A fast branch-and-prune algorithm for the position analysis of spherical mechanisms

The final publication is available at link.springer.comDifferent branch-and-prune schemes can be found in the literature for numerically solving the position analysis of spherical mechanisms. For the prune operation, they all rely on the propagation of motion intervals. They differ in the way the problem is algebraically formulated. This paper exploits the fact that spherical kinematic loop equations can be formulated as sets of 3 multi-affine polynomials. Multi-affinity has an important impact on how the propagation of motion intervals can be performed because a multi-affine polynomial is uniquely determined by its values at the vertices of a closed hyperbox defined in its domain.Peer ReviewedPostprint (author's final draft

BMP2 Is Essential for Post Natal Osteogenesis but Not for Recruitment of Osteogenic Stem Cells

The effects of BMP2 on bone marrow stromal cell differentiation and bone formation after bone marrow ablation were determined using C57 BL/6J (B6) mice. Inhibition of BMP2 expression with lentiviral BMP2 shRNA prevented both mineralized nodule formation in vitro and bone formation in vivo, and blocked the expression of Runx2 and osterix, transcriptional determinants of terminal osteogenic differentiation. No effect was observed on the expression of Sox9, a transcription factor, which is the one of the first transcriptional determinant to be expressed in committed chondroprogenitor and osteoprogenitor cells. In vitro studies showed that exogenously added BMP7 rescued the expression of osterix and enhanced the expression of Sox9, but had no effect on the expression of Runx2, while it only partially recovered the development of mineral deposition in the cultures. On the other hand, the exogenous addition of BMP2 rescued both Runx2 and osterix expression, did not enhance the expression of Sox9, but fully recovered the inhibition of mineral deposition in the cultures. Using antibodies against CD146 and Sox9, immunohistological examination of the cell populations found in the medullary space three days after bone marrow ablation, showed qualitatively equal numbers of cells expressing these skeletal progenitor and stem cell markers in control and BMP2 shRNA treated animals. Fluorescence Activated Cell Sorting (FACS) analysis of the cells found with the marrow cavities at three days after marrow ablation using CD146 antibody showed near equal numbers of immunopositive cells in both control and shRNA treated animals. In summary, the differences observed in vitro for BMP2 and BMP7 on osteogenic gene expression and mineralization suggest that they have differing effects on bone cell differentiation. These results further demonstrate that in vivo BMP2 is a central morphogenetic regulator of post natal osteoprogenitor differentiation, but does not affect recruitment of progenitors to the osteoblastic lineage

Aortic valve replacement in patients aged 50 to 70 years: Improved outcome with mechanical versus biologic prostheses

ObjectiveImproved durability of bioprostheses has led some surgeons to recommend biologic rather than mechanical prostheses for patients younger than 65 years. We compared late results of contemporary bioprostheses and bileaflet mechanical prostheses in patients who underwent aortic valve replacement between 50 and 70 years old.MethodsIn this retrospective study, patients received either St Jude bileaflet valves or Carpentier–Edwards bioprostheses. Operations were performed between January 1991 and December 2000, and groups were matched one-to-one according to age, sex, need for coronary artery bypass grafting, and valve size.ResultsFour hundred forty patients were matched, and follow-up was 92% complete, with median durations of 9.1 years for patients who received mechanical valves and 6.2 years for patients who received bioprostheses. The 5- and 10-year unadjusted survivals were 87% and 68% for mechanical valves and 72% and 50% for bioprostheses, respectively (P < .01). Freedoms from reoperation at 10 years were 98% for mechanical valves and 91% for bioprostheses (P = .06). Rates of late stroke or other embolic events and of endocarditis were similar between groups. Hemorrhagic complications necessitating hospitalization occurred in 15% of patients with mechanical valves and 7% of patients with bioprostheses (P = .01). Notably, 19% of patients with bioprostheses were receiving warfarin sodium at last follow-up. After adjustment for unmatched variables, including diabetes, renal failure, lung disease, New York Heart Association functional class, ejection fraction, and stroke, the use of a mechanical valve was protective against late mortality (hazard ratio 0.46, P < .01).ConclusionIn this study, patients aged 50 to 70 years who underwent aortic valve replacement with mechanical valves had a survival advantage relative to matched patients who received bioprostheses. These findings question recommendations of bioprostheses for younger patients and suggest that a randomized trial may be warranted

Using the Conservation Planning Tool to Effectively Recover Northern Bobwhites: An Example for States to Effectively Step-Down the NBCI Plan

The National Bobwhite Conservation Initiative (NBCI) 2.0 provides a sound foundation for recovering northern bobwhites (Colinus virginianus) range-wide, regionally and, to some extent, even locally. However, the NBCI does not provide detailed guidance to states on how to step-down the plan for efficacious delivery of on-the-ground management actions prescribed via biologists within the plan itself. States often must incorporate multiple planning efforts (e.g., state wildlife action plans) and geospatial layers not directly included in the NBCI plan (see NBCI Appendix in these Proceedings) to make tenable decisions which best guide allocation of resources and benefit multiple species of greatest conservation concern. The Conservation Planning Tool (CPT), developed as part of NBCI 2.0, provides the infrastructure for states and conservation organizations to capture biologist information coalesced in the plan while incorporating other data (e.g., species emphasis areas, current CRP implementation, etc.) germane to conservation planning. We use 3 states (Kansas, Florida, and Virginia) to demonstrate the utility of the CPT and to develop a step-down implementation plan, via creation of a habitat prioritization model, for recovery of bobwhites in each state. We explore the implications associated with creation of focal areas with respect to high versus medium ranked areas and underscore the importance of inclusion of major land-use opportunities and constraints prescribed within the plan to garner successful bobwhite recovery. We propose a framework for the integration of monitoring efforts into the step-down model to assess bird response and evaluate NBCI success through estimating bobwhite population density

Exploring patients’ experiences of analgesia after major lower limb amputation: A qualitative study

OBJECTIVES: To explore patient experiences, understanding and perceptions of analgesia following major lower limb amputation. DESIGN: Qualitative interview study, conducted as part of a randomised controlled feasibility trial. SETTING: Participants were recruited from two general hospitals in South Wales. PARTICIPANTS: Interview participants were patients enrolled in PLACEMENT (Perineural Local Anaesthetic Catheter aftEr Major lowEr limb amputatioN Trial): a randomised controlled feasibility trial comparing the use of perineural catheter (PNC) versus standard care for postoperative pain relief following major lower limb amputation. PLACEMENT participants who completed 5-day postoperative follow-up, were able and willing to participate in a face-to-face interview, and had consented to be contacted, were eligible to take part in the qualitative study. A total of 20 interviews were conducted with 14 participants: 10 male and 4 female. METHODS: Semi-structured, face-to-face interviews were conducted with participants over two time points: (1) up to 1 month and (2) at least 6 months following amputation. Interviews were audio-recorded, transcribed verbatim and analysed using a framework approach. RESULTS: Interviews revealed unanticipated benefits of PNC usage for postoperative pain relief. Participants valued the localised and continuous nature of this mode of analgesia in comparison to opioids. Concerns about opioid dependence and side effects of pain relief medication were raised by participants in both treatment groups, with some reporting trying to limit their intake of analgesics. CONCLUSIONS: Findings suggest routine placement of a PNC following major lower limb amputation could reduce postoperative pain, particularly for patient groups at risk of postoperative delirium. This method of analgesic delivery also has the potential to reduce preoperative anxiety, alleviate the burden of pain management and minimise opioid use. Future research could further examine the comparison between patient-controlled analgesia and continuous analgesia in relation to patient anxiety and satisfaction with pain management. TRIAL REGISTRATION NUMBER: ISRCTN: 85710690; EudraCT: 2016-003544-37

Genetic diversity and phylogenetic analysis of the native mountain ponies of Britain and Ireland reveal a novel rare population

The conservation of unique populations of animals is critical in order to preserve valuable genetic diversity and, where populations are free-living, maintain their irreplaceable influence upon habitat ecology. An accurate assessment of genetic diversity and structure within and between populations is crucial in order to design and implement conservation strategies in natural and domesticated species. Moreover, where it is possible to identify relic populations that are related to a structured breed an ideal opportunity presents itself to model processes that reveal historical factors that have shaped genetic diversity. The origins of native UK mountain and moorland ponies are uncertain, but they may have directly descended from prehistoric populations and potentially harbour specific adaptations to the uplands of Britain and Ireland. To date, there have been no studies of population structure and genetic diversity present within a free-living group of ponies in the Carneddau mountain range of North Wales. Herein, we describe the use of microsatellites and SNPs together with analysis of the mitochondrial control region to quantify the extent and magnitude of genetic diversity present in the feral Carneddau pony and relate this to several recognised British and Irish pony breeds. Our results establish that the feral Carneddau ponies represent a unique and distinctive population that merits recognition as a defined population and conservation priority. We discuss the implications for conservation of this population as a unique pool of genetic diversity adapted to the British uplands and potentially of particular value in maintaining the biodiversity of these habitats

Caveolin-1 is Associated with Tumor Progression and Confers a Multi-Modality Resistance Phenotype in Pancreatic Cancer

Caveolin-1 (Cav-1) is a 21 kDa protein enriched in caveolae, and has been implicated in oncogenic cell transformation, tumorigenesis, and metastasis. We explored roles for Cav-1 in pancreatic cancer (PC) prognostication, tumor progression, resistance to therapy, and whether targeted downregulation could lead to therapeutic sensitization. Cav-1 expression was assessed in cell lines, mouse models, and patient samples, and knocked down in order to compare changes in proliferation, invasion, migration, response to chemotherapy and radiation, and tumor growth. We found Cav-1 is overexpressed in human PC cell lines, mouse models, and human pancreatic tumors, and is associated with worse tumor grade and clinical outcomes. In PC cell lines, disruption/depletion of caveolae/Cav-1 reduces proliferation, colony formation, and invasion. Radiation and chemotherapy up-regulate Cav-1 expression, while Cav-1 depletion induces both chemosensitization and radiosensitization through altered apoptotic and DNA repair signaling. In vivo, Cav-1 depletion significantly attenuates tumor initiation and growth. Finally, Cav-1 depletion leads to altered JAK/STAT, JNK, and Src signaling in PC cells. Together, higher Cav-1 expression is correlated with worse outcomes, is essential for tumor growth and invasion (both in vitro and in vivo), is responsible for promoting resistance to therapies, and may serve as a prognostic/predictive biomarker and target in PC