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In situ river discharge estimation is a critical component of studying rivers. A dominant method for establishing discharge monitoring in situ is a temporary gauge, which uses a rating curve to relate stage to discharge. However, this approach is constrained by cost and the time to develop the stage‐discharge rating curve, as rating curves rely on numerous flow measurements at high and low stages. Here, we offer a novel alternative approach to traditional temporary gauges: estimating Discharge via Arrays of Pressure Transducers (DAPT). DAPT uses a Bayesian discharge algorithm developed for the upcoming Surface Water Ocean Topography satellite (SWOT) to estimate in situ discharge from automated water surface elevation measurements. We conducted sensitivity tests over 4,954 model runs on five gauged rivers and conclude that the DAPT method can robustly reproduce discharge with an average Nash‐Sutcliffe Efficiency (NSE) of 0.79 and Kling‐Gupta Efficiency of 0.78. Further, we find that the DAPT method estimates discharge similarly to an idealized temporary gauge created from the same input data (NSE differences of less than 0.1), and that results improve significantly with accurate priors. Finally, we test the DAPT method in nine poorly gauged rivers in a realistic and complex field setting in the Peace‐Athabasca Delta, and show that the DAPT method largely outperforms a temporary gauge in this time and budget constrained setting. We therefore recommend DAPT as an effective tool for in situ discharge estimation in cases where there is not enough time or resources to develop a temporary gauge. Key Points: We adapt a discharge algorithm designed for an upcoming satellite mission for in situ discharge estimationThe method relies on an array of pressure transducers installed along a mass conserved channelEstimating river discharge using multiple pressure transducers is a viable alternative to installing a temporary gauge [ABSTRACT FROM AUTHOR]

Lakes are central components of the inland water system distinct from, yet inextricably connected to, river networks. Currently, existing network‐scale biogeochemistry research, although robust, typically treats each of these components separately or reductively. Here, we incorporate lake morphometry into a fully connected stream/lake network for the Connecticut River watershed and model potential evasion of terrestrially sourced headwater CO2 as transported through the network, ignoring in‐stream production. We found that approximately 25%–30% of total potential soil CO2 evasion occurs in lakes, and percent evasion is inversely related to streamflow. A lake's ability to evade CO2 is controlled by residence time and size: most lakes with residence time over 7 days or surface area greater than 0.004 km2 evade functionally all terrestrial CO2 entering from upstream, precluding further downstream transport. We conclude that lakes are important for soil CO2 degassing and that this coupled river/lake approach is promising for CO2 studies henceforth. Plain Language Summary: River networks are both delivery systems and active transformers of constituents (sediment, nutrients, biota, heat) as they carry them to the sea. An important and overlooked component of these networks are lakes: lakes dominate total water storage of surface water in river networks and have vastly different hydraulics than rivers. Despite this knowledge, most greenhouse gas (GHG) research addresses lakes and rivers separately or reductively. To address this, we built a fully connected model for over 98,000 rivers and lakes in the Connecticut River watershed and found that lakes emit substantially more carbon dioxide than rivers per unit (potentially 25%–30% of the total emission from the system), and that almost all lakes emit almost all the carbon dioxide that enters their waters. These findings demonstrate the importance of connected lakes to drainage network GHG exchange and corroborate the need to better integrate lakes into our understandings of GHG emissions from freshwater systems in a formalized framework. Key Points: We model potential evasion of terrestrially sourced headwater CO2 from over 98,000 river and lake units in the Connecticut River watershedLakes are responsible for approximately 25%–30% of potential CO2 evasion, as influenced by streamflow and stream orderLake CO2 evasion efficiency is a function of residence time and size, where larger lakes evade functionally 100% of CO2 from upstream [ABSTRACT FROM AUTHOR]

The article discusses the role of CD103 negative memory T cells in making regulatory T-cell enriched environments in skin tumors. Topics discussed include obtaining T cells from basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (SCC), the adjacent skin and the distant normal skin for flow cytometry; immunofluorescence studies that demonstrated a higher proportion of CD103 cells in the CD4+ cells in skin tumors; and the proportion of Treg that was increased in both BCC and SCC.

Acral lentiginous melanoma and mucosal melanoma expressed less programmed-death 1 ligand than cutaneous melanoma: a retrospective study of 73 Japanese melanoma patients GLO:3NZ/01nov19:jdv15742-fig-0001.jpg PHOTO (COLOR): (a, b) The proportion of BRAF mutations (a) and PD-L1-positive tumours (b) in cutaneous melanoma (CM), acral lentiginous melanoma (ALM) and mucosal melanoma (MCM). Although the efficacy of anti-PD-1 antibodies in subungual ALM treatment has yet to be shown, our study suggests that subungual ALM might respond more poorly to anti-PD-1 antibodies than non-subungual ALM. [Extracted from the article]

The article presents a case study of a 59-year-old Japanese woman who was diagnosed with unresectable melanoma. It notes that typical sarcoid reaction pattern with multiple discrete epithelioid granulomas was revealed after examination. The author suggests that the melanoma patients went through intralesional and tine methods which resulted in higher rate of granulomatosis in them.

A letter to the editor is in response to an article "Facial nerve grading system," by J.W. House and D.E. Brackmann in a previous issue is presented.

Lakes are central components of the inland water system distinct from, yet inextricably connected to, river networks. Currently, existing network‐scale biogeochemistry research, although robust, typically treats each of these components separately or reductively. Here, we incorporate lake morphometry into a fully connected stream/lake network for the Connecticut River watershed and model potential evasion of terrestrially sourced headwater CO2 as transported through the network, ignoring in‐stream production. We found that approximately 25%–30% of total potential soil CO2 evasion occurs in lakes, and percent evasion is inversely related to streamflow. A lake's ability to evade CO2 is controlled by residence time and size: most lakes with residence time over 7 days or surface area greater than 0.004 km2 evade functionally all terrestrial CO2 entering from upstream, precluding further downstream transport. We conclude that lakes are important for soil CO2 degassing and that this coupled river/lake approach is promising for CO2 studies henceforth. Plain Language Summary: River networks are both delivery systems and active transformers of constituents (sediment, nutrients, biota, heat) as they carry them to the sea. An important and overlooked component of these networks are lakes: lakes dominate total water storage of surface water in river networks and have vastly different hydraulics than rivers. Despite this knowledge, most greenhouse gas (GHG) research addresses lakes and rivers separately or reductively. To address this, we built a fully connected model for over 98,000 rivers and lakes in the Connecticut River watershed and found that lakes emit substantially more carbon dioxide than rivers per unit (potentially 25%–30% of the total emission from the system), and that almost all lakes emit almost all the carbon dioxide that enters their waters. These findings demonstrate the importance of connected lakes to drainage network GHG exchange and corroborate the need to better integrate lakes into our understandings of GHG emissions from freshwater systems in a formalized framework. Key Points: We model potential evasion of terrestrially sourced headwater CO2 from over 98,000 river and lake units in the Connecticut River watershedLakes are responsible for approximately 25%–30% of potential CO2 evasion, as influenced by streamflow and stream orderLake CO2 evasion efficiency is a function of residence time and size, where larger lakes evade functionally 100% of CO2 from upstream [ABSTRACT FROM AUTHOR]

Several studies have demonstrated the usefulness of negative pressure closure (NPC) for the stabilization of skin grafts because it provides a uniform pressure to the graft. The results of our previous retrospective study also suggested the superiority of NPC over tie-over methods for the stabilization of split-thickness skin graft (STSG) in large or muscle-exposing defects. However, the usefulness of NPC for graft stabilization is yet to be fully established. This prospective, phase II clinical study was conducted to investigate the safety and efficacy of NPC for the stabilization of STSG in large or muscle-exposing defects. Patients who would require STSG for reconstruction of defects in the trunk and extremities other than hands and feet measuring >10 cm in the longest diameter or with muscle exposure were enrolled. NPC was applied for skin graft stabilization. Seven patients who had received wide excision of malignant tumors and resulted in muscle-exposed skin defects were included. All patients underwent meshed STSG. The mean size of the defect was 94.5 cm 2 (range 63.6-164.9). The mean time from the skin graft harvesting to the NPC stabilization was 15.6 min (range 10.7-19.5). The mean survival rate of the skin graft at postoperative day 7 and 10 was 98.7% (range 97-100) and 96.5% (range 89.4-98.4), respectively. No adverse events associated with the procedure were observed. This prospective study provided further evidence of the safety and efficacy of NPC for STSG stabilization in patients with large or muscle-exposing skin defects., (© 2021 Japanese Dermatological Association.)

Recent clinical trials revealed that both immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors significantly prolonged survival in melanoma patients when used for both advanced stage disease and postoperative adjuvant therapy. Although BRAF/MEK inhibitors are associated with a higher objective response rate than ICI, most patients relapse during treatment. However, progression patterns during treatment with BRAF/MEK inhibitors have not been extensively investigated. Here, we retrospectively collected the data of melanoma patients initially treated with BRAF/MEK inhibitors or anti-programmed death 1 (PD-1) antibody monotherapy at the University of Tsukuba Hospital and compared their results. The χ 2 -test revealed that frequency of brain metastasis (BM) development was significantly higher in cases treated with BRAF/MEK inhibitors compared with those with anti-PD-1 antibody monotherapy. In addition, BM-free survival in cases treated with BRAF/MEK inhibitors was significantly shorter than those treated with anti-PD-1 antibody monotherapy. Our results indicate that BM development during treatment with BRAF/MEK inhibitors may be more frequent than anti-PD-1 antibody monotherapy, even though the extracranial metastases are well controlled. Therefore, we recommend frequent brain examinations during treatment with BRAF/MEK inhibitors to detect BM at an early stage and to promptly administrate ICI with local radiation therapy., (© 2020 Japanese Dermatological Association.)

Angiomatoid Spitz nevus (ASN) is a rare histological variant of Spitz nevus (SN) that is characterized by prominent blood vessel proliferation around the intradermal melanocytes of SN. In contrast, SN may have pagetoid components, which are characterized by epidermal proliferation of single melanocytes. However, cases of ASN with predominant pagetoid melanocytic proliferation in the epidermis have not been reported. Here, we report a case of ASN with surrounding pagetoid melanocytic proliferation without formation of tumor nests in the epidermis in the plantar region. A 12-year-old girl presented with a bright red nodule surrounded by a brown macule on the sole of her right foot. Histologically, the nodule showed tumor nests in the dermis, composed of spindle or epithelioid melanocytes containing abundant cytoplasm and large nuclei. Around the nests, numerous blood vessels were seen. In the overlying epidermis of the nodule, numerous eosinophilic Kamino bodies were found along the dermal-epidermal interface. In the macule, proliferation of oval melanocytes was present as single-cell units in the epidermis. Theses melanocytes had abundant cytoplasm with large nuclei, which were larger than those of the surrounding keratinocytes. From these findings, a diagnosis of ASN with surrounding pagetoid melanocytic proliferation was made. Vascular endothelial growth factor and fibroblast growth factor 2 were strongly expressed in the melanocytes as well as in the endothelial cells in our case. Therefore, angiogenic factors produced by the melanocytes of SN might have played important roles in the surrounding angiogenesis of this case., (© 2020 Japanese Dermatological Association.)

Morphea profunda refers to inflammatory and sclerotic lesions that start primarily from the deep dermis, subcutaneous fat and fascia. Its pediatric case published work is limited. Here, we report the case of an 8-year-old girl with a 5-year history of multiple subcutaneous nodules on her extremities and a right wrist joint contracture who had been previously diagnosed with juvenile idiopathic arthritis and treated with salazosulfapyridine, low-dose prednisolone (PSL) and methotrexate. We performed biopsies of two subcutaneous nodules, which revealed the typical morphology of morphea profunda. She was administrated a tapered course of oral PSL then cyclosporin A (CyA) for 20 weeks which completely resolved her joint contracture and subcutaneous nodules. We reviewed 11 previously reported cases of morphea profunda and found that some include circumscribed/linear morphea that develop into subcutaneous tissues, indicating that "classical" morphea profunda arising within the deep tissues has rarely been reported. Our report is the first to demonstrate the efficacy of CyA for treatment of morphea profunda, and the possibility of CyA as a treatment option to reduce oral steroid doses in juvenile cases., (© 2019 Japanese Dermatological Association.)

Although recent clinical trials have revealed that immune checkpoint inhibitors significantly improved the overall survival (OS) of patients with advanced melanoma, these previous studies comprised mainly white populations, in which superficial spreading melanoma (SSM) and lentigo maligna melanoma are the major clinical types of melanoma. In contrast, Asians manifest a distinct clinicopathological type of melanoma from that of whites and show much higher frequencies of acral lentiginous melanoma (ALM) and mucosal melanoma, which have been shown to be less susceptible to immune checkpoint inhibitors. Because no comparative studies have been published showing improvement of OS by immune checkpoint inhibitors in Asian melanoma patients, we retrospectively collected the data for 45 melanoma patients treated with checkpoint inhibitors and 24 melanoma patients treated with chemotherapy alone before immune checkpoint inhibitors became available, and compared their OS. The results showed that the patients treated with immune checkpoint inhibitors had significantly better OS than did those treated with chemotherapy alone (P < 0.0001). Improved OS was observed in both the SSM and the ALM patients. In addition, multivariate Cox regression analyses revealed that use of immune checkpoint inhibitors was associated with favorable prognosis (P = 0.0001), indicating that use of immune checkpoint inhibitors is an independent factor for favorable survival. Our study showed that immune checkpoint inhibitors may also improve the prognosis of Asian melanoma patients., (© 2018 Japanese Dermatological Association.)

Skin grafts are frequently used for the reconstruction of skin defects, and optimal stabilization of the graft is essential for successful reconstruction. Although the tie-over technique has been widely used as a standard method in Japan, we sometimes encounter cases with significant graft loss due to suboptimal stabilization of the graft. Reported risk factors for increased graft loss include the following: defects of a large size, with muscle exposure, and located in the trunk and extremities. Recent studies have demonstrated the usefulness of negative-pressure closure (NPC) for the stabilization of skin grafts due to the uniform pressure it provides across the graft. Therefore, since March 2017, we have used NPC for skin graft stabilization in patients with defects in the trunk and extremities of more than 10 cm in size or with muscle exposure. We carried out a retrospective comparative study of the outcome of the conventional tie-over technique versus NPC. Mann-Whitney U-test revealed that NPC showed significantly higher graft survival rate than tie-over method (P = 0.0012). In addition, NPC showed a tendency toward shorter operative times (from skin graft harvest to the completion of the graft stabilization) than the tie-over method (P = 0.0931). These results suggest that NPC may be superior to the tie-over method for stabilization of skin grafts especially in large or muscle-exposing defects in the trunk or extremities., (© 2018 Japanese Dermatological Association.)

Recent progress in genotyping technology and the development of public databases has enabled large-scale genome-wide association tests with diseases. We performed a two-stage genome-wide association study (GWAS) of bipolar disorder (BD) in Japanese cohorts. First we used Affymetrix 100K GeneChip arrays in the analysis of 107 cases with bipolar I disorder and 107 controls, and selected markers that were nominally significant (P < 0.01) in at least one of the three models (1,577 markers in total). In the follow-up stage, we analyzed these markers using an Illumina platform (1,526 markers; 51 markers were not designable for the platform) and an independent sample set, which consisted of 395 cases (bipolar I + II) and 409 controls. We also assessed the population stratification of current samples using principal components analysis. After the two-stage analysis, 89 markers remained nominally significant (allelic P < 0.05) with the same allele being consistently over-represented in both the first and the follow-up stages. However, none of these were significant after correction for multiple-testing by false discovery rates. Sample stratification was virtually negligible. Collectively, this is the first GWAS of BD in the Japanese population. But given the small sample size and the limited genomic coverage, these results should be taken as preliminary., (2009 Wiley-Liss, Inc.)