Repurposing rapid diagnostic tests to detect falsified vaccines in supply chains.

Substandard (including degraded) and falsified (SF) vaccines are a relatively neglected issue with serious global implications for public health. This has been highlighted during the rapid and widespread rollout of COVID-19 vaccines. There has been increasing interest in devices to screen for SF non-vaccine medicines including tablets and capsules to empower inspectors and standardise surveillance. However, there has been very limited published research focussed on repurposing or developing new devices for screening for SF vaccines. To our knowledge, rapid diagnostic tests (RDTs) have not been used for this purpose but have important potential for detecting falsified vaccines. We performed a proof-in-principle study to investigate their diagnostic accuracy using a diverse range of RDT-vaccine/falsified vaccine surrogate pairs. In an initial assessment, we demonstrated the utility of four RDTs in detecting seven vaccines. Subsequently, the four RDTs were evaluated by three blinded assessors with seven vaccines and four falsified vaccines surrogates. The results provide preliminary data that RDTs could be used by multiple international organisations, national medicines regulators and vaccine manufacturers/distributors to screen for falsified vaccines in supply chains, aligned with the WHO global 'Prevent, Detect and Respond' strategy.

Lessons Learned from a Citywide Abandoned Housing Experiment.

Problem research strategy and findings: The negative impact of vacant and abandoned housing in city neighborhoods is extreme, affecting health and quality of life, promoting violence, and leading to further abandonment. One approach to addressing abandoned housing is to intervene with low-cost interventions that provide a visual sense of ownership. We tested whether a low-cost remediation of abandoned and vacant houses or a trash cleanup intervention would make a noticeable difference in the levels of nearby disrepair, disorder, and public safety. The abandoned housing remediation and trash cleanup interventions were a test of compliance with municipal ordinances. We used an experimental design to test the causal effects of the ordinances, and because the scale of abandonment was too large to provide treatment to all abandoned houses in the city. We used systematic social observation methods to rate changes in disrepair, disorder, and litter at housing sites and on the city blocks they were located, and police reported data on gun violence and illegal substance uses. Our experimental design allowed us to see if observed disrepair, disorder, and public safety improved after working windows and doors were installed on abandoned houses compared with a trash cleanup around properties or a no-intervention control condition. Our results showed significant changes in observed disrepair, disorder, and gun violence and illustrate the benefits of experimental evaluations of place-based changes to the built environment. Takeaway for practice: Improving compliance with ordinances to remediate abandoned housing can make a noticeable difference in disrepair in neighborhoods and contribute improved public safety. We illustrate how planners can use field experiments in partnership with city agencies, nonprofit community groups, and local universities to discover novel approaches to advance place-based changes to the built environment that can help economically disadvantaged communities abate problems of physical disorder.

Innovative method for rapid detection of falsified COVID-19 vaccines through unopened vials using handheld Spatially Offset Raman Spectroscopy (SORS).

Preventing, detecting, and responding to substandard and falsified vaccines is of critical importance for ensuring the safety, efficacy, and public trust in vaccines. This is of heightened importance in context of public health crisis, such as the COVID-19 pandemic, in which extreme world-wide shortages of vaccines provided a fertile ground for exploitation by falsifiers. Here, a proof-of-concept study explored the feasibility of using a handheld Spatially Offset Raman Spectroscopy (SORS) device to authenticate COVID-19 vaccines through rapid analysis of unopened vaccine vials. The results show that SORS can verify the chemical identity of dominant excipients non-invasively through vaccine vial walls. The ability of SORS to identify potentially falsified COVID-19 vaccines was demonstrated by measurement of surrogates for falsified vaccines contained in vaccine vials. In all cases studied, the SORS technique was able to differentiate between surrogate samples from the genuine COVISHIELD™ vaccine. The genuine vaccines tested included samples from six batches across two manufacturing sites to account for any potential variations between batches or manufacturing sites. Batch and manufacturing site variations were insignificant. In conjunction with existing security features, for example on labels and packaging, SORS provided an intrinsic molecular fingerprint of the dominant excipients of the vaccines. The technique could be extended to other COVID-19 and non-COVID-19 vaccines, as well as other liquid medicines. As handheld and portable SORS devices are commercially available and widely used for other purposes, such as airport security, they are rapidly deployable non-invasive screening tools for vaccine authentication.

Detection & identification of hazardous narcotics and new psychoactive substances using Fourier transform infrared spectroscopy (FTIR).

According to the latest World Drug Report, released by the United Nations Office on Drugs and Crime (UNODC), drug use is up 30% over the past decade and there are more drugs, and more types of drugs, than ever. Herein we use Fourier Transform Infrared Spectroscopy (FTIR) for the rapid ID of narcotics in a range of concentrations - from pure forms (as it is likely to be smuggled & transported) to street forms, often mixed with conventional cutting agents. Using FTIR, 75% of "street sample" narcotics were rapidly identified, and the effects of cutting agents on identification (ID) were also investigated. The limit of detection of MDMA was assessed, with a correct ID shown from 25% w/v. Concentration was correlated with Hit Quality Index, showing the capability of FTIR use in concentration estimation.

Attribution of the taxon name Echinoidea to Schumacher, 1817.

The World Register of Marine Species (WoRMS), The Interagency Taxonomic Information System (ITIS, Report Taxonomic Serial No 157821), and Wikispecies all identify Leske (1778) as the author of the taxon Echinoidea. They base this attribution on the synonymy of Durham et al. (1966: U297) who stated Class ECHINOIDEA Leske, 1778 [nom. transl. Bronn, 1860, p. 295 (ex order Echinoidea dOrbigny, 1852 [sic], p. 114, nom correct. pro ordo Echinus Leske, 1778, p. xvi [sic])]. This confusing construction led to a strange result in which the taxon Echinoidea was attributed to an author who never used that name (Leske), whilst it deprived the author who established it (Schumacher) and the one who first conceived the grouping (Bruguire) of any credit. This note examines the works of various authors credited with the authorship of the taxon Echinoidea, particularly Leske, dOrbigny, von Zittel, and Bronn, and concludes that the taxon Echinoidea should be attributed to Schumacher, 1817.

The works on echinoids by Klein and Leske, the confusion concerning the authorship of Klein (1778), and the problem of citation of some species.

The three most important eighteenth century works on echinoids were by Klein (1734, 1778) and Leske (1778). Confusion about the authorship of Kleins 1778 publication has led many subsequent, and most current, workers to attribute both 1778 works to Leske. It is clear that Leske himself recognised Klein as the author of the volume published first. Following the International Code of Zoological Nomenclature (ICZN, 1999), the names for taxa in Klein (1734) are unavailable because they are pre-1758 (as are those in the French translation of 1754); the names in Klein (1778) are unavailable because of the lack of consistency in binominal nomenclature; only the names adopted by Leske (1778) are available for species and genera.

A Semi-quantitative method for the detection of fentanyl using surface-enhanced Raman scattering (SERS) with a handheld Raman instrument.

A handheld, spatially offset Raman spectroscopy (SORS) system was successfully used to obtain Surface-enhanced Raman Scattering (SERS) spectra of fentanyl under simulated field conditions. A series of aqueous fentanyl solutions were prepared with commercially available gold nanoparticle solution, at concentrations ranging from 0.003 to 1697 µM. These SERS spectra were then used to generate two concentration calibration models (via a plot of peak area (1026 cm-1 ) versus concentration, and quantitative spectral decomposition using partial least squares (PLS1)). For both models, the relationship followed Langmuir adsorption and became non-linear at concentrations above ~0.2 µM, with a limit of detection (LOD) of approximately 3 nM. The same technique was successfully used to measure fentanyl in the presence of two common "cutting agents," heroin and glucose, at 1% and 2% fentanyl proportions (w/w). Fentanyl detection was successfully achieved, but mixture interference from the cutting agents prevented a calibration model being generated. Four fentanyl analogues were also investigated-butyrylfentanyl, furanylfentanyl, acetylfentanyl, and ocfentanyl. A concentration calibration model for each species was successfully generated, but differentiation from fentanyl proved more challenging, although several potential diagnostic peaks were identified. These results identified a pathway forward in using handheld equipment for the reliable detection of ultra-low concentrations of fentanyl and fentanyl analogues via SERS, even when mixed with diluents. However, quantitative detection is negatively impacted in the presence of heroin and glucose. This also provides a starting point for a SERS-based spectral library of fentanyl analogues, in combination with a range of different diluents.

Repeatability and accuracy of a foot muscle strength dynamometer.

Toe flexor strength is a pivotal biomechanical contributor for effecting balance and gait. However, there are limited reports that evaluate measurement accuracy and repeatability of this important attribute. Dynamometers are designed to measure force which can be used to derive joint torque if the perpendicular distance to the joint axis is known. However, an accurate and reliable measurement method to assess the ability of the toe flexor muscles to produce torque, is lacking. Here we describe a new device and method, designed to quantify the toe flexor torque developed at the metatarsal phalangeal joint. We evaluate measurement bias and the ability of the instrument to consistently measure what it is supposed to measure (Interclass Correlation Coefficient). Results suggest that our device is an accurate tool for measuring angle and torque with a small (0.10° and 0.07 Nm, respectively) bias. When tested for reliability and repeatability in measuring toe flexor torque (n = 10), our device showed high interclass correlation (ICC = 0.99), small bias (-1.13 Nm) and small repeatability coefficient (CR = 3.9). We suggest mean bias and CR to be reported for future measurement methods and our protocol used as standard approach to measure maximal toe flexor torque.

Correction: Introducing dip pen nanolithography as a tool for controlling stem cell behaviour: unlocking the potential of the next generation of smart materials in regenerative medicine.

Correction for 'Introducing dip pen nanolithography as a tool for controlling stem cell behaviour: unlocking the potential of the next generation of smart materials in regenerative medicine' by Judith M. Curran et al., Lab Chip, 2010, 10, 1662-1670.

Analysis of intracellular enzyme activity by surface enhanced Raman scattering.

Dysfunctional intracellular enzymatic activity is believed to be an underlying cause of a myriad of diseases. We present the first use of surface enhanced Raman scattering (SERS) as a detection technique capable of reporting intracellular activity of a specific enzyme. Careful choice of reagents allowed the preparation of high resolution cellular activity maps highlighting the specific conversion of the commonly used ELISA reagent 5-bromo-4-chloro-3-indolyl ß-D-galactopyranoside (X-Gal), by wild type ß-galactosidase enzymes. Further, through co-addition of X-Gal substrate and inhibitors we were able to demonstrate that intracellular substrate conversion occurred predominantly through an enzymatically specific pathway. The data presented therefore supports the application of SERS probes as sensitive, specific sensors of biochemical activity and demonstrates the use of SERS probes for the first time as beacons capable of high resolution subcellular localisation of native enzymes.

The effect of business improvement districts on the incidence of violent crimes.

OBJECTIVE: To examine whether business improvement districts (BID) contributed to greater than expected declines in the incidence of violent crimes in affected neighbourhoods. METHOD: A Bayesian hierarchical model was used to assess the changes in the incidence of violent crimes between 1994 and 2005 and the implementation of 30 BID in Los Angeles neighbourhoods. RESULTS: The implementation of BID was associated with a 12% reduction in the incidence of robbery (95% posterior probability interval -2 to 24) and an 8% reduction in the total incidence of violent crimes (95% posterior probability interval -5 to 21). The strength of the effect of BID on robbery crimes varied by location. CONCLUSION: These findings indicate that the implementation of BID can reduce the incidence of violent crimes likely to result in injury to individuals. The findings also indicate that the establishment of a BID by itself is not a panacea, and highlight the importance of targeting BID efforts to crime prevention interventions that reduce violence exposure associated with criminal behaviours.

The effect of light rail transit on body mass index and physical activity.

BACKGROUND: The built environment can constrain or facilitate physical activity. Most studies of the health consequences of the built environment face problems of selection bias associated with confounding effects of residential choice and transportation decisions. PURPOSE: To examine the cross-sectional associations between objective and perceived measures of the built environment; BMI; obesity (BMI>30 kg/m(2)); and meeting weekly recommended physical activity (RPA) levels through walking and vigorous exercise. To assess the effect of using light rail transit (LRT) system on BMI, obesity, and weekly RPA levels. METHODS: Data were collected on individuals before (July 2006-February 2007) and after (March 2008-July 2008) completion of an LRT system in Charlotte NC. BMI, obesity, and physical activity levels were calculated for a comparison of these factors pre- and post-LRT construction. A propensity score weighting approach adjusted for differences in baseline characteristics among LRT and non-LRT users. Data were analyzed in 2009. RESULTS: More-positive perceptions of one's neighborhood at baseline were associated with a -0.36 (p<0.05) lower BMI; 15% lower odds (95% CI=0.77, 0.94) of obesity; 9% higher odds (95% CI=0.99, 1.20) of meeting weekly RPA through walking; and 11% higher odds (95% CI=1.01, 1.22) of meeting RPA levels of vigorous exercise. The use of LRT to commute to work was associated with an average -1.18 reduction in BMI (p<0.05) and an 81% reduced odds (95% CI=0.04, 0.92) of becoming obese over time. CONCLUSIONS: The results of this study suggest that improving neighborhood environments and increasing the public's use of LRT systems could provide improvements in health outcomes for millions of individuals.

Introducing dip pen nanolithography as a tool for controlling stem cell behaviour: unlocking the potential of the next generation of smart materials in regenerative medicine.

Reproducible control of stem cell populations, regardless of their original source, is required for the true potential of these cells to be realised as medical therapies, cell biology research tools and in vitro assays. To date there is a lack of consistency in successful output when these cells are used in clinical trials and even simple in vitro experiments, due to cell and material variability. The successful combination of single chemistries in nanoarray format to control stem cell, or any cellular behaviour has not been previously reported. Here we report how homogenously nanopatterned chemically modified surfaces can be used to initiate a directed cellular response, particularly mesenchymal stem cell (MSC) differentiation, in a highly reproducible manner without the need for exogenous biological factors and heavily supplemented cell media. Successful acquisition of these data should lead to the optimisation of cell selective properties of materials, further enhancing the role of nanopatterned substrates in cell biology and regenerative medicine. The successful design and comparison of homogenously molecularly nanopatterned surfaces and their direct effect on human MSC adhesion and differentiation are reported in this paper. Planar gold surfaces were patterned by dip pen nanolithography (DPN) to produce arrays of nanodots with optimised fixed diameter of 70 nanometres separated by defined spacings, ranging from 140 to 1000 nm with terminal functionalities of simple chemistries including carboxyl, amino, methyl and hydroxyl. These nanopatterned surfaces exhibited unprecedented control of initial cell interactions and subsequent control of cell phenotype and offer significant potential for the future.

Dynamic Imaging Analysis of SERS-Active Nanoparticle Clusters in Suspension.

A novel wide-field approach for the real-time Surface Enhanced Raman Scattering (SERS) imaging of multiple silver nanoparticle clusters suspended in solution is described. This method enables direct correlation of the SERS activity of a single nanoparticle aggregate and its size through measurement of the cluster diffusion coefficient and can also be performed in a high-throughput basis. As a first demonstration, we investigate the salt-induced aggregation of silver nanoparticles in the presence of a reporter tag molecule, which has a high affinity for the nanoparticle surface. In addition to tracking individual particles, direct comparison of Rayleigh and SERS videos of the same colloid solution enabled measurement of the fraction of individual clusters that are SERS active and the dependence of this value on the relative concentration of the tag molecule. Furthermore, given the ability to also rapidly profile any nonuniformity in particle size distributions, we expect this approach will not only provide a new tool for the fundamental understanding of SERS but also significantly contribute to the development of an array of emerging nanoparticle-enhanced biomolecule and imaging detection platforms.

Nanoscale definition of substrate materials to direct human adult stem cells towards tissue specific populations.

The development of homogenously nano-patterned chemically modified surfaces that can be used to initiate a cellular response, particularly stem cell differentiation, in a highly controlled manner without the need for exogenous biological factors has never been reported, due to that fact that precisely defined and reproducible systems have not been available that can be used to study cell/material interactions and unlock the potential of a material driven cell response. Until now material driven stem cell (furthermore any cell) responses have been variable due to the limitations in definition and reproducibility of the underlying substrate and the lack of true homogeneity of modifications that can dictate a cellular response at a sub-micron level that can effectively control initial cell interactions of all cells that contact the surface. Here we report the successful design and use of homogenously molecularly nanopatterned surfaces to control initial stem cell adhesion and hence function. The highly specified nano-patterned arrays were compared directly to silane modified bulk coated substrates that have previously been proven to initiate mesenchymal stem cell (MSC) differentiation in a heterogenous manner, the aim of this study was to prove the efficiency of these previously observed cell responses could be enhanced by the incorporation of nano-patterns. Nano-patterned surfaces were prepared by Dip Pen Nanolithography (DPN) to produce arrays of 70 nm sized dots separated by defined spacings of 140, 280 and 1000 nm with terminal functionalities of carboxyl, amino, methyl and hydroxyl and used to control cell growth. These nanopatterned surfaces exhibited unprecedented control of initial cell interactions and will change the capabilities for stem cell definition in vitro and then cell based medical therapies. In addition to highlighting the ability of the materials to control stem cell functionality on an unprecedented scale this research also introduces the successful scale-up of DPN and the novel chemistries and systems to facilitate the production of homogeneously patterned substrates (5 mm2) that are applicable for use in in vitro cell conditions over prolonged periods for complete control of material driven cell responses.

Imaging inflammation in real time--future of nanoparticles.

The detection of subclinical early inflammation in autoimmune diseases is an important but currently technically demanding approach to direct initial diagnosis and subsequent choice of therapy. Recent advances in imaging using NP provides the potential to detect cellular recruitment, vascular activation or leakage at a subclinically stage of disease and may provide predictive "biomarkers" of future pathogenesis. The NP used are either untargeted and taken up by phagocytic cells, or are linked to a ligand, targeting localisation to the site of inflammation. Techniques, varying from MRI and fluorescence to Raman spectroscopy are being employed. In this short review, we summarise many of the recent developments in the field of NP imaging related to inflammation.

Functionalized nanoparticles for bioanalysis by SERRS.

Metallic nanoparticles can be used as basic materials for a wide variety of purposes including building blocks for nanoassemblies, substrates for enhanced spectroscopies such as fluorescence and Raman and as labels for biomolecules. In the present paper, we report how silver and gold nanoparticles can be functionalized with specific biomolecular probes to interact in a specific manner with a target molecule to provide a change in the properties of the nanoparticles which can be measured to indicate the molecular recognition event. Examples of this approach include DNA hybridization to switch on SERRS (surface-enhanced resonance Raman scattering) when a specific target sequence is present, the use of nanoparticles for in vivo SERRS imaging and the use of nanoparticles functionalized with antibodies to provide a new type of immunoassay. These examples indicate how nanoparticles can be used to provide highly sensitive and informative data from a variety of biological systems when used in combination with SERRS.

Functionalized nanoparticles for nucleic acid sequence analysis using optical spectroscopies.

SERRS (surface-enhanced resonance Raman scattering) is a vibrational spectroscopy which allows extremely sensitive and selective detection of labelled DNA sequences with detection limits which rival, and in most cases surpass, that of fluorescence. SERRS relies on a visible chromophore adsorbing on to an enhancing surface. DNA itself is not SERRS-active, as it lacks a suitable visible chromophore and has poor adsorption properties on to the surfaces used for enhancement. The surface normally used for enhancement in these sorts of studies are metallic nanoparticles and, through modification of DNA probes by the addition of suitable SERRS labels, signals can be obtained that are highly sensitive and very selective. The aggregation state of the nanoparticles is critical to the sensitivity, and, in the present paper, we show how straightforward detection of labelled DNA probes can be achieved using SERRS in a quantitative manner and with a variety of different commercially available labels. In a second approach, we show how the properties of aggregation to turn on the SERRS effect can be exploited through DNA hybridization to give identification of a particular DNA sequence. This approach lends itself to closed-tube formats and is a promising way forward for molecular diagnostics using SERRS.