Communicating Effectively With People Experiencing Homelessness to Prevent Infectious Diseases.

BACKGROUND: People experiencing homelessness (PEH) are disproportionately affected by many infectious diseases, including coronavirus disease 2019 (COVID-19). However, communication efforts during public health emergencies like the COVID-19 pandemic often do not consider the unique needs of PEH. We examined how PEH seek and receive health information and how traditional health communication methods resonate with them. METHODS: We conducted in-person focus groups with PEH in 4 jurisdictions (Cincinnati, Ohio; Denver, Colorado; Sacramento, California; and the Bronx, New York) during July 2021. RESULTS: Findings from 15 focus groups with PEH (n = 53) revealed the need for trusted messengers and consistent messaging across local organizations, as PEH seek to verify information they receive from multiple sources. PEH overwhelmingly preferred to receive health information through face-to-face conversations, especially with healthcare providers with whom they had an established relationship, but they also cited news media, the internet, and social media as their main sources for obtaining health information. PEH reported that effective communication products pair a recommended action with instructions and resources about how to take that action within their community. CONCLUSIONS: These findings support healthcare providers collaborating with public health agencies to ensure that infectious disease prevention messages for PEH are provided by trusted messengers, multimodal, paired with resources, and consistent.

Ultrasound-Guided Peripheral Intravenous Catheter Training Results in Physician-Level Success for Emergency Department Technicians.

OBJECTIVES: To report our success and complication rates with emergency department (ED) technician-performed ultrasound (US)-guided peripheral intravenous (IV) catheter placement and to compare our results to similar studies in the literature. METHODS: We conducted a retrospective review of a prospective database of patients who underwent US-guided peripheral IV catheter placement attempts for clinical care in the ED. All patients meeting difficult IV access criteria who had a US-guided peripheral IV catheter placement attempted by a trained ED technician were included. Average attempts per success and overall success rates were compared to similar published studies. RESULTS: There were 830 participants, with an overall success rate of ED technician- performed US-guided peripheral IV catheter placement of 97.5%. Clinicians categorized 82.6% of participants as having difficult IV access and reported that in 46.5%, a central venous catheter would have been necessary if the US-guided peripheral IV catheter failed. Of successful catheter attempts, 86.8% were placed on the first attempt; 11.6% were placed on the second attempt; and 1.6% were placed on the third attempt. For this study, the average number of attempts per success was 1.15 (95% confidence interval, 1.12-1.18), which was lower than in 6 other published studies, ranging from 1.27 to 1.70. The overall success rate of our ED technician-performed attempts was 0.970 (95% confidence interval, 0.956-0.983), which was higher than that reported in previous ED technician studies (0.79-0.80), and closer to that reported for physicians or nurses (0.87-0.97). The arterial puncture complication rate was 0.8%, which was also lower than in other published studies (1.25%-9.80%). CONCLUSIONS: With brief but comprehensive training, ED technicians can successfully obtain US-guided peripheral IV catheter access in patients with difficult IV access.

Raccoon contact networks predict seasonal susceptibility to rabies outbreaks and limitations of vaccination.

Infectious disease transmission often depends on the contact structure of host populations. Although it is often challenging to capture the contact structure in wild animals, new technology has enabled biologists to obtain detailed temporal information on wildlife social contacts. In this study, we investigated the effects of raccoon contact patterns on rabies spread using network modelling. Raccoons (Procyon lotor) play an important role in the maintenance of rabies in the United States. It is crucial to understand how contact patterns influence the spread of rabies in raccoon populations in order to design effective control measures and to prevent transmission to human populations and other animals. We constructed a dynamic system of contact networks based on empirical data from proximity logging collars on a wild suburban raccoon population and then simulated rabies spread across these networks. Our contact networks incorporated the number and duration of raccoon interactions. We included differences in contacts according to sex and season, and both short-term acquaintances and long-term associations. Raccoons may display different behaviours when infectious, including aggression (furious behaviour) and impaired mobility (dumb behaviour); the network model was used to assess the impact of potential behavioural changes in rabid raccoons. We also tested the effectiveness of different vaccination coverage levels. Our results demonstrate that when rabies enters a suburban raccoon population, the likelihood of a disease outbreak affecting the majority of the population is high. Both the magnitude of rabies outbreaks and the speed of rabies spread depend strongly on the time of year that rabies is introduced into the population. When there is a combination of dumb and furious behaviours in the rabid raccoon population, there are similar outbreak sizes and speed of spread to when there are no behavioural changes due to rabies infection. By incorporating detailed data describing the variation in raccoon contact rates into a network modelling approach, we were able to show that suburban raccoon populations are highly susceptible to rabies outbreaks, that the risk of large outbreaks varies seasonally and that current vaccination target levels may be inadequate to prevent the spread of rabies within these populations. Our findings provide new insights into rabies dynamics in raccoon populations and have important implications for disease control.

A conversation analysis of verbal interactions and social processes in interpreter-mediated primary care encounters.

Language asymmetry between patients with limited English proficiency and health care providers increases the complexity of patient-provider communication. In this research, we used conversation analysis to examine the content and processes of five triadic clinical communication encounters between Spanish-speaking adult patients, English-speaking nurse practitioners, and clinic-based interpreters. Data collection included audio-recordings of the triadic clinical encounters and self-administered post-encounter surveys of the nurse practitioners and interpreters. Our findings revealed communication trouble spots that, when directly addressed by the interactants, facilitated processes of negotiating relationships, and coming to a mutual understanding. Exemplars labeled Making Assumptions; Colloquialisms as Signaling Potential for Trouble; Repairing a Mis-Statement; and Turn-Taking, Silences, and Laughter illustrated how the parties identified and navigated such trouble spots. The final exemplar, Attaining Intersubjectivity, represented a successful multi-lingual triadic communication. While the role of the interpreter often is seen as a conduit of information from one language to another, in practice they also enacted roles of communication collaborators and coconstructors. Future interdisciplinary research can include closer examination of occurrences of communication trouble spots and further exploration of how interpretermediated communication is conceptualized and problematized in diverse clinical settings, to promote language interpretation policies and practices that contribute to reducing health disparities among limited-English-proficient populations.

Examining multiracial youth in context: ethnic identity development and mental health outcomes.

Although multiracial individuals are the fastest growing population in the United States, research on the identity development of multiracial adolescents remains scant. This study explores the relationship between ethnic identity, its components (affirmation, exploration), and mental health outcomes (anxiety, depressive symptoms) within the contexts of schools for multiracial adolescents. The participants were multiracial and monoracial minority and majority high school students (n = 4,766; 54.6% female). Among the participants, 88.1% were Caucasian, 7.4% were African American, and 4.5% were multiracial. The research questions examined the relationship between ethnic identity exploration and affirmation on mental health outcomes and explored the role school context plays in this relationship. The findings suggested that multiracial youth experience more exploration and less affirmation than African Americans, but more than Caucasians. In addition, multiracial youth were found to have higher levels of mental health issues than their monoracial minority and majority peers. Specifically, multiracial youth had higher levels of depressive symptoms than their African American and Caucasian counterparts. Multiracial and Caucasian youth had similar levels of anxiety but these levels were significantly higher than African Americans. School diversity did not influence mental health outcomes for multiracial youth. These findings provide insight into the experiences of multiracial youth and underscore the importance of further investigating factors that contribute to their mental health outcomes.

Effectively engaging faith-based leaders on syringe services programs: U.S. pastors' knowledge, perceptions, and questions.

OBJECTIVE: To identify faith-based leaders' (FBLs') knowledge, perceptions, and questions about syringe services programs (SSPs). METHODS: We conducted a one-time, national online survey of 461 Christian FBLs August-September 2022. RESULTS: 56% of FBLs agreed they support having SSPs in their communities; only 7% strongly disagreed. We identified 15 main questions FBLs have about SSPs. We found statistically significant differences based on FBL Protestant affiliations. Mainline FBLs are more knowledgeable about SSPs, likely to believe a larger number of SSP services would benefit their community, supportive of SSPs, interested in data related to SSPs, and likely to look to local public health officials to shape their opinions on SSPs compared with non-mainline FBLs. CONCLUSIONS: SSP advocates can address questions that FBLs have about SSPs before beginning outreach. By understanding common Protestant denominational affiliations, advocates can focus initial engagement efforts on FBLs in their communities who are more likely to support SSPs. Our findings suggest that local public health officials can influence FBLs' opinions about SSPs.

Crystal structures of cholesteryl ester transfer protein in complex with inhibitors.

Human plasma cholesteryl ester transfer protein (CETP) transports cholesteryl ester from the antiatherogenic high-density lipoproteins (HDL) to the proatherogenic low-density and very low-density lipoproteins (LDL and VLDL). Inhibition of CETP has been shown to raise human plasma HDL cholesterol (HDL-C) levels and is potentially a novel approach for the prevention of cardiovascular diseases. Here, we report the crystal structures of CETP in complex with torcetrapib, a CETP inhibitor that has been tested in phase 3 clinical trials, and compound 2, an analog from a structurally distinct inhibitor series. In both crystal structures, the inhibitors are buried deeply within the protein, shifting the bound cholesteryl ester in the N-terminal pocket of the long hydrophobic tunnel and displacing the phospholipid from that pocket. The lipids in the C-terminal pocket of the hydrophobic tunnel remain unchanged. The inhibitors are positioned near the narrowing neck of the hydrophobic tunnel of CETP and thus block the connection between the N- and C-terminal pockets. These structures illuminate the unusual inhibition mechanism of these compounds and support the tunnel mechanism for neutral lipid transfer by CETP. These highly lipophilic inhibitors bind mainly through extensive hydrophobic interactions with the protein and the shifted cholesteryl ester molecule. However, polar residues, such as Ser-230 and His-232, are also found in the inhibitor binding site. An enhanced understanding of the inhibitor binding site may provide opportunities to design novel CETP inhibitors possessing more drug-like physical properties, distinct modes of action, or alternative pharmacological profiles.

Canadian Nutrition Society Dialogue on disease-related malnutrition: a commentary from the 2022 Food For Health Workshop.

This commentary represents a dialogue on key aspects of disease-related malnutrition (DRM) from leaders and experts from academia, health across disciplines, and several countries across the world. The dialogue illuminates the problem of DRM, what impact it has on outcomes, nutrition care as a human right, and practice, implementation, and policy approaches to address DRM. The dialogue allowed the germination of an idea to register a commitment through the Canadian Nutrition Society and the Canadian Malnutrition Task Force in the UN/WHO Decade of Action on Nutrition to advance policy-based approaches for DRM. This commitment was successfully registered in October 2022 and is entitled CAN DReaM (Creating Alliances Nationally for Policy in Disease-Related Malnutrition). This commitment details five goals that will be pursued in the Decade of Action on Nutrition. The intent of this commentary is to record the proceedings of the workshop as a stepping stone to establishing a policy-based approach to DRM that is relevant in Canada and abroad.

Nonvolatile copolymer compositions for fabricating gel element microarrays.

By modifying polymer compositions and cross-linking reagents, we have developed a simple yet effective manufacturing strategy for copolymerized three-dimensional gel element arrays. A new gel-forming monomer, 2-(hydroxyethyl) methacrylamide (HEMAA), was used. HEMAA possesses low volatility and improves the stability of copolymerized gel element arrays to on-chip thermal cycling procedures relative to previously used monomers. Probe immobilization efficiency within the new polymer was 55%, equivalent to that obtained with acrylamide (AA) and methacrylamide (MA) monomers. Nonspecific binding of single-stranded targets was equivalent for all monomers. Increasing cross-linker chain length improved hybridization kinetics and end-point signal intensities relative to N,N-methylenebisacrylamide (Bis). The new copolymer formulation was successfully applied to a model orthopox array. Because HEMAA greatly simplifies gel element array manufacture, we expect it (in combination with new cross-linkers described here) to find widespread application in microarray science.

Delayed induced silica defences in grasses and their potential for destabilising herbivore population dynamics.

Some grass species mount a defensive response to grazing by increasing their rate of uptake of silica from the soil and depositing it as abrasive granules in their leaves. Increased plant silica levels reduce food quality for herbivores that feed on these grasses. Here we provide empirical evidence that a principal food species of an herbivorous rodent exhibits a delayed defensive response to grazing by increasing silica concentrations, and present theoretical modelling that predicts that such a response alone could lead to the population cycles observed in some herbivore populations. Experiments performed under greenhouse conditions revealed that the rate of deposition of silica defences in the grass Deschampsia caespitosa is a time-lagged, nonlinear function of grazing intensity and that, upon cessation of grazing, these defences take around one year to decay to within 5 % of control levels. Simple coupled grass-herbivore population models incorporating this functional response, and parameterised with empirical data, consistently predict population cycles for a wide range of realistic parameter values for a (Microtus) vole-grass system. Our results support the hypothesis that induced silica defences have the potential to strongly affect the population dynamics of their herbivores. Specifically, the feedback response we observed could be a driving mechanism behind the observed population cycles in graminivorous herbivores in cases where grazing levels in the field become sufficiently large and sustained to trigger an induced silica defence response.

The effects of a brief mindfulness-based intervention on pain perceptions in patients with chronic pelvic pain: A case series.

INTRODUCTION: Chronic pelvic pain affects 15-20% of women, and patients frequently do not find relief with first-line therapies. Mindfulness-based meditation programs are effective in improving outcomes for patients with chronic pain conditions, but limited data exists for patients with chronic pelvic pain. We describe the effect of a brief mindfulness-based program, incorporated into pelvic-floor physical therapy visits, on perceived pain in patients with chronic pelvic pain. CASE SERIES: Patients being treated for pelvic pain participated in this 8-week program. Pelvic-floor physical therapists delivered a brief mindfulness-based exercise during routine physical therapy visits. Patients reported pain scores and pain catastrophizing scores at the beginning and end of the program. Ten patients completed the program. Paired-samples t-tests showed that pain catastrophizing significantly decreased from baseline to 8 weeks in patients who completed the mindfulness training and increased among patients who withdrew. CONCLUSION: Mindfulness-based exercises may be a useful complementary therapy for the treatment of chronic pelvic pain.

Gaming My Way to Recovery: A Systematic Scoping Review of Digital Game Interventions for Young People's Mental Health Treatment and Promotion.

Nearly all young people use the internet daily. Many youth with mental health concerns, especially since the Covid-19 pandemic, are using this route to seek help, whether through digital mental health treatment, illness prevention tools, or supports for mental wellbeing. Videogames also have wide appeal among young people, including those who receive mental health services. This review identifies the literature on videogame interventions for young people, ages 12-29, and maps the data on game use by those with mental health and substance use problems, focusing on evidence for the capacity of games to support treatment in youth mental health services; how stakeholders are involved in developing or evaluating games; and any potential harms and ethical remedies identified. A systematic scoping review methodology was used to identify and assess relevant studies. A search of multiple databases identified a total of 8,733 articles. They were screened, and 49 studies testing 32 digital games retained. An adapted stepped care model, including four levels, or steps, based on illness manifestation and severity, was used as a conceptual framework for organizing target populations, mental health conditions and corresponding digital games, and study results. The 49 selected studies included: 10 studies (20.4%) on mental health promotion/prevention or education for undiagnosed youth (Step 0: 7 games); 6 studies (12.2%) on at-risk groups or suspected mental problems (Step 1: 5 games); 24 studies (49.0%) on mild to moderate mental conditions (Steps 2-3: 16 games); and 9 studies (18.4%) focused on severe and complex mental conditions (Step 4: 7 games). Two interventions were played by youth at more than one level of illness severity: the SPARX game (Steps 1, 2-3, 4) and Dojo (Steps 2-3 and 4), bringing the total game count to 35 with these repetitions. Findings support the potential integration of digital games in youth services based on study outcomes, user satisfaction, relatively high program retention rates and the potential usefulness of most games for mental health treatment or promotion/prevention. Most studies included stakeholder feedback, and involvement ratings were very high for seven games. Potential harms were not addressed in this body of research. This review provides an important initial repository and evaluation of videogames for use in clinical settings concerned with youth mental health.

The population dynamical consequences of density-dependent prophylaxis.

When infectious disease transmission is density-dependent, the risk of infection will tend to increase with host population density. Since host defence mechanisms can be costly, individual hosts may benefit from increasing their investment in immunity in response to increasing population density. Such "density-dependent prophylaxis" (DDP) has now indeed been demonstrated experimentally in several species. However, it remains unclear how DDP will affect the population dynamics of the host-pathogen interaction, with previous theoretical work making conflicting predictions. We develop a general host-pathogen model and assess the role of DDP on the population dynamics. The ability of DDP to drive population cycles is critically dependent on the time delay between the change in density and the subsequent phenotypic change in the level of resistance. When the delay is absent or short, DDP destabilises the system. As the delay increases, its destabilising effect first diminishes and then DDP becomes increasingly stabilising. Our work highlights the significance of the time delay and suggests that it must be estimated experimentally or varied in theoretical investigations in order to understand the implications of DDP for the population dynamics of particular systems.

Enhanced photoprotection pathways in symbiotic dinoflagellates of shallow-water corals and other cnidarians.

Photoinhibition, exacerbated by elevated temperatures, underlies coral bleaching, but sensitivity to photosynthetic loss differs among various phylotypes of Symbiodinium, their dinoflagellate symbionts. Symbiodinium is a common symbiont in many cnidarian species including corals, jellyfish, anemones, and giant clams. Here, we provide evidence that most members of clade A Symbiodinium, but not clades B-D or F, exhibit enhanced capabilities for alternative photosynthetic electron-transport pathways including cyclic electron transport (CET). Unlike other clades, clade A Symbiodinium also undergo pronounced light-induced dissociation of antenna complexes from photosystem II (PSII) reaction centers. We propose these attributes promote survival of most cnidarians with clade A symbionts at high light intensities and confer resistance to bleaching conditions that conspicuously impact deeper dwelling corals that harbor non-clade A Symbiodinium.

Lottery promotions at the point-of-sale in Ontario, Canada.

We documented the extent of point-of-sale (POS) lottery promotions in Ontario, Canada and the relationship between lottery promotions and store and city characteristics. This is the first quantitative study of POS lottery promotions. A total of 366 stores-independent and chain convenience stores, gas stations and grocery stores-were visited across 20 cities in Ontario. Data collectors unobtrusively observed the type of lottery promotions in each store and completed a data collection checklist. A lottery promotion index was created and hierarchical linear modeling (HLM) was conducted to examine the relationship between extent of lottery promotions and independent variables such as neighbourhood socioeconomic status and city prevalence of lottery ticket purchasing. POS lottery promotions were widespread across Ontario, with the highest level of promotion found in independent convenience stores. In the multivariable HLM model, none of the remaining independent variables remained statistically significant, except for store type. Lottery promotions are extensive at the POS in Ontario. These findings can help initiate discussions around the appropriateness and possible future regulation of this form of advertising.

A public health approach to gambling regulation: countering powerful influences.

Often portrayed as a harmless leisure activity in the UK, gambling is being increasingly recognised as a public health concern. However, a gambling policy system that explicitly tackles public health concerns and confronts the dependencies and conflicts of interest that undermine the public good is absent in the UK. Although there is a window of opportunity to change the gambling policy system, with the UK Government's launch of a review of the Gambling Act 2005, the adoption of a comprehensive and meaningful public health approach is not guaranteed. Too often, government policy has employed discourses that align more closely with those of the gambling industry than with those of the individuals, families, and communities affected by the harms of gambling. In view of the well described commercial determinants of health and corporate behaviour, an immense effort will be needed to shift the gambling discourse to protect public health. In this Viewpoint, we seek to advance this agenda by identifying elements that need challenging and stimulating debate.

Digital Game Interventions for Youth Mental Health Services (Gaming My Way to Recovery): Protocol for a Scoping Review.

BACKGROUND: Digital or video games are played by millions of adolescents and young adults around the world and are one of the technologies used by youths to access mental health services. Youths with mental health problems strongly endorse the use of technologies, including mobile and online platforms, to receive information, support their treatment journeys (eg, decision-making tools), and facilitate recovery. A growing body of literature explores the advantages of playing digital games for improving attention span and memory, managing emotions, promoting behavior change, and supporting treatment for mental illness (eg, anxiety, depression, or posttraumatic stress disorder). The research field has also focused on the negative impact of video games, describing potential harms related to aggression, addiction, and depression. To promote clarity on this matter, there is a great need for knowledge synthesis offering recommendations on how video games can be safely and effectively adopted and integrated into youth mental health services. OBJECTIVE: The Gaming My Way to Recovery scoping review project assesses existing evidence on the use of digital game interventions within the context of mental health services for youths (aged 11-29 years) using the stepped care model as the conceptual framework. The research question is as follows: For which youth mental health conditions have digital games been used and what broad objectives (eg, prevention, treatment) have they addressed? METHODS: Using the methodology proposed by Arksey and O'Malley, this scoping review will map the available evidence on the use of digital games for youths between 11 and 29 years old with mental health or substance use problems, or both. RESULTS: The review will bring together evidence-based knowledge to assist mental health providers and policymakers in evaluating the potential benefits and risks of these interventions. Following funding of the project in September 2018, we completed the search in November 2018, and carried out data screening and stakeholder engagement activities during preparation of the protocol. We will conduct a knowledge synthesis based on specific disorders, treatment level and modality, type of service, population, settings, ethical practices, and user engagement and offer recommendations concerning the integration of video game technologies and programs, future research and practice, and knowledge dissemination. CONCLUSIONS: Digital game interventions employ unique, experiential, and interactive features that potentially improve skills and facilitate learning among players. Digital games may also provide a new treatment platform for youths with mental health conditions. Assessing current knowledge on video game technology and interventions may potentially improve the range of interventions offered by youth mental health services while supporting prevention, intervention, and treatment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/13834.

Health communication campaigns to drive demand for evidence-based practices and reduce stigma in the HEALing communities study.

BACKGROUND: The HEALing Communities Study (HCS) is testing whether the Communities that Heal (CTH) intervention can decrease opioid overdose deaths through the implementation of evidence-based practices (EBPs) in highly impacted communities. One of the CTH intervention components is a series of communications campaigns to promote the implementation of EBPs, increase demand for naloxone and medications for opioid use disorder (MOUD), and decrease stigma toward people with opioid use disorder and the use of EBPs, especially MOUD. This paper describes the approach to developing and executing these campaigns. METHODS: The HCS communication campaigns are developed and implemented through a collaboration between communication experts, research site staff, and community coalitions using a three-stage process. The Prepare phase identifies priority groups to receive campaign messages, develops content for those messages, and identifies a "call to action" that asks people to engage in a specific behavior. In the Plan phase, campaign resources are produced, and community coalitions develop plans to distribute campaign materials. During the Implement stage, these distribution plans guide delivery of content to priority groups. Fidelity measures assess how community coalitions follow their distribution plan as well as barriers and facilitators to implementation. An evaluation of the communication campaigns is planned. CONCLUSIONS: If successful, the Prepare-Plan-Implement process, and the campaign materials, could be adapted and used by other communities to address the opioid crisis. The campaign evaluation will extend the evidence base for how communication campaigns can be developed and implemented through a community-engaged process to effectively address public health crises.

Feline immunodeficiency virus in puma: Estimation of force of infection reveals insights into transmission.

Determining parameters that govern pathogen transmission (such as the force of infection, FOI), and pathogen impacts on morbidity and mortality, is exceptionally challenging for wildlife. Vital parameters can vary, for example across host populations, between sexes and within an individual's lifetime.Feline immunodeficiency virus (FIV) is a lentivirus affecting domestic and wild cat species, forming species-specific viral-host associations. FIV infection is common in populations of puma (Puma concolor), yet uncertainty remains over transmission parameters and the significance of FIV infection for puma mortality. In this study, the age-specific FOI of FIV in pumas was estimated from prevalence data, and the evidence for disease-associated mortality was assessed.We fitted candidate models to FIV prevalence data and adopted a maximum likelihood method to estimate parameter values in each model. The models with the best fit were determined to infer the most likely FOI curves. We applied this strategy for female and male pumas from California, Colorado, and Florida.When splitting the data by sex and area, our FOI modeling revealed no evidence of disease-associated mortality in any population. Both sex and location were found to influence the FOI, which was generally higher for male pumas than for females. For female pumas at all sites, and male pumas from California and Colorado, the FOI did not vary with puma age, implying FIV transmission can happen throughout life; this result supports the idea that transmission can occur from mothers to cubs and also throughout adult life. For Florida males, the FOI was a decreasing function of puma age, indicating an increased risk of infection in the early years, and a decreased risk at older ages.This research provides critical insight into pathogen transmission and impact in a secretive and solitary carnivore. Our findings shed light on the debate on whether FIV causes mortality in wild felids like puma, and our approach may be adopted for other diseases and species. The methodology we present can be used for identifying likely transmission routes of a pathogen and also estimating any disease-associated mortality, both of which can be difficult to establish for wildlife diseases in particular.