Bilateral orbital myositis in a patient with rheumatoid arthritis on treatment with tofacitinib: a report and review of literature.

Orbital myositis is a rare inflammatory condition affecting the extraocular muscles of the eyes. It has also been linked to systemic autoimmune diseases. We present a case of orbital myositis in a 57-year-old male undergoing treatment for rheumatoid arthritis (RA) with tofacitinib, a Janus kinase inhibitor (JAK). Prompt administration of intravenous steroids led to rapid symptom improvement. To date, only six published cases have documented the association between RA and orbital myositis. This is the first description of orbital myositis occurring during treatment with the anti-inflammatory drug tofacitinib, an increasingly used disease-modifying anti-rheumatic drug (DMARD). We review the literature and emphasize the importance of ongoing vigilance regarding adverse events linked to tofacitinib.

Simple method for estimating the fractional Raman contribution.

We propose a novel and simple method for estimating the fractional Raman contribution, fR, based on an analysis of a full model of modulation instability (MI) in waveguides. An analytical expression relating fR to the MI peak gain beyond the cutoff power is explicitly derived, allowing for an accurate estimation of fR from a single measurement of the Raman gain spectrum.

Optical diagnostics studies of air flow and powder fluidisation in Nexthaler®. Part II: Use of fluorescent imaging to characterise transient release of fines from a dry powder inhaler.

The fine particle fraction is a key indicator of therapeutic effectiveness of inhaled pharmaceutical aerosols. This paper presents a fluorescence imaging technique to visualise and characterise the emission of active pharmaceutical ingredient (API) fines in model formulations containing coarse lactose carrier and 1.5-2 µm diameter fluorescent microspheres (model API fines). A two-camera arrangement was used to acquire simultaneous images of spatial and temporal distribution of model API fines and fluidised powder formulation near the mouthpiece exit of a DPI. Digital image analysis showed that the model API fines were released along with the bulk of the powder dose. More rapidly accelerating airflows were found to cause earlier release of API fines. The fluorescence imaging technique analyses a substantial fraction of the aerosol plume and was found to provide effective time-resolved characterisation of the de-aggregation and release of API fines with consistent results across a wide range of model API concentrations. Future studies should demonstrate the usefulness of the fluorescence imaging technique across different formulations and DPI devices.

40 Gb/s indoor optical wireless system enabled by a cyclically arranged optical beamsteering receiver.

Indoor optical wireless communication with optical beamsteering capability is currently attracting a lot of attention. One major two-dimensional (2D) optical beamsteering scheme is realized by 2D grating or its active counterpart, which is usually based on a spatial light modulator (SLM). However, there is a fundamental trade-off between the field of view (FoV) and power efficiency due to the inherent feature of gratings. In this Letter, we propose a new class of 2D beamsteering, named cyclically arranged optical beamsteering (CAO-BS), which can break that trade-off. Traditional 2D gratings extend the optical beam in the Cartesian coordinates (1D grating in horizontal + 1D grating in vertical), while CAO-BS extends the optical beam in the polar coordinates (1D grating + angular rotation). Since only 1D grating is engaged, the power efficiency increases with the number of grating lobes reduced. In the polar coordinates, the angle rotation tuning in a SLM is quasi-continuous in a full 2π range. The CAO-BS is demonstrated at the receiving end in an indoor experimental system. The FoV is 18° by 360° in polar coordinates without any additional mechanical parts. Based on the CAO-BS, 40 Gbit/s on-off keying data is also successfully transmitted over 1 km single-mode fiber and 0.5 m free space.

Point-by-point femtosecond laser micro-processing of independent core-specific fiber Bragg gratings in a multi-core fiber.

Four 3rd order fiber Bragg gratings were inscribed into separate cores of a 7 core multi-core fiber using the point-by-point inscription technique. A 1030 nm, 206 ± 5 fs laser was used, operating at a frequency of 1 kHz and pulse energy of 2.1 ± 0.2 µJ. Independent Bragg resonances at λB = 1541.01 ± 0.02, 1547.82 ± 0.02, 1532.66 ± 0.02, and 1537.42 ± 0.02 nm and extinction ratios of 13.97 ± 0.4, 16.02 ± 0.4, 10.08 ± 0.4 and 13.40 ± 0.4 dB were recorded. Our data analysis shows that refractive index changes, Δn, of the order 10-3 were induced. Core-specific inscription of fiber Bragg gratings in a multi-core fiber can provide a flexible and versatile platform to address the needs of recent space division multiplexed transmission and optical sensor networks.

Orbital angular momentum beam excitation using an all-fiber weakly fused mode selective coupler.

Orbital angular momentum beam excitation through direct phase-matched coupling is experimentally demonstrated using an all-fiber weakly fused mode selective coupler consisting of a single-mode fiber and a ring-core fiber. Experimental results showing the excited OAM mode purity of up to 75% measured through the standard ring technique not only demonstrate the proof of concept but also provide a baseline for further improvement.

Pathogenic Escherichia coli and enteric viruses in biosolids and related top soil improvers in Italy.

AIMS: To investigate the presence of genomic traits associated with a set of enteric viruses as well as pathogenic Escherichia coli in top soil improvers (TSI) from Italy. METHODS AND RESULTS: Twenty-four TSI samples originating from municipal sewage sludges, pig manure, green and household wastes were analysed by real time PCR for the presence of hepatitis E virus (HEV), porcine and human adenovirus (HuAdV), norovirus, rotavirus and diarrhoeagenic E. coli. None of the samples was found positive for HEV or rotavirus. Four samples were positive for the presence of nucleic acids from human norovirus, two of them being also positive for HuAdV. Real time PCR screening gave positive results for many of the virulence genes characteristic of diarrhoeagenic E. coli in 21 samples. These included the verocytotoxin-coding genes, in some cases associated with intimin-coding gene, and markers of enteroaggregative, enterotoxigenic and enteroinvasive E. coli. CONCLUSIONS: These results provide evidence that enteric viruses and pathogenic E. coli may be released into the environment through the use of sludge-derived TSI. SIGNIFICANCE AND IMPACT OF THE STUDY: The results highlight that the TSI-related environmental risk for the food chain should be more deeply assessed.

Exploring the impact of sample flowrate on in vitro measurements of metered dose inhaler performance.

Pharmacopoeial methods for measurement of the aerodynamic particle size distribution (APSD) of metered dose inhalers (MDIs) by cascade impaction specify a sampling flow rate of 28.3L/min. However, there is little data within the literature to rationalize this figure, or to support its clinical relevance. In addition, the standard United States Pharmacopoeia Induction Port (USP IP) used for testing is known to inaccurately reflect deposition behavior in the upper airway, further compromising the relevance of testing, for product development. This article describes experimental studies of the effect of sampling flow rate on APSD data gathered using an Andersen Cascade Impactor (ACI). Tests were carried out using two different formulations to assess the influence of formulation composition. In addition, comparative testing with an Alberta Idealised Throat, in place of the USP IP, to ensure more realistic representation of the upper airway. The results show how measured APSD and fine particle dose, the dose than on the basis of size would be expected to deposit in the lung, vary as a function of test methodology, providing insight as to how the testing can be modified towards greater clinical relevance.

Cluster categorization of urban roads to optimize their noise monitoring.

Road traffic in urban areas is recognized to be associated with urban mobility and public health, and it is often the main source of noise pollution. Lately, noise maps have been considered a powerful tool to estimate the population exposure to environmental noise, but they need to be validated by measured noise data. The project Dynamic Acoustic Mapping (DYNAMAP), co-funded in the framework of the LIFE 2013 program, is aimed to develop a statistically based method to optimize the choice and the number of monitoring sites and to automate the noise mapping update using the data retrieved from a low-cost monitoring network. Indeed, the first objective should improve the spatial sampling based on the legislative road classification, as this classification is mainly based on the geometrical characteristics of the road, rather than its noise emission. The present paper describes the statistical approach of the methodology under development and the results of its preliminary application to a limited sample of roads in the city of Milan. The resulting categorization of roads, based on clustering the 24-h hourly L Aeqh, looks promising to optimize the spatial sampling of noise monitoring toward a description of the noise pollution due to complex urban road networks more efficient than that based on the legislative road classification.

Potential impact on food safety and food security from persistent organic pollutants in top soil improvers on Mediterranean pasture.

The organic carbon of biosolids from civil wastewater treatment plants binds persistent organic pollutants (POPs), such as polychlorodibenzo -dioxins and -furans (PCDD/Fs), dioxin and non-dioxin -like polychlorobiphenyls (DL and NDL-PCBs), polybrominated diphenyl ethers (PBDEs), and perfluorooctane sulfonic acid (PFOS). The use of such biosolids, derived digestates and composts as top soil improvers (TSIs) may transfer POPs into the food chain. We evaluated the potential carry-over of main bioavailable congeners from amended soil-to-milk of extensive farmed sheep. Such estimates were compared with regulatory limits (food security) and human intakes (food safety). The prediction model was based on farming practices, flocks soil intake, POPs toxicokinetics, and dairy products intake in children, of the Mediterranean area. TSI contamination ranged between 0.20-113 ng WHO-TEQ/kg dry matter for PCDD/Fs and DL-PCBs (N = 56), 3.40-616 µg/kg for ∑6 NDL-PCBs (N = 38), 0.06-17.2 and 0.12-22.3 µg/kg for BDE no. 47 and no. 99, 0.872-89.50 µg/kg for PFOS (N = 27). For a 360 g/head/day soil intake of a sheep with an average milk yield of 2.0 kg at 6.5% of fat percentage, estimated soil quality standards supporting milk safety and security were 0.75 and 4.0 ng WHO-TEQ/kg for PCDD/Fs and DL-PCBs, and 3.75 and 29.2 µg/kg for ∑6 NDL-PCBs, respectively. The possibility to use low-contaminated TSIs to maximize agriculture benefits and if the case, to progressively mitigate highly contaminated soils is discussed.

Optical diagnostics study of air flow and powder fluidisation in Nexthaler®--Part I: Studies with lactose placebo formulation.

Effective drug delivery to the lungs by a DPI device requires the air-stream through the device to have sufficient power to aerosolise the powder. Furthermore, sufficient turbulence must be induced, along with particle-wall and particle-particle collisions, in order to de-aggregate small drug particles from large carrier particles. As a result, the emitted and the fine particle doses produced by many commercially available DPI devices tend to be strongly affected by the natural inter-patient variability of the inhaled air flow. The Nexthaler® is a multi-dose breath-actuated dry-powder inhaler with minimum drug delivery-flow rate dependency and incorporating a dose protector. The actuation mechanism of the dose-protector ensures that the dose is only exposed to the inhaled air flow if the flow has sufficient power to cause complete aerosolisation. For this study, a proprietary lactose placebo powder blend was filled into "transparent" Nexthaler® to allow application of high-speed imaging and particle image velocimetry (PIV) techniques to successfully interrogate and reveal details of the powder entrainment and emission processes coupled with characterisation of the flow environment in the vicinity of the mouthpiece exit. The study showed that fluidisation of the bulk of the powder occurs very quickly (∼20ms) after withdrawal of the dose protector followed by powder emission from the device within ∼50ms thereafter. The bulk of the metered placebo dose was emitted within 100-200ms. The visualisation study also revealed that a very small fraction of powder fines is emitted whilst the dose protector still covers the dosing cup as the flow rate through the device accelerates. The PIV results show that the flow exiting the device is highly turbulent with a rotating flow structure, which forces the particles to follow internal paths having a high probability of wall impacts, suggesting that the flow environment inside the Nexthaler® DPI will be very beneficial for carrier-drug de-aggregation.

Exposure to priority organochlorine contaminants in the Italian general population. Part 2: Fifteen priority polychlorinated biphenyl congeners in blood serum.

Concentrations of 36 polychlorinated biphenyl (PCB) congeners were measured in serum of 372 Italian residents of general population living in Novafeltria, Pavia, and Milan. Total PCB level differed significantly between these sites (p < 0.0001) with median concentrations of 836.50, 1354.57, and 2062.08 pmol/g lipid, respectively. However, there is no evidence for the difference in distribution of total PCB levels by genders. Total dioxin-like PCBs differed significantly (p < 0.0001) between the sites (median 109.78, 50.88, and 166.99 pmol/g lipid, respectively) and genders of Novafeltria and Pavia (p = 0.011 and 0.009, respectively). PCB 138, 153, 170, and 180 differed significantly between the places of residence (p < 0.0001) with higher values in Milan population. In the overall population, total PCB and PCB 138, 153, 156, 170, and 180 correlated positively with age (correlations range between 0.320 and 0.569, p < 0.0001). In Novafeltria, the correlations ranged between 0.545 and 0.670, and in Pavia, the correlations ranged between 0.516 and 0.666. In Milan, correlations with age range between 0.327 and 0.417 for total PCB and congeners 138, 153, and 180. With an exception of PCB 170, there was no evidence of significant difference in the distribution of most abundant PCB congeners and total PCB across the body mass index categories.

Simultaneous measurement of the microscopic dynamics and the mesoscopic displacement field in soft systems by speckle imaging.

The constituents of soft matter systems such as colloidal suspensions, emulsions, polymers, and biological tissues undergo microscopic random motion, due to thermal energy. They may also experience drift motion correlated over mesoscopic or macroscopic length scales, e.g. in response to an internal or applied stress or during flow. We present a new method for measuring simultaneously both the microscopic motion and the mesoscopic or macroscopic drift. The method is based on the analysis of spatio-temporal cross-correlation functions of speckle patterns taken in an imaging configuration. The method is tested on a translating Brownian suspension and a sheared colloidal glass.

Dual mode fused optical fiber couplers suitable for mode division multiplexed transmission.

We experimentally demonstrate 2 × 2 and 3 × 3 fused fiber couplers made from dual mode fiber. A unique mode dependent power transfer characteristics as a function of pulling length is obtained that support various optical functionalities. Exploiting this we demonstrate several devices of interest for mode division multiplexed data transmission including LP11 mode filter, LP11 mode tap coupler, and 50:50 power splitter for both LP01 and LP11 modes.

Exposure to priority organochlorine contaminants in the Italian general population. Part 1. Eight priority organochlorinated pesticides in blood serum.

Despite extensive use of organochlorinated pesticides (OCPs) such as dichlorodiphenyltrichloroethane (DDT) in Italy in the 1940s to 1970s, especially for public health control of malaria mosquitoes, information on their exposure levels among the general population is limited. These OCPs can be a source of health risk to human. A total of 137 blood samples were collected from residents of the general population of three Italian towns, Novafeltria, Pavia and Milan, to determine the levels of eight OCPs in blood serum. The concentrations of beta-hexachlorocyclohexane, hexachlorobenzene (HCB), 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethylene, 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE), 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane, 1,1-dichloro-2,2-bis (4-chlorophenyl)ethane, 1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)-ethane and 1,1,1-trichloro-2,2-bis(p-chlorophenyl) ethane were measured by gas chromatography-mass spectrometry. Variations in serum concentrations of OCPs with respect to place of residence, gender, age and body mass index (BMI) were evaluated by non-parametric tests. p,p'-DDE and HCB were the most abundant and major contributors of total OCP concentration. Their levels differed significantly between the three towns with a trend Milan > Novafeltria > Pavia (p < 0.0001). Females had significantly higher concentrations of HCB and p,p'-DDE than males in the overall population sample. HCB concentrations were significantly higher in females than in males of Milan (p = 0.029). We observed positive correlations of p,p'-DDE and HCB with age in Novafeltria subjects (r = 0.468, p = 0.004). Total OCP concentrations differed significantly across BMI categories (p = 0.018) in overall population. We have demonstrated a clear pattern of the main OCPs in a fairly large population. Generally, our study provides information on OCPs exposure among the Italian general population and provides indications for further investigations.

Impact of body mass index and waist circumference on the cardiovascular risk and all-cause death in a general population: data from the PAMELA study.

BACKGROUND AND AIMS: Elevated values of body mass index (BMI) and waist circumference (WC) are associated with an augmented cardiovascular (CV) risk. It is debated, however, whether and to what extent this depends on the body fat increase 'per se' or on the related cardiometabolic alterations. METHODS AND RESULTS: In 2005 subjects randomly selected from the general population of Monza (Italy), we assessed BMI, WC, office, home and 24 h blood pressure (BP), heart rate and metabolic variables. The impact of BMI and WC on the incidence of CV events, CV and all-cause mortality was estimated during a 148-month follow-up. Progressively higher values of BMI and WC were associated with a progressive increase in office, home and 24 h BP and in erratic BP variability (P < 0.0001 for trend). Metabolic variables were directly and significantly (P < 0.0001) related to BMI and WC, while an inverse significant relationship was detected with high-density lipoprotein (HDL)-cholesterol. The incidence of CV events, CV and all-cause deaths increased progressively from the lowest to the highest quintile of BMI and WC (P for trend always <0.005). Baseline BMI and WC higher by respectively 1 kg m⁻² and 1 cm were associated with an increased risk of CV events, CV and all-cause death by 8%, 12% and 7% (for baseline BMI) and 4%, 5% and 4% (for baseline WC), respectively. After adjustment for confounders, only the increased risk of CV death related to higher baseline BMI remained significant (hazard ratio (HR) 1.062, confidence interval (CI) 95% 1.003-1.126, P < 0.05). CONCLUSION: The adverse prognostic impact of the accumulation of body fat is mediated by the associated haemodynamic and metabolic alterations. Baseline values of BMI, however, are an independent predictor of CV mortality.

Polychlorinated dibenzodioxins, dibenzofurans, and biphenyls in fresh water fish from Campania Region, southern Italy.

Twenty-eight fish muscle specimens from the main water bodies of the Campania Region were analyzed in our laboratory. On average, results showed a low contamination by PCDDs+PCDFs and a relatively more important presence of DL-PCBs. All specimens were compliant with EU regulatory maximum levels. Cumulative PCDD+PCDF+DL-PCB concentrations (TEQ(TOT)) were comprised in the range 0.223-11.4 pgWHO(97)-TEQ g(-1) fresh weight (fw). DL-PCB contribution to TEQ(TOT) was on average greater than 86% (range, 50.2-97.1%). The cumulative concentrations of 30 non-dioxin-like PCB congeners (Σ(30)(NDL-PCBs)) and of the six indicators (Σ(6)(NDL-PCBs)) were respectively in the ranges 3.30-515 and 1.30-195 ng g(-1) fw. The hybrid clustering approach adopted to analyze the sample-specific congener profiles indentified the main analytical patterns present in the database and, in particular, two main diverse exposure macro-areas that seem to exist north and south of the city of Naples. The distribution of PCDD and PCDF congeners among different species showed significant variations from chub (Leuciscus cephalus), characterized by a higher proportion of low-chlorinated congeners (e.g. 2,3,7,8-T(4)CDD), to eel (Anguilla anguilla), whose contamination consisted mainly of highly chlorinated congeners (e.g. O(8)CDD). To have a more complete perspective in relation to the contaminants present in the environment, the study suggestion is to use benthic as well as pelagic species to obtain an integrated characterization of fish tissue contamination.

Psychiatric disorders in patients suffering from an acute cerebrovascular accident or traumatic injury, and their effects on rehabilitation: an observational study.

BACKGROUND: The presence of a post-traumatic psychiatric disorder in patients with acute injuries may have adverse effects on outcomes. AIM: In this study our aims were: (1) to assess the frequency of psychiatric disorders after a cerebrovascular accident or traumatic injury requiring rehabilitation; (2) to examine whether there was any correlation between psychiatric disorders and patients' baseline demographic and clinical variables. DESIGN: The study consisted of two phases: the first was cross-sectional and the second prospective with a 12-month follow-up. The period of recruitment was two years. The results of the first phase are presented here. SETTING: The study sample consisted of a consecutive series of patients admitted to hospital because of an acute cerebrovascular accident or a traumatic injury and referred for a rehabilitation program. Two inpatient Rehabilitation Hospitals were involved in the study. POPULATION: The sample consisted of 230 consecutive patients with a recent cerebrovascular accident or trauma included in a rehabilitation program. METHODS: The sample included: 89 men (39%) and 141 women (61%) aged 20-97 years. Psychiatric disorders and motor disabilities were assessed through psychiatric interview and the mini-international neuropsychiatric interview plus (MINI Plus) and, respectively, with the functional independent measure (FIM). In case of post-traumatic stress disorder (PTSD), severity was assessed through the Davidson's Trauma scale. Psychiatric disorders were correlated to demographic and clinical variables through univariate and multivariate analyses, the latter with logistic regression models. RESULTS: The most frequent entry diagnoses were traumatic fracture (41.3%) and stroke (37.0%). Ninety-three patients (40.4%) had one or more psychiatric disturbances at study entry, the commonest being depression (56 cases, 24.7%) and anxiety (23 cases, 10.0%). PTSD was present in 8 cases (3.5%). A history of psychiatric disorder was reported by 55 patients (24.2%) Compared to the rest of the study population, these subjects had more psychopathologic complaints (P<0.001). Mean total FIM score was 54.4 (SD=17.8) and 61.2 (SD=19.6) in patients with and without psychopathology (P<0.01) Independent predictors of psychopathology included past psychiatric history, lower total FIM scores, and limb amputation. Depression was predicted by history of psychiatric disorders and lack of partner. CONCLUSION: History of psychiatric disorders is the most relevant factor associated with psychopathology in patients with an acute cerebrovascular accident or traumatic injury, followed by lower total FIM scores, and type of pathologic event. CLINICAL REHABILITATION IMPACT: The presence of psychiatric disorders may potentially influence the rehabilitation process and outcomes; thus their recognition and management are key factors during a rehabilitation program.