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Background Older adults are recommended to receive influenza vaccination annually, and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk. Methods Using the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and nonusers aged ≥66 years during the 2010–2011 to 2018–2019 influenza seasons. We also estimated the odds ratio for influenza infection comparing statin users and nonusers by vaccination status. Results Among persons tested for influenza across the 9 seasons, 54 243 had continuous statin exposure before testing and 48 469 were deemed unexposed. The VE against laboratory-confirmed influenza was similar between statin users and nonusers (17% [95% confidence interval, 13%–20%] and 17% [13%–21%] respectively; test for interaction, P = .87). In both vaccinated and unvaccinated persons, statin users had higher odds of laboratory-confirmed influenza than nonusers (odds ratios for vaccinated and unvaccinated persons 1.15 [95% confidence interval, 1.10–1.21] and 1.15 [1.10–1.20], respectively). These findings were consistent by mean daily dose and statin type. VE did not differ between users and nonusers of other cardiovascular drugs, except for β-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated β-blocker users. Conclusions Influenza VE did not differ between statin users and nonusers. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated persons, but these associations might be affected by residual confounding.

Lake ecosystems, as integrators of watershed and climate stressors, are sentinels of change. However, there is an inherent time-lag between stressors and whole-lake response. Aquatic metabolism, including gross primary production (GPP) and respiration (R), of stream-lake transitional zones may bridge the time-lag of lake response to allochthonous inputs. In this study, we used high-frequency dissolved oxygen data and inverse modeling to estimate daily rates of summer epilimnetic GPP and R in a nutrient-limited oligotrophic lake at two littoral sites located near different major inflows and at a pelagic site. We examined the relative importance of stream variables in comparison to meteorological and in-lake predictors of GPP and R. One of the inflow streams was substantially warmer than the other and primarily entered the lake's epilimnion, whereas the colder stream primarily mixed into the metalimnion or hypolimnion. Maximum GPP and R rates were 0.2-2.5 mg O-2 L-1 day(-1) (9-670%) higher at littoral sites than the pelagic site. Ensemble machine learning analyses revealed that > 30% of variability in daily littoral zone GPP and R was attributable to stream depth and stream-lake transitional zone mixing metrics. The warm-stream inflow likely stimulated littoral GPP and R, while the cold-stream inflow only stimulated littoral zone GPP and R when mixing with the epilimnion. The higher GPP and R observed near inflows in our study may provide a sentinel-of-the-sentinel signal, bridging the time-lag between stream inputs and in-lake processing, enabling an earlier indication of whole-lake response to upstream stressors. NSF [ICER1517823, DEB-1753639, DBI-1933102, DBI-1933016]; Virginia Tech College of Science Make-A-Difference Scholarship Published version This work was financially supported by NSF Grants ICER1517823, DEB-1753639, DBI-1933102, and DBI-1933016, and a Virginia Tech College of Science Make-A-Difference Scholarship.

Ecosystem metabolism is an integrative measure of the production and respiration of carbon in aquatic ecosystems. However, under-ice regions and mixing periods are infrequently sampled because of l...

The limiting nutrient for freshwater phytoplankton productivity can vary within and between geographic regions. Understanding how local (i.e., lake and catchment) and regional (i.e., multiple catchment) factors shift the relative importance of nitrogen (N) and phosphorus (P) limitation presents a key research challenge for freshwater ecosystems and may enhance our understanding of how lakes could be managed to control eutrophication. Here, we used in situ microcosm incubations with factorial N and P amendments to determine the type of limitation in 16 lakes across the northeastern United States. Study lakes had similar climate but varied in geography, trophic status, and chemistry. Limitation by both N and P was most common (colimitation n = 5 and serial limitation n = 3); however, we also observed single nutrient N (n = 3) and P limitation (n = 4). The type of limitation was related to background phytoplankton biomass, longitude, and land use. The magnitude of response to combined nutrient enrichment was negatively related to background P concentrations. This multi-lake experiment suggests that both N and P often play a role in regulating productivity and that local and regional characteristics affect nutrient limitation patterns.

Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change., Measurement(s) temperature of water • temperature profile Technology Type(s) digital curation Factor Type(s) lake location • temporal interval Sample Characteristic - Environment lake • reservoir Sample Characteristic - Location global Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.14619009

PURPOSE Seasonal influenza vaccination is recommended for patients with cancer despite concerns of disease or treatment-associated immunosuppression. The objective of this study was to evaluate vaccine effectiveness (VE) against laboratory-confirmed influenza for patients with cancer. PATIENTS AND METHODS We conducted an observational test-negative design study of previously diagnosed patients with cancer 18 years of age and older who underwent influenza testing during the 2010-2011 to 2015-2016 influenza seasons in Ontario, Canada. We linked individual-level cancer registry, respiratory virus testing, and health administrative data to identify the study population and outcomes. Vaccination status was determined from physician and pharmacist billing claims. We used multivariable logistic regression to estimate VE, adjusting for age, sex, rurality, income quintile, cancer characteristics, chemotherapy exposure, comorbidities, previous health care use, influenza season, and calendar time. RESULTS We identified 26,463 patients with cancer who underwent influenza testing, with 4,320 test-positive cases (16%) and 11,783 (45%) vaccinated. Mean age was 70 years, 52% were male, mean time since diagnosis was 6 years, 69% had solid tumor malignancies, and 23% received active chemotherapy. VE against laboratory-confirmed influenza was 21% (95% CI, 15% to 26%), and VE against laboratory-confirmed influenza hospitalization was 20% (95% CI, 13% to 26%). For patients with solid tumor malignancies, VE was 25% (95% CI, 18% to 31%), compared with 8% (95% CI, –5% to 19%) for patients with hematologic malignancies ( P = .015). Active chemotherapy usage did not significantly affect VE, especially among patients with solid tumor cancer. CONCLUSION Our results support recommendations for influenza vaccination for patients with cancer. VE was decreased for patients with hematologic malignancies, and there was no significant difference in VE among patients with solid tumor cancer receiving active chemotherapy. Strategies to optimize influenza prevention among patients with cancer are warranted.

Background Annual influenza immunization is recommended for people with chronic obstructive pulmonary disease (COPD) by all major COPD clinical practice guidelines. We sought to determine the seasonal influenza vaccine effectiveness (VE) against laboratory-confirmed influenza-associated hospitalizations among older adults with COPD. Methods We conducted a test-negative study of influenza VE in community-dwelling older adults with COPD in Ontario, Canada using health administrative data and respiratory specimens collected from patients tested for influenza during the 2010–11 to 2015–16 influenza seasons. Influenza vaccination was ascertained from physician and pharmacist billing claims. Multivariable logistic regression was used to estimate the adjusted odds ratio of influenza vaccination in people with, compared to those without, laboratory-confirmed influenza. Results Receipt of seasonal influenza vaccine was associated with an adjusted 22% (95% confidence interval [CI], 15%–27%) reduction in laboratory-confirmed influenza-associated hospitalization. Adjustment for potential misclassification of vaccination status increased this to 43% (95% CI, 35%–52%). Vaccine effectiveness was not found to vary by patient- or influenza-related variables. Conclusions During the studied influenza seasons, influenza vaccination was at least modestly effective in reducing laboratory-confirmed influenza-associated hospitalizations in people with COPD. The imperfect effectiveness emphasizes the need for better influenza vaccines and other preventive strategies.

New species introductions can change lakes rapidly by directly affecting trophic levels through predator–prey interactions or by indirectly affecting ecosystem structure and function. When ...

Background Linking data on laboratory specimens collected during clinical practice with health administrative data permits highly powered vaccine effectiveness (VE) studies to be conducted at relatively low cost, but bias from using convenience samples is a concern. We evaluated the validity of using such data for estimating VE. Methods We created the Flu and Other Respiratory Viruses Research (FOREVER) Cohort by linking individual-level data on respiratory virus laboratory tests, hospitalizations, emergency department visits, and physician services. For community-dwelling adults aged > 65 years, we assessed the presence and magnitude of information and selection biases, generated VE estimates under various conditions, and compared our VE estimates with those from other studies. Results We included 65,648 unique testing episodes obtained from 54,434 individuals during the 2010–11 to 2015–16 influenza seasons. To examine information bias, we found the proportion testing positive for influenza for patients with unknown interval from illness onset to specimen collection was more similar to patients for whom illness onset date was ≤ 7 days before specimen collection than to patients for whom illness onset was > 7 days before specimen collection. To assess the presence of selection bias, we found the likelihood of influenza testing was comparable between vaccinated and unvaccinated individuals, although the adjusted odds ratios were significantly greater than 1 for some healthcare settings and during some influenza seasons. Over 6 seasons, VE estimates ranged between 36% (95%CI, 27–44%) in 2010–11 and 5% (95%CI, –2, 11%) in 2014–15. VE estimates were similar under a range of conditions, but were consistently higher when accounting for misclassification of vaccination status through a quantitative sensitivity analysis. VE estimates from the FOREVER Cohort were comparable to those from other studies. Conclusions Routinely collected laboratory and health administrative data contained in the FOREVER Cohort can be used to estimate influenza VE in community-dwelling older adults.

© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adap- tation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statu- tory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. ake surfaces are warming worldwide, raising concerns about lake organism responses to thermal habitat changes. Species may cope with temperature increases by shifting their seasonality or their depth to track suitable thermal habitats, but these responses may be constrained by ecological interactions, life histories or limiting resources. Here we use 32 million temperature measurements from 139 lakes to quantify thermal habitat change (percentage of non-overlap) and assess how this change is exacerbated by potential habitat constraints. Long-term temperature change resulted in an average 6.2% non-overlap between thermal habitats in baseline (1978–1995) and recent (1996–2013) time periods, with non-overlap increasing to 19.4% on aver- age when habitats were restricted by season and depth. Tropical lakes exhibited substantially higher thermal non-overlap com- pared with lakes at other latitudes. Lakes with high thermal habitat change coincided with those having numerous endemic species, suggesting that conservation actions should consider thermal habitat change to preserve lake biodiversity. Faculty yes

Introduction Annual influenza vaccination is recommended for older adults, but evidence regarding the impact of repeated vaccination has been inconclusive. Aim We investigated vaccine effectiveness (VE) against laboratory-confirmed influenza and the impact of repeated vaccination over 10 previous seasons on current season VE among older adults. Methods We conducted an observational test-negative study in community-dwelling adults aged > 65 years in Ontario, Canada for the 2010/11 to 2015/16 seasons by linking laboratory and health administrative data. We estimated VE using multivariable logistic regression. We assessed the impact of repeated vaccination by stratifying by previous vaccination history. Results We included 58,304 testing episodes for respiratory viruses, with 11,496 (20%) testing positive for influenza and 31,004 (53%) vaccinated. Adjusted VE against laboratory-confirmed influenza for the six seasons combined was 21% (95% confidence interval (CI): 18 to 24%). Patients who were vaccinated in the current season, but had received no vaccinations in the previous 10 seasons, had higher current season VE (34%; 95%CI: 9 to 52%) than patients who had received 1–3 (26%; 95%CI: 13 to 37%), 4–6 (24%; 95%CI: 15 to 33%), 7–8 (13%; 95%CI: 2 to 22%), or 9–10 (7%; 95%CI: −4 to 16%) vaccinations (trend test p = 0.001). All estimates were higher after correcting for misclassification of current season vaccination status. For patients who were not vaccinated in the current season, residual protection rose significantly with increasing numbers of vaccinations received previously. Conclusions Although VE appeared to decrease with increasing numbers of previous vaccinations, current season vaccination likely provides some protection against influenza regardless of the number of vaccinations received over the previous 10 influenza seasons.

© The Author(s) 2020. Published by Nature Research. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/. Globally, lake surface water temperatures have warmed rapidly relative to air temperatures, but changes in deepwater temperatures and vertical thermal structure are still largely unknown. We have compiled the most comprehensive data set to date of long-term (1970–2009) summertime vertical temperature profiles in lakes across the world to examine trends and drivers of whole-lake vertical thermal structure. We found significant increases in surface water temperatures across lakes at an average rate of + 0.37 °C decade−1, comparable to changes reported previously for other lakes, and similarly consistent trends of increasing water column stability (+ 0.08 kg m−3 decade−1). In contrast, however, deepwater temperature trends showed little change on average (+ 0.06 °C decade−1), but had high variability across lakes, with trends in individual lakes ranging from − 0.68 °C decade−1 to + 0.65 °C decade−1. The variability in deepwater temperature trends was not explained by trends in either surface water temperatures or thermal stability within lakes, and only 8.4% was explained by lake thermal region or local lake characteristics in a random forest analysis. These findings suggest that external drivers beyond our tested lake characteristics are important in explaining long-term trends in thermal structure, such as local to regional climate patterns or additional external anthropogenic influences. Funding in support of this work came from the following sources: Belarus Republican Foundation for Fundamental Research; IGB Long-Term Research; the European Commission within the MANTEL project; the DFG within the LimnoScenES project (AD 91/22-1); OLA-IS, AnaEE-France, INRAE of Thonon-les-Bains, CIPEL, SILA, CISALB; Universidad del Valle de Guatemala; Archbold Biological Station; the Oklahoma Department of Wildlife Conservation, the Oklahoma Water Resources Board, the Grand River Dam Authority, the US Army Corps of Engineers, and the City of Tulsa; the Ministry of Business, Innovation, and Employment (UOW X1503); the Natural Environment Research Council of the UK; the IGB’s International Postdoctoral Fellowship; NSERC, Canada Foundation for Innovation, Canada Research Chairs, Province of Saskatchewan; University of Regina; Queen’s University Belfast; Natural Environment Research Council; US-NSF, California Air Resources Board, NASA, and US National Park Service; the Ministry of Higher Education and Research (projects № FZZE-2020-0026; № FZZE-2020-0023) and RSCF 20-64-46003; US National Science Foundation Long Term Research in Environmental Biology program (DEB-1242626); the Environmental Agency of Verona; US National Science Foundation, the Gordon and Betty Moore Foundation, the Mellon Foundation, and the University of Washington; KMFRI, LVEMP, University of Innsbruck, OeAD, IFS, and LVFO-EU; Waikato Regional Council and Bay of Plenty Regional Council; Swedish Environmental Protection Agency and the Swedish Infrastructure for Ecosystem Sciences; US National Science Foundation grants DEB-1754276 and DEB-1950170. Faculty yes

Background: Carbapenemase-producing Enterobacteriaceae (CPE) infections are a rapidly evolving global threat. With bacteremia mortality rates exceeding 40%, limited consensus exists regarding optimal antimicrobial treatment. Objectives: To characterize our institution’s CPE bacteremia population and describe the antimicrobial regimens used for treatment. Methods: A dual-centre retrospective chart review was conducted of adult CPE bacteremia patients admitted between January 1, 2010 and April 30, 2017. Baseline demographics included out-of-country hospitalization, causative organism, and susceptibilities. Treatment details included antimicrobial agent, dosing regimen, and use of monotherapy or combination therapy. Clinical outcomes included 30-day all-cause mortality and 30-day re-admission rates. Results: Thirteen cases of CPE bacteremia were reviewed. Nine patients had previously been hospitalized in the Indian subcontinent. Twelve isolates produced the New Delhi metallo-beta-lactamase-1 (NDM-1). All isolates were sensitive (n = 8) or intermediate (n = 5) to tigecycline. An equal number of cases were treated with monotherapy (n = 6) and combination therapy (n = 6). The most commonly prescribed antimicrobials were colistin (n = 7) and tigecycline (n = 8). The overall 30-day mortality and re-admission rates were 54% (7/13) and 50% (3/6), respectively, although the effect of potential confounders such as causative CPE, monomicrobial or polymicrobial infection, or delay in therapy were not considered. Conclusions: This study highlights the largest Canadian CPE bacteremia cohort to date. CPE bacteremia most commonly occurred in patients with prior hospitalization in the Indian subcontinent. Based on our antimicrobial susceptibility testing results, tigecycline may have a role as part of empiric therapy at our institution.

Acute myocardial infarction can be triggered by acute respiratory infections. Previous studies have suggested an association between influenza and acute myocardial infarction, but those studies used nonspecific measures of influenza infection or study designs that were susceptible to bias. We evaluated the association between laboratory-confirmed influenza infection and acute myocardial infarction.We used the self-controlled case-series design to evaluate the association between laboratory-confirmed influenza infection and hospitalization for acute myocardial infarction. We used various high-specificity laboratory methods to confirm influenza infection in respiratory specimens, and we ascertained hospitalization for acute myocardial infarction from administrative data. We defined the "risk interval" as the first 7 days after respiratory specimen collection and the "control interval" as 1 year before and 1 year after the risk interval.We identified 364 hospitalizations for acute myocardial infarction that occurred within 1 year before and 1 year after a positive test result for influenza. Of these, 20 (20.0 admissions per week) occurred during the risk interval and 344 (3.3 admissions per week) occurred during the control interval. The incidence ratio of an admission for acute myocardial infarction during the risk interval as compared with the control interval was 6.05 (95% confidence interval [CI], 3.86 to 9.50). No increased incidence was observed after day 7. Incidence ratios for acute myocardial infarction within 7 days after detection of influenza B, influenza A, respiratory syncytial virus, and other viruses were 10.11 (95% CI, 4.37 to 23.38), 5.17 (95% CI, 3.02 to 8.84), 3.51 (95% CI, 1.11 to 11.12), and 2.77 (95% CI, 1.23 to 6.24), respectively.We found a significant association between respiratory infections, especially influenza, and acute myocardial infarction. (Funded by the Canadian Institutes of Health Research and others.).

In northeastern North America, acidification of precipitation and freshwater ecosystems is due to increased anthropogenic emissions of sulfate (SO42−) and nitrogen oxides (NOx). Legislative changes...

OBJECTIVETo measure transmission frequencies and risk factors for household acquisition of community-associated and healthcare-associated (HA-) methicillin-resistant Staphylococcus aureus (MRSA).DESIGNProspective cohort study from October 4, 2008, through December 3, 2012.SETTINGSeven acute care hospitals in or near Toronto, Canada.PARTICIPANTSTotal of 99 MRSA-colonized or MRSA-infected case patients and 183 household contacts.METHODSBaseline interviews were conducted, and surveillance cultures were collected monthly for 3 months from household members, pets, and 8 prespecified high-use environmental locations. Isolates underwent pulsed-field gel electrophoresis and staphylococcal cassette chromosome mec typing.RESULTSOverall, of 183 household contacts 89 (49%) were MRSA colonized, with 56 (31%) detected at baseline. MRSA transmission from index case to contacts negative at baseline occurred in 27 (40%) of 68 followed-up households. Strains were identical within households. The transmission risk for HA-MRSA was 39% compared with 40% (P=.95) for community-associated MRSA. HA-MRSA index cases were more likely to be older and not practice infection control measures (P=.002–.03). Household acquisition risk factors included requiring assistance and sharing bath towels (P=.001–.03). Environmental contamination was identified in 78 (79%) of 99 households and was more common in HA-MRSA households.CONCLUSIONHousehold transmission of community-associated and HA-MRSA strains was common and the difference in transmission risk was not statistically significant.Infect Control Hosp Epidemiol 2016;1–7

Background Respiratory illnesses are a major contributor to pediatric hospitalizations, with influenza and respiratory syncytial virus (RSV) causing substantial morbidity and cost each season. We compared the characteristics and outcomes of children 0-59 months of age who were hospitalized with laboratory-confirmed influenza or RSV between 2009 and 2014 in Ontario, Canada. Methods We included hospitalized children who were tested for influenza A, influenza B and RSV and were positive for a single virus. We characterized individuals by their demographics and healthcare utilization patterns and compared their hospital outcomes, in-hospital cost and postdischarge healthcare use by virus type and by presence of underlying comorbidities. Results We identified and analyzed 7659 hospitalizations during which a specimen tested positive for influenza or RSV. Children with RSV were the youngest whereas children with influenza B were the oldest [median ages 6 months (interquartile range: 2-17 months) and 25 months (interquartile range: 10-45 months), respectively]. Complex chronic conditions were more prevalent among children with all influenza (sub)types than RSV (31%-34% versus 20%). In-hospital outcomes were similar by virus type, but in children with comorbidities, postdischarge outcomes varied. We observed no differences in in-hospital cost between viruses or by presence of comorbidities [overall median cost: $4150 Canadian dollars (interquartile range: $3710-$4948)]. Conclusions Influenza and RSV account for large numbers of pediatric hospitalizations. RSV and influenza were similar in terms of severity and cost in hospitalized children. Influenza vaccination should be promoted in pregnant women and young children, and a vaccine against RSV would mitigate the high burden of RSV.

Lake acidification is a major problem in northeastern US lakes that can control fish presence or absence. We examined the history of fish populations in Lake Minnewaska, in eastern New York. We examined historical documents and found that Lake Minnewaska was fishless from 1922-2008 because of high lake-acidity. Following 30 years of recovery from acidic conditions, Notemigonus crysoleucas (Golden Shiner), a small minnow species, was introduced in 2008 and quickly proliferated, peaking at ~15,000 individuals in 2013. In 2012, the piscivorous species Micropterus salmoides (Largemouth Bass) was introduced, and the minnow population was effectively removed by 2014. We present a conceptual model of the history of fish in Lake Minnewaska as fish disappeared and reappeared over 100 years as a consequence of acid rain and human introductions.

We measured under-ice thermal stratification from before ice-on through after ice-off in Lake Sunapee, New Hampshire, a large, deep, north temperate lake, using a high-frequency monitoring buoy in the winter season of 2007–2008 to quantify how lake thermal stratification varies throughout the under-ice season. We examined potential drivers of variation in under-ice stability, identified diel-scale patterns in under-ice stratification, and used this dataset to test the hypothesis that there are two distinct under-ice phases driven by heat flux from the sediment followed by increased solar radiation as winter progresses. High-frequency measurements demonstrated that only a small fraction of the under-ice period exhibited the traditional inverse stratification previously thought to prevail, based on temporally discrete under-ice temperature profiles. Local short-term weather conditions altered under-ice conditions throughout the ice season with brief periods of snow melt, resulting in several days of disrupted thermal stratification. Our data indicate that thermal structure under the ice in Lake Sunapee is dynamic, and in contrast to smaller, shallower lakes, may be categorized in three, not two, distinct phases. As the under-ice season continues to become shorter due to climate change, under-ice thermal stratification in lakes will likely decrease further.

This paper describes the current update on macromolecular model validation services that are provided at the MolProbity website, emphasizing changes and additions since the previous review in 2010. There have been many infrastructure improvements, including rewrite of previous Java utilities to now use existing or newly written Python utilities in the open‐source CCTBX portion of the Phenix software system. This improves long‐term maintainability and enhances the thorough integration of MolProbity‐style validation within Phenix. There is now a complete MolProbity mirror site at http://molprobity.manchester.ac.uk. GitHub serves our open‐source code, reference datasets, and the resulting multi‐dimensional distributions that define most validation criteria. Coordinate output after Asn/Gln/His “flip” correction is now more idealized, since the post‐refinement step has apparently often been skipped in the past. Two distinct sets of heavy‐atom‐to‐hydrogen distances and accompanying van der Waals radii have been researched and improved in accuracy, one for the electron‐cloud‐center positions suitable for X‐ray crystallography and one for nuclear positions. New validations include messages at input about problem‐causing format irregularities, updates of Ramachandran and rotamer criteria from the million quality‐filtered residues in a new reference dataset, the CaBLAM Cα‐CO virtual‐angle analysis of backbone and secondary structure for cryoEM or low‐resolution X‐ray, and flagging of the very rare cis‐nonProline and twisted peptides which have recently been greatly overused. Due to wide application of MolProbity validation and corrections by the research community, in Phenix, and at the worldwide Protein Data Bank, newly deposited structures have continued to improve greatly as measured by MolProbity's unique all‐atom clashscore.

Lake surface water temperatures are warming worldwide, raising concerns about the future integrity of valuable lake ecosystem services. In contrast to surface water temperatures, we know far less about what is happening to water temperature beneath the surface, where most organisms live. Moreover, we know little about which characteristics make lakes more or less sensitive to climate change and other environmental stressors. We examined changes in lake thermal structure for 231 lakes across northeastern North America (NENA), a region with an exceptionally high density of lakes. We determined how lake thermal structure has changed in recent decades (1975–2012) and assessed which lake characteristics are related to changes in lake thermal structure. In general, NENA lakes had increasing near-surface temperatures and thermal stratification strength. On average, changes in deepwater temperatures for the 231 lakes were not significantly different than zero, but individually, half of the lakes experienced warming and half cooling deepwater temperature through time. More transparent lakes (Secchi transparency >5 m) tended to have higher near-surface warming and greater increases in strength of thermal stratification than less transparent lakes. Whole-lake warming was greatest in polymictic lakes, where frequent summer mixing distributed heat throughout the water column. Lakes often function as important sentinels of climate change, but lake characteristics within and across regions modify the magnitude of the signal with important implications for lake biology, ecology and chemistry. Published version

Ecologists are increasingly analyzing long-term and high-frequency sensor datasets as part of their research. As ecology becomes a more data-rich scientific discipline, the next generation of ecologists needs to develop the quantitative literacy required to effectively analyze,visualize, and interpret large datasets. We developed and assessed three modules to teach undergraduate freshwater ecology students both scientific concepts and quantitative skills needed to work with large datasets. These modules covered key ecological topics of phenology, physical mixing, and the balance between primary production and respiration, using lakes as model systems with high-frequency or long-term data. Our assessment demonstrated that participating in these modules significantly increased student comfort using spreadsheet software and their self-reported competence in performing a variety of quantitative tasks. Interestingly, students with the lowest pre-module comfort and skills achieved the biggest gains. Furthermore, students reported that participating in the modules helped them better understand the concepts presented and that they appreciated practicing quantitative skills. Our approach demonstrates that working with large datasets in ecology classrooms helps undergraduate students develop the skills and knowledge needed to help solve complex ecological problems and be more prepared for a data-intensive future. Project EDDIE-NSF TUES [1245707] We thank the students who participated in this study, Randy Fuller for contributing to the initial development of the Lake Mixing module, Janet Stromberg for help with qualitative data analysis, and Jon Doubek and Kate Hamre for teaching assistance. We also thank our Project EDDIE colleagues, Nick Bader, Devin Castendyk, Randy Fuller, Cathy Gibson, Luke Nave, Catherine O'Reilly, Dax Soule, Tom Meixner,and Kathleen Weathers, for helpful discussions. Project EDDIE is funded by NSF TUES 1245707, with administrative support from CeMaST (Center for Mathematics, Science and Technology at Illinois State University).

Didymosphenia geminata has recently and rapidly greatly expanded its range and abundance, sometimes as an exotic invasive and other times as a nuisance (‘native invader’) within its hypothesized native range, including the northeastern United States. D. geminata mats are visually conspicuous and can grow >10 cm thick. Mats first appeared in the eastern Catskill mountains (New York) in 2009. Our objectives were to (1) document D. geminata growth in three impounded or regulated rivers in the eastern Catskill mountains from 2010 to 2012 and (2) measure the effects of D. geminata mats on macroinvertebrates. The highest D. geminata cell densities were downstream of reservoir outflows in two of three streams. D. geminata mat development peaked in the summer each year, but maximum coverage and cell density was variable among years. D. geminata cover was negatively correlated with 10 days maximum antecedent shear stress, and the year with lowest mean D. geminata cover had multiple tropical storms and floods, suggesting that low variation in flow allows for D. geminata mat proliferation. Across sites, D. geminata density was negatively correlated with nitrate concentrations. D. geminata density was negatively related to macroinvertebrate richness suggesting that D. geminata mats may negatively affect aquatic food webs. D. geminata appears to be a nuisance species with similar habitat characteristics and growth where it is both a native invader and an invasive species.

H. T. Odum’s influential Limnology and Oceanography 1956 publication compared gross primary production (GPP) and ecosystem respiration (ER) among aquatic ecosystems. Few syntheses of aquatic ecosystem metabolism have been completed since. We used Odum’s conceptual framework to compare GPP and ER from open-water diel oxygen curves in lakes, wetlands, estuaries, and streams (n 5 350). We also documented environmental drivers of metabolism among ecosystems. GPP and ER were strongly related in lakes and estuaries, but weakly related in streams and wetlands. GPP and ER were highest in estuaries, and GPP:ER was lowest in streams. Differences in the magnitude and variability of metabolism among ecosystems were attributable to landscape and water-column factors. Watershed size and phosphorus (P) concentrations were positively related to GPP and ER across all ecosystems. Considered independently, lake and estuary GPP were driven by P concentrations. In contrast, land-use and canopy cover drove stream metabolism, not nutrient concentrations. Results confirmed the classic paradigm that estuaries are the most productive aquatic ecosystem; however, our synthesis showed that relative to streams and estuaries, there was higher variation in lake GPP and ER than previously documented. Results will be valuable for management, restoration, and carbon budgets, which incorporate metabolism measurements at both the catchment and landscape scales. As metabolism datasets grow, future syntheses will address challenges including seasonality, sensor deployment time and location, hydrology, and variation in analytical conventions by discipline. Ongoing technological and computational advancements, combined with increased communication among subdisciplines, should also expand insights generated by subsequent metabolism syntheses.

Integrated carbon budgets of terrestrial and aquatic ecosystems indicate that particulate organic carbon (POC) plays an important role in the transport, storage, and turnover of carbon during its transit from land to sea. However, little is known about the rates at which POC in suspension is metabolized during downstream transport. We address this deficiency by improving existing respiration methods and models to assess the biological lability of POC suspended in a headwater stream. Our method involves concentration of stream particles by tangential flow filtration, extended incubations (35-40 d) using conditions to ensure particle suspension and prevent particle aggregation, correction for the simultaneous respiration of dissolved organic carbon, and conversion from oxygen measurements into carbon with a respiratory oxidation ratio (OR) of 1.30 O2:C. We include analysis of the choice of OR. The POC turnover times estimated with the improved methods in this study are ~10 days. These respiration rates are among the highest reported for either suspended or benthic POC in streams and suggest that suspended POC is mineralized closer to its point of origin than was previously assumed. During incubation, keeping POC in suspension can increase respiration rates as much as 2-fold compared with allowing particles to settle and physical inhibition of POC aggregation can increase rates by 1.2-fold compared with allowing POC to aggregate. Methods that explicitly incorporate suspension and discourage aggregation of POC and longer incubation times during respiration measurements will generate data that improve our understanding of the dynamic role of POC in aquatic ecosystems.

Here we describe the updated MolProbity rotamer-library distributions derived from an order-of-magnitude larger and more stringently quality-filtered dataset of about 8000 (vs. 500) protein chains, and we explain the resulting changes and improvements to model validation as seen by users. To include only side-chains with satisfactory justification for their given conformation, we added residue-specific filters for electron-density value and model-to-density fit. The combined new protocol retains a million residues of data, while cleaning up false-positive noise in the multi- χ datapoint distributions. It enables unambiguous characterization of conformational clusters nearly 1000-fold less frequent than the most common ones. We describe examples of local interactions that favor these rare conformations, including the role of authentic covalent bond-angle deviations in enabling presumably strained side-chain conformations. Further, along with favored and outlier, an allowed category (0.3-2.0% occurrence in reference data) has been added, analogous to Ramachandran validation categories. The new rotamer distributions are used for current rotamer validation in MolProbity and PHENIX, and for rotamer choice in PHENIX model-building and refinement. The multi-dimensional χ distributions and Top8000 reference dataset are freely available on GitHub. These rotamers are termed "ultimate" because data sampling and quality are now fully adequate for this task, and also because we believe the future of conformational validation should integrate side-chain with backbone criteria. Proteins 2016; 84:1177-1189. © 2016 Wiley Periodicals, Inc.