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A correction to the article "Safety of long-term denosumab therapy: results from the open label extension phase of two phase 3 studies in patients with metastatic breast and prostate cancer" that was published in the October 19, 2015 issue is presented.

Sustainable drainage systems are an alternative and holistic approach to conventional urban stormwater management that use and enhance natural processes to mimic pre-development hydrology, adding a number of well-recognized, although not so often quantified benefits. However, transitions towards regenerative urban built environments that widely incorporate sustainable drainage systems are “per se” innovative journeys that encounter barriers which include the limited evidence on the performance of these systems which, in many countries, are still unknown to professionals and decision makers. A further important barrier is the frequently poor interaction among stakeholders; key items such as sustainable drainage systems provide collective benefits which also demand collective efforts. With the aim of overcoming such innovation-driven barriers, six showcase projects (including rain gardens acting as infiltration basins, swales and a green roof) to demonstrate the feasibility and suitability of sustainable drainage systems were developed and/or retrofitted in two cities of the Valencian region of Spain as a part of an European project, and their performance was monitored for a year. The data acquired, after being fully analyzed and presented to a group of key regional stakeholders, is proving to be a valuable promoter of the desired transition (for instance in influencing the support to SuDS in recent regional legislation). This paper presents detailed data on how these urban ecological drainage infrastructure elements reduce runoff (peak flows and volumes) and improve its quality, contributing to the goal of healthier and livable cities. The data show that the pilots have good hydraulic performance under a typical Mediterranean climate and also provided water quality benefits. Furthermore, it shows how engagement can contribute to smarter governance in the sense of smoothing the difficulties faced by innovation when being presented, understood, and endorsed by professionals and decision-makers in the field of stormwater management. Finally, activities undertaken in the demonstration sites monitored, show how they have been drivers of innovation and transition towards a new stormwater paradigm in Spain, serving as a reference to other urban areas in the Mediterranean. [ABSTRACT FROM AUTHOR]

Summary Loss-of-function mutations in TET2 occur frequently in patients with clonal hematopoiesis, myelodysplastic syndrome (MDS), and acute myeloid leukemia (AML) and are associated with a DNA hypermethylation phenotype. To determine the role of TET2 deficiency in leukemia stem cell maintenance, we generated a reversible transgenic RNAi mouse to model restoration of endogenous Tet2 expression. Tet2 restoration reverses aberrant hematopoietic stem and progenitor cell (HSPC) self-renewal in vitro and in vivo. Treatment with vitamin C, a co-factor of Fe2 + and α-KG-dependent dioxygenases, mimics TET2 restoration by enhancing 5-hydroxymethylcytosine formation in Tet2 -deficient mouse HSPCs and suppresses human leukemic colony formation and leukemia progression of primary human leukemia PDXs. Vitamin C also drives DNA hypomethylation and expression of a TET2-dependent gene signature in human leukemia cell lines. Furthermore, TET-mediated DNA oxidation induced by vitamin C treatment in leukemia cells enhances their sensitivity to PARP inhibition and could provide a safe and effective combination strategy to selectively target TET deficiency in cancer. PaperClip [ABSTRACT FROM AUTHOR]

The article discusses the evidence-based studies which suggested that regular and moderate-intensity aerobic exercise has improved the symptoms of people with McArdle disease, a glycogen storage disease type V. A study extracted from the Spanish national registry reveals that physically active patients are more likely to improve their clinical course. Other studies affirmed the correlation between physical activity (PA) and functional capacity based on peak oxygen uptake (VO2peak).

Isolated polyarteritis nodosa is a rare condition that may be triggered by local exposure to certain agents capable of provoking local immunostimulation without a systemic immune reaction. Isolated polyarteritis nodosa in the testes presents similar histologic characteristics as those of systemic inflammation, although infarcted areas in the testis are more common in generalized polyarteritis nodosa. Definitive diagnosis requires histologic study. We present the case of a 26-year-old patient with isolated testicular polyarteritis nodosa whose symptoms consisted predominantly of intense testicular pain and slight enlargement of both testes. [Copyright &y& Elsevier]

Foot-and-mouth disease virus (FMDV) is the causative agent of a highly contagious vesicular disease of cloven-hoofed animals. In the present study we use FMDV serotype C infection of swine to determine, by analytical techniques, the direct ex vivo visualization of virus-infected immune cells during the first 17 days of infection. We report, for the first time, that FMDV C-S8c1 can infect T and B cells at short periods of time postinoculation, corresponding with the peak of the viremia. There is a significant lymphopenia that involves CD3+ CD4- CD8+/-, CD3+ CD4- CD8+Tc, and CD3+ CD4+ CD8+ memory Th but not CD3+ CD4+ CD8- naïve Th lymphocytes. In addition, a profound depletion of the vast majority of peripheral T cells in lymph nodes and spleen is observed. This selective depletion of T cells is not due mainly to in situ death via apoptosis as visualized by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique. Thus, early infection of T cells by FMDV may be the main cause of the observed T-cell depletion. Importantly, this lack of T cells is reflected in a reduced response to mitogen activation, which in many cases is totally eliminated. These data suggest a mechanism by which the virus causes a transient immunosuppression, subvert the immune systems, and spreads. These results have important implications for our understanding of early events in the development of a robust immune response against FMDV. [ABSTRACT FROM AUTHOR]