Alternative prioritization strategies have been proposed to safeguard biodiversity over macroevolutionary time scales. The first prioritizes the most distantly related species—maximizing phylogenetic ...diversity (PD)—in the hopes of capturing at least some lineages that will successfully diversify into the future. The second prioritizes lineages that are currently speciating, in the hopes that successful lineages will continue to generate species into the future. These contrasting schemes alsomap onto contrasting predictions about the role of slow diversifiers in the production of biodiversity over palaeontological time scales. We consider the performance of the two schemes across 10 dated species-level palaeo-phylogenetic trees ranging from Foraminifera to dinosaurs. We find that prioritizing PD for conservation generally led to fewer subsequent lineages, while prioritizing diversifiers led to modestly more subsequent diversity, compared with random sets of lineages. Importantly for conservation, the tree shape when decisions are made cannot predict which scheme will be most successful. These patterns are inconsistent with the notion that long-lived lineages are the source of new species. While there may be sound reasons for prioritizing PD for conservation, long-term species production might not be one of them.
The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study was a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic ...drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on learning and memory functions in 221 six-year-old children (including four sets of twins) whose mothers took one of these AEDs during pregnancy. Their performance was compared with that of a national sample of normally developing six year olds from the standardization sample of the Children's Memory Scale (CMS). The major results of this study indicate that the mean performance levels of children exposed to valproate were significantly below that of the children in the normal comparison group across all seven of the CMS Indexes. With one exception, this finding held up at the subtest level as well. These findings taken together with nonsignificant verbal and nonverbal forgetting scores appear to indicate that, as a group, children exposed to valproate experienced significant difficulty in their ability to process, encode, and learn both auditory/verbal as well as visual/nonverbal material. In addition, they exhibited significant difficulty holding and manipulating information in immediate auditory working memory. However, once the information was learned and stored, the valproate-exposed children appeared to be able to retrieve the information they did learn at normal levels. Finally, the processing, working memory, and learning deficits demonstrated by the valproate-exposed children are dose-related. In contrast to valproate, the findings pertaining to the children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy are less clear. Therefore, further research will be required to delineate the potential risks to learning and memory functions in children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy during pregnancy. Additional research employing larger prospective studies will be required to confirm the long-term cognitive and behavioral risks to children of mothers who are prescribed these four AEDs during pregnancy as well as to delineate any potential risks of newer AEDs and to understand the underlying mechanisms of adverse AED effects on the immature brain.
•Fetal valproate exposure is associated with difficulty with learning and working memory.•Valproate-exposed children retrieve learned information at normal levels.•Learning and memory deficits associated with fetal valproate exposure are dose-related.•Risks to learning and memory from fetal exposure to other antiepileptic drugs are unclear.
Regression of left ventricular hypertrophy (LVH) after aortic valve replacement has traditionally been measured by echocardiography. However, cardiovascular magnetic resonance (CMR) can be used to ...measure left ventricular function and mass more accurately and reproducibly. This translates into fewer patients being needed to demonstrate significant changes. The study aim was to demonstrate the feasibility of using CMR to measure left ventricular mass index (LVMI) and function in patients from a prospective randomized trial, and to compare homografts with the Medtronic Freestyle root replacement.
Among 23 patients recruited, 17 had LVMI and function (end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF)) measured pre- and postoperatively using CMR (eight homograft, nine Freestyle).
Significant regression of LVH was seen in both groups one year postoperatively (homograft LVMI 145+/-44 g/m2 preoperative versus 83+/-23 g/m2 one year postoperatively; Freestyle LVMI 140+/-28 g/m2 versus 93+/-21 g/m2, respectively). At six months there was significant regression in the xenograft group (from 140+/-28 to 106+/-22 g/m2; p <0.05) and a trend towards regression in the homograft group (from 145+/-44 to 103+/-25 g/m2; p = NS). There was also a trend towards a reduction in EDV, ESV and SV, and an increase in EF over one year in both groups.
Regression of LVH was measured using CMR in patients after aortic root replacement and coronary implantation with the homograft and Medtronic Freestyle root replacement. Despite the small number of patients studied, it was possible to demonstrate the extent and pattern of regression of left ventricular mass in the two groups.
We report three cases of dilated cardiomyopathy treated with left ventricular assist devices (LVAD), subsequently explanted. These mechanical devices are being increasingly used to support left ...ventricular function in the short and long term. We used cine and gadolinium-enhanced cardiovascular magnetic resonance (CMR) to examine the consequences of previous LVAD implantation. In all cases, there was apical akinesis and tethering on cine imaging. Early (<5 minutes) imaging after gadolinium demonstrated apical hypo-enhancement, an avascular area of scar or thrombus, while late (>10 minutes) imaging demonstrated transmural apical infarction which in one case extended into the inferior wall. The findings suggest that LVAD insertion may cause permanent myocardial fibrosis at the site of ventricular insertion, and the cases demonstrate the use of contrast-enhanced CMR in this scenario of iatrogenic ventricular scarring.
The United States Environmental Protection Agency (USEPA) is finalizing its vapor intrusion guidelines. One of the important issues related to vapor intrusion is background concentrations of volatile ...organic compounds (VOCs) in indoor air, typically attributed to consumer products and building materials. Background concentrations can exist even in the absence of vapor intrusion and are an important consideration when conducting site assessments. In addition, the development of accurate conceptual models that depict pathways for vapor entry into buildings is important during vapor intrusion site assessments. Sewer gas, either as a contributor to background concentrations or as part of the site conceptual model, is not routinely evaluated during vapor intrusion site assessments. The research described herein identifies an instance where vapors emanating directly from a sanitary sewer pipe within a residence were determined to be a source of tetrachloroethylene (PCE) detected in indoor air. Concentrations of PCE in the bathroom range from 2.1 to 190 µg/m3 and exceed typical indoor air concentrations by orders of magnitude resulting in human health risk classified as an “Imminent Hazard” condition. The results suggest that infiltration of sewer gas resulted in PCE concentrations in indoor air that were nearly two orders of magnitude higher as compared to when infiltration of sewer gas was not known to be occurring. This previously understudied pathway whereby sewers serve as sources of PCE (and potentially other VOC) vapors is highlighted. Implications for vapor intrusion investigations are also discussed.
Right ventricular (RV) coupling to the pulmonary circulation influences the response of the RV to the increased afterload caused by pulmonary hypertension (PH), which ultimately determines prognosis. ...A methodology that accounts for pulsatile flow is required when assessing ventriculo-arterial coupling. We applied wave intensity analysis (WIA) methods to assess the compliance of the main pulmonary artery (PA) in patients with or without PH and compared this to PA distensibility, RV function and clinical outcomes.
High-fidelity blood pressure and Doppler flow velocity tracings were obtained simultaneously during cardiac catheterisation for suspected PH. RV volumes, main PA distensibility and ventriculo-arterial coupling (Emax/Ea) were analysed using cardiovascular magnetic resonance.
The study included 17 PH patients and 6 controls. Wave speed, reservoir and excess pressure were higher in PH patients compared to controls (p < 0.01 for all). Waveforms relating to RV ejection, microvascular wave reflection and late systolic proximal deceleration were higher in PH patients compared to controls (p < 0.01 for all) and related to echocardiographic findings, including PA Doppler notching and shortened acceleration time. Wave speed, reservoir pressure and excess pressure were strongly correlated to main PA distensibility, RV function and Emax/Ea. A higher total pressure integral was associated with an increased risk of death (all-cause mortality).
The reservoir-excess pressure model, in combination with conventional clinical imaging, provides valuable information on the pathophysiology of PH that standard haemodynamic parameters do not. Future studies should further investigate the prognostic implications of WIA in PH, and its potential role in clinical practice.
Parkinson's disease (PD) is primarily thought of as a disease of aging. However, recent evidence points to the potential for exposure to xenobiotics during development to increase risk of PD. Here, ...we report that developmental exposure to the organochlorine pesticide heptachlor alters the dopamine system and increases neurotoxicity in an animal model of PD. Exposure of pregnant mice to heptachlor led to increased levels of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) levels at both the protein and mRNA level in their offspring. Increased DAT and VMAT2 levels were accompanied by alterations of mRNA levels of nuclear transcription factors that control dopamine neuron development and regulate DAT and VMAT2 levels in adulthood. At 12 weeks of age, control and heptachlor-exposed offspring were administered a moderate dose (2×
10
mg/kg) of the parkinsonism-inducing agent MPTP. Greater neurotoxicity as evidenced by a greater loss of striatal dopamine and potentiation of increased levels of glial fibrillary acidic protein and α-synuclein was observed in heptachlor-exposed offspring. The neurotoxicity observed was greater in the male offspring than the female offspring, suggesting that males are more susceptible to the long-term effects of developmental heptachlor exposure. These data suggest that developmental heptachlor exposure causes long-term alterations of the dopamine system thereby rendering it more susceptible to dopaminergic damage in adulthood.
Screening has become one of our best tools for early detection and prevention of cancer. The group-randomized trial is the most rigorous experimental design for evaluating multilevel interventions. ...However, identifying the proper sample size for a group-randomized trial requires reliable estimates of intraclass correlation (ICC) for screening outcomes, which are not available to researchers. We present crude and adjusted ICC estimates for cancer screening outcomes for various levels of aggregation (physician, clinic, and county) and provide an example of how these ICC estimates may be used in the design of a future trial.MethodsInvestigators working in the area of cancer screening were contacted and asked to provide crude and adjusted ICC estimates using the analysis of variance method estimator.ResultsOf the 29 investigators identified, estimates were obtained from 10 investigators who had relevant data. ICC estimates were calculated from 13 different studies, with more than half of the studies collecting information on colorectal screening. In the majority of cases, ICC estimates could be adjusted for age, education, and other demographic characteristics, leading to a reduction in the ICC. ICC estimates varied considerably by cancer site and level of aggregation of the groups.ConclusionsPreviously, only two articles had published ICCs for cancer screening outcomes. We have complied more than 130 crude and adjusted ICC estimates covering breast, cervical, colon, and prostate screening and have detailed them by level of aggregation, screening measure, and study characteristics. We have also demonstrated their use in planning a future trial and the need for the evaluation of the proposed interval estimator for binary outcomes under conditions typically seen in GRTs.
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