonstrates that the evaluation of the GEF activity in transformed lymphocytes represents an interesting alternative test to the systematic screening of the five EIF2B genes. This relevant cellular model may also be used to test the functional impact of different molecules on the GEF activity for future therapeutic strategies.

Metaliron powders of well controlled size and morphology were synthesised by thermal decomposition under hydrogen of precipitated ferrous oxalates. Green compacts were prepared by uniaxial pressing of metal powders at 290 MPa. The bending green strengths of compacts were measured. The precipitation of β-FeC 2 O 4 .2H 2 O oxalate from ammonium oxalate gives rise to the formation of spherical particles by aggregation ofelongated grains. Thermal decomposition of this oxalate from 400 to 500°C under hydrogen permits metal iron particles with a rough surface to be obtained. Decomposition occurring above 500°C induces a smoothness of the particle surface. Metal particles synthesised at 500°C show both surface roughness and micrometer sized primary grains.This specific microstructure has allowed the highest value ofcompact green strength (31·7 MPa) to be obtained. Acicular shaping of the β-FeC 2 O 4 .2H 2 O particles precipitated from oxalic acid involves, after decomposition, an increase in the surface roughness and shape irregularity of the metal particles, owing to an entanglement of the elementary grains. An exceptional value (about 60 MPa) for the metal compact green strength was thus obtained for this type of powder.