Disruption of the bacterial OLE RNP complex impairs growth on alternative carbon sources.

Ornate, large, extremophilic (OLE) RNAs comprise a class of large noncoding RNAs in bacteria whose members form a membrane-associated ribonucleoprotein (RNP) complex. This complex facilitates cellular adaptation to diverse stresses such as exposure to cold, short-chain alcohols, and elevated Mg2+ concentrations. Here, we report additional phenotypes exhibited by Halalkalibacterium halodurans (formerly called Bacillus halodurans) strains lacking functional OLE RNP complexes. Genetic disruption of the complex causes restricted growth compared to wild-type cells when cultured in minimal media (MM) wherein glucose is replaced with alternative carbon/energy sources. Genetic suppressor selections conducted in glutamate MM yielded isolates that carry mutations in or near genes relevant to Mn2+ homeostasis (ykoY and mntB), phosphate homeostasis (phoR), and putative multidrug resistance (bmrCD). These functional links between OLE RNA, carbon/energy management, and other fundamental processes including protein secretion are consistent with the hypothesis that the OLE RNP complex is a major contributor to cellular adaptation to unfavorable growth conditions.

Trichomoniasis and retesting in Durham County, North Carolina, United States, 2021 - 2022.

BACKGROUND: The Centers for Disease Control and Prevention recommends universal retesting within 3 months after treatment of Trichomonas vaginalis infection given high rates of persistent infection or reinfection, or if this is not possible, within 12 months following treatment. Data is lacking on how often this is actually done. METHODS: We analyzed the demographic and clinical characteristics, rate of return for the recommended retesting, concordance between wet prep and nucleic acid amplification testing, and percent positivity for T. vaginalis on repeat vaginal specimens at a local public health department in Durham, North Carolina, United States. RESULTS: Of 193 females treated for trichomoniasis between March 1, 2021 - May 31, 2022, 83% were Black or African American and 44% between the ages of 20 and 29 years. Of these individuals, 32% had retesting performed within 3 months and 50% within 365 days after treatment. Females between the ages of 20 and 29 years were more likely to return for retesting than those between the ages of 30 and 39 years. Of those who returned for retesting, 10% were positive on repeat testing. CONCLUSION: In this study, 50% of females diagnosed with trichomoniasis completed retesting within 365 days. Improved scheduling of clients at the time of trichomoniasis treatment and improved identification in our electronic health record of individuals diagnosed with trichomoniasis within the prior year would likely improve retesting rates. Given the high prevalence of trichomoniasis, expanded screening of asymptomatic females in settings where this is feasible may be warranted.

Evidence that OLE RNA is a component of a major stress-responsive ribonucleoprotein particle in extremophilic bacteria.

OLE RNA is a ~600-nucleotide noncoding RNA present in many Gram-positive bacteria that thrive mostly in extreme environments, including elevated temperature, salt, and pH conditions. The precise biochemical functions of this highly conserved RNA remain unknown, but it forms a ribonucleoprotein (RNP) complex that localizes to cell membranes. Genetic disruption of the RNA or its essential protein partners causes reduced cell growth under various stress conditions. These phenotypes include sensitivity to short-chain alcohols, cold intolerance, reduced growth on sub-optimal carbon sources, and intolerance of even modest concentrations of Mg2+ . Thus, many bacterial species appear to employ OLE RNA as a component of an intricate RNP apparatus to monitor fundamental cellular processes and make physiological and metabolic adaptations. Herein we hypothesize that the OLE RNP complex is functionally equivalent to the eukaryotic TOR complexes, which integrate signals from various diverse pathways to coordinate processes central to cell growth, replication, and survival.

Context and Considerations for the Development of Community-Informed Health Communication Messaging to Support Equitable Uptake of COVID-19 Vaccines Among Communities of Color in Washington, DC.

BACKGROUND: Communities of color have been disproportionately impacted by COVID-19. We explored barriers and facilitators to COVID-19 vaccine uptake among African American, Latinx, and African immigrant communities in Washington, DC. METHODS: A total of 76 individuals participated in qualitative interviews and focus groups, and 208 individuals from communities of color participated in an online crowdsourcing contest. RESULTS: Findings documented a lack of sufficient, accurate information about COVID-19 vaccines and questions about the science. African American and African immigrant participants spoke about the deeply rooted historical underpinnings to their community's vaccine hesitancy, citing the prior and ongoing mistreatment of people of color by the medical community. Latinx and African immigrant participants highlighted how limited accessibility played an important role in the slow uptake of COVID-19 vaccines in their communities. Connectedness and solidarity were found to be key assets that can be drawn upon through community-driven responses to address social-structural challenges to COVID-19 related vaccine uptake. CONCLUSIONS: The historic and ongoing socio-economic context and realities of communities of color must be understood and respected to inform community-based health communication messaging to support vaccine equity for COVID-19 and other infectious diseases.

Ornate, large, extremophilic (OLE) RNA forms a kink turn necessary for OapC protein recognition and RNA function.

Ornate, large, extremophilic (OLE) RNAs represent a class of noncoding RNAs prevalent in Gram-positive, extremophilic/anaerobic bacterial species. OLE RNAs (∼600 nt), whose precise biochemical functions remain mysterious, form an intricate secondary structure interspersed with regions of highly conserved nucleotides. In the alkali-halophilic bacterium Bacillus halodurans, OLE RNA is a component of a ribonucleoprotein (RNP) complex involving at least two proteins named OapA and OapB, but additional components may exist that could point to functional roles for the RNA. Disruption of the genes for either OLE RNA, OapA, or OapB result in the inability of cells to overcome cold, alcohol, or Mg2+ stresses. In the current study, we used in vivo crosslinking followed by OLE RNA isolation to identify the protein YbxF as a potential additional partner in the OLE RNP complex. Notably, a mutation in the gene for this same protein was also reported to be present in a strain wherein the complex is nonfunctional. The B. halodurans YbxF (herein renamed OapC) is homologous to a bacterial protein earlier demonstrated to bind kink turn (k-turn) RNA structural motifs. In vitro RNA-protein binding assays reveal that OLE RNA forms a previously unrecognized k-turn that serves as the natural binding site for YbxF/OapC. Moreover, B. halodurans cells carrying OLE RNAs with disruptive mutations in the k-turn exhibit phenotypes identical to cells lacking functional OLE RNP complexes. These findings reveal that the YbxF/OapC protein of B. halodurans is important for the formation of a functional OLE RNP complex.

Architectures and complex functions of tandem riboswitches.

Riboswitch architectures that involve the binding of a single ligand to a single RNA aptamer domain result in ordinary dose-response curves that require approximately a 100-fold change in ligand concentration to cover nearly the full dynamic range for gene regulation. However, by using multiple riboswitches or aptamer domains in tandem, these ligand-sensing structures can produce additional, complex gene control outcomes. In the current study, we have computationally searched for tandem riboswitch architectures in bacteria to provide a more complete understanding of the diverse biological and biochemical functions of gene control elements that are made exclusively of RNA. Numerous different arrangements of tandem homologous riboswitch architectures are exploited by bacteria to create more 'digital' gene control devices, which operate over a narrower ligand concentration range. Also, two heterologous riboswitch aptamers are sometimes employed to create two-input Boolean logic gates with various types of genetic outputs. These findings illustrate the sophisticated genetic decisions that can be made by using molecular sensors and switches based only on RNA.

Primary Care Practitioner Perceptions on the Follow-up of Abnormal Cancer Screening Test Results.

Importance: Health care systems focus on delivering routine cancer screening to eligible individuals, yet little is known about the perceptions of primary care practitioners (PCPs) about barriers to timely follow-up of abnormal results. Objective: To describe PCP perceptions about factors associated with the follow-up of abnormal breast, cervical, colorectal, and lung cancer screening test results. Design, Setting, and Participants: Survey study of PCPs from 3 primary care practice networks in New England between February and October 2020, prior to participating in a randomized clinical trial to improve follow-up of abnormal cancer screening test results. Participants were physicians and advanced practice clinicians from participating practices. Main Outcomes and Measures: Self-reported process, attitudes, knowledge, and satisfaction about the follow-up of abnormal cancer screening test results. Results: Overall, 275 (56.7%) PCPs completed the survey (range by site, 34.9%-71.9%) with more female PCPs (61.8% [170 of 275]) and general internists (73.1% [201 of 275]); overall, 28,7% (79 of 275) were aged 40 to 49 years. Most PCPs felt responsible for managing abnormal cancer screening test results with the specific cancer type being the best factor (range, 63.6% [175 of 275] for breast to 81.1% [223 of 275] for lung; P < .001). The PCPs reported limited support for following up on overdue abnormal cancer screening test results. Standard processes such as automated reports, reminder letters, or outreach workers were infrequently reported. Major barriers to follow-up of abnormal cancer screening test results across all cancer types included limited electronic health record tools (range, 28.5% [75 of 263]-36.5%[96 of 263]), whereas 50% of PCPs felt that there were major social barriers to receiving care for abnormal cancer screening test results for colorectal cancer. Fewer than half reported being very satisfied with the process of managing abnormal cancer screening test results, with satisfaction being greatest for breast cancer (46.9% [127 of 271]) and lowest for cervical (21.8% [59 of 271]) and lung cancer (22.4% [60 of 268]). Conclusions and Relevance: In this survey study of PCPs, important deficiencies in systems for managing abnormal cancer screening test results were reported. These findings suggest a need for comprehensive organ-agnostic systems to promote timely follow-up of abnormal cancer screening results using a primary care-focused approach across the range of cancer screening tests.

Natural Language Processing to Identify Abnormal Breast, Lung, and Cervical Cancer Screening Test Results from Unstructured Reports to Support Timely Follow-up.

Cancer screening and timely follow-up of abnormal results can reduce mortality. One barrier to follow-up is the failure to identify abnormal results. While EHRs have coded results for certain tests, cancer screening results are often stored in free-text reports, which limit capabilities for automated decision support. As part of the multilevel Follow-up of Cancer Screening (mFOCUS) trial, we developed and implemented a natural language processing (NLP) tool to assist with real-time detection of abnormal cancer screening test results (including mammograms, low-dose chest CT scans, and Pap smears) and identification of gynecological follow-up for higher risk abnormalities (i.e. colposcopy) from free-text reports. We demonstrate the integration and implementation of NLP, within the mFOCUS system, to improve the follow-up of abnormal cancer screening results in a large integrated healthcare system. The NLP pipelines have detected scenarios when guideline-recommended care was not delivered, in part because the provider mis-identified the text-based result reports.

Integrating tobacco treatment into lung cancer screening practices: Study protocol for the Screen ASSIST randomized clinical trial.

BACKGROUND: Integrating tobacco treatment services into lung cancer screening (LCS) has the potential to leverage a 'teachable moment' to promote cessation among long-term smokers and reduce disparities in tobacco treatment access. This protocol paper describes the Screen ASSIST (Aiding Screening Support In Stopping Tobacco) trial, which will identify how to best deliver evidence-driven tobacco treatment in the context of LCS. METHODS: Screen ASSIST is a randomized clinical trial with a 3-factor, fully crossed factorial design that enrolls current smokers (any cigarette use in the past 30 days) scheduled to attend LCS at multiple sites in the Mass General Brigham healthcare system. To maximize reach, recruitment is conducted at 3 time points: 1) at the time of LCS scheduling, 2) at the LCS visit, and 3) after the participant has received their LCS results. Participants are stratified by LCS study site and recruitment point and randomly assigned into 8 groups that test intervention components varying on telehealth counseling duration (4 weeks vs. 8 weeks), nicotine replacement therapy duration (2 weeks vs. 8 weeks), and systematic screening and referral for social determinants of health via a service named 'AuntBertha' (referral vs. no referral). The primary study outcome is self-reported past 7-day tobacco abstinence at 6-month follow-up. This trial will also assess systems integration and evaluate implementation of the intervention. DISCUSSION: Screen ASSIST will identify the most effective combination of tobacco cessation treatments within the LCS context, in order to improve the cost-effectiveness of LCS and quality of life among long-term heavy smokers.

Multilevel Follow-up of Cancer Screening (mFOCUS): Protocol for a multilevel intervention to improve the follow-up of abnormal cancer screening test results.

INTRODUCTION: While substantial attention is focused on the delivery of routine preventive cancer screening, less attention has been paid to systematically ensuring that there is timely follow-up of abnormal screening test results. Barriers to completion of timely follow-up occur at the patient, provider, care team and system levels. METHODS: In this pragmatic cluster randomized controlled trial, primary care sites in three networks are randomized to one of four arms: (1) standard care, (2) "visit-based" reminders that appear in a patient's electronic health record (EHR) when it is accessed by either patient or providers (3) visit based reminders with population health outreach, and (4) visit based reminders, population health outreach, and patient navigation with systematic screening and referral to address social barriers to care. Eligible patients in participating practices are those overdue for follow-up of an abnormal results on breast, cervical, colorectal and lung cancer screening tests. RESULTS: The primary outcome is whether an individual receives follow-up, specific to the organ type and screening abnormality, within 120 days of becoming eligible for the trial. Secondary outcomes assess the effect of intervention components on the patient and provider experience of obtaining follow-up care and the delivery of the intervention components. CONCLUSIONS: This trial will provide evidence for the role of a multilevel intervention on improving the follow-up of abnormal cancer screening test results. We will also specifically assess the relative impact of the components of the intervention, compared to standard care. TRIAL REGISTRATION: ClinicalTrials.gov NCT03979495.

Patient, provider, and clinic factors associated with the use of cervical cancer screening.

Cervical cancer screening delivery remains suboptimal. Understanding the multiple influences on use of screening is important to designing interventions. We describe the influence of patient, primary care provider (PCP), and clinic characteristics on whether a woman is up-to-date with cervical screening as of December 2016. PCPs (n = 194) and their female screen-eligible patients age 21-65 years (n = 32,115) were included in this cross-sectional analysis of patients from two primary care networks linked to a contemporaneous PCP survey. Principal independent variables for patients included: age, race, insurance, continuity of care; for PCP included: overall satisfaction with the practice of medicine, gender, hours worked per week, financial support for achieving clinical targets; and for clinic included: routine receipt of data on preventive care performance and language translation resources. Overall, 66.6% of women were up-to-date. Women were less likely to be up-to-date with cervical cancer screening if they were younger and were more likely to be screened if they were Black, Hispanic or Asian vs. White. Women with greater continuity of primary care or with a female PCP were more likely to be up-to-date (1.52; 1.33-1.75); those who received care in a clinic that was less prepared to manage language translation were less likely to be up-to-date (0.78; 0.65-0.95). Patient, provider, and clinic factors all influence use of cervical cancer screening. Systems interventions like improving continuity of care, promoting translation services, or enhanced efforts to track screening among patients of male PCPs may improve delivery.

Structure of a bacterial OapB protein with its OLE RNA target gives insights into the architecture of the OLE ribonucleoprotein complex.

The OLE (ornate, large, and extremophilic) RNA class is one of the most complex and well-conserved bacterial noncoding RNAs known to exist. This RNA is known to be important for bacterial responses to stress caused by short-chain alcohols, cold, and elevated Mg2+ concentrations. These biological functions have been shown to require the formation of a ribonucleoprotein (RNP) complex including at least two protein partners: OLE-associated protein A (OapA) and OLE-associated protein B (OapB). OapB directly binds OLE RNA with high-affinity and specificity and is believed to assist in assembling the functional OLE RNP complex. To provide the atomic details of OapB-OLE RNA interaction and to potentially reveal previously uncharacterized protein-RNA interfaces, we determined the structure of OapB from Bacillus halodurans alone and in complex with an OLE RNA fragment at resolutions of 1.0 Å and 2.0 Å, respectively. The structure of OapB exhibits a K-shaped overall architecture wherein its conserved KOW motif and additional unique structural elements of OapB form a bipartite RNA-binding surface that docks to the P13 hairpin and P12.2 helix of OLE RNA. These high-resolution structures elucidate the molecular contacts used by OapB to form a stable RNP complex and explain the high conservation of sequences and structural features at the OapB-OLE RNA-binding interface. These findings provide insight into the role of OapB in the assembly and biological function of OLE RNP complex and can guide the exploration of additional possible OLE RNA-binding interactions present in OapB.

Bacillus halodurans OapB forms a high-affinity complex with the P13 region of the noncoding RNA OLE.

Noncoding RNAs (ncRNAs) longer than 200 nucleotides are rare in bacteria, likely because bacterial genomes are under strong evolutionary pressures to maintain a small genome size. Of the long ncRNAs unique to bacteria, the OLE (ornate, large, extremophilic) RNA class is among the largest and most structurally complex. OLE RNAs form a ribonucleoprotein (RNP) complex by partnering with at least two proteins, OapA and OapB, that directly bind OLE RNA. The biochemical functions of the OLE RNP complex remain unknown, but are required for proper adaptation to certain environmental stresses, such as cold temperatures, short chain alcohols, and high magnesium concentrations. In the current study, we used electrophoretic mobility shift assays to examine the binding of OLE RNA fragments by OapB and found that OapB recognizes a small subregion of OLE RNA, including stem P13, with a dissociation constant (KD ) of ∼700 pm Analyses with mutated RNA constructs, and the application of in vitro selection, revealed that strong binding of OLE RNA by OapB requires a stem containing a precisely located single-nucleotide bulge and a GNRA tetraloop. Although the vast majority of bacteria with the ole gene also have the oapB gene, there are many whose genomes contain oapB but lack ole, suggesting that OapB has other RNA partners in some species that might exhibit similar structural features.

A Novel Point-of-Care Solution to Streamline Local Wound Formulary Development and Promote Cost-effective Wound Care.

OBJECTIVE: To develop and implement a point-of-care digital solution to streamline the creation and maintenance of wound care product formularies and promote cost-effective wound management. METHODS: Researchers used Design Thinking methodology to develop the Formulary Module, a point-of-care digital solution within a clinical and reimbursement decision support web application for wound care and hyperbaric clinicians. The module was implemented in a US hospital-based outpatient wound clinic as follows: A baseline list of products was established, with brands automatically grouped by product category. Brands within each dressing category were compared, and redundancy eliminated. Study authors assessed the financial impact of formulary implementation in the wound clinic by comparing inventory expenditure before and after implementation. RESULTS: Implementation of the digital Formulary Module resulted in a 36% decrease in products (67 to 43 across 22 types), 38.73% decrease in the monthly average dollar spent on chargeable products, 29.56% decrease in the average dollar amount spent on chargeable products per patient visit, and increased staff efficiency. CONCLUSIONS: The Formulary Module has the potential to increase the adoption of cost-effective practices in wound care significantly.

Functional Analysis of the SIM1 Variant p.G715V in 2 Patients With Obesity.

CONTEXT: Single-minded homologue 1 (SIM1) is a transcription factor with several physiological and developmental functions. Haploinsufficiency of SIM1 is associated with early-onset obesity with or without Prader-Willi-like (PWL) features and may exhibit incomplete penetrance. CASE DESCRIPTION: Next-generation sequencing was performed for 2 male patients with obesity, including 1 man presenting with intellectual disability (ID), body mass index (BMI) of 47.4, and impulse-control disorder, and the other man with early obesity (BMI of 36); sequencing revealed a missense variant in SIM1 (c.2144G>T; p.G715V) in both individuals. Previous studies have identified several disease-associated variants that fall near the p.G715V variant within the C-terminal domain of SIM1. We examined p.G715V variant stability and activity in a doxycycline-inducible stable cell line transfected with an artificial reporter construct and either ARNT or ARNT2 as a partner protein. CONCLUSIONS: Functional testing of the p.G715V variant revealed a significant reduction in SIM1-mediated transcriptional activity. We also generated the first ab initio hybrid protein model for full-length SIM1 to show the predicted spatial relationship between p.G715V and other previously described variants in this region and identified a putative mutation hotspot within the C-terminus. Significant clinical heterogeneity has been observed in patients with SIM1 variants, particularly with regards to the PWL phenotype. In the patient with ID, a second variant of uncertain significance in CHD2 was identified that may contribute to his ID and behavioral disturbances, emphasizing the role of additional genetic modifiers.

Disruption of the OLE ribonucleoprotein complex causes magnesium toxicity in Bacillus halodurans.

OLE RNAs represent an unusual class of bacterial noncoding RNAs common in Gram-positive anaerobes. The OLE RNA of the alkaliphile Bacillus halodurans is highly expressed and naturally interacts with at least two RNA-binding proteins called OapA and OapB. The phenotypes of the corresponding knockouts include growth inhibition when exposed to ethanol or other short-chain alcohols or when incubated at modestly reduced temperatures (e.g. 20°C). Intriguingly, the OapA 'PM1' mutant, which carries two amino acid changes to a highly conserved region, yields a dominant-negative phenotype that causes more severe growth defects under these same stress conditions. Herein, we report that the PM1 strain also exhibits extreme sensitivity to elevated Mg2+ concentrations, beginning as low as 2 mM. Suppressor mutants predominantly map to genes for aconitate hydratase and isocitrate dehydrogenase, which are expected to alter cellular citrate concentrations. Citrate reduces the severity of the Mg2+ toxicity phenotype, but neither the genomic mutations nor the addition of citrate to the medium overcomes ethanol toxicity or temperature sensitivity. These findings reveal that OLE RNA and its protein partners are involved in biochemical responses under several stress conditions, wherein the unusual sensitivity to Mg2+ can be independently suppressed by specific genomic mutations.

Training as an Intervention to Decrease Medical Record Abstraction Errors Multicenter Studies.

Studies often rely on medical record abstraction as a major source of data. However, data quality from medical record abstraction has long been questioned. Electronic Health Records (EHRs) potentially add variability to the abstraction process due to the complexity of navigating and locating study data within these systems. We report training for and initial quality assessment of medical record abstraction for a clinical study conducted by the IDeA States Pediatric Clinical Trials Network (ISPCTN) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) using medical record abstraction as the primary data source. As part of overall quality assurance, study-specific training for medical record abstractors was developed and deployed during study start-up. The training consisted of a didactic session with an example case abstraction and an independent abstraction of two standardized cases. Sixty-nine site abstractors from thirty sites were trained. The training was designed to achieve an error rate for each abstractor of no greater than 4.93% with a mean of 2.53%, at study initiation. Twenty-three percent of the trainees exceeded the acceptance limit on one or both of the training test cases, supporting the need for such training. We describe lessons learned in the design and operationalization of the study-specific, medical record abstraction training program.

Randomized Trial of Personalized Breast Density and Breast Cancer Risk Notification.

BACKGROUND: Despite widespread implementation of mammographic breast density (MBD) notification laws, the impact of these laws on knowledge of MBD and knowledge of breast cancer risk is limited by the lack of tools to promote informed decision-making in practice. OBJECTIVE: To develop and evaluate whether brief, personalized informational videos following a normal mammogram in addition to a legislatively required letter about MBD result can improve knowledge of MBD and breast cancer risk compared to standard care (i.e., legislatively required letter about MBD included with the mammogram result). DESIGN/PARTICIPANTS: Prospective randomized controlled trial of English-speaking women, age 40-74 years, without prior history of breast cancer, receiving a screening mammogram with a normal or benign finding (intervention group n = 235, control group n = 224). INTERVENTION: brief (3-5 min) video, personalized to a woman's MBD result and breast cancer risk. MAIN MEASURES: Primary outcomes were a woman's knowledge of her MBD and risk of breast cancer. Secondary outcomes included whether a woman reported that she discussed the results of her mammogram with her primary care provider (PCP). KEY RESULTS: Relative to women in the control arm, women in the intervention arm had greater improvement in their knowledge of both their personal MBD (intervention pre/post 39.2%/ 77.5%; control pre/post 36.2%/ 37.5%; odds ratio (OR) 5.34 for change for intervention vs. control, 95% confidence interval (CI) 3.87-7.36; p < 0.001) and risk of breast cancer (intervention pre/post: 66.8%/74.0%; control pre/post 67.9%/ 65.2%; OR 1.42, 95% confidence interval (CI) 1.09-1.84; p = 0.01). Women in the intervention group were more likely than those in the control group to report discussing the results of their mammogram with their PCP (p = 0.05). CONCLUSIONS: Brief, personalized videos following mammography can improve knowledge of MBD and personal risk of breast cancer compared to a legislatively mandated informational letter. Trial Registration Clinicaltrials.gov (NCT02986360).

Multi-level Influences on Breast Cancer Screening in Primary Care.

BACKGROUND: Use of breast cancer screening is influenced by factors associated with patients, primary care providers, practices, and health systems. OBJECTIVE: We examined the relative effects of these nested levels on four breast cancer screening metrics. DESIGN: A web-based survey was completed at 15 primary care practices within two health systems representing 306 primary care providers (PCPs) serving 46,944 women with a primary care visit between 1/2011-9/2014. Analyses occurred between 1/2017 and 5/2017. MAIN MEASURES: Across four nested levels (patient, PCP, primary care practice, and health system), frequency distributions and adjusted rates of primary care practice characteristics and survey results for four breast screening metrics (percent screened overall, and percent screened age 40-49, 50-74, and 75+) were reported. We used hierarchical multi-level mixed and random effects analysis to assess the relative influences of PCP, primary care practice, and health system on the breast screening metrics. KEY RESULTS: Overall, the proportion of women undergoing breast cancer screening was 73.1% (73.4% for ages 40-49, 76.5% for 50-74, and 51.1% for 75+). Patient ethnicity and number of primary care visits were strongly associated with screening rates. After adjusting for woman-level factors, 24% of the overall variation among PCPs was attributable to the primary care practice level, 35% to the health system level, and 41% to the residual variation among PCPs within practice. No specific provider-level characteristics were found to be statistically significant determinants of screening rates. CONCLUSIONS: After accounting for woman-level characteristics, the remaining variation in breast cancer screening was largely due to provider and health system variation.

Large Noncoding RNAs in Bacteria.

Bacterial noncoding RNA (ncRNA) classes longer than 200 nucleotides are rare but are responsible for performing some of the most fundamental tasks in living cells. RNAs such as 16S and 23S rRNA, group I and group II introns, RNase P ribozymes, transfer-messenger RNAs, and coenzyme B12 riboswitches are diverse in structure and accomplish biochemical functions that rival the activities of proteins. Over the last decade, a number of new classes of large ncRNAs have been uncovered in bacteria. A total of 21 classes with no established functions have been identified through the use of bioinformatics search strategies. Based on precedents for bacterial large ncRNAs performing sophisticated functions, it seems likely that some of these structured ncRNAs also will prove to carry out complex functions. Thus, determining their roles will provide a better understanding of fundamental biological processes. A few studies have produced data that provide clues to the purposes of some of these recently found classes, but the true functions of most classes remain mysterious.