The simplicial volume of closed manifolds covered by H^2 x H^2

We compute the value of the simplicial volume for closed, oriented Riemannian manifolds covered by $\mathbb{H}^{2}\times\mathbb{H}^{2}$ explicitly, thus in particular for products of closed hyperbolic surfaces. This gives the first exact value of a nonvanishing simplicial volume for a manifold of nonconstant curvature.Comment: 19 pages; added consequences: Milnor-Wood type inequality, nonexistence of affine structur

The simplicial volume of 3-manifolds with boundary

We provide sharp lower bounds for the simplicial volume of compact $3$-manifolds in terms of the simplicial volume of their boundaries. As an application, we compute the simplicial volume of several classes of $3$-manifolds, including handlebodies and products of surfaces with the interval. Our results provide the first exact computation of the simplicial volume of a compact manifold whose boundary has positive simplicial volume. We also compute the minimal number of tetrahedra in a (loose) triangulation of the product of a surface with the interval.Comment: 24 pages, 5 figures. Section 6 has been removed, and will appear in a separate paper by the same authors. This version has been accepted for publication by the Journal of Topolog

Degree theorems and Lipschitz simplicial volume for non-positively curved manifolds of finite volume

We study a metric version of the simplicial volume on Riemannian manifolds, the Lipschitz simplicial volume, with applications to degree theorems in mind. We establish a proportionality principle and a product inequality from which we derive an extension of Gromov's volume comparison theorem to products of negatively curved manifolds or locally symmetric spaces of non-compact type. In contrast, we provide vanishing results for the ordinary simplicial volume; for instance, we show that the ordinary simplicial volume of non-compact locally symmetric spaces with finite volume of Q-rank at least 3 is zero.Comment: 33 pages; corrected the vanishing result (and adapted Section 5 accordingly), minor expository changes in the introductio

Treatment with Anti-HER2 Chimeric Antigen Receptor Tumor-Infiltrating Lymphocytes (CAR-TILs) Is Safe and Associated with Antitumor Efficacy in Mice and Companion Dogs

Patients with metastatic melanoma have a historically poor prognosis, but recent advances in treatment options, including targeted therapy and immunotherapy, have drastically improved the outcomes for some of these patients. However, not all patients respond to available treatments, and around 50% of patients with metastatic cutaneous melanoma and almost all patients with metastases of uveal melanoma die of their disease. Thus, there is a need for novel treatment strategies for patients with melanoma that do not benefit from the available therapies. Chimeric antigen receptor-expressing T (CAR-T) cells are largely unexplored in melanoma. Traditionally, CAR-T cells have been produced by transducing blood-derived T cells with a virus expressing CAR. However, tumor-infiltrating lymphocytes (TILs) can also be engineered to express CAR, and such CAR-TILs could be dual-targeting. To this end, tumor samples and autologous TILs from metastasized human uveal and cutaneous melanoma were expanded in vitro and transduced with a lentiviral vector encoding an anti-HER2 CAR construct. When infused into patient-derived xenograft (PDX) mouse models carrying autologous tumors, CAR-TILs were able to eradicate melanoma, even in the absence of antigen presentation by HLA. To advance this concept to the clinic and assess its safety in an immune-competent and human-patient-like setting, we treated four companion dogs with autologous anti-HER2 CAR-TILs. We found that these cells were tolerable and showed signs of anti-tumor activity. Taken together, CAR-TIL therapy is a promising avenue for broadening the tumor-targeting capacity of TILs in patients with checkpoint immunotherapy-resistant melanoma

Careful in the crisis? Determinants of older people's informal care receipt in crisis-struck European countries

Macroeconomic downturns can have an important impact on the receipt of informal and formal long-term care, since recessions increase the number of unemployed and affect net wealth. This paper investigates how the market for informal care changed during and after the Great Recession in Europe, with particular focus on their various determinants. We use data from the Survey of Health, Aging and Retirement in Europe, which includes a rich set of variables covering waves before and after the Great Recession. We find evidence of an increase in the availability of informal care after the economic downturn when controlling for year and country fixed effects. This trend is mainly driven by changes in care provision of individuals not cohabiting with the care recipient. We also find evidence of several determinants of informal care receipt changing during the crisis such as physical needs, personal wealth and household structures

Effective-Range Expansion of the Neutron-Deuteron Scattering Studied by a Quark-Model Nonlocal Gaussian Potential

The S-wave effective range parameters of the neutron-deuteron (nd) scattering are derived in the Faddeev formalism, using a nonlocal Gaussian potential based on the quark-model baryon-baryon interaction fss2. The spin-doublet low-energy eigenphase shift is sufficiently attractive to reproduce predictions by the AV18 plus Urbana three-nucleon force, yielding the observed value of the doublet scattering length and the correct differential cross sections below the deuteron breakup threshold. This conclusion is consistent with the previous result for the triton binding energy, which is nearly reproduced by fss2 without reinforcing it with the three-nucleon force.Comment: 21 pages, 6 figures and 6 tables, submitted to Prog. Theor. Phy

CNS-targeted glucocorticoid reduces pathology in mouse model of amyotrophic lateral sclerosis

Hallmarks of CNS inflammation, including microglial and astrocyte activation, are prominent features in post-mortem tissue from amyotrophic lateral sclerosis (ALS) patients and in mice overexpressing mutant superoxide dismutase-1 (SOD1 G93A ). Administration of non-targeted glucocorticoids does not significantly alter disease progression, but this may reflect poor CNS delivery. Here, we sought to discover whether CNS-targeted, liposomal encapsulated glucocorticoid would inhibit the CNS inflammatory response and reduce motor neuron loss. SOD1 G93A mice were treated with saline, free methylprednisolone (MP, 10 mg/kg/week) or glutathione PEGylated liposomal MP (2B3-201, 10 mg/kg/week) and compared to saline treated wild-type animals. Animals were treated weekly with intravenous injections for 9 weeks from 60 days of age. Weights and motor performance were monitored during this period. At the end of the experimental period (116 days) mice were imaged using T 2-weighted MRI for brainstem pathology; brain and spinal cord tissue were then collected for histological analysis

Biomarkers of acute lung injury: worth their salt?

The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI) and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy