Contrasting prefrontal cortex contributions to episodic memory dysfunction in behavioural variant frontotemporal dementia and alzheimer's disease

Recent evidence has questioned the integrity of episodic memory in behavioural variant frontotemporal dementia (bvFTD), where recall performance is impaired to the same extent as in Alzheimer's disease (AD). While these deficits appear to be mediated by divergent patterns of brain atrophy, there is evidence to suggest that certain prefrontal regions are implicated across both patient groups. In this study we sought to further elucidate the dorsolateral (DLPFC) and ventromedial (VMPFC) prefrontal contributions to episodic memory impairment in bvFTD and AD. Performance on episodic memory tasks and neuropsychological measures typically tapping into either DLPFC or VMPFC functions was assessed in 22 bvFTD, 32 AD patients and 35 age- and education-matched controls. Behaviourally, patient groups did not differ on measures of episodic memory recall or DLPFC-mediated executive functions. BvFTD patients were significantly more impaired on measures of VMPFC-mediated executive functions. Composite measures of the recall, DLPFC and VMPFC task scores were covaried against the T1 MRI scans of all participants to identify regions of atrophy correlating with performance on these tasks. Imaging analysis showed that impaired recall performance is associated with divergent patterns of PFC atrophy in bvFTD and AD. Whereas in bvFTD, PFC atrophy covariates for recall encompassed both DLPFC and VMPFC regions, only the DLPFC was implicated in AD. Our results suggest that episodic memory deficits in bvFTD and AD are underpinned by divergent prefrontal mechanisms. Moreover, we argue that these differences are not adequately captured by existing neuropsychological measures

Impact of the COVID-19 crisis on imaging in oncological trials

The unprecedented demand for hospital services during the SARS-CoV-2 (COVID-19) pandemic has dramatically reduced the capability for dealing with non-acute health needs, including cancer care [1, 2]. To alleviate burden on health care systems, including imaging and laboratory services, curtailment of non-COVID-19-related research activity has been necessary [3]. Measures that reduce hospital visits have been adopted to limit risk of infection and death, which is critical in a cancer population whose age and immunocompromised status increases their risk [4]. Imaging, however, requires hospital visits and close contact with staff and equipment; both are sources of disease transmission. Equipment used to image COVID-19 cases may retain virus on its surface for days [5, 6] unless disinfected. The need for social distancing and for disinfecting equipment substantially slows imaging workflow and reduces throughput. This article discusses the specific impact of pandemics such as SARS-CoV-2 on imaging in oncological trials

A state-of-the-art review of curve squeal noise: Phenomena, mechanisms, modelling and mitigation

[EN] Curve squeal is an intense tonal noise occurring when a rail vehicle negotiates a sharp curve. The phenomenon can be considered to be chaotic, with a widely differing likelihood of occurrence on different days or even times of day. The term curve squeal may include several different phenomena with a wide range of dominant frequencies and potentially different excitation mechanisms. This review addresses the different squeal phenomena and the approaches used to model squeal noise; both time-domain and frequency-domain approaches are discussed and compared. Supporting measurements using test rigs and field tests are also summarised. A particular aspect that is addressed is the excitation mechanism. Two mechanisms have mainly been considered in previous publications. In many early papers the squeal was supposed to be generated by the so-called falling friction characteristic in which the friction coefficient reduces with increasing sliding velocity. More recently the mode coupling mechanism has been raised as an alternative. These two mechanisms are explained and compared and the evidence for each is discussed. Finally, a short review is given of mitigation measures and some suggestions are offered for why these are not always successful.Squicciarini, G.; Thompson, D.; Ding, B.; Baeza González, LM. (2018). A state-of-the-art review of curve squeal noise: Phenomena, mechanisms, modelling and mitigation. Notes on Numerical Fluid Mechanics and Multidisciplinary Design. 139:3-41. https://doi.org/10.1007/978-3-319-73411-8_1S341139Anderson, D., Wheatley, N., Fogarty, B., Jiang, J., Howie, A., Potter, W.: Mitigation of curve squeal noise in Queensland, New South Wales and South Australia. In: Conference on Railway Engineering. pp. 625–636, Perth, Australia (2008)Hanson, D., Jiang, J., Dowdell, B., Dwight, R.: Curve squeal: causes, treatments and results. 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Veh. Syst. Dyn. 44(sup1), 261–271 (2006)Giménez, J.G., Alonso, A., Gómez, E.: Introduction of a friction coefficient dependent on the slip in the FastSim algorithm. Veh. Syst. Dyn. 43(4), 233–244 (2005)Chiello, O., Ayasse, J.B., Vincent, N., Koch, J.R.: Curve squeal of urban rolling stock—part 3: theoretical model. J. Sound Vib. 293(3), 710–727 (2006)Collette, C.: Importance of the wheel vertical dynamics in the squeal noise mechanism on a scaled test bench. Shock Vibr. 19(2), 145–153 (2012)Brunel, J.F., Dufrénoy, P., Naït, M., Muñoz, J.L., Demilly, F.: Transient models for curve squeal noise. J. Sound Vib. 293(3), 758–765 (2006)Glocker, C., Cataldi-Spinola, E., Leine, R.I.: Curve squealing of trains: measurement, modelling and simulation. J. Sound Vib. 324(1), 365–386 (2009)Pieringer, A.: A numerical investigation of curve squeal in the case of constant wheel/rail friction. J. 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Springer, Heidelberg (2015)Zenzerovic, I., Kropp, W., Pieringer, A.: An engineering time-domain model for curve squeal: tangential point-contact model and Green’s functions approach. J. Sound Vib. 376, 149–165 (2016)Pieringer, A., Torstensson, P.T., Giner, J., Baeza, L.: Investigation of railway curve squeal using a combination of frequency- and time-domain models. In: Anderson, D., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 139, pp 81–93. Springer, Heidelberg (2018)Chen, G.X., Xiao, J.B., Liu, Q.Y., Zhou. Z.R.: Complex eigenvalue analysis of railway curve squeal. In: Schulte-Werning, B., et al. (eds.) Noise and Vibration Mitigation for Rail Transportation Systems. NNFM, vol. 99, pp. 433–439. Springer, Heidelberg (2008)Fourie, D.J., Gräbe, P.J., Heyns, P.S., Fröhling, R.D.: Analysis of wheel squeal due to unsteady longitudinal creepage using the complex eigenvalue method. In: Anderson, D., et al. (eds.) 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Wear 265(9), 1309–1316 (2008)Fletcher, D.I., Lewis, S.: Creep curve measurement to support wear and adhesion modelling, using a continuously variable creep twin disc machine. Wear 298–299, 57–65 (2013)Fletcher, D.I.: A new two-dimensional model of rolling–sliding contact creep curves for a range of lubrication types. Proc. Inst. Mech. Eng. Part J: J. Eng. Tribol. 227(6), 529–537 (2013)Matsumoto, A., Sato, Y., Ono, H., Wang, Y., Yamamoto, M., Tanimoto, M., Oka, Y.: Creep force characteristics between rail and wheel on scaled model. Wear 253(1), 199–203 (2002)Janssens, M.H.A., van Vliet, W.J., Kooijman, P.P., De Beer, F.G.: Curve squeal of railbound vehicles (part 3): measurement method and results. In: Proceedings of Internoise, vol. 3, pp. 1568–1571, Nice, France (2000)Monk-Steel, A.D., Thompson, D.J., De Beer, F.G., Janssens, M.H.A.: An investigation into the influence of longitudinal creepage on railway squeal noise due to lateral creepage. J. 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Prostaglandin E2 Signals Through PTGER2 to Regulate Sclerostin Expression

The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations in antagonists of Wnt signaling influence skeletal integrity, in an inverse relation to Lrp receptor mutations. Loss of the Wnt antagonist Sclerostin (Sost) produces the generalized skeletal hyperostotic condition of sclerosteosis, which is characterized by increased bone mass and density due to hyperactive osteoblast function. Here we demonstrate that prostaglandin E2 (PGE2), a paracrine factor with pleiotropic effects on osteoblasts and osteoclasts, decreases Sclerostin expression in osteoblastic UMR106.01 cells. Decreased Sost expression correlates with increased expression of Wnt/TCF target genes Axin2 and Tcf3. We also show that the suppressive effect of PGE2 is mediated through a cyclic AMP/PKA pathway. Furthermore, selective agonists for the PGE2 receptor EP2 mimic the effect of PGE2 upon Sost, and siRNA reduction in Ptger2 prevents PGE2-induced Sost repression. These results indicate a functional relationship between prostaglandins and the Wnt/β-catenin signaling pathway in bone

Effects of Trophic Skewing of Species Richness on Ecosystem Functioning in a Diverse Marine Community

Widespread overharvesting of top consumers of the world’s ecosystems has “skewed” food webs, in terms of biomass and species richness, towards a generally greater domination at lower trophic levels. This skewing is exacerbated in locations where exotic species are predominantly low-trophic level consumers such as benthic macrophytes, detritivores, and filter feeders. However, in some systems where numerous exotic predators have been added, sometimes purposefully as in many freshwater systems, food webs are skewed in the opposite direction toward consumer dominance. Little is known about how such modifications to food web topology, e.g., changes in the ratio of predator to prey species richness, affect ecosystem functioning. We experimentally measured the effects of trophic skew on production in an estuarine food web by manipulating ratios of species richness across three trophic levels in experimental mesocosms. After 24 days, increasing macroalgal richness promoted both plant biomass and grazer abundance, although the positive effect on plant biomass disappeared in the presence of grazers. The strongest trophic cascade on the experimentally stocked macroalgae emerged in communities with a greater ratio of prey to predator richness (bottom-rich food webs), while stronger cascades on the accumulation of naturally colonizing algae (primarily microalgae with some early successional macroalgae that recruited and grew in the mesocosms) generally emerged in communities with greater predator to prey richness (the more top-rich food webs). These results suggest that trophic skewing of species richness and overall changes in food web topology can influence marine community structure and food web dynamics in complex ways, emphasizing the need for multitrophic approaches to understand the consequences of marine extinctions and invasions

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Habitat partitioning and vulnerability of sharks in the Great Barrier Reef Marine Park

Sharks present a critical conservation challenge, but little is known about their spatial distribution and vulnerability, particularly in complex seascapes such as Australia's Great Barrier Reef Marine Park (GBRMP). We review (1) the distribution of shark species among the primary habitats of the GBRMP (coral reefs, inshore/shelf, pelagic and deep-water habitats) (2) the relative exploitation of each species by fisheries, and (3) how current catch rates interact with their vulnerability and trophic index. Excluding rays and chimaeras, we identify a total of 82 shark species in the GBRMP. We find that shark research in the GBRMP has yielded little quantitative information on most species. Reef sharks are largely site-fidelic, but can move large distances and some regularly use non-reef habitats. Inshore and shelf sharks use coastal habitats either exclusively or during specific times in their life cycle (e.g. as nurseries). Virtually nothing is known about the distribution and habitat use of the GBRMP's pelagic and deep-water sharks. At least 46 species (53.5 %) are caught in one or more fisheries, but stock assessments are lacking for most. At least 17 of the sharks caught are considered highly vulnerable to exploitation. We argue that users of shark resources should be responsible for demonstrating that a fishery is sustainable before exploitation is allowed to commence or continue. This fundamental change in management principle will safeguard against stock collapses that have characterised many shark fisheries