Mathematics achievement gaps between suburban students and their rural and urban peers increase over time

In this brief, authors Suzanne Graham and Lauren Provost examine whether attending a school in a rural, urban, or suburban community is related to children’s mathematics achievement in kindergarten, and whether increases in mathematics achievement between kindergarten and eighth grade differ for children in rural, urban, and suburban schools. They also consider whether achievement differs by region of the country and for children of different racial and ethnic groups. Finally, they discuss the impact of a family’s socioeconomic status, and the ways in which place and socioeconomic status together affect both early mathematics achievement levels and change over time. They report that rural and urban kindergarten students have slightly lower average mathematics achievement levels than their suburban peers. In addition, the average increase in mathematics achievement from kindergarten to eighth grade for rural and urban children is smaller than the increase for suburban children, resulting in a widening achievement gap over time

Bioanalytical measurements enabled by surface-enhanced Raman scattering (SERS) probes

Since its discovery in 1974, surface-enhanced Raman scattering (SERS) has gained momentum as an important tool in analytical chemistry. SERS is used widely for analysis of biological samples, ranging from in vitro cell culture models, ex vivo tissue and blood samples, and direct in vivo application. New insights have been gained into biochemistry, with an emphasis on biomolecule detection, from small molecules such as glucose and amino acids to larger biomolecules such as DNA, proteins, and lipids. These measurements have increased our understanding of biological systems, and significantly, they have improved diagnostic capabilities. SERS probes display unique advantages in their detection sensitivity and multiplexing capability. We highlight key considerations that are required when performing bioanalytical SERS measurements, including sample preparation, probe selection, instrumental configuration, and data analysis. Some of the key bioanalytical measurements enabled by SERS probes with application to in vitro, ex vivo, and in vivo biological environments are discussed

A Comparative Analysis of Martin Luther\u27s Works

In this study we sought to analyze the inclusion of themes from Martin Luther\u27s 95 Theses (1517) in his later writings and the possible development of such themes. We sought to analyze selected works by Luther in order to answer the following question: Of the themes of the 95 Theses, which remain unchanged, which change, and which disappear in his later writings? After translating and analyzing the 95 Theses as a group, we discussed and agreed upon six themes: purgatory, the pope and the clergy, canonical law, indulgences, the gospel and salvation, and repentance. We then individually compared these themes to selected works of Luther’s writings (or his hymns in general). Due to the different natures and purposes of each work, we found varying results. Ultimately, we concluded that the 95 Theses neither summarizes nor predicts Luther’s theology. Luther in fact continues to develop his theology over time and tailors his content for the particular audiences for which he writes

Through tissue imaging of a live breast cancer tumour model using handheld surface enhanced spatially offset Resonance Raman Spectroscopy

In order to improve patient survival and reduce the amount of unnecessary and traumatic biopsies, non-invasive detection of cancerous tumours is of imperative and urgent need. Multicellular tumour spheroids (MTS) can be used as an ex vivo cancer tumour model, to model in vivo nanoparticle (NP) uptake by the enhanced permeability and retention (EPR) effect. Surface enhanced spatially offset Raman spectroscopy (SESORS) combines both surface enhanced Raman spectroscopy (SERS) and spatially offset Raman spectroscopy (SORS) to yield enhanced Raman signals at much greater sub-surface levels. By utilizing a reporter that has an electronic transition in resonance with the laser frequency, surface enhanced resonance Raman scattering (SERRS) yields even greater enhancement in Raman signal. Using a handheld SORS spectrometer with back scattering optics, we demonstrate the detection of live breast cancer 3D multicellular tumour spheroids (MTS) containing SERRS active NPs through 15 mm of porcine tissue. False color 2D heat intensity maps were used to determine tumour model location. In addition, we demonstrate the tracking of SERRS-active NPs through porcine tissue to depths of up to 25 mm. This unprecedented performance is due to the use of red-shifted chalcogenpyrylium-based Raman reporters to demonstrate the novel technique of surface enhanced spatially offset resonance Raman spectroscopy (SESORRS) for the first time. Our results demonstrate a significant step forward in the ability to detect vibrational fingerprints from a tumour model at depth through tissue. Such an approach offers significant promise for the translation of NPs into clinical applications for non-invasive disease diagnostics based on this new chemical principle of measurement

Surface-enhanced Raman spectroscopy for in vivo biosensing

Surface-enhanced Raman scattering (SERS) is of interest for biomedical analysis and imaging because of its sensitivity, specificity and multiplexing capabilities. The successful application of SERS for in vivo biosensing requires probes to be biocompatible and procedures to be minimally invasive, challenges that have respectively been met by developing new nanoprobes and instrumentation. This Review presents recent developments in these areas, describing case studies in which sensors have been implemented, as well as outlining shortcomings that must be addressed before SERS sees clinical use

Ratiometric analysis using Raman spectroscopy as a powerful predictor of structural properties of fatty acids

Raman spectroscopy has been used extensively for analysis of biological samples in vitro, ex vivo and in vivo. While important progress has been made towards using this analytical technique in clinical applications, there is a limit to how much chemically specific information can be extracted from a spectrum of a biological sample, which consists of multiple overlapping peaks from a large number of species in any particular sample. In an attempt to elucidate more specific information regarding individual biochemical species, as opposed to very broad assignments by species class, we propose a bottom up approach beginning with detailed analysis of pure biochemical components. Here we demonstrate a simple ratiometric approach applied to fatty acids, a subsection of the lipid class, to allow the key structural features, in particular degree of saturation and chain length, to be predicted. This is proposed as a starting point for allowing more chemically and species specific information to be elucidated from the highly multiplexed spectrum of multiple overlapping signals found in a real biological sample. The power of simple ratiometric analysis is also demonstrated by comparing the prediction of degree of unsaturation in food oil samples using ratiometric and multivariate analysis techniques which could be used for food oil authentication

Cis-interactions between Notch and Delta generate mutually exclusive signalling states

The Notch–Delta signalling pathway allows communication between neighbouring cells during development^1. It has a critical role in the formation of ‘fine-grained’ patterns, generating distinct cell fates among groups of initially equivalent neighbouring cells and sharply delineating neighbouring regions in developing tissues. The Delta ligand has been shown to have two activities: it transactivates Notch in neighbouring cells and cis-inhibits Notch in its own cell. However, it remains unclear how Notch integrates these two activities and how the resulting system facilitates pattern formation. Here we report the development of a quantitative time-lapse microscopy platform for analysing Notch–Delta signalling dynamics in individual mammalian cells, with the aim of addressing these issues. By controlling both cis- and trans-Delta concentrations, and monitoring the dynamics of a Notch reporter, we measured the combined cis–trans input–output relationship in the Notch–Delta system. The data revealed a striking difference between the responses of Notch to trans- and cis-Delta: whereas the response to trans-Delta is graded, the response to cis-Delta is sharp and occurs at a fixed threshold, independent of trans-Delta. We developed a simple mathematical model that shows how these behaviours emerge from the mutual inactivation of Notch and Delta proteins in the same cell. This interaction generates an ultrasensitive switch between mutually exclusive sending (high Delta/low Notch) and receiving (high Notch/low Delta) signalling states. At the multicellular level, this switch can amplify small differences between neighbouring cells even without transcription-mediated feedback. This Notch–Delta signalling switch facilitates the formation of sharp boundaries and lateral-inhibition patterns in models of development, and provides insight into previously unexplained mutant behaviours

A new class of ratiometric small molecule intracellular pH sensors for Raman microscopy

Intracellular pH (pHi) homeostasis is intertwined with a myriad of normal cellular behaviors as well as pathological processes. As such, small molecule probes for the measurement of pHi are invaluable tools for chemical biology, facilitating the study of the role of pH in cellular function and disease. The field of small molecule pHi sensors has traditionally been dominated with probes based on fluorescent scaffolds. In this study, a series of low molecular weight (<260) oligoyne compounds have been developed which exhibit pH sensitive alkyne stretching frequencies (νalkyne) in Raman spectroscopy. The modular design of the compounds enabled tuneability of their pKa(H) through simple structural modification, such that continuous pH sensitivity is achieved over the range 2-10. Alkyne stretching bands reside in the 'cell-silent' region of the Raman spectrum (1800-2600 cm-1) and are readily detectable in a cellular environment with subcellular spatial resolution. This enabled the application of a pH sensitive oligoyne compound to the ratiometric sensing of pHi in prostate cancer (PC3) cells in response to drug treatment. We propose that probes based on Alkyne Tag Raman Imaging offer an entirely new platform for the sensing of pHi, complementary to fluorescence microscopy

Extravascular fibrinogen in the white matter of Alzheimer's disease and normal aged brains : implications for fibrinogen as a biomarker for Alzheimer's disease

The research was supported by the Alzheimer’s Society (grant numbers AS-PG-2013-011 and AS-JF-18-01). Tissue for this study was provided by the Newcastle Brain Tissue Resource, which is funded in part by a grant from the UK Medical Research Council (G0400074) and by Brains for Dementia research, a joint venture between Alzheimer’s Society and Alzheimer’s Research UK.The blood‐brain barrier (BBB) regulates cerebrovascular permeability and leakage of blood‐derived fibrinogen has been associated with cerebral arteriolosclerosis small vessel disease (SVD) and subsequent white matter lesions (WML). Furthermore, BBB‐dysfunction is associated with the pathogenesis of Alzheimer's disease (AD) with the presence of CSF plasma proteins suggested to be a potential biomarker of AD. We aimed to determine if extravascular fibrinogen in the white matter was associated with the development of AD hallmark pathologies, i.e., hyperphosphorylated tau (HPτ) and amyloid‐β (Aβ), SVD, cerebral amyloid angiopathy (CAA) and measures of white matter damage. Using human post‐mortem brains, parietal tissue from 20 AD and 22 non‐demented controls was quantitatively assessed for HPτ, Aβ, white matter damage severity, axonal density, demyelination and the burden of extravascular fibrinogen in both WML and normal appearing white matter (NAWM). SVD severity was determined by calculating sclerotic indices. WML‐ and NAWM fibrinogen burden was not significantly different between AD and controls nor was it associated with the burden of HPτ or Aβ pathology, or any measures of white matter damage. Increasing severity of SVD was associated with and a predictor (both p < 0.05) of both higher WML‐ and NAWM fibrinogen burden (both P<0.05) in controls only. In cases with minimal SVD NAWM fibrinogen burden was significantly higher in the AD cases (p<0.05). BBB dysfunction was present in both non‐demented and AD brains and was not associated with the burden of AD‐associated cortical pathologies. BBB dysfunction was strongly associated with SVD but only in the non‐demented controls. In cases with minimal SVD, BBB dysfunction was significantly worse in AD cases possibly indicating the influence of CAA. In conclusions, extravascular fibrinogen is not associated with AD hallmark pathologies but indicates SVD, suggesting that the presence of fibrinogen in the CSF is not a surrogate marker for AD pathology.PostprintPeer reviewe

Through barrier detection of ethanol using handheld Raman spectroscopy — Conventional Raman versus spatially offset Raman spectroscopy (SORS)

Spatially offset Raman spectroscopy (SORS) provides chemical analysis at depth even when obscuring barriers such as plastic or tissue are present. As the collection probe is moved further away from the point of laser excitation, scattered photons from deeper layers begin to dominate the acquired spectra, thus giving rise to through barrier detection. Here, we demonstrate the potential of conventional Raman (CR) and SORS for through barrier detection using handheld spectrometers. We report the collection of Raman signals from an ethanol solution through plastic at thicknesses of up to 21 mm using SORS in combination with multivariate analysis. SORS is compared to CR, where we also demonstrate impressive through barrier detection of ethanol at depths up to 9 mm. We also highlight the advantage of applying multivariate analysis for through barrier detection using CR or SORS, particularly when peaks with similar spectral features are present in both the barrier and analyte spectra. In addition, to the best of our knowledge, this is the first report of the assessment of the maximum level of through barrier detection using handheld CR and SORS instruments with a backscattering geometry