SHoC-IVC: Does assessment of the inferior vena cava by point-of-care ultrasound independently predict fluid status in spontaneously breathing patients with undifferentiated hypotension?

BACKGROUND: Accurately determining the fluid status of a patient during resuscitation in the emergency department (ED) helps guide appropriate fluid administration in the setting of undifferentiated hypotension. Our goal was to determine the diagnostic utility of point-of-care ultrasound (PoCUS) for inferior vena cava (IVC) size and collapsibility in predicting a volume overload fluid status in spontaneously breathing hypotensive ED patients. METHODS: This was a post hoc secondary analysis of the SHOC-ED data, a prospective randomized controlled trial investigating PoCUS in patients with undifferentiated hypotension. We prospectively collected data on IVC size and collapsibility for 138 patients in the PoCUS group using a standard data collection form, and independently assigned a fluid status (volume overloaded, normal, volume deplete) from a composite clinical chart review blinded to PoCUS findings. The primary outcome was the diagnostic performance of IVC characteristics on PoCUS in the detection of a volume overloaded fluid status. RESULTS: One hundred twenty-nine patients had completed determinant IVC assessment by PoCUS, with one hundred twenty-five receiving successful final fluid status determination, of which one hundred and seven were classified as volume deplete, thirteen normal, and seven volume overloaded. A receiver operating characteristic (ROC) curve was plotted using several IVC size and collapsibility categories. The best overall performance utilized the combined parameters of a dilated IVC (> 2.5 cm) with minimal collapsibility (less than 50%) which had a sensitivity of 85.7% and specificity of 86.4% with an area under the curve (AOC) of 0.92 for predicting an volume overloaded fluid status. CONCLUSION: IVC PoCUS is feasible in spontaneously breathing hypotensive adult ED patients, and demonstrates potential value as a predictor of a volume overloaded fluid status in patients with undifferentiated hypotension. IVC size may be the preferred measure.

RéSUMé: CONTEXTE: La détermination précise de l'état du liquide d'un patient pendant la réanimation au service des urgences (SU) aide à guider l'administration appropriée du liquide dans le cadre d'une hypotension indifférenciée. Notre objectif était de déterminer l'utilité diagnostique de l'échographie au point de soins (PoCUS) pour la taille de la veine cave inférieure (IVC) et l'collapsibilité dans la prédiction d'un état de liquide de surcharge volumique chez les patients souffrant d'une hypotension respiratoire spontanée. MéTHODES: Il s'agissait d'une analyse secondaire post-hoc des données SHOC-ED, un essai contrôlé randomisé prospectif examinant PoCUS chez des patients atteints d'hypotension indifférenciée. Nous avons collecté prospectivement des données sur la taille et la collapsibilité des IVC pour 138 patients du groupe PoCUS à l'aide d'un formulaire de collecte de données standard, et attribué indépendamment un état de fluide (volume surchargé, normal, épuisement du volume) à partir d'une revue de dossier clinique composite mise en aveugle aux résultats PoCUS. Le résultat principal était la performance diagnostique des caractéristiques IVC sur PoCUS dans la détection d'un état de fluide surchargé en volume. RéSULTATS: 129 patients avaient terminé l'évaluation IVC des déterminants par PoCUS, dont 125 ont reçu une détermination finale du statut hydrique, dont 107 ont été classés comme étant une diminution du volume, 13 normaux et 7 surchargés. Une courbe des caractéristiques de fonctionnement du récepteur (ROC) a été tracée en utilisant plusieurs catégories de taille et d'affaissement IVC. La meilleure performance globale a utilisé les paramètres combinés d'une IVC dilatée (> 2,5 cm) avec une collapsibilité minimale (moins de 50%) qui avait une sensibilité de 85,7% et une spécificité de 86,4% avec une zone sous la courbe (AOC) de 0,92 pour prédire un état de fluide surchargé en volume. CONCLUSION: IVC PoCUS est faisable chez les patients adultes souffrant d'une hypotension respiratoire spontanée et démontre une valeur potentielle en tant que prédicteur d'un état de liquide surchargé en volume chez les patients atteints d'hypotension indifférenciée. La taille IVC peut être la mesure préférée.

Sediment Spatial Distribution and Quality Assessment of Metals in Chinook Salmon and Resident Killer Whale Marine Habitat in British Columbia, Canada.

At-risk resident killer whale (Orcinus orca) populations of the northeastern Pacific, Canada, and their main prey, Chinook Salmon (Oncorhynchus tshawytscha), are exposed to a variety of contaminants including chemical elements from both natural and anthropogenic sources, which may be constraining their recovery. Concentrations of 36 chemical elements in subtidal surface sediments (1-435 m depth) collected from 98 sites along the British Columbia coast were used to characterize coast-wide patterns, and a subset of metals (mercury (Hg), cadmium (Cd), arsenic (As), nickel (Ni), copper (Cu), and lead (Pb)) were selected to assess Chinook Salmon and resident killer whale marine habitat quality. Principal component analysis (PCA) showed a dominance of Hg, antimony (Sb), Pb, Cu, and zinc (Zn) for Prince Rupert Harbour, Victoria Harbour, and Burrard Inlet, suggesting local sources. Based on the PCA, geochemical properties such as total organic carbon (TOC), acid volatile sulfide (AVS), and pH explained the spatial distribution of all elements in sediment (p < 0.001). Mercury, Cd, As, Ni, Cu, and Pb hotspots were identified along the coast of Vancouver Island, the central and north coast, in the Strait of Georgia, and Haida Gwaii. Bischof Island of Haida Gwaii and Ardmillan Bay on the central coast were most contaminated and enriched by Cd, determined by geoaccumulation index (Igeo) and enrichment factor (EF), respectively. Marine habitat quality was assessed by comparing metal concentrations to Canadian Sediment Quality Guidelines (SQGs). Chinook Salmon populations may be indirectly affected by metal toxicity (As > Cd and Cu > Ni > Hg > Pb) to lower trophic level prey species. Toxicity related impacts to benthic organisms as a result of exposure to elevated Cd and As concentrations in Northern Resident Killer Whale critical habitat and to Hg, Cd, As, Ni, Cu, and Pb concentrations in Southern Resident Killer Whale critical habitat may indirectly pose a threat to resident killer whale populations, highlighting a need for management actions to reduce risks associated with these metals.

Declining concentrations of chlorinated paraffins in endangered St. Lawrence Estuary belugas (Delphinapterus leucas): Response to regulations or a change in diet?

Very high levels of industrial contaminants in St. Lawrence Estuary (SLE) beluga whales represent one of the major threats to this population classified as endangered under the Species at Risk Act in Canada. Elevated concentrations of short-chained chlorinated paraffins (SCCPs) were recently reported in blubber of adult male SLE belugas. Recent regulations for SCCPs in North America, combined with their replacement by medium- (MCCPs) and long-chained chlorinated paraffins (LCCPs), highlight the importance of tracking this toxic chemical class. The objectives of this study were to evaluate (1) levels and profiles of chlorinated paraffins (CPs) in samples obtained from carcasses of adult male, adult female, juvenile, newborn, and fetus beluga, and (2) trends in adult male belugas between 1997 and 2018. Factors potentially influencing CP temporal trends such as age, feeding ecology and sampling year were also explored. SCCPs dominated (64 to 100%) total CP concentrations across all age and sex classes, MCCPs accounted for the remaining proportion of total CPs, and LCCPs were not detected in any sample. The chlorinated paraffin homolog that dominated the most in beluga blubber was C12Cl8. Adult male SCCP concentrations from this study were considerably lower (> 2000-fold) than those recently reported in Simond et al. (2020), likely reflecting a previously erroneous overestimate due to the lack of a suitable analytical method for SCCPs at the time. Both SCCPs and total CPs declined over time in adult males in our study (rate of 1.67 and 1.33% per year, respectively), presumably due in part to the implementation of regulations in 2012. However, there is a need to better understand the possible contribution of a changing diet to contaminant exposure, as stable isotopic ratios of carbon also changed over time.

Microplastics distribution in sediment and mussels along the British Columbia Coast, Canada.

Microplastics (MPs) were characterized in surficial marine sediment (n = 36) and mussel (n = 29) samples collected along the British Columbia (BC) coast, Canada, using visual identification and Fourier Transform Infrared Spectrometry. MPs counts averaged 32.6 ± 5.3 particles per kg in sediment and 0.38 ± 0.04 particles per individual mussel (0.24 ± 0.04 /g of tissue). Victoria Harbour and the North Coast (Prince Rupert area) were MP hotspots, likely resulting from a combination of local sources and oceanographic conditions. Microfibers <1000 µm dominated the pattern in both matrices (61.1 % in sediment; 65.4 % mussels) highlighting the suspected role of textiles in the widespread distribution of MPs in the marine environment. Overall, polyester was dominant in sediment and mussels (54.1 % and 63.5 %, respectively), followed by polyethylene (16.2 % and 11.5 %, respectively). This is the first report of MPs in sediment and mussels along the coast of BC using standardized methods.

Characterization and Interpolation of Sediment Polychlorinated Biphenyls and Polybrominated Diphenyl Ethers in Resident Killer Whale Habitat along the Coast of British Columbia, Canada.

The northeastern Pacific northern and southern resident killer whale (Orcinus orca) populations are listed as threatened and endangered in Canada, respectively, with persistent, bioaccumulative contaminants, such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), posing threats to their recovery. Concentrations of PCBs and PBDEs in subtidal surface sediments collected from 97 sites along the British Columbia (BC) coast were used to identify their distribution and profiles, and to assess killer whale habitat quality. Victoria Harbour (VH3(site ID: 1) ) sediments exhibited the highest PCB and PBDE concentrations. For PCBs, PCB-138 was found at the highest concentration, followed by PCB-153, PCB-110, PCB-149, PCB-101, and PCB-118. For PBDEs, individual congeners were ranked as follows: BDE-209 > BDE-207 > BDE-206 > BDE-208 > BDE-47 > BDE-99. Principal component analyses (PCA) illustrated the variations in contaminant profiles, with PC1 for PCBs and PBDEs correlated with the octanol-water partition coefficient (log KOW , p < 0.003). Based on the PCA, sediment particle size, total organic carbon (TOC), and water depth at collection were other factors associated with the distribution of PBDEs, while PCB profiles were associated with TOC. Total PCB and PBDE concentrations at 100% and 34% of the sites, respectively, exceeded the recently adopted British Columbia's Ministry of Environment and Climate Change Strategy Working Sediment Quality Guidelines (PCBs 3.7 pg/g dry wt and PBDEs 1000 pg/g dry wt), considered protective of killer whales. Our findings suggest that the legacy of banned PCBs and PBDEs has the potential to constrain the recovery of killer whales as a result of their mobilization from sediments and consequent uptake by marine food webs. Environ Toxicol Chem 2022;41:2139-2151. © 2022 SETAC.

Cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab in patients with a history of myocardial infarction in Sweden.

AIMS: To assess the cost-effectiveness of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to standard-of-care lipid-lowering treatment [maximum tolerated dose (MTD) of statin and ezetimibe] in Swedish patients with a history of myocardial infarction (MI). METHODS AND RESULTS: Cost-effectiveness was evaluated using a Markov model based on Swedish observational data on cardiovascular event rates and efficacy from the FOURIER trial. Three risk profiles were considered: recent MI in the previous year; history of MI with a risk factor; and history of MI with a second event within 2 years. For each population, three minimum baseline low-density lipoprotein cholesterol (LDL-C) levels were considered: 2.5 mmol/L (≈100 mg/dL), based on the current reimbursement recommendation in Sweden; 1.8 mmol/L (≈70 mg/dL), based on 2016 ESC/EAS guidelines; and 1.4 mmol/L (≈55 mg/dL), or 1.0 mmol/L (≈40 mg/dL) for MI with a second event, based on 2019 ESC/EAS guidelines. Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab was associated with increased quality-adjusted life-years and costs vs. standard-of-care therapy. Incremental cost-effectiveness ratios (ICERs) were below SEK700 000 (∼€66 500), the generally accepted willingness-to-pay threshold in Sweden, for minimum LDL-C levels of 2.3 (recent MI), 1.7 (MI with a risk factor), and 1.7 mmol/L (MI with a second event). Sensitivity analyses demonstrated that base-case results were robust to changes in model parameters. CONCLUSION: Proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab added to MTD of statin and ezetimibe may be considered cost-effective at its list price for minimum LDL-C levels of 1.7-2.3 mmol/L, depending on risk profile, with ICERs below the accepted willingness-to-pay threshold in Sweden.

Xanthomatous hypophysitis causing hypogonadotropic hypogonadism resulting in delayed presentation of slipped capital femoral epiphysis.

An 18-year-old man who underwent bilateral pinning of his hip joints after a left unstable Slipped Capital Femoral Epiphysis (right pinned prophylactically) was noted to have delayed secondary sexual characteristics and post-operative diabetes insipidus. The patient also described a history of fatigue, headache and polydipsia for the past 4 years. Endocrine investigations revealed reduced androgen levels, hypocortisolism, a borderline normal Serum ACE and secondary hypothyroidism. Magnetic Resonance Imaging of the pituitary gland identified an enhancing mass and a thickened stalk which trans-nasal endoscopic biopsy found to be necrotic with pus. Histology confirmed a diagnosis of Xanthomatous Hypophysitis, an inflammatory condition likely related to a partial rupture of a Rathke cleft cyst. The patient was subsequently commenced on Androgen, Thyroxine, Desmopressin and Hydrocortisone therapy with on-going endocrine follow-up. Although endocrine dysfunction & hypogonadism has been recognised to be a risk factor for SCFE at an atypically older age, due to reduced androgen levels leading to a weakened physeal plate, this is the first known case of a Xanthomatous Hypophysitis resulting in pituitary dysfunction and eventual SCFE. This case highlights that an increased range of pituitary disorders should be considered in late presentations of SCFE; and vice versa the risk of SCFE should be considered in patients with prolonged hypogonadotropic hypogonadism.

Estimating Progression Rates Across the Spectrum of Alzheimer's Disease for Amyloid-Positive Individuals Using National Alzheimer's Coordinating Center Data.

INTRODUCTION: Published estimates of Alzheimer's disease (AD) progression do not capture the full disease continuum. This study provides transition probabilities of individuals with amyloid-ß (Aß+) pathology across the disease continuum. METHODS: Patient-level longitudinal data from the National Alzheimer's Coordinating Center were used to estimate progression rates. Progression rates through five clinically defined AD stages-asymptomatic, mild cognitive impairment due to AD (MCI-AD), mild AD dementia, moderate AD dementia, severe AD dementia-and death were measured as transition probabilities. Rates were assessed in "incident" patients who recently entered the stage, controlling for covariates. Transition probabilities were generated from multinomial logit regression models that predicted an individual's health state as a function of health state at the previous visit and adjusted for time between initial and follow-up visits, age, sex, years of education, and concomitant symptomatic AD medications. RESULTS: Annual transition probabilities to more severe dementia stages for surviving incident Aß+ patients were as follows: asymptomatic to MCI-AD, 40.8%; MCI-AD to mild AD dementia or worse, 21.8%; mild AD dementia to moderate AD dementia or worse, 35.9%; moderate AD dementia to severe AD dementia, 28.6%. Transition probabilities to less severe dementia stages were: 5.3% annual reversion from MCI-AD to asymptomatic, 3.0% mild AD dementia to MCI-AD, 1.8% moderate AD dementia to mild AD dementia, and 1.3% for severe AD dementia to moderate AD dementia. CONCLUSIONS: These transition probabilities reflect the full continuum of AD progression in Aß+ individuals and can be used to assess the impact of treatment on expected transitions.

Predicted Lifetime Health Outcomes for Aducanumab in Patients with Early Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that places a substantial burden on patients and caregivers. Aducanumab is the first AD therapy approved by the US Food and Drug Administration to reduce a defining pathophysiological feature of the disease, brain amyloid plaques. In the phase 3 clinical trial EMERGE (NCT02484547), aducanumab reduced clinical decline in patients with mild cognitive impairment (MCI) due to AD and mild AD dementia and confirmed amyloid pathology. METHODS: We used a Markov modeling approach to predict the long-term clinical benefits of aducanumab for patients with early AD based on EMERGE efficacy data. In the model, patients could transition between AD severity levels (MCI due to AD; mild, moderate, and severe AD dementia) and care settings (community vs. institution) or transition to death. The intervention was aducanumab added to standard of care (SOC), and the comparator was SOC alone. Data sources for base-case and scenario analyses included EMERGE, published National Alzheimer's Coordinating Center analyses, and other published literature. RESULTS: Per patient over a lifetime horizon, aducanumab treatment corresponded to 0.65 incremental patient quality-adjusted life-years (QALYs) and 0.09 fewer caregiver QALYs lost compared with patients treated with SOC. Aducanumab treatment translated to a lower lifetime probability of transitioning to AD dementia, a lower lifetime probability of transitioning to institutionalization (25.2% vs. 29.4%), delays in the median time to transition to AD dementia (7.50 vs. 4.92 years from MCI to moderate AD dementia or worse), and an incremental median time in the community of 1.32 years compared with SOC. CONCLUSION: The model predicted long-term benefits of aducanumab treatment in patients with MCI due to AD and mild AD dementia and their caregivers. The predicted outcomes provide a foundation for healthcare decision-makers and policymakers to understand the potential clinical and socioeconomic value of aducanumab.

Domestic laundry and microfiber pollution: Exploring fiber shedding from consumer apparel textiles.

Synthetic fibers are increasingly seen to dominate microplastic pollution profiles in aquatic environments, with evidence pointing to textiles as a potentially important source. However, the loss of microfibers from textiles during laundry is poorly understood. We evaluated microfiber release from a variety of synthetic and natural consumer apparel textile samples (n = 37), with different material types, constructions, and treatments during five consecutive domestic laundry cycles. Microfiber loss ranged from 9.6 mg to 1,240 mg kg-1 of textile per wash, or an estimated 8,809 to > 6,877,000 microfibers. Mechanically-treated polyester samples, dominated by fleeces and jerseys, released six times more microfibers (161 ± 173 mg kg-1 per wash) than did nylon samples with woven construction and filamentous yarns (27 ± 14 mg kg-1 per wash). Fiber shedding was positively correlated with fabric thickness for nylon and polyester. Interestingly, cotton and wool textiles also shed large amounts of microfibers (165 ± 44 mg kg-1 per wash). The similarity between the average width of textile fibers here (12.4 ± 4.5 µm) and those found in ocean samples provides support for the notion that home laundry is an important source of microfiber pollution. Evaluation of two marketed laundry lint traps provided insight into intervention options for the home, with retention of up to 90% for polyester fibers and 46% for nylon fibers. Our observation of a > 850-fold difference in the number of microfibers lost between low and high shedding textiles illustrates the strong potential for intervention, including more sustainable clothing design.

Estimation of the increased risk associated with recurrent events or polyvascular atherosclerotic cardiovascular disease in the United Kingdom.

AIMS: The aims of this study were to re-estimate the international REduction of Atherothrombosis for Continued Health (REACH) risk equation using United Kingdom data and to distinguish different relative hazards for specific atherosclerotic cardiovascular disease event histories. METHODS AND RESULTS: Patients in the UK Clinical Research Practice Datalink (CPRD) were included as of 1 January 2005 if they were 40 years or older, had 2 or more years of prior data, received one or more moderate or high-intensity statin in the previous year, and had a history of myocardial infarction, ischemic stroke, or other atherosclerotic cardiovascular disease. Patients were followed until a composite endpoint of myocardial infarction, ischemic stroke or cardiovascular death, loss to follow-up, or end of observation. We re-estimated the REACH risk equation hazard ratios (HRs) using CPRD data (re-estimated REACH model). Our event history model replaced the REACH vascular bed variables with more specific event histories. There were 60,838 patients with 5.25 years of mean follow-up. In the validation model, HRs were in the same direction, and generally greater than REACH. In the event history model, HRs compared to other atherosclerotic cardiovascular disease alone included: recurrent myocardial infarction (HR 1.19, 95% confidence interval (CI) 1.05-1.34), recurrent ischemic stroke (HR 1.36, 95% CI 1.03-1.80), myocardial infarction and other atherosclerotic cardiovascular disease (HR 1.31, 95% CI 1.23-1.38), ischemic stroke and other atherosclerotic cardiovascular disease (HR 1.40, 95% CI 1.23-1.60), myocardial infarction and ischemic stroke (HR 1.94, 95% CI 1.23-3.04), and myocardial infarction, ischemic stroke and other atherosclerotic cardiovascular disease (HR 1.93, 95% CI 1.47-2.54). CONCLUSION: A detailed cardiovascular event history may be useful for estimating the relative risk of future cardiovascular events.

Pervasive distribution of polyester fibres in the Arctic Ocean is driven by Atlantic inputs.

Microplastics are increasingly recognized as ubiquitous global contaminants, but questions linger regarding their source, transport and fate. We document the widespread distribution of microplastics in near-surface seawater from 71 stations across the European and North American Arctic - including the North Pole. We also characterize samples to a depth of 1,015 m in the Beaufort Sea. Particle abundance correlated with longitude, with almost three times more particles in the eastern Arctic compared to the west. Polyester comprised 73% of total synthetic fibres, with an east-to-west shift in infra-red signatures pointing to a potential weathering of fibres away from source. Here we suggest that relatively fresh polyester fibres are delivered to the eastern Arctic Ocean, via Atlantic Ocean inputs and/or atmospheric transport from the South. This raises further questions about the global reach of textile fibres in domestic wastewater, with our findings pointing to their widespread distribution in this remote region of the world.

The COVID-19 pandemic: impact on NHS England PET-CT services and lessons learnt.

PURPOSE: The purpose of the study was to examine the impact of the first wave of COVID-19 on National Health Service (NHS) 18F-fluorodeoxyglucose positron emission tomography computed tomography (FDG PET-CT) scanning activity across England. METHODS: Monthly FDG PET-CT scanning activity was collected from 41/48 NHS England provider sites. Data from 31/41 sites were stratified by nononcology/oncology, cancer type, with lung cancer and lymphoma split into specific indications, turn-around times and delays due to radiotracer. RESULTS: In April and May 2020, a 32 and 31% decrease in activity was observed, a larger decrease for noncancer compared with cancer FDG PET-CT. In June 2020, activity started to recover with 6% fewer scans recorded compared with June 2019. Of the six most common indications, lung and oesophageal cancer had the largest decrease in activity and slowest recovery. Lymphoma and melanoma showed the smallest decrease and fastest recovery. Lung cancer scans for initial diagnosis/staging saw the largest fall and slowest recovery compared with scans for known lung cancer. There was no percentage increase in overall turn-around time compared with the same months in 2019, and no increase in turn-around time of more than 7 working days due to FDG supply during April and May 2020 compared with the 3 previous months. CONCLUSIONS: There is no correlation between FDG PET-CT activity (fall and recovery) in England and the ability to provide the service by NHS England. It most likely reflects a combination of changes in health-seeking behaviour, NHS health policy and a decrease in the use of investigations that carry a high risk of COVID-19 transmission.

Challenges in demonstrating the value of disease-modifying therapies for Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is a complex neurodegenerative disease, affecting millions of people worldwide and imposing heavy economic burdens to societies. Currently, only symptomatic treatments are available for patients, but there is ongoing research on potential therapies that can modify the course of disease. The main objective of this work is to identify and explore the challenges surrounding decision modeling for economic evaluation of interventions for AD. AREAS COVERED: This article discusses the challenges in modeling the natural history of disease, particularly regarding the selection of disease progression and outcome measures, the inclusion of biomarker status in models, and the approach to model mortality. Challenges stemming from the use of long-term assumptions regarding treatment effects and the need for real-world evidence to fill data gaps are discussed. Lastly, the overwhelming economic impact of disease and the challenges in estimating these costs for modeling are addressed. EXPERT OPINION: Value assessment frameworks need to be reconsidered in order to demonstrate the full benefit of new disease-modifying therapies spanning beyond the scope of health systems. Data collection efforts that expand the evidence base, upon which economic models are based, will reduce the uncertainties surrounding the long-term outcomes of interventions in AD.

Fluorimetric assay with a novel substrate for quantification of galactocerebrosidase activity in dried blood spot specimens.

BACKGROUND: Decreased galactocerebrosidase (GALC) enzyme activity is causative for Krabbe disease, a lysosomal storage disorder with devastating neurodegenerative consequences. Quantitative fluorimetric assays for GALC activity in isolated blood and skin cells have been described; however, no such assay has been described using dried blood spot (DBS) specimens. METHODS: GALC enzyme activity was measured quantitatively using fluorescence from a novel glycosidic substrate: carboxy derived from 6-hexadecanoylamino-4-methylumbelliferone. GALC activity was demonstrated on newborn DBS specimens, known Krabbe disease patient specimens, proficiency testing and quality control samples. RESULTS: We present data on characterization of the novel substrate and assay, including pH optimization and enzyme kinetics using a fluorimetric profile. Single and multi-day precision analyses revealed tight analytical measurements with %CV ranging from 5.2% to 14.1%. GALC enzyme activity was linear over the range of 0.31 - 12.04 µmol/l/h with a limit of detection of 0.066 µmol/l/h. Our results with this assay show a clear discrimination between GALC activities in samples from Krabbe disease patients versus presumed normal newborn samples. CONCLUSIONS: A fluorimetric assay for GALC enzyme activity measurement on dried blood spot specimens is feasible. Improvements to the assay including novel substrate design, increased substrate concentration and removal of sodium chloride maximize the specificity of the assay and minimize interference from ß-galactosidase.

How 'Blue' Is 'Green' Energy?

Often perceived as environmentally benign, 'green' renewable energy technologies have ecological costs that are often overlooked, especially those occurring below the waterline. After briefly discussing the impacts of hydropower on freshwater and marine organisms, we focus this review on the impacts of marine renewable energy devices (MREDs) on underwater marine organisms, particularly offshore wind farms and marine energy converters (e.g., tidal turbines). We consider both cumulative impacts and synergistic interactions with other anthropogenic pressures, using offshore wind farms and the Taiwanese white dolphin (Sousa chinensis taiwanensis) as an example. While MREDs undoubtedly can help mitigate climate change, variability in the sensitivity of different species and ecosystems means that rigorous case-by-case assessments are needed to fully comprehend the consequences of MRED use.

Resurgence of malaria infection after mass treatment: a simulation study.

BACKGROUND: Field studies are evaluating if mass drug administration (MDA) might shorten the time to elimination of Plasmodium falciparum malaria, when vector control measures and reactive surveillance strategies are scaled-up. A concern with this strategy is that there may be resurgence of transmission following MDA. METHODS: A conceptual model was developed to classify possible outcomes of an initial period of MDA, followed by continuously implementing other interventions. The classification considered whether elimination or a new endemic stable state is achieved, and whether changes are rapid, transient, or gradual. These categories were informed by stability analyses of simple models of vector control, case management, and test-and-treat interventions. Individual-based stochastic models of malaria transmission (OpenMalaria) were then used to estimate the probability and likely rates of resurgence in realistic settings. Effects of concurrent interventions, including routine case management and test-and-treat strategies were investigated. RESULTS: Analysis of the conceptual models suggest resurgence will occur after MDA unless transmission potential is very low, or the post-MDA prevalence falls below a threshold, which depends on both transmission potential and on the induction of bistability. Importation rates are important only when this threshold is very low. In most OpenMalaria simulations the approximately stable state achieved at the end of the simulations was independent of inclusion of MDA and the final state was unaffected by importation of infections at plausible rates. Elimination occurred only with high effective coverage of case management, low initial prevalence, and high intensity test-and-treat. High coverage of case management but not by test-and-treat induced bistability. Where resurgence occurred, its rate depended mainly on transmission potential (not treatment rates). CONCLUSIONS: A short burst of high impact MDA is likely to be followed by resurgence. To avert resurgence, concomitant interventions need either to substantially reduce average transmission potential or to be differentially effective in averting or clearing infections at low prevalence. Case management at high effective coverage has this differential effect, and should suffice to avert resurgence caused by imported cases at plausible rates of importation. Once resurgence occurs, its rate depends mainly on transmission potential, not on treatment strategies.

An interlaboratory comparison exercise for the determination of microplastics in standard sample bottles.

An interlaboratory comparison exercise was conducted to assess the consistency of microplastic quantification across several laboratories. The test samples were prepared by mixing one liter seawater free of plastics, microplastics made from polypropylene, high- and low-density polyethylene, and artificial particles in two plastic bottles, and analyzed concurrently in 12 experienced laboratories around the world. The minimum requirements to quantify microplastics were examined by comparing actual numbers of microplastics in these sample bottles with numbers measured in each laboratory. The uncertainty was due to pervasive errors derived from inaccuracies in measuring sizes and/or misidentification of microplastics, including both false recognition and overlooking. The size distribution of microplastics should be smoothed using a running mean with a length of >0.5 mm to reduce uncertainty to less than ±20%. The number of microplastics <1 mm was underestimated by 20% even when using the best practice for measuring microplastics in laboratories.

Theory of reactive interventions in the elimination and control of malaria.

BACKGROUND: Reactive case detection (RCD) is an integral part of many malaria control and elimination programmes and can be conceived of as a way of gradually decreasing transmission. However, it is unclear under what circumstances RCD may have a substantial impact on prevalence, how likely it is to lead to local elimination, or how effective it needs to be to prevent reintroduction after transmission has been interrupted. METHODS: Analyses and simulations of a discrete time compartmental susceptible-infectious-susceptible (SIS) model were used to understand the mechanisms of how RCD changes transmission dynamics and estimate the impact of RCD programmes in a range of settings with varying patterns of transmission potential and programme characteristics. Prevalence survey data from recent studies in Zambia were used to capture the effects of spatial clustering of patent infections. RESULTS: RCD proved most effective at low prevalence. Increasing the number of index cases followed was more important than increasing the number of neighbours tested per index case. Elimination was achieved only in simulations of situations with very low transmission intensity and following many index cases. However, RCD appears to be helpful in maintaining the disease-free state after achieving malaria elimination (through other interventions). CONCLUSION: RCD alone can eliminate malaria in only a very limited range of settings, where transmission potential is very low, and improving the coverage of RCD has little effect on this range. In other settings, it is likely to reduce disease burden. RCD may also help maintain the disease-free state in the face of imported infections. Prevalence survey data can be used to estimate a targeting ratio (the ratio of prevalence found through RCD to that in the general population) which is an important determinant of the effect of RCD.