Acceleration and transport of relativistic electrons in the jets of the microquasar SS 433.

SS 433 is a microquasar, a stellar binary system that launches collimated relativistic jets. We observed SS 433 in gamma rays using the High Energy Stereoscopic System (H.E.S.S.) and found an energy-dependent shift in the apparent position of the gamma-ray emission from the parsec-scale jets. These observations trace the energetic electron population and indicate that inverse Compton scattering is the emission mechanism of the gamma rays. Our modeling of the energy-dependent gamma-ray morphology constrains the location of particle acceleration and requires an abrupt deceleration of the jet flow. We infer the presence of shocks on either side of the binary system, at distances of 25 to 30 parsecs, and that self-collimation of the precessing jets forms the shocks, which then efficiently accelerate electrons.

Zinc Switch in Pig Heart Lipoamide Dehydrogenase: Steady-State and Transient Kinetic Studies of the Diaphorase Reaction.

Elevation of intracellular Zn2+ following ischemia contributes to cell death by affecting mitochondrial function. Zn2+ is a differential regulator of the mitochondrial enzyme lipoamide dehydrogenase (LADH) at physiological concentrations (Ka = 0.1 µM free zinc), inhibiting lipoamide and accelerating NADH dehydrogenase activities. These differential effects have been attributed to coordination of Zn2+ by LADH active-site cysteines. A detailed kinetic mechanism has now been developed for the diaphorase (NADH-dehydrogenase) reaction catalyzed by pig heart LADH using 2,6-dichlorophenol-indophenol (DCPIP) as a model quinone electron acceptor. Anaerobic stopped-flow experiments show that two-electron reduced LADH is 15-25-fold less active towards DCPIP reduction than four-electron reduced enzyme, or Zn2+-modified reduced LADH (the corresponding values of the rate constants are (6.5 ± 1.5) × 103 M-1·s-1, (9 ± 2) × 104 M-1·s-1, and (1.6 ± 0.5) × 105 M-1·s-1, respectively). Steady-state kinetic studies with different diaphorase substrates show that Zn2+ accelerates reaction rates exclusively for two-electron acceptors (duroquinone, DCPIP), but not for one-electron acceptors (benzoquinone, ubiquinone, ferricyanide). This implies that the two-electron reduced form of LADH, prevalent at low NADH levels, is a poor two-electron donor compared to the four-electron reduced or Zn2+-modified reduced LADH forms. These data suggest that zinc binding to the active-site thiols switches the enzyme from one- to two-electron donor mode. This zinc-activated switch has the potential to alter the ratio of superoxide and H2O2 generated by the LADH oxidase activity.

Multi-modal sexual displays in Australian humpback dolphins.

Sexual displays enriched by object carrying serve to increase individual male fitness, yet are uncommon phenomena in the animal kingdom. While they have been documented in a variety of taxa, primarily birds, they are rare outside non-human mammals. Here, we document marine sponge presenting associated with visual and acoustic posturing found in several, geographically widespread populations of Australian humpback dolphins (Sousa sahulensis) over ten years of observation. Only adult males presented marine sponges, typically doing so in the presence of sexually mature females, although social groups predominantly consisted of mixed age and sex classes. Male humpback dolphins appear to be using sponges for signalling purposes in multi-modal sexual displays. Further, based on limited behavioural and genetic data, we hypothesise that pairs of adult male Sousa form at least temporary coalitions or alliances. The use of objects in sexual displays by non-human mammals is rare and, moreover, cooperation between males in the pursuit of an indivisible resource is an evolutionary hurdle relatively few species have overcome. These findings suggest a hitherto unrecognised level of social complexity in humpback dolphins.

Clinical effectiveness of very-low-energy diets in the management of weight loss: a systematic review and meta-analysis of randomized controlled trials.

Guidelines suggest that very-low-energy diets (VLEDs) should be used to treat obesity only when rapid weight loss is clinically indicated because of concerns about rapid weight regain. Literature databases were searched from inception to November 2014. Randomized trials were included where the intervention included a VLED and the comparator was no intervention or an intervention that could be given in a general medical setting in adults that were overweight. Two reviewers characterized the population, intervention, control groups, outcomes and appraised quality. The primary outcome was weight change at 12 months from baseline. Compared with a behavioural programme alone, VLEDs combined with a behavioural programme achieved -3.9 kg [95% confidence interval (CI) -6.7 to -1.1] at 1 year. The difference at 24 months was -1.4 kg (95%CI -2.6 to -0.2) and at 38-60 months was -1.3 kg (95%CI -2.9 to 0.2). Nineteen per cent of the VLED group discontinued treatment prematurely compared with 20% of the comparator groups, relative risk 0.96 (0.56 to 1.66). One serious adverse event, hospitalization with cholecystitis, was reported in the VLED group and none in the comparator group. Very-low-energy diets with behavioural programmes achieve greater long-term weight loss than behavioural programmes alone, appear tolerable and lead to few adverse events suggesting they could be more widely used than current guidelines suggest.

Evidence for Astrophysical Muon Neutrinos from the Northern Sky with IceCube.

Results from the IceCube Neutrino Observatory have recently provided compelling evidence for the existence of a high energy astrophysical neutrino flux utilizing a dominantly Southern Hemisphere data set consisting primarily of ν(e) and ν(τ) charged-current and neutral-current (cascade) neutrino interactions. In the analysis presented here, a data sample of approximately 35,000 muon neutrinos from the Northern sky is extracted from data taken during 659.5 days of live time recorded between May 2010 and May 2012. While this sample is composed primarily of neutrinos produced by cosmic ray interactions in Earth's atmosphere, the highest energy events are inconsistent with a hypothesis of solely terrestrial origin at 3.7σ significance. These neutrinos can, however, be explained by an astrophysical flux per neutrino flavor at a level of Φ(E(ν))=9.9(-3.4)(+3.9)×10(-19) GeV(-1) cm(-2) sr(-1) s(-1)(E(ν)/100 TeV(-2), consistent with IceCube's Southern-Hemisphere-dominated result. Additionally, a fit for an astrophysical flux with an arbitrary spectral index is performed. We find a spectral index of 2.2(-0.2)(+0.2), which is also in good agreement with the Southern Hemisphere result.

Flavor Ratio of Astrophysical Neutrinos above 35 TeV in IceCube.

A diffuse flux of astrophysical neutrinos above 100 TeV has been observed at the IceCube Neutrino Observatory. Here we extend this analysis to probe the astrophysical flux down to 35 TeV and analyze its flavor composition by classifying events as showers or tracks. Taking advantage of lower atmospheric backgrounds for showerlike events, we obtain a shower-biased sample containing 129 showers and 8 tracks collected in three years from 2010 to 2013. We demonstrate consistency with the (fe:fµ:fτ)⊕≈(1:1:1)⊕ flavor ratio at Earth commonly expected from the averaged oscillations of neutrinos produced by pion decay in distant astrophysical sources. Limits are placed on nonstandard flavor compositions that cannot be produced by averaged neutrino oscillations but could arise in exotic physics scenarios. A maximally tracklike composition of (0:1:0)⊕ is excluded at 3.3σ, and a purely showerlike composition of (1:0:0)⊕ is excluded at 2.3σ.

Development of a general analysis and unfolding scheme and its application to measure the energy spectrum of atmospheric neutrinos with IceCube: IceCube Collaboration.

We present the development and application of a generic analysis scheme for the measurement of neutrino spectra with the IceCube detector. This scheme is based on regularized unfolding, preceded by an event selection which uses a Minimum Redundancy Maximum Relevance algorithm to select the relevant variables and a random forest for the classification of events. The analysis has been developed using IceCube data from the 59-string configuration of the detector. 27,771 neutrino candidates were detected in 346 days of livetime. A rejection of 99.9999 % of the atmospheric muon background is achieved. The energy spectrum of the atmospheric neutrino flux is obtained using the TRUEE unfolding program. The unfolded spectrum of atmospheric muon neutrinos covers an energy range from 100 GeV to 1 PeV. Compared to the previous measurement using the detector in the 40-string configuration, the analysis presented here, extends the upper end of the atmospheric neutrino spectrum by more than a factor of two, reaching an energy region that has not been previously accessed by spectral measurements.

NKD2, a negative regulator of Wnt signaling, suppresses tumor growth and metastasis in osteosarcoma.

Osteosarcoma (OS) is the most frequent pediatric malignant bone tumor that has a high propensity for metastases. Through osteoblast-specific alteration of p53 status, we developed a genetically engineered mouse model of localized and metastatic OS to gain an understanding into the molecular pathogenesis of OS. Microarray analysis of both localized tumors and metastatic tumors identified the downregulation of the naked cuticle homolog 2 (NKD2) gene, a negative regulator of Wnt signaling. Overexpression of NKD2 in metastatic human and mouse OS cells significantly decreases cell proliferation, migration and invasion ability in vitro and drastically diminishes OS tumor growth and metastasis in vivo, whereas downregulation enhances migratory and invasive potential. Evaluation of NKD2-overexpressing tumors revealed upregulation of tumor-suppressor genes and downregulation of molecules involved in blood vessel formation and cell migration. Furthermore, assessment of primary human OS revealed downregulation of NKD2 in metastatic and recurrent OS. Finally, we provide biological evidence that use of small-molecule inhibitors targeting the Wnt pathway can have therapeutic efficacy in decreasing metastatic properties in OS. Our studies provide compelling evidence that downregulation of NKD2 expression and alterations in associated regulated pathways have a significant role in driving OS tumor growth and metastasis.

Does morphology predict trophic position and habitat use of ant species and assemblages?

A functional traits-based theory of organismal communities is critical for understanding the principles underlying community assembly, and predicting responses to environmental change. This is particularly true for terrestrial arthropods, of which only 20% are described. Using epigaeic ant assemblages, we asked: (1) can we use morphological variation among species to predict trophic position or preferred microhabitat; (2) does the strength of morphological associations suggest recent trait divergence; (3) do environmental variables at site scale predict trait sets for whole assemblages? We pitfall-trapped ants from a revegetation chronosequence and measured their morphology, trophic position [using C:N stoichiometry and stable isotope ratios (δ)] and characteristics of microhabitat and macrohabitat. We found strong associations between high trophic position (low C:N and high δ(15)N) in body tissue and morphological traits: predators were larger, had more laterally positioned eyes, more physical protection and tended to be monomorphic. In addition, morphological traits were associated with certain microhabitat features, e.g. smaller heads were associated with the bare ground microhabitat. Trait-microhabitat relationships were more pronounced when phylogenetic adjustments were used, indicating a strong influence of recent trait divergences. At the assemblage level, our fourth corner analysis revealed associations between the prevalence of traits and macrohabitat, although these associations were not the same as those based on microhabitat associations. This study shows direct links between species-level traits and both diet and habitat preference. Trait-based prediction of ecological roles and community structure is thus achievable when integrating stoichiometry, morphology and phylogeny, but scale is an important consideration in such predictions.

Observation of high-energy astrophysical neutrinos in three years of IceCube data.

A search for high-energy neutrinos interacting within the IceCube detector between 2010 and 2012 provided the first evidence for a high-energy neutrino flux of extraterrestrial origin. Results from an analysis using the same methods with a third year (2012-2013) of data from the complete IceCube detector are consistent with the previously reported astrophysical flux in the 100 TeV-PeV range at the level of 10(-8) GeV cm-2 s-1 sr-1 per flavor and reject a purely atmospheric explanation for the combined three-year data at 5.7σ. The data are consistent with expectations for equal fluxes of all three neutrino flavors and with isotropic arrival directions, suggesting either numerous or spatially extended sources. The three-year data set, with a live time of 988 days, contains a total of 37 neutrino candidate events with deposited energies ranging from 30 to 2000 TeV. The 2000-TeV event is the highest-energy neutrino interaction ever observed.

Evidence for high-energy extraterrestrial neutrinos at the IceCube detector.

We report on results of an all-sky search for high-energy neutrino events interacting within the IceCube neutrino detector conducted between May 2010 and May 2012. The search follows up on the previous detection of two PeV neutrino events, with improved sensitivity and extended energy coverage down to about 30 TeV. Twenty-six additional events were observed, substantially more than expected from atmospheric backgrounds. Combined, both searches reject a purely atmospheric origin for the 28 events at the 4σ level. These 28 events, which include the highest energy neutrinos ever observed, have flavors, directions, and energies inconsistent with those expected from the atmospheric muon and neutrino backgrounds. These properties are, however, consistent with generic predictions for an additional component of extraterrestrial origin.

Measurement of atmospheric neutrino oscillations with IceCube.

We present the first statistically significant detection of neutrino oscillations in the high-energy regime (>20 GeV) from an analysis of IceCube Neutrino Observatory data collected in 2010 and 2011. This measurement is made possible by the low-energy threshold of the DeepCore detector (~20 GeV) and benefits from the use of the IceCube detector as a veto against cosmic-ray-induced muon background. The oscillation signal was detected within a low-energy muon neutrino sample (20-100 GeV) extracted from data collected by DeepCore. A high-energy muon neutrino sample (100 GeV-10 TeV) was extracted from IceCube data to constrain systematic uncertainties. The disappearance of low-energy upward-going muon neutrinos was observed, and the nonoscillation hypothesis is rejected with more than 5σ significance. In a two-neutrino flavor formalism, our data are best described by the atmospheric neutrino oscillation parameters |Δm(32)(2)|=(2.3(-0.5)(+0.6))×10(-3) eV(2) and sin(2)(2θ(23))>0.93, and maximum mixing is favored.

First observation of PeV-energy neutrinos with IceCube.

We report on the observation of two neutrino-induced events which have an estimated deposited energy in the IceCube detector of 1.04±0.16 and 1.14±0.17 PeV, respectively, the highest neutrino energies observed so far. These events are consistent with fully contained particle showers induced by neutral-current ν(e,µ,τ) (ν(e,µ,τ)) or charged-current ν(e) (ν(e)) interactions within the IceCube detector. The events were discovered in a search for ultrahigh energy neutrinos using data corresponding to 615.9 days effective live time. The expected number of atmospheric background is 0.082±0.004(stat)(-0.057)(+0.041)(syst). The probability of observing two or more candidate events under the atmospheric background-only hypothesis is 2.9×10(-3) (2.8σ) taking into account the uncertainty on the expected number of background events. These two events could be a first indication of an astrophysical neutrino flux; the moderate significance, however, does not permit a definitive conclusion at this time.

Search for dark matter annihilations in the sun with the 79-string IceCube detector.

We have performed a search for muon neutrinos from dark matter annihilation in the center of the Sun with the 79-string configuration of the IceCube neutrino telescope. For the first time, the DeepCore subarray is included in the analysis, lowering the energy threshold and extending the search to the austral summer. The 317 days of data collected between June 2010 and May 2011 are consistent with the expected background from atmospheric muons and neutrinos. Upper limits are set on the dark matter annihilation rate, with conversions to limits on spin-dependent and spin-independent scattering cross sections of weakly interacting massive particles (WIMPs) on protons, for WIMP masses in the range 20-5000 GeV/c2. These are the most stringent spin-dependent WIMP-proton cross section limits to date above 35 GeV/c2 for most WIMP models.

Measurement of the atmospheric νe flux in IceCube.

We report the first measurement of the atmospheric electron neutrino flux in the energy range between approximately 80 GeV and 6 TeV, using data recorded during the first year of operation of IceCube's DeepCore low-energy extension. Techniques to identify neutrinos interacting within the DeepCore volume and veto muons originating outside the detector are demonstrated. A sample of 1029 events is observed in 281 days of data, of which 496±66(stat)±88(syst) are estimated to be cascade events, including both electron neutrino and neutral current events. The rest of the sample includes residual backgrounds due to atmospheric muons and charged current interactions of atmospheric muon neutrinos. The flux of the atmospheric electron neutrinos is consistent with models of atmospheric neutrinos in this energy range. This constitutes the first observation of electron neutrinos and neutral current interactions in a very large volume neutrino telescope optimized for the TeV energy range.

Xenon-enhanced cerebral blood flow at 28% xenon provides uniquely safe access to quantitative, clinically useful cerebral blood flow information: a multicenter study.

BACKGROUND AND PURPOSE: Xe-CT measures CBF and can be used to make clinical treatment decisions. Availability has been limited, in part due to safety concerns. Due to improvements in CT technology, the concentration of inhaled xenon gas has been decreased from 32% to 28%. To our knowledge, no data exist regarding the safety profile of this concentration. We sought to better determine the safety profile of this lower concentration through a multicenter evaluation of adverse events reported by all centers currently performing xenon/CT studies in the US. MATERIALS AND METHODS: Patients were prospectively recruited at 7 centers to obtain safety and efficacy information. All studies were performed to answer a clinical question. All centers used the same xenon delivery system. CT imaging was used during a 4.3-minute inhalation of 28% xenon gas. Vital signs were monitored on all patients throughout each procedure. Occurrence and severity of adverse events were recorded by the principal investigator at each site. RESULTS: At 7 centers, 2003 studies were performed, 1486 (74.2%) in nonventilated patients. The most common indications were occlusive vascular disease and ischemic stroke; 93% of studies were considered clinically useful. Thirty-nine studies (1.9%) caused respiratory suppression of >20 seconds, all of which resolved spontaneously. Shorter respiratory pauses occurred in 119 (5.9%), and hyperventilation, in 34 (1.7%). There were 53 additional adverse events (2.9%), 7 of which were classified as severe. No adverse event resulted in any persistent neurologic change or other sequelae. CONCLUSIONS: Xe-CT CBF can be performed safely, with a very low risk of adverse events and, to date, no risk of permanent morbidity or sequelae. On the basis of the importance of the clinical information gained, Xe-CT should be made widely available.

Limits on neutrino emission from gamma-ray bursts with the 40 string IceCube detector.

IceCube has become the first neutrino telescope with a sensitivity below the TeV neutrino flux predicted from gamma-ray bursts if gamma-ray bursts are responsible for the observed cosmic-ray flux above 10(18) eV. Two separate analyses using the half-complete IceCube detector, one a dedicated search for neutrinos from pγ interactions in the prompt phase of the gamma-ray burst fireball and the other a generic search for any neutrino emission from these sources over a wide range of energies and emission times, produced no evidence for neutrino emission, excluding prevailing models at 90% confidence.

The Brøset Violence Checklist: clinical utility in a secure psychiatric intensive care setting.

Violence towards health-care workers, especially in areas such as mental health/psychiatry, has become increasingly common, with nursing staff suggesting that a fear of violence from their patients may affect the quality of care they provide. Structured clinical tools have the potential to assist health-care providers in identifying patients who have the potential to become violent or aggressive. The Brøset Violence Checklist (BVC), a six-item instrument that uses the presence or absence of three patient characteristics and three patient behaviours to predict the potential for violence within a subsequent 24-h period, was trialled for 3 months on an 11-bed secure psychiatric intensive care unit. Despite the belief on the part of some nurses that decisions related to risk for violence and aggression rely heavily on intuition, there was widespread acceptance of the tool. During the trial, use of seclusion decreased suggesting that staff were able to intervene before seclusion was necessary. The tool has since been implemented as a routine part of patient care on two units in a 92-bed psychiatric centre. Five-year follow-up data and implications for practice are presented.

Application of principal component analysis to pharmacogenomic studies in Canada.

Ethnicity can confound results in pharmacogenomic studies. Allele frequencies of loci that influence drug metabolism can vary substantially between different ethnicities and underlying ancestral genetic differences can lead to spurious findings in pharmacogenomic association studies. We evaluated the application of principal component analysis (PCA) in a pharmacogenomic study in Canada to detect and correct for genetic ancestry differences using genotype data from 2094 loci in 220 key drug biotransformation genes. Using 89 Coriell worldwide reference samples, we observed a strong correlation between principal component values and geographic origin. We further applied PCA to accurately infer the genetic ancestry in our ethnically diverse Canadian cohort of 524 patients from the GATC study of severe adverse drug reactions. We show that PCA can be successfully applied in pharmacogenomic studies using a limited set of markers to detect underlying differences in genetic ancestry thereby maximizing power and minimizing false-positive findings.

Tracheostomy tape: more trouble than it's worth?

In many units where microvascular free-tissue transfer in the head and neck region is practised, tracheostomy is completed with the suturing of the tube in place and the removal of the supporting struts from the tube flange. The thinking is that in removing the struts the risk of occlusion of the vascular pedicle of the free flap, as it lies in the neck, is reduced as the cervical tape cannot be applied. The evidence base for vascular obstruction resulting from a correctly positioned tape is lacking. Presented here is a case in which potential flap failure, as a result of a cervical tracheostomy tape, was avoided by early detection of ischaemia using microdialysis.