How well do existing surveys track fish community performance measures in the St. Clair-Detroit River System?

The St. Clair-Detroit River System (SCDRS) connects Lake Huron to Lake Erie and provides important habitats for many fishes of economic and ecological importance. Portions of the SCDRS are designated as Great Lakes Areas of Concern and fish production and conservation may be compromised. Efforts to address beneficial use impairments have focused on restoring habitat for native fishes and improving aquatic ecosystem health. Considerable site-specific research and long-term, annual fish surveys have examined responses to habitat improvements. However, there is uncertainty surrounding whether individual studies and surveys can assess (1) population-level benefits of habitat enhancements and (2) whether management objectives are being met. To identify monitoring gaps and inform long-term monitoring program development, we compared outputs from SCDRS fish monitoring surveys (based on discussions with regional agencies) with performance measures specified in management plans (obtained through gray literature searches). Performance measures for harvested species aligned well with outputs of existing surveys. In contrast, at-risk fishes often had objectives and performance measures that reflected knowledge gaps and study needs. Although harvested species were well-monitored relative to specified performance measures, at-risk fishes were less reliably collected by existing surveys, except for lake sturgeon Acipenser fulvescens. Effective evaluation of restoration efforts for at-risk fishes may require additional survey efforts that target species-specific habitat use and life history characteristics.

Structural Approach to Assessing the Innovativeness of New Drugs Finds Accelerating Rate of Innovation.

Measuring innovation in the pharmaceutical industry is challenging. Counts of new molecular entities (NMEs) approved by the Food and Drug Administration (FDA) are commonly used, but this measure only gauges quantity not innovativeness. A new indicator of innovation for small molecule and peptide drugs based on structural novelty is proposed and used to analyze recent trends in pharmaceutical innovation. We show pharmaceutical innovation has significantly increased over the last several decades despite recent concerns over an innovation crisis and find Pioneers (a NME whose shape and scaffold were not used in any previously FDA-approved drugs) are significantly more likely to be the source of promising new therapies. Analysis of the underlying source of structural innovation indicates that scaffolds first reported in the CAS REGISTRY five or less years prior to their Investigational New Drug application (IND) or on scaffolds populated with 50 or less other compounds at the time of IND tend to be the main source of Pioneers. Our analysis also shows a widening structural innovation gap between large pharmaceutical companies (Big Pharma) and the rest of the ecosystem even though the number of Big Pharma originated Pioneers has increased.

Impact of Chemist-In-The-Loop Molecular Representations on Machine Learning Outcomes.

The development of molecular descriptors is a central challenge in cheminformatics. Most approaches use algorithms that extract atomic environments or end-to-end machine learning. However, a looming question is that how do these approaches compare with the critical eye of trained chemists. The CAS fingerprint engages expert chemists to curate chemical motifs, which they deem could influence bioactivity. In this paper, we benchmark the CAS fingerprint against commonly used fingerprints using a well-established benchmark set of 88 targets. We show that the CAS fingerprint outperforms most of the commonly used molecular fingerprints. Analysis of the CAS fingerprint reveals that experts tend to select features that are rarely reported in the literature, though not all rare features are selected. Our analysis also shows that the CAS fingerprint provides a different source of information compared to other commonly used fingerprints. These results suggest that anthropomorphic insights do have predictive power and highlight the importance of a chemist-in-the-loop approach in the era of machine learning.

Recent Changes in the Scaffold Diversity of Organic Chemistry As Seen in the CAS Registry.

A large set of organic compounds extracted from the CAS Registry is analyzed to study recent changes in structural diversity. The diversity is characterized using the framework content of the compounds; the framework of a molecule is the scaffold consisting of all its ring systems and all the chain fragments connecting them. The compounds are partitioned based on their year of first report in the literature, which allows framework occurrence frequencies to be compared across a 10-year interval. The results are consistent with a process in which frameworks with the greatest frequency of use in the past are the most likely to be used again, but it is also found that the frequency ordering changes over time. These fluctuations in ordering are attributed to stochastic factors, scientific and economic, that can affect how chemical space is explored. Framework diversity is found to have increased over time despite the extensive reuse of a relatively small number of frameworks; this increase is due to the large number of new frameworks. The long tail of the framework distribution, composed of frameworks that occur in few compounds or only one compound, is found to be a large and growing part of framework space.

Medical Faculty Beliefs: Self-Rated Importance and Confidence in Teaching Geriatrics Primary Care.

OBJECTIVES: To evaluate and contrast 25 content areas essential to the primary care of older adults by medical faculty, thus identifying faculty beliefs and areas of possible improvement. DESIGN: Using measures from the Healthcare Effectiveness Data and Information Set, the Consumer Assessment of Healthcare Providers and Systems, and Healthy People 2020, nine practicing clinical faculty identified 25 content areas essential to the primary care of older adults. SETTING: A large academic health center in southeastern United States. PARTICIPANTS: Eighty-two university medical faculty. MEASUREMENTS: Faculty rated importance, knowledge, and confidence in teaching the 25 content areas on a scale from 1 (low) to 10 (high). Gap scores reflecting the difference in ratings for importance and confidence in teaching were calculated and assessed. The survey had high internal consistency within each of the three domains-Cronbach's α > .94. RESULTS: The most important content areas were being able to explain details about patient's condition and taking medication clearly, followed by taking age-appropriate history. The three largest gaps were: "evaluating sensory impairment," "identifying and counseling at-risk drivers," and "evaluating cognition." The three smallest gaps were: "explaining prescribed medications," "explaining health conditions in easy-to-understand language," and "taking an age-appropriate patient history and performing a physical assessment." CONCLUSION: Medical faculty were comfortable with topics reflecting primary care expertise but expressed less confidence with more specialized topics, such as sensory or cognitive impairment and driving. This may represent key areas for geriatrics training applicable to all those involved in education and training of future healthcare professionals. Integration of specialists (eg, neurologists, psychiatrists) may improve the geriatrics curricula. J Am Geriatr Soc 67:576-580, 2019.

Divergent migration within lake sturgeon (Acipenser fulvescens) populations: Multiple distinct patterns exist across an unrestricted migration corridor.

Population structure, distribution, abundance and dispersal arguably underpin the entire field of animal ecology, with consequences for regional species persistence, and provision of ecosystem services. Divergent migration behaviours among individuals or among populations are an important aspect of the ecology of highly mobile animals, allowing populations to exploit spatially or temporally distributed food and space resources. This study investigated the spatial ecology of lake sturgeon (Acipenser fulvescens) within the barrier free Huron-Erie Corridor (HEC), which connects Lake Huron and Lake Erie of the North American Laurentian Great Lakes. Over 6 years (2011-2016), movements of 268 lake sturgeon in the HEC were continuously monitored across the Great Lakes using acoustic telemetry (10 years battery life acoustic transmitters). Five distinct migration behaviours were identified with hierarchical cluster analysis, based on the phenology and duration of river and lake use. Lake sturgeon in the HEC were found to contain a high level of intraspecific divergent migration, including partial migration with the existence of residents. Specific behaviours included year-round river residency and multiple lake-migrant behaviours that involved movements between lakes and rivers. Over 85% of individuals were assigned to migration behaviours as movements were consistently repeated over the study, which suggested migration behaviours were consistent and persistent in lake sturgeon. Differential use of specific rivers or lakes by acoustic-tagged lake sturgeon further subdivided individuals into 14 "contingents" (spatiotemporally segregated subgroups). Contingents associated with one river (Detroit or St. Clair) were rarely detected in the other river, which confirmed that lake sturgeon in the Detroit and St. Clair represent two semi-independent populations that could require separate management consideration for their conservation. The distribution of migration behaviours did not vary between populations, sexes, body size or among release locations, which indicated that intrapopulation variability in migratory behaviour is a general feature of the spatial ecology of lake sturgeon in unfragmented landscapes.

Use of navigation channels by Lake Sturgeon: Does channelization increase vulnerability of fish to ship strikes?

Channelization for navigation and flood control has altered the hydrology and bathymetry of many large rivers with unknown consequences for fish species that undergo riverine migrations. In this study, we investigated whether altered flow distributions and bathymetry associated with channelization attracted migrating Lake Sturgeon (Acipenser fulvescens) into commercial navigation channels, potentially increasing their exposure to ship strikes. To address this question, we quantified and compared Lake Sturgeon selection for navigation channels vs. alternative pathways in two multi-channel rivers differentially affected by channelization, but free of barriers to sturgeon movement. Acoustic telemetry was used to quantify Lake Sturgeon movements. Under the assumption that Lake Sturgeon navigate by following primary flow paths, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River were expected to choose navigation channels over alternative pathways and to exhibit greater selection for navigation channels than conspecifics in the less-channelized lower St. Clair River. Consistent with these predictions, acoustic-tagged Lake Sturgeon in the more-channelized lower Detroit River selected the higher-flow and deeper navigation channels over alternative migration pathways, whereas in the less-channelized lower St. Clair River, individuals primarily used pathways alternative to navigation channels. Lake Sturgeon selection for navigation channels as migratory pathways also was significantly higher in the more-channelized lower Detroit River than in the less-channelized lower St. Clair River. We speculated that use of navigation channels over alternative pathways would increase the spatial overlap of commercial vessels and migrating Lake Sturgeon, potentially enhancing their vulnerability to ship strikes. Results of our study thus demonstrated an association between channelization and the path use of migrating Lake Sturgeon that could prove important for predicting sturgeon-vessel interactions in navigable rivers as well as for understanding how fish interact with their habitat in landscapes altered by human activity.

Mycobacterium abscessus ventriculoperitoneal shunt infection and review of the literature.

A 30-year-old man with history of neonatal hydrocephalus requiring ventriculoperitoneal shunt placement presented with Mycobacterium abscessus shunt infection despite no shunt manipulation over 10 years prior to presentation. Cure was not achieved until complete removal of all CNS shunt foreign body was performed despite initial adequate antimicrobial therapy.

Management of Scedosporium apiospermum in a pre- and post-lung transplant patient with cystic fibrosis.

Although the predominant type of infection seen in the cystic fibrosis lung remains bacterial, fungal organisms are being isolated more frequently and are associated with a high mortality rate in lung transplant recipients. We present a case of a patient with CF with sputum cultures positive for Scedosporium apiospermum prior to a successful lung transplant. She remains without evidence of infection 18 months later following treatment with a combination of triazoles and terbinafine.

Elvitegravir: a once-daily inhibitor of HIV-1 integrase.

INTRODUCTION: Elvitegravir (EVG) is a potent inhibitor of HIV-1 integrase (IN) undergoing Phase III clinical trials. It blocks the strand-transfer step in a multi-step process that allows double-stranded cDNA to be irreversibly incorporated within the host DNA. It is the second member of the HIV-1 IN inhibitor class, following raltegravir. Co-administration with a CYP3A inhibitor, such as ritonavir or cobicistat, substantially increases EVG plasma exposure and prolongs elimination half-life. AREAS COVERED: A Medline review of Phase II and III trials involving EVG as well as a review of abstracts from major HIV and infectious disease conferences from 2010 to 2011 was conducted. EVG produces rapid and durable virologic suppression when combined with active background therapy. Trials investigating the efficacy of once-daily co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) demonstrate a high rate of virologic suppression with fewer CNS and psychiatric adverse events compared with co-formulated efavirenz/emtricitabine/tenofovir. The resistance profile for EVG is similar to raltegravir. EXPERT OPINION: Co-formulated EVG/COBI/FTC/TDF is an option for the treatment of antiretroviral naïve and experienced patients. Once-daily dosing offers an advantage over raltegravir, but the requirement for pharmacologic boosting increases regimen complexity. Dolutegravir in development offers a favorable resistance profile and no requirement for pharmacologic boosting.

Blastoschizomyces capitatus pneumonia in an immunocompetent male.

Blastoschizomyces capitatus is an emerging fungal pathogen. It has been well characterized as a cause of local and disseminated disease in immunocompromised hosts, especially in the setting of neutropenia. We describe a case of B. capitatus pneumonia in an otherwise healthy man and review the clinical presentation, microbiologic characteristics, and treatment strategies for B. capitatus infections.

Anemia prevalence and associated risk factors in a single-center ambulatory HIV clinical cohort.

The prevalence of anemia in HIV-infected persons has not been well characterized in the HAART era. In a single-center, retrospective study, anemia prevalence and risk factors, including use of HAART, were assessed in an ambulatory clinical cohort of 758 HIV-infected patients for the calendar year 2000. The relationships between anemia (hemoglobin level less than 12.5 g/dL) and demographic variables, antiretroviral treatment regimens, and disease markers were analyzed. Mean baseline patient characteristics were hemoglobin level, 13.7 +/- 1.9 g/dL; CD4+ cell count, 405 +/- 293/microL; and HIV RNA level, 77,841 +/- 148,394 copies/mL. Overall anemia prevalence was 30.3%. Multivariate logistic regression analysis demonstrated that anemia was associated with a CD4+ cell count below 50/microL, female sex, black race, a viral load above 100,000 copies/mL, zidovudine use, and older age. Severe anemia was less prevalent in this study population than in historical comparators; however, mild to moderate anemia rates remain high.