Any near-term gains in reducing extreme poverty will be maintained only if environmental sustainability is also achieved.
The Millennium Development Goals (MDGs) are designed to inspire efforts to ...improve people's lives by, among other priorities, halving extreme poverty by 2015 (
1
). Analogously, concern about global decline in biodiversity and degradation of ecosystem services (
2
) gave rise in 1992 to the Convention on Biological Diversity (CBD). The CBD target “to achieve by 2010 a significant reduction of the current rate of biodiversity loss” was incorporated into the MDGs in 2002. Our lack of progress toward the 2010 target (
3
,
4
) could undermine achievement of the MDGs and poverty reduction in the long term. With increasing global challenges, such as population growth, climate change, and overconsumption of ecosystem services, we need further integration of the poverty alleviation and biodiversity conservation agendas.
The relationship of choline acetyltransferase (ChAT) activity and high affinity binding of the potent and selective sodium-dependent choline uptake inhibitor 3Hhemicholinium-3 (3HHC-3) to ...high-affinity binding of the muscarinic agonist 3H(+)-cis-methyldioxolane (3H(+)CD), the putative M1 selective antagonist 3Hpirenzepine (3HPZ) and the classical antagonist 3H(-)-quinuclidinyl benzilate (3H(-)QNB) in homogenates of the rat neocortex was studied. ChAT activity was 42% lower in rats with ibotenate-induced lesions of the nucleus basalis magnocellularis (nbm) when compared to controls, and 3HHC-3 binding was similarly reduced by 44%. However, equilibrium dissociation constants (Kd values) for 3HHC-3 (0.8-1.0 nM), 3H(-)QNB (11-24 pM), 3HPZ (4.0-4.3 nM) and 3H(+)CD (2.1-2.9 nM) were each unchanged. Mean Bmax values (total binding site densities) for 3H(+)CD were significantly altered in both hemispheres of the anterior cerebral cortex, showing a 25% reduction in the number of sites which display the highest affinity conformation for this potent muscarinic agonist. The decreased ChAT activity and 3HHC-3 binding after nbm lesions were associated with only slight reductions in putative M1 muscarinic site density (14%) and 3H(-)QNB binding site density (13%). Thus, it appears that while 3HPZ and 3H(-)QNB label predominantly postsynaptic muscarinic binding sites, a significant number of sites labeled by 3H(+)CD may be associated with presynaptic cholinergic nerve terminals. These data suggest that cholinergic input differentially regulates the drug binding sites of anterior cerebral cortical muscarinic receptors, exerting a substantial effect upon the highest affinity conformational state for agonists.
The Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) is one of Europe's oldest sentinel systems, working with the UK Health Security Agency (UKHSA) and its ...predecessor bodies for 55 years. Its surveillance report now runs twice weekly, supplemented by online observatories. In addition to conducting sentinel surveillance from a nationally representative group of practices, the RSC is now also providing data for syndromic surveillance.
The aim of this study was to describe the cohort profile at the start of the 2021-2022 surveillance season and recent changes to our surveillance practice.
The RSC's pseudonymized primary care data, linked to hospital and other data, are held in the Oxford-RCGP Clinical Informatics Digital Hub, a Trusted Research Environment. We describe the RSC's cohort profile as of September 2021, divided into a Primary Care Sentinel Cohort (PCSC)-collecting virological and serological specimens-and a larger group of syndromic surveillance general practices (SSGPs). We report changes to our sampling strategy that brings the RSC into alignment with European Centre for Disease Control guidance and then compare our cohort's sociodemographic characteristics with Office for National Statistics data. We further describe influenza and COVID-19 vaccine coverage for the 2020-2021 season (week 40 of 2020 to week 39 of 2021), with the latter differentiated by vaccine brand. Finally, we report COVID-19-related outcomes in terms of hospitalization, intensive care unit (ICU) admission, and death.
As a response to COVID-19, the RSC grew from just over 500 PCSC practices in 2019 to 1879 practices in 2021 (PCSC, n=938; SSGP, n=1203). This represents 28.6% of English general practices and 30.59% (17,299,780/56,550,136) of the population. In the reporting period, the PCSC collected >8000 virology and >23,000 serology samples. The RSC population was broadly representative of the national population in terms of age, gender, ethnicity, National Health Service Region, socioeconomic status, obesity, and smoking habit. The RSC captured vaccine coverage data for influenza (n=5.4 million) and COVID-19, reporting dose one (n=11.9 million), two (n=11 million), and three (n=0.4 million) for the latter as well as brand-specific uptake data (AstraZeneca vaccine, n=11.6 million; Pfizer, n=10.8 million; and Moderna, n=0.7 million). The median (IQR) number of COVID-19 hospitalizations and ICU admissions was 1181 (559-1559) and 115 (50-174) per week, respectively.
The RSC is broadly representative of the national population; its PCSC is geographically representative and its SSGPs are newly supporting UKHSA syndromic surveillance efforts. The network captures vaccine coverage and has expanded from reporting primary care attendances to providing data on onward hospital outcomes and deaths. The challenge remains to increase virological and serological sampling to monitor the effectiveness and waning of all vaccines available in a timely manner.
Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma ...in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10−9). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma.
Traumatic brain injury (TBI) is a major cause of morbidity and mortality in children; survivors experience long-term cognitive and motor deficits. To date, studies predicting outcome following ...pediatric TBI have primarily focused on acute behavioral responses and proxy measures of injury severity; unsurprisingly, these measures explain very little of the variance following heterogenous injury. In adults, certain acute imaging biomarkers help predict cognitive and motor recovery following moderate to severe TBI. This multi-center, retrospective study, characterizes the day-of-injury computed tomographic (CT) reports of pediatric, adolescent, and young adult patients (2 months to 21 years old) who received inpatient rehabilitation services for TBI (
= 247). The study also determines the prognostic utility of CT findings for cognitive and motor outcomes assessed by the Pediatric Functional Independence Measure, converted to age-appropriate developmental functional quotient (DFQ), at discharge from rehabilitation. Subdural hematomas (66%), contusions (63%), and subarachnoid hemorrhages (59%) were the most common lesions; the majority of subjects had less severe Rotterdam CT scores (88%, ≤ 3). After controlling for age, gender, mechanism of injury, length of acute hospital stay, and admission DFQ in multivariate regression analyses, the highest Rotterdam score (β = -25.2,
< 0.01) and complete cisternal effacement (β = -19.4,
< 0.05) were associated with lower motor DFQ, and intraventricular hemorrhage was associated with lower motor (β = -3.7,
< 0.05) and cognitive DFQ (β = -4.9,
< 0.05). These results suggest that direct detection of intracranial injury provides valuable information to aid in prediction of recovery after pediatric TBI, and needs to be accounted for in future studies of prognosis and intervention.
Micrometastatic cells detected in the bone marrow have prognostic significance in breast cancer. These cells are heterogeneous and likely do not exhibit uniform biological behavior. To understand the ...molecular diversity of disseminated cancer cells that reside in bone marrow, we enriched this cell population and did global gene expression profiling in the context of a prospective clinical trial involving women with clinical stage II/III breast cancer undergoing neoadjuvant chemotherapy.
Enrichment of TACSTD1 (EpCAM)-expressing cells from bone marrow of breast cancer patients was achieved using immunomagnetic beads. Gene expression profiles were compared between enriched cell populations and whole bone marrow from 5 normal volunteers and 23 breast cancer patients after neoadjuvant chemotherapy treatment. Enriched cells from bone marrow samples of breast cancer patients before treatment or at 1 year follow-up were also analyzed (total of 87 data sets). The expression of transcripts specifically detected in enriched cell populations from breast cancer patients was correlated with 1-year clinical outcome using quantitative reverse transcription-PCR in an independent cohort of bone marrow samples.
Analysis of EpCAM-enriched bone marrow cells revealed specific expression of a subgroup of transcripts, including the metastasis regulator, TWIST1. Most transcripts identified, including TWIST1, were not expressed in enriched populations of bone marrow from normal volunteers, suggesting that this expression profile reflects a signature of breast cancer bone marrow micrometastases that persist after chemotherapy. In an independent set of bone marrow samples obtained before any treatment, TWIST1 expression correlated with early disease relapse.
Disseminated breast cancer cells present in bone marrow after chemotherapy possess unique transcriptional signatures. Genes whose expression is overrepresented in these cell populations, such as TWIST1, may prove to be excellent markers of early distant relapse in breast cancer patients.
We have identified the marine fish taxa that are most vulnerable to exploitation, by compiling an index of intrinsic vulnerability based on life history traits. Since 1950, the global fish catch has ...been increasingly dominated by species with low intrinsic vulnerability, indicated by a decline in mean vulnerability of the taxa in the catches. This decline is strongest in catches of coral reef fishes, probably as a result of overexploitation of the more vulnerable species. The change is less apparent in estuaries, where fish communities are more transient. The opposite is observed at seamounts, where more vulnerable species have become exploited and serially depleted in recent years. Rates of change in the mean vulnerability index in the catches from different areas are negatively correlated with the number of threatened fishes on the IUCN Red List. Particularly, catches from the Indo-Pacific and Caribbean regions are characterized by a high abundance of threatened fishes and by strong declines in the mean vulnerability index. Our findings suggest that fishing largely alters the community structure of coral reef fishes, which may detrimentally affect the ecosystem. Attention should also be given to deep water demersal and benthopelagic fish assemblages, especially those around seamounts, which are intrinsically vulnerable to fishing. The index of intrinsic vulnerability thus provides a novel tool for fisheries management and conservation.
Understanding the mechanisms driving fisheries production is essential if we are to accurately predict changes under climate change and exploit fish stocks in a sustainable manner. Traditionally, ...studies have sought to distinguish between the two most prominent drivers, ‘bottom‐up’ (resource driven) and ‘top‐down’ (consumer driven); however, this dichotomy is increasingly proving to be artificial as the relative importance of each mechanism has been shown to vary through space and time. Nevertheless, the reason why one predominates over another within a region remains largely unknown. To address this gap in understanding, we identified the dominant driver of commercial landings within 47 ecosystems, encompassing a wide range of biogeochemical conditions and fishing practices to elucidate general patterns. We show that bottom‐up and top‐down effects vary consistently with past fishing pressure and oceanographic conditions; bottom‐up control predominates within productive, overfished regions and top‐down in relatively unproductive and under‐exploited areas. We attribute these findings to differences in the species composition and oceanographic properties of regions, together with variation in fishing practices and (indicative) management effectiveness. Collectively, our analyses suggest that despite the complexity of ecological systems, it is possible to elucidate a number of generalities. Such knowledge could be used to increase the parsimony of ecosystem models and to move a step forward in predicting how the global ocean, particularly fisheries productivity, will respond to climate change.
The Truncated Disk of CoKu Tau/4 D’Alessio, Paola; Hartmann, Lee; Calvet, Nuria ...
Astrophysical journal/The Astrophysical journal,
03/2005, Letnik:
621, Številka:
1
Journal Article
Recenzirano
Odprti dostop
We present a model of a dusty disk with an inner hole that accounts for the Spitzer Space Telescope Infrared Spectrograph observations of the low-mass pre-main-sequence star CoKu Tau/4. We have ...modeled the mid-infrared spectrum (between 8 and 25 mu m) as arising from the inner wall of a disk. Our model disk has an evacuated inner zone of radius similar to 10 AU, with a dusty inner "wall" of half-height similar to 2 AU that is illuminated at normal incidence by the central star. The radiative equilibrium temperature decreases from the inner disk edge outward through the optically thick disk; this temperature gradient is responsible for the emission of the silicate bands at 10 and 20 mu m. The observed spectrum is consistent with being produced by Fe-Mg amorphous glassy olivine and/or pyroxene, with no evidence of a crystalline component. The mid-infrared spectrum of CoKu Tau/4 is reminiscent of that of the much older star TW Hya, where it has been suggested that the significant clearing of its inner disk is due to planet formation. However, no inner disk remains in CoKu Tau/4, consistent with the star being a weak-emission (nonaccreting) T Tauri star. The relative youth of CoKu Tau/4 ( similar to 1 Myr) may indicate much more rapid planet formation than typically assumed.
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