A literature review of magnetic resonance imaging sequence advancements in visualizing functional neurosurgery targets

OBJECTIVE: Historically, preoperative planning for functional neurosurgery has depended on the indirect localization of target brain structures using visible anatomical landmarks. However, recent technological advances in neuroimaging have permitted marked improvements in MRI-based direct target visualization, allowing for refinement of "first-pass" targeting. The authors reviewed studies relating to direct MRI visualization of the most common functional neurosurgery targets (subthalamic nucleus, globus pallidus, and thalamus) and summarize sequence specifications for the various approaches described in this literature. METHODS: The peer-reviewed literature on MRI visualization of the subthalamic nucleus, globus pallidus, and thalamus was obtained by searching MEDLINE. Publications examining direct MRI visualization of these deep brain stimulation targets were included for review. RESULTS: A variety of specialized sequences and postprocessing methods for enhanced MRI visualization are in current use. These include susceptibility-based techniques such as quantitative susceptibility mapping, which exploit the amount of tissue iron in target structures, and white matter attenuated inversion recovery, which suppresses the signal from white matter to improve the distinction between gray matter nuclei. However, evidence confirming the superiority of these sequences over indirect targeting with respect to clinical outcome is sparse. Future targeting may utilize information about functional and structural networks, necessitating the use of resting-state functional MRI and diffusion-weighted imaging. CONCLUSIONS: Specialized MRI sequences have enabled considerable improvement in the visualization of common deep brain stimulation targets. With further validation of their ability to improve clinical outcomes and advances in imaging techniques, direct visualization of targets may play an increasingly important role in preoperative planning

Single Gene Deletions of Orexin, Leptin, Neuropeptide Y, and Ghrelin Do Not Appreciably Alter Food Anticipatory Activity in Mice

Timing activity to match resource availability is a widely conserved ability in nature. Scheduled feeding of a limited amount of food induces increased activity prior to feeding time in animals as diverse as fish and rodents. Typically, food anticipatory activity (FAA) involves temporally restricting unlimited food access (RF) to several hours in the middle of the light cycle, which is a time of day when rodents are not normally active. We compared this model to calorie restriction (CR), giving the mice 60% of their normal daily calorie intake at the same time each day. Measurement of body temperature and home cage behaviors suggests that the RF and CR models are very similar but CR has the advantage of a clearly defined food intake and more stable mean body temperature. Using the CR model, we then attempted to verify the published result that orexin deletion diminishes food anticipatory activity (FAA) but observed little to no diminution in the response to CR and, surprisingly, that orexin KO mice are refractory to body weight loss on a CR diet. Next we tested the orexigenic neuropeptide Y (NPY) and ghrelin and the anorexigenic hormone, leptin, using mouse mutants. NPY deletion did not alter the behavior or physiological response to CR. Leptin deletion impaired FAA in terms of some activity measures, such as walking and rearing, but did not substantially diminish hanging behavior preceding feeding time, suggesting that leptin knockout mice do anticipate daily meal time but do not manifest the full spectrum of activities that typify FAA. Ghrelin knockout mice do not have impaired FAA on a CR diet. Collectively, these results suggest that the individual hormones and neuropepetides tested do not regulate FAA by acting individually but this does not rule out the possibility of their concerted action in mediating FAA

People of the British Isles: preliminary analysis of genotypes and surnames in a UK control population

There is a great deal of interest in fine scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to play a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. Here we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK control population that can be used as a resource by the research community as well as providing fine scale genetic information on the British population. So far, some 4,000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3,865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1,057 samples demonstrates the value of these samples for investigating fine scale population structure within the UK, and shows how this can be enhanced by the use of surnames

Food Anticipatory Activity Behavior of Mice across a Wide Range of Circadian and Non-Circadian Intervals

When rodents are fed in a limited amount during the daytime, they rapidly redistribute some of their nocturnal activity to the time preceding the delivery of food. In rats, anticipation of a daily meal has been interpreted as a circadian rhythm controlled by a food-entrained oscillator (FEO) with circadian limits to entrainment. Lesion experiments place this FEO outside of the light-entrainable circadian pacemaker in the suprachiasmatic nucleus. Mice also anticipate a fixed daily meal, but circadian limits to entrainment and anticipation of more than 2 daily meals, have not been assessed. We used a video-based behavior recognition system to quantify food anticipatory activity in mice receiving 2, 3, or 6 daily meals at intervals of 12, 8, or 4-hours (h). Individual mice were able to anticipate as many as 4 of 6 daily meals, and anticipation persisted during meal omission tests. On the 6 meal schedule, pre-prandial activity and body temperature were poorly correlated, suggesting independent regulation. Mice showed a limited ability to anticipate an 18 h feeding schedule. Finally, mice showed concurrent circadian and sub-hourly anticipation when provided with 6 small meals, at 30 minute intervals, at a fixed time of day. These results indicate that mice can anticipate feeding opportunities at a fixed time of day across a wide range of intervals not previously associated with anticipatory behavior in studies of rats. The methods described here can be exploited to determine the extent to which timing of different intervals in mice relies on common or distinct neural and molecular mechanisms

Multilevel latent class casemix modelling: a novel approach to accommodate patient casemix

<p>Abstract</p> <p>Background</p> <p>Using routinely collected patient data we explore the utility of multilevel latent class (MLLC) models to adjust for patient casemix and rank Trust performance. We contrast this with ranks derived from Trust standardised mortality ratios (SMRs).</p> <p>Methods</p> <p>Patients with colorectal cancer diagnosed between 1998 and 2004 and resident in Northern and Yorkshire regions were identified from the cancer registry database (n = 24,640). Patient age, sex, stage-at-diagnosis (Dukes), and Trust of diagnosis/treatment were extracted. Socioeconomic background was derived using the Townsend Index. Outcome was survival at 3 years after diagnosis. MLLC-modelled and SMR-generated Trust ranks were compared.</p> <p>Results</p> <p>Patients were assigned to two classes of similar size: one with reasonable prognosis (63.0% died within 3 years), and one with better prognosis (39.3% died within 3 years). In patient class one, all patients diagnosed at stage B or C died within 3 years; in patient class two, all patients diagnosed at stage A, B or C survived. Trusts were assigned two classes with 51.3% and 53.2% of patients respectively dying within 3 years. Differences in the ranked Trust performance between the MLLC model and SMRs were all within estimated 95% CIs.</p> <p>Conclusions</p> <p>A novel approach to casemix adjustment is illustrated, ranking Trust performance whilst facilitating the evaluation of factors associated with the patient journey (e.g. treatments) and factors associated with the processes of healthcare delivery (e.g. delays). Further research can demonstrate the value of modelling patient pathways and evaluating healthcare processes across provider institutions.</p

Low atmospheric CO2 levels during the Little Ice Age due to cooling-induced terrestrial uptake

Low atmospheric carbon dioxide (CO2) concentration during the Little Ice Age has been used to derive the global carbon cycle sensitivity to temperature. Recent evidence confirms earlier indications that the low CO2 was caused by increased terrestrial carbon storage. It remains unknown whether the terrestrial biosphere responded to temperature variations, or there was vegetation re-growth on abandoned farmland. Here we present a global numerical simulation of atmospheric carbonyl sulfide concentrations in the pre-industrial period. Carbonyl sulfide concentration is linked to changes in gross primary production and shows a positive anomaly during the Little Ice Age. We show that a decrease in gross primary production and a larger decrease in ecosystem respiration is the most likely explanation for the decrease in atmospheric CO2 and increase in atmospheric carbonyl sulfide concentrations. Therefore, temperature change, not vegetation re-growth, was the main cause of the increased terrestrial carbon storage. We address the inconsistency between ice-core CO2 records from different sites measuring CO2 and δ13CO2 in ice from Dronning Maud Land (Antarctica). Our interpretation allows us to derive the temperature sensitivity of pre-industrial CO2 fluxes for the terrestrial biosphere (γL = -10 to -90 Pg C K-1), implying a positive climate feedback and providing a benchmark to reduce model uncertainties

The Nature of the Dietary Protein Impacts the Tissue-to-Diet 15N Discrimination Factors in Laboratory Rats

Due to the existence of isotope effects on some metabolic pathways of amino acid and protein metabolism, animal tissues are 15N-enriched relative to their dietary nitrogen sources and this 15N enrichment varies among different tissues and metabolic pools. The magnitude of the tissue-to-diet discrimination (Δ15N) has also been shown to depend on dietary factors. Since dietary protein sources affect amino acid and protein metabolism, we hypothesized that they would impact this discrimination factor, with selective effects at the tissue level. To test this hypothesis, we investigated in rats the influence of a milk or soy protein-based diet on Δ15N in various nitrogen fractions (urea, protein and non-protein fractions) of blood and tissues, focusing on visceral tissues. Regardless of the diet, the different protein fractions of blood and tissues were generally 15N-enriched relative to their non-protein fraction and to the diet (Δ15N>0), with large variations in the Δ15N between tissue proteins. Δ15N values were markedly lower in tissue proteins of rats fed milk proteins compared to those fed soy proteins, in all sampled tissues except in the intestine, and the amplitude of Δ15N differences between diets differed between tissues. Both between-tissue and between-diet Δ15N differences are probably related to modulations of the relative orientation of dietary and endogenous amino acids in the different metabolic pathways. More specifically, the smaller Δ15N values observed in tissue proteins with milk than soy dietary protein may be due to a slightly more direct channeling of dietary amino acids for tissue protein renewal and to a lower recycling of amino acids through fractionating pathways. In conclusion, the present data indicate that natural Δ15N of tissue are sensitive markers of the specific subtle regional modifications of the protein and amino acid metabolism induced by the protein dietary source

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT