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Despite being one of the most prominent and best-documented northern client states of the Ur III state, the city of Asimānum/Šimānum remained unlocalized. Here, we demonstrate through both historical-geographical and philological argumentation and archaeological evidence that it must correspond to later Middle and Neo-Assyrian Šibaniba, modern Tell Billa, northern Iraq. Building upon this finding, we propose a new history of Tell Billa during the Early and Middle Bronze Age.

The Neo-Assyrian site Šibaniba (modern Tell Billa) served as a provincial center at the very edge of what is traditionally known as the “Assyrian Heartland”. Excavations in the early 1900s under Dr. Speiser of the University of Pennsylvania uncovered architecture in the southwestern portion of the mound, but a loss of records and lack of publication have prevented any comprehensive publications or analysis of the archaeological material. The architecture from Level I in the southwest corner is the remains of a palace from the latter half of the Neo-Assyrian period – comprised of an inner, paved courtyard and surrounding rooms. The analysis of this palace complex is carried out herein, with a discussion of its positioning and importance, especially during Nineveh's tenure as imperial capital. Overall, Šibaniba, despite being located so close to the Heartland, was an important administrative center in its own right – illustrated by a restructuring of the citadel's organization in the later Neo-Assyrian period and its inclusion in Sennacherib's irrigation program.

Repetitive sequences including transposable elements and transposon-derived fragments account for nearly half of the human genome. While transposition-competent transposable elements must be repressed to maintain genomic stability, mutated and fragmented transposable elements comprising the bulk of repetitive sequences can also contribute to regulation of host gene expression and broader genome organization. Here, we analyzed published ChIP-seq data sets to identify proteins broadly enriched on transposable elements in the human genome. We show 2 of the proteins identified, C2H2 zinc finger-containing proteins ZNF146 (also known as OZF) and ZNF507, are targeted to distinct sites within LINE-1 ORF2 at thousands of locations in the genome. ZNF146 binding sites are found at old and young LINE-1 elements. In contrast, ZNF507 preferentially binds at young LINE-1 sequences correlated to sequence changes in LINE-1 elements at ZNF507’s binding site. To gain further insight into ZNF146 and ZNF507 function, we disrupt their expression in HEK293 cells using CRISPR/Cas9 and perform RNA sequencing, finding modest gene expression changes in cells where ZNF507 has been disrupted. We further identify a physical interaction between ZNF507 and PRMT5, suggesting ZNF507 may target arginine methylation activity to LINE-1 sequences.

Introduction Pediatric hospitalists are expected to lead resuscitative efforts for cardiopulmonary arrests, but the infrequency of these events and pediatric advanced life support (PALS) re-certifications are insufficient to maintain skill proficiency.We created a novel resuscitation refresher curriculum for pediatric hospitalists with strategic pauses during simulations for expert and peer coaching of procedural skills. Methods In a tertiary care academic pediatric hospital between September 2018 to June 2019, pediatric hospitalists and fellows voluntarily participated in a series of three quarterly two-hour training sessions taught by expert peer facilitators. Sessions focused on the thirty-second rapid cardiopulmonary assessment and each of the pediatric advanced life support (PALS) algorithms. Scenarios were strategically paused to practice critical hands-on skills. Cases centered on the themes of shock, respiratory, and cardiac emergencies and took place in a high-fidelity simulation lab requiring a technician and expert peer facilitator. Participants anonymously completed Likert scale-based evaluations after each session and again at the end of the year that focused on participants’ own perceived change in their comfort levels in performing various resuscitation skills and in knowing basic resuscitation steps. As part of our institutional and personal assessment of the curriculum, an end-of-year survey additionally asked participants to reflect on the overall simulation curriculum and resultant changes in their clinical practice. Results Comfort in all skills practiced across the three sessions increased. The end-of-year survey showed a significant rise in comfort above baseline but some decrements when compared to that immediately post-training. Ninety-six percent of pediatric hospitalists rated the overall quality of the training “better” or “much better” than other resuscitation training (including PALS classes and traditional simulations with skills training after the scenario). The overall effect of the curriculum on perceived knowledge, skills, and confidence levels was significant (p

The prevalence of cardiopulmonary arrest in pediatric inpatients is roughly 1 in every 1300 admissions.1 These code situations can be both clinically challenging and anxiety producing for the anticipated code team leaders. Hospitalists practicing at tertiary children’s hospitals have the luxury of a robust, highly trained, and experienced PICU team that takes over the resuscitative efforts, usually within 5 minutes of the code call. That is not necessarily the case in many community hospitals where pediatric hospitalists practice. Most often they are expected to lead resuscitative efforts through to resolution, including a postresuscitative phase while awaiting critical care transport. Delays in transport or rapid decompensation may leave pediatric hospitalists vulnerable to self-doubt and burnout if they are not confident in their resuscitation efforts.2 Despite an almost universal mandate for cardiopulmonary resuscitation (CPR) training (Basic Life Support and Pediatric Advanced Life Support [PALS]) every 2 years, the rarity of participation in actual arrest events or other opportunities to refresh these skills leads to significant skill decrements over time. In a study with military pediatric residents, researchers demonstrated this point. When residents were trained to “mastery” levels, 92% maintained their mastery at 2 months, but only 56% retained mastery by 6 months.3 Hospitalists are expected to perform better than pediatric residents, yet their routine exposure to refresher training is usually much less frequent. Additionally, there is a significant discrepancy between resuscitation knowledge and skill retention.4 Proficiency in cognitive matters does not necessarily indicate proficiency in the practical life-saving, hands-on skills.5 Fortunately, many pediatric inpatient …

Understanding mortuary ritual provides new perspectives for interpreting spatial collective memory and the relationship between elite and non-elite practices. Assur serves as a case study to invest...

Digital methods provide archaeologists with ever-increasing opportunities to collect more data about the past in new formats. These larger evidentiary datasets, in turn, help us to address questions about the human past with increasing precision. To take full advantage of these opportunities, archaeologists must develop digital literacy skills and learn how to lead digital projects. Here, we describe seven digitally-based projects we have undertaken at the University of Pennsylvania in order to create new tools for archaeological data collection and sharing, as well as to test collaborative models for the digital humanities programming process. In these projects, archaeology students work directly with engineering students. Through this interface, the students from both areas gain valuable transdisciplinary experience while experimenting with new ways to accomplish programming goals and to collect archaeological data. The learning potential for these students was a key motivation for our initiative. Our projects have already led to several websites and digital applications that are available as open source downloads. We present our impressions of this collaborative process with the goal of encouraging other archaeologists to form similar digital humanities partnerships.

Here we provide a brief review of relevant background before presenting results of our investigation into the interplay between scaffold attachment factor A (SAF-A), chromatin-associated RNAs, and DNA condensation. SAF-A, also termed heterogenous nuclear protein U (hnRNP U), is a ubiquitous nuclear scaffold protein that was implicated in XIST RNA localization to the inactive X-chromosome (Xi) but also reported to maintain open DNA packaging in euchromatin. Here we use several means to perturb SAF-A and examine potential impacts on the broad association of RNAs on euchromatin, and on chromatin compaction. SAF-A has an N-terminal DNA binding domain and C-terminal RNA binding domain, and a prominent model has been that the protein provides a single-molecule bridge between XIST RNA and chromatin. Here analysis of the impact of SAF-A on broad RNA-chromatin interactions indicate greater biological complexity. We focus on SAF-A’s role with repeat-rich C0T-1 hnRNA (repeat-rich heterogeneous nuclear RNA), shown recently to comprise mostly intronic sequences of pre-mRNAs and diverse long non-coding RNAs (lncRNAs). Our results show that SAF-A mutants cause dramatic changes to cytological chromatin condensation through dominant negative effects on C0T-1 RNA’s association with euchromatin, and likely other nuclear scaffold factors. In contrast, depletion of SAF-A by RNA interference (RNAi) had no discernible impact on C0T-1 RNA, nor did it cause similarly marked chromatin changes as did three different SAF-A mutations. Overall results support the concept that repeat-rich, chromatin-associated RNAs interact with multiple RNA binding proteins (RBPs) in a complex dynamic meshwork that is integral to larger-scale chromatin architecture and collectively influences cytological-scale DNA condensation.

Introduction The authors compared pediatric thoracic patients in the Joint Theatre Trauma Registry (JTTR) to those in the National Trauma Data Bank (NTDB) to assess differences in patient mortality rates and mortality risk accounting for age, injury patterns, and injury severity. Materials and Methods Patients less than 19 years of age with thoracic trauma were identified in both the JTTR and NTDB. Multiple logistic regression, χ2, Student’s t-test, or Mann-Whitney U test were used as indicated to compare the two groups. Results Pediatric thoracic trauma patients seen in Iraq and Afghanistan (n = 955) had a significantly higher mortality rate (15.1 vs. 6.0%, P Discussion Pediatric patients with thoracic trauma in Iraq and Afghanistan in the JTTR had similar mortality rates compared to the civilian population in the NTDB after accounting for confounding covariates. These findings indicate that deployed military medical professionals are providing comparable quality of care in extremely challenging circumstances. This information has important implications for military preparedness, medical training, and casualty care.

Nuclear chromosomes transcribe far more RNA than required to encode protein. Here we investigate whether non-coding RNA broadly contributes to cytological-scale chromosome territory architecture. We develop a procedure that depletes soluble proteins, chromatin, and most nuclear RNA from the nucleus but does not delocalize XIST, a known architectural RNA, from an insoluble chromosome "scaffold." RNA-seq analysis reveals that most RNA in the nuclear scaffold is repeat-rich, non-coding, and derived predominantly from introns of nascent transcripts. Insoluble, repeat-rich (C0T-1) RNA co-distributes with known scaffold proteins including scaffold attachment factor A (SAF-A), and distribution of these components inversely correlates with chromatin compaction in normal and experimentally manipulated nuclei. We further show that RNA is required for SAF-A to interact with chromatin and for enrichment of structurally embedded "scaffold attachment regions" prevalent in euchromatin. Collectively, the results indicate that long nascent transcripts contribute a dynamic structural role that promotes the open architecture of active chromosome territories.

Maintenance of the correct level and organisation of nucleosomes is crucial for genome function. Here, we uncover a role for a conserved bromodomain AAA-ATPase, Abo1, in the maintenance of nucleosome architecture in fission yeast. Cells lacking abo1+ experience both a reduction and mis-positioning of nucleosomes at transcribed sequences in addition to increased intragenic transcription, phenotypes that are hallmarks of defective chromatin re-establishment behind RNA polymerase II. Abo1 is recruited to gene sequences and associates with histone H3 and the histone chaperone FACT. Furthermore, the distribution of Abo1 on chromatin is disturbed by impaired FACT function. The role of Abo1 extends to some promoters and also to silent heterochromatin. Abo1 is recruited to pericentromeric heterochromatin independently of the HP1 ortholog, Swi6, where it enforces proper nucleosome occupancy. Consequently, loss of Abo1 alleviates silencing and causes elevated chromosome mis-segregation. We suggest that Abo1 provides a histone chaperone function that maintains nucleosome architecture genome-wide.

Introduction The objective of this study is to review available data on pediatric thoracic trauma seen at U.S. military treatment facilities in Iraq and Afghanistan and describe the scope of injuries, patterns seen, and associated mortality. The results were compared with adults injured in Iraq and Afghanistan and other reports of pediatric thoracic trauma in the literature. Materials and methods The investigators received approval from the Uniformed Services University of the Health Sciences' institutional review board before the study. The Joint Theatre Trauma Registry was queried for all patients with an ICD-9 code for thoracic trauma. Two-tailed Student's t-test, Mann-Whitney rank sum, χ2, ANOVA, or multiple logistic regression was used as indicated. Results There were 955 patients under the age of 18 yr, just over 12% of all thoracic trauma. Penetrating injuries were common (73.6%), including gunshot wounds. The most common pediatric diagnoses were contusions (45%), pneumothorax (40%), and rib and/or sternal fractures (18%). The overall mortality for children was 15.2% compared with 13.8% and 9% for civilian adults and Coalition members with thoracic trauma, respectively. Mortality was inversely related to age among pediatric patients. Children under 2 yr of age had the highest mortality (25.1%). Patients under 12 yr of age were more likely to die than those between 12 and 18 (OR 2.02, 95% CI 1.27-3.22) yr. Thoracic vascular injuries and cardiac injuries resulted in the highest mortality among pediatric patients. The presence of a hemothorax was independently associated with an increased risk for mortality (OR 1.78, 95% CI 1.06-2.99) as was a concomitant head injury (OR 2.17, 95% CI 1.33-3.54). There was a 2.7% incidence of burns among pediatric patients with a high associated mortality (46.2%). Nearly one-half of all the children identified required a transfusion (47%). Conclusion Penetrating injuries predominated and these children commonly required a transfusion. Mortality was inversely related to age. Children with a hemothorax or a concomitant head injury had significant increases in mortality. Children with thoracic injury as the result of a burn suffered the highest mortality.

A nine year-old boy with a complex medical history, including Phelan-McDermid syndrome, autism spectrum disorder, and focal epilepsy was admitted from Infectious Disease (ID) clinic for persistent fever for over three weeks. Laboratory studies were significant for leukocytosis, elevated inflammatory markers, transaminitis, and anemia. He was initially thought to have an infected duodenal duplication cyst with secondary parapneumonic involvement on imaging. Exploration revealed a densely inflamed suprarenal cyst with a communication to the duodenum. Pathology revealed an infected and hemorrhagic adrenal pseudocyst. We speculate that he had a relatively old or subacute hemorrhagic adrenal pseudocyst that subsequently became infected and perforated into the duodenum and sub-diaphragmatic space. Keywords: Adrenal pseudocyst, Adrenal hemorrhage, Persistent fevers

Mit1 is the putative chromatin remodeling subunit of the fission yeast Snf2/histone deacetylase (HDAC) repressor complex (SHREC) and is known to repress transcription at regions of heterochromatin. However, how Mit1 modifies chromatin to silence transcription is largely unknown. Here we report that Mit1 mobilizes histone octamers in vitro and requires ATP hydrolysis and conserved chromatin tethering domains, including a previously unrecognized chromodomain, to remodel nucleosomes and silence transcription. Loss of Mit1 remodeling activity results in nucleosome depletion at specific DNA sequences that display low intrinsic affinity for the histone octamer, but its contribution to antagonizing RNA polymerase II (Pol II) access and transcription is not restricted to these sites. Genetic epistasis analyses demonstrate that SHREC subunits and the transcription-coupled Set2 histone methyltransferase, which is involved in suppression of cryptic transcription at actively transcribed regions, cooperate to silence heterochromatic transcripts. In addition, we have demonstrated that Mit1's remodeling activity contributes to SHREC function independently of Clr3's histone deacetylase activity on histone H3 K14. We propose that Mit1 is a chromatin remodeling factor that cooperates with the Clr3 histone deacetylase of SHREC and other chromatin modifiers to stabilize heterochromatin structure and to prevent access to the transcriptional machinery.

In recent years, a bevy of evidence has been unearthed indicating that 'silent' heterochromatin is not as transcriptionally inert as once thought. In the unicellular yeast Schizosaccharomyces pombe, the processing of transcripts derived from centromeric repeats into homologous short interfering RNA (siRNA) is essential for the formation of centromeric heterochromatin. Deletion of genes required for siRNA biogenesis showed that core components of the canonical RNA interference (RNAi) pathway are essential for centromeric heterochromatin assembly as well as for centromere function. Subsequent purification of the RNA-induced initiation of transcriptional gene silencing (RITS) complex provided the critical link between siRNAs and heterochromatin assembly, with RITS acting as a physical bridge between noncoding RNA scaffolds and chromatin. Here, we review current understanding of how RITS promotes heterochromatin formation and how it participates in transcription-coupled silencing. WIREs RNA 2011 2 632-646 DOI: 10.1002/wrna.80 For further resources related to this article, please visit the WIREs website.

Introduction/Background SISTERS is the first multicenter randomized trial demonstrating superiority of intrathecal baclofen (ITB) therapy versus conventional medical management (CMM) with oral antispastic in decreasing muscle hypertonia in lower and upper limbs of post-stroke patients with severe spasticity. Here we report Numeric Pain Rating Scale (NPRS), Quality of Life (QoL) assessed by EQ-5D and Stroke Specific QoL (SS-QoL), satisfaction and safety. Material and method Sixty stroke patients with spasticity in ≥ 2 extremities and an Ashworth Scale score ≥ 3 in ≥ 2 affected muscle groups in the lower limbs were randomized to ITB or CMM group and both arms received physiotherapy. Results Mean changes (SD) from baseline to month 6 in ITB patients versus CMM group were −1.17 (3.17) vs. 0.00 (3.29) for NPRS actual pain, −1.61 (2.29) vs. 0.24 (3.07) for NPRS least pain and 0.09 (0.26) vs. 0.01 (0.16) for EQ-5D utility score. These between-group differences were statistically significant (P Conclusion Reduction of muscle tone with ITB therapy is associated with improvements in pain and QoL in post-stroke patients with severe spasticity.

Over 3,500 infants and children, many critically ill and injured, have been admitted to military combat support hospitals (CSH) in Afghanistan and Iraq, which are not doctrinally staffed or equipped to provide their care. This report details how the military medical system is adapting to create a data driven and comprehensive response to optimize the medical and surgical pediatric care being provided.Information from multiple sources was used over time to craft the military medical response to the pediatric wartime mission. Pediatric data from both the Joint Theater Trauma Registry (JTTR) and the Patient Administration Systems and Biostatistics Activity (PASBA) database were utilized extensively. The resulting educational, supply, and personnel adaptations implemented by the U.S. military will be highlighted, and innovations currently under development will also be described on the basis of this demonstrated need.This information helped drive pediatric-specific, just-in-time education for CSH personnel, modified CSH equipment and supply lists, inspired the 24/7 pediatric critical care teleconsultation service, and resulted in new initiatives in the predeployment training for CSH personnel.Military physicians are routinely asked to perform outside their traditional scopes of practice while deployed. Given this reality, military pediatric specialists in medicine and surgery have initiated several successful multidisciplinary programs designed to improve in-theater care of injured children. These innovative efforts include drafting a pediatric addendum to the Army's "Emergency War Surgery" manual, development of instructional compact discs, augmenting and refining the pediatric portion of the Joint Forces Combat Trauma Management course, formation of a pediatric augmentation team to the CSH, and a comprehensive hyperlinked Web-based pediatric critical care and trauma educational platform.

Component balanced resuscitation and avoidance of crystalloids in traumatically injured adults requiring massive transfusion are beneficial. Evidence for children is lacking.After institutional review board approval was obtained, the Department of Defense Trauma Database identified 1,311 injured children 14 years or younger requiring transfusion after an injury and admitted to a deployed US military hospital from 2002 to 2012. Logistic regression determined risk factors for high-volume (≥40 mL/kg) or massive (≥70 mL/kg) transfusions. The effects of crystalloid and balanced component resuscitation in the first 24 hours were assessed.Nine hundred seven patients had recorded data sufficient for analysis. Two hundred twenty-four children received high-volume transfusion, and 77 received massive transfusions. Mortality was significantly higher for massive transfusions and high-volume transfusions than others (25% vs. 10% and 19% vs. 9%, respectively). Age of less than 4 years, penetrating injury, and Injury Severity Score (ISS) greater than 15 were associated with high-volume transfusions; an ISS greater than 15 and penetrating injury were associated with massive transfusions. Increased crystalloid administration showed a significant positive association with hospital days and intensive care unit days for both massive and high-volume transfusions, as well as a significant positive association with increased ventilator days in patients with high-volume transfusions. Balanced component resuscitation was not associated with improved measured outcomes and was independently associated with a higher mortality when all transfused patients were considered.In this cohort, heavy reliance on crystalloid for resuscitation had an adverse effect on outcomes. Balanced component resuscitation did not improve outcomes and was associated with higher mortality when all transfused patients were considered. Further study is needed regarding efficacy and clinical triggers for the implementation of massive transfusion in children.Prognostic study, level IV.

The development of regional dialysis units and the expanding indications for dialysis has led to increased demand for vascular access surgery. Consequently, the provision and maintenance of access, and the management of related complications has created a considerable burden on vascular surgical units in hospitals providing renal replacement therapy (RRT).The objectives of our study were to review our experience with a variety of vascular access modalities for haemodialysis and to quantify the associated surgical workload.We reviewed our experience in a consecutive group of dialysis patients who had access surgery for RRT in a regional hospital setting.Between January 1995 and January 2000, 69 patients entered the long-term dialysis programme in the Mid-Western region (population = 320,000). Of the 158 procedures performed, 138 (87%) were for access creation, and 20 (13%) related to access revision procedures. Twenty patients (29%) developed a total of 30 access related complications. Vascular access procedures accounted for 10% of the vascular surgical workload (1598 procedures) in the five-year period.Vascular access is an important part of the haemodialysis services and surgical expertise should be available at local level to cope with likely demand.

Objective. Sleep deprivation is commonly used to enhance the effectiveness of pediatric sedation and to decrease sedation failures. We reviewed our sedation database to evaluate the efficacy of sleep deprivation.Methods. The entire pediatric sedation unit database (n = 5640) was reviewed retrospectively. Patients without complete data sets were excluded. The remaining patients were separated into 2 groups: 3272 patients who underwent noninvasive procedures and 1210 who underwent invasive procedures. A subgroup of noninvasive procedure patients Results. In the noninvasive procedure group, the sedation failure rate was 5.7% for the sleep-deprived patients and 5.6% for the non-sleep-deprived patients, whereas the sedation failure rate for children Conclusions. Sleep deprivation had no effect in reducing the pediatric sedation failure rate. The patients having noninvasive procedures who were sleep deprived required significantly more nursing care hours than their non-sleep-deprived counterparts. Routine use of sleep deprivation for pediatric sedation should be critically reevaluated.

In this issue of Molecular Cell, Ishida et al. (2012) and Keller et al. (2012) show distinct outcomes for heterochromatic RNAs that bind different chromodomain proteins; Chp1 tethers transcripts to centromeres, whereas Swi6(HP1)-bound transcripts are evicted from chromatin and destroyed.

Objective. To develop a pathway to provide safe, effective, and efficient sedation for pediatric diagnostic imaging studies using non-radiology personnel. Materials and methods. A multidisciplinary team considered manpower and training requirements and national sedation standards before designing a sedation pathway, which included scheduling, pre-sedation history and physical, medication protocols, and monitoring. Oral and IV medication protocols were developed based on patient age and weight. Sedation delays were defined as >15 min (IV) or >30 min (PO) from start of sedation to start of imaging. A sedation failure resulted in an incomplete diagnostic imaging study. Failure rates of 124 sedations before and 388 sedations after the pathway were compared. Results. The sedation failure rate for 7 months prior to pathway initiation was 15% (19/124). In the first 25 months after pathway initiation, failures were significantly reduced to 1.5% (6/388) (P 55 min). Deviation from the recommended medication protocol accounted for most of the 115 delays. Only minor adverse events were seen (12/388, 3.1%). Conclusion. Implementing a pediatric sedation pathway significantly decreases the sedation failure rate. Pediatric residents and nurses can safely, effectively and efficiently sedate pediatric patients for routine diagnostic imaging procedures without the need for a radiology department sedation team in a department with a small-to-moderate volume of pediatric patients.

XISTRNA triggers the transformation of an active X chromosome into a condensed, inactive Barr body and therefore provides a unique window into transitions of higher-order chromosome architecture. Despite recent progress, howXISTRNA localizes and interacts with the X chromosome remains poorly understood. Genetic engineering ofXISTinto a trisomic autosome demonstrates remarkable capacity ofXISTRNA to localize and comprehensively silence that autosome. Thus,XISTdoes not require X chromosome-specific sequences but operates on mechanisms available genome-wide. Prior results suggestedXISTlocalization is controlled by attachment to the insoluble nuclear scaffold. Our recent work affirms that scaffold attachment factor A (SAF-A) is involved in anchoringXIST, but argues against the view that SAF-A provides a unimolecular bridge between RNA and the chromosome. Rather, we suggest that a complex meshwork of architectural proteins interact withXISTRNA. Parallel work studying the territory of actively transcribed chromosomes suggests that repeat-rich RNA ‘coats’ euchromatin and may impact chromosome architecture in a manner opposite ofXIST. A model is discussed whereby RNA may not just recruit histone modifications, but more directly impact higher-order chromatin condensation via interaction with architectural proteins of the nucleus.This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.

Objective: To develop an easy-to-use system for initiating and monitoring enteral and parenteral nutrition support for pediatric inpatients. Design: A multidisciplinary pediatric nutrition support team developed a system to deliver appropriate nutrition support to pediatric inpatients. The package was devised and implemented to improve timeliness, safety, and efficacy of pediatric inpatient nutrition support. The goals included an easy to complete nutrition assessment, a system for early appropriate initiation of nutrition, advancement toward projected goal calories, and monitoring parameters for improved outcomes. Results The comprehensive evidence based package consisted of a four-sided laminated pocket reference with flow charts and tables; concise enteral and parenteral clinical nutrition support pathways; and computerized parenteral nutrition order form, a lab order set, and four one-page information sheets for initiation and advancement of age specific parenteral nutrition. A lecture summarizing this manuscript with handouts and bibliography heightened awareness in each department primarily responsible for the care for pediatric patients (Pediatrics, Family Practice, and Surgery) in our hospital. Conclusion: This package is a comprehensive educational tool for our housestaff. We believe it increases the likelihood of appropriate nutrition assessment and delivery by physicians working with pediatric inpatients at our hospital. It is easily adaptable to fit the needs of any inpatient pediatric nutrition support practice setting.

Objective: We hypothesized that pentoxifylline, administered after phorbol myristate acetate (PMA), would diminish the severity of lung injury. Setting: Animal research laboratory. Design: Comparative study. Subjects: Mongrel dogs (n 5 33). Interventions: Baseline measurements were obtained from the isolated blood-perfused dog lung lobes afte r1ho fstable perfusion and ventilation. Four different measures of lung compliance were obtained along with WBC and neutrophil counts. Pulmonary vascular resistance (PVR) and capillary filtration coefficient (Kf) were calculated, and the ratio of a normalized maximal enzymatic conversion rate to the Michaelis-Menten constant (Amax/Km) was used to assess perfused capillary surface area. The control lobes (n 5 8) were ventilated and perfused for an additional 40 min while the injured lobes (n 5 17) received PMA (0.1 mg/mL of perfusate). The pentoxifylline-protected lobes (n 5 8) were treated with pentoxifylline (1 mg/mL of perfusate) 10 min after injury with PMA. All measurements were then repeated. Measurement and main results: The three groups did not differ significantly at baseline. The control lobes remained relatively stable over time. The injured lobes demonstrated marked deterioration in compliance: 8.79 6 0.7 to 5.97 6 0.59 mL/cm H2 O( p< 0.05) vs 10.1 6 1.0 to 8.07 6 0.72 mL/cm H2O and 9.6 6 1.1 to 9.9 6 0.85 mL/cm H2O in the control and protected lobes, respectively. Both groups receiving PMA had similar drops in WBC and neutrophil counts, but the pentoxifylline-protected lobes had preservation of all four compliance measures. PVR increased from 37.8 6 1.8 to 118.6 6 12.7 cm H2O/L/min (p < 0.05) in the injured lobes vs 35.4 6 0.5 to 36.3 6 2.8 cm H2O/L/min and 40.4 6 0.04 to 46.7 6 2.8 cm H2O/L/min (p < 0.05) in the control and protected lobes, respectively. Kf increased < 25% in the protected group but more than tripled in the injured group. Amax/Km dropped from 559 6 36 to 441 6 33 mL/min (p < 0.05) in the injured lobes vs 507 6 14 to 490 6 17 mL/min and 609 6 34 to 616 6 37 mL/min in the control and pentoxifylline-protected lobes, respectively. Conclusions: The use of pentoxifylline as a rescue agent prevented the PMA-induced deterioration of lung compliance, vascular integrity, and endothelial metabolic function in this acute lung injury model, despite significant pulmonary neutrophil sequestration. (CHEST 2001; 119:1893‐1900)

A 2-week-old infant developed respiratory failure due to a mediastinal Kaposiform hemangioendothelioma that was complicated by thrombocytopenia and consumptive coagulopathy. Initial surgery was unsuccessful at removing the tumorous infiltration of mediastinal structures. Multiple transfusions with fresh frozen plasma, platelets, and red blood cells were needed for the consumptive coagulopathy, and ventilatory support was required for 5 months. Therapy for the tumor included methylprednisolone, aminocaproic acid, and vincristine, but a sustained response was achieved only after the initiation of alpha interferon. The patient was monitored closely and did not develop neurologic toxicity. This case demonstrates that interferon can be used to treat infants with Kaposiform hemangioendothelioma in life-threatening situations that do not respond to other forms of treatment.

The aim of this study was to determine the relationship of pulmonary vascular resistance (PVR) hysteresis and lung volume, with special attention to the effects of ventilation around closing volume (CV). Isolated, blood-perfused canine left lower lung lobes (LLL) were incrementally inflated and deflated. Airway and pulmonary artery pressures (PAP) were recorded after each stepwise volume change. Constant blood flow was provided (600 ml/min) and the pulmonary vein pressure (PVP) was held constant at 5 cm H2O. PAP changes, therefore, were a direct index of PVR changes. Group 1 lobes underwent a full inflation from complete collapse to total lobe capacity (TLC) followed by a full deflation. Group 2 lobes underwent two deflation/inflation cycles, after an initial full inflation. These cycles, both beginning at TLC, had deflation end above and below CV, respectively. Significant PVR hysteresis was noted when the first inflation and deflation were compared. The maximum difference in PAP on deflation was 3.3 cm H2O or 11%. The mean decrease was 2.7 cm H2O for 18 lobes (p0.0001). The PAPs on all subsequent inflations or deflations that began above CV remained 9% lower than the initial inflation (n = 9, p0.0001), but were not different from each other. However, the final inflation which began from below CV resulted in a 30% return of PVR hysteresis (mean increase in PAP of 0.8 cm H2O, n = 7, p0.004). We conclude that there is hysteresis in the PVR response during ventilation, with decreased PVR during deflation relative to the initial inflation, that this hysteresis is absent when lung volume is maintained greater than CV, and that hysteresis returns when inflation occurs after deflation below CV.

Stage 4S neuroblastoma is an unusual malignancy that has an excellent prognosis, except in young infants. A 2-month-old with 4S neuroblastoma complicated by massive hepatomegaly, managed by abdominal decompression surgery and a negative-pressure dressing system is presented. Diffuse alveolar hemorrhage also developed, which was treated with high-dose corticosteroids.

The United States Coast Guard is responsible for the design, procurement, installation, and operation of reference stations, broadcast facilities, monitor sites, and control stations to provide a Differential GPS (DGPS) service for coastal and other critical waterways of the United States. The DGPS service is intended to support a number of applications where system accuracy, reliability, and integrity are all critical to safe and efficient navigation. As part of the design effort, the Coast Guard has analyzed the accuracy, reliability, and integrity requirements of four DGPS applications: harbor and harbor approach navigation, vessel traffic service (VTS) surveillance, aids to navigation (ATON) positioning, and exclusive economic zone (EEZ) surveying. This paper provides an overview of the DGPS design efforts, and describes the analysis methodologies used to derive the DGPS reliability and integrity requirements.

Formation of centromeric heterochromatin in fission yeast requires the combined action of chromatin modifying enzymes and small RNAs derived from centromeric transcripts. Positive feedback mechanisms that link the RNAi pathway and the Clr4/Suv39h1 histone H3K9 methyltransferase complex (Clr-C) result in requirements for H3K9 methylation for full siRNA production and for siRNA production to achieve full histone methylation. Nonetheless, it has been proposed that the Argonaute protein, Ago1, is the key initial trigger for heterochromatin assembly via its association with Dicer-independent “priRNAs.” The RITS complex physically links Ago1 and the H3-K9me binding protein Chp1. Here we exploit an assay for heterochromatin assembly in which loss of silencing by deletion of RNAi or Clr-C components can be reversed by re-introduction of the deleted gene. We showed previously that a mutant version of the RITS complex (Tas3WG) that biochemically separates Ago1 from Chp1 and Tas3 proteins permits maintenance of heterochromatin, but prevents its formation when Clr4 is removed and re-introduced. Here we show that the block occurs with mutants in Clr-C, but not mutants in the RNAi pathway. Thus, Clr-C components, but not RNAi factors, play a more critical role in assembly when the integrity of RITS is disrupted. Consistent with previous reports, cells lacking Clr-C components completely lack H3K9me2 on centromeric DNA repeats, whereas RNAi pathway mutants accumulate low levels of H3K9me2. Further supporting the existence of RNAi–independent mechanisms for establishment of centromeric heterochromatin, overexpression of clr4+ in clr4Δago1Δ cells results in some de novo H3K9me2 accumulation at centromeres. These findings and our observation that ago1Δ and dcr1Δ mutants display indistinguishable low levels of H3K9me2 (in contrast to a previous report) challenge the model that priRNAs trigger heterochromatin formation. Instead, our results indicate that RNAi cooperates with RNAi–independent factors in the assembly of heterochromatin., Author Summary Centromeres are the chromosomal regions that promote chromosome movement during cell division. They consist of repetitive DNA sequences that are packaged into heterochromatin. Disruption of centromeric heterochromatin leads to chromosome loss that can result in miscarriages and genetic disorders. We have sought to define the precise steps leading to heterochromatin assembly using fission yeast as the model system. To accomplish this we employed our novel Tas3WG mutant strain that can propagate preassembled heterochromatin but cannot support its de novo establishment. Current models suggest that small RNAs initiate heterochromatin assembly by targeting the RNAi machinery and subsequently the Clr-C chromatin-modifying complex to the centromere. Here, we demonstrate that transient depletion of components of the RNAi pathway that generate or bind small RNAs does not perturb heterochromatin assembly in our Tas3WG strain. Instead, transient depletion of the Clr-C complex blocks heterochromatin assembly, suggesting a critical role for continuous Clr-C activity during heterochromatin assembly in Tas3WG cells. We have directly tested whether Clr-C can target centromeres when expressed in cells deficient for RNAi and Clr-C. We find that RNAi–independent recruitment of Clr-C can occur and likely contributes to the critical initiating mechanisms of heterochromatin assembly.

This resource is a training curriculum on pediatric procedural skills. It was developed as a yearly procedural skills training day, which allows incoming interns the opportunity to practice several of the required Accreditation Council for Graduate Medical Education pediatric procedural skills on patient simulators prior to performing the procedures on real patients. The curriculum includes a slide-show presentation and a procedural skills checklist, which can be used as evidence of procedural competency. Much of the literature devoted to pediatric simulation training has focused on simulation technology and the effectiveness of simulation-based education. Relatively little has been published on simulation curricula. Here, we present a detailed pediatric procedural skills simulation curriculum that has been designed for use in pediatric graduate medical education programs. Preliminary feedback from residents who have experienced the training is encouraging. Efforts are currently underway to collect outcome data on the effectiveness of the training. The authors hope this curriculum will help others who wish to implement a procedural skills simulation curriculum within their training program.

Humanitarian and civilian emergency care accounts for up to one-third of US military combat support hospital (CSH) admissions. Almost half of these admissions are children. The purpose of this study is to describe the features of pediatric wartime admissions to deployed CSHs in Iraq and Afghanistan.A retrospective database review was conducted using the Patient Administration Systems and Biostatistics Activity. Details of 2,060 pediatric admissions to deployed CSHs were analyzed.Nontraumatic diagnoses were responsible for 25% of all pediatric admissions. Penetrating injuries (76.3%) dominate the trauma admissions. The primary mechanisms of injury were gunshot wound (39%) followed by explosive injuries (32%). Categorizing the injuries by location revealed 38.3% extremity wounds, 23.6% torso injuries, 23.5% head, face, and neck injuries, and 13.3% burns. More than half of the children required two or more invasive or surgical procedures, 19.8% needed a transfusion, and 5.6% required mechanical ventilation. The mortality rate was 6.9%. The primary cause of death involved head trauma (29.5%) and burns (27.3%), followed by infectious diagnoses (7.2%). The case fatality rate for head injury and burn patients was 20.1% and 15.9%, respectively, in contrast to the fatality rate for all other diagnoses at 3.8% (p0.01). Excluding emergency department deaths, mortality rates for Afghanistan (6.2%) and Iraq (3.9%) significantly differ (p0.02).Pediatric patients account for approximately 10% of all CSH admissions in Afghanistan and Iraq. Burns and penetrating head injury account for the majority of pediatric mortality at the CSH.

This single blinded observational study compared the bispectral index (BIS) monitor with a validated pediatric sedation scale, the University of Michigan Sedation Scale (UMSS), to evaluate whether the BIS score can be used to judge the depth of sedation in pediatric outpatients. Thirty-eight children, with a mean age of 5.8 years, undergoing routine sedation for both noninvasive and gastrointestinal procedures, had simultaneous BIS and UMSS scores recorded. Sedation categories were defined as light, moderate, and deep for both UMSS and BIS. There was a moderate correlation between BIS and the UMSS, Spearman’s r

Background: Family presence during cardiopulmonary resuscitation is becoming a more common and accepted practice. Objectives: We wanted to determine the views held by pediatricians on family presence during pediatric cardiopulmonary resuscitation. We hypothesized that physicians who had more experience with critical illness and death would be more willing to allow parental presence. Additionally, we hypothesized that recently trained physicians, who may have had more educational exposure to family presence, would be more open to the practice than physicians who had been practicing longer. Methods: A 10-question survey was distributed to attendees of the American Academy of Pediatrics annual Uniformed Services Pediatric Seminar meeting, as well as pediatric staff and residents at both Tripler Army Medical Center and Kapiolani Women's and Children's Medical Center, Honolulu, Hawaii. Responses were compared using X 2 analysis, with significance indicated by a P value < 0.05. Results: Of the 245 respondents, 65% indicated that they would not allow parental presence. There was no significant difference in the responses based on gender, military affiliation, or years of experience. Those involved in inpatient-oriented specialties and residents were significantly more likely to allow parental presence during resuscitation than respondents involved in outpatient-oriented specialties (57.5%, 50%, and 26.4%, respectively; P < 0.01). Although only one third of respondents had been involved in a resuscitation during which parents were allowed to be present, the majority (63%) indicated that they would be willing to repeat the practice. Conclusions: Although in the minority, one third of the pediatricians surveyed are comfortable allowing parental presence during cardiopulmonary resuscitation. We conclude that pediatricians who have more frequent contact with seriously ill children are more likely to accept parental presence. Additionally, the exposure to parental presence during resuscitation efforts increases the likelihood of allowing parental presence in future resuscitation efforts.