Background: Nipocalimab is a human IgG1 monoclonal antibody targeting FcRn that selectively reduces IgG levels without impacting antigen presentation, T- and B-cell functions. This study describes the effect of nipocalimab on vaccine response. Methods: Open-label, parallel, interventional study randomized participants 1:1 to receive intravenous 30mg/kg nipocalimab at Week0 and 15mg/kg at Week2 and Week4 (active) or no drug (control). On Day 3, participants received Tdap and PPSV®23 vaccinations and were followed through Wk16. Results: Twenty-nine participants completed the study and are included (active, n=15; control, n=14). Participants with a positive anti-tetanus IgG response was comparable between groups at Wk2 and Wk16, but lower at Wk4 (nipocalimab 3/15 [20%] vs control 7/14 [50%]; P=0.089). All maintained anti-tetanus IgG above the protective threshold (0.16IU/mL) through Wk16. While anti-pneumococcal-capsular-polysaccharide (PCP) IgG levels were lower during nipocalimab treatment, the percent increase from baseline at Wk2 and Wk16 was comparable between groups. Post-vaccination, anti-PCP IgG remained above 50mg/L and showed a 2-fold increase from baseline throughout the study in both groups. Nipocalimab co-administration with vaccines was safe and well-tolerated. Conclusions: These findings suggest that nipocalimab does not impact the development of an adequate IgG response to T-cell–dependent/independent vaccines and that nipocalimab-treated patients can follow recommended vaccination schedules.

This study quantifies the effect of fertilizer and irrigation management on water use efficiency (WUE), crop growth and crop yield in sub-humid to semi-arid conditions of Limpopo Province, South Africa. An approach of coupling a cropping system model (DSSAT) with an agro-hydrological model (SWAT) was developed and applied to simulate crop yield at the field and catchment scale. Simulation results indicated that the application of fertilizer has a greater positive effect on maize yield than irrigation. WUE ranged from 0.10–0.57 kg/m3 (rainfed) to 0.84–1.39 kg/m3 (irrigated) and was positively correlated with fertilizer application rate. The combined application of the variants with deficit irrigation and fertilizer rate (120:60 kg N:P/ha) for maize turned out to be the best option, giving the highest WUE and increasing average yield by up to 5.7 t/ha compared to no fertilization and rainfed cultivation (1.3 t/ha). The simulated results at the catchment scale showed the considerable spatial variability of maize yield across agricultural fields with different soils, slopes and climate conditions. The average annual simulated maize yield across the catchment corresponding to the highest WUE ranged from 4.0 to 7.0 t/ha. The yield gaps ranged from 3.0 to 6.0 t/ha under deficit irrigation combined with 120N:60P kg/ha and ranged from 0.2 to 1.5 t/ha when only applying deficit irrigation but no fertilizer. This information can support regional decision makers to find appropriate interventions that aim at improving crop yield and WUE for catchments/regions.

BACKGROUND: Meningiomas are the most common primary benign brain tumors in adults. Given the extended life expectancy of most meningiomas, consideration of quality of life (QOL) is important when selecting the optimal management strategy. There is currently a dearth of meningioma-specific QOL tools in the literature. OBJECTIVE: In this systematic review, we analyze the prevailing themes and propose toward building a meningioma-specific QOL assessment tool. METHODS: A systematic search was conducted, and only original studies based on adult patients were considered. QOL tools used in the various studies were analyzed for identification of prevailing themes in the qualitative analysis. The quality of the studies was also assessed. RESULTS: Sixteen articles met all inclusion criteria. Fifteen different QOL assessment tools assessed social and physical functioning, psychological, and emotional well-being. Patient perceptions and support networks had a major impact on QOL scores. Surgery negatively affected social functioning in younger patients, while radiation therapy had a variable impact. Any intervention appeared to have a greater negative impact on physical functioning compared to observation. CONCLUSION: Younger patients with meningiomas appear to be more vulnerable within social and physical functioning domains. All of these findings must be interpreted with great caution due to great clinical heterogeneity, limited generalizability, and risk of bias. For meningioma patients, the ideal QOL questionnaire would present outcomes that can be easily measured, presented, and compared across studies. Existing scales can be the foundation upon which a comprehensive, standard, and simple meningioma-specific survey can be prospectively developed and validated.

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.

Following the B777 accident at Heathrow in 2008, the certification authorities required Boeing, Airbus, and Rolls-Royce to conduct icing analysis and tests of their Rolls-Royce Trent engined aircraft fuel systems. The experience and the test data gained from these activities were distilled and released by Airbus to the EASA ICAR project for research and analysis. This paper provided an overview of the Airbus ice accretion and release tests. Brief narratives on the test rigs, the test procedure and methodology were given and key findings from the ice release investigations were presented. The accreted ice thickness was non-uniform; however, it is found typically c. $\mathrm{2\;\mathrm{m}\mathrm{m}}$ thick. Analysis of the accreted ice collected from the rig tests showed the ice was very porous. The porosity is very much dependant on how the water was introduced and mixed in the icing test rigs. The standard Airbus method produced accreted ice of higher porosity compared to that produced by the injection method. The porosity of the accreted ice from Airbus icing investigations was found to be c. 0.90. The relationship of permeability with porosity was inferred from published data and models for freshly fallen snow in the atmosphere. Derived permeability $\mathrm{7.0\times 10^{-9}\;\mathrm{\mathrm{\mathrm{m}}^{\mathrm{2}}}}$ was then applied in the CFD analysis of pipe flow with a porous wall lining to determine the shear stress on the accreted ice. It showed that 25%, 50% and 75% of the accreted ice has interface shear strength of less than $\mathrm{15.3\;\mathrm{Pa}}$, $\mathrm{20.7\;\mathrm{Pa}}$ and $\mathrm{26.1\;\mathrm{Pa}}$, respectively.

OBJECTIVES/SPECIFIC AIMS: Obstructive lung disease following particulate matter (PM) exposure is a major health concern. Coexisting metabolic syndrome (MetSyn) often occurs. Receptor for advanced glycation end products (RAGE) is highly expressed in the lung, is a strong predictor of FEV1, and is a key mediator of MetSyn. To determine if the loss of RAGE protects from the persistence of effects of particulate associated lung injury in a murine model. METHODS/STUDY POPULATION: Wild type (WT) and RAGE knockout (RKO) mice were exposed to 100 μg of PM (WTC-Aggregate, PM53) or PBS control by oropharyngeal aspiration. Lung function, methacholine challenge, and bronchoalveolar lavage (BAL) were quantified 28 days after PM exposure using flexiVent (Scireq Montreal, QC). BAL was obtained and cell differentials, cytokines and transcription factors were assayed. Bio-volume to airspace ratio and mean chord length were measured (Image J and Adobe Photoshop). RESULTS/ANTICIPATED RESULTS: WT mice were hyper-reactive to methacholine compared with their PBS controls 28 days after a single exposure to PM. They recovered from increased neutrophilia, loss of FEV, decreased compliance, and increased resistance, which were previously observed 24-hours after exposure. RKO were not hyper-reactive when compared with their own PBS controls. Lung histology shows persistence of loss of alveolar space in WT mice exposed to PM after 28 days. Area fraction was significantly higher in PM exposed WT mice after 28 days which was not significant after 24 hours. Mean chord length was significantly shorter for PM exposed at both time points for WT mice. The relative expression of phosphorylated to total CREB and ERK1/2 proteins was lower in RKO PM exposed mice compared with WT PM while STAT3 expression was lower in WT PM compared with WT PBS. PM induced a lower fold change of total proteins from the PBS controls in RKO for CREB, p38, ERK1/2, STAT3, and STAT5. JNK and p70S6k total proteins expressed a decreased fold change in WT PM exposed mice compared with WT PBS controls. DISCUSSION/SIGNIFICANCE OF IMPACT: A single dose of PM can produce persistent airway hyper-reactivity after 28 days of exposure. This PM induced injury is alleviated in the absence of RAGE, similar to what was seen at 24 hours. Inhibiting RAGE may be key to limiting the persistent inflammatory effects of high intensity PM exposure.

The increasing tropospheric ozone concentration [O3] strongly affects plant growth. However, the response of belowground processes in rice (Oryza sativa L.) systems to higher O3 is not well understood. The grain production, belowground biomass partitioning, root morphology and activity of rice (cv. Shanyou 63) were investigated in a free-air O3 enrichment platform at four key growth stages. Elevated O3 (EO3, 50% above the ambient O3) significantly decreased the grain yield and total biomass at the grain milky mature stage, root biomass at the tillering stage and root to shoot ratios (RRS) at the flowering and grain filling stages. The effects of EO3 on root morphology and activity varied among rice growth stage. EO3 significantly decreased root length, density, area, diameter and volume at the flowering stage, but EO3 significantly decreased various root morphological indices at the tillering, grain filling and milky mature stages. EO3 significantly increased the specific root respiration rate (root activity) and root respiration rate (autotrophic respiration) at grain filling and milky mature stages. Higher root autotrophic respiration and lower RRS in response to EO3 would reduce allocation of assimilated carbon to root growth, adversely affecting rice productivity. Our findings are critical for understanding the O3-induced impairment of belowground processes and carbon cycling in rice cropping systems and breeding of O3-tolerant cultivars under higher [O3] scenarios.

In Hong Kong, universal varicella vaccination started in July 2014. Before this, children could receive varicella vaccine via the private market. We analysed the epidemiology of varicella and zoster before universal vaccination. We estimated varicella vaccination coverage through surveys in preschool children. We estimated the burden of varicella and zoster with varicella notifications from 1999/00 to 2013/14, Accident and Emergency Department (A&E) attendance and inpatient admissions to public hospitals from 2004/05 to 2013/14. We fitted a catalytic model to serological data on antibodies against varicella-zoster virus to estimate the force of infection. We found that varicella vaccination coverage gradually increased to about 50% before programme inception. In children younger than 5 years, the annual rate of varicella notifications, varicella admission and zoster A&E attendance generally declined. The annual notification, A&E attendance and hospitalisation rate of varicella and zoster generally increased for individuals between 10 and 59 years old. Varicella serology indicated an age shift during the study period towards a higher proportion of infections in slightly older individuals, but the change was most notable before vaccine licensure. In conclusion, we observed a shift in the burden of varicella to slightly older age groups with a corresponding increase in incidence but it cannot necessarily be attributed to private market vaccine coverage alone. Increasing varicella vaccination uptake in the private market might affect varicella transmission and epidemiology, but not to the level of interrupting transmission.

During 1990 we surveyed the southern sky using a multi-beam receiver at frequencies of 4850 and 843 MHz. The half-power beamwidths were 4 and 25 arcmin respectively. The finished surveys cover the declination range between +10 and −90 degrees declination, essentially complete in right ascension, an area of 7.30 steradians. Preliminary analysis of the 4850 MHz data indicates that we will achieve a five sigma flux density limit of about 30 mJy. We estimate that we will find between 80 000 and 90 000 new sources above this limit. This is a revised version of the paper presented at the Regional Meeting by the first four authors; the surveys now have been completed.

Sudden release of accreted ice in fuel systems could pose a serious challenge in aircraft operation. The resultant snowshower may reach the filter and fuel-oil heat exchanger, causing a restriction in fuel flow to the engine. It is fundamental to have an appreciation of the character and the interface shear strength of the accreted ice in aircraft fuel systems. This helps to recognise factors for the sudden release of the accreted ice and the intensity of the consequential snowshower. An experimental study was carried out to quantify the character and the interface shear strength of accreted ice on subcooled surfaces submerged in jet fuel. Ice was accreted on naked aluminium, painted aluminium and carbon fibre composite surfaces at various subcooled temperatures. The accreted ice was akin to fresh snow and exhibited soft and fluffy attributes. The character may be expressed quantitatively in terms of the porosity and was found to be c. 0·95. The ice weakly adhered to the substrate surfaces, and the interface shear strength was found to be c. 0·36Pa and c. 2·19Pa at the top surface and at the vertical surface of a specimen block, respectively. It was not possible to detect any variation in the porosity and the interface shear strength for different types of surface finishes and differences in water affnity in fuels due to the crude approach in the estimation of these parameters.

In traditional transit timing variations (TTVs) analysis of multi-planetary systems, the individual TTVs are first derived from transit fitting and later modelled using n-body dynamic simulations to constrain planetary masses. We show that fitting simultaneously the transit light curves with the system dynamics (photo-dynamical model) increases the precision of the TTV measurements and helps constrain the system architecture. We exemplify the advantages of applying this photo-dynamical model to a multi-planetary system found in K2 data very close to 3:2 mean motion resonance, K2-19. In this case the period of the larger TTV variations (libration period) is much longer (>1.5 years) than the duration of the K2 observations (80 days). However, our method allows to detect the short period TTVs produced by the orbital conjunctions between the planets that in turn permits to uniquely characterise the system. Therefore, our method can be used to constrain the masses of near-resonant systems even when the full libration curve is not observed.