Two Cases of Cerebral Involvement in Malignant Lymphoma (CD20+) That Responded to Combination Therapy with Rituximab and Cladribine

Cerebral involvement frequently occurs in association with progression or relapse of malignant lymphoma. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone, the standard chemotherapy for malignant lymphoma, is an ineffective treatment for cerebral involvement because these drugs cannot cross the blood-brain barrier. Therefore, various alternative strategies have been attempted. Although high-dose methotrexate combined with whole-brain radiotherapy is widely used to treat primary central nervous system lymphoma, there is no standard therapy to treat cerebral involvement in malignant lymphoma. Furthermore, high-dose methotrexate in combination with whole-brain radiotherapy is not always effective, and high rates of neurotoxicity are often observed, particularly in the elderly. To expand the therapeutic options for central nervous system involvement in recent years, systemic chemotherapies, including rituximab, high-dose methotrexate, and other agents that act during the S, G2, and M phases of the cell cycle, have been attempted. In our hospital, cladribine, a purine analogue with a cytocidal effect on resting malignant cells (G0/G1 phase of the cell cycle), has been used in combination with rituximab, which exhibits antitumor effects on nodal and extranodal lesions of relapsed and/or refractory B cell lymphomas, particularly cerebral lesions. Here, we report 2 representative cases of patients who were treated with cladribine plus rituximab and survived for 30 months (died of sepsis) and 52 months (still alive), respectively. The outcomes of these cases suggest that cladribine plus rituximab combination therapy with whole-brain radiotherapy may be very useful as salvage therapy for secondary central nervous system lymphoma and as initial therapy for primary central nervous system lymphoma

Influence of dietary nitrate supplementation on local sweating and cutaneous vascular responses during exercise in a hot environment.

Purpose We investigated the influence of inorganic nitrate (NO−3) supplementation on local sweating and cutaneous vascular responses during exercise in hot conditions. Method Eight healthy, young subjects were assigned in a randomized, double-blind, crossover design to receive NO−3 -rich beetroot (BR) juice (140 mL/day, containing ~8 mmol of NO−3) and NO−3-depleted placebo (PL) juice (140 mL/day, containing ~0.003 mmol of NO−3) for 3 days. On day 3 of supplementation, subjects cycled at an intensity corresponding to 55% of V̇ O2max for 30 min in hot conditions (30 °C, 50% relative humidity). Chest and forearm sweat rate (SR) and skin blood flow (SkBF), were measured continuously. Cutaneous vascular conductance (CVC) was calculated by SkBF/mean arterial pressure (MAP). Results Prior to exercise, plasma NO− 3 (21±6 and 581±161 µM) and nitrite (NO− 2 , 87±28 and 336±156 nM) concentrations were higher after BR compared to PL supplementation (P≤0.011, n=6). Oesophageal, mean skin, and mean body temperatures during exercise were not different between conditions. In addition, BR supplementation did not affect SR, SkBF, and CVC during exercise. A lower MAP was found after 30 min of exercise following BR supplementation (112±6 and 103±6 mmHg for PL and BR, respectively, P=0.021). Conclusion These results suggest that inorganic NO− 3 supplementation, which increases the potential for O2-independent NO production, does not affect local sweating and cutaneous vascular responses, but attenuates blood pressure in young healthy subjects exercising in a hot environment

Aggregate consequences of credit subsidy policies: Firm dynamics and misallocation

Government policies that attempt to alleviate credit constraints faced by small and young firms are widely adopted across countries. We study the aggregate impact of such targeted credit subsidies in a heterogeneous firm model with collateral constraints and endogenous entry and exit. A defining feature of our model is a non-Gaussian process of firm-level productivity, which allows us to capture the skewed firm size distribution seen in the Business Dynamics Statistics (BDS). We compare the welfare and aggregate productivity implications of our non-Gaussian process to those of a standard AR(1) process. While credit subsidies resolve misallocation of resources and enhance aggregate productivity, increased factor prices, in equilibrium, reduce the number of firms in production, which in turn depresses aggregate productivity. We show that the latter indirect general equilibrium effects dominate the former direct productivity gains in a model with the standard AR(1) process, as compared to our non-Gaussian process, under which both welfare and aggregate productivity increase by subsidy policies

Severe Liver Damage and Nonallergic Bronchitis with Eosinophilia in a Patient with Follicular Lymphoma Treated with Bendamustine plus Rituximab

A 66-year-old female with follicular lymphoma developed severe liver dysfunction and nonallergic bronchitis after 1 cycle of treatment with bendamustine and rituximab (BR) therapy. Simultaneously, eosinophilia was observed. Further examination revealed negative results for both hepatitis virus-induced liver damage and lymphoma cell invasion into the liver. No bacterial, fungal, or cytomegaloviral infections of the respiratory tract were observed. The patient was treated with steroid pulse therapy followed by prednisolone with complete resolution of her symptoms. This suggests that eosinophilia induced by the treatment with BR may result in liver dysfunction and nonallergic bronchitis

Firm dynamics, misallocation and targeted policies

Access to external finance is a major obstacle for small and young firms; thus, providing subsidized credit to small and young firms is a widely-used policy option across countries. We study the impact of such targeted policies on aggregate output and productivity and highlight indirect general equilibrium effects. To do so, we build a model of heterogeneous firms with endogenous entry and exit, wherein each firm may be subject to forward-looking collateral constraints for their external borrowing. Subsidized credit alleviates credit constraints small and young firms face, which helps them to achieve the efficient and larger scale of production. This direct effect is, however, either reinforced or offset by indirect general equilibrium effects. Factor prices increase as subsidized firm demand more capital and labor. As a result, higher production costs induce more unproductive incumbents to exit, while replacing them selectively with productive entrants. This cleansing effect reinforces the direct effect by enhancing the aggregate productivity. However, the number of firms in operation decreases in equilibrium, and this, in turn, depresses the aggregate productivity

Automatic Detection of Cracks in Asphalt Pavement Using Deep Learning to Overcome Weaknesses in Images and GIS Visualization

The crack ratio is one of the indices used to quantitatively evaluate the soundness of asphalt pavement. However, since the inspection of pavement requires much labor and cost, automatic inspection of pavement damage by image analysis is required in order to reduce the burden of such work. In this study, a system was constructed that automatically detects and evaluates cracks from images of pavement using a convolutional neural network, a kind of deep learning. The most novel aspect of this study is that the accuracy was recursively improved through retraining the convolutional neural network (CNN) by collecting images which had previously been incorrectly analyzed. Then, study and implementation were conducted of a system for plotting the results in a GIS. In addition, an experiment was carried out applying this system to images actually taken from an MMS (mobile mapping system), and this confirmed that the system had high crack evaluation performance