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Microbes can initiate developmental gene regulatory cascades in animals. The molecular mechanisms underlying microbe-induced animal development and the evolutionary steps to integrate microbial signals into regulatory programs remain poorly understood. In the upside-down jellyfishCassiopea xamachana, a dinoflagellate endosymbiont initiates the life stage transition from the sessile polyp to the sexual medusa. We found that metabolic products derived from symbiont carotenoids may be important to initiateC. xamachanadevelopment, in addition to expression of conserved genes involved in medusa development of non-symbiotic jellyfish. We also revealed the transcription factor COUP is expressed during metamorphosis, potentially as a co-regulator of nuclear receptor RXR. These data suggest relatively few steps may be necessary to integrate symbiont signals into gene regulatory networks and cements the role of the symbiont as a key trigger for life history transition inC. xamachana.

Background: College health pracitioners are often the primary contact for students with concussion. The aim of this case report is to describe concussion management of a convoluted journey to recovery for a student over the course of an acadmic year.Case presentation: The case starts with an initial presenting event which is further complicated by repeated head traumas, co-morbid mental health conditions, and inconsistency with follow-up. Interprofessional collaboration and inclusion of the Zurich protocol eventually lead to resolution of symptoms. Conclusion: The emphasis on a multidisciplinary approach to the medical and academic progress is described. Identifying information was changed to protect the student.

OBJECTIVE Pregnancy and type 1 diabetes are each associated with increased anxiety and depression, but the combined impact on well-being is unresolved. We compared the mental health of women with and without type 1 diabetes during pregnancy and postpartum and examined the relationship between mental health and glycemic control. RESEARCH DESIGN AND METHODS Participants were women enrolled from 2016 to 2020 in the Environmental Determinants of Islet Autoimmunity (ENDIA) study, a pregnancy to birth prospective cohort following children with a first-degree relative with type 1 diabetes. Edinburgh Postnatal Depression Scale (EPDS) and Perceived Stress Scale (PSS) were completed during the third trimester (T3) (median [interquartile range] 34 [32, 36] weeks) and postpartum (14 [13, 16] weeks) by 737 women (800 pregnancies) with (n = 518) and without (n = 282) type 1 diabetes. RESULTS EPDS and PSS scores did not differ between women with and without type 1 diabetes during T3 and postpartum. EPDS scores were marginally higher in T3: predicted mean (95% CI) 5.7 (5.4, 6.1) than postpartum: 5.3 (5.0, 5.6), independent of type 1 diabetes status (P = 0.01). HbA1c levels in type 1 diabetes were 6.3% [5.8, 6.9%] in T3 and did not correlate with EPDS or PSS scores. Reported use of psychotropic medications was similar in women with (n = 44 of 518 [8%]) and without type 1 diabetes (n = 17 of 282 [6%]), as was their amount of physical activity. CONCLUSIONS Overall, mental health in late pregnancy and postpartum did not differ between women with and without type 1 diabetes, and mental health scores were not correlated with glycemic control.

Cities are increasingly expected to bring urban stakeholders together to deploy smart solutions that address urban challenges and deliver long-term positive impacts. Yet, existing theory and practice struggle to explain how such impacts can be achieved, measured or evidenced. This paper makes two major contributions. Firstly, the paper shows how the Quadruple Helix (QH) innovation approach can be used as the basis for co-producing smart city projects in order to better capture their impacts. In doing so we present a synthesis of current smart city and QH literatures to argue that assessment criteria and indicators must be co-produced with the full set of smart city stakeholders to ensure relevance to context and needs. Secondly, we present an example of a co-produced monitoring and assessment framework and methodology, developed to capture and measure the impacts of smart and sustainable city solutions with the stakeholder teams involved in the European Union Triangulum smart city programme. The paper draws on experiences working with 27 smart city demonstration projects involving public, private and third-sector organisations and communities across Manchester (United Kingdom), Eindhoven (The Netherlands) and Stavanger (Norway). We show how involving QH stakeholders in co-producing impact assessment improves the ability of projects to deliver and measure impacts that matter to cities and citizens. We conclude with a series of lessons and recommendations intended to be of use to the range of organisations and communities currently involved in smart city initiatives across Europe and the world.

We conducted baited camera-trap surveys in eastern Kentucky during October 2017–April 2018 to assess the efficacy of survey duration and attractant type in detecting Spilogale putorius (Eastern Spotted Skunk) and other Appalachian meso-mammals. We surveyed 16 sites across 10 counties over more than 1200 trap-nights. We observed meso-mammals of 9 species, including 3 records of Eastern Spotted Skunks. Our results indicated that a 2-week survey duration with sardine bait yielded meso-mammal detection rates, richness estimates, and species accumulation curves comparable to a 4-week survey duration with sardine bait; the addition of fatty acid scent tablets did not affect results. However, Eastern Spotted Skunks were not recorded until an average of 15 days after deployment, suggesting that species-specific trapping rates must be considered in the duration of camera-trap surveys.

Cities must change rapidly to address a range of sustainability challenges. While urban experimentation has prospered as a framework for innovation, it has struggled to stimulate broader transformation. We offer a novel contribution to this debate by focusing on what municipalities learn from experimentation and how this drives organisational change. The practicalities of how municipalities learn and change has received relatively little attention, despite the recognised importance of learning within the literature on urban experiments and the central role of municipalities in enabling urban transformation. We address this research gap, drawing on four years of in-depth research coproduced with European municipal project coordinators responsible for designing and implementing the largest urban research and innovation projects ever undertaken. This cohort of professionals plays a critical role in urban experimentation and transformation, funnelling billions of Euros into trials of new solutions to urban challenges and coordinating large public-private partnerships to deliver them. For our respondents, learning how to experiment more effectively and embedding these lessons into their organisations was the most important outcome of these projects. We develop the novel concept of process learning to capture the importance of experimentation in driving organisational change. Process learning is significant because it offers a new way to understand the relationship between experimentation and urban transformation and should form the focus of innovation projects that seek to prompt broader urban transformation, rather than technical performance. We conclude by identifying implications for urban planning and innovation funding.

Type 1 diabetes results from autoimmune-mediated destruction of β cells. The tyrosine kinase inhibitor imatinib might affect relevant immunological and metabolic pathways, and preclinical studies show that it reverses and prevents diabetes. Our aim was to evaluate the safety and efficacy of imatinib in preserving β-cell function in patients with recent-onset type 1 diabetes.We did a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Patients with recent-onset type 1 diabetes (100 days from diagnosis), aged 18-45 years, positive for at least one type of diabetes-associated autoantibody, and with a peak stimulated C-peptide of greater than 0·2 nmol LPatients were screened and enrolled between Feb 12, 2014, and May 19, 2016. 45 patients were assigned to receive imatinib and 22 to receive placebo. After withdrawals, 43 participants in the imatinib group and 21 in the placebo group were included in the primary ITT analysis at 12 months. The study met its primary endpoint: the adjusted mean difference in 2-h C-peptide AUC at 12 months for imatinib versus placebo treatment was 0·095 (90% CI -0·003 to 0·191; p=0·048, one-tailed test). This effect was not sustained out to 24 months. During the 24-month follow-up, 32 (71%) of 45 participants who received imatinib had a grade 2 severity or worse adverse event, compared with 13 (59%) of 22 participants who received placebo. The most common adverse events (grade 2 severity or worse) that differed between the groups were gastrointestinal issues (six [13%] participants in the imatinib group, primarily nausea, and none in the placebo group) and additional laboratory investigations (ten [22%] participants in the imatinib group and two [9%] in the placebo group). Per the trial protocol, 17 (38%) participants in the imatinib group required a temporary modification in drug dosing and six (13%) permanently discontinued imatinib due to adverse events; five (23%) participants in the placebo group had temporary modifications in dosing and none had a permanent discontinuation due to adverse events.A 26-week course of imatinib preserved β-cell function at 12 months in adults with recent-onset type 1 diabetes. Imatinib might offer a novel means to alter the course of type 1 diabetes. Future considerations are defining ideal dose and duration of therapy, safety and efficacy in children, combination use with a complimentary drug, and ability of imatinib to delay or prevent progression to diabetes in an at-risk population; however, careful monitoring for possible toxicities is required.Juvenile Research Diabetes Foundation.

The tomosyn/Sro7 family is thought to play an important role in cell surface trafficking both as an effector of Rab family GTPases and as a regulator of plasma-membrane SNARE function. Recent work has determined the binding site of GTP-bound Sec4 on Sro7. Here we examine the effect of mutations in Sro7 that block Sec4 binding in determining the role of this interaction in Sro7 function. Using an in vitro vesicle:vesicle tethering assay, we find that most of Sro7’s ability to tether vesicles is blocked by mutations that disrupt binding to Sec4-GTP. Similarly, genetic analysis demonstrates that the interaction with Sec4 is important for most of Sro7’s functions in vivo. The interaction of Sro7 with Sec4 appears to be particularly important when exocyst function is compromised. This provides strong evidence that Sro7 and the exocyst act as dual effector pathways downstream of Sec4. We also demonstrate that Sro7 tethering requires the presence of Sec4 on both opposing membranes and that homo-oligomerization of Sro7 occurs during vesicle tethering. This suggests a simple model for Sro7 function as a Rab effector in tethering post-Golgi vesicles to the plasma membrane in a pathway parallel to that of the exocyst complex.

The business case for wellbeing is now an influential agenda in the built environment. Increasing demand for user-centred environments means evidence-based design proven to deliver wellbeing outcomes for end users is essential. The challenge is to effectively capture and disseminate this evidence to a range of expert and non-expert audiences. Further, being able to make the link between increased wellbeing and an increase in the productivity, or performance, of building users requires new definitions and methods. An innovative wellbeing valuation approach is presented, consisting of a multi-item scale to measure and quantify the wellbeing outcomes experienced by building users, and impact reporting techniques using Social Return on Investment to produce transferable, monetised evaluation metrics. This combination has the capability to communicate the value of design in a powerful and accessible manner. Wellbeing valuation metrics represent an opportunity to develop new user-driven knowledge and shape the built environment in positive ways. Practical application: Wellbeing has become an influential agenda in the built environment in recent years, suggesting that user-centred priorities will become increasingly significant to the design and construction sector. The wellbeing valuation approach presented represents an innovative blend of a psychological wellbeing model, quantitative measurement and financial reporting to produce transferable metrics to communicate the value of design in a powerful and transformative manner. Wellbeing valuation is a nascent practice, but it provides the professions with opportunities to collaborate with end users and develop new knowledge about buildings, enhancing the ability of practitioners to shape the built environment in positive ways.

Within public lands across the United States, “natural” environments are given boundaries, subject to regulation, and managed for various uses. However, the effective and judicious management of these socionatural spaces for the greater good of both long-term sustainability and the mutual benefit of disparate stakeholders remains a challenge. One such stakeholder group includes forest-dependent communities, specifically, harvesters and producers of nontimber forest products (NTFPs). Relying on a case study of honey producers in rural northwest Florida, this article demonstrates how competing notions of forest management create tensions between local resource users and resource managers. NTFP research engages in timely discussions of diverse economic practices, resource politics, and issues of contested land use and access within a post-industrial context.

Scientific narratives surrounding colony collapse disorder (CCD) are often played against one another. However, oppositional knowledge politics do not neatly segregate the materiality and causal properties of the ecological phenomena they represent. Thus the challenge with CCD is not just to describe the partisan character of how knowledge about it is socially produced. It is also about how to integrate these politics through their less antagonistic material ecologies. We review three dominant discourses underlying CCD and honey bee decline and present a synthesis that conveys how their socially embedded perceptions about ecological causality are more compatible. We invoke a theoretical framework from complexity theory to demonstrate how multiple kinds of ecological causality, from the identifiable and addressable to the more emergent and unpredictable, can align under conflicting policy positions. We argue that this continuum of ecological explanations is a more conciliatory framework for responding to CCD. It provides an alternative to the antagonistic politics that tend to reify and defend either a restrictive search for a singular cause, a paralyzing documentation of all possible permutations of CCD, or a return to a utopian agrarian past. Relating how ecological knowledge is socially produced can illuminate stakeholder positions and strategies. But it is also constructive to map out how the ecological suppositions underlying them relate and inform one under.

The gap between the anticipated and measured environmental performance of energy-efficient buildings is a well-documented issue for the sustainability of the indoor and built environment. The significance of building users and their social practices is persistently underestimated in relation to this performance gap. The sociotechnical research agenda advocates the consideration of design/user interactions and the significance of building management is also being recognised. Conceptual development through the application of social practice theory has sought to overcome the established dualism between building technologies and user behaviour, and the changeable nature of practices in response to active sustainable design technologies has been evidenced. This research paper presents the findings of a qualitative study of an office building in an urban context in the UK. The building constitutes a passive sustainable design solution combining various natural ventilation technologies, including thermal mass, cross-ventilation, operable window design and solar shading. The analysis investigates the underperformance of the building’s energy efficient design in relation to building management as an intermediation process in driving and embedding new practices of natural ventilation.

Intracellular traffic in yeast between the Golgi and the cell surface is mediated by vesicular carriers that tether and fuse in a fashion that depends on the function of the Rab GTPase, Sec4. Overexpression of either of two Sec4 effectors, Sro7 or Sec15, results in the formation of a cluster of post-Golgi vesicles within the cell. Here, we describe a novel assay that recapitulates post-Golgi vesicle clustering in vitro utilizing purified Sro7 and vesicles isolated from late secretory mutants. We show clustering in vitro closely replicates the in vivo clustering process as it is highly dependent on both Sro7 and GTP-Sec4. We also make use of this assay to characterize a novel mutant form of Sro7 that results in a protein that is specifically defective in vesicle clustering both in vivo and in vitro. We show that this mutation acts by effecting a conformational change in Sro7 from the closed to a more open structure. Our analysis demonstrates that the N-terminal propeller needs to be able to engage the C-terminal tail for vesicle clustering to occur. Consistent with this, we show that occupancy of the N terminus of Sro7 by the t-SNARE Sec9, which results in the open conformation of Sro7, also acts to inhibit vesicle cluster formation by Sro7. This suggests a model by which a conformational switch in Sro7 acts to coordinate Rab-mediated vesicle tethering with SNARE assembly by requiring a single conformational state for both of these processes to occur.

Approximately 25% of all nursing home residents take antipsychotics for behavioral disturbances, despite limited efficacy and warnings against their use. The purpose of this quality improvement project was to test the utility of an educational in-service to facilitate the appropriate use of antipsychotics for nursing home residents with dementia. A single group pre/post design targeting the reduction of antipsychotic medications in older adults was guided by Rogers' Diffusion of Innovations theory. Descriptive analyses were done to evaluate antipsychotic use and supporting documentation at baseline and 2 months following an educational intervention that focused on appropriate antipsychotic use, documentation requirements and non-pharmacologic interventions. The prescribing rate for antipsychotics showed a reduction from 20.3% to 15.4% and nursing documentation of non-pharmacological interventions increased from 16.7% to 75%. Assuring appropriate use of antipsychotics is currently mandated and is consistent with high quality, person centered care. This simple, yet individualized educational intervention and assessment can serve as a model for use in other long term care facilities.

The Apalachicola–Chattahoochee–Flint (ACF) River basin is an important ecological and economic component of a three-state region (Florida, Alabama and Georgia) in the southeastern U.S. Along the Apalachicola River in northwest Florida, the duration of floodplain inundation has decreased as a result of declining river levels. Spring and summer flows have diminished in volume because of water use, storage and evaporation in reservoirs, and other anthropogenic and climatic changes in the basin upstream. Channel erosion from dam construction and navigation improvements also caused river levels to decline in an earlier period. In this paper, we document trends in floodplain forest tree species composition for the interval spanning these influences. Historic tree inventories from the 1970s were compared to present-day forests through non-metric multidimensional scaling, indicator species analysis (ISA) and outlier detection. Forests are compositionally drier today than in the 1970s. Overstory to understory compositional differences within habitats (levees, high/low bottomland forest and backswamps) are as large as the species contrasts between habitats. Present-day forests are also compositionally noisier with fewer indicator species. The largest individual declines in species density and dominance were in backswamps, particularly for Fraxinus caroliniana Nyssa ogeche and Nyssa aquatica. We discuss how contrasts in the compositional change signal for levee and backswamp landform habitats reflect a complex biogeomorphic response to fluctuating river flows for alluvial rivers in humid climates. Copyright # 2009 John Wiley & Sons, Ltd.

The objectives of the present study were to evaluate whether investigator bias influenced the Convergence Insufficiency Symptom Survey (CISS) scores of children with normal binocular vision (NBV) in our original validation study, reevaluate the usefulness of the cutoff score of 16, and reexamine the validity of the CISS.Six clinical sites participating in the Convergence Insufficiency Treatment Trial (CITT) enrolled 46 children 9 to18 years with NBV. Examiners masked to the child's binocular vision status administered the CISS. The mean CISS score was compared with that from the children with NBV in the original, unmasked CISS study and also to that of the 221 symptomatic convergence insufficiency (CI) children enrolled in the CITT.The mean (+/-standard deviation) CISS score for 46 subjects with NBV was 10.4 (+/-8.1). This was comparable with our prior unmasked NBV study (mean = 8.1 (+/-6.2); p = 0.11) but was significantly different from that of the CITT CI group (mean = 29.8 +/- 9.0; p0.001). Eighty-three percent of these NBV subjects scored16 on the CISS, which is not statistically different from the 87.5% found in the original unmasked study (p = 0.49).Examiner bias did not affect the CISS scores for subjects with NBV in our prior study. The CISS continues to be a valid instrument for quantifying symptoms in 9 to18-year-old children. These results also confirm the validity of a cut-point ofor = 16 in distinguishing children with symptomatic CI from those with NBV.

Brazil is the largest economy in Latin America and the world's leading producer and exporter of coffee. Smallholders are the predominant producers of Brazilian coffee and have been significantly impacted by post-ISI (import substitution industrialisation) neoliberal reforms that swept the nation's agricultural sector beginning in the 1980s. These reforms stimulated increased coffee production while simultaneously diminishing state interventions, including agricultural subsidies, farmer credits, research and development programmes, extension services, and rural development initiatives. These changes were closely followed by major restructuring of the global coffee market and the elimination of international coffee export quotas. Our research joins a growing body of recent literature exploring how changes related to market liberalisation and globalisation affect localities and regions where producers supply coffee for conventional markets. Through a case study, we describe the impacts of neoliberal globalisation on the lives, livelihoods, and environment of small-scale coffee producers in Minas Gerais, Brazil. We explore how neoliberal reform, reflected in the specific historical, geographical, and environmental context of Brazilian coffee production, has resulted in the increased marginalisation of small-scale farmers, the degradation of soils, and overall rural decline.

Sro7, a downstream effector of the Sec4 Rab GTPase, acts during Golgi-to-cell surface transport. The binding site for Sec4 occurs within a cleft on Sro7 formed by the junction of two adjacent β-propeller structures. In silico docking and mutational validation experiments point to a precise model for interaction of Sec4-GTP with Sro7., Members of the tomosyn/Lgl/Sro7 family play important roles in vesicle trafficking and cell polarity in eukaryotic cells. The yeast homologue, Sro7, is believed to act as a downstream effector of the Sec4 Rab GTPase to promote soluble N-ethylmaleimide–sensitive factor adaptor protein receptor (SNARE) assembly during Golgi-to–cell surface vesicle transport. Here we describe the identification of a Sec4 binding site on the surface of Sro7 that is contained within a cleft created by the junction of two adjacent β-propellers that form the core structure of Sro7. Computational docking experiments suggested four models for interaction of GTP-Sec4 with the Sro7 binding cleft. Further mutational and biochemical analyses confirmed that only one of the four docking arrangements is perfectly consistent with our genetic and biochemical interaction data. Close examination of this docking model suggests a structural basis for the high substrate and nucleotide selectivity in effector binding by Sro7. Finally, analysis of the surface variation within the homologous interaction site on tomosyn-1 and Lgl-1 structural models suggests a possible conserved Rab GTPase effector function in tomosyn vertebrate homologues.

Melanoma, the most aggressive form of skin cancer, which accounts for 75% of all skin cancer-related deaths, continues to rise at an alarming rate worldwide. Despite a favorable cure rate when surgically removed at an early stage, the response rate of patients with metastatic disease to single agent chemotherapy is less than 15%, and biologic therapies are only marginally effective. Given this bleak picture, there is a great need to identify and characterize genes that play an important role in the advanced stages of melanoma and thus, may represent valuable targets for clinical therapy. The cell adhesion molecules N-cadherin, MCAM and beta3 integrin have been suggested to represent melanoma progression markers; yet, little is known as to whether they may constitute therapeutic targets for the disease. To provide information regarding this aspect, we determined by way of whole-genome and tissue microarray analysis, their level of expression concordant with melanoma progression, and via RNA interference and antisense technology, their role in melanoma cell proliferation, migration, and invasion. The results of these studies demonstrate that N-cadherin and beta3 integrin expression correlates with progression to advanced-stage melanoma, whereas expression of MCAM does not. On the other hand, MCAM and beta3 integrin are the two adhesion molecules that play a pivotal role in melanoma cell migration and invasion, and for this reason, may represent valuable targets for melanoma therapy.

Background: Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are associated with otitis media (OM). Indigenous children experience particularly high rates of OM. Few studies worldwide have described upper respiratory tract (URT) carriage in Indigenous and non-Indigenous children living in the same area. Aim: The aim of this study was to describe URT bacterial carriage in Aboriginal and non-Aboriginal children in the Kalgoorlie-Boulder area, Western Australia, as part of an investigation into causal pathways to OM. Methods: Five hundred four and 1045 nasopharyngeal aspirates were collected from 100 Aboriginal and 180 non-Aboriginal children, respectively, followed from birth to age 2 years. Standard procedures were used to identify bacteria. Results: Overall carriage rates of S. pneumoniae, M. catarrhalis and H. influenzae in Aboriginal children were 49%, 50% and 41%, respectively, and 25%, 25% and 11% in non-Aboriginal children. By age 2 months S. pneumoniae and M. catarrhalis had been isolated from 37% and 36% of Aboriginal children and from 11% and 12% of non-Aboriginal children, respectively. From age 3 months onward, carriage rates in Aboriginal children were 51% to 67% for S. pneumoniae and M. catarrhalis and 42% to 62% for H. influenzae; corresponding figures for non-Aboriginal children were 26% to 37% for S. pneumoniae and M. catarrhalis and 11% to 18% for H. influenzae. Non-Aboriginal children had higher carriage rates in winter than in summer, but season had little effect in Aboriginal children. Staphylococcus aureus carriage was highest under age 1 month (55% Aboriginal, 61% non-Aboriginal) and was always higher in non-Aboriginal than Aboriginal children. Conclusions: Interventions are needed to reduce high transmission and carriage rates, particularly in Aboriginal communities, to avoid the serious consequences of OM.

Sepsis is defined by the systemic response to an infection, governed by dynamic interactions between the tissues, immune cells and inflammatory mediators. We used the Immunetrics platform to build a large-scale mathematical model that encompasses these biological components. The model incorporates a virtual clinician, an automated system to examine simulated patients' status at clinically relevant intervals and administer standard of care interventions as necessary, thereby altering the dynamics of the disease state. The model reproduces many characteristics of systemic response to an infection, including the time course of cytokines, coagulation factors, clinical markers, early and late organ failure, and early versus late deaths.

Summary Thirteen temperature-sensitive (ts) mutants of HSV-1 were analysed for their capacity to establish latent infections in the brains of mice. Eleven of the mutants could be classified as latency-positive or -negative; two could not be assigned to either group. Leakiness of mutants in the brain and differences in particle/infectivity ratios were found not to play a role in the results. Ts + revertants of selected latency-negative mutants regained the capacity to establish latent infections, indicating that it was the ts lesion in these agents which was involved in latency. Ultrastructural studies of neuroblastoma cells infected with various mutants and maintained at the restrictive temperature showed that no absolute correlations could be made between capacity to establish latent infection and synthesis of various morphologically identifiable virus products. Finally, from a comparison of latency characteristics with previously established polypeptide phenotypes of the mutants it was concluded that one immediate early and one or more later virus functions are necessary for establishment and/or maintenance of the latent state.