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Land regularization is an essential ingredient in the formalization on land rights and it plays an important role in improving tenure security of the urban poor. In order to facilitate the process of land regularization, there is need to have up to date spatial information on the settlements earmarked for the regularization process. Ground based survey methods have proved to be time consuming and costly. Thus there is need to adopt cost effective methodology in the acquisition of spatial data. In this study, an approach based on Unmanned Aerial Vehicles (UAVs) was trialed for rapid assessment of a settlement earmarked for land regularization. The approach involved image acquisition for an area of 0.75km2 and processing to generate orthomosaic to aid in the regularization process. The developed approach demonstrates the utility of UAVs in the acquisition of spatial data for urban land regularization.

Background. Mendelian susceptibility to mycobacterial diseases (MSMD) is an inborn error of immunity categorized as defects in intrinsic and innate immunity. MSMD is characterized by vulnerability to less virulent mycobacteria, such as Bacillus Calmette-Guérin (BCG) vaccine strains, as well as environmental mycobacteria (EM). The definitive diagnosis is made by genetic analysis. Treatments constitute antimycobacterial, interferon-gamma, surgery, and hematopoietic stem cell transplantation (HSCT), which is the only known curative treatment. The mortality rate ranges from 40% to 80% depending on the severity of the mutation. Case. A 13-year-old female patient had multiple hospital visits since the age of 6 months. The most striking diagnosis was repeated mycobacterial infections. She had tuberculosis affecting lymph nodes, skin and soft tissue, bone and joints, the lungs, and epidural and paraspinal regions. She has taken all the childhood vaccines, including BCG. She has been treated four times with first-line and once with second-line antituberculosis drugs. Currently, she is on treatment for nontuberculous mycobacteria and is receiving interferon-gamma. Genetic studies showed autosomal dominant Mendelian susceptibility to mycobacterial disease due to IFNG-R1 defect. Conclusion. To the authors’ knowledge, this is the first case report of Mendelian susceptibility to mycobacterial diseases secondary to interferon gamma receptor 1(IFNG-R1) defect in Ethiopia. Although it has been immensely challenging, our multidisciplinary team has learned a lot from the clinical presentation, diagnosis, and management of this child.

Advances in Global Navigation Satellite Systems (GNSS) have revolutionized the geospatial industry around the globe. Recently, the Government of Zimbabwe realized the need to adopt GNSS- Continuously Operating Reference Stations (CORS) for boundary mapping of farms to ensure security of tenure. In order to fully utilize the proposed CORS network there is need to ascertain the readiness of stakeholders involved in the land delivery value chain. This study was conducted to evaluate the perceptions of Zimbabwean geospatial practitioners concerning CORS and their readiness to adopt the technology. The readiness of stakeholders was evaluated based on their level of awareness to the CORS technology, access to GNSS equipment compatible with CORS, prior experience with CORS and skills on manipulation of CORS data. Data were gathered in the form of questionnaires and focus group discussions. The study showed positive results in terms of access to GNSS equipment and level of awareness to CORS, where more than 50% of the participants responded positively. However, in terms of frequency of use and preparedness of stakeholders to upgrade their GNSS equipment to become compatible with CORS technology, the results were discouraging.

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in hospitalized patients. Where appropriate, evidence-based methods of prophylaxis are implemented and the burden of VTE can be reduced substantially. Obesity, including morbid obesity, is associated with a high risk of VTE and, unfortunately, fixed doses of US FDA-approved anticoagulant regimens, including unfractionated heparins, low-molecular-weight heparins and factor Xa inhibitors, may not provide optimal VTE prophylaxis in these patients. Although the data are still limited, a rapidly growing body of literature and cumulative evidence suggests that anticoagulant dose adjustments in morbidly obese patients may optimize pharmacodynamic activity and reduce VTE risk. With the prevalence of morbid obesity continuing to rise, more high-quality clinical data are needed to better understand the pathobiology of VTE in obesity and provide effective, yet safe, prevention strategies. [ABSTRACT FROM AUTHOR]

Abstract The inverse of the gametic covariance matrix between relatives, G-1, for a marked quantitative trait locus (QTL) is required in best linear unbiased prediction (BLUP) of breeding values if marker data are available on a QTL. A rapid method for computing the inverse of a gametic relationship matrix for a marked QTL without building G itself is presented. The algorithm is particularly useful due to the approach taken in computing inbreeding coefficients by having to compute only few elements of G. Numerical techniques for determining, storing, and computing the required elements of G and the nonzero elements of the inverse are discussed. We show that the subset of G required for computing the inbreeding coefficients and hence the inverse is a tiny proportion of the whole matrix and can be easily stored in computer memory using sparse matrix storage techniques. We also introduce an algorithm to determine the maximum set of nonzero elements that can be found in G-1 and a strategy to efficiently store and access them. Finally, we demonstrate that the inverse can be efficiently built using the present techniques for very large and inbred populations.

Abstract Background While India has made significant progress in reducing maternal mortality, attaining further declines will require increased skilled birth attendance and institutional delivery among marginalized and difficult to reach populations. Methods A population-based survey was carried out among 16 randomly selected rural villages in rural Mysore District in Karnataka, India between August and September 2008. All households in selected villages were enumerated and women with children 6 years of age or younger underwent an interviewer-administered questionnaire on antenatal care and institutional delivery. Results Institutional deliveries in rural areas of Mysore District increased from 51% to 70% between 2002 and 2008. While increasing numbers of women were accessing antenatal care and delivering in hospitals, large disparities were found in uptake of these services among different castes. Mothers belonging to general castes were almost twice as likely to have an institutional birth as compared to scheduled castes and tribes. Mothers belonging to other backward caste or general castes had 1.8 times higher odds (95% CI: 1.21, 2.89) of having an institutional delivery as compared to scheduled castes and tribes. In multivariable analysis, which adjusted for inter- and intra-village variance, Below Poverty Line status, caste, and receiving antenatal care were all associated with institutional delivery. Conclusion The results of the study suggest that while the Indian Government has made significant progress in increasing antenatal care and institutional deliveries among rural populations, further success in lowering maternal mortality will likely hinge on the success of NRHM programs focused on serving marginalized groups. Health interventions which target SC/ST may also have to address both perceived and actual stigma and discrimination, in addition to providing needed services. Strategies for overcoming these barriers may include sensitization of healthcare workers, targeted health education and outreach, and culturally appropriate community-level interventions. Addressing the needs of these communities will be critical to achieving Millennium Development Goal Five by 2015.

Abstract Introduction Epithelioid hemangioma is a rare vascular tumor found in the penis. It is essential to avoid misdiagnosis with Peyronie's disease and penile cancer, as management differs significantly. Case presentation We present a case of epithelioid hemangioma of the penis in a 50-year-old Caucasian man. We also review the literature to evaluate the incidence of benign vascular anomalies of the penis and their management. Conclusions Epithelioid hemangioma of the penis should be considered in the differential diagnosis of patients presenting with painful penile lumps. A thorough histological and immunohistochemical examination is required to make the diagnosis. Optimal management is complete local excision and periodic physical examination for local recurrence.

Abstract In the last fifteen years, rapid progress has been made in delineating the cellular response to DNA damage. The DNA damage response network is composed of a large number of proteins with different functions that detect and signal the presence of DNA damage in order to coordinate DNA repair with a variety of cellular processes, notably cell cycle progression. This signal, which radiates from the chromatin template, is driven primarily by phosphorylation events, mainly on serine and threonine residues. While we have accumulated detailed information about kinases and their substrates our understanding of the role of phosphatases in the DNA damage response is still preliminary. Identifying the phosphatases and their regulation will be instrumental to obtain a complete picture of the dynamics of the DNA damage response. Here we give an overview of the DNA damage response in mammalian cells and then review the data on the role of different phosphatases and discuss their biological relevance.

Purpose: The null hypothesis is that there would be no difference in medial gapping under valgus load between the intact MCL and the ruptured MCL with an internal brace in place., Methods: Eight pairs of cadaver knees were used (16 knees). Alternating sides, one knee from each pair was used for one of two "internal brace" constructs. The constructs involved different methods of fixation for securing FiberTape (Arthrex, Naples, FL) to both the femur and tibia in an effort to brace the MCL. The knees were then subjected to valgus stress by applying 10 N m of torque with the knee at 20 degrees of flexion. The amount of medial joint space opening was measured on radiographs. The stress testing was conducted with three MCL states: intact, grade 2 tear, and grade 3 tear., Results: In the Construct I specimens, gapping increased from 0.7 mm with the MCL intact to 1.1 mm with grade 2 tearing (p < 0.01), and to 1.3 mm with grade 3 tearing (p < 0.01). In the Construct II specimens, gapping increased from 0.7 mm with the MCL intact to 1.0 mm with grade 2 tearing (p < 0.01), and to 1.1 mm with grade 3 tearing (n.s.). Construct I specimens failed primarily at the femoral attachment. All Construct II specimens survived the valgus stress testing., Conclusion: Construct I did not maintain tension. Construct II did maintain tension during application of valgus load, but did not restore valgus opening to the intact state. It is important for clinicians who are considering using this commercially available technique to be aware of how the construct performs under valgus stress testing compared to the intact MCL., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Background: Bone autograft options may be limited in revision spinal fusion cases. Reconstruction of the iliac bone graft (IBG) donor site with cancellous bone allograft allows for reharvest for patients who subsequently have another fusion. This study examined viability of the reconstructed IBG (RIBG) donor sites. Secondarily, we assessed the feasibility of whether the RIBG sites could be reharvested for obtaining a successful arthrodesis for a secondary fusion., Methods: Prospectively collected data of 154 consecutive lumbar revision fusions were reviewed, of which 17 cases had their IBG donor site backfilled with allograft bone at the time of their primary fusion and subsequently had secondary surgery for a pseudarthrosis repair or fusion extension. Biopsies of the RIBG and computed tomography (CT) images were obtained at the time of secondary fusion. Histology analyzed the ratio of filled to unfilled lacunae and marrow cellularity. Histology controls were from normal iliac crest. Clinically, postoperative CT and >2-year outcomes (visual analog scale [VAS] and Oswestry Disability Index [ODI]) evaluated the feasibility of the secondary fusion surgery using RIBG. The RIBG fusion rate and outcomes were compared with clinical control revision groups that had IBG and/or bone morphogenetic protein (BMP) used for their revision fusion., Results: CT images prior to RIBG harvest found bony healing of the original graft donor site in all except 1 case. RIBG bone marrow histology found lower cellularity vs controls, but this characteristic did not appear to compromise bone viability with filled lacunae in 83% ± 14% in the RIBG group, vs 88% ± 8% for iliac controls. After revision fusion, often combined with bone growth stimulator or BMP, repeat CT demonstrated solid spinal fusions in 16 of 17 patients, whereas control revision group fusion rates were approximately 80%. Clinical improvement was significant (VAS decrease = 3.8, ODI decrease = 16.5) and comparable with the IBG revision controls., Conclusion: RIBG using allograft remodels into viable predominately cancellous bone and is clinically feasible for revision fusion if IBG or BMP is unavailable., Clinical Relevance: Reconstructed iliac bone graft is viable and may be used as a bone graft option., Competing Interests: Declaration of Conflicting Interests: The authors report no conflicts of interest in this work., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2023 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.)

Early in the pandemic, New York City's public hospital system partnered with multiple philanthropic foundations to offer an unconditional cash transfer program for low-income New Yorkers affected by COVID-19. The $1000 cash transfers were designed to help people meet their most immediate health and social needs and were incorporated into healthcare delivery and contact tracing workflows as a response to the public health emergency. To better understand program recipients' experiences, researchers conducted 150 telephone surveys with randomly sampled cash transfer recipients and 20 in-depth qualitative interviews with purposefully sampled survey participants. Survey participants were predominantly Latinx (87%) and women (65%). The most common reported uses of the $1000 were food and rent. Most participants (79%) reported that without the $1000 cash transfer they would have had difficulty paying for basic expenses or making ends meet, with specific positive effects reported related to food, housing, and ability to work. The majority of survey participants reported that receiving the cash assistance somewhat or greatly improved their physical health (83%) and mental health (89%). Qualitative interview results generally supported the survey findings., (© 2022. The New York Academy of Medicine.)

Objectives: To help people make decisions about the most effective mitigation measures against SARS-CoV-2 transmission in different scenarios, the likelihoods of transmission by different routes need to be quantified to some degree (however uncertain). These likelihoods need to be communicated in an appropriate way to illustrate the relative importance of different routes in different scenarios, the likely effectiveness of different mitigation measures along those routes, and the level of uncertainty in those estimates. In this study, a pragmatic expert elicitation was undertaken to supply the underlying quantitative values to produce such a communication tool., Participants: Twenty-seven individual experts from five countries and many scientific disciplines provided estimates., Outcome Measures: Estimates of transmission parameters, assessments of the quality of the evidence, references to relevant literature, rationales for their estimates and sources of uncertainty., Results and Conclusion: The participants' responses showed that there is still considerable disagreement among experts about the relative importance of different transmission pathways and the effectiveness of different mitigation measures due to a lack of empirical evidence. Despite these disagreements, when pooled, the majority views on each parameter formed an internally consistent set of estimates (for example, that transmission was more likely indoors than outdoors, and at closer range), which formed the basis of a visualisation to help individuals and organisations understand the factors that influence transmission and the potential benefits of different mitigation measures., Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests. SF is a co-investigator on the UKRI AIRBODS research programme, CN is principal investigator on the UKRI TRACK, Breathing Cities and HECOIRA projects and co-investigator on the NIHR CONTACT study. SP is co-investigator on the UKRI TRACK project. HR, SF, AS, CN were on the working group for the Royal Academy of Engineering Infection Resilient Environments report. CN was on the working group for the Academy of Medical Sciences reports on COVID-19 in 2020 and 2021.AF, SP, CN, SF, AS, RM and HR are members of SAGE-EMG., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The sacroiliac joint (SIJ) is responsible for 15%-30% of chronic low back pain and fusion is increasingly used to alleviate chronic SIJ pain in adults. However, questions remain as to the most effective implant patterns to stabilize the joint. The objective of this biomechanical study was to evaluate how different implant spacing, configuration and quantity effect range of motion (ROM) of a synthetic foam SIJ model., Methods: Triangular SIJ fusion implants were tested in six patterns using three implants, and two patterns with two implants (n = 5/pattern). Linear, triangular, and angled (10° or 20°) implant patterns were used with spacing of 13 or 22 mm between implants. Implants were placed through a denser polyurethane foam block (0.32 g/cm 3 ) representing the ilium and into a less dense block representing the sacrum (0.16 g/cm 3 ) to a depth 30 mm with a 2-mm gap between blocks. Cyclic torsion and shear testing were conducted for 10,000 cycles and ROM was recorded. Pullout testing was conducted on non-cycled (n = 10) implants and individually on all implants after construct cycling., Results: ROM was significantly lower for all 22-mm implant patterns compared to the 13 mm linear pattern after cyclic loading in both torsion and shear. The use of three implants provided 60% and 86% greater stability, respectively, than two implants with spacing of 22 and 13 mm. Pullout resistance followed similar trends with the lowest forces occurring in closely spaced patterns that used two implants., Conclusions: This study demonstrated that the use of three implants and maximizing the spacing between implants might provide greater stability to the SIJ. If implants must be placed closely, then nonlinear patterns may improve construct stability., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2021 ISASS.)

Objective: Describe demographical, social and psychological correlates of willingness to receive a COVID-19 vaccine., Setting: Series of online surveys undertaken between March and October 2020., Participants: A total of 25 separate national samples (matched to country population by age and sex) in 12 different countries were recruited through online panel providers (n=25 334)., Primary Outcome Measures: Reported willingness to receive a COVID-19 vaccination., Results: Reported willingness to receive a vaccine varied widely across samples, ranging from 63% to 88%. Multivariate logistic regression analyses reveal sex (female OR=0.59, 95% CI 0.55 to 0.64), trust in medical and scientific experts (OR=1.28, 95% CI 1.22 to 1.34) and worry about the COVID-19 virus (OR=1.47, 95% CI 1.41 to 1.53) as the strongest correlates of stated vaccine acceptance considering pooled data and the most consistent correlates across countries. In a subset of UK samples, we show that these effects are robust after controlling for attitudes towards vaccination in general., Conclusions: Our results indicate that the burden of trust largely rests on the shoulders of the scientific and medical community, with implications for how future COVID-19 vaccination information should be communicated to maximise uptake., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess the effects of different official information on public interpretation of a personal COVID-19 PCR test result., Design: A 5×2 factorial, randomised, between-subjects experiment, comparing four wordings of information about the test result and a control arm of no additional information; for both positive and negative test results., Setting: Online experiment using recruitment platform Respondi., Participants: UK participants (n=1744, after a pilot of n=1657) quota-sampled to be proportional to the UK national population on age and sex., Interventions: Participants were given a hypothetical COVID-19 PCR test result for 'John' who was presented as having a 50% chance of having COVID-19 based on symptoms alone. Participants were randomised to receive either a positive or negative result for 'John', then randomised again to receive either no more information, or text information on the interpretation of COVID-19 test results copied in September 2020 from the public websites of the UK's National Health Service, the USA's Centers for Disease Control, New Zealand's Ministry of Health or a modified version of the UK's wording. Information identifying the source of the wording was removed., Main Outcome Measures: Participants were asked 'What is your best guess as to the percent chance that John actually had COVID-19 at the time of his test, given his result?'; questions about their feelings of trustworthiness in the result, their perceptions of the quality of the underlying evidence and what action they felt 'John' should take in the light of his result., Results: Of those presented with a positive COVID-19 test result for 'John', the mean estimate of the probability that he had the virus was 73% (71.5%-74.5%); for those presented with a negative result, 38% (36.7%-40.0%). There was no main effect of information (wording) on these means. However, those participants given the official information from the UK website, which did not mention the possibility of false negatives or false positives, were more likely to give a categorical (100% or 0%) answer (UK: 68/343, 19.8% (15.9%-24.4%); control group: 42/356, 11.8% (8.8%-15.6%)); the reverse was true for those viewing the New Zealand (NZ) wording, which highlighted the uncertainties most explicitly (20/345: 5.8% (3.7%-8.8%)). Aggregated across test result (positive/negative), there was a main effect of wording (p<0.001) on beliefs about how 'John' should behave, with those seeing the NZ wording marginally more likely to agree that 'John' should continue to self-isolate than those viewing the control or the UK wording. The proportion of participants who felt that a symptomatic individual who tests negative definitely should not self-isolate was highest among those viewing the UK wording (31/178, 17.4% (12.5%-23.7%)), and lowest among those viewing the NZ wording (6/159, 3.8% (1.6%-8.2%)). Although the NZ wording was rated harder to understand, participants reacted to the uncertainties given in the text in the expected direction: there was a small main effect of wording on trust in the result (p=0.048), with people perceiving the test result as marginally less trustworthy after having read the NZ wording compared with the UK wording. Positive results were generally viewed as more trustworthy and as having higher quality of evidence than negative results (both p<0.001)., Conclusions: The public's default assessment of the face value of both the positive and negative test results (control group) indicate an awareness that test results are not perfectly accurate. Compared with other messaging tested, participants shown the UK's 2020 wording about the interpretation of the test results appeared to interpret the results as more definitive than is warranted. Wording that acknowledges uncertainty can help people to have a more nuanced and realistic understanding of what a COVID-19 test result means, which supports decision making and behavioural response., Preregistration and Data Repository: Preregistration of pilot at osf.io/8n62f, preregistration of main experiment at osf.io/7rcj4, data and code available online (osf.io/pvhba)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

From April 2016 to June 2017, the Health + Housing Project employed four community health workers who engaged residents of two subsidized housing buildings in New York City to address individuals' broadly defined health needs, including social and economic risk factors. Following the intervention, we observed significant improvements in residents' food security, ability to pay rent, and connection to primary care. No immediate change was seen in acute health care use or more narrowly defined health outcomes.

Health and housing consortia in New York City offer a model for bridging the divide between the health care and housing sectors. While staff in these sectors often recognize the need to better integrate their services, there are few models for doing so. In this article we describe the formation of a health and housing consortium in the Bronx, New York City, as well as the successful replication of its model in Brooklyn. While each consortium has some features specific to its service area, the primary goal of both is the same: to provide a neutral space for health care and housing organizations to collaborate in what is otherwise often competitive and fragmented territory. In addition, the work of both consortia coalesces around training and resource development, cross-sector communication, and research and advocacy. We provide examples of the Bronx Consortium's activities in each of these core areas, highlight tangible results to date, and offer recommendations for people interested in undertaking similar efforts.

Study Design: Experimental and computational study of posterior spinal instrumentation and growing rod constructs per ASTM F1717-15 vertebrectomy methodology for static compressive bending., Objective: Assess mechanical performance of standard fusion instrumentation and growing rod constructs., Summary of Background Data: Growing rod instrumentation utilizes fewer anchors and spans longer distances, increasing shared implant loads relative to fusion. There is a need to evaluate growing rod's mechanical performance. ASTM F1717-15 standard assesses performance of spinal instrumentation; however, effects of growing rods with side-by-side connectors have not been evaluated., Methods: Standard and growing rod constructs were tested per ASTM F1717-15 methodology; setup was modified for growing rod constructs to allow for connector offset. Three experimental groups (standard with active length 76 mm, and growing rods with active lengths 76 and 376 mm; n = 5/group) were tested; stiffness, yield load, and load at maximum displacement were calculated. Computational models were developed and used to locate stress concentrations., Results: For both constructs at 76 mm active length, growing rod stiffness (49 ± 0.8 N/mm) was significantly greater than standard (43 ± 0.4 N/mm); both were greater than growing rods at 376 mm (10 ± 0.3 N/mm). No significant difference in yield load was observed between growing rods (522 ± 12 N) and standard (457 ± 19 N) constructs of 76 mm. Growing rod constructs significantly decreased from 76 mm (522 ± 12 N) to 376 mm active length (200 ± 2 N). Maximum load of growing rods at 76 mm (1084 ± 11 N) was significantly greater than standard at 76 mm (1007 ± 7 N) and growing rods at 376 mm active length (392 ± 5 N). Simulations with active length of 76 mm were within 10% of experimental mechanical characteristics; stress concentrations were at the apex and cranial to connector-rod interaction for standard and growing rod models, respectively., Conclusion: Growing rod constructs are stronger and stiffer than spinal instrumentation constructs; with an increased length accompanied a decrease in strength. Growing rod construct stress concentration locations observed during computational simulation are consistent with clinically observed failure locations., Level of Evidence: 5.

Background: S1 screw failure and L5/S1 non-union are issues with long fusions to S1. Improved construct stiffness and S1 screw offloading can help avoid this. S2AI screws have shown to provide similar stiffness to iliac screws when added to L3-S1 constructs. We sought to examine and compare the biomechanical effects on an L2-S1 pedicle screw construct of adding S2AI screws, AxiaLIF, L5-S1 interbody support via transforaminal lumbar interbody fusion (TLIF), and to examine the effect of the addition of cross connectors to each of these constructs., Methods: Two S1 screws and one rod with strain gauges (at L5/S1) were used in L2-S1 screw-rod constructs in 7 L1-pelvis specimens (two with low BMD). ROM, S1 screw and rod strain were assessed using a pure-moment flexibility testing protocol. Specimens were tested intact, and then in five instrumentation states consisting of: (I) Pedicle screws (PS) L2-S1; (II) PS + S2AI screws; (III) PS + TLIF L5/S1; (IV) PS + AxiaLIF L5/S1; (V) PS + S2AI + AxiaLIF L5/S1. The five instrumentation conditions were also tested with crosslinks at L2/3 and S1/2. Tests were conducted in flexion-extension, lateral bending and axial torsion with no compressive preload., Results: S2A1 produces reduced S1 screw strain for flexion-extension, lateral bending and axial torsion, as well as reduced rod strain in lateral bending and axial torsion in comparison to AxiaLIF and interbody instrumentation, at the expense of increased rod flexion-extension strain. Cross-connectors may have a role in further reduction of S1 screw and rod strain., Conclusions: From a biomechanical standpoint, the use of the S2AI technique is at least equivalent to traditional iliac screws, but offers lower prominence and ease of assembly compared to conventional sacroiliac stabilization., Competing Interests: Chester E. Sutterlin III is a consultant for LifeHealthcare and receives royalties from K2M (for an implant unrelated to this research). The other authors have no conflicts of interest to declare.

Background Context: Although approximately 30% of chronic lumbar pain can be attributed to the facets, limited surgical options exist for patients. Interpositional facet arthroplasty (IFA) is a novel treatment for lumbar facetogenic pain designed to provide patients who gain insufficient relief from medical interventional treatment options with long-term relief, filling a void in the facet pain treatment continuum., Purpose: This study aimed to quantify the effect of IFA on segmental range of motion (ROM) compared with the intact state, and to observe device position and condition after 10,000 cycles of worst-case loading., Study Design/setting: In situ biomechanical analysis of the lumbar spine following implantation of a novel IFA device was carried out., Methods: Twelve cadaveric functional spinal units (L2-L3 and L5-S1) were tested in 7.5 Nm flexion-extension, lateral bending, and torsion while intact and following device implantation. Additionally, specimens underwent 10,000 cycles of worst-case complex loading and were testing in ROM again. Load-displacement and fluoroscopic data were analyzed to determine ROM and to evaluate device position during cyclic testing. Devices and facets were evaluated post testing. Institutional support for implant evaluation was received by Zyga Technology., Results: Range of motion post implantation decreased versus intact, and then was restored post cyclic-testing. Of the tested devices, 6.5% displayed slight movement (0.5-2 mm), all from tight L2-L3 facet joints with misplaced devices or insufficient cartilage. No damage was observed on the devices, and wear patterns were primarily linear., Conclusions: The results from this in situ cadaveric biomechanics and cyclic fatigue study demonstrate that a low-profile, conformable IFA device can maintain position and facet functionality post implantation and through 10,000 complex loading cycles. In vivo conditions were not accounted for in this model, which may affect implant behavior not predictable via a biomechanical study. However, these data along with published 1-year clinical results suggest that IFA may be a valid treatment option in patients with chronic lumbar zygapophysial pain who have exhausted medical interventional options., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

The spinous processes and supraspinous and interspinous ligaments (SSL and ISL, respectively) limit flexion and may relate to spinal curvature. Spinous process angles and mechanical properties of explanted human thoracic posterior SSL/ISL complexes were compared for scoliosis (n=14) vs. kyphosis (n=8) patients. The median thoracic coronal Cobb angle for scoliosis patients was 48°, and sagittal angles for kyphosis patients was 78°. Spinous processes were gripped and four strain steps of 4% were applied and held. Percent relaxation was calculated over each step, equilibrium load data were fit to an exponential equation, and a Kelvin model was fit to the load from all four curves. Failure testing was also performed. Median ligament complex dimensions from scoliosis and kyphosis patients were, respectively: ISL width=16.5mm and 16.0mm; SSL width=4.3mm and 3.8mm; ISL+SSL area=17.2mm and 25.7mm; these differences were not significant. Significant differences did exist in terms of spinous process angle vs. spine axis (47° for scoliosis and 32° for kyphosis) and SSL thickness (2.1mm for scoliosis and 3.0mm for kyphosis). Fourth-step median relaxation was 42% for scoliosis and 49% for kyphosis. Median linear region stiffness was 42N/mm for scoliosis and 51N/mm for kyphosis. Median failure load was 191N for scoliotic and 175N for kyphotic ligaments. Differences in loading, relaxation, viscoelastic and failure parameters were not statistically significant, except for a trend for greater initial rate of relaxation (T1) for scoliosis ligaments. However, we found significant morphological differences related to the spinous processes, which suggests a need for future biomechanical studies related to the musculoskeletal aspects of spinal alignment and posture., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: This study was undertaken to quantify the in vitro range of motion (ROM) of oblique as compared with anterior lumbar interbody devices, pullout resistance, and subsidence in fatigue., Methods: Anterior and oblique cages with integrated plate fixation (IPF) were tested using lumbar motion segments. Flexibility tests were conducted on the intact segments, cage, cage + IPF, and cage + IPF + pedicle screws (6 anterior, 7 oblique). Pullout tests were then performed on the cage + IPF. Fatigue testing was conducted on the cage + IPF specimens for 30,000 cycles., Results: No ROM differences were observed in any test group between anterior and oblique cage constructs. The greatest reduction in ROM was with supplemental pedicle screw fixation. Peak pullout forces were 637 ± 192 N and 651 ± 127 N for the anterior and oblique implants, respectively. The median cage subsidence was 0.8 mm and 1.4 mm for the anterior and oblique cages, respectively., Conclusions: Anterior and oblique cages similarly reduced ROM in flexibility testing, and the integrated fixation prevented device displacement. Subsidence was minimal during fatigue testing, most of which occurred in the first 2500 cycles.

Objective: To test ex vivo mechanical properties of 4 allograft fixation techniques for cranial cruciate ligament (CCL) replacement., Sample: 30 stifle joints from canine cadavers., Procedures: CCL-deficient stifle joints repaired by 1 of 4 techniques (n = 6/group) and CCL-intact stifle joints (control group; 6) were mechanically tested. Three repair techniques involved a patella-patella ligament segment (PPL) allograft: a tibial and femoral interference screw (PPL-2S), a femoral interference screw and the patella seated in a tapering bone tunnel in the tibia (PPL-1S), or addition of a suture and a bone anchor to the PPL-1S (PPL-SL). The fourth technique involved a deep digital flexor tendon (DDFT) allograft secured with transverse femoral fixation and stabilized with a tibial interference screw and 2 spiked washers on the tibia (DDFT-TF). The tibia was axially loaded at a joint angle of 135°. Loads to induce 3, 5, and 10 mm of femoral-tibia translation; stiffness; and load at ultimate failure with the corresponding displacement were calculated. Group means were compared with a multivariate ANOVA., Results: Mean ± SD load for the intact (control) CCL was 520.0 ± 51.3 N and did not differ significantly from the load needed to induce 3 mm of femoral-tibial translation for fixation techniques PPL-SL (422.4 ± 46.3 N) and DDFT-TF (654.2 ± 117.7 N). Results for the DDFT-TF were similar to those of the intact CCL for all outcome measures., Conclusions and Clinical Relevance: The DDFT-TF yielded mechanical properties similar to those of intact CCLs and may be a viable technique to test in vivo.

Study Design: A cadaveric lumbosacral spondylolytic spondylolisthesis model was used to evaluate the biomechanical function of 2 different interbody spacers., Objective: To analyze and compare the reduction in pedicle screw strain and spine range of motion (ROM) between transforaminal lumbar interbody fusion (TLIF) and an axial interbody threaded rod (AxialITR) in a destabilized L5-S1 spondylolisthesis model., Summary of Background Data: Symptomatic spondylolytic spondylolisthesis is often treated with posterior instrumented fusion augmented by a variety of different interbody devices. Interbody spacers rely primarily on posterior instrumentation to stabilize the spine during fusion, but there may be advantages to the more rigid support offered by an anterior threaded rod., Methods: Pure-moment flexibility testing was performed on L3-S1 cadaveric specimens in 4 conditions: (1) Intact, (2) L5-S1 pedicle screws (PS) + L5-S1 disc destabilization (DDS), (3) TLIF at L5-S1 + PS + DDS, and (4) AxialITR at L5-S1 + PS + DDS. Specimens were destabilized by performing a complete denucleation at L5-S1 and sectioning two-thirds of the annulus' width from anterior to posterior. The S1 PSs were instrumented with strain gauges to measure screw-bending moments and ROM was quantified with a noncontact camera system., Results: S1 screw strains were highest with PS but were significantly reduced by 73% in flexion and 31% in extension with TLIF (P ≤ 0.004). AxialITR significantly reduced strain by 78% in flexion and 81% in extension (P ≤ 0.001). ROM was smallest with AxialITR in each test direction at 1.7 ± 1.8° in flexion-extension, 1.6 ± 0.9° in lateral bending and 1.3 ± 0.8° in torsion., Conclusion: This study demonstrated that ROM and S1 screw-bending moments were reduced with the use of AxialITR and TLIF. Although the TLIF and AxialITR both reduced strains and motion, the AxialITR provided a significant reduction in extension strain when compared with TLIF., Level of Evidence: N/A.

The wound healing process includes filling the void between implant and tissue edges by collagenous connective repair tissue. This fibrous repair tissue may load share or stabilize implants such as spinal disc replacements. The objective of this study was the biomechanical characterization of human fibrous tissue compared to annulus fibrosus and nucleus pulposus. Human lumbar discs (10 nucleus and annulus) and 10 lumbar deep wound fibrous tissue specimens were sectioned into 12mm diameter×6mm high cylindrical samples. Confined compression testing, after 2h swelling at 0.11MPa, was performed at 5%, 10% and 15% strain over 3.5h. Unconfined dynamic testing (2-0.001Hz) was performed at 5-15% strain. Semi-quantitative histology estimated the proportion of proteoglycan to collagen. Fibrous tissue exhibited a decrease in height during the swelling period whereas annulus and nucleus tissues did not. The aggregate modulus was significantly less for fibrous tissue (p<0.002). Percent stress relaxation was greatest for the fibrous tissue and similar for annulus and nucleus. Dynamic testing found the storage modulus (E') was greater than the loss modulus (E″) for all tissues. Annulus were found to have greater E' and E″ than nucleus, whereas E' and E″ were similar between annulus and fibrous tissue. Fibrous tissue had the greatest increase in both moduli at greater frequencies, but had the lowest hydration and proteoglycan content. Fibrous tissue would not be a substitute for native tissue within the disc space but if adjacent to a disc prosthesis may impart some degree of intersegmental stability during acute loading activities., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Many hospitalized Medical Service patients are at risk for venous thromboembolism in the months after discharge. We conducted a multicenter randomized controlled trial to test whether a hospital staff member's thromboprophylaxis alert to an Attending Physician before discharge will increase the rate of extended out-of-hospital prophylaxis and, in turn, reduce the incidence of symptomatic venous thromboembolism at 90 days., Methods: From April 2009 to January 2010, we enrolled hospitalized Medical Service patients using the point score system developed by Kucher et al to identify those at high risk for venous thromboembolism who were not ordered to receive thromboprophylaxis after discharge. There were 2513 eligible patients from 18 study sites randomized by computer in a 1:1 ratio to the alert group or the control group., Results: Patients in the alert group were more than twice as likely to receive thromboprophylaxis at discharge as controls (22.0% vs 9.7%, P <.0001). Based on an intention-to-treat analysis, symptomatic venous thromboembolism at 90 days (99.9% follow-up) occurred in 4.5% of patients in the alert group, compared with 4.0% of controls (hazard ratio 1.12; 95% confidence interval, 0.74-1.69). The rate of major bleeding at 30 days in the alert group was similar to that of the control group (1.2% vs 1.2%, hazard ratio 0.94; 95% confidence interval, 0.44-2.01)., Conclusions: Alerting providers to extend thromboprophylaxis after hospital discharge in Medical Service patients increased the rate of prophylaxis but did not decrease the rate of symptomatic venous thromboembolism., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Previous methods of pedicle screw strain measurement have utilized complex, time consuming methods of strain gauge application, experience high failure rates, do not effectively measure resultant bending moments, and cannot predict moment orientation. The purpose of this biomechanical study was to validate an improved method of quantifying pedicle screw bending moment orientation and magnitude. Pedicle screws were instrumented to measure biplanar screw bending moments by positioning four strain gauges on flat, machined surfaces below the screw head. Screws were calibrated to measure bending moments by hanging certified weights a known distance from the strain gauges. Loads were applied in 30 deg increments at 12 different angles while recording data from two independent strain channels. The data were then analyzed to calculate the predicted orientation and magnitude of the resultant bending moment. Finally, flexibility tests were performed on a cadaveric motion segment implanted with the instrumented screws to demonstrate the implementation of this technique. The difference between the applied and calculated orientation of the bending moments averaged (±standard error of the mean (SEM)) 0.3 ± 0.1 deg across the four screws for all rotations and loading conditions. The calculated resultant bending moments deviated from the actual magnitudes by an average of 0.00 ± 0.00 Nm for all loading conditions. During cadaveric testing, the bending moment orientations were medial/lateral in flexion-extension, variable in lateral bending, and diagonal in axial torsion. The technique developed in this study provides an accurate method of calculating the orientation and magnitude of screw bending moments and can be utilized with any pedicle screw fixation system.

In vitro spine flexibility testing has been performed using a variety of laboratory-specific loading apparatuses and conditions, making test results across laboratories difficult to compare. The application of pure moments has been well established for spine flexibility testing, but to our knowledge there have been no attempts to quantify differences in range of motion (ROM) resulting from laboratory-specific loading apparatuses. Seven fresh-frozen lumbar cadaveric motion segments were tested intact at four independent laboratories. Unconstrained pure moments of 7.5 Nm were applied in each anatomic plane without an axial preload. At laboratories A and B, pure moments were applied using hydraulically actuated spinal loading fixtures with either a passive (A) or controlled (B) XY table. At laboratories C and D, pure moments were applied using a sliding (C) or fixed ring (D) cable-pulley system with a servohydraulic test frame. Three sinusoidal load-unload cycles were applied at laboratories A and B while a single quasistatic cycle was applied in 1.5 Nm increments at laboratories C and D. Non-contact motion measurement systems were used to quantify ROM. In all test directions, the ROM variability among donors was greater than single-donor ROM variability among laboratories. The maximum difference in average ROM between any two laboratories was 1.5° in flexion-extension, 1.3° in lateral bending and 1.1° in axial torsion. This was the first study to quantify ROM in a single group of spinal motion segments at four independent laboratories with varying pure moment systems. These data support our hypothesis that given a well-described test method, independent laboratories can produce similar biomechanical outcomes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background Context: Unstable burst fractures of the thoracolumbar spine may be treated surgically. Vertebral body replacements (VBRs) give anterior column support and, when used with supplemental fixation, impart rigidity to the injured segments. Although some VBRs are expandable, device congruity to the vertebral end plates is imprecise and may lead to stress risers and device subsidence., Purpose: The objective of this study was to compare the rigidity of a VBR that self-adjusts to the adjacent vertebral end plates versus structural bone allograft and with an unsupported anterior column in a traumatic burst fracture reconstruction model., Study Design: Biomechanical flexibility testing with rod strain measurement., Patient Sample: Twelve T11-L3 human spine segments., Outcome Measures: Range of motion, neutral zone, and posterior fixation rod stress (moments)., Methods: Flexibility testing was performed to ± 6 Nm in flexion-extension, lateral bending, and axial rotation on 12 intact human T11-L3 specimens. Burst fractures were created in L1, and flexibility testing was repeated in three additional states: subtotal corpectomy with posterior instrumentation (PI) only from T12 to L2, reconstruction with a femoral strut allograft and PI, and reconstruction with a VBR (with self-adjusting end plates) and PI. The PI consisted of pedicle screws and strain gage instrumented rods that were calibrated to measure rod stress via flexion-extension bending moments., Results: There was no statistical difference in range of motion or neutral zone between the strut graft and VBR constructs, which both had less motion than the PI-only construct in flexion/extension and torsion and were both less than the intact values in flexion/extension and lateral bending (p < .05). Posterior rod moments were significantly greater for the PI-only construct in flexion/extension relative to the strut graft and VBR states (p = .03)., Conclusions: This study, which simulated the immediate postoperative state, suggests that a VBR with self-adjusting end plate components has rigidity similar to the standard strut graft when combined with PI. Posterior rod stress was not significantly increased with this type of VBR compared with the strut graft reconstruction. The benefits of burst fracture stabilization using a self-adjusting VBR ultimately will not be known until long-term clinical studies are performed., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Study Design: An in vitro cadaveric biomechanics study., Objective: To evaluate the biomechanical contribution of the integration of screws into a polyether-ether-ketone (PEEK) spacer, and to compare the resulting construct to standard anterior lumbar interbody fusion constructs., Summary of Background Data: Pedicular fixation is often performed to increase the rigidity of anterior lumbar interbody fusion constructs but also increases the risk of morbidity. Integration of screws into a PEEK spacer (investigational device, ID) may increase construct rigidity and prevent migration without the drawbacks associated with supplementary fixation., Methods: Twenty cadaveric motion segments were potted and tested under pure moments of + or - 7.5 Nm in flexion-extension, lateral bending, and axial torsion. Discectomies were performed and specimens were instrumented with the ID + or - screws, dual threaded cages, structural graft+anterior plate, and graft+pedicle screws. The ID+screws and threaded cage constructs were then pulled out at a constant rate., Results: All constructs reduced the mean range of motion (ROM) below the intact level in flexion-extension and lateral bending (P<0.001) and for all devices except cages in torsion (P < or = 0.05). The median flexion-extension/bending/torsion ROM was 9.5/9.4/4.1 degrees for the intact segments, 6.1/5.1/1.8 degrees with the ID+screws, 4.9/5.2/2.4 degrees with threaded cages, 3.3/4.4/1.1 degrees with plates and 1.4/1.6/1.7 degrees with pedicle screws, respectively. The addition of the integrated screws decreased the mean ROM of the ID constructs by 0.9 degrees in flexion-extension, 1.8 degrees in bending, and 2.8 degrees in flexion-extension. The peak pullout force was 962 N for the ID and 337 N for threaded cages., Conclusions: The incorporation of screws into a PEEK interbody device was evaluated alongside traditional constructs in terms of construct rigidity and resistance to pullout. The greatest contributions of the integrated screws are in limiting torsional motion and in the containment of the interbody device. Pedicular fixation produces the most rigid constructs, but integrating screws into a PEEK spacer produces a stand-alone construct that is similar to threaded cages and provides more resistance to anterior displacement.

Background Context: Stand-alone nonbiologic interbody fusion devices for the lumbar spine have been used for interbody fusion since the early 1990s. However, most devices lack the stability found in clinically successful circumferential fusion constructs. Stability results from cage geometry and device/vertebral endplate interface integrity. To date, there has not been a published comparative biomechanical study specifically evaluating the effects of endplate engagement of interbody devices., Purpose: Lumbar motion segments implanted with three different interbody devices were tested biomechanically to compare the effects of endplate engagement on motion segment rigidity. The degree of additional effect of supplemental posterior and anterior fixation was also investigated., Study Design/setting: A cadaveric study of interbody fusion devices with varying degrees of endplate interdigitation., Outcome Measures: Implanted motion segment range of motion (ROM), neutral zone (NZ), stiffness, and disc height., Methods: Eighteen human L23 and L45 motion segments were distributed into three interbody groups (n=6 each) receiving a polymeric (polyetheretherketone) interbody spacer with small ridges; a modular interbody device with endplate spikes (InFix, Abbott Spine, Austin, TX, USA); or dual tapered threaded interbody cages (LT [Lordotic tapered] cage; Medtronic, Memphis, TN, USA). Specimens were tested intact using a 7.5-Nm flexion-extension, lateral bending, and axial torsion flexibility protocol. Testing was repeated after implantation of the interbody device, anterior plate fixation, and posterior interpedicular fixation. Radiographic measurements determined changes in disc height and intervertebral lordosis. ROM and NZ were calculated and compared using analysis of variance., Results: The interbody cages with endplate spikes or threads provided a statistically greater increase in disc height versus the polymer spacer (p=.01). Relative to intact, all stand-alone devices significantly reduced ROM in lateral bending by a mean 37% to 61% (p< or =.001). The cages with endplate spikes or threads reduced ROM by approximately 50% and NZ by approximately 60% in flexion-extension (p< or =.02). Only the cage with endplate spikes provided a statistically significant reduction in axial torsion ROM compared with the intact state (50% decrease, p<.001). Posterior fixation provided a significant reduction in ROM in all directions versus the interbody device alone (p<.001). Anterior plating decreased ROM over interbody device alone in flexion-extension and torsion but did not have additional effect on lateral bending ROM., Conclusion: The cages with endplate spikes or threads provide substantial motion segment rigidity compared with intact in bending modes. Only the cages with endplate spikes were more rigid than intact in torsion. All devices experienced increased rigidity with anterior plating and even greater rigidity with posterior fixation. It appears that the endplate engagement with spikes may be beneficial in limiting torsion, which is generally difficult with other "stand-alone" devices tested in the current and prior reports.

Bioresorbable plates have recently been used with anterior cervical discectomy and fusion (ACDF). Compared with metallic plates, bioresorbable plates provide segmental stabilization with minimal imaging artifact, eventual resorption, and increased load sharing. The objectives of the present study were to determine whether a bioresorbable plate can withstand simulated physiologic static and cyclic loading, to compare the reduction in flexibility provided by bioresorbable and titanium plates, and to quantify load sharing between the plate and spine with graft. Sixteen human cervical motion segments were tested to +/-2.5 Nm in flexion-extension, lateral bending, and axial rotation. Range of motion (ROM) was measured (1) in the intact state, (2) with ACDF without plating, (3) after addition of either a bioresorbable or titanium plate, and (4) after 500 cycles of combined flexion-extension and axial torsion. Load sharing was evaluated by applying the same fixed rotation both without and with the plate, and was calculated as the moment resisted by the uninstrumented ACDF expressed as a percentage of the plated ACDF state. No plate failures or graft migration occurred during testing. Compared with the uninstrumented ACDF, bioresorbable plates reduced mean ROM by 49% in flexion-extension and 25% in lateral bending, with very little change in torsion. Titanium plates reduced uninstrumented ACDF ROM by 69% in flexion-extension, 45% in lateral bending, and 27% in torsion. Differences between bioresorbable and titanium plates were significant in flexion-extension and lateral bending. Cyclic loading did not significantly change ROM for either plate. More moment was shared in lateral bending by the spine/graft with bioresorbable plates (78%) compared with titanium plating (63%). Bioresorbable plates contained an intervertebral graft, provided some stabilization, remained intact throughout the simulated immediate postoperative loading, and shared more load with the graft and osteoligamentous spine than titanium plates.

Receptor tyrosine kinases of the Eph family are up-regulated in different types of cancer. EphB4 and its ligand ephrin-B2 have been linked to breast cancer, but little is known about how this receptor-ligand complex may contribute to oncogenesis. The Eph receptors transmit forward signals via their kinase domain and reverse signals via their transmembrane ephrin-B ligands. Therefore, we used EphB4 that were lacking the kinase domain and tagged with EGFP (EphB4 Delta C-EGFP) to differentiate between EphB4 and ephrin-B2 signaling. Interestingly, we found that expression of EphB4 Delta C-EGFP in breast cancer cells increases tumor growth in a mouse xenograft model. Given the undetectable EphB4 activation in the tumor cells, dominant negative effects of EphB4 Delta C-EGFP are unlikely to explain the increased tumor growth. Examination of the tumors revealed that ephrin-B2 is primarily expressed in the vasculature and that the EphB4 Delta C-EGFP tumors have a higher blood content than control tumors, concomitant with increased size of blood vessels. In support of an effect on the vasculature, the extracellular domain of EphB4 attracts endothelial cells in vitro and stimulates endothelial cell invasion, survival, and proliferation, all crucial factors for angiogenesis. These results support a model in which EphB4 promotes tumor growth by stimulating angiogenesis through ephrin-B2.

Eph receptor tyrosine kinases and their ephrin ligands have been implicated in embryonic vascular development and in in vivo models of angiogenesis. Eph proteins may also regulate tumor neovascularization, but this role has not been previously investigated. To screen for Eph proteins expressed in tumor blood vessels, we used tumor xenografts grown in nude mice from MDA-MB-435 human breast cancer cells or KS1767 human Kaposi's sarcoma cells. By immunohistochemistry, the ephrin-A1 ligand and one of its receptors, EphA2, were detected throughout tumor vasculature. Double-labeling with anti-CD34 antibodies demonstrated that both ephrin-A1 and EphA2 were expressed in xenograft endothelial cells and also tumor cells. Furthermore, EphA2 was tyrosine-phosphorylated in the xenograft tumors, indicating that it was activated, presumably by interacting with ephrin-A1. Ephrin-A1 and EphA2 were also detected in both the vasculature and tumor cells of surgically removed human cancers. In an in vitro angiogenesis model, a dominant negative form of EphA2 inhibited capillary tube-like formation by human umbilical vein endothelial cells (HUVECs), demonstrating a requirement for EphA receptor signaling. These data suggest that ephrin-A1 and EphA2 play a role in human cancers, at least in part by influencing tumor neovascularization. Eph proteins may represent promising new targets for antiangiogenic cancer treatments.

Eph receptor tyrosine kinases play key roles in pattern formation during embryonic development, but little is known about the mechanisms by which they elicit specific biological responses in cells. Here, we investigate the role of tyrosines 605 and 611 in the juxtamembrane region of EphB2, because they are conserved Eph receptor autophosphorylation sites and demonstrated binding sites for the SH2 domains of multiple signaling proteins. Mutation of tyrosines 605 and 611 to phenylalanine impaired EphB2 kinase activity, complicating analysis of their function as SH2 domain binding sites and their contribution to EphB2-mediated signaling. In contrast, mutation to the negatively charged glutamic acid disrupted SH2 domain binding without reducing EphB2 kinase activity. By using a panel of EphB2 mutants, we found that kinase activity is required for the changes in cell-matrix and cell - cell adhesion, cytoskeletal organization, and activation of mitogen-activated protein (MAP) kinases elicited by EphB2 in transiently transfected cells. Instead, the two juxtamembrane SH2 domain binding sites were dispensable for these effects. These results suggest that phosphorylation of tyrosines 605 and 611 is critical for EphB2-mediated cellular responses because it regulates EphB2 kinase activity.

The purpose of this study was to determine whether dopamine (DA) systems modulate kappa opioid-mediated ultrasonic vocalizations (USVs), antinociception, and locomotion in young rats. Seventeen-day-old rats were injected with the kappa agonist U-50,488 (0.0-7.5 mg/kg) and saline, the D2-like receptor agonist R(-)-propylnorapomorphine (NPA; 0.1 or 1.0 mg/kg), the indirect DA agonist cocaine (10 or 20 mg/kg), or the DA antagonist flupenthixol (0.25 or 0.5 mg/kg). USVs and locomotion were measured for 6 min, with antinociception being assessed with a tail-flick test. Kappa receptor stimulation produced analgesia and increased USVs and locomotion. U-50,488-induced analgesia was potentiated by NPA, whereas U-50,488-induced USVs were attenuated by both DA agonists. NPA and flupenthixol depressed U-50,488's locomotor effects. These results show that DA systems interact with kappa opioid systems to modulate USVs, antinociception, and locomotion in preweanling rats.

kappa-Opioid receptor agonists (e.g., enadoline or U-50,488) increase the locomotor activity of preweanling rats, while the same drugs depress the locomotor activity of adults. Curiously, direct stimulation of dopamine (DA) D2-like receptors fully attenuates the U-50,488-induced locomotor activity of preweanling rats. The purpose of the present study was to determine whether indirect DA agonists (i.e., cocaine, methylphenidate, and amphetamine) would also attenuate U-50,488's behavioral effects. In two experiments, 17-day-old rats were injected with saline or U-50,488 (5 mg/kg, sc) and locomotor activity and stereotyped sniffing were assessed. After 20 min, the saline- and U-50,488-pretreated rats were injected with saline, cocaine (5, 10, or 20 mg/kg, i.p.), methylphenidate (10 or 20 mg/kg, i.p.), amphetamine (2.5 or 5 mg/kg, i.p.), or the direct D2-like receptor agonist NPA (1 mg/kg, i.p.). As expected, U-50,488 dramatically enhanced the locomotor activity of 17-day-old rats, while attenuating the stereotyped sniffing caused by indirect and direct DA agonists. All three indirect DA agonists augmented U-50,488's locomotor activating effects across the initial 10 min of testing and then activity declined to U-50,488 control values. Direct stimulation of DA receptors produced nearly opposite effects because NPA attenuated U-50,488-induced locomotor activity across the entire testing session. It is uncertain why direct and indirect DA agonists affected U-50,488-induced locomotor activity differently, but the relative amount of DA D1-like receptor activation is probably not responsible.

Pneumopericardium arises most commonly as a result of a bronchial or oesophageal neoplasm which erodes the pericardial cavity. A case of pneumopericardium associated with amoebic liver abscess, a complication of invasive amoebiasis not previously reported, is described.