Bleeding Control Protections Within US Good Samaritan Laws.

INTRODUCTION: In the United States, all 50 states and the District of Columbia have Good Samaritan Laws (GSLs). Designed to encourage bystanders to aid at the scene of an emergency, GSLs generally limit the risk of civil tort liability if the care is rendered in good faith. Nation-wide, a leading cause of preventable death is uncontrolled external hemorrhage. Public bleeding control initiatives aim to train the public to recognize life-threatening external bleeding, perform life-sustaining interventions (including direct pressure, tourniquet application, and wound packing), and to promote access to bleeding control equipment to ensure a rapid response from bystanders. METHODS: This study sought to identify the GSLs in each state and the District of Columbia to identify what type of responder is covered by the law (eg, all laypersons, only trained individuals, or only licensed health care providers) and if bleeding control is explicitly included or excluded in their Good Samaritan coverage. RESULTS: Good Samaritan Laws providing civil liability qualified immunity were identified in all 50 states and the District of Columbia. One state, Oklahoma, specifically includes bleeding control in its GSLs. Six states - Connecticut, Illinois, Kansas, Kentucky, Michigan, and Missouri - have laws that define those covered under Good Samaritan immunity, generally limiting protection to individuals trained in a standard first aid or resuscitation course or health care clinicians. No state explicitly excludes bleeding control from their GSLs, and one state expressly includes it. CONCLUSION: Nation-wide across the United States, most states have broad bystander coverage within GSLs for emergency medical conditions of all types, including bleeding emergencies, and no state explicitly excludes bleeding control interventions. Some states restrict coverage to those health care personnel or bystanders who have completed a specific training program. Opportunity exists for additional research into those states whose GSLs may not be inclusive of bleeding control interventions.

Structural basis for intra- and intermolecular interactions on RAD9 subunit of 9-1-1 checkpoint clamp implies functional 9-1-1 regulation by RHINO.

Eukaryotic DNA clamp is a trimeric protein featuring a toroidal ring structure that binds DNA on the inside of the ring and multiple proteins involved in DNA transactions on the outside. Eukaryotes have two types of DNA clamps: the replication clamp PCNA and the checkpoint clamp RAD9-RAD1-HUS1 (9-1-1). 9-1-1 activates the ATR-CHK1 pathway in DNA damage checkpoint, regulating cell cycle progression. Structure of 9-1-1 consists of two moieties: a hetero-trimeric ring formed by PCNA-like domains of three subunits and an intrinsically disordered C-terminal region of the RAD9 subunit, called RAD9 C-tail. The RAD9 C-tail interacts with the 9-1-1 ring and disrupts the interaction between 9-1-1 and DNA, suggesting a negative regulatory role for this intramolecular interaction. In contrast, RHINO, a 9-1-1 binding protein, interacts with both RAD1 and RAD9 subunits, positively regulating checkpoint activation by 9-1-1. This study presents a biochemical and structural analysis of intra- and inter-molecular interactions on the 9-1-1 ring. Biochemical analysis indicates that RAD9 C-tail binds to the hydrophobic pocket on the PCNA-like domain of RAD9, implying that the pocket is involved in multiple protein-protein interactions. The crystal structure of the 9-1-1 ring in complex with a RHINO peptide reveals that RHINO binds to the hydrophobic pocket of RAD9, shedding light on the RAD9-binding motif. Additionally, the study proposes a structural model of the 9-1-1-RHINO quaternary complex. Together, these findings provide functional insights into the intra- and inter-molecular interactions on the front side of RAD9, elucidating the roles of RAD9 C-tail and RHINO in checkpoint activation.

Impact of the Coronavirus Disease 2019 Pandemic on Utilization of Emergency Medical Services in New York City.

Background: This study evaluates trends in the utilization of emergency medical services (EMS) in New York City, the "epicenter" of the first "wave" of the coronavirus pandemic. We hypothesize that EMS call volumes decreased overall in New York City during the first year of the pandemic, specifically with respect to trauma/injury calls. Contrarily, we posit that calls for "sick" events increased given pervasive fear of virus transmission. Materials and Methods: Retrospective New York City EMS calls data (January 1, 2019 to December 31, 2020) were obtained from the NYC Open Data/EMS Incident Dispatch database. Total EMS calls, trauma/injury calls, and "sick" event calls were collected for New York City and for all five boroughs. Census data for each borough were used to weigh daily EMS calls per 100,000 individuals. Mann-Whitney U tests were used to compare pre-pandemic (2019 to March 2020) versus pandemic (April 2020 to December 2020) EMS call volumes, p = 0.05. Results: Median daily EMS calls per 100,000 individuals decreased 21.6% at the start of the pandemic across New York City (pre-pandemic, 3,262 calls; pandemic, 2,556 calls; p < 0.001) and similarly decreased when stratified by borough (all, p < 0.001). Median daily trauma/injury and sick event calls per 100,000 also decreased in New York City and the five boroughs from pre-pandemic to pandemic time periods (all, p < 0.001). Discussion and Conclusions: These data reflect an unprecedented window into EMS utilization during an infectious disease pandemic. As decreased EMS utilization for multiple conditions likely reflects delayed or impeded access to care, utilization data have important implications for provision of acute care services during possible future disruptions related to the pandemic.

Effect of Mandatory and Voluntary Overtime Hours on Stress Among 9-1-1 Telecommunicators.

BACKGROUND: 9-1-1 telecommunicators are frequently exposed to indirect traumatic events that impact their mental and physical health and are often required to work overtime with rotating shifts. Previous studies reported various harmful effects of overtime on the health and well-being of workers, such as musculoskeletal injuries, burnout, low job satisfaction, fatigue, and intent to leave. However, there is limited research on the impact of overtime hours on 9-1-1 telecommunicators' stress symptoms, especially mandatory overtime hours. This study aimed to examine the relationship between overtime hours-mandatory and voluntary-and the level of stress symptoms among 9-1-1 telecommunicators. METHODS: We used secondary data from the surveys of the "Multi-tasking to hyper-tasking: Investigating the impact of Next Generation 9-1-1" study for analysis. Linear mixed-effects regression was applied to examine the association of overtime hours with the stress level. RESULTS: Of the 403 participants, 47.6% reported that they were required to work mandatory overtime, and the mean mandatory overtime was 7.51 (SD = 12.78) hours in the past month. 58.3% reported working voluntary overtime, and the mean voluntary overtime was 11.63 (SD = 17.48) hours. This study found that mandatory overtime hours were associated with an increase in self-reported stress symptoms (ß = 0.30, p = .002), whereas no significant association was found between voluntary overtime and the level of stress symptoms (ß = -0.01, p = .885). CONCLUSION/APPLICATION TO PRACTICE: Study results highlight the importance of reducing mandatory overtime in call centers as one possible strategy for reducing stress levels among this critical workforce.

The Daily Patterns of Emergency Medical Events.

This study examines population-level daily patterns of time-stamped emergency medical service (EMS) dispatches to establish their situational predictability. Using visualization, sinusoidal regression, and statistical tests to compare empirical cumulative distributions, we analyzed 311,848,450 emergency medical call records from the US National Emergency Medical Services Information System (NEMSIS) for years 2010 through 2022. The analysis revealed a robust daily pattern in the hourly distribution of distress calls across 33 major categories of medical emergency dispatch types. Sinusoidal regression coefficients for all types were statistically significant, mostly at the p < 0.0001 level. The coefficient of determination (R2) ranged from 0.84 and 0.99 for all models, with most falling in the 0.94 to 0.99 range. The common sinusoidal pattern, peaking in mid-afternoon, demonstrates that all major categories of medical emergency dispatch types appear to be influenced by an underlying daily rhythm that is aligned with daylight hours and common sleep/wake cycles. A comparison of results with previous landmark studies revealed new and contrasting EMS patterns for several long-established peak occurrence hours-specifically for chest pain, heart problems, stroke, convulsions and seizures, and sudden cardiac arrest/death. Upon closer examination, we also found that heart attacks, diagnosed by paramedics in the field via 12-lead cardiac monitoring, followed the identified common daily pattern of a mid-afternoon peak, departing from prior generally accepted morning tendencies. Extended analysis revealed that the normative pattern prevailed across the NEMSIS data when reorganized to consider monthly, seasonal, daylight-savings versus civil time, and pre-/post-COVID-19 periods. The predictable daily EMS patterns provide impetus for more research that links daily variation with causal risk and protective factors. Our methods are straightforward and presented with detail to provide accessible and replicable implementation for researchers and practitioners.

The dynamic subcellular localisation of Rad1 is cell cycle dependent in Leishmania major.

The subcellular localisation of Rad1, a subunit of the Leishmania major 9-1-1 complex, remains unexplored. Herein, we reveal that Rad1 localises predominantly to the nucleus. Upon hydroxyurea treatment, the diffuse nuclear localisation of Rad1 becomes more punctate, suggesting that Rad1 is responsive to replication stress. Moreover, Rad1 localisation correlates with cell cycle progression. In the majority of G1 to early S-phase cells, Rad1 localises predominantly to the nucleus. As cells progress from late-S phase to mitosis, Rad1 relocalizes to both the nucleus and the cytoplasm in ∼90 % of cells. This pattern of distribution is different from Rad9 and Hus1, which remain nuclear throughout the cell cycle, suggesting Leishmania Rad1 may regulate 9-1-1 activities and/or perform relevant functions outside the 9-1-1 complex.

The PP2A phosphatase counteracts the function of the 9-1-1 axis in checkpoint activation.

DNA damage elicits a checkpoint response depending on the Mec1/ATR kinase, which detects the presence of single-stranded DNA and activates the effector kinase Rad53/CHK2. In Saccharomyces cerevisiae, one of the signaling circuits leading to Rad53 activation involves the evolutionarily conserved 9-1-1 complex, which acts as a platform for the binding of Dpb11 and Rad9 (referred to as the 9-1-1 axis) to generate a protein complex that allows Mec1 activation. By examining the effects of both loss-of-function and hypermorphic mutations, here, we show that the Cdc55 and Tpd3 subunits of the PP2A phosphatase counteract activation of the 9-1-1 axis. The lack of this inhibitory function results in DNA-damage sensitivity, sustained checkpoint-mediated cell-cycle arrest, and impaired resection of DNA double-strand breaks. This PP2A anti-checkpoint role depends on the capacity of Cdc55 to interact with Ddc1 and to counteract Ddc1-Dpb11 complex formation by preventing Dpb11 recognition of Ddc1 phosphorylated on Thr602.

Challenges in recruiting frequent users of ambulance services for a community paramedic home visit program.

BACKGROUND: The Community Paramedicine at Home (CP@home) program is a health promotion program where community paramedics conduct risk assessments with frequent 9-1-1 callers in their homes, with a goal of reducing the frequency of 9-1-1 calls in this vulnerable population. The effectiveness of the CP@home program was investigated through a community-based RCT conducted in four regions in Ontario, Canada. The purpose of this current recruitment study is to examine the challenges met when recruiting for a community randomized control trial on high frequency 9-1-1 callers. METHODS: Eligible participants were recruited from one of four regions participating in the CP@home program and were randomly assigned to an intervention group (n = 1142) or control group (n = 1142). Data were collected during the recruitment process from the administrative database of the four paramedic services. Whether they live alone, their parental ethnicity, age, reason for calling 9-1-1, reason for not participating, contact method, and whether they were successfully contacted were recorded. Statistical significance was calculated using the Chi-Squared Test and Fisher's Exact Test to evaluate the effectiveness of the recruitment methods used to enroll eligible participants in the CP@home Program. RESULTS: Of the people who were contacted, 48.0% answered their phone when called and 53.9% answered their door when a home visit was attempted. In Total, 110 (33.1%) of people where a contact attempt was successful participated in the CP@home program. Most participants were over the age of 65, even though people as young as 18 were contacted. Older adults who called 9-1-1 for a lift assist were more likely to participate, compared to any other individual reason recorded, and were most often recruited through a home visit. CONCLUSIONS: This recruitment analysis successfully describes the challenges experienced by researchers when recruiting frequent 9-1-1 callers, which are considered a hard-to-reach population. The differences in age, contact method, and reason for calling 9-1-1 amongst people contacted and participants should be considered when recruiting this population for future research.

Older Adult Frequent 9-1-1 Callers for Emergency Medical Services in a Large Metropolitan City: Individual- and System-Level Considerations.

BACKGROUND: High utilizers of 9-1-1 place a substantial burden on emergency medical services (EMS). Results of a retrospective review of records data of the City of Los Angeles Fire Department (LAFD) showed a significant increase in older adult high utilizers of 9-1-1. OBJECTIVE: The objective of this study was to explore individual- and system-level factors implicated in EMS use among older adults, and to provide system recommendations to mitigate overuse. METHODS: A phenomenological study was conducted, drawing from LAFD EMS records between 2012 and 2016 to identify and contact high-utilizing patients older than 50 years, their family, agency representatives, and LAFD personnel. Interviews were recorded, transcribed, and coded and a thematic analysis was completed. RESULTS: We conducted in-depth interviews with 27 participants, including patients (n = 8), their families (n = 6), social service agency representatives (n = 3), and LAFD personnel (n = 10). The following cross-cutting themes emerged: nature of 9-1-1 calls, barriers to access, and changing the system. In addition, LAFD and social service agency representatives identified the role of EMS responders and social agency representatives. Patients and their families agreed that previous encounters and interactions with emergency care responders were relevant factors. CONCLUSIONS: This study described reasons for 9-1-1 calls related to medical and social service needs, including mental health care. Our analysis offers insight from different stakeholders' perspectives on access to medical care and types of barriers that interfere with medical care. All groups shared recommendations to advance access to medical and mental health care.

The C-terminal tail of Rad17, iVERGE, binds the 9‒1‒1 complex independently of AAA+ ATPase domains to provide another clamp-loader interface.

The ATR pathway plays a crucial role in maintaining genome integrity as the major DNA damage checkpoint. It also attracts attention as a therapeutic target in cancer treatment. The Rad17-RFC2-5 complex loads the Rad9-Hus1-Rad1 (9-1-1) DNA clamp complex onto damaged chromatin to activate the ATR pathway. We previously reported that phosphorylation of a polyanionic C-terminal tail of human Rad17, iVERGE, is essential for the interaction between Rad17 and the 9-1-1 complex. However, the molecular mechanism has remained unclear. Here, we show that iVERGE directly interacts with the Hus1 subunit of the 9-1-1 complex through Rad17-S667 phosphorylation independently of the AAA+ ATPase domains. An exogenous iVERGE peptide interacted with the 9-1-1 complex in vivo. The binding conformation of the iVERGE peptide was analyzed by de novo modeling with docking simulation, simulated annealing-molecular dynamics simulation, and the fragment molecular orbital method. The in silico analyses predicted the association of the iVERGE peptide with the hydrophobic and basic patches on the Hus1 protein, and the corresponding Hus1 mutants were deficient in the interaction with the iVERGE peptide in vivo. The iVERGE peptide occupied the same position as the C-terminus of Saccharomyces cerevisiae RAD24 on MEC3. The interaction energy calculation suggested that the Rad17 KYxxL motif and the iVERGE peptide are the primary and secondary interaction surfaces between the Rad17-RFC2-5 and 9-1-1 complexes. Our data reveal a novel molecular interface, iVERGE, between the Rad17-RFC2-5 and 9-1-1 complexes in vertebrates and implicate that Rad17 utilizes two distinct molecular interfaces to regulate the 9-1-1 complex.

Structures of 9-1-1 DNA checkpoint clamp loading at gaps from start to finish and ramification on biology.

Rad24-RFC (replication factor C) loads the 9-1-1 checkpoint clamp onto the recessed 5' ends by binding a 5' DNA at an external surface site and threading the 3' single-stranded DNA (ssDNA) into 9-1-1. We find here that Rad24-RFC loads 9-1-1 onto DNA gaps in preference to a recessed 5' end, thus presumably leaving 9-1-1 on duplex 3' ss/double-stranded DNA (dsDNA) after Rad24-RFC ejects from DNA. We captured five Rad24-RFC-9-1-1 loading intermediates using a 10-nt gap DNA. We also determined the structure of Rad24-RFC-9-1-1 using a 5-nt gap DNA. The structures reveal that Rad24-RFC is unable to melt DNA ends and that a Rad24 loop limits the dsDNA length in the chamber. These observations explain Rad24-RFC's preference for a preexisting gap of over 5-nt ssDNA and suggest a direct role of the 9-1-1 in gap repair with various TLS (trans-lesion synthesis) polymerases in addition to signaling the ATR kinase.

The effect of recognition on survival after out-of-hospital cardiac arrest and implications for biosensor technologies.

BACKGROUND: Biosensor technologies have been proposed as a solution to provide recognition and facilitate earlier responses to unwitnessed out-of-hospital cardiac arrest (OHCA) cases. We sought to estimate the effect of recognition on survival and modelled the potential incremental impact of increased recognition of unwitnessed cases on survival to hospital discharge, to demonstrate the potential benefit of biosensor technologies. METHODS: We included cases from the British Columbia Cardiac Arrest Registry (2019-2020), which includes Emergency Medical Services (EMS)-assessed OHCAs. We excluded cases that would not have benefitted from early recognition (EMS-witnessed, terminal illness, or do-not-resuscitate). Using a mediation analysis, we estimated the relative benefits on survival of a witness recognizing vs. intervening in an OHCA; and estimated the expected additional number of survivors resulting from increasing recognition alone using a bootstrap logistic regression framework. RESULTS: Of 13,655 EMS-assessed cases, 11,412 were included (6314 EMS-treated, 5098 EMS-untreated). Survival to hospital discharge was 191/8879 (2.2%) in unwitnessed cases and 429/2533 (17%) in bystander-witnessed cases. Of the total effect attributable to a bystander witness, recognition accounted for 84% (95% CI: 72, 86) of the benefit. If all previously unwitnessed cases had been bystander witnessed, we would expect 1198 additional survivors. If these cases had been recognized, but no interventions performed, we would expect 912 additional survivors. CONCLUSION: Unwitnessed OHCA account for the majority of OHCAs, yet survival is dismal. Methods to improve recognition, such as with biosensor technologies, may lead to substantial improvements in overall survival.

The 9-1-1 DNA clamp subunit RAD1 forms specific interactions with clamp loader RAD17, revealing functional implications for binding-protein RHINO.

The RAD9-RAD1-HUS1 complex (9-1-1) is a eukaryotic DNA clamp with a crucial role at checkpoints for DNA damage. The ring-like structure of 9-1-1 is opened for loading onto 5' recessed DNA by the clamp loader RAD17 RFC-like complex (RAD17-RLC), in which the RAD17 subunit is responsible for specificity to 9-1-1. Loading of 9-1-1 is required for activation of the ATR-CHK1 checkpoint pathway and the activation is stimulated by a 9-1-1 interacting protein, RHINO, which interacts with 9-1-1 via a recently identified RAD1-binding motif. This discovery led to the hypothesis that other interacting proteins may contain a RAD1-binding motif as well. Here, we show that vertebrate RAD17 proteins also have a putative RAD1-binding motif in their N-terminal regions, and we report the crystal structure of human 9-1-1 bound to a human RAD17 peptide incorporating the motif at 2.1 Å resolution. Our structure confirms that the N-terminal region of RAD17 binds to the RAD1 subunit of 9-1-1 via specific interactions. Furthermore, we show that the RAD1-binding motif of RHINO disturbs the interaction of the N-terminal region of RAD17 with 9-1-1. Our results provide deeper understanding of how RAD17-RLC specifically recognizes 9-1-1 and imply that RHINO has a functional role in 9-1-1 loading/unloading and checkpoint activation.

Development and Evaluation of an Online Toolkit for Managers of 9-1-1 Emergency Communications Centers to Reduce Occupational Stress.

This article describes the development and evaluation of an online workplace stress reduction toolkit for use by managers of 9-1-1 emergency communication centers (ECCs). A three-step process for development and testing of digital learning resources was used: (1) establishing need and focus through ECC manager stakeholder engagement, (2) pretesting of the toolkit with the target ECC manager audience, and (3) toolkit utilization and evaluation. The toolkit was developed in close partnership with stakeholders throughout the entire process. Toolkit usage was documented via registration data. The evaluation utilized an online survey that included closed and open-ended questions, which were analyzed using descriptive statistics and qualitative thematic analysis. Over a 20-month period, 274 people registered for the toolkit and, of those, 184 (67%) accessed the content. Respondents to the evaluation survey (N = 156) scored the toolkit highly on satisfaction, self-efficacy, and perceived utility measures. Survey respondents reported intent to apply toolkit content through the following: providing organizational resources to help workers take better care of themselves (41%); creating a lower stress worksite environment (35%) and sharing resources with staff to (1) reduce stress (19%), (2) support conflict resolution (21%), and (3) prevent and/or stop bullying (17%). In delivering actionable content to ECC managers, the toolkit shows promise in addressing and mitigating occupational stress in ECCs. Further research needs to determine the relationship of this strategy for reducing ECC stress.

Yeast 9-1-1 complex acts as a sliding clamp for DNA synthesis by DNA polymerase ε.

Eukaryotic cells harbor two DNA-binding clamps, proliferating cell nuclear antigen (PCNA), and another clamp commonly referred to as 9-1-1 clamp. In contrast to the essential role of PCNA in DNA replication as a sliding clamp for DNA polymerase (Pol) δ, no such role in DNA synthesis has been identified for the human 9-1-1 clamp or the orthologous yeast 17-3-1 clamp. The only role identified for either the 9-1-1 or 17-3-1 clamp is in the recruitment of signal transduction kinases, which affect the activation of cell cycle checkpoints in response to DNA damage. However, unlike the loading of PCNA by the replication factor C (RFC) clamp loader onto 3'-recessed DNA junctions for processive DNA synthesis by Polδ, the 17-3-1 clamp or the 9-1-1 clamp is loaded by their respective clamp loader Rad24-RFC or RAD17-RFC onto the 5'-recessed DNA junction of replication protein A-coated DNA for the recruitment of signal transduction kinases. Here, we identify a novel role of 17-3-1 clamp as a sliding clamp for DNA synthesis by Polε. We provide evidence that similar to the loading of PCNA by RFC, the 17-3-1 clamp is loaded by the Rad24-RFC clamp loader at the 3'-recessed DNA junction in an ATP-dependent manner. However, unlike PCNA, the 17-3-1 clamp does not enhance the processivity of DNA synthesis by Polε; instead, it greatly increases the catalytic efficiency of Polε for correct nucleotide incorporation. Furthermore, we show that the same PCNA-interacting peptide domain in the polymerase 2 catalytic subunit mediates Polε interaction with the 17-3-1 clamp and with PCNA.

The dynamic subcellular localisation of Rad1 is cell cycle dependent in Leishmania major

The subcellular localisation of Rad1, a subunit of the Leishmania major 9-1-1 complex, remains unexplored. Herein, we reveal that Rad1 localises predominantly to the nucleus. Upon hydroxyurea treatment, the diffuse nuclear localisation of Rad1 becomes more punctate, suggesting that Rad1 is responsive to replication stress. Moreover, Rad1 localisation correlates with cell cycle progression. In the majority of G1 to early S-phase cells, Rad1 localises predominantly to the nucleus. As cells progress from late-S phase to mitosis, Rad1 relocalizes to both the nucleus and the cytoplasm in ∼90 % of cells. This pattern of distribution is different from Rad9 and Hus1, which remain nuclear throughout the cell cycle, suggesting Leishmania Rad1 may regulate 9-1-1 activities and/or perform relevant functions outside the 9-1-1 complex.

Emergency Interhospital Transfer of Patients With ST-Segment-Elevation Myocardial Infarction: Call 9-1-1-The American Heart Association Mission: Lifeline Program.

The American Heart Association Mission: Lifeline program objectives are to improve the quality of care and outcomes for patients with ST-segment-elevation myocardial infarction. Every minute of delay in treatment adversely affects 1-year mortality. Transfer of patients safely and timely to hospitals with primary percutaneous coronary intervention capability is needed to improve outcomes. But treatment times continue to show delays, especially during interhospital transfers. A simple 3-step process of an interhospital "Call 9-1-1" protocol may expedite this process. This STAT TRANSFER process uses a systems approach that considers diverse ways in which patients access care, how EMS responds and determines destinations, how referring hospital transfers are performed, urban and rural differences, and how receiving hospitals prepare for an incoming patient with ST-segment-elevation myocardial infarction. This initiative suggests a strategy to reduce variability in interhospital transfer times using a STAT TRANSFER and a Call 9-1-1 process in a system of care that involves all stakeholders.

Unexpected new insights into DNA clamp loaders: Eukaryotic clamp loaders contain a second DNA site for recessed 5' ends that facilitates repair and signals DNA damage: Eukaryotic clamp loaders contain a second DNA site for recessed 5' ends that facilitates repair and signals DNA damage.

Clamp loaders are pentameric AAA+ assemblies that use ATP to open and close circular DNA sliding clamps around DNA. Clamp loaders show homology in all organisms, from bacteria to human. The eukaryotic PCNA clamp is loaded onto 3' primed DNA by the replication factor C (RFC) hetero-pentameric clamp loader. Eukaryotes also have three alternative RFC-like clamp loaders (RLCs) in which the Rfc1 subunit is substituted by another protein. One of these is the yeast Rad24-RFC (Rad17-RFC in human) that loads a 9-1-1 heterotrimer clamp onto a recessed 5' end of DNA. Recent structural studies of Rad24-RFC have discovered an unexpected 5' DNA binding site on the outside of the clamp loader and reveal how a 5' end can be utilized for loading the 9-1-1 clamp onto DNA. In light of these results, new studies reveal that RFC also contains a 5' DNA binding site, which functions in gap repair. These studies also reveal many new features of clamp loaders. As reviewed herein, these recent studies together have transformed our view of the clamp loader mechanism.

Sensor technologies to detect out-of-hospital cardiac arrest: A systematic review of diagnostic test performance.

Aim: Cardiac arrest (CA) is the cessation of circulation to vital organs that can only be reversed with rapid and appropriate interventions. Sensor technologies for early detection and activation of the emergency medical system could enable rapid response to CA and increase the probability of survival. We conducted a systematic review to summarize the literature surrounding the performance of sensor technologies in detecting OHCA. Methods: We searched the academic and grey literature using keywords related to cardiac arrest, sensor technologies, and recognition/detection. We included English articles published up until June 6, 2022, including investigations and patent filings that reported the sensitivity and specificity of sensor technologies to detect cardiac arrest on human or animal subjects. (Prospero# CRD42021267797). Results: We screened 1666 articles and included four publications examining sensor technologies. One tested the performance of a physical sensor on human participants in simulated CA, one tested performance on audio recordings of patients in cardiac arrest, and two utilized a hybrid design for testing including human participants and ECG databases. Three of the devices were wearable and one was an audio detection algorithm utilizing household smart technologies. Real-world testing was limited in all studies. Sensitivity and specificity for the sensors ranged from 97.2 to 100% and 90.3 to 99.9%, respectively. All included studies had a medium/high risk of bias, with 2/4 having a high risk of bias. Conclusions: Sensor technologies show promise for cardiac arrest detection. However, current evidence is sparse and of high risk of bias. Small sample sizes and databases with low external validity limit the generalizability of findings.

Automated referral to community paramedicine during 9-1-1 fall calls for resource activation.

BACKGROUND: We sought to improve the referral process to a community paramedicine (CP) program following a 9-1-1 encounter. METHODS: An electronic health record (EHR) for CP records with the ability to link to emergency EHR was identified and implemented with a single-click referral to the CP program. Referrals were tracked for 15 months before and after implementation. RESULTS: Referral capacity increased from an average of 14.2 referrals per month to 44.9 referrals per month. CONCLUSION: The results of this study suggest an EHR is a useful investment for CP programs and may be integral to efficient program operations.