Field study of air change and flow rate in six automobiles

For many people, a relatively large proportion of daily exposure to a multitude of pollutants may occur inside an automobile. A key determinant of exposure is the amount of outdoor air entering the cabin (i.e. air change or flow rate). We have quantified this parameter in six passenger vehicles ranging in age from 18 years to <1 year, at three vehicle speeds and under four different ventilation settings. Average infiltration into the cabin with all operable air entry pathways closed was between 1 and 33.1 air changes per hour (ACH) at a vehicle speed of 60 km/h, and between 2.6 and 47.3 ACH at 110 km/h, with these results representing the most (2005 Volkswagen Golf) and least air-tight (1989 Mazda 121) vehicles, respectively. Average infiltration into stationary vehicles parked outdoors varied between ~0 and 1.4 ACH and was moderately related to wind speed. Measurements were also performed under an air recirculation setting with low fan speed, while airflow rate measurements were conducted under two non-recirculate ventilation settings with low and high fan speeds. The windows were closed in all cases, and over 200 measurements were performed. The results can be applied to estimate pollutant exposure inside vehicles.

Interfacing Jack and anybody : towards anthropometric musculoskeletal digital human modeling

Virtual prototyping emerges as a new technology to replace existing physical prototypes for product evaluation, which are costly and time consuming to manufacture. Virtualization technology allows engineers and ergonomists to perform virtual builds and different ergonomic analyses on a product. Digital Human Modelling (DHM) software packages such as Siemens Jack, often integrate with CAD systems to provide a virtual environment which allows investigation of operator and product compatibility. Although the integration between DHM and CAD systems allows for the ergonomic analysis of anthropometric design, human musculoskeletal, multi-body modelling software packages such as the AnyBody Modelling System (AMS) are required to support physiologic design. They provide muscular force analysis, estimate human musculoskeletal strain and help address human comfort assessment. However, the independent characteristics of the modelling systems Jack and AMS constrain engineers and ergonomists in conducting a complete ergonomic analysis. AMS is a stand alone programming system without a capability to integrate into CAD environments. Jack is providing CAD integrated human-in-the-loop capability, but without considering musculoskeletal activity. Consequently, engineers and ergonomists need to perform many redundant tasks during product and process design. Besides, the existing biomechanical model in AMS uses a simplified estimation of body proportions, based on a segment mass ratio derived scaling approach. This is insufficient to represent user populations anthropometrically correct in AMS. In addition, sub-models are derived from different sources of morphologic data and are therefore anthropometrically inconsistent. Therefore, an interface between the biomechanical AMS and the virtual human model Jack was developed to integrate a musculoskeletal simulation with Jack posture modeling. This interface provides direct data exchange between the two man-models, based on a consistent data structure and common body model. The study assesses kinematic and biomechanical model characteristics of Jack and AMS, and defines an appropriate biomechanical model. The information content for interfacing the two systems is defined and a protocol is identified. The interface program is developed and implemented through Tcl and Jack-script(Python), and interacts with the AMS console application to operate AMS procedures.

A comprehensive literature review of the pelvis and the lower extremity digital human models under quasi-static conditions

Finite Element Modeling (FEM) has become a vital tool in the automotive design and development processes. FEM of the human body is a technique capable of estimating parameters that are difficult to measure in experimental studies with the human body segments being modeled as complex and dynamic entities. Several studies have been dedicated to attain close-to-real FEMs of the human body (Pankoke and Siefert 2007; Amann, Huschenbeth et al. 2009; ESI 2010). The aim of this paper is to identify and appraise the state of-the art models of the human body which incorporate detailed pelvis and/or lower extremity models. Six databases and search engines were used to obtain literature, and the search was limited to studies published in English since 2000. The initial search results identified 636 pelvis-related papers, 834 buttocks-related papers, 505 thigh-related papers, 927 femur-related papers, 2039 knee-related papers, 655 shank-related papers, 292 tibia-related papers, 110 fibula-related papers, 644 ankle related papers, and 5660 foot-related papers. A refined search returned 100 pelvis-related papers, 45 buttocks related papers, 65 thigh-related papers, 162 femur-related papers, 195 kneerelated papers, 37 shank-related papers, 80 tibia-related papers, 30 fibula-related papers and 102 ankle-related papers and 246 foot-related papers. The refined literature list was further restricted by appraisal against a modified LOW appraisal criteria. Studies with unclear methodologies, with a focus on populations with pathology or with sport related dynamic motion modeling were excluded. The final literature list included fifteen models and each was assessed against the percentile the model represents, the gender the model was based on, the human body segment/segments included in the model, the sample size used to develop the model, the source of geometric/anthropometric values used to develop the model, the posture the model represents and the finite element solver used for the model. The results of this literature review provide indication of bias in the available models towards 50th percentile male modeling with a notable concentration on the pelvis, femur and buttocks segments.

Determinants of driver vs. second row occupant posture modelling

Digital human modeling (DHM), as a convenient and cost-effective tool, is increasingly incorporated into product and workplace design. In product design, it is predominantly used for the development of driver-vehicle systems. Most digital human modeling software tools, such as JACK, RAMSIS and DELMIA HUMANBUILDER provide functions to predict posture and positions for drivers with selected anthropometry according to SAE (Society of Automotive Engineers) Recommended Practices and other ergonomics guidelines. However, few studies have presented 2nd row passenger postural information, and digital human modeling of these passenger postures cannot be performed directly using the existing driver posture prediction functions. In this paper, the significant studies related to occupant posture and modeling were reviewed and a framework of determinants of driver vs. 2nd row occupant posture modeling was extracted. The determinants which are regarded as input factors for posture modeling include target population anthropometry, vehicle package geometry and seat design variables as well as task definitions. The differences between determinants of driver and 2nd row occupant posture models are significant, as driver posture modeling is primarily based on the position of the foot on the accelerator pedal (accelerator actuation point AAP, accelerator heel point AHP) and the hands on the steering wheel (steering wheel centre point A-Point). The objectives of this paper are aimed to investigate those differences between driver and passenger posture, and to supplement the existing parametric model for occupant posture prediction. With the guide of the framework, the associated input parameters of occupant digital human models of both driver and second row occupant will be identified. Beyond the existing occupant posture models, for example a driver posture model could be modified to predict second row occupant posture, by adjusting the associated input parameters introduced in this paper. This study combines results from a literature review and the theoretical modeling stage of a second row passenger posture prediction model project.

Effects of whole-body cryotherapy (-110 degrees C) on proprioception and indices of muscle damage

The purpose of this study was to investigate the effects of whole-body cryotherapy (WBC) on proprioceptive function, muscle force recovery following eccentric muscle contractions and tympanic temperature (TTY). Thirty-six subjects were randomly assigned to a group receiving two 3-min treatments of −110 ± 3 °C or 15 ± 3 °C. Knee joint position sense (JPS), maximal voluntary isometric contraction (MVIC) of the knee extensors, force proprioception and TTY were recorded before, immediately after the exposure and again 15 min later. A convenience sample of 18 subjects also underwent an eccentric exercise protocol on their contralateral left leg 24 h before exposure. MVIC (left knee), peak power output (PPO) during a repeated sprint on a cycle ergometer and muscles soreness were measured pre-, 24, 48 and 72 h post-treatment. WBC reduced TTY, by 0.3 °C, when compared with the control group (P<0.001). However, JPS, MVIC or force proprioception was not affected. Similarly, WBC did not effect MVIC, PPO or muscle soreness following eccentric exercise. WBC, administered 24 h after eccentric exercise, is ineffective in alleviating muscle soreness or enhancing muscle force recovery. The results of this study also indicate no increased risk of proprioceptive-related injury following WBC.

Syntaxin 11 binds Vti1b and regulates late endosome to lysosome fusion in macrophages

Syntaxin 11 (Stx11) is a SNARE protein enriched in cells of the immune system. Loss or mutation of Stx11 results in familial hemophagocytic lymphohistiocytosis type-4 (FHL-4), an autosomal recessive disorder of immune dysregulation characterized by high levels of inflammatory cytokines along with defects in T-cell and natural killer cell function. We show here Stx11 is located on endosomalmembranes including late endosomes and lysosomes in macrophages. While Stx11 did not form a typical trans-SNARE complex, it did bind to the Q-SNARE Vti1b and was able to regulate the availability of Vti1b to form the Q-SNARE complexes Stx6/Stx7/Vtib and Stx7/Stx8/Vti1b. The mutant form of Stx11 sequestered Vti1b from forming the Q-SNARE complex that mediates late endosome to lysosome fusion. Depletion of Stx11 in activated macrophages leads to an accumulation of enlarged late endocytic compartments, increased trafficking to the cell surface and inhibition of late endosome to lysosome fusion. These phenotypes arerescued by the expression of an siRNA-resistant Stx11 construct in Stx11-depleted cells. Our results suggest that by regulating the availability of Vti1b, Stx11 regulates trafficking steps between late endosomes, lysosomes and the cell surface in macrophages.

Recycling endosome membrane incorporation into the leading edge regulates lamellipodia formation and macrophage migration

In comparison to our knowledge of the recycling of adhesion receptors and actin assembly, exactly how the cell controls its surface membrane to form a lamellipodium during migration is poorly understood. Here, we show the recycling endosome membrane is incorporated into the leading edge of a migrating cell to expand lamellipodia membrane. We have identified the SNARE complex that is necessary for fusion of the recycling endosome with the cell surface, as consisting of the R-SNARE VAMP3 on the recycling endosome partnering with the surface Q-SNARE Stx4/SNAP23, which was found to translocate and accumulate on the leading edge of migrating cells. Increasing VAMP3-mediated fusion of the recycling endosome with the surface increased membrane ruffling, while inhibition of VAMP3-mediated fusion showed that incorporation of the recycling endosome is necessary for efficient lamellipodia formation. At the same time, insertion of this recycling endosome membrane also delivers its cargo integrin α5β1 to the cell surface. The loss of this extra membrane for lamellipodia expansion and delivery of cargo in cells resulted in macrophages with a diminished capacity to effectively migrate. Thus, the recycling endosome membrane is incorporated into the leading edge and this aids expansion of the lamellipodia and simultaneously delivers integrins necessary for efficient cell migration.

A tan in a test tube -in vitro models for investigating ultraviolet radiation-induced damage in skin

Presently, global rates of skin cancers induced by ultraviolet radiation (UVR) exposure are on the rise. In view of this, current knowledge gaps in the biology of photocarcinogenesis and skin cancer progression urgently need to be addressed. One factor that has limited skin cancer research has been the need for a reproducible and physiologically-relevant model able to represent the complexity of human skin. This review outlines the main currently-used in vitro models of UVR-induced skin damage. This includes the use of conventional two-dimensional cell culture techniques and the major animal models that have been employed in photobiology and photocarcinogenesis research. Additionally, the progression towards the use of cultured skin explants and tissue-engineered skin constructs, and their utility as models of native skin's responses to UVR are described. The inherent advantages and disadvantages of these in vitro systems are also discussed.

A randomised, feasibility trial of a tele-health intervention for Acute Coronary Syndrome patients with depression ('MoodCare')

Background Coronary heart disease (CHD) and depression are leading causes of disease burden globally and the two often co-exist. Depression is common after Myocardial Infarction (MI) and it has been estimated that 15-35% of patients experience depressive symptoms. Co-morbid depression can impair health related quality of life (HRQOL), decrease medication adherence and appropriate utilisation of health services, lead to increased morbidity and suicide risk, and is associated with poorer CHD risk factor profiles and reduced survival. We aim to determine the feasibility of conducting a randomised, multi-centre trial designed to compare a tele-health program (MoodCare) for depression and CHD secondary prevention, with Usual Care (UC). Methods Over 1600 patients admitted after index admission for Acute Coronary Syndrome (ACS) are being screened for depression at six metropolitan hospitals in the Australian states of Victoria and Queensland. Consenting participants are then contacted at two weeks post-discharge for baseline assessment. One hundred eligible participants are to be randomised to an intervention or a usual medical care control group (50 per group). The intervention consists of up to 10 × 30-40 minute structured telephone sessions, delivered by registered psychologists, commencing within two weeks of baseline screening. The intervention focuses on depression management, lifestyle factors (physical activity, healthy eating, smoking cessation, alcohol intake), medication adherence and managing co-morbidities. Data collection occurs at baseline (Time 1), 6 months (post-intervention) (Time 2), 12 months (Time 3) and 24 months follow-up for longer term effects (Time 4). We are comparing depression (Cardiac Depression Scale [CDS]) and HRQOL (Short Form-12 [SF-12]) scores between treatment and UC groups, assessing the feasibility of the program through patient acceptability and exploring long term maintenance effects. A cost-effectiveness analysis of the costs and outcomes for patients in the intervention and control groups is being conducted from the perspective of health care costs to the government. Discussion This manuscript presents the protocol for a randomised, multi-centre trial to evaluate the feasibility of a tele-based depression management and CHD secondary prevention program for ACS patients. The results of this trial will provide valuable new information about potential psychological and wellbeing benefits, cost-effectiveness and acceptability of an innovative tele-based depression management and secondary prevention program for CHD patients experiencing depression.

The delta opioid receptor antagonist, SoRI-9409, decreases yohimbine stress-induced reinstatement of ethanol-seeking

A major problem in treating alcohol use disorders (AUDs) is the high rate of relapse due to stress and re-exposure to cues or an environment previously associated with alcohol use. Stressors can induce relapse to alcohol-seeking in humans or reinstatement in rodents. Delta opioid peptide receptors (DOP-Rs) play a role in cue-induced reinstatement of ethanol-seeking; however, their role in stress-induced reinstatement of ethanol-seeking is not known. The objective of this study was to determine the role of DOP-Rs in yohimbine-stress-induced reinstatement of ethanol-seeking. Male, Long-Evans rats were trained to self-administer 10% ethanol in daily 30-minute operant self-administration sessions using a FR3 schedule of reinforcement, followed by extinction training. Once extinction criteria were met, we examined the effects of the DOP-R antagonist, SoRI-9409 (0–5 mg/kg, i.p.) on yohimbine (2 mg/kg, i.p.) stress-induced reinstatement. Additionally, DOP-R-stimulated [35S]GTPS binding was measured in brain membranes and plasma levels of corticosterone (CORT) were determined. Pre-treatment with SoRI-9409 decreased yohimbine stress-induced reinstatement of ethanol-seeking but did not affect yohimbine-induced increases in plasma CORT levels. Additionally, yohimbine increased DOP-R-stimulated 35[S]GTPS binding in brain membranes of ethanol-trained rats, an effect that was inhibited by SoRI-9409. This suggests that the DOP-R plays an important role in yohimbine-stress-induced reinstatement of ethanol-seeking behavior, and DOP-R antagonists may be promising candidates for further development as a treatment for AUDs.

Detection of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2(PAI-2) in gingival crevicular fluid from healthy, gingivitis and periodontitis patients

Background: The regulation of plasminogen activation is a key element in controlling proteolytic events in the extracellular matrix. Our previous studies had demonstrated that in inflamed gingival tissues, tissue-type plasminogen activator (t-PA) is significantly increased in the extracellular matrix of the connective tissue and that interleukin 1β (IL-1β) can up regulate the level of t-PA and plasminogen activator inhibitor-2 (PAI-2) synthesis by human gingival fibroblasts. Method: In the present study, the levels of t-PA and PAI-2 in gingival crevicular fluid (GCF) were measured from healthy, gingivitis and periodontitis sites and compared before and after periodontal treatment. Crevicular fluid from106 periodontal sites in 33 patients were collected. 24 sites from 11 periodontitis patients received periodontal treatment after the first sample collection and post-treatment samples were collected 14 days after treatment. All samples were analyzed by enzyme-linked immunosorbent assay (ELISA) for t-PA and PAI-2. Results: The results showed that significantly high levels of t-PA and PAI-2 in GCF were found in the gingivitis and periodontitis sites. Periodontal treatment led to significant decreases of PAI-2, but not t-PA, after 14 days. A significant positive linear correlation was found between t-PA and PAI-2 in GCF (r=0.80, p<0.01). In the healthy group, different sites from within the same subject showed little variation of t-PA and PAI-2 in GCF. However, the gingivitis and periodontitis sites showed large variation. These results suggest a good correlation between t-PA and PAI-2 with the severity of periodontal conditions. Conclusion: This study indicates that t-PA and PAI-2 may play a significant rôle in the periodontal tissue destruction and tissue remodeling and that t-PA and PAI-2 in GCF may be used as clinical markers to evaluate the periodontal diseases and assess treatment.

Nitric oxide synthase type-II is synthesized by human gingival tissue and cultured human gingival fibroblasts

Nitric oxide is known to be an important inflammatory mediator, and is implicated in the pathophysiology of a range of inflammatory disorders. The aim of this study was to determine the localization and distribution of endothelial NOS (NOS-II) in human gingival tissue, and to ascertain if human gingival fibroblasts express NOS-II when stimulated with interferon gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS). The distribution of NOS-II in inflamed and non-inflamed specimens of human gingivae was studied using a monoclonal antibody against nitric oxide synthase II. Cultures of fibroblasts derived from healthy human gingivae were used for the cell culture experiments. The results from immunohistochemical staining of the tissues indicated an upregulation of NOS-II expression in inflamed compared to non-inflamed gingival tissue. Fibroblasts and inflammatory cells within the inflamed connective tissue were positively stained for NOS-II. In addition, basal keratinocytes also stained strongly for NOS-II, in both healthy and inflamed tissue sections. When cultured human gingival fibroblasts were stimulated by INF-gamma and Porphyromonas gingivalis LPS, NOS-II was more strongly expressed than when the cells were exposed to LPS or IFN-gamma alone. These data suggest that, as for other inflammatory diseases, NO plays a role in the pathophysiology of periodontitis.

Expression and distribution of cell-surface proteoglycans in the normal Lewis rat molar periodontium

Cell-surface proteoglycans participate in several biological functions such as cell cell and cell-matrix interactions, cell adhesion, the binding to various growth factors as co-receptors and repair. To understand better the expression and distribution of cell-surface proteoglycans in the periodontal tissues, an immunohistochemical evaluation of the normal Lewis rat molar periodontium using panels of antibodies for syndecan-1, -2, -4, glypican and betaglycan was carried out. Our results demonstrated the expression and distribution of all proteoglycans in the suprabasal gingival epithelium, soft and hard connective tissues. Both cellular and matrix localization was evident within the various periodontal compartments. The presence of these cell-surface proteoglycans indicates the potential for roles in the process of tissue homeostasis, repair or regeneration in periodontium of which each function requires further study.

Effect of lipopolysaccharide from periodontal pathogens on the production of tissue plasminogen activator and plasminogen activator inhibitor 2 by human gingival fibroblasts.

Both tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 2 (PAI-2) are important proteolysis factors present in inflamed human periodontal tissues. The aim of the present study was to investigate the effect of lipopolysaccharide (LPS) on the synthesis of t-PA and PAI-2 by human gingival fibroblasts (HGF). LPS from different periodontal pathogens including Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum were extracted by the hot phenol water method. The levels of t-PA and PAI-2 secreted into the cell culture media were measured by enzyme-linked immunosorbent assays (ELISA). The mRNA for t-PA and PAI-2 were measured by RT-PCR. The results showed t-PA synthesis was increased in response to all types of LPS studied and PAI-2 level was increased by LPS from A. actinomycetemcomitans and F. nucleatum, but not P. gingivalis. When comparing the effects of LPS from non-periodontal bacteria (Escherichia coli and Salmonella enteritidis) with the LPS from periodontal pathogens, we found that the ratio of t-PA to PAI-2 was greater following exposure of the cells to LPS from periodontal pathogens. The highest ratio of t-PA to PAI-2 was found in those cells exposed to LPS from P. gingivalis. These results indicate that LPS derived from periodontal pathogens may cause unbalanced regulation of plasminogen activator and plasminogen activator inhibitor by HGF and such an effect may, in part, contribute to the destruction of periodontal connective tissue through dysregulated pericellular proteolysis.