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BACKGROUND: Online discussion forums allow individuals who otherwise may be strangers to create a community where they can seek and share information. Patients with bone sarcomas and their support networks use discussion forums dedicated to cancer support. There is a paucity of published reports regarding the care experience of patients with bone sarcomas because studies on online discussion groups have primarily focused on some of the more common cancers, including breast and prostate cancer. Understanding commonly discussed themes among patients with bone sarcomas would allow treating physicians to have a better understanding of patient concerns when providing patient education and counseling. QUESTION/PURPOSE: We performed this study to review posts from bone sarcoma internet discussion boards to establish common themes related to the care experience of patients with sarcomas. METHODS: Online discussion forums were identified using the search term sarcoma discussion forum. After identifying 12 websites, we excluded closed forum groups, websites with missing or invalid links to forums, and nonpublic forums, such as groups on Facebook. These websites include profiles and photos that are personal, and sufficient author anonymity could not be achieved for this study. Posts written between January 1, 2012, and May 1, 2022, posted on five discussion boards were reviewed and collected until we reached a point of data saturation in which we agreed that the collection of additional posts would not reveal new themes. Discussion threads were filtered to identify posts pertaining to the most common bone sarcomas: chondrosarcoma, Ewing sarcoma, and osteosarcoma. Grounded theory-the methodology of repeated analyses of qualitative data to identify recurring themes or concepts-was used to analyze posts. Caregiver posts were delineated from patient posts and categorized separately for subgroup analysis. Grounded theory, although a qualitative method, endeavors to integrate the strengths inherent in quantitative methods with qualitative approaches. Grounded theory categorizes words, language, and the meanings these imply and seeks to organize and reduce the data gathered into themes or essences, which, in turn, can be fed into descriptions, models, or theories. Our analysis used three reviews of text to assign and group codes based on repeating ideas or concepts. The first review (open coding) aims to assign codes based on the verbatim text included by the author to capture the specific thoughts and ideas of the post. The second review (axial coding) aims to consolidate the ideas of posts by applying broader concepts to each post. The third and final review (selective coding) aims to further consolidate the themes of each post by trying to embody the main message contained in a post. A total of 570 posts from 139 threads were collected and analyzed using grounded theory. Twenty-five axial codes and four selective codes were created. We defined data saturation by the absence of a new open code in the analysis of a block of 50 posts to ensure that signals of saturation were not accepted too early in the analysis. RESULTS: The four selective codes included emotional aspects or connecting with others, information support: diagnosis, information support: treatment, and information support: recovery. Of these four codes, emotional aspects and connecting with others was the most prevalent theme (78% [445 of 570] of posts) followed by information support: treatment (49% [282 of 570] of posts). Information support: diagnosis and information support: recovery were each captured in 15% of posts. CONCLUSION: Analysis of posts reveals that the two most common themes involve seeking out emotional support and information about the experiences of others with various treatment modalities. Although most of the posts we assessed contained experiential information and emotional support rather than directed medical advice, future studies should assess the accuracy of information shared among online sarcoma forums. CLINICAL RELEVANCE: Physicians caring for patients with sarcomas should not only address patient concerns related to medical care, but also provide emotional support directly and assist patients by providing resources to peer support outlets, including online discussion forums. Although we cannot ascertain the proportion of patients who use online sites given the anonymity of posts included, these findings suggest common experiential themes across patients with sarcomas outside their doctors offices. It is important that providers be aware of reputable forums to provide as resources for their patients. The Musculoskeletal Tumor Society may further benefit from endorsing one or more of these forums and providing physician oversight to monitor misinformation.

In animal social groups, the extent to which individuals consistently win agonistic interactions and their ability to monopolize resources represent 2 core aspects of their competitive regime. However, whether these two aspects are closely correlated within groups has rarely been studied. Here, we tested the hypothesis that hierarchy steepness, which is generally used to represent power differentials between group members, predicts the variation in the distribution of fitness-related benefits (i.e. fecundity, infant survival, mating success, and feeding success) in relation to individual dominance ranks. We tested this hypothesis in primate groups using comparative phylogenetic meta-analytical techniques. Specifically, we reviewed published and unpublished studies to extract data on individual dominance ranks, their access to fitness-related benefits, and hierarchy steepness. We collected and included in our analysis a total of 153 data points, representing 27 species (including 2 chimpanzee sub-species). From these, we used 4 common methods to measure individual dominance ranks and hierarchy steepness, i.e. D ij -based normalized Davids scores, randomized Elo-ratings, and Davids scores and Elo-ratings estimated in Bayesian frameworks. We found that hierarchy steepness had no effect on the strength of the relationship between dominance rank and access to fitness-related benefits. Our results suggest that hierarchy steepness does not reflect between-group variation in the extent to which individual dominance affects the acquisition of fitness-related benefits in primates. Although the ability to win agonistic encounters is essential, we speculate that other behavioral strategies adopted by individuals may play crucial roles in resource acquisition in animal competitive regimes.

BACKGROUND: Proximal femur replacements (PFRs) are an effective surgical option to treat primary and metastatic tumors causing large bony defects in the proximal femur. Given the relative rarity of these indications, current studies on PFR for oncologic indications are generally limited by patient volume or relatively short-term follow-up. Because recent advances in systemic therapy have improved the prognosis of patients who undergo limb salvage surgery for musculoskeletal tumors, data on the long-term durability of endoprosthetic reconstructions have become increasingly important. QUESTIONS/PURPOSES: (1) How does the long-term survival of cemented bipolar PFRs compare with patient survival in patients who underwent PFR for benign, aggressive, and metastatic tumors? (2) What are common reasons for revisions of primary PFRs? (3) Which factors are associated with survival of primary PFRs? (4) What is the survivorship free from conversion of bipolar PFRs to THA? METHODS: Between January 1, 1980, and December 31, 2020, we treated 812 patients with an endoprosthetic reconstruction for an oncologic indication. All patients who underwent a primary PFR for an oncologic indication were included in this study. The study cohort consisted of 122 patients receiving a primary PFR. Eighteen patients did not reach a censored endpoint such as death, revision, or amputation within 2 years. Thirty-three patients died within 2 years of their surgery. Of the 122 patients with primary PFRs, 39 did not reach a censored endpoint and have not been seen within the past 5 years. However, the mean follow-up time for these patients was longer than 10 years. The Social Security Death Index was queried to identify any patients who may have died but might not have been captured by our database To allow for adequate follow-up, endoprosthetic reconstructions performed after December 31, 2020 were excluded. The mean age at the time of the index surgery was 48 ± 22 years. The mean follow-up time of surviving patients was 7 ± 8 years. All PFRs were performed using a bipolar hemiarthroplasty with a cemented stem, and all implants were considered comparable. Demographic, oncologic, procedural, and outcome data including prosthesis survival, patient survival, complication rates, and rates of conversion to THA were analyzed. Patient, prosthesis, and limb salvage survival rates were generated, with implant revision as the endpoint and death as a competing risk. Statistical significance was defined as p < 0.05. RESULTS: Generally, patients with benign or low-grade (Stage I) disease outlived their implants (100% patient survival through 30 years; p = 0.02), whereas the opposite was true in patients with high-grade, localized Stage II disease (64% patient survival at 5 years [95% CI 49% to 76%]; p = 0.001) or widespread Stage III metastatic disease (6.2% patient survival at 5 years [95% CI 0.5% to 24%]; p < 0.001). Primary PFR implant survival at 5, 10, 20, and 30 years was 97% (95% CI 90% to 99%), 81% (95% CI 67% to 90%), 69% (95% CI 46% to 84%), and 51% (95% CI 24% to 73%), respectively. Eight percent (10 of 122) of primary PFRs were revised for any reason. The most common causes of revision were aseptic loosening (3% [four of 122]), infection (3% [three of 122]), breakage of the implant (2% [two of 122]), and tumor progression (1% [one of 122]). Follow-up time was the only factor that was associated with revision of primary PFRs. Neither segment length nor stem length were associated with revision of primary. Six percent (seven of 122) of PFRs were converted to THA at a mean 15 ± 8 years from the index procedure. Survivorship free from conversion to THA (accounting for death as a competing risk) was 94% (95% CI 85% to 99%), 86% (95% CI 68% to 94%). and 77% (95% CI 51% to 91%) at 10, 20, and 30 years, respectively. CONCLUSION: Cemented bipolar PFRs for an oncologic indication are a relatively durable reconstruction technique. Given the relative longevity and efficacy of PFRs demonstrated in our study, especially in patients with high-grade or metastatic disease where implant survival until all-cause revision was longer than patient survival, surgeons should continue to seriously consider PFRs in appropriate patients. The relative rarity of these reconstructions limits the number of patients in this study as well as in current research; thus, further multi-institutional collaborations are needed to provide the most accurate prognostic data for our patients. LEVEL OF EVIDENCE: Level III, therapeutic study.

Objective To describe the development process of a patient-centered initiative focused on improving primary care health outcomes of patients with intellectual and developmental disabilities (IDD) and needle-related anxiety using evidence-based practices and novel approaches that can be implemented in outpatient settings. The overall outcome of the program is to increase vaccine uptake and accessibility in the IDD population as well as improve needle-related procedures in primary care settings to be more humane and effective. Methods The development process occurred in the context of a large healthcare system serving a diverse patient population in the U.S. and was led by an expert committee made of an multidisciplinary team of physicians, psychologists, ambulatory and clinic nurses, pharmacists, and anesthesiologists committed to promoting quality healthcare for the IDD population. Committee members were recruited within the healthcare system based on their relevant expertise. The methodology included an iterative and collaborative process that took place over three development phases: ideation and design, literature review and synthesis, and expert engagement. The ideation and design phase included a series of planning meetings among the expert committee, in which committee members identified preliminary concerns based on their expertise in the field and background knowledge on the current procedures related to improving routine care for individuals with IDD and/or needle-related anxiety. The literature review and synthesis phase led to the development of an annotated bibliography of research and clinical guidelines that synthesized findings on needle anxiety in clinical care. The expert engagement phase included all Committee members meeting for a final discussion to establish a tiered approach to utilizing evidence-based strategies that could be implemented across clinics within the healthcare system.  Results The multidisciplinary team of experts developed a three-tier system, deployed sequentially as needed. The first tier focuses on training nurses in evidence-based behavioral modification strategies to implement as standard of care. The second tier uses the addition of a distraction device and topical analgesic to reduce anxiety in patients with slightly elevated procedural anxiety. The third tier involves a novel minimal sedation protocol using intranasal midazolam for patients with needle phobia that can be administered in an outpatient setting. Conclusion The Needle Anxiety Program eases the administration of needle-related medical procedures in the primary care setting for patients with IDD and needle-related anxiety. The use of evidence-based practices and a novel minimal sedation protocol for individuals with needle phobia assists in the completion of routine healthcare procedures, such as vaccinations and phlebotomy, in a patient-preferred setting. The purpose of delineating needle-related processes and procedures through the Needle Anxiety Program is to reduce health disparities for patients with IDD and promote uptake of the Needle Anxiety Program in similar healthcare settings.

Objective Patients with intellectual and developmental disabilities (IDD) experience needle phobia at greater rates than individuals in the general population. Needle phobia deters patients with IDD from receiving routine medical procedures, which impacts their physical health outcomes. The aim of this quality improvement study was to assess the feasibility of a minimal sedation protocol in an outpatient care setting for patients with IDD and needle phobia. Methods The sample included 18 patients characterized as having a diagnosis of IDD only or IDD and needle phobia compared to patients with only a diagnosis of needle phobia. Reasons for referral to intervention included routine lab work, therapeutic drug monitoring, and routine vaccination. The minimal sedation intervention involved intranasal administration of a benzodiazepine (midazolam) by a registered nurse. Outcomes of interest were administration of the sedation and administration of medical orders. Results Nearly a third of patients were children (33.3%, n=6), and 39% of patients were female (n=7). Individuals with IDD (including those both with and without needle phobias) comprised 72.2% of patients (n=13). Half of intervention encounters were successful in both administering the sedation and performing the medical orders (n=9). Among individuals with IDD, 38.4% successfully completed the intervention (n=5). Conclusion This pilot study assessed the feasibility of implementing a minimal sedation protocol in primary care outpatient care settings. The preliminary results suggest that the minimal sedation protocol may improve the uptake of needle-related medical procedures for patients with IDD and/or needle phobia. The minimal sedation protocol should be studied in a larger sample and among multiple outpatient settings to establish effectiveness of the intervention.

Background and objectivesGiven advances in therapies, endoprosthetic reconstruction (EPR) in metastatic bone disease (MBD) may be increasingly indicated. The objectives were to review the indications, and implant and patient survivorship in patients undergoing EPR for MBD.MethodsA review of patients undergoing EPR for extremity MBD between 1992 and 2022 at two centers was performed. Surgical data, implant survival, patient survival, and implant failure modes were examined.ResultsOne hundred fifteen patients were included with a median follow-up of 14.9 months (95% confidence interval [CI]: 9.2-19.3) and survival of 19.4 months (95% CI: 13.6-26.1). The most common diagnosis was renal cell carcinoma (34/115, 29.6%) and the most common location was proximal femur (43/115, 37.4%). Indications included: actualized fracture (58/115, 50.4%), impending fracture (30/115, 26.1%), and failed fixation (27/115, 23.5%). Implant failure was uncommon (10/115, 8.7%). Patients undergoing EPR for failed fixation were more likely to have renal or lung cancer (p = 0.006).ConclusionsEPRs were performed most frequently for renal cell carcinoma and in patients with a relatively favorable survival. EPR was indicated for failed previous fixation in 23.5% of cases, emphasizing the importance of predictive survival modeling. EPR can be a reliable and durable surgical option for patients with MBD.

Nanoparticles that undergo a localized morphology change to target areas of inflammation have been previously developed but are limited by their lack of biodegradability. In this paper, we describe a low-ring-strain cyclic olefin monomer, 1,3-dimethyl-2-phenoxy-1,3,4,7-tetrahydro-1,3,2-diazaphosphepine 2-oxide (MePTDO), that rapidly polymerizes via ring-opening metathesis polymerization at room temperature to generate well-defined degradable polyphosphoramidates with high monomer conversion (>84%). Efficient MePTDO copolymerizations with norbornene-based monomers are demonstrated, including a norbornenyl monomer functionalized with a peptide substrate for inflammation-associated matrix metalloproteinases (MMPs). The resulting amphiphilic peptide brush copolymers self-assembled in aqueous solution to generate micellar nanoparticles (30 nm in diameter) which exhibit excellent cyto- and hemocompatibility and undergo MMP-induced assembly into micron-scale aggregates. As MMPs are upregulated in the heart postmyocardial infarction (MI), the MMP-responsive micelles were applied to target and accumulate in the infarcted heart following intravenous administration in a rat model of MI. These particles displayed a distinct biodistribution and clearance pattern in comparison to nondegradable analogues. Specifically, accumulation at the site of MI competed with elimination predominantly through the kidney rather than the liver. Together, these results suggest this as a promising new biodegradable platform for inflammation targeted delivery.

We develop a conceptual framework for studying collective adaptation in complex socio-cognitive systems, driven by dynamic interactions of social integration strategies, social environments and problem structures. Going beyond searching for 'intelligent' collectives, we integrate research from different disciplines and outline modelling approaches that can be used to begin answering questions such as why collectives sometimes fail to reach seemingly obvious solutions, how they change their strategies and network structures in response to different problems and how we can anticipate and perhaps change future harmful societal trajectories. We discuss the importance of considering path dependence, lack of optimization and collective myopia to understand the sometimes counterintuitive outcomes of collective adaptation. We call for a transdisciplinary, quantitative and societally useful social science that can help us to understand our rapidly changing and ever more complex societies, avoid collective disasters and reach the full potential of our ability to organize in adaptive collectives.

Accreditation is gaining ground in human services as leaders find ways to demonstrate the quality and legitimacy of services. This study examined site-level accreditation for SafeCare®, an evidence-based practice designed to prevent and reduce child maltreatment. We leveraged two waves of qualitative data to explore the perspectives of trainers, organizational and system leaders, and program developers who participated in an initial rollout of a site-level accreditation process for SafeCare. Institutional theory was used to frame accreditations potential benefits, burden, and impact. Findings highlight specific considerations for the human service environment, including the inherent resource scarcity, interdependence among organizations, and the impact of cost and slow-moving bureaucratic processes.

BackgroundDengue is the most prevalent arboviral infection causing an estimated 50-60 million cases of febrile illness globally per year, exacting considerable disease burden. Few instruments exist to assess the patient illness experience, with most based on healthcare provider assessment, lacking standardization in timepoints and symptom assessment. This study aimed to evaluate the content validity of the novel 'Dengue Virus Daily Diary (DENV-DD)', designed to measure symptom intensity and disease burden within outpatient infant to adult populations.MethodsThe Dengue Illness Index Report Card was used as a foundation to create the DENV-DD, consisting of patient- and observer-reported outcome (PRO/ObsRO) instruments. In two South American dengue-endemic communities, qualitative combined concept elicitation and cognitive debriefing interviews were conducted among individuals and caregivers of children with symptomatic laboratory-confirmed dengue. Interviews were conducted across two rounds allowing DENV-DD modifications. A small-scale quantitative assessment of the DENV-DD was also conducted with data from an independent Dengue Human Infection Model (DHIM) to generate early evidence of feasibility of DENV-DD completion, instrument performance and insight into the sign/symptom trajectory over the course of illness.ResultsForty-eight participants were interviewed (20 adults, 20 older children/adolescents with their caregivers, 8 caregivers of younger children). A wide spectrum of signs/symptoms lasting 3-15 days were reported with fever, headache, body ache/pain, loss of appetite, and body weakness each reported by > 70% participants. DENV-DD instructions, items and response scales were understood, and items were considered relevant across ages. DHIM data supported feasibility of DENV-DD completion.ConclusionsFindings demonstrate content validity of the DENV-DD (PRO/ObsRO instruments) in dengue-endemic populations. Psychometric and cultural validity studies are ongoing to support use of the DENV-DD in clinical studies.

Seasonal windows of opportunity are intervals within a year that provide improved prospects for growth, survival, or reproduction. However, few studies have sufficient temporal resolution to examine how multiple factors combine to constrain the seasonal timing and extent of developmental opportunities. Here, we document seasonal changes in milkweed (Asclepias fascicularis)-monarch (Danaus plexippus) interactions with high resolution throughout the last three breeding seasons prior to a precipitous single-year decline in the western monarch population. Our results show early- and late-season windows of opportunity for monarch recruitment that were constrained by different combinations of factors. Early-season windows of opportunity were characterized by high egg densities and low survival on a select subset of host plants, consistent with the hypothesis that early-spring migrant female monarchs select earlier-emerging plants to balance a seasonal trade-off between increasing host plant quantity and decreasing host plant quality. Late-season windows of opportunity were coincident with the initiation of host plant senescence, and caterpillar success was negatively correlated with heatwave exposure, consistent with the hypothesis that late-season windows were constrained by plant defense traits and thermal stress. Throughout this study, climatic and microclimatic variations played a foundational role in the timing and success of monarch developmental windows by affecting bottom-up, top-down, and abiotic limitations. More exposed microclimates were associated with higher developmental success during cooler conditions, and more shaded microclimates were associated with higher developmental success during warmer conditions, suggesting that habitat heterogeneity could buffer the effects of climatic variation. Together, these findings show an important dimension of seasonal change in milkweed-monarch interactions and illustrate how different biotic and abiotic factors can limit the developmental success of monarchs across the breeding season. These results also suggest the potential for seasonal sequences of favorable or unfavorable conditions across the breeding range to strongly affect monarch population dynamics.

Australia is experiencing mounting pressures related to processes of urbanisation, biodiversity loss and climate change felt at large in cities. At the same time, it is cities that can take the leading role in pioneering approaches and solutions to respond to those coupling emergencies. In this perspective piece we respond to the following question: What are the required transformations for prioritising, valuing, maintaining and embracing nature in cities in Australia? We adopt the mission framework as an organising framework to present proposed pathways to transform Australian cities as nature-positive places of the future. We propose three interconnected pathways as starting actions to steer urban planning, policy and governance in Australian cities: First, cities need to establish evidence-based planning for nature in cities and mainstream new planning tools that safeguard and foreground urban nature. Second, collaborative planning needs to become a standard practice in cities and inclusive governance for nature in cities needs to prioritise Aboriginal knowledge systems and practices as well as look beyond what local governments can do. Third, for progressing to nature-positive cities, it is paramount to empower communities to innovate with nature across Australian cities. Whilst we focus on Australian cities, the lessons and pathways are broadly applicably globally and can inspire science-policy debates for the post COP15 biodiversity and COP26 climate change implementation processes.

BackgroundThe COVID-19 pandemic has remarkably altered community mental health service delivery through the rapid implementation of telehealth. This study reports provider perspectives on the impact that COVID-19 and the transition to telehealth had on their work and their ability to deliver evidence-based practices (EBPs).MethodsProviders (n = 93) completed online surveys with quantitative measures and open-ended items exploring their reactions to COVID-19 and to the transition to providing services via telehealth.ResultsPerceptions of personal risk and rumination around COVID-19 were low, while telehealth was viewed positively by providers. Three major themes emerged regarding the major impacts of COVID-19 on work: (1) the altered nature of interactions between patient/client and provider due to telehealth implementation, (2) changes in provider expectations regarding productivity, and (3) challenges maintaining work-life balance. In regard to the major impacts of COVID-19 on EBP delivery, three themes emerged: (1) increased difficulty delivering certain therapies via telehealth, (2) potential limitations to session confidentiality, and (3) challenge of engaging children in telehealth.ConclusionsIn the context of the COVID-19 pandemic, community mental health providers continued to engage with clients and deliver EBPs while navigating a number of changes related to the rapid transition to and implementation of telehealth. This study highlights the need for further work on what supports providers need to effectively engage with clients and deliver EBPs via telehealth, and has implications for how telehealth is sustained or de-implemented post-COVID-19.

IntroductionAdolescent HIV prevention and treatment is a high priority for youth healthcare in sub-Saharan Africa.MethodsThis study employed concept mapping to identify factors that impact the implementation of HIV prevention and intervention programs for adolescents in sub-Saharan Africa. Key stakeholders including researchers, policymakers, and non-governmental organization (NGO) personnel constituting membership of the NIH-sponsored Adolescent HIV Prevention and Treatment Implementation Science Alliance responded to the question: "In your experience, what factors have facilitated or hindered implementation of evidence-based HIV prevention or treatment for adolescents in sub-Saharan Africa?" Participants generated statements in response to the focus question, sorted them into thematically relevant groups, and rated each statement on its importance and changeability.ResultsThrough data analyses and participant feedback, 15 distinct themes were derived. "Workforce/Workflow" and "HIV Stigma and Adolescent Development" were rated highest for importance, and "Threshold Conditions for Treatment" and "Structure of Implementation Efforts" were rated most changeable.ConclusionsUnderstanding implementation science determinants and mechanisms can facilitate the uptake of successful implementation and sustainment strategies for the prevention and treatment of HIV in a given context. We placed determinants and mechanisms within the Exploration, Preparation, Implementation, Sustainment (EPIS) framework to provide greater contextual integration with broader theories in implementation science. Implementers across multiple disciplines can use these findings to improve the scale-up of evidence-based practices for adolescent HIV prevention and treatment in sub-Saharan Africa. Implementation approaches that consider the determinants and mechanisms identified in this study and integrated in implementation frameworks will likely have utility for other health conditions and contexts.

IntroductionAdolescent HIV prevention and treatment is a high priority for youth healthcare in sub-Saharan Africa.MethodsThis study employed concept mapping to identify factors that impact the implementation of HIV prevention and intervention programs for adolescents in sub-Saharan Africa. Key stakeholders including researchers, policymakers, and non-governmental organization (NGO) personnel constituting membership of the NIH-sponsored Adolescent HIV Prevention and Treatment Implementation Science Alliance responded to the question: "In your experience, what factors have facilitated or hindered implementation of evidence-based HIV prevention or treatment for adolescents in sub-Saharan Africa?" Participants generated statements in response to the focus question, sorted them into thematically relevant groups, and rated each statement on its importance and changeability.ResultsThrough data analyses and participant feedback, 15 distinct themes were derived. "Workforce/Workflow" and "HIV Stigma and Adolescent Development" were rated highest for importance, and "Threshold Conditions for Treatment" and "Structure of Implementation Efforts" were rated most changeable.ConclusionsUnderstanding implementation science determinants and mechanisms can facilitate the uptake of successful implementation and sustainment strategies for the prevention and treatment of HIV in a given context. We placed determinants and mechanisms within the Exploration, Preparation, Implementation, Sustainment (EPIS) framework to provide greater contextual integration with broader theories in implementation science. Implementers across multiple disciplines can use these findings to improve the scale-up of evidence-based practices for adolescent HIV prevention and treatment in sub-Saharan Africa. Implementation approaches that consider the determinants and mechanisms identified in this study and integrated in implementation frameworks will likely have utility for other health conditions and contexts.

BackgroundSustainment, an outcome indicating an intervention continues to be implemented over time, has been comparatively less studied than other phases of the implementation process. This may be because of methodological difficulties, funding cycles, and minimal attention to theories and measurement of sustainment. This review synthesizes the literature on sustainment measures, evaluates the qualities of each measure, and highlights the strengths and gaps in existing sustainment measures. Results of the review will inform recommendations for the development of a pragmatic, valid, and reliable measure of sustainment.MethodsA narrative review of published sustainment outcome and sustainability measures (i.e., factors that influence sustainment) was conducted, including appraising measures in the Society of Implementation Research Collaboration (SIRC) instrument review project (IRP) and the Dissemination and Implementation Grid-Enabled Measures database initiative (GEM-D&I). The narrative review used a snowballing strategy by searching the reference sections of literature reviews and definitions of sustainability and sustainment. Measures used frequently and judged to be comprehensive and/or validated by a team of implementation scientists were extracted for analysis.ResultsEleven measures were evaluated. Three of the included measures were found in the SIRC-IRP, three in the GEM-D&I database, (one measure was in both databases) and six were identified in our additional searches. Thirteen constructs relating to sustainment were coded from selected measures. Measures covered a range of determinants for sustainment (i.e., construct of sustainability) as well as constructs of sustainment as an outcome. Strengths of the measures included, development by expert panels knowledgeable about particular interventions, fields or contexts, and utility in specific scenarios. A number of limitations were found in the measures analyzed including inadequate assessment of psychometric characteristics, being overly intervention or context specific, being lengthy and/or complex, and focusing on outer context factors.ConclusionThere is a lack of pragmatic and psychometrically sound measures of sustainment that can be completed by implementation stakeholders within inner context settings (e.g., frontline providers, supervisors).

BackgroundSustainment, an outcome indicating an intervention continues to be implemented over time, has been comparatively less studied than other phases of the implementation process. This may be because of methodological difficulties, funding cycles, and minimal attention to theories and measurement of sustainment. This review synthesizes the literature on sustainment measures, evaluates the qualities of each measure, and highlights the strengths and gaps in existing sustainment measures. Results of the review will inform recommendations for the development of a pragmatic, valid, and reliable measure of sustainment.MethodsA narrative review of published sustainment outcome and sustainability measures (i.e., factors that influence sustainment) was conducted, including appraising measures in the Society of Implementation Research Collaboration (SIRC) instrument review project (IRP) and the Dissemination and Implementation Grid-Enabled Measures database initiative (GEM-D&I). The narrative review used a snowballing strategy by searching the reference sections of literature reviews and definitions of sustainability and sustainment. Measures used frequently and judged to be comprehensive and/or validated by a team of implementation scientists were extracted for analysis.ResultsEleven measures were evaluated. Three of the included measures were found in the SIRC-IRP, three in the GEM-D&I database, (one measure was in both databases) and six were identified in our additional searches. Thirteen constructs relating to sustainment were coded from selected measures. Measures covered a range of determinants for sustainment (i.e., construct of sustainability) as well as constructs of sustainment as an outcome. Strengths of the measures included, development by expert panels knowledgeable about particular interventions, fields or contexts, and utility in specific scenarios. A number of limitations were found in the measures analyzed including inadequate assessment of psychometric characteristics, being overly intervention or context specific, being lengthy and/or complex, and focusing on outer context factors.ConclusionThere is a lack of pragmatic and psychometrically sound measures of sustainment that can be completed by implementation stakeholders within inner context settings (e.g., frontline providers, supervisors).

IntroductionScientific endeavors are increasingly carried out by teams of scientists. While there is growing literature on factors associated with effective science teams, little is known about processes that facilitate the success of dissemination and implementation (D&I) teams studying the uptake of healthcare innovations. This study aimed to identify strategies used by D&I scientists to promote team science.MethodsUsing a nominal group technique, a sample of 27 D&I scholars responded to the question, "What strategies have you or others used to promote team science?" Participants were asked to individually respond and then discuss within a small group to determine the group's top three strategies. Through a facilitated consensus discussion with the full sample, a rank-ordered list of three strategies was determined.ResultsA total of 126 individual responses (M = 9; SD = 4.88) were submitted. Through small group discussion, six groups ranked their top three strategies to promote team science. The final ranked list of strategies determined by the full sample included: (1) developing and maintaining clear expectations, (2) promoting and modeling effective communication, and (3) establishing shared goals and a mission of the work to be accomplished.ConclusionsBecause of its goal of translating knowledge to practice, D&I research necessitates the use of team science. The top strategies are in line with those found to be effective for teams in other fields and hold promise for improving D&I team cohesion and innovation, which may ultimately accelerate the translation of health innovations and the improvement of care quality and outcomes.

IntroductionScientific endeavors are increasingly carried out by teams of scientists. While there is growing literature on factors associated with effective science teams, little is known about processes that facilitate the success of dissemination and implementation (D&I) teams studying the uptake of healthcare innovations. This study aimed to identify strategies used by D&I scientists to promote team science.MethodsUsing a nominal group technique, a sample of 27 D&I scholars responded to the question, "What strategies have you or others used to promote team science?" Participants were asked to individually respond and then discuss within a small group to determine the group's top three strategies. Through a facilitated consensus discussion with the full sample, a rank-ordered list of three strategies was determined.ResultsA total of 126 individual responses (M = 9; SD = 4.88) were submitted. Through small group discussion, six groups ranked their top three strategies to promote team science. The final ranked list of strategies determined by the full sample included: (1) developing and maintaining clear expectations, (2) promoting and modeling effective communication, and (3) establishing shared goals and a mission of the work to be accomplished.ConclusionsBecause of its goal of translating knowledge to practice, D&I research necessitates the use of team science. The top strategies are in line with those found to be effective for teams in other fields and hold promise for improving D&I team cohesion and innovation, which may ultimately accelerate the translation of health innovations and the improvement of care quality and outcomes.

Abnormal sensory responses associated with Fragile X Syndrome (FXS) and autism spectrum disorders include hypersensitivity and impaired habituation to repeated stimuli. Similar sensory deficits are also observed in adult Fmr1 knock-out (KO) mice and are reversed by genetic deletion of Matrix Metalloproteinase-9 (MMP-9) through yet unknown mechanisms. Here we present new evidence that impaired development of parvalbumin (PV)-expressing inhibitory interneurons may underlie hyper-responsiveness in auditory cortex of Fmr1 KO mice via MMP-9-dependent regulation of perineuronal nets (PNNs). First, we found that PV cell development and PNN formation around GABAergic interneurons were impaired in developing auditory cortex of Fmr1 KO mice. Second, MMP-9 levels were elevated in P12-P18 auditory cortex of Fmr1 KO mice and genetic reduction of MMP-9 to WT levels restored the formation of PNNs around PV cells. Third, in vivo single-unit recordings from auditory cortex neurons showed enhanced spontaneous and sound-driven responses in developing Fmr1 KO mice, which were normalized following genetic reduction of MMP-9. These findings indicate that elevated MMP-9 levels contribute to the development of sensory hypersensitivity by influencing formation of PNNs around PV interneurons suggesting MMP-9 as a new therapeutic target to reduce sensory deficits in FXS and potentially other autism spectrum disorders.

Abnormal sensory responses associated with Fragile X Syndrome (FXS) and autism spectrum disorders include hypersensitivity and impaired habituation to repeated stimuli. Similar sensory deficits are also observed in adult Fmr1 knock-out (KO) mice and are reversed by genetic deletion of Matrix Metalloproteinase-9 (MMP-9) through yet unknown mechanisms. Here we present new evidence that impaired development of parvalbumin (PV)-expressing inhibitory interneurons may underlie hyper-responsiveness in auditory cortex of Fmr1 KO mice via MMP-9-dependent regulation of perineuronal nets (PNNs). First, we found that PV cell development and PNN formation around GABAergic interneurons were impaired in developing auditory cortex of Fmr1 KO mice. Second, MMP-9 levels were elevated in P12-P18 auditory cortex of Fmr1 KO mice and genetic reduction of MMP-9 to WT levels restored the formation of PNNs around PV cells. Third, in vivo single-unit recordings from auditory cortex neurons showed enhanced spontaneous and sound-driven responses in developing Fmr1 KO mice, which were normalized following genetic reduction of MMP-9. These findings indicate that elevated MMP-9 levels contribute to the development of sensory hypersensitivity by influencing formation of PNNs around PV interneurons suggesting MMP-9 as a new therapeutic target to reduce sensory deficits in FXS and potentially other autism spectrum disorders.

Abnormal sensory responses associated with Fragile X Syndrome (FXS) and autism spectrum disorders include hypersensitivity and impaired habituation to repeated stimuli. Similar sensory deficits are also observed in adult Fmr1 knock-out (KO) mice and are reversed by genetic deletion of Matrix Metalloproteinase-9 (MMP-9) through yet unknown mechanisms. Here we present new evidence that impaired development of parvalbumin (PV)-expressing inhibitory interneurons may underlie hyper-responsiveness in auditory cortex of Fmr1 KO mice via MMP-9-dependent regulation of perineuronal nets (PNNs). First, we found that PV cell development and PNN formation around GABAergic interneurons were impaired in developing auditory cortex of Fmr1 KO mice. Second, MMP-9 levels were elevated in P12-P18 auditory cortex of Fmr1 KO mice and genetic reduction of MMP-9 to WT levels restored the formation of PNNs around PV cells. Third, in vivo single-unit recordings from auditory cortex neurons showed enhanced spontaneous and sound-driven responses in developing Fmr1 KO mice, which were normalized following genetic reduction of MMP-9. These findings indicate that elevated MMP-9 levels contribute to the development of sensory hypersensitivity by influencing formation of PNNs around PV interneurons suggesting MMP-9 as a new therapeutic target to reduce sensory deficits in FXS and potentially other autism spectrum disorders.

Working in an interdisciplinary manner at the crossroads of alcohol and HIV research is a challenge. This paper presents six novel approaches that could be applied to activities at the intersection of alcohol and HIV. These approaches are (i) address the fact that the availability of new technology is unevenly distributed around the world, (ii) use technology to move beyond both paper and digital surveys, (iii) introduce a focus on advocacy and partnerships with large technology companies, (iv) harness technological innovation to utilise digital counselling, (v) explore the use of virtual reality in both research and delivering interventions, and (vi) consider alternative funding models to those currently in existence to improve efficiencies and innovations. Aiming to understand the interplay of alcohol and HIV will require creativity. The six approaches outlines in this paper provide possible directions from which new approaches may emerge.

Working in an interdisciplinary manner at the crossroads of alcohol and HIV research is a challenge. This paper presents six novel approaches that could be applied to activities at the intersection of alcohol and HIV. These approaches are (i) address the fact that the availability of new technology is unevenly distributed around the world, (ii) use technology to move beyond both paper and digital surveys, (iii) introduce a focus on advocacy and partnerships with large technology companies, (iv) harness technological innovation to utilise digital counselling, (v) explore the use of virtual reality in both research and delivering interventions, and (vi) consider alternative funding models to those currently in existence to improve efficiencies and innovations. Aiming to understand the interplay of alcohol and HIV will require creativity. The six approaches outlines in this paper provide possible directions from which new approaches may emerge.

Accurate assessment of upper respiratory tract and ocular irritation is critical for identifying and remedying problems related to overexposure to volatile chemicals, as well as for establishing parameters of irritation useful for regulatory purposes. This paper (a) describes the basic anatomy and physiology of the human upper respiratory tract and ocular mucosa, (b) discusses how airborne chemicals induce irritative sensations, and (c) reviews practical means employed for assessing such phenomena, including psychophysical (e.g., threshold and suprathreshold perceptual measures), physiological (e.g., cytology), electrophysiological (e.g., event-related potentials), and imaging (e.g., magnetic resonance imaging) techniques. Although traditionally animal models have been used as the first step in assessing such irritation, they are not addressed here since (a) there are numerous reviews available on this topic and (b) many rodents and rabbits are obligate nose breathers whose nasal passages differ considerably from those of humans, potentially limiting generalization of animal-based data to humans. A major goal of this compendium is to inform the reader of procedures for assessing irritation in humans and to provide information of value in the continued interpretation and development of empirical databases upon which future reasoned regulatory health decisions can be made.

Genetic malleability and amenability to behavioral assays make Drosophila an attractive model for dissecting the molecular mechanisms of complex behaviors, such as learning and memory. At a cellular level, Drosophila has contributed a wealth of information on the mechanisms regulating membrane excitability and synapse formation, function, and plasticity. Until recently, however, these studies have relied almost exclusively on analyses of the peripheral neuromuscular junction, with a smaller body of work on neurons grown in primary culture. These experimental systems are, by themselves, clearly inadequate for assessing neuronal function at the many levels necessary for an understanding of behavioral regulation. The pressing need is for access to physiologically relevant neuronal circuits as they develop and are modified throughout life. In the past few years, progress has been made in developing experimental approaches to examine functional properties of identified populations of Drosophila central neurons, both in cell culture and in vivo. This review focuses on these exciting developments, which promise to rapidly expand the frontiers of functional cellular neurobiology studies in Drosophila. We discuss here the technical advances that have begun to reveal the excitability and synaptic transmission properties of central neurons in flies, and discuss how these studies promise to substantially increase our understanding of neuronal mechanisms underlying behavioral plasticity.