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Introduction: Radium-223 dichloride (radium-223) is a bone-targeting radioisotope therapy that aids in the survival of patients with metastatic castration-resistant prostate cancer (mCRPC) to bones. This study aimed to describe the clinical characteristics and outcomes of patients with mCRPC treated with radium-223 in a real-world setting. Methods: This was a retrospective study of patients with mCRPC treated with radium-223 between 2016 and 2020 at the London Health Sciences Centre in London, Canada. The baseline characteristics between the patients receiving 1–3 and 4–6 treatment cycles were compared using a two-sample t-test and Chi-square test. ANOVA was used to determine if there was a difference in each diagnostic variable per treatment cycle. Kaplan–Meier curves were generated to estimate progression-free survival (PFS) and overall survival in the patients treated with different numbers of cycles. Results: Fifty eligible patients were identified. The median age was 71 years (IQR: 66–76). Most patients (62%) received radium-223 beyond the third-line treatment. The mean number of radium-223 treatments was four. While 60% of the patients received 4–6 injections, 40% received 1–3 injections. Fifty-eight percent (58%) of the patients demonstrated a clinical benefit, with the remainder expressing either disease progression (28%) or stable disease (10%). The patients treated with 4–6 cycles had a delay to disease progression compared to those given 1–3 cycles of radium-223 (F5,35 = 10.52, p < 0.001). A higher alkaline phosphatase level prior to treatment was associated with a longer PFS (z33 = 2.362, p = 0.018). Treatment-related hospitalization for skeletal-related events was noted in 8% of the patients, and 14% required treatment discontinuation due to hematologic toxicity. Conclusions: This study confirms the safety of radium-223 in patients with mCRPC in a real-world setting. The radium-223 treatment was associated with a clinical benefit in the majority of the patients, particularly in those with higher pre-treatment serum alkaline phosphatase levels. Further studies to identify the predictive biomarkers are warranted to better guide the contemporary use of radium-223.

Abstract The gleno-acetabular distance D GA , a conventional proxy for the size of a quadrupedal trackmaker, is often estimated as the distance GA between the midpoint between a left and right pair of pes tracks and the midpoint between a selected pair of left and right manus tracks. While frequently used to estimate trackmaker size from fossil trackways, the relationship between GA and D GA depends upon the gait (which is unknown for extinct trackmakers), and is subject to multiple additional sources of uncertainty including which specific pair of manus tracks to associate with a given pair of pes tracks. Here a generalization is introduced, termed coupling length, which does not require any presumption about trackmaker gait of the degree of overstepping. On the contrary, a systematic analysis of a trackway in terms of coupling length can permit estimation of both the size and the gait with which the trackmaker progressed. Coupling length can be computed at successive points along a trackway, allowing exploration of a range of hypothetical gaits and body sizes for the trackmaker responsible. A fitness function quantifying persistent variation in coupling length along a trackway is used to indicate whether a given trackway could have been created by a fairly consistent gait, and if so, a range of high-fitness solution gaits and their associated D GA . The method was applied to selected quasi-regular sauropod trackways and a solution found for a narrow range of gaits with limb phase of about 0.3 and D GA = 1.6 ± 0.2 m. This is the first estimation of sauropod trackmaker gait, and introduces a novel method by which irregularity along a trackway is used as a source of information to constrain inferences of trackmaker behavior. The computed D GA for this sauropod suggests significantly smaller trackmakers than conventional estimations based on track dimensions and hip height estimates. Size estimation by this approach offers greatly reduced uncertainty compared to conventional estimates.

Aim: To evaluate optimal systemic therapy sequencing (first-line targeted therapy (1L-TT) vs. first-line immunotherapy (1L-IO)) in patients with BRAF-mutated metastatic melanoma. Methods: Nation-wide prospective data of patients with newly diagnosed BRAF-mutated metastatic melanoma were retrieved from the Canadian Melanoma Research Network. Results: Our study included 79 and 107 patients in the 1L-IO and 1L-TT groups, respectively. There were more patients with ECOG 0–1 (91% vs. 72%, p = 0.023) in the 1L-IO group compared to the 1L-TT group. Multivariable Cox analysis suggested no OS differences between the two groups (HR 0.838, 95%CI 0.502–1.400, p = 0.500). However, patients who received 1L-TT then 2L-IO had the longest OS compared to 1L-IO without 2L therapy, 1L-IO then 2L-TT, and 1L-TT without 2L therapy (38.3 vs. 32.2 vs. 16.9 vs. 6.3 months, p < 0.001). For patients who received 2L therapy, those who received 2L-IO had a trend towards OS improvement compared with the 2L-TT group (21.7 vs. 8.9 months, p = 0.053). Conclusions: Our nation-wide prospective study failed to establish any optimal systemic therapy sequencing in advanced BRAF-mutant melanoma patients. Nevertheless, we provided evidence that immunotherapy has durable efficacy in advanced BRAF-mutant melanoma patients, regardless of treatment line, and that Canadian medical oncologists were selecting the appropriate treatment sequences in a real-world setting, based on patients’ clinical and tumour characteristics.

This paper will propose that Beckett’s affinity for crime and mystery fiction also contributes to Murphy. The novel will be examined on the proposed hypothesis that Murphy’s death, so-called, is conspicuously left ambiguous to a certain degree, rendering it a type of mystery narrative. Approaching the mysterious death as something like a detective fiction “cold case”, the events of Murphy, and clues left by Beckett throughout the prose that follows, I will investigate whether or not Murphy does actually die toward the end of the book. Although Beckett does not present these aspects in the traditional form of “thriller” fiction, he does use them to create a modernist aesthetic which challenges traditions, identifications of being, identity, representation and space regarding both the individual and the social context of the Irish “postmortem situation” depicted in Murphy.

Extragonadal germ cell tumors account for 2–5.7% of germ cell tumors (GCTs). Of these, primary mediastinal GCTs (PMGCTs) are responsible for 16–36% of cases. Given the rarity of these tumors, specific treatment strategies have not been well defined. We report our experience in treating these complex patients. In total, 318 men treated at our institution with chemotherapy for GCTs between 1980 and 2016 were reviewed. PMGCT was defined as clinically diagnosed mediastinal GCT with no evidence of testicular GCT (physical exam/ultrasound). We identified nine patients diagnosed with PMGCT. All patients presented with an anterior mediastinal mass and no gonadal lesion; four patients also had metastatic disease. Median age at diagnosis was 30 years (range, 14–56) and median mass size at diagnosis was 9 cm (range, 3.4–19). Eight patients had non-seminoma and one had pure seminoma. All patients received cisplatin-based chemotherapy initially. Surgical resection was performed in four patients; three patients had a complete resection and one patient was found to have an unresectable tumor. At a median follow-up of 2 years (range, 3 months–28 years) six patients had progressed. Progression-free survival was short with a median of 4.1 months from diagnosis (range 1.5–122.2 months). Five patients died at a median of 4.4 months from diagnosis. One and 5-year overall survivals were 50% and 38%, respectively. PMGCT are rare and aggressive. Our real-life Canadian experience is consistent with current literature suggesting that non-seminoma PMGCT has a poor prognosis despite prompt cisplatin-based chemotherapy followed by aggressive thoracic surgery.

Background: We present the 2-year results of a randomised trial comparing 4- versus 12-weekly bone-targeting agents (BTAs) in patients with bone metastases from breast or castration-resistant prostate cancer (CRPC). Patients and Methods: Patients with bone metastases from breast or CRPC, who were going to start or were already receiving BTAs, were randomised to 4- or 12-weekly BTA treatment for 2 years. The endpoints were: symptomatic skeletal events (SSE) rates, time to SSEs, toxicity and cost-effectiveness. Results: Of 263 patients (160 breast cancer, 103 CRPC), 133 (50.6%) and 130 (49.4%) were randomised to the 4- and 12-weekly groups, respectively. BTAs included denosumab (56.3%), zoledronate (24.0%) and pamidronate (19.8%). After 2 years, the cumulative incidence rate (95% CI) of SSEs was 32.7% (24.6% to 41.1%) and 28.1% (20.3% to 36.4%) for the 4- and 12-weekly intervention groups respectively. The hazard ratio for time to first SSE was 0.96 (95% CI = 0.63 to 1.47). However, in a post hoc analysis, those patients who had an on-study SSE, there was a small non-statistical increased risk of subsequent SSEs among patients on the 12-weekly dosing arm (HR = 1.14; 95% CI – 0.90–1.44). BTA-related toxicity rates were similar between study arms. A cost-utility analysis showed that 12-weekly BTA is cost-effective from a public payer’s perspective. Conclusion: These results in addition to those previously reported for de-escalating zoledronate, would support that de-escalation of commonly used BTAs is a reasonable and economically valid treatment option. While not statistically significant, the increase in subsequent SSEs in the 12-weekly arm requires further exploration.

Guest Editor's Note

Acting as the primary link between mother and fetus, the placenta is involved in regulating nutrient, oxygen, and waste exchange; thus, healthy placental development is crucial for a successful pregnancy. In line with the increasing demands of the fetus, the placenta evolves throughout pregnancy, making it a particularly difficult organ to study. Research into placental development and dysfunction poses a unique scientific challenge due to ethical constraints and the differences in morphology and function that exist between species. Recently, there have been increased efforts towards generating in vitro models of the human placenta. Advancements in the differentiation of human induced pluripotent stem cells (hiPSCs), microfluidics, and bioprinting have each contributed to the development of new models, which can be designed to closely match physiological in vivo conditions. By including relevant placental cell types and control over the microenvironment, these new in vitro models promise to reveal clues to the pathogenesis of placental dysfunction and facilitate drug testing across the maternal-fetal interface. In this minireview, we aim to highlight current in vitro placental models and their applications in the study of disease and discuss future avenues for these in vitro models.

Background and purposeSex and race disparities in recombinant tissue plasminogen activator (rt-PA) use have been reported. We sought to explore sex and race differences in the utilization of rt-PA at primary stroke centers (PSCs) compared to non-PSCs across the US.MethodsData from the National (Nationwide) Inpatient Sample (NIS) 2004–2010 was utilized to assess sex differences in treatment for ischemic stroke in PSCs compared to non-PSCs.ResultsThere were 304,152 hospitalizations with a primary diagnosis of ischemic stroke between 2004 and 2010 in the analysis: 75,160 (24.7%) patients were evaluated at a PSC. A little over half of the patients evaluated at PSCs were female (53.8%). A lower proportion of women than men received rt-PA at both PSCs (6.8 vs. 7.5%, p

Eudaimonistic identity theory posits a link between activity and identity, where a self-defining activity promotes the strength of a person’s identity. An activity engaged in with high enjoyment, full involvement, and high concentration can facilitate the subjective experience of flow. In the present paper, we hypothesised in accordance with the theory of psychological selection that beyond the promotion of individual development and complexity at the personal level, the relationship between flow and identity at the social level is also positive through participation in self-defining activities. Three different samples (i.e., American, Chinese, and Spanish) filled in measures for flow and social identity, with reference to four previously self-reported activities, characterized by four different combinations of skills (low versus high) and challenges (low versus high). Findings indicated that flow was positively associated with social identity across each of the above samples, regardless of participants’ gender and age. The results have implications for increasing social identity via participation in self-defining group activities that could facilitate flow.

A correct understanding of passive force-deflection response is important for lateral load evaluations of bridges during extreme events such as earthquakes and from thermal expansion and contraction of the superstructure. In these cases, the ultimate passive force is highly sensitive to the interface friction between the abutment wall and the adjacent geomaterials. These geomaterials may simply consist of compacted sand or gravel; however, for geosynthetic reinforced soil (GRS) backfill a geosynthetic fabric may be placed between the abutment wall and soil which can reduce the interface friction. In still other cases, a zone of compressible material such as geofoam may be used as a barrier between the soil and abutment to reduce lateral earth pressures. To evaluate the effect of the interface friction on passive force-deflection curves, large-scale testing was performed with a test abutment that was 3.35 m wide and 1.68 m high. Backfill materials consisted of sand, gravel, GRS backfill, and a geofoam inclusion between a sand backfill and the abutment. As a result of lower interface friction, the GRS backfills only developed 80% of the force developed by the unreinforced gravel. The geofoam inclusion decreased the passive force by about 70% as a result of reduced interface friction.

When large carnivores occupy peripheral human lands conflict with humans becomes inevitable, and the reduction of human-carnivore interactions must be the first consideration for those concerned with conflict mitigation. Studies designed to identify areas of high human-bear interaction are crucial for prioritizing management actions. Due to a surge in conflicts, against a background of social intolerance to wildlife and the prevalent use of lethal control throughout Japan, Asiatic black bears (Ursus thibetanus) are now threatened by high rates of mortality. There is an urgent need to reduce the frequency of human-bear encounters if bear populations are to be conserved. To this end, we estimated the habitats that relate to human-bear interactions by sex and season using resource selection functions (RSF). Significant seasonal differences in selection for and avoidance of areas by bears were estimated by distance-effect models with interaction terms of land cover and sex. Human-bear boundaries were delineated on the basis of defined bear-habitat edges in order to identify areas that are in most need of proactive management strategies. Asiatic black bears selected habitats in close proximity to forest edges, forest roads, rivers, and red pine and riparian forests during the peak conflict season and this was correctly predicted in our human-bear boundary maps. Our findings demonstrated that bears selected abandoned forests and agricultural lands, indicating that it should be possible to reduce animal use near human lands by restoring season-specific habitat in relatively remote areas. Habitat-based conflict mitigation may therefore provide a practical means of creating adequate separation between humans and these large carnivores.

Background. This study tested the hypothesis that data from random digit-dial telephone surveys underestimate the prevalence of cigarette smoking among African-American adults. Method. A novel, community-sampling method was used to obtain a statewide, random sample of N= 2118 California (CA) African-American/Black adults, surveyed door-to-door. This Black community sample was compared to the Blacks in the CA Health Interview Survey (N = 2315), a statewide, random digit-dial telephone-survey conducted simultaneously. Results. Smoking prevalence was significantly higher among community (33%) than among telephone-survey (19%) Blacks, even after controlling for sample-differences in demographics.Conclusions. Telephone surveys underestimate smoking among African-Americans and probably underestimate other health risk behaviors as well. Alternative methods are needed to obtain accurate data on African-American health behaviors and on the magnitude of racial disparities in them.

The authors wish to make the following changes to the published paper [1].[...]

Current logistics and transportation (L&T) systems include heterogeneous fleets consisting of common internal combustion engine vehicles as well as other types of vehicles using “green” technologies, e.g., plug-in hybrid electric vehicles and electric vehicles (EVs). However, the incorporation of EVs in L&T activities also raise some additional challenges from the strategic, planning, and operational perspectives. For instance, smart cities are required to provide recharge stations for electric-based vehicles, meaning that investment decisions need to be made about the number, location, and capacity of these stations. Similarly, the limited driving-range capabilities of EVs, which are restricted by the amount of electricity stored in their batteries, impose non-trivial additional constraints when designing efficient distribution routes. Accordingly, this paper identifies and reviews several open research challenges related to the introduction of EVs in L&T activities, including: (a) environmental-related issues; and (b) strategic, planning and operational issues associated with “standard” EVs and with hydrogen-based EVs. The paper also analyzes how the introduction of EVs in L&T systems generates new variants of the well-known Vehicle Routing Problem, one of the most studied optimization problems in the L&T field, and proposes the use of metaheuristics and simheuristics as the most efficient way to deal with these complex optimization problems.

Purpose: We evaluated whether IDO-inhibitor BMS986205 (IDOi) + PD-1 inhibitor nivolumab enhanced T-cell activity and augmented immune-mediated antitumor responses in untreated, resectable HNSCC. We employed response-adaptive surgical timing to identify responders to immunotherapy and enhance their response., Patients and Methods: Patients with HNSCC were 3:1 randomized to receive nivolumab with or without BMS986205 PO daily (NCT03854032). In the combination arm, BMS986205 was initiated 7 days prior to nivolumab. Patients were stratified by HPV status. Response-adaptive surgical timing involved response assessment by radiographic criteria 4 weeks after nivolumab in both arms. Non-responders underwent surgical resection, while responders received 4 more weeks of randomized therapy before surgery. Biomarker analysis utilized pathologic treatment response (pTR) and RNA sequencing., Results: Forty-two patients were enrolled, and the addition of IDOi to nivolumab did not result in greater rate of radiographic response (p=0.909). Treatment was well-tolerated with only 2 (5%) patients experiencing grade 3 immune-related adverse events. The addition of IDO-inhibitor augmented rates of pTR in patients with high baseline IDO RNA expression (p<0.05). Response-adaptive surgical timing demonstrated reliability in differentiating pathologic responders versus non-responders (p=0.009). A pretreatment NK cell signature, PD-L1 status, and IFN-g expression in the HPV- cohort correlated with response. HPV+ cohort found B-cell and CAF signatures predictive of response/non-response., Conclusions: Response-adaptive surgical timing enhanced treatment response. IDO-inhibitor BMS986205 augmented pTR in patients with high IDO1-expression in baseline samples, indicating a need for identifying and targeting resistant nodes to immunotherapy. HPV-status-dependent signatures predicting response to immunotherapy in HNSCC warrant further study.

Habitat fragmentation remains a major focus of research by ecologists decades after being put forward as a threat to the integrity of ecosystems. While studies have documented myriad biotic changes in fragmented landscapes, including the local extinction of species from fragments, the demographic mechanisms underlying these extinctions are rarely known. However, many of them-especially in lowland tropical forests-are thought to be driven by one of two mechanisms: (1) reduced recruitment in fragments resulting from changes in the diversity or abundance of pollinators and seed dispersers or (2) increased rates of individual mortality in fragments due to dramatically altered abiotic conditions, especially near fragment edges. Unfortunately, there have been few tests of these potential mechanisms due to the paucity of long-term and comprehensive demographic data collected in both forest fragments and continuous forest sites. Here we report 11 years (1998-2009) of demographic data from populations of the Amazonian understory herb Heliconia acuminata (LC Rich.) found at Brazil's Biological Dynamics of Forest Fragments Project (BDFFP). The data set comprises >66,000 plant × year records of 8586 plants, including 3464 seedlings established after the first census. Seven populations were in experimentally isolated fragments (one in each of four 1-ha fragments and one in each of three 10-ha fragments), with the remaining six populations in continuous forest. Each population was in a 50 × 100 m permanent plot, with the distance between plots ranging from 500 m to 60 km. The plants in each plot were censused annually, at which time we recorded, identified, marked, and measured new seedlings, identified any previously marked plants that died, and recorded the size of surviving individuals. Each plot was also surveyed four to five times during the flowering season to identify reproductive plants and record the number of inflorescences each produced. These data have been used to investigate topics ranging from the way fragmentation-related reductions in germination influence population dynamics to statistical methods for analyzing reproductive rates. This breadth of prior use reflects the value of these data to future researchers. In addition to analyses of plant responses to habitat fragmentation, these data can be used to address fundamental questions in plant demography and the evolutionary ecology of tropical plants and to develop and test demographic models and tools. Though we welcome opportunities to collaborate with interested users, there are no restrictions on the use of this data set. However, we do request that those using the data for teaching or research purposes inform us of how they are doing so and cite this paper and the data archive when appropriate. Any publication using the data must also include a BDFFP Technical Series Number in the Acknowledgments. Authors can request this series number upon the acceptance of their article by contacting the BDFFP's Scientific Coordinator or E. M. Bruna., (© 2023 The Ecological Society of America.)

Background: Recent advancements in personal biosensing technology support the shift from standardized to personalized health interventions, whereby biological data are used to motivate health behavior change. However, the implementation of interventions using biological feedback as a behavior change technique has not been comprehensively explored., Objective: The purpose of this review was to (1) map the domains of research where biological feedback has been used as a behavior change technique and (2) describe how it is implemented in behavior change interventions for adults., Methods: A comprehensive systematic search strategy was used to query 5 electronic databases (Ovid MEDLINE, Elsevier Embase, Cochrane Central Register of Controlled Trials, EBSCOhost PsycINFO, and ProQuest Dissertations & Theses Global) in June 2021. Eligible studies were primary analyses of randomized controlled trials (RCTs) in adults that incorporated biological feedback as a behavior change technique. DistillerSR was used to manage the literature search and review., Results: After removing 49,500 duplicates, 50,287 articles were screened and 767 articles were included. The earliest RCT was published in 1972 with a notable increase in publications after 2000. Biological feedback was most used in RCTs aimed at preventing or managing diabetes (n=233, 30.4%), cardiovascular disease (n=175, 22.8%), and obesity (n=115, 15%). Feedback was often given on multiple biomarkers and targeted multiple health behaviors. The most common biomarkers used were anthropometric measures (n=297, 38.7%), blood pressure (n=238, 31%), and glucose (n=227, 29.6%). The most targeted behaviors were diet (n=472, 61.5%), physical activity (n=417, 54.4%), and smoking reduction (n=154, 20.1%). The frequency and type of communication by which biological feedback was provided varied by the method of biomarker measurement. Of the 493 (64.3%) studies where participants self-measured their biomarker, 476 (96.6%) received feedback multiple times over the intervention and 468 (94.9%) received feedback through a biosensing device., Conclusions: Biological feedback is increasingly being used to motivate behavior change, particularly where relevant biomarkers can be readily assessed. Yet, the methods by which biological feedback is operationalized in intervention research varied, and its effectiveness remains unclear. This scoping review serves as the foundation for developing a guiding framework for effectively implementing biological feedback as a behavior change technique., Trial Registration: Open Science Framework Registries; https://doi.org/10.17605/OSF.IO/YP5WAd., International Registered Report Identifier (irrid): RR2-10.2196/32579., (©Kelli M Richardson, Michelle R Jospe, Ahlam A Saleh, Thanatcha Nadia Clarke, Arianna R Bedoya, Nick Behrens, Kari Marano, Lacey Cigan, Yue Liao, Eric R Scott, Jessica S Guo, April Aguinaga, Susan M Schembre. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 25.09.2023.)

Objective: This study sought to validate alternative pain management strategies that can reduce reliance on opioids for postoperative pain management in otology., Study Design: Prospective cohort study., Setting: Single tertiary-care facility., Methods: Adult patients who underwent outpatient otologic surgery from September 2021 to July 2022 were randomized into treatment cohorts. The opioid monotherapy cohort received a standard opioid prescription. The multimodal analgesia cohort received the same opioid prescription, prescriptions for acetaminophen and naproxen, and additional pain management education with a flyer on discharge. All patients completed a questionnaire 1 week after surgery to evaluate opioid usage and pain scores., Results: Eighty-six patients completed the study. The opioid monotherapy cohort (n = 42) and multimodal analgesia cohort (n = 44) were prescribed an average of 42.1 ± 20.4 morphine milligram equivalents (MME) and 38.4 ± 5.7 MME, respectively (p = 0.373). Four patients (9.52%) in the opioid monotherapy cohort required opioid refills compared to 1 patient (2.27%) in the multimodal analgesia cohort (p = 0.156). Multivariate analysis demonstrated that the multimodal analgesia cohort consumed significantly fewer opioids on average than the opioid monotherapy cohort (11.9 ± 15.9 MME vs 22.8 ± 28.0 MME, respectively). There were no significant differences in postoperative rehospitalizations (p = 0.317) or Emergency Department visits (p = 0.150). Pain scores on the day of surgery, postoperative day (POD) 1, POD3, and POD7 were not significantly different between cohorts (p = 0.395, 0.896, 0.844, 0.765, respectively)., Conclusion: The addition of patient education, acetaminophen, and naproxen to postoperative opioid prescriptions significantly reduced opioid consumption without affecting pain scores, refill rates, or complication rates after otologic surgery., (© 2023 American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

3D printing is a growing tool in surgical education to visualize and teach complex procedures. Previous studies demonstrating the usefulness of 3D models as teaching tools for partial nephrectomy used highly detailed models costing between $250 and 1000. We aimed to create thorough, inexpensive 3D models to accelerate learning for trainees and increase health literacy in patients. Patient-specific, cost-effective ($30-50) 3D models of the affected urologic structures were created using pre-operative imaging of 40 patients undergoing partial nephrectomy at Thomas Jefferson University Hospital (TJUH) between July 2020 and May 2021. Patients undergoing surgery filled out a survey before and after seeing the model to assess patient understanding of their kidney, pathophysiology, surgical procedure, and risks of surgery. Three urological residents, one fellow, and six attendings filled out separate surveys to assess their surgical plan and confidence before and after seeing the model. In a third survey, they ranked how much the model helped their comprehension and confidence during surgery. Patient understanding of all four subjects significantly improved after seeing the 3D model (P < 0.001). The urology residents (P < 0.001) and fellow (P < 0.001) reported significantly increased self-confidence after interacting with the model. Attending surgeon confidence increased significantly after seeing the 3D model (P < 0.01) as well. Cost-effective 3D models are effective learning tools and assist with the evaluation of patients presenting with renal masses, and increase patient, resident, and fellow understanding in partial nephrectomies. Further research should continue to explore the utility of inexpensive models in other urologic procedures., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Background: The diagnosis of infective endocarditis (IE) can be difficult, particularly if blood cultures fail to yield a pathogen. This study evaluates the potential utility of microbial cell-free DNA (mcfDNA) as a tool to identify the microbial etiology of IE., Methods: Blood samples from patients with suspected IE were serially collected. mcfDNA was extracted from plasma and underwent next-generation sequencing. Reads were aligned against a library containing DNA sequences belonging to >1400 different pathogens. mcfDNA from organisms present above a statistical threshold were reported and quantified in molecules per milliliter (MPM). Additional mcfDNA was collected on each subject every 2-3 days for a total of 7 collections or until discharge., Results: Of 30 enrolled patients with suspected IE, 23 had definite IE, 2 had possible IE, and IE was rejected in 5 patients by modified Duke Criteria. Only the 23 patients with definite IE were included for analysis. Both mcfDNA and blood cultures achieved a sensitivity of 87%. The median duration of positivity from antibiotic treatment initiation was estimated to be approximately 38.1 days for mcfDNA versus 3.7 days for blood culture (proportional odds, 2.952; P = .02771), using a semiparametric survival analysis. mcfDNA (log10) levels significantly declined (-0.3 MPM log10 units, 95% credible interval -0.45 to -0.14) after surgical source control was performed (pre- vs postprocedure, posterior probability >0.99)., Conclusion: mcfDNA accurately identifies the microbial etiology of IE. Sequential mcfDNA levels may ultimately help to individualize therapy by estimating a patient's burden of infection and response to treatment., Competing Interests: Potential conflicts of interests. The authors of this manuscript have conflicts of interest to disclose. V. G. F. reports personal fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, and Roche, and receives royalties from UpToDate. V. G. F. has received grants to his institution from the National Institutes of Health, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, Contrafect, Karius, Genentech, Regeneron, Basilea, Janssen. V. G. F. receives support for attending meetings and/or travel to present phase 2 data at 2019 ECCMID from Contrafect. V. G. F. has a sepsis diagnostics patent pending and has stock or stock options at ArcBio and Valanbio and is an Associate Editor at Clinical Infectious Diseases. A. A. A., N. D., E. R. S., and E. C. report they are employees at Karius Inc. D. Hong, D. Hollemon, C. D. V., C. H., L. B., S. D., and J. B. report they are former employees of Karius Inc. A. A. A. and N. D. report registration fees for conferences from Karius, and patents planned, issued or pending from Karius Inc. L. B. reports stock or stock options with Karius, Inc. S. D. reports consulting fees from Karius Inc. C. H. reports stock or stock options from Karius, Inc. D. Hong reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events as an employee of Vir Biotechnology and Janssen Biopharma. E. R. S. reports personal fees from Sema4 and is a former employee of Karius., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To determine the phase of NUDT15 sequence variants for more comprehensive star (*) allele diplotyping, we developed a novel long-read single-molecule real-time HiFi amplicon sequencing method. A 10.5 kb NUDT15 amplicon assay was validated using reference material positive controls and additional samples for specimen type and blinded accuracy assessment. Triplicate NUDT15 HiFi sequencing of two reference material samples had nonreference genotype concordances of >99.9%, indicating that the assay is robust. Notably, short-read genome sequencing of a subset of samples was unable to determine the phase of star (*) allele-defining NUDT15 variants, resulting in ambiguous diplotype results. In contrast, long-read HiFi sequencing phased all variants across the NUDT15 amplicons, including a *2/*9 diplotype that previously was characterized as *1/*2 in the 1000 Genomes Project v3 data set. Assay throughput was also tested using 8.5 kb amplicons from 100 Ashkenazi Jewish individuals, which identified a novel NUDT15 *1 suballele (c.-121G>A) and a rare likely deleterious coding variant (p.Pro129Arg). Both novel alleles were Sanger confirmed and assigned as *1.007 and *20, respectively, by the PharmVar Consortium. Taken together, NUDT15 HiFi amplicon sequencing is an innovative method for phased full-gene characterization and novel allele discovery, which could improve NUDT15 pharmacogenomic testing and subsequent phenotype prediction., (© 2022 Wiley Periodicals LLC.)

The Helically Symmetric eXperiment (HSX) Thomson Scattering (TS) diagnostic is being upgraded to decrease uncertainty in electron temperature and density measurements. Upgrades to the HSX TS diagnostic will consist of a novel redesign of polychromator electronics and digitization of the TS output signal. Here, we also present a study of the benefits of an additional spectral channel that will sample the red-shifted band of the scattered spectrum. To maximize system bandwidth (BW) and gain, while minimizing noise, the existing low-BW polychromator electronics on HSX will be replaced by high-BW, high gain circuitry designed in-house.

Background: Microbial cell-free DNA (mcfDNA) sequencing of plasma can identify the presence of a pathogen in a host. In this study, we evaluated the duration of pathogen detection by mcfDNA sequencing vs conventional blood culture in patients with bacteremia., Methods: Blood samples from patients with culture-confirmed bloodstream infection were collected within 24 hours of the index positive blood culture and 48 to 72 hours thereafter. mcfDNA was extracted from plasma, and next-generation sequencing was applied. Reads were aligned against a curated pathogen database. Statistical significance was defined with Bonferroni adjustment for multiple comparisons (P < .0033)., Results: A total of 175 patients with Staphylococcus aureus bacteremia (n = 66), gram-negative bacteremia (n = 74), or noninfected controls (n = 35) were enrolled. The overall sensitivity of mcfDNA sequencing compared with index blood culture was 89.3% (125 of 140), and the specificity was 74.3%. Among patients with bacteremia, pathogen-specific mcfDNA remained detectable for significantly longer than conventional blood cultures (median 15 days vs 2 days; P < .0001). Each additional day of mcfDNA detection significantly increased the odds of metastatic infection (odds ratio, 2.89; 95% confidence interval, 1.53-5.46; P = .0011)., Conclusions: Pathogen mcfDNA identified the bacterial etiology of bloodstream infection for a significantly longer interval than conventional cultures, and its duration of detection was associated with increased risk for metastatic infection. mcfDNA could play a role in the diagnosis of partially treated endovascular infections., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Deforestation often results in landscapes where remaining forest habitat is highly fragmented, with remnants of different sizes embedded in an often highly contrasting matrix. Local extinction of species from individual fragments is common, but the demographic mechanisms underlying these extinctions are poorly understood. It is often hypothesized that altered environmental conditions in fragments drive declines in reproduction, recruitment, or survivorship. The Amazon basin, in addition to experiencing continuing fragmentation, is experiencing climate change-related increases in the frequency and intensity of droughts and unusually wet periods. Whether plant populations in tropical forest fragments are particularly susceptible to extremes in precipitation remains unclear. Most studies of plants in fragments are relatively short (1-6 years), focus on a single life-history stage, and often do not compare to populations in continuous forest. Even fewer studies consider delayed effects of climate on demographic vital rates despite the importance of delayed effects in studies that consider them. Using a decade of demographic and climate data from an experimentally fragmented landscape in the Central Amazon, we assess the effects of climate on populations of an understory herb (Heliconia acuminata, Heliconiaceae). We used distributed lag nonlinear models to understand the delayed effects of climate (measured as standardized precipitation evapotranspiration index, SPEI) on survival, growth, and flowering. We detected delayed effects of climate up to 36 months. Extremes in SPEI in the previous year reduced survival, drought in the wet season 8-11 months prior to the February census increased growth, and drought two dry seasons prior increased flowering probability. Effects of extremes in precipitation on survival and growth were more pronounced in forest fragments compared to continuous forest. The complex delayed effects of climate and habitat fragmentation in our study point to the importance of long-term demography experiments in understanding the effects of anthropogenic change on plant populations., (© 2021 John Wiley & Sons Ltd.)

Study Objectives: The objective was to determine the prevalence and predictors of comorbid insomnia in patients presenting for sleep surgery evaluation. The insomnia severity index (ISI) was utilized to evaluate patients' insomnia severity., Methods: A retrospective chart review was performed in patients presenting to an otolaryngology sleep surgery clinic; patients also completed a sleep history questionnaire. Patients were divided between those with and without clinically significant insomnia defined as ISI ≥ 15., Results: A total of 119 patients were included in the study: 50 (42%) with an ISI ≥ 15 and 69 (58%) with an ISI < 15. Clinically significant insomnia was associated with respiratory disturbance index ( P = .028) but not apnea-hypopnea index or SaO 2 nadir ( P > .05). Clinically significant insomnia was associated with frequency of wake ups ( P = .008), time to fall back asleep ( P = .049), history of continuous positive airway pressure device use ( P = .012), Epworth Sleepiness Scale ( P = .008), and Sino-nasal Outcome Test (SNOT-22) ( P < .001)., Conclusions: Patients reporting to a sleep surgery clinic are at an elevated risk for comorbid insomnia. The relationship between increased respiratory event-related arousals and nonsleep SNOT-22 scores to related sleep-maintenance insomnia supports the connection between insomnia, nasal obstruction, and continuous positive airway pressure intolerance., Citation: Sagheer SH, Scott ER, Ananth A, Boon M, Huntley C. Incidence and predictors of comorbid insomnia in a sleep surgery clinic. J Clin Sleep Med . 2021;17(11):2165-2169., (© 2021 American Academy of Sleep Medicine.)

3D printing has been growing in many surgical fields including Urology. The primary use has been to print kidneys with tumors to better understand anatomy and to assist with surgical planning and education. Previous studies that utilized 3D printing of kidneys for partial nephrectomies have been limited by the cost and complexity of model creation, rendering them highly impractical to be used on a routine basis. Using a simpler and more cost-effective design and materials allow the 3D kidney models to be used in a wider range and number of patients. We describe our streamlined process to create 3D kidney models costing $30 on average and we believe this process can be repeated by others.

The increasing number of genetic counselors participating directly in clinical pharmacogenomic post-test counseling prompted our evaluation of pharmacogenomic education across genetic counseling training programs in North America. Thirty-one program leadership participants from both the United States (U.S.) and Canada responded to a survey assessing pharmacogenomics education and the role of genetic counselors. Eighty-five percent of respondents agreed pharmacogenomics is currently within the scope of genetic counseling practice, and 96.3% indicated their training programs currently provide education on pharmacogenomics, with the majority reporting < 7 hr of education. Lectures on pharmacogenomics were the most common method for didactics; however, some programs also included practical modalities (e.g., case studies, clinical rotations) and online resources. Barriers to expanding pharmacogenomic education included the constrained timeline of training, and lack of resources and local expertise. Moreover, participants suggested that genetic counselors ideally should be able to order pharmacogenomic tests and counsel patients on pharmacogenomics, including result interpretation, as they believe pharmacogenomics does fall within the scope of practice of genetic counseling. Our novel results also confirm that training program leadership support a pharmacogenomic service delivery model that includes a combined effort between genetic counselors and pharmacists to utilize their synergistic expertise. However, this model likely still necessitates expanding pharmacogenomic didactics in genetic counseling training programs through more practical training and/or by leveraging online pharmacogenomic courses dedicated to supporting clinical implementation., (© 2021 National Society of Genetic Counselors.)

Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak 1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X) 2 , a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas 3,4 . The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible 1,5 . Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization., (© 2021. The Author(s).)

Ecologists often collect data with the aim of determining which of many variables are associated with a particular cause or consequence. Unsupervised analyses (e.g. principal components analysis, PCA) summarize variation in the data, without regard to the response. Supervised analyses (e.g., partial least squares, PLS) evaluate the variables to find the combination that best explain a causal relationship. These approaches are not interchangeable, especially when the variables most responsible for a causal relationship are not the greatest source of overall variation in the data-a situation that ecologists are likely to encounter. To illustrate the differences between unsupervised and supervised techniques, we analyze a published dataset using both PCA and PLS and compare the questions and answers associated with each method. We also use simulated datasets representing situations that further illustrate differences between unsupervised and supervised analyses. For simulated data with many correlated variables that were unrelated to the response, PLS was better than PCA at identifying which variables were associated with the response. There are many applications for both unsupervised and supervised approaches in ecology. However, PCA is currently overused, at least in part because supervised approaches, such as PLS, are less familiar.

To develop a novel pharmacogenetic genotyping panel, a multidisciplinary team evaluated available evidence and selected 29 genes implicated in interindividual drug response variability, including 130 sequence variants and additional copy number variants (CNVs). Of the 29 genes, 11 had guidelines published by the Clinical Pharmacogenetics Implementation Consortium. Targeted genotyping and CNV interrogation were accomplished by multiplex single-base extension using the MassARRAY platform (Agena Biosciences) and multiplex ligation-dependent probe amplification (MRC Holland), respectively. Analytical validation of the panel was accomplished by a strategic combination of > 500 independent tests performed on 170 unique reference material DNA samples, which included sequence variant and CNV accuracy, reproducibility, and specimen (blood, saliva, and buccal swab) controls. Among the accuracy controls were 32 samples from the 1000 Genomes Project that were selected based on their enrichment of sequence variants included in the pharmacogenetic panel (VarCover.org). Coupled with publicly available samples from the Genetic Testing Reference Materials Coordination Program (GeT-RM), accuracy validation material was available for the majority (77%) of interrogated sequence variants (100% with average allele frequencies > 0.1%), as well as additional structural alleles with unique copy number signatures (e.g., CYP2D6*5, *13, *36, *68; CYP2B6*29; and CYP2C19*36). Accuracy and reproducibility for both genotyping and copy number were > 99.9%, indicating that the optimized panel platforms were precise and robust. Importantly, multi-ethnic allele frequencies of the interrogated variants indicate that the vast majority of the general population carries at least one of these clinically relevant pharmacogenetic variants, supporting the implementation of this panel for pharmacogenetic research and/or clinical implementation programs., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

The SLC6A4 gene has been implicated in psychiatric disorder susceptibility and antidepressant response variability. The SLC6A4 promoter is defined by a variable number of homologous 20-24 bp repeats (5-HTTLPR), and long (L) and short (S) alleles are associated with higher and lower expression, respectively. However, this insertion/deletion variant is most informative when considered as a haplotype with the rs25531 and rs25532 variants. Therefore, we developed a long-read single molecule real-time (SMRT) sequencing method to interrogate the SLC6A4 promoter region. A total of 120 samples were subjected to SLC6A4 long-read SMRT sequencing, primarily selected based on available short-read sequencing data. Short-read genome sequencing from the 1000 Genomes (1KG) Project (~5X) and the Genetic Testing Reference Material Coordination Program (~45X), as well as high-depth short-read capture-based sequencing (~330X), could not identify the 5-HTTLPR short (S) allele, nor could short-read sequencing phase any identified variants. In contrast, long-read SMRT sequencing unambiguously identified the 5-HTTLPR short (S) allele (frequency of 0.467) and phased SLC6A4 promoter haplotypes. Additionally, discordant rs25531 genotypes were reviewed and determined to be short-read errors. Taken together, long-read SMRT sequencing is an innovative and robust method for phased resolution of the SLC6A4 promoter, which could enable more accurate pharmacogenetic testing for both research and clinical applications.

Insect herbivores have dramatic effects on the chemical composition of plants. Many of these induced metabolites contribute to the quality (e.g., flavor, human health benefits) of specialty crops such as the tea plant ( Camellia sinensis ). Induced chemical changes are often studied by comparing plants damaged and undamaged by herbivores. However, when herbivory is quantitative, the relationship between herbivore pressure and induction can be linearly or non-linearly density dependent or density independent, and induction may only occur after some threshold of herbivory. The shape of this relationship can vary among metabolites within plants. The tea green leafhopper ( Empoasca onukii ) can be a widespread pest on tea, but some tea farmers take advantage of leafhopper-induced metabolites in order to produce high-quality "bug-bitten" teas such as Eastern Beauty oolong. To understand the effects of increasing leafhopper density on tea metabolites important for quality, we conducted a manipulative experiment exposing tea plants to feeding by a range of E. onukii densities. After E. onukii feeding, we measured volatile and non-volatile metabolites, and quantified percent damaged leaf area from scanned leaf images. E. onukii density had a highly significant effect on volatile production, while the effect of leaf damage was only marginally significant. The volatiles most responsive to leafhopper density were mainly terpenes that increased in concentration monotonically with density, while the volatiles most responsive to leaf damage were primarily fatty acid derivatives and volatile phenylpropanoids/benzenoids. In contrast, damage (percent leaf area damaged), but not leafhopper density, significantly reduced total polyphenols, epigallocatechin gallate (EGCG), and theobromine concentrations in a dose-dependent manner. The shape of induced responses varied among metabolites with some changing linearly with herbivore pressure and some responding only after a threshold in herbivore pressure with a threshold around 0.6 insects/leaf being common. This study illustrates the importance of measuring a diversity of metabolites over a range of herbivory to fully understand the effects of herbivores on induced metabolites. Our study also shows that any increases in leafhopper density associated with climate warming, could have dramatic effects on secondary metabolites and tea quality., (Copyright © 2020 Scott, Li, Wei, Kfoury, Morimoto, Guo, Agyei, Robbat, Ahmed, Cash, Griffin, Stepp, Han and Orians.)

Public acceptance is critical for sharing of genomic data at scale. This paper examines how acceptance of data sharing pertains to the perceived similarities and differences between DNA and other forms of personal data. It explores the perceptions of representative publics from the USA, Canada, the UK and Australia (n = 8967) towards the donation of DNA and health data. Fifty-two percent of this public held 'exceptionalist' views about genetics (i.e., believed DNA is different or 'special' compared to other types of medical information). This group was more likely to be familiar with or have had personal experience with genomics and to perceive DNA information as having personal as well as clinical and scientific value. Those with personal experience with genetics and genetic exceptionalist views were nearly six times more likely to be willing to donate their anonymous DNA and medical information for research than other respondents. Perceived harms from re-identification did not appear to dissuade publics from being willing to participate in research. The interplay between exceptionalist views about genetics and the personal, scientific and clinical value attributed to data would be a valuable focus for future research.

The Charge Exchange Recombination Spectroscopy (CXRS) diagnostic has become a routine diagnostic on almost all major high temperature fusion experimental devices. For the optimized stellarator Wendelstein 7-X (W7-X), a highly flexible and extensive CXRS diagnostic has been built to provide high-resolution local measurements of several important plasma parameters using the recently commissioned neutral beam heating. This paper outlines the design specifics of the W7-X CXRS system and gives examples of the initial results obtained, including typical ion temperature profiles for several common heating scenarios, toroidal flow and radial electric field derived from velocity measurements, beam attenuation via beam emission spectra, and normalized impurity density profiles under some typical plasma conditions.

To facilitate reference-material selection for clinical genetic testing laboratories, we developed VarCover, open-source software hosted on GitHub, which accepts a file of variants and returns an approximately minimum set (min-set) of samples covering the targeted alleles. VarCover employs the SetCoverPy package, sample weights, and preselection of singleton-possessing samples to efficiently solve the min-set cover problem. As a test case, we attempted to find a min-set of reference samples from the 1000 Genomes Project to cover 237 variants considered putatively pathogenic (of which 12 were classified as pathogenic or likely pathogenic) in the original 56 medically actionable genes recommended by the American College of Medical Genetics and Genomics (ACMG). The number of samples, number of alleles, and processing time were measured in subsets of the 237 target alleles. VarCover identified 140 reference-material samples from the 1000 Genomes Project covering the 237 alleles in the 56 ACMG-recommended genes. Sample weights derived from the minor allele frequency spectrum increased the number of alleles in the solution set. Preselection of samples that possessed singleton target alleles reduced computational processing time when the target set size exceeded 100 alleles. VarCover provides a simple programmatic interface for identifying an approximately min-set of reference samples, thereby reducing clinical laboratory effort and molecular genetic test-validation costs., (Copyright © 2020 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Smoking tobacco products is the leading cause of preventable death worldwide. Coordinated efforts have successfully reduced tobacco cigarette smoking in the United States; however, electronic cigarettes (e-cigarette) and other electronic nicotine delivery systems (ENDS) recently have replaced traditional cigarettes for many users. While the clinical risks associated with long-term ENDS use remain unclear, advancements in preclinical rodent models will enhance our understanding of their overall health effects. This review examines the peripheral and central effects of ENDS-mediated exposure to nicotine and other drugs of abuse in rodents and evaluates current techniques for implementing ENDS in preclinical research., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Climatic conditions affect the chemical composition of edible crops, which can impact flavor, nutrition and overall consumer preferences. To understand these effects, we sampled tea ( Camellia sinensis (L.) Kuntze) grown in different environmental conditions. Using a target/nontarget data analysis approach, we detected 564 metabolites from tea grown at two elevations in spring and summer over 3 years in two major tea-producing areas of China. Principal component analysis and partial least squares-discriminant analysis show seasonal, elevational, and yearly differences in tea from Yunnan and Fujian provinces. Independent of location, higher concentrations of compounds with aromas characteristic of farmers' perceptions of high-quality tea were found in spring and high elevation teas. Yunnan teas were distinct from Fujian teas, but the effects of elevation and season were different for the two locations. Elevation was the largest source of metabolite variation in Yunnan yet had no effect in Fujian. In contrast seasonal differences were strong in both locations. Importantly, the year-to-year variation in chemistry at both locations emphasizes the importance of doing multi-year studies, and further highlights the challenge farmers face when trying to produce teas with specific flavor/health (metabolite) profiles., (Copyright © 2019 Kfoury, Scott, Orians, Ahmed, Cash, Griffin, Matyas, Stepp, Han, Xue, Long and Robbat.)

Background and Aims: Future shifts in precipitation regimes and temperature are expected to affect plant traits dramatically. To date, many studies have explored the effects of acute stresses, but few have investigated the consequences of prolonged shifts in climatic conditions on plant growth and chemistry., Methods: Plant size and metabolite profiles were assessed on naturally occurring Plantago lanceolata plants growing under different precipitation (ambient, 50 % less than ambient = drought) and temperature (ambient, +0.8, +2.4 and +4.0 °C above ambient) treatments at the Boston Area Climate Experiment (constructed in 2007)., Key Results: The analysis of primary and secondary metabolites revealed pronounced effects of drought, and a precipitation × temperature interaction. Strikingly, the effects of precipitation were minimal at the two lower temperatures but marked at the two higher temperatures. Compared with the ambient condition, plants in the drought plots had lower concentrations of foliar nitrogen, amino acids and most sugars, and higher concentrations of sorbitol, citrate and malate, common stress-induced metabolites. This pattern was especially evident at high temperatures. Moreover, drought-exposed plants showed lower concentrations of catalpol, an iridoid glycoside., Conclusions: While the effect of warming on the metabolite profiles was less pronounced, differences were marked when combined with drought. Given the interactive effect of environmental variables on leaf chemistry, and the fact that woody and herbaceous plants seem to differ in their responses to temperature and precipitation, future studies should account for the direct and indirect effects of the community response to multifactorial field conditions., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This paper reports about a novel approach to the absolute intensity calibration of an electron cyclotron emission (ECE) spectroscopy system. Typically, an ECE radiometer consists of tens of separated frequency channels corresponding to different plasma locations. An absolute calibration of the overall diagnostic including near plasma optics and transmission line is achieved with blackbody sources at LN 2 temperature and room temperature via a hot/cold calibration mirror unit. As the thermal emission of the calibration source is typically a few thousand times lower than the receiver noise temperature, coherent averaging over several hours is required to get a sufficient signal to noise ratio. A forward model suitable for any radiometer calibration using the hot/cold method and a periodic switch between them has been developed and used to extract the voltage difference between the hot and cold temperature source via Bayesian analysis. In contrast to the classical analysis which evaluates only the reference temperatures, the forward model takes into account intermediate effective temperatures caused by the finite beam width and thus uses all available data optimally. This allows the evaluation of weak channels where a classical analysis would not be feasible, is statistically rigorous, and provides a measurement of the beam width. By using a variance scaling factor, a model sensitive adaptation of the absolute uncertainties can be implemented, which will be used for the combined diagnostic Bayesian modeling analysis.

A new method for in situ spectral calibration of Thomson scattering diagnostics is proposed. The idea of the method is to apply a wavelength tunable optical parametric oscillator for measurements of Rayleigh scattering at different wavelengths, from which relative sensitivities can be calculated. This extends the usual approach where Rayleigh scattering is used only at a single wavelength for the absolute calibration and spectral sensitivities are obtained separately. With the new approach, the full diagnostic setup is spectrally calibrated at once. Such a calibration can be repeated at regular intervals during an experimental campaign since it does not require a break of the vacuum. In this paper, the Rayleigh scattering calibration is tested in a laboratory setup with a sample Wendelstein 7-X (W7-X) polychromator. It is shown that relative sensitivities of spectral channels can be recovered with a sufficient resolution even under conditions of significant stray light. The stray light is overcome by measuring the linear dependence of the scattered signal on the gas pressure. Good results of laboratory tests motivate the installation of the new calibration system for the Thomson scattering diagnostic at W7-X.

Climate effects on crop quality at the molecular level are not well-understood. Gas and liquid chromatography-mass spectrometry were used to measure changes of hundreds of compounds in tea at different elevations in Yunnan Province, China. Some increased in concentration while others decreased by 100's of percent. Orthogonal projection to latent structures-discriminant analysis revealed compounds exhibiting analgesic, antianxiety, antibacterial, anticancer, antidepressant, antifungal, anti-inflammatory, antioxidant, anti-stress, and cardioprotective properties statistically (p = 0.003) differentiated high from low elevation tea. Also, sweet, floral, honey-like notes were higher in concentration in the former while the latter displayed grassy, hay-like aroma. In addition, multivariate analysis of variance showed low elevation tea had statistically (p = 0.0062) higher concentrations of caffeine, epicatechin gallate, gallocatechin, and catechin; all bitter compounds. Although volatiles represent a small fraction of the total mass, this is the first comprehensive report illustrating how normal variations in temperature, 5 °C, due to elevational effects impact tea quality., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Widespread adoption of smart mobile platforms coupled with a growing ecosystem of sensors including passive location tracking and the ability to leverage external data sources create an opportunity to generate an unprecedented depth of data on individuals. Mobile health technologies could be utilized for chronic disease management as well as research to advance our understanding of common diseases, such as asthma. We conducted a prospective observational asthma study to assess the feasibility of this type of approach, clinical characteristics of cohorts recruited via a mobile platform, the validity of data collected, user retention patterns, and user data sharing preferences. We describe data and descriptive statistics from the Asthma Mobile Health Study, whereby participants engaged with an iPhone application built using Apple's ResearchKit framework. Data from 6346 U.S. participants, who agreed to share their data broadly, have been made available for further research. These resources have the potential to enable the research community to work collaboratively towards improving our understanding of asthma as well as mobile health research best practices.

The unprecedented early spring frost that appears as a cold stress adversely affects growth and productivity in tea ( Camellia sinensis L.); therefore, it is indispensable to develop approaches to improve the cold tolerance of tea. Here, we investigated the effect of pretreatment with exogenous melatonin on the net photosynthetic rate, the maximum photochemical efficiency of PSII, chlorophyll content, lipid peroxidation, reactive oxygen species (ROS) accumulation, antioxidant potential, and redox homeostasis in leaves of tea plants following cold stress. Our results revealed that cold treatment induced oxidative stress by increasing ROS accumulation, which in turn affected the photosynthetic process in tea leaves. However, treatment with melatonin mitigated cold-induced reductions in photosynthetic capacity by reducing oxidative stress through enhanced antioxidant potential and redox homeostasis. This study provides strong evidence that melatonin could alleviate cold-induced adverse effects in tea plants., Competing Interests: There is no conflict of interest to declare.