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Shared family meals have important implications for child health and wellbeing, however, mealtimes with children on the autism spectrum are often characterized by stress and problematic behavior. A better understanding of the underlying processes can elucidate the mealtimes challenges that families with children on the spectrum face as well as how families overcome those challenges in order to promote family health and wellbeing. Through a grounded theory analysis of mealtime observations, parent interviews, and child interviews with 16 families in the United States, we identified a theory of A Dialectic of Control and Acceptance. Integral to the role of mealtimes is for parents to express love through control and acceptance, however, these parallel processes are in tension with one another. How parents negotiate this tension dictates the degree to which their expectations are well aligned with their children's strengths and challenges and are able to provide effective support., (Copyright © 2021. Published by Elsevier Ltd.)

Purpose: A previous study showed that assessment of language laterality could be improved by adding grammar tests to the recovery phase of the intracarotid amobarbital procedure (IAP) (Połczyńska et al. 2014). The aim of this study was to further investigate the extent to which grammar tests lateralize language function during the recovery phase of the IAP in a larger patient sample., Methods: Forty patients with drug-resistant epilepsy (14 females, thirty-two right-handed, mean age 38.5years, SD=10.6) participated in this study. On EEG, 24 patients had seizures originating in the left hemisphere (LH), 13 in the right hemisphere (RH), and 4 demonstrated mixed seizure origin. Thirty participants (75%) had bilateral injections, and ten (25%) had unilateral injections (five RH and five LH). Based on results from the encoding phase, we segregated our study participants to a LH language dominant and a mixed dominance group. In the recovery phase of the IAP, the participants were administered a new grammar test (the CYCLE-N) and a standard language test. We analyzed the laterality index measure and effect sizes in the two tests., Key Findings: In the LH-dominant group, the CYCLE-N generated more profound language deficits in the recovery phase than the standard after injection to either hemisphere (p<0.001). At the same time, the laterality index for the grammar tasks was still higher than for the standard tests. Critically, the CYCLE-N administered in the recovery phase was nearly as effective as the standard tests given during the encoding phase., Significance: The results may be significant for individuals with epilepsy undergoing IAP. The grammar tests may be a highly efficient measure for lateralizing language function in the recovery phase., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Brain surgery in the language dominant hemisphere remains challenging due to unintended post-surgical language deficits, despite using pre-surgical functional magnetic resonance (fMRI) and intraoperative cortical stimulation. Moreover, patients are often recommended not to undergo surgery if the accompanying risk to language appears to be too high. While standard fMRI language mapping protocols may have relatively good predictive value at the group level, they remain sub-optimal on an individual level. The standard tests used typically assess lexico-semantic aspects of language, and they do not accurately reflect the complexity of language either in comprehension or production at the sentence level. Among patients who had left hemisphere language dominance we assessed which tests are best at activating language areas in the brain., Method: We compared grammar tests (items testing word order in actives and passives, wh -subject and object questions, relativized subject and object clauses and past tense marking) with standard tests (object naming, auditory and visual responsive naming), using pre-operative fMRI. Twenty-five surgical candidates (13 females) participated in this study. Sixteen patients presented with a brain tumor, and nine with epilepsy. All participants underwent two pre-operative fMRI protocols: one including CYCLE-N grammar tests (items testing word order in actives and passives, wh-subject and object questions, relativized subject and object clauses and past tense marking); and a second one with standard fMRI tests (object naming, auditory and visual responsive naming). fMRI activations during performance in both protocols were compared at the group level, as well as in individual candidates., Results: The grammar tests generated more volume of activation in the left hemisphere (left/right angular gyrus, right anterior/posterior superior temporal gyrus) and identified additional language regions not shown by the standard tests (e.g., left anterior/posterior supramarginal gyrus). The standard tests produced more activation in left BA 47. Ten participants had more robust activations in the left hemisphere in the grammar tests and two in the standard tests. The grammar tests also elicited substantial activations in the right hemisphere and thus turned out to be superior at identifying both right and left hemisphere contribution to language processing., Conclusion: The grammar tests may be an important addition to the standard pre-operative fMRI testing.

Introduction: Grammar is a core component of the language system, yet it is rarely assessed during the Wada (intracarotid amobarbital) test. It is hypothesized that adding grammar tests to the recovery phase of the Wada test will increase our ability to lateralize language function., Method: Sixteen individuals (nine females, fifteen right-handed, mean age 38.4 years, SD=10.7) with medically refractory temporal lobe epilepsy participated in the study. On EEG ten patients had seizures originating in the left hemisphere (LH), five in the right hemisphere (RH), and one was insufficiently lateralized. We included only patients who were LH-dominant on the standard test in the encoding phase of the Wada test. In the recovery phase of Wada testing the participants underwent evaluation with a standard language and a new test of grammar, the CYCLE-N. Ten patients underwent bilateral injections, six unilateral (one RH, five LH)., Results: As expected, injection in the LH decreased language performance to a greater extent than injection to the RH on both tests. However, the CYCLE-N produced more profound language deficits in the injected LH compared to the RH (p=0.01), whereas the standard tests did not cause such pronounced differences (p=0.2)., Conclusion: The results suggest that the standard tests did not significantly differentiate the effects of the injections and the CYCLE-N, for the most part, did. Our results are of particular relevance to patients who are too obtunded to speak in the encoding phase. In sum, the CYCLE-N may be helpful in assessing hemispheric dominance for language., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The primary goal of the Human Connectome Project (HCP) is to delineate the typical patterns of structural and functional connectivity in the healthy adult human brain. However, we know that there are important individual differences in such patterns of connectivity, with evidence that this variability is associated with alterations in important cognitive and behavioral variables that affect real world function. The HCP data will be a critical stepping-off point for future studies that will examine how variation in human structural and functional connectivity play a role in adult and pediatric neurological and psychiatric disorders that account for a huge amount of public health resources. Thus, the HCP is collecting behavioral measures of a range of motor, sensory, cognitive and emotional processes that will delineate a core set of functions relevant to understanding the relationship between brain connectivity and human behavior. In addition, the HCP is using task-fMRI (tfMRI) to help delineate the relationships between individual differences in the neurobiological substrates of mental processing and both functional and structural connectivity, as well as to help characterize and validate the connectivity analyses to be conducted on the structural and functional connectivity data. This paper describes the logic and rationale behind the development of the behavioral, individual difference, and tfMRI batteries and provides preliminary data on the patterns of activation associated with each of the fMRI tasks, at both group and individual levels., (Copyright © 2013. Published by Elsevier Inc.)

Allografting and autografting of osteochondral tissues is a promising strategy to treat articular cartilage lesions in damaged joints. We developed a new model of fresh osteochondral allografting using the entire rabbit trochlea. The objective of the current study was to demonstrate that this model would achieve reproducible graft-host healing and maintain normal articular cartilage histologic, immunolocalization, and biochemical characteristics after transplantation under diverse storage and transplantation conditions. New Zealand white (n = 8) and Dutch belted (n = 8) rabbits underwent a 2-stage transplantation operation using osteochondral grafts that had been stored for 2 or 4 wk. Trochlear grafts harvested from the left knee were transplanted to the right knee as either autografts or allografts. Grafts were fixed with 22-gauge steel wire or 3-0 nylon suture. Rabbits were euthanized for evaluation at 1, 2, 4, 6, and 12 wk after transplantation. All grafts that remained in vivo for at least 4 wk demonstrated 100% interface healing by microCT. Trabecular bridging was present at the host-graft interface starting at 2 wk after transplantation, with no significant difference in cartilage histology between the various groups. The combined histology scores indicated minimal evidence of osteoarthritis. Immunostaining revealed that superficial zone protein was localized at the surface of all transplants. The rabbit trochlear model met our criteria for a successful model in regard to the ease of the procedure, low rate of surgical complications, relatively large articular cartilage surface area, and amount of host-graft bone interface available for analysis.

Purpose: We compare the biomechanical properties of a volar hybrid construct to an all-locking construct in an osteoporotic and normal comminuted distal radius fracture model., Methods: Groups of 28 normal, 28 osteoporotic, and 28 over-drilled osteoporotic left distal radius synthetic bones were used. The normal group consisted of synthetic bone with a standard foam core. The osteoporotic group consisted of synthetic bone with decreased foam core density. The over-drilled osteoporotic group consisted of synthetic bone with decreased foam core density and holes drilled with a 2.3 mm drill, instead of the standard 2.0 mm drill, to simulate the lack of purchase in osteoporotic bone. Within each group, 14 synthetic bones were plated with a volar locking plate using an all-locking screw construct, and 14 synthetic bones were plated with a volar locking plate using a hybrid screw construct (ie, both locking and nonlocking screws). A 1-cm dorsal wedge osteotomy was created with the apex 2 cm from the volar surface of the lunate facet. Each specimen was mounted to a materials testing machine, using a custom-built, standardized axial compression jig. Axial compression was delivered at 1 N/s over 3 cycles from 20 N to 100 N to establish stiffness. Each sample was stressed to failure at 1 mm/s until 5 mm of permanent deformation occurred., Results: Our results show no difference in construct stiffness and load at failure between the all-locking and hybrid constructs in the normal, osteoporotic, or over-drilled osteoporotic synthetic bone models. All specimens failed by plate bending at the osteotomy site with loss of height., Clinical Relevance: Although volar locking plates are commonly used for the treatment of distal radius fractures, the ideal screw configuration has not been determined. Hybrid fixation has comparable biomechanical properties to all locking constructs in the fixation of metaphyseal fractures about the knee and shoulder and might also have a role in the fixation of distal radius fractures., (Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Study Design: Benchtop biomechanics study examining kinematic effects of progressive resection in a human cadaveric spine model., Objective: To determine the effects of posterior longitudinal ligament (PLL) resection, unilateral and bilateral foraminotomy, and laminectomy on cervical intervertebral rotation and translation after cervical disc arthroplasty (CDA)., Summary of Background Data: Although the clinical results after CDA have been studied, there remain unanswered questions regarding the surgical techniques used at the time of device insertion. For example, it is unclear whether a surgeon should retain or resect the PLL and uncinate processes at the time of primary surgical intervention. Further, the effect of a subsequent posterior decompression (foraminotomy or laminectomy) on the stability of a motion segment containing a disc arthroplasty is unknown., Methods: Three-dimensional intervertebral motion was measured by biplanar videography in human cadaveric spines at C4-C5 or at C5-C6 subjected to a 1.5-Nm moment applied to induce motion in the sagittal plane. Coupled motions were not constrained. After measuring intact spine motion, disc arthroplasty with bilateral ventral foraminotomy was performed without PLL resection. Sequentially, rotations and translations were measured after PLL resection, unilateral foraminotomy, bilateral foraminotomy, and laminectomy., Results: CDA with bilateral ventral foraminotomy increased sagittal rotation by 0.4 degrees (16%) compared with the intact spine. The addition of PLL resection increased rotation by 0.5 degrees (14% increase). Unilateral and bilateral foraminotomy had negligible effects on sagittal rotation or anteroposterior (AP) translation. Laminectomy resulted in an additional sagittal plane rotation of 2 degrees. The sagittal-plane interverterbal rotation resultant after all interventions was 6 degrees , with 1.5 mm of AP translation occurring only., Conclusion: Given that a greater degree of motion was seen with PLL resection combined with ventral foraminotomy, we recommend that PLL resection be performed when performing CDA. In our benchtop model, unilateral and bilateral posterior foraminotomies were not associated with the creation of significant sagittal rotational or AP translational instability.

Advances in 3-dimensional (3D) data capture, tracking, and computer modeling now allow for more appropriate measurement and analysis of the face. 3D video not only enables precise analysis of facial symmetry, it broadens our capabilities to accurately study facial volume and facial movement and the forces generated within tissue. Research in facial plastics outcomes has traditionally been evaluated with subjective measures. Current 3D methods are far superior and generate reproducible, accurate, and objective data for such clinical studies. As these technologies become more readily available, there will be a paradigm shift in how aesthetics research is conducted. 3D videography and newer technologies on the horizon will not only change current research methods; they will be much more pervasive in the clinical practice of aesthetic surgeons as they are incorporated into preoperative planning and used to improve patient communication., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: To determine the force requirements, optimal vector, and appropriate materials of a novel eyelid sling device that will be used to rehabilitate eyelid closure (blink) in congenital or acquired permanent facial paralysis with an artificial muscle., Methods: The force required to close the eyelids in human cadavers (n = 6) were measured using a load cell system. The eyelid sling using either expanded polytetrafluoroethylene (ePTFE) or temporalis muscle fascia was implanted. The ideal vector of force and placement within the eyelid for a natural eyelid closure were compared., Results: The eyelid sling concept was successful at creating eyelid closure in a cadaver model using an upper eyelid sling attached to the distal tarsal plate. Less force was necessary to create eyelid closure using a temporalis muscle fascia sling (627 +/- 128 mN) than for the ePTFE eyelid sling (1347 +/- 318 mN)., Conclusions: The force and stroke required to close an eyelid with the eyelid sling are well within the attainable range of the electroactive polymer artificial muscle (EPAM). This may allow the creation of a realistic and functional eyelid blink that is symmetric and synchronous with the contralateral, normally functioning blink. Future aims include consideration of different sling materials and development of both the EPAM device and an articulation between the EPAM and sling. The biocompatibility and durability studies of EPAM in a gerbil model are under way. The successful application of artificial muscle technology to create an eyelid blink would be the first of many potential applications.

The development of an engineered tissue requires a clear understanding of the interactions between the individual components. In this study, we investigated how the addition of hyaluronic acid (HA) to a cartilage tissue engineered scaffold alters chondrocytic expression, and specifically the expression of insulin-like growth factor-1 (IGF-1) signaling molecules. Bovine chondrocytes were embedded (7 million cells/mL) in 2.0% w/v alginate hydrogels containing varying HA concentrations (0, 0.05, 0.50, and 5.00 mg/mL). In vitro constructs were cultured with exogenous IGF-1, and gene expression was monitored at days 1, 4, and 8 for IGF-1, IGF-1 receptor (IGF-1R), IGF binding protein 3 (IGFBP-3), type II collagen and type I collagen. In vivo constructs were precultured for 24 h with exogenous IGF-1 before being implanted subcutaneously in severe combined immunodeficient mice; samples were analyzed using histology at days 7, 14, and 21. Results indicate that, with the addition of high levels (5.00 mg/mL) of HA, IGF-1 can become entrapped within the matrix and therefore interfere with the delivery of IGF-1 to chondrocytes. In vitro and in vivo data showed that increasing the concentration of HA in an alginate hydrogel can decrease chondrocyte IGF-1 expression. IGF-1R expression did not change with HA concentration, and the addition of any HA did not significantly alter IGFBP-3 expression. Chondrocytes continuously expressed phenotypic type II collagen in vitro and in vivo throughout the study for all the groups. However, for all the HA concentrations investigated, chondrocytes showed more of a fibroblastic phenotype, as indicated by greater expression of type I collagen than with no HA, in vitro and in vivo. In conclusion, these results indicate that HA interferes with the delivery of IGF-1 to chondrocytes, affecting the endogenous expression of IGF-1 signaling molecules and the resulting chondrocyte phenotype, and therefore demonstrating the critical effect of biomaterial scaffolds on encapsulated cell function.

Background: To compare the stability achieved using two 6.5-mm screws versus two or four 3.5-mm screws for the fixation of a unicondylar distal femur fracture., Methods: A fracture model was created in femoral synthetic composite bones to simulate a lateral femoral condyle fracture (AO/OTA 33-B1). Fixation was performed using three different types of screw constructs: 1) two 6.5-mm cancellous screws inserted using the lag technique, 2) two 3.5-mm cortical screws inserted using the lag technique, and 3) four 3.5-mm cortical screws, with two inserted using the lag technique and two as position screws. After reduction and fixation, the constructs were axially loaded in a material-testing machine. Main outcome measurements were the mean load required to displace the osteotomy site 1 and 2 mm as well as the mean stiffness of the different fixation methods., Results: The 6.5-mm construct required 56% more load to displace the osteotomy fragment 1 mm than the two 3.5-mm construct required (p < 0.0001), and 40% more load than the four 3.5-mm construct required (p < 0.0001). At loads that caused 2 mm of osteotomy displacement, these differences increased to 62% (p < 0.0001) and 48% (p < 0.0001), respectively. The mean loads needed to displace the osteotomy site were 28% higher for 1 mm of displacement (p = 0.003) and 27% higher for 2 mm of displacement (p = 0.03) for the four 3.5-mm screw construct compared with those needed for the two 3.5-mm group. The mean stiffness for the 6.5-mm group (1312.5 N/mm) was significantly higher than for the four 3.5-mm construct (784.2 N/mm; p < 0.0001) and the two 3.5-mm screw construct (409.4 N/mm; p < 0.0001). The difference in stiffness between the 3.5-mm groups was significant as well (p < 0.0001)., Conclusion: Stabilization of a unicondylar distal femur fracture with two 6.5-mm cancellous screws provides the most rigid and stable fixation. If small fragment screws are used, a minimum of four 3.5-mm cortical screws should be used to approximate the mechanical stability of two 6.5-mm screws.

The purpose of this study was to evaluate the influence of age on the effectiveness of rhBMP-7 treatment in a fracture with severe periosteal damage that is known to result in non-union formation. Closed stabilized femur fractures were produced in 3-month-old and 18-month-old rats. The fracture site was exposed and 2 mm of the periosteum cauterized circumferentially to impair normal fracture healing. The cauterized fracture site was immediately treated with either 100 microg rhBMP-7 (BMP-7 group), or with 25 microL of vehicle alone (control group). Fracture healing was evaluated with radiographs taken at 3 and 6 weeks. Animals were sacrificed at 3 and 6 weeks and specimens subjected to biomechanical and histological evaluation. In both age groups, none of the control animals healed throughout the 6 weeks experimental duration. All of the rhBMP-7-treated 3-month-old animals were radiographically healed at 3 weeks. In comparison, only 56% (9/16) of the rhBMP-7-treated 18-month-old animals were radiographically healed at 3 weeks. At 6 weeks, however, all of the 18-month-old rhBMP-7-treated animals had healed. Histology revealed slower healing in the 18-month-old animals. Treatment with rhBMP-7 significantly increased all of the biomechanical properties in both age groups. In the 3-month-old animals the mechanical strength approached that of the intact femur at 3 weeks, while in the 18-month-old animals this did not occur until 6 weeks. In conclusion, rhBMP-7 can effectively stimulate fracture repair in both young (3-month-old) and old (18-month-old) rats. However, the effect of rhBMP-7 on the rate of fracture healing is greater in young rats compared to old rats.

This study evaluated different fixation methods in posterior femoral condyle coronal fractures. A standardised osteotomy was created in synthetic composite femurs and fixed with one of four methods (one 3.5 mm diameter screw, two 3.5 mm screws, one 6.5 mm screw, two 6.5 mm screws). The stiffness and mean loads to specified displacements were measured. The stiffness of two 6.5 mm screws was significantly greater than both single 3.5 mm screw (3567 versus 2584N/mm; p=0.0075) and double 3.5 mm screws (3567 versus 2080N/mm; p=0.003). There was no statistical difference in the stiffness of one 6.5 mm screw compared to either the single or double 3.5mm screws. Increasing the screw diameter and using two screws increased the load at 1, 2 and 3 mm of displacement. In the fixation of posterior femoral condyle fractures, two 6.5 mm screws are more rigid than either single or double 3.5 mm screws. The use of a second screw marginally increases the rigidity of fixation. If 3.5 mm screws are used in the fixation of posterior femoral condyle fractures, at least two screws should be used to approximate the biomechanical stability of a single 6.5 mm screw.

Severe periosteal and soft tissue disruption at the time of fracture may result in the formation of an atrophic nonunion. We have developed a reproducible atrophic nonunion in an animal model. The purpose of this study was to evaluate whether the immediate application of recombinant human BMP-7 to the fracture site could rescue the healing process in this nonunion model. A total of 56 three month old Fisher 344 rats were utilized. A 1.25 mm diameter K-wire was inserted into the femur in a retrograde fashion, and a mid-diaphyseal closed transverse fracture was created using a standard three point bending device. To create a nonunion, the fracture site was exposed and 2 mm of the periosteum was cauterized on each side of the fracture. The fracture site was immediately treated with either the application of rhBMP-7 50 microg in 25 microl of rat tail tendon collagen buffer (BMP-7 group), or with 25 microl of rat tail tendon collagen buffer only (Control group). Fracture healing was evaluated with serial radiographs every two weeks for an eight weeks period. Specimens at four and eight weeks were subjected to biomechanical and histological evaluation. None of the Control group healed throughout the eight weeks experimental duration. At four weeks 63% of the BMP-7 group had healed, and all had healed by six weeks. This investigation showed pronounced differences between the BMP-7 group and the Control group both histologically and biomechanically. In conclusion, we have demonstrated that the immediate application of BMP-7 may rescue the fracture healing process and prevent the development of nonunion following severe periosteal disruption.

This article presents a rationale and description of GCS, or Grammatical Coding System. GCS is a general-use grammatical coding system designed for research on the language of normal and language-impaired children or adults and is especially useful for studies in which a relatively large number of participants are involved. It implements recent theoretical developments in linguistics to characterize development and/or language disorder in children and adults. In addition to the coding system, a computerized method for reading coded transcripts and calculating relevant descriptive statistics is presented. A full coded transcription is included in the Appendix. A detailed GCS manual may be downloaded from www.psychonomic.org/archive.

Background: Intraoperative ultrasound has been used extensively during open surgery to assess bowel viability, to identify vascular structures, and to assess for congenital abnormalities. The extension of this technology in laparoscopic procedures has been hampered by the size of the equipment and the significant learning curve that accompanies its use., Methods: Using a readily available Parks Inst. Co. Doppler Probe (8.1 MHz) and a 15-inch section of thick-walled, 9.5-mm OD Stainless Steel tubing, a Laparoscopic Doppler Probe was constructed. The parts were separately gas-sterilized, and a small segment of Penrose drain was used to create an airtight seal. The probe was passed through a 10-mm port, allowing assessment of vascular structures., Results: Two Laparoscopic Doppler Probes were available for evaluation during a 1-month period at our hospital. Surgeons were then surveyed at the end of the 1-month period as to the utility of the devices., Conclusions: The Laparoscopic Doppler probe was used to identify the cystic artery during gallbladder dissection, to assess mesenteric blood vessels during laparoscopic colectomy, and to identify femoral vessels during laparoscopic preperitoneal hernia repair. It was found to be quick to construct, easy to use, and provided useful information to the operating surgeon.

This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants--cisplatin, gentamicin, and puromycin--to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for 21 days), gentamicin (2-240 mg/kg/day for 7 days), or a single dose of cisplatin (0.1-5 mg/kg). Groups of rats were sacrificed at various times after administration of these compounds for standard clinical chemistry, urine analysis, and histological evaluation of the kidney. RNA was extracted from the kidney for microarray analysis. Principal component analysis and gene expression-based clustering of compound effects confirmed sample separation based on dose, time, and degree of renal toxicity. In addition, analysis of the profile components revealed some novel changes in the expression of genes that appeared to be associated with injury in specific portions of the nephron and reflected the mechanism of action of these various nephrotoxicants. For example, although puromycin is thought to specifically promote injury of the podocytes in the glomerulus, the changes in gene expression after chronic exposure of this compound suggested a pattern similar to the known proximal tubular nephrotoxicants cisplatin and gentamicin; this prediction was confirmed histologically. We conclude that renal gene expression profiling coupled with analysis of classical end points affords promising opportunities to reveal potential new mechanistic markers of renal toxicity.

A review of the literature on the developmental outcome of medically and surgically treated symptomatic infantile spasms (IS) indicates that poor seizure control, severe mental retardation, and marked behavioral disorders are found at long-term outcome of symptomatic IS. The 2-year outcome findings of the UCLA Pediatric Epilepsy Surgery Research Group in children with symptomatic infantile spasms and in children with early onset intractable symptomatic epilepsy other than IS (non-IS) demonstrate impaired development of cognition, language, and social communication despite improved seizure control. The social communication deficits of these children are similar to those found in autistic children. Finally, the underlying pathology of the resected brain, rather than ongoing seizures and seizure type, plays an important role in development of the remaining brain tissue and the outcome of early onset symptomatic IS and non-IS.

We analyzed postsurgery linguistic outcomes of 43 hemispherectomy patients operated on at UCLA. We rated spoken language (Spoken Language Rank, SLR) on a scale from 0 (no language) to 6 (mature grammar) and examined the effects of side of resection/damage, age at surgery/seizure onset, seizure control postsurgery, and etiology on language development. Etiology was defined as developmental (cortical dysplasia and prenatal stroke) and acquired pathology (Rasmussen's encephalitis and postnatal stroke). We found that clinical variables were predictive of language outcomes only when they were considered within distinct etiology groups. Specifically, children with developmental etiologies had lower SLRs than those with acquired pathologies (p =.0006); age factors correlated positively with higher SLRs only for children with acquired etiologies (p =.0006); right-sided resections led to higher SLRs only for the acquired group (p =.0008); and postsurgery seizure control correlated positively with SLR only for those with developmental etiologies (p =.0047). We argue that the variables considered are not independent predictors of spoken language outcome posthemispherectomy but should be viewed instead as characteristics of etiology., (Copyright 2001 Elsevier Science.)

We studied the spoken language of 49 children who had undergone hemispherectomy as part of the UCLA Pediatric Epilepsy Surgery Research Program and analyzed, among a number of clinical factors, the relation between acquired vs developmental pathology and spoken language outcomes. In this paper we will briefly review the results of our study and attempt to explain (1) why "the early" is not always better, (2) why so many right hemispherectomies fail to develop language, and (3) why some left hemispherectomized children develop remarkably good language despite removal of the "language" hemisphere. This account will rest on the proposed model of brain maturation and progressive lateralization.

We report on the effects of etiology and age on the linguistic outcomes in a large pediatric hemispherectomy population. Four populations were considered separately: cortical dysplasia (multilobar involvement), Rasmussen's encephalitis, infarction as a primary etiology and, fourth, children who failed to develop language, regardless of etiology. We argue against the 'the-earlier-the-better' hypothesis and propose our own hypothesis that weds maturational factors to etiological factors to predict language outcomes following pervasive brain insult. The implications of our 'critical impact point' hypothesis are discussed., (Copyright 1999 S. Karger AG, Basel)

Purpose: To perform a retrospective analysis of chronic limb ischemia and determine whether endovascular surgery can be performed safely and cost effectively on an ambulatory basis., Methods: Among 42 patients undergoing endovascular interventions for lower limb ischemia over a 12-month period ending October 1997, 32 (18 men, mean age 68 years, range 44 to 89) were treated solely by endovascular interventions. These patients were grouped according to time inhospital: 20 (63%) patients had endovascular procedures performed on an ambulatory basis, 7 (22%) were hospitalized for > 24 hours, and 5 (16%) required an overnight stay. The angioplasty procedures, which included placement of 21 stents, were performed in the abdominal aorta (n = 1) and the common iliac (n = 9), external iliac (n =7), superficial femoral (n = 11), popliteal (n = 5), tibioperoneal (n = 7), and subclavian (n = 1) arteries. Hospital charges were compared for the 3 groups., Results: Other than the presence of coronary artery disease, there were no significant differences in demographics or risk factors among the 3 groups. Angioplasty was technically successful in all patients, and there were no procedural complications. Patients with tissue loss required hospitalization more frequently compared to those with claudication. Significantly more patients who were hospitalized had epidural anesthesia as opposed to local when compared to the ambulatory group, 43% versus 5%, respectively (p = 0.04). Excluding professional fees, mean total hospital cost differed significantly between the ambulatory group and the group of patients with a hospital stay > 24 hours ($8227 versus $40,383, respectively; p = 0.03) and between the 2 hospitalized groups ($9476 for overnight stay versus $40,383 for > 24-hour stay, p = 0.03)., Conclusions: Peripheral endovascular interventions can be performed safely on an ambulatory basis resulting in decreased hospital cost. Patients who receive epidural anesthesia, require concomitant open vascular reconstruction, present with tissue loss, or have unstable medical conditions are more likely to require hospitalization.

The remarkable technologic and methodologic advances spurred on by the Human Genome Project are being applied throughout the life sciences. In the field of toxicology, high-resolution assays now make it possible to discover virtually all the differences in gene expression brought on by exposure to a particular xenobiotic. There are 2 principal approaches used to build a catalog of changes in gene expression: hybridization microarrays and gel-based methods, such as differential display and AFLP-based mRNA finger-printing. The power of such approaches is exemplified by the identification of more than 300 genes that differ in expression level by at least 2-fold in response to the nongenotoxic rodent liver carcinogen phenobarbital.

The tumorigenic potential of phenobarbital was examined in a 26-wk carcinogenesis bioassay using p53 heterozygous mice and wild-type controls. Fifteen mice/sex/genotype were exposed to either 500 or 1,000 ppm phenobarbital in the diet. Dietary administration of 3,750 ppm p-cresidine, a transspecies mutagenic carcinogen, to both heterozygous and wild-type mice served as a positive control. Phenobarbital treatment caused increases in liver:body weight ratios and histologic evidence of centrilobular hepatocellular hypertrophy. No tumors were observed in any phenobarbital-treated mice. Mice given p-cresidine exhibited a moderate reduction in body weight gain over the course of the study. Heterozygous mice treated with p-cresidine exhibited a high incidence of urinary bladder tumors. Similar tumors were also present in a small number of p-cresidine-treated wild-type mice. Our results demonstrate the lack of a hepatic tumor response to phenobarbital, a compound that is a potent and potent and prototypic hepatic microsomal enzyme inducer, a nongenotoxic rodent carcinogen, and a human noncarcinogen. This finding supports the continued utility of this model as an alternative to the mouse bioassay for human carcinogenic safety assessment of potentially genotoxic carcinogenes because it did not produce a false-positive response to this potent nongenotoxic agent.

Background: Thoracoabdominal esophagogastrectomy is associated with a number of potential life-threatening complications., Patients: We describe a patient with intraoperative hypotension in which a number of therapeutic maneuvers eventually led to the diagnosis of cardiac tamponade., Results: Once the diagnosis of tamponade was made, it was successfully treated by the release of intrapericardial blood., Conclusions: Although rare, tamponade should be considered as a cause of hemodynamic instability whenever intraoperative manipulation of the heart has occurred.

Background: This study was designed to evaluate the effect of donor hyperosmolarity secondary to diabetes insipidus, an almost universal occurrence among brain-dead patients, on hepatic function., Methods: In vitro (isolated liver perfusion) and in vivo (hyaluronic acid and indocyanine green uptake, arterial ketone body ratio, orthotopic liver transplantation) experiments were conducted using Brattleboro rats, with hereditary hypothalamic diabetes insipidus, and Sprague-Dawley rats, with normal pituitary function. ATP content and recovery after cold preservation were measured during the perfusion., Results: Cold-preserved livers from hyperosmolar rats were observed to have elevated hepatic enzyme release and decreased bile production compared with normosmolar controls. Moreover, in these livers, the recovery of ATP after cold preservation was completely absent. Transmission electron microscopy of liver biopsies collected from hyperosmolar rats demonstrated profound ultrastructural changes, particularly in the mitochondria, that were not evident in the biopsies from normosmolar rats. All the experimental groups demonstrated similar hyaluronic acid uptake, whereas indocyanine green uptake was markedly impaired in the hyperosmolar group, suggesting that hepatocyte and not sinusoidal endothelial cell function is adversely affected by hyperosmolarity. The arterial ketone body ratio was profoundly compromised by chronic and, to an even greater degree, by acute hyperosmolarity. Survival after transplantation using hyperosmolar donors was not affected in this study., Conclusions: These results are an important step toward understanding the mechanism whereby brain death, a complicated pathophysiologic phenomenon, adversely affects the hepatic allograft.

Cytokines, produced by both the recipient and the newly vascularized allograft, are central mediators in the inflammatory response to allografted tissue. This study examines the relationship between pre- and intraoperative levels of TNF, IL-1, IL-6, and IL-8 and hepatic allograft function in the early postoperative period and also determines which cytokines are produced in a significant amount by the newly vascularized allograft. Baseline levels of IL-6 and IL-8 tended to be higher in patients with more advanced disease and showed an increase during the anhepatic period. TNF and IL-1 remained stable from baseline to anhepatic phase. IL-1 showed an increase from portal vein to effluent samples, suggesting that the graft has an important contribution to circulating IL-1 levels. Analysis of the data according to early graft performance revealed extremely high levels of effluent IL-1, IL-6 and IL-8, and the prolonged elevation of the latter two cytokines in patients with poor early graft function. Our findings demonstrate that sequential perioperative measurements of proinflammatory cytokines can be useful in monitoring graft function.

Although loss of heterozygosity (LOH) for loci on chromosome 3p is a common event in cervical carcinoma (CC), the frequency and affected regions of 3p are inconsistent among studies. Here we report a comprehensive analysis of LOH on 3p in 66 primary tumors and 16 CC-derived cell lines using a high density of marker loci. Clonal LOH was found in over 70% of primary tumors, and the patterns of loss indicated four to five target regions, with 3p14 being the most frequent. The majority of tumors had complex patterns of allelic imbalance, with regions of subclonal and clonal losses often present in individual tumors. We exploited marker homozygosity in CC-derived cell lines as an indirect measure of LOH and identified four homozygous deletions (HDs) during this analysis at loci located within the 3p14.2 region to which the FHIT gene has been mapped recently. This led to a careful reevaluation of the LOH patterns in primary CCs, which showed apparent retention of heterozygosity for loci in this region indicative of the presence of several additional HDs. To our knowledge, this is the first report of HDs encompassing the FHIT gene region in primary tumor samples and underscores the usefulness of high resolution genetic analysis of tumor genomes in determining the chromosomal aberrations underlying the malignant progression of CC.

This prospective case study examined social communication (i.e., formal thought disorder, cohesion), language, positron emission tomography glucose utilization, and neuropathology in four children with Rasmussen encephalitis who achieved seizure control following right hemispherectomy. Prior to hemispherectomy, all four children had illogical thinking, loose associations, cohesive deficits, and impaired performance on formal language tests. Their postoperative improvement in social communication and language appeared to be related to age of onset, duration of illness, and postsurgical reversibility of hypometabolism in the nonresected prefrontal cortex. These changes were not associated with increase in IQ scores. The variability in the type and extent of pathologic change across subjects reflected the severity and duration of the illness. The study's findings imply that early surgical intervention might have mitigated certain aspects of the social communication and linguistic deficits found in these children.

Background: Gastrointestinal neuroendocrine tumors are slow growing, and metastases are often limited to the liver. Whereas in asymptomatic patients, observation alone may be reasonable, in patients with neuroendocrine tumors and unresectable hepatic metastases, transplantation of the liver may be beneficial. We have developed a protocol in which patients with multiple hepatic metastases are initially treated with chemotherapy and embolization to control symptoms and inhibit tumor growth. Hepatic transplantation is reserved for patients in whom tumor progresses or symptoms of hormone production or mass effect persist., Study Design: This is a retrospective review of eight patients with neuroendocrine tumor metastases who were referred to the Mount Sinai Hospital for evaluation for hepatic transplantation., Results: Of the eight patients, three have undergone transplantation; all are alive, with no evidence of tumor recurrence at 12 to 30 months. In two patients, symptoms have been controlled by embolization of the hepatic artery or chemotherapy, or both; another has had massive hepatomegaly as a result of tumor progression, with wasting and portal hypertension, and currently awaits transplantation. Two patients died as a result of progressive disease, soon after referral., Conclusion: Transplantation of the liver may be an important treatment modality for a selected group of patients with neuroendocrine tumors unresponsive to conventional therapy.

Samples of conversational language were elicited with a standardized interview protocol from 24 children, aged 2:6 to 7:8, half with specific language impairment (SLI), half with normally developing language (LN), matched for language level. Samples were analyzed to determine whether there were associations between adult questioning and children's use of ellipsis. For the SLI children, but not the LN children, increased proportions of questions were significantly correlated to increased proportions of ellipsis. This finding has implications for the use of MLU measures in clinical and research practice.

Objective: Investigate longitudinally the course of development of preschool learning impaired (LI) children to better understand the interaction between neurodevelopmental delay, behavioral/emotional disorders, and language development and disorders., Method: Relationships between developmental language disorders and emotional problems were investigated in 99 8-year-old specifically language impaired and control children originally assessed at age 4 years using the Achenbach Child Behavior Checklist and the Conners' Parents Questionnaire., Results: LI children received higher behavior problem scores and were more likely to score in the clinical range than were control children. Neither degree of early language impairment nor amount of language improvement predicted 8-year behavioral/emotional status. LI children with the largest drop in IQ between ages 4 and 8 received the highest behavior problem scores. No significant comorbid relationship was seen between LI and attention-deficit hyperactivity disorder., Conclusions: The enhanced incidence of behavior problems reported heretofore may be related more to lower IQ than to linguistic deficit per se. Care must be taken to differentiate the symptoms of neurodevelopmental delay and emotional disturbance, however, preschool children with scores in the clinical range on such measures should be referred for additional evaluation.

This study investigates whether language-impaired (LI) children show deficits in rapid automatized naming and whether RAN performance is specific to verbal output (or to rapid motor output in general). A total of 67 LI and 54 age-matched control children were tested with the Rapid Automatized Naming (RAN) test (Denckla & Rudel, 1976) and with a manual version of the RAN (RAN-manual) in which subjects were required to provide a nonverbal, pantomime response. Subjects also completed tests of rapid oral and manual sequencing skills and standardized tests of reading ability. Each subject was tested at 4, 6, and 8 years old. The results showed that LI children perform significantly poorer on both versions of the RAN than age-matched controls. Correlations between RAN scores and tests of reading ability were significant for normal and LI subjects and were particularly high for 8-year-old LI children. RAN-manual scores also correlated with 8-year-old LI children's reading scores. Further, RAN and RAN-manual scores for the LI children correlated significantly with these children's manual sequencing abilities, whereas this was not the case for the control subjects. These findings suggest that LI children's rapid sequential processing deficits are not limited to verbal output, but also generalize to other motoric domains.

To investigate the issue of delay versus deviance in the language acquisition of language-impaired (LI) children, the order of acquisition of a set of linguistic structures and the relationship obtaining between one structure and another were examined in comprehension and production over a 5-year period in a group of LI and language-matched normal children. The results demonstrated a marked similarity between groups, both in the point at which mastery of individual structures was achieved and in the overall patterns of acquisition demonstrated. These data suggest that LI children are constructing grammars based on the same rules and principles as those of linguistically normal control subjects, and that their linguistic impairments may be principally processing, not representational, in nature.

Although etiological influences in developmental language impairment (dysphasia) are not well defined, a significant increase of family aggregation for the disorder has been reported. We report data from a large cohort of language-impaired (LI) children participating in the San Diego longitudinal study in which we examined whether children with or without positive family histories show different phenotypic profiles. Due to the longitudinal design of the study, questions pertaining to change over time are also addressed. Second, a subgroup of the most impaired children were reevaluated to obtain additional information pertaining to family history and phenotypic outcome. Approximately 70% of the LI children met criteria for inclusion as family history positive, with fathers reporting a history of language or learning problems one and a half to two times as frequently as mothers. LI children with or without a positive family history were not significantly different on language skills or IQ. However, subjects having a positive family history for developmental language/learning problems were significantly lower in socioeconomic status and were rated by parents and teachers as having more attention-related behavior problems than their family history negative counterparts. Similarly, family history positive LI children performed more poorly on standardized academic tests as well as on tests of auditory processing and attention.

The need for a standardized approach to the selection of research subjects for studies on language impairment has long been an area of controversy in the literature. The data obtained from the selection of language-impaired and control subjects for the San Diego Longitudinal Study allows one to evaluate the effects a two-stage subject-selection procedure has on the characteristics of the language-impaired and normal subjects selected for research studies. Specifically, what effect do quantitative measures, as compared to clinical judgements and referrals, have on the characteristics of subjects selected for research studies? Explicit and detailed oral and written descriptions of subjects sought for both a language-impaired group and a control group were given to teachers and clinicians. However, only 39 of the first 100 children referred as language-impaired and 29 of the first 60 referred as normal controls were found on standardized testing to meet the study criteria and to be matched on important variables, such as IQ and socioeconomic status. These results demonstrate the importance of establishing quantitative inclusionary as well as exclusionary criteria for selecting and matching subjects in clinical research studies.

Studies from several laboratories have demonstrated the existence of multiple tropoelasting mRNAs and protein isoforms. The present study was designed to examine the developmental expression of a specific tropoelastin mRNA, its encoded isoform, and the fate of that isoform in the extracellular matrix. A chick genomic DNA library was screened with a chick tropoelastin cDNA. Seven unique, overlapping clones spanning 39 kilobases were isolated. A synthetic oligonucleotide complementary to a variable tropoelastin mRNA sequence was used to identify a 1.5-kilobase PstI-BamHI genomic fragment. Nucleotide sequence data revealed that the putative exon was surrounded by intron sequences possessing canonical splice sites at the exon/intron borders. Using both immunologic and molecular probes specific to the tropoelastin isoform and mRNA, quantitative protein and RNA analyses were performed. Results demonstrate that total tropoelastin mRNAs increased significantly during aortic embryogenesis whereas the amount of mRNA containing the variable exon remained relatively constant. The amount of total tropoelastins within the same developmental period reflect the level of total tropoelastin mRNA. The amount of the tropoelastin isoform containing the variable exon essentially mirrored the corresponding mRNA with the exception that a decrease in the isoform at day 15 was not seen in the mRNA level. Immunoelectron micrographs of 13-day chick aortic tissue using both total and isoform-specific antisera showed ultrastructural localization to definable elastic fibers. Antibodies to the variable tropoelastin isoform occurred preferentially at sites where elastic fiber microfibril structures were evident.

A total of 2.7 X 10(6) chromosomes have been screened for deficiencies that extend into some portion of the 14A-15A segment of the X-chromosome. Mutants have been identified on the basis of their paralysis at high temperature (the para ts phenotype) in a stock which contains a para ts allele on the X-chromosome and a para+ allele on the Dp(1;4)r+f+ chromosome. Several hundred mutants have been genetically characterized and a large percentage are deficiencies. Cytological characterization of a sub-set suggests that breakpoints are distributed throughout the 14B-15A region, but in a non-random fashion.

The purpose of the study was to characterize the early pragmatic-semantic communicative development of young hearing-impaired children learning spoken English as a first language. Twelve children with impaired hearing, ranging in age from 22 months to 60 months, were videotaped. Approximately 13 hours of videotaped data from four different communicative settings were analyzed. The pragmatic and semantic categories used by these children varied across age groups. Results are discussed with regard to age, expressive modality, mean length of utterance (MLU), and hearing loss. There was much variation among these parameters in communicative development across children.

Language ability of 20 patients with probable Alzheimer's disease (AD) was evaluated. Analysis of spontaneous speech revealed a normal range and frequency of syntactic constructions but poor lexical use. A writing task showed a similar divergence, with the ability to use syntactic cues significantly more intact than the ability to use semantic cues. The results are taken to indicate that syntactic ability is selectively preserved in AD. These findings are consistent with a modular theory of grammar and of mental functions more generally. A tentative explanation of these phenomena is proposed in which the overlearned and automatic nature of syntactic ability helps account for its resilience to cognitive dissolution and cortical degeneration.

Self-report data from the families of children participating in the San Diego Longitudinal Study of specific developmental language impairment were used to assess familial aggregation in the disorder. Families of impaired children reported higher rates of affected first-degree relatives than did families of matched controls. Significantly higher incidence of maternal and paternal childhood language and/or learning disabilities, as well as sibling disability rates, were reported. The extent to which familial aggregation reflects genetic or environmental influences in specific language disorders remains to be determined.

There is a well-documented propensity of males affected with developmental language/learning impairment. Results from this study demonstrate, unexpectedly, that this sex-ratio difference of males to females with developmental language/learning disorders was found to occur significantly only in families with a language/learning-impaired mother. In addition, a remarkably aberrant offspring sex-ratio was found in families of language/learning-impaired children who had an affected mother, but not father. Mothers who were developmentally language/learning-impaired had three times as many sons as daughters, and five times as many language/learning-impaired sons as daughters. Genetic and hormonal influences that might affect both sex-ratio and neuroanatomical development and disorders are discussed.

An important issue for the cognitive sciences is whether grammar is to any nontrivial extent an autonomous cognitive system. Current cognitive hypotheses of language acquisition would argue against an autonomous linguistic system and would support the notion that language emerges from more general cognitive knowledge and is throughout its development fundamentally tied to a nonlinguistic cognitive base. This paper explores this issue and presents data from case studies of children showing clear dissociations between language and nonlanguage cognitive abilities. The implications of such data are discussed. The major implications appear to be that lexical and relational semantic abilities are deeply linked to broader conceptual development but morphological and syntactic abilities are not. The development of a normal linguistic system, however, one in which grammar is systematically related to meaning, requires concurrent and concomitant linguistic and nonlingustic cognitive development.