Predicting the outcome of renal transplantation

ObjectiveRenal transplantation has dramatically improved the survival rate of hemodialysis patients. However, with a growing proportion of marginal organs and improved immunosuppression, it is necessary to verify that the established allocation system, mostly based on human leukocyte antigen matching, still meets today's needs. The authors turn to machine-learning techniques to predict, from donor-recipient data, the estimated glomerular filtration rate (eGFR) of the recipient 1 year after transplantation.DesignThe patient's eGFR was predicted using donor-recipient characteristics available at the time of transplantation. Donors' data were obtained from Eurotransplant's database, while recipients' details were retrieved from Charite Campus Virchow-Klinikum's database. A total of 707 renal transplantations from cadaveric donors were included.MeasurementsTwo separate datasets were created, taking features with <10% missing values for one and <50% missing values for the other. Four established regressors were run on both datasets, with and without feature selection.ResultsThe authors obtained a Pearson correlation coefficient between predicted and real eGFR (COR) of 0.48. The best model for the dataset was a Gaussian support vector machine with recursive feature elimination on the more inclusive dataset. All results are available at http://transplant.molgen.mpg.de/.LimitationsFor now, missing values in the data must be predicted and filled in. The performance is not as high as hoped, but the dataset seems to be the main cause.ConclusionsPredicting the outcome is possible with the dataset at hand (COR=0.48). Valuable features include age and creatinine levels of the donor, as well as sex and weight of the recipient

A Role for Actin, Cdc1p, and Myo2p in the Inheritance of Late Golgi Elements in \u3cem\u3eSaccharomyces cerevisiae\u3c/em\u3e

In Saccharomyces cerevisiae, Golgi elements are present in the bud very early in the cell cycle. We have analyzed this Golgi inheritance process using fluorescence microscopy and genetics. In rapidly growing cells, late Golgi elements show an actin-dependent concentration at sites of polarized growth. Late Golgi elements are apparently transported into the bud along actin cables and are also retained in the bud by a mechanism that may involve actin. A visual screen for mutants defective in the inheritance of late Golgi elements yielded multiple alleles of CDC1. Mutations in CDC1 severely depolarize the actin cytoskeleton, and these mutations prevent late Golgi elements from being retained in the bud. The efficient localization of late Golgi elements to the bud requires the type V myosin Myo2p, further suggesting that actin plays a role in Golgi inheritance. Surprisingly, early and late Golgi elements are inherited by different pathways, with early Golgi elements localizing to the bud in a Cdc1p- and Myo2p-independent manner. We propose that early Golgi elements arise from ER membranes that are present in the bud. These two pathways of Golgi inheritance in S. cerevisiae resemble Golgi inheritance pathways in vertebrate cells

Backward masked fearful faces enhance contralateral occipital cortical activity for visual targets within the spotlight of attention

Spatial attention has been argued to be adaptive by enhancing the processing of visual stimuli within the ‘spotlight of attention’. We previously reported that crude threat cues (backward masked fearful faces) facilitate spatial attention through a network of brain regions consisting of the amygdala, anterior cingulate and contralateral visual cortex. However, results from previous functional magnetic resonance imaging (fMRI) dot-probe studies have been inconclusive regarding a fearful face-elicited contralateral modulation of visual targets. Here, we tested the hypothesis that the capture of spatial attention by crude threat cues would facilitate processing of subsequently presented visual stimuli within the masked fearful face-elicited ‘spotlight of attention’ in the contralateral visual cortex. Participants performed a backward masked fearful face dot-probe task while brain activity was measured with fMRI. Masked fearful face left visual field trials enhanced activity for spatially congruent targets in the right superior occipital gyrus, fusiform gyrus and lateral occipital complex, while masked fearful face right visual field trials enhanced activity in the left middle occipital gyrus. These data indicate that crude threat elicited spatial attention enhances the processing of subsequent visual stimuli in contralateral occipital cortex, which may occur by lowering neural activation thresholds in this retinotopic location

The potential of low-cost 3D imaging technologies for forestry applications: Setting a research agenda for low-cost remote sensing inventory tasks

Limitations with benchmark light detection and ranging (LiDAR) technologies in forestry have prompted the exploration of handheld or wearable low-cost 3D sensors (<2000 USD). These sensors are now being integrated into consumer devices, such as the Apple iPad Pro 2020. This study was aimed at determining future research recommendations to promote the adoption of terrestrial low-cost technologies within forest measurement tasks. We reviewed the current literature surrounding the application of low-cost 3D remote sensing (RS) technologies. We also surveyed forestry professionals to determine what inventory metrics were considered important and/or difficult to capture using conventional methods. The current research focus regarding inventory metrics captured by low-cost sensors aligns with the metrics identified as important by survey respondents. Based on the literature review and survey, a suite of research directions are proposed to democratise the access to and development of low-cost 3D for forestry: (1) the development of methods for integrating standalone colour and depth (RGB-D) sensors into handheld or wearable devices; (2) the development of a sensor-agnostic method for determining the optimal capture procedures with low-cost RS technologies in forestry settings; (3) the development of simultaneous localisation and mapping (SLAM) algorithms designed for forestry environments; and (4) the exploration of plot-scale forestry captures that utilise low-cost devices at both terrestrial and airborne scales

Phase II Study of Sequential Gemcitabine Followed by Docetaxel for Recurrent Ewing Sarcoma, Osteosarcoma, or Unresectable or Locally Recurrent Chondrosarcoma: Results of Sarcoma Alliance for Research Through Collaboration Study 003

Background.Gemcitabine and docetaxel have a broad spectrum of clinical activity in patients with carcinoma. The Sarcoma Alliance for Research Through Collaboration conducted a phase II trial of gemcitabine in combination with docetaxel in children and adults with recurrent Ewing sarcoma (EWS), osteosarcoma (OS), or unresectable or recurrent chondrosarcoma. The primary objective was to determine the objective response rate using Response Evaluation Criteria in Solid Tumors (RECIST).Methods.Gemcitabine (675 mg/m2 i.v. over 90 minutes on days 1 and 8) was administered in combination with docetaxel (75 mg/m2 i.v. over 1 hour on day 8) every 21 days. All patients received filgrastim or pegfilgrastim. A Bayesian formulation was used to determine the probability of achieving the target response rate for each subtype—0.35 for EWS and OS or 0.20 for chondrosarcoma. If the probability of achieving the target response rate was <0.05, the combination was considered inactive. Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0.Results.Fifty‐three eligible patients were enrolled in the three subtype groups—OS (n = 14), EWS (n = 14), and chondrosarcoma (n = 25). Toxicities included neutropenia, thrombocytopenia, fatigue, dyspnea, bronchospasm, edema, neuropathy, and liver function abnormalities. Dose modification for toxicity was required for eight patients during cycle 1 and 16 patients in subsequent cycles. Seven patients withdrew from therapy as a result of toxicity. No complete responses were observed. Partial responses were observed in OS (n = 1), EWS (n = 2), and chondrosarcoma (n = 2) patients.Conclusion.Gemcitabine in combination with docetaxel was associated with a probability of reaching the target 35% response rate of <5% in OS patients and 5.6% in EWS patients; the probability of reaching a 20% response rate in chondrosarcoma patients was 14%.摘要背景. 吉西他滨与多西他赛对癌症患者有广谱的临床疗效。 肉瘤研究联盟协作组在复发的尤文肉瘤 （EWS）、 骨肉瘤 （OS）、 不可切除或复发的软骨肉瘤成人和儿童患者中开展了吉西他滨联合多西他赛的 II 期试验。 主要目的为通过实体瘤疗效评估标准 （RECIST） 确定客观缓解率。方法. 吉西他滨 （675 mg/m2， 静脉滴注 90 分钟以上， 第 1 和 8 天） 联合多西他赛 （75 mg/m2， 静脉滴注 1 小时以上， 第 8 天） 每 21 天给药 1 次。 全部患者均同时接受非格司亭或乙二醇化非格司亭。 利用贝叶斯公式来确定各个亚型达到目标缓解率的概率——EWS 和 OS 为 0.35， 软骨肉瘤为 0.20。 如果达到目标缓解率的概率 < 0.05， 则认为联合方案无效。 毒性反应根据不良事件通用术语标准 （CTCAE） 3.0 版来分级。结果. 53 例合格患者入组 3 个亚型组 ： OS （n=14）、 EWS （n=14）、 软骨肉瘤 （n=25）。 毒性反应包括中性粒细胞减少、 血小板减少、 乏力、 呼吸困难、 支气管痉挛、 水肿、 神经病变以及肝功能异常。 第 1 个周期有 8 例患者、 其后周期有 16 例患者因毒性反应而需要剂量调整。 7 例患者因毒性反应而撤出治疗。 未观察到完全缓解。 OS （n=1）、 EWS （n=2） 和软骨肉瘤 （n=2） 组均有患者达到部分缓解。结论. 吉西他滨联合多西他赛在 < 5% 的 OS 患者、 5.6% 的 EWS 患者中达到目标缓解率的概率为 35%； 14% 软骨肉瘤患者中达到目标缓解率的概率为 20%。讨论. 贝叶斯公式能够评估各个亚型在分别进行缓解率评估后预测达到目标缓解率的概率。 通过多角度来看这些数据， 在考量达到目标缓解率的概率以及入组率之后即能发现本研究设计方案阻碍了研究的继续开展。 因为这一设计方案并未设定判断治疗为 “有效” 的规则， 所以并不适合与标准的分 2 阶段进行的 II 期试验设计直接比较。 关闭 EWS 和软骨肉瘤亚组的决定， 某种程度上是基于入组缓慢， 另外达到目标缓解率的概率较低也支持这一决定。 入组率而不是统计设计， 对试验周期有显著影响。The Oncologist 2012;17:321‐e329Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139909/1/onco0321-sup-0002.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139909/2/onco0321-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139909/3/onco0321.pd