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Methane (CH4) emissions from natural landscapes constitute roughly half of global CH4 contributions to the atmosphere, yet large uncertainties remain in the absolute magnitude and the seasonality of emission quantities and drivers. Eddy covariance (EC) measurements of CH4 flux are ideal for constraining ecosystem-scale CH4 emissions due to quasi-continuous and high-temporal-resolution CH4 flux measurements, coincident carbon dioxide, water, and energy flux measurements, lack of ecosystem disturbance, and increased availability of datasets over the last decade. Here, we (1) describe the newly published dataset, FLUXNET-CH4 Version 1.0, the first open-source global dataset of CH4 EC measurements (available at https://fluxnet.org/data/fluxnet-ch4-community-product/, last access: 7 April 2021). FLUXNET-CH4 includes half-hourly and daily gap-filled and non-gap-filled aggregated CH4 fluxes and meteorological data from 79 sites globally: 42 freshwater wetlands, 6 brackish and saline wetlands, 7 formerly drained ecosystems, 7 rice paddy sites, 2 lakes, and 15 uplands. Then, we (2) evaluate FLUXNET-CH4 representativeness for freshwater wetland coverage globally because the majority of sites in FLUXNET-CH4 Version 1.0 are freshwater wetlands which are a substantial source of total atmospheric CH4 emissions; and (3) we provide the first global estimates of the seasonal variability and seasonality predictors of freshwater wetland CH4 fluxes. Our representativeness analysis suggests that the freshwater wetland sites in the dataset cover global wetland bioclimatic attributes (encompassing energy, moisture, and vegetation-related parameters) in arctic, boreal, and temperate regions but only sparsely cover humid tropical regions. Seasonality metrics of wetland CH4 emissions vary considerably across latitudinal bands. In freshwater wetlands (except those between 20g g€¯S to 20g g€¯N) the spring onset of elevated CH4 emissions starts 3g€¯d earlier, and the CH4 emission season lasts 4g€¯d longer, for each degree Celsius increase in mean annual air temperature. On average, the spring onset of increasing CH4 emissions lags behind soil warming by 1 month, with very few sites experiencing increased CH4 emissions prior to the onset of soil warming. In contrast, roughly half of these sites experience the spring onset of rising CH4 emissions prior to the spring increase in gross primary productivity (GPP). The timing of peak summer CH4 emissions does not correlate with the timing for either peak summer temperature or peak GPP. Our results provide seasonality parameters for CH4 modeling and highlight seasonality metrics that cannot be predicted by temperature or GPP (i.e., seasonality of CH4 peak). FLUXNET-CH4 is a powerful new resource for diagnosing and understanding the role of terrestrial ecosystems and climate drivers in the global CH4 cycle, and future additions of sites in tropical ecosystems and site years of data collection will provide added value to this database. All seasonality parameters are available at 10.5281/zenodo.4672601 (Delwiche et al., 2021). Additionally, raw FLUXNET-CH4 data used to extract seasonality parameters can be downloaded from https://fluxnet.org/data/fluxnet-ch4-community-product/ (last access: 7 April 2021), and a complete list of the 79 individual site data DOIs is provided in Table 2 of this paper.

Large datasets of greenhouse gas and energy surface-atmosphere fluxes measured with the eddy-covariance technique (e.g., FLUXNET2015, AmeriFlux BASE) are widely used to benchmark models and remote-sensing products. This study addresses one of the major challenges facing model-data integration: To what spatial extent do flux measurements taken at individual eddy-covariance sites reflect model- or satellite-based grid cells? We evaluate flux footprints—the temporally dynamic source areas that contribute to measured fluxes—and the representativeness of these footprints for target areas (e.g., within 250–3000 m radii around flux towers) that are often used in flux-data synthesis and modeling studies. We examine the land-cover composition and vegetation characteristics, represented here by the Enhanced Vegetation Index (EVI), in the flux footprints and target areas across 214 AmeriFlux sites, and evaluate potential biases as a consequence of the footprint-to-target-area mismatch. Monthly 80% footprint climatologies vary across sites and through time ranging four orders of magnitude from 103 to 107 m2 due to the measurement heights, underlying vegetation- and ground-surface characteristics, wind directions, and turbulent state of the atmosphere. Few eddy-covariance sites are located in a truly homogeneous landscape. Thus, the common model-data integration approaches that use a fixed-extent target area across sites introduce biases on the order of 4%–20% for EVI and 6%–20% for the dominant land cover percentage. These biases are site-specific functions of measurement heights, target area extents, and land-surface characteristics. We advocate that flux datasets need to be used with footprint awareness, especially in research and applications that benchmark against models and data products with explicit spatial information. We propose a simple representativeness index based on our evaluations that can be used as a guide to identify site-periods suitable for specific applications and to provide general guidance for data use.

We describe a new coordination activity and initial results for a global synthesis of eddy covariance CH4 flux measurements.

Wetlands are the largest global natural methane (CH4/ source, and emissions between 50 and 70° N latitude contribute 10-30% to this source. Predictive capability of land models for northern wetland CH4 emissions is still low due to limited site measurements, strong spatial and temporal variability in emissions, and complex hydrological and biogeochemical dynamics. To explore this issue, we compare wetland CH4 emission predictions from the Community Land Model 4.5 (CLM4.5-BGC) with siteto regional-scale observations. A comparison of the CH4 fluxes with eddy flux data highlighted needed changes to the model's estimate of aerenchyma area, which we implemented and tested. The model modification substantially reduced biases in CH4 emissions when compared with CarbonTracker CH4 predictions. CLM4.5 CH4 emission predictions agree well with growing season (May-September) CarbonTracker Alaskan regional-level CH4 predictions and sitelevel observations. However, CLM4.5 underestimated CH4 emissions in the cold season (October-April). The monthly atmospheric CH4 mole fraction enhancements due to wetland emissions are also assessed using the Weather Research and Forecasting-Stochastic Time-Inverted Lagrangian Transport (WRF-STILT) model coupled with daily emissions from CLM4.5 and compared with aircraft CH4 mole fraction measurements from the Carbon in Arctic Reservoirs Vulnerability Experiment (CARVE) campaign. Both the tower and aircraft analyses confirm the underestimate of cold-season CH4 emissions by CLM4.5. The greatest uncertainties in predicting the seasonal CH4 cycle are from the wetland extent, coldseason CH4 production and CH4 transport processes. We recommend more cold-season experimental studies in highlatitude systems, which could improve the understanding and parameterization of ecosystem structure and function during this period. Predicted CH4 emissions remain uncertain, but we show here that benchmarking against observations across spatial scales can inform model structural and parameter improvements.

BACKGROUND: Breast cancer is one of the most common malignancies in women. Genome-wide association studies have identified FGFR2 as a breast cancer susceptibility gene. Common variation in other fibroblast growth factor (FGF) receptors might also modify risk. We tested this hypothesis by studying genotyped single-nucleotide polymorphisms (SNPs) and imputed SNPs in FGFR1, FGFR3, FGFR4 and FGFRL1 in the Breast Cancer Association Consortium. METHODS: Data were combined from 49 studies, including 53 835 cases and 50 156 controls, of which 89 050 (46 450 cases and 42 600 controls) were of European ancestry, 12 893 (6269 cases and 6624 controls) of Asian and 2048 (1116 cases and 932 controls) of African ancestry. Associations with risk of breast cancer, overall and by disease sub-type, were assessed using unconditional logistic regression. RESULTS: Little evidence of association with breast cancer risk was observed for SNPs in the FGF receptor genes. The strongest evidence in European women was for rs743682 in FGFR3; the estimated per-allele odds ratio was 1.05 (95% confidence interval=1.02-1.09, P=0.0020), which is substantially lower than that observed for SNPs in FGFR2. CONCLUSION: Our results suggest that common variants in the other FGF receptors are not associated with risk of breast cancer to the degree observed for FGFR2.

Saki Yamamoto,1 Akira Iwata,1 Yuki Yano,1 Toshimitsu Ohmine,1 Keisuke Honma,1 Kazuma Senzaki,1 Minami Fujiwara,1 Takayuki Murakami,1 Junji Inoue,1 Yuki Sano,2 Shuji Okagawa,3 Yuta Otsuki,4 Hideyuki Wanaka,5 Masataka Kataoka,1 Hiroshi Iwata61Department of Physical Therapy, Faculty of Comprehensive Rehabilitation, Osaka Prefecture University, Habikino, Osaka, Japan; 2Department of Rehabilitation, Osaka General Medical Center, Osaka, Osaka, Japan; 3Department of Rehabilitation, Tatsumi Hospital, Ikeda, Osaka, Japan; 4Department of Rehabilitation, Kisei Hospital, Osaka, Osaka, Japan; 5Department of Rehabilitation, Kobe Rosai Hospital, Kobe, Hyogo, Japan; 6Department of Cardiovascular Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, JapanPurpose: Movement velocity of the limbs or trunk plays an important determinant of gait speed in older adults. Movement velocity-focused training of the lower limbs or trunk has recently been shown to be an effective intervention to improve gait ability. Because movement velocities of various body regions are significantly correlated, movement velocity training of the upper limbs may also be effective for improving gait speed. Therefore, the purpose of this study was to investigate whether movement velocity training of the upper limbs in a seated position is effective for improving gait ability.Patients and methods: This study was a nonrandomized controlled trial. The participants were older adults residing in geriatric health service facilities. They were assigned to the movement velocity training of the upper limbs group (n=26) or control group (n=15). The participants in the training group performed exercises (three times per week for 10 weeks) to move the upper limbs as quickly as possible. The outcomes were gait speed, movement velocity, and quadriceps strength. These measurements were performed preintervention and 4, 8, and 10 weeks after intervention.Results: A significant time–group interaction was found for maximum gait speed and movement velocity of the upper limbs. Bonferroni post-hoc test showed significant improvement in gait speed between preintervention and 10 weeks after intervention in the training group. The movement velocity of the upper limbs was significantly improved between preintervention and 4, 8, and 10 weeks after intervention.Conclusion: Movement velocity training of the upper limbs showed significant and clinically relevant improvements in maximum gait speed at 10 weeks after intervention. This training is a potentially useful intervention and can be safely performed.Keywords: older people, movement velocity training, arm, gait speed, seated position

Proton therapy (PT) remains much controversy about its routine use in localized prostate cancer treatment. Particularly, comprehensive data on the efficacy and safety of gold fiducial marker matching in PT is less abundant compared to bone matching. We have previously reported on acute toxicity and quality of life changes of image-guided PT (IGPT) for localized prostate cancer. The aim of this study was to evaluate long-term efficacy and safety of IGPT for localized prostate cancer. We sequentially started prospective studies for normofractionated PT (NFPT: 74-78 GyRBE/37-39 Fr) in February 2013, and moderately hypofractionated PT (MHPT: 60-63 GyRBE/20-21 Fr) in October 2014. After the start of MHPT, patients could choose either NFPT or MHPT. Main eligibility criteria included: (1) histologically confirmed primary prostate cancer; (2) T1-T3bN0M0 staged by UICC; (3) age ≥ 20 years; (4) no serious underlying disease or other cancers, and (5) written informed consent. Patients with castration-resistant prostate cancer or enrolled in other clinical trials were excluded from the analysis. The NCCN classification was used. The biochemical relapse free survival (bRFS) was based on the Phoenix definition (nadir + 2.0 ng/mL). The rates of bRFS, overall survival (OS) and incidence of late gastrointestinal (GI) and genitourinary (GU) toxicities were estimated using the Kaplan-Meier methods. Toxicities were evaluated with the CTCAE version 5.0. The dose constraints were partially changed in August 2014, and hydrogel spacer was introduced in May 2018. In principle, low-risk patients received no androgen-deprivation therapy (ADT), intermediate-risk patients received 6-month neoadjuvant ADT, and high- or very-high-risk patients received two-year neoadjuvant and adjuvant ADT. Patients registered until March 2021, before the transition to the new fractionation protocol, were analyzed. The total number of prostate cancer patients who received PT at our institution until March 2021 was 1,643. A total of 327 patients treated using NFPT and 1243 patients treated using MHPT were analyzed (Total 1570). The number of patients in the low-risk, intermediate-risk, and high- or very-high-risk groups were 228, 715, and 627, respectively. The median follow-up period of surviving patients was 68.0 months (range = 20-130). The 5-year rates of bRFS and OS in the low-risk, intermediate-risk, and high- or very-high-risk patients were 95.7%, 96.5%, 91.8% for bRFS, and 97.1%, 97.5%, 97.7% for OS, respectively. Of the 76 patients who died, 71 of them were due to other disease. Biochemical relapse was observed in 62 patients, 31 of whom showed clinical relapse. Local recurrence was noted in 4 patients. The incidence of grade 2 and 3 late GI and GU toxicities were 4.4%, 0.8% and 2.9%, 0.1%, retrospectively. IGPT with gold fiducial marker for localized prostate cancer is favorable and well tolerated. Further hypofractionated IGPT with hydrogel spacer is expected. [ABSTRACT FROM AUTHOR]