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The primary objective was to quantify postoperative opioid use after laparoscopic surgery for endometriosis or pelvic pain. The secondary objective was to identify patient characteristics associated with greater postoperative opioid requirements.Prospective, survey-based study in which subjects completed 1 preoperative and 7 postoperative surveys within 28 days of surgery regarding medication usage and pain control.Tertiary care, academic center.A total of 100 women with endometriosis or pelvic pain.Laparoscopic same-day discharge surgery by fellowship-trained minimally invasive gynecologists.A total of 100 patients were recruited and 8 excluded, for a final sample size of 92 patients. All patients completed the preoperative survey. Postoperative response rates ranged from 70.7% to 80%. The mean number of pills (5 mg oxycodone tablets) taken by day 28 was 6.8. The average number of pills prescribed was 10.2, with a minimum of 4 (n = 1) and maximum of 20 (n = 3). Previous laparoscopy for pelvic pain was associated with a significant increase in postoperative narcotic use (8.2 vs 5.6; p = .044). Hysterectomy was the only surgical procedure associated with a significant increase in postoperative narcotic use (9.7 vs 5.4; p = .013). There were no difference in number of pills taken by presence of deep endometriosis or pathology-confirmed endometriosis (all p.36). There was a trend of greater opioid use in patients with diagnoses of self-reported chronic pelvic pain, anxiety, and depression (7.9 vs 5.7, p = .051; 7.7 vs 5.2, p = .155; 8.1 vs 5.6, p = .118).Most patients undergoing laparoscopic surgery for endometriosis and pelvic pain had a lower postoperative opioid requirement than prescribed, suggesting surgeons can prescribe fewer postoperative narcotics in this population. Patients with a previous surgery for pelvic pain, self-reported chronic pelvic pain syndrome, anxiety, and depression may represent a subset of patients with increased postoperative opioid requirements.

Judicious antimicrobial use (AMU) is important for preserving therapeutic effectiveness. Large-scale studies of antimicrobial prescribing can provide clinical benchmarks and help identify opportunities for improved stewardship.To describe systemic AMU in UK equine practice and identify factors associated with systemic and Category B (third and fourth generation cephalosporins, quinolones and polymixins) AMU.Retrospective cohort.Anonymised electronic patient records (EPRs) for all equids attended by 39 UK veterinary practices between 1 January and 31 December 2018 were collected via the VetCompass programme. Systemic antimicrobial prescriptions were identified using electronic keyword searches. Indications for AMU were determined through manual review of a randomly selected subset of EPRs. The types and frequency of systemic antimicrobials prescribed and indications were summarised using descriptive statistics. Mixed-effects logistic regression was used to evaluate practice- and horse-related risk factors.Systemic antimicrobials were prescribed to 12 538 (19.5%, 95% confidence interval [CI]: 19.2%-19.8%) of 64 322 equids attended in 2018. Category B antimicrobials were prescribed to 1.9% (95% CI: 1.8%-2.0%) of attended equids and in 8.9% (95% CI: 8.5%-9.4%) of antimicrobial courses. Bacteriological culture was performed in 19.1% (95% CI: 17.1%-21.3%) of Category B antimicrobial courses. The most commonly prescribed antimicrobial classes were potentiated sulphonamides (50.2% of equids receiving antimicrobials) and tetracyclines (33.5% of equids receiving antimicrobials). Integumentary disorders were the most common reason for systemic AMU (40.5% of courses). Urogenital disorders were the most common reason for Category B AMU (31.1% of courses). Increased odds of systemic and Category B AMU were observed in equids1 year compared with those aged 5-14 years. Breed was associated with AMU, with odds of systemic and Category B AMU highest in Thoroughbreds and Thoroughbred crosses.Convenience sample of practices may limit generalisability.Empirical use of Category B antimicrobials remains commonplace.Ein umsichtiger Umgang mit antimikrobiellen Medikamenten (AMU) ist wichtig für die Erhaltung der therapeutischen Wirksamkeit. Gross angelegte Studien über die Verschreibung antimikrobieller Medikamente können klinische Vergleichswerte liefern und dazu beitragen Möglichkeiten für eine verbesserte Anwendung zu ermitteln.Beschreibung der systemischen AMU in der britischen Pferdepraxis und Ermittlung von Faktoren, di mit systemischer AMU und AMU der Kategorie B (Cephalosporine der dritten und vierten Generation, Chinolone und Polymyxine) in Verbindung stehen.Retrospektive Kohorte.Anonymisierte elektronische Patientenakten (EPRs) für alle Equiden, die zwischen dem 1. Januar und dem 31. Dezember 2018 in 39 britischen Tierarztpraxen behandelt wurden, wurden über das Programm VetCompass™ erfasst. Systemische Verschreibungen von antimikrobiellen Medikamenten wurden durch elektronische Stichwortsuche identifiziert. Die Indikationen für AMU wurden durch manuelle Überprüfung einer zufällig ausgewählten Teilmenge von EPRs ermittelt. Die Arten und die Häufigkeit der verschriebenen systemischen antimikrobiellen Medikamente sowie die Indikationen wurden anhand von deskriptiven Statistiken zusammengefasst. Eine logistische Regression mit gemischten Effekten wurde verwendet, um praxis- und pferdebezogene Risikofaktoren zu bewerten.Systemische antimikrobielle Medikamente wurden 12 538 (19.5%, 95% CI 19.2-19.8%) von 64 322 im Jahr 2018 behandelten Equiden verschrieben. Antimikrobielle Medikamente der Kategorie B wurden bei 1.9% (95% KI 1.8-2.0%) der behandelten Equiden und in 8.9% (95% KI 8.5-9.4%) der antimikrobiellen Medikamente verschrieben. Bei 19.1% (95% KI 17.1-21.3%) der antimikrobiellen Medikamente der Kategorie B wurde eine bakteriologische Kultur angelegt. Die am häufigsten verschriebenen antimikrobiellen Klassen waren potenzierte Sulfonamide (50.2% der mit antimikrobiellen Medikamenten behandelten Equiden) und Tetracycline (33.5% der mit antimikrobiellen Medikamenten behandelten Equiden). Dermatologische Erkrankungen waren der häufigste Grund für systemische AMU (40.5% der Behandlungen). Urogenitale Erkrankungen waren der häufigste Grund für AMU der Kategorie B (31.1% der Behandlungen). Eine erhöhte Wahrscheinlichkeit für systemische AMU und AMU der Kategorie B wurde bei Equiden unter 1 Jahr im Vergleich zu Equiden im Alter von 5-14 Jahren beobachtet. Die Rasse wurde mit AMU in Verbindung gebracht, wobei die Wahrscheinlichkeit einer systemischen AMU und einer AMU der Kategorie B bei Vollblütern und Vollblutkreuzungen am höchsten war. WICHTIGSTE EINSCHRÄNKUNGEN: Die Verallgemeinerung der Ergebnisse ist möglicherweise durch eine Zufallsstichprobe von Praxen beeinträchtigt.Der empirische Einsatz von antimikrobiellen Medikamenten der Kategorie B ist nach wie vor weit verbreitet.

Abdominal wall endometriosis (AWE) is rare with limited evidence guiding diagnosis and treatment. The purpose of this review is to provide an update of the diagnosis, perioperative considerations, and treatment of AWE.Recent studies further characterize presenting symptoms and locations of AWE. Prior abdominal surgery remains the greatest risk factor for the development of AWE. Newer evidence suggests that increasing BMI may also be a risk factor. Ultrasound is first-line imaging for diagnosis. Magnetic resonance image is preferred for surgical planning for deep or extensive lesions. Laparotomy with wide local excision is considered standard treatment for AWE with great success. Novel techniques in minimally invasive surgery have been described as effective for the treatment of AWE. A multidisciplinary surgical approach is often warranted for successful excision and reapproximation of skin and/or fascial defects. Noninvasive therapies including ultrasonic ablation or cryotherapy are also emerging as promising treatment strategies in select patients.Recent studies provide further evidence to guide diagnosis through physical exam and imaging as well as pretreatment planning. Treatment options for AWE are rapidly expanding with novel approaches in minimally invasive and noninvasive therapies now available.

PURPOSE OF REVIEW Abdominal wall endometriosis (AWE) is rare with limited evidence guiding diagnosis and treatment. The purpose of this review is to provide an update of the diagnosis, perioperative considerations, and treatment of AWE. RECENT FINDINGS Recent studies further characterize presenting symptoms and locations of AWE. Prior abdominal surgery remains the greatest risk factor for the development of AWE. Newer evidence suggests that increasing BMI may also be a risk factor. Ultrasound is first-line imaging for diagnosis. Magnetic resonance image is preferred for surgical planning for deep or extensive lesions. Laparotomy with wide local excision is considered standard treatment for AWE with great success. Novel techniques in minimally invasive surgery have been described as effective for the treatment of AWE. A multidisciplinary surgical approach is often warranted for successful excision and reapproximation of skin and/or fascial defects. Noninvasive therapies including ultrasonic ablation or cryotherapy are also emerging as promising treatment strategies in select patients. SUMMARY Recent studies provide further evidence to guide diagnosis through physical exam and imaging as well as pretreatment planning. Treatment options for AWE are rapidly expanding with novel approaches in minimally invasive and noninvasive therapies now available.

Long-lived basaltic volcanic eruptions are a globally important source of environmentally reactive, volatile metal pollutant elements such as selenium, cadmium and lead. The 2018 eruption of Kīlauea, Hawai’i produced exceptionally high discharge of metal pollutants, and was an unprecedented opportunity to track them from vent to deposition. Here we show, through geochemical sampling of the plume that volatile metal pollutants were depleted in the plume up to 100 times faster than refractory species, such as magnesium and iron. We propose that this rapid wet deposition of complexes containing reactive and potentially toxic volatile metal pollutants may disproportionately impact localised areas close to the vent. We infer that the relationship between volatility and solubility is an important control on the atmospheric behaviour of elements. We suggest that assessment of hazards from volcanic emissions should account for heterogeneous plume depletion of metal pollutants. Volatile metal pollutants in basaltic volcanic plumes can be deposited up to 100 times faster than refractory species, and may produce disproportionate impacts at proximal locations, according to extensive sampling of Kīlauea’s 2018 eruption plume.

As increasing atmospheric carbon dioxide (CO2) and temperatures accompany modern climate change, ancient hothouse periods become a focal point for understanding ecosystem function under similar conditions. The early Eocene exhibited high temperatures, high CO2 levels, and similar tectonic plate configuration to today, so it has been invoked as an analog to modern climate change. During the early Eocene, the greater Green River Basin (GGRB) of southwest Wyoming was covered by an ancient hypersaline lake (Lake Gosiute; Green River Formation) and associated fluvial and floodplain systems (Wasatch and Bridger Formations). The volcaniclastic Bridger Formation was deposited by an inland delta that drained from the northwest into freshwater Lake Gosiute and is known for its vast paleontological assemblages. The Blue Rim escarpment exposes approximately 100 meters of the lower Bridger Formation, which includes plant and mammal fossils, paleosols and organic remains suitable for geochemical analyses, as well as ash beds and volcaniclastic sandstone beds suitable for radioisotopic dating. New 40Ar/39Ar ages from the middle and top of the Blue Rim escarpment constrain age of its strata to ~49.5–48.5 Ma ago, during the “falling limb” of the early Eocene climatic optimum. Using several geochemical tools, we reconstructed provenance and parent material in both the paleosols and the associated sediments and found no change in sediment input source despite significant variation in sedimentary facies and organic carbon burial. We also reconstructed environmental conditions at the time, including temperature and precipitation (from paleosols) and the isotopic composition of CO2 from plants found in the floral assemblages, before comparing them to reconstructions for the same time made using leaf physiognomic techniques and marine proxies. The paleosol-based reconstructions (near the base of the section) of precipitation (608–1167 mm yr−1) and temperature (10.4 to 12.0 °C) were within error of, although lower than, those based on floral assemblages, which were stratigraphically higher in the section. Geochemistry and detrital feldspar geochronology indicate a consistent provenance for Blue Rim sediments, sourcing predominantly from the Idaho paleoriver, which drained the active Challis volcanic field. Thus, because there was neither significant climatic change nor significant provenance change, variation in sedimentary facies and organic carbon burial likely reflected localized geomorphic controls, and the relative height of the water table. The ecosystem can be characterized as a wet, subtropical forest throughout the interval based upon the floral humidity province and Holdridge life zone schemes. Given the mid-paleolatitude position of the Blue Rim Escarpment, those results are consistent with marine proxies that indicate that globally warm climatic conditions continued beyond the peak warm conditions of the early Eocene climatic optimum. The reconstructed atmospheric δ13C value (−5.3 to −5.8 ‰) closely matches both the independently reconstructed value from marine microfossils (−5.4 ‰), as well as the isotopic composition of the mantle (−5.4 ‰), suggesting that the warm conditions were maintained by volcanic outgassing.

CRISPR/Cas9 has emerged as a powerful technology for tissue-specific mutagenesis. However, tissue-specific CRISPR/Cas9 tools currently available in Drosophila remain deficient in three significant ways. First, many existing gRNAs are inefficient, such that further improvements of gRNA expression constructs are needed for more efficient and predictable mutagenesis in both somatic and germline tissues. Second, it has been difficult to label mutant cells in target tissues with current methods. Lastly, application of tissue-specific mutagenesis at present often relies on Gal4-driven Cas9, which hampers the flexibility and effectiveness of the system. Here, we tackle these deficiencies by building upon our previous CRISPR-mediated tissue-restricted mutagenesis (CRISPR-TRiM) tools. First, we significantly improved gRNA efficiency in somatic tissues by optimizing multiplexed gRNA design. Similarly, we also designed efficient dual-gRNA vectors for the germline. Second, we developed methods to positively and negatively label mutant cells in tissue-specific mutagenesis by incorporating co-CRISPR reporters into gRNA expression vectors. Lastly, we generated genetic reagents for convenient conversion of existing Gal4 drivers into tissue-specific Cas9 lines based on homology-assisted CRISPR knock-in. In this way, we expand the choices of Cas9 for CRISPR-TRiM analysis to broader tissues and developmental stages. Overall, our upgraded CRISPR/Cas9 tools make tissue-specific mutagenesis more versatile, reliable, and effective in Drosophila. These improvements may be also applied to other model systems.

Postcopulatory sexual selection (PCSS), comprised of sperm competition and cryptic female choice, has emerged as a widespread evolutionary force among polyandrous animals. There is abundant evidence that PCSS can shape the evolution of sperm. However, sperm are not the whole story: they are accompanied by seminal fluid substances that play many roles, including influencing PCSS. Foremost among seminal fluid models is Drosophila melanogaster, which displays ubiquitous polyandry, and exhibits intraspecific variation in a number of seminal fluid proteins (Sfps) that appear to modulate paternity share. Here, we first consolidate current information on the identities of D. melanogaster Sfps. Comparing between D. melanogaster and human seminal proteomes, we find evidence of similarities between many protein classes and individual proteins, including some D. melanogaster Sfp genes linked to PCSS, suggesting evolutionary conservation of broad-scale functions. We then review experimental evidence for the functions of D. melanogaster Sfps in PCSS and sexual conflict. We identify gaps in our current knowledge and areas for future research, including an enhanced identification of PCSS-related Sfps, their interactions with rival sperm and with females, the role of qualitative changes in Sfps and mechanisms of ejaculate tailoring. This article is part of the theme issue ‘Fifty years of sperm competition’.

Volcanoes are a large global source of almost every element, including ~20 environmentally reactive trace elements classified as metal pollutants (e.g. selenium, cadmium and lead). Fluxes of metal pollutants from individual eruptions can be comparable to total anthropogenic emissions from large countries such as China.The 2018 Lower East Rift Zone eruption of Kīlauea, Hawaii produced exceptionally high emission rates of major and trace chemical species compared to other basaltic eruptions over 3 months (200 kt/day of SO2; Kern et al. 2019). We tracked the volcanic plume from vent to exposed communities over 0-240 km distance using in-situ sampling and atmospheric dispersion modelling. This is the first time that trace elements in volcanic emissions (~60 species) are mapped over such distances. In 2019, we repeated the field campaign during a no-eruption period and showed that volcanic emissions had caused 3-5 orders of magnitude increase in airborne metal pollutant concentrations across the Island of Hawai’i.We show that the volatility of the elements (the ease with which they are degassed from the magma) controls their particle-phase speciation, which in turn determines how fast they are depleted from the plume after emission. Elements with high magmatic volatilities (e.g. selenium, cadmium and lead) have up to 6 orders of magnitude higher depletion rates compared to non-volatile elements (e.g. magnesium, aluminium and rare earth metals).Previous research and hazard mitigation efforts on volcanic emissions have focussed on sulphur and it has been assumed that other pollutants follow the same dispersion patterns. Our results show that the atmospheric fate of sulphur, and therefore the associated hazard distribution, does not represent an accurate guide to the behaviour and potential impacts of other species in volcanic emissions. Metal pollutants are predominantly volatile in volcanic plumes, and their rapid deposition (self-limited by their volatility) places disproportionate environmental burdens on the populated areas in the immediate vicinity of the active and, in turn, reduces the impacts on far-field communities.Reference: Kern, C., T. Elias, P. Nadeau, A. H. Lerner, C. A. Werner, M. Cappos, L. E. Clor, P. J. Kelly, V. J. Realmuto, N. Theys, S. A. Carn, AGU, 2019; https://agu.confex.com/agu/fm19/meetingapp.cgi/Paper/507140.

Crossmodal correspondences have been of interest to researchers for nearly a century, although it is only more recently that interactions related to timbre have been examined systematically. Timbre is often described using crossmodal adjectives (e.g., bright, smooth). However, it is not clear whether these semantic conventions are primarily the result of low-level multisensory interactions or are more a product of associative learning and musical training. Do young children exhibit crossmodal correspondences involving timbre? The aim of this study was to investigate the effects of timbre, age, and sensory modality (visual and tactile) on the consistency and congruency of young children's patterns of crossmodal mappings. Preschool children (N = 69, M age = 4.51) completed a novel audio-visual and audio-tactile association task. Results indicate that children are moderately consistent in their associations; mappings are largely congruent with adult associations; and results suggest a possible developmental time course for the establishment of crossmodal correspondences between approximately ages 3 and 6. However, congruency is dependent on modality, with robust agreement in the tactile-auditory domain but a good deal more variance and a stronger developmental influence on visual-auditory associations. These results are the first to demonstrate that crossmodal correspondences are a feature of timbre perception early in development.

We measured the extent to which motor skill performance is advantaged by break intervals that include varied types of cognitive activity interposed early in a training session, directly comparing the performances of musicians and nonmusicians. Participants ( N = 118; 59 music majors, 59 nonmusicians) learned a 5-element keypress sequence on a digital piano during 12 min training sessions. Participants in three conditions took a 5 min break after 3 min of practice, and either practiced a new 5-element sequence (Break-motor), memorized word pairs (Break-word pair), or conversed with the proctor (Break-talk). Those in the fourth condition took no break (No-break). Participants were tested 12 hr later, following a night of sleep. Participants made significant performance gains across training and test, but musicians significantly outperformed nonmusicians at all timepoints. Nonmusicians made greater percentage gains than did musicians over the 5 min break interval and overnight, and participants in the Break-motor condition made significantly smaller gains over the 5 min break interval than did participants in the Break-talk and Break-word pair conditions. These results demonstrate that tasks involving declarative memories do not diminish performance enhancements that accrue during breaks early in motor skill practice, but these enhancements can be inhibited by engaging in competing motor tasks.

Premise of research. Permineralized wood along with fossil leaves, reproductive structures, and dispersed pollen and spores are preserved in the uppermost Lower Eocene (∼49.0 Ma) Blue Rim escarpment of the Bridger Formation in southwestern Wyoming. Each component of the flora provides a slightly different view of the diversity and environment, but the wood assemblage provides additional information on the taxonomic composition, forest structure, and local seasonality and climate.Methodology. Fossil wood specimens, including occasional in situ stumps, were collected from Bridger strata exposed at Blue Rim, north of Green River, Wyoming. Thin sections in the three standard orientations were prepared of each specimen and examined by light microscopy. Specific gravity and vulnerability index values were calculated for well-preserved specimens. Tree height was estimated from diameter measurements obtained from 10 specimens.Pivotal results. Seven wood types are recognized in the assemblage, including a single s...

We tested the sensitivity of paleoclimate estimates to different resolutions of leaf morphotype distinction by grouping one paleofloral collection three ways and comparing the results. We examined the different morphotype resolutions using a recently collected Eocene (34 Ma) fossil leaf assemblage from Florissant Fossil Beds National Monument Collection Site 9 (CS-9, Florissant, Colorado), an exposure that yields one of the most diverse sets of dicotyledonous angiosperm (‘dicot’) morphotypes yet analyzed from a single site within this well-studied formation. We grouped this collection using what are herein referred to as ‘Splitter’ (number of morphotypes n = 129), ‘Intermediate’ (n = 96), and ‘Lumper’ (n = 53) morphotyping approaches, which differed in their degree of delineating foliar morphotypes. Leaf Margin Analysis (LMA) and Leaf Area Analysis (LAA) were used to obtain paleotemperature and paleoprecipitation estimates from the morphotype datasets and Climate Leaf Analysis Multivariate Program (CLAMP) was employed to examine further parameters. We perform an additional paleoclimatic analysis of CS-9 in which we divide the site into three stratigraphic sections, and finally we perform an analysis on sample collections above and below a volcanic event horizon within CS-9. Whole collection results across the three morphotype resolutions indicate a mean annual temperature between 10.8 and 12.5 °C, and annual precipitation between 61.8 and 130.7 cm at the time of deposition. The ‘Splitter,’ ‘Intermediate,’ and ‘Lumper’ approaches provide very similar estimates by all methods of analysis and suggest that morphotype resolution specificity has very little effect on climatic results using these leaf physiognomic techniques.

Objective We assessed whether requiring >1 medication for blood pressure control is associated with adverse pregnancy outcomes. Study Design Retrospective cohort of 974 singletons with chronic hypertension at a tertiary care center. Subjects on >1 antihypertensive agent were compared to those on 1 agent < 20 weeks gestational age with results stratified by average blood pressure (

Objective To examine the relationship between baseline renal function tests in pregnant patients with chronic hypertension and adverse pregnancy outcomes. Methods This was a retrospective cohort study of women with a singleton pregnancy and chronic hypertension with assessment of renal function (urine protein-to-creatinine ratio and serum creatinine) before 20 weeks of gestation. The primary outcome was severe preeclampsia at less than 34 weeks of gestation. Secondary outcomes were severe preeclampsia at any gestational age, any preeclampsia, preterm birth at less than 35 weeks of gestation, composite perinatal outcome (perinatal death, assisted ventilation, cord pH less than 7, 5-minute Apgar score 3 or less, or neonatal seizures), and small for gestational age. The association between baseline renal function and the primary outcome was assessed with receiver operating characteristic (ROC) curves and objective cutoffs determined. Outcomes were compared between those with values above and below the cutoffs using univariable and multivariable analyses. Results Seven hundred fifty-five pregnant women with chronic hypertension had baseline renal function assessment. The urine protein-to-creatinine ratio and creatinine cutoffs for severe preeclampsia at less than 34 weeks of gestation were 0.12 or greater and 0.75 mg/dL or greater, respectively. The area under the ROC curves for severe preeclampsia at less than 34 weeks of gestation was 0.74 (95% confidence interval [CI] 0.7-0.8) for urine protein-to-creatinine ratio and 0.67 (95% CI 0.6-0.8) for creatinine. A urine protein-to-creatinine ratio 0.12 or greater was associated with an increased risk of developing severe preeclampsia at less than 34 weeks of gestation (16.4% compared with 2.6%, adjusted odds ratio [OR] 7.5, 95% CI 3.9-14.6) as was a creatinine 0.75 mg/dL or greater (15.7% compared with 4.6%, adjusted OR 3.5, 95% CI 1.9-6.3). Severe preeclampsia at less than 34 weeks of gestation occurred in only 1.6% of patients if their baseline tests were below both cutoffs. Conclusion Baseline assessment of renal function can be used as a risk stratification tool in pregnant patients with chronic hypertension.

The uppermost Eocene Florissant Formation of central Colorado, U.S.A. contains a diverse flora and fauna preserved in lacustrine facies and represents a key episode in Earth history immediately preceding the Eocene-Oligocene boundary. Laminated shales contain impressions of non-monocot angiosperm leaves that were used to estimate paleoecological and paleoclimatic parameters using leaf physiognomic methods including: leaf mass per area (MA), digital leaf physiognomy (DiLP), leaf margin analysis (LMA), and leaf area analysis (LAA). The majority (58%) of the morphotypes analyzed for MA suggested a semi-evergreen leaf lifespan, whereas another 27% indicated a deciduous habit and 15% an evergreen habit. There was no significant relationship between MA and insect damage based on a small subset of Florissant's leaves. Higher MA values (~73% of leaves ≥ one-year lifespan), coupled with a tendency toward long and narrow leaf shapes and small leaf areas, indicate the existence of sclerophyllous vegetation. Using the global regression for mean annual temperature (MAT), the DiLP estimate of MAT was anomalously cold: 5.5 ± 4 °C. However, using a Northern Hemisphere regression the DiLP MAT estimate of 11.6 ± 3.3 °C was more plausible. Using DiLP, mean annual precipitation (MAP) was estimated at 740 + 608/−334 mm∙yr−1, which supports dry conditions. Estimates for MAT and MAP using the univariate LMA and LAA methods overlapped within uncertainty of the DiLP results. In addition, those taxa classified as growing in wet areas (riparian) had significantly more teeth than non-riparian taxa. These paleoclimatic and paleoecological results suggest that outside the riparian forest, the Florissant flora sampled a seasonally dry temperate sclerophyllous shrubland to woodland, perhaps similar to modern chaparral forests, in the western interior of the U.S.A. just before the transition into the cooler Oligocene.

Premise of research. Numerous trimerous fossil flowers have been collected from Eocene strata in Wyoming, Utah, and Colorado. While many specimens have been assigned tentatively to Arecaceae, they have not been described formally, and their systematic placement within this large family has not been determined.Methodology. Fossils from the Eocene Bridger, Green River, and Wind River Formations were photographed, described, and measured. Pollen extracted from a stamen was studied by transmitted light, epifluorescence, and scanning electron microscopy. The floral and pollen morphological characters were compared to extant and fossil genera of angiosperms with a focus on Arecaceae.Pivotal results. Both macromorphological and palynological characters agree with assignment of the fossils to the extant genus Phoenix (L.). This is significant because Phoenix is native to Africa and southeast Asia today, but these fossils indicate a much broader distribution in the past. In addition, Phoenix cannot tolerate extens...

PREMISE OF THE STUDY The Icacinaceae are a pantropical family of trees, shrubs, and climbers with an extensive Paleogene fossil record. Our improved understanding of phylogenetic relationships within the family provides an excellent context for investigating new fossil fruit and leaf material from the Eocene of western North America. METHODS We examined fossils from early and middle Eocene sediments of western Wyoming, northeastern Utah, northwestern Colorado, and Oregon and compared them with extant species of Iodes and other icacinaceous genera as well as previously described fossils of the family. KEY RESULTS Three new fossil species are described, including two based on endocarps (Iodes occidentalis sp. nov. and Icacinicaryites lottii sp. nov.) and one based on leaves (Goweria bluerimensis sp. nov.). The co-occurrence of I. occidentalis and G. bluerimensis suggests these might represent detached organs of a single species. A new genus, Biceratocarpum, is also established for morphologically distinct fossil fruits of Icacinaceae previously placed in Carpolithus. Biceratocarpum brownii gen. et comb. nov. resembles the London Clay species "Iodes" corniculata in possessing a pair of subapical protrusions. CONCLUSIONS These fossils increase our knowledge of Icacinaceae in the Paleogene of North America and highlight the importance of the Northern Hemisphere in the early diversification of the family. They also document interchange with the Eocene flora of Europe and biogeographic connections with modern floras of Africa and Asia, where Icacinaceae are diverse today. The present-day restriction of this family to tropical regions offers ecological implications for the Eocene floras in which they occur.

Purpose: Technological advances in intensive care unit may lead physicians to question or omit portions of the physical exam. Our goal is to assess the opinions of intensive care unit physicians about physical examination in modern day medicine. Methods: Subjects included physicians on medical intensive care unit teams at one university hospital and two university-affiliated teaching hospitals. Participants responded to an interview divided into two sections: (1) A semistructured interview including open-ended questions on the management of four critical care scenarios and on the utility of physical exam; (2) Multiple-choice questions about physical exam. Main Results: The response rate was 100%. A total of 122 individuals, 16(13%) attendings, 24(20%) fellows and 82(67%) residents, responded. Half 61 (50%) considered physical examination to be of limited utility in the intensive care unit. Fifteen percent of answers to the clinical scenarios were reasoned based on physical examination. Most extended the definition of physical examination to include data derived from monitoring 119(97%), life support 121(99%) and bedside imaging devices 112(92%). Residents 45(37%), students 35(29%) and nurses 35(29%) were recognized as the team members who examine patients the most. Conclusion: Physical examination was considered useful by half of the

This study was designed to investigate the extent to which the presentation of an auditory model prior to learning a novel melody affects performance during active practice and the overnight consolidation of procedural memory. During evening training sessions, 32 nonpianist musicians practiced a 13-note keyboard melody with their left (nondominant) hand in twelve 30-s practice intervals separated by 30-s rest intervals. Participants were instructed to play the sequence “as quickly, accurately, and evenly as possible.” Approximately half the participants, prior to the first practice interval, listened to 10 repetitions of the target melody played at 552 tones per minute (half note = 138). All participants were tested on the target melody the following morning, approximately 12 hr after training, in three 30-s blocks separated by 30-s rest intervals. Performance was measured in terms of the mean number of correct key presses per 30-s block (CKP/B). Consistent with previous research, participants made considerable improvements in CKP/B during the evening training sessions and between the end of training and the morning test sessions. Learners who listened to the model made significantly larger gains in performance during training and between the end of training and test than did those who did not hear the model.

During evening practice sessions, 32 nonpianist musicians learned a short melody on piano, and then either learned a second short piano melody, learned a difficult unfamiliar piece on their principal instruments, practiced familiar material on their principal instruments, or engaged in no other music-related motor behavior prior to sleep; practice on the target melody was limited in terms of time and number of repetitions. All participants returned the next morning and were tested on their performance of the target piano melody. Previous research has revealed overnight enhancement of skills as a result of sleep. In the current study, however, our participants showed significant decrements in performance between evening training and morning test, though the extent of the decrements varied. We speculate that the lack of overnight improvements may have resulted from our regulating participants’ practice of the target melody during the training sessions and that strict, limited practice protocols may interfere with consolidation-based memory enhancement.

Summary In the ciliated protozoan Paramecium tetraurelia, Piwi-associated small RNAs are generated upon the elimination of tens of thousands of short transposon-derived DNA segments as part of development. These RNAs then target complementary DNA for elimination in a positive feedback process, contributing to germline defense and genome stability. In this work, we investigate the formation of these RNAs, which we show to be transcribed directly from the short (length mode 27 bp) excised DNA segments. Our data support a mechanism whereby the concatenation and circularization of excised DNA segments provides a template for RNA production. This process allows the generation of a double-stranded RNA for Dicer-like protein cleavage to give rise to a population of small regulatory RNAs that precisely match the excised DNA sequences. Video Abstract, Graphical Abstract, Highlights • In Paramecium, pieces of deleted DNA are transcribed to form regulatory RNAs • Ultra-short DNA segments are concatenated and circularized, allowing transcription • This concatenation is carried out by Ligase IV, which also repairs DNA ends • Concatenation is random, which leads to diversity in the resulting sRNA population, “Junk” DNA can be ligated into circles and transcribed to generate regulatory RNAs.

Objective To provide a review on the current use of antimicrobials with a discussion on the pharmacokinetic and pharmacodynamic profiles of antimicrobials in critically ill patients, the challenges of drug resistance, the use of diagnostic testing to direct therapy, and the selection of the most likely efficacious antimicrobial protocol. Etiology Patients in the intensive care unit often possess profound pathophysiologic changes that can complicate antimicrobial therapy. Although many antimicrobials have known pharmacodynamic profiles, critical illness can cause wide variations in their pharmacokinetics. The two principal factors affecting pharmacokinetics are volume of distribution and drug clearance. Understanding the interplay between critical illness, drug pharmacokinetics, and antimicrobial characteristics (ie, time-dependent vs concentration-dependent) may improve antimicrobial efficacy and patient outcome. Diagnosis Utilizing bacterial culture and susceptibility can aid in identifying drug resistant infections, selecting the most appropriate antimicrobials, and hindering the future development of drug resistance. Therapy Having a basic knowledge of antimicrobial function and how to use diagnostics to direct therapeutic treatment is paramount in managing this patient population. Diagnostic testing is not always available at the time of initiation of antimicrobial therapy, so empiric selections are often necessary. These empiric choices should be made based on the location of the infection and the most likely infecting bacteria. Prognosis Studies have demonstrated the importance of moving away from a "one dose fits all" approach to antimicrobial therapy. Instead there has been a move toward an individualized approach that takes into consideration the pharmacokinetic and pharmacodynamic variabilities that can occur in critically ill patients.

Procedural memory consolidation has been shown to enhance a variety of perceptual and motor skills during sleep, but only recently has this effect been investigated in trained musicians performing music. I tested the extent to which expected music performance skill improves over a night of sleep and to what extent the new skill memory may be fragile following initial learning. Musicians ( N = 60) learned a 13-note piano melody in individual evening training sessions under one of four practice conditions. Performance of the target melody was tested the next morning following a night of sleep. In line with previous research findings, subjects showed evidence of overnight gains in performance speed and accuracy. However, these results reveal, for the first time with musicians, that additional practice on a second, similar melody seems to inhibit these overnight gains, perhaps indicating that the overnight consolidation of new skill memories is susceptible to interference from similar tasks.

To test the extent to which learners performing a simple keyboard passage would be affected by directing their focus of attention to different aspects of their movements, 16 music majors performed a brief keyboard passage under each of four focus conditions arranged in a counterbalanced design—a total of 64 experimental sessions. As they performed the test passage, participants were directed to focus their attention on either their fingers, the piano keys, the piano hammers, or the sound produced. Complete MIDI data for all responses were digitally recorded by software written specifically for this experiment. Consistent with findings obtained in tests of other physical skills, the results show that performance was most accurate and generalizable when participants focused on the effects their movements produced rather than on the movements themselves, and that the more distal the focus of attention, the more accurate the motor control.

In two experiments, we tested the extent to which overnight procedural memory consolidation is affected by extended rest breaks during training. In the first experiment, nonmusicians practiced a 5-element keypress sequence with their nondominant hand in 12 30-s practice intervals separated by 30-s pauses. In the second experiment, nonpianist musicians practiced a 13-note keyboard melody using the same procedures. In both experiments, approximately one-third of the subjects took a 5-min break after the first three blocks of practice; another third took a break after nine blocks of practice; the remaining participants did not take an extended break. All were trained in the evening and were retested the following morning. Participants in both experiments made dramatic improvements over the course of the training and retest sessions, and participants who took an extended rest break early in practice made the largest gains in performance between the end of training and the beginning of retest.

Objective: To review the physiology of lactate production and metabolism, the causes of lactic acidosis, and the current applications of lactate monitoring in humans and animals. Data sources: Human and veterinary studies. Summary: Lactate production is the result of anaerobic metabolism. Tissue hypoxia due to hypoperfusion is the most common cause of lactic acidosis. Studies in critically ill humans have shown that serial lactate monitoring can be used to assess the severity of illness and response to therapy. Several veterinary studies have also shown lactate as a useful tool to assess severity of illness. Conclusions: Lactate measurement in critically ill veterinary patients is practical and can provide information to assess severity of illness. Further veterinary studies are needed to establish the value of serial lactate measurements for prognostic and therapeutic purposes. Information regarding lactate measurement in cats is limited, and further studies are warranted.

Ciliates have evolved highly complex and intricately controlled pathways to ensure the precise and complete removal of all genomic sequences not required for vegetative growth. At the same time, they retain a reference copy of all their genetic information for future generations. This chapter describes how different ciliates use RNA-mediated DNA comparison processes to form new somatic nuclei from germline nuclei. While these processes vary in their precise mechanisms, they all use RNA to target genomic DNA sequences—either for retention or elimination. They also all consist of more than one individual pathway acting cooperatively—the two subsets of small RNAs in Paramecium and the guide RNAs and Piwi-interacting RNAs in Oxytricha—to ensure a strong belt-and-braces approach to consistent and precise somatic nucleus development. Nonetheless, this genome comparison approach to somatic nucleus development provides an elegant method for trans-generational environmental adaptation. Conceptually, it is easy to imagine how somatic changes that occur during vegetative growth could be transferred to meiotic offspring, while an unaltered germline genome is retained. Further research in this area will have far-reaching implications for the trans-generational adaptation of more distantly related eukaryotes, such as humans.

Factors affecting the development of the embryos and production of larvae of the spiny lobster Sagmariasus verreauxi were investigated. Mature lobsters were collected from the fishery in New Zealand and held in captivity until they moulted, mated, and extruded eggs. For females, moulting took place in winter (July/August) and mating occurred 58–88 days later in early spring. The ovigerous females were then held at three temperatures and embryo development monitored at approximately weekly intervals. Mean times to hatch were 55, 75, and 130 days at 20°C, 17°C, and 13°C respectively. The total number of larvae that hatched from each female ranged from 0.97 to 1.4 million. The theoretical temperature at which embryo development ceases (a biological zero) for S. verreauxi, of 9.4°C, was calculated from data on the appearance of the median eye, the eyes and the chromatophores, and the time to hatch. An eye index formula was also derived to allow prediction of time to hatch at a range of temperatures u...

The paternally expressed imprinted Retrotransposon-like 1 (Rtl1/Peg11) is a retrotransposon-derived gene that has evolved a function in eutherian placentation. Seven miRNAs, including miR-127, are processed from a maternally expressed antisense Rtl1 transcript (Rtl1as) and regulate Rtl1 levels through RNAi-mediated post-transcriptional degradation. To determine the relative functional role of Rtl1as miRNAs in Rtl1 dosage, we generated a mouse specifically deleted for miR-127. The miR-127 knockout mice exhibit placentomegaly with specific defects within the labyrinthine zone involved in maternal-fetal nutrient transfer. Although fetal weight is unaltered, specific Rtl1 transcripts and protein levels are increased in both the fetus and placenta. Phenotypic analysis of single (ΔmiR-127/Rtl1 or miR-127/ΔRtl1) and double (ΔmiR-127/ΔRtl1) heterozygous miR-127 and Rtl1 deficient mice indicate that Rtl1 is the main target gene of miR-127 in placental development. Our results demonstrate that miR-127 is an essential regulator of Rtl1 mediated by a trans-homologue interaction between reciprocally imprinted genes on the maternally and paternally inherited chromosomes.

Balamuthia mandrillaris is a free-living amoeba that can cause granulomatous amebic encephalitis (GAE). We report a case in an individual with a history of alcohol abuse, cocaine use, and ditch water exposure. This is the first reported case of GAE due to B mandrillaris in New Mexico.

Nontuberculous mycobacteria (NTM) are becoming increasingly important cutaneous pathogens as the number of susceptible patients increases. Nevertheless, primary cutaneous infection by one particular species, Mycobacterium avium complex (MAC), remains relatively unusual, particularly in immunocompetent patients. We review the English-language literature on primary cutaneous MAC in patients who were neither immunocompromised nor pharmacologically immunosuppressed. We offer an additional report of a healthy patient who presented to our clinic with primary cutaneous MAC following seemingly innocuous trauma to the leg.

MicroRNAs (miRs) recently emerged as prominent regulators of cancer processes. In the current study we aimed at elucidating regulatory pathways and mechanisms through which miR-494, one of the miR species found to be down-regulated in cholangiocarcinoma (CCA), participates in cancer homeostasis. miR-494 was identified as down-regulated in CCA based on miR arrays. Its expression was verified with quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). To enforce miR expression, we employed both transfection methods, as well as a retroviral construct to stably overexpress miR-494. Up-regulation of miR-494 in cancer cells decreased growth, consistent with a functional role. mRNA arrays of cells treated with miR-494, followed by pathway analysis, suggested that miR-494 impacts cell cycle regulation. Cell cycle analyses demonstrated that miR-494 induces a significant G1/S checkpoint reinforcement. Further analyses demonstrated that miR-494 down-regulates multiple molecules involved in this transition checkpoint. Luciferase reporter assays demonstrated a direct interaction between miR-494 and the 3′-untranslated region of cyclin-dependent kinase 6 (CDK6). Last, xenograft experiments demonstrated that miR-494 induces a significant cancer growth retardation in vivo. Conclusion: Our findings demonstrate that miR-494 is down-regulated in CCA and that its up-regulation induces cancer cell growth retardation through multiple targets involved in the G1-S transition. These findings support the paradigm that miRs are salient cellular signaling pathway modulators, and thus represent attractive therapeutic targets. miR-494 emerges as an important regulator of CCA growth and its further study may lead to the development of novel therapeutics. (HEPATOLOGY 2011)