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OBJECTIVE: to present the evidence for inclusion of selected midwifery tasks (skills) as essential practice competencies for midwives throughout the world. The tasks addressed are those presented to the International Confederation of Midwives (ICM) Council of Delegates in 2002 for discussion and adoption, based on the fact that during field-testing, notable variance was encountered. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: evidence-based practice should be characterised by the use of best practices derived from rigorous research, combined with and balanced by client perspectives and the expert judgement based on the critical thinking of the clinician. Much of midwifery practice is considered an art based on common sense, tradition, and woman-centred approaches to caring, as most of the women who seek midwifery care are healthy and require a health-promotion model of care that may not easily lend itself to examination by scientists or clinicians. However, when intervention is indicated to save the lives of mother, baby, or both, those interventions must be based on the best available evidence from a variety of sources leading to the most effective choices for action. The ICM Essential Competencies for Midwifery Practice (2002) are based on evidence derived from a variety of quantitative and qualitative methodologies. Expert clinical consensus may serve as to the best form of evidence at certain points in the evolution of knowledge. Every midwife needs to understand where the gaps exist in supporting traditional practices that have yet to be fully examined in a scientific manner. In summary, a multi-matrix or triangulated approach may be most appropriate to the delineation of evidence underpinning best midwifery practice. [ABSTRACT FROM AUTHOR]

Background: Right ventricular dysfunction (RVD) is an important prognostic factor in several cardiac conditions, including acute and chronic heart failure. The impact of baseline RVD on clinical outcomes of patients undergoing high-risk percutaneous coronary intervention (HRPCI) supported by Impella is unknown., Methods: Patients from the single-arm, multicenter PROTECT III study of Impella-supported HRPCI were stratified based on the presence or absence of RVD. RVD was quantitatively assessed by an echocardiography core laboratory and was defined as fractional area change < 35%, tricuspid annular plane systolic excursion < 17 mm or pulsed-wave Doppler S-wave of the lateral tricuspid annulus < 9.5 cm/s. Procedural outcomes, 90-day major adverse cardiac and cerebrovascular events (MACCE: the composite of all-cause mortality, myocardial infarction, stroke/TIA, and repeat revascularization), and 1-year mortality were assessed., Results: Of the 239 patients who underwent RV function assessment, 124 were found to have RVD. Lower left ventricular ejection fraction, higher blood urea nitrogen levels, and more severe RV dilation were independently associated with RVD. The incidence of hypotensive episodes during PCI, the proportion of patients requiring prolonged Impella support, the completeness of revascularization, and the rate of in-hospital mortality did not differ significantly between patients with vs without RVD. However, 90-day MACCE rates were higher in those with RVD, and RVD was a robust predictor of 1-year mortality in multivariable Cox-regression analyses., Conclusion: In patients undergoing HRPCI with Impella, RVD was associated with more advanced biventricular failure. The use of Impella support during HRPCI facilitated effective revascularization, even in those with concomitant RVD. Nevertheless, RVD was associated with unfavorable long-term prognoses., Competing Interests: Disclosures AJL has received speaker fees from Keystone Heart. BR has received consultant fees from Pfizer and Boehringer Ingelheim. JFG is the cofounder of Cephea Valve Technologies (Abbott) and is the president and CEO of Cardiovascular Research Foundation. ASB reports consulting and speaker fees from Abiomed, Shockwave Medical, and Cardiovascular Systems. MBB has been a consultant/speaker for Abiomed, Boston Scientific, Chiesi, Saranas, and Zoll. WWO reports grant/research support from St. Jude Medical, Edwards Life Sciences and Biomed, consulting fees/honoraria from Medtronic and Abiomed, and major stock shareholder/equity in Synecor, Accumed, Neovasc, Tendyne, and Mitralign. DB has received institutional grants from Abiomed, Ancora Heart, and Fire-1, and consulting fees from PVLoops and Axon Therapeutics. All other authors report no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Our understanding of the complexity of forces at play in the rise of major angiosperm lineages remains incomplete. The diversity and heterogeneous distribution of most angiosperm lineages is so extraordinary that it confounds our ability to identify simple drivers of diversification. Using machine learning in combination with phylogenetic modelling, we show that five separate abiotic and biotic variables significantly contribute to the diversification of Cactaceae. We reconstruct a comprehensive phylogeny, build a dataset of 39 abiotic and biotic variables, and predict the variables of central importance, while accounting for potential interactions between those variables. We use state-dependent diversification models to confirm that five abiotic and biotic variables shape diversification in the cactus family. Of highest importance are diurnal air temperature range, soil sand content and plant size, with lesser importance identified in isothermality and geographic range size. Interestingly, each of the estimated optimal conditions for abiotic variables were intermediate, indicating that cactus diversification is promoted by moderate, not extreme, climates. Our results reveal the potential primary drivers of cactus diversification, and the need to account for the complexity underlying the evolution of angiosperm lineages., (© 2024. The Author(s).)

There is growing interest in intercropping as a practice to increase productivity per unit area and ecosystem functioning in agricultural systems. Relay intercropping with soy and winter wheat may benefit soil health due to increased diversity and longer undisturbed soil cover, yet this remains largely unstudied. Using a field experiment in Eastern Germany, we studied the temporal dynamics of chemical, biological, and physical indicators of soil health in the topsoil over a year of cultivation to detect early effects of soy-wheat relay intercropping compared to sole cropping. Indicators included microbial abundance, permanganate-oxidizable carbon, carbon fractions, pH, and water infiltration. Relay intercropping showed no unique soil health benefits compared to sole cropping, likely affected by drought that stressed intercropped soy. Relay intercropping did, however, maintain several properties of both sole crops including an increased MAOM C:N ratio and higher soil water infiltration. The MAOM C:N ratio increased by 4.2 and 6.2% in intercropping and sole soy and decreased by 5% in sole wheat. Average near-saturated soil water infiltration rates were 12.6, 14.9, and 6.0 cm hr -1 for intercropping, sole wheat, and sole soy, respectively. Cropping system did not consistently affect other indicators but we found temporal patterns of these indicators, showing their sensitivity to external changes., (© 2024. The Author(s).)

Background: Anemia is prevalent among patients with cardiovascular disease and is associated with adverse outcomes. However, data regarding the impact of anemia in high-risk percutaneous coronary intervention (HRPCI) are limited., Objectives: This study aimed to evaluate the impact of anemia in patients undergoing Impella-supported HRPCI in the PROTECT III study., Methods: Patients undergoing Impella-supported HRPCI in the multicenter PROTECT III study were assessed for anemia based on baseline hemoglobin levels according to World Health Organization criteria. Patients were stratified into three groups, namely, no anemia, mild anemia, and moderate or severe anemia. Major adverse cardiovascular and cerebrovascular events (MACCE: all-cause death, myocardial infarction, stroke/transient ischemic attack, and repeat revascularization) at 30 and 90 days, and major bleeding events were compared across groups., Results: Of 1,071 patients with baseline hemoglobin data, 37.9% had no anemia, 43.4% had mild anemia, and 18.7% had moderate or severe anemia. Anemic patients were older and more likely to have comorbidities. Anemia was associated with higher MACCE rates at 30 days (moderate to severe, 12.3%; mild, 9.8%; no anemia, 5.4%; p  = 0.02) and at 90 days (moderate to severe, 18.7%; mild, 14.6%; none, 8.3%; p  = 0.004). These differences persisted after adjustment for potential confounders at 30 and 90 days, and sensitivity analysis excluding dialysis showed similar results. Major bleeding at 30 days was also higher in anemic patients (5.5% vs. 1.2%, p  = 0.002)., Conclusion: Baseline anemia in Impella-supported HRPCI is common and independently associated with MACCE and major bleeding, emphasizing its significance as a prognostic factor . Specific management strategies to reduce anemia-associated MACCE risk after HRPCI should be examined. Clinical Trial Information Trial Name: The Global cVAD Study (cVAD)ClinicalTrial.gov Identifier: NCT04136392URL: https://clinicaltrials.gov/ct2/show/NCT04136392?term=cvad&draw=2&rank=2., Competing Interests: BR reports consultant fees from Pfizer and Boehringer Ingelheim. ASB reports consulting and speaker fees from Abiomed, Shockwave Medical, and Cardiovascular Systems, Inc. MBB discloses consultant/speaker fees from Abiomed, Boston Scientific, Chiesi, Saranas, and Zoll. RAGP reports consultant/speaker fees from Abiomed; speaker honoraria Boston Scientific. WBB reports consultant fees from Abbott, Medtronic, Abiomed, and Boston Scientific. CLG reports participation on the advisory boards for Philips and Abiomed. WWO reports grant/research support from St. Jude Medical, Edwards Lifesciences, and BioMed; consulting fees/honoraria from Medtronic and Abiomed; and major stock shareholder/equity in Synecor, Accumed, Neovasc, Tendyne, and Mitralign. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Falah, Redfors, Zhao, Bharadwaj, Basir, Thompson, Patel, Schonning, Abu-Much, Zhang, Batchelor, Grines and O'Neill.)

Competing Interests: Declaration of competing interest Dr. Bharadwaj reports consulting and speaker fees from Abiomed, Shockwave Medical, and Cardiovascular Systems, Inc. Dr. Truesdell reports consultant fees from Abiomed, Inc., and speaker's bureau membership for Abiomed, Inc. Dr. Lemor reports speaker fees from Abiomed. Dr. Cohen has received research grant support from Edwards Lifesciences, Abbott, Boston Scientific, Corvia Medical, Philips, Brain-Q, Saranas, Zoll Medical, CathWorks, and ANCORA, and has received consultant fees from Medtronic, Edwards Lifesciences, Abbott, Boston Scientific, Corvia Medical, Impulse Dynamics, AngioInsight, and HeartBeam. Dr. Lansky has received speaker fees from Keystone Heart. Dr. O'Neill reports grant/research support from St. Jude Medical, Edwards Life Sciences, and Biomed; consulting fees/honoraria from Medtronic and Abiomed; and major stock shareholder/equity in Synecor, Accumed, Neovasc, Tendyne, and Mitralign. The remaining authors have no competing interests to declare.

Background: Patients with complex coronary artery disease, as defined by high SYNTAX scores, undergoing percutaneous coronary intervention (PCI) have poorer outcomes when compared with patients with lower SYNTAX I scores. This study aimed to assess if mechanical circulatory support using Impella mitigates the effect of the SYNTAX I score on outcomes after high-risk percutaneous coronary intervention (HRPCI)., Methods: Using data from the PROTECT III study, patients undergoing Impella-assisted HRPCI between March 2017 and March 2020 were divided into 3 cohorts based on SYNTAX I score-low (≤22), intermediate (23-32), and high (≥33). Procedural and clinical outcomes out to 90 days were compared between groups. Multivariable regression analysis was used to assess the impact of SYNTAX I score on major adverse cardiovascular and cerebrovascular events (MACCE) at 90 days., Results: A total of 850 subjects with core laboratory-adjudicated SYNTAX I scores were identified (low: n = 310; intermediate: n = 256; high: n = 284). Patients with high SYNTAX I scores were older than those with low or intermediate SYNTAX I scores (72.7 vs 69.7 vs 70.1 years, respectively; P < .01). After adjustment for covariates, high SYNTAX I score remained a significant predictor of 90-day MACCE (hazard ratio [HR], 2.14; 95% CI, 1.42-3.69; P < .01 vs low), whereas intermediate SYNTAX I score was not (HR, 0.92; 95% CI, 0.47-1.77; P = .80 vs low). These findings persisted after adjustment for post-PCI SYNTAX I score., Conclusions: A high SYNTAX I score was associated with higher rates of 90-day MACCE in patients who underwent Impella-assisted HRPCI. Further research is needed to understand the patient and procedural factors driving this finding., (© 2024 The Author(s).)

Background: There are limited data on the clinical characteristics and outcomes of patients who require prolonged mechanical circulatory support (MCS) after Impella-supported high-risk percutaneous coronary intervention (HR-PCI)., Aims: The aim of this study is to describe the contemporary clinical characteristics, outcomes, and predictors associated with prolonged MCS support after assisted HR-PCI., Methods: Patients enrolled in the prospective, multicentre, clinical endpoint-adjudicated PROTECT III study who had undergone HR-PCI using Impella were evaluated. Patient and procedural characteristics and outcomes for those who received prolonged MCS beyond the duration of their index procedure were compared to those in whom MCS was successfully weaned and explanted at the conclusion of the index PCI., Results: Among 1,155 patients who underwent HR-PCI with Impella between 2017 and 2020 and had sufficient data to confirm the duration of Impella support, 16.5% received prolonged MCS (mean duration 25.2±31.1 hours compared with 1.8±5.8 hours for those who only received intraprocedural MCS). Patients receiving prolonged support presented with more urgent indications (e.g., acute coronary syndromes [ACS], lower ejection fraction [EF], elevated baseline heart rate and lower systolic blood pressure). Use of the Impella CP, intraprocedural complications, periprocedural complications and in-hospital mortality were all more common amongst the prolonged MCS group. Prolonged MCS was associated with increased rates of major adverse cardiovascular and cerebrovascular events, cardiovascular death, and all-cause mortality at 90-day follow-up., Conclusions: Patients receiving prolonged MCS after Impella-supported HR-PCI presented with more ACS, reduced EF and less favourable haemodynamics. Additionally, they were more likely to experience intraprocedural and periprocedural complications as well as increased in-hospital and post-discharge mortality.

The Cretaceous-Palaeogene mass extinction event (K-Pg) witnessed upwards of 75% of animal species going extinct, most notably among these are the non-avian dinosaurs. A major question in macroevolution is whether this extinction event influenced the rise of flowering plants (angiosperms). The fossil record suggests that the K-Pg event had a strong regional impact on angiosperms with up to 75% species extinctions, but only had a minor impact on the extinction rates of major lineages (families and orders). Phylogenetic evidence for angiosperm extinction dynamics through time remains unexplored. By analysing two angiosperm mega-phylogenies containing approximately 32 000-73 000 extant species, here we show relatively constant extinction rates throughout geological time and no evidence for a mass extinction at the K-Pg boundary. Despite high species-level extinction observed in the fossil record, our results support the macroevolutionary resilience of angiosperms to the K-Pg mass extinction event via survival of higher lineages.

Although climate change has been implicated as a major catalyst of diversification, its effects are thought to be inconsistent and much less pervasive than localized climate or the accumulation of species with time. Focused analyses of highly speciose clades are needed in order to disentangle the consequences of climate change, geography, and time. Here, we show that global cooling shapes the biodiversity of terrestrial orchids. Using a phylogeny of 1,475 species of Orchidoideae, the largest terrestrial orchid subfamily, we find that speciation rate is dependent on historic global cooling, not time, tropical distributions, elevation, variation in chromosome number, or other types of historic climate change. Relative to the gradual accumulation of species with time, models specifying speciation driven by historic global cooling are over 700 times more likely. Evidence ratios estimated for 212 other plant and animal groups reveal that terrestrial orchids represent one of the best-supported cases of temperature-spurred speciation yet reported. Employing >2.5 million georeferenced records, we find that global cooling drove contemporaneous diversification in each of the seven major orchid bioregions of the Earth. With current emphasis on understanding and predicting the immediate impacts of global warming, our study provides a clear case study of the long-term impacts of global climate change on biodiversity.

Background: Pathologic response at the time of surgery after neoadjuvant therapy for HER2 positive early breast cancer impacts both prognosis and subsequent adjuvant therapy. Comprehensive descriptions of the tumor microenvironment (TME) in patients with HER2 positive early breast cancer is not well described. We utilized standard stromal pathologist-assessed tumor infiltrating lymphocyte (TIL) quantification, quantitative multiplex immunofluorescence, and RNA-based gene pathway signatures to assess pretreatment TME characteristics associated pathologic complete response in patients with hormone receptor positive, HER2 positive early breast cancer treated in the neoadjuvant setting., Methods: We utilized standard stromal pathologist-assessed TIL quantification, quantitative multiplex immunofluorescence, and RNA-based gene pathway signatures to assess pretreatment TME characteristics associated pathologic complete response in 28 patients with hormone receptor positive, HER2 positive early breast cancer treated in the neoadjuvant setting., Results: Pathologist-assessed stromal TILs were significantly associated with pathologic complete response (pCR). By quantitative multiplex immunofluorescence, univariate analysis revealed significant increases in CD3+, CD3+CD8-FOXP3-, CD8+ and FOXP3+ T-cell densities as well as increased immune cell aggregates in pCR patients. In subsets of paired pre/post-treatment samples, we observed significant changes in gene expression signatures in non-pCR patients and significant decreases in CD8+ densities after treatment in pCR patients. No RNA based pathway signature was associated with pCR., Conclusion: TME characterization HER2 positive breast cancer patients revealed several stromal T-cell densities and immune cell aggregates associated with pCR. These results demonstrate the feasibility of these novel methods in TME evaluation and contribute to ongoing investigations of the TME in HER2+ early breast cancer to identify robust biomarkers to best identify patients eligible for systemic de-escalation strategies., (Copyright © 2022. Published by Elsevier Inc.)

Assessing the role of cannabinoid (CB) receptors in behavior is relevant given the trend toward the legalization of medicinal and recreational marijuana. The present research aims at bridging a gap in our understanding of CB-receptor function in animal models of frustrative nonreward. These experiments were designed to (1) determine the effects of chronic administration of the nonselective CB1-receptor agonist WIN 55,212-2 (WIN) on reward downshift in rats and (2) determine whether the effects of chronic WIN were reducible to acute effects. In Experiment 1, chronic WIN (7 daily injections, 10 mg/kg, ip) accelerated the recovery of consummatory behavior after a 32-to-4% sucrose downshift relative to vehicle controls. In addition, chronic WIN eliminated the preference for an unshifted lever when the other lever was subject to a 12-to-2 pellet downshift in free-choice trials, but only in animals with previous experience with a sucrose downshift. In Experiment 2, acute WIN (1 mg/kg, ip) reduced consummatory behavior, but did not affect recovery from a 32-to-4% sucrose downshift. The antagonist SR 141716A (3 mg/kg, ip) also failed to interfere with recovery after the sucrose downshift. In Experiment 3, acute WIN administration (1 mg/kg, ip) did not affect free-choice behavior after a pellet downshift, although it reduced lever pressing and increased magazine entries relative to vehicle controls. The effects of chronic WIN on frustrative nonreward were not reducible to acute effects of the drug. Chronic WIN treatment in rats, like chronic marijuana use in humans, seems to increase resistance to the effects of frustrative nonreward., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Pacific lamprey (Entosphenus tridentatus) are important anadromous fish throughout their range in western North America. As conservation programs for lamprey expand, disease surveillance is becoming more prevalent. During routine surveillance, Yersinia ruckeri biotype II was isolated from Pacific lamprey. This is the first documented Y. ruckeri detection in Pacific lamprey., (© Wildlife Disease Association 2021.)

Rodents are generally reluctant to consume high concentrations of alcohol. However, few experiments have reported the behavior of rats when they are given access to high alcohol concentrations. Four experiments with food-deprived Wistar rats were designed to determine whether 66% alcohol could be used as a positive reinforcer for operant responses. In Experiment 1, animals learned to lick an empty sipper to gain access to 66% alcohol in a second tube; licking extinguished after it if provided a only access to water (operant licking task, OL). Experiment 2 used the OL task combined with a progressive ratio (PR) schedule in a within-subject design with the order of alcohol concentrations counterbalanced across subjects. The breakpoint (the last completed ratio in the PR schedule) was higher for 10% and 66% alcohol concentrations than for water. In Experiment 3, animals trained in the same PR task gained access to water, 10%, or 66% alcohol in a between-subject design. Breakpoints were higher for 66% alcohol than for water, but not for 10% alcohol relative to water. Experiment 4 tested the effects of the orexin-1 receptor antagonist SB-334,867 on licking reinforced with access to 66% alcohol in the PR task. The antagonist reduced the breakpoint at 1- and 5-mg/kg doses, but not at 10 mg/kg. These results suggest that 66% alcohol can be used to reinforce operant behavior. Although the effects were modest, they were reliable. The estimated amount of alcohol consumed in the OL task suggests that these reinforcing effects were not dependent on the pharmacological effects of 66% alcohol, but could perhaps reflect a sensation-seeking effect., (Copyright © 2021 Elsevier Inc. All rights reserved.)

After ten 5-min sessions of access to 32% sucrose, a reward downshift (RD) to 2% sucrose induces a transient rejection of the reward. Animals were segregated according to the speed of recovery from RD into Fast-recovery and Slow-recovery subgroups. Animals were subsequently trained in an operant licking (OL) task in which licking at an empty tube provided 10 s of access to a second tube containing 66% alcohol. Licking on the first tube was subjected to a progressive ratio (PR) schedule with a step of 4 licks. Fast-recovery animals (both males and females) licked to a higher ratio than Slow-recovery animals. Animals were also exposed to a well-lit open field (OF) for 20 min. Fast- and Slow-recovery males and females exhibited equal levels of activity in the OF. Tissue samples from tails were assessed for two well-known allelic variations of the human opioid receptor gene, OPRM1, known to affect mu opioid sensitivity: The C17T and A118G single nucleotide polymorphisms. There was no evidence of a relationship between genotype and behavior, suggesting that these genetic mechanisms in humans do not account for the individual differences in recovery from RD and OL for alcohol in rats., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Sleep deprivation has been shown to negatively impact health outcomes, leading to decreased immune responses, memory loss, increased activity of stress and inflammatory pathways, weight gain, and even behavioral changes. These observations suggest that sleep deprivation substantially interferes with important physiological functions, including metabolic pathways of energy utilization. Many of those phenotypes are correlated with age, suggesting that disrupted sleep may interfere with the aging process. However, little is known about how sleep disruption affects aging and longevity. Here, we investigate this relationship using eight representative fruit fly lines from the Sleep Inbred Panel (SIP). The SIP consists of 39 inbred lines that display extreme short- and long-sleep patterns, and constitutes a crucial Drosophila community resource for investigating the mechanisms of sleep regulation. Our data show that flies with short-sleep periods have ∼16% longer life span, as well as reduced aging rate, compared to flies with long-sleep. In contrast, disrupting normal circadian rhythm reduces fly longevity. Short-sleep SIP flies moreover show slight metabolic differences to long-sleep lines, and to flies with disrupted circadian rhythm. These data suggest that the inbred SIP lines engage sleep mechanisms that are distinct from the circadian clock system., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Objective: To explore how the International Confederation of Midwives Global Standards for Midwifery Education are currently used and their influence, if any, on the development of education programs globally. Secondarily, to identify current challenges to midwifery education., Design: Cross-sectional exploratory descriptive qualitative study using focus groups and one-on-one interviews to collect data about knowledge of and use of the Education Standards and participants perceived current challenges to midwifery education. Interviews conducted in English, Spanish, and French., Setting and Participants: Midwife educators, education directors, or regulators attending one of four national/international conferences or one-on-one interviews in person or via internet. Thematic analysis was employed using the Framework approach for data analysis., Findings: There were 11 focus groups and 19 individual interviews involving 145 midwives from 61 countries. There was a general awareness of the Education Standards amongst the participants although knowledge about the specifics of the document was lacking. The Standards were mainly used as a reference and greater use was made when developing new educational programs. The Standards identified as most difficult to meet included: organization and administration of the program, ensuring that teachers were formally prepared as teachers, meeting targets for teacher to student ratios and that 50% of educational time took place in the clinical setting. Universally endorsed challenges to midwifery education were: 1) inability to accommodate the increase in curricular content without compromising prior content or lengthening programs; 2) insufficient resources including lack of classroom and clinical teachers; 3) medicalization of childbirth and health system changes limiting student exposure to the midwifery care model; 4) role conflict and competition for clinical experience with other health professionals., Key Conclusions: The Education Standards need to be more widely disseminated and implemented. Stronger collaborations with clinical settings and government systems are required to solve the current challenges to midwifery education., Implication of Practice: Well-educated midwives can provide the majority of maternal and neonatal care, however it will require an investment in strengthening midwifery programs globally for this goal to be achieved., (Copyright © 2019. Published by Elsevier Ltd.)

Rats exposed to unexpected reward loss increase voluntary oral consumption of ethanol. Such consumption has been assumed to attenuate loss-induced negative affect (called emotional self-medication). To test this assumption, food-deprived male Wistar rats were exposed to 10 sessions of access to 32% sucrose followed by 5 sessions of access to 4% sucrose (reward downshift). A two-bottle preference test was initiated immediately after each consummatory session to assess ethanol intake. The experimental group received access to 2% ethanol and water, whereas the control group received access to two water bottles. On sessions 11, 12, and 15, immediately after the preference test, animals were tested in the elevated plus maze (EPM) for signs of anxiety. Sucrose consumption was reduced after the 32-to-4% sucrose downshift on sessions 11 and 12, but behavior recovered by session 15. Consummatory suppression was followed by increased ethanol intake in the preference test after sessions 11 and 12, but intake was reduced to preshift levels by session 15; no changes were observed in water controls. Finally, general activity (closed-arm entries and total arm entries) in the EPM increased in the ethanol group on session 12, but not on session 15, relative to water controls. The increase in ethanol consumption induced by reward downshift had measurable effects on activity as assessed in the EPM. These results show that voluntary oral 2% ethanol consumption after reward downshift can affect subsequent behavior, but fall short of providing unambiguous evidence that such ethanol consumption reduces negative affect., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Premise of the Study: Field methodology and image analysis protocols using acoustic tomography were developed and evaluated as a tool to estimate the amount of internal decay and damage of living trees, with special attention to tropical rainforest trees with irregular trunk shapes., Methods and Results: Living trunks of a diversity of tree species in tropical rainforests in the Republic of Panama were scanned using an Argus Electronic PiCUS 3 Sonic Tomograph and evaluated for the amount and patterns of internal decay. A protocol using ImageJ analysis software was used to quantify the proportions of intact and compromised wood. The protocols provide replicable estimates of internal decay and cavities for trees of varying shapes, wood density, and bark thickness., Conclusions: Sonic tomography, coupled with image analysis, provides an efficient, noninvasive approach to evaluate decay patterns and structural integrity of even irregularly shaped living trees.

A series of N1 acetamide substituted naphthyridinone HIV-1 integrase inhibitors have been explored to understand structure-activity relationships (SAR) with various C3 amide groups. Investigations were evaluated using integrase enzyme inhibition, antiviral activity and protein binding effects to optimize the sub-structures. Lipophilicity was also incorporated to understand ligand lipophilic efficiency as a function of the structural modifications. Three representative analogs were further examined in a peripheral blood mononuclear cell (PBMC) antiviral assay as well as in vitro and in vivo drug metabolism and pharmacokinetic studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Splenosis is a rare occurrence that is defined as autotransplantation of splenic tissue usually after splenic rupture due to trauma and subsequent splenectomy. Although splenosis most commonly occurs in the abdomen, the authors report a rare case of thoracic splenosis after remote thoracoabdominal trauma. A 62-year-old woman was found to have lower-lobe, pleural-based nodular lesions in juxtaposition to the posteromedial segment of the lung during workup for an abdominal hernia. Surgical excision of the mass confirmed the diagnosis of ectopic splenic tissue, and splenosis was diagnosed. This woman was among the rare 18% of people who are found to have splenosis in the intrathoracic space. In the workup of pulmonary nodules in patients with a history of trauma, splenosis should be a consideration.

Background: many articles published in the decade since promulgation of the Millennium Development Goals have acknowledged the distinct advantages to maternal and newborn health outcomes that can be achieved as a result of expanding access to skilled birth attendant (including midwifery) services. However, these advantages are often predicated on the assumption that the midwifery workforce shares a common definition and identity. Regrettably, a clear delineation of midwifery competencies is rarely addressed. A core set of midwifery competencies is essential to providing the high quality services that lead to the desirable health outcomes described in that body of research. Attribution of improved outcomes to access to midwifery cannot be made without a common understanding of a defined set of services provided to standard by the midwifery workforce across the inter-conceptional and childbearing time frame. The International Confederation of Midwives (ICM) has developed a clear list of competencies that delineate the domains of practice for the fully qualified, professional midwife. These domains frame the educational outcomes that must be conveyed within competency-based education programmes., Purpose: this article explores the concept of competency-based education for midwives; first exploring the concept of competency itself, then providing examples of what is already known about competency-based approaches to curriculum design, teacher preparation, teacher support and assessment of student learning. These concepts are linked to the ICM competencies as the unifying construct for education of individuals who share a common definition and identity as midwives., (© 2013 Elsevier Ltd. All rights reserved.)

Substituent effects of a series of N1 protio and methyl naphthyridinone HIV-1 integrase strand-transfer inhibitors has been explored. The effects of combinations of the N1 substituent and C3 amide groups was extensively studied to compare enzyme inhibition, antiviral activity and protein binding effects on potency. The impact of substitution on ligand efficiency was considered and several compounds were advanced into in vivo pharmacokinetic studies ultimately leading to the clinical candidate GSK364735., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

GPR119 is a 7-transmembrane receptor that is expressed in the enteroendocrine cells in the intestine and in the islets of Langerhans in the pancreas. Indolines and 6,7-dihydro-5H-pyrrolo[2,3-a]pyrimidines were discovered as G protein-coupled receptor 119 (GPR119) agonists, and lead optimization efforts led to the identification of 1-methylethyl 4-({7-[2-fluoro-4-(methylsulfonyl)phenyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)-1-piperidinecarboxylate (GSK1104252A) (3), a potent and selective GPR119 agonist. Compound 3 showed excellent pharmacokinetic properties and sufficient selectivity with in vivo studies supporting a role for GPR119 in glucose homeostasis in the rodent. Thus, 3 appeared to modulate the enteroinsular axis, improve glycemic control, and strengthen previous suggestions that GPR119 agonists may have utility in the treatment of type 2 diabetes.

Objective: Shared decision making is widely recognized to facilitate effective health care. The purpose of this study was to assess the applicability and usefulness of a scale to measure the presence and extent of shared decision making in clinical decisions in psychiatric practice., Methods: A coding scheme assessing shared decision making in general medical settings was adapted to mental health settings, and a manual for using the scheme was created. Trained raters used the adapted scale to analyze 170 audio-recordings of medication check-up visits with either psychiatrists or nurse practitioners. The scale assessed the level of shared decision making based on the presence of nine specific elements. Interrater reliability was examined, and the frequency with which elements of shared decision making were observed was documented. The association between visit length and extent of shared decision making was also examined., Results: Interrater reliability among three raters on a subset of 20 recordings ranged from 67% to 100% agreement for the presence of each of the nine elements of shared decision making and 100% for the agreement between provider and consumer on decisions made. Of the 170 sessions, 128 (75%) included a clinical decision. Just over half of the decisions (53%) met minimum criteria for shared decision making. Shared decision making was not related to visit length after the analysis controlled for the complexity of the decision., Conclusions: The rating scale appears to reliably assess shared decision making in psychiatric practice and could be helpful for future research, training, and implementation efforts.

Aim: The aim of the present study was to investigate the relative importance of a wide array of patient demographic, procedural, anatomic and perioperative variables as potential risk factors for early saphenous vein graft (SVG) thrombosis after coronary artery bypass graft (CABG) surgery., Methods: The patency of 611 SVGs in 291 patients operated on at four different hospitals enrolled in the Reduction in Graft Occlusion Rates (RIGOR) study was assessed six months after CABG surgery by multidetector computed tomography coronary angiography or clinically-indicated coronary angiography. The odds of graft occlusion versus patency were analyzed using multilevel multivariate logistic regression with clustering on patient., Results: SVG failure within six months of CABG surgery was predominantly an all-or-none phenomenon with 126 (20.1%) SVGs totally occluded, 485 (77.3%) widely patent and only 16 (2.5%) containing high-grade stenoses. Target vessel diameter ≤ 1.5 mm (adjusted OR 2.37, P=0.003) and female gender (adjusted OR 2.46, P=0.01) were strongly associated with early SVG occlusion. In a subgroup analysis of 354 SVGs in which intraoperative graft blood flow was measured, lower mean flow was also significantly associated with SVG occlusion when analyzed as a continuous variable (adjusted OR 0.984, P=0.006) though not when analyzed dichotomously, <40 mL/min versus ≥ 40 mL/min (adjusted OR 1.86, P=0.08)., Conclusion: Small target vessel diameter, female gender and low mean graft blood flow are significant risk factors for SVG thrombosis within six months of CABG surgery in patients on postoperative aspirin therapy. This information may be useful in guiding revascularization strategies in selected patients.

A series of naphthyridinone HIV-1 integrase strand-transfer inhibitors have been designed based on a psdeudo-C2 symmetry element present in the two-metal chelation pharmacophore. A combination of two distinct inhibitor binding modes resulted in potent inhibition of the integrase strand-transfer reaction in the low nM range. Effects of aryl and N1 substitutions are disclosed including the impact on protein binding adjusted antiviral activity., (Copyright © 2011. Published by Elsevier Ltd.)

Objective: a 2-year study was conducted to update the core competencies for basic midwifery practice, first delineated by the International Confederation of Midwives in 2002. A competency domain related to abortion-related care services was newly developed., Design: a modified Delphi survey process was conducted in two phases: a pilot item affirmation study, and a global field survey., Setting: a global survey conducted in 90 countries., Participants: midwifery educators or clinicians associated with midwifery education schools and programmes located in any of the ICM member association countries. Additional participants represented the fields of nursing, medicine, and midwifery regulatory authorities. A total of 232 individuals from 63 member association and five non-member countries responded to one or both of the surveys. The achieved sample represented 42% of member association countries, which was less than the 51% target. However, the sample was proportionally representative of ICM's nine global regions., Measurements: survey respondents expressed an opinion whether to retain or to delete any of 255 statements of midwifery knowledge, skill, or professional behaviour. They also indicated whether the item should be a basic (core) item of midwifery knowledge or skill that would be included as mandatory content in a programme of midwifery pre-service education, or whether the item could be added to the fund of knowledge or acquired as an additional skill by those who would need or wish to include the item within the scope of their clinical practice., Findings: a majority consensus of .85 was required to accept the item without further deliberation. An expert panel made final decisions in all instances where consensus was not achieved. The panel also amended the wording of selected items, or added new items based on feedback received from survey respondents. The final document contains 268 items organised within seven competency domains., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: a 2-year study was conducted to develop Global Standards for Midwifery Education in keeping with core documents of the International Confederation of Midwives. Elements of the standards were based on evidence available in the published and unpublished literature. Companion Guidelines to assist in implementing the standards were also developed., Design: a modified Delphi survey process was conducted in two rounds following item validation by a panel of midwifery education experts., Setting: a global survey conducted in 88 countries., Participants: midwifery educators and clinicians associated with midwifery education located in any of the ICM member association countries. Additional participants included an Expert Midwifery Resource Group, other Key Stakeholders, midwifery regulators and policy makers. A total of 241 individuals from 46 ICM member association countries and ten non-member countries responded to one or both of the survey rounds., Measurements: survey respondents expressed an opinion on whether to retain or to delete any of the proposed components of the standards. Version one had 109 proposed components and version two had 111 items for consideration., Findings: a majority consensus of .80 was required to accept an item without further deliberation. The Education Standards Task Force (expert panel) made final decisions in the four instances where this level of consensus was not reached, retaining all four items. The panel also amended the wording of selected items or added new items based on feedback received from survey respondents. The final document contains 10 Preface items, 35 glossary terms, and 37 discrete standards with 27 sub-sections., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Recent work in zebra finches suggests that genes and hormones may act together to masculinize the brain. This study tested the effects of exogenous estradiol (E2) on 17β-hydroxysteroid dehydrogenase type IV (HSD17B4) and the co-localization of HSD17B4 and androgen receptor (AR) mRNA. We asked three primary questions: First, how does post-hatching E2 treatment affect HSD17B4 mRNA expression in males and females? Second, is this gene expressed in the same cells as AR. Third, if so does E2 modulate co-expression? Female finches implanted with 50 μg of E2 on the third day post-hatching showed a significant increase in the density of cells expressing HSD17B4 and AR in HVC at day 25. Co-localization of AR cells that also expressed HSD17B4 was high across groups (>81%). We found significant sex differences in co-localization in both the HVC and Area X of control animals, with males showing a higher percentage of cells expressing AR mRNA that also expressed HSD17B4 in comparison to females. However, although E2 treatments significantly increased the number of cells expressing HSD17B4 mRNA and AR mRNA in the HVC of females, the percentage of HSD17B4 cells co-expressing AR was reduced in HVC and Area X in E2-treated animals. These results lend support to the hypothesis that genes and hormones may act in concert to modulate the sexually differentiation of the zebra finch song system. Further, the data suggest that a single hormonal mechanism cannot mimic the complex development of male singing behavior and associated song nuclei., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: This paper uses comparisons and contrasts identified during an assessment of pre-service education for midwives in three countries in sub-Saharan Africa. The purpose of the paper is to stimulate discussion about issues that must be carefully considered in the context of midwifery educational programming and the expansion of the midwifery workforce., Design and Setting: A mixed qualitative and quantitative participatory assessment was conducted in Ethiopia, Ghana and Malawi, in the context of a final review of outcomes of a USAID-funded global project (ACCESS). Quantitative surveys were distributed. Individual and focus group interviews were conducted., Participants: Participants included key informants at donor, government and policy-making levels, representatives of collaborating and supporting agencies, midwives and students in education programmes, and midwives in clinical practice., Findings: Information is presented concerning the challenges encountered by those responsible for midwifery pre-service education related to issues in programming including: pathways to midwifery, student recruitment and admission, midwifery curricula, preparation of faculty to engage in academic teaching and clinical mentorship, modes of curriculum dissemination and teaching/learning strategies, programme accreditation, qualifications for entry-into practice and the assessment of continued competence., Key Conclusions: Quality issues must be carefully considered when designing and implementing midwifery pre-service education programmes, and planning for the integration of new graduates into the health workforce. These issues, such as the availability of qualified tutors and clinical teachers, and measures for the implementation of competency-based teaching and learner-assessment strategies, are particularly relevant in countries that experience health manpower shortages., Implications for Practice: This review highlights important strategic choices that can be made to enhance the quality of pre-service midwifery education. The deployment, appropriate utilisation and increased number of highly qualified midwifery graduates can improve the quality of maternal and newborn health-care service, and reduce maternal and newborn mortality., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Whirling disease has been implicated in salmonid population declines in several western states. To determine the risk of a species or strain of salmonid to whirling disease it is critical to establish its relative susceptibility to Myxobolus cerebralis infection. Gila trout Oncorhynchus gilae and Apache trout Oncorhynchus gilae apache were exposed to various doses of M. cerebralis triactinomyxons (TAMs) in laboratory experiments. In trials conducted in consecutive years, fish were exposed to TAMs in doses ranging from 25 to 2,000/fish at ages ranging from 66 to 201 d posthatch (dph). All fish were held for 900 degree-days, and then the infection intensity of each fish was determined by histological examination. In 2002, 98% of the Gila trout died during exposure or within 48 h postexposure. Seventy-four percent of the Apache trout died before the end of the 90-d study period. Those that survived the entire study period had an average histological score of more than 4.0. In subsequent trials, the TAM dosage was decreased to 25-1,000/fish. Also, the age of the fish was increased from 66-72 dph to 89-201 dph. The survival rate increased from 16.0% to 49.1%. Average histological grades ranged from 1.6 to 4.8. Based on this data, it can be concluded that both Apache and Gila trout are highly susceptible to M. cerebralis in laboratory trials.

The medicinal chemistry and structure-activity relationships for a novel series of 7-benzyl-4-hydroxy-1,5-naphthyridin-2(1H)-one HIV-integrase inhibitors are disclosed. Substituent effects were evaluated at the N-1, C-3, and 7-benzyl positions of the naphthyridinone ring system. Low nanomolar IC(50) values were achieved in an HIV-integrase strand transfer assay with both carboxylic ester and carboxamide groups at C-3. More importantly, several carboxamide congeners showed potent antiviral activity in cellular assays. A 7-benzyl substituent was found to be critical for potent enzyme inhibition, and an N-(2-methoxyethyl)carboxamide moiety at C-3 significantly reduced plasma protein binding effects in vitro. Pharmacokinetic data in rats for one carboxamide analogue demonstrated oral bioavailability and reasonable in vivo clearance.

A scale-up of diazaindoline 1 was achieved in four stages and 32% overall yield. The key step involved rapid reductive amination of aldehyde 8 with aniline 5 by sodium triacetoxyborohydride (STAB-H) and TFA followed by ring closure of intermediate amine 9 to compound 1 in the same pot. These reaction conditions were also applied to facile reductive aminations with anilines known to have little reactivity under STAB-H/AcOH conditions. Spectral data supported the tris(trifluoroacetoxy)borohydride anion (16) as the active reducing agent.

The use of a 1,3,4-oxadiazole in combination with an 8-hydroxy-1,6-naphthyridine ring system has been shown to deliver potent enzyme and antiviral activity through inhibition of viral DNA integration. This report presents a detailed structure-activity investigation of the C5 position resulting in low nM potency for several analogs with an excellent therapeutic index.

A series of HIV-1 integrase inhibitors containing a novel metal binding motif consisting of the 8-hydroxy-1,6-naphthyridine core and either an oxadiazole or triazole has been identified. The design of the key structural components was based on a two-metal coordination pharmacophore. This report presents initial structure-activity data that shows the new chelation architecture delivers potent inhibition in both enzymatic and antiviral assays.