Increased hyperphosphorylated tau and the formation of intracellular neurofibrillary tangles are associated with the loss of neurons and cognitive decline in Alzheimer's disease, and related ...neurodegenerative conditions. We applied two diffusion models, diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI), to in vivo diffusion magnetic resonance images (dMRI) of a mouse model of human tauopathy (rTg4510) at 8.5months of age. In grey matter regions with the highest degree of tau burden, microstructural indices provided by both NODDI and DTI discriminated the rTg4510 (TG) animals from wild type (WT) controls; however only the neurite density index (NDI) (the volume fraction that comprises axons or dendrites) from the NODDI model correlated with the histological measurements of the levels of hyperphosphorylated tau protein. Reductions in diffusion directionality were observed when implementing both models in the white matter region of the corpus callosum, with lower fractional anisotropy (DTI) and higher orientation dispersion (NODDI) observed in the TG animals. In comparison to DTI, histological measures of tau pathology were more closely correlated with NODDI parameters in this region. This in vivo dMRI study demonstrates that NODDI identifies potential tissue sources contributing to DTI indices and NODDI may provide greater specificity to pathology in Alzheimer's disease.
•We analyzed the microstructural changes in rTg4510 and wild type mice at 8.5months.•We correlated microstructural findings with histological measures of tau burden•We compare two diffusion MR models: DTI and NODDI.•Both models revealed changes in tissue microstructure due to tau pathology.•The NODDI metrics demonstrated a good correlation with histological measures of tau burden.
Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and ...locally to the affected site in poly (methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally-deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerisation. To examine the efficacy of localised, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50 % of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100 % of the bones treated with vancomycin monotherapy using PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics.
Update
This article was updated on September 4, 2020, because of a previous error. On page 1211, in the author affiliation section, “W.L. Walter, MBBS, PhD
3
” now reads “W.L. Walter, MBBS, PhD
3,4
...,” the affiliation for Dr. Van Onsem that had read “
3
Specialist Orthopedic Group, The Mater Clinic, North Sydney, New South Wales, Australia” now reads “
3
Royal North Shore Hospital, St. Leonards, New South Wales, Australia,” and the affiliation for Dr. Walter that had read “
3
Specialist Orthopedic Group, The Mater Clinic, North Sydney, New South Wales, Australia” now reads “
3
Royal North Shore Hospital, St. Leonards, New South Wales, Australia” and “
4
University of Sydney, Sydney, New South Wales, Australia.”
An erratum has been published: J Bone Joint Surg Am. 2020 Oct 7;102(19):e113
» As we resume elective surgical procedures, it is important to understand what practices and protocols should be altered or implemented in order to minimize the risk of pathogen transfer during the severe acute respiratory syndrome (SARS)-CoV-2 pandemic.
» Each hospital and health system should consider their unique situation in terms of SARS-CoV-2 prevalence, staffing capabilities, personal protection equipment supply, and so on when determining how and when to implement these recommendations.
» All patients should be screened for SARS-CoV-2 by means of a thorough history and physical examination, as well as reverse transcription-polymerase chain reaction (RT-PCR) testing whenever possible, prior to undergoing elective surgery.
» Patients who are currently infected with coronavirus disease 2019 (COVID-19) should not undergo elective surgery.
» These guidelines are based on the available scientific evidence, albeit scant. The recommendations have been reviewed and voted on by the expert delegates who produced this document.
Adding a nonadsorbing polymer to passive colloids induces an attraction between the particles via the "depletion" mechanism. High enough polymer concentrations lead to phase separation. We combine ...experiments, theory, and simulations to demonstrate that using active colloids (such as motile bacteria) dramatically changes the physics of such mixtures. First, significantly stronger interparticle attraction is needed to cause phase separation. Secondly, the finite size aggregates formed at lower interparticle attraction show unidirectional rotation. These micro-rotors demonstrate the self-assembly of functional structures using active particles. The angular speed of the rotating clusters scales approximately as the inverse of their size, which may be understood theoretically by assuming that the torques exerted by the outermost bacteria in a cluster add up randomly. Our simulations suggest that both the suppression of phase separation and the self-assembly of rotors are generic features of aggregating swimmers and should therefore occur in a variety of biological and synthetic active particle systems.
There are, to date, no MR imaging diagnostic markers for Lewy body dementia. Nigrosome 1, containing dopaminergic cells, in the substantia nigra pars compacta is hyperintense on SWI and has been ...called the swallow tail sign, disappearing with Parkinson disease. We aimed to study the swallow tail sign and its clinical applicability in Lewy body dementia and hypothesized that the sign would be likewise applicable in Lewy body dementia.
This was a retrospective cross-sectional multicenter study including 97 patients (mean age, 65 ± 10 years; 46% women), consisting of the following: controls (
= 21) and those with Lewy body dementia (
= 19), Alzheimer disease (
= 20), frontotemporal lobe dementia (
= 20), and mild cognitive impairment (
= 17). All patients underwent brain MR imaging, with susceptibility-weighted imaging at 1.5T (
= 46) and 3T (
= 51). The swallow tail sign was assessed independently by 2 neuroradiologists.
Interrater agreement was moderate (κ = 0.4) between raters. An abnormal swallow tail sign was most common in Lewy body dementia (63%; 95% CI, 41%-85%;
< .001) and had a predictive value only in Lewy body dementia with an odds ratio of 9 (95% CI, 3-28;
< .001). The consensus rating for Lewy body dementia showed a sensitivity of 63%, a specificity of 79%, a negative predictive value of 89%, and an accuracy of 76%; values were higher on 3T compared with 1.5T. The usefulness of the swallow tail sign was rater-dependent with the highest sensitivity equaling 100%.
The swallow tail sign has diagnostic potential in Lewy body dementia and may be a complement in the diagnostic work-up of this condition.
We analysed 1040 individual trees, located in 62 plots across the Amazon Basin for leaf mass per unit area (MA), foliar carbon isotopic composition (δ13C) and leaf level concentrations of C, N, P, ...Ca, Mg, K and Al. All trees were identified to the species level with the dataset containing 58 families, 236 genera and 508 species, distributed across a wide range of soil types and precipitation regimes. Some foliar characteristics such as MA, C, N and Mg emerge as highly constrained by the taxonomic affiliation of tree species, but with others such as P, K, Ca and δ13C also strongly influenced by site growing conditions. By removing the environmental contribution to trait variation, we find that intrinsic values of most trait pairs coordinate, although different species (characterised by different trait suites) are found at discrete locations along a common axis of coordination. Species that tend to occupy higher fertility soils are characterised by a lower MA and have a higher intrinsic N, P, K, Mg and δ13C than their lower fertility counterparts. Despite this consistency, different scaling patterns were observed between low and high fertility sites. Inter-relationships are thus substantially modified by growth environment. Analysing the environmental component of trait variation, we found soil fertility to be the most important predictor, influencing all leaf nutrient concentrations and δ13C and reducing MA. Mean annual temperature was negatively associated with leaf level N, P and K concentrations. Total annual precipitation positively influences MA, C and δ13C, but with a negative impact on Mg. These results provide a first basis for understanding the relationship between the physiological functioning and distribution of tree species across Amazonia.
Context. Cassiopeia A is one of the best-studied supernova remnants. Its bright radio and X-ray emission is due to shocked ejecta. Cas A is rather unique in that the unshocked ejecta can also be ...studied: through emission in the infrared, the radio-active decay of 44Ti, and the low-frequency free-free absorption caused by cold ionised gas, which is the topic of this paper. Aims. Free-free absorption processes are affected by the mass, geometry, temperature, and ionisation conditions in the absorbing gas. Observations at the lowest radio frequencies can constrain a combination of these properties. Methods. We used Low Frequency Array (LOFAR) Low Band Antenna observations at 30–77 MHz and Very Large Array (VLA) L-band observations at 1–2 GHz to fit for internal absorption as parametrised by the emission measure. We simultaneously fit multiple UV-matched images with a common resolution of 17″ (this corresponds to 0.25 pc for a source at the distance of Cas A). The ample frequency coverage allows us separate the relative contributions from the absorbing gas, the unabsorbed front of the shell, and the absorbed back of the shell to the emission spectrum. We explored the effects that a temperature lower than the ~100–500 K proposed from infrared observations and a high degree of clumping can have on the derived physical properties of the unshocked material, such as its mass and density. We also compiled integrated radio flux density measurements, fit for the absorption processes that occur in the radio band, and considered their effect on the secular decline of the source. Results. We find a mass in the unshocked ejecta of M = 2.95 ± 0.48 M⊙ for an assumed gas temperatureof T = 100 K. This estimate is reduced for colder gas temperatures and, most significantly, if the ejecta are clumped. We measure the reverse shock to have a radius of 114″± 6″ and be centred at 23:23:26, +58:48:54 (J2000). We also find that a decrease in the amount of mass in the unshocked ejecta (as more and more material meets the reverse shock and heats up) cannot account for the observed low-frequency behaviour of the secular decline rate. Conclusions. To reconcile our low-frequency absorption measurements with models that reproduce much of the observed behaviour in Cas A and predict little mass in the unshocked ejecta, the ejecta need to be very clumped or the temperature in the cold gas needs to be low (~10 K). Both of these options are plausible and can together contribute to the high absorption value that we find.
The purpose of this study is to evaluate the association of Electrical Cardiometry (EC)-derived cardiac output indexed to weight (CO) and its changes during the first 48 h in relation to adverse ...short-term outcome in very preterm infants. In this prospective observational study of preterm infants < 32 weeks gestational age (GA), the combined adverse outcome was defined as mortality or abnormal cranial ultrasound (any grade intracranial hemorrhage (ICH) or periventricular leukomalacia) within the first 2 weeks postnatally. Logistic regression models were used to investigate the association between median CO and outcome and mixed-effects models for the time trajectory of CO. In the absence of device-specific thresholds for low or high CO, no thresholds were used in our analysis. Fifty-three infants (median (IQR) GA 29.0 (25.4–30.6) weeks, birthweight 1020 (745–1505) g) were included in the analysis. Median CO was 241 (197–275) mL/kg/min for the adverse outcome and 198 (175–227) mL/kg/min for normal outcome (odds ratio (OR) (95% confidence interval (95% CI)), 1.01 (1.00 to 1.03);
p
= 0.028). After adjustment for GA, the difference was not significant (adjusted OR (95% CI), 1.01 (0.99 to 1.02);
p
= 0.373). CO trajectory did not differ by outcome (
p
= 0.352). A post hoc analysis revealed an association between CO time trajectory and ICH ≥ grade 2.
Conclusions
: EC-derived CO estimates within 48 h postnatally were not independently associated with brain injury (any grade) or mortality in the first 14 days of life. CO time trajectory was found to be associated with ICH ≥ grade 2.
What is Known:
• Bioreactance-derived cardiac output indexed to bodyweight (CO) in the transitional period has been associated with adverse short-term outcome in preterm infants.
What is New:
• Electrical Cardiometry (EC)-derived CO measurements in very preterm infants during the transitional period are not independently associated with adverse outcome (death or ultrasound detected brain damage) within 2 weeks postnatally.
• In the first 48 h EC-derived CO increases over time and is higher in extremely preterm infants compared to very preterm and differs from previously reported bioreactance-derived CO values.
We report results from the BICEP2 experiment, a cosmic microwave background (CMB) polarimeter specifically designed to search for the signal of inflationary gravitational waves in the B-mode power ...spectrum around ℓ∼80. The telescope comprised a 26 cm aperture all-cold refracting optical system equipped with a focal plane of 512 antenna coupled transition edge sensor 150 GHz bolometers each with temperature sensitivity of ≈300 μK(CMB)√s. BICEP2 observed from the South Pole for three seasons from 2010 to 2012. A low-foreground region of sky with an effective area of 380 square deg was observed to a depth of 87 nK deg in Stokes Q and U. In this paper we describe the observations, data reduction, maps, simulations, and results. We find an excess of B-mode power over the base lensed-ΛCDM expectation in the range 30 < ℓ < 150, inconsistent with the null hypothesis at a significance of >5σ. Through jackknife tests and simulations based on detailed calibration measurements we show that systematic contamination is much smaller than the observed excess. Cross correlating against WMAP 23 GHz maps we find that Galactic synchrotron makes a negligible contribution to the observed signal. We also examine a number of available models of polarized dust emission and find that at their default parameter values they predict power ∼(5-10)× smaller than the observed excess signal (with no significant cross-correlation with our maps). However, these models are not sufficiently constrained by external public data to exclude the possibility of dust emission bright enough to explain the entire excess signal. Cross correlating BICEP2 against 100 GHz maps from the BICEP1 experiment, the excess signal is confirmed with 3σ significance and its spectral index is found to be consistent with that of the CMB, disfavoring dust at 1.7σ. The observed B-mode power spectrum is well fit by a lensed-ΛCDM+tensor theoretical model with tensor-to-scalar ratio r = 0.20_(-0.05)(+0.07), with r = 0 disfavored at 7.0σ. Accounting for the contribution of foreground, dust will shift this value downward by an amount which will be better constrained with upcoming data sets.
PDF
