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Vagal sensory neurons monitor mechanical and chemical stimuli in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many distinct subtypes of vagal sensory neurons. Here, we use genetically guided anatomical tracing, optogenetics, and electrophysiology to identify and characterize vagal sensory neuron subtypes expressing Prox2 and Runx3 in mice. We show that three of these neuronal subtypes innervate the esophagus and stomach in regionalized patterns, where they form intraganglionic laminar endings. Electrophysiological analysis revealed that they are low-threshold mechanoreceptors but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal peristalsis in freely behaving mice. Our work defines the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain and could lead to better understanding and treatment of esophageal motility disorders.

Congenital Central Hypoventilation Syndrome (CCHS) is a rare, but life-threatening, respiratory disorder that is classically diagnosed in children. This disease is characterized by pronounced alveolar hypoventilation and diminished chemoreflexes, particularly to abnormally high levels of arterial pCO2. Mutations in the transcription factors PHOX2B and LBX1 have been identified in CCHS patients, but the dysfunctional circuit responsible for this disease remains unknown. Here, we show that distinct sets of medullary neurons co-expressing both transcription factors (dB2 neurons) account for specific respiratory functions and phenotypes seen in CCHS. By combining murine intersectional chemogenetics, intersectional labeling, and the selective targeting of the CCHS disease-causing Lbx1FS mutation to specific subgroups of dB2 neurons, we uncovered novel sets of these cells key for i) respiratory tidal volumes and the hypercarbic reflex, ii) neonatal respiratory stability and iii) neonatal survival. These data provide functional evidence for the essential role of dB2 neurons in neonatal respiratory physiology and will be instrumental for the development of therapeutic strategies for the management of CCHS. In summary, our work uncovers new neural components of the central circuit regulating breathing and establishes dB2 neuron dysfunction to be causative of CCHS.

SummarySensory neurons of the vagus nerve monitor distention and stretch in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many distinct subtypes of vagal sensory neurons. Here, we used genetically guided anatomical tracing, optogenetics and electrophysiology to identify and characterize three vagal sensory neuronal subtypes expressing Prox2 and Runx3. We show that these neuronal subtypes innervate the esophagus and stomach where they display regionalized innervation patterns. Their electrophysiological analysis showed that they are all low threshold mechanoreceptors, but possess different adaptation properties. Lastly, genetic ablation of Prox2+ and Runx3+ neurons demonstrated their essential roles for esophageal peristalsis and swallowing in freely behaving animals. Our work reveals the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain, and could lead to better understanding and treatment of esophageal motility disorders.

The type I transmembrane protein BT-IgSF is predominantly localized in the testes and brain. It belongs to the CAR subgroup of Ig cell adhesion proteins, which have been hypothesized to regulate connexin expression or localization. Here, we studied the putative link between mouse BT-IgSF and connexins in astrocytes, ependymal cells and neurons of the mouse. Global knockout of BT-IgSF caused an increase in the clustering of connexin43 (Gja1), but not of connexin30 (Gjb6), on astrocytes and ependymal cells. Additionally, we also found reduced expression levels of connexin43 protein in the cortex and hippocampus of knockout animals. Analysis of biocytin spread in hippocampal or cortical slices from mature mice of either sex revealed a decrease in astrocytic cell-cell coupling in the absence of BT-IgSF. The localization and expression of connexin36 (Gjd2) on neurons was not affected by the absence of BT-IgSF. Overall, our data indicate that the IgCAM BT-IgSF is essential for correct gap junction-mediated astrocyte-to-astrocyte and ependymal cell-to-ependymal cell communication. These data are discussed in the context of results obtained with knockouts of other members of the CAR protein subgroup.Summary statementIn the brain astrocytes are organized in vast networks communicating through gap-junctions. Here, we demonstrate that the cell adhesion molecule BT-IgSF controls connexin43-mediated coupling in astrocytes and ependymal cells.

The mature cerebellum controls motor skill precision and participates in other sophisticated brain functions that include learning, cognition, and speech. Different types of GABAergic and glutamatergic cerebellar neurons originate in temporal order from two progenitor niches, the ventricular zone and rhombic lip, which express the transcription factors Ptf1a and Atoh1, respectively. However, the molecular machinery required to specify the distinct neuronal types emanating from these progenitor zones is still unclear. Here, we uncover the transcription factor Olig3 as a major determinant in generating the earliest neuronal derivatives emanating from both progenitor zones in mice. In the rhombic lip, Olig3 regulates progenitor cell proliferation. In the ventricular zone, Olig3 safeguards Purkinje cell specification by curtailing the expression of Pax2, a transcription factor that suppresses the Purkinje cell differentiation program. Our work thus defines Olig3 as a key factor in early cerebellar development.

Syncytial skeletal muscle cells contain hundreds of nuclei in a shared cytoplasm. We investigated nuclear heterogeneity and transcriptional dynamics in the uninjured and regenerating muscle using single-nucleus RNA-sequencing (snRNAseq) of isolated nuclei from muscle fibers. This revealed distinct nuclear subtypes unrelated to fiber type diversity, previously unknown subtypes as well as the expected ones at the neuromuscular and myotendinous junctions. In fibers of the Mdx dystrophy mouse model, distinct subtypes emerged, among them nuclei expressing a repair signature that were also abundant in the muscle of dystrophy patients, and a nuclear population associated with necrotic fibers. Finally, modifications of our approach revealed the compartmentalization in the rare and specialized muscle spindle. Our data identifies nuclear compartments of the myofiber and defines a molecular roadmap for their functional analyses; the data can be freely explored on the MyoExplorer server (https://shiny.mdc-berlin.de/MyoExplorer/)., The transcriptional programs of nuclei in the muscle syncytium were assumed to be homogenous except at the neuromuscular and myotendinous junctions. Here, using single-nucleus transcriptomics, the authors reveal a previously unrecognized diversity and dynamics of myonuclear transcriptional programs.

Background.The diagnostic and prognostic utility of coronary flow reserve(CFR) during dipyridamole Stress echo(EchoDipi) has been recognized when the contractile response is positive and even in absence of wall motion abnormalities. Less studied is the behavior of regional longitudinal strain(RLS) and global(GLS) in relation of CFR in the territory of the left anterior descending artery(LADA). Objectives Compare the behavior of the Apical LS and GLS with the value of the CFR in the LADA and as a secondary objective to compare these responses with a simultaneous visual analysis of the motility during EchoDipi. Materials and methods 179 patients (p) were included (age 68.7 ± 7 years). Of them, 113p(65%) were men. At the peak of the effect of Dipi(0.84mg/kg in 4m) the CFR was measured in the distal region of the LADA(Normal Value≥2). The subjects were divided into 2 groups(G): G1: p with CFR of the LAD≥2 and G2 p with LADA CFR Results Of 179 p, 113p(63.12%) were included in G1 and 66p(36.87%) in G2. G1 were older(65.9 ± 10.27 vs 72.2 ± 9.31,p Conclusions.There was a close correlation between LADA coronary flow reserve and the contractile reserve evaluated by regional longitudinal strain of the 4 apical segments, which was superior to the use of global longitudinal strain. The Apical Strain showed a better correlation with the LADA coronary flow reserve than with the visual analysis of wall motion.

Exposure to prolonged, uncontrollable stress reduces reward-seeking behavior, resulting in anhedonia in neuropsychiatric disorders, such as posttraumatic stress disorder. However, it is unclear to what degree stressed subjects lose interest in rewards themselves or in reward-related cues that instigate reward-seeking behavior. In the present study, we investigated the effects of single prolonged stress (SPS) on cue-directed behavior in two different procedures: Pavlovian conditioned approach (PCA) and cue-induced reinstatement of cocaine-seeking. In Experiment 1, rats were exposed to SPS and tested for the acquisition of sign-tracking (cue-directed) and goal-tracking (reward-directed) behaviors during a PCA procedure. In Experiment 2, rats were exposed to SPS and tested for the expression of sign- and goal-tracking as well as cue-induced reinstatement of cocaine-seeking. Because dopaminergic activity in the nucleus accumbens is known to play a central role in many cue-directed behaviors, including both sign-tracking and cue-induced reinstatement, Experiment 3 used in vivo microdialysis to measure the effect of SPS on baseline and evoked dopamine levels in the nucleus accumbens. SPS decreased sign-tracking and increased goal-tracking during the acquisition of PCA behavior without affecting reward consumption. In addition, SPS decreased cue-induced reinstatement without affecting cocaine self-administration. Finally, SPS decreased evoked but not baseline levels of dopamine in the nucleus accumbens. These results suggest that SPS decreases the motivational, but not consummatory, aspects of reward-seeking behavior, which may result from long-term, SPS-induced reductions in dopamine release in the nucleus accumbens.

Although splicing is widespread and evolves rapidly among species, the mechanisms driving this evolution, as well as its functional implications, are not yet fully understood. We analyzed the evolution of splicing patterns based on transcriptome data from five tissues of humans, chimpanzees, rhesus macaques, and mice. In total, 1,526 exons and exon sets from 1,236 genes showed significant splicing differences among primates. More than 60% of these differences represent constitutive-to-alternative exon transitions while an additional 25% represent changes in exon inclusion frequency. These two dominant evolutionary patterns have contrasting conservation, regulation, and functional features. The sum of these features indicates that, despite their prevalence, constitutive-to-alternative exon transitions do not substantially contribute to long-term functional transcriptome changes. Conversely, changes in exon inclusion frequency appear to be functionally relevant, especially for changes taking place in the brain on the human evolutionary lineage.

Background: Traditional practice for alveolar cleft closure requires postoperative hospital convalescence in an unfamiliar, disruptive hospital setting. An outpatient iliac crest alveolar bone grafting protocol was devised to optimize patient care. Methods: A retrospective review of the senior author's experience over 5 years (1998 to 2004) of ambulatory alveolar cleft closure was compared with the previous 5-year period (1993 to 1998) of inpatient convalescence. An iliac crest donor site and standard techniques of alveolar grafting were followed in both groups. Although local analgesia with lidocaine and epinephrine was used in both groups, the ambulatory group received preemptive local anesthesia augmented with Marcaine. Postoperative nausea also was treated preemptively in the outpatient group with the addition of dexamethasone (Decadron) and ondansetron (Zofran), whereas the control patients were treated as needed. Patient charts were reviewed for demographic information, technical aspects, length of donor-site incision, bone graft volume, and time of operation. A Fisher's exact test was used for statistical analysis. Complications including morbidity, readmission, and reoperations were recorded. Results: Twenty consecutive patients were treated on an outpatient basis. Eight consecutive patients were convalesced as inpatients in the previous 5-year period. The ambulatory series average patient age was 12.1 years (range, 8 to 15 years). Four bilateral procedures were performed. The follow-up period averaged 3.5 years (range, 5 to 76 months). Two minor complications were identified: cellulitis at a donor site and a recipient suture line dehiscence with minor graft exposure. There were no readmissions, revision operations, hernias, wound infections, or graft losses identified. In the inpatient series, the average stay was 1.8 days (range, 1 to 3 days). One gingival suture line dehiscence requiring no further intervention was identified, for an average complication rate of 12.5 percent, which was not significant compared with the ambulatory group (10 percent) (p = 1.00). Conclusions: Alveolar cleft bone grafting using the iliac crest donor site can be safely performed on an outpatient basis when local pain control is followed by predictable anesthetic recovery and sufficient oral intake, and reliable motivated parents or caregivers provide a comfortable postoperative setting. Safe outpatient surgery provides patients and family the opportunity to recover in the familiar home environment.

Hip simulator studies show that the wear of ultra-high molecular weight polyethylene against a cobalt alloy head depends on the wear path, especially the combination of a predominantly linear wear direction on which is superimposed motions in different directions. We postulated that multidirectional motion was necessary to generate realistic wear rates in pin-on-disk testing. To assess this hypothesis, a new pin-on-disk tester was developed, capable of unidirectional and bidirectional motion. Unidirectional motion produced no detectable wear. The rectangular motion produced wear rates, surface morphologies, and wear particles consistent with human acetabular specimens. The results for 1 Hz and 2 Hz were similar.

Seizures in the developing brain pose a challenge to the clinician. In addition to the acute effects of the seizure, there are questions regarding the impact of severe or recurrent seizures on the developing brain. Whether provoked seizures cause brain damage, synaptic reorganization, or epilepsy is of paramount importance to patients and physicians. Such questions are especially relevant in the decision to treat or not treat febrile seizures, a common occurrence in childhood. These clinical questions have been addressed using clinical and animal research. The largest prospective studies do not find a causal connection between febrile seizures and later temporal lobe epilepsy. The immature brain seems relatively resistant to the seizure-induced neuronal loss and new synapse formation seen in the mature brain. Laboratory investigations using a developmental rat model corresponding to human febrile seizures find that even though structural changes do not result from hyperthermic seizures, synaptic function may be chronically altered. The increased understanding of the cellular and synaptic mechanisms of seizure-induced damage may benefit patients and clinicians in the form of improved therapies to attenuate damage and changes induced by seizures and to prevent the development of epilepsy.

Wear of ultrahigh-molecular-weight polyethylene and the subsequent lytic response to the particulate wear debris are the dominant problems in total joint arthroplasty surgery. Wear testing apparatus can play a vital role in the in vitro evaluation of the many factors involved in wear, such as head size, surface roughness, materials for the head, and new materials for the socket. Wear of ultrahigh-molecular-weight polyethylene may be influenced by the wear path. For the related polymer, high-density polyethylene, the wear path is critical to wear magnitude. What is the actual path taken by a single point (or by multiple representative points) on the femoral head of a total hip arthroplasty as it passes through the gait cycle? The goal of this computer simulation study was to trace the paths of specific points on the femoral head as they moved against the polyethylene cup during a single cycle of normal gait to illustrate the motions occurring at the intraarticular surface of the hip joint. This study also yielded unusual data on the “distance traversed” by these points during a single gait cycle. It was found that there was not one path, but rather there were many, and the paths varied widely in both shape and length depending on the location on the femoral head. Moreover, the differences in excursion and direction at different sites during the loaded phase were great. In addition, distances traveled by different points on the femoral head of any given size varied by a factor greater than 2. Most of the points traced quasielliptical paths. This automatically means that the paths of neighboring points cross each other, creating multidirectional shear forces on the acetabular cup surface which may be important in the localization and extent of wear. The plots of traces of the points derived from this study can serve as benchmarks for the ability of hip simulators to reproduce the actual distances and paths of travel of individual points on the femoral head.

This article describes the design and initial tests of the GPS portion of a system for making seafloor geodesy measurements. In the planned system, GPS antennas on a floating platform will be used to measure the location of an acoustic transducer, attached below the platform, which interrogates an array of transponders on the seafloor. Since the GPS antennas are necessarily some distance above the transducer, a short-baseline GPS interferometer consisting of three antennas is used to measure the platform's orientation. A preliminary test of several crucial elements of the system was performed. The test involved a fixed antenna on the pier and a second antenna floating on a buoy about 80 m away. GPS measurements of the vertical component of this baseline, analyzed independently by two groups using different software, agree with each other and with an independent measurement within a centimeter. The first test of an integrated GPS/acoustic system took place in the Santa Cruz Basin off the coast of southern California in May 1990. In this test a much larger buoy, designed and built at SIO, was equipped with three GPS antennas and an acoustic transducer that interrogated a transponder on the ocean floor. Preliminary analysis indicates that the horizontal position of the transponder can be determined with a precision of about a centimeter.

The RHIC 2003 Physics Run required collisions between gold ions and deuterons. The injector necessarily had to deliver adequate quality (transverse and longitudinal emittance) and quantity of both species. For gold this was a continuing evolution from past work. For deuterons it was new territory. For the filling of the RHIC the injector not only had to deliver quality beams but also had to switch between these species quickly. This paper details the collider requirements and our success in meeting these. Some details of the configurations employed are given.

Seizures in the developing brain pose a challenge to the clinician. In addition to the acute effects of the seizure, there are questions regarding the impact of severe or recurrent seizures on the developing brain. Whether provoked seizures cause brain damage, synaptic reorganization, or epilepsy is of paramount importance to patients and physicians. Such questions are especially relevant in the decision to treat or not treat febrile seizures, a common occurrence in childhood. These clinical questions have been addressed using clinical and animal research. The largest prospective studies do not find a causal connection between febrile seizures and later temporal lobe epilepsy. The immature brain seems relatively resistant to the seizure-induced neuronal loss and new synapse formation seen in the mature brain. Laboratory investigations using a developmental rat model corresponding to human febrile seizures find that even though structural changes do not result from hyperthermic seizures, synaptic function may be chronically altered. The increased understanding of the cellular and synaptic mechanisms of seizure-induced damage may benefit patients and clinicians in the form of improved therapies to attenuate damage and changes induced by seizures and to prevent the development of epilepsy.

The Rapid Cycling Medical Synchrotron (RCMS) delivers more than 3 10 protons per minute at a maximum extraction energy of 270 MeV, with single turn \fast extraction" at a repetition rate of 15 Hz. Upgrade paths are available to deliver substantially more protons per minute, to increase the extraction energy to 320 MeV, and to enable \slow extraction". The main advantages for proton therapy are: easy pulse-by-pulse adjustment of energy and intensity less beam on more frequent cycles in digital dose delivery upgradability: wobbling, scanning, proton radiography identical simple light magnets in both synchrotron and gantry easy installation and maintenance with small modular components Three key design choices account for these advantages { fast extraction, rapid cycling, and strong focussing. At all levels the underlying design goals are: reliability, simplicity, and modularity early and economic patient treatment In its initial con guration the RCMS delivers fast extracted beam into a double scattering system at the end of a xed beamline, or at the end of a gantry. The energy of the extracted beam is easily adjusted to any desired value between 70 MeV and 270 MeV. Three dimensional voxel scanning is also best performed using fast extraction. Nonetheless, the RCMS can easily be upgraded to include slow extraction capabilities, if this is deemed necessary for scanning or for other purposes. Less beam is accelerated per cycle in a rapid cycling sycnchrotron, making the accelerator performance more reliable, the design simpler, and the commissioning more rapid. Fast extraction and rapid cycling together make possible dose delivery with digital accuracy. Strong focusing is achieved by building the synchrotron from \FODO cell" modules containing dipole (bending) magnets, and quadrupole (focusing) magnets.

Several factors contribute to the success of stable bony ingrowth into the porous coated surfaces of orthopaedic implants used in hip arthroplasty. Despite having good bony apposition, bony ingrowth might not occur if the relative motion between bone and implant is large. Therefore, determining the limiting micromotion value that inhibits stable bony ingrowth is important. From a previous canine in vivo micromotion study performed at our laboratory, this limiting value was found to be 20 microns. Initially, cementless orthopaedic implants are stabilized only by frictional forces at the bone-implant interface. Therefore, other parameters such as the coefficient of friction and the compressive force normal to the interface should be considered as important factors which stabilize the interface along with micromotion. The purpose of this analytical study was to elucidate how the stability at the bone-implant interface is influenced by various factors, namely, motion of the implant, the coefficient of friction, the degree of pres fit, and the modulus of the surrounding cancellous bone in determining the stability of the bone-implant interface. Nonlinear and linear finite element models which simulated the immediate postsurgical condition and the end point of the canine in vivo micromotion experiment, respectively, were used to this end. From the results of the finite element models it was possible to identify the displacement magnitude for which the implant slipped relative to the bone as the motion of the implant was increased incrementally. This was done for combinations of the coefficient of friction, press fit, and Young's modulus of cancellous bone. This was used as an indicator of the limiting implant motion value beyond which bony ingrowth will be inhibited. The stress distribution in the surrounding cancellous bone bed was also obtained from the results of the finite element analyses for different press-fit conditions. The results of the study indicated that under slight press-fit conditions, the implant slipped relative to bone for implant motions as low as 20 microns. For higher degrees of press fit and reasonable values for the coefficient of friction, no slip occurred for implant motions as much as 100 microns. Although higher degrees of press fit were theoretically conducive to better implant stability, the concomitant high stresses in the adjacent cancellous bone will tend to compromise the integrity of the press fit. This was also evident when the results of an analytical model with a lower degree of press fit correlated well with those of the canine in vivo experiment in which a higher press fit was used, suggesting a possibility of achieving a less than desired press fit during the process of implantation. Through this study the importance of factors other than implant motion was emphasized. The results of the study suggest that the limiting value of implant motion that inhibits bone ingrowth might vary with the degree of press fit for reasonable coefficients of friction.

Cylindrical porous-coated implants were placed in the distal femoral metaphyses of twenty dogs and were subjected to zero, twenty, forty, or 150 micrometers of oscillatory motion for eight hours each day for six weeks with use of a specially designed loading apparatus. The in vivo skeletal responses to the different magnitudes of relative motion were evaluated. Histological analysis demonstrated growth of bone into the porous coatings of all of the implants, including those that had been subjected to 150 micrometers of motion. However, the ingrown bone was in continuity with the surrounding bone only in the groups of implants that had not been subjected to motion or that had been subjected to twenty micrometers of motion; in contrast, the implants that had been subjected to forty micrometers of motion were surrounded in part by trabecular bone but also in part by fibrocartilage and fibrous tissue, and those that had been subjected to 150 micrometers of motion were surrounded by dense fibrous tissue. Trabecular microfractures were identified around three of the five implants that had been subjected to forty micrometers of motion and around four of the five that had been subjected to 150 micrometers of motion, suggesting that the ingrown bone had failed at the interface because of the large movements. The architecture of the surrounding trabecular bone also was altered by the micromotion of the implant. The implants that had stable ingrowth of bone were surrounded by a zone of trabecular atrophy, whereas those that had unstable ingrowth of bone were surrounded by a zone of trabecular hypertrophy. The trabeculae surrounding the fibrocartilage or fibrous tissue that had formed around the implants that had been subjected to forty or 150 micrometers of motion had been organized into a shell of dense bone tangential to the implant (that is, a neocortex outside the non-osseous tissue). CLINICAL RELEVANCE: The findings of the present study quantitate the in vivo patterns of bone ingrowth and remodeling that occur in association with different magnitudes of micromovement of porous-coated implants. Small movements (zero and twenty micrometers) are compatible with stable ingrowth of bone and atrophy of the surrounding trabecular bone, whereas larger movements (forty and 150 micrometers) result in less stable or unstable ingrowth of bone, the formation of fibrocartilage or fibrous tissue around the implant, and hypertrophy of the surrounding trabecular bone. This study not only quantified the magnitudes of relative micromotion that cause these different skeletal responses but also may help in the interpretation of radiographs of patients who have a porous-coated prosthesis.

Four yttrium-stabilized alumina ceramic-on-polyethylene articulations obtained from patients who were undergoing revision surgery for sepsis (3) or recurrent dislocation (I) between 34 and 73 months were evaluated to assess their in vivo wear performance. The annual volumetric wear of the acetabular components determined directly by a fluid displacement method ranged from 58 to 140 mm3/y. Scanning electron microscope examination of these four ceramic heads revealed similar surface damage in all cases from a variety of causes. These included differential granular wear (alumina grains and yttrium-stabilized alumina grains at different depths), multidirectional scratches with heaped up boundaries, and incompletely sintered grains, as well as the formation of craters and separation of grain boundaries. The femoral heads in this small series of revision cases show that yttrium-stabilized alumina ceramic heads may develop surface irregularities from either manufacturing processes or in vivo use. The wear rates of this type of alumina-on-polyethylene articulation up to the time of revision were not substantially different from those found in other metal-on-polyethylene articulations retrieved at revision surgery.

To determine the mechanical properties of the interface between the tissue ingrowth into porous coatings and the implant, porous-coated cylindrical implants were inserted into the distal femur in 20 mature dogs and oscillated in vivo 8 hours per day for 6 weeks at fixed amounts of micromotion (0, 20, 40 and 150 microns). Applied torques and resulting displacements were recorded. The torsional resistance per unit angular displacement (TR/AD), reflecting the stiffness of the bone-porous coating interface, was 0.88 +/- 0.25 N-M/deg immediately after implantation in the 20-micron displacement group. It increased with time after surgery, reaching a maximum of 1.25 +/- 0.60 N-M/deg at 6 weeks. The TR/AD was lower initially (0.77 +/- 0.43 N-M/deg) in the 40-micron group and gradually decreased with time after surgery, reaching a maximum of 0.54 +/- 0.13 N-M/deg at 6 weeks. The TR/AD was even lower (0.24 +/- 0.10 N-M/deg) in the 150-micron group initially and remained the same (0.16 +/- 0.09 N-M/deg) with time after surgery. Histologic evaluation showed bone ingrowth in continuity with the surrounding bone in the 20-micron group consistent with the high stiffness values at sacrifice. In contrast, a mixture of fibrocallus and bone were found at the bone-porous coating interface in the 40-micron group, consistent with the intermediate stiffness values. In contrast, despite the fact that bone was found in the depth of the porous coating in the dogs in the 150-micron group, the low stiffness values were a reflection of fibrous tissue formation at the interface in that group, because of the large motion disrupting bony ingrowth at the bone-porous coating interface. By monitoring the torsional resistance per unit of angular displacement dynamically in vivo, it was possible to evaluate the mechanical properties of the bone-porous coating interface as tissue ingrowth proceeded. Twenty microns of oscillating displacement was compatible with stable bone ingrowth with high interface stiffness, whereas 40 and 150 microns of motion was not.

Wear of ultrahigh-molecular-weight polyethylene and the subsequent lytic response to the particulate wear debris are the dominant problems in total joint arthroplasty surgery. Wear testing apparatus can play a vital role in the in vitro evaluation of the many factors involved in wear, such as head size, surface roughness, materials for the head, and new materials for the socket. Wear of ultrahigh-molecular-weight polyethylene may be influenced by the wear path. For the related polymer, high-density polyethylene, the wear path is critical to wear magnitude. What is the actual path taken by a single point (or by multiple representative points) on the femoral head of a total hip arthroplasty as it passes through the gait cycle? The goal of this computer simulation study was to trace the paths of specific points on the femoral head as they moved against the polyethylene cup during a single cycle of normal gait to illustrate the motions occurring at the intraarticular surface of the hip joint. This study also yielded unusual data on the "distance traversed" by these points during a single gait cycle. It was found that there was not one path, but rather there were many, and the paths varied widely in both shape and length depending on the location on the femoral head. Moreover, the differences in excursion and direction at different sites during the loaded phase were great. In addition, distances traveled by different points on the femoral head of any given size varied by a factor greater than 2. Most of the points traced quasielliptical paths. This automatically means that the paths of neighboring points cross each other, creating multidirectional shear forces on the acetabular cup surface which may be important in the localization and extent of wear. The plots of traces of the points derived from this study can serve as benchmarks for the ability of hip simulators to reproduce the actual distances and paths of travel of individual points on the femoral head.

The development of a new hip simulator for the study of bearing materials used in total hip replacements has led to several findings which add important new information to the understanding of wear process of ultra-high molecular weight polyethylene, the most commonly used bearing material today for total joint replacements. Using this hip simulator which is capable of applying the physiological motion pathways occurring during gait to total hip components which are held in the correct anatomical position under the complex loading conditions of the hip in gait, the authors have shown that physiological motion pathways produce very different wear rates and morphology of the wear surface than unidirectional reciprocating pathways. Scanning electron microscopy studies show striking differences in the morphology of the wear surfaces of the polyethylene depending upon the relative motions of the components. Wear rates, surface morphology and particle debris generation consistent with clinical and retrieved studies are achieved when physiological conditions are simulated.

In the Brookhaven National Laboratory 20.8-GeV/c negative-hyperon beam, we have measured the production ratios ..sigma../sup -//..pi../sup -/, ..xi../sup -//..pi../sup -/, and ..sigma../sup -//..xi../sup -/ by 29.4-GeV/c protons incident on A1 and A1/sub 2/O/sub 3/ targets. We have also measured the asymmetry parameter in the decay ..xi../sup -/ ..-->.. ..lambda pi../sup -/ and find ..cap alpha../sub ..xi../-=-0.49 +- 0.04.

The relative yields on three different targets for the inclusive production of two π − are fitted to σ ∼ A α for proton-nucleus interaction at p lab = 28.5 GeV/ c at different transverse pion momenta. The exponent α increases with p T and becomes greater than 1 at p T > 1.1 GeV/ c . The data are compared with fireball models to determine the lifetime τ and dimension R of the fireball. For beryllium, we found τ = (1.4 −0.6 +0.5 ) × 10 −24 sec and R = 0.8 ± 0.4 fm.

Superconducting magnets exposed to intense primary proton beams in high energy physics applications are subject to potentially extreme heat deposition. The beam power density, its duration and spatial distribution, the current density in the superconductor and, potentially, in the normal metal substrate, as well as the construction and cooling details of the magnet, are all relevant parameters. We will discuss an extension of some earlier work in which 28.5 GeV/c proton beams with up to 50 k joules of energy were targeted upstream from a 4 m long, 4 T dipole magnet used to deflect the protons through an angle of 8°. Quench thresholds much greater than the enthalpy limit of the magnet materials were observed. In the beam exposure experiment described in this paper, intense beams of 1.5 GeV/c protons have been deflected directly into the magnet coil at relatively steep angles of incidence. The magnet quench threshold was studied by varying the beam currents and beam sizes.

We analyzed the accuracy of TRISS and a revised TRISS to predict survival outcome in a group of 1,562 consecutive children less than 15 years old admitted with blunt trauma to a pediatric trauma center. TRISS is an index that computes a probability of survival for each patient based on Trauma Score, Injury Severity Score, and age. R-TRISS uses the Revised Trauma Score instead of the Trauma Score. We used a statistical method based on TRISS and R-TRISS to compare patient outcomes from the pediatric study group with those of an adult baseline control group from the Major Trauma Outcome Study. Both TRISS and R-TRISS have the capability to accurately quantify survival outcome for children with blunt trauma; there was no statistical difference between the two methods to do so.

The decays ..sigma../sup -/ ..-->.. ..lambda..e/sup -/..nu.. and ..xi../sup -/ ..-->.. ..lambda..e/sup -/..nu.. are studied in a counter--spark-chamber experiment using unpolarized hyperons from the BNL hyperon beam. A threshold Cerenkov counter identifies the electron. From a sample of 119 reconstructed ..sigma../sup -/ ..-->.. ..lambda..e/sup -/..nu.. events (including approx. 5 background events), we find (..sigma../sup -/ ..-->.. ..lambda..e/sup -/..nu..)/(..sigma../sup -/ ..-->.. n..pi..) = (0.63 +- 0.10) x 10/sup -4/ and g/sub V//g/sub A/=-0.32 +- 0.30, g/sub W/M=-0.6 +- 3.6 (with sign convention of the Particle Data Group tables). We find Im(g/sub V//g/sub A/) =0.2 +- 0.7, consistent with time-reversal invariance. From a sample of 14 ..xi../sup -/ ..-->.. ..lambda..e/sup -/..nu.. events (including approx. = 3.4 background events) we find (..xi../sup -/ ..-->.. ..lambda..e/sup -/..nu..)/(..xi../sup -/ ..-->.. ..lambda pi..= (0.30 +- 0.14) x 10/sup -3/. We also searched for ..xi../sup -/ ..-->.. ..lambda mu nu.. and ..xi../sup -/ ..-->.. ..sigma../sup 0/e..nu.. and set upper limits on these decays from our data.