Kufor-Rakeb syndrome, pallido-pyramidal degeneration with supranuclear upgaze paresis and dementia, maps to 1p36

Kufor-Rakeb syndrome is an autosomal recessive nigro-striatal-pallidal-pyramidal neurodegeneration. The onset is in the teenage years with clinical features of Parkinson’s disease plus spasticity, supranuclear upgaze paresis, and dementia. Brain scans show atrophy of the globus pallidus and pyramids and, later, widespread cerebral atrophy. We report linkage in Kufor- Rakeb syndrome to a 9 cM region of chromosome 1p36 delineated by the markers D1S436 and D1S2843, with a maximum multipoint lod score of 3.6. (J Med Genet 2001;38:680–682

Recommendations to the Musculoskeletal Health Network, Health Department of Western Australia related to the Spinal Pain Model of Care made on behalf of the Chiropractors Association of Australia (Western Australian Branch)

The 2009 Spinal Model of Care published by the Western Australian Health Department via the Musculoskeletal Health Network would benefit from an update. Best-evidence synthesis and cost-risks-benefits estimations suggest that such guidelines should provide: (1) the early assessment of patients with non-malignant spinal pain (particularly low back) by a musculoskeletal clinician, be it a chiropractor, musculoskeletal physician, osteopath or musculoskeletal physiotherapist with referral within the early stages of the disorder; and (2) the provision of manipulative therapy, where indicated, as a first-line treatment while also providing rehabilitation, health promotion, and contemporary wellness/wellbeing management with the intention of avoiding chronicity. Emerging workforce capacity suggests that early assessment and evidence-based management of non-malignant spinal pain is feasible, leading to better patient outcomes. The authors and the association are hopeful that providing this submission in open access may prove useful for advocates of the chiropractic profession in other jurisdictions

Pre-analytical practices for routine coagulation tests in European laboratories. A collaborative study from the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM)

Background: Correct handling and storage of blood samples for coagulation tests are important to assure correct diagnosis and monitoring. The aim of this study was to assess the pre-analytical practices for routine coagulation testing in European laboratories. Methods: In 2013–2014, European laboratories were invited to fill in a questionnaire addressing pre-analytical requirements regarding tube fill volume, citrate concentration, sample stability, centrifugation and storage conditions for routine coagulation testing (activated partial thromboplastin time [APTT], prothrombin time in seconds [PT-sec] and as international normalised ratio [PT-INR] and fibrinogen). Results: A total of 662 laboratories from 28 different countries responded. The recommended 3.2% (105–109 mmol/L) citrate tubes are used by 74% of the laboratories. Tube fill volumes ≥90% were required by 73%–76% of the laboratories, depending upon the coagulation test and tube size. The variation in centrifugation force and duration was large (median 2500 g [10- and 90-percentiles 1500 and 4000] and 10 min [5 and 15], respectively). Large variations were also seen in the accepted storage time for different tests and sample materials, for example, for citrated blood at room temperature the accepted storage time ranged from 0.5–72 h and 0.5–189 h for PT-INR and fibrinogen, respectively. If the storage time or the tube fill requirements are not fulfilled, 72% and 84% of the respondents, respectively, would reject the samples. Conclusions: There was a large variation in pre-analytical practices for routine coagulation testing in European laboratories, especially for centrifugation conditions and storage time requirements.publishedVersio

Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure

High frequency oscillations during magnetar flares

The recent discovery of high frequency oscillations during giant flares from the Soft Gamma Repeaters SGR 1806-20 and SGR 1900+14 may be the first direct detection of vibrations in a neutron star crust. If this interpretation is correct it offers a novel means of testing the neutron star equation of state, crustal breaking strain, and magnetic field configuration. We review the observational data on the magnetar oscillations, including new timing analysis of the SGR 1806-20 giant flare using data from the Ramaty High Energy Solar Spectroscopic Imager (RHESSI) and the Rossi X-ray Timing Explorer (RXTE). We discuss the implications for the study of neutron star structure and crust thickness, and outline areas for future investigation.Comment: 5 pages, 1 figure, to appear in the proceedings of the conference "Isolated Neutron Stars: from the Interior to the Surface" (April 2006, London), eds. D. Page, R. Turolla, & S. Zane, Astrophysics & Space Science in pres

Anisotropic Superparamagnetism of Monodispersive Cobalt-Platinum Nanocrystals

Based on the high-temperature organometallic route (Sun et al. Science 287, 1989 (2000)), we have synthesized powders containing CoPt_3 single crystals with mean diameters of 3.3(2) nm and 6.0(2) nm and small log-normal widths sigma=0.15(1). In the entire temperature range from 5 K to 400 K, the zero-field cooled susceptibility chi(T) displays significant deviations from ideal superparamagnetism. Approaching the Curie temperature of 450(10) K, the deviations arise from the (mean-field) type reduction of the ferromagnetic moments, while below the blocking temperature T_b, chi(T) is suppressed by the presence of energy barriers, the distributions of which scale with the particle volumes obtained from transmission electron microscopy (TEM). This indication for volume anisotropy is supported by scaling analyses of the shape of the magnetic absorption chi''(T,omega) which reveal distribution functions for the barriers being also consistent with the volume distributions observed by TEM. Above 200 K, the magnetization isotherms M(H,T) display Langevin behavior providing 2.5(1) mu_B per CoPt_3 in agreement with reports on bulk and thin film CoPt_3. The non-Langevin shape of the magnetization curves at lower temperatures is for the first time interpreted as anisotropic superparamagnetism by taking into account an anisotropy energy of the nanoparticles E_A(T). Using the magnitude and temperature variation of E_A(T), the mean energy barriers and 'unphysical' small switching times of the particles obtained from the analyses of chi''(T,omega) are explained. Below T_b hysteresis loops appear and are quantitatively described by a blocking model, which also ignores particle interactions, but takes the size distributions from TEM and the conventional field dependence of E_A into account.Comment: 12 pages with 10 figures and 1 table. Version accepted for publication in Phys. Rev. B . Two-column layou

A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers

Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. In addition, devils are affected by two of the three known transmissible cancers in mammals. Immune checkpoint immunotherapy has transformed human medicine, but a lack of species-specific reagents has limited checkpoint immunology in most species. We developed a cut-and-paste reagent development system and used the fluorescent fusion protein system to show that immune checkpoint interactions are conserved across 160,000,000 years of evolution, CD200 is highly expressed on transmissible tumor cells, and coexpression of CD200R1 can block CD200 surface expression. The system’s versatility across species was demonstrated by fusing a fluorescent reporter to a camelid-derived nanobody that binds human programmed death ligand 1. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can be used to advance our understanding of cancer and immunological tolerance.</p

The composition of the protosolar disk and the formation conditions for comets

Conditions in the protosolar nebula have left their mark in the composition of cometary volatiles, thought to be some of the most pristine material in the solar system. Cometary compositions represent the end point of processing that began in the parent molecular cloud core and continued through the collapse of that core to form the protosun and the solar nebula, and finally during the evolution of the solar nebula itself as the cometary bodies were accreting. Disentangling the effects of the various epochs on the final composition of a comet is complicated. But comets are not the only source of information about the solar nebula. Protostellar disks around young stars similar to the protosun provide a way of investigating the evolution of disks similar to the solar nebula while they are in the process of evolving to form their own solar systems. In this way we can learn about the physical and chemical conditions under which comets formed, and about the types of dynamical processing that shaped the solar system we see today. This paper summarizes some recent contributions to our understanding of both cometary volatiles and the composition, structure and evolution of protostellar disks.Comment: To appear in Space Science Reviews. The final publication is available at Springer via http://dx.doi.org/10.1007/s11214-015-0167-

Frequency spectrum of toroidal Alfv\'en mode in a neutron star with Ferraro's form of nonhomogeneous poloidal magnetic field

Using the energy variational method of magneto-solid-mechanical theory of a perfectly conducting elastic medium threaded by magnetic field, the frequency spectrum of Lorentz-force-driven global torsional nodeless vibrations of a neutron star with Ferraro's form of axisymmetric poloidal nonhomogeneous internal and dipole-like external magnetic field is obtained and compared with that for this toroidal Alfv\'en mode in a neutron star with homogeneous internal and dipolar external magnetic field. The relevance of considered asteroseismic models to quasi-periodic oscillations of the X-ray flux during the ultra powerful outbursts of SGR 1806-20 and SGR 1900+14 is discussed.Comment: Accepted for publication in Astrophysics & Space Scienc