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Hox genes are highly conserved transcription factors renowned for their roles in the segmental patterning of the embryonic anterior-posterior (A/P) axis. We report functions for Hox genes in A/P tissue segmentation and transverse fission behavior underlying asexual reproduction in adult planarian flatworms, Schmidtea mediterranea. Silencing of each of the Hox family members identifies 5 Hox genes required for asexual reproduction. Among these, silencing of hox3 genes results in supernumerary fission segments, while silencing of post2b eliminates segmentation altogether. The opposing roles of hox3 and post2b in segmentation are paralleled in their respective regulation of fission behavior. Silencing of hox3 increases the frequency of fission behavior initiation while silencing of post2b eliminates fission behavior entirely. Furthermore, we identify a network of downstream effector genes mediating Hox gene functions, providing insight into their respective mechanisms of action. In particular, we resolve roles for post2b and effector genes in the functions of the marginal adhesive organ in fission behavior regulation. Collectively, our study establishes adult stage roles for Hox genes in the regulation of tissue segmentation and behavior associated with asexual reproduction., Hox genes are highly conserved and well-known for their role in segmental patterning during early development. Here, the authors identify an unreported role for Hox genes in the adult tissue patterning and fission behavior required for asexual reproduction in planarian flatworms.

SummarySuccessful regeneration of missing tissues requires seamless integration of positional information along the body axes. Planarians, which regenerate from almost any injury, use conserved, developmentally important signaling pathways to pattern the body axes. However, the molecular mechanisms which facilitate crosstalk between these signaling pathways to integrate positional information remain poorly understood. Here, we report a p21-activated kinase (smed-pak1) which functionally integrates the anterior-posterior (AP) and the medio-lateral (ML) axes. pak1 inhibits WNT/β-catenin signaling along the AP axis and, functions synergistically with the β-catenin-independent WNT signaling of the ML axis. Furthermore, this functional integration is dependent on warts and merlin - the components of the Hippo/Yorkie (YKI) pathway. Hippo/YKI pathway is a critical regulator of body size in flies and mice, but our data suggest the pathway is required to pattern body axes in planarians. Our study provides a signaling network integrating positional information which can mediate coordinated growth and patterning during planarian regeneration.

SUMMARYStem cells enable regeneration by self-renewing and differentiating as instructed by a local microenvironment called a niche1–3. In most cases, the repair or replacement of tissues is fueled by tissue-specific or lineage-restricted stem cells that proliferate in response to local injury and apoptosis4–11. However, in organisms that regenerate using abundant adult pluripotent stem cells, the stem cell niches that support tissue repair have not been identified or characterized. Since these adult pluripotent stem cells are often more widely distributed and plentiful than lineage-restricted stem cells of other organisms, defining their microenvironments may uncover alternative forms of stem cell regulation12–14. Here we used unbiased spatial transcriptomics to define the cellular and molecular environments that support pluripotency in the highly regenerative freshwater planarianSchmidtea mediterranea. We determined that stem cells associate with a diverse collection of differentiated cell types, and these associations are highly dynamic during regeneration. We explored associations with two distinct cell types: secretory cells we term ‘hecatonoblasts,’ and intestinal cells. While both cell types regulate stem cell proliferation, their spatial relationships to stem cells defy the concept of a single regenerative niche. Thus, the planarian stem cell pool is likely maintained by a dynamic collection of distinct microenvironments that cooperatively power whole-body regeneration.

Whole-mount in situ hybridization (WISH) is a powerful and widely used technique to visualize the expression pattern of genes in different biological systems. Here we describe a new protocol for ISH and immunostaining in the planarian Schmidtea mediterranea. The new Nitric Acid/Formic Acid (NAFA) protocol is compatible with both assays and prevents degradation of the epidermis or blastema. Instead of proteinase K digestion, formic acid treatment is used to permeabilize tissues and preserve antigen epitopes. We show that the NAFA protocol successfully permits development of chromogenic and fluorescent signals in situ, while preserving the anatomy of the animal. Further, the immunostaining of different proteins was compatible with the NAFA protocol following fluorescent in situ hybridization. Finally, we demonstrate with high resolution confocal imaging that the regeneration blastema is preserved when using the new method. This new NAFA protocol will be a valuable technique to study the process of wounding response and regeneration.

The extracellular matrix (ECM) is a three-dimensional network of macromolecules that provides a microenvironment capable of supporting and regulating cell functions. However, only a few research organisms are available for the systematic dissection of the composition and functions of the ECM, particularly during regeneration. We utilized the free-living flatworm Schmidtea mediterranea to develop an integrative approach consisting of decellularization, proteomics, and RNAi to characterize and investigate ECM functions during tissue homeostasis and regeneration. ECM-enriched samples were isolated from planarians, and their proteomes were characterized by LC–MS/MS. The functions of identified ECM components were interrogated using RNA interference. Using this approach, we found that heparan sulfate proteoglycan is essential for tissue regeneration. Our strategy provides an experimental approach for identifying both known and novel ECM components involved in regeneration., Graphical Abstract, Highlights • Decellularization method developed to isolate ECM from complete animals. • Optimization of decellularization method for protein MS compatibility. • Identification of known and novel ECM components for their function in tissue regeneration., In Brief The ECM is a three-dimensional network of macromolecules that supports and regulates cell functions. Yet, only a few research organisms are available for the systematic dissection of the composition and functions of the ECM, particularly during regeneration. In this study, we report an integrative approach involving whole animal decellularization, protein mass spectrometry (LC–MS/MS), and RNA interference-based loss-of-function assays to identify both known and novel ECM components involved in regeneration.

SummaryHox genes are highly conserved transcription factors renowned for their roles in the segmental patterning of the embryonic anterior-posterior (A/P) axis1. Emerging evidence for Hox gene expression and function in postnatally derived structures has fueled interest in their additional roles beyond embryogenesis2,3. We report novel functions for Hox genes in A/P adult tissue segmentation and transverse fission behavior underlying asexual reproduction in the planarian flatworm, Schmidtea mediterranea. Silencing of each of the planarian Hox family members identified 5 Hox genes required for asexual reproduction. Among these, silencing of hox3 genes resulted in supernumerary segments, while silencing of post2b eliminated segmentation altogether. The opposing roles of hox3 and post2b in segmentation are paralleled in their respective regulation of fission behavior. Silencing of hox3 increased the frequency of fission behavior initiation, while silencing of post2b eliminated fission behavior entirely. Furthermore, we identified a network of downstream effector genes mediating Hox gene regulation of asexual reproduction, thereby providing insight into their respective mechanisms of action. Our study establishes postembryonic roles for Hox genes in regulating the emergence of tissue segmentation and specific behaviors associated with asexual reproduction in adult animals.

The extracellular matrix (ECM) is a three-dimensional network of macromolecules that provides a microenvironment capable of supporting and regulating cell functions. However, only a few research organisms are available for the systematic dissection of the composition and functions of the ECM, particularly during regeneration. We utilized a free-living flatwormSchmidtea mediterraneato develop an integrative approach consisting of decellularization, proteomics, and RNA-interference (RNAi) to characterize and investigate ECM functions during tissue homeostasis and regeneration. High-quality ECM was isolated from planarians, and its matrisome profile was characterized by LC-MS/MS. The functions of identified ECM components were interrogated using RNAi. Using this approach, we discovered that heparan sulfate proteoglycan and kyphoscoliosis peptidase are essential for both tissue homeostasis and regeneration. Our strategy provides a robust experimental approach for identifying novel ECM components involved in regeneration that might not be discovered bioinformatically.

Regeneration requires functional coordination of stem cells, their progeny, and differentiated cells. Past studies have focused on regulation of stem cell identity and proliferation near to the wound-site, but less is known about contributions made by differentiated cells distant to the injury. Here, we present a comprehensive atlas of whole-body regeneration over time and identify rare, transient, somatic cell states induced by injury and required for regeneration. To characterize amputation-specific signaling across a whole animal, 299,998 single-cell transcriptomes were captured from planarian tissue fragments competent and incompetent to regenerate. Amputation-specific cell states were rare, non-uniformly distributed across tissues, and particularly enriched in muscle (mesoderm), epidermis (ectoderm), and intestine (endoderm). Moreover, RNAi-mediated knockdown of genes up-regulated in amputation-specific cell states drastically reduced regenerative capacity. These results identify novel cell states and molecules required for whole-body regeneration and indicate that regenerative capacity requires transcriptional plasticity in a rare subset of differentiated cells.

Background: Hemorrhage from wounds in the extremities is the leading cause of preventable death on the battlefield. To successfully treat these injuries, the exact source of bleeding must be localized. Objective: The purpose of this study was to determine the feasibility of using Doppler ultrasound to precisely detect and localize peripheral vascular bleeding. Methods: Injuries were produced in common femoral arteries (diameter of ∼5 mm) of 28 pigs in vivo. Single puncture injuries were produced using 6 French (F) (n = 10), 9 F (n = 22), and 12 F (n = 12) catheters. In addition, multiple punctures were made (using 6 F and 9 F catheters) in eight common femoral arteries to simulate bleeding from multiple injuries. Finally, laceration injuries were produced using a scalpel in 10 femoral vessels. Results: In color Doppler images, bleeding was observed as a turbulent jet flow originating from the injury site in the vessel. This jet flow had checkered red-blue color pattern at the bleeding site, as opposed to a uniform color pattern in an intact artery. Peak systolic velocity at the injury site, measured using pulsed Doppler, was elevated to up to 152.0 ± 81.6 cm/s, as compared to 78.8 ± 17.5 cm/s in normal arteries. Further, end diastolic velocity increased from 6.1 ± 4.9 cm/s before the injury to up to 59.1 ± 33.1 cm/s after the injury. Resistance index was significantly lower (0.6 for 9 F and 12 F punctures, and 0.8 for 6 F punctures) at the bleeding site in injured arteries as compared to the resistance index of intact arteries (of 0.9). Conclusion: Our results showed a characteristic change in the systolic and diastolic velocities, as well as resistance indices at the injury site in peripheral arteries. These findings may serve as groundwork for development of automated bleeding detection and localization methods, and facilitate various hemorrhage control treatments.

Nuclear wastes from Hanford’s processing for separation of plutonium are stored in massive, buried, single-shell tanks in 18 tank farms. These so-called tank wastes were initially thermally hot because of radioactive decay, and many exhibited extreme chemical character in terms of pH, salinity, and radionuclide concentration. At present, 67 of the 149 single shell tanks are suspected to have released over 1.9 million L of tank waste to the vadose zone, with most leak events occurring between 1950 and 1975. Boreholes have been placed through the largest vadose zone plumes to defi ne the extent of contaminant migration and to develop conceptual models of processes governing the transformation, retardation, and overall transport of tank waste residuals. Laboratory studies with sediments so collected have shown that ion exchange, precipitation and dissolution, and surface complexation reactions have occurred between the tank wastes and subsurface sediments, moderating their chemical character and retarding the migration of select contaminants. Processes suspected to facilitate the far-fi eld migration of immobile radionuclides including stable aqueous complex formation and mobile colloids were found to be potentially operative but unlikely to occur in the fi eld, with the exception of cyanide-facilitated migration of 60 Co. Certain fi ssion product oxyanions (Mo, Ru, Se, Tc) and nitrates are the most mobile of tank waste constituents because their adsorption is suppressed by large concentrations of waste anions, the vadose zone clay fraction is negative in surface charge, and, unlike Cr, their reduced forms are unstable in oxidizing environments. Reaction/process-based transport modeling is beginning to be used for predictions of future contaminant mobility and plume evolution.

The USDOE has initiated an impact assessment of existing vadose zone contamination at the Hanford Site SX tank farm in southeastern Washington State. The assessment followed the Resource Conservation and Recovery Act (RCRA) Corrective Action process to address the impacts of past tank waste releases to the vadose zone at the single-shell tank farm. Numerical models were developed that consider the extent of contamination presently within the vadose zone and predict contaminant movement through the vadose zone to groundwater. The transport of representative mobile (technetium-99) and immobile (cesium-137) constituents was evaluated in modeling. The model considered the accelerated movement of moisture around and beneath single-shell tanks that is attributed to bare, gravel surfaces resulting from the construction of the underground storage tanks. Infiltration, possibly nearing 100 mm yr{sup -1}, is further amplified in the tank farm because of the umbrella effect created by percolating moisture being diverted by the impermeable, sloping surface of the large, 24-m-diameter, buried tank domes. For both the base case (no-action alternative) simulation and a simulation that considered placement of an interim surface barrier to minimize infiltration, predicted, groundwater concentrations for technetium-99 at the SX tank farm boundary were exceedingly high, on the order of 10{supmore » 6} pCi L{sup -1}. The predicted concentrations are, however, somewhat conservative because of our use of two-dimensional modeling for a three-dimensional problem. A series of simulations were performed, using recharge rates of 50, 30, and 10 mm yr{sup -1}, and compared to the basecase(100 mm yr{sup -1}) results. As expected, lowering meteoric recharge delayed peak arrival times and reduced peak concentrations at the tank farm boundary.« less

Clinically important diagnostic errors are relatively common among polytrauma patients (2-40%). Errors are not random; they are more frequent in the spine and periarticular appendicular skeleton, especially in hemodynamically unstable patients who require resuscitation or operative intervention before completion of secondary or tertiary clinical survey. Misleading history, distracting findings, and misjudgments all contribute to risks of diagnostic errors.

Computed tomography has revolutionized the diagnosis and treatment planning of the acutely injured spine. In the cervical spine, its appropriate use can improve outcome and save money. Although there are no clinical prediction rules validated outside of the cervical spine, these proven capabilities have been extrapolated to the thoracolumbar spine.

We proposed to characterize the radiologic spectrum of occipital condyle fractures in a large series of patients and to correlate fracture pathology with neurosurgical treatment and patient outcome.We conducted a retrospective review of the findings on conventional radiography, CT, and MR imaging in 95 patients with 107 occipital condyle fractures. We described fracture patterns according to two previously published classification systems. Clinical findings, neurosurgical management, and patient outcome were obtained from the medical records.Inferomedial avulsions (Anderson and Montesano type III) were the most common type of occipital condyle fracture, constituting 80 (75%) of 107 overall fractures. Unilateral occipital condyle fractures were found in 73 (77%) of 95 patients, and 58 patients were treated nonoperatively; occipitocervical fusion was required in nine patients for complex C1-C2 injuries, and six patients died. Bilateral occipital condyle fractures or occipitoatlantoaxial joint injuries were seen in 22 (23%) of 95 patients. Occipitocervical fusion or halo traction for the craniocervical junction was required in 12 patients, all of whom had CT evidence of bilateral occipitoatlantoaxial joint disruption and six of whom showed normal craniocervical relationships on conventional radiographs. Six patients with nondisplaced fractures were treated nonoperatively, and four patients died. Thirty (32%) of 95 patients showed continued disability, whereas 55 (57.5%) of 95 patients had good outcomes at 1 month. Associated cervical spine injuries were present in 29 (31%) of 95 patients.Given their associated traumatic brain and cervical spine injuries, occipital condyle fractures are markers of high-energy traumas. That conventional radiographs alone may miss up to half of the patients with acute craniocervical instability has not been well established. Avulsion fracture type and fracture displacement are associated with both injury mechanism and the need for surgical stabilization. In this series, most unilateral occipital condyle fractures were treated nonoperatively, whereas bilateral occipitoatlantoaxial joint injuries with findings of instability usually required surgical stabilization.

Our objective was to describe types and distribution of cervical spine injuries in elderly patients in regard to causative trauma mechanism and patient age.The distribution and type of 225 cervical spine injuries in 149 consecutive patients 65 years old and older over a 5-year interval were retrospectively assessed. For each patient, initial admission imaging studies were reviewed, and injuries were classified. Trauma mechanism (falls from standing or seated height vs higher energy mechanisms) and initial clinical and neurologic status were recorded. Data were correlated according to patients' age (65-75 years and75 years) and causative trauma mechanism.Ninety-five (64%) of 149 patients had upper cervical spine injuries. Fifty-nine (40%) of 149 patients had multilevel injuries. Main causes for cervical spine injuries were motor vehicle crashes in "young elderly" (65-75 years old; 36/59, 61%) and falls from standing or seated height in "old elderly" (75 years old; 36/90, 40%). Fracture patterns at risk for neurologic deterioration were common (50%), even in the absence of acute myelopathy or radiculopathy. Patients older than 75 years, independent of causative mechanism, and patients who fell from standing height, independent of age, were more likely to have injuries of the upper cervical spine (p = 0.026 and p = 0.006, respectively).Cervical spine injuries in elderly patients tend to involve more than one level with consistent clinical instability and commonly occur at the atlantoaxial complex. Old elderly patients and patients who fall from standing height are more prone to injuries of the upper cervical spine.

The purpose of this study was to describe the agreement between two hospitals on either side of the Atlantic Ocean in reading first day plain radiographs of suspected scaphoid fractures. Two groups of observers, one North American and one European, consisting of observers at various levels of training were compared. Kappa statistics were used to determine inter- and intra-observer agreement. The receiver-operating characteristics (ROC) curves and area under this curve (AUC) for each observer were calculated to determine test performance. Scaphoid radiographs of 80 consecutive patients seen with clinically suspected scaphoid fracture were included in the study. The results of the bone scan were used as the reference standard. There is an acceptable agreement between the USA and Europe for both radiologists and orthopaedic surgeons at various levels of training (kappa 0.45-0.88). Intra-observer agreement is acceptable as well (kappa 0.46-0.86). Considering all normal or equivocal radiographs, there is slight to moderate agreement at all levels of training in and between both centres and specialities (kappa 0-0.64). Overall test performance was acceptable for all consecutive radiographs (AUC 0.65-0.82) and poor for the normal radiographs (AUC 0.46-0.65). We could not detect differences in performance due to location of the readers' hospital or institution of training. The use of more sensitive techniques should be restricted to patients with negative or equivocal radiographs in clinically suspected scaphoid fractures.

This review provides a summary of the cost-effectiveness, clinical utility, performance, and interpretation of screening helical cervical spine CT for trauma patients. Recent evidence supports the use of helical CT as a cost-effective method for screening the cervical spine in high-risk trauma patients. Screening cervical spine CT can be performed at the time of head CT to lower the cost of the evaluation, and when all short- and long-term costs are considered, CT may actually save money when compared with traditional radiographic screening. In addition to having higher sensitivity and specificity for cervical spine injury, CT screening also allows more rapid radiological clearance of the cervical spine than radiography. Patients who are involved in high-energy trauma, who sustain head injury, or who have neurological deficits are candidates for CT screening. Screening with CT may enhance detection of other potentially important injuries of the cervical region.

Injuries to the atlanto-occipital region, which range from complete atlanto-occipital or atlantoaxial dislocation to nondisplaced occipital condyle avulsion fractures, are usually of critical clinical importance. At initial cross-table lateral radiography, measurement of the basion-dens and basion-posterior axial line intervals and comparison with normal measurements may help detect injury. Computed tomography (CT) with sagittal and coronal reformatted images permits optimal detection and evaluation of fracture and luxation. CT findings that may suggest atlanto-occipital injury include joint incongruity, focal hematomas, vertebral artery injury, capsular swelling, and, rarely, fractures through cranial nerve canals. Magnetic resonance (MR) imaging of the cervical spine with fat-suppressed gradient-echo T2-weighted or short-inversion-time inversion recovery sequences can demonstrate increased signal intensity in the atlantoaxial and atlanto-occipital joints, craniocervical ligaments, prevertebral soft tissues, and spinal cord. Axial gradient-echo MR images may be particularly useful in assessing the integrity of the transverse atlantal ligament. All imaging studies should be conducted with special attention to bone integrity and the possibility of soft-tissue injury. Atlanto-occipital injuries are now recognized as potentially survivable, although commonly with substantial morbidity. Swift diagnosis by the trauma radiologist is crucial for ensuring prompt, effective treatment and preventing delayed neurologic deficits in patients who survive such injuries.

Objective: The study objective was to determine the sensitivity and specificity of a helical CT technique to screen for cervical spine injury in a high-risk trauma population. Materials and methods: The helical CT reports for a consecutive series of 601 high-risk adult blunt trauma victims were reviewed. Findings were confirmed using an independent reference standard, which consisted of additional cervical spine imaging (CT, MRI, or radiography), operative findings, autopsy results or clinical outcome. Results: Sensitivity and specificity of helical CT for injury were 77/81 (95 %; 95 % confidence limits: 90–100 %) and 484/520 (93 %; 95 % confidence limits 91–95 %) respectively. Four false negative cases were comprised of three missed ligamentous injuries and one missed fracture. False positive cases (n = 36) were mostly attributed to possible facet fracture (n = 6), possible ligamentous injury (n = 8) or technically inadequate scan (n = 6).The overall accuracy of the helical CT protocol for cervical spine injury in this population was 561/601 (93 %; 95 % confidence limits 91–95 %). Conclusion: Helical CT has high accuracy for cervical spine injury. We believe that helical CT should be the preferred imaging strategy in high-risk blunt trauma patients.

Purpose: To enumerate host and vector factors that affect each phase of cervical spine injury (CSI) among the elderly, and to attribute specific pathoanatomic characteristics of CSI to host and/or vector factors. Methods: Structured review of English literature references selected from MEDLINE keyword search using PUBMED and OVID search engines. Only articles addressing the role of “aging” or being “elderly” (using a variety of definitions) in CSI were included. The following information was abstracted: journal; year of publication; authors' specialty or departmental affiliation; study design; inclusion and exclusion criteria; year(s) of data collection; number of CSI vs. controls; summary findings, including rate estimates, obvious study weaknesses. Results: Seven of 13 articles were medical-record-based case series, most derived from institutional trauma registries. Four were population-based surveys. One was an assessment of Medicare claims data for all-cause trauma and one a review paper. Blunt-force CSI was most commonly related to domestic falls, then to vehicular-pedestrian collisions and finally to vehicular crashes. More than two-thirds of fractures involved CO-C3, especially in individuals with cervical spondylosis and/or osteoporosis. In 15 to 40 % of CO-C3 fractures there is a delay in diagnosis. An adult forme fruste of SCIWORA (spinal cord injury without radiographic abnormality) was a relatively common cause of central and anterior cord syndromes in the absence of observable fractures or dislocations. Conclusions: The epidemiology of CSI in elderly patients should inform triage and imaging decisions. Since most CSI diagnostic errors involve the upper cervical spine, additional attention to the radiographic anatomy of the craniocervical junction and diligent search for abnormalities in this region are warranted.

Trauma surgeons must balance the risk and benefits of diagnostic radiographic procedures on potentially pregnant patients and should know the range and likelihood of effects that radiation might have on pregnancy.We present guidelines for assessing such radiation risks. Knowledge of a patient's pregnancy status and an estimate of radiation dose to the conceptus (low,10 mGy [milligray]; intermediate, 10-250 mGy; high,250 mGy) allow provisional assessment of radiation-induced risks.Dose estimates may be estimated at 2 mGy per exposure (radiographs), 5 mGy per slice (computed tomography), and 10 mGy per minute of fluoroscopy, when the conceptus is within the x-ray field. A formal radiation exposure assessment is appropriate when provisional estimates exceed 10 mGy.A simple qualitative dose assessment can inform clinical decisions and guide appropriate triage to more formal quantitative assessment.

To investigate the cost-effectiveness of computed tomography (CT) relative to radiography for cervical spine screening in trauma patients.A decision analysis model was constructed to compare the incremental cost-effectiveness of radiography and CT as primary cervical spine screening modalities in trauma patients. Analyses were performed from a societal perspective, and probability and cost estimates from the literature and institutional experience were used. In separate cost-effectiveness analyses, hypothetical cohorts of trauma patients from three defined clinical scenarios were considered: high, moderate, and low risk for cervical spine fracture. Outcome measures included cases of paralysis prevented, total cost of screening strategies, and incremental cost-effectiveness ratios.In high-risk patients, screening with CT is a dominant strategy that prevents cases of paralysis and saves money for society. In moderate-risk patients, screening with CT is cost-effective with reference-case assumptions and within the range of most sensitivity analyses. In the low-risk group, CT screening helps prevent cases of paralysis, but the incremental cost-effectiveness ratio is high ($80,000 per quality-adjusted life year).CT is the preferred cervical spine screening modality in trauma patients at high and moderate risk for cervical spine fracture.

Phantom studies were performed to develop a technique for linear tomography of the craniocervical junction with a digital fluoroscopic angiographic C-arm unit. Section thicknesses were similar to those used at conventional tomography, and the radiation dose was lower. C-arm tomography was possible with a 6-second exposure and a 40 degrees arc. C-arm tomography is a practical method for decreasing patient turnaround time.

To determine whether supine 45° oblique radiographs of the cervical spine can accurately detect and quantify anteroposterior intervertebral plane displacements, an observer performance study was performed. A normally aligned dry cervicothoracic vertebral specimen and the same specimen with varying degrees of subluxation at one or more levels were radiographed in anteroposterior, lateral, and 45° oblique projections, in a simulated supine position. Twenty-five sets of radiographs were obtained, of which three were normal. In the remaining 22 sets, there were 43 intervertebral segments with an abnormal anteroposterior displacement. Since each intervertebral level (C2-T1) was individually evaluated, the study sample consisted of 150 intervertebral segments. Blinded to experimental conditions, six observers evaluated every intervertebral level on each lateral and oblique image in isolation. The data for each projection were compared using alternative free-response operator characteristic and free-response forced-error methodologies. Significant differences in diagnostic accuracy were detected between the horizontal lateral and the supine oblique views to detect malalignment. Although supine oblique views detected many subluxations, they produced numerous false-negative and false-positive results. The findings of this study suggest that supine oblique views may be a useful part of the standard evaluation of the acutely injured cervical spine; however, they may not reliably portray clinically important anteroposterior displacements.

To understand the molecular processes underlying aging, we screened modENCODE ChIP-seq data to identify transcription factors that bind to age-regulated genes in C. elegans. The most significant hit was the GATA transcription factor encoded by elt-2, which is responsible for inducing expression of intestinal genes during embryogenesis. Expression of ELT-2 decreases during aging, beginning in middle age. We identified genes regulated by ELT-2 in the intestine during embryogenesis, and then showed that these developmental genes markedly decrease in expression as worms grow old. Overexpression of elt-2 extends lifespan and slows the rate of gene expression changes that occur during normal aging. Thus, our results identify the developmental regulator ELT-2 as a major driver of normal aging in C. elegans., Author Summary A central question in aging is to uncover the molecular drivers of the normal aging process. Using the roundworm C. elegans as a model organism, we found that the ELT-2 GATA transcription factor regulates many gene expression changes that occur during aging. During development, elt-2 functions as a key regulator of intestinal development. During aging, the levels of ELT-2 transcription factor decline, which causes expression of its target genes to decline and this limits lifespan. Reduction of elt-2 GATA activity in young worms induces gene expression changes resembling those that normally occur in old age. Overexpression of elt-2 slows down the rate of aging, and extends lifespan by about 25%. This work finds that worm lifespan is limited by the declining expression of a key developmental regulator.

Calculations were performed to compare the neutronics of two neutron source concepts which are candidates for an international fusion materials irradiation facility (IFMIF). One concept, d-Li, produces neutrons by stopping 35 MeV deuterons in a flowing lithium target. Criticism of this concept because of the high energy tail above 14 MeV gave rise to the t-H20 concept proposed by Cierjacks. It would generate neutrons below 14.6 MeV (< 1% extending to 22 MeV) by stopping 21 MeV tritons in a flowing water target. The comparison was made at equal beam power for single, uniform, 1 × 3 cm beams at 100 mA for d-Li and 170 mA for t-H20. Test volumes that met certain damage parameter criteria were estimated. Because of the softer spectra and somewhat lower yields for t-H20, the d-Li concept was found to have a test volume advantage of a factor of 2 or more, depending on the material to be irradiated.

The authors assessed whether the addition of a second-year diagnostic radiology resident assigned to cover the night shift at a major urban university hospital has a sustained effect on the number and clinical significance of “missed” radiologic findings. Radiographs interpreted overnight in the emergency department by radiology residents between January 1992 and December 1992 were reviewed daily by emergency radiology attending staff. A list of patients for whom there was a modification in the final radiologic interpretation was given to the emergency department physicians, who reviewed each case, scored the urgency of patient recall, and estimated the likelihood of patient morbidity attributable to the miss. The relative performance of after-hours residents was compared on the five nights per week with the dedicated night resident vs. the two nights per week without the dedicated night resident (control group).

Conventional radiography remains the appropriate initial screening evaluation of the chest in patients with major trauma. Computed tomography (CT) is appropriate for the definitive evaluation of abnormalities identified on initial radiography. Clinical evidence of hemodynamic instability or ongoing blood loss is the strongest indicator for operative intervention in the abdomen. Among patients with such indication of ongoing hemorrhage, transabdominal ultrasound and diagnostic peritoneal lavage (DPL) are diagnostically equivalent in identifying patients with intraperitoneal hemorrhage from solid organ injury. CT has high sensitivity for surgically important injuries of the liver and spleen, but CT grading of injury shows poor correlation with outcome. In patients with clinical suspicion of retroperitoneal injury, CT is the diagnostic procedure of choice. CT is the preferred imaging modality for identification of hollow viscus injury, although DPL may have higher sensitivity at the expense of lower specificity.