A catchment and location-allocation analysis of mammography access in Delaware, US: implications for disparities in geographic access to breast cancer screening.

BACKGROUND: Despite a 40% reduction in breast cancer mortality over the last 30 years, not all groups have benefited equally from these gains. A consistent link between later stage of diagnosis and disparities in breast cancer mortality has been observed by race, socioeconomic status, and rurality. Therefore, ensuring equitable geographic access to screening mammography represents an important priority for reducing breast cancer disparities. Access to breast cancer screening was evaluated in Delaware, a state that experiences an elevated burden from breast cancer but is otherwise representative of the US in terms of race and urban-rural characteristics. We first conducted a catchment analysis of mammography facilities. Finding evidence of disparities by race and rurality, we next conducted a location-allocation analysis to identify candidate locations for the establishment of new mammography facilities to optimize equitable access. METHODS: A catchment analysis using the ArcGIS Pro Service Area analytic tool characterized the geographic distribution of mammography sites and Breast Imaging Centers of Excellence (BICOEs). Poisson regression analyses identified census tract-level correlates of access. Next, the ArcGIS Pro Location-Allocation analytic tool identified candidate locations for the placement of additional mammography sites in Delaware according to several sets of breast cancer screening guidelines. RESULTS: The catchment analysis showed that for each standard deviation increase in the number of Black women in a census tract, there were 68% (95% CI 38-85%) fewer mammography units and 89% (95% CI 60-98%) fewer BICOEs. The more rural counties in the state accounted for 41% of the population but only 22% of the BICOEs. The results of the location-allocation analysis depended on which set of screening guidelines were adopted, which included increasing mammography sites in communities with a greater proportion of younger Black women and in rural areas. CONCLUSIONS: The results of this study illustrate how catchment and location-allocation analytic tools can be leveraged to guide the equitable selection of new mammography facility locations as part of a larger strategy to close breast cancer disparities.

Neonates as intrinsically worthy recipients of pain management in neonatal intensive care.

One barrier to optimal pain management in the neonatal intensive care unit (NICU) is how the healthcare community perceives, and therefore manages, neonatal pain. In this paper, we emphasise that healthcare professionals not only have a professional obligation to care for neonates in the NICU, but that these patients are intrinsically worthy of care. We discuss the conditions that make neonates worthy recipients of pain management by highlighting how neonates are (1) vulnerable to pain and harm, and (2) completely dependent on others for pain management. We argue for a relational account of ethical decision-making in the NICU by demonstrating how an increase in vulnerability and dependence may be experienced by the healthcare community and the neonate's family. Finally, an ethical framework for decisions around neonatal pain management is proposed, focussing on surrogate decision-making and the importance of compassionate action through both a reflective and an affective empathy. As empathy can be highly motivating against pain, we propose that, in addition to educational programs that raise awareness and knowledge of neonatal pain and pain management, healthcare professionals must cultivate empathy in a collective manner, where all members of the NICU team, including parents, are compassionate decision-makers.

Demonstrating the impact of your teaching: benefits of Higher Education Academy Fellowship for librarians.

This feature suggests that health librarians who teach or support Higher Education (HE) students can and should gain accreditation and recognition for their teaching by the route of HEA Fellowship. We outline the process by which Fellowship could be attained by those working within HE and those in NHS libraries who work with HE students, suggesting which aspects of librarianship practice could provide the necessary evidence for Fellowship. The synergies between Fellowship and Chartership are examined and the criteria for HEA (UK Professional Standards Framework or UKPSF) are mapped against those for Chartership (Professional Knowledge and Skills Base (PKSB). D.I.

Regulator trafficking on bacterial transcription units in vivo.

The trafficking patterns of the bacterial regulators of transcript elongation sigma(70), rho, NusA, and NusG on genes in vivo and the explanation for promoter-proximal peaks of RNA polymerase (RNAP) are unknown. Genome-wide, E. coli ChIP-chip revealed distinct association patterns of regulators as RNAP transcribes away from promoters (rho first, then NusA, then NusG). However, the interactions of elongating complexes with these regulators did not differ significantly among most transcription units. A modest variation of NusG signal among genes reflected increased NusG interaction as transcription progresses, rather than functional specialization of elongating complexes. Promoter-proximal RNAP peaks were offset from sigma(70) peaks in the direction of transcription and co-occurred with NusA and rho peaks, suggesting that the RNAP peaks reflected elongating, rather than initiating, complexes. However, inhibition of rho did not increase RNAP levels within genes downstream from the RNAP peaks, suggesting the peaks are caused by a mechanism other than rho-dependent attenuation.

Surface hydrolysis of sphingomyelin by the outer membrane protein Rv0888 supports replication of Mycobacterium tuberculosis in macrophages.

Sphingomyelinases secreted by pathogenic bacteria play important roles in host-pathogen interactions ranging from interfering with phagocytosis and oxidative burst to iron acquisition. This study shows that the Mtb protein Rv0888 possesses potent sphingomyelinase activity cleaving sphingomyelin, a major lipid in eukaryotic cells, into ceramide and phosphocholine, which are then utilized by Mtb as carbon, nitrogen and phosphorus sources, respectively. An Mtb rv0888 deletion mutant did not grow on sphingomyelin as a sole carbon source anymore and replicated poorly in macrophages indicating that Mtb utilizes sphingomyelin during infection. Rv0888 is an unusual membrane protein with a surface-exposed C-terminal sphingomyelinase domain and a putative N-terminal channel domain that mediated glucose and phosphocholine uptake across the outer membrane in an M. smegmatis porin mutant. Hence, we propose to name Rv0888 as SpmT (sphingomyelinase of Mycobacterium tuberculosis). Erythrocyte membranes contain up to 27% sphingomyelin. The finding that Rv0888 accounts for half of Mtb's hemolytic activity is consistent with its sphingomyelinase activity and the observation that Rv0888 levels are increased in the presence of erythrocytes and sphingomyelin by 5- and 100-fold, respectively. Thus, Rv0888 is a novel outer membrane protein that enables Mtb to utilize sphingomyelin as a source of several essential nutrients during intracellular growth.

Compartment-dependent activities of Wnt3a/ß-catenin signaling during vertebrate axial extension.

Extension of the vertebrate body results from the concerted activity of many signals in the posterior embryonic end. Among them, Wnt3a has been shown to play relevant roles in the regulation of axial progenitor activity, mesoderm formation and somitogenesis. However, its impact on axial growth remains to be fully understood. Using a transgenic approach in the mouse, we found that the effect of Wnt3a signaling varies depending on the target tissue. High levels of Wnt3a in the epiblast prevented formation of neural tissues, but did not impair axial progenitors from producing different mesodermal lineages. These mesodermal tissues maintained a remarkable degree of organization, even within a severely malformed embryo. However, from the cells that failed to take a neural fate, only those that left the epithelial layer of the epiblast activated a mesodermal program. The remaining tissue accumulated as a folded epithelium that kept some epiblast-like characteristics. Together with previously published observations, our results suggest a dose-dependent role for Wnt3a in regulating the balance between renewal and selection of differentiation fates of axial progenitors in the epiblast. In the paraxial mesoderm, appropriate regulation of Wnt/ß-catenin signaling was required not only for somitogenesis, but also for providing proper anterior-posterior polarity to the somites. Both processes seem to rely on mechanisms with different requirements for feedback modulation of Wnt/ß-catenin signaling, once segmentation occurred in the presence of high levels of Wnt3a in the presomitic mesoderm, but not after permanent expression of a constitutively active form of ß-catenin. Together, our findings suggest that Wnt3a/ß-catenin signaling plays sequential roles during posterior extension, which are strongly dependent on the target tissue. This provides an additional example of how much the functional output of signaling systems depends on the competence of the responding cells.

The scope of pediatric physical therapy practice in health promotion and fitness for youth with disabilities.

PURPOSE: The purpose of this report is to discuss the scope of pediatric physical therapy practice in health promotion and fitness for youth with disabilities. SUMMARY OF KEY POINTS: Evidence is provided that supports integration of health promotion and fitness strategies in physical therapy clinical management. Physical therapists' roles in community-based adapted sports and fitness interventions and reimbursement considerations are discussed. CONCLUSIONS: Physical therapists are in a unique position to provide expertise in the design and implementation of health promotion and fitness programs for youth with disabilities. These programs are important to promote active, healthy lifestyles and reduce comorbidities associated with sedentary behaviors and unhealthy weight, which are often seen in youth with disabilities. RECOMMENDATIONS FOR CLINICAL PRACTICE: Pediatric physical therapists should incorporate health promotion and fitness strategies into practice.

Concerted involvement of Cdx/Hox genes and Wnt signaling in morphogenesis of the caudal neural tube and cloacal derivatives from the posterior growth zone.

Decrease in Cdx dosage in an allelic series of mouse Cdx mutants leads to progressively more severe posterior vertebral defects. These defects are corrected by posterior gain of function of the Wnt effector Lef1. Precocious expression of Hox paralogous 13 genes also induces vertebral axis truncation by antagonizing Cdx function. We report here that the phenotypic similarity also applies to patterning of the caudal neural tube and uro-rectal tracts in Cdx and Wnt3a mutants, and in embryos precociously expressing Hox13 genes. Cdx2 inactivation after placentation leads to posterior defects, including incomplete uro-rectal septation. Compound mutants carrying one active Cdx2 allele in the Cdx4-null background (Cdx2/4), transgenic embryos precociously expressing Hox13 genes and a novel Wnt3a hypomorph mutant all manifest a comparable phenotype with similar uro-rectal defects. Phenotype and transcriptome analysis in early Cdx mutants, genetic rescue experiments and gene expression studies lead us to propose that Cdx transcription factors act via Wnt signaling during the laying down of uro-rectal mesoderm, and that they are operative in an early phase of these events, at the site of tissue progenitors in the posterior growth zone of the embryo. Cdx and Wnt mutations and premature Hox13 expression also cause similar neural dysmorphology, including ectopic neural structures that sometimes lead to neural tube splitting at caudal axial levels. These findings involve the Cdx genes, canonical Wnt signaling and the temporal control of posterior Hox gene expression in posterior morphogenesis in the different embryonic germ layers. They shed a new light on the etiology of the caudal dysplasia or caudal regression range of human congenital defects.

Behavior change techniques implemented in electronic lifestyle activity monitors: a systematic content analysis.

BACKGROUND: Electronic activity monitors (such as those manufactured by Fitbit, Jawbone, and Nike) improve on standard pedometers by providing automated feedback and interactive behavior change tools via mobile device or personal computer. These monitors are commercially popular and show promise for use in public health interventions. However, little is known about the content of their feedback applications and how individual monitors may differ from one another. OBJECTIVE: The purpose of this study was to describe the behavior change techniques implemented in commercially available electronic activity monitors. METHODS: Electronic activity monitors (N=13) were systematically identified and tested by 3 trained coders for at least 1 week each. All monitors measured lifestyle physical activity and provided feedback via an app (computer or mobile). Coding was based on a hierarchical list of 93 behavior change techniques. Further coding of potentially effective techniques and adherence to theory-based recommendations were based on findings from meta-analyses and meta-regressions in the research literature. RESULTS: All monitors provided tools for self-monitoring, feedback, and environmental change by definition. The next most prevalent techniques (13 out of 13 monitors) were goal-setting and emphasizing discrepancy between current and goal behavior. Review of behavioral goals, social support, social comparison, prompts/cues, rewards, and a focus on past success were found in more than half of the systems. The monitors included a range of 5-10 of 14 total techniques identified from the research literature as potentially effective. Most of the monitors included goal-setting, self-monitoring, and feedback content that closely matched recommendations from social cognitive theory. CONCLUSIONS: Electronic activity monitors contain a wide range of behavior change techniques typically used in clinical behavioral interventions. Thus, the monitors may represent a medium by which these interventions could be translated for widespread use. This technology has broad applications for use in clinical, public health, and rehabilitation settings.

A Novel Approach for Conducting a Catchment Area Analysis of Breast Cancer by Age and Stage for a Community Cancer Center.

BACKGROUND: The U.S. Preventive Services Task Force recently issued an updated draft recommendation statement to initiate breast cancer screening at age 40, reflecting well-documented disparities in breast cancer-related mortality that disproportionately impact younger Black women. This study applied a novel approach to identify hotspots of breast cancer diagnosed before age 50 and/or at an advanced stage to improve breast cancer detection within these communities. METHODS: Cancer registry data for 3,497 women with invasive breast cancer diagnosed or treated between 2012 and 2020 at the Helen F. Graham Cancer Center and Research Institute (HFGCCRI) and who resided in the HFGCCRI catchment area, defined as New Castle County, Delaware, were geocoded and analyzed with spatial intensity. Standardized incidence ratios stratified by age and race were calculated for each hotspot. RESULTS: Four hotspots were identified, two for breast cancer diagnosed before age 50, one for advanced breast cancer, and one for advanced breast cancer diagnosed before age 50. Younger Black women were overrepresented in these hotspots relative to the full-catchment area. CONCLUSIONS: The novel use of spatial methods to analyze a community cancer center catchment area identified geographic areas with higher rates of breast cancer with poor prognostic factors and evidence that these areas made an outsized contribution to racial disparities in breast cancer. IMPACT: Identifying and prioritizing hotspot breast cancer communities for community outreach and engagement activities designed to improve breast cancer detection have the potential to reduce the overall burden of breast cancer and narrow racial disparities in breast cancer.

A multicopper oxidase is required for copper resistance in Mycobacterium tuberculosis.

Mycobacterium tuberculosis, the causative agent of tuberculosis, is one of the most important bacterial pathogens. Recent work has revealed that the natural bactericidal properties of copper are utilized by the host immune system to combat infections with bacteria, including M. tuberculosis. However, M. tuberculosis employs multiple mechanisms to reduce the internal copper amount by efflux and sequestration, which are required for virulence of M. tuberculosis. Here, we describe an alternative mechanism of copper resistance by M. tuberculosis. Deletion of the rv0846c gene increased the susceptibility of M. tuberculosis to copper at least 10-fold, establishing Rv0846c as a major component of copper resistance in M. tuberculosis. In vitro assays showed that Rv0846c oxidized organic substrates and Fe(II). Importantly, mutation of the predicted copper-coordinating cysteine 486 resulted in inactive Rv0846c protein which did not protect M. tuberculosis against copper stress. Hence, Rv0846c is a multicopper oxidase of M. tuberculosis and was renamed mycobacterial multicopper oxidase (MmcO). MmcO is membrane associated, probably by lipidation after export across the inner membrane by the twin-arginine translocation system. However, mutation of the lipidation site did not affect the oxidase activity or the copper protective function of MmcO. Our study revealed MmcO as an important copper resistance mechanism of M. tuberculosis, which possibly acts by oxidation of toxic Cu(I) in the periplasm.

Porins increase copper susceptibility of Mycobacterium tuberculosis.

Copper resistance mechanisms are crucial for many pathogenic bacteria, including Mycobacterium tuberculosis, during infection because the innate immune system utilizes copper ions to kill bacterial intruders. Despite several studies detailing responses of mycobacteria to copper, the pathways by which copper ions cross the mycobacterial cell envelope are unknown. Deletion of porin genes in Mycobacterium smegmatis leads to a severe growth defect on trace copper medium but simultaneously increases tolerance for copper at elevated concentrations, indicating that porins mediate copper uptake across the outer membrane. Heterologous expression of the mycobacterial porin gene mspA reduced growth of M. tuberculosis in the presence of 2.5 µM copper by 40% and completely suppressed growth at 15 µM copper, while wild-type M. tuberculosis reached its normal cell density at that copper concentration. Moreover, the polyamine spermine, a known inhibitor of porin activity in Gram-negative bacteria, enhanced tolerance of M. tuberculosis for copper, suggesting that copper ions utilize endogenous outer membrane channel proteins of M. tuberculosis to gain access to interior cellular compartments. In summary, these findings highlight the outer membrane as the first barrier against copper ions and the role of porins in mediating copper uptake in M. smegmatis and M. tuberculosis.

A Catchment and Location-Allocation Analysis of Mammography Access in Delaware, US: Implications for disparities in geographic access to breast cancer screening.

Background: Despite a 40% reduction in breast cancer mortality over the last 30 years, not all groups have benefited equally from these gains. A consistent link between later stage of diagnosis and disparities in breast cancer mortality has been observed by race, socioeconomic status, and rurality. Therefore, ensuring equitable geographic access to screening mammography represents an important priority for reducing breast cancer disparities. This study conducted a catchment and location-allocation analysis of mammography access in Delaware, a state that is representative of the US in terms of race and urban-rural characteristics and experiences an elevated burden from breast cancer. Methods: A catchment analysis using the ArcGIS Pro Service Area analytic tool characterized the geographic distribution of mammography sites and Breast Imaging Centers of Excellence (BICOEs). Poisson regression analyses identified census tract-level correlates of access. Next, the ArcGIS Pro Location-Allocation analytic tool identified candidate locations for the placement of additional mammography sites in Delaware according to several sets of breast cancer screening guidelines. Results: The catchment analysis showed that for each standard deviation increase in the number of Black women in a census tract, there were 64% (95% CI, 0.18-0.66) fewer mammography units and 85% (95% CI, 0.04-0.48) fewer BICOEs. The more rural counties in the state accounted for 41 % of the population but only 22% of the BICOEs. The results of the location-allocation analysis depended on which set of screening guidelines were adopted, which included increasing mammography sites in communities with a greater proportion of younger Black women and in rural areas. Conclusions: The results of this study illustrate how catchment and location-allocation analytic tools can be leveraged to guide the equitable selection of new mammography facility locations as part of a larger strategy to close breast cancer disparities.

Effect of a Nursing Research Council on System-Wide Practice Changes: An Evidence-Based Practice Process Improvement.

Ensuring that evidence-based practice is adopted across hospital systems is difficult. A system-wide Nursing Research Council in a large academic health care system in Maryland implemented a unique strategy to support the evidence-based practice process by collaborating with other system-wide councils. As a result, new system-wide evidence-based practices were adopted and improved organizational outcomes were seen. [J Contin Educ Nurs. 2023;54(1):25-31.].

Rho directs widespread termination of intragenic and stable RNA transcription.

The transcription termination factor Rho is a global regulator of RNA polymerase (RNAP). Although individual Rho-dependent terminators have been studied extensively, less is known about the sites of RNAP regulation by Rho on a genome-wide scale. Using chromatin immunoprecipitation and microarrays (ChIP-chip), we examined changes in the distribution of Escherichia coli RNAP in response to the Rho-specific inhibitor bicyclomycin (BCM). We found approximately 200 Rho-terminated loci that were divided evenly into 2 classes: intergenic (at the ends of genes) and intragenic (within genes). The intergenic class contained noncoding RNAs such as small RNAs (sRNAs) and transfer RNAs (tRNAs), establishing a previously unappreciated role of Rho in termination of stable RNA synthesis. The intragenic class of terminators included a previously uncharacterized set of short antisense transcripts, as judged by a shift in the distribution of RNAP in BCM-treated cells that was opposite to the direction of the corresponding gene. These Rho-terminated antisense transcripts point to a role of noncoding transcription in E. coli gene regulation that may resemble the ubiquitous noncoding transcription recently found to play myriad roles in eukaryotic gene regulation.

The association between gestational diabetes and ASD and ADHD: a systematic review and meta-analysis.

There is growing evidence for a role of maternal diabetes in the pathogenesis of neurodevelopmental disorders. However, the specific association between gestational diabetes (GDM), as opposed to pre-gestational diabetes, has been poorly isolated. Thus the aim was to systematically review and meta-analyse literature pertaining to prevalence and risk for two neurodevelopmental disorders: autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), when exposed to GDM. PubMed, Cochrane Library, EMBASE, PsycINFO and CINAHL were systematically searched for eligible literature, with forward and backward citation tracking. Screening for eligibility, risk of bias assessment and data extraction were performed by two independent reviewers. 18 studies measuring ASD and 15 measuring ADHD met inclusion criteria. On meta-analysis there was an increased risk of ASD (OR 1.42; 95% CI 1.22, 1.65) but not ADHD (OR 1.01; 95% CI 0.79, 1.28). We discuss potential mechanisms for these differing risks. Greater understanding of risk factors, including GDM, for these neurodevelopmental disorders and potential mechanisms may help inform strategies aimed at prevention of exposure to these adversities during pregnancy.

Microbial Inoculants: Silver Bullet or Microbial Jurassic Park?

The appeal of using microbial inoculants to mediate plant traits and productivity in managed ecosystems has increased over the past decade, because microbes represent an alternative to fertilizers, pesticides, and direct genetic modification of plants. Using microbes bypasses many societal and environmental concerns because microbial products are considered a more sustainable and benign technology. In our desire to harness the power of plant-microbial symbioses, are we ignoring the possibility of precipitating microbial invasions, potentially setting ourselves up for a microbial Jurassic Park? Here, we outline potential negative consequences of microbial invasions and describe a set of practices (Testing, Regulation, Engineering, and Eradication, TREE) based on the four stages of invasion to prevent microbial inoculants from becoming invasive. We aim to stimulate discussion about best practices to proactively prevent microbial invasions.

Multiple Salmonella-pathogenicity island 2 effectors are required to facilitate bacterial establishment of its intracellular niche and virulence.

The pathogenesis of Salmonella Typhimurium depends on the bacterium's ability to survive and replicate within host cells. The formation and maintenance of a unique membrane-bound compartment, termed the Salmonella-containing vacuole (SCV), is essential for S. Typhimurium pathogenesis. SCV-bound S. Typhimurium induces formation of filamentous tubules that radiate outwards from the SCV, termed Salmonella-induced filaments (SIFs). SIF formation is concomitant with the onset of replication within host epithelial cells. SIF biogenesis, formation and maintenance of the SCV, and the intracellular positioning of the SCV within the host cell requires translocation of bacterial proteins (effectors) into the host cell. Effectors secreted by the type III secretion system encoded on Salmonella pathogenicity island 2 (T3SS2) function to interfere with host cellular processes and promote both intracellular survival and replication of S. Typhimurium. Seven T3SS2-secreted effectors, SifA, SopD2, PipB2, SteA, SseJ, SseF, and SseG have previously been implicated to play complementary, redundant, and/or antagonistic roles with respect to SIF biogenesis, intracellular positioning of the SCV, and SCV membrane dynamics modulation during infection. We undertook a systematic study to delineate the contribution of each effector to these processes by (i) deleting all seven of these effectors in a single S. Typhimurium strain; and (ii) deleting combinations of multiple effectors based on putative effector function. Using this deletion mutant library, we show that each of SIF biogenesis, intracellular SCV localization, intramacrophage replication, colonization, and virulence depends on the activities of multiple effectors. Together, our data demonstrates the complex interplay between these seven effectors and highlights the necessity to study T3SS2-secreted effectors as groups, rather than studies of individual effectors.

Imaging Phenotypes of Breast Cancer Heterogeneity in Preoperative Breast Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Scans Predict 10-Year Recurrence.

PURPOSE: Identifying imaging phenotypes and understanding their relationship with prognostic markers and patient outcomes can allow for a noninvasive assessment of cancer. The purpose of this study was to identify and validate intrinsic imaging phenotypes of breast cancer heterogeneity in preoperative breast dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) scans and evaluate their prognostic performance in predicting 10 years recurrence. EXPERIMENTAL DESIGN: Pretreatment DCE-MRI scans of 95 women with primary invasive breast cancer with at least 10 years of follow-up from a clinical trial at our institution (2002-2006) were retrospectively analyzed. For each woman, a signal enhancement ratio (SER) map was generated for the entire segmented primary lesion volume from which 60 radiomic features of texture and morphology were extracted. Intrinsic phenotypes of tumor heterogeneity were identified via unsupervised hierarchical clustering of the extracted features. An independent sample of 163 women diagnosed with primary invasive breast cancer (2002-2006), publicly available via The Cancer Imaging Archive, was used to validate phenotype reproducibility. RESULTS: Three significant phenotypes of low, medium, and high heterogeneity were identified in the discovery cohort and reproduced in the validation cohort (P < 0.01). Kaplan-Meier curves showed statistically significant differences (P < 0.05) in recurrence-free survival (RFS) across phenotypes. Radiomic phenotypes demonstrated added prognostic value (c = 0.73) predicting RFS. CONCLUSIONS: Intrinsic imaging phenotypes of breast cancer tumor heterogeneity at primary diagnosis can predict 10-year recurrence. The independent and additional prognostic value of imaging heterogeneity phenotypes suggests that radiomic phenotypes can provide a noninvasive characterization of tumor heterogeneity to augment personalized prognosis and treatment.