The Two-Tier Fecal Occult Blood Test: Cost-Effective Screening

The two-tier test represents a strategy combining HO Sensa and Hemeselect fecal occult blood tests (FOBTs) with the aim of greater specificity and consequent economic advantages. If patients register a positive result on any HO Sensa guaiac test, they are once again tested by a hemoglobin-specific Hemeselect test. This concept was applied to a multicentre study involving persons 40 years or older. One component of the study enrolled 573 high risk patients while the second arm recruited an additional 1301 patients (52% asymptomatic/48% symptomatic) stratified according to personal history and symptoms. The two-tier test produced fewer false positives than traditional tests in both groups evaluated in the study. In the high risk group, specificity (88.7% for two-tier versus 80.6% for Hemoccult and 69.5% for HO Sensa) was higher and false positive rates were lower (11.3% for two-tier versus 19.5% for Hemoccultand 30.5% for HO Sensa) for the two-tier test versus Hemoccult and HO Sensa FOBTs (95% CI for all colorectal cancers [CRCs] and polyps greater than 1 cm, α=0.05 ). No significant differences in sensitivity were observed between tests in the same group. Also, in the high risk group, benefits of the two-tier test outweighed the costs. Due to the small number of cancers and polyps in the second arm of the study, presentation of data is meant to be descriptive and representative of trends in a ‘normal’ population. Nevertheless, specificity of the two-tier test was higher (96.8% for two-tier versus 87.2% for Hemoccult and 69.5% for HO Sensa) and false positive rate lower (3.2% for two-tier versus 12.8% for Hemoccult and 22.3% for HO Sensa) than either the Hemoccult or HO Sensa FOBT (95% CI for all CRCs and polyps greater than 1 cm). This initial study, focusing on the cost-benefit relationship of increased specificity, represents a new way of economically evaluating existing FOBTs

Modular and predictable assembly of porous organic molecular crystals

Nanoporous molecular frameworks are important in applications such as separation, storage and catalysis. Empirical rules exist for their assembly but it is still challenging to place and segregate functionality in three-dimensional porous solids in a predictable way. Indeed, recent studies of mixed crystalline frameworks suggest a preference for the statistical distribution of functionalities throughout the pores rather than, for example, the functional group localization found in the reactive sites of enzymes. This is a potential limitation for 'one-pot' chemical syntheses of porous frameworks from simple starting materials. An alternative strategy is to prepare porous solids from synthetically preorganized molecular pores. In principle, functional organic pore modules could be covalently prefabricated and then assembled to produce materials with specific properties. However, this vision of mix-and-match assembly is far from being realized, not least because of the challenge in reliably predicting three-dimensional structures for molecular crystals, which lack the strong directional bonding found in networks. Here we show that highly porous crystalline solids can be produced by mixing different organic cage modules that self-assemble by means of chiral recognition. The structures of the resulting materials can be predicted computationally, allowing in silico materials design strategies. The constituent pore modules are synthesized in high yields on gram scales in a one-step reaction. Assembly of the porous co-crystals is as simple as combining the modules in solution and removing the solvent. In some cases, the chiral recognition between modules can be exploited to produce porous organic nanoparticles. We show that the method is valid for four different cage modules and can in principle be generalized in a computationally predictable manner based on a lock-and-key assembly between modules

Noiseonomics: The relationship between ambient noise levels in the sea and global economic trends

In recent years, the topic of noise in the sea and its effects on marine mammals has attracted considerable attention from both the scientific community and the general public. Since marine mammals rely heavily on acoustics as a primary means of communicating, navigating, and foraging in the ocean, any change in their acoustic environment may have an impact on their behavior. Specifically, a growing body of literature suggests that low-frequency, ambient noise levels in the open ocean increased approximately 3.3 dB per decade during the period 1950–2007. Here we show that this increase can be attributed primarily to commercial shipping activity, which in turn, can be linked to global economic growth. As a corollary, we conclude that ambient noise levels can be directly related to global economic conditions. We provide experimental evidence supporting this theory and discuss its implications for predicting future noise levels based on global economic trends

Kinetic Characterisation of a Single Chain Antibody against the Hormone Abscisic Acid: Comparison with Its Parental Monoclonal

A single-chain Fv fragment antibody (scFv) specific for the plant hormone abscisic acid (ABA) has been expressed in the bacterium Escherichia coli as a fusion protein. The kinetics of ABA binding have been measured using surface plasmon resonance spectrometry (BIAcore 2000) using surface and solution assays. Care was taken to calculate the concentration of active protein in each sample using initial rate measurements under conditions of partial mass transport limitation. The fusion product, parental monoclonal antibody and the free scFv all have low nanomolar affinity constants, but there is a lower dissociation rate constant for the parental monoclonal resulting in a three-fold greater affinity. Analogue specificity was tested and structure-activity binding preferences measured. The biologically-active (+)-ABA enantiomer is recognised with an affinity three orders of magnitude higher than the inactive (-)-ABA. Metabolites of ABA including phaseic acid, dihydrophaseic acid and deoxy-ABA have affinities over 100-fold lower than that for (+)-ABA. These properties of the scFv make it suitable as a sensor domain in bioreporters specific for the naturally occurring form of ABA

Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema

Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. © 2013 D'Armiento et al

Intradialytic versus home based exercise training in hemodialysis patients: a randomised controlled trial

Background: Exercise training in hemodialysis patients improves fitness, physical function, quality of life and markers of cardiovascular disease such as arterial stiffness. The majority of trials investigating this area have used supervised exercise training during dialysis (intradialytic), which may not be feasible for some renal units. The aim of this trial is to compare the effects of supervised intradialytic with unsupervised home-based exercise training on physical function and arterial stiffness

Acoustic scattering from a one-dimensional array; Tail-end asymptotics for efficient evaluation of the quasi-periodic Green's function

© 2019 The Authors Motivated by the problem of acoustic plane wave scattering from an infinite periodic array of cylindrical scatterers, we present a new and easily-implemented way of calculating the quasi-periodic Green's function. This approach is based on an asymptotic expansion of the summand in the quasi-periodic Green's function in order to derive a tail-end correction term, allowing for a rapid and accurate approximation of the function. The tail-end approximation is shown to have much better and faster convergence properties than the usual truncation approach and competes very well with state-of-the-art alternative techniques. This method is then combined with a boundary element scheme to calculate the transmission and reflection coefficients associated with arrays of cylinders of different cross-sections and varying aspect ratios. The results are validated against the existing literature and by independent finite element calculations.EPSRC grant EP/R014604/

The flavor puzzle in multi-Higgs models

We reconsider the flavor problem in the models with two Higgs doublets. By studying two generation toy models, we look for flavor basis independent constraints on Yukawa couplings that will give us the mass hierarchy while keeping all Yukawa couplings of the same order. We then generalize our findings to the full three generation Standard Model. We find that we need two constraints on the Yukawa couplings to generate the observed mass hierarchy, and a slight tuning of Yukawa couplings of order 10%, much less than the Standard Model. We briefly study how these constraints can be realized, and show how flavor changing currents are under control for $K-\bar{K}$ mixing in the near-decoupling limit.Comment: 26 pages, typos are corrected, references are added, the final versio