Outdoor environmental exposome and the burden of tuberculosis: Findings from nearly two million adults in northwestern China.

We simultaneously assessed the associations for a range of outdoor environmental exposures with prevalent tuberculosis (TB) cases in a population-based health program with 1940,622 participants ≥ 15 years of age. TB status was confirmed through bacteriological and clinical assessment. We measured 14 outdoor environmental exposures at residential addresses. An exposome-wide association study (ExWAS) approach was used to estimate cross-sectional associations between environmental exposures and prevalent TB, an adaptive elastic net model (AENET) was implemented to select important exposure(s), and the Extreme Gradient Boosting algorithm was subsequently applied to assess their relative importance. In ExWAS analysis, 12 exposures were significantly associated with prevalent TB. Eight of the exposures were selected as predictors by the AENET model: particulate matter ≤ 2.5 µm (odds ratio [OR]=1.01, p = 0.3295), nitrogen dioxide (OR=1.09, p < 0.0001), carbon monoxide (OR=1.19, p < 0.0001), and wind speed (OR=1.08, p < 0.0001) were positively associated with the odds of prevalent TB while sulfur dioxide (OR=0.95, p = 0.0017), altitude (OR=0.97, p < 0.0001), artificial light at night (OR=0.98, p = 0.0001), and proportion of forests, shrublands, and grasslands (OR=0.95, p < 0.0001) were negatively associated with the odds of prevalent TB. Air pollutants had higher relative importance than meteorological and geographical factors, and the outdoor environment collectively explained 11% of TB prevalence.

Effects of long-term ambient air pollution exposure on township-level pulmonary tuberculosis notification rates during 2005-2017 in Ningxia, China.

Studies examining long-term effects of ambient air pollution exposure, measured as annual averages, on pulmonary tuberculosis (TB) incidence are scarce, particularly in endemic, rural settings. We performed a small-area study in Ningxia Hui Autonomous Region (NHAR), a high TB-burden area in rural China, using township-level (n = 358 non-overlapping townships) annual TB notification data (2005-2017). We aimed to determine if annual average concentrations of ambient air pollution (particulate matter <2·5 µm [PM2·5], nitrogen dioxide [NO2] ozone [O3]) were associated with TB notification rates (as a proxy for incidence). Air pollution effects on TB notification rates at township-level were estimated as incidence rate ratios (IRR), fitted using a generalised estimating equation (GEE) adjusted for covariates (age, sex, occupation, education, ethnicity, remoteness [urban or rural], household crowding and solid fuel use). A total of 38,942 TB notifications were reported in NHAR between 2005 and 2017. The mean annual TB notification rate was 67 (standard deviation [SD]; 7) per 100,000 people. Median concentrations of PM2·5, NO2, and O3 were 42 µg/m3 (interquartile range [IQR]; 38-48 µg/m3), 15 ppb (IQR; 12-16 ppb), and 56 ppb (IQR; 56-57 ppb), respectively. In single pollutant models, adjusted for covariates, an interquartile range (IQR) increase (10 µg/m3) in PM2·5 was significantly associated with higher TB notification rates (IRR: 1∙35; 95% CI: 1·25-1·48). Comparable effects on notifications of TB were observed for increases in NO2 exposure (IRR: 1·20 per IQR (4 ppb) increase; 95% CI: 1·08-1·31). Ground-level ozone was not associated with TB notification rate in any models. The observed effects were consistent over time, in multi-pollutant models, and appeared robust to additional adjustment for indicators of household crowding, solid fuel use and remoteness. More rigorous study designs are needed to understand if improving air quality has population-level benefits on TB disease incidence in endemic settings.

Development and Validation of a Sub-National, Satellite-Based Land-Use Regression Model for Annual Nitrogen Dioxide Concentrations in North-Western China.

Existing national- or continental-scale models of nitrogen dioxide (NO2) exposure have a limited capacity to capture subnational spatial variability in sparsely-populated parts of the world where NO2 sources may vary. To test and validate our approach, we developed a land-use regression (LUR) model for NO2 for Ningxia Hui Autonomous Region (NHAR) and surrounding areas, a small rural province in north-western China. Using hourly NO2 measurements from 105 continuous monitoring sites in 2019, a supervised, forward addition, linear regression approach was adopted to develop the model, assessing 270 potential predictor variables, including tropospheric NO2, optically measured by the Aura satellite. The final model was cross-validated (5-fold cross validation), and its historical performance (back to 2014) assessed using 41 independent monitoring sites not used for model development. The final model captured 63% of annual NO2 in NHAR (RMSE: 6 ppb (21% of the mean of all monitoring sites)) and contiguous parts of Inner Mongolia, Gansu, and Shaanxi Provinces. Cross-validation and independent evaluation against historical data yielded adjusted R2 values that were 1% and 10% lower than the model development values, respectively, with comparable RMSE. The findings suggest that a parsimonious, satellite-based LUR model is robust and can be used to capture spatial contrasts in annual NO2 in the relatively sparsely-populated areas in NHAR and neighbouring provinces.

Enhancing functional abilities and cognitive integration of the lower limb prosthesis.

Lower limb amputation (LLA) destroys the sensory communication between the brain and the external world during standing and walking. Current prostheses do not restore sensory feedback to amputees, who, relying on very limited haptic information from the stump-socket interaction, are forced to deal with serious issues: the risk of falls, decreased mobility, prosthesis being perceived as an external object (low embodiment), and increased cognitive burden. Poor mobility is one of the causes of eventual device abandonment. Restoring sensory feedback from the missing leg of above-knee (transfemoral) amputees and integrating the sensory feedback into the sensorimotor loop would markedly improve the life of patients. In this study, we developed a leg neuroprosthesis, which provided real-time tactile and emulated proprioceptive feedback to three transfemoral amputees through nerve stimulation. The feedback was exploited in active tasks, which proved that our approach promoted improved mobility, fall prevention, and agility. We also showed increased embodiment of the lower limb prosthesis (LLP), through phantom leg displacement perception and questionnaires, and ease of the cognitive effort during a dual-task paradigm, through electroencephalographic recordings. Our results demonstrate that induced sensory feedback can be integrated at supraspinal levels to restore functional abilities of the missing leg. This work paves the way for further investigations about how the brain interprets different artificial feedback strategies and for the development of fully implantable sensory-enhanced leg neuroprostheses, which could drastically ameliorate life quality in people with disability.

A systematic literature review and critical appraisal of epidemiological studies on outdoor air pollution and tuberculosis outcomes.

Ambient air pollution is the leading environmental risk factor for disease globally. Air pollutants can increase the risk of some respiratory infections, but their effects on tuberculosis (TB) are unclear. In this systematic literature review, we aimed to assess epidemiological studies on the association between outdoor air pollutants and TB incidence, hospital admissions and death (collectively referred to here as 'TB outcomes'). We sought to consolidate available evidence on this topic and propose recommendations for future studies. Following PRISMA guidelines, we searched PubMed, Web of Science, Google Scholar, and Scopus with no restrictions imposed on year of publication. A total of 11 epidemiological studies, performed in Asia, Europe and North America, met our inclusion criteria (combined sample size: 215,337 people). We extracted key study characteristics from each eligible publication, including design, exposure assessment, analytical approaches and effect estimates. The studies were assessed for overall quality and risk of bias using standard criteria. The pollutant most frequently associated with statistically significant effects on TB outcomes was fine particulate matter ( < 2.5 µm; PM2.5); 6/11 studies assessed PM2.5, of which 4/6 demonstrated a significant association). There was some evidence of significant associations between PM10 ( < 10 µm), nitrogen dioxide (NO2) and sulfur dioxide (SO2) and TB outcomes, but these associations were inconsistent. The existing epidemiological evidence is limited and shows mixed results. However, it is plausible that exposure to air pollutants, particularly PM2.5, may suppress important immune defence mechanisms, increasing an individual's susceptibility to development of active TB and TB-related mortality. Considering the small number of studies relative to the demonstrably large global health burdens of air pollution and TB, further research is required to corroborate the findings in the current literature. Based on a critical assessment of existing evidence, we conclude with methodological suggestions for future studies.

A somatotopic bidirectional hand prosthesis with transcutaneous electrical nerve stimulation based sensory feedback.

According to amputees, sensory feedback is amongst the most important features lacking from commercial prostheses. Although restoration of touch by means of implantable neural interfaces has been achieved, these approaches require surgical interventions, and their long-term usability still needs to be fully investigated. Here, we developed a non-invasive alternative which maintains some of the advantages of invasive approaches, such as a somatotopic sensory restitution scheme. We used transcutaneous electrical nerve stimulation (TENS) to induce referred sensations to the phantom hand of amputees. These sensations were characterized in four amputees over two weeks. Although the induced sensation was often paresthesia, the location corresponded to parts of the innervation regions of the median and ulnar nerves, and electroencephalographic (EEG) recordings confirmed the presence of appropriate responses in relevant cortical areas. Using these sensations as feedback during bidirectional prosthesis control, the patients were able to perform several functional tasks that would not be possible otherwise, such as applying one of three levels of force on an external sensor. Performance during these tasks was high, suggesting that this approach could be a viable alternative to the more invasive solutions, offering a trade-off between the quality of the sensation, and the invasiveness of the intervention.

Short- and Long-Term Learning of Feedforward Control of a Myoelectric Prosthesis with Sensory Feedback by Amputees.

Human motor control relies on a combination of feedback and feedforward strategies. The aim of this study was to longitudinally investigate artificial somatosensory feedback and feedforward control in the context of grasping with myoelectric prosthesis. Nine amputee subjects performed routine grasping trials, with the aim to produce four levels of force during four blocks of 60 trials across five days. The electrotactile force feedback was provided in the second and third block using multipad electrode and spatial coding. The first baseline and last validation block (open-loop control) evaluated the effects of long- (across sessions) and short-term (within session) learning, respectively. The outcome measures were the absolute error between the generated and target force, and the number of force saturations. The results demonstrated that the electrotactile feedback improved the performance both within and across sessions. In the validation block, the performance did not significantly decrease and the quality of open-loop control (baseline) improved across days, converging to the performance characterizing closed-loop control. This paper provides important insights into the feedback and feedforward processes in prosthesis control, contributing to the better understanding of the role and design of feedback in prosthetic systems.

Electrotactile Feedback Improves Performance and Facilitates Learning in the Routine Grasping Task.

Aim of this study was to investigate the feasibility of electrotactile feedback in closed loop training of force control during the routine grasping task. The feedback was provided using an array electrode and a simple six-level spatial coding, and the experiment was conducted in three amputee subjects. The psychometric tests confirmed that the subjects could perceive and interpret the electrotactile feedback with a high success rate. The subjects performed the routine grasping task comprising 4 blocks of 60 grasping trials. In each trial, the subjects employed feedforward control to close the hand and produce the desired grasping force (four levels). First (baseline) and the last (validation) session were performed in open loop, while the second and the third session (training) included electrotactile feedback. The obtained results confirmed that using the feedback improved the accuracy and precision of the force control. In addition, the subjects performed significantly better in the validation vs. baseline session, therefore suggesting that electrotactile feedback can be used for learning and training of myoelectric control.

Integrated and flexible multichannel interface for electrotactile stimulation.

OBJECTIVE: The aim of the present work was to develop and test a flexible electrotactile stimulation system to provide real-time feedback to the prosthesis user. The system requirements were to accommodate the capabilities of advanced multi-DOF myoelectric hand prostheses and transmit the feedback variables (proprioception and force) using intuitive coding, with high resolution and after minimal training. APPROACH: We developed a fully-programmable and integrated electrotactile interface supporting time and space distributed stimulation over custom designed flexible array electrodes. The system implements low-level access to individual stimulation channels as well as a set of high-level mapping functions translating the state of a multi-DoF prosthesis (aperture, grasping force, wrist rotation) into a set of predefined dynamic stimulation profiles. The system was evaluated using discrimination tests employing spatial and frequency coding (10 able-bodied subjects) and dynamic patterns (10 able-bodied and 6 amputee subjects). The outcome measure was the success rate (SR) in discrimination. MAIN RESULTS: The more practical electrode with the common anode configuration performed similarly to the more usual concentric arrangement. The subjects could discriminate six spatial and four frequency levels with SR >90% after a few minutes of training, whereas the performance significantly deteriorated for more levels. The dynamic patterns were intuitive for the subjects, although amputees showed lower SR than able-bodied individuals (86% ± 10% versus 99% ± 3%). SIGNIFICANCE: The tests demonstrated that the system was easy to setup and apply. The design and resolution of the multipad electrode was evaluated. Importantly, the novel dynamic patterns, which were successfully tested, can be superimposed to transmit multiple feedback variables intuitively and simultaneously. This is especially relevant for closing the loop in modern multifunction prostheses. Therefore, the proposed system is convenient for practical applications and can be used to implement sensory perception training and/or closed-loop control of myoelectric prostheses, providing grasping force and proprioceptive feedback.

Application of Analytical Quality by Design concept for bilastine and its degradation impurities determination by hydrophilic interaction liquid chromatographic method.

This paper deals with the development of hydrophilic interaction liquid chromatographic (HILIC) method for the analysis of bilastine and its degradation impurities following Analytical Quality by Design approach. It is the first time that the method for bilastine and its impurities is proposed. The main objective was to identify the conditions where an adequate separation in minimal analysis duration could be achieved within a robust region. Critical process parameters which have the most influence on method performance were defined as acetonitrile content in the mobile phase, pH of the aqueous phase and ammonium acetate concentration in the aqueous phase. Box-Behnken design was applied for establishing a relationship between critical process parameters and critical quality attributes. The defined mathematical models and Monte Carlo simulations were used to identify the design space. Fractional factorial design was applied for experimental robustness testing and the method is validated to verify the adequacy of selected optimal conditions: the analytical column Luna(®) HILIC (100mm×4.6mm, 5µm particle size); mobile phase consisted of acetonitrile-aqueous phase (50mM ammonium acetate, pH adjusted to 5.3 with glacial acetic acid) (90.5:9.5, v/v); column temperature 30°C, mobile phase flow rate 1mLmin(-1), wavelength of detection 275nm.

Chromatographic analysis of olopatadine in hydrophilic interaction liquid chromatography.

In this paper, chromatographic analysis of active substance olopatadine hydrochloride, which is used in eye drops as antihistaminic agent, and its impurity E isomer by hydrophilic interaction liquid chromatography (HILIC) and application of design of experiments (DoE) methodology are presented. In addition, benzalkonium chloride is very often used as a preservative in eye drops. Therefore, the evaluation of its chromatographic behavior in HILIC was carried out as well. In order to estimate chromatographic behavior and set optimal chromatographic conditions, DoE methodology was applied. After the selection of important chromatographic factors, Box-Behnken design was utilized, and on the basis of the obtained models factor effects were examined. Then, multi-objective robust optimization is performed aiming to obtain chromatographic conditions that comply with several quality criteria simultaneously: adequate and robust separation of critical peak pair and maximum retention of the first eluting peak. The optimal conditions are identified by using grid point search methodology. The experimental verification confirmed the adequacy of the defined optimal conditions. Finally, under optimal chromatographic conditions, the method was validated and applicability of the proposed method was confirmed.

Listeria: an Australian perspective (2001-2010).

Despite having a low occurrence rate, Listeria monocytogenes is one of the most prominent foodborne pathogens in Australia. The organism is responsible for severe outbreaks with high case fatality and substantial economic losses due to food recalls. In this study, we analyze the incidence trends of listeriosis in Australia during 2001-2010, discuss the relevance of food recalls, and investigate the pathogen's role in foodborne outbreaks. A significant epidemiological finding was a consistently high national age-specific rate recorded for individuals aged 60 years and over. Analysis of Australian Listeria outbreak and food recall data suggests deficiencies in food safety programs of food manufacturing businesses implicated in Listeria outbreaks and revealed that ready-to-eat foods are high-risk vehicles for transmitting listeriosis. Highlighted is Australia's highly efficient Listeria management and surveillance systems bolstered by the introduction of Listeria molecular subtyping in 2010 coupled with a nationally standardized questionnaire by the "Australian foodborne disease surveillance network (OzFoodNet)." The detection of clusters and therefore outbreaks was now possible, allowing cases to be linked across multiple jurisdictions and enabling timely public health action. Considering current changes in food production and consumption patterns, continuous monitoring and improvement of surveillance systems will provide ongoing public health benefits and be crucial to future development of food safety policy for Australia.

Computer-assisted optimization and validation of LC analysis of trimetazidine dihydrochloride and its impurities.

Trimetazidine dihydrochloride is an anti-anginal drug, which possesses protective properties against ischemia inducing heart damage. In this paper, a new procedure for liquid chromatographic analysis was successfully developed, optimized, and applied in assessment of trimetazidine dihydrochloride content and its impurities, Y-145, Y-235, and Y-234 at most 1.0%, 0.2%, and 0.2%, respectively, in commercially available pharmaceutical preparation containing 35 mg of trimetazidine dihydrochloride. The retention behavior of trimetazidine dihydrochloride and its impurities is investigated by using several stationary and mobile phases to settle a simple, sensitive, and precise RP-HPLC method. The separation conditions are optimized by DryLab 2000 Plus Chromatography Optimization Software version 3.5.00. Separations are performed on PurospherSTAR RP18 endcapped (150 x 4.6 mm, 5 microm particle size) column at 20 degrees C with UV detection at 210 nm. The mobile phase composition is acetonitrile-aqueous phase (10 mmol/L disodium hydrogenphosphate and 2 mmol/L sodium dihydrogen phosphate, pH 7.6) (30:70 v/v). Afterwards, the method is validated; the important statistical parameters for selectivity/specificity, linearity, precision, limit of detection, and quantitation are defined. The recovery value of the trimetazidine dihydrochloride is 98.06%, and the content of impurities is 0.23% for Y-145, less than 0.02% for Y-235, and less than 0.01% for Y-234. In addition, this method is used for analyzing trimetazidine dihydrochloride and its impurities in pharmaceuticals and bulk drug.