Do High Flyers Maintain Their Altitude? Performance Trends of Top Students

"Do High Flyers Maintain Their Altitude? Performance Trends of Top Students," is the first study to examine the performance of America's highest-achieving children over time at the individual-student level. Produced in partnership with the Northwest Evaluation Association, it finds that many high-achieving students struggle to maintain their elite performance over the years and often fail to improve their reading ability at the same rate as their average and below-average classmates. The study raises troubling questions: Is our obsession with closing achievement gaps and "leaving no child behind" coming at the expense of our "talented tenth" -- and America's future international competitiveness

T-cell libraries allow simple parallel generation of multiple peptide-specific human T-cell clones

Isolation of peptide-specific T-cell clones is highly desirable for determining the role of T-cells in human disease, as well as for the development of therapies and diagnostics. However, generation of monoclonal T-cells with the required specificity is challenging and time-consuming. Here we describe a library-based strategy for the simple parallel detection and isolation of multiple peptide-specific human T-cell clones from CD8+ or CD4+ polyclonal T-cell populations. T-cells were first amplified by CD3/CD28 microbeads in a 96U-well library format, prior to screening for desired peptide recognition. T-cells from peptide-reactive wells were then subjected to cytokine-mediated enrichment followed by single-cell cloning, with the entire process from sample to validated clone taking as little as 6 weeks. Overall, T-cell libraries represent an efficient and relatively rapid tool for the generation of peptide-specific T-cell clones, with applications shown here in infectious disease (Epstein–Barr virus, influenza A, and Ebola virus), autoimmunity (type 1 diabetes) and cancer

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease:results from the IMmunogenicity to Second Anti-TNF therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF Therapy (IMSAT) therapeutic drug monitoring study

BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD).AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Developing proxies in secondary carbonates with application to ENSO variability and basin-wide paleo-hydrology

This thesis develops new, and expands existing, methods of reconstructing paleoclimate from geochemical proxies hosted in secondary carbonate precipitates. This is done by: i) Developing a new multi-proxy approach for using lacustrine cave carbonates (LCCs) to reconstruct past shifts in precipitation-evaporation (P-E) over lake drainage basins, and ii) Investigating the suitability of speleothems as paleo-ENSO archives. Chapters 2 and 3 use modelled and measured values from LCC samples to generate a framework for understanding how Mg/Ca, U/Ca and δ44/42Ca in LCCs can be used as a combined multi-proxy approach to reconstruct past shifts in P-E. This multi-proxy approach is subsequently used to generate a novel reconstruction of P-E over the Bonneville Basin (a terminal basin in the Great Basin region of the southwestern United States), during Heinrich Stadial 1. Results suggest that moisture supply to the Great Basin region was impacted by a southwards shift of the ITCZ and variations in the elevation of North American ice sheets during Heinrich Stadial 1. Chapter 4 investigates the suitability of applying speleothem BA03 as a paleo-ENSO archive. Firstly, the impacts of age model and δ18O uncertainties on speleothem ENSO variability reconstructions are quantified. A total of eight high resolution (> 2 samples per year) δ18O time-series are then used to reconstruct shifts in ENSO variability over the Holocene. This new ENSO variability reconstruction suggests a reduction in ENSO variability during the mid-Holocene (5.68 kyr BP – 3.78 kyr BP), the termination of which coincides with the end of the so called “4.2 Kyr Event”. This thesis advances the paleoclimate application of numerous geochemical proxies, expanding the use of precisely dated, high-resolution secondary carbonate archives

Hubungan Media Yang Efektif

Bagi banyak praktisi public relation (humas), sebagian besar waktu mereka digunakan untuk membina hubungan dengan media. Buku ini bertujuan untuk menginformasikan pada para praktisi humas tentang aspek-aspek perkembangan media yang mempengaruhi pekerjan mereka saat ini, dengan memberikan pedoman praktis tentang bgaimana bekerja dengan media dengan sukses. Para pakar yang menulis buku ini memberikan pengetahuan dan pedoman praktis untuk orang-orang yang ingin bekerja dengan media secara efektif. Bagian pertama mengulas tentang konteks media. Pengetahuan tentang sejarah media dan pengetahuan tentang bentuk tanggapan yang akan diperoleh atas publikasi yang dilakukan sangatlah penting. Bagian selanjutnya mengulas tentang pers cetak. Dan bagian akhir buku ini mengulas tentang hal-hal yang ada di balik layar dalam wawancara di radio dan televisi. Selain itu diberikan juga pedoman yang mudah untuk diikuti tentang bagaimana memperoleh hasil yang lebih baik dari suatu wawancara, sambil memberikan apa yang diinginkan oleh para wartawan.xvi, 142 hal : 24 c

Effective Media Relations: How to Get Results -3/E.

The power of the media is unquestionable-the impact it can have on public opinion and decision making is unique-and knowing how to use it effectively I an essential skill for all public relations professionals give clear, practical guidance on how to work journalist to get the best possible media coverage. In part 1, Alison theaker looks at the media context and provides an overview of the law, ownership, ethics, newm information on the growing importance of e-mail and internet use. In part 2, david wragg looks at the opportunities that are available in the traditional press and gives practical advice on how to wrk with them. There is also new information on the growing importance of e-mail and internet use

Prediction of ring-bore conformance and contact condition and experimental validation

One of the key conjunctions in the IC engine is that made by the top compression ring to the cylinder liner. Although the compression ring has seen considerable improvements since its introduction into steam engines by John Ramsbottom in the 1850s, its multiple and often contradictory functions still remain a challenge today. The primary aim has always been to seal the combustion chamber and guard against leakage of combustion gasses. The ring is also required to conduct some of the generated heat away. These requirements call for good ring-bore conformance, but often at the expense of increased friction. A simplified inter-ring gas flow model, as well as the measured chamber pressure using a Kistler pressure transducer is carried out under motored conditions to obtain the net gas pressure acting behind the ring. This and the elastic pressure as the result of ring restoring tension force in fitment constitute the contact load, which is usually carried by a mixed-hydrodynamic regime of lubrication. The conjunction pressures are treated as a combination of hydrodynamic generated pressures and asperity-pair interactions. The former is obtained by solution of two dimensional Reynolds equation, whilst the latter is determined assuming a Gaussian distribution of asperities on the counterfaces. Surface topography of the bounding solids; the compression ring and the liner are measured and used as appropriate statistical functions in the Greenwood and Tripp model. Using an analytical flow model, pressure acting behind the ring (on the inner periphery of the ring) is obtained, leading to the calculation of ring-bore friction. A floating liner is used to measure friction of piston and ringpack in situ. The characteristic of the predicted variations are compared with the measured data. However, a quantitative comparison is not possible as the measured data corresponds to all the conjunctions of piston system, including the oil control rings as well as the piston skirt. The results show that variation of gas force behind the ring significantly changes the ring-bore contact, thus friction and the nature of interactions