Pain in patients with dementia: A review of pain assessment and treatment challenges

Pain represents a major treatment challenge in older people with dementia. The majority of healthy older people experience regular pain and around 50% take regular analgesics. Pain is likely to be equally prevalent in people with dementia, yet only a small minority are prescribed regular analgesics. This is a key issue since recent work has provided evidence that untreated pain may be a major contributor to reduced quality of life and increases the likelihood of emergence of behavioural and psychological symptoms such as agitation. Better assessment and treatment of pain may therefore substantially improve outcomes for people with dementia. In this context, we reviewed the literature and summarised the best available evidence regarding the frequency of pain and pain diagnosis in patients with dementia based on pain assessment and treatment recommendations for these individuals. Hardly any randomized, controlled studies of pain treatment efficacy in patients with dementia are available, with the consequence that most pain treatment recommendations are not based on the highest level of evidence

Lrp4 Regulates Initiation of Ureteric Budding and Is Crucial for Kidney Formation – A Mouse Model for Cenani-Lenz Syndrome

Background: Development of the kidney is initiated when the ureteric bud (UB) branches from the Wolffian duct and invades the overlying metanephric mesenchyme (MM) triggering the mesenchymal/epithelial interactions that are the basis of organ formation. Multiple signaling pathways must be integrated to ensure proper timing and location of the ureteric bud formation. Methods and Principal Findings: We have used gene targeting to create an Lrp4 null mouse line. The mutation results in early embryonic lethality with a subpenetrant phenotype of kidney agenesis. Ureteric budding is delayed with a failure to stimulate the metanephric mesenchyme in a timely manner, resulting in failure of cellular differentiation and resulting absence of kidney formation in the mouse as well as comparable malformations in humans with Cenani-Lenz syndrome. Conclusion: Lrp4 is a multi-functional receptor implicated in the regulation of several molecular pathways, including Wnt and Bmp signaling. Lrp4 2/2 mice show a delay in ureteric bud formation that results in unilateral or bilateral kidney agenesis. These data indicate that Lrp4 is a critical regulator of UB branching and lack of Lrp4 results in congenital kidne

Viscous modes within the compressible boundary-layer flow due to a broad rotating cone

Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications.We investigate the effects of compressibility and wall cooling on the stationary, viscous (Type II) instability mode within the 3D boundary layer over rotating cones with half-angle greater than 40∘ 40∘ . The stationary mode is characterised by zero shear stress at the wall and a triple-deck solution is presented in the isothermal case. Asymptotic solutions are obtained which describe the structure of the wavenumber and the orientation of this mode as a function of local Mach number. It is found that a stationary mode is possible only over a finite range of local Mach number. Our conclusions are entirely consistent with the results of Seddougui 1990 , A nonlinear investigation of the stability models of instability of the trhee-dimensional Compresible boundary layer due to a rotating disc Q. J. Mech. Appl. Math. , 43, pt. 4. It is suggested that wall cooling has a significant stabilising effect, while reducing the half-angle is marginally destabilising. Solutions are presented for air

Book Reviews

With the observation of high-energy astrophysical neutrinos by the IceCube Neutrino Observatory, interest has risen in models of PeV-mass decaying dark matter particles to explain the observed flux. We present two dedicated experimental analyses to test this hypothesis. One analysis uses 6 years of IceCube data focusing on muon neutrino ‘track’ events from the Northern Hemisphere, while the second analysis uses 2 years of ‘cascade’ events from the full sky. Known background components and the hypothetical flux from unstable dark matter are fitted to the experimental data. Since no significant excess is observed in either analysis, lower limits on the lifetime of dark matter particles are derived: we obtain the strongest constraint to date, excluding lifetimes shorter than $10^{28}$ s at 90% CL for dark matter masses above 10 TeV

Neutrinos below 100 TeV from the southern sky employing refined veto techniques to IceCube data

Many Galactic sources of gamma rays, such as supernova remnants, are expected to produce neutrinos with a typical energy cutoff well below 100 TeV. For the IceCube Neutrino Observatory located at the South Pole, the southern sky, containing the inner part of the Galactic plane and the Galactic Center, is a particularly challenging region at these energies, because of the large background of atmospheric muons. In this paper, we present recent advancements in data selection strategies for track-like muon neutrino events with energies below 100 TeV from the southern sky. The strategies utilize the outer detector regions as veto and features of the signal pattern to reduce the background of atmospheric muons to a level which, for the first time, allows IceCube searching for point-like sources of neutrinos in the southern sky at energies between 100 GeV and several TeV in the muon neutrino charged current channel. No significant clustering of neutrinos above background expectation was observed in four years of data recorded with the completed IceCube detector. Upper limits on the neutrino flux for a number of spectral hypotheses are reported for a list of astrophysical objects in the southern hemisphere.Comment: 19 pages, 17 figures, 2 table

Differential limit on the extremely-high-energy cosmic neutrino flux in the presence of astrophysical background from nine years of IceCube data

We report a quasi-differential upper limit on the extremely-high-energy (EHE) neutrino flux above $5\times 10^{6}$ GeV based on an analysis of nine years of IceCube data. The astrophysical neutrino flux measured by IceCube extends to PeV energies, and it is a background flux when searching for an independent signal flux at higher energies, such as the cosmogenic neutrino signal. We have developed a new method to place robust limits on the EHE neutrino flux in the presence of an astrophysical background, whose spectrum has yet to be understood with high precision at PeV energies. A distinct event with a deposited energy above $10^{6}$ GeV was found in the new two-year sample, in addition to the one event previously found in the seven-year EHE neutrino search. These two events represent a neutrino flux that is incompatible with predictions for a cosmogenic neutrino flux and are considered to be an astrophysical background in the current study. The obtained limit is the most stringent to date in the energy range between $5 \times 10^{6}$ and $5 \times 10^{10}$ GeV. This result constrains neutrino models predicting a three-flavor neutrino flux of $E_\nu^2\phi_{\nu_e+\nu_\mu+\nu_\tau}\simeq2\times 10^{-8}\ {\rm GeV}/{\rm cm}^2\ \sec\ {\rm sr}$at$10^9\ {\rm GeV}$. A significant part of the parameter-space for EHE neutrino production scenarios assuming a proton-dominated composition of ultra-high-energy cosmic rays is excluded.Comment: The version accepted for publication in Physical Review

Search for transient optical counterparts to high-energy IceCube neutrinos with Pan-STARRS1

In order to identify the sources of the observed diffuse high-energy neutrino flux, it is crucial to discover their electromagnetic counterparts. IceCube began releasing alerts for single high-energy ($E > 60$ TeV) neutrino detections with sky localisation regions of order 1 deg radius in 2016. We used Pan-STARRS1 to follow-up five of these alerts during 2016-2017 to search for any optical transients that may be related to the neutrinos. Typically 10-20 faint ($m < 22.5$ mag) extragalactic transients are found within the Pan-STARRS1 footprints and are generally consistent with being unrelated field supernovae (SNe) and AGN. We looked for unusual properties of the detected transients, such as temporal coincidence of explosion epoch with the IceCube timestamp. We found only one transient that had properties worthy of a specific follow-up. In the Pan-STARRS1 imaging for IceCube-160427A (probability to be of astrophysical origin of $\sim$50 %), we found a SN PS16cgx, located at 10.0' from the nominal IceCube direction. Spectroscopic observations of PS16cgx showed that it was an H-poor SN at z = 0.2895. The spectra and light curve resemble some high-energy Type Ic SNe, raising the possibility of a jet driven SN with an explosion epoch temporally coincident with the neutrino detection. However, distinguishing Type Ia and Type Ic SNe at this redshift is notoriously difficult. Based on all available data we conclude that the transient is more likely to be a Type Ia with relatively weak SiII absorption and a fairly normal rest-frame r-band light curve. If, as predicted, there is no high-energy neutrino emission from Type Ia SNe, then PS16cgx must be a random coincidence, and unrelated to the IceCube-160427A. We find no other plausible optical transient for any of the five IceCube events observed down to a 5$\sigma$ limiting magnitude of $m \sim 22$ mag, between 1 day and 25 days after detection.Comment: 20 pages, 6 figures, accepted to A&

A Search for Neutrino Emission from Fast Radio Bursts with Six Years of IceCube Data

We present a search for coincidence between IceCube TeV neutrinos and fast radio bursts (FRBs). During the search period from 2010 May 31 to 2016 May 12, a total of 29 FRBs with 13 unique locations have been detected in the whole sky. An unbinned maximum likelihood method was used to search for spatial and temporal coincidence between neutrinos and FRBs in expanding time windows, in both the northern and southern hemispheres. No significant correlation was found in six years of IceCube data. Therefore, we set upper limits on neutrino fluence emitted by FRBs as a function of time window duration. We set the most stringent limit obtained to date on neutrino fluence from FRBs with an $E^{-2}$ energy spectrum assumed, which is 0.0021 GeV cm$^{-2}$ per burst for emission timescales up to \textasciitilde10$^2$ seconds from the northern hemisphere stacking search.Comment: 15 pages, 9 figure

The instability of the boundary layer over a disk rotating in an enforced axial flow

We consider the convective instability of stationary and traveling modes within the boundary layer over a disk rotating in a uniform axial flow. Complementary numerical and high Reynolds number asymptotic analyses are presented. Stationary and traveling modes of type I (crossflow) and type II (streamline curvature) are found to exist within the boundary layer at all axial flow rates considered. For low to moderate axial flows, slowly traveling type I modes are found to be the most amplified, and quickly traveling type II modes are found to have the lower critical Reynolds numbers. However, near-stationary type I modes are expected to be selected due to a balance being struck between onset and amplification. Axial flow is seen to stabilize the boundary layer by increasing the critical Reynolds numbers and reducing amplification rates of both modes. However, the relative importance of type II modes increases with axial flow and they are, therefore, expected to dominate for sufficiently high rates. The application to chemical vapour deposition(CVD) reactors is considered