Project SIGNAL: A Dashboard for Supporting Community Confidence in Making Data-Driven Decisions.

CONTEXT: Data dashboards have emerged as critical tools for surveillance and informing resource allocation. Despite their utility and popularity during COVID-19, there is a growing need to understand what tools and training are tailored to nonprofit community-based organizations that may partner with public health officials. PROGRAM: In June 2021, the Rhode Island Department of Health and Brown University partnered to create Project SIGNAL (Spatiotemporal Insights to Guide Nuanced Actions Locally), which utilizes spatiotemporal analytics to identify Rhode Island's largest disparities in COVID-19-related outcomes (eg, testing, diagnosis, vaccinations) at the neighborhood level. Results were hosted in an interactive online dashboard (signal-ri.org) designed using principles of the CDC Clear Communication Index. The target audience included a network of 15 geographic areas called Health Equity Zones, funded by the health department to provide critical grassroots public health programs to address social, health, and economic outcomes in their communities. IMPLEMENTATION: To disseminate the dashboard, a 6-hour virtual workshop series was created to train leaders to use the dashboard and increase their confidence in understanding common public health data terminology and concepts and better prepare attendees for rapid decision making during future public health emergencies. EVALUATION: The Project SIGNAL dashboard was launched in August 2022 and has been accessed over 7500 times. A total of 84 community leaders were trained to use this dashboard, increasing their confidence in applying common public health metrics to make decisions about their COVID-19-related activities. DISCUSSION: While several studies have outlined best practices for data dashboards, this is among the first to examine incorporating these practices into a spatiotemporal decision tool designed specifically for community organizations. Project SIGNAL demonstrates that by incorporating design best practices and pairing data dashboards with hands-on training, we can empower community leaders to utilize advanced spatiotemporal methods to identify health disparities and take localized action.

Reaching the potential of electron diffraction.

Microcrystal electron diffraction (MicroED) is an emerging structural technique in which submicron crystals are used to generate diffraction data for structural studies. Structures allow for the study of molecular-level architecture and drive hypotheses about modes of action, mechanisms, dynamics, and interactions with other molecules. Combining cryoelectron microscopy (cryo-EM) instrumentation with crystallographic techniques, MicroED has led to three-dimensional structural models of small molecules, peptides, and proteins and has generated tremendous interest due to its ability to use vanishingly small crystals. In this perspective, we describe the current state of the field for MicroED methodologies, including making and detecting crystals of the appropriate size for the technique, as well as ways to best handle and characterize these crystals. Our perspective provides insight into ways to unlock the full range of potential for MicroED to access previously intractable samples and describes areas of future development.

Preparing research samples for safe arrival at centers and facilities: recipes for successful experiments.

Preparation of biomacromolecules for structural biology studies is a complex and time-consuming process. The goal is to produce a highly concentrated, highly pure product that is often shipped to large facilities with tools to prepare the samples for crystallization trials or for measurements at synchrotrons and cryoEM centers. The aim of this article is to provide guidance and to discuss general considerations for shipping biomacromolecular samples. Details are also provided about shipping samples for specific experiment types, including solution- and cryogenic-based techniques. These guidelines are provided with the hope that the time and energy invested in sample preparation is not lost due to shipping logistics.

Applying 3D ED/MicroED workflows toward the next frontiers.

We report on the latest advancements in Microcrystal Electron Diffraction (3D ED/MicroED), as discussed during a symposium at the National Center for CryoEM Access and Training housed at the New York Structural Biology Center. This snapshot describes cutting-edge developments in various facets of the field and identifies potential avenues for continued progress. Key sections discuss instrumentation access, research applications for small molecules and biomacromolecules, data collection hardware and software, data reduction software, and finally reporting and validation. 3D ED/MicroED is still early in its wide adoption by the structural science community with ample opportunities for expansion, growth, and innovation.

Pragmatic Expansion of a Neonatal Antibiotic Stewardship Program in a Community Health Care System.

BACKGROUND: Previously published neonatal antibiotic stewardship efforts have been primarily implemented in single centers. Piedmont Athens Regional began work to decrease antibiotic use in the NICU with spread to the newborn nursery (NBN) and, subsequently, 13 other NICUs and NBNs throughout a health care system over a 4-year period. METHODS: This quality improvement initiative was conducted in the context of a multicenter learning collaborative from 2016 to 2019. The primary aim was a 10% reduction in antibiotic days per 1000 patient days (antibiotic utilization rate [AUR]) among newborns in the NICU and NBN at each hospital by December 2018. Change ideas were implemented by using plan-do-study-act cycles. The primary outcome measure was AUR with a balancing measure of antibiotic restarts. RESULTS: Piedmont Athens Regional decreased the NICU AUR by 46% and NBN AUR by 83%. Piedmont Healthcare decreased the NICU AUR by 40% and NBN AUR by 74%. Seven of 8 NICUs and 5 of 7 NBNs achieved a >10% reduction in AUR and 8 of 8 intervention hospitals showed a sustained drop in AUR in the NBN, NICU, or both during the 1.5-year postobservation period. Decreases in antibiotic initiation resulted in 335 fewer antibiotic courses in the NICU and 189 fewer infants started on antibiotics in the NBN in 2020 versus 2017. CONCLUSIONS: This initiative achieved reductions in AUR across multiple hospitals in the network. The system-wide approach facilitated information technology (IT) and electronic health record modifications. Common drivers of NICU improvement were involvement for at least 2 years, multidisciplinary teams, and the highest baseline AUR. The common driver of nursery improvement was the implementation of a neonatal sepsis risk calculator.

The Stability and Validity of Automated Indices of Vocal Development in Infants With Autistic and Non-Autistic Siblings.

PURPOSE: This study evaluates the extent to which automated indices of vocal development are stable and valid for predicting language in infants at increased familial likelihood for autism and/or language impairment and relatively lower likelihood infants. METHOD: A group of infants with autistic siblings (Sibs-autism; 20 infants) and a comparison group of infants with non-autistic siblings (Sibs-NA; 20 infants) wore Language ENvironment Analysis (LENA) recording devices for 16 hr on 2 days within a 1-week period. Extant software was used to derive several putative indices of vocal development from these recordings. Stability of these variables was examined across and within groups. Expressive and receptive language aggregates were calculated for each participant. Multiple regression analyses were used to (a) evaluate zero-order correlations for variables derived from LENA recordings with concurrent and future language and (b) test whether those associations were moderated by group status. RESULTS: Both stability and validity differed by variable and group status. All variables reached acceptable stability in the Sibs-autism group within two to three observations, whereas stability of most variables was attenuated in the Sibs-NA group. No variables were associated with concurrent language in the theoretically motivated direction across groups, but two variables were strongly associated with concurrent expressive language in only the Sibs-NA group. Additionally, two variables were associated with later expressive language, though these correlations were again stronger in the Sibs-NA versus Sibs-autism group. CONCLUSIONS: Although selected automated indices of vocal development were stable in Sibs-autism and/or valid for predicting expressive language within Sibs-NA, no scores showed strong, theoretically motivated associations with language within the Sibs-autism group. Automated indices of vocal development may, thus, have limited validity or clinical utility for predicting language development in infants at elevated familial likelihood for autism. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24415735.

Reconnecting with the Warrior Within: Australian Indigenous perspectives on the development of a social and emotional wellbeing program.

ISSUE ADDRESSED: Australian Indigenous youth are at high risk of developing mental health problems. Historical determinants and socioeconomic disadvantage continue to impact their social and emotional wellbeing (SEWB) and sense of identity. Previous literature suggests connecting to culture significantly impacts SEWB in Indigenous youth. Given the diversity of Indigenous culture, collaboration and consultation with specific cultural groups is required to develop appropriate and relevant psychological treatments for SEWB. The Warrior Within Program was developed to improve SEWB in Indigenous youth by assisting them to better understand their identity through participation in group-based cultural activities. This research aimed to understand Central Queensland Indigenous Development staff perspectives around (1) the process of developing the program and (2) how group-based cultural activities contributed to staff perceived improvements in SEWB of program participants. METHODS: In this qualitative study, semi-structured individual interviews of 60-90 min were conducted with four Warrior Within Program staff of Central Queensland Indigenous Development. Transcripts were thematically analysed and the subthemes identified were categorised into main themes. RESULTS: The process of developing the Warrior Within Program, cultural and Indigenous identity, reconnecting and knowledge emerged as the four main themes. CONCLUSIONS: This study makes a unique and important contribution to the Australian Indigenous literature regarding the role and nature of culture in group-based programs and the importance of collaborating with Indigenous groups to increase our understanding of their usefulness and efficacy. This study also helps to bridge the gap between Indigenous ways of knowing in program development and non-Indigenous methods of evaluation. SO WHAT?: Acknowledging Australian Indigenous methods and ways of knowing are essential to the development and delivery of culturally appropriate group problems for addressing the psychological needs of this population. The methods used in this study could be used by others seeking to legitimise cultural ways of knowing.

The future of clinical trials-is it virtual?

INTRODUCTION: Participant recruitment to clinical trials is often sub-optimal. Decentralized clinical trials have the potential to address challenges in traditional site-based clinical trial recruitment. SOURCES OF DATA: This review is based on recently published literature and the experience of running a large industry-sponsored interventional trial using both traditional and decentralized methods. AREAS OF AGREEMENT: Efficient delivery of clinical trials is essential to continue to provide therapeutic improvements in a timely and cost-efficient way. Clinical trial designs are constantly evolving to achieve effective trial delivery, manage the complexity of new therapeutic algorithms and conform to cultural developments. AREAS OF CONTROVERSY: Digitally innovative decentralized clinical trials may be a solution to improve recruitment and retention. Although many trials incorporate digital innovations to reduce patient burden, decentralized clinical trials allow remote access to clinical research, potentially enhancing geographical diversity as well as reducing participant burden. GROWING POINTS: Areas for development currently being discussed are developing a 'recruitment platform' that exploits the reach of digital connectivity, automated identification of eligible participants from volunteers, employing technology for remote interaction and exploring the logistic process of delivering the interventions. AREAS TIMELY FOR RELEVANT RESEARCH: The focus of development must ensure that the overall impact will widen participation and reduce inequalities in healthcare.

20 years of crystal hits: progress and promise in ultrahigh-throughput crystallization screening.

Diffraction-based structural methods contribute a large fraction of the biomolecular structural models available, providing a critical understanding of macromolecular architecture. These methods require crystallization of the target molecule, which remains a primary bottleneck in crystal-based structure determination. The National High-Throughput Crystallization Center at Hauptman-Woodward Medical Research Institute has focused on overcoming obstacles to crystallization through a combination of robotics-enabled high-throughput screening and advanced imaging to increase the success of finding crystallization conditions. This paper will describe the lessons learned from over 20 years of operation of our high-throughput crystallization services. The current experimental pipelines, instrumentation, imaging capabilities and software for image viewing and crystal scoring are detailed. New developments in the field and opportunities for further improvements in biomolecular crystallization are reflected on.

High-Throughput Screening to Obtain Crystal Hits for Protein Crystallography.

X-ray crystallography is the most commonly employed technique to discern macromolecular structures, but the crucial step of crystallizing a protein into an ordered lattice amenable to diffraction remains challenging. The crystallization of biomolecules is largely experimentally defined, and this process can be labor-intensive and prohibitive to researchers at resource-limited institutions. At the National High-Throughput Crystallization (HTX) Center, highly reproducible methods have been implemented to facilitate crystal growth, including an automated high-throughput 1,536-well microbatch-under-oil plate setup designed to sample a wide breadth of crystallization parameters. Plates are monitored using state-of-the-art imaging modalities over the course of 6 weeks to provide insight into crystal growth, as well as to accurately distinguish valuable crystal hits. Furthermore, the implementation of a trained artificial intelligence scoring algorithm for identifying crystal hits, coupled with an open-source, user-friendly interface for viewing experimental images, streamlines the process of analyzing crystal growth images. Here, the key procedures and instrumentation are described for the preparation of the cocktails and crystallization plates, imaging the plates, and identifying hits in a way that ensures reproducibility and increases the likelihood of successful crystallization.

"A Tremendous Outpouring of Love and Affection": A Template Analysis of Positive Experiences During a Major LGBTQ Rights Campaign.

Human rights for lesbian, gay, bisexual, transgender, and queer or questioning (LGBTQ) people have frequently been decided via popular vote. Australia conducted one such vote on the topic of marriage equality in 2017. Research has tended to focus on the negative experiences reported by LGBTQ people during such votes, with little attention paid to any positive experiences identified. This paper seeks to redress that imbalance, reporting the findings of two qualitative studies asking LGBTQ Australians about positive experiences during the marriage equality vote. The first study analyzed 673 typed responses collected during the two-month voting period, while the second analyzed interview data from 19 LGBTQ Australians collected two-and-a-half years after the vote. Both were analyzed using template analysis. Results identified sources of support, types of support, empowerment through activism, changes in general and LGBTQ communities, and positive personal changes. As public votes continue to be used to determine LGBTQ human rights, the findings may guide interventions to help LGBTQ people and their allies cope with such campaigns.

ASL Phonological Fluency: How Do Deaf Signers Retrieve and Produce Signs?

Researchers have focused on how deaf signing children acquire and use American Sign Language (ASL). One sub-skill of ASL proficiency is ASL phonology. This includes the ability to isolate and manipulate parameters within signs (i.e., handshape, location, and movement). Expressively, signed language phonological fluency tasks have investigated signers' abilities to produce signs given handshape constraints. We expanded the handshape task with the addition of sign production for two given locations with deaf adults and students. We also investigated how adjacent signs were recalled and produced within semantic and phonological clusters. Deaf adults frequently recalled signs with semantic connections and shared location. Students did the same, although shared handshape also facilitated their sign production. Finally, we present implications for ASL instruction with deaf students.

Longitudinal Relations Between Early Sensory Responsiveness and Later Communication in Infants with Autistic and Non-autistic Siblings.

Early differences in sensory responsiveness may contribute to difficulties with communication among autistic children; however, this theory has not been longitudinally assessed in infants at increased familial versus general population-level likelihood for autism (Sibs-autism vs. Sibs-NA) using a comprehensive battery of sensory responsiveness and communication. In a sample of 40 infants (20 Sibs-autism, of whom six were later diagnosed with autism; 20 Sibs-NA), we tested (a) associations between sensory responsiveness at 12-18 months and communication 9 months later and (b) evaluated whether such associations were moderated by sibling group, autism diagnosis, or age. We found negative zero-order correlations between sensory responsiveness (i.e., caregiver reported hyperresponsiveness and hyporesponsiveness; an observational measure of hyperresponsiveness) and later communication. Additionally, caregiver reported sensory seeking was negatively associated with later expressive communication only in Sibs-NA. Limitations include our relatively small sample size of infants diagnosed with autism. Implications for future research are discussed.

Assessing Gender Dysphoria: Development and Validation of the Gender Preoccupation and Stability Questionnaire - 2nd Edition (GPSQ-2).

The Gender Preoccupation and Stability Questionnaire (GPSQ) is a 14-item measure used to assess the effectiveness of medical, surgical, social, and psychological interventions in trans and gender diverse adults who experience gender dysphoria. One major limitation of the GPSQ is that it was not developed for use with adolescents. This study aims to validate a revised version of the GPSQ, the Gender Preoccupation and Stability Questionnaire-2nd Edition (GPSQ-2) with the aim of adapting the measure to be applicable to individuals aged 13 and above. This research was conducted in three stages: 1) development of the GPSQ-2 to address previously identified issues with validity and comprehensibility of the GPSQ and to increase the applicability of the measure to adolescents; 2) pilot testing, using a purposive sample and semi-structured interviews, to assess the relevance, comprehensibility, and comprehensiveness of the GPSQ-2; and 3) validation using a community sample to assess the psychometric properties of the GPSQ-2. The pilot study was conducted with seven participants (Mage = 28.43, SD = 15.50; age range: 13-59). The GPSQ-2 was found to be easy to understand, relevant to individuals who experienced gender dysphoria, and that it did not have any identifiable omissions. The validation study was conducted with 141 participants (Mage = 36.44; SD = 14.76; age range 14-73). The GPSQ-2 was found to be a reliable and valid 14-item scale with two factors: preoccupation and stability. The GPSQ-2 is a structurally sound measure of gender dysphoria that can be used in populations aged 13 and above.

Computational identification of a systemic antibiotic for gram-negative bacteria.

Discovery of antibiotics acting against Gram-negative species is uniquely challenging due to their restrictive penetration barrier. BamA, which inserts proteins into the outer membrane, is an attractive target due to its surface location. Darobactins produced by Photorhabdus, a nematode gut microbiome symbiont, target BamA. We reasoned that a computational search for genes only distantly related to the darobactin operon may lead to novel compounds. Following this clue, we identified dynobactin A, a novel peptide antibiotic from Photorhabdus australis containing two unlinked rings. Dynobactin is structurally unrelated to darobactins, but also targets BamA. Based on a BamA-dynobactin co-crystal structure and a BAM-complex-dynobactin cryo-EM structure, we show that dynobactin binds to the BamA lateral gate, uniquely protruding into its ß-barrel lumen. Dynobactin showed efficacy in a mouse systemic Escherichia coli infection. This study demonstrates the utility of computational approaches to antibiotic discovery and suggests that dynobactin is a promising lead for drug development.

Mechanisms by which Early Eye Gaze to the Mouth During Multisensory Speech Influences Expressive Communication Development in Infant Siblings of Children with and without Autism.

Looking to the mouth of a talker early in life predicts expressive communication. We hypothesized that looking at a talker's mouth may signal that infants are ready for increased supported joint engagement and that it subsequently facilitates prelinguistic vocal development and translates to broader gains in expressive communication. We tested this hypothesis in 50 infants aged 6-18 months with heightened and general population-level likelihood of autism diagnosis (Sibs-autism and Sibs-NA; respectively). We measured infants' gaze to a speaker's face using an eye tracking task, supported joint engagement during parent-child free play sessions, vocal complexity during a communication sample, and broader expressive communication. Looking at the mouth was indirectly associated with expressive communication via increased higher-order supported joint engagement and vocal complexity. This indirect effect did not vary according to sibling status. This study provides preliminary insights into the mechanisms by which looking at the mouth may influence expressive communication development.

Statewide Evaluation of SARS-CoV-2 Diagnoses and Sexual Orientation and Gender Identity.

OBJECTIVE: Understanding and identifying disparities in COVID-19 testing outcomes can help allocate resources to where they are most needed. The objective of this study was to estimate the association between lesbian, gay, bisexual, transgender, and queer (LGBTQ+) identity and SARS-CoV-2 test positivity. METHODS: Data were from the Rhode Island SARS-CoV-2 surveillance database and included tests scheduled from June 8, 2020, through January 15, 2021. We used multivariable generalized estimating equations accounting for repeat testing to estimate the odds of receiving a positive test result for SARS-CoV-2 by LGBTQ+ identity and race/ethnicity, adjusting for sociodemographic and temporal confounders. RESULTS: In multivariable analysis of 232 025 tests, LGBTQ+ people had lower odds of receiving a positive test result than cisgender heterosexual people (5.4% vs 8.7%; adjusted odds ratio [aOR] = 0.63; 95% CI, 0.59-0.68). Compared with cisgender heterosexual White people, LGBTQ+ White people were significantly less likely (aOR = 0.67; 95% CI, 0.61-0.73) and cisgender heterosexual people of color were significantly more likely (aOR = 1.71; 95% CI, 1.64-1.78) to receive a positive test result. LGBTQ+ people of color had similar test positivity (aOR = 0.90; 95% CI, 0.79-1.02) as cisgender heterosexual White people. People in sexual minority groups were significantly less likely than heterosexual people to receive a positive test result, but we found no significant differences in test results among cisgender, transgender, and gender nonconforming people. CONCLUSIONS: LGBTQ+ people may be less likely than heterosexual people to receive a positive test result for SARS-CoV-2, potentially related to protective health practices and greater social isolation. Addressing racial and ethnic disparities among both LGBTQ+ people and cisgender heterosexual people should be a priority of the public health workforce.

Recruitment and retention in longitudinal studies of people with intellectual disability: A case study of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA).

BACKGROUND: Longitudinal study of people with intellectual disability and other difficult to reach populations requires specific recruitment and retention strategies to be successful. AIMS: This paper provides a case study of participant recruitment and retention for a longitudinal study of ageing among older adults with intellectual disability in Ireland. METHODS AND PROCEDURES: Development and implementation of strategies to recruit and retain participants with intellectual disability aged 40+ years, for a longitudinal study comprising four data collection waves over more than a decade, are reported. Recruitment and retention outcomes are assessed alongside factors of successful implementation. OUTCOMES AND RESULTS: A nationally representative sample of 753 individuals with intellectual disability was recruited for wave 1 of the study. Multiple retention strategies aimed to reduce barriers to participation and create a project community and study bond, underpinned by a Values Framework and commitment to PPI. After four waves over 11 years, 87.1 % of surviving participants were retained. CONCLUSIONS AND IMPLICATIONS: Successful recruitment and retention of people with intellectual disabilities in longitudinal studies is possible when the approach taken is personal, flexible, and innovative; participant burden is minimised; the research team is skilled and sensitive to needs of participants; and where involvement of the study population guides development and implementation of specific and bespoke strategies.

Contributions to cytochrome c inner- and outer-sphere reorganization energy.

Cytochromes c are small water-soluble proteins that catalyze electron transfer in metabolism and energy conversion processes. Hydrogenobacter thermophilus cytochrome c 552 presents a curious case in displaying fluxionality of its heme axial methionine ligand; this behavior is altered by single point mutation of the Q64 residue to N64 or V64, which fixes the ligand in a single configuration. The reorganization energy (λ) of these cytochrome c 552 variants is experimentally determined using a combination of rotating disc electrochemistry, chronoamperometry and cyclic voltammetry. The differences between the λ determined from these complementary techniques helps to deconvolute the contribution of the active site and its immediate environment to the overall λ (λ Total). The experimentally determined λ values in conjunction with DFT calculations indicate that the differences in λ among the protein variants are mainly due to the differences in contributions from the protein environment and not just inner-sphere λ. DFT calculations indicate that the position of residue 64, responsible for the orientation of the axial methionine, determines the geometric relaxation of the redox active molecular orbital (RAMO). The orientation of the RAMO with respect to the heme is key to determining electron transfer coupling (H AB) which results in higher ET rates in the wild-type protein relative to the Q64V mutant despite a 150 mV higher λ Total in the former.

COVID-19 associated pancreatitis: A mini case-series.

INTRODUCTION: One of the recognized causes of acute pancreatitis is viral-induced pancreatitis. The SARS-COV-2 virus has been linked to pancreatic injury and hence the causation of acute pancreatitis. This paper reports three cases of acute pancreatitis linked to COVID-19 infection adding to serving to further consolidate evidence. CASE PRESENTATION: Three patients aged between 63 and 87 years were diagnosed with acute pancreatitis and concomitant or previous COVID-19 infection. Criteria for diagnosis of pancreatitis were according to the revised Atlanta criteria. None of the patients had had previous episodes of pancreatitis and other aetiologies were not suggestive. The patients were not vaccinated against SARS-CoV-2. Supportive treatment was instituted for the three patients, and all made an uneventful recovery. Mean hospital stay was 4 days. DISCUSSION: The diagnosis of acute pancreatitis in the presented cases is being linked to COVID-19 infection, as other causes were not evident. There is however a confounding factor, as the patient in case 2 had slightly elevated triglyceride levels and had been on long-term low dose atorvastatin, both of which are associated with a low risk of acute pancreatitis. However, she had never had pancreatitis prior to this presentation. CONCLUSION: The novel virus SARS-COV-2 has also been linked to pancreatic damage and thus a possible causative factor in acute pancreatitis. This mini-case series presents three cases of acute pancreatitis in COVID-19 positive patients, in the absence of other risk factors. This phenomenon linking COVID-19 and pancreatitis has been expounded by other case reports and cohort studies from around the world. It is reasonable to acknowledge that, like other viruses, SARS CoV-2 may cause acute pancreatitis, although sounder evidence from the international community needs to be compiled.