BESI: Behavioral and Environmental Sensing and Intervention for Dementia Caregiver Empowerment-Phases 1 and 2.

BACKGROUND AND OBJECTIVES: Caregiver burden associated with dementia-related agitation is one of the commonest reasons a community-dwelling person with dementia (PWD) transitions to a care facility. Behavioral and Environmental Sensing and Intervention for Dementia Caregiver Empowerment (BESI) is a system of body-worn and in-home sensors developed to provide continuous, noninvasive agitation assessment and environmental context monitoring to detect early signs of agitation and its environmental triggers. RESEARCH DESIGN AND METHODS: This mixed methods, remote ethnographic study is explored in a 3-phase, multiyear plan. In Phase 1, we developed and refined the BESI system and completed usability studies. Validation of the system and the development of dyad-specific models of the relationship between agitation and the environment occurred in Phase 2. RESULTS: Phases 1 and 2 results facilitated targeted changes in BESI, thus improving its overall usability for the final phase of the study, when real-time notifications and interventions will be implemented. CONCLUSION: Our results show a valid relationship between the presence of dementia related agitation and environmental factors and that persons with dementia and their caregivers prefer a home-based monitoring system like BESI.

Strategy for peptide quantification using LC-MS in regulated bioanalysis: case study with a glucose-responsive insulin.

AIM: Advances in technology have led to a shift for peptide quantification from traditional ligand-binding assays to LC-MS/MS-based analysis, which presents challenges, in other assay sensitivity, specificity and ruggedness, in addition to lacking of regulatory guidance, especially for the hybrid assay format. Methodology & results: This report communicates a strategy that has been employed in our laboratories for method development and assay validation, and exemplified in a case study of MK-2640, a glucose-responsive insulin, in multiple matrices. Intact MK-2640 was monitored, while immunoaffinity purification and SPE were used to support the rat/dog GLP and clinical studies, respectively. The rationale and considerations behind our approach, as well as the acceptance criteria applied to the assay validation are discussed.

Elaborating the Human Aspect of the NIST Framework for Cyber-Physical Systems.

The National Institute of Standards and Technology (NIST) has developed a Framework for Cyber-Physical Systems (CPS Framework) that supports system engineering analysis, design, development, operation, validation and assurance of CPS. Cyber-physical systems (CPS) comprise interacting digital, analog, physical, and human components engineered for function through integrated physics and logic. For instance, a city implementing an advanced traffic management system including real-time predictive analytics and adaptation/optimization must consider all aspects of such a CPS system of systems' functioning and integrations with other systems, including interactions with humans. One Aspect (or grouping of stakeholder concerns) of the CPS Framework is the Human Aspect. NIST is engaging HFES in a panel discussion to elaborate Human Aspect concerns, especially relevant constructs, measures, methods, and tools.

Open plan offices as sociotechnical systems: What matters and to whom?

BACKGROUND: Open plan offices have proliferated for the past several decades with more and more workers being concentrated in office buildings. Several studies have identified a number of negative factors associated with open plan offices, and those include noise, speech interference, lack of privacy, and a perceived loss of control over work. While negative factors have been identified several times in the literature, many studies rely on either surveys or highly controlled environments. OBJECTIVE: The objective of this study was to use a quasi-naturalistic environment based on a scaled world model to test three hypotheses of the impacts of office interference on editing and web navigation performance and mental workload. METHOD: A mixed factor design was used that utilized continuous speech recordings, discontinuous speech recordings, and a quiet condition. Individual differences questionnaires were administered to measure focused attention, stress, and cognitive failures. After task completion, participants recorded mental workload ratings. RESULTS: Participants had higher performance accuracy in the document editing task across the speech interference conditions. Mental workload ratings were higher in the web navigation task in the discontinuous speech condition compared to the continuous speech condition. In contrast to the hypothesis, those reporting stronger focused attention performed more poorly across all speech conditions. Overall, the results were mixed. CONCLUSIONS: OPO work design must focus on individual differences among workers to determine how to customize design to facilitate performance.

Disposition into Adipose Tissue Determines Accumulation and Elimination Kinetics of the Cholesteryl Ester Transfer Protein Inhibitor Anacetrapib in Mice.

The cholesteryl ester transfer protein (CETP) inhibitor anacetrapib exhibits a long terminal half-life (t½) in humans; however, the dispositional mechanisms that lead to this long t½ are still being elucidated. As it is hypothesized that disposition into adipose tissue and binding to CETP might play a role, we sought to delineate the relative importance of these factors using a preclinical animal model. A multiple-dose pharmacokinetic study was conducted in C57BL6 wild-type (WT) lean, WT diet-induced obese (DIO), natural flanking region (NFR) CETP-transgenic lean, and NFR-DIO mice. Mice were dosed orally with 10 mg/kg anacetrapib daily for 42 days. Drug concentrations in blood, brown and white adipose tissue, liver, and brain were measured up to 35 weeks postdose. During dosing, a 3- to 9-fold accumulation in 72-hour postdose blood concentrations of anacetrapib was observed. Drug concentrations in white adipose tissue accumulated ∼20- to 40-fold, whereas 10- to 17-fold accumulation occurred in brown adipose and approximately 4-fold in liver. Brain levels were very low (<0.1 µM), and a trend of accumulation was not seen. The presence of CETP as well as adiposity seems to play a role in determining the blood concentrations of anacetrapib. The highest blood concentrations were observed in NFR DIO mice, whereas the lowest concentrations were seen in WT lean mice. In adipose and liver tissue, higher concentrations were seen in DIO mice, irrespective of the presence of CETP. This finding suggests that white adipose tissue serves as a potential depot and that disposition into adipose tissue governs the long-term kinetics of anacetrapib in vivo.

Haptic perception of users with low vision and their needs in haptic-incorporated user interfaces.

PURPOSE: This paper reports on research aimed at advancing understanding haptic capability and needs of users with low vision. The objective is to apply this understanding to the design of haptic-incorporated user interfaces. METHOD: Study 1 investigated the haptic perception between sighted participants and those with low vision through the magnitude estimation technique, and Study 2 explored the degree to which similar user interface needs were observed among the two vision groups. RESULTS: Overall, our findings indicate there was no significant difference between the two vision groups in terms of haptic perception and user interface needs. A few differences in user interface preference did exist, however, and designers should take these into account. CONCLUSIONS: Participants with low vision were a group who relied on their vision in everyday life instead of touch. Thus, their haptic capability was less likely to be enhanced via brain plasticity, which probably contributed to no significant difference in haptic-incorporated user interface needs. IMPLICATIONS FOR REHABILITATION: No significant different haptic capability and haptic user interface (UI) needs exists between cited participants and those with low vision. UI designers should take into consideration that a certain range of magnitude/type of haptic feedback is available to accommodate preferences of both vision groups, which would ultimately increase the likelihood of successfully developing universal designs.

The effects of sign design features on bicycle pictorial symbols for bicycling facility signs.

The inanimate bicycle symbol has long been used to indicate the animate activity of bicycling facility signs. In contrast, either the inanimate bicycle symbol or the animate bicycle symbol has been used interchangeably for the standard pavement symbols in bike lanes. This has led to confusion among pedestrians and cyclists alike. The purpose of this study was to examine two different designs (inanimate symbol vs. animate symbol) involved in the evaluation of perceived preference and glance legibility, and investigate sign design features on bicycle pictorial symbols. Thirty-five participants compared current bicycle signs (inanimate symbols) to alternative designs (animate symbols) in a controlled laboratory setting. The results indicated that the alternative designs (animate symbols) showed better performance in both preference and glance legibility tests. Conceptual compatibility, familiarity, and perceptual affordances were found to be important factors as well.

Identifying fall-protection training needs for residential roofing subcontractors.

Falls remain the leading cause of injuries and fatalities in the small residential roofing industry and analogous investigations are underrepresented in the literature. To address this issue, fall-protection training needs were explored through 29 semi-structured interviews among residential roofing subcontractors with respect to recommendations for the design of fall-protection training. Content analysis using grounded theory was conducted to analyze participants' responses. Results of the analysis revealed six themes related to the design of current fall-protection training: (1) barriers to safety training; (2) problems of formal safety-training programs; (3) recommendations for training implementation; (4) important areas for fall-protection training; (5) training delivery means; and (6) design features of training materials. Results of the study suggest the need for informal jobsite safety training to complement what had been covered in formalized safety training. This work also provides recommendations for the design of a more likely adopted fall-protection training program.

Validation of noninvasive body sensor network technology in the detection of agitation in dementia.

OBJECTIVE: Agitated behaviors are one of the most frequent reasons that patients with dementia are placed in long-term care settings. This study aims to validate the ability of a custom Body Sensor Network (BSN) to capture the presence of agitation against currently accepted subjective measures, the Cohen-Mansfield Agitation Inventory (CMAI) and the Aggressive Behavior Scale (ABS) and to discriminate between agitation and cognitive decline. METHODS: Six patients identified as being at high risk for agitated behaviors were enrolled in this study. The devices were applied at three sites for three hours while behaviors were annotated simultaneously and subsequently repeated twice for each enrolled subject. RESULTS: We found that the BSN was a valid measure of agitation based on construct validity testing and secondary validation using non-parametric ANOVAs. DISCUSSION: The BSN shows promise from these pilot results. Further testing with a larger sample is needed to replicate these results.

Effects of video placement and spatial context presentation on path reconstruction tasks with contextualized videos.

Many interesting and promising prototypes for visualizing video data have been proposed, including those that combine videos with their spatial context (contextualized videos). However, relatively little work has investigated the fundamental design factors behind these prototypes in order to provide general design guidance. Focusing on real-time video data visualization, we evaluated two important design factors--video placement method and spatial context presentation method--through a user study. In addition, we evaluated the effect of spatial knowledge of the environment. Participants' performance was measured through path reconstruction tasks, where the participants followed a target through simulated surveillance videos and marked the target paths on the environment model. We found that embedding videos inside the model enabled realtime strategies and led to faster performance. With the help of contextualized videos, participants not familiar with the real environment achieved similar task performance to participants that worked in that environment. We discuss design implications and provide general design recommendations for traffic and security surveillance system interfaces.

Evaluation of pictorial assembly instructions for young children.

OBJECTIVE: We examined the usability of common formats of pictorial toy assembly instructions for 6- and 9-year-old children. BACKGROUND: Interlocking building toys and models are increasingly prevalent and important for developing spatial abilities and fine motor skills among children. Little is known about how effectively the intended child users can interpret and carry out the instructions. METHOD: Twenty-four children used five sets of manufacturer-supplied pictorial toy assembly instructions. We evaluated the impact of toy instruction set, age, gender, and previous experience on usability problems, assembly speed and accuracy, instruction gaze time, and subjective ratings. RESULTS: The children had difficulty with all but the simplest instructions and assemblies. As predicted, older participants assembled more quickly, with fewer errors and fewer instruction looks. However, the 6-year-old girls assembled the fewest parts correctly, and the 9-year-old girls reported having the least fun. Instruction look time and frequency revealed differences in instruction complexity and were correlated with subjective ratings of fun. Thirty-two usability problems were observed, and 10 are described in detail. CONCLUSION: Product age recommendations may not reflect developmentally appropriate instructions. Small design changes should contribute to improved instruction usability among young children. For instance, designers should avoid complex graphic syntax, depict colors accurately, select clear angles of view, and support natural tendencies to assemble top to bottom. APPLICATION: This research provides pictorial assembly instruction guidelines to inform instruction designers and describes performance and look-time benchmarks for future usability studies.

Effects of psychosocial and individual factors on physiological risk factors for upper extremity musculoskeletal disorders while typing.

Psychosocial factors are hypothesized to contribute to work-related musculoskeletal disorder (WMSD) development, although previous research has been largely epidemiological or has focused primarily on the shoulders, back and neck. The objective of this study was to quantify the effects of mental workload and time pressure on perceived workload and physiological responses of the distal upper extremity. A total of 18 typists completed nine 5-min typing sessions representing three levels of time pressure and mental workload. Levels were manipulated by adjusting typing speed and by requiring participants to perform arithmetic tasks while typing. Outcomes were measured in muscle activation levels, wrist postures and movements, key strike force and subjective assessments of workload. In general, increased time pressure increased muscle activation, key strike force and wrist deviations; and increased mental workload increased key strike force. Mental workload and time pressure mediated physical risk factors during typing to increase WMSD risk for the distal upper extremity.

Defined genetic events associated with the spontaneous in vitro transformation of ElA/Ras-expressing human IMR90 fibroblasts.

In contrast to rodent cells, normal human fibroblasts are generally resistant to neoplastic transformation in vitro. Here, we report the derivation and characterization of a spontaneously transformed cell line from normal human IMR90 fibroblasts transduced with E1A and Ras oncogenes. Unlike the parental, non-tumorigenic E1A/Ras-expressing IMR90 cells, these spontaneously transformed cells displayed aberrant growth potential in vitro and were capable of tumorigenesis in vivo. In contrast to the parental E1A/Ras-expressing cells, both the spontaneously transformed cells and cells derived from resultant tumors displayed specific t(7q;8q) and t(5q;17) structural chromosomal changes. Chromosome 8q contains c-Myc, which is capable of activating the telomerase catalytic subunit hTERT. Notably, upregulation of c-Myc, hTERT and telomerase activity were detected only in the tumorigenic cells. Transduction of Myc siRNA into the tumorigenic cells led to a concomitant downregulation of hTERT. Furthermore, transduction of Myc or hTERT into the non-tumorigenic E1A/Ras-expressing IMR90 cells was able to confer tumorigenesis on these cells. These studies suggest that the t(7;8) translocation may result in Myc overexpression and its subsequent activation of hTERT, which may contribute to the tumorigenicity of the IMR90 cells. Furthermore, this report describes additional successful neoplastic transformation of human IMR90 fibroblasts by defined genetic elements. The spontaneously transformed cells we have derived provide a valuable model system for the study of neoplastic transformation.

Expression of p16INK4A variants in senescent human fibroblasts independent of protein phosphorylation.

Upregulation of the p16 tumor suppressor is a hallmark of senescence in human fibroblasts. In this study, we investigated potential protein modification of p16 in senescent human fibroblasts using 2D SDS-PAGE analysis. Three distinct p16 variants with isoelectric points of 5.2, 5.4, and 5.6, were consistently detected in normal human IMR90 fibroblasts that had undergone senescence due to forced expression of oncogenic H-ras or culture passage. Moreover, in contrast to short-term serum starvation, which induces quiescence, IMR90 fibroblasts cultured in low serum for a prolonged period exhibited senescent phenotypes and expression of the three p16 variants. All three p16 variants are unlikely phosphoproteins since they failed to react with antibodies against phospho-serine, and were resistant to the treatment with phosphatases. Functionally, co-immunoprecipitation assays using antibodies against cdk4 and/or cdk6 revealed that only the two most acidic p16 variants associated with cdk4/6. Moreover, senescence induced by the forced expression of p16 in early passage IMR90 fibroblasts or osteosarcoma U2OS cells was accompanied by expression of the two most acidic p16 variants, which also associated with cdk4/6. In summary, we report that prolonged serum starvation-induced senescence may provide an additional model for studying biochemical changes in senescence, including p16 regulation. Furthermore, induction of endogenous p16 in senescent human fibroblasts correlates with the expression of three distinct p16 variants independent of protein phosphorylation. Lastly, expression of the two cdk-bound variants is sufficient to induce senescence in human cells.

Differential oncogenic Ras signaling and senescence in tumor cells.

Several studies have shown that forced expression of oncogenic H-ras can induce a senescence-like permanent growth arrest in normal cells. Here we report that expression of oncogenic H-ras in human osteosarcoma U2OS cells also resulted in a senescence-like flat and enlarged cell morphology and permanent growth arrest. In contrast to normal human fibroblasts, U2OS cells were arrested independently of the p16 and ARF tumor suppressors. Treatment with a MEK inhibitor or a p38MAPK inhibitor interrupted oncogenic H-ras-induced growth arrest in U2OS cells, suggesting that activation of MAPK pathways is important. To further determine whether this process is unique to oncogenic H-ras signaling, we examined the effect of oncogenic K-ras on normal cells and human osteosarcoma cells. Similar to oncogenic H-ras, oncogenic K-ras also induced senescence in normal fibroblasts, while transforming immortalized mouse fibroblasts. However, in contrast to oncogenic H-ras, oncogenic K-ras failed to induce a permanent growth arrest in osteosarcoma U2OS cells. Additionally, cells transduced with oncogenic K-ras exhibited distinguishable cellular changes compared to those transduced with oncogenic H-ras. In summary, we report for the first time that oncogenic H-ras signaling can trigger a senescence-like growth arrest in tumor cells, independent of the p16 and ARF tumor suppressors. This result suggests that tumor cells may harbor a senescence-like program that can be activated by ras signaling. Moreover, our study uncovered a cell type-dependent differential response to oncogenic K-ras, as compared to oncogenic H-ras.

Molecular signature of oncogenic ras-induced senescence.

Senescence irreversibly arrests the proliferation of cells that have sustained significant cellular stress. Replicative senescence, due to the shortening and dysfunction of telomeres, appears to provide a barrier to the immortalization of cells and development of cancer. In normal human fibroblasts, senescence induced by oncogenic H-ras displays a nearly identical cellular phenotype to that of replicative senescence, suggesting the activation of a common senescence mechanism. In this study, we investigated the gene expression profile of oncogenic H-ras-induced senescent human diploid fibroblasts. We found altered gene expression of various cell cycle regulators in both oncogenic H-ras-induced senescent cells and replicative senescent cells. Similar to replicative senescent cells, H-ras-induced senescent cells exhibited specific downregulation of genes involved in G2/M checkpoint control and contained tetraploid cells that were arrested in a G1 state. This observation suggests that the inactivation of G2/M checkpoints may be involved in senescence and may play a role in the generation of senescent G1 tetraploid cells. Lastly, we have identified two genes, topoisomerase IIalpha and HDAC9, whose expression was specifically altered under several conditions associated with senescence, suggesting that these two molecules may be novel biomarkers for senescent human fibroblasts.

The effect of maternal smoking on respiratory and arousal patterns in preterm infants during sleep.

Prenatal exposure to cigarette smoke is associated with an increased risk of sudden infant death syndrome. The effect of maternal smoking on apnea and arousal patterns in preterm infants is currently unknown. Multichannel polysomnographic studies were performed in preterm infants. Thirty infants were enrolled into the study: 16 exposed prenatally to cigarette smoke (S) and 14 control infants (C). There was no difference in the gestational and postconceptional ages at the time of study. Maternal smoking was associated with a significant increase in the apneic index in these infants (28.6 +/- 6.4/hour [S] vs. 13.2 +/- 3.9 [C]; p<0.05), and the difference was noted for obstructive events and only during active sleep. The arousal index was significantly decreased in the maternal smoking group (34.5 +/- 2.3/hour [S] vs. 46.3 +/- 5.6/hour [C]; p<0.05), with a specific decrease in percentage of arousal after respiratory events (10.7 +/- 2.1% [S] vs. 29.4 +/- 5.4% [C]; p<0.05). In conclusion, preterm infants exposed prenatally to cigarette smoke have increased respiratory events during active sleep, predominantly due to obstructive apnea, and possibly a higher arousal threshold during apneic events. These alterations in respiratory and arousal patterns in preterm infants born to smoking mothers may lead to significant vulnerability in this population.

Accessible cell phone design: development and application of a needs analysis framework.

PURPOSE: This research describes the development and use of the Needs Analysis and Requirements Acquisition (NARA) framework to elicit and construct user requirements for the design of cell phones (which are a type of assistive technology) that are both usable and accessible to persons with disabilities. METHOD: Semi-structured interviews and a focus group were used to elicit information and a systematic approach was used to translation information into requirements (construct). Elicitation and construction are the first two stages of NARA. RESULTS: Requirements for general and feature-specific phone attributes were identified, and several requirements were found to match six of the seven universal design principles. CONCLUSIONS: The study demonstrated that NARA is both a straight-forward and cost-effective method to develop user requirements and can be used throughout the development cycle.

Research-based guidelines for warning design and evaluation.

During the past two decades, the body of empirical research on warning design and evaluation has grown. Consequently, there are now basic principles and guidelines addressing warning design (e.g., signal words, color, symbols, and text/content), placement (e.g., location within product instructions), and how to enhance the usability of designs by considering factors internal to the user (e.g., beliefs, perceptions of risk, stress). Similarly, evaluation methods have been developed that can be used to measure the effectiveness of warnings such as the degree to which warnings are communicated to recipients and the degree to which they encourage or influence behavioral compliance. An overview of the empirical literature on warning guidelines and evaluation approaches is provided. Researchers, practitioners, and manufacturers can use these guidelines in various contexts to reduce the likelihood that injury and product damage from exposure to a hazard will occur.

Cultural ergonomics in Ghana, West Africa: a descriptive survey of industry and trade workers' interpretations of safety symbols.

Globalization and technology transfer have led to the diffusion of risk communications to users from cultures that were not initially viewed as the target users. This study examined industry and trade workers' overall impressions of symbols used to convey varying degrees of hazardousness. Six symbols, including symbols from the American National Standards Institute (ANSI) Z535 Standard (ANSI, 1998) and the International Organization for Standardization (ISO) 3864:1984 Standard (ISO, 1984) were selected. With the exception of the SKULL symbol, results showed wide discrepancies between users' perceptions of the symbols and their intended meanings. Implications for cross-cultural research on warning components and risk communications are discussed.