New Basic Chromosome Numbers For Genera Of Neotropical Ferns

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141121/1/ajb207703.pd

Childhood Cancer Incidence in Georgia: Descriptive Epidemiology, Geographic Trends, and Disparities in Insurance Coverage, and Health Care Access

Background: Limited research has been conducted concerning childhood cancer (CC) incidence in Georgia, which is a leading cause of death for children in the US. The purpose of this study was to determine if county-level CC incidence rates differed by geography or race and if health care access disparities exist. Methods: Incidence data were obtained from the Georgia Comprehensive Cancer Registry for 2000-2011. Age-adjusted incidence rates per 100,000 were analyzed by sex, race, and county. Hotspots and coldspots of CC incidence were analyzed using the Getis-Ord GI* statistic. Health care access data for children under 19 were obtained using US Census Bureau’s Small Area Health Insurance Estimates for 2011. Georgia’s three children’s oncology group (COG) treatment facilities with 40-mile buffer zones were geographically overlaid with CC incidence rate maps and health insurance maps using Geographic Information Systems (GIS). Results: For leukemia and central nervous system cancers, incidence rates were significantly different between Whites [7.8, 95% confidence interval (CI) (7.4, 8.2)] and Blacks [5.2, 95% CI (4.8, 5.6)]. Statistical hotspots of CC were observed in north Georgia. A lower percentage of insurance coverage among children was observed in southeast GA. Approximately 25% of Georgia counties that were not within a COG buffer had a higher percentage of children who were uninsured (mean ± SD: 10.28% ±1.86%). Conclusion: Higher CC incidence rates and disparities in access to care were evident in north Georgia. Future research is needed in these geographies to investigate potential risk factors associated with CC incidence patterns and racial differences in Georgia

Resilience and the self-righting power of development : observations of impoverished Brazilian children in person-centred playtherapy

A chapter on observations of impoverished Brazilian children in person-centred playtherap

Examination of Cybersecurity Technologies, Practices, Challenges, and Wish List in K-12 School Districts

With the growth in digital teaching and learning, there has been a sharp rise in the number of cybersecurity attacks on K-12 school networks. This has demonstrated a need for security technologies and cybersecurity education. This study examined security technologies used, effective security practices, challenges, concerns, and wish list of technology leaders in K-12 settings. Data collected from 23 district websites and from interviews with 12 district technology leaders were analyzed. Top security practices included cloud-based technologies, segregated network/V-LAN, two-factor authentication, limiting access, and use of Clever or Class Link. Top challenges included keeping users informed, lack of buy-in from staff and decision-makers, lack of expertise to implement modern best practices, and cost of resources. Top concerns included possible cyberattacks, leaked student data, and lack of user awareness. Finally, their wish list included technology personnel, access to Clever of Class Link, external system diagnostic checks, professional development for staff, and replacing aging infrastructure. The findings have implications for K-12 administrators, technology leaders, and teachers

Do monosymptomatic stroke patients with dizziness present a vestibular syndrome without nystagmus? An underestimated entity.

BACKGROUND AND PURPOSE Vestibular symptoms are common in emergency department (ED) patients and have various causes, including stroke. Accurate identification of stroke in patients with vestibular symptoms is crucial for timely management. We conducted a prospective cross-sectional study from 2015 to 2019 to determine stroke prevalence and associated symptoms in ED patients with vestibular symptoms, aiming to improve diagnosis and outcomes. METHODS As part of the DETECT project, we screened 1647 ED patients with acute vestibular symptoms. Following a retrospective analysis of 961 head and neck magnetic resonance imaging (MRI) scans, we included 122 confirmed stroke cases and assessed them for vestibular signs and symptoms. RESULTS Stroke prevalence in dizzy patients was 13% (122/961 MRI scans). Most patients (95%) presented with acute vestibular symptoms with or without nystagmus, whereas 5% had episodic vestibular syndrome (EVS). Nystagmus was present in 50% of stroke patients. Eighty percent had a purely posterior circulation stroke, and nystagmus was absent in 46% of these patients. Seven patients (6%) had lesions in both the anterior and posterior circulation. Vertigo was experienced by 52% regardless of territory. CONCLUSIONS A stroke was identified in 13% of ED patients presenting with acute vestibular symptoms. In 5%, it was EVS. Most strokes were in the posterior circulation territory; vertigo occurred with similar frequency in anterior and posterior circulation stroke, and absence of nystagmus was common in both

Vestibular syndromes, diagnosis and diagnostic errors in patients with dizziness presenting to the emergency department: a cross-sectional study.

OBJECTIVES We aimed to determine the frequency of vestibular syndromes, diagnoses, diagnostic errors and resources used in patients with dizziness in the emergency department (ED). DESIGN Retrospective cross-sectional study. SETTING Tertiary referral hospital. PARTICIPANTS Adult patients presenting with dizziness. PRIMARY AND SECONDARY OUTCOME MEASURES We collected clinical data from the initial ED report from July 2015 to August 2020 and compared them with the follow-up report if available. We calculated the prevalence of vestibular syndromes and stroke prevalence in patients with dizziness. Vestibular syndromes are differentiated in acute (AVS) (eg, stroke, vestibular neuritis), episodic (EVS) (eg, benign paroxysmal positional vertigo, transient ischaemic attack) and chronic (CVS) (eg, persistent postural-perceptual dizziness) vestibular syndrome. We reported the rate of diagnostic errors using the follow-up diagnosis as the reference standard. RESULTS We included 1535 patients with dizziness. 19.7% (303) of the patients presented with AVS, 34.7% (533) with EVS, 4.6% (71) with CVS and 40.9% (628) with no or unclassifiable vestibular syndrome. The three most frequent diagnoses were stroke/minor stroke (10.1%, 155), benign paroxysmal positional vertigo (9.8%, 150) and vestibular neuritis (9.6%, 148). Among patients with AVS, 25.4% (77) had stroke. The cause of the dizziness remained unknown in 45.0% (692) and 18.0% received a false diagnosis. There was a follow-up in 662 cases (43.1%) and 58.2% with an initially unknown diagnoses received a final diagnosis. Overall, 69.9% of all 1535 patients with dizziness received neuroimaging (MRI 58.2%, CT 11.6%) in the ED. CONCLUSIONS One-fourth of patients with dizziness in the ED presented with AVS with a high prevalence (10%) of vestibular strokes. EVS was more frequent; however, the rate of undiagnosed patients with dizziness and the number of patients receiving neuroimaging were high. Almost half of them still remained without diagnosis and among those diagnosed were often misclassified. Many unclear cases of vertigo could be diagnostically clarified after a follow-up visit

Patient Experience Shows Little Relationship with Hospital Quality Management Strategies.

OBJECTIVES: Patient-reported experience measures are increasingly being used to routinely monitor the quality of care. With the increasing attention on such measures, hospital managers seek ways to systematically improve patient experience across hospital departments, in particular where outcomes are used for public reporting or reimbursement. However, it is currently unclear whether hospitals with more mature quality management systems or stronger focus on patient involvement and patient-centered care strategies perform better on patient-reported experience. We assessed the effect of such strategies on a range of patient-reported experience measures. MATERIALS AND METHODS: We employed a cross-sectional, multi-level study design randomly recruiting hospitals from the Czech Republic, France, Germany, Poland, Portugal, Spain, and Turkey between May 2011 and January 2012. Each hospital contributed patient level data for four conditions/pathways: acute myocardial infarction, stroke, hip fracture and deliveries. The outcome variables in this study were a set of patient-reported experience measures including a generic 6-item measure of patient experience (NORPEQ), a 3-item measure of patient-perceived discharge preparation (Health Care Transition Measure) and two single item measures of perceived involvement in care and hospital recommendation. Predictor variables included three hospital management strategies: maturity of the hospital quality management system, patient involvement in quality management functions and patient-centered care strategies. We used directed acyclic graphs to detail and guide the modeling of the complex relationships between predictor variables and outcome variables, and fitted multivariable linear mixed models with random intercept by hospital, and adjusted for fixed effects at the country level, hospital level and patient level. RESULTS: Overall, 74 hospitals and 276 hospital departments contributed data on 6,536 patients to this study (acute myocardial infarction n = 1,379, hip fracture n = 1,503, deliveries n = 2,088, stroke n = 1,566). Patients admitted for hip fracture and stroke had the lowest scores across the four patient-reported experience measures throughout. Patients admitted after acute myocardial infarction reported highest scores on patient experience and hospital recommendation; women after delivery reported highest scores for patient involvement and health care transition. We found no substantial associations between hospital-wide quality management strategies, patient involvement in quality management, or patient-centered care strategies with any of the patient-reported experience measures. CONCLUSION: This is the largest study so far to assess the complex relationship between quality management strategies and patient experience with care. Our findings suggest absence of and wide variations in the institutionalization of strategies to engage patients in quality management, or implement strategies to improve patient-centeredness of care. Seemingly counterintuitive inverse associations could be capturing a scenario where hospitals with poorer quality management were beginning to improve their patient experience. The former suggests that patient-centered care is not yet sufficiently integrated in quality management, while the latter warrants a nuanced assessment of the motivation and impact of involving patients in the design and assessment of services

Design, Synthesis, and Evaluation of Hydroxamic Acid-Based Molecular Probes for In Vivo Imaging of Histone Deacetylase (HDAC) in Brain

Hydroxamic acid-based histone deacetylase inhibitors (HDACis) are a class of molecules with therapeutic potential currently reflected in the use of suberoylanilide hydroxamic acid (SAHA; Vorinostat) to treat cutaneous T-cell lymphomas (CTCL). HDACis may have utility beyond cancer therapy, as preclinical studies have ascribed HDAC inhibition as beneficial in areas such as heart disease, diabetes, depression, neurodegeneration, and other disorders of the central nervous system (CNS). However, little is known about the pharmacokinetics (PK) of hydroxamates, particularly with respect to CNS-penetration, distribution, and retention. To explore the rodent and non-human primate (NHP) brain permeability of hydroxamic acid-based HDAC inhibitors using positron emission tomography (PET), we modified the structures of belinostat (PXD101) and panobinostat (LBH-589) to incorporate carbon-11. We also labeled PCI 34051 through carbon isotope substitution. After characterizing the in vitro affinity and efficacy of these compounds across nine recombinant HDAC isoforms spanning Class I and Class II family members, we determined the brain uptake of each inhibitor. Each labeled compound has low uptake in brain tissue when administered intravenously to rodents and NHPs. In rodent studies, we observed that brain accumulation of the radiotracers were unaffected by the pre-administration of unlabeled inhibitors. Knowing that CNS-penetration may be desirable for both imaging applications and therapy, we explored whether a liquid chromatography, tandem mass spectrometry (LC-MS-MS) method to predict brain penetrance would be an appropriate method to pre-screen compounds (hydroxamic acid-based HDACi) prior to PET radiolabeling. LC-MS-MS data were indeed useful in identifying additional lead molecules to explore as PET imaging agents to visualize HDAC enzymes in vivo. However, HDACi brain penetrance predicted by LC-MS-MS did not strongly correlate with PET imaging results. This underscores the importance of in vivo PET imaging tools in characterizing putative CNS drug lead compounds and the continued need to discover effect PET tracers for neuroepigenetic imaging.Chemistry and Chemical Biolog

Loss of LGR4/GPR48 causes severe neonatal salt-wasting due to disrupted WNT signaling altering adrenal zonation.

Disorders of isolated mineralocorticoid deficiency causing potentially life-threatening salt-wasting crisis early in life have been associated with gene variants of aldosterone biosynthesis or resistance, but in some patients no such variants are found. WNT/β-catenin signaling is crucial for differentiation and maintenance of the aldosterone producing adrenal zona glomerulosa (zG). We describe a highly consanguineous family with multiple perinatal deaths or infants presenting at birth with failure to thrive, severe salt-wasting crises associated with isolated hypoaldosteronism, nail anomalies, short stature, and deafness. Whole exome sequencing revealed a homozygous splice variant in the R-SPONDIN receptor LGR4 gene (c.618-1G>C) regulating WNT signaling. The resulting transcripts affected protein function and stability, and resulted in loss of Wnt/β-catenin signaling in vitro. The impact of LGR4 inactivation was analyzed by adrenal cortex specific ablation of Lgr4, using Lgr4Flox/Flox mated with Sf1:Cre mice. Inactivation of Lgr4 within the adrenal cortex in the mouse model caused decreased WNT signaling, aberrant zonation with deficient zG and reduced aldosterone production. Thus, human LGR4 mutations establish a direct link between LGR4 inactivation and decreased canonical WNT signaling with abnormal zG differentiation and endocrine function. Therefore, variants in WNT signaling and its regulators should systematically be considered in familial hyperreninemic hypoaldosteronism