Attribute Analytics Performance Metrics from the MAM Consortium Interlaboratory Study.

The multi-attribute method (MAM) was conceived as a single assay to potentially replace multiple single-attribute assays that have long been used in process development and quality control (QC) for protein therapeutics. MAM is rooted in traditional peptide mapping methods; it leverages mass spectrometry (MS) detection for confident identification and quantitation of many types of protein attributes that may be targeted for monitoring. While MAM has been widely explored across the industry, it has yet to gain a strong foothold within QC laboratories as a replacement method for established orthogonal platforms. Members of the MAM consortium recently undertook an interlaboratory study to evaluate the industry-wide status of MAM. Here we present the results of this study as they pertain to the targeted attribute analytics component of MAM, including investigation into the sources of variability between laboratories and comparison of MAM data to orthogonal methods. These results are made available with an eye toward aiding the community in further optimizing the method to enable its more frequent use in the QC environment.

Perceptions of the Moral Obligations of Pediatric Nurses During an Active Shooter Event in a Children's Hospital.

PURPOSE: To explore and compare the perceptions of nurses and parent/family advisors regarding pediatric nurses' moral obligations to children and families during an active shooter event in a children's hospital. DESIGN AND METHODS: This was a descriptive, exploratory study using survey methodology. A convenience sample of all licensed nurses and parent/family advisors from four children's hospitals across the United States were recruited. Surveys consisted of five primary domains including Appropriateness of National Guidelines, Personal Preparedness, Moral Accountability, Professional/Legal Concerns, and Personal Risk Expectations. Frequency counts and percentages were calculated for each survey item. RESULTS: Data from 874 pediatric nurses and 81 parent/family advisors were analyzed. Most respondents believed the Run-Hide-Fight campaign should be changed to Secure-Preserve-Fight. Only 30% of nurses felt mentally prepared to respond to an active shooter event. Most respondents agreed that nurses have a professional duty to protect their patients, but agreed that it was a personal choice, not a moral obligation, to accept potentially fatal risks. Hospital setting and patient vulnerability often influenced nurses' perceived obligations to patients. Most respondents reported they would not leave their patient/child during an active shooter event. CONCLUSIONS: Nurses feel morally obligated to patients, but must balance their own personal risk tolerance level against the need to protect patients and families. PRACTICE IMPLICATIONS: Hospitals need in-depth active shooter training for both nurses and parents as well as safety plans that address both evacuation protocols and measures to secure in place to protect the lives of patients, families, and staff.

New Peak Detection Performance Metrics from the MAM Consortium Interlaboratory Study.

The Multi-Attribute Method (MAM) Consortium was initially formed as a venue to harmonize best practices, share experiences, and generate innovative methodologies to facilitate widespread integration of the MAM platform, which is an emerging ultra-high-performance liquid chromatography-mass spectrometry application. Successful implementation of MAM as a purity-indicating assay requires new peak detection (NPD) of potential process- and/or product-related impurities. The NPD interlaboratory study described herein was carried out by the MAM Consortium to report on the industry-wide performance of NPD using predigested samples of the NISTmAb Reference Material 8671. Results from 28 participating laboratories show that the NPD parameters being utilized across the industry are representative of high-resolution MS performance capabilities. Certain elements of NPD, including common sources of variability in the number of new peaks detected, that are critical to the performance of the purity function of MAM were identified in this study and are reported here as a means to further refine the methodology and accelerate adoption into manufacturer-specific protein therapeutic product life cycles.

And the Beat Goes On: Heartbeat Recordings through Music Therapy for Parents of Children with Progressive Neurodegenerative Illnesses.

Background: Music is a powerful therapeutic intervention to promote physical and psychological health, healing, and well-being. In pediatric palliative care, music therapists are often involved in preloss care. Heartbeat recordings (HBRs) synchronize the rhythm of the heartbeat into a favorite song. In preloss care, HBRs show promise in helping parents of children with progressive neurodegenerative illnesses (PNDI) cope with their chronic sorrow and the loss of their child. Objective: To explore the lived experience of HBRs for bereavement in the lives of parents of children with PNDI. Design: Phenomenological study. Setting/Subjects: Purposeful sample of 11 English-speaking parents of children with PNDI receiving palliative care services in an academic pediatric hospital were interviewed three months after receiving their child's HBR. Measurements: A semistructured interview guide was used to collect data concurrently with the mind mapping process. Results: Data from interviews revealed 4 major themes and 10 subthemes: (1) Bifocal View (parental lens vs. medical lens); (2) Navigating Life and Relationships (caregiver fatigue, grief and loss, marriage, job, brought us together, paying it forward); (3) Coping through Spirituality; and, (4) Legacy Creation (HBR as a connection, song selection). Conclusions: Parents of children with PNDI experience chronic sorrow. The HBR assisted in meaning-making that validated the child's life and supported the parents' expression of grief and their ability to cope. Further research is needed to validate the impact of HBRs in diverse populations.

Genomic selection for resistance to spruce budworm in white spruce and relationships with growth and wood quality traits.

With climate change, the pressure on tree breeding to provide varieties with improved resilience to biotic and abiotic stress is increasing. As such, pest resistance is of high priority but has been neglected in most tree breeding programs, given the complexity of phenotyping for these traits and delays to assess mature trees. In addition, the existing genetic variation of resistance and its relationship with productivity should be better understood for their consideration in multitrait breeding. In this study, we evaluated the prospects for genetic improvement of the levels of acetophenone aglycones (AAs) in white spruce needles, which have been shown to be tightly linked to resistance to spruce budworm. Furthermore, we estimated the accuracy of genomic selection (GS) for these traits, allowing selection at a very early stage to accelerate breeding. A total of 1,516 progeny trees established on five sites and belonging to 136 full-sib families from a mature breeding population in New Brunswick were measured for height growth and genotyped for 4,148 high-quality SNPs belonging to as many genes along the white spruce genome. In addition, 598 trees were assessed for levels of AAs piceol and pungenol in needles, and 578 for wood stiffness. GS models were developed with the phenotyped trees and then applied to predict the trait values of unphenotyped trees. AAs were under moderate-to-high genetic control (h 2: 0.43-0.57) with null or marginally negative genetic correlations with other traits. The prediction accuracy of GS models (GBLUP) for AAs was high (PAAC: 0.63-0.67) and comparable or slightly higher than pedigree-based (ABLUP) or BayesCπ models. We show that AA traits can be improved and that GS speeds up the selection of improved trees for insect resistance and for growth and wood quality traits. Various selection strategies were tested to optimize multitrait gains.

Genetic control and evolutionary potential of a constitutive resistance mechanism against the spruce budworm (Choristoneura fumiferana) in white spruce (Picea glauca).

Insect herbivory may drive evolution by selecting for trees with heritable resistance against defoliation. The spruce budworm (Choristoneura fumiferana, SBW) is a highly damaging forest insect pest that can affect population structure of white spruce (Picea glauca) in North America. Resistance against SBW was recently described in white spruce and was linked to three constitutive resistance biomarkers: the phenolic compounds piceol and pungenol, and expression of a beta-glucosidase encoding gene (Pgßglu-1). We investigated the phenotypic variability and heritability of these resistance biomarkers and of picein, the precursor of piceol, in the foliage of 874 trees belonging to 33 full-sib families and 71 clonal lines under evaluation in seven field locations in Eastern Canada. We aimed to (i) determine their genetic control, (ii) estimate the genetic and phenotypic correlations among defense biomarkers, and (iii) determine whether their constitutive levels are associated with detrimental trade-offs on growth. Quantitative genetics analyses indicated that all four traits are moderately to highly heritable. The full-sib and clonal analyses showed that additive and non-additive genetic effects play major and minor roles, respectively. Positive genetic and phenotypic correlations between resistance biomarkers and primary growth indicated that there is no trade-off between total height and height increment and resistance traits, contradicting the GDBH (Growth Differentiation Balance Hypothesis). Our findings about the predominant additive genetic basis of the resistance biomarkers show that adaptive evolution of white spruce natural populations to resist to SBW is possible and that potentially important gains could also be expected from artificial selection.

The Emotional Cost of Caring for Others: One Pediatric Hospital's Journey to Reduce Compassion Fatigue.

OBJECTIVE: This study examined the prevalence of compassion fatigue and life stress of pediatric nurses. BACKGROUND: Distressing patient situations over time may affect nurses' professional quality of life and result in compassion fatigue. If not addressed, compassion fatigue may have personal and organizational consequences. METHODS: Using a descriptive, correlational design, a convenience sample of 268 nurses completed a web-based survey. RESULTS: High compassion satisfaction and moderate to low burnout and secondary traumatic stress were described by 49% of participants. Education was statistically associated with burnout and secondary traumatic stress. Life stress scores were significantly associated with age, experience, organizational tenure, and professional engagement. Narrative commentary yielded 5 themes: staffing, recognition, boundaries, expectations, and hopelessness. Organizational initiatives to prevent or mitigate compassion fatigue focused on awareness, balance, and connections. CONCLUSIONS: Nurses are negatively impacted by the emotional cost of caring. Future studies need to identify interventions to minimize compassion fatigue.

Deficit awareness and cognitive performance in individuals with acquired brain injury.

BACKGROUND: Anosognosia is commonly reported after acquired brain injury (ABI) or stroke and often hinders an ABI survivor's ability to perceive the social consequences of their behavior and to modify it. OBJECTIVE: This study concerned the question of whether awareness discrepancy scores could predict cognitive performance with a focus on the acquired brain injured (ABI) population. It was hypothesized that lack of awareness would predict performance on cognitive tasks. METHOD: Archival data was assessed for a total of 21 patients; 10 learning disabled (LD) and 11 with a brain injury with each person having one "observer". Data consisted of patient and observer ratings on the Acquired Deficit Awareness Management System (ADAMS) profile, a 36-item survey that measured both patient self-report and observer assessment of awareness. These data yielded two discrepancy scores: deficit with awareness (DWA) and deficit without awareness (DWoA). The discrepancy scores were used to predict IQ scores from the Wechsler Adult Intelligence Scale, academic performance on the Woodcock-Johnson Psychoeducational Battery, memory functioning on the Wechsler Memory Scale, and a measure of fine motor skill. RESULTS: The DWoA measure correlated significantly with several cognitive variables and with finger tapping speed on the non-dominant hand. These correlations were not apparent in the LD group. CONCLUSIONS: Measures of lack of awareness predicted cognitive performance in the ABI population. Therapeutic interventions are discussed that address lack of awareness after ABI.

Bereaved caregivers as educators in pediatric palliative care: their experiences and impact.

BACKGROUND: With the continuing growth of pediatric palliative care, there is an increasing need to develop effective training for health care professionals. Bereaved parents have participated in the training of health care professionals utilizing curriculum from the Initiative for Pediatric Palliative Care (IPPC), but the experience of bereaved parents as educators has not been studied. OBJECTIVES: This qualitative research examined the experience of bereaved parents involved in pediatric palliative care education of health care professionals and the challenges and possible benefits for the health care professionals. METHODS: Nine bereaved parents and eleven health care professionals were interviewed about their experiences in a pediatric palliative care education program utilizing the IPPC curriculum. The interviews were recorded, transcribed, coded and analyzed for themes and subthemes. RESULTS: Major themes found were a sense of purpose for the parents and benefits and challenges for both parents and professionals. The experience for parents contributed to their meaning-making for both their children's lives and deaths. Parents and professionals identified mutual learning and increased mutual understanding. Some professionals noted that the presence of parents may have limited the openness of discussion of the professionals and parents acknowledged challenges of emotional management in their participation in the educational program. Both parents and professionals recognized and described challenges involved in working sensitively with patients and families without being overwhelmed by the intensity of situations where children die. CONCLUSION: More benefits than burdens were experienced by both parents and health care professionals from the participation of bereaved parents in the palliative care trainings.

Why do genotypes of Picea glauca differ in their growth response to elevated CO2?

Meta-analyses reveal that fast-growing species have a greater growth response to elevated CO(2) than slow-growing species. It is unknown whether this is a direct response or whether inter-specific differences in growth are simply correlated with other physiological or morphological differences among species that affect the growth response to CO(2). Here we use intra-specific variation in Picea glauca to examine the mechanistic basis for this relationship. Relative growth rate (RGR) of 29 genotypes grown at ambient (370 µl l(-1)) or elevated (740 µl 1(-1)) CO(2) was measured. Physiological and morphological traits describing differences in allocation, canopy structure, stomatal function and photosynthesis were determined. Most variation in RGR (74%) was explained by traits associated with canopy structure. Although there was a strong correlation between RGR(740) and RGR(370), we found no evidence that genotypes that grew fast at ambient CO(2) had a greater relative growth response to CO(2). Given that the pattern found at the intra-specific level differed from that reported at the inter-specific level, our results suggest that RGR per se does not affect the growth response to CO(2). Rather, the CO(2) growth response is determined by traits that may or may not be correlated with RGR.

Recent findings on biosolids cake odor reduction--results of WERF phase 3 biosolids odor research.

The Water Environment Research Foundation (WERF) has sponsored three phases of a long-term project entitled "Identifying and Controlling Odors in the Municipal Wastewater Environment." The current (third) phase focuses on reduction of odors from dewatered biosolids cakes, and is entitled "Biosolids Processing Modifications for Cake Odor Reduction." This phase encompasses nine research agenda items developed from the results of the prior phase of research (Phase 2), which was completed in December 2003 as WERF Report No. 00-HHE-5T and was entitled "Impacts of In-Plant Parameters on Biosolids Odor Quality." The current phase (Phase 3) was a 2.5-year project, the first half of which was dedicated to testing several of the more promising hypotheses from Phase 2 in the laboratory to help determine the cause-effect relationships of odor generation from biosolids, and to develop odor reduction techniques. It is important to note that this research project covers the reduction or prevention of odorous emissions from dewatered biosolids cake, not odor control by means of containment or adsorption or absorption of malodorous emissions. In the remainder of the Phase 3 project, promising laboratory findings are being applied to biosolids handling processes at one or more wastewater treatment plants (WWTPs), with the goal of achieving significant cake odor reduction in a realistic, full-scale setting. The Phase 3 laboratory results were used to identify the relative effectiveness of methods for reducing biosolids cake odors, using techniques and measurements of biosolids cake odor production potential that have been developed by the WERF Project Team. Plans to demonstrate the most promising research findings at full-scale biosolids digestion and dewatering facilities constitute the final, fourth phase of the project. Contacts have been made with wastewater treatment facilities that have an interest or need to reduce their biosolids cake odors. The main goal of the next phase of the project will be to match wastewater or biosolids facilities that need to reduce biosolids odors with specific technologies, chemicals, or biological agents, in order to demonstrate the efficacy of promising laboratory findings full scale at a real WWTP.

High prevalence rates of diabetes and hypertension among refugee psychiatric patients.

There is increasing evidence that immigrants and traumatized individuals have elevated prevalence of medical disease. This study focuses on 459 Vietnamese, Cambodian, Somali, and Bosnian refugee psychiatric patients to determine the prevalence of hypertension and diabetes. The prevalence of hypertension was 42% and of diabetes was 15.5%. This was significantly higher than the US norms, especially in the groups younger than 65. Diabetes and hypertension were higher in the high-trauma versus low-trauma groups. However, in the subsample with body mass index (BMI) measurements subjected to logistic regression, only BMI was related to diabetes, and BMI and age were related to hypertension. Immigrant status, presence of psychiatric disorder, history of psychological trauma, and obesity probably all contributed to the high prevalence rate. With 2.5 million refugees in the country, there is a strong public health concern for cardiovascular disease in this group.

Space cycle: a human-powered centrifuge that can be used for hypergravity resistance training.

INTRODUCTION: This study represents the first step toward testing the hypothesis that hypergravity can be used as a unique resistance training modality for maintaining the health and function of skeletal muscle in microgravity. The primary objectives of this study were to use a human-powered short-arm centrifuge for the following: 1) to determine whether subjects could perform squats under hypergravity conditions without developing motion sickness or illusory motion; 2) to measure foot forces while performing squats under hypergravity conditions; and 3) to determine the mechanical power required to produce 1.5, 2.0, 2.5, and 3.0 Gz (head to foot) at the feet. METHODS: Subjects (22 males and 19 females) performed 10 squats each at 1.5, 2.0, 2.5, and 3.0 Gz on a human-powered short-arm centrifuge, the space cycle. Foot forces during each squat were monitored using insole force sensors, and normalized to foot forces measured at 1 Gz (relative foot forces). RESULTS: Illusory motion was minimized using a visual focal point, and did not affect the ability of subjects to perform squats. The mean standing relative foot forces at 3.0 Gz were 2.3 and 2.4 for the male and female subjects, respectively. The work rate required to power the space cycle was a linear function of Gz, and is well within the aerobic scope of untrained individuals. DISCUSSION: The findings of this study demonstrate that hypergravity can be used as an effective modality for loading skeletal muscle and that subjects can perform squat resistance exercise without developing motion sickness or illusory motion.

Molecular and cellular defects of skeletal muscle in an animal model of acute quadriplegic myopathy.

Muscle denervation and concomitant high-dose dexamethasone treatment in rodents produces characteristic pathologic features of severe muscle atrophy and selective myosin heavy filament (MyHC) depletion, identical to those seen in acute quadriplegic myopathy (AQM), also known as critical illness myopathy. We tested the hypothesis that defective pre-translational processes contribute to the atrophy and selective MyHC depletion in this model. We examined the effects of combined glucocorticoid-denervation treatment on MyHC and actin mRNA populations; we also studied mRNA expression of the myogenic regulatory factors (MRFs), primary transcription factors for MyHC. Adult female rats were subjected to proximal sciatic denervation followed by high-dose dexamethasone (DD) treatment (5 mg/kg body weight daily) for 7 days. Disease controls included rats treated with denervation alone (DN) or dexamethasone alone (DX). At 1 week the plantaris atrophied by approximately 42% in DD muscles. DD treatment resulted in selective MyHC protein depletion; actin protein concentration was not significantly changed. Despite an increase in total RNA concentration in DN and DD muscles, MyHC and actin mRNA concentrations were significantly decreased in these muscles. MyHC mRNA showed a significantly more extensive depletion relative to actin mRNA in DD muscles. Glucocorticoid treatment did not influence a denervation-induced increase in the mRNA expression of the MRFs. We conclude that a deleterious interaction between glucocorticoid and denervation treatments in skeletal muscle is responsible for pre-translational defects that reduce actin and MyHC mRNA substrates in a disproportionate fashion. The resultant selective MyHC depletion contributes to the severe muscle atrophy.

Metastatic adenocarcinoma of prostate in a healing sternotomy site.

Metastatic prostate cancer has a strong predilection for osseous sites, where the disease spreads in 80% of advanced cases. The molecular mechanisms involved in prostate cancer establishment in bone are largely unknown; however, local tissue factors, including those involved in wound healing, have been suggested to play a critical role. We present a case of tumor explosion in a median sternotomy wound after local prostate cancer therapy. This case highlights that novel therapeutic interventions that disrupt the apparent synergistic relationship between tumor cells and the pro-tumorigenic microenvironment may hold great promise in constraining the proliferation of prostate cancer metastases.

Hemodynamic and metabolic responses to hypergravity on a human-powered centrifuge.

INTRODUCTION: Microgravity causes the deconditioning of many physiological systems, and there is great interest in developing effective countermeasures. We recently developed a short-arm human-powered centrifuge, and the primary objective of this study was to assess the hemodynamic and metabolic responses to exercise under hypergravity conditions. METHODS: Phase I compared the hemodynamic and metabolic responses to 1 Gz (upright cycle ergometry) and 2 Gz conditions (Space Cycle) at the same work rate. Phase II contrasted the hemodynamic and metabolic responses at 2 and 3 Gz and at the same work rate. Phase III examined the BP and heart rate (HR) responses during passive and active centrifugation. Phase IV examined the relationship between work rate and oxygen uptake. RESULTS: In Phase I, the HR and BP responses were very similar between the two Gz conditions, with the exception that 2 Gz produced a lower diastolic BP in female subjects. In Phase II, both systolic and diastolic BPs were similar under the two different Gz conditions. However, there was a significant increase in HR at 3 Gz. In Phase III, the slope of the HR/Gz relationship was greater for passive conditions, suggesting that venous return is facilitated by the skeletal muscle pump. In Phase IV, it was found that there was a highly linear relationship between work rate and oxygen uptake. CONCLUSION: The results of this study demonstrate that exercise under low hypergravity conditions on the Space Cycle is well tolerated from a hemodynamic perspective.

Effects of distraction on muscle length: mechanisms involved in sarcomerogenesis.

Although a great deal of interest has been given to understanding the mechanisms involved in regulating the radial growth that occurs because of resistance training, much less has been given to studying the longitudinal growth of skeletal muscle that occurs because of passive stretch. The current authors provide a brief overview of key issues relevant to the longitudinal growth of skeletal muscle that occurs during distraction osteogenesis. Specifically, five key issues are addressed: (1) the pattern of sarcomerogenesis during distraction; (2) sarcomerogenesis and altered expression of sarcomeric and nonsarcomeric genes; (3) the satellite cell hypothesis; (4) mitogenic factors; and (5) new approaches for studying the longitudinal growth of skeletal muscle. A discussion is provided that revolves around the concept of a negative feedback loop. One of the most interesting issues to be resolved in muscle biology is the role of satellite cells in regulating the growth of skeletal muscle. Currently, it is not known whether satellite cell activation is a prerequisite for the longitudinal growth of skeletal muscle. Gene chip analyses provide a paradoxical view, showing that distraction osteogenesis results in the upregulation of a gene, GADD45, involved with growth arrest and deoxyribonucleic acid destruction.