Domains controlling cell polarity and proliferation in the Drosophila tumor suppressor Scribble

Cell polarity and cell proliferation can be coupled in animal tissues, but how they are coupled is not understood. In Drosophila imaginal discs, loss of the neoplastic tumor suppressor gene scribble (scrib), which encodes a multidomain scaffolding protein, disrupts epithelial organization and also causes unchecked proliferation. Using an allelic series of mutations along with rescuing transgenes, we have identified domain requirements for polarity, proliferation control, and other Scrib functions. The leucine-rich repeats (LRR) tether Scrib to the plasma membrane, are both necessary and sufficient to organize a polarized epithelial monolayer, and are required for all proliferation control. The PDZ domains, which recruit the LRR to the junctional complex, are dispensable for overall epithelial organization. PDZ domain absence leads to mild polarity defects accompanied by moderate overproliferation, but the PDZ domains alone are insufficient to provide any Scrib function in mutant discs. We suggest a model in which Scrib, via the activity of the LRR, governs proliferation primarily by regulating apicobasal polarity

Development of a Fan for Future Space Suit Applications

NASA's next generation space suit system will place new demands on the fan used to circulate breathing gas through the ventilation loop of the portable life support system. Long duration missions with frequent extravehicular activities (EVAs), the requirement for significant increases in reliability and durability, and a mission profile that imposes strict limits on weight, volume and power create the basis for a set of requirements that demand more performance than is available from existing fan designs. This paper describes the development of a new fan to meet these needs. A centrifugal fan was designed with a normal operating speed of approximately 39,400 rpm to meet the ventilation flow requirements while also meeting the aggressive minimal packaging, weight and power requirements. The prototype fan also operates at 56,000 rpm to satisfy a second operating condition associated with a single fan providing ventilation flow to two spacesuits connected in series. This fan incorporates a novel nonmetallic "can" to keep the oxygen flow separate from the motor electronics, thus eliminating ignition potential. The nonmetallic can enables a small package size and low power consumption. To keep cost and schedule within project bounds a commercial motor controller was used. The fan design has been detailed and implemented using materials and approaches selected to address anticipated mission needs. Test data is presented to show how this fan performs relative to anticipated ventilation requirements for the EVA portable life support system. Additionally, data is presented to show tolerance to anticipated environmental factors such as acoustics, shock, and vibration. Recommendations for forward work to progress the technology readiness level and prepare the fan for the next EVA space suit system are also discussed

A call for responsible innovation in mobile mental health:findings from a content analysis and ethical review of the depression app marketplace

Mobile mental health presents many ethical challenges in the wild. These ethical issues and associated values were explored through a content analysis and ethical review of the depression app marketplace. App search and data collection was performed in Google Play Store (UK) and Apple iTunes (UK) between October to November 2018. Iterative data extraction and coding of ethical variables and values were conducted prior to synthetization of issues and themes. Search found 353 unique apps for depression. Analysis uncovered a range of ethical issues including: limited evidence of intervention validity, fidelity, and outcomes; insufficient safeguarding and duty of care; non-multisector development teams; lack of independent certification and regulation; lack of information and transparency for informed user choices; and concerns with privacy, confidentiality, and user permissions. These findings highlighted the presence and absence of ethical values in apps for depression, with most apps failing to reflect many key values. Our findings suggest a need for greater ethical value sensitive design in mobile mental health. This is challenging given the field’s multidisciplinarity and value conflicts. We encourage designers to adopt a responsible innovation approach to creating technologies that meet these ethical demands

Cleavage of the signaling mucin Msb2 by the aspartyl protease Yps1 is required for MAPK activation in yeast

Signaling mucins are cell adhesion molecules that activate RAS/RHO guanosine triphosphatases and their effector mitogen-activated protein kinase (MAPK) pathways. We found that the Saccharomyces cerevisiae mucin Msb2p, which functions at the head of the Cdc42p-dependent MAPK pathway that controls filamentous growth, is processed into secreted and cell-associated forms. Cleavage of the extracellular inhibitory domain of Msb2p by the aspartyl protease Yps1p generated the active form of the protein by a mechanism incorporating cellular nutritional status. Activated Msb2p functioned through the tetraspan protein Sho1p to induce MAPK activation as well as cell polarization, which involved the Cdc42p guanine nucleotide exchange factor Cdc24p. We postulate that cleavage-dependent activation is a general feature of signaling mucins, which brings to light a novel regulatory aspect of this class of signaling adhesion molecule

Content Validity Analyses of Qualitative Feedback on the Revised Assessment, Evaluation, and Programming System for Infants and Children (AEPS) Test

Early childhood assessment practices, procedures, and tools can lay the foundation for an effective intervention program. The purpose of this article is to report the results of a content validity study conducted on a revision of Assessment, Evaluation, and Programming System for infants and children (AEPS®) Test, a widely used early childhood assessment/evaluation instrument. A panel of early childhood and early childhood special educator experts was assembled and asked to provide qualitative feedback on the content of the revised AEPS Test. Experts were asked to address five specific questions about item content, developmental sequences, and if assessment items represented quality teaching targets for young children. Qualitative results were used to modify items, developmental sequences, and area content

Trends in Resource Utilization by Children with Neurological Impairment in the United States Inpatient Health Care System: A Repeat Cross-Sectional Study

Jay Berry and colleagues report findings from an analysis of hospitalization data in the US, examining the proportion of inpatient resources attributable to care for children with neurological impairment

A systemic ethical framework for mobile mental health:From design to implementation

The burgeoning field of mobile mental health has brought increased awareness of the need for greater ethical and regulatory frameworks to guide the design, use, and implementation of innovative interventions for vulnerable populations. Mental healthcare has long been guided and regulated by ethical principles and codes of conduct aimed at ensuring standards of practice, professional behaviour, and good and fair delivery of care. Key ethical concepts, such as safety, privacy, and competency, form an integral part of the language and behaviours of mental health practitioners. These issues pervade mobile mental health in much of the same way as traditional mental healthcare. Yet, the multidisciplinary nature of mobile mental health demands a broader conceptualisation and application of these ideas. At its most basic level, mobile mental health unites the fields of mental health, computer science, and human computer interaction. Each of these unique disciplines has its own ethical considerations and standards. There is need for greater integration of all disciplines and a more unified approach to understanding these shared and unique ethical concepts. Without a holistic approach to these critical matters, we risk the development and implementation of mobile mental health which falls short of accepted standards and which pose potential risks to individuals and society. The present research seeks to address this challenge with the development of a systemic ethical framework for mobile mental health. Guided by preliminary review of literature, we conceptualised a systems-based framework capturing the interrelation of pertinent ethical concepts across various disciplines and stakeholder groups, from the fundamental unit of the individual user to practitioners, developers, health agencies, and governance

A content analysis and ethical review of mobile applications for depression:Exploring the app marketplace

BACKGROUND Research investigating commercial mobile applications for depression have shown a range of concerns from limited research evidence, poor treatment fidelity, and issues with privacy and data security. This study advances this work through a content analysis and ethical review of app store listings of apps for depression. Whilst past content analyses and app reviews have highlighted some ethical and safety concerns, there has been no focussed ethical review to consider how these issues may present to potential users who seek to find help and support through the app stores. METHODS We conducted search of the Google Play Store and Apple iOS App Store in October and November 2018. Apps were included in the review if their description mentioned use for depression. Apps were reviewed for treatment information and ethical issues. RESULTS We identified 353 eligible depression apps. Treatment approach varied across apps, with 24 different treatment approaches being described by developers. Treatment strategies also varied, with 34 different strategies being listed. The review showed the use of several non-evidence-based approaches and strategies. Also evident was the continued lack of research evidence for most apps (314/353) and a general lack of transparency in the information provided to potential users. These ethical issues were further explored within the framework of psychological ethical principles, with the review highlighting issues in areas of beneficence/nonmaleficence, fidelity and responsibility, integrity, justice, and respect of person’s rights and dignity. DISCUSSION Despite advances in mobile mental health, commercial mental health apps continue to trail in evidence and practice. There is need for greater research into the efficacy and outcomes of treatment strategies and combinations of approaches. There is also great need for increased transparency of information to help users to make informed and safe choices. Many of the ethical issues discussed can be addressed by presenting potential users with clear and accurate information

Resilience Testing of Health Systems : How Can It Be Done?

The resilience of health systems has received considerable attention as of late, yet little is known about what a resilience test might look like. We develop a resilience test concept and methodology. We describe key components of a toolkit and a 5-phased approach to implementation of resilience testing that can be adapted to individual health systems. We develop a methodology for a test that is balanced in terms of standardization and system-specific characteristics/needs. We specify how to work with diverse stakeholders from the health ecosystem via participatory processes to assess and identify recommendations for health system strengthening. The proposed resilience test toolkit consists of “what if” adverse scenarios, a menu of health system performance elements and indicators based on an input-output-outcomes framework, a discussion guide for each adverse scenario, and a traffic light scorecard template. The five phases of implementation include Phase 0, a preparatory phase to adapt the toolkit materials; Phase 1: facilitated discussion groups with stakeholders regarding the adverse scenarios; Phase 2: supplemental data collection of relevant quantitative indicators; Phase 3: summarization of results; Phase 4: action planning and health system transformation. The toolkit and 5-phased approach can support countries to test resilience of health systems, and provides a concrete roadmap to its implementation

Examining Implicit Attitudes towards Exercisers with a Physical Disability

Background. Using measures of explicit attitudes, physical activity status has been established as a factor that reduces the stigma able-bodied people hold towards people with physical disabilities. This phenomenon is called the exerciser stereotype. However, whether the exerciser stereotype exists when using measures of implicit attitudes remains unknown. Objective. The aims of this study were to evaluate the prevalence of negative implicit attitudes towards people with physical disabilities and determine whether implicit attitudes towards people with physical disabilities were influenced by the exerciser stereotype. Methods. One hundred able-bodied participants (82 females, 18 males) completed two implicit association tests (IATs): the Disability-Attitudes IAT and the Disability-Activity IAT. The Disability-Attitudes IAT measured implicit attitudes towards people who were not disabled relative to disabled; the Disability-Activity IAT measured attitudes towards people with a physical disability who were active relative to inactive. Results. Results revealed that 83.8% of participants had negative implicit attitudes towards people with a disability. Participants held more positive attitudes towards active versus inactive people with a physical disability. Conclusions. The study findings indicate that the exerciser stereotype exists implicitly and may undermine negative attitudes towards people with physical disabilities