Does preoperative calcium and 1, 25 OH vitamin D supplementation impact postoperative hypocalcemia and length of stay following pediatric thyroidectomy?

OBJECTIVE: To investigate whether perioperative calcium and 1,25 OH vitamin D supplementation (PCDS) influences the rates of postoperative hypocalcemia and length of stay (LOS) following pediatric thyroidectomy. STUDY DESIGN: Retrospective Cohort Review. SETTING: Tertiary children's hospital. METHODS: 94 patients who underwent completion or total thyroidectomy with or without concomitant neck dissection from 2010 to 2020 at a single institution were included. Patients with pre-existing hypocalcemia or preoperative vitamin D insufficiency were excluded. Rates of postoperative hypocalcemia and LOS were compared for patients receiving PCDS to those receiving no supplementation. RESULTS: Thirty percent of patients with PCDS had documented postoperative hypocalcemia compared to 64% of patients without PCDS (p = 0.01). Patients with PCDS had a median LOS of 30 h compared to 36 h (p = 0.002). Multivariable analyses confirmed that patients with PCDS had lower odds of postoperative hypocalcemia (OR: 0.32, CI: 0.11, 0.89) and shorter LOS by 17 h (SE: 8, p = 0.04) after adjustment for confounders. CONCLUSION: PCDS is associated with significantly lower risk of hypocalcemia and shorter LOS. Standardizing preoperative care for pediatric patients undergoing thyroidectomy may decrease variability and improve outcomes following surgery.

Airway disease decreases the therapeutic potential of epithelial stem cells.

BACKGORUND: Tissue-engineered tracheal grafts (TETG) can be recellularized by the host or pre-seeded with host-derived cells. However, the impact of airway disease on the recellularization process is unknown. METHODS: In this study, we determined if airway disease alters the regenerative potential of the human tracheobronchial epithelium (hTBE) obtained by brushing the tracheal mucosa during clinically-indicated bronchoscopy from 48 pediatric and six adult patients. RESULTS: Our findings revealed that basal cell recovery and frequency did not vary by age or region. At passage 1, all samples produced enough cells to cellularize a 3.5 by 0.5 cm2 graft scaffold at low cell density (~ 7000 cells/cm2), and 43.75% could cellularize a scaffold at high cell density (~ 100,000 cells/cm2). At passage 2, all samples produced the number of cells required for both recellularization models. Further evaluation revealed that six pediatric samples (11%) and three (50%) adult samples contained basal cells with a squamous basal phenotype. These cells did not form a polarized epithelium or produce differentiated secretory or ciliated cells. In the pediatric population, the squamous basal cell phenotype was associated with degree of prematurity (< 28 weeks, 64% vs. 13%, p = 0.02), significant pulmonary history (83% vs. 34%, p = 0.02), specifically with bronchopulmonary dysplasia (67% vs. 19%, p = 0.01), and patients who underwent previous tracheostomy (67% vs. 23%, p = 0.03). CONCLUSIONS: In summary, screening high-risk pediatric or adult population based on clinical risk factors and laboratory findings could define appropriate candidates for airway reconstruction with tracheal scaffolds. LEVEL OF EVIDENCE: Level III Cohort study.

Association of Vibrotactile Biofeedback With Reduced Ergonomic Risk for Surgeons During Tonsillectomy.

Importance: Work-related musculoskeletal disorders are common among otolaryngologists and can be associated with decreased productivity, missed workdays, and reduced quality of life. Ergonomic risk for surgeons is elevated during common otolaryngology procedures; current ergonomic interventions lack the ability to provide real-time feedback. The ability to quantify and mitigate ergonomic risk during surgery may reduce work-related musculoskeletal disorders. Objective: To quantify the association of vibrotactile biofeedback with intraoperative ergonomic risk to surgeons during tonsillectomy. Design, Setting, and Participants: This cross-sectional study was conducted between June 2021 and October 2021 at a freestanding tertiary care children's hospital and included 11 attending pediatric otolaryngologists. Data analysis was conducted from August to October 2021. Interventions: Real-time quantification of ergonomic risk during tonsillectomy and the use of a vibrotactile biofeedback posture monitor. Main Outcomes and Measures: Association of vibrotactile biofeedback with objective measures of ergonomic risk. Assessment tools included the Rapid Upper Limb Assessment, craniovertebral angle, and time spent in an at-risk posture. Results: Eleven surgeons (mean [SD] age 42 [7] years; 2 women [18%]) performed 126 procedures with continuous posture monitoring in the presence (80 [63%]) and absence (46 [37%]) of vibrotactile biofeedback. No complications or delays associated with the device were reported. Intraoperative vibrotactile biofeedback was associated with improved Rapid Upper Limit Assessment neck, trunk, and leg scores by 0.15 (95% CI, 0.05-0.25), improved craniovertebral angle by 1.9 (95% CI, 0.32-3.40), and decreased overall time spent in an at-risk posture by 30% (95% CI, 22%-39%). Conclusions and Relevance: The results of this cross-sectional study suggest that use of a vibrotactile biofeedback device to quantify and mitigate ergonomic risk for surgeons is feasible and safe while performing surgery. Vibrotactile biofeedback was associated with reduced ergonomic risk during tonsillectomy and may have a role in improving surgical ergonomics and preventing work-related musculoskeletal disorders.

Dynamic Volumetric Computed Tomography Angiography is an Effective Method to Evaluate Tracheomalacia in Children.

OBJECTIVE: Standard methods to evaluate tracheal pathology in children, including bronchoscopy, may require general anesthesia. Conventional dynamic proximal airway imaging in noncooperative children requires endotracheal intubation and/or medically induced apnea, which may affect airway mechanics and diagnostic performance. We describe a technique for unsedated dynamic volumetric computed tomography angiography (DV-CTA) of the proximal airway and surrounding vasculature in children and evaluate its performance compared to the reference-standard of rigid bronchoscopy. METHODS: Children who had undergone DV-CTA and bronchoscopy in one-year were retrospectively identified. Imaging studies were reviewed by an expert reader blinded to the bronchoscopy findings of primary or secondary tracheomalacia. Airway narrowing, if present, was characterized as static and/or dynamic, with tracheomalacia defined as >50% collapse of the tracheal cross-sectional area in exhalation. Pearson correlation was used for comparison. RESULTS: Over a 19-month period, we identified 32 children (median age 8 months, range 3-14 months) who had undergone DV-CTA and bronchoscopy within a 90-day period of each other. All studies were unsedated and free-breathing. The primary reasons for evaluation included noisy breathing, stridor, and screening for tracheomalacia. There was excellent agreement between DV-CTA and bronchoscopy for diagnosis of tracheomalacia (κ = 0.81, p < 0.001), which improved if children (n = 25) had the studies within 30 days of each other (κ = 0.91, p < 0.001). CTA provided incremental information on severity, and cause of secondary tracheomalacia. CONCLUSION: For most children, DV-CTA requires no sedation or respiratory manipulation and correlates strongly with bronchoscopy for the diagnosis of tracheomalacia. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:410-416, 2023.

Biobanked tracheal basal cells retain the capacity to differentiate.

Objective: While airway epithelial biorepositories have established roles in the study of bronchial progenitor stem (basal) cells, the utility of a bank of tracheal basal cells from pediatric patients, who have or are suspected of having an airway disease, has not been established. In vitro study of these cells can enhance options for tracheal restoration, graft design, and disease modeling. Development of a functional epithelium in these settings is a key measure. The aim of this study was the creation a tracheal basal cell biorepository and assessment of recovered cells. Methods: Pediatric patients undergoing bronchoscopy were identified and endotracheal brush (N = 29) biopsies were collected. Cells were cultured using the modified conditional reprogramming culture (mCRC) method. Samples producing colonies by day 14 were passaged and cryopreserved. To explore differentiation potential, cells were thawed and differentiated using the air-liquid interface (ALI) method. Results: No adverse events were associated with biopsy collection. Of 29 brush biopsies, 16 (55%) were successfully cultured to passage 1/cryopreserved. Samples with higher initial cell yields were more likely to achieve this benchmark. Ten unique donors were then thawed for analysis of differentiation. The average age was 2.2 ± 2.2 years with five donors (50%) having laryngotracheal pathology. Nine donors (90%) demonstrated differentiation capacity at 21 days of culture, as indicated by detection of ciliated cells (ACT+) and mucous cells (MUC5B+). Conclusion: Pediatric tracheal basal cells can be successfully collected and cryopreserved. Recovered cells retain the ability to differentiate into epithelial cell types in vitro. Level of Evidence: Level 3.

Organotypic stromal cells impact endothelial cell transcriptome in 3D microvessel networks.

Endothelial cells line all major blood vessels and serve as integral regulators of many functions including vessel diameter, cellular trafficking, and transport of soluble mediators. Despite similar functions, the phenotype of endothelial cells is highly organ-specific, yet our understanding of the mechanisms leading to organ-level differentiation is incomplete. We generated 3D microvessel networks by combining a common naïve endothelial cell with six different stromal cells derived from the lung, skin, heart, bone marrow, pancreas, and pancreatic cancer. Single cell RNA-Seq analysis of the microvessel networks reveals five distinct endothelial cell populations, for which the relative proportion depends on the stromal cell population. Morphologic features of the organotypic vessel networks inversely correlate with a cluster of endothelial cells associated with protein synthesis. The organotypic stromal cells were each characterized by a unique subpopulation of cells dedicated to extracellular matrix organization and assembly. Finally, compared to cells in 2D monolayer, the endothelial cell transcriptome from the 3D in vitro heart, skin, lung, and pancreas microvessel networks are more similar to the in vivo endothelial cells from the respective organs. We conclude that stromal cells contribute to endothelial cell and microvessel network organ tropism, and create an endothelial cell phenotype that more closely resembles that present in vivo.

Lumbar spine intervertebral disc gene delivery of BMPs induces anterior spine fusion in lewis rats.

Minimally invasive techniques and biological autograft alternatives such as the bone morphogenetic proteins (BMPs) can reduce morbidity associated with spinal fusions. This study was a proof-of-concept for gene-therapy-mediated anterior spine fusion that could be adapted to percutaneous technique for clinical use. Isogeneic bone marrow stromal cells genetically programmed to express b-galactosidase (LACZ, a marker gene), BMP2, BMP7, a mixture of BMP2 and BMP7 infected cells (homodimers, HM), or BMP2/7 heterodimers (HT) were implanted into the discs between lumbar vertebrae 4 and 5 (L4/5) and L5/6 of male Lewis rats. Spine stiffening was monitored at 4, 8 and 12 weeks using noninvasive-induced angular displacement (NIAD) testing. At 12 weeks isolated spines were assessed for fusion and bone formation by palpation, biomechanical testing [four-point bending stiffness, moment to failure in extension, and in vitro angular displacement (IVAD)], faxitron x-rays, microCT, and histology. Progressive loss of NIAD occurred in only the HT group (p < 0.001), and biomechanical tests correlated with the NIAD results. Significant fusion occurred only in the HT group (94% of animals with one or both levels) as assessed by palpation (p < 0.001), which predicted HT bone production assessed by faxitron (p ≤ 0.001) or microCT (p < 0.023). Intervertebral bridging bone was consistently observed only in HT-treated specimens. Induced bone was located anterior and lateral to the disc space, with no bone formation noted within the disc. Percutaneous anterior spine fusions may be possible clinically, but induction of bone inside the disc space remains a challenge.

Bone mass and adaptation to mechanical loading are sexually dimorphic in adult osteoblast-specific ERα knockout mice.

Estrogen receptor-alpha (ERα) regulates bone mass and is implicated in bone tissue's response to mechanical loading. The effects of ERα deletion in mice depend on sex, anatomical location, and the cellular stage at which ERα is removed. Few studies have investigated the effect of age on the role of ERα in skeletal maintenance and functional adaptation. We previously demonstrated that bone mass and adaptation to loading were altered in growing 10-week-old female and male mice lacking ERα in mature osteoblasts and osteocytes (pOC-ERαKO). Here our goal was to determine the effects of ERα and mechanical loading in skeletally-mature adult mice. We subjected 26-week-old skeletally-mature adult pOC-ERαKO and littermate control (LC) mice of both sexes to two weeks of in vivo cyclic tibial loading. ERα deletion in male mice did not alter bone mass or the response to loading. Adult female pOC-ERαKO mice had reduced cancellous and cortical bone mass and increased adaptation to high-magnitude mechanical loading compared to LC mice. Thus, ERα deletion from mature osteoblasts reduced the bone mass and increased the mechanoadaptation of adult female but not male mice. Additionally, compared to our previous work in young mice, adult female mice had greatly reduced mechanoadaptation and adult male mice retained most of their mechanoadaptation with age.

Assessing the use of telehealth for the surgical management of recurrent otitis media.

OBJECTIVE: To compare the incidence of middle ear effusion (MEE) at the time of bilateral tympanostomy tube insertion (BTI) for recurrent acute otitis media (rAOM) patients initially seen in-office or via telehealth. METHODS: After obtaining IRB approval from Nationwide Children's Hospital, a total of 524 patients evaluated for rAOM were retrospectively reviewed after being divided into two cohorts: those seen via a telehealth visit from April to June of 2020 (n = 140), and those seen via an in-person visit from April to June of 2019 (n = 384). Recommendation for BTI was captured for each patient following their visit. Clinical characteristics documented at the time of the visit, such as history of intramuscular (IM) antibiotic use and hearing or speech concerns were also captured to determine whether both telehealth and in-person cohorts were similar in clinical presentation. For BTI patients, the presence or absence of MEE in either ear at the time of BTI was recorded. Patients with cleft palate or prior BTI were excluded. RESULTS: 51.43% (72/140) of patients in the telehealth cohort were recommended for BTI. Of those recommended, 87.50% (63/72) underwent BTI. Of these, 31.75% (20/63) had a MEE at the time of BTI. In the in-office cohort, 69.01% (265/384) of patients were recommended for BTI. Of those recommended, 92.83% (246/265) underwent BTI. Of these, 69.92% (172/246) had a MEE at the time of BTI. CONCLUSION: There were significantly less middle ear effusions in the telehealth cohort compared to the in-office cohort (p < 0.0001). It is well understood that telehealth is limited in its physical exam capabilities. It is possible that the use of telehealth for the surgical management of rAOM may lead to more procedures on patients without MEE.

Using the Craniovertebral Angle to Quantify Intraoperative Ergonomic Risk.

OBJECTIVE: To measure the craniovertebral angle during tonsillectomy, assess the interrater reliability of our methodology, and investigate the correlations of the Rapid Upper Limb Assessment and the craniovertebral angle to quantify ergonomic risk. STUDY DESIGN: Prospective, observational study. SETTING: Tertiary care pediatric institution. METHODS: Neck posture was evaluated for 92 images with 7 surgeons. Lateral images of the surgeon were captured every minute in a standardized method. Images were assessed by 3 raters, measuring the craniovertebral angle, defined as the angle between a horizontal line through the C7 vertebrae and another line through C7 and the tragus of the ear. Interrater reliability of the craniovertebral angle was evaluated using the κ statistic. Per prior publications, reports of neck pain were frequent when the craniovertebral angle value was <50°; thus, we defined an abnormal posture if the craniovertebral angle was <50°. RESULTS: Mean (SD) craniovertebral angle during tonsillectomy was 26.0° (11.3°). One hundred percent of procedures had at least 1 assessment of abnormal posture. The lowest interrater reliability was 0.77 (CI: 0.67-0.87). Rapid Upper Limb Assessment and craniovertebral angle (CA) correlation was -0.12 (P = .27) and, therefore, null. CONCLUSION: Poor posture during tonsillectomy places otolaryngologists at intraoperative ergonomic risk. The craniovertebral angle is a predictor of future neck pain, and a pathologic neck position during tonsillectomy was identified. Given the high interrater reliability, our approach to assessing intraoperative surgical ergonomics was validated. Overall, RULA and the CA are not a substitute for one another but complementary.

Reduction of Distress and Attrition in a 6-Week Psychoeducational Group: A Pilot Study.

Purpose: The distress and unique needs of AYAs (adolescent/young adults) with an oncology diagnosis have been well explored and documented in the literature. However, effective means of reducing distress and meeting needs has been more elusive. This study explored the impact of a 6-week psychoeducational pilot group on AYA distress. Methods: Patient surveys and literature review were conducted to develop content for a 6-week psychoeducational group to reduce AYA distress through peer support and increased knowledge related to symptom management, physician communication, body image, family relationships, autonomy, sexuality, fertility, and coping skills. Distress was measured using the Hospital Anxiety and Depression Scale (HADS). Results: Twenty-one AYAs receiving oncology treatment enrolled in the group. Thirteen completed the program. Reasons for attrition included transportation, severity of symptoms, procedures, disinterest, and death. A correlated t-test demonstrated a significant decrease in HADS total score from pre- to post-test. Conclusion: This pilot study suggests that providing AYAs with information relative to their unique developmental needs and opportunities to process those needs in an environment of peers is challenging but can have benefit. nCT01817335.

Low bone mass resulting from impaired estrogen signaling in bone increases severity of load-induced osteoarthritis in female mice.

OBJECTIVE: Reduced subchondral bone mass and increased remodeling are associated with early stage OA. However, the direct effect of low subchondral bone mass on the risk and severity of OA development is unclear. We sought to determine the role of low bone mass resulting from a bone-specific loss of estrogen signaling in load-induced OA development using female osteoblast-specific estrogen receptor-alpha knockout (pOC-ERαKO) mice. METHODS: Osteoarthritis was induced by cyclic mechanical loading applied to the left tibia of 26-week-old female pOC-ERαKO and littermate control mice at peak loads of 6.5N, 7N, or 9N for 2 weeks. Cartilage damage and thickness, osteophyte development, and joint capsule fibrosis were assessed from histological sections. Subchondral bone morphology was analyzed by microCT. The correlation between OA severity and intrinsic bone parameters was determined. RESULTS: The loss of ERα in bone resulted in an osteopenic subchondral bone phenotype, but did not directly affect cartilage health. Following two weeks of cyclic tibial loading to induce OA pathology, pOC-ERαKO mice developed more severe cartilage damage, larger osteophytes, and greater joint capsule fibrosis compared to littermate controls. Intrinsic bone parameters negatively correlated with measures of OA severity in loaded limbs. CONCLUSIONS: Subchondral bone osteopenia resulting from bone-specific loss of estrogen signaling was associated with increased severity of load-induced OA pathology, suggesting that reduced subchondral bone mass directly exacerbates load-induced OA development. Bone-specific changes associated with estrogen loss may contribute to the increased incidence of OA in post-menopausal women.

The Role of Collagen-Based Biomaterials in Chronic Wound Healing and Sports Medicine Applications.

Advancements in tissue engineering have taken aim at treating tissue types that have difficulty healing naturally. In order to achieve improved healing conditions, the balance of exogenous matrix, cells, and different factors must be carefully controlled. This review seeks to explore the aspects of tissue engineering in specific tissue types treated in sports medicine and advanced wound management from the perspective of the matrix component. While the predominant material to be discussed is collagen I, it would be remiss not to mention its relation to the other contributing factors to tissue engineered healing. The main categories of materials summarized here are (1) reconstituted collagen scaffolds, (2) decellularized matrix tissue, and (3) non-decellularized tissue. These three groups are ordered by their increase in additional components beyond simply collagen.

Validation of presence-only models for conservation planning and the application to whales in a multiple-use marine park.

Identification of species' Biologically Important Areas (BIAs) is fundamental to conservation planning and species distribution models (SDMs) are a powerful tool commonly used to do this. Presence-only data are increasingly being used to develop SDMs to aid the conservation decision-making process. The application of presence-only SDMs for marine species' is particularly attractive due to often logistical and economic costs of obtaining systematic species' distribution data. However, robust model validation is important for conservation management applications that require accurate and reliable species' occurrence data (e.g., spatially explicit risk assessments). This is commonly done using a random subset of the data and less commonly with fully independent test data. Here, we apply a spatial block cross-validation (CV) approach to validate a MaxEnt presence-only model using independent presence/absence survey data for a highly mobile, marine species (humpback whale, Megaptera novaengliae) in the Great Barrier Reef (GBR). A MaxEnt model was developed using opportunistic whale sightings (2003-2007) and then used to identify areas differing in habitat suitability (low, medium, high) to conduct a systematic, line-transect, aerial survey (2012) and derive a density surface model. A spatial block CV buffering strategy was used to validate the MaxEnt model, using the opportunistic sightings as training data and independent aerial survey sightings data as test data. Moderate performance measures indicate MaxEnt was reliable in identifying the distribution patterns of a mobile whale species on their breeding ground, indicated by areas of high density aligned to areas of high habitat suitability. Furthermore, we demonstrate that MaxEnt models can be useful and cost-effective for designing a sampling scheme to undertake systematic surveys that significantly reduces sampling effort. In this study, higher quality information on whale reproductive class (calf vs. non-calf groups) was obtained that the presence-only data lacked, while sampling only 18% of the GBR World Heritage Area. The validation approach using fully independent data provides greater confidence in the MaxEnt model, which indicates significant overlap with the main breeding ground of humpback whales and the inner shipping route. This is important when evaluating presence-only models within certain conservation management applications, such as spatial risk assessments.

Adaptation of an Intervention to Reduce Disparities in School HRQOL for Latino Childhood Cancer Survivors.

OBJECTIVE: Survivors of childhood leukemia, especially those from low socioeconomic status households, often experience persistent neurocognitive and academic impairment. This study adapted an existing parent training intervention to improve outcomes for low-acculturated, Spanish-speaking Latino parents of children with leukemia and pilot tested that intervention for feasibility. METHODS: Semistructured interviews were conducted with a focus group of 20 Latino parents of children treated for leukemia. Ten Latino families participated in a pilot study of the adapted parenting intervention, consisting of eight sessions over 6 months. RESULTS: Focus groups revealed that parents unanimously supported a parenting intervention but barriers to participation included time constraints, transportation issues, and anxiety in the hospital environment. The parents also highlighted cultural factors that could contribute to the health disparity, such as lack of knowledge and efficacy in facilitating their child's progress with learning and school. In the pilot study, adherence was 90%, establishing feasibility, and the adapted intervention was considered beneficial. The median parenting efficacy scores improved from preintervention to postintervention (median 3.40 vs. 3.94; p < .011), as did parent-reported school functioning of the child (median 50.00 vs. 60.00; p = .088). CONCLUSIONS: This study addressed a health disparity by culturally adapting a parenting intervention, which was designed to improve school functioning, to meet the needs and preferences of low-acculturated, Spanish-speaking families of children with leukemia in Southern California. The pilot study demonstrated that the adapted intervention is feasible and acceptable in the target population. A larger trial is underway to test the efficacy of this adapted parenting intervention.

Quantitative Assessment of Surgical Ergonomics in Otolaryngology.

OBJECTIVES: Objective evaluation of the ergonomic risk of common otolaryngology procedures and assessment of work-related musculoskeletal pain and injury. STUDY DESIGN: Cross-sectional intraoperative assessment and survey. SETTING: Department of Otolaryngology at a tertiary children's hospital. SUBJECTS AND METHODS: Sixteen otolaryngology attendings, fellows, and residents participated in a blinded study. Intraoperative ergonomics was assessed for tonsillectomies, adenoidectomies, and tympanostomy tube insertions using the Rapid Upper Limb Assessment (RULA). Follow-up surveys were sent to all participating surgeons to determine the prevalence of musculoskeletal pain and formal ergonomic training. RESULTS: Zero percent (N = 0/275) of intraoperative observations were found to have a negligible level of ergonomic risk, with 47% low risk, 37% high risk, and 16% very high risk. Tympanostomy tube insertions conferred less risk than tonsillectomy and adenoidectomy, while the use of headlamp or loupes conferred increased risk. Eighty percent of respondents reported having musculoskeletal pain and 40% reported experiencing pain while operating within the past year. The most common area of pain was the cervical spine. No surgeons reported formal ergonomic training. CONCLUSIONS: Our study demonstrates an unacceptable level of ergonomic risk for common procedures in otolaryngology. Furthermore, most participants reported experiencing musculoskeletal pain despite the duration of examined procedures being relatively short. The high prevalence of work-related musculoskeletal pain and the lack of ergonomic training in our cohort highlight the need for increased awareness of ergonomics as well as the development of formal ergonomic curricula.

Single cell RNA-sequencing reveals cellular heterogeneity and trajectories of lineage specification during murine embryonic limb development.

The coordinated spatial and temporal regulation of gene expression in the murine hindlimb determines the identity of mesenchymal progenitors and the development of diversity of musculoskeletal tissues they form. Hindlimb development has historically been studied with lineage tracing of individual genes selected a priori, or at the bulk tissue level, which does not allow for the determination of single cell transcriptional programs yielding mature cell types and tissues. To identify the cellular trajectories of lineage specification during limb bud development, we used single cell mRNA sequencing (scRNA-seq) to profile the developing murine hindlimb between embryonic days (E)11.5-E18.5. We found cell type heterogeneity at all time points, and the expected cell types that form the mouse hindlimb. In addition, we used RNA fluorescence in situ hybridization (FISH) to examine the spatial locations of cell types and cell trajectories to understand the ancestral continuum of cell maturation. This data provides a resource for the transcriptional program of hindlimb development that will support future studies of musculoskeletal development and generate hypotheses for tissue regeneration.

Descriptive Usability Study of CirrODS: Clinical Decision and Workflow Support Tool for Management of Patients With Cirrhosis.

BACKGROUND: There are gaps in delivering evidence-based care for patients with chronic liver disease and cirrhosis. OBJECTIVE: Our objective was to use interactive user-centered design methods to develop the Cirrhosis Order Set and Clinical Decision Support (CirrODS) tool in order to improve clinical decision-making and workflow. METHODS: Two work groups were convened with clinicians, user experience designers, human factors and health services researchers, and information technologists to create user interface designs. CirrODS prototypes underwent several rounds of formative design. Physicians (n=20) at three hospitals were provided with clinical scenarios of patients with cirrhosis, and the admission orders made with and without the CirrODS tool were compared. The physicians rated their experience using CirrODS and provided comments, which we coded into categories and themes. We assessed the safety, usability, and quality of CirrODS using qualitative and quantitative methods. RESULTS: We created an interactive CirrODS prototype that displays an alert when existing electronic data indicate a patient is at risk for cirrhosis. The tool consists of two primary frames, presenting relevant patient data and allowing recommended evidence-based tests and treatments to be ordered and categorized. Physicians viewed the tool positively and suggested that it would be most useful at the time of admission. When using the tool, the clinicians placed fewer orders than they placed when not using the tool, but more of the orders placed were considered to be high priority when the tool was used than when it was not used. The physicians' ratings of CirrODS indicated above average usability. CONCLUSIONS: We developed a novel Web-based combined clinical decision-making and workflow support tool to alert and assist clinicians caring for patients with cirrhosis. Further studies are underway to assess the impact on quality of care for patients with cirrhosis in actual practice.

Aerial surveys for Antarctic minke whales (Balaenoptera bonaerensis) reveal sea ice dependent distribution patterns.

This study investigates the distribution of Antarctic minke whales (AMW) in relation to sea ice concentration and variations therein. Information on AMW densities in the sea ice-covered parts of the Southern Ocean is required to contextualize abundance estimates obtained from circumpolar shipboard surveys in open waters, suggesting a 30% decline in AMW abundance. Conventional line-transect shipboard surveys for density estimation are impossible in ice-covered regions, therefore we used icebreaker-supported helicopter surveys to obtain information on AMW densities along gradients of 0%-100% of ice concentration. We conducted five helicopter surveys in the Southern Ocean, between 2006 and 2013. Distance sampling data, satellite-derived sea-ice data, and bathymetric parameters were used in generalized additive models (GAMs) to produce predictions on how the density of AMWs varied over space and time, and with environmental covariates. Ice concentration, distance to the ice edge and distance from the shelf break were found to describe the distribution of AMWs. Highest densities were predicted at the ice edge and through to medium ice concentrations. Medium densities were found up to 500 km into the ice edge in all concentrations of ice. Very low numbers of AMWs were found in the ice-free waters of the West Antarctic Peninsula (WAP). A consistent relationship between AMW distribution and sea ice concentration weakens the support for the hypothesis that varying numbers of AMWs in ice-covered waters were responsible for observed changes in estimated abundance. The potential decline in AMW abundance stresses the need for conservation measures and further studies into the AMW population status. Very low numbers of AMWs recorded in the ice-free waters along the WAP support the hypothesis that this species is strongly dependent on sea ice and that forecasted sea ice changes have the potential of heavily impacting AMWs.

Incorporating Guideline Adherence and Practice Implementation Issues into the Design of Decision Support for Beta-Blocker Titration for Heart Failure.

BACKGROUND: The recognition of and response to undertreatment of heart failure (HF) patients can be complicated. A clinical reminder can facilitate use of guideline-concordant ß-blocker titration for HF patients with depressed ejection fraction. However, the design must consider the cognitive demands on the providers and the context of the work. OBJECTIVE: This study's purpose is to develop requirements for a clinical decision support tool (a clinical reminder) by analyzing the cognitive demands of the task along with the factors in the Cabana framework of physician adherence to guidelines, the health information technology (HIT) sociotechnical framework, and the Promoting Action on Research Implementation in Health Services (PARIHS) framework of health services implementation. It utilizes a tool that extracts information from medical records (including ejection fraction in free text reports) to identify qualifying patients at risk of undertreatment. METHODS: We conducted interviews with 17 primary care providers, 5 PharmDs, and 5 Registered Nurses across three Veterans Health Administration outpatient clinics. The interviews were based on cognitive task analysis (CTA) methods and enhanced through the inclusion of the Cabana, HIT sociotechnical, and PARIHS frameworks. The analysis of the interview data led to the development of requirements and a prototype design for a clinical reminder. We conducted a small pilot usability assessment of the clinical reminder using realistic clinical scenarios. RESULTS: We identified organizational challenges (such as time pressures and underuse of pharmacists), knowledge issues regarding the guideline, and information needs regarding patient history and treatment status. We based the design of the clinical reminder on how to best address these challenges. The usability assessment indicated the tool could help the decision and titration processes. CONCLUSION: Through the use of CTA methods enhanced with adherence, sociotechnical, and implementation frameworks, we designed a decision support tool that considers important challenges in the decision and execution of ß-blocker titration for qualifying HF patients at risk of undertreatment.