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Increasing evidence demonstrates the psychological benefits of nature contact. However, the evidence is often established at the population level, and the individual differences in the psychological benefits gained from nature are considered negligible variations. In this study, we performed a cross-sectional online survey in Brisbane and Sydney, Australia, from April 15th and May 15th, 2021 around one year after the first covid-19 pandemic lockdowns. The results show that individuals with a stronger connection to nature are linked with a lower level of stress and anxiety with increased frequency in public greenspace visits, while such an association is less clear for individuals with a weaker connection to nature. We also find that, through the answer to an open-ended question, individuals with a lower connection to nature tend to mention nature-related words less as the reason for visiting greenspace. This indicates that a person’s connection to nature is linked with how they interact with nature and thus might determine whether and how much psychological benefit a person gains from experiencing nature.

There is a significant amount of evidence highlighting the health, wellbeing and social benefits of gardening during previous periods of crises. These benefits were also evident during the COVID-19 pandemic. This paper presents a narrative review exploring gardening during the early stages of the COVID-19 pandemic to understand the different forms of gardening that took place during this crisis and key elements of this activity. Research about gardening during the pandemic focused on food (in)security and disrupted food systems, the health and wellbeing benefits of gardening, and the social dimensions of gardening. We offer three vignettes of our own research to highlight key insights from local, national and international perspectives of gardening during the pandemic. The papers conclusion outlines how researchers, policy makers and public health practitioners can harness what has been learned from gardening during the pandemic to ensure these benefits are more widely available and do not exacerbate already entrenched health inequalities in society., Funding Agencies|European Union; Institute of Sociology of the Czech Academy of Sciences [RVO: 68378025]

There is a significant amount of evidence highlighting the health, wellbeing and social benefits of gardening during previous periods of crises. These benefits were also evident during the COVID-19 pandemic. This paper presents a narrative review exploring gardening during the early stages of the COVID-19 pandemic to understand the different forms of gardening that took place during this crisis and key elements of this activity. Research about gardening during the pandemic focused on food (in)security and disrupted food systems, the health and wellbeing benefits of gardening, and the social dimensions of gardening. We offer three vignettes of our own research to highlight key insights from local, national and international perspectives of gardening during the pandemic. The papers conclusion outlines how researchers, policy makers and public health practitioners can harness what has been learned from gardening during the pandemic to ensure these benefits are more widely available and do not exacerbate already entrenched health inequalities in society., Funding Agencies|European Union; Institute of Sociology of the Czech Academy of Sciences [RVO: 68378025]

New urban models increasingly seek to create more sustainable, livable, and healthier cities by reinvigorating green space. In this article, we highlight and briefly review several main but disconnected areas of study in which the factors that frame human–environment interactions and therefore also influence the potential well-being outcomes of those interactions are studied. We then use the intersection of affordance theory and socio-institutional programming to provide a conceptual framework that ties together these spheres of research, and we discuss some critical keys for enabling different positive green space experiences. Urban communities are not homogeneous, and accounting for the intersection between individual differences and landscape programming opens up more diverse pathways for affording positive human–environment interactions and different well-being outcomes.

Urban dwellers' use of public and private green spaces may have changed during the early years of the Covid-19 pandemic due to movement restriction. A survey was deployed in Brisbane and Sydney, Australia 1 year after the start of Covid-19 restrictions (April 2021) to explore relationships of mental health and wellbeing to different patterns of private yard versus public green space visitation. More frequent yard use during the initial year of Covid-19 was correlated with lower stress, depression, and anxiety and higher wellbeing. However, greater duration of yard visits (week prior to survey) was associated with higher stress, anxiety, and depression scores, potentially because individuals may seek to use nature spaces immediately available for emotional regulation during difficult times. The results highlight the importance of yards for mental health and wellbeing during the Covid-19 pandemic and that relationships between nature interaction and mental health may be context and timeframe dependent.

Urban ecological communities are shaped by an array of environmental and physical factors that include climate, biogeography, species interactions, dispersal, and ecological filters at the habitat and landscape scales. In addition, many social dynamics, decision-making processes, and other social characteristics, such as development, policy, government actions, as well as socioeconomic status of residents – the so-called ‘luxury’ effect – may also play strong roles in shaping which species occur within the urban context. This interaction between ecological and social drivers may impact species richness and may also influence functional traits and functional diversity, with important implications for ecosystem services provided within urban spaces. Urban agroecosystems provide food and other well-being benefits to urban residents, and are valuable green spaces in the city that provide refuges for biodiversity. Despite this fact, one of the biggest risks to gardens is insecure land tenure. While plant communities within gardens may be shaped by gardener demographics, food cultures, and ecological processes, little is known about how factors such as luxury and land tenure security may impact plant diversity, plant functional traits, and functional diversity, as well as species and trait composition. In this study, we ask how garden physical features, luxury, and land tenure security influence plant species richness, functional diversity, and species and trait composition within gardens in the California central coast. We surveyed vegetation, assessed plant traits related to growth form, plant defense, and floral characteristics, and collected information on multiple factors associated with land tenure and luxury. We found that land tenure secure gardens had higher plant and crop richness. Variables associated with garden luxury boosted ornamental plant richness, flower abundance and height, lowered crop richness, and strongly impacted plant species composition. Garden

There is a significant amount of evidence highlighting the health, wellbeing and social benefits of gardening during previous periods of crises. These benefits were also evident during the COVID-19 pandemic. This paper presents a narrative review exploring gardening during the early stages of the COVID-19 pandemic to understand the different forms of gardening that took place during this crisis and key elements of this activity. Research about gardening during the pandemic focused on food (in)security and disrupted food systems, the health and wellbeing benefits of gardening, and the social dimensions of gardening. We offer three vignettes of our own research to highlight key insights from local, national and international perspectives of gardening during the pandemic. The papers conclusion outlines how researchers, policy makers and public health practitioners can harness what has been learned from gardening during the pandemic to ensure these benefits are more widely available and do not exacerbate already entrenched health inequalities in society., Funding Agencies|European Union; Institute of Sociology of the Czech Academy of Sciences [RVO: 68378025]

There is a significant amount of evidence highlighting the health, wellbeing and social benefits of gardening during previous periods of crises. These benefits were also evident during the COVID-19 pandemic. This paper presents a narrative review exploring gardening during the early stages of the COVID-19 pandemic to understand the different forms of gardening that took place during this crisis and key elements of this activity. Research about gardening during the pandemic focused on food (in)security and disrupted food systems, the health and wellbeing benefits of gardening, and the social dimensions of gardening. We offer three vignettes of our own research to highlight key insights from local, national and international perspectives of gardening during the pandemic. The papers conclusion outlines how researchers, policy makers and public health practitioners can harness what has been learned from gardening during the pandemic to ensure these benefits are more widely available and do not exacerbate already entrenched health inequalities in society., Funding Agencies|European Union; Institute of Sociology of the Czech Academy of Sciences [RVO: 68378025]

Jonathan B Lin,1 Kristen M Pitts,1 Hani El Helwe,1 Cameron Neeson,1 Nathan E Hall,1 Henisk Falah,1 Stephanie A Schultz,2 Silas L Wang,1 Kristine Lo,1 Christian Song,1 Milica A Margeta,1,* David Solá-Del Valle1,* 1Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear, Boston, MA, USA; 2Department of Neurology, Harvard Medical School and Massachusetts General Hospital, Boston, MA, USA*These authors contributed equally to this workCorrespondence: David Solá-Del Valle; Milica A Margeta, Assistant Professor of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, 243 Charles Street, Boston, MA, 02114, USA, Email david_sola-delvalle@meei.harvard.edu; milica_margeta@meei.harvard.eduPurpose: Neurofilament light chain (NfL) is a neuronal cytoskeletal protein that has been identified as a marker of neurodegeneration in diseases of the central nervous system. In this study, we investigated whether NfL in the aqueous humor (AH) can serve as a marker of neurodegeneration in glaucoma in a racially diverse North American population.Design: Single-center, case–control study.Participants: We enrolled patients with various types and stages of glaucoma undergoing planned ophthalmic surgery as part of their routine care and compared them with patients without glaucoma undergoing phacoemulsification for age-related cataract.Methods: We collected AH from 39 glaucoma patients and 10 patients without glaucoma. AH NfL was quantified using the Single-Molecule Array (Simoa)® NF-light assay (Quanterix). Demographic information, such as age, body mass index, sex, and self-reported race, as well as clinical information, such as pre-operative intraocular pressure (IOP), maximum IOP, and number of pre-operative glaucoma medications, was obtained by reviewing the medical record.Main Outcome Measures: Levels of AH NfL.Results: In a model controlling for age and body mass index (BMI), NfL was significantly elevated in AH from glauco

There is a significant amount of evidence highlighting the health, wellbeing and social benefits of gardening during previous periods of crises. These benefits were also evident during the COVID-19 pandemic. This paper presents a narrative review exploring gardening during the early stages of the COVID-19 pandemic to understand the different forms of gardening that took place during this crisis and key elements of this activity. Research about gardening during the pandemic focused on food (in)security and disrupted food systems, the health and wellbeing benefits of gardening, and the social dimensions of gardening. We offer three vignettes of our own research to highlight key insights from local, national and international perspectives of gardening during the pandemic. The papers conclusion outlines how researchers, policy makers and public health practitioners can harness what has been learned from gardening during the pandemic to ensure these benefits are more widely available and do not exacerbate already entrenched health inequalities in society., Funding Agencies|European Union; Institute of Sociology of the Czech Academy of Sciences [RVO: 68378025]

Cities are sometimes characterized as homogenous with species assemblages composed of abundant, generalist species having similar ecological functions. Under this assumption, rare species, or species observed infrequently, would have especially high conservation value in cities for their potential to increase functional diversity. Management to increase the number of rare species in cities could be an important conservation strategy in a rapidly urbanizing world. However, most studies of species rarity define rarity in relatively pristine environments where human management and disturbance is minimized. We know little about what species are rare, how many species are rare, and what management practices promote rare species in urban environments. Here, we identified which plants and species of birds and bees that control pests and pollinate crops are rare in urban gardens and assessed how social, biophysical factors, and cross-taxonomic comparisons influence rare species richness. We found overwhelming numbers of rare species, with more than 50% of plants observed classified as rare. Our results highlight the importance of women, older individuals, and gardeners who live closer to garden sites in increasing the number of rare plants within urban areas. Fewer rare plants were found in older gardens and gardens with more bare soil. There were more rare bird species in larger gardens and more rare bee species for which canopy cover was higher. We also found that in some cases, rarity begets rarity, with positive correlations found between the number of rare plants and bee species and between bee and bird species. Overall, our results suggest that urban gardens include a high number of species existing at low frequency and that social and biophysical factors promoting rare, planned biodiversity can cascade down to promote rare, associated biodiversity.

Gardening has the potential to improve health and wellbeing, especially during crises. Using an international survey of gardeners (n = 3743), this study aimed to understand everyday gardening experiences, perspectives and attitudes during early stages of the COVID-19 pandemic in 2020. Our qualitative reflexive thematic and sentiment analyses show that during the first months of the COVID-19 pandemic, gardening seemed to create a safe and positive space where people could socially connect, learn and be creative. Participants had more time to garden during the pandemic, which led to enhanced connections with family members and neighbours, and the ability to spend time in a safe outdoor environment. More time gardening allowed for innovative and new gardening practices that provided enjoyment for many participants. However, our research also highlighted barriers to gardening (e.g. lack of access to garden spaces and materials). Our results illustrate the multiple benefits of gardening apparent during COVID-19 through a lens of the social-ecological model of health.

Background: Ustekinumab, a human immunoglobulin G1 monoclonal antibody that binds to and inhibits interleukin (IL)-12/IL-23, is indicated for multiple immune-mediated diseases. Ustekinumab is actively transported across the placenta and theoretically could impact pregnancy outcomes. Limited data on pregnancy outcomes with ustekinumab exposure are available. Aim: To assess pregnancy outcomes in patients exposed to ustekinumab during pregnancy. Methods: Cumulative data on medically confirmed ustekinumab-exposed pregnancies from the manufacturer's Global Safety Database were summarised. Descriptive data for pregnancy outcomes were presented overall and by patient subgroups. Results: As of 31 August 2020, 408 medically confirmed, prospective, maternal ustekinumab-exposed pregnancies with reported outcomes were identified. The mean maternal age was 31 years. Of the 420 pregnancy outcomes (including 4 sets of twins),a,b 340 (81%) were live births, 51 (12.1%) spontaneous abortions, 25 (6%) elective/induced abortions, 3 (0.7%) stillbirths and 1 (0.2%) ongoing pregnancy with foetal congenital anomaly (CA). Among 340 live births, 33 (9.7%) were born pre-term. The rate of major CAs was similar by indication (Crohn's disease vs psoriasis), ustekinumab dose (45 mg vs 90 mg) and timing and duration of maternal exposure to ustekinumab. Prospective outcomes of pregnancies with paternal periconceptional ustekinumab exposure (n = 87) included 92% live births (1.2% major CA), 5.7% spontaneous abortions and 2.3% elective/induced abortions. Conclusions: Rates of adverse pregnancy outcomes or CAs with ustekinumab exposure were consistent with rates reported for the US general population and do not suggest a higher risk associated with maternal or paternal exposure to ustekinumab.

Using the concepts of category and functor, we provide some insights and prove an intrinsic property of the category ${\bf AprS}$ of approximation spaces and relation-preserving functions, the category ${\bf RCls}$ of rough closure spaces and continuous functions, and the category ${\bf RInt}$ of rough interior spaces and continuous functions. Furthermore, we define the category ${\bf IS}$ of information systems and O-A-D homomorphisms, and establish the relationship between the category ${\bf IS}$ and the category ${\bf AprS}$ by considering a subcategory ${\bf NeIS}$ of ${\bf IS}$ whose objects are information systems and whose arrows are non-expensive O-A-D homomorphisms with surjective attribute mappings., Comment: 15 pages

Record climate extremes are reducing urban liveability, compounding inequality, and threatening infrastructure. Adaptation measures that integrate technological, nature-based, and social solutions can provide multiple co-benefits to address complex socioecological issues in cities while increasing resilience to potential impacts. However, there remain many challenges to developing and implementing integrated solutions. In this Viewpoint, we consider the value of integrating across the three solution sets, the challenges and potential enablers for integrating solution sets, and present examples of challenges and adopted solutions in three cities with different urban contexts and climates (Freiburg, Germany; Durban, South Africa; and Singapore). We conclude with a discussion of research directions and provide a road map to identify the actions that enable successful implementation of integrated climate solutions. We highlight the need for more systematic research that targets enabling environments for integration; achieving integrated solutions in different contexts to avoid maladaptation; simultaneously improving liveability, sustainability, and equality; and replicating via transfer and scale-up of local solutions. Cities in systematically disadvantaged countries (sometimes referred to as the Global South) are central to future urban development and must be prioritised. Helping decision makers and communities understand the potential opportunities associated with integrated solutions for climate change will encourage urgent and deliberate strides towards adapting cities to the dynamic climate reality.

Urban gardens are vital green spaces, providing food for residents and space for engaged citizenry and community development. In California, climate change conditions (heat and drought) are becoming more extreme, threatening the resilience of urban gardens. Water use restrictions limit the timing and amount of water that gardeners can access, exacerbating these climate challenges for urban food production. Together with volunteer gardeners, we examined how ambient temperature, water use, vegetation, ground cover, and soil management affect rates of soil moisture gain and loss in urban gardens for a six-week period in the summer of 2017, during the hottest part of the growing season. We found that plot-level management of soils is essential for creating urban garden plots that maintain stable levels of water within garden soils. Although plots with better soil quality (i.e. water holding capacity) experienced slower rates of soil moisture gain after a watering event, they also experienced slower rates of soil moisture loss after the event, leading to soils with more stable, less fluctuating moisture profiles over time. This may benefit gardeners because under extreme climates (such as heat and drought) and water use restrictions, maintaining more stable soils for their plants means that the soils will retain water over a longer period after each watering event. Overall, such results highlight that better soil management that improves soil quality measures such as water holding capacity are potential solutions for maintaining soil moisture and reducing water use under changing climate conditions.

Urban gardens are vital green spaces, providing food for residents and space for engaged citizenry and community development. In California, climate change conditions (heat and drought) are becoming more extreme, threatening the resilience of urban gardens. Water use restrictions limit the timing and amount of water that gardeners can access, exacerbating these climate challenges for urban food production. Together with volunteer gardeners, we examined how ambient temperature, water use, vegetation, ground cover, and soil management affect rates of soil moisture gain and loss in urban gardens for a six-week period in the summer of 2017, during the hottest part of the growing season. We found that plot-level management of soils is essential for creating urban garden plots that maintain stable levels of water within garden soils. Although plots with better soil quality (i.e. water holding capacity) experienced slower rates of soil moisture gain after a watering event, they also experienced slower rates of soil moisture loss after the event, leading to soils with more stable, less fluctuating moisture profiles over time. This may benefit gardeners because under extreme climates (such as heat and drought) and water use restrictions, maintaining more stable soils for their plants means that the soils will retain water over a longer period after each watering event. Overall, such results highlight that better soil management that improves soil quality measures such as water holding capacity are potential solutions for maintaining soil moisture and reducing water use under changing climate conditions.

The synthesis of graphene nanoribbons (GNRs) that contain site-specifically substituted backbone heteroatoms is one of the essential goals that must be achieved in order to control the electronic properties of these next generation organic materials. We have exploited our recently reported solid-state topochemical polymerization/cyclization-aromatization strategy to convert the simple 1,4-bis(3-pyridyl)butadiynes 3a,b into the fjord-edge nitrogen-doped graphene nanoribbon structures 1a,b (fjord-edge N2[8]GNRs). Structural assignments are confirmed by CP/MAS 13C NMR, Raman, and XPS spectroscopy. The fjord-edge N2[8]GNRs 1a,b are promising precursors for the novel backbone nitrogen-substituted N2[8]AGNRs 2a,b. Geometry and band calculations on N2[8]AGNR 2c indicate that this class of nanoribbons should have unusual bonding topology and metallicity.

Purpose:To demonstrate that rifabutin-related corneal deposits are localized to the deep stroma using anterior segment optical coherence tomography (OCT) and confocal microscopy. Observations:A 55-year-old male with a history of human immunodeficiency virus (HIV) and disseminated mycobacterium avium complex on rifabutin treatment for 3 years presented with bilateral corneal deposits. Confocal microscopy and anterior segment OCT confirm that rifabutin-related corneal deposits are located in the deep stroma, rather than in the endothelium. Conclusions:And Importance: Rifabutin deposits localize to the deep corneal stroma, and can be seen with both confocal microscopy and anterior segment OCT. Anterior segment OCT is a widely available and easily used diagnostic tool, and can provide utility in the diagnosis of corneal deposits.

The synthesis of graphene nanoribbons (GNRs) that contain site-specifically substituted backbone heteroatoms is one of the essential goals that must be achieved in order to control the electronic properties of these next generation organic materials. We have exploited our recently reported solid-state topochemical polymerization/cyclization-aromatization strategy to convert the simple 1,4-bis(3-pyridyl)butadiynes 3a,b into the fjord-edge nitrogen-doped graphene nanoribbon structures 1a,b (fjord-edge N2[8]GNRs). Structural assignments are confirmed by CP/MAS 13C NMR, Raman, and XPS spectroscopy. The fjord-edge N2[8]GNRs 1a,b are promising precursors for the novel backbone nitrogen-substituted N2[8]AGNRs 2a,b. Geometry and band calculations on N2[8]AGNR 2c indicate that this class of nanoribbons should have unusual bonding topology and metallicity.

PurposeTo demonstrate that rifabutin-related corneal deposits are localized to the deep stroma using anterior segment optical coherence tomography (OCT) and confocal microscopy.ObservationsA 55-year-old male with a history of human immunodeficiency virus (HIV) and disseminated mycobacterium avium complex on rifabutin treatment for 3 years presented with bilateral corneal deposits. Confocal microscopy and anterior segment OCT confirm that rifabutin-related corneal deposits are located in the deep stroma, rather than in the endothelium.ConclusionsAnd Importance: Rifabutin deposits localize to the deep corneal stroma, and can be seen with both confocal microscopy and anterior segment OCT. Anterior segment OCT is a widely available and easily used diagnostic tool, and can provide utility in the diagnosis of corneal deposits.

Continental rifting has been linked to the thinning and destruction of cratonic lithosphere and to the release of enough CO2 to impact the global climate. This fundamental plate tectonic process facilitates the infiltration and mobilisation of smallvolume carbonated melts, which may interact with mantle peridotite to form wehrlite through the reaction: enstatite thorn dolomite (melt) = forsterite thorn diopside thorn CO2 (vapour). Application to mantle xenolith suites from various rifts and basins shows that 2.9 to 10.2 kg CO2 are released per 100 kg of wehrlite formed. For the Eastern Rift (Africa), this results in estimated CO2 fluxes of 6.5 +/- 4.1 Mt yr(-1), similar to estimates of mantle contributions based on surficial CO2 surveys. Thus, wehrlite-bearing xenolith suites can be used to monitor present and past CO2 mobility through the continental lithosphere, ultimately with diffuse degassing to the atmosphere. They may also reveal the CO2 flux in lithospheric provinces where carbonated melts or continent-scale rifts are not observed at the surface.

The native extracellular matrix (ECM) contains a host of matricellular proteins and bioactive factors that regulate cell behavior, and many ECM components have been leveraged to guide cell fate. However, the large size and chemical characteristics of these constituents complicate their incorporation into biomaterials without interfering with material properties, motivating the need for alternative approaches to regulate cellular responses. Mesenchymal stromal cells (MSCs) can promote osseous regeneration in vivo directly or indirectly through multiple means including (1) secretion of proangiogenic and mitogenic factors to initiate formation of a vascular template and recruit host cells into the tissue site or (2) direct differentiation into osteoblasts. As MSC behavior is influenced by the properties of engineered hydrogels, we hypothesized that the biochemical and biophysical properties of alginate could be manipulated to promote the dual contributions of encapsulated MSCs toward bone formation. We functionalized alginate with QK peptide to enhance proangiogenic factor secretion and RGD to promote adhesion, while biomechanical-mediated osteogenic cues were controlled by modulating viscoelastic properties of the alginate substrate. A 1:1 ratio of QK:RGD resulted in the highest levels of both proangiogenic factor secretion and mineralization in vitro. Viscoelastic alginate outperformed purely elastic gels in both categories, and this effect was enhanced by stiffness up to 20 kPa. Furthermore, viscoelastic constructs promoted vessel infiltration and bone regeneration in a rat calvarial defect over 12 weeks. These data suggest that modulating viscoelastic properties of biomaterials, in conjunction with dual peptide functionalization, can simultaneously enhance multiple aspects of MSC regenerative potential and improve neovascularization of engineered tissues.

In this paper, a model predictive current control (MPCC) strategy with a fixed switching frequency to control the dual boost bridgeless power factor corrected (PFC) converter is proposed. The improved MPCC strategy solves the problem of filter design and the high electromagnetic interference (EMI) which caused by the traditional MPCC. With the consideration of a nonlinear inductor, a formula is fitted to represent the change of the inductance, and the improved strategy has strong robustness. The simulation and experiment shows that the quality of current and power factor of the system is improved by the proposed control strategy.

Christoph F Gfeller,1 Rita Wanser,2 Harish Mahalingam,2 David J Moore,3 Xuying Wang,4 Connie B Lin,4 Gilbert Shanga,5 Gary Grove,6 Anthony V Rawlings7 1GlaxoSmithKline Consumer Healthcare, Medical Affairs Skin Health, Weybridge, Surrey, UK; 2GlaxoSmithKline Consumer Healthcare, Medical Affairs Skin Health, Warren, NJ, USA; 3GlaxoSmithKline Consumer Healthcare, R&D Innovation Skin Health, Weybridge, Surrey, UK; 4GlaxoSmithKline Consumer Healthcare, R&D Innovation Skin Health, Collegeville, PA, USA; 5GSK Consumer Healthcare, Biostatistics, Warren, NJ, USA; 6cyberDERM, Inc., Broomall, PA, USA; 7AVR Consulting, Ltd., Cheshire, UK Purpose: These studies describe the testing of a novel, daily-use lip cream designed for individuals with lips prone to recurrent herpes labialis (RHL) that protects against environmental triggers.Subjects and methods: In vitro occlusive and in vitro and in vivo photoprotection analyses, a characterization of normal vs dry lips, and a randomized, evaluator-blinded, clinical trial that assessed the lip cream in healthy subjects with dry lips were conducted. In the clinical trial, subjects applied the lip cream or were untreated and evaluated using transepidermal water loss (TEWL), corneometry, visual assessments of lip dryness, expert photographic evaluations, and subject-rated outcomes.Results: The lip cream’s in vitro water vapor transmission rate (84.1 g/(m2 h)) indicated moderate occlusivity. The lip cream, but not placebo or control (water), reduced ultraviolet A (UVA)- and UVB-induced DNA damage, and tumor necrosis factor-α (EpiDermFT) and prostaglandin E2 release (EpiDermFT and EpiGingival™). The lip cream’s in vivo sun protection factor (SPF) was 12.2 (lower confidence limit, 11.3) and SPF/UVA protection factor ratio was 0.9. The characterization of dry vs normal lips identified differences in moisturization. In the clinical trial, the lip cream significantly decreased TEWL (differe

Characterized by pain, cartilage degradation, and inflammation, osteoarthritis is often treated with anti-inflammatory therapies that provide short-term relief but can have adverse side effects; intra-articular drug delivery systems with controlled release of anti-inflammatory peptides using degradable poly(N-isopropylacrylamide) (pNIPAM) nanoparticles could prolong relief and minimize these side effects. Nanoparticles provide a biocompatible drug carrier that can protect encapsulated therapeutics from enzymatic degradation and increase payload delivery upon encountering a degradation stimulus. Here we demonstrate passive targeting of inflamed cartilage ex vivo by uptake of PEGylated pNIPAM nanoparticles with degradable disulfide crosslinks (abbreviated as NGPEGSS) into chondrocytes and subsequent intracellular release of an anti-inflammatory peptide KAFAKLAARLYRKALARQLGVAA (KAFAK). The KAFAK-loaded NGPEGSS treatment reduced ex vivo inflammation to a greater extent compared to its non-degradable counterparts. This study highlights a nanoparticle system that delivers therapeutics intracellularly with improved efficacy by triggered degradation and suppresses inflammation in multiple cell types within an inflamed joint.

BackgroundTimely thrombolytic therapy can improve stroke outcomes. Nevertheless, the ability of US hospitals to meet guidelines for intravenous tissue plasminogen activator (tPA) remains suboptimal. What is unclear is whether hospitals accurately perceive their rate of tPA "door-to-needle" (DTN) time within 60 minutes and how DTN rates compare across different hospitals.Methods and resultsDTN performance was defined by the percentage of treated patients who received tPA within 60 minutes of arrival. Telephone surveys were obtained from staff at 141 Get With The Guidelines hospitals, representing top, middle, and low DTN performance. Less than one-third (29.1%) of staff accurately identified their DTN performance. Among middle- and low-performing hospitals (n=92), 56 sites (60.9%) overestimated their performance; 42% of middle performers and 85% of low performers overestimated their performance. Sites that overestimated tended to have lower annual volumes of tPA administration (median 8.4 patients [25th to 75th percentile 5.9 to 11.8] versus 10.2 patients [25th to 75th percentile 8.2 to 17.3], P=0.047), smaller percentages of eligible patients receiving tPA (84.7% versus 89.8%, P=0.008), and smaller percentages of DTN ≤60 minutes among treated patients (10.6% versus 16.6%, P=0.002).ConclusionsHospitals often overestimate their ability to deliver timely tPA to treated patients. Our findings indicate the need to routinely provide comparative provider performance rates as a key step to improving the quality of acute stroke care.

Timely thrombolytic therapy can improve stroke outcomes. Nevertheless, the ability of US hospitals to meet guidelines for intravenous tissue plasminogen activator (tPA) remains suboptimal. What is unclear is whether hospitals accurately perceive their rate of tPA "door-to-needle" (DTN) time within 60 minutes and how DTN rates compare across different hospitals. DTN performance was defined by the percentage of treated patients who received tPA within 60 minutes of arrival. Telephone surveys were obtained from staff at 141 Get With The Guidelines hospitals, representing top, middle, and low DTN performance. Less than one-third (29.1%) of staff accurately identified their DTN performance. Among middle- and low-performing hospitals (n=92), 56 sites (60.9%) overestimated their performance; 42% of middle performers and 85% of low performers overestimated their performance. Sites that overestimated tended to have lower annual volumes of tPA administration (median 8.4 patients [25th to 75th percentile 5.9 to 11.8] versus 10.2 patients [25th to 75th percentile 8.2 to 17.3], P=0.047), smaller percentages of eligible patients receiving tPA (84.7% versus 89.8%, P=0.008), and smaller percentages of DTN ≤60 minutes among treated patients (10.6% versus 16.6%, P=0.002). Hospitals often overestimate their ability to deliver timely tPA to treated patients. Our findings indicate the need to routinely provide comparative provider performance rates as a key step to improving the quality of acute stroke care.

BACKGROUND#ENTITYSTARTX02014;: Emergency medical services (EMS) hospital prenotification of an incoming stroke patient is guideline recommended as a means of increasing the timeliness with which stroke patients are evaluated and treated. Still, data are limited with regard to national use of, variations in, and temporal trends in EMS prenotification and associated predictors of its use. METHODS AND RESULTS#ENTITYSTARTX02014;: We examined 371 988 patients with acute ischemic stroke who were transported by EMS and enrolled in 1585 hospitals participating in Get With The Guidelines-Stroke from April 1, 2003, through March 31, 2011. Prenotification occurred in 249 197 EMS-transported patients (67.0%) and varied widely by hospital (range, 0% to 100%). Substantial variations by geographic regions and by state, ranging from 19.7% in Washington, DC, to 93.4% in Montana, also were noted. Patient factors associated with lower use of prenotification included older age, diabetes mellitus, and peripheral vascular disease. Prenotification was less likely for black patients than for white patients (adjusted odds ratio 0.94, 95% confidence interval 0.92-0.97, P<0.0001). Hospital factors associated with greater EMS prenotification use were absence of academic affiliation, higher annual volume of tissue plasminogen activator administration, and geographic location outside the Northeast. Temporal improvements in prenotification rates showed a modest general increase, from 58.0% in 2003 to 67.3% in 2011 (P temporal trend <0.0001). CONCLUSIONS#ENTITYSTARTX02014;: EMS hospital prenotification is guideline recommended, yet among patients transported to Get With The Guidelines-Stroke hospitals it is not provided for 1 in 3 EMS-arriving patients with acute ischemic stroke and varies substantially by hospital, state, and region. These results support the need for enhanced implementation of stroke systems of care. (J Am Heart Assoc. 2012;1:e002345 doi: 10.1161/JAHA.112.002345.).

BACKGROUND#ENTITYSTARTX02014;: Emergency medical services (EMS) hospital prenotification of an incoming stroke patient is guideline recommended as a means of increasing the timeliness with which stroke patients are evaluated and treated. Still, data are limited with regard to national use of, variations in, and temporal trends in EMS prenotification and associated predictors of its use. METHODS AND RESULTS#ENTITYSTARTX02014;: We examined 371 988 patients with acute ischemic stroke who were transported by EMS and enrolled in 1585 hospitals participating in Get With The Guidelines-Stroke from April 1, 2003, through March 31, 2011. Prenotification occurred in 249 197 EMS-transported patients (67.0%) and varied widely by hospital (range, 0% to 100%). Substantial variations by geographic regions and by state, ranging from 19.7% in Washington, DC, to 93.4% in Montana, also were noted. Patient factors associated with lower use of prenotification included older age, diabetes mellitus, and peripheral vascular disease. Prenotification was less likely for black patients than for white patients (adjusted odds ratio 0.94, 95% confidence interval 0.92-0.97, P<0.0001). Hospital factors associated with greater EMS prenotification use were absence of academic affiliation, higher annual volume of tissue plasminogen activator administration, and geographic location outside the Northeast. Temporal improvements in prenotification rates showed a modest general increase, from 58.0% in 2003 to 67.3% in 2011 (P temporal trend <0.0001). CONCLUSIONS#ENTITYSTARTX02014;: EMS hospital prenotification is guideline recommended, yet among patients transported to Get With The Guidelines-Stroke hospitals it is not provided for 1 in 3 EMS-arriving patients with acute ischemic stroke and varies substantially by hospital, state, and region. These results support the need for enhanced implementation of stroke systems of care. (J Am Heart Assoc. 2012;1:e002345 doi: 10.1161/JAHA.112.002345.).

We report on the crystal growth, structural and spectroscopic investigation of a novel trigonal calcium vanadate crystal, Tm3+:Ca9La(VO4)(7). Polarized absorption, stimulated-emission and gain cross-section spectra are determined for this material. The maximum sigma(SE) corresponding to the F-3(4) -> H-3(6) transition amounts to 1.28 x 10(-20) cm(2) at 1854 nm for sigma-polarization. The measured lifetime of the Tm3+ ions in the F-3(4) state is 1.19 ms. The Judd-Ofelt analysis performed yielded intensity parameters of Omega(2) = 4.682, Omega(4) = 0.659 and Omega(6) = 0.475 [10(-20) cm(2)]. The polarized Raman spectra indicate a strong and broad band centered at 867 cm(-1). Owing to the disordered nature of Ca9La(VO4)(7), the Tm3+ ions exhibit a broad and smooth gain profile at similar to 2 mu m. The spectroscopic properties of Tm3+:Ca9La(VO4)(7) are very promising for broadly tunable and ultrashort pulse lasers near 2 mu m. (C) 2017 Optical Society of America

Since its discovery and isolation, exogenous insulin has dramatically changed the outlook for patients with diabetes. However, even when patients strictly follow an insulin regimen, serious complications can result as patients experience both hyperglycemic and hypoglycemic states. Several chemically or genetically modified insulins have been developed that tune the pharmacokinetics of insulin activity for personalized therapy. Here, we demonstrate a strategy for the chemical modification of insulin intended to promote both long-lasting and glucose-responsive activity through the incorporation of an aliphatic domain to facilitate hydrophobic interactions, as well as a phenylboronic acid for glucose sensing. These synthetic insulin derivatives enable rapid reversal of blood glucose in a diabetic mouse model following glucose challenge, with some derivatives responding to repeated glucose challenges over a 13-h period. The best-performing insulin derivative provides glucose control that is superior to native insulin, with responsiveness to glucose challenge improved over a clinically used long-acting insulin derivative. Moreover, continuous glucose monitoring reveals responsiveness matching that of a healthy pancreas. This synthetic approach to insulin modification could afford both long-term and glucose-mediated insulin activity, thereby reducing the number of administrations and improving the fidelity of glycemic control for insulin therapy. The described work is to our knowledge the first demonstration of a glucose-binding modified insulin molecule with glucose-responsive activity verified in vivo., Leona M. and Harry B. Helmsley Charitable Trust (Award 2014PG-T1D002), Tayebati Family Foundation, National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award F32DK101335), Juvenile Diabetes Research Foundation International (Postdoctoral Fellowship 3-2011-310), Juvenile Diabetes Research Foundation International (Postdoctoral Fellowship 3-2013-56)

No instruments are currently available to help health systems identify target areas for reducing door-to-needle times for the administration of intravenous tissue plasminogen activator to eligible patients with ischemic stroke. A 67-item Likert-scale survey was administered by telephone to stroke personnel at 252 U.S. hospitals participating in the "Get With The Guidelines-Stroke" quality improvement program. Factor analysis was used to refine the instrument to a four-factor 29-item instrument that can be used by hospitals to assess their readiness to administer intravenous tissue plasminogen activator within 60 minutes of patient hospital arrival.

BACKGROUND: Although there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated. METHODS: Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, ≥200x) to leukocytederived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47). We validated candidate mutations with the use of Sanger sequencing and, for variants present at unequal read depths, subcloning followed by colony sequencing. RESULTS: Validated, causal mutations were found in 27 persons (17%; range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing but were validated through subcloning and subsequent sequencing of the subcloned DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria. CONCLUSIONS: Targeted sequencing was found to be useful for detecting somatic mutations in patients with brain malformations. High-coverage sequencing panels provide an important complement to whole-exome and whole-genome sequencing in the evaluation of somatic mutations in neuropsychiatric disease. Copyright © 2014 Massachusetts Medical Society., SCOPUS: ar.j, info:eu-repo/semantics/published

No instruments are currently available to help health systems identify target areas for reducing door-to-needle times for the administration of intravenous tissue plasminogen activator to eligible patients with ischemic stroke. A 67-item Likert-scale survey was administered by telephone to stroke personnel at 252 U.S. hospitals participating in the "Get With The Guidelines-Stroke" quality improvement program. Factor analysis was used to refine the instrument to a four-factor 29-item instrument that can be used by hospitals to assess their readiness to administer intravenous tissue plasminogen activator within 60 minutes of patient hospital arrival.

BACKGROUND: Although there is increasing recognition of the role of somatic mutations in genetic disorders, the prevalence of somatic mutations in neurodevelopmental disease and the optimal techniques to detect somatic mosaicism have not been systematically evaluated. METHODS: Using a customized panel of known and candidate genes associated with brain malformations, we applied targeted high-coverage sequencing (depth, ≥200x) to leukocytederived DNA samples from 158 persons with brain malformations, including the double-cortex syndrome (subcortical band heterotopia, 30 persons), polymicrogyria with megalencephaly (20), periventricular nodular heterotopia (61), and pachygyria (47). We validated candidate mutations with the use of Sanger sequencing and, for variants present at unequal read depths, subcloning followed by colony sequencing. RESULTS: Validated, causal mutations were found in 27 persons (17%; range, 10 to 30% for each phenotype). Mutations were somatic in 8 of the 27 (30%), predominantly in persons with the double-cortex syndrome (in whom we found mutations in DCX and LIS1), persons with periventricular nodular heterotopia (FLNA), and persons with pachygyria (TUBB2B). Of the somatic mutations we detected, 5 (63%) were undetectable with the use of traditional Sanger sequencing but were validated through subcloning and subsequent sequencing of the subcloned DNA. We found potentially causal mutations in the candidate genes DYNC1H1, KIF5C, and other kinesin genes in persons with pachygyria. CONCLUSIONS: Targeted sequencing was found to be useful for detecting somatic mutations in patients with brain malformations. High-coverage sequencing panels provide an important complement to whole-exome and whole-genome sequencing in the evaluation of somatic mutations in neuropsychiatric disease. Copyright © 2014 Massachusetts Medical Society., SCOPUS: ar.j, info:eu-repo/semantics/published

The tasks performed and the progress made in the project included carrying out research on developing non-invasive near infrared (NIR) diffuse optical imaging (DOI) approaches for detection of breast tumors in early stages of growth when those are more amenable to treatment, and developing a training program for physical scientists in biological aspects of cancer research. In particular, the following NIR-DOI approaches for locating absorbing, scattering and fluorescent targets, and estimating their size and optical properties were developed and evaluated: (i) time reversal optical tomography (TROT); (ii) optical tomography based on Non-negative Matrix Factorization (NMF-OT), and Principal Component Analysis (PCA-OT). Previously developed OT based on Independent Component Analysis (Optica) was further extended. The work on Trot was highlighted in Optics in 2012, a special issue of the Optics and Photonics News as one of the 30 most exciting peer-reviewed optics research to have emerged over the past 12 months. A graduate student working on the project defended his Ph.D. thesis.. The results were disseminated in several publications and presentations. Several research proposals and pre-proposals were submitted. A breast cancer research program has been established at CCNY, a minority institution., The original document contains color images.

We present the analysis of a deep Chandra observation of a ~2L_* late-type galaxy, ESO 137-002, in the closest rich cluster A3627. The Chandra data reveal a long (>40 kpc) and narrow tail with a nearly constant width (~3 kpc) to the southeast of the galaxy, and a leading edge ~1.5 kpc from the galaxy center on the upstream side of the tail. The tail is most likely caused by the nearly edge-on stripping of ESO 137-002's ISM by ram pressure, compared to the nearly face-on stripping of ESO 137-001 discussed in our previous work. Spectral analysis of individual regions along the tail shows that the gas throughout it has a rather constant temperature, ~1 keV, very close to the temperature of the tails of ESO 137-001, if the same atomic database is used. The derived gas abundance is low (~0.2 solar with the single-kT model), an indication of the multiphase nature of the gas in the tail. The mass of the X-ray tail is only a small fraction (<5%) of the initial ISM mass of the galaxy, suggesting that the stripping is most likely at an early stage. However, with any of the single-kT, double-kT and multi-kT models we tried, the tail is always "over-pressured" relative to the surrounding ICM, which could be due to the uncertainties in the abundance, thermal vs. non-thermal X-ray emission, or magnetic support in the ICM. The H-alpha data from SOAR show a ~21 kpc tail spatially coincident with the X-ray tail, as well as a secondary tail (~12 kpc long) to the east of the main tail diverging at an angle of ~23 degrees and starting at a distance of ~7.5 kpc from the nucleus. At the position of the secondary H-alpha tail, the X-ray emission is also enhanced at the ~2 sigma level. We compare the tails of ESO 137-001 and ESO 137-002, and also compare the tails to simulations. Both the similarities and differences of the tails pose challenges to the simulations. Several implications are briefly discussed., Comment: 15 pages, 6 figures, accepted for publication in ApJ

We present the analysis of a deep Chandra observation of a ~2L_* late-type galaxy, ESO 137-002, in the closest rich cluster A3627. The Chandra data reveal a long (>40 kpc) and narrow tail with a nearly constant width (~3 kpc) to the southeast of the galaxy, and a leading edge ~1.5 kpc from the galaxy center on the upstream side of the tail. The tail is most likely caused by the nearly edge-on stripping of ESO 137-002's ISM by ram pressure, compared to the nearly face-on stripping of ESO 137-001 discussed in our previous work. Spectral analysis of individual regions along the tail shows that the gas throughout it has a rather constant temperature, ~1 keV, very close to the temperature of the tails of ESO 137-001, if the same atomic database is used. The derived gas abundance is low (~0.2 solar with the single-kT model), an indication of the multiphase nature of the gas in the tail. The mass of the X-ray tail is only a small fraction (<5%) of the initial ISM mass of the galaxy, suggesting that the stripping is most likely at an early stage. However, with any of the single-kT, double-kT and multi-kT models we tried, the tail is always "over-pressured" relative to the surrounding ICM, which could be due to the uncertainties in the abundance, thermal vs. non-thermal X-ray emission, or magnetic support in the ICM. The H-alpha data from SOAR show a ~21 kpc tail spatially coincident with the X-ray tail, as well as a secondary tail (~12 kpc long) to the east of the main tail diverging at an angle of ~23 degrees and starting at a distance of ~7.5 kpc from the nucleus. At the position of the secondary H-alpha tail, the X-ray emission is also enhanced at the ~2 sigma level. We compare the tails of ESO 137-001 and ESO 137-002, and also compare the tails to simulations. Both the similarities and differences of the tails pose challenges to the simulations. Several implications are briefly discussed., Comment: 15 pages, 6 figures, accepted for publication in ApJ

The tasks performed and the progresses made during the fourth year include the following: (1) carrying out research on the development of noninvasive near-infrared (NIR) diffuse optical imaging (DOI) approaches for the detection of breast tumors in the early stages of growth when they are more amenable to treatment; and (2) training of CCNY researchers at MSKCC in magnetic resonance spectroscopic imaging (MRSI) for the detection of lactate in tumors. The NIR optical imaging research involved the development of time reversal optical tomography (TROT) for imaging single absorbing and single scattering targets as a function of position, and two targets as a function of separation between them; and the adaptation and comparison of Principal Component Analysis (PCA) and Nonnegative Matrix Factorization (NMF) methods to the DOI problem and comparing them with previously developed OPTICA (optical tomography using independent component analysis). These approaches were demonstrated to be suited for detecting and locating small targets in tissue-simulating turbid media. MRSI investigation of lactate holds promise for assessment of tumor aggressiveness. We also have initiated the development of numerical algorithms for fluorescence tomography, since it has the potential to provide higher contrast as well as molecular and functional information through the use of exogenous fluorophores. A new research pre-proposal was developed and submitted to CDMRP 2011 BCRP Idea Award category for funding., The original document contains color images.