Long-term ecological research in freshwaters enabled by regional biodiversity collections, stable isotope analysis, and environmental informatics.

Biodiversity collections are experiencing a renaissance fueled by the intersection of informatics, emerging technologies, and the extended use and interpretation of specimens and archived databases. In this article, we explore the potential for transformative research in ecology integrating biodiversity collections, stable isotope analysis (SIA), and environmental informatics. Like genomic DNA, SIA provides a common currency interpreted in the context of biogeochemical principles. Integration of SIA data across collections allows for evaluation of long-term ecological change at local to continental scales. Challenges including the analysis of sparse samples, a lack of information about baseline isotopic composition, and the effects of preservation remain, but none of these challenges is insurmountable. The proposed research framework interfaces with existing databases and observatories to provide benchmarks for retrospective studies and ecological forecasting. Collections and SIA add historical context to fundamental questions in freshwater ecological research, reference points for ecosystem monitoring, and a means of quantitative assessment for ecosystem restoration.

Relative Genetic Homogeneity within a Phenotypically Diverse group: The Case of Lake Tana Labeobarbus (Cyprinidae) Species Flock, Ethiopia.

The Lake Tana Labeobarbus species flock represents one of the world's most famous examples of lacustrine species radiations. Previous studies of this group have resulted in the description of at least 15 species based on their differences in functional morphology and definition of two clades (lacustrine and riverine spawning clades) based on life history traits. A total of 166 fish representing 14 Labeobarbus species were genotyped using 10 lineage-specific hexaploid microsatellite loci. Six of these loci were developed for this study based on DNA sequence contigs derived from a microsatellite-enriched genomic library of Labeobarbus intermedius from Lake Tana; the remaining four loci were obtained from a previous study. The genotypes of the 10 loci were analyzed to examine genetic diversity and population structure within Lake Tana Labeobarbus. Overall mean allelic richness (NA) was 17.6 alleles per locus and observed (Ho) and expected (He) heterozygosities were 0.84 ± 0.14 and 0.73 ± 0.09, respectively, across all Lake Tana Labeobarbus samples examined. Our analyses reveal that there is little genetic differentiation among species (FST = 0.020-0.099; only 10 of 91 species comparisons were significant), but moderate differentiation (FST = 0.11, p < 0.05) between lacustrine and riverine spawning populations. Relative to previous phylogenetic hypotheses, our phenetic analysis employing the R-based Analysis of Phylogenetics and Evolution (APE) program seems to perform marginally better in revealing lineages within Lake Tana Labeobarbus. Herein, our results are compared to a previous microsatellite-based study of the same populations.

Marine and freshwater fishes of Alabama: a revised checklist and discussion of taxonomic issues.

Checklists are fundamental and important tools for organizing information about biodiversity that provide a basis for conservation and additional scientific research. While Alabama is recognized as an aquatic biodiversity hotspot with the highest native freshwater fish diversity in the contiguous United States, we currently lack an up-to-date list of the states fishes. In particular, much has changed over the past ~20 years regarding our knowledge of fishes from Alabama and the Mobile River Basin, rendering past comprehensive treatments by Mettee et al. (1996) and Boschung and Mayden (2004) out of date. Here, we provide a revised checklist of marine and freshwater fishes known from the coastal and inland waters of Alabama that includes 463 species (335 primarily freshwater fishes, and 128 marine or diadromous fishes) in 35 orders, 78 families, and 176 genera. Extant, extirpated, and extinct species are included, as are putative candidate species. The checklist is based on prior work, searches of the literature and online sources, as well as parsing a large compilation of >140,000 fish records for Alabama and the Mobile River Basin from 37 data providers in the global Fishnet2 database (www.fishnet2.net) and >4000 marine survey records from the SEAMAP database (https://www.gsmfc.org/seamap.php). After editing and quality control checks, the final combined database contained 144,215 collection records, ~95% of which were georeferenced. We discuss the species descriptions, nomenclatural changes, and updates to marine species that account for changes to the state list, and we close with a discussion of ~13 candidate species forms that remain undescribed, which represent outstanding taxonomic issues in need of further research attention.

Body mass index, diet, physical inactivity, and the incidence of dementia in 1 million UK women.

OBJECTIVE: To help determine whether midlife obesity is a cause of dementia and whether low body mass index (BMI), low caloric intake, and physical inactivity are causes or merely consequences of the gradual onset of dementia by recording these factors early in a large 20-year prospective study and relating them to dementia detection rates separately during follow-up periods of <5, 5 to 9, 10 to 14, and 15+ years. METHODS: A total of 1,136,846 UK women, mean age 56 (SD 5) years, were recruited in 1996 to 2001 and asked about height, weight, caloric intake, and inactivity. They were followed up until 2017 by electronic linkage to National Health Service records, detecting hospital admissions with mention of dementia. Cox regression yielded adjusted rate ratios (RRs) for first dementia detection during particular follow-up periods. RESULTS: Fifteen years after the baseline survey, only 1% were lost to follow-up, and 89% remained alive with no detected dementia, of whom 18,695 had dementia detected later, at a mean age of 77 (SD 4) years. Dementia detection during years 15+ was associated with baseline obesity (BMI 30+ vs 20-24 kg/m2: RR 1.21, 95% confidence interval 1.16-1.26, p < 0.0001) but not clearly with low BMI, low caloric intake, or inactivity at baseline. The latter 3 factors were associated with increased dementia rates during the first decade, but these associations weakened substantially over time, approaching null after 15 years. CONCLUSIONS: Midlife obesity may well be a cause of dementia. In contrast, behavioral changes due to preclinical disease could largely or wholly account for associations of low BMI, low caloric intake, and inactivity with dementia detection during the first decade of follow-up.

Phylogeny and divergence times of suckers (Cypriniformes: Catostomidae) inferred from Bayesian total-evidence analyses of molecules, morphology, and fossils.

Catostomidae ("suckers") is a diverse (76 species) and broadly distributed family of Holarctic freshwater fishes with a rich fossil record and a considerable number (∼35%) of threatened and imperiled species. We integrate DNA sequences (three mitochondrial genes, three nuclear genes), morphological data, and fossil information to infer sucker phylogenetic relationships and divergence times using Bayesian "total-evidence" methods, and then test hypotheses about the temporal diversification of the group. Our analyses resolved many nodes within subfamilies and clarified Catostominae relationships to be of the form ((Thoburniini, Moxostomatini), (Erimyzonini, Catostomini)). Patterns of subfamily relationships were incongruent, but mainly supported two placements of the Myxocyprininae; distinguishing these using Bayes factors lent strongest support to a model with Myxocyprininae sister to all remaining sucker lineages. We improved our Bayesian total-evidence dating analysis by excluding problematic characters, using a clock-partitioning scheme identified by Bayesian model selection, and employing a fossilized birth-death tree prior accommodating morphological data and fossils. The resulting chronogram showed that suckers evolved since the Late Cretaceous-Eocene, and that the Catostomini and Moxostomatini clades have accumulated species diversity since the early to mid-Miocene. These results agree with the fossil record and confirm previous hypotheses about dates for the origins of Catostomide and catostomine diversification, but reject previous molecular hypotheses about the timing of divergence of ictiobines, and between Asian-North American lineages. Overall, our findings from a synthesis of multiple data types enhance understanding of the phylogenetic relationships, taxonomic classification, and temporal diversification of suckers, while also highlighting practical methods for improving Bayesian divergence dating models by coupling phylogenetic informativeness profiling with relaxed-clock partitioning.

Implantable cardioverter-defibrillator therapy in Australia, 2002-2015.

OBJECTIVES: To quantify the number of implantable cardioverter-defibrillator (ICD) procedures in Australia by year, patient age and sex, and to estimate age group-specific population rates and the associated costs. Design, setting: Retrospective observational study; analysis of Australian National Hospital Morbidity Database hospital procedures data. PARTICIPANTS: Patients with an ICD insertion, replacement, adjustment, or removal procedure code, July 2002 - June 2015. MAIN OUTCOME MEASURES: Number of ICD procedures by procedure year, patient age (0-34, 35-69, 70 years or more) and sex; age group-specific population procedure rates; number of procedures associated with complications. RESULTS: The number of ICD procedures increased from 1844 in 2002-03 to 6504 in 2014-15; more than 75% of procedures were in men. In 2014-15, the ICD insertion rate for people aged 70 years or more was 78.1 per 100 000 population, 22 per 100 000 for those aged 35-69 years, and 1.40 per 100 000 people under 35. The reported complication rate decreased from 45% in 2002-03 to 19% in 2014-15, partly because of a change in the coding of complications. The number of removals corresponded to at least 4% of the number of insertions each year. The aggregate cost of hospitalisations with an ICD procedure during 2011-14 was $445 644 566. CONCLUSION: ICD procedures are becoming more frequent in Australia, particularly in people aged 70 or more. Patterns of care associated with ICD therapy, particularly patient- and hospital-related factors associated with adverse events, should be investigated to better understand and improve patient outcomes.

Norleual, a hepatocyte growth factor and macrophage stimulating protein dual antagonist, increases pancreatic cancer sensitivity to gemcitabine.

Pancreatic cancer is a leading cause of cancer deaths in the USA and is characterized by an exceptionally poor long-term survival rate compared with other major cancers. The hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP) growth factor systems are frequently over-activated in pancreatic cancer and significantly contribute to cancer progression, metastasis, and chemotherapeutic resistance. Small molecules homologous to the 'hinge' region of HGF, which participates in its dimerization and activation, had been developed and shown to bind HGF with high affinity, antagonize HGF's actions, and possess anticancer activity. Encouraged by sequence homology between HGF's hinge region and a similar sequence in MSP, our laboratory previously investigated and determined that these same antagonists could also block MSP-dependent cellular responses. Thus, the purpose of this study was to establish that the dual HGF/MSP antagonist Norleual could inhibit the prosurvival activity imparted by both HGF and MSP to pancreatic cancer cells in vitro, and to determine whether this effect translated into an improved chemotherapeutic impact for gemcitabine when delivered in combination in a human pancreatic cancer xenograft model. Our results demonstrate that Norleual does indeed suppress HGF's and MSP's prosurvival effects as well as sensitizing pancreatic cancer cells to gemcitabine in vitro. Most importantly, treatment with Norleual in combination with gemcitabine markedly inhibited in-vivo tumor growth beyond the suppression observed with gemcitabine alone. These results suggest that dual functional HGF/MSP antagonists like Norleual warrant further development and may offer an improved therapeutic outcome for pancreatic cancer patients.

Novel evolutionary lineages in Labeobarbus (Cypriniformes; Cyprinidae) based on phylogenetic analyses of mtDNA sequences.

Phylogenetic relationships within Labeobarbus, the large-sized hexaploid cyprinids, were examined using cytochrome b gene sequences from a broad range of geographic localities and multiple taxa. Maximum likelihood and Bayesian methods revealed novel lineages from previously unsampled drainages in central (Congo River), eastern (Genale River) and southeastern (Revue and Mussapa Grande rivers) Africa. Relationships of some species of Varicorhinus in Africa (excluding 'V.' maroccanus) render Labeobarbus as paraphyletic. 'Varicorhinus' beso, 'V.' jubae, 'V.' mariae, 'V.' nelspruitensis, and 'V.' steindachneri are transferred to Labeobarbus. Bayesian estimation of time to most recent common ancestor suggested that Labeobarbus originated in the Late Miocene while lineage diversification began during the Late Miocene-Early Pliocene and continued to the late Pleistocene. The relationships presented herein provide phylogenetic resolution within Labeobarbus and advances our knowledge of genetic diversity within the lineage as well as provides some interesting insight into the hydrographic and geologic history of Africa.

The influence of life-history strategy on genetic differentiation and lineage divergence in darters (Percidae: Etheostomatinae).

Recent studies determined that darters with specialized breeding strategies can exhibit deep lineage divergence over fine geographic scales without apparent physical barriers to gene flow. However, the extent to which intrinsic characteristics interact with extrinsic factors to influence population divergence and lineage diversification in darters is not well understood. This study employed comparative phylogeographic and population genetic methods to investigate the influence of life history on gene flow, dispersal ability, and lineage divergence in two sympatric sister darters with differing breeding strategies. Our results revealed highly disparate phylogeographic histories, patterns of genetic structure, and dispersal abilities between the two species suggesting that life history may contribute to lineage diversification in darters, especially by limiting dispersal among large river courses. Both species also showed striking differences in demographic history, indicating that extrinsic factors differentially affected each species during the Pleistocene. Collectively, our results indicate that intrinsic and extrinsic factors have influenced levels of gene flow among populations within both species examined. However, we suggest that life-history strategy may play a more important role in lineage diversification in darters than previously appreciated, a finding that has potentially important implications for understanding diversification of the rich North American freshwater fish fauna.

Caspase-8 and RIP kinases regulate bacteria-induced innate immune responses and cell death.

A number of pathogens cause host cell death upon infection, and Yersinia pestis, infamous for its role in large pandemics such as the "Black Death" in medieval Europe, induces considerable cytotoxicity. The rapid killing of macrophages induced by Y. pestis, dependent upon type III secretion system effector Yersinia outer protein J (YopJ), is minimally affected by the absence of caspase-1, caspase-11, Fas ligand, and TNF. Caspase-8 is known to mediate apoptotic death in response to infection with several viruses and to regulate programmed necrosis (necroptosis), but its role in bacterially induced cell death is poorly understood. Here we provide genetic evidence for a receptor-interacting protein (RIP) kinase-caspase-8-dependent macrophage apoptotic death pathway after infection with Y. pestis, influenced by Toll-like receptor 4-TIR-domain-containing adapter-inducing interferon-ß (TLR4-TRIF). Interestingly, macrophages lacking either RIP1, or caspase-8 and RIP3, also had reduced infection-induced production of IL-1ß, IL-18, TNF, and IL-6; impaired activation of the transcription factor NF-κB; and greatly compromised caspase-1 processing. Cleavage of the proform of caspase-1 is associated with triggering inflammasome activity, which leads to the maturation of IL-1ß and IL-18, cytokines important to host responses against Y. pestis and many other infectious agents. Our results identify a RIP1-caspase-8/RIP3-dependent caspase-1 activation pathway after Y. pestis challenge. Mice defective in caspase-8 and RIP3 were also highly susceptible to infection and displayed reduced proinflammatory cytokines and myeloid cell death. We propose that caspase-8 and the RIP kinases are key regulators of macrophage cell death, NF-κB and inflammasome activation, and host resistance after Y. pestis infection.

Interspecific relationships and the evolution of sexual dimorphism in pygmy sunfishes (Centrarchidae: Elassoma).

The genus Elassoma represents a small but unique component of the aquatic biodiversity hotspot in southeastern North America. We present the first phylogeny of the seven described species, corroborated by sequence data from mitochondrial and nuclear protein coding genes. This analysis reveals a Coastal Plain clade sister to the geographically isolated, and federally protected, Elassoma alabamae. The Coastal Plain clade contains the widespread E. zonatum, which is sister to a clade primarily restricted to lowland Neogene subprovinces. We analyzed morphometric data in a phylogenetic context to illustrate the evolution of sexual shape dimorphism within the genus. Sixteen univariate and three multivariate traits were tested for significant sexual dimorphism for each species, and relative transformation rates were inferred from the time tree. A simple index of interspecific sexual dimorphism revealed greater disparity among sympatric species comparisons than among allopatric comparisons. Results implicate geology as a primary factor influencing ecological diversification, and sexual selection as a mechanism reinforcing reproductive isolation in areas of secondary contact. We discuss putative roles of geological history and sexual selection in the generation and maintenance of the aquatic biodiversity gradient in southeastern North America.

Limits and phylogenetic relationships of East Asian fishes in the subfamily Oxygastrinae (Teleostei: Cypriniformes: Cyprinidae).

The cyprinid subfamily Oxygastrinae is composed of a diverse group of fishes that has been taxonomically and phylogenetically problematic. Their great variation in appearance, life histories, and trophic diversity resulted in uncertainty regarding their relationships, which led to their historical classification across many disparate subfamilies. The phylogenetic relationships of Oxygastrinae are resolved based on sequence data from four loci: cytochrome b, cytochrome c oxidase I, opsin, and recombination activating gene 1. A combined data matrix consisting of 4114 bp for 144 taxa was compiled and analyzed using maximum likelihood and parsimony optimality criteria. The subfamily Oxygastrinae is recovered as a monophyletic group that includes Ancherythroculter, Aphyocypris, Candidia, Chanodichthys, Ctenopharyngodon, Culter, Distoechodon, Elopichthys, Hainania, Hemiculter, Hemiculterella, Hemigrammocypris, Hypophthalmichthys, Ischikauia, Macrochirichthys, Megalobrama, Metzia, Mylopharyngodon, Nicholsicypris, Nipponocypris, Ochetobius, Opsariichthys, Oxygaster, Parabramis, Parachela, Paralaubuca, Pararasbora, Parazacco, Plagiognathops, Pseudobrama, Pseudohemiculter, Pseudolaubuca, Sinibrama, Squaliobarbus, Toxabramis, Xenocyprioides, Xenocypris, Yaoshanicus, and Zacco. Of these genera, the following were found to be monophyletic: Aphyocypris, Distoechodon, Hypophthalmichthys, Nipponocypris, Opsariichthys, Parachela, Paralaubuca, Plagiognathops, Xenocyprioides, and Xenocypris. The following genera were not monophyletic: Metzia, Hemiculter, Toxabramis, Ancherythroculter, Chanodichthys, Culter, Megalobrama. The remainder are either monotypic or were represented by only a single species. Four genera not examined in this study are provisionally classified in Oxygastrinae: Anabarilius, Longiculter, Pogobrama, and Rasborichthys.

Transition to total one-stop wide-awake hand surgery service-audit: a retrospective review.

OBJECTIVES: To document the transition to a totally one-stop (patient seen and treated in one appointment) wide-awake (local anaesthesia only) hand surgery service. DESIGN: Retrospective review of 10 year service with detailed analysis of last 1000 cases including process and cost-effectiveness and efficiency analysis. SETTING: Purpose-built CQC-certified day-case surgical facility where we have pioneered the UK's first totally one-stop wide-awake orthopaedic service. PARTICIPANTS: Approximately five thousand orthopaedic patients treated in the last ten years. MAIN OUTCOME MEASURES: Surgical outcomes, patient satisfaction and cost-effectiveness and efficiency. RESULTS: The OSWA model is safe, efficient and effective; with a low complication rate, extremely high patient satisfaction; and cost-savings to the NHS of 50-75% of the national tariff. The service saved the NHS approximately £750,000 for the 1000 cases presented; and over £2 million since the inception of the service. CONCLUSIONS: A totally one-stop wide-awake hand surgery service is a practicable and feasible alternative to the conventional treatment pathway with benefits in terms of efficiency and cost-effectiveness.

Umbilical endometriosis, a pathology that a gynecologist may encounter when inserting the Veres needle.

OBJECTIVE: To raise awareness between laparoscopists about umbilical endometriosis and to recommend the appropriate management measure for this rare but easily treatable condition. DESIGN: Case reports and literature review. SETTING: Women presented to general surgeon with umbilical masses. PATIENT(S): Women of reproductive age with histologic diagnosis of umbilical endometriosis. INTERVENTION(S): Excision with histopathologic examination. MAIN OUTCOME MEASURE(S): Definite diagnosis and clinical improvement. RESULT(S): Umbilical endometriosis is best diagnosed and cured with excisional biopsy. Other diagnostic methods have been proven to be nonspecific and unreliable in the literature. CONCLUSION(S): Clinical diagnosis of this condition can be difficult even with the aid of cytology and imaging. Surgical excision with removal and histopathology is recommended for both diagnostic and therapeutic purposes. Simultaneous laparoscopy should be recommended to the patient with suspected pelvic endometriosis.

Cost-effectiveness of rehabilitation after an acute coronary event: a randomised controlled trial.

OBJECTIVE: To estimate the incremental effects on cost and quality of life of cardiac rehabilitation after an acute coronary syndrome. DESIGN: Open randomised controlled trial with 1 year's follow-up. Analysis was on an intention-to-treat basis. SETTING: Two tertiary hospitals in Sydney. INTERVENTION: 18 sessions of comprehensive exercise-based outpatient cardiac rehabilitation or conventional care as provided by the treating doctor. PARTICIPANTS: 113 patients aged 41-75 years who were self-caring and literate in English. Patients with uncompensated heart failure, uncontrolled arrhythmias, severe and symptomatic aortic stenosis or physical impairment were excluded. MAIN OUTCOME MEASURES: Costs (hospitalisations, medication use, outpatient visits, investigations, and personal expenses); and measures of quality of life. Incremental cost per quality-adjusted life year (QALY) saved at 1 year (this estimate combines within-study utility effects with reported 1-year risk of survival and treatment effects of rehabilitation on mortality). Sensitivity analyses around a base case estimate included alternative assumptions of no treatment effect on survival, 3 years of treatment effect on survival and variations in utility. RESULTS: The estimated incremental cost per QALY saved for rehabilitation relative to standard care was 42,535 US dollars when modelling included the reported treatment effect on survival. This increased to 70,580 US dollars per QALY saved if treatment effect on survival was not included. The results were sensitive to variations in utility and ranged from 19,685 US dollars per QALY saved to rehabilitation not being cost-effective. CONCLUSIONS: The effects on quality of life tend to reinforce treatment advantages on survival for patients having postdischarge rehabilitation after an acute coronary syndrome. The estimated base case incremental cost per QALY saved is consistent with those historically accepted by decision making authorities such as the Pharmaceutical Benefits Advisory Committee.

Effect of pravastatin compared with placebo initiated within 24 hours of onset of acute myocardial infarction or unstable angina: the Pravastatin in Acute Coronary Treatment (PACT) trial.

BACKGROUND: The efficacy of statin drugs after an acute coronary event is now well established, but the evidence for statin use in the early treatment of acute coronary events remains unclear. METHODS: We tested the effects of administering pravastatin within 24 hours of the onset of symptoms in patients with unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction. Patient recruitment of 10,000 with 1200 end points was planned, but the trial was stopped early. A total of 3408 patients were randomly assigned to treatment with pravastatin (1710 patients) or matching placebo (1698 patients). Treatment was continued for 4 weeks. The primary end point of the study was a composite of death, recurrence of myocardial infarction, or readmission to hospital for unstable angina within 30 days of random assignment. RESULTS: The primary end point occurred in 199 of patients allocated to pravastatin (11.6%) and in 211 patients allocated to placebo (12.4%). A relative risk reduction of 6.4% favored allocation to pravastatin but was not statistically significant (95% CI, -13.2% to 27.6%). No adverse effects were seen. CONCLUSIONS: We conclude that 20 to 40 mg of pravastatin can be safely administered within 24 hours of the onset of symptoms of an acute coronary event, with a favorable but not significant trend in outcome at 30 days compared with placebo.