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We have previously demonstrated that PD-1 blockade decreased the incidence of high-grade dysplasia in a carcinogen-induced murine model of oral squamous cell carcinoma (OSCC). It remains unknown, however, whether there are additional factors involved in escape from immune surveillance that could serve as additional targets for immunoprevention. We performed this study to further characterize the immune landscape of oral premalignant lesions (OPL) and determine the impact of targeting of the PD-1, CTLA-4, CD40, or OX40 pathways on the development of OPLs and oral carcinomas in the 4-nitroquinoline 1-oxide model. The immune pathways were targeted using mAbs or, in the case of the PD-1/PD-L1 pathway, using PD-L1–knockout (PD-L1ko) mice. After intervention, tongues and cervical lymph nodes were harvested and analyzed for malignant progression and modulation of the immune milieu, respectively. Targeting of CD40 with an agonist mAb was the most effective treatment to reduce transition of OPLs to OSCC; PD-1 alone or in combination with CTLA-4 inhibition, or PD-L1ko, also reduced progression of OPLs to OSCC, albeit to a lesser extent. Distinct patterns of immune system modulation were observed for the CD40 agonists compared with blockade of the PD-1/PD-L1 axis with or without CTLA-4 blockade; CD40 agonist generated a lasting expansion of experienced/memory cytotoxic T lymphocytes and M1 macrophages, whereas PD-1/CTLA-4 blockade resulted in a pronounced depletion of regulatory T cells among other changes. These data suggest that distinct approaches may be used for targeting different steps in the development of OSCC, and that CD40 agonists merit investigation as potential immunoprevention agents in this setting.Prevention Relevance:PD-1/PD-L1 pathway blockade, as well as activation of the CD40 pathway, were able to prevent OPL progression into invasive OSCC in a murine model. A distinct pattern of immune modulation was observed when either the CD40 or the PD-1/PD-L1 pathways were targeted.

Background and Methods. In Southeast Asia and particularly in Thailand, β0-thalassemia/hemoglobin E (HbE) disease is a common hereditary hematological disease. In a retrospective analysis, we investigated the outcomes of blastocyst preimplantation genetic diagnosis (PGD) for α- and β-thalassemia exclusion, with human leukocyte antigen (PGD-HLA) matching, from 2007 to 2016 at Superior A.R.T. (Bangkok, Thailand) and subsequent hematopoietic stem cell transplantation (HSCT) treatment of affected siblings. The main outcome measures included the proportion of biopsied cycles with at least one screened embryo suitable for transfer, implantation rate, live birth rate, and curative HSCT post-PGD-HLA. Results. In 221 cycles from 138 patients (104 cycles requiring HLA matching), 90.5% had embryo(s) biopsied for genetic testing. There were 119 embryo transfers for thalassemia (76) and thalassemia-HLA cases (43), respectively, resulting in overall clinical pregnancy rates of 54.6%, implantation rates of 45.7%, and live birth rates of 44.1%. Our dataset included fifteen PGD-HLA live births with successful HSCT in twelve affected siblings, 67% using umbilical cord blood stem cells (UCBSC) as the only SC source. Conclusions. We report favorable thalassemia PGD and PGD-HLA laboratory and clinical outcomes from a single center. The ultimate success in PGD-HLA is of course the cure of a thalassemia-affected sibling by HSCT. Our PGD-HLA HSCT series is the first and largest performed entirely in Asia with twelve successful and two pending cures and predominant UCBSC use.

Item does not contain fulltext BACKGROUND: Sepsis is a leading cause of morbidity and mortality after surgery. Most studies regarding sepsis do not differentiate between patients who have had recent surgery and those without. Few data exist regarding the risk factors for poor outcomes in pediatric postsurgical sepsis. Our hypothesis is pediatric postsurgical, and medical patients with severe sepsis have unique risk factors for mortality. METHODS: Data were extracted from a secondary analysis of an international point prevalence study of pediatric severe sepsis. Sites included 128 pediatric intensive care units from 26 countries. Pediatric patients with severe sepsis were categorized into those who had recent surgery (postsurgical sepsis) versus those that did not (medical sepsis) before sepsis onset. Multivariable logistic regression models were used to determine risk factors for mortality. RESULTS: A total of 556 patients were included: 138 with postsurgical and 418 with medical sepsis. In postsurgical sepsis, older age, admission from the hospital ward, multiple organ dysfunction syndrome at sepsis recognition, and cardiovascular and respiratory comorbidities were independent risk factors for death. In medical sepsis, resource-limited region, hospital-acquired infection, multiple organ dysfunction syndrome at sepsis recognition, higher Pediatric Index of Mortality-3 score, and malignancy were independent risk factors for death. CONCLUSIONS: Pediatric patients with postsurgical sepsis had different risk factors for mortality compared with medical sepsis. This included a higher mortality risk in postsurgical patients presenting to the intensive care unit from the hospital ward. These data suggest an opportunity to develop and test early warning systems specific to pediatric sepsis in the postsurgical population.

Background Population aging and lung cancer screening strategies may lead to an increase in detection of early-stage lung cancer in medical inoperable patients. Recent advances in peripheral bronchoscopy have made it a suitable platform for ablation of small peripheral tumors. Methods We investigated the tissue-ablative effect of a diode laser bronchoscopically applied by a laser delivery fiber (LDF) with wide aperture on porcine lung parenchyma. Laser was tested ex vivo and in vivo to identify the most effective power settings and LDF. Chest computed tomography (CT) were obtained immediately after ablation and after 3 days of observation. At day 3, necropsy was performed. Results On the basis of our ex vivo and in vivo experiments, we selected the round-tip LDF to be activated at 25 W for 20 seconds. Ten ablations were performed in 5 pigs. One ablation resulted in a pneumothorax requiring aspiration. All animals remained stable for 72 hours. CT findings at days 1 and 3 showed an area of cavitation surrounded by consolidation and ground glass. Median size of CT findings (long axis) was 26 mm (range, 24 to 38) at day 1, and 34 mm (range, 30 to 44) at day 3. Necropsy showed an area of central char measuring from 0.8×0.7×0.9 cm to 2.4×3.5×1.2 cm, surrounded by a gray-brown to dark red area. On histology, variable degrees of necrosis were evident around the charred areas. Conclusion Bronchoscopic laser interstitial thermal therapy can achieve relatively large areas of ablation of normal lung parenchyma with a low rate of periprocedural complications.

Advances in radiology and imaging technologies and the emergent scope of practice have led to the capacity to provide services to a growing population of high-acuity patients with comorbid conditions. These procedures are often performed with the radiology nurse administering procedural sedation. Monitoring patients is challenging due to certain patient conditions and the unique environment, that is, the radiology procedure suite. The addition of capnography monitoring, along with standard monitoring, is a valuable modality that provides a continuous objective assessment of the patient's ventilatory status even when direct visualization of the patient is compromised. The purpose of this article is to provide clinical practice recommendations for the use of capnography by procedural sedation nurses outside the operating room setting.

Purpose To assess for nanopore formation in bone marrow cells after irreversible electroporation (IRE) and to evaluate the antitumoral effect of IRE, used alone or in combination with doxorubicin (DOX)-loaded superparamagnetic iron oxide (SPIO) nanoparticles (SPIO-DOX), in a VX2 rabbit tibial tumor model. Materials and Methods All experiments were approved by the institutional animal care and use committee. Five porcine vertebral bodies in one pig underwent intervention (IRE electrode placement without ablation [n = 1], nanoparticle injection only [n = 1], and nanoparticle injection followed by IRE [n = 3]). The animal was euthanized and the vertebrae were harvested and evaluated with scanning electron microscopy. Twelve rabbit VX2 tibial tumors were treated, three with IRE, three with SPIO-DOX, and six with SPIO-DOX plus IRE; five rabbit VX2 tibial tumors were untreated (control group). Dynamic T2*-weighted 4.7-T magnetic resonance (MR) images were obtained 9 days after inoculation and 2 hours and 5 days after treatment. Antitumor effect was expressed as the tumor growth ratio at T2*-weighted MR imaging and percentage necrosis at histologic examination. Mixed-effects linear models were used to analyze the data. Results Scanning electron microscopy demonstrated nanopores in bone marrow cells only after IRE (P , .01). Average volume of total tumor before treatment (503.1 mm3 ± 204.6) was not significantly different from those after treatment (P = .7). SPIO-DOX was identified as a reduction in signal intensity within the tumor on T2*-weighted images for up to 5 days after treatment and was related to the presence of iron. Average tumor growth ratios were 103.0% ± 75.8 with control treatment, 154.3% ± 79.7 with SPIO-DOX, 77% ± 30.8 with IRE, and -38.5% ± 24.8 with a combination of SPIO-DOX and IRE (P = .02). The percentage residual viable tumor in bone was significantly less for combination therapy compared with control (P = .02), SPIO-DOX (P , .001), and IRE (P = .03) treatment. The percentage residual viable tumor in soft tissue was significantly less with IRE (P = .005) and SPIO-DOX plus IRE (P = .005) than with SPIO-DOX. Conclusion IRE can induce nanopore formation in bone marrow cells. Tibial VX2 tumors treated with a combination of SPIO-DOX and IRE demonstrate enhanced antitumor effect as compared with individual treatments alone. © RSNA, 2017 Online supplemental material is available for this article.

Objective To assess the impact of multiple blastocyst biopsy and vitrification-warming procedures on clinical outcomes. Design Retrospective study. Setting Private fertility clinic. Patient(s) Preimplantation genetic diagnosis (PGD) patients undergoing comprehensive chromosome screening, including monogenic disorder and chromosome rearrangement cases. Intervention(s) Warming and transfer of euploid blastocysts biopsied and vitrified-warmed once (group 1 [G1, control]; n=2,130), biopsied once but vitrified-warmed twice (group 2 [G2]; n=34), or biopsied and vitrified-warmed twice (group 3 [G3]; n=29). Main Outcome Measure(s) Thaw (for transfer) survival rate and clinical pregnancy rate (CPR). Result(s) The thaw survival rates were 98.4% for G1, 97.3% for G2, and 93.3% for G3, with once biopsied and vitrified-warmed embryos being significantly higher than twice biopsied and vitrified-warmed embryos (G1 vs. G3; P =.032). There was a slight reduction in CPR with an additional vitrification-warming (G1 54.3% vs. G2 47.1%) and larger reduction with an additional embryo biopsy (G2 47.1% vs. G3 31.0%), but neither difference was statistically significant. However, the combined effect of both additional biopsy and vitrification-warming resulted in a significantly reduced CPR (G1 54.3% vs. G3 31.0%; P =.013). Conclusion(s) This study indicates that blastocysts biopsied and vitrified-warmed twice have reduced clinical outcomes compared with blastocysts biopsied and vitrified-warmed once. PGD patients should be advised that performing a second biopsy and vitrification-warming in cases of failure to obtain a result from initial biopsy will reduce the chance of pregnancy. Patients with inherited disorders may elect to proceed with the second biopsy and vitrification to avoid transfer of embryos with the genetic condition.

Purpose To evaluate the immediate and long-term safety as well as thrombus-capturing efficacy for 5 weeks after implantation of an absorbable inferior vena cava (IVC) filter in a swine model. Materials and Methods This study was approved by the institutional animal care and use committee. Eleven absorbable IVC filters made from polydioxanone suture were deployed via a catheter in the IVC of 11 swine. Filters remained in situ for 2 weeks (n = 2), 5 weeks (n = 2), 12 weeks (n = 2), 24 weeks (n = 2), and 32 weeks (n = 3). Autologous thrombus was administered from below the filter in seven swine from 0 to 35 days after filter placement. Fluoroscopy and computed tomography follow-up was performed after filter deployment from weeks 1-6 (weekly), weeks 7-20 (biweekly), and weeks 21-32 (monthly). The infrarenal IVC, lungs, heart, liver, kidneys, and spleen were harvested at necropsy. Continuous variables were evaluated with a Student t test. Results There was no evidence of IVC thrombosis, device migration, caval penetration, or pulmonary embolism. Gross pathologic analysis showed gradual device resorption until 32 weeks after deployment. Histologic assessment demonstrated neointimal hyperplasia around the IVC filter within 2 weeks after IVC filter deployment with residual microscopic fragments of polydioxanone suture within the caval wall at 32 weeks. Each iatrogenic-administered thrombus was successfully captured by the filter until resorbed (range, 1-4 weeks). Conclusion An absorbable IVC filter can be safely deployed in swine and resorbs gradually over the 32-week testing period. The device is effective for the prevention of pulmonary embolism for at least 5 weeks after placement in swine.

Aims The anterior pelvic internal fixator is increasingly used for the treatment of unstable, or displaced, injuries of the anterior pelvic ring. The evidence for its use, however, is limited. The aim of this paper is to describe the indications for its use, how it is applied and its complications. Patients and Methods We reviewed the case notes and radiographs of 50 patients treated with an anterior pelvic internal fixator between April 2010 and December 2015 at a major trauma centre in the United Kingdom. The median follow-up time was 38 months (interquartile range 24 to 51). Results Three patients were excluded from the analysis leaving 47 patients with complete follow-up data. Of the 47 patients, 46 achieved radiological union and one progressed to an asymptomatic nonunion. Of the remaining patients, 45 required supplementary posterior fixation with percutaneous iliosacral screws, 2 of which required sacral plating. The incidence of injury to the lateral femoral cutaneous nerve (LFCN) was 34%. The rate of infection was 2%. There were no other significant complications. Without this treatment, 44 patients (94%) would have needed unilateral or bilateral open reduction and plate fixation extending laterally to the hip joint. Conclusion The anterior pelvic internal fixator reduces the need for extensive open surgery and is a useful addition to the armamentarium for the treatment of anterior pelvic injuries. It is associated with injury to the LFCN in a third of patients. Cite this article: Bone Joint J 2017;99-B.1232–6.

To address the need for efficient and biocompatible delivery systems for systemic siRNA delivery, we developed 1,2-Dioleoyl-sn-Glycero-3-Phosphatidylcholine (DOPC) nanoliposomal EphA2-targeted therapeutic (EPHARNA). Here, we performed safety studies of EPHARNA in murine and primate models. Single dosing of EPHARNA was tested at 5 concentrations in mice (N = 15 per group) and groups were sacrificed on days 1, 14, and 28 for evaluation of clinical pathology and organ toxicity. Multiple dosing of EPHARNA was tested in mice and Rhesus macaques twice weekly at two dose levels in each model. Possible effects on hematologic parameters, serum chemistry, coagulation, and organ toxicity were assessed. Following single-dose EPHARNA administration to mice, no gross pathologic or dose-related microscopic findings were observed in either the acute (24 hours) or recovery (14 and 28 days) phases. The no-observed-adverse-effect level (NOAEL) for EPHARNA is considered >225 μg/kg when administered as a single injection intravenously in CD-1 mice. With twice weekly injection, EPHARNA appeared to stimulate a mild to moderate inflammatory response in a dose-related fashion. There appeared to be a mild hemolytic reaction in the female mice. In Rhesus macaques, minimal to moderate infiltration of mononuclear cells was found in some organs including the gastrointestinal tract, heart, and kidney. No differences attributed to EPHARNA were observed. These results demonstrate that EPHARNA is well tolerated at all doses tested. These data, combined with previously published in vivo validation studies, have led to an ongoing first-in-human phase I clinical trial (NCT01591356). Mol Cancer Ther; 16(6); 1114–23. ©2017 AACR.

The question of how to best integrate BIM into the curriculum is one of significant debate, especially at the university level. This paper presents the ongoing development of a third-year BIM integration curriculum within an Architectural Science undergraduate program, with a specific focus on a project designed to introduce students to data-driven design. This project has students create a series of massing models in Autodesk Revit, which are analyzed for both initial cost and life-cycle energy performance and these iterations guide studio project development. This paper presents the pedagogical approach developed to introduce students to advanced BIM use cases such as cost analysis and energy simulation and evaluates the first three years of integration of these topics into an architectural curriculum. From 2015 to 2017, over 300 students participated in this project, creating and evaluating over 1000 model iterations. Student feedback obtained through surveys and course evaluations demonstrates that this project is effective not only to provide students with increased BIM capabilities, but also encourage them to synthesize a broad range of data generated through simulation to refine and develop their designs.

Background. Most hand injuries in children can be managed non-operatively and are associated with excellent outcomes. Whilst the majority of our patients are discharged to the care of hand therapists, there is no literature to support this protocol. Our aim was to ensure this is safe and effective practice. Material and methods. We conducted a retrospective analysis of all patients referred to our paediatric hand trauma clinic for closed injuries over a four month period between December 2014 and March 2015. Data related to demographics, injury pattern and clinical outcomes was recorded and analysed. A telephone interview with a patient satisfaction questionnaire was attempted with all patients discharged to the care of hand therapists. Results. 139 patients were seen in the study period, including 90 males and 49 females. Phalangeal fractures (39%), volar plate injuries (19%) and metacarpal fractures (16%) were the commonest causes of hand trauma. The majority of patients (88%) were managed non-operatively. 97 patients were discharged to hand therapy follow-up and we managed to contact 51 patients (53%). Fifty-one patients (100%) completed a patient satisfaction questionnaire. 100% of the parents were happy with the care, 96% were not disappointed they did not see a doctor and 96% denied any complications. Conclusion. 1. The majority of paediatric hand injuries can be managed non-operatively with excellent outcomes. 2. Hand therapy led follow-up is appropriate for a selected group of paediatric hand injuries. This study pro­ves that it is safe and effective for the majority of closed hand trauma, as illustrated by low complication rates. 3. Hand therapist led follow up for paediatric hand injuries is associated with high patient satisfaction.

The signaling mechanisms between prostate cancer cells and infiltrating immune cells may illuminate novel therapeutic approaches. Here, utilizing a prostate adenocarcinoma model driven by loss of Pten and Smad4, we identify polymorphonuclear myeloid-derived suppressor cells (MDSC) as the major infiltrating immune cell type, and depletion of MDSCs blocks progression. Employing a novel dual reporter prostate cancer model, epithelial and stromal transcriptomic profiling identified CXCL5 as a cancer-secreted chemokine to attract CXCR2-expressing MDSCs, and, correspondingly, pharmacologic inhibition of CXCR2 impeded tumor progression. Integrated analyses identified hyperactivated Hippo–YAP signaling in driving CXCL5 upregulation in cancer cells through the YAP–TEAD complex and promoting MDSC recruitment. Clinicopathologic studies reveal upregulation and activation of YAP1 in a subset of human prostate tumors, and the YAP1 signature is enriched in primary prostate tumor samples with stronger expression of MDSC-relevant genes. Together, YAP-driven MDSC recruitment via heterotypic CXCL5–CXCR2 signaling reveals an effective therapeutic strategy for advanced prostate cancer. Significance: We demonstrate a critical role of MDSCs in prostate tumor progression and discover a cancer cell nonautonomous function of the Hippo–YAP pathway in regulation of CXCL5, a ligand for CXCR2-expressing MDSCs. Pharmacologic elimination of MDSCs or blocking the heterotypic CXCL5–CXCR2 signaling circuit elicits robust antitumor responses and prolongs survival. Cancer Discov; 6(1); 80–95. ©2015 AACR. This article is highlighted in the In This Issue feature, p. 1

Aims The aim of this study was to inform a definitive trial which could determine the clinical effectiveness of the X-Bolt Dynamic Hip Plating System compared with the sliding hip screw for patients with complex pertrochanteric fragility fractures of the femur. Patients and Methods This was a single centre, participant blinded, randomised, standard-of-care controlled pilot trial. Patients aged 60 years and over with AO/ASIF A2 and A3 type femoral pertrochanteric fractures were eligible. Results The primary outcome was the EuroQoL 5 Dimension Score (EQ-5D-3L) at one year following index fixation. A total of 100 participants were recruited, and primary outcome data were available for 88 patients following losses to follow-up and withdrawals. The mean difference in EQ-5D was 0.03 (95% confidence interval -0.17, 0.120; p = 0.720.) There were no significant differences in any of the secondary outcomes measures. The recruitment and follow-up rates from this feasibility study were as predicted. Conclusion A definitive trial with 90% power to find a clinically important difference in EQ-5D would require 964 participants based upon the data from this study. We plan to start recruitment to this trial in Spring 2016. Take home message: A definitive trial of X-Bolt Dynamic Hip Plating System is feasible and should be conducted now in order to quantify the clinical effectiveness of this novel implant. Cite this article: Bone Joint J 2016;98-B:686–9.

Background: The epidemiology of traumatic, nonbattle, Combat Zone hand injuries has not been well explored. Methods: This was a retrospective chart review of Emergency Department visits occurring at the Ibn Sina Hospital in Baghdad Iraq. Results: During the 24-month period from May 2007 to June 2009, 7,520 patients were seen at the Ibn Sina Hospital Emergency Department. Three hundred thirty-one cases met the inclusion criteria. Seventy-four cases were found to have required near-term evacuation from area of operation. Conclusions: Traumatic, nonbattle hand injuries are common and appear to be a significant problem in the Combat Zone. Injuries occurring because of the closure of vehicle doors, hatches, and turrets make up a large portion of these injuries and represent an optimal area of intervention for possible injury mitigation.

Ultrasound is emerging as a promising tool for the diagnosis of skeletal fractures, particularly in environments where conventional radiography may be absent or limited. This article presents a high-fidelity, practical simulation model for the ultrasound diagnosis of long-bone fractures and also examines the ability of physicians to diagnose the presence or absence of different fracture patterns using this model.The bony component of the model is a bare turkey leg bone that is mechanically fractured and housed in a shallow plastic container within a gelatin-based solution. Twenty physicians sonographically evaluated five models with different fracture patterns for the presence or absence of a fracture and were then queried regarding their opinion of this model as a teaching tool.Physicians were able to correctly identify the presence or absence of a fractured model with 100% sensitivity and 100% specificity across all fracture patterns and expressed agreement that this would be a useful teaching model.This high-fidelity, practical model is simple to construct, and the creation of a variety of fracture patterns is possible. Physicians found this to be a potentially useful teaching tool and correctly identified the presence or absence of different simulated fractures. Further studies may validate this simulation model as a teaching tool in the sonographic assessment of long bones for the presence of fractures and examine the potential clinical impact of this trainer.

This paper details the application of a Multi-Agent software system used in the qualification of an ultrasonic NDT inspection using theoretical flaw-response modelling. Flaw- response models provide a fast and cheap alternative to test- piece trials but their use involves prior knowledge about the model's theory and application, requiring an experienced NDT engineer. Due to the disparate nature of these software models they are unable to integrate with other NDT software tools, making the selection and application of the most appropriate model for a given inspection complex. A Multi-Agent System approach creates a flexible software environment that permits the integration of software tools that display autonomous behaviour, allowing them to share data and collaborate with other tools despite their heterogeneous characteristics. A prototype Inspection Qualification Multi-Agent System has been developed that is capable of performing flaw-response model selection through the use of a rule-based software system incorporated within a Model Facilitator agent. Importantly, the design and implementation of this system utilises expert knowledge elucidated from senior NDT engineers. The performance of the Model Facilitator will be analysed through case studies, illustrating the benefits of this approach with regard to computational speed and accuracy over conventional techniques used in the ultrasonic qualification process.

Corporate Real Estate (CRE) management has several functional components, which are often owned by different departments and stored on different data management systems. A Building Information Modelling (BIM) centralized software framework is an efficient way to document, manage, share, analyze and present information used in CRE management operations and provide a single source of truth to allow evidence-based decision-making regarding individual buildings as well as property portfolios. This paper explores previous examples from the literature and presents a case study whereby BIM models were created for two existing small commercial offices to display information related to corporate real estate management, facility management and space use, building operations and maintenance, and thermal comfort and complaint tracking. These case studies demonstrate the data visualization benefits of this tool within this context and its potential for scaling to the portfolio level, as information in each of these models can be interfaced with its associated centralized data management system.

Emergency physicians come across a wide variety of painful conditions and perform a large number of uncomfortable procedures on a typical shift. This article describes the local anesthetic agents and their potential applications. The peripheral nerve blocks that are regularly done in the emergency department are described. Lastly, procedural sedation and analgesia are covered, to include general principles and specific agents for its use in the emergency department.

Meeting abstracts Myeloid-derived suppressor cells (MDSCs) represent a phenotypically heterogeneous population of immature myeloid cells that play a tumor-promoting role by maintaining a state of immunological anergy and tolerance. Similar to other solid tumor types, Prostate cancer (PCa) is

PATIENTS WHO HAVE EXPERIENCED multiple traumatic injuries present one of the greatest challenges for perioperative teams. IN A TRAUMA PATIENT who is hemorrhaging, increased risk of death arises from a vicious cycle of hypothermia, coagulopathy, and metabolic acidosis known as the triad of death. A STAGED SURGICAL APPROACH predicated on specific priorities for treating multiply injured patients can help save the lives of these patients.

A participatory rural appraisal (PRA) conducted in East Timor in 2004 as part of an agricultural development project provided the basis for a number of community-based participatory extension initiatives. The PRA involved several communities throughout a watershed and also served as a training exercise for local agriculture ministry staff. Despite the poverty of many of the communities involved, and in contrast to published literature on the local agricultural situation, farmers clearly expressed their need for more marketable crops and alternative sources of livelihoods. Their desires contrasted with the project's initial assumption that the major need was for increased production of staple crops to alleviate food scarcity. The project consequently branched out from concentrating on basic agronomy of staple crops into developing marketable crops, improving livestock production and facilitating development of a local business. Farmers' groups were set up to allow farmers to develop their own agricultural ...

This article describes the setting up and evaluation of a course for ward-based nurses, which is designed to improve their skills in caring for highly dependent patients. The authors suggest such courses can increase nurses' confidence and competence and, as well as enhancing care, can improve communication with senior staff about issues of concern.

Collectively, these presentations introduced the audience to the roles of ES cells in generating phenotypes of transgenic animals,and they provided examples where the GEMs were used to define molecular mechanisms of disease or where ES cells were used as a therapeutic modality. Points of discussion among audience members reinforced the importance of strain-associated background lesions in animal models, technological advances in imaging functional biology, opportunities for stem cell therapies, and ubiquitination in regulation of cell proliferation. The 2012 American College of Veterinary Pathologists symposium ‘‘Evolutionary Aspects of Animal Models’’ will focus on the proper selection of a relevant animal model in biomedical research as critical to investigative success. Recent work characterizing rapid evolutionary changes and differences in physiology between species questions the validity of some comparative models. Dr. Robert Hamlin will be speaking on cardiovascular disease in ‘‘Animals as Models of Human Cardiovascular Disease: Or the Search to Overcome Outdated Evolutionary Homeostatic Mechanisms.’’ Dr. Stefan Niewiesk will discuss evolutionary factors that affect modeling the human immune system in ‘‘Of Mice and Men: Evolutionarily, What Are the Best Rodent Models of the Human Immune System for Infectious Disease Research?’’ Dr. Steven Austad will consider evolution in ‘‘Evolutionary Aspects of Animal Models of Aging.’’Finally, Dr. Elizabeth Uhl will conclude the session with ‘‘Modeling Disease Phenotypes: How an Evolutionary Perspective Enhances the Questions.’’

Objective The objectives of this study were to evaluate tensile strength retention of polydioxanone as a function of time in a swine venous system and to assess the feasibility of an absorbable inferior vena cava (IVC) filter made from polydioxanone in a pilot swine study. Methods Twenty strands (60 cm each) of size 1 polydioxanone absorbable suture (Ethicon, Somerville, NJ) were placed in the central venous system of domestic swine. Strands were harvested at weekly intervals during 10 weeks for tensile strength testing. Results were compared with control samples obtained from an in vitro engineered circulation system containing sodium phosphate buffer solution. Three IVC filters braided from polydioxanone suture were also catheter deployed in three swine to assess absorbable IVC filter feasibility. Results Polydioxanone retained 82% tensile strength in vitro vs 79% in vivo at 35 days (P > .22), the desired prophylactic duration. For IVC filters made from polydioxanone, technical success of placement was achieved in all three filters deployed (100%). Autologous thrombus deployed inferior to the filter remained trapped in the filter until thrombus resorption, with no evidence of pulmonary emboli on follow-up computed tomography. There were no instances of caval penetration, filter-induced IVC thrombosis, filter migration, or tilt >15 degrees with imaging and clinical follow-up carried out to 32 weeks. Conclusions Strength retention of polydioxanone suture placed in the venous system of swine is similar to earlier in vitro studies out to 10 weeks (P > .06 for all weeks) and is more than sufficient (8.20 ± 0.37 kg mean load at break for size 1) to trap thrombus. Pilot animal study suggests that an absorbable polydioxanone IVC filter can be catheter deployed to capture and to hold iatrogenically administered autologous thrombus through resorption.

Small farms make up about seventy-five percent of all the farms in the United States and form a vital part of many rural and peri-urban communities. We examine the potential of Farming Systems Research and Extension (FSR/E), a set of concepts and methodologies that has been used widely in overseas agricultural development activities, to address the diverse needs, goals and objectives of small farmers in North America. We discuss the major characteristics of FSR/E and use the example of Waimanalo, a diverse peri-urban community in Hawaii, to propose some ways that FSR/E has been and could be further incorporated into extension efforts.

The transdermal extraction of interstitial fluid by low‐frequency ultrasound offers a potential minimally invasive method of obtaining a fluid sample for at‐home blood glucose monitoring. Here we show that the application of low‐frequency ultrasound (20 kHz) enhances the transdermal transport of interstitial fluid across hairless rat skin. Using 3 H 2 O as a tracer injected intravenously, a measurable amount of water (>1 μL) was extracted without producing any histologic evidence of injury, even after repeated exposures. Piezoelectric transducers were imbedded in the extraction chamber and used to correlate ultrasound spectral properties to the amount of fluid extracted. Results indicate that the highest amount of water extracted occurs when the acoustic coupling media on the surface of the skin is cavitating, resulting in mild ablation of the stratum corneum and a reduction in its resistance to water mass transfer. © 2000 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 1170–1179, 2000

Objective To compare pregnancy and neonatal outcomes after fresh and vitrified-warmed single-blastocyst transfers. Design Retrospective study. Setting Private in vitro fertilization (IVF) clinic. Patient(s) 1,209 infertile patients who underwent a total of 1,157 fresh and 645 vitrified-warmed embryo transfers. Intervention(s) Day-5 single-blastocyst transfers using fresh or vitrified-warmed (Cryotop method) grade I and grade II embryos. Main Outcome Measure(s) Fetal heart pregnancy rate, live-birth rate, gestational age, and live-birth weight. Result(s) The overall blastocyst thaw survival rate was 94.4% and was not significantly different between blastocyst grades or developmental stages. Similar clinical outcomes were achieved for fresh and vitrified-warmed blastocyst transfers; for example, grade I blastocysts had a live-birth rate of 52.8% versus 55.3%, respectively, and grade II blastocysts had a rate of 34.9% versus 30.4%, respectively. Significantly improved neonatal outcomes were evident for vitrified-warmed blastocyst transfers for gestational age, being on average 0.3 weeks longer, and for live-birth weight with babies born on average 145 g heavier (3,296 g versus 3,441 g for fresh and vitrified-warmed groups, respectively), as compared with fresh transfers. Conclusion(s) Embryo transfer of vitrified-warmed blastocysts yields equivalent live-birth rates and improved neonatal outcomes compared with fresh transfers.

Many burns surgeons avoid excision and direct closure of acute burns owing to concerns over wound dehiscence, scarring and infection. There is no evidence in the literature to support this practice. We present outcomes of a prospective series of 100 patients who underwent excision and direct closure of 138 burns over a 2-year period, along with results from a survey sent to 33 senior burns surgeons to gauge attitudes towards direct closure in burns surgery. 47% of survey respondents never perform direct closure. Dehiscence was cited as the most common concern, followed by hypertrophic scarring (HTS). In our cohort, the superficial dehiscence rate was 12% and the HTS rate was 16%, with no scarring contractures. Patients with healing time greater than 14 days were more likely to develop HTS (p = 0.008), as were those with wound dehiscence (p = 0.014). Patients undergoing part-grafting in addition to direct closure took significantly longer to heal than those undergoing direct closure alone (p = 0.0002), with the donor site or graft delaying healing in the majority. Excision and direct closure of acute burn wounds avoids donor site morbidity and has an acceptable complication rate. It is a safe and effective treatment for full thickness burns in selected cases.

Background A 4-year-old rhesus macaque presented with acute, progressive paresis of the extremities. Methods A complete blood count, serum biochemical analysis, neurologic exam and necropsy were performed. Results The clinical, histopathological, and immunohistochemical findings confirmed a high-grade intramedullary glial tumor of the spinal cord that was most consistent with an ependymoma. Conclusions We describe a case of a naturally occurring spontaneous spinal cord neoplasia in a non-human primate.

To compare the effects of opioid and nonopioid sedation on gastric emptying. Prospective, randomized trial. University teaching hospital ICU. 21 brain injured patients requiring sedation, mechanical ventilation and intracranial pressure (ICP) monitoring for >24h. Patients were randomized to receive infusions of either morphine plus midazolam (M), or propofol (P). Gastric emptying was assessed by the paracetamol absorption technique and by residual volumes following a 200 ml test feed. Pre-sedation Glasgow Coma Score, mean ICP and the presence of bowel sounds were noted. Plasma concentrations of paracetamol were measured over 3 h following a 1 g gastric dose. There were no differencese in median peak paracetamol concentration (M, 18.5 versus P, 20.8 mg/l), median time to peak concentration (M, 20 versus P, 25 min), median area under the concentration-time curve (AUC), or in the median residual volumes at 1 h (M, 14 versus P, 10.5 ml) and 2 h (M, 5 versus P, 3 ml). In patients with ICP>20 mmHg, paracetamol concentrations were lower (p

The ability of dopamine to reverse oliguria has led to its ubiquitous renal protective use in patients at risk of acute renal failure. However, this diuresis is due primarily to inhibition of distal tubular sodium reabsorption and not renal vasodilation. Recent controlled clinical studies have been unable to demonstrate a renal protective effect independent of changes in cardiac output. Selective decontamination of the digestive tract (SDD) has the appealing theoretical ability to minimize upper gastrointestinal colonization with gram-negative bacteria and fungi, and subsequently reduce nosocomial infection and mortality. Such modification of flora does occur, but the initial studies showing a reduction in lower respiratory tract infections have not been supported by recent large double-blind randomized controlled trials. A reduction in mortality or length of stay of general intensive care patients given SDD has never been demonstrated, and it remains an experimental therapy with possible application for some patient subgroups. Upper gastrointestinal hemorrhage (UGH) in the critically ill is associated with prolonged ventilatory support and coagulopathy, but clinically important bleeding is now uncommon. Prophylaxis with agents that increase gastric pH is effective in reducing UGH, but may be associated with a higher incidence of nosocomial pneumonia than occurs with alternatives such as sucralfate. Prophylaxis does not alter mortality, and it is now controversial which patients, if any, should routinely receive such treatment.

Many forward units are being deployed with portable ultrasound capability. We describe a case of a patient with a complete patellar tendon rupture that was diagnosed in the deployed environment using a portable ultrasound. Military physicians can benefit from sonographic evaluation of patients with musculoskeletal injuries in a deployed setting. The information they gain can assist them in giving better care to their patients and in making decisions on patient evacuation.

Fractures are a common emergency department (ED) diagnosis. Ultrasound is a useful tool to evaluate for the presence of long bone fractures and can be performed by minimally trained individuals. We examined the ability of ED nurses to sonographically detect long bone fractures using a recently described training model. The fracture model consisted of a turkey long bone within a firm gelatin matrix. Emergency nurses examined five fracture models with a portable ultrasound machine to determine the presence or absence of a fracture. Overall accuracy was compared via chi-square analysis to the ability of physicians to complete the same assessment. Thirty nurses sonographically assessed the models. An overall sensitivity of 98% (95% confidence interval: 92-99%) and specificity of 93% (95% confidence interval: 76-99%) was observed for the detection of a fractured model. No difference in fracture detection accuracy (p>0.05) was revealed compared to an evaluation by 30 ED physicians. While the clinical impact of this ability remains uncertain, future utilization of nursing ability to detect fractures by ultrasound may improve patient care in ways such as more efficient triaging of radiographs and the mobilization of resources for fracture reduction.