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Overweight and obesity are increasing health problems that are not restricted to adults only. Childhood obesity is associated with metabolic, psychological and musculoskeletal comorbidities. However, knowledge about the effect of obesity on the foot function across maturation is lacking. Decreased foot function with disproportional loading characteristics is expected for obese children. The aim of this study was to examine foot loading characteristics during gait of normal-weight, overweight and obese children aged 1-12 years. A total of 10382 children aged one to twelve years were enrolled in the study. Finally, 7575 children (m/f: n = 3630/3945; 7.0±2.9 yr; 1.23±0.19 m; 26.6±10.6 kg; BMI: 17.1±2.4 kg/m2) were included for (complete case) data analysis. Children were categorized to normal-weight (≥3rd and <90th percentile; n = 6458), overweight (≥90rd and <97th percentile; n = 746) or obese (>97th percentile; n = 371) according to the German reference system that is based on age and gender-specific body mass indices (BMI). Plantar pressure measurements were assessed during gait on an instrumented walkway. Contact area, arch index (AI), peak pressure (PP) and force time integral (FTI) were calculated for the total, fore-, mid- and hindfoot. Data was analyzed descriptively (mean ± SD) followed by ANOVA/Welch-test (according to homogeneity of variances: yes/no) for group differences according to BMI categorization (normal-weight, overweight, obesity) and for each age group 1 to 12 yrs (post-hoc Tukey Kramer/Dunnett's C; α = 0.05). Mean walking velocity was 0.95 ± 0.25 m/s with no differences between normal-weight, overweight or obese children (p = 0.0841). Results show higher foot contact area, arch index, peak pressure and force time integral in overweight and obese children (p<0.001). Obese children showed the 1.48-fold (1 year-old) to 3.49-fold (10 year-old) midfoot loading (FTI) compared to normal-weight. Additional body mass leads to higher overall load, with disproportional impact on the midfoot area and longitudinal foot arch showing characteristic foot loading patterns. Already the feet of one and two year old children are significantly affected. Childhood overweight and obesity is not compensated by the musculoskeletal system. To avoid excessive foot loading with potential risk of discomfort or pain in childhood, prevention strategies should be developed and validated for children with a high body mass index and functional changes in the midfoot area. The presented plantar pressure values could additionally serve as reference data to identify suspicious foot loading patterns in children.

A long-held dogma posits that strong presentation to the immune system of the dominant influenza virus glycoprotein antigens neuraminidase (NA) and hemagglutinin (HA) is paramount for inducing protective immunity against influenza virus infection. We have deliberately violated this dogma by constructing a recombinant influenza virus strain of A/PR8/34 (H1N1) in which expression of NA and HA genes was suppressed. We down-regulated NA and HA expression by recoding the respective genes with suboptimal codon pair bias, thereby introducing hundreds of nucleotide changes while preserving their codon use and protein sequence. The variants PR8-NA Min , PR8-HA Min , and pR8-(NA+HA) Min (Min, minimal expression) were used to assess the contribution of reduced glycoprotein expression to growth in tissue culture and pathogenesis in BALB/c mice. All three variants proliferated in Madin–Darby canine kidney cells to nearly the degree as WT PR8. In mice, however, they expressed explicit attenuation phenotypes, as revealed by their LD₅₀ values: PR8, 32 plaque-forming units (PFU); HA Min , 1.7 × 10³ PFU; NA Min , 2.4 × 10⁵ PFU; (NA+HA) Min , ≥3.16 × 10⁶ PFU. Remarkably, (NA+HA) Min was attenuated > 100,000-fold, with NA Min the major contributor to attenuation. In vaccinated mice (NA+HA) Min was highly effective in providing long-lasting protective immunity against lethal WT challenge at a median protective dose (PD₅₀) of 2.4 PFU. Moreover, at a PD₅₀ of only 147 or 237, (NA+HA) Min conferred protection against heterologous lethal challenges with two mouse-adapted H3N2 viruses. We conclude that the suppression of HA and NA is a unique strategy in live vaccine development.

As a result of the redundancy of the genetic code, adjacent pairs of amino acids can be encoded by as many as 36 different pairs of synonymous codons. A species-specific \"codon pair bias\" provides that some synonymous codon pairs are used more or less frequently than statistically predicted. We synthesized de novo large DNA molecules using hundreds of over-or underrepresented synonymous codon pairs to encode the poliovirus capsid protein. Underrepresented codon pairs caused decreased rates of protein translation, and polioviruses containing such amino acid-independent changes were attenuated in mice. Polioviruses thus customized were used to immunize mice and provided protective immunity after challenge. This \"death by a thousand cuts\" strategy could be generally applicable to attenuating many kinds of viruses.

Maize is a major biofuel feedstock, accounting for 64% of the global share of ethanol production. Recent improvements in life cycle analyses (LCAs) have accounted for temporal changes in the improved efficiency of farming practices, with reductions in the carbon intensity (CI) of maize grain production over time. There has been little progress on understanding the spatial variation of the CI of maize grain production. The average life cycle CI of US maize production at the farm gate converts to a contribution of 251 g CO2e/kg of maize produced, used in policy calculations related to biofuel production. The objective of this work was to understand the spatial variation in CI scores using Illinois, USA as a case study to conduct life cycle analysis for modeling county‐level CI score. The average CI score of maize produced in Illinois has a range of 9%–12% lower than the national average CI when averaged across the state using county‐level yield and fertilizer application data. Maize grown within 56 km of ethanol facilities in Illinois has scores 14%–17% lower than the national average, when adjusted for ethanol output. This is mainly due to the high yields in Illinois and more efficient use of fertilizer across counties delivering to ethanol plants. There was spatial variation in the impact of cover crop seeding and conservation tillage across a transect of counties. Further refinement of life cycle models will provide more accurate assessments of the carbon intensity of maize production at smaller spatial scales than national averages. Spatial life cycle analysis (LCA) shows that the carbon intensity (CI) of maize grain used for ethanol production in Illinois, USA varies across the state, with an average carbon intensity of 14%–17% lower than the national average used in policy decisions.

•We generated a 2009 pH1N1 vaccine virus with codon pair bias de-optimized HA & NA genes.•The vaccine virus was clinically attenuated and immunogenic in a ferret model.•The vaccine virus protected ferrets from challenge with wt 2009 pH1N1 virus.•Additional de-optimization is needed to reduce vaccine virus replication in ferrets. Codon-pair bias de-optimization (CPBD) of viruses involves re-writing viral genes using statistically underrepresented codon pairs, without any changes to the amino acid sequence or codon usage. Previously, this technology has been used to attenuate the influenza A/Puerto Rico/8/34 (H1N1) virus. The de-optimized virus was immunogenic and protected inbred mice from challenge. In order to assess whether CPBD could be used to produce a live vaccine against a clinically relevant influenza virus, we generated an influenza A/California/07/2009 pandemic H1N1 (2009 pH1N1) virus with de-optimized HA and NA gene segments (2009 pH1N1-(HA+NA)Min), and evaluated viral replication and protein expression in MDCK cells, and attenuation, immunogenicity, and efficacy in outbred ferrets. The 2009 pH1N1-(HA+NA)Min virus grew to a similar titer as the 2009 pH1N1 wild type (wt) virus in MDCK cells (∼106TCID50/ml), despite reduced HA and NA protein expression on western blot. In ferrets, intranasal inoculation of 2009 pH1N1-(HA+NA)Min virus at doses ranging from 103 to 105 TCID50 led to seroconversion in all animals and protection from challenge with the 2009 pH1N1 wt virus 28 days later. The 2009 pH1N1-(HA+NA)Min virus did not cause clinical illness in ferrets, but replicated to a similar titer as the wt virus in the upper and lower respiratory tract, suggesting that de-optimization of additional gene segments may be warranted for improved attenuation. Taken together, our data demonstrate the potential of using CPBD technology for the development of a live influenza virus vaccine if the level of attenuation is optimized.

Declining union density in many industrialized countries increases interest in alternative forms of employee representation, such as works councils. The German works council is one of the most powerful forms of worker representation in developed countries, but little is known of its causal effect on productivity. The author used a large linked employer-employee panel data set to examine this issue. Comparing firms with and without a works council, the author finds that establishments with a works council are on average 6.4% more productive; but he also presents evidence that this figure underestimates the true productivity effect of works councils.

This study investigates the relationship between consumer discrimination, racial matching strategies, and employer discrimination in Major League Baseball (MLB) from 1985 to 2016. Specifically, we assess the extent to which both fan attendance and team performance respond to changes in teams’ and their local market areas’ racial compositions. To this end, we use game-level data (N = 69,239) that we aggregate to the team-season level (N = 866). Using facial recognition software and pictures on more than 7,000 players, each player is assigned to one of three race groups: white, black, and other (Asian or Hispanic). We find both consumer and employer discrimination; discrimination varies across leagues, over time, by race and athlete groups, and regional racial composition. However, league-specific fan and employer racial preferences only partially align, indicating that employer discrimination is not primarily driven by fans’ racial preferences.

BackgroundIn infants and young children, a wide heterogeneity of foot shape is typical. Therefore, children, who are additionally influenced by rapid growth and maturation, are a very special cohort for foot measurements and the footwear industry. The importance of foot measurements for footwear fit, design, as well as clinical applications has been sufficiently described. New measurement techniques (3D foot scanning) allow the assessment of the individual foot shape. However, the validity in comparison to conventional methods remains unclear. Therefore, the purpose of this study was to compare 3D foot scanning with two established measurement methods (2D digital scanning/manual foot measurements).MethodsTwo hundred seventy seven children (125 m / 152 f; mean ± SD: 8.0 ± 1.5yrs; 130.2 ± 10.7cm; 28.0 ± 7.3kg) were included into the study. After collection of basic data (sex, age (yrs), body height (cm), body weight (kg)) geometry of the right foot was measured in static condition (stance) with three different measurement systems (fixed order): manual foot measurement, 2D foot scanning (2D desk scanner) and 3D foot scanning (hand-held 3D scanner). Main outcomes were foot length, foot width (projected; anatomical; instep), heel width and anatomical foot ball breadth. Analysis of variances for dependent samples was applied to test for differences between foot measurement methods (Post-hoc analysis: Tukey-Kramer-Test; α=0.05).ResultsSignificant differences were found for all outcome measures comparing the three methods (p<0.0001). The span of foot length differences ranged from 3 to 6mm with 2D scans showing the smallest and 3D scans the largest deviations. Foot width measurements in comparison of 3D and 2D scans showed consistently higher values for 3D measurements with the differences ranging from 1mm to 3mm.ConclusionsThe findings suggests that when comparing foot data, it is important to consider the differences caused by new measurement methods. Differences of about 0.6cm are relevant when measuring foot length, as this is the difference of a complete shoe size (Parisian point). Hence, correction factors may be required to compare the results of different measurements appropriately. The presented results may have relevance in the field of ergonomics (shoe industry) as well as clinical practice.

Significance Human respiratory syncytial virus (RSV) is the most important viral agent of serious pediatric respiratory-tract disease. We designed new live attenuated RSV vaccine candidates by codon-pair deoptimization (CPD). Specifically, viral ORFs were recoded to increase the usage of underrepresented codon pairs, leaving amino acid coding unchanged. CPD viruses were temperature-sensitive and grew less efficiently in vitro than wild-type RSV. In addition, the CPD viruses exhibited a range of restriction in mice and African green monkeys that compared favorably with existing attenuated strains presently in clinical studies. This study produced examples of a new type of vaccine candidate for RSV and showed that CPD of a nonsegmented negative-strand RNA virus can rapidly generate vaccine candidates with a range of attenuation.

The protein synthesis machineries of two distinct phyla of the Animal kingdom, insects of Arthropoda and mammals of Chordata, have different preferences for how to best encode proteins. Nevertheless, arboviruses (arthropod-borne viruses) are capable of infecting both mammals and insects just like arboviruses that use insect vectors to infect plants. These organisms have evolved carefully balanced genomes that can efficiently use the translational machineries of different phyla, even if the phyla belong to different kingdoms. Using dengue virus as an example, we have undone the genome encoding balance and specifically shifted the encoding preference away from mammals. These mammalian-attenuated viruses grow to high titers in insect cells but low titers in mammalian cells, have dramatically increased LD ₅₀s in newborn mice, and induce high levels of protective antibodies. Recoded arboviruses with a bias toward phylum-specific expression could form the basis of a new generation of live attenuated vaccine candidates. Significance Arboviruses (arthropod-borne viruses), a large group of RNA viruses, replicate in insects that transmit them to mammals, their second host. Insects and mammals have evolved different protein encoding strategies (codon pair bias); hence, arboviruses must delicately balance their encodings between two phyla. Using dengue virus (DENV), the most important human arbovirus pathogen, as a model, we have, by computer design and chemical synthesis, undone this balance in codon pair bias in favor of insects. Recoded DENVs grow well in insect cells but are highly attenuated in mammalian cells and in suckling mice. This unique approach offers a previously unidentified possibility to rapidly develop new vaccine candidates against DENV and perhaps against many different human arboviruses.