Preparing the Way for New Policy Regarding Adaptation of US Electricity Infrastructure to Climate Change

The following pages represent the status of policy regarding adaptation of the electric grid to climate change and proposed directions for new policy development. While strides are being made to understand the current climate and to predict hazards it may present to human systems, both the science and the policy remain at present in an analytical state. The policy proposed in this document involves first continued computational modeling of outcomes which will produce a portfolio of options to be considered in light of specific region-related risks. It is proposed that the modeling continue not only until reasonable policy at various levels of jurisdiction can be derived from its outcome but also on a continuing basis so that as improvements in the understanding of the state and trajectory of climate science along with advancements in technology arise, they can be incorporated into an appropriate and evolving policy

Preparing the Way for New Policy Regarding Adaptation of US Electricity Infrastructure to Climate Change

The following pages represent the status of policy regarding adaptation of the electric grid to climate change and proposed directions for new policy development. While strides are being made to understand the current climate and to predict hazards it may present to human systems, both the science and the policy remain at present in an analytical state. The policy proposed in this document involves first continued computational modeling of outcomes which will produce a portfolio of options to be considered in light of specific region-related risks. It is proposed that the modeling continue not only until reasonable policy at various levels of jurisdiction can be derived from its outcome but also on a continuing basis so that as improvements in the understanding of the state and trajectory of climate science along with advancements in technology arise, they can be incorporated into an appropriate and evolving policy

Can changing the timing of outdoor air intake reduce indoor concentrations of traffic-related pollutants in schools?

Traffic emissions have been associated with a wide range of adverse health effects. Many schools are situated close to major roads, and as children spend much of their day in school, methods to reduce traffic‐related air pollutant concentrations in the school environment are warranted. One promising method to reduce pollutant concentrations in schools is to alter the timing of the ventilation so that high ventilation time periods do not correspond to rush hour traffic. Health Canada, in collaboration with the Ottawa‐Carleton District School Board, tested the effect of this action by collecting traffic‐related air pollution data from four schools in Ottawa, Canada, during October and November 2013. A baseline and intervention period was assessed in each school. There were statistically significant (P < 0.05) reductions in concentrations of most of the pollutants measured at the two late‐start (9 AM start) schools, after adjusting for outdoor concentrations and the absolute indoor–outdoor temperature difference. The intervention at the early‐start (8 AM start) schools did not have significant reductions in pollutant concentrations. Based on these findings, changing the timing of the ventilation may be a cost‐effective mechanism of reducing traffic‐related pollutants in late‐start schools located near major roads

Using mobile sensing data to assess stress: Associations with perceived and lifetime stress, mental health, sleep, and inflammation

Background Although stress is a risk factor for mental and physical health problems, it can be difficult to assess, especially on a continual, non-invasive basis. Mobile sensing data, which are continuously collected from naturalistic smartphone use, may estimate exposure to acute and chronic stressors that have health-damaging effects. This initial validation study validated a mobile-sensing collection tool against assessments of perceived and lifetime stress, mental health, sleep duration, and inflammation. Methods Participants were 25 well-characterized healthy young adults (Mage = 20.64 years, SD = 2.74; 13 men, 12 women). We collected affective text language use with a custom smartphone keyboard. We assessed participants’ perceived and lifetime stress, depression and anxiety levels, sleep duration, and basal inflammatory activity (i.e. salivary C-reactive protein and interleukin-1β). Results Three measures of affective language (i.e. total positive words, total negative words, and total affective words) were strongly associated with lifetime stress exposure, and total negative words typed was related to fewer hours slept (all large effect sizes: r = 0.50 – 0.78). Total positive words, total negative words, and total affective words typed were also associated with higher perceived stress and lower salivary C-reactive protein levels (medium effect sizes; r = 0.22 – 0.32). Conclusions Data from this initial longitudinal validation study suggest that total and affective text use may be useful mobile sensing measures insofar as they are associated with several other stress, mental health, behavioral, and biological outcomes. This tool may thus help identify individuals at increased risk for stress-related health problems

Gp41-targeted antibodies restore infectivity of a fusion-deficient HIV-1 envelope glycoprotein

The HIV-1 envelope glycoprotein (Env) mediates viral entry via conformational changes associated with binding the cell surface receptor (CD4) and coreceptor (CCR5/CXCR4), resulting in subsequent fusion of the viral and cellular membranes. While the gp120 Env surface subunit has been extensively studied for its role in viral entry and evasion of the host immune response, the gp41 transmembrane glycoprotein and its role in natural infection are less well characterized. Here, we identified a primary HIV-1 Env variant that consistently supports \u3e300% increased viral infectivity in the presence of autologous or heterologous HIV-positive plasma. However, in the absence of HIV-positive plasma, viruses with this Env exhibited reduced infectivity that was not due to decreased CD4 binding. Using Env chimeras and sequence analysis, we mapped this phenotype to a change Q563R, in the gp41 heptad repeat 1 (HR1) region. We demonstrate that Q563R reduces viral infection by disrupting formation of the gp41 six-helix bundle required for virus-cell membrane fusion. Intriguingly, antibodies that bind cluster I epitopes on gp41 overcome this inhibitory effect, restoring infectivity to wild-type levels. We further demonstrate that the Q563R change increases HIV-1 sensitivity to broadly neutralizing antibodies (bNAbs) targeting the gp41 membrane-proximal external region (MPER). In summary, we identify an HIV-1 Env variant with impaired infectivity whose Env functionality is restored through the binding of host antibodies. These data contribute to our understanding of gp41 residues involved in membrane fusion and identify a mechanism by which host factors can alleviate a viral defect

Liganded Androgen Receptor Interaction with β-Catenin: NUCLEAR CO-LOCALIZATION AND MODULATION OF TRANSCRIPTIONAL ACTIVITY IN NEURONAL CELLS

A yeast two-hybrid assay was employed to identify androgen receptor (AR) protein partners in gonadotropin-releasing hormone neuronal cells. By using an AR deletion construct (AR-(Delta371-485)) as a bait, beta-catenin was identified as an AR-interacting protein from a gonadotropin-releasing hormone neuronal cell library. Immunolocalization of co-transfected AR and FLAG-beta-catenin demonstrated that FLAG-beta-catenin was predominantly cytoplasmic in the absence of androgen. In the presence of 5alpha-dihydrotestosterone, FLAG-beta-catenin completely co-localized to the nucleus with AR. This effect was specific to AR because liganded progesterone, glucocorticoid, or estrogen alpha receptors did not translocate FLAG-beta-catenin to the nucleus. Agonist-bound AR was required because the AR antagonists casodex and hydroxyflutamide failed to translocate beta-catenin. Time course experiments demonstrated that co-translocation occurred with similar kinetics. Nuclear co-localization was independent of the glycogen synthase kinase-3beta, p42/44 ERK mitogen-activated protein kinase, and phosphatidylinositol 3-kinase pathways because inhibitors of these pathways had no effect. Transcription assays demonstrated that liganded AR repressed beta-catenin/T cell factor-responsive reporter gene activity. Conversely, co-expression of beta-catenin/T cell factor repressed AR stimulation of AR-responsive reporter gene activity. Our data suggest that liganded AR shuttles beta-catenin to the nucleus and that nuclear interaction of AR with beta-catenin may modulate transcriptional activity in androgen target tissues

A Long-Term Vision for an Ecologically Sound Platte River

The Platte River extends about 310 mi (499 km) from North Platte, Nebraska, to its terminus at the Missouri River confluence near Plattsmouth, Nebraska. The Platte River Valley is a continentally significant ecosystem that serves as a major stopover for migratory waterbirds in the Central Flyway including the endangered Whooping Crane (Grus americana) and \u3e1 million Sandhill Cranes (Antigone canadensis) at the peak of spring migration. However, the Platte River Valley also supports a great diversity of avifauna including grassland breeding birds, native stream fish, vascular plants, herpetofauna, mammals, pollinators, and aquatic macroinvertebrates. Despite ongoing conservation efforts since the mid-1970s the ecosystem remains largely conservation dependent and an increasing number of species across taxa are being considered at risk of regional extirpation or outright extinction. However, given the attention provided to conservation in the Platte River Valley and the need to maintain ecologically functional stopover sites in the Central Flyway, there is a great opportunity to create a resilient refugium for biodiversity conservation in the central Great Plains. To that end we convened a working group of \u3e18 individuals representing \u3e9 organizations including representatives from non-profit conservation organizations, universities, and state and federal natural resource agencies to develop a long-term vision for an ecologically sound Platte River Valley (PRV). We met in groups of varying size for \u3e170 hours throughout a more than 3-year period and developed conservation priorities and objectives using a landscape design process. Landscape design is an interdisciplinary conservation planning process that incorporates components of landscape ecology and social dimensions of natural resources with the explicit intention of improving conservation implementation.https://digitalcommons.unl.edu/zeabook/1128/thumbnail.jp

Operationalising kangaroo Mother care before stabilisation amongst low birth Weight Neonates in Africa (OMWaNA): protocol for a randomised controlled trial to examine mortality impact in Uganda.

BACKGROUND: There are 2.5 million neonatal deaths each year; the majority occur within 48 h of birth, before stabilisation. Evidence from 11 trials shows that kangaroo mother care (KMC) significantly reduces mortality in stabilised neonates; however, data on its effect among neonates before stabilisation are lacking. The OMWaNA trial aims to determine the effect of initiating KMC before stabilisation on mortality within seven days relative to standard care. Secondary objectives include exploring pathways for the intervention's effects and assessing incremental costs and cost-effectiveness between arms. METHODS: We will conduct a four-centre, open-label, individually randomised, superiority trial in Uganda with two parallel groups: an intervention arm allocated to receive KMC and a control arm receiving standard care. We will enrol 2188 neonates (1094 per arm) for whom the indication for KMC is 'uncertain', defined as receiving ≥ 1 therapy (e.g. oxygen). Admitted singleton, twin and triplet neonates (triplet if demise before admission of ≥ 1 baby) weighing ≥ 700-≤ 2000 g and aged ≥ 1-< 48 h are eligible. Treatment allocation is random in a 1:1 ratio between groups, stratified by weight and recruitment site. The primary outcome is mortality within seven days. Secondary outcomes include mortality within 28 days, hypothermia prevalence at 24 h, time from randomisation to stabilisation or death, admission duration, time from randomisation to exclusive breastmilk feeding, readmission frequency, daily weight gain, infant-caregiver attachment and women's wellbeing at 28 days. Primary analyses will be by intention-to-treat. Quantitative and qualitative data will be integrated in a process evaluation. Cost data will be collected and used in economic modelling. DISCUSSION: The OMWaNA trial aims to assess the effectiveness of KMC in reducing mortality among neonates before stabilisation, a vulnerable population for whom its benefits are uncertain. The trial will improve understanding of pathways underlying the intervention's effects and will be among the first to rigorously compare the incremental cost and cost-effectiveness of KMC relative to standard care. The findings are expected to have broad applicability to hospitals in sub-Saharan Africa and southern Asia, where three-quarters of global newborn deaths occur, as well as important policy and programme implications. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02811432. Registered on 23 June 2016

Inhibition of CaMKK2 Enhances Fracture Healing by Stimulating Indian Hedgehog Signaling and Accelerating Endochondral Ossification

Approximately 10% of all bone fractures do not heal, resulting in patient morbidity and healthcare costs. However, no pharmacological treatments are currently available to promote efficient bone healing. Inhibition of Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) reverses age-associated loss of trabecular and cortical bone volume and strength in mice. In the current study, we investigated the role of CaMKK2 in bone fracture healing and show that its pharmacological inhibition using STO-609 accelerates early cellular and molecular events associated with endochondral ossification, resulting in a more rapid and efficient healing of the fracture. Within 7 days postfracture, treatment with STO-609 resulted in enhanced Indian hedgehog signaling, paired-related homeobox (PRX1)-positive mesenchymal stem cell (MSC) recruitment, and chondrocyte differentiation and hypertrophy, along with elevated expression of osterix, vascular endothelial growth factor, and type 1 collagen at the fracture callus. Early deposition of primary bone by osteoblasts resulted in STO-609–treated mice possessing significantly higher callus bone volume by 14 days following fracture. Subsequent rapid maturation of the bone matrix bestowed fractured bones in STO-609–treated animals with significantly higher torsional strength and stiffness by 28 days postinjury, indicating accelerated healing of the fracture. Previous studies indicate that fixed and closed femoral fractures in the mice take 35 days to fully heal without treatment. Therefore, our data suggest that STO-609 potentiates a 20% acceleration of the bone healing process. Moreover, inhibiting CaMKK2 also imparted higher mechanical strength and stiffness at the contralateral cortical bone within 4 weeks of treatment. Taken together, the data presented here underscore the therapeutic potential of targeting CaMKK2 to promote efficacious and rapid healing of bone fractures and as a mechanism to strengthen normal bones

Developing a sustainability science approach for water systems

We convened a workshop to enable scientists who study water systems from both social science and physical science perspectives to develop a shared language. This shared language is necessary to bridge a divide between these disciplines’ different conceptual frameworks. As a result of this workshop, we argue that we should view socio-hydrological systems as structurally co-constituted of social, engineered, and natural elements and study the “characteristic management challenges” that emerge from this structure and reoccur across time, space, and socioeconomic contexts. This approach is in contrast to theories that view these systems as separately conceptualized natural and social domains connected by bi-directional feedbacks, as is prevalent in much of the water systems research arising from the physical sciences. A focus on emergent characteristic management challenges encourages us to go beyond searching for evidence of feedbacks and instead ask questions such as: What types of innovations have successfully been used to address these challenges? What structural components of the system affect its resilience to hydrological events and through what mechanisms? Are there differences between successful and unsuccessful strategies to solve one of the characteristic management challenges? If so, how are these differences affected by institutional structure and ecological and economic contexts? To answer these questions, social processes must now take center stage in the study and practice of water management. We also argue that water systems are an important class of coupled systems with relevance for sustainability science because they are particularly amenable to the kinds of systematic comparisons that allow knowledge to accumulate. Indeed, the characteristic management challenges we identify are few in number and recur over most of human history and in most geographical locations. This recurrence should allow us to accumulate knowledge to answer the above questions by studying the long historical record of institutional innovations to manage water systems