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"Barrett, N."
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Decadal trends in marine reserves reveal differential rates of change in direct and indirect effects
Decadal-scale observations of marine reserves suggest that indirect effects on taxa that occur through cascading trophic interactions take longer to develop than direct effects on target species. Combining and analyzing a unique set of long-term time series of ecologic data in and out of fisheries closures from disparate regions, we found that the time to initial detection of direct effects on target species (±SE) was 5.13 ± 1.9 years, whereas initial detection of indirect effects on other taxa, which were often trait mediated, took significantly longer (13.1 ± 2.0 years). Most target species showed initial direct effects, but their trajectories over time were highly variable. Many target species continued to increase, some leveled off, and others decreased. Decreases were due to natural fluctuations, fishing impacts from outside reserves, or indirect effects from target species at higher trophic levels. The average duration of stable periods for direct effects was 6.2 ± 1.2 years, even in studies of more than 15 years. For indirect effects, stable periods averaged 9.1 ± 1.6 years, although this was not significantly different from direct effects. Populations of directly targeted species were more stable in reserves than in fished areas, suggesting increased ecologic resilience. This is an important benefit of marine reserves with respect to their function as a tool for conservation and restoration.
Journal Article
Drug-specific laterality effects on frontal lobe activation of atomoxetine and methylphenidate in attention deficit hyperactivity disorder boys during working memory
The catecholamine reuptake inhibitors methylphenidate (MPH) and atomoxetine (ATX) are the most common treatments for attention deficit hyperactivity disorder (ADHD). This study compares the neurofunctional modulation and normalization effects of acute doses of MPH and ATX within medication-naive ADHD boys during working memory (WM).
A total of 20 medication-naive ADHD boys underwent functional magnetic resonance imaging during a parametric WM n-back task three times, under a single clinical dose of either MPH, ATX or placebo in a randomized, double-blind, placebo-controlled, cross-over design. To test for normalization effects, brain activations in ADHD under each drug condition were compared with that of 20 age-matched healthy control boys.
Relative to healthy boys, ADHD boys under placebo showed impaired performance only under high WM load together with significant underactivation in the bilateral dorsolateral prefrontal cortex (DLPFC). Both drugs normalized the performance deficits relative to controls. ATX significantly enhanced right DLPFC activation relative to MPH within patients, and significantly normalized its underactivation relative to controls. MPH, by contrast, both relative to placebo and ATX, as well as relative to controls, upregulated the left inferior frontal cortex (IFC), but only during 2-back. Both drugs enhanced fronto-temporo-striatal activation in ADHD relative to control boys and deactivated the default-mode network, which were negatively associated with the reduced DLPFC activation and performance deficits, suggesting compensation effects.
The study shows both shared and drug-specific effects. ATX upregulated and normalized right DLPFC underactivation, while MPH upregulated left IFC activation, suggesting drug-specific laterality effects on prefrontal regions mediating WM.
Journal Article
The Epidemiology of Invasive Group A Streptococcal Infection and Potential Vaccine Implications: United States, 2000–2004
Background. Invasive group A Streptococcus (GAS) infection causes significant morbidity and mortality in the United States. We report the current epidemiologic characteristics of invasive GAS infections and estimate the potential impact of a multivalent GAS vaccine. Methods. From January 2000 through December 2004, we collected data from Centers for Disease Control and Prevention's Active Bacterial Core surveillance (ABCs), a population-based system operating at 10 US sites (2004 population, 29.7 million). We defined a case of invasive GAS disease as isolation of GAS from a normally sterile site or from a wound specimen obtained from a patient with necrotizing fasciitis or streptococcal toxic shock syndrome in a surveillance area resident. All available isolates were emm typed. We used US census data to calculate rates and to make age- and race-adjusted national projections. Results. We identified 5400 cases of invasive GAS infection (3.5 cases per 100,000 persons), with 735 deaths (case-fatality rate, 13.7%). Case-fatality rates for streptococcal toxic shock syndrome and necrotizing fasciitis were 36% and 24%, respectively. Incidences were highest among elderly persons (9.4 cases per 100,000 persons), infants (5.3 cases per 100,000 persons), and black persons (4.7 cases per 100,000 persons) and were stable over time. We estimate that 8950–11,500 cases of invasive GAS infection occur in the United States annually, resulting in 1050–1850 deaths. The emm types in a proposed 26-valent vaccine accounted for 79% of all cases and deaths. Independent factors associated with death include increasing age; having streptococcal toxic shock syndrome, meningitis, necrotizing fasciitis, pneumonia, or bacteremia; and having emm types 1, 3, or 12. Conclusions. GAS remains an important cause of severe disease in the United States. The introduction of a vaccine could significantly reduce morbidity and mortality due to these infections.
Journal Article
Assessing Mangrove Forest Recovery in the British Virgin Islands After Hurricanes Irma and Maria with Sentinel-2 Imagery and Google Earth Engine
Mangroves form the dominant coastal plant community of low-energy tropical intertidal habitats and provide critical ecosystem services to humans and the environment. However, more frequent and increasingly powerful hurricanes and storm surges are creating additional pressure on the natural resilience of these threatened coastal ecosystems. Advances in remote sensing techniques and approaches are critical to providing robust quantitative monitoring of post-storm mangrove forest recovery to better prioritize the often-limited resources available for the restoration of these storm-damaged habitats. Here, we build on previously utilized spatial and temporal ranges of European Space Agency (ESA) Sentinel satellite imagery to monitor and map the recovery of the mangrove forests of the British Virgin Islands (BVI) since the occurrence of back-to-back category 5 hurricanes, Irma and Maria, on September 6 and 19 of 2017, respectively. Pre- to post-storm changes in coastal mangrove forest health were assessed annually using the normalized difference vegetation index (NDVI) and moisture stress index (MSI) from 2016 to 2023 using Google Earth Engine. Results reveal a steady trajectory towards forest health recovery on many of the Territory’s islands since the storms’ impacts in 2017. However, some mangrove patches are slower to recover, such as those on the islands of Virgin Gorda and Jost Van Dyke, and, in some cases, have shown a continued decline (e.g., Prickly Pear Island). Our work also uses a linear ANCOVA model to assess a variety of geospatial, environmental, and anthropogenic drivers for mangrove recovery as a function of NDVI pre-storm and post-storm conditions. The model suggests that roughly 58% of the variability in the 7-year difference (2016 to 2023) in NDVI may be related by a positive linear relationship with the variable of population within 0.5 km and a negative linear relationship with the variables of northwest aspect vs. southwest aspect, island size, temperature, and slope.
Journal Article
Facilitation of Australia’s southernmost reef-building coral by sea urchin herbivory
Competition for space between corals and macroalgae represents a key threatening process for coral reefs, yet the influence of climate change on this competitive interaction is poorly understood, particularly at the poleward margins of coral distribution. Here we describe the discovery of Australia’s southernmost hermatypic corals and explore novel dynamics facilitating the presence and extent of high-latitude coral communities. Examination of 607 shallow reef sites across temperate Australia revealed hard corals to be negatively associated with increasing kelp bed cover, but positively associated with increasing sea surface temperature, herbivorous fishes, grazing sea urchins, and increasing cover of turf algae, which proliferates in the absence of kelp. However, the nature of these effects varied across different regions of temperate Australia consistent with regional variability in the presence/absence of key functional groups for temperate reefs, such as guilds of subtropical herbivorous fishes and/or prevalence of overgrazing sea urchins. For the southernmost coral communities, in eastern Bass Strait Tasmania, the dominant reef-building coral Plesiastrea versipora was negatively associated with kelp and positively associated with the southward range-extending diadematid sea urchin Centrostephanus rodgersii, which has caused extensive kelp bed overgrazing since first locally reported in 1974. Facilitation of coral establishment was strongest on overgrazed barrens where urchin density was relatively low, but sufficient to maintain the reef kelp-free, while corals were less frequent at high urchin densities and completely absent from barrens colonised by intensively grazing limpets. In contrast to tropical Australian coral reefs and other temperate regions (e.g. Western Australia), assays of herbivory confirmed sea urchin grazing, not herbivorous fishes, as chiefly responsible for kelp consumption within this high-latitude system. Size structure of P. versipora in eastern Bass Strait was dominated by small colonies (~ 20 cm2), suggesting an expanding population at the poleward edge of the species’ range. Nevertheless, colonies up to a maximum area of 500 cm2 were observed, which are likely > 40 yrs old based on growth rates established in warmer waters. This research highlights novel patterns and processes structuring the interface between subtropical and temperate reef communities under climate change and specifically highlights the role of herbivores in releasing corals from competition with kelp under warming ocean regimes.
Journal Article
Digital PCR Analysis of Maternal Plasma for Noninvasive Detection of Sickle Cell Anemia
Cell-free fetal DNA (cffDNA) constitutes approximately 10% of the cell-free DNA in maternal plasma and is a suitable source of fetal genetic material for noninvasive prenatal diagnosis (NIPD). The objective of this study was to determine the feasibility of using digital PCR for NIPD in pregnancies at risk of sickle cell anemia.
Minor-groove binder (MGB) TaqMan probes were designed to discriminate between wild-type hemoglobin A and mutant (hemoglobin S) alleles encoded by the HBB (hemoglobin, beta) gene in cffDNA isolated from maternal plasma samples obtained from pregnancies at risk of sickle cell anemia. The fractional fetal DNA concentration was assessed in male-bearing pregnancies with a digital PCR assay for the Y chromosome-specific marker DYS14. In pregnancies with a female fetus, a panel of biallelic insertion/deletion polymorphism (indel) markers was developed for the quantification of the fetal DNA fraction. We used digital real-time PCR to analyze the dosage of the variant encoding hemoglobin S relative to that encoding wild-type hemoglobin A.
The sickle cell genotype was correctly determined in 82% (37 of 45) of male fetuses and 75% (15 of 20) of female fetuses. Mutation status was determined correctly in 100% of the cases (25 samples) with fractional fetal DNA concentrations >7%. The panel of indels was informative in 65% of the female-bearing pregnancies.
Digital PCR can be used to determine the genotype of fetuses at risk for sickle cell anemia. Optimization of the fractional fetal DNA concentration is essential. More-informative indel markers are needed for this assay's comprehensive use in cases of a female fetus.
Journal Article
Implementing Prenatal Diagnosis Based on Cell-Free Fetal DNA: Accurate Identification of Factors Affecting Fetal DNA Yield
Cell-free fetal DNA is a source of fetal genetic material that can be used for non-invasive prenatal diagnosis. Usually constituting less than 10% of the total cell free DNA in maternal plasma, the majority is maternal in origin. Optimizing conditions for maximizing yield of cell-free fetal DNA will be crucial for effective implementation of testing. We explore factors influencing yield of fetal DNA from maternal blood samples, including assessment of collection tubes containing cell-stabilizing agents, storage temperature, interval to sample processing and DNA extraction method used.
Microfluidic digital PCR was performed to precisely quantify male (fetal) DNA, total DNA and long DNA fragments (indicative of maternal cellular DNA). Real-time qPCR was used to assay for the presence of male SRY signal in samples.
Total cell-free DNA quantity increased significantly with time in samples stored in K(3)EDTA tubes, but only minimally in cell stabilizing tubes. This increase was solely due to the presence of additional long fragment DNA, with no change in quantity of fetal or short DNA, resulting in a significant decrease in proportion of cell-free fetal DNA over time. Storage at 4 °C did not prevent these changes.
When samples can be processed within eight hours of blood draw, K(3)EDTA tubes can be used. Prolonged transfer times in K(3)EDTA tubes should be avoided as the proportion of fetal DNA present decreases significantly; in these situations the use of cell stabilising tubes is preferable. The DNA extraction kit used may influence success rate of diagnostic tests.
Journal Article
Future innovations in anti‐platelet therapies
Platelets have long been recognized to be of central importance in haemostasis, but their participation in pathological conditions such as thrombosis, atherosclerosis and inflammation is now also well established. The platelet has therefore become a key target in therapies to combat cardiovascular disease. Anti‐platelet therapies are used widely, but current approaches lack efficacy in a proportion of patients, and are associated with side effects including problem bleeding. In the last decade, substantial progress has been made in understanding the regulation of platelet function, including the characterization of new ligands, platelet‐specific receptors and cell signalling pathways. It is anticipated this progress will impact positively on the future innovations towards more effective and safer anti‐platelet agents. In this review, the mechanisms of platelet regulation and current anti‐platelet therapies are introduced, and strong, and some more speculative, potential candidate target molecules for future anti‐platelet drug development are discussed. British Journal of Pharmacology (2008) 154, 918–939; doi:10.1038/bjp.2008.151; published online 21 April 2008
Journal Article
Measurement of fetal fraction in cell-free DNA from maternal plasma using a panel of insertion/deletion polymorphisms
Cell-free DNA from maternal plasma can be used for non-invasive prenatal testing for aneuploidies and single gene disorders, and also has applications as a biomarker for monitoring high-risk pregnancies, such as those at risk of pre-eclampsia. On average, the fractional cell-free fetal DNA concentration in plasma is approximately 15%, but can vary from less than 4% to greater than 30%. Although quantification of cell-free fetal DNA is straightforward in the case of a male fetus, there is no universal fetal marker; in a female fetus measurement is more challenging. We have developed a panel of multiplexed insertion/deletion polymorphisms that can measure fetal fraction in all pregnancies in a simple, targeted sequencing reaction.
A multiplex panel of primers was designed for 35 indels plus a ZFX/ZFY amplicon. cfDNA was extracted from plasma from 157 pregnant women, and maternal genomic DNA was extracted for 20 of these samples for panel validation. Sixty-one samples from pregnancies with a male fetus were subjected to whole genome sequencing on the Ion Proton sequencing platform, and fetal fraction derived from Y chromosome counts was compared to fetal fraction measured using the indel panel. A total of 157 cell-free DNA samples were sequenced using the indel panel, and informativity was assessed, along with the proportion of fetal DNA.
Using gDNA we optimised the indel panel, removing amplicons giving rise to PCR bias. Good correlation was found between fetal fraction using indels and using whole genome sequencing of the Y chromosome (Spearmans r = 0.69). A median of 12 indels were informative per sample. The indel panel was informative in 157/157 cases (mean fetal fraction 14.4% (±0.58%)).
Using our targeted next generation sequencing panel we can readily assess the fetal DNA percentage in male and female pregnancies.
Journal Article