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OBJECTIVES/SPECIFIC AIMS: The serotonin receptor 6 (5-HT6) is a potential therapeutic target given its distribution in brain regions that are important in depression, anxiety, and cognition. This study sought to investigate the effects of age on 5-HT6 receptor availability using 11C GSK215083, a PET ligand with affinity for 5-HT6 in the striatum and 5-HT2A in the cortex. METHODS/STUDY POPULATION: In total, 28 healthy male subjects (age range: 23–52 years) were scanned with 11C-GSK215083 on the HR+PET scanner. Time-activity curves in regions-of-interest were fitted with multilinear analysis-1 method. Binding potentials (BPND) were calculated using cerebellum as the reference region and corrected for partial volume effects. RESULTS/ANTICIPATED RESULTS: In 5-HT6 rich areas, regional 11C-GSK215083 displayed a negative correlation between BPND and age in the caudate (r=−0.41, p=0.03) (14% change per decade), and putamen (r=−0.30, p=0.04) (11% change per decade), but not in the ventral striatum and pallidum. Negative correlation with age was also seen in cortical regions (r=−0.41, p=0.03) (7% change per decade), consistent with the literature on 5-HT2A availability. DISCUSSION/SIGNIFICANCE OF IMPACT: This is the first in vivo study in humans to examine the effect of age on 5-HT6 receptor availability. The study demonstrated a significant age-related decline in 5-HT6 availability (BPND) in the caudate and putamen.
Feeding behaviors may differ between past and current predators due to differences in the environments inhabited by these species at different times. We provide an example of this behavioral variability in spotted hyena (Crocuta crocuta), for which our analysis of a late Pleistocene micromammal assemblage indicates that hyenas preyed upon small rodents, a feeding habit that is rarely observed today among hyenas.
The Bois Roche cave site is situated at the edge of a low bluff overlooking the floodplain of a small stream in Cherves-Richemont (Charente, France). The deposits are dated by electron spin resonance (ESR) to about 69.7 ± 4.1 Ka. Excavations at the site recovered fossil bones and teeth of large and small mammals, together with hyena coprolites. Water screening of the sediments produced large accumulations of rodent remains with low taxonomic diversity. Small mammal bones were recovered from hyena coprolites as well. Descriptions of small mammal bone modification, both from the sediments and coprolites, are reported here. The analysis yielded a distinct taphonomic pattern representative of large carnivores (over 30 kg), which differs from any other modern or fossil predator-accumulated microfaunal assemblage taphonomically analyzed to date. To our knowledge, previous studies of hyena diet have not recorded high concentrations of a single-rodent prey species. We conclude that the low species diversity of this small mammal assemblage most likely relates to a local abundance of the prey species due to an outbreak in the rodent population, rather than from specialist predator behavior and hunting technique.
Extracorporeal membrane oxygenation within CPR (ECPR) may improve survival for refractory out-of-hospital cardiac arrest (OHCA). We developed a prehospital, emergency department (ED), and hospital-based clinical and educational protocol to improve the key variable of time-to-ECPR (TTE).
In a single urban health region we involved key prehospital, clinical, and administrative stakeholders over a 2-year period, to develop a regional ECPR program with destination to a single urban tertiary care hospital. We developed clear and reproducible inclusion criteria and processes, including measures of program efficiency. We conducted seminars and teaching modules to paramedics and hospital-based clinicians including monthly simulator sessions, and performed detailed reviews of each treated case in the form of report cards. In this before-and-after study we compared patients with ECPR attempted prior to, and after, protocol implementation. The primary outcome was TTE, defined as the time of initial professional CPR to establishment of extracorporeal circulation. We compared the median TTE for patients in the two groups using the Wilcoxon signed rank test.
Four patients were identified prior to the protocol and managed in an ad hoc basis; for nine patients the protocol was utilized. Overall favourable neurological outcomes among ECPR-treated patients were 27%. The median TTE was 136 minutes (IQR 98 - 196) in the pre-protocol group, and 60 minutes (IQR 49 - 81) minutes in the protocol group (p=0.0165).
An organized clinical and educational protocol to initiate ECPR for patients with OHCA is feasible and significantly reduces the key benchmark of time-to-ECPR flows.
Current models of class II methanol masers are able to describe the brightnesses of the strongest masers and provide a basis for explaining observed line ratios. Determination of the physical parameters in the source requires observational data in many maser transitions. In order to provide observational constraints for models we searched for and detected 7 new methanol masers. This allowed us to constrain the physical parameters of the 3 sources with the greatest number of detected methanol maser lines: W3(OH), NGC6334F, and G345.01 + 1.79. The models accurately account for the fluxes of the bulk of the detected maser lines. Remaining discrepancies most probably reflect the fact that the most prominent components of the different maser lines are formed under different conditions. This is supported by comparison of the line profiles. We outline directions for future studies in the field.
Ten ice-sheet models are used to study sensitivity of the Greenland and Antarctic ice sheets to prescribed changes of surface mass balance, sub-ice-shelf melting and basal sliding. Results exhibit a large range in projected contributions to sea-level change. In most cases, the ice volume above flotation lost is linearly dependent on the strength of the forcing. Combinations of forcings can be closely approximated by linearly summing the contributions from single forcing experiments, suggesting that nonlinear feedbacks are modest. Our models indicate that Greenland is more sensitive than Antarctica to likely atmospheric changes in temperature and precipitation, while Antarctica is more sensitive to increased ice-shelf basal melting. An experiment approximating the Intergovernmental Panel on Climate Change’s RCP8.5 scenario produces additional first-century contributions to sea level of 22.3 and 8.1 cm from Greenland and Antarctica, respectively, with a range among models of 62 and 14 cm, respectively. By 200 years, projections increase to 53.2 and 26.7 cm, respectively, with ranges of 79 and 43 cm. Linear interpolation of the sensitivity results closely approximates these projections, revealing the relative contributions of the individual forcings on the combined volume change and suggesting that total ice-sheet response to complicated forcings over 200 years can be linearized.
To estimate the folate status of New Zealand women of childbearing age following the introduction, in 2010, of a new voluntary folic acid fortification of bread programme.
The 2011 Folate and Women’s Health Survey was a cross-sectional survey of women aged 18–44 years carried out in 2011. The survey used a stratified random sampling technique with the Electoral Roll as the sampling frame. Women were asked about consumption of folic-acid-fortified breads and breakfast cereals in a telephone interview. During a clinic visit, blood was collected for serum and erythrocyte folate measurement by microbiological assay.
A North Island (Wellington) and South Island (Dunedin) city centre in New Zealand.
Two hundred and eighty-eight women, of whom 278 completed a clinic visit.
Geometric mean serum and erythrocyte folate concentrations were 30 nmol/l and 996 nmol/l, respectively. Folate status was 30–40 % higher compared with women of childbearing age sampled as part of a national survey in 2008/09, prior to the introduction of the voluntary folic acid bread fortification programme. In the 2011 Folate and Women’s Health Survey, reported consumption of fortified bread and fortified breakfast cereal in the past week was associated with 25 % (P=0·01) and 15 % (P=0·04) higher serum folate concentrations, respectively.
Serum and erythrocyte folate concentrations have increased in New Zealand women of childbearing age since the number of folic-acid-fortified breads was increased voluntarily in 2010. Consumption of fortified breads and breakfast cereals was associated with a higher folate status.
Imaging biomarkers for Alzheimer's disease include medial temporal lobe
atrophy (MTLA) depicted on computed tomography (CT) or magnetic resonance
imaging (MRI) and patterns of reduced metabolism on fluorodeoxyglucose
positron emission tomography (FDG-PET).
To investigate whether MTLA on head CT predicts the diagnostic usefulness
of an additional FDG-PET scan.
Participants had a clinical diagnosis of Alzheimer's disease
(n = 37) or dementia with Lewy bodies (DLB;
n = 30) or were similarly aged controls
(n = 30). We visually rated MTLA on coronally
reconstructed CT scans and, separately and blind to CT ratings, abnormal
appearances on FDG-PET scans.
Using a pre-defined cut-off of MTLA ⩾5 on the Scheltens (0–8) scale, 0/30
controls, 6/30 DLB and 23/30 Alzheimer's disease had marked MTLA. FDG-PET
performed well for diagnosing Alzheimer's disease v. DLB
in the low-MTLA group (sensitivity/specificity of 71%/79%), but in the
high-MTLA group diagnostic performance of FDG-PET was not better than
In the presence of a high degree of MTLA, the most likely diagnosis is
Alzheimer's disease, and an FDG-PET scan will probably not provide
significant diagnostic information. However, in cases without MTLA, if
the diagnosis is unclear, an FDG-PET scan may provide additional
clinically useful diagnostic information.
Positron emission tomography (PET) and single photon emission computed tomography (SPECT) brain imaging are widely used as diagnostic tools for suspected dementia but no studies have directly compared participant views of the two procedures. We used a range of methods to explore preferences for PET and SPECT.
Patients and controls (and accompanying carers) completed questionnaires immediately after undergoing PET and SPECT brain scans. Pulse rate data were collected during each scan. Scan attributes were prioritized using a card sorting exercise; carers and controls additionally answered willingness to pay (WTP) questions.
Few differences were found either between the scans or groups of participants, although carers marginally preferred SPECT. Diagnostic accuracy was prioritized over other scan characteristics. Mean heart rate during both scans was lower than baseline heart rate measured at home (p < 0.001).
Most participants viewed PET and SPECT scans as roughly equivalent and did not have a preference for either scan. Carer preference for SPECT is likely to reflect their desire to be with the patient (routine practice for SPECT but not for PET), suggesting that they should be able to accompany vulnerable patients throughout imaging procedures wherever possible. Pulse rate data indicated that brain imaging was no more stressful than a home visit (HV) from a researcher. The data do not support the anecdotal view that PET is a more burdensome procedure and the use of PET or SPECT scans in dementia should be based on diagnostic accuracy of the technique.
The contributions in the final part explore and point to new directions for corporate governance research and reforms as a post-crisis agenda. Peer Zumbansen begins by questioning the current functional and ahistorical approach in comparative law and corporate governance research, which is more interested in exploring and designing regulatory responses towards the quick ‘fixing’ of the system failures, without a fundamental understanding of the changing, evolving and increasingly complex nature of the business corporation and its regulatory environment. Examining the evolution of European capital market law and corporate governance harmonization, he recognizes the increasingly multilevel and trans-territorialized norm production in corporate governance as an ephemeral ‘double movement’: the attempted liberation of the national regulatory constraints as required by business globalization on the one side, and the inevitably embedded nature of corporate norms in distinct socio-economic cultures and historically grown legal and institutional frameworks on the other side. Zumbansen argues that the rapid developments of globalization of markets, information technology, knowledge economy and the ‘financialization’ of the corporation have opened up regulatory spaces and transformed formal rule creation in politically embedded state legal systems towards an emerging system of decentralized and specialized transnational regulatory regimes that unfolds in a web of hard and soft laws, which blur the regulatory boundaries between national and international, public and private, formal and informal. This phenomenon is what he calls ‘transnational legal pluralism’, the new embeddedness of the firm.
Over the last two decades there has been a notable increase in the number of corporate governance codes and principles, as well as a range of improvements in structures and mechanisms. Despite this, corporate governance failed to prevent a widespread default of fiduciary duties of corporate boards and managerial responsibilities in the finance industry, which contributed to the 2007–10 global financial crisis. This book brings together leading scholars from North America, Europe, Asia-Pacific and the Middle East to provide fresh and critical analytical insights on the systemic failures of corporate governance linked to the global financial crisis. Contributors draw from a range of disciplines to demonstrate the severe limitations of the dominant corporate governance framework and its associated market-oriented approach. They provide suggestions on how the governance problems could be tackled to prevent or mitigate any future financial crisis and explore new directions for post-crisis corporate governance research and reforms.
The five chapters in Part I explore the failures of corporate governance that contributed to the global financial crisis, with a focus on examining the limitations of the market-oriented approach to corporate governance, which in a broad sense is characterized by deregulation, self-regulation, the market for corporate control and other market discipline mechanisms. Thomas Clarke begins by examining the specifically corporate governance causes of the global financial crisis. He identifies the origins of the crisis in the enthusiasm for deregulation of financial institutions and markets, resulting in the rapid growth of securitization. The huge explosion of global derivatives set the context in which risk management and corporate governance were abandoned by major financial institutions. The rating agencies and executive incentives played roles in encouraging rather than managing risk. He suggests that international efforts to coordinate a regulatory response to the crisis should be considered.