A model of hope as a protective measure to lower burnout and secondary traumatic stress among employees working in developmental and intellectual disabilities services.

BACKGROUND: Burnout and secondary traumatic stress (STS) are problems for the workforce supporting people with developmental disabilities. This study investigated hope as a potential protective resource for burnout and STS among the developmental disability services workforce. METHOD: One hundred and fifty-two non-supervisor caseworkers from a state agency, developmental disabilities division were recruited to participate in an anonymous web-based survey. RESULTS: The analyses showed that hope was negatively associated with the three dimensions of STS (intrusion, avoidance, and arousal) and burnout. Controlling for tenure in the workforce and STS, the results of the hierarchical regression analyses showed that hope accounted for a significant incremental variance to burnout. CONCLUSION: These findings provide support for emerging literature showing hope as a protective resource to workforce burnout.

Incentivizing Students to Learn More About Gerontological Practice.

Enticing students to expand their knowledge of aging-related issues and careers can be fraught with challenges. Intrinsic and curricula-related factors associated with pursuit of aging-related careers have been identified, but little evidence exists demonstrating the effectiveness of external factors at motivating students to learn more about gerontological practice. This brief report presents findings from a survey of 214 students enrolled in at a single university in the mid-west to assess how likely they would be motivated to learn more about aging by twelve possible incentives with additional opportunities to write in other thoughts. Credit toward required field work, financial incentives such as stipends, scholarships, tuition waivers, and raffles were the most frequently mentioned incentives. Some variation was noted based on race/ethnicity, age, and program of study. Themes emerging from other suggestions provided by students included curricula enhancements, employment incentives, and the suggestion that nothing could entice some students. Findings can be used by scholars in program development and funding requests.

The Contribution of Mutation to Variation in Temperature-Dependent Sprint Speed in Zebrafish, Danio rerio.

AbstractThe contribution of new mutations to phenotypic variation and the consequences of this variation for individual fitness are fundamental concepts for understanding genetic variation and adaptation. Here, we investigated how mutation influenced variation in a complex trait in zebrafish, Danio rerio. Typical of many ecologically relevant traits in ectotherms, swimming speed in fish is temperature dependent, with evidence of adaptive evolution of thermal performance. We chemically induced novel germline point mutations in males and measured sprint speed in their sons at six temperatures (between 16°C and 34°C). Heterozygous mutational effects on speed were strongly positively correlated among temperatures, resulting in statistical support for only a single axis of mutational variation, reflecting temperature-independent variation in speed (faster-slower mode). These results suggest pleiotropic effects on speed across different temperatures; however, spurious correlations arise via linkage or heterogeneity in mutation number when mutations have consistent directional effects on each trait. Here, mutation did not change mean speed, indicating no directional bias in mutational effects. The results contribute to emerging evidence that mutations may predominantly have synergistic cross-environment effects, in contrast to conditionally neutral or antagonistic effects that underpin thermal adaptation. We discuss several aspects of experimental design that may affect resolution of mutations with nonsynergistic effects.

Prevalence and Characteristics of Diagnostic Error in Pediatric Critical Care: A Multicenter Study.

OBJECTIVES: Effective interventions to prevent diagnostic error among critically ill children should be informed by diagnostic error prevalence and etiologies. We aimed to determine the prevalence and characteristics of diagnostic errors and identify factors associated with error in patients admitted to the PICU. DESIGN: Multicenter retrospective cohort study using structured medical record review by trained clinicians using the Revised Safer Dx instrument to identify diagnostic error (defined as missed opportunities in diagnosis). Cases with potential errors were further reviewed by four pediatric intensivists who made final consensus determinations of diagnostic error occurrence. Demographic, clinical, clinician, and encounter data were also collected. SETTING: Four academic tertiary-referral PICUs. PATIENTS: Eight hundred eighty-two randomly selected patients 0-18 years old who were nonelectively admitted to participating PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 882 patient admissions, 13 (1.5%) had a diagnostic error up to 7 days after PICU admission. Infections (46%) and respiratory conditions (23%) were the most common missed diagnoses. One diagnostic error caused harm with a prolonged hospital stay. Common missed diagnostic opportunities included failure to consider the diagnosis despite a suggestive history (69%) and failure to broaden diagnostic testing (69%). Unadjusted analysis identified more diagnostic errors in patients with atypical presentations (23.1% vs 3.6%, p = 0.011), neurologic chief complaints (46.2% vs 18.8%, p = 0.024), admitting intensivists greater than or equal to 45 years old (92.3% vs 65.1%, p = 0.042), admitting intensivists with more service weeks/year (mean 12.8 vs 10.9 wk, p = 0.031), and diagnostic uncertainty on admission (77% vs 25.1%, p < 0.001). Generalized linear mixed models determined that atypical presentation (odds ratio [OR] 4.58; 95% CI, 0.94-17.1) and diagnostic uncertainty on admission (OR 9.67; 95% CI, 2.86-44.0) were significantly associated with diagnostic error. CONCLUSIONS: Among critically ill children, 1.5% had a diagnostic error up to 7 days after PICU admission. Diagnostic errors were associated with atypical presentations and diagnostic uncertainty on admission, suggesting possible targets for intervention.

The emotional journey of adapting to prenatally identified trisomy X.

There is a paucity of research on the experiences of parents of children with trisomy X (47,XXX). Increased prenatal diagnoses associated with advances in noninvasive prenatal screening necessitate a better understanding of how trisomy X impacts family systems. This qualitative investigation aimed to describe the lived experience of parents of young daughters with prenatally identified trisomy X to guide genetic counseling. Semi-structured qualitative interviews were conducted via teleconferencing with parents (n = 11) of girls with trisomy X, ages 6-44 months. A descriptive phenomenological approach was used to code transcripts for significant statements and reduce data into themes describing the experience of receiving a diagnosis of trisomy X and the experience of early parenting in this population. Participants described an emotional journey of adapting to prenatally identified trisomy X. Four descriptive themes included two related, yet distinct, life stages: Negative Diagnostic Experience and a Hopeful Early Childhood, as well as two ongoing experiences: Persistent Ambiguity and Coping with and Adapting to Uncertainty. Results suggest providers should carefully consider word choice and timing in delivery of diagnosis, and genetic counseling should provide expectant parents with current research specific to trisomy X, facilitate connections with other parents of young girls with trisomy X, introduce developmental monitoring approaches, and be prepared to support families with a range of emotional responses to the diagnosis and decisions regarding disclosure.

Sex-specific microhabitat use is associated with sex-biased thermal physiology in Anolis lizards.

If fitness optima for a given trait differ between males and females in a population, sexual dimorphism may evolve. Sex-biased trait variation may affect patterns of habitat use, and if the microhabitats used by each sex have dissimilar microclimates, this can drive sex-specific selection on thermal physiology. Nevertheless, tests of differences between the sexes in thermal physiology are uncommon, and studies linking these differences to microhabitat use or behavior are even rarer. We examined microhabitat use and thermal physiology in two ectothermic congeners that are ecologically similar but differ in their degree of sexual size dimorphism. Brown anoles (Anolis sagrei) exhibit male-biased sexual size dimorphism and live in thermally heterogeneous habitats, whereas slender anoles (Anolis apletophallus) are sexually monomorphic in body size and live in thermally homogeneous habitats. We hypothesized that differences in habitat use between the sexes would drive sexual divergence in thermal physiology in brown anoles, but not slender anoles, because male and female brown anoles may be exposed to divergent microclimates. We found that male and female brown anoles, but not slender anoles, used perches with different thermal characteristics and were sexually dimorphic in thermal tolerance traits. However, field-active body temperatures and behavior in a laboratory thermal arena did not differ between females and males in either species. Our results suggest that sexual dimorphism in thermal physiology can arise from phenotypic plasticity or sex-specific selection on traits that are linked to thermal tolerance, rather than from direct effects of thermal environments experienced by males and females.

Factors that influence flow through intravascular catheters: the clinical relevance of Poiseuille's law.

BACKGROUND: The physics of ideal fluid flow is well characterized. However, the effect of catheter size, tubing types, injection port adjuncts, and viscosity on flow is not well described. We used a simulated environment to determine how various permutations of common elements affect fluid flow. STUDY DESIGN AND METHODS: We tested 16 peripheral and central venous catheters to assess flow through several standard infusion sets and a rapid infuser set; tested flow through standard and blood infusion sets with the addition of intravenous extension tubing, stopcocks, and a needleless connector; and compared the relative viscosity of commonly used blood products and colloids to that of normal saline. RESULTS: The maximal flow rate was 200 mL/min for the standard infusion set but 800 mL/min for the rapid infusion set. Choice of infusion tubing was the rate-limiting component for many larger catheters. A 14-gauge, single-lumen central venous catheter (CVC) and 18-gauge peripheral intravenous catheter (PIV) had equivalent flow rates with all infusion sets. A 16-gauge single-lumen CVC allowed a flow rate that was slower than that of a 20-gauge PIV, and faster than that of a 22-gauge PIV. The addition of adjuncts slowed flow rate. Needleless connectors had the greatest impact, reducing flow by 75% for the blood infusion set. Packed red blood cells had a viscosity 4.5 times that of normal saline and thereby reduced flow. CONCLUSION: Catheter and tubing choice, adjuncts, and fluid viscosity influence flow rates. Our results will help inform adequate vascular access planning in the perioperative environment.

Anomalous pH-Dependent Enhancement of p-Methyl Benzoic Acid Sum-Frequency Intensities: Cooperative Surface Adsorption Effects.

Vibrational sum-frequency generation (SFG) spectroscopy is used to determine the surface pKa of p-methyl benzoic acid (pMBA) at the air-water interface by monitoring the carbonyl and carboxylate stretching modes over the pH range of 2 to 12. The SFG intensities of pMBA and its conjugate base, p-methyl benzoate (pMBA-), exhibit an anomalously large enhancement over a narrow pH range (∼0.5) centered at pH 6.3 near the SFG-determined surface pKa, 5.9 ± 0.1. The increase in the surface pKa relative to the bulk value of 4.34 is consistent with the trend previously observed for long chain carboxylic acids in which the surface pKa is higher than the bulk solution pKa. SFG polarization studies help distinguish the orientation and number density contributions to this observed anomalous surface phenomenon. The large SFG intensity increase is attributed to an increase in the pMBA and pMBA- surface concentrations in this narrow pH range due to a cooperative adsorption effect between pMBA and pMBA-. This cooperativity is manifested only on the 2D air-water interface, where the interactions between the acid and base are not as dielectrically screened as in the aqueous bulk phase. Surface effects are critical to understanding and controlling the reactivity, solubility, and behavior of organic acids at interfaces and can have an impact on biomedical applications.

Training novice anaesthesiology trainees to speak up for patient safety.

BACKGROUND: Effectively communicating patient safety concerns in the operating theatre is crucial, but novice trainees often struggle to develop effective speaking up behaviour. Our primary objective was to test whether repeated simulation-based practice helps trainees speak up about patient management concerns. We also tested the effect of an additional didactic intervention over standard simulation education. METHODS: This prospective observational study with a nested double-blind, randomised controlled component took place during a week-long simulation boot camp. Participants were randomised to receive simulation education (SE), or simulation education plus a didactic session on speaking up behaviour (SE+). Outcome measures were: changes in intrapersonal factors for speaking up (self-efficacy, social outcome expectations, and assertiveness), and speaking up performance during four simulated scenarios. Participants self-reported intrapersonal factors and blinded observers scored speaking up behaviour. Cognitive burden for each simulation was also measured using the National Aeronautics and Space Administration Task Load Index. Mixed-design analysis of variance was used to analyse scores. RESULTS: Twenty-two participants (11 per group) were included. There was no significant interaction between group and time for any outcome measure. There was a main effect for time for self-efficacy (P<0.001); for social outcome expectations (P<0.001); for assertive attitude (P=0.003); and for speaking up scores (P=0.001). The SE+ group's assertive attitude scores increased at follow-up whereas the SE group reverted to near baseline scores (P=0.025). CONCLUSIONS: In novice anaesthesia trainees, intrapersonal factors and communication performance benefit from repeated simulation training. Focused teaching may help trainees develop assertive behaviours.

Supporting Latina Breast Health with Community-based Navigation.

Latina women continue to face disproportionate breast cancer risk and well-documented breast health care barriers in Philadelphia. In response to breast health needs among Latinas in Philadelphia, a health-focused community-based organization, in partnership with a network of social and health service providers, began offering community-based navigation in 2005. Later, through funding from a federal agency, the organization launched the Naveguemos con Salud (NCS) Breast Health Partnership Project from 2010 to 2013. NCS offered breast health awareness and education to a broad audience of Latinas in Philadelphia and community-based navigation services to all interested in accessing a clinical breast exam (CBE) and/or mammogram. A 2017 survey revisited breast health needs among the same core population to inform next steps. Here, we explore how findings and lessons learned from a past program and an assessment of current needs can inform future community-clinical linkage and community-based navigation to improve access to breast cancer screening and a continuum of care for Latinas.

Gadolinium Chelate Safety in Pregnancy: Barely Detectable Gadolinium Levels in the Juvenile Nonhuman Primate after in Utero Exposure.

Purpose To determine whether gadolinium remains in juvenile nonhuman primate tissue after maternal exposure to intravenous gadoteridol during pregnancy. Materials and Methods Gravid rhesus macaques and their offspring (n = 10) were maintained, as approved by the institutional animal care and utilization committee. They were prospectively studied as part of a pre-existing ongoing research protocol to evaluate the effects of maternal malnutrition on placental and fetal development. On gestational days 85 and 135, they underwent placental magnetic resonance imaging after intravenous gadoteridol administration. Amniocentesis was performed on day 135 prior to administration of the second dose of gadoteridol. After delivery, the offspring were followed for 7 months. Tissue samples from eight different organs and from blood were harvested from each juvenile macaque. Gadolinium levels were measured by using inductively coupled plasma mass spectrometry. Results Gadolinium concentration in the amniotic fluid was 0.028 × 10-5 %ID/g (percentage injected dose per gram of tissue) 50 days after administration of one gadoteridol dose. Gadolinium was most consistently detected in the femur (mean, 2.5 × 10-5 %ID/g; range, [0.81-4.1] × 10-5 %ID/g) and liver (mean, 0.15 × 10-5 %ID/g; range, [0-0.26] × 10-5 %ID/g). Levels were undetectable in the remaining sampled tissues, with the exception of one juvenile skin sample (0.07 × 10-5 %ID/g), one juvenile spleen sample (0.039 × 10-5 %ID/g), and one juvenile brain (0.095 × 10-5 %ID/g) and kidney (0.13 × 10-5 %ID/g) sample. Conclusion The presence of gadoteridol in the amniotic fluid after maternal injection enables confirmation that it crosses the placenta. Extremely low levels of gadolinium are found in juvenile macaque tissues after in utero exposure to two doses of gadoteridol, indicating that a very small amount of gadolinium persists after delivery. © RSNA, 2017.

Micro-ribonucleic acid-155 is a direct target of Meis1, but not a driver in acute myeloid leukemia.

Micro-ribonucleic acid-155 (miR-155) is one of the first described oncogenic miRNAs. Although multiple direct targets of miR-155 have been identified, it is not clear how it contributes to the pathogenesis of acute myeloid leukemia. We found miR-155 to be a direct target of Meis1 in murine Hoxa9/Meis1 induced acute myeloid leukemia. The additional overexpression of miR-155 accelerated the formation of acute myeloid leukemia in Hoxa9 as well as in Hoxa9/Meis1 cells in vivo However, in the absence or following the removal of miR-155, leukemia onset and progression were unaffected. Although miR-155 accelerated growth and homing in addition to impairing differentiation, our data underscore the pathophysiological relevance of miR-155 as an accelerator rather than a driver of leukemogenesis. This further highlights the complexity of the oncogenic program of Meis1 to compensate for the loss of a potent oncogene such as miR-155. These findings are highly relevant to current and developing approaches for targeting miR-155 in acute myeloid leukemia.

Combining natural sequence variation with high throughput mutational data to reveal protein interaction sites.

Many protein interactions are conserved among organisms despite changes in the amino acid sequences that comprise their contact sites, a property that has been used to infer the location of these sites from protein homology. In an inter-species complementation experiment, a sequence present in a homologue is substituted into a protein and tested for its ability to support function. Therefore, substitutions that inhibit function can identify interaction sites that changed over evolution. However, most of the sequence differences within a protein family remain unexplored because of the small-scale nature of these complementation approaches. Here we use existing high throughput mutational data on the in vivo function of the RRM2 domain of the Saccharomyces cerevisiae poly(A)-binding protein, Pab1, to analyze its sites of interaction. Of 197 single amino acid differences in 52 Pab1 homologues, 17 reduce the function of Pab1 when substituted into the yeast protein. The majority of these deleterious mutations interfere with the binding of the RRM2 domain to eIF4G1 and eIF4G2, isoforms of a translation initiation factor. A large-scale mutational analysis of the RRM2 domain in a two-hybrid assay for eIF4G1 binding supports these findings and identifies peripheral residues that make a smaller contribution to eIF4G1 binding. Three single amino acid substitutions in yeast Pab1 corresponding to residues from the human orthologue are deleterious and eliminate binding to the yeast eIF4G isoforms. We create a triple mutant that carries these substitutions and other humanizing substitutions that collectively support a switch in binding specificity of RRM2 from the yeast eIF4G1 to its human orthologue. Finally, we map other deleterious substitutions in Pab1 to inter-domain (RRM2-RRM1) or protein-RNA (RRM2-poly(A)) interaction sites. Thus, the combined approach of large-scale mutational data and evolutionary conservation can be used to characterize interaction sites at single amino acid resolution.

[Lidline Tattoo Associated with Basal Cell Carcinoma of the Lid Margin - Coincidence or Association?] / Lidstrichtattoo assoziiert mit Lidkantenbasaliom ­ Zufall oder Assoziation?

A cystic lesion of the lid margin was excised suspecting basal cell carcinoma. On histology, black-turquoise pigment was seen in the dermis adjacent to the basal cell carcinoma. It was pronounced perivascular, intracellular in macrophages and fibroblasts, but also extracellular as free pigment in the tissue, compatible with an eyelid line tattoo. Typical tissue reactions to tattoo ink, meibomian gland dysfunction after lid margin tattoo, as well as inflammatory reactions in the retina and choroid associated with tattoos distant from the eye are discussed. The correlation of lid tumors and lid margin tattoos seems coincidental.

Severe Sarcopenia and Increased Fat Stores in Pediatric Patients With Liver, Kidney, or Intestine Failure.

OBJECTIVES: Malnutrition and wasting predict clinical outcomes in children with severe chronic illness. Objectively calculated malnutrition in children with end-stage organ failure has not been well studied. This analysis compares children with kidney, liver or intestine failure to healthy controls to quantitate the disparity in muscle and fat stores. METHODS: Children younger than 19 years with end-stage liver, kidney, or intestine failure and with pretransplant computed tomography (CT) imaging were selected from the transplant database. Age- and sex-matched healthy controls were selected from the trauma database. Measures of nutrition status included a scaled scoring of core muscle mass, and visceral and subcutaneous fat stores. Analysis was conducted using the pooled and individually matched subject-control differences. RESULTS: There were 81 subjects included in the final analysis (liver [n = 35], kidney [n = 20], and intestine [n = 26]). Children with end-stage liver disease had a 23% reduction in muscle mass, a 69% increase in visceral fat, and a 29% increase in subcutaneous fat. End-stage renal disease patients had a 19% reduction in muscle mass and a 258% increase in subcutaneous fat. Intestine failure patients had a 24% reduction in muscle mass, a 30% increase in visceral fat, and a 46% increase in subcutaneous fat. CONCLUSIONS: These results demonstrate significant sarcopenia and increased fat stores in end-stage organ failure patients, which supports the idea of an active physiologic mechanism to store fat while losing muscle mass. Sarcopenia may be related to total protein loss from a catabolic state, or from decreased synthesis (liver), wasting (kidney), or malabsorption (intestine).

Spectroscopic evidence for the origin of odd-even effects in self-assembled monolayers and effects of substrate roughness.

This paper reports the effects of substrate roughness on the odd-even effect in n-alkanethiolate self-assembled monolayers (SAMs) probed by vibrational sum frequency generation (SFG) spectroscopy. By fabricating SAMs on surfaces across the so-called odd-even limit, we demonstrate that differentiation of the vibrational frequencies of CH3 from SAMs derived from alkyl thiols with either odd (SAMO) or even (SAME) numbers of carbons depends on the roughness of the substrate on which they are formed. Odd-even oscillation in SFG susceptibility amplitudes was observed for spectra derived from SAME and SAMO fabricated on flat surfaces (RMS roughness = 0.4 nm) but not on rougher surfaces (RMS roughness = 2.38 nm). In addition, we discovered that local chemical environments for the terminal CH3 group have a chain-length dependence. There seems to be a transition at around C13, beyond which SAMs become "solid-like".

Evaluation of a short-term topical interferon α-2b treatment for histologically proven melanoma and primary acquired melanosis with atypia.

OBJECTIVE: To evaluate the efficiency of series of 6-week treatments with brief intervals (6-week = 1 cycle) of topical Interferon α-2b (IFNα-2b) treatment in primary acquired melanosis (PAM) with atypia and melanoma of the conjunctiva. PATIENTS AND METHODS: Five patients with biopsy-proven PAM with atypia and seven patients with melanoma of the conjunctiva, treated with topical IFNα-2b (1 million units/ml, 5 times daily), were included in the study. All patients had colour photographs and the tumour area was measured manually for each patient before and after treatment. RESULTS: The median age of 12 patients at initiation of treatment was 61.5 years (range 39-75 years). The mean therapy duration was 2.4 cycles (range 1-6 cycle). Compared to pretreatment lesion dimension, the mean decrease in tumour size were after the first cycle 66% (range 18-98%; p = 0.004; n = 10 patients), after the second cycle 55% (range 10-100%; p = 0.016; n = 7 patients), and after the third cycle 74% (range 23-100%; n = 3 patients). In one patient 6 cycles of topical IFNα-2b were needed. The decrease in size was 22% after the 4(th) cycle, 34% after the 5(th) cycle, and 98% after the 6(th) cycle. CONCLUSION: Our clinical experience demonstrates promising results of topical IFNα-2b treatment for PAM with atypia and melanoma of the conjunctiva without any local or systemic side effects. However, future multicenter prospective studies are recommended to confirm the efficiency and safety of topical IFNα-2b treatment.

Deep mutational scanning of an RRM domain of the Saccharomyces cerevisiae poly(A)-binding protein.

The RNA recognition motif (RRM) is the most common RNA-binding domain in eukaryotes. Differences in RRM sequences dictate, in part, both RNA and protein-binding specificities and affinities. We used a deep mutational scanning approach to study the sequence-function relationship of the RRM2 domain of the Saccharomyces cerevisiae poly(A)-binding protein (Pab1). By scoring the activity of more than 100,000 unique Pab1 variants, including 1246 with single amino acid substitutions, we delineated the mutational constraints on each residue. Clustering of residues with similar mutational patterns reveals three major classes, composed principally of RNA-binding residues, of hydrophobic core residues, and of the remaining residues. The first class also includes a highly conserved residue not involved in RNA binding, G150, which can be mutated to destabilize Pab1. A comparison of the mutational sensitivity of yeast Pab1 residues to their evolutionary conservation reveals that most residues tolerate more substitutions than are present in the natural sequences, although other residues that tolerate fewer substitutions may point to specialized functions in yeast. An analysis of ∼40,000 double mutants indicates a preference for a short distance between two mutations that display an epistatic interaction. As examples of interactions, the mutations N139T, N139S, and I157L suppress other mutations that interfere with RNA binding and protein stability. Overall, this study demonstrates that living cells can be subjected to a single assay to analyze hundreds of thousands of protein variants in parallel.

Mixed-species biofilm compromises wound healing by disrupting epidermal barrier function.

In chronic wounds, biofilm infects host tissue for extended periods of time. This work establishes the first chronic preclinical model of wound biofilm infection aimed at addressing the long-term host response. Although biofilm-infected wounds did not show marked differences in wound closure, the repaired skin demonstrated compromised barrier function. This observation is clinically significant, because it leads to the notion that even if a biofilm infected wound is closed, as observed visually, it may be complicated by the presence of failed skin, which is likely to be infected and/or further complicated postclosure. Study of the underlying mechanisms recognized for the first time biofilm-inducible miR-146a and miR-106b in the host skin wound-edge tissue. These miRs silenced ZO-1 and ZO-2 to compromise tight junction function, resulting in leaky skin as measured by transepidermal water loss (TEWL). Intervention strategies aimed at inhibiting biofilm-inducible miRNAs may be productive in restoring the barrier function of host skin.