Relaxation and creep response of the alveolar lung to diagnosis and treatments for respiratory and lung disorders.

BACKGROUND: The lung Extracellular Matrix (ECM) contains a considerable part of the parenchymal cells. It contains three essential components: elastin and collagen within a proteoglycan (PG) viscoelastic network. Elastin provides the lung's elasticity property, a necessity for normal breathing, while collagen prepares structural support and strength, and PGs give stability and cushioning within tissue loading. Bacterial and viral respiratory diseases are dependent on changes in the ECM ingredients, which result in an alteration of the lung tissue strength. PURPOSE: In the present study, this variation was investigated by changing the volume ratio of the ECM ingredients in the viscoelastic model. RESULTS: As a result, the relaxation curves continuously declined by reducing the volume ratios of elastin, collagen, and PGs; subsequently, the lung stiffness decreased. Also, the Standard Linear Solid (SLS) model-based results demonstrated excellent accordance with empirical data with only minor deviations. The resting relaxation modulus and the creep modulus for the ECM tissue were 51 kPa and approximately 0.02 kPa, respectively, and the maximum total modulus of elasticity reached 121 kPa. CONCLUSIONS: Moreover, this model demonstrates individual alveolar mechanical behaviours and adds another pathway to the generalized Kelvin-Voigt and Maxwell models in predicting the progress of lung diseases.

Parametric human modelling to determine body surface area covered by sun-protective clothing.

Solar ultraviolet radiation (UVR) is the main environmental risk-factor for cancer of the skin. Sun-protective clothing provides a physical barrier that reduces the UVR dose reaching the skin and European and Australian standards for sun-protective clothing set minimum clothing coverage requirements. Body Surface Area Coverage by clothing (BSAC) is calculated by means of indirect or direct methods, which are laborious and do not support computer-based apparel design. To support the sun-safe specification and design of garments, parametric digital human models and protective clothing mesh covering the minimum Body Surface Area specified in AS/NZS 4399:2017, were created making use of MakeHuman v1.1.1 and Blender software. The Whole Body Surface Area (WBSA) and the BSAC were calculated employing code developed in Blender. Thus, different groups of subjects were analysed to explore BSAC. The method assists in the evaluation of exposed body areas in a wider spectrum of different occupations. Practitioner summary: Sun-protective clothing provides a physical barrier that reduces the UVR dose reaching the skin's surface. Body Surface Area Coverage (BSAC) by clothing is an important determinant of the sun protective capabilities of a garment. In this study, BSAC is calculated using parametric digital human modelling. Abbreviation: UVR: (Solar) ultraviolet radiation; DHM: digital human modeling; BSA: body surface area; BSAC: body surface area coverage (by clothing); BSANC: body surface area not covered (by clothing); WBSA: whole body surface area; BCC: basal cell carcinoma; SCC: squamous cell carcinoma; UPF: ultraviolet protection factor; GPF: garment protection factor.

Efficiency of soft tissue incision with a novel 445-nm semiconductor laser.

Using a 445-nm semiconductor laser for tissue incision, an effective cut is expected due to the special absorption properties of blue laser light in soft tissues. The aim of the present study was the histological evaluation of tissue samples after incision with a 445-nm diode laser. Forty soft tissue specimens were obtained from pork oral mucosa and mounted on a motorized linear translation stage. The handpiece of a high-frequency surgery device, a 970-nm semiconductor laser, and a 445-nm semiconductor laser were connected to the slide, allowing a constant linear movement (2 mm/s) and the same distance of the working tip to the soft tissue's surface. Four incisions were made each: (I) 970-nm laser with conditioned fiber tip, contact mode at 3-W cw; (II-III): 445-nm laser with non-conditioned fiber tip, contact mode at 2-W cw, and non-contact mode (1 mm) at 2 W; and (IV): high-frequency surgery device with straight working tip, 90° angulation, contact mode at 50 W. Histological analysis was performed after H&E staining of the embedded specimens at 35-fold magnification. The comparison of the incision depths showed a significant difference depending on the laser wavelength and the selected laser parameters. The highest incision depth was achieved with the 445-nm laser contact mode (median depth 0.61 mm, min 0.26, max 1.17, interquartile range 0.58) (p < 0.05) with the lowest amount of soft tissue denaturation (p < 0.05). The lowest incision depth was measured for the high-frequency surgical device (median depth 0.36 mm, min 0.12, max 1.12, interquartile range 0.23) (p < 0.05). Using a 445-nm semiconductor laser, a higher cutting efficiency can be expected when compared with a 970-nm diode laser and high-frequency surgery. Even the 445-nm laser application in non-contact mode shows clinically acceptable incision depths without signs of extensive soft tissue denaturation.

Effects of in utero and Postnatal Exposure to Secondhand Smoke on Lung Function by Gender and Asthma Status: The Seven Northeastern Cities (SNEC) Study.

BACKGROUND: Little information exists on whether gender or asthma status modifies the effects of secondhand smoke (SHS) exposure on lung function. OBJECTIVE: To evaluate whether gender or asthma status modifies the association of SHS exposure with lung function. METHODS: A total of 6,740 children (average 11.6 years) were recruited from 24 districts of 7 cities in northeast China in 2012. SHS exposure included exposure to environmental and maternal smoking both in utero and during early childhood (postnatal). Lung function was measured using electronic spirometers. Two-step regressions were used to analyze the association between SHS and lung function. RESULTS: In utero and postnatal exposure to SHS was independently associated with decreased lung function in both genders; however, this association was greater among males. For example, when exposed to maternal smoking during pregnancy, the adjusted odds ratio (aOR) for decreased forced vital capacity (FVC) was 6.46 (95% confidence interval [CI]: 2.58-16.17) among males, while only 2.16 (95% CI: 0.96-4.88) among females. More positive associations between SHS exposure and decreased lung function were detected among nonasthmatic compared with asthmatic children. Nonasthmatics had significantly larger deficits from in utero exposure to maternal smoking, which concerned decreased lung FVC function (aOR = 2.58, 95% CI: 1.28-5.21) and decreased lung forced expiratory volume in 1 s (FEV1) function (aOR = 2.32, 95% CI: 1.01-5.33). A similar pattern was also observed for the associations between SHS exposure and continuous pulmonary function test measurements. CONCLUSIONS: SHS exposure was associated with decreased lung function. Males and nonasthmatics seem to be more susceptible than their respective counterparts.

The enhancing effect of a laser photochemotherapy with cisplatin or zolendronic acid in primary human osteoblasts and osteosarcoma cells in vitro.

BACKGROUND: Photodynamic therapies (PDT) have become increasingly popular in the adjuvant treatment of different tumour entities. Chemotherapeutic agents, such as cisplatin may be used in combination with low-level laser therapy (LLLT) as laser photochemotherapy. The aim of this study was to investigate the effect of LLLT on cell bioviability of normal and malignant bone cells under chemotherapeutic conditions with either cisplatin or zolendronic acid in vitro. METHODS: Primary human osteoblasts (HOB) and an osteosarcoma cell line (Saos-2) were treated with different concentrations of zolendronic acid or cisplatin and irradiated twice with a diode laser (wavelength 670 nm, 120 s, energy outputs of 100mW/cm2 , continuous wave mode). Cell viability was tested by XTT-assay and via histomorphological analysis. RESULTS: LLLT alone increased bioviability for both cell lines. LLLT lowered HOB viability at the three highest concentrations of cisplatin and zolendronic acid. For Saos-2, LLLT reduced cell viability at every concentration of cisplatin. In cases of incubation with zolendronic acid, similar to osteoblasts, LLLT lowered cell viability at the highest concentration only. CONCLUSIONS: Based on the conditions of this study, laser photochemotherapy may be able to raise the cytotoxicity of cisplatin and zolendronic acid in benign and malignant bone cells. This could be of interest in the development of new therapeutic treatment modalities against neoplastic bone diseases like osteosarcoma.

Testosterone-Mediated Endocrine Function and TH1/TH2 Cytokine Balance after Prenatal Exposure to Perfluorooctane Sulfonate: By Sex Status.

Little information exists about the evaluation of potential developmental immunotoxicity induced by perfluorooctane sulfonate (PFOS), a synthetic persistent and increasingly ubiquitous environmental contaminant. To assess potential sex-specific impacts of PFOS on immunological health in the offspring, using male and female C57BL/6 mice, pups were evaluated for developmental immunotoxic effects after maternal oral exposure to PFOS (0.1, 1.0 and 5.0 mg PFOS/kg/day) during Gestational Days 1-17. Spontaneous TH1/TH2-type cytokines, serum levels of testosterone and estradiol were evaluated in F1 pups at four and eight weeks of age. The study showed that male pups were more sensitive to the effects of PFOS than female pups. At eight weeks of age, an imbalance in TH1/TH2-type cytokines with excess TH2 cytokines (IL-4) was found only in male pups. As for hormone levels, PFOS treatment in utero significantly decreased serum testosterone levels and increased estradiol levels only in male pups, and a significant interaction between sex and PFOS was observed for serum testosterone at both four weeks of age (pinteraction = 0.0049) and eight weeks of age (pinteraction = 0.0227) and for estradiol alternation at four weeks of age (pinteraction = 0.0351). In conclusion, testosterone-mediated endocrine function may be partially involved in the TH1/TH2 imbalance induced by PFOS, and these deficits are detectable among both young and adult mice and may affect males more than females.

Oral ponesimod in patients with chronic plaque psoriasis: a randomised, double-blind, placebo-controlled phase 2 trial.

BACKGROUND: We assessed the efficacy, safety, and tolerability of ponesimod, an oral, selective, reversible modulator of sphingosine 1-phosphate receptor 1, in patients with moderate to severe chronic plaque psoriasis. METHODS: Between Sept 22, 2010, and Oct 24, 2012, patients with psoriasis area and severity index (PASI) scores higher than 10 were enrolled into this multicentre double-blind, phase 2 study. They received 20 mg or 40 mg ponesimod or placebo once daily for 16 weeks. Those with at least 50% reduction in PASI score at 16 weeks and who were receiving ponesimod were rerandomised to receive maintenance ponesimod therapy or placebo until week 28. The primary endpoint was reduction in PASI score from baseline of at least 75% (PASI75) at week 16. This study is registered with ClinicalTrials.gov, number NCT01208090. FINDINGS: Of 326 patients initially randomised (20 mg ponesimod n=126, 40 mg ponesimod n=133, and placebo n=67) PASI75 was achieved at week 16 in 58 (46·0%), 64 (48·1%), and nine (13·4%), respectively. The treatment effect was significant for the two ponesimod doses (both p<0·0001). Of 219 patients who entered the maintenance period, PASI75 was achieved by week 28 in 35 (71·4%) of 49 who continued on 20 mg ponesimod and 41 (77·4%) of 53 on 40 mg ponesimod, and in 19 (42·2%) of 45 who swapped from 20 mg to placebo and 19 (40·4%) of 47 from 40 mg to placebo. Ponesimod was associated with dyspnoea, raised liver enzyme concentrations, and dizziness. INTERPRETATION: Significant clinical benefit was seen at week 16 that increased with maintenance therapy. FUNDING: Actelion Pharmaceuticals.

Next-generation low-cost motion capture systems can provide comparable spatial accuracy to high-end systems.

The objective quantification of three-dimensional kinematics during different functional and occupational tasks is now more in demand than ever. The introduction of new generation of low-cost passive motion capture systems from a number of manufacturers has made this technology accessible for teaching, clinical practice and in small/medium industry. Despite the attractive nature of these systems, their accuracy remains unproved in independent tests. We assessed static linear accuracy, dynamic linear accuracy and compared gait kinematics from a Vicon MX20 system to a Natural Point OptiTrack system. In all experiments data were sampled simultaneously. We identified both systems perform excellently in linear accuracy tests with absolute errors not exceeding 1%. In gait data there was again strong agreement between the two systems in sagittal and coronal plane kinematics. Transverse plane kinematics differed by up to 3° at the knee and hip, which we attributed to the impact of soft tissue artifact accelerations on the data. We suggest that low-cost systems are comparably accurate to their high-end competitors and offer a platform with accuracy acceptable in research for laboratories with a limited budget.

Standardisation of digital human models.

Digital human models (DHM) have evolved as useful tools for ergonomic workplace design and product development, and found in various industries and education. DHM systems which dominate the market were developed for specific purposes and differ significantly, which is not only reflected in non-compatible results of DHM simulations, but also provoking misunderstanding of how DHM simulations relate to real world problems. While DHM developers are restricted by uncertainty about the user need and lack of model data related standards, users are confined to one specific product and cannot exchange results, or upgrade to another DHM system, as their previous results would be rendered worthless. Furthermore, origin and validity of anthropometric and biomechanical data is not transparent to the user. The lack of standardisation in DHM systems has become a major roadblock in further system development, affecting all stakeholders in the DHM industry. Evidently, a framework for standardising digital human models is necessary to overcome current obstructions. Practitioner Summary: This short communication addresses a standardisation issue for digital human models, which has been addressed at the International Ergonomics Association Technical Committee for Human Simulation and Virtual Environments. It is the outcome of a workshop at the DHM 2011 symposium in Lyon, which concluded steps towards DHM standardisation that need to be taken.

Design for All - Design for Disabled: How important is anthropometry?

BACKGROUND: Design for All or Universal Design is a relatively new domain in Ergonomics. With globally ageing populations, it has however recently gained significant interest. OBJECTIVE: This position paper summarizes the outcomes of a workshop held at the virtual 21st Triennial Congress of the International Ergonomics Association. The paper expands the horizon of traditional Ergonomics into a domain where people are differently abled and establishes a platform for the essential needs of future ergonomic standards which are required to inform inclusive design guidelines, or Design for All, extending the range of users. METHODS: The paper includes contributions from Asian, Australian, European and US workshop participants who are accessibility design experts in their respective geographic regions. The paper summarizes issues related to anthropometry in the Design for All, based on recent work in the US (Access board) and actual developments in various national and international accessibility standardization bodies, such as the Standards Australia/Standards New Zealand, the European Standardization Organization (EN 17210:2021; EN 17161:2019) and the International Organization for Standardization (ISO 21542:2021 and BS ISO 7176-5:2008). CONCLUSIONS: The paper concludes that despite the identification of a significant gap in knowledge of the anthropometry of people with disabilities as far back as 1990, work towards bridging the gap and enabling ergonomic standardization has not progressed since then globally. The lack of standardization in anthropometric data on people with a physical disability continues to complicate provision of data for mobility and accessibility design and hampers accessibility standardization efforts.

Efficacy of two different methods of cold air analgesia for pain relief in PDT of actinic keratoses of the head region - a randomized controlled comparison study.

BACKGROUND: Photodynamic therapy (PDT) is an effective method for treating actinic keratosis (AK) with pain during illumination representing the major side effect. The efficacy of two different cooling methods for pain relief in PDT of AK in the head region was compared. METHODS: Randomized, assessor-blinded, half side comparison study in 20 patients with symmetrically distributed AK on the head. Conventional PDT was performed on both halves of the scalp or face by applying 20% aminolevulinic acid cream (ALA) and subsequent illumination with incoherent red light. During illumination one side was cooled with a cold air blower (CAB) and the other with a standard fan (FAN) in a randomized fashion. Pain and skin temperature were recorded during and after PDT. The phototoxic skin reaction was evaluated up to seven days after PDT. The clearance rate of AK was assessed at 3 and 6 months after PDT. RESULTS: Mean pain (VASmean), maximum pain intensity (VASmax) and the mean skin temperature during PDT were significantly lower with CAB as compared to FAN (VASmean: 2.7 ± 1.4 vs. 3.7 ± 2.1, p = 0.003; VASmax: 3.8 ± 2.0 vs. 4.8 ± 2.5, p = 0.002; 26.8 ± 2.0 °C vs. 32.1 ± 1.7 °C; p=<0.001). The severity of the phototoxic skin reaction and the clearance rate of AK did not differ between the two cooling methods. CONCLUSION: Cooling with CAB during PDT has a greater analgesic effect than cooling with FAN. Patients with a lower skin temperature during illumination tended to experience less pain, however, this effect did not reach the level of statistical significance.

Serum levels of glycoprotein Dickkopf-1 in patients with cutaneous malignant melanoma: a prospective pilot study.

BACKGROUND: Dickkopf-1 (Dkk-1) glycoprotein is an inhibitor of the canonical Wnt pathway. Recent studies have demonstrated elevated Dkk-1 serum levels in patients with diverse malignancies. In vitro studies with melanoma cell lines showed that loss of Dkk-1 expression may contribute to tumor progression. OBJECTIVE: The present study is the first in vivo investigation of Dkk-1 serum levels in patients with cutaneous malignant melanoma. METHODS: We analyzed serum levels of Dkk-1 protein in 82 patients with cutaneous melanoma. RESULTS: Serum levels were significantly increased (mean 83.01 pmol/l) in comparison to healthy controls (mean 29.36 pmol/l). No statistical difference in Dkk-1 serum levels neither between patients without or with lymph node metastases (p = 0.719) nor between patients with or without visceral metastases (p = 0.929) was found. Patients before excision had moderately higher Dkk-1 serum levels than after excision or with florid metastases. CONCLUSION: Our data suggest that increased Dkk-1 expression is an early event in melanoma, decreasing in later tumor stages. It was shown previously that Dkk-1 activates cell death in melanoma cells. Our in vivo data indicate that a decrease in Dkk-1 could be a sign of loss of tumor control.

A Review and Qualitative Meta-Analysis of Digital Human Modeling and Cyber-Physical-Systems in Ergonomics 4.0.

Occupational ApplicationsFounded in an empirical case study and theoretical work, this paper reviews the scientific literature to define the role of Digital Human Modeling (DHM), Digital Twin (DT), and Cyber-Physical Systems (CPS) to inform the emerging concept of Ergonomics 4.0. We find that DHM evolved into DT is a core element in Ergonomics 4.0. A solid understanding and agreement on the nature of Ergonomics 4.0 is essential for the inclusion of ergonomic values and considerations in the larger conceptual framework of Industry 4.0. In this context, we invite Ergonomists from various disciplines to broaden their understanding and application of DHM and DT.

Technical AbstractBackground Industry 4.0 presents itself as an ecosystem; a collection of elements endowed with Cyber-Physical Systems and Augmented Reality/Virtual Reality devices, which are connected through the Internet of Things, and uploaded to Cloud Platforms for analysis, knowledge extraction, and diagnostics through Cognitive Computing based on a large amount of data. The concept is centered around data: managing data, analyzing data, and controlling data. Many factors influence this interconnected working environment, and for that reason planning and implementing the digital transformation implies many challenges. Industry 4.0 and Ergonomics are being integrated using a variety of tools and approaches, thus supporting the development of an Ergonomics 4.0 concept.Purpose This paper reviews studies focusing on the determinants of Ergonomics 4.0, identifying the main elements and their interrelationships with a focus on Digital Human Modeling and Cyber-Physical Systems. We consider approaches such as Operator 4.0 and 'Modeling and Simulation for Digital Twin Creation', which aim to accelerate the decision-making and adaptation processes. We identify the leading technologies, operations, and worker-related aspects through a qualitative meta-analysis, to establish elements and interrelationships of Ergonomics 4.0 determinants.Methods Literature was selected from articles recent journal publications, and a qualitative evaluation was performed using semantic meta-analysis. The findings were then used to develop a theoretical taxonomy of determinants of Ergonomics 4.0 in Industry 4.0 based on various classifiers, which were structured and interlinked.Results The five areas categorized include: Industry 4.0 technology, Human-Cyber-Physical Systems, Operator 4.0, Human-Robot collaboration, Digital Twin and Digital Human Modeling. The proposed conceptual framework for Ergonomics 4.0 describes processes, technology, information, and structures, which occur in Industry 4.0 as Operator 4.0, Human-Robot collaboration, Digital Twin, Digital Human Modeling and eventually define Ergonomics 4.0. The concepts of Digital Twin and Digital Human Modeling are analyzed in detail, as they form the core of Ergonomics 4.0.Conclusions We propose a conceptual framework for Ergonomics 4.0 as a Cyber-Physical System and discuss aspects of Digital Human Modeling and Digital Twin that are essential to understanding the role of Ergonomics and the integration of Ergonomics into Industry 4.0.

SARS CoV-2 aerosol: How far it can travel to the lower airways?

The recent outbreak of the SARS CoV-2 virus has had a significant effect on human respiratory health around the world. The contagious disease infected a large proportion of the world population, resulting in long-term health issues and an excessive mortality rate. The SARS CoV-2 virus can spread as small aerosols and enters the respiratory systems through the oral (nose or mouth) airway. The SARS CoV-2 particle transport to the mouth-throat and upper airways is analyzed by the available literature. Due to the tiny size, the virus can travel to the terminal airways of the respiratory system and form a severe health hazard. There is a gap in the understanding of the SARS CoV-2 particle transport to the terminal airways. The present study investigated the SARS CoV-2 virus particle transport and deposition to the terminal airways in a complex 17-generation lung model. This first-ever study demonstrates how far SARS CoV-2 particles can travel in the respiratory system. ANSYS Fluent solver was used to simulate the virus particle transport during sleep and light and heavy activity conditions. Numerical results demonstrate that a higher percentage of the virus particles are trapped at the upper airways when sleeping and in a light activity condition. More virus particles have lung contact in the right lung than the left lung. A comprehensive lobe specific deposition and deposition concentration study was performed. The results of this study provide a precise knowledge of the SARs CoV-2 particle transport to the lower branches and could help the lung health risk assessment system.

Polydisperse Aerosol Transport and Deposition in Upper Airways of Age-Specific Lung.

A comprehensive understanding of airflow characteristics and particle transport in the human lung can be useful in modelling to inform clinical diagnosis, treatment, and management, including prescription medication and risk assessment for rehabilitation. One of the difficulties in clinical treatment of lung disorders lies in the patients' variable physical lung characteristics caused by age, amongst other factors, such as different lung sizes. A precise understanding of the comparison between different age groups with various flow rates is missing in the literature, and this study aims to analyse the airflow and aerosol transport within the age-specific lung. ANSYS Fluent solver and the large-eddy simulation (LES) model were employed for the numerical simulation. The numerical model was validated with the available literature and the computational results showed airway size-reduction significantly affected airflow and particle transport in the upper airways. This study reports higher deposition at the mouth-throat region for larger diameter particles. The overall deposition efficiency (DE) increased with airway size reduction and flow rate. Lung aging effected the pressure distribution and a higher pressure drop was reported for the aged lung as compared to the younger lung. These findings could inform medical management through individualised simulation of drug-aerosol delivery processes for the patient-specific lung.

How severe acute respiratory syndrome coronavirus-2 aerosol propagates through the age-specific upper airways.

The recent outbreak of the COVID-19 causes significant respirational health problems, including high mortality rates worldwide. The deadly corona virus-containing aerosol enters the atmospheric air through sneezing, exhalation, or talking, assembling with the particulate matter, and subsequently transferring to the respiratory system. This recent outbreak illustrates that the severe acute respiratory syndrome (SARS) coronavirus-2 is deadlier for aged people than for other age groups. It is evident that the airway diameter reduces with age, and an accurate understanding of SARS aerosol transport through different elderly people's airways could potentially help the overall respiratory health assessment, which is currently lacking in the literature. This first-ever study investigates SARS COVID-2 aerosol transport in age-specific airway systems. A highly asymmetric age-specific airway model and fluent solver (ANSYS 19.2) are used for the investigation. The computational fluid dynamics measurement predicts higher SARS COVID-2 aerosol concentration in the airway wall for older adults than for younger people. The numerical study reports that the smaller SARS coronavirus-2 aerosol deposition rate in the right lung is higher than that in the left lung, and the opposite scenario occurs for the larger SARS coronavirus-2 aerosol rate. The numerical results show a fluctuating trend of pressure at different generations of the age-specific model. The findings of this study would improve the knowledge of SARS coronavirus-2 aerosol transportation to the upper airways which would thus ameliorate the targeted aerosol drug delivery system.

Effectiveness and clinical predictors of drug survival in psoriasis patients receiving apremilast: A registry analysis.

BACKGROUND: Little is known about the effectiveness and drug survival associated with apremilast under real-world conditions. OBJECTIVE: To investigate the influence of patient and disease characteristics on drug survival associated with apremilast and to elucidate clinical effectiveness with regard to the psoriasis area and severity index (PASI) reduction. METHODS: This was an observational, retrospective, multicenter analysis from the Austrian Psoriasis Registry. RESULTS: Data from 367 patients were eligible for analysis. The 12-month drug survival rate associated with apremilast (ie, the proportion of patients on the drug) was 57.3% and decreased significantly in patients younger than 40 years (relative hazard ratio = 1.49, P = .007918). Sex; concomitant arthritis; previous biologic therapy; obesity; and palmoplantar, scalp, nail, and intertriginous involvement did not significantly affect drug survival. At 12 months, the response rates in patients receiving apremilast per protocol with a PASI of 50, 75, 90, and 100 were 80.0%, 56.4%, 38.2%, and 22.7%, respectively. LIMITATIONS: Inclusion of a substantial number of patients with no record of absolute PASI at study entry and lack of PASI reduction follow-up data of 103 patients (28.1%) after starting apremilast treatment. CONCLUSION: Apremilast is a robust antipsoriatic drug for which the drug survival is not strongly influenced by most patient- or disease-related factors except age. Drug survival is significantly shorter in patients younger than 40 years.

Air Pollution Emissions 2008-2018 from Australian Coal Mining: Implications for Public and Occupational Health.

Occupational exposure limits for respirable coal dust are based on exposure during working hours, but coal miners may experience additional community-based exposures during nonworking hours. We analyzed Australia National Pollutant Inventory (NPI) data for the years 2008-2018 to estimate air pollutants (metals, nitrogen oxides, particulate matter ≤ 10 micrometers (PM10) and ≤2.5 micrometers (PM2.5)) originating from coal mines. PM10 levels from community-based air monitors in Queensland and New South Wales were also compared between mining and nonmining communities. Results indicated that tons of coal mined increased over the study period, and that levels of particulate matter, metals, and nitrogen oxides increased significantly over time as well. Coal mines accounted for 42.1% of national PM10 air emissions from NPI sites. PM2.5 from coal mines accounted for 19.5% of the national total, metals for 12.1%, and nitrogen oxides for 10.1%. Coal mining occurred in 57 different post codes; the 20 coal-mining post codes with the highest PM10 emissions were home to 160,037 people. Emissions of all studied pollutants were significantly higher from coal mining sites than from other types of NPI sites. Results from community-based air monitoring stations indicated significantly higher population PM10 exposure in coal mining communities than in nonmining communities. The health of the public at large is impacted by coal mining, but to the extent that miners also live near coal mining operations, their total exposure is underestimated by consideration of exposure only during working hours.

Helium-Oxygen Mixture Model for Particle Transport in CT-Based Upper Airways.

The knowledge of respiratory particle transport in the extra-thoracic pathways is essential for the estimation of lung health-risk and optimization of targeted drug delivery. The published literature reports that a significant fraction of the inhaled aerosol particles are deposited in the upper airways, and available inhalers can deliver only a small amount of drug particles to the deeper airways. To improve the targeted drug delivery efficiency to the lungs, it is important to reduce the drug particle deposition in the upper airways. This study aims to minimize the unwanted aerosol particle deposition in the upper airways by employing a gas mixture model for the aerosol particle transport within the upper airways. A helium-oxygen (heliox) mixture (80% helium and 20% oxygen) model is developed for the airflow and particle transport as the heliox mixture is less dense than air. The mouth-throat and upper airway geometry are extracted from CT-scan images. Finite volume based ANSYS Fluent (19.2) solver is used to simulate the airflow and particle transport in the upper airways. Tecplot software and MATLAB code are employed for the airflow and particle post-processing. The simulation results show that turbulence intensity for heliox breathing is lower than in the case of air-breathing. The less turbulent heliox breathing eventually reduces the deposition efficiency (DE) at the upper airways than the air-breathing. The present study, along with additional patient-specific investigation, could improve the understanding of particle transport in upper airways, which may also increase the efficiency of aerosol drug delivery.

Airflow and Particle Transport Prediction through Stenosis Airways.

Airflow and particle transport in the human lung system is influenced by biological and other factors such as breathing pattern, particle properties, and deposition mechanisms. Most of the studies to date have analyzed airflow characterization and aerosol transport in idealized and realistic models. Precise airflow characterization for airway stenosis in a digital reference model is lacking in the literature. This study presents a numerical simulation of airflow and particle transport through a stenosis section of the airway. A realistic CT-scan-based mouth-throat and upper airway model was used for the numerical calculations. Three different models of a healthy lung and of airway stenosis of the left and right lung were used for the calculations. The ANSYS FLUENT solver, based on the finite volume discretization technique, was used as a numerical tool. Proper grid refinement and validation were performed. The numerical results show a complex-velocity flow field for airway stenosis, where airflow velocity magnitude at the stenosis section was found to be higher than that in healthy airways. Pressure drops at the mouth-throat and in the upper airways show a nonlinear trend. Comprehensive pressure analysis of stenosis airways would increase our knowledge of the safe mechanical ventilation of the lung. The turbulence intensities at the stenosis sections of the right and left lung were found to be different. Deposition efficiency (DE) increased with flow rate and particle size. The findings of the present study increase our understanding of airflow patterns in airway stenosis under various disease conditions. More comprehensive stenosis analysis is required to further improve knowledge of the field.