Characterisation and calibration of low-cost PM sensors at high temporal resolution to reference-grade performance.

Particulate Matter (PM) low-cost sensors (LCS) present a cost-effective opportunity to improve the spatiotemporal resolution of airborne PM data. Previous studies focused on PM-LCS-reported hourly data and identified, without fully addressing, their limitations. However, PM-LCS provide measurements at finer temporal resolutions. Furthermore, government bodies have developed certifications to accompany new uses of these sensors, but these certifications have shortcomings. To address these knowledge gaps, PM-LCS of two models, 8 Sensirion SPS30 and 8 Plantower PMS5003, were collocated for one year with a Fidas 200S, MCERTS-certified PM monitor and were characterised at 2 min resolution, enabling replication of certification processes, and highlighting their limitations and improvements. Robust linear models using sensor-reported particle number concentrations and relative humidity, coupled with 2-week biannual calibration campaigns, achieved reference-grade performance, at median PM2.5 background concentration of 5.5 µg/m3, demonstrating that, with careful calibration, PM-LCS may cost-effectively supplement reference equipment in multi-nodes networks with fine spatiotemporality.

Enhanced Reproducibility and Precision of High-Throughput Quantification of Bacterial Growth Data Using a Microplate Reader.

This study aimed to develop a repeatable, reliable, high-throughput protocol to monitor bacterial growth in 96-well plates and analyze the maximum growth rate. The growth curves and maximum growth rates of two bacterial species were determined. Issues including (i) lid condensation, (ii) pathlength correction, (iii) inoculation size, (iv) sampling time interval, and (v) spatial bias were investigated. The repeatability of the protocol was assessed with three independent technical replications, with a standard deviation of 0.03 between the runs. The maximum growth rates of Bacillus mycoides and Paenibacillus tundrae were determined to be (mean ± SD) 0.99 h-1 ±  0.03 h-1 and 0.85 h-1 ± 0.025 h-1, respectively. These bacteria are more challenging to monitor optically due to their affinity to clump together. This study demonstrates the critical importance of inoculation size, path length correction, lid warming, sampling time intervals, and well-plate spatial bias to obtain reliable, accurate, and reproducible data on microplate readers. The developed protocol and its verification steps can be expanded to other methods using microplate readers and high-throughput protocols, reducing the researchers' innate errors and material costs.

Author Correction: Long-term field comparison of multiple low-cost particulate matter sensors in an outdoor urban environment.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

LoRaWAN for Smart City IoT Deployments: A Long Term Evaluation.

LoRaWAN is a Low-PowerWide Area Network (LPWAN) technology designed for Internetof Things (IoT) deployments; this paper presents experiences from deploying a city-scale network across Southampton, UK. This network was deployed to support an installation of air quality monitors and to explore the capabilities of . This deployment uses a mixture of commercial off-the-shelf gateways and custom gateways. These gateway locations were chosen based on network access, site permission and accessibility, and are not necessarily the best locations theoretically. Over 135,000 messages have been transmitted by the twenty devices analysed. Over the course of the complete deployment, 72 . 4 of the messages were successfully received by the data server. Of the messages that were received, 99 were received within 10 s of transmission. We conclude that is an applicable communication technology for city-scale air quality monitoring and other smart city applications.

Long-term field comparison of multiple low-cost particulate matter sensors in an outdoor urban environment.

Exposure to ambient particulate matter (PM) air pollution is a leading risk factor for morbidity and mortality, associated with up to 8.9 million deaths/year worldwide. Measurement of personal exposure to PM is hindered by poor spatial resolution of monitoring networks. Low-cost PM sensors may improve monitoring resolution in a cost-effective manner but there are doubts regarding data reliability. PM sensor boxes were constructed using four low-cost PM micro-sensor models. Three boxes were deployed at each of two schools in Southampton, UK, for around one year and sensor performance was analysed. Comparison of sensor readings with a nearby background station showed moderate to good correlation (0.61 < r < 0.88, p < 0.0001), but indicated that low-cost sensor performance varies with different PM sources and background concentrations, and to a lesser extent relative humidity and temperature. This may have implications for their potential use in different locations. Data also indicates that these sensors can track short-lived events of pollution, especially in conjunction with wind data. We conclude that, with appropriate consideration of potential confounding factors, low-cost PM sensors may be suitable for PM monitoring where reference-standard equipment is not available or feasible, and that they may be useful in studying spatially localised airborne PM concentrations.

City Scale Particulate Matter Monitoring Using LoRaWAN Based Air Quality IoT Devices.

Air Quality (AQ) is a very topical issue for many cities and has a direct impact on citizen health. The AQ of a large UK city is being investigated using low-cost Particulate Matter (PM) sensors, and the results obtained by these sensors have been compared with government operated AQ stations. In the first pilot deployment, six AQ Internet of Things (IoT) devices have been designed and built, each with four different low-cost PM sensors, and they have been deployed at two locations within the city. These devices are equipped with LoRaWAN wireless network transceivers to test city scale Low-Power Wide Area Network (LPWAN) coverage. The study concludes that (i) the physical device developed can operate at a city scale; (ii) some low-cost PM sensors are viable for monitoring AQ and for detecting PM trends; (iii) LoRaWAN is suitable for city scale sensor coverage where connectivity is an issue. Based on the findings from this first pilot project, a larger LoRaWAN enabled AQ sensor network is being deployed across the city of Southampton in the UK.

The in vitro zebrafish heart as a model to investigate the chronotropic effects of vapor anesthetics.

In addition to their intended clinical actions, all general anesthetic agents in common use have detrimental intrasurgical and postsurgical side effects on organs and systems, including the heart. The major cardiac side effect of anesthesia is bradycardia, which increases the probability of insufficient systemic perfusion during surgery. These side effects also occur in all vertebrate species so far examined, but the underlying mechanisms are not clear. The zebrafish heart is a powerful model for studying cardiac electrophysiology, employing the same pacemaker system and neural control as do mammalian hearts. In this study, isolated zebrafish hearts were significantly bradycardic during exposure to the vapor anesthetics sevoflurane (SEVO), desflurane (DES), and isoflurane (ISO). Bradycardia induced by DES and ISO continued during pharmacological blockade of the intracardiac portion of the autonomic nervous system, but the chronotropic effect of SEVO was eliminated during blockade. Bradycardia evoked by vagosympathetic nerve stimulation was augmented during DES and ISO exposure; nerve stimulation during SEVO exposure had no effect. Together, these results support the hypothesis that the cardiac chronotropic effect of SEVO occurs via a neurally mediated mechanism, while DES and ISO act directly upon cardiac pacemaker cells via an as yet unknown mechanism.

L-Carnitine/Simvastatin Reduces Lipoprotein (a) Levels Compared with Simvastatin Monotherapy: A Randomized Double-Blind Placebo-Controlled Study.

Lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. There are currently limited therapeutic options to lower Lp(a) levels. L-Carnitine has been reported to reduce Lp(a) levels. The aim of this study was to compare the effect of L-carnitine/simvastatin co-administration with that of simvastatin monotherapy on Lp(a) levels in subjects with mixed hyperlipidemia and elevated Lp(a) concentration. Subjects with levels of low-density lipoprotein cholesterol (LDL-C) >160 mg/dL, triacylglycerol (TAG) >150 mg/dL and Lp(a) >20 mg/dL were included in this study. Subjects were randomly allocated to receive L-carnitine 2 g/day plus simvastatin 20 mg/day (N = 29) or placebo plus simvastatin 20 mg/day (N = 29) for a total of 12 weeks. Lp(a) was significantly reduced in the L-carnitine/simvastatin group [-19.4%, from 52 (20-171) to 42 (15-102) mg/dL; p = 0.01], but not in the placebo/simvastatin group [-6.7%, from 56 (26-108) to 52 (27-93) mg/dL, p = NS versus baseline and p = 0.016 for the comparison between groups]. Similar significant reductions in total cholesterol, LDL-C, apolipoprotein (apo) B and TAG were observed in both groups. Co-administration of L-carnitine with simvastatin was associated with a significant, albeit modest, reduction in Lp(a) compared with simvastatin monotherapy in subjects with mixed hyperlipidemia and elevated baseline Lp(a) levels.

Pharmacological management of diabetic dyslipidemia.

INTRODUCTION: Diabetes mellitus is associated with increased cardiovascular disease (CVD) risk. Areas covered: Main goal of hypolipidemic treatment in diabetic patients is low-density lipoprotein cholesterol (LDL-C) lowering with the use of statins. Addition of ezetimibe is useful in diabetic patients who cannot achieve their LDL-C target. However, many diabetic patients have increased residual CVD risk, which is mainly attributed to high triglycerides and low high-density lipoprotein (HDL-C) values. The addition of fenofibrate targets these variables and possibly reduces residual CVD risk, but a possible beneficial effect has been shown only in a pre-specified subgroup analysis in patients with high triglycerides and low HDL-C values. The newer proprotein convertase subtilisin/kexin type 9 inhibitors lower substantially LDL-C levels, but data from specifically designed trials in diabetic patients are not currently available. Although the cholesterol ester transfer protein (CETP) inhibitors have shown harmful effects or lack of efficacy in completed clinical trials, the newer CETP inhibitors have promising effects on lipid profile and carbohydrate metabolism, but their effects on CVD risk and safety profile have not been assessed. Expert commentary: Clinicians have a range of pharmacological options to reduce the CVD risk of diabetic patients.

Data on horizontal and vertical movements of zebrafish during appetitive conditioning.

This article provides supporting data for the research article "A simple automated system for appetitive conditioning of zebrafish in their home tanks" (J.M. Doyle, N. Merovitch, R.C. Wyeth, M.R. Stoyek, M. Schmidt, F. Wilfart, A. Fine, R.P. Croll, 2016) [1]. In that article, we described overall movements of zebrafish toward a food source as a response to auditory or visual cues as conditioned stimuli in a novel learning paradigm. Here, we describe separate analyses of the vertical and horizontal components of the learned response. These data provide evidence that the conditioning might result from both classical conditioning of an innate response of zebrafish to move to the surface in response to food cues and secondary conditioning of the fish to associate a food presentation with a specific location in the tank. Movement data from the twenty trial acquisition period and probe trials from 2-32 days post conditioning are included.

Anticoagulant drugs: what is new?

Heparins and vitamin K antagonists have been the cornerstones of anticoagulation treatment for several decades. Despite their effectiveness, these agents have limitations which can include food and drug interactions and the need for monitoring. It follows that there is a need for new anticoagulants. There are numerous promising agents at various stages of evaluation. Those in the most advanced stages of development are the oral factor Xa and the thrombin inhibitors, which are the focus of this review.

Valores hematológicos de referencia en caninos adultos aparentemente sanos, que concurren a una clínica privada de Asunción / Hematological reference values in apparently healthy adult dogs attending a private clinic in Asuncion

El hemograma es el examen de laboratorio de mayor uso diagnóstico en el canino, por lo que se hace necesario disponer de valores referenciales adecuados para poder interpretar correctamente los resultados y así obtener una conclusión válida. El presente estudio tiene como objetivo determinar los valores hematológicos en caninos adultos aparentemente sanos en la ciudad de Asunción. Este estudio descriptivo de corte transversal se desarrolló en un grupo de caninos aparentemente sanos, pacientes habituales de la Clínica “Tacuary 2”. Se determinaron los valores hematológicos de 100 caninos adultos de 23 razas diferentes por técnicas manuales. Los valores de referencia se hallaron utilizando el método clásico o parámetrico que se calcula en base al valor de la media, más menos el doble de la desviación típica (x ± 2s). Los valores fueron número de eritrocitos (4,3 - 7,1 x 106/µL), hemoglobina (9,2 - 15,6 g/dL), hematocrito (28,2 - 48,2 %), VCM (63 - 71 fL), CHCM (30 - 35 g/dL), HCM (20 - 23 pg), número de leucocitos (7,8 - 12,5 x 103/µL), neutrófilos segmentados (62 - 86%), (5,7 - 9,3 x 103/µL), neutrófilos en banda (0 -2%), (0 - 231 x 103/µL), eosinófilos (0 - 5 %), (0 - 0,56 x 103/µL), linfocitos (11 - 29%), (1 - 3 x103/µL), monocitos (0 - 7,6%), (0 - 0.4 x 103/µL), proteína total (4,5 - 7,05 g/L).Llama la atención los valores más bajos de eritrocitos, hemoglobina, hematocrito y proteína total de los individuos estudiados al compararlos a los reportados por la literatura.

The hemogram is the laboratory test most commonly used for diagnosis in dogs, therefore it is necessary to have adequate reference values to interpret correctly the results and obtain a valid conclusion.The objective of the present study is to determine the hematological values in apparently healthy adult dogs in the city of Asuncion. This cross-sectional descriptive study was performed in a group of apparently healthy dogs, regular patients of the Clinic "Tacuary 2" The hematologic values of 100 adult dogs of 23 different breeds were determined by manual techniques.The reference values were found using the classical or parametric method which is calculated based on the mean value plus minus twice the standard deviation (x±2s). The values were number of erythrocytes (4.3 - 7.1 x 106/µl), hemoglobin (9.2 - 15.6 g/dl), hematocrit (28.2 - 48.2%), MCV (63 - 71 fL), MCHC (30 - 35 g/dL), MCH (20 - 23 pg), number of leukocytes (7.8 - 12.5 x 103/µL), segmented neutrophils (62 - 86%), (5.7 - 9.3 x 103/µL), band neutrophils (0 -2%), (0 - 231 x 103/µL), eosinophils (0 - 5%), (0 to 0.56 x 103/µL), lymphocytes (11 - 29%), (1 - 3 x103/µL), monocytes (0 - 7.6%) (0 - 0.4 x 103/µL), total protein (4.5 to 7.05 g/L). It should be noticed the lower values of erythrocytes, hemoglobin, hematocrit and total protein of the study population when compared to those reported in the literature.

Fenofibrate in primary biliary cirrhosis: a pilot study.

BACKGROUND: Most patients with primary biliary cirrhosis (PBC) are treated with ursodeoxycholic acid (UDCA); however, some do not respond fully. PBC is also associated with dyslipidemia, but a link with vascular risk has not been confirmed. METHODS AND RESULTS: In this study we compared UDCA monotherapy with fenofibrate plus UDCA in PBC patients with incomplete biochemical response to UDCA monotherapy for >/= 8 months. Ten patients (57.2+/-13.3 years old) with PBC and persistent elevations of liver enzymes after treatment with UDCA (600 mg/day) were randomized to continue UDCA (4 patients) or to receive micronized fenofibrate (200 mg/day) plus UDCA (6 patients) for 8 weeks. Significant reductions in total cholesterol, triglycerides and non-high density lipoprotein cholesterol were observed in the combination treatment group. The serum activities of alkaline phosphatase, gamma-glutamyl transpeptidase and alanine aminotranferase also decreased in this group compared with baseline (-32.6%; p=0.012, -44%; p=0.031 and -16.9%; p=0.029, respectively). In contrast, no significant alterations in liver enzymes or lipid profile were observed in patients who continued UDCA monotherapy. The changes in the lipid and enzyme variables differed significantly (p<0.03) between the 2 groups. Fenofibrate was well tolerated. CONCLUSIONS: The administration of fenofibrate plus UDCA seems to be safe and may improve lipid and liver indices in patients with PBC who do not respond fully to UDCA monotherapy. Whether the improved lipid profile translates into a decreased risk of vascular events remains to be established.

Aliskiren, a direct renin inhibitor, in clinical practice: a new approach in the treatment of hypertension.

OBJECTIVE: Arterial hypertension is an important risk factor for the development and progression of cardiovascular disease (CVD). The renin angiotensin aldosterone system (RAAS) plays a crucial role in the pathophysiology of hypertension and associated complications. Direct renin inhibitors (DRIs) are novel antihypertensive drugs which inhibit the first step of RAAS. Aliskiren is the first orally active DRI approved as monotherapy or in combination with other antihypertensive agents for the treatment of hypertension. SCOPE: This article reviews the efficacy and safety of aliskiren as monotherapy and in combination with other antihypertensive agents and comments on its potential role in clinical practice. METHODS: Relevant articles were identified through a PubMed search (up to 17 August 2009). FINDINGS: Aliskiren, used alone or in combination with other antihypertensive agents, has a favourable effect on blood pressure (BP). Specifically, aliskiren is equally effective with other RAAS inhibitors and probably superior to hydrochlorothiazide in the reduction of systolic and diastolic BP. The combination of aliskiren with other antihypertensive drugs seems to be an effective and safe therapeutic option. In addition, aliskiren may have favourable effects in terms of ameliorating several microvascular and macrovascular complications of hypertension and diabetes. CONCLUSIONS: Aliskiren appears to be an effective and safe antihypertensive drug. Whether the BP lowering effect of aliskiren is associated with improvements in cardiovascular outcomes remains to be elucidated.

Drug combinations for dyslipidemia and obesity treatment in metabolic syndrome.

Metabolic syndrome (MetS) is a cluster of risk factors, each one individually associated with increased cardiovascular disease risk. Treatment of all components of MetS is expected to result in reduced risk. Treatment of MetS mainly includes lifestyle changes. In addition, drug therapy may be considered, especially combinations of different drugs, in order to tackle all the features of MetS. We review the therapeutic strategies currently used for obesity and dyslipidemia treatment in patients with MetS, with a focus on drug combinations.

TLR2 engagement on memory CD8(+) T cells improves their cytokine-mediated proliferation and IFN-gamma secretion in the absence of Ag.

Persistence of memory CD8(+) T cells is known to be largely controlled by common gamma chain cytokines, such as IL-2, IL-7 and IL-15. However, other molecules may be involved in this phenomenon. We show here that TLR2(-/-) mice have a decreased frequency of memory phenotype CD8(+) T cells when compared with WT mice. This prompted us to investigate the role of TLR2 in the homeostasis of memory CD8(+) T cells. We describe here a new TLR2-dependent mechanism which, in the absence of specific antigen, directly controls memory CD8(+) T-cell proliferation and IFN-gamma secretion. We demonstrate that TLR2 engagement on memory CD8(+) T cells increases their proliferation and expansion induced by IL-7 both in vitro and in vivo. We also show that TLR2 ligands act in synergy with IL-2 to induce IFN-gamma secretion in vitro. Both conclusions are obtained with spontaneously arising memory phenotype and antigen-specific memory CD8(+) T cells. Altogether, our data support the idea that continuous TLR2 signaling in response to microbial stimuli or endogenous danger signals might directly contribute to the maintenance of the diversity memory CD8(+) T cells in the organism.

Effect of rimonabant, micronised fenofibrate and their combination on cardiometabolic risk factors in overweight/obese patients: a pilot study.

OBJECTIVE: To assess the effect of rimonabant, micronised fenofibrate and their combination on anthropometric and metabolic parameters in overweight/obese patients with dyslipidaemia. METHODS: All patients (n = 30) received a hypocaloric diet ( approximately 600 kcal/day deficit) and were randomly allocated to receive open-label rimonabant (R) 20 mg/day (n = 10), micronised fenofibrate (F) 200 mg/day (n = 10) or rimonabant 20 mg/day plus fenofibrate 200 mg/day (RF) (n = 10). Anthropometric and metabolic parameters were assessed at baseline and 3 months after treatment initiation. RESULTS: Compared with baseline similar significant reductions in body weight, body mass index and waist circumference were observed in the R (-6, -5 and -5%, respectively; p < 0.01) and RF group (-5% for all, p < 0.05), while improvements in these parameters were smaller in the F group (-2, -2.5 and -2%, respectively; p < 0.05). Triglycerides were reduced by 18% in the R group (p = NS), by 39% in the F group (p < 0.001) and by 46% in the RF group (p < 0.05). Importantly, combination treatment resulted in a 42% increase in high-density lipoprotein cholesterol (HDL-C) levels (p < 0.05), while HDL-C was not significantly altered in the two monotherapy groups. Subsequently, a more pronounced increase in apolipoprotein A-I (ApoA-I) levels (+25%) was observed in the RF group compared with changes in both monotherapy groups (p < 0.0001 vs R and p < 0.005 vs F group). Low-density lipoprotein cholesterol (LDL-C) levels were not significantly altered in any group. Apolipoprotein B (apoB) levels were reduced in all groups and this reduction was significantly more pronounced in the RF group (p < 0.05 vs baseline as well as p < 0.005 and p < 0.01 for RF vs R and F groups, respectively). ApoB/apoA-I ratio decreased by 3% with R (p = NS), by 18% with F (p < 0.05) and by 40% with RF treatment (p < 0.01). Total cholesterol to HDL-C ratio decreased by 20% with F (p < 0.0001) and by 33% with RF therapy (p < 0.005), while it was not significantly altered in R group. CONCLUSION: The combination of rimonabant and fenofibrate may further improve metabolic parameters in overweight/obese patients with dyslipidaemia compared with each monotherapy. This improvement is particularly pronounced for HDL-C levels.

Sitagliptin in clinical practice: a new approach in the treatment of type 2 diabetes.

BACKGROUND: Sitagliptin is a novel agent for the treatment of type 2 diabetes either as monotherapy or in combination with metformin or a thiazolidinedione. OBJECTIVE: To review the efficacy and safety of sitagliptin in clinical trials and comment on drug interactions and safety issues arising from its use. METHODS: Relevant articles were identified through a PubMed search (up to May 2008). RESULTS/CONCLUSIONS: Sitagliptin either used alone or in combination with other hypoglycemic agents has a favorable glucose-lowering effect and safety profile. It has been associated with few side effects, mainly involving the gastrointestinal system and with a low incidence of hypoglycemia, while it generally demonstrated a neutral effect on body weight. Sitagliptin is a safe alternative or complementary option for patients with type 2 diabetes who do not reach the recommended glycosylated hemoglobin level with lifestyle interventions and/or current oral antidiabetic agents.

Fibrate-associated adverse effects beyond muscle and liver toxicity.

Fibrate derivatives have a 40-year history in the management of dyslipidemia. Although this class of drugs is generally well tolerated, several safety issues have arisen from their use. In the present article we review the literature describing side effects associated with the use of fibrates except for those that are liver and muscle related. These effects are less well known but are clinically relevant.

Colesevelam hydrochloride in clinical practice: a new approach in the treatment of hypercholesterolaemia.

OBJECTIVE: Hypercholesterolaemia is a major risk factor for atherosclerosis and coronary heart disease. Treatment with lipid lowering agents reduces the risk of vascular events. Colesevelam is a novel bile acid sequestrant (BAS) indicated for the treatment of hypercholesterolaemia, either as monotherapy or in combination with statins. SCOPE: This article reviews the efficacy, tolerability and safety of colesevelam in clinical practice. The literature search was based on a PubMed search up to January 2008. FINDINGS: Colesevelam, used alone or in combination with other hypolipidaemic agents (statins, ezetimibe and fenofibrate), has an overall favourable effect on lipid profile. Specifically, colesevelam reduces total and low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B levels and increases high-density lipoprotein cholesterol and apolipoprotein AI. However, colesevelam may slightly raise triglyceride levels. Colesevelam can improve glycaemic control in diabetic patients. Moreover, it may have anti-inflammatory properties, as it can reduce high sensitivity C-reactive protein concentration. Colesevelam almost lacks the intense side effects of previously used BASs, thus resulting in better patient compliance. However, the dose regimen consisting of up to 7 tablets/day and high cost may limit its use. CONCLUSIONS: Colesevelam is a safe alternative for those intolerant to other lipid lowering medication. This BAS also provides an option for patients who do not reach their LDL-C goal despite treatment with a statin.