As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and energy expenditure, but decreased heart rate and had little effect on metabolites. Importantly, cold increased BAT activity as measured by 18 F-fluorodeoxyglucose PET-CT in every volunteer, whereas ephedrine failed to stimulate BAT. Thus, at doses leading to broad activation of the sympathetic nervous system, ephedrine does not stimulate BAT in humans. In contrast, mild cold exposure stimulates BAT energy expenditure with fewer other systemic effects, suggesting that cold activates specific sympathetic pathways. Agents that mimic cold activation of BAT could provide a promising approach to treating obesity while minimizing systemic effects.metabolism | thermogenesis | respiratory quotient | norepinephrine | white adipose tissue B rown adipose tissue (BAT) is a type of fat that consumes calories to generate heat. Multiple recent studies have shown that adult humans have functional BAT that can be activated in response to cold exposure in a process called nonshivering thermogenesis (1-4). In both small and large population studies (1, 2, 4, 5), there is an inverse correlation between BAT activity and obesity, suggesting that activating BAT, through pharmacological, environmental, or potentially nutritional interventions, could become a therapeutic means to treat obesity and diabetes. Indeed, human BAT energy expenditure may be a critical counterbalance to the weight gain and metabolic dysregulation caused by excess energy storage in white adipose tissue.Human BAT has a high density of both nerves and blood vessels (6), providing two general approaches to activate BAT. Based on studies in rodents, it is known that the sensation of cold by the skin and body core sends signals via peripheral neurons to the spinal cord and then up to the preoptic area of the hypothalamus for processing. From the hypothalamus, some signals go to the cerebral cortex for conscious thermal perception and localization, and others go to premotor neurons in the rostral raphe pallidus of the brainstem, projecting to neurons of the peripheral sympathetic nervous system (SNS) (reviewed in ref. 7). Ultimately, postganglionic SNS nerves release norepinephrine to activate BAT via induction of uncoupling protein-1, the tissue-specific protein that allows BAT to generate heat by uncoupling aerobic respiration from the generation of ATP.Because the endogenous pathways by cold exposure are complex and indirect, an attractive alternative for stimulation of BAT has been the use of pharmacological agents. As norepinephrine itself has too many adverse effects on the ...

Measurements of the intra-tidal and spring-neap variation in the vertical flux of nitrate into the base of the sub-surface chlorophyll maximum (SCM) were made at the shelf edge of the Celtic Sea, a region with strong internal mixing driven by an internal tide. The neap tide daily mean nitrate flux was 1.3 (0.9-1.8, 95% confidence interval) mmol m 22 d 21 . The spring tide flux was initially estimated as 3.5 (2.3-5.2, 95% confidence interval) mmol m 22 d 21 . The higher spring tide nitrate flux was the result of turbulent dissipation occurring within the base of the SCM as compared to deeper dissipation during neap tides and was dominated by short events associated with the passage of internal solitons. Taking into account the likely under-sampling of these short mixing events raised the spring tide nitrate flux estimate to about 9 mmol m 22 d 21 . The neap tide nitrate flux was sufficient to support substantial new production and a considerable fraction of the observed rates of carbon fixation. Spring tide fluxes were potentially in excess of the capacity of the phytoplankton community to uptake nitrate. This potential excess nitrate flux during spring tides may be utilized to support new production during the lower mixing associated with the transition toward neap tide. The shelf edge is shown to be a region with a significantly different phytoplankton community as compared to the adjacent Celtic Sea and northeast Atlantic Ocean, highlighting the role of gradients in physical processes leading to gradients in ecosystem structure.3 Present address: Proudman Oceanographic Laboratory, 6 Brownlow Street, Liverpool, L3 5DA, United Kingdom. AcknowledgmentsOur thanks to the crew of the RRS Charles Darwin (cruise CD173) and the technical staff of the U.K. National Marine Facilities. We are grateful for the constructive comments from two anonymous reviewers, which helped improve this paper.

PET/CT imaging with 18 F-FDG has been used to detect inflammation in carotid and aortic plaque; its use in detecting coronary plaque has been limited by avid 18 F-FDG uptake by the myocardium. We investigated whether 18 F-FDG PET/CT could be used to image inflammation in coronary arteries as a potential noninvasive method to detect vulnerable plaque. Methods: We retrospectively studied 32 patients treated for malignancy who underwent 18 F-FDG PET/CT and concomitant cardiac catheterization. As part of the recently described protocol, all patients were instructed to eat a low-carbohydrate, high-fat meal the night before and drink a vegetable oil drink the morning of the study. We reviewed the patients' baseline characteristics and their 18 F-FDG PET/CT scans for adequacy of myocardial uptake suppression and correlated the presence of angiographically apparent plaque with 18 F-FDG uptake in the major coronary arteries. Two independent observers assessed the angiographic images and 18 F-FDG PET scans. Results: A total of 95% of patients had 2 or more coronary disease risk factors, and 25% had unstable symptoms; 30% of index catheterizations resulted in intervention. In 20 of 32 patients (63%), myocardial suppression was good (12) or adequate (8). Inadequate suppression was due to self-reported dietary nonadherence. Patients with good, adequate, and poor suppression had maximal myocardial standardized uptake values of 2.8 6 0.7, 5.0 6 1.3, and 17.0 6 9.7, respectively. We identified 18 F-FDG uptake in 15 patients in 1 or more coronary segments. A trend to significance in correlation between presence of angiographic disease and signal in the vessel was observed (P 5 0.07; 80 vessels examined). A total of 7 patients with significant coronary artery disease had aortic 18 F-FDG uptake. Conclusion: In this retrospective study, we demonstrated the potential use of 18 F-FDG PET in imaging of inflammation in coronary arteries. The potential of 18 F-FDG PET is also being investigated in a prospective study.

A phase I trial was designed to evaluate normal tissue tolerance to neutron capture therapy (NCT); tumor response was also followed as a secondary endpoint. Between July 1996 and May 1999, 24 subjects were entered into a phase I trial evaluating cranial NCT in subjects with primary or metastatic brain tumors. Two subjects were excluded due to a decline in their performance status and 22 subjects were irradiated at the MIT Nuclear Reactor Laboratory. The median age was 56 years (range 24-78). All subjects had a pathologically confirmed diagnosis of either glioblastoma (20) or melanoma (2) and a Karnofsky of 70 or higher. Neutron irradiation was delivered with a 15 cm diameter epithermal beam. Treatment plans varied from 1 to 3 fields depending upon the size and location of the tumor. The 10B carrier, L-p-boronophenylalanine-fructose (BPA-f), was infused through a central venous catheter at doses of 250 mg kg(-1) over 1 h (10 subjects), 300 mg kg(-1) over 1.5 h (two subjects), or 350 mg kg(-1) over 1.5-2 h (10 subjects). The pharmacokinetic profile of 10B in blood was very reproducible and permitted a predictive model to be developed. Cranial NCT can be delivered at doses high enough to exhibit a clinical response with an acceptable level of toxicity. Acute toxicity was primarily associated with increased intracranial pressure; late pulmonary effects were seen in two subjects. Factors such as average brain dose, tumor volume, and skin, mucosa, and lung dose may have a greater impact on tolerance than peak dose alone. Two subjects exhibited a complete radiographic response and 13 of 17 evaluable subjects had a measurable reduction in enhanced tumor volume following NCT.

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The OceanGliders program started in 2016 to support active coordination and enhancement of global glider activity. OceanGliders contributes to the international efforts of the Global Ocean Observation System (GOOS) for Climate, Ocean Health, and Operational Services. It brings together marine scientists and engineers operating gliders around the world: (1) to observe the long-term physical, biogeochemical, and biological ocean processes and phenomena that are relevant for societal applications; and, (2) to contribute to the GOOS through real-time and delayed mode data dissemination. The OceanGliders program is distributed across national and regional observing systems and significantly contributes to integrated, multi-scale and multi-platform sampling strategies. OceanGliders shares best practices, requirements, and scientific knowledge needed for glider operations, data collection and analysis. It also monitors global glider activity and supports the dissemination of glider data through regional and global databases, in realtime and delayed modes, facilitating data access to the wider community. OceanGliders currently supports national, regional and global initiatives to maintain and expand the capabilities and application of gliders to meet key global challenges such as improved measurement of ocean boundary currents, water transformation and storm forecast.

Observations of vertical gradients in phytoplankton community structure were made through the water column of the seasonally stratified Celtic Sea, including within the thermocline. A deep chlorophyll maximum (DCM) was located within the thermocline at all stations, coupled to the nitracline. Vertical gradients in phytoplankton community composition were routinely observed within the thermocline. The cell abundance maxima for Synechococcus occurred in the upper part of the DCM coincident with a picoeukaryote abundance minima. Picoeukaryote abundance typically increased at or just above the peak of the DCM. Diatoms were observed occasionally at the DCM peak. Pigment compositions and phytoplankton absorption spectra indicated that the different phytoplankton communities were chromatically well adapted to the spectral composition of irradiance at the depths where they occurred in the water column. Profiles of vertical eddy diffusivity revealed that timescales for mixing between the phytoplankton layers within the thermocline were in excess of typical phytoplankton growth rates. The observed vertical gradients in community structure could therefore result from selection and niche partitioning of phytoplankton types on the light and nutrient gradient within the thermocline. The data further indicate that the pigments, light absorption characteristics, and cell size contribute to the phytoplankton selection process.The Celtic Sea, part of the temperate Northwest European shelf, is a tidally dynamic environment where water column structure is strongly influenced by the balance of solar heating and tidally generated mixing (Simpson and Hunter 1974). Much of the region becomes thermally stratified in April, initiating the spring phytoplankton bloom (Pingree et al. 1976). The water column remains stratified throughout the summer, with the thermocline forming a boundary between nutrient-depleted surface mixed layer (SML) above and the nutrient-rich bottom mixed layer (BML) below (Pingree et al. 1977). During this seasonal stratification, a deep chlorophyll maximum (DCM) is present within the thermocline (Pingree et al. 1977). The DCM is typically located toward the base of the density gradient, lies within the euphotic zone, and is strongly coupled to the nitracline (Holligan et al. 1984a,b;Sharples et al. 2001).Energy from tidally induced turbulence is dissipated at the base of the thermocline, causing upward mixing of nitrate into the thermocline from the BML and downward mixing of phytoplankton from the base of the DCM (Sharples et al. 2001). Previous observations in the Celtic Sea have revealed a vertical flux of nitrate into the thermocline of around 2 mmol N m 22 d 21 with the DCM maintained at a depth corresponding to ,5% of surface irradiance (Sharples et al. 2001). The DCM is often observed to be a biomass and photosynthesis maximum as well as a pigment maximum (Holligan et al. 1984a,b;Pemberton et al. 2004;Moore et al. 2006). Monospecific blooms with chlorophyll a (Chl a) concentrations .10 mg Chl a m 23...

Prospective monthly magnetic resonance imaging (MRI) studies were done over 6 months in seven relapsing MS patients. MRI and neurologic evaluations were compared for sensitivity in detecting disease activity. Four patients were clinically stable throughout the study. Three patients had five clinical relapses, two localized to the spinal cord and three to the brainstem. Eighteen new and ten enlarging MRI lesions were seen in five patients. Most lesions were less than 10 mm in diameter. All were clinically silent. Two patients developed major enlarging MRI lesions (seen in three slices) which increased in size over 2 months and then gradually became smaller over 2 months, leaving behind small residual areas of abnormality. There were 36 follow-up scans, 17 of which (47%) showed evidence for increasing activity. Thirteen (36%) of the scans had new lesions, most of them being small. This study shows that MRI evidence for disease activity in MS is much more frequent than is clinical evidence.