Atomic spectrometry update : a review of advances in environmental analysis

This is the 31st annual review of the application of atomic spectrometry to the chemical analysis of environmental samples. This update refers to papers published approximately between August 2014 and July 2015 and continues the series of Atomic Spectrometry Updates (ASUs) in Environmental Analysis that should be read in conjunction with other related ASUs in the series, namely: clinical and biological materials, foods and beverages; advances in atomic spectrometry and related techniques; elemental speciation; X-ray spectrometry; and metals, chemicals and functional materials. In the field of air analysis, highlights within this review period included: the development of a new laser fluorescence instrument for the ultratrace determination of mercury vapour; single particle ICP-MS studies and the coupling of elemental analysers to mass spectrometers for the improved characterisation of carbonaceous aerosols. In the arena of water analysis, methods continue to be developed: for the extraction and preconcentration of elements, As, Cr, Hg and Sb species and determination of elemental constituents in colloidal and NP fractions. Emerging elements of interest include Gd derived from MRI agents discharged at low level from medical facilities in water courses. Instrumental developments reported included the use of MC-ICP-MS for isotopic tracer studies and a review of TXRF techniques and associated preconcentration procedures for trace element analysis. In the period covered by this update several articles have explored the analysis of soil extracts for geochemical prospecting. There has been widening interest in the use of CS-AAS and in the application of techniques capable of direct sample analysis such as slurry sampling ETAAS and ETV-ICP-AES. Portable XRF instrumentation is now being used in many disciplines to quantify trace elements in soils – bringing a need for better transfer of analytical knowledge to non-specialist users – and the growing use of portable XRF in proximal sensing is also noteworthy. Recent research indicates that geological applications still drive many of the instrumental and methodological advances in LA-ICP-MS. Fundamental studies continued to shed light on the processes involved and hence ways of improving the analysis of laser-produced aerosols and to minimise matrix and fractionation effects. A new technique LA-DOF-MS (distance of flight) was described. The utility of LIBS and portable XRF for in situ survey work continues to show promise but issues such as appropriate calibration regimes and data processing protocols will still need to be addressed

Widespread Tau Seeding Activity at Early Braak Stages

Transcellular propagation of tau aggregates may underlie the progression of pathology in Alzheimer\u27s disease (AD) and other tauopathies. Braak staging (B1, B2, B3) is based on phospho-tau accumulation within connected brain regions: entorhinal cortex (B1); hippocampus/limbic system (B2); and frontal and parietal lobes (B3). We previously developed a specific and sensitive assay that uses flow cytometry to quantify tissue seeding activity based on fluorescence resonance energy transfer (FRET) in cells that stably express tau reporter proteins. In a tauopathy mouse model, we have detected seeding activity far in advance of histopathological changes. It remains unknown whether individuals with AD also develop seeding activity prior to accumulation of phospho-tau. We measured tau seeding activity across four brain regions (hippocampus, frontal lobe, parietal lobe, and cerebellum) in 104 fresh-frozen human AD brain samples from all Braak stages. We observed widespread seeding activity, notably in regions predicted to be free of phospho-tau deposition, and in detergent-insoluble fractions that lacked tau detectable by ELISA. Seeding activity correlated positively with Braak stage and negatively with MMSE. Our results are consistent with early transcellular propagation of tau seeds that triggers subsequent development of neuropathology. The FRET-based seeding assay may also complement standard neuropathological classification of tauopathies

Atomic spectrometry update: a review of advances in environmental analysis

This is the 33th annual review of the application of atomic spectrometry to the chemical analysis of environmental samples. This update refers to papers published approximately between August 2016 and June 2017 and continues the series of Atomic Spectrometry Updates (ASUs) in environmental analysis that should be read in conjunction with other related ASUs in the series, namely: clinical and biological materials, foods and beverages; advances in atomic spectrometry and related techniques; elemental speciation; X-ray spectrometry; and metals, chemicals and functional materials. In the field of air analysis, highlights within this review period included the fabrication of new air samplers using 3D printer technology, development of a portable aerosol concentrator unit based upon electrostatic precipitation and instrumental developments such as a prototype portable spark emission spectrometer to quantify metal particles in workplace air. The advent of ICP-MS/MS systems has enabled analysts to develop improved methods for the determination of PGEs and radioactive elements present in airborne particles. With such instruments, the capacity to eliminate or minimise many isobaric interferences now enables analysts to forego the use of many onerous sample clean-up procedures. Improvements in the capabilities of aerosol mass spectrometers were noted as were developments in other complimentary measurement techniques such as Raman. In the arena of water analysis there are growing concerns regarding engineered NPs e.g. Ag NPs, entering water courses resulting in the development and optimisation of new methods based upon FFF and sp-ICP-MS techniques to measure such inputs. Similar concerns exist for MRI contrasting agents e.g. Gd-based compounds and here improved methodologies that involve the use of sample preconcentration using chelating columns and ICP-MS analysis have been proposed. In the field of plant and soil analysis, similar to developments in the water sector, there has been increased interest in the measurement of NPs. Many comparisons of sample digestion or extraction methods have been reported but a key issue rarely addressed is transferability, i.e. whether methods preferred by one group of researchers using particular apparatus are also optimal in a different laboratory using different apparatus. New sample preconcentration methods continued to appear although – as in previous years – the CRMs selected for method validation often failed to reflect the nature of the intended sample(s). A noteworthy advance is the use of HR-CS-ETMAS for elemental analysis. Developments in LIBS included greater use of TEA CO2 lasers in place of Nd:YAG lasers and increased use of stand-off measurement. The past year has also seen a rise in proximal sensing using LIBS and pXRFS. In the field of geological analysis, the quest continues for well-characterised matrix-matched materials suitable for the calibration of elemental and, particularly, isotopic measurements by microanalytical techniques. Increasing interest in stable isotope analysis by SIMS is reflected by the number of matrix-matched RMs developed specifically for this technique. Much work continues on ways of improving isotope ratio measurements by ICP-MS and TIMS for a wide range of different isotope systems relevant to geochemical studies. High spatial resolution analysis by LIBS, LA-ICP-MS and SIMS to obtain data on chemical and isotopic variations in minerals and biogenic materials in two and three dimensions are the foundation for many new insights in geoscientific research. In XRFS and LIBS, the advantages and limitations of portable instrumentation continue to be major focus of activity

Atomic spectrometry update – a review of advances in environmental analysis

This is the 34th annual review of the application of atomic spectrometry to the chemical analysis of environmental samples. This Update refers to papers published approximately between August 2017 and June 2018 and continues the series of Atomic Spectrometry Updates (ASUs) in Environmental Analysis that should be read in conjunction with other related ASUs in the series, namely: clinical and biological materials, foods and beverages; advances in atomic spectrometry and related techniques; elemental speciation; X-ray spectrometry; and metals, chemicals and functional materials. The review is not intended to be a comprehensive overview but selective with the aim of providing a critical insight into developments in instrumentation, methodologies and data handling that represent a significant advance in the use of atomic spectrometry in the environmental science

The jellification of north temperate lakes.

Calcium (Ca) concentrations are decreasing in softwater lakes across eastern North America and western Europe. Using long-term contemporary and palaeo-environmental field data, we show that this is precipitating a dramatic change in Canadian lakes: the replacement of previously dominant pelagic herbivores (Ca-rich Daphnia species) by Holopedium glacialis, a jelly-clad, Ca-poor competitor. In some lakes, this transformation is being facilitated by increases in macro-invertebrate predation, both from native (Chaoborus spp.) and introduced (Bythotrephes longimanus) zooplanktivores, to which Holopedium, with its jelly coat, is relatively invulnerable. Greater representation by Holopedium within cladoceran zooplankton communities will reduce nutrient transfer through food webs, given their lower phosphorus content relative to daphniids, and greater absolute abundances may pose long-term problems to water users. The dominance of jelly-clad zooplankton will likely persist while lakewater Ca levels remain low.This work was primarily supported by grants from the Natural Sciences and Engineering Research Council of Canada and funding from the Ontario Ministry of the Environment.This is the accepted manuscript. The final version is available at http://rspb.royalsocietypublishing.org/content/282/1798/20142449

Response comparison of multiple myeloma and monoclonal gammopathy of undetermined significance to the same anti-myeloma therapy: a retrospective cohort study

BackgroundMultiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS), which is usually only treated by a form of anti-multiple myeloma therapy if it is causing substantial disease through deposition of secreted M proteins. However, studies comparing how MGUS and multiple myeloma plasma cell clones respond to these therapies are scarce. Biclonal gammopathy multiple myeloma is characterised by the coexistence of an active multiple myeloma clone and a benign MGUS clone, and thus provides a unique model to assess the responses of separate clones to the same anti-multiple myeloma therapy, in the same patient, at the same time. We aimed to identify how MGUS and multiple myeloma plasma cell clones responded to anti-multiple myeloma therapy in patients newly diagnosed with biclonal gammopathy multiple myeloma.MethodsIn this retrospective cohort study, we identified patients with biclonal gammopathy multiple myeloma by central laboratory analysis of 6399 newly diagnosed patients with multiple myeloma enrolled in three UK clinical trials (Myeloma IX, Myeloma XI, and TEAMM) between July 7, 2004, and June 2, 2015. In addition to the inclusion criteria of these trials, our study necessitated at trial entry the presence of two distinct M proteins in immunofixation electrophoresis. The primary endpoint was difference in response achieved with anti-multiple myeloma therapy on MGUS (which we defined as M2) and multiple myeloma (M1) clones—overall, within patients, and between therapy types—with international therapy response criteria assessed with χ2 analyses. We analysed by intention to treat.Findings44 patients with biclonal gammopathy multiple myeloma with IgG or IgA MGUS clones were subsequently identified from the three trials and then longitudinally monitored. 41 (93%) of M1 clones had a response to therapy (either complete response, very good partial response, partial response, or minor response) compared with only 28 (64%) of M2 clones (p=0·0010). For the 20 patients who received intensive therapy, there was no difference between the proportion of responding clones in M1 (19 [95%]) and M2 (15 [75%], p=0·13). However, for the 17 patients who received non-intensive therapy, 16 (94%) of M1 clones had a response compared with ten [59%] of M2 clones (p=0·031). When examining clones within the same patient, 30 (68%) of 44 individual patients had different levels of responses within the M1 and M2 clones. One patient exhibited M2 progression to myeloma and subsequently died.InterpretationThese results show that, in patients with biclonal gammopathy multiple myeloma, anti-multiple myeloma therapies exert a greater depth of response against multiple myeloma plasma cell clones than MGUS plasma cell clones. Although some MGUS clones exhibited a complete response, many did not respond, which suggests that the underlying features that render multiple myeloma plasma cells susceptible to therapy are present in only some MGUS plasma cell clones. To determine MGUS clone susceptibly to therapy, future studies might seek to identify, with biclonal gammopathy multiple myeloma as an investigative model, the genetic and epigenetic alterations that affect whether MGUS plasma cell clones are responsive to anti-multiple myeloma therapy

Loss of ELK1 has differential effects on age-dependent organ fibrosis and integrin expression

ETS domain-containing protein-1 (ELK1) is a transcription factor important in regulating αvβ6 integrin expression. αvβ6 integrins activate the profibrotic cytokine Transforming Growth Factor β1 (TGFβ1) and are increased in the alveolar epithelium in idiopathic pulmonary fibrosis (IPF). IPF is a disease associated with aging and therefore we hypothesised that aged animals lacking Elk1 globally would develop spontaneous fibrosis in organs where αvβ6 mediated TGFβ activation has been implicated. Here we identify that Elk1-knockout (Elk1−/0) mice aged to one year developed spontaneous fibrosis in the absence of injury in both the lung and the liver but not in the heart or kidneys. The lungs of Elk1−/0 aged mice demonstrated increased collagen deposition, in particular collagen 3α1, located in small fibrotic foci and thickened alveolar walls. Despite the liver having relatively low global levels of ELK1 expression, Elk1−/0 animals developed hepatosteatosis and fibrosis. The loss of Elk1 also had differential effects on Itgb1, Itgb5 and Itgb6 expression in the four organs potentially explaining the phenotypic differences in these organs. To understand the potential causes of reduced ELK1 in human disease we exposed human lung epithelial cells and murine lung slices to cigarette smoke extract, which lead to reduced ELK1 expression andmay explain the loss of ELK1 in human disease. These data support a fundamental role for ELK1 in protecting against the development of progressive fibrosis via transcriptional regulation of beta integrin subunit genes, and demonstrate that loss of ELK1 can be caused by cigarette smoke

Quantifying regional α -synuclein, amyloid β, and tau accumulation in Lewy body dementia

OBJECTIVE: Parkinson disease (PD) is defined by the accumulation of misfolded α-synuclein (α-syn) in Lewy bodies and Lewy neurites. It affects multiple cortical and subcortical neuronal populations. The majority of people with PD develop dementia, which is associated with Lewy bodies in neocortex and referred to as Lewy body dementia (LBD). Other neuropathologic changes, including amyloid β (Aβ) and tau accumulation, occur in some LBD cases. We sought to quantify α-syn, Aβ, and tau accumulation in neocortical, limbic, and basal ganglia regions. METHODS: We isolated insoluble protein from fresh frozen postmortem brain tissue samples for eight brains regions from 15 LBD, seven Alzheimer disease (AD), and six control cases. We measured insoluble α-syn, Aβ, and tau with recently developed sandwich ELISAs. RESULTS: We detected a wide range of insoluble α-syn accumulation in LBD cases. The majority had substantial α-syn accumulation in most regions, and dementia severity correlated with neocortical α-syn. However, three cases had low neocortical levels that were indistinguishable from controls. Eight LBD cases had substantial Aβ accumulation, although the mean Aβ level in LBD was lower than in AD. The presence of Aβ was associated with greater α-syn accumulation. Tau accumulation accompanied Aβ in only one LBD case. INTERPRETATION: LBD is associated with insoluble α-syn accumulation in neocortical regions, but the relatively low neocortical levels in some cases suggest that other changes contribute to impaired function, such as loss of neocortical innervation from subcortical regions. The correlation between Aβ and α-syn accumulation suggests a pathophysiologic relationship between these two processes

Disease Progression in Hemodynamically Stable Patients Presenting to the Emergency Department With Sepsis

Aggressive diagnosis and treatment of patients presenting to the emergency department (ED) with septic shock has been shown to reduce mortality. To enhance the ability to intervene in patients with lesser illness severity, a better understanding of the natural history of the early progression from simple infection to more severe illness is needed