Autologous osteochondral plug transplantation for osteochondrosis of the second metatarsal head: a case report

<p>Abstract</p> <p>Introduction</p> <p>Osteochondrosis of the second or third metatarsal head is a rare condition called Freiberg's disease. To relieve foot pain, conservative treatment with a foot orthosis to reduce weight-bearing and immobilize the foot are recommended. In cases in which such treatments have proved to be ineffective, several surgical treatments have been performed. The appropriate surgical treatment for Freiberg's disease remains controversial.</p> <p>Case presentation</p> <p>We describe the case of a 20-year-old Japanese woman with a three-year history of right forefoot pain and no history of trauma. Two years after treatment by autologous osteochondral plug transplantation, she has neither complaints nor symptoms.</p> <p>Conclusion</p> <p>Autologous osteochondral plug transplantation represents a potentially successful surgical arthroplastic option in preserving the metatarsophalangeal joint in patients with Freiberg's disease.</p

Inclusive School Community: Why is it so Complex?

This paper addresses the question: why is it so hard for school communities to respond to diversity in learners, staff and parents in inclusive ways? The authors draw on theory and recent professional experience in Queensland, Australia, to offer four guiding principles that address traditional assumptions about learning that result in inequality of opportunity and outcomes for students. The authors suggest these principles to support the development of a more inclusive school community: (1) develop a learning community incorporating a critical friend; (2) value and collaborate with parents and the broader community; (3) engage students as citizens in school review and develop¬ment; and (4) support teachers’ critical engagement with inclusive ideals and practices. The authors describe how the principles can work in concert in a school community

Don't Stop Thinking About Leptoquarks: Constructing New Models

We discuss the general framework for the construction of new models containing a single, fermion number zero scalar leptoquark of mass $\simeq 200-220$ GeV which can both satisfy the D0/CDF search constraints as well as low energy data, and can lead to both neutral and charged current-like final states at HERA. The class of models of this kind necessarily contain new vector-like fermions with masses at the TeV scale which mix with those of the Standard Model after symmetry breaking. In this paper we classify all models of this type and examine their phenomenological implications as well as their potential embedding into SUSY and non-SUSY GUT scenarios. The general coupling parameter space allowed by low energy as well as collider data for these models is described and requires no fine-tuning of the parameters.Comment: Modified text, added table, and updated reference

Mission impossible? The paradoxes of stretch goal setting

© 2016, © The Author(s) 2016. Stretch goal setting is a process involving multiple and nested paradoxes. The paradoxical side of stretch is attractive because it holds great promise yet dangerous because it triggers processes that are hard to control. Paradoxes are not readily managed by assuming a linear relation between the here and now and the intended future perfect. Before adopting stretch goal setting, managers should thus be prepared for the tensions and contradictions created by nested or interwoven paradoxes. Achieving stretch goals can be as difficult for the managers seeking to direct the process as for designated delegates. While the increasing popularity of stretch goal setting is understandable, its unexpected consequences must be taken into account. The inadequate use of stretch goals can jeopardize the social sustainability of organizations as well as their societal support systems

CAR links hypoxia signaling to improved survival after myocardial infarction

The coxsackievirus and adenovirus receptor (CAR) mediates homo- and heterotopic interactions between neighboring cardiomyocytes at the intercalated disc. CAR is upregulated in the hypoxic areas surrounding myocardial infarction (MI). To elucidate whether CAR contributes to hypoxia signaling and MI pathology, we used a gain- and loss-of-function approach in transfected HEK293 cells, H9c2 cardiomyocytes and CAR knockout mice. CAR overexpression increased RhoA activity, HIF-1α expression and cell death in response to chemical and physical hypoxia. In vivo, we subjected cardiomyocyte-specific CAR knockout (KO) and wild-type mice (WT) to coronary artery ligation. Survival was drastically improved in KO mice with largely preserved cardiac function as determined by echocardiography. Histological analysis revealed a less fibrotic, more compact lesion. Thirty days after MI, there was no compensatory hypertrophy or reduced cardiac output in hearts from CAR KO mice, in contrast to control mice with increased heart weight and reduced ejection fraction as signs of the underlying pathology. Based on these findings, we suggest CAR as a therapeutic target for the improved future treatment or prevention of myocardial infarction

Central nervous system immune interactome is a function of cancer lineage, tumor microenvironment, and STAT3 expression.

BACKGROUNDImmune cell profiling of primary and metastatic CNS tumors has been focused on the tumor, not the tumor microenvironment (TME), or has been analyzed via biopsies.METHODSEn bloc resections of gliomas (n = 10) and lung metastases (n = 10) were analyzed via tissue segmentation and high-dimension Opal 7-color multiplex imaging. Single-cell RNA analyses were used to infer immune cell functionality.RESULTSWithin gliomas, T cells were localized in the infiltrating edge and perivascular space of tumors, while residing mostly in the stroma of metastatic tumors. CD163+ macrophages were evident throughout the TME of metastatic tumors, whereas in gliomas, CD68+, CD11c+CD68+, and CD11c+CD68+CD163+ cell subtypes were commonly observed. In lung metastases, T cells interacted with CD163+ macrophages as dyads and clusters at the brain-tumor interface and within the tumor itself and as clusters within the necrotic core. In contrast, gliomas typically lacked dyad and cluster interactions, except for T cell CD68+ cell dyads within the tumor. Analysis of transcriptomic data in glioblastomas revealed that innate immune cells expressed both proinflammatory and immunosuppressive gene signatures.CONCLUSIONOur results show that immunosuppressive macrophages are abundant within the TME and that the immune cell interactome between cancer lineages is distinct. Further, these data provide information for evaluating the role of different immune cell populations in brain tumor growth and therapeutic responses.FUNDINGThis study was supported by the NIH (NS120547), a Developmental research project award (P50CA221747), ReMission Alliance, institutional funding from Northwestern University and the Lurie Comprehensive Cancer Center, and gifts from the Mosky family and Perry McKay. Performed in the Flow Cytometry & Cellular Imaging Core Facility at MD Anderson Cancer Center, this study received support in part from the NIH (CA016672) and the National Cancer Institute (NCI) Research Specialist award 1 (R50 CA243707). Additional support was provided by CCSG Bioinformatics Shared Resource 5 (P30 CA046592), a gift from Agilent Technologies, a Research Scholar Grant from the American Cancer Society (RSG-16-005-01), a Precision Health Investigator Award from University of Michigan (U-M) Precision Health, the NCI (R37-CA214955), startup institutional research funds from U-M, and a Biomedical Informatics & Data Science Training Grant (T32GM141746)

Assessing the life cycle environmental impacts of titania nanoparticle production by continuous flow solvo/hydrothermal synthesis

Continuous-flow hydrothermal and solvothermal syntheses offer substantial advantages over conventional processes, producing high quality materials from a wide range of precursors. In this study, we evaluate the “cradle-to-gate” life cycle environmental impacts of alternative titanium dioxide (TiO₂) nanoparticle production parameters, considering a range of operational conditions, precursors, material properties and production capacities. A detailed characterisation of the nano-TiO₂ products allows us, for the first time, to link key nanoparticle characteristics to production parameters and environmental impacts, providing a useful foundation for future studies evaluating nano-TiO₂ applications. Five different titanium precursors are considered, ranging from simple inorganic precursors, like titanium oxysulphate (TiOS), to complex organic precursors such as titanium bis(ammonium-lactato)dihydroxide (TiBALD). Synthesis at the laboratory scale is used to determine the yield, size distribution, crystallinity and phase of the nanoparticles. The specifications and operating experience of a full scale plant (>1000 t per year) are used to estimate the mass and energy inputs of industrial scale production for the life cycle assessment. Overall, higher process temperatures are linked to larger, more crystalline nanoparticles and higher conversion rates. Precursor selection also influences nano-TiO₂ properties: production from TiOS results in the largest particle sizes, while TiBALD achieves the smallest particles and narrowest size distribution. Precursor selection is the main factor in determining cradle-to-gate environmental impacts (>80% in some cases), due to the production impact of complex organic precursors. Nano-TiO2 production from TiOS shows the lowest global warming potential (GWP) (<12 kg CO₂-eq. per kg TiO₂) and cumulative energy demand (CED) (<149 MJ kg¯¹ TiO₂) due to the low environmental impact of the precursor, the use of water as a solvent and its high yield even at lower temperatures. Conversely, the TiBALD precursor shows the highest impact (86 kg CO₂-eq. per kg TiO₂ and 1952 MJ kg¯¹ TiO₂) due to the need for additional post-synthesis steps and complexity of precursor manufacturing. The main purpose of this study is not a direct comparison of the environmental impacts of TiO₂ nanoparticles manufactured utilizing various precursors under different conditions, but to provide an essential foundation for future work evaluating potential applications of nano-TiO₂ and their life cycle environmental impacts

A randomized, phase III trial of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in first-line treatment of metastatic colorectal cancer: The AIO KRK 0110 Trial/ML22011 Trial

<p>Abstract</p> <p>Background</p> <p>Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question whether this statement holds true also for bevacizumab-based first-line treatment including escalation- and de-escalation strategies.</p> <p>Methods/Design</p> <p>The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m²bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m²BID for 14d (d1-14), irinotecan 200 mg/m²(d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumour tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are overall response rate (ORR), overall survival, progression-free survival, safety and quality of life.</p> <p>Conclusion</p> <p>The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov Identifier <a href="http://www.clinicaltrials.gov/ct2/show/NCT01249638">NCT01249638</a></p> <p>EudraCT-No.: 2009-013099-38</p