A modular microfluidic device that uses magnetically actuatable microposts for enhanced magnetic bead-based workflows.

Magnetic beads have been widely and successfully used for target enrichment in life science assays. There exists a large variety of commercially available magnetic beads functionalized for specific target capture, as well as options that enable simple surface modifications for custom applications. While magnetic beads are ideal for use in the macrofluidic context of typical laboratory workflows, their performance drops in microfluidic contexts, such as consumables for point-of-care diagnostics. A primary cause is the diffusion-limited analyte transport in these low Reynolds number environments. A new method, BeadPak, uses magnetically actuatable microposts to enhance analyte transport, improving yield of the desired targets. Critical parameters were defined for the operation of this technology and its performance characterized in canonical life-science assays. BeadPak achieved up to 1000× faster capture than a microfluidic chamber relying on diffusion alone, enabled a significant specimen concentration via volume reduction, and demonstrated compatibility with a range of biological specimens. The results shown in this work can be extended to other systems that utilize magnetic beads for target capture, concentration, and/or purification.

Adolescent abdominal pain due to rare mullerian duct anomaly.

Abdominal pain is a common presenting complaint to the Emergency Department (ED). Often, rare etiologies can be discovered in the work up of this common complaint. Here we present the case of an adolescent female who presented with abdominal pain and was found to have obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) or Herlyn-Werner-Wunderlich Syndrome. A 12 year old female with known renal agenesis presented with 5 days of left sided abdominal pain that then developed into right lower quadrant pain. She had regular menses for the last 2 years. Ultrasound (US) showed a fluid collection in the lower uterine segment and a complex cystic structure anterior to the uterus. Magnetic resonance imaging (MRI) showed the patient to have didelphys uterus with "severe dilatation of the cervix/vaginal canal… extending from the right uterine horn" and left-sided ovarian and Fallopian tube torsion. She was taken to the operating room where she underwent vaginal septum excision and a left salpingo-oopherectomy. OHVIRA includes the triad of obstructed hemivagina, uterine didelphys, and ipsilateral renal agenesis. This occurs due to embryologic arrest of the mullerian and mesonephric ducts at 8 weeks of gestation. Most abnormalities are right sided which leads to right lower abdominal and pelvic pain approximately 4 months post-menarche. Diagnosis of OHVIRA is made utilizing US and CT scans. MRI can also be useful to further delineate specific anatomy. It is important for the emergency physician to be aware of this entity as most patients don't present to care until acute, severe symptoms develop. This makes it more likely for them to seek care in the ED as opposed to the outpatient setting.

Spontaneous isolated celiac and splenic artery dissection with splenic infarction.

Spontaneous isolated celiac artery dissection is considered an uncommon clinical condition. Rarer still is spontaneous isolated celiac and splenic artery dissection, with a total of 42 reported cases. There is no known definitive cause of visceral artery dissections, but risk factors include male sex, age in 5th or 6th decade, hypertension, and connective tissue disorders. The presentation varies, diagnosis is principally radiographic, and the mainstay of treatment is anticoagulation or antiplatelet therapy. Splenic infarction is a common finding with splenic artery dissection, although the strength of this association has not previously been reported. Herein we present a case of spontaneous isolated celiac and splenic artery dissection with splenic infarction that was successfully managed with blood pressure control and antiplatelet therapy. We review previous literature, principles of diagnosis and management, and incidence and outcomes of splenic infarction as it related to splenic artery dissection.

Pediatric chest pain: using evidence to reduce diagnostic testing in the emergency department.

Pediatric chest pain is a relatively common presenting complaint, but identifying serious pathologies without overtesting patients with less-serious pathologies can be a challenge for emergency clinicians. This issue reviews the available literature to provide evidence-based recommendations to support a more standardized approach to the evaluation and management of pediatric patients with chest pain. This issue will help the emergency clinician identify red flags associated with cardiac causes of pediatric chest pain, recognize life-threatening causes of cardiac and non- cardiac chest pain, clinically diagnose the most common causes of non-cardiac chest pain, and appropriately utilize diagnostic tests in the evaluation of chest pain patients.

Clinical Spectrum of Pediatric Heat Illness and Heatstroke in a North American Desert Climate.

ABSTRACT: The spectrum of historical features and clinical presentations of heat illness and heatstroke in the pediatric population has received limited focus in the emergency medicine literature. The majority of published cases involve children trapped in closed spaces and adolescent athletes undergoing high-intensity training regimens in geographical regions with moderately high ambient temperatures and high humidity. There has been less research on the potential impact of extreme temperatures and radiant heat that are the hallmarks of the US southwest region. We performed a retrospective review of pediatric heat illness at our facility located in a North American desert climate.

Mixing and oxygen transfer characteristics of a microplate bioreactor with surface-attached microposts.

Bioprocess optimization for cell-based therapies is a resource heavy activity. To reduce the associated cost and time, process development may be carried out in small volume systems, with the caveat that such systems be predictive for process scale-up. The transport of oxygen from the gas phase into the culture medium, characterized using the volumetric mass transfer coefficient, kL a, has been identified as a critical parameter for predictive process scale-up. Here, we describe the development of a 96-well microplate with integrated Redbud Posts to provide mixing and enhanced kL a. Mixing in the microplate is characterized by observation of dyes and analyzed using the relative mixing index (RMI). The kL a is measured via dynamic gassing out method. Actuating Redbud Posts are shown to increase rate of planar homogeneity (2 min) verse diffusion alone (120 min) and increase oxygenation, with increasing stirrer speed (3500-9000 rpm) and decreasing fill volume (150-350 µL) leading to an increase in kL a (4-88 h-1 ). Significant increase in Chinese Hamster Ovary growth in Redbud Labs vessel (580,000 cells mL-1 ) versus the control (420,000 cells mL-1 ); t(12.814) = 8.3678, p ≤ .001), and CD4+ Naïve cell growth in the microbioreactor indicates the potential for this technology in early stage bioprocess development and optimization.

Rapid and severe neurologic deterioration due to influenza associated encephalopathy in a healthy child.

Rapid neurologic deterioration is rare in healthy school age children, particularly in the absence of trauma or toxic exposure. Hemorrhagic or ischemic stroke, infectious etiologies and metabolic causes must be emergently considered. We present the clinical details of a previously well child with two days of mild viral symptoms who progressed from playful and active to severe neurologic injury over the course of eight hours.

One-dimensional spatial patterning along mitotic chromosomes: A mechanical basis for macroscopic morphogenesis.

Spatial patterns are ubiquitous in both physical and biological systems. We have recently discovered that mitotic chromosomes sequentially acquire two interesting morphological patterns along their structural axes [L. Chu et al., Mol. Cell, 10.1016/j.molcel.2020.07.002 (2020)]. First, axes of closely conjoined sister chromosomes acquire regular undulations comprising nearly planar arrays of sequential half-helices of similar size and alternating handedness, accompanied by periodic kinks. This pattern, which persists through all later stages, provides a case of the geometric form known as a "perversion." Next, as sister chromosomes become distinct parallel units, their individual axes become linked by bridges, which are themselves miniature axes. These bridges are dramatically evenly spaced. Together, these effects comprise a unique instance of spatial patterning in a subcellular biological system. We present evidence that axis undulations and bridge arrays arise by a single continuous mechanically promoted progression, driven by stress within the chromosome axes. We further suggest that, after sister individualization, this same stress also promotes chromosome compaction by rendering the axes susceptible to the requisite molecular remodeling. Thus, by this scenario, the continuous presence of mechanical stress within the chromosome axes could potentially underlie the entire morphogenetic chromosomal program. Direct analogies with meiotic chromosomes suggest that the same effects could underlie interactions between homologous chromosomes as required for gametogenesis. Possible mechanical bases for generation of axis stress and resultant deformations are discussed. Together, these findings provide a perspective on the macroscopic changes of organized chromosomes.

The 3D Topography of Mitotic Chromosomes.

A long-standing conundrum is how mitotic chromosomes can compact, as required for clean separation to daughter cells, while maintaining close parallel alignment of sister chromatids. Pursuit of this question, by high resolution 3D fluorescence imaging of living and fixed mammalian cells, has led to three discoveries. First, we show that the structural axes of separated sister chromatids are linked by evenly spaced "mini-axis" bridges. Second, when chromosomes first emerge as discrete units, at prophase, they are organized as co-oriented sister linear loop arrays emanating from a conjoined axis. We show that this same basic organization persists throughout mitosis, without helical coiling. Third, from prophase onward, chromosomes are deformed into sequential arrays of half-helical segments of alternating handedness (perversions), accompanied by correlated kinks. These arrays fluctuate dynamically over <15 s timescales. Together these discoveries redefine the foundation for thinking about the evolution of mitotic chromosomes as they prepare for anaphase segregation.

Critical procedure performance in pediatric patients: Results from a national emergency medicine group.

STUDY OBJECTIVE: We sought to examine the frequency of pediatric critical procedures performed in a national group of emergency physicians. METHODS: We performed a retrospective analysis of an administrative billing and coding dataset for procedural performance documentation verification from 2014 to 2018. We describe and compare incident rates of pediatric (age <18 years) patient critical procedure performance by emergency physicians in general emergency departments (EDs), pediatric EDs, and freestanding ED/urgent care centers. Critical procedures were endotracheal intubation, electrical cardioversion, central venous placement, intraosseous access, and chest tube insertion. RESULTS: Among 2290 emergency physicians working in 186 EDs (1844 working in 129 general EDs, 125 in 8 pediatric EDs, and 321 in 49 freestanding EDs/urgent cares), a total of 2233 pediatric critical procedures were performed during the study period. Many physicians at general EDs and freestanding EDs/urgent cares performed zero pediatric procedures per year (53.9% and 89% respectively). Per 1000 ED visits seen (All patient ages), physicians working in general EDs performed fewer pediatric critical procedures than physicians in pediatric EDs (0.12/1000 visits vs 0.68/1000 visits; rate difference = 0.56, 95% confidence interval [CI] 0.51-0.61). Per 1000 clinical hours worked, physicians working in general EDs performed 0.26 procedures compared to 1.66 for physicians in pediatric EDs (rate difference = 1.39; 95% CI 1.27-1.52). CONCLUSION: Pediatric critical procedures are rarely performed by emergency physicians and are exceedingly rare in general EDs and freestanding EDs/urgent cares. The rarity of performance of these skills has implications for ED pediatric readiness.

A tibioperoneal trunk mycotic pseudoaneurysm successfully treated with ligation.

We present the case of a 68-year-old man with a tibioperoneal trunk mycotic pseudoaneurysm, a rarity in the modern age of antibiotics. We describe the patient's hospitalizations and workups that ultimately led to this diagnosis and our management with open ligation without bypass. This case highlights the importance of combining a thorough history and physical examination with laboratory and imaging data while keeping in mind a broad differential diagnosis.

Nonsurgical management of an asymptomatic popliteal venous aneurysm.

An 81-year-old male with a history of poorly controlled congestive heart failure, chronic obstructive pulmonary disease and atrial fibrillation among other comorbidities was admitted to the hospital for worsening bilateral leg swelling and cellulitis. The patient had an injury to his left medial malleolus 2 weeks prior, which failed outpatient care. During the physical exam, a soft mobile mass was palpated in the right popliteal fossa along with bilateral varicose veins, +1 pitting edema in bilateral lower extremities up to mid-calf. Duplex ultrasound revealed a saccular dilation in the right popliteal vein measuring 2.2 × 1.8 × 2.8 cm, without any evidence of superficial or deep vein thrombosis. After an extended conversation with the patient and his care team, a decision to continue with medical management with close monitoring was made. Follow-up ultrasounds performed at 1, 6 and 12 months show no changes.

Initial ED oxygen saturation ≤90% increases the risk of a complicated hospital course in pediatric asthmatics requiring admission.

Emergency physicians are responsible for admitting children with asthma who do not respond to initial therapy. We examined the hypothesis that an initial room air pulse oximetry ≤90% elevates the risk of a complicated hospital course in children who require admission with acute asthma. METHODS: Charts of all patients ages 2 years-17 years admitted for asthma from January 2017 to December 2017 were reviewed. An explicit chart review was performed by trained data extractors using a standardized form. RESULTS: A total of 244 children meeting inclusion criteria were admitted for asthma from the ED during the study period. All patients had an initial room air pulse oximetry documented. Sixty-five were admitted to PICU status (27%), and 179 (73%) were admitted to floor status. The relative risk of a complicated course in those patients presenting with a saturation of ≤90% was 11.3 (95% CI 3.9-32.6). The mean initial pulse oximetry on patients with a complicated course was 85% versus 93% for those without a complicated course (p < 0.005). CONCLUSION: Our data suggest that in pediatric asthmatics that require admission from the ED, those with pulse oximetry readings less than or equal to 90% on presentation are at higher risk of a complicated hospital course.

Emergency department presentation of 'delusional parasitosis by proxy'. Delusional parent, injured child.

We report a case of 'delusional parasitosis by proxy'. A sixyear old child was brought to the emergency department by a mother with concerns that her son had a skin and scalp infestation. Despite the absence of any clinical findings being found on exam, the mother remained disproportionately concerned. Follow up care was recommended with the child's primary care. The mother returned to the ED with her child three weeks later with concerns that her son had an inflamed scalp and eyes. The mother remained insistent that the child was infested with bugs and she had sought care at two other locations where the child was prescribed permethrin on both visits. She had been applying the medication repeatedly. On exam the boy's scalp had been shaved and was erythematous and irritated; his eyebrows and eyelashes had also been shaved off and likely contributed to an irritant conjunctivitis from repeated applications of topical permethrin lotion. No evidence of infestation was identified. We recruited the assistance of the maternal grandparents, child protective services and primary care pediatrics and the child was removed from the mother's custody and placed into the custody of the grandparents. Six weeks later with basic skin care and erythromycin ophthalmic ointment for the eyes, the child's hair, eyebrows and eyelashes grew had grown in, and the scalp irritation had resolved. The mother had sought and received psychiatric care and was improving.

Clinical spectrum of previously undiagnosed pediatric cardiac disease.

Previously undiagnosed pediatric cardiac disease represents a clinical challenge for the emergency physician. The clinical presentation of these disorders can mimic other conditions of the respiratory, gastrointestinal and neurologic systems at a time when the need for early identification and treatment is at a premium. A high index of suspicion and superb clinical acumen is required to make a timely diagnosis and initiate optimal care. METHODS: A retrospective chart review using explicit criteria and a structured data collection process was performed on all children presenting with previously undiagnosed cardiac disease over a five and half year period. RESULTS: Thirty-six patients were identified over a five and a half year period representing one patient per 4838 pediatric ED presentations. A diverse set of chief complaints, triage categories, clinical presentations and diagnoses were identified. Undiagnosed congenital lesions, acquired cardiac disease, dysrhythmias and infectious diseases of the heart were represented. The need for surgical intervention (22%) and mortality (6%) was substantial. CONCLUSION: In the aggregate, these conditions occur at an important rate and represent a high risk subset of pediatric patients presenting to the emergency department. Individually, the conditions occur infrequently and 'pattern recognition' may not aid the clinician. Early diagnosis and prompt intervention is important in this population.

Trends in Route of Hysterectomy after the Implementation of a Comprehensive Robotic Training Program.

OBJECTIVE: To evaluate trends in surgical approach for hysterectomy following the introduction and implementation of a comprehensive robotic surgery program. METHODS: A retrospective review of all hysterectomies done at two institutions, a community hospital and a suburban, tertiary-care teaching hospital, in the same health system over a five-year period, January 2010 through December 2014. A robotic surgery training program was implemented during the first year of the study and trends in route of hysterectomy were evaluated in the subsequent years. RESULTS: A total of 5175 patients undergoing hysterectomy, for both benign and malignant indications, were included in the study. There was a significant decrease in the percent of cases performed through an abdominal approach at both the community and teaching hospitals (19.3% decline at each institution). There was an inversely related significant increase in the percent of robotic procedures at both the community and teaching hospitals (44.5% and 17%, respectively). A decrease in number of cases performed vaginally over this period was only noted in the community hospital site (25.2% decrease), and there was a slightly higher rate of vaginal hysterectomies at the teaching hospital over this study period (21.9% in 2010, 24.1% in 2014). CONCLUSION: The decrease in number of abdominal and laparoscopic hysterectomies and increase in number of robotic hysterectomies that was seen are consistent with national trends. The initiation of a robotic training program did not prevent the proliferation of use of the robot but did aim to ensure proficiency on the robot prior to gaining privileges for patient use. This type of comprehensive training and monitoring program could be applied to future technologic advances to ensure a standard level of surgical proficiency. Trends in route of hysterectomy are clearly multifactorial and involve patient, provider, and location-specific factors that are likely to continue to change.

Pediatric bacterial meningitis: an update on early identification and management.

The presentation of bacterial meningitis can overlap with viral meningitis and other conditions, and emergency clinicians must remain vigilant to avoid delaying treatment for a child with bacterial meningitis. Inflammatory markers, such as procalcitonin, in the serum and cerebrospinal fluid may help distinguish between bacterial meningitis and viral meningitis. Appropriate early antibiotic treatment and management for bacterial meningitis is critical for optimal outcomes. Although debated, corticosteroids should be considered in certain cases. This issue provides evidence-based recommendations for the early identification and appropriate management of bacterial meningitis in pediatric patients.

Coordination of Growth, Chromosome Replication/Segregation, and Cell Division in E. coli.

Bacterial cells growing in steady state maintain a 1:1:1 relationship between an appropriate mass increase, a round of DNA replication plus sister chromosome segregation, and cell division. This is accomplished without the cell cycle engine found in eukaryotic cells. We propose here a formal logic, and an accompanying mechanism, for how such coordination could be provided in E. coli. Completion of chromosomal and divisome-related events would lead, interactively, to a "progression control complex" (PCC) which provides integrated physical coupling between sister terminus regions and the nascent septum. When a cell has both (i) achieved a sufficient mass increase, and (ii) the PCC has developed, a conformational change in the PCC occurs. This change results in "progression permission," which triggers both onset of cell division and release of terminus regions. Release of the terminus region, in turn, directly enables a next round of replication initiation via physical changes transmitted through the nucleoid. Division and initiation are then implemented, each at its own rate and timing, according to conditions present. Importantly: (i) the limiting step for progression permission may be either completion of the growth requirement or the chromosome/divisome processes required for assembly of the PCC; and, (ii) the outcome of the proposed process is granting of permission to progress, not determination of the absolute or relative timings of downstream events. This basic logic, and the accompanying mechanism, can explain coordination of events in both slow and fast growth conditions; can accommodate diverse variations and perturbations of cellular events; and is compatible with existing mathematical descriptions of the E. coli cell cycle. Also, while our proposition is specifically designed to provide 1:1:1 coordination among basic events on a "per-cell cycle" basis, it is a small step to further envision permission progression is also the target of basic growth rate control. In such a case, the rate of mass accumulation (or its equivalent) would determine the length of the interval between successive permission events and, thus, successive cell divisions and successive replication initiations.

Implementation of a CT scan practice guideline for pediatric trauma patients reduces unnecessary scans without impacting outcomes.

INTRODUCTION: Computed tomography (CT) scans are useful in the evaluation of trauma patients, but are costly and pose risks from ionizing radiation in children. Recent literature has demonstrated the use of CT scan guidelines in the management of pediatric trauma. The study objective is to review our treatment of pediatric blunt trauma patients and evaluate CT use before and after CT-guideline implementation. METHODS: Our Pediatric Level 2 Trauma Center (TC) implemented a CT scan practice guideline for pediatric trauma patients in March 2014. The guideline recommended for or against CT of the head and abdomen/pelvis using published criteria from the Pediatric Emergency Care and Research Network. There was no chest CT guideline. We reviewed all pediatric trauma patients for CT scans obtained during initial evaluation before and after guideline implementation, excluding inpatient scans. The Trauma Registry Database was queried to include all pediatric (age < 15) trauma patients seen in our TC from 2010 to 2016, excluding penetrating mechanism and deaths in the TC. Scans were considered positive if organ injury was detected. Primary outcome was the proportion of patients undergoing CT and percent positive CTs. Secondary outcomes were hospital length of stay, readmissions, and mortality. Categorical and continuous variables were analyzed with χ and Wilcoxon rank-sum tests, respectively. p < 0.05 was considered significant. RESULTS: We identified 1,934 patients: 1,106 pre- and 828 post-guideline. Absolute reductions in head, chest, and abdomen/pelvis CT scans were 17.7%, 11.5%, and 18.8%, respectively (p < 0.001). Percent positive head CTs were equivalent, but percent positive chest and abdomen CT increased after implementation. Secondary outcomes were unchanged. CONCLUSIONS: Implementation of a pediatric CT guideline significantly decreases CT use, reducing the radiation exposure without a difference in outcome. Trauma centers treating pediatric patients should adopt similar guidelines to decrease unnecessary CT scans in children. LEVEL OF EVIDENCE: Therapeutic study, level IV.

New Magnetostrictive Transducer Designs for Emerging Application Areas of NDE.

Magnetostrictive transduction has been widely utilized in nondestructive evaluation (NDE) applications, specifically for the generation and reception of guided waves for the long-range inspection of components such as pipes, vessels, and small tubes. Transverse-motion guided wave modes (e.g., torsional vibrations in pipes) are the most common choice for long-range inspection applications, because the wave motion is in the plane of the structure surface, and therefore does not couple well to the surrounding material. Magnetostrictive-based sensors for these wave modes using the Wiedemann effect have been available for several years. An alternative configuration of a sensor for generating and receiving these transverse-motion guided waves swaps the biasing and time-varying magnetic field directions. This alternative design is a reversed Wiedemann effect magnetostrictive transducer. These transducers exhibit a number of unique features compared with the more conventional Wiedemann sensor, including: (1) the use of smaller rare earth permanent magnets to achieve large, uniform, and self-sustained bias field strengths; (2) the use of more efficient electric coil arrangements to induce a stronger time-varying magnetic field for a given coil impedance; (3) beneficial non-linear operating characteristics, given the efficiency improvements in both magnetic fields; and (4) the ability to generate unidirectional guided waves when the field arrangement is combined with a magnetically soft ferromagnetic strip (patch). Reversed Wiedemann effect magnetostrictive transducers will be presented that are suitable for different inspection applications, one using electromagnetic generation and reception directly in a ferromagnetic material, and another design that integrates a magnetostrictive patch to improve its efficiency and enable special operating characteristics.