Ligamentous healing potential of the acromioclavicular ligament following acute anatomical reconstruction.

BACKGROUND: Horizontal instability following acute acromioclavicular joint (ACJ) reconstruction still occurs with a high prevalence. Although the human acromioclavicular ligament complex (ACLC) represents the major horizontal ACJ stabilizer, experimental studies on healing characteristics are lacking. Therefore, the purpose of this histological study was to investigate the healing potential of the ACLC following acute anatomical reconstruction METHODS: In this prospective clinical-experimental study, 28 ACLC biopsies were performed in patients with complete ACJ dislocations (Rockwood type 4 or 5) during acute hook plate stabilization (IG: implantation group; n = 14) and hook plate removal (EG: explantation group; n = 14). Histological analyses included Giemsa staining, polarized light microscopy and immunostaining against CD68, αSMA and collagen type I and type III. Histomorphological evaluation entailed cell counts, collagen expression score, ligament tissue maturity index (LTMI) and descriptive analysis of specific ligamentous structures. Statistics consisted of nonparametric Mann-Whitney U tests and a level of significance of P < .05. RESULTS: Total cell counts (cells/mm2 1491 ± 296 vs. 635 ± 430; P < 0.001) and collagen III expression (3.22 ± 0.22 vs. 1.78 ± 0.41; P < 0.001) were higher in EG compared to IG. Inversely αSMA + (11 ± 9 vs. 179 ± 186; P < 0.001) and CD68 + cell counts (56 ± 20 vs. 100 ± 57; P 0.009) were significantly lower in the EG. The EG revealed a comparable reorientation of ligamentous structures. Consistently, ACLC samples of the EG (21.6 ± 2.4) displayed a high total but differently composed LTMI score (IG: 24.5 ± 1.2; P < 0.001). CONCLUSIONS: This experimental study proved the ligamentous healing potential of the human ACLC following acute anatomical reconstruction. Histomorphologically, the ACLC reliably showed a ligamentous state of healing at a mean of about 12 weeks after surgery. However, processes of ligamentous remodeling were still evident. These experimental findings support recent clinical data showing superior horizontal ACJ stability with additional AC stabilization in the context of acute ACJ reconstruction. Though, prospective clinical and biomechanical studies are warranted to evaluate influencing factors on ACLC healing and potential impacts of acute ACLC repair on clinical outcome. STUDY TYPE: Controlled Laboratory Study.

The tissue-renin-angiotensin-system of the human intervertebral disc.

Symptomatic intervertebral disc (IVD) degeneration accounts for significant socioeconomic burden. Recently, the expression of the tissue renin-angiotensin system (tRAS) in rat and bovine IVD was demonstrated. The major effector of tRAS is angiotensin II (AngII), which participates in proinflammatory pathways. The present study investigated the expression of tRAS in human IVDs, and the correlation between tRAS, inflammation and IVD degeneration. Human IVD tissue was collected during spine surgery and distributed according to principal diagnosis. Gene expression of tRAS components, proinflammatory and catabolic markers in the IVD tissue was assessed. Hydroxyproline (OHP) and glycosaminoglycan (GAG) content in the IVD tissue were determined. Tissue distribution of tRAS components was investigated by immunohistochemistry. Gene expression of tRAS components such as angiotensin-converting enzyme (ACE), Ang II receptor type 2 (AGTR2), angiotensinogen (AGT) and cathepsin D (CTSD) was confirmed in human IVDs. IVD samples that expressed tRAS components (n = 21) revealed significantly higher expression levels of interleukin 6 (IL-6), tumour necrosis factor α (TNF-α), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 and 5 compared to tRAS-negative samples (n = 37). Within tRAS-positive samples, AGT, matrix-metalloproteinases 13 and 3, IL-1, IL-6 and IL-8 were more highly expressed in traumatic compared to degenerated IVDs. Total GAG/DNA content of non-tRAS expressing IVD tissue was significantly higher compared to tRAS positive tissue. Immunohistochemistry confirmed the presence of AngII in the human IVD. The present study identified the existence of tRAS in the human IVD and suggested a correlation between tRAS expression, inflammation and ultimately IVD degeneration.

Low-Energy Physics Reach of Xenon Detectors for Nuclear-Recoil-Based Dark Matter and Neutrino Experiments.

Dual-phase xenon detectors lead the search for keV-scale nuclear recoil signals expected from the scattering of weakly interacting massive particle (WIMP) dark matter, and can potentially be used to study the coherent nuclear scattering of MeV-scale neutrinos. New capabilities of such experiments can be enabled by extending their nuclear recoil searches down to the lowest measurable energy. The response of the liquid xenon target medium to nuclear recoils, however, is not well characterized below a few keV, leading to large uncertainties in projected sensitivities. In this work, we report a new measurement of ionization signals from nuclear recoils in liquid xenon down to the lowest energy reported to date. At 0.3 keV, we find that the average recoil produces approximately one ionization electron; this is the first measurement of nuclear recoil signals at the single-ionization-electron level, approaching the physical limit of liquid xenon ionization detectors. We discuss the implications of these measurements on the physics reach of xenon detectors for nuclear-recoil-based WIMP dark matter searches and the detection of coherent elastic neutrino-nucleus scattering.

Results of a Search for Sub-GeV Dark Matter Using 2013 LUX Data.

The scattering of dark matter (DM) particles with sub-GeV masses off nuclei is difficult to detect using liquid xenon-based DM search instruments because the energy transfer during nuclear recoils is smaller than the typical detector threshold. However, the tree-level DM-nucleus scattering diagram can be accompanied by simultaneous emission of a bremsstrahlung photon or a so-called "Migdal" electron. These provide an electron recoil component to the experimental signature at higher energies than the corresponding nuclear recoil. The presence of this signature allows liquid xenon detectors to use both the scintillation and the ionization signals in the analysis where the nuclear recoil signal would not be otherwise visible. We report constraints on spin-independent DM-nucleon scattering for DM particles with masses of 0.4-5 GeV/c^{2} using 1.4×10^{4} kg day of search exposure from the 2013 data from the Large Underground Xenon (LUX) experiment for four different classes of mediators. This analysis extends the reach of liquid xenon-based DM search instruments to lower DM masses than has been achieved previously.

Diagnosis of warm dense conditions in foil targets heated by intense femtosecond laser pulses using Kα imaging spectroscopy.

Warm dense conditions in titanium foils irradiated with intense femtosecond laser pulses are diagnosed using an x-ray imaging spectroscopy technique. The line shapes of radially resolved titanium Kα spectra are measured with a toroidally bent GaAs crystal and an x-ray charge-coupled device. Measured spectra are compared with the K-shell emissions modeled using an atomic kinetics - spectroscopy simulation code. Kα line shapes are strongly affected by warm (5-40 eV) bulk electron temperatures and imply multiple temperature distributions in the targets. The spatial distribution of temperature is dependent on the target thickness, and a thin target shows an advantage to generate uniform warm dense conditions in a large area.

Limits on Spin-Dependent WIMP-Nucleon Cross Section Obtained from the Complete LUX Exposure.

We present experimental constraints on the spin-dependent WIMP-nucleon elastic cross sections from the total 129.5 kg yr exposure acquired by the Large Underground Xenon experiment (LUX), operating at the Sanford Underground Research Facility in Lead, South Dakota (USA). A profile likelihood ratio analysis allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ_{n}=1.6×10^{-41} cm^{2} (σ_{p}=5×10^{-40} cm^{2}) at 35 GeV c^{-2}, almost a sixfold improvement over the previous LUX spin-dependent results. The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.

First Searches for Axions and Axionlike Particles with the LUX Experiment.

The first searches for axions and axionlike particles with the Large Underground Xenon experiment are presented. Under the assumption of an axioelectric interaction in xenon, the coupling constant between axions and electrons g_{Ae} is tested using data collected in 2013 with an exposure totaling 95 live days ×118 kg. A double-sided, profile likelihood ratio statistic test excludes g_{Ae} larger than 3.5×10^{-12} (90% C.L.) for solar axions. Assuming the Dine-Fischler-Srednicki-Zhitnitsky theoretical description, the upper limit in coupling corresponds to an upper limit on axion mass of 0.12 eV/c^{2}, while for the Kim-Shifman-Vainshtein-Zhakharov description masses above 36.6 eV/c^{2} are excluded. For galactic axionlike particles, values of g_{Ae} larger than 4.2×10^{-13} are excluded for particle masses in the range 1-16 keV/c^{2}. These are the most stringent constraints to date for these interactions.

Results from a Search for Dark Matter in the Complete LUX Exposure.

We report constraints on spin-independent weakly interacting massive particle (WIMP)-nucleon scattering using a 3.35×10^{4} kg day exposure of the Large Underground Xenon (LUX) experiment. A dual-phase xenon time projection chamber with 250 kg of active mass is operated at the Sanford Underground Research Facility under Lead, South Dakota (USA). With roughly fourfold improvement in sensitivity for high WIMP masses relative to our previous results, this search yields no evidence of WIMP nuclear recoils. At a WIMP mass of 50 GeV c^{-2}, WIMP-nucleon spin-independent cross sections above 2.2×10^{-46} cm^{2} are excluded at the 90% confidence level. When combined with the previously reported LUX exposure, this exclusion strengthens to 1.1×10^{-46} cm^{2} at 50 GeV c^{-2}.

Release behavior of VAN from four types of CaP-ceramic granules using various loading methods at two different degrees of acidity.

The release behavior of vancomycin (VAN) from beta-tricalciumphosphate (ßTCP), hydroxyapatite (HA), glass ceramic (GC) and sponge-like collagen ßTCP granule composite (sponge) was studied. Vacuum and drip loading methods were compared. The influence of VAN concentration and pH on release behavior was analyzed with respect to a stable release level of VAN above the minimum inhibitory concentration over 14 days. Initially the morphology of the granule carrier systems was examined with ESEM, stereomicroscopy, µCT-imaging and Camsizer® regarding porosity, interconnecting pores and granule size. Drug release patterns following a vacuum and a drip loading method with VAN at concentrations of 5 and 50 mg/ml were compared. The influence of pH 7.4 compared to pH 5.0 on release behavior was studied. The drug was released in bidistilled water at 37 °C, the concentration determined by photometry at 220 nm. For statistical purposes, the mean and standard deviation were calculated and analyzed by Origin 9.1 Professional SR1 (OriginLab). Due to low interconnectivity and low porosity, the vacuum loading method was unable to attain complete drug loading of the ceramic granules. The sponge showed an inhomogeneous distribution of ßTCP granules. Drug release was high at pH 7.4, at pH 5.0 it practically did not occur. All samples except for the collagen-complex show an initial VAN burst release with a following steady release. Loading with 5 mg/ml concentrated VAN resulted in a higher percentage of available drug being released. However, when loaded with 50 mg/ml, the absolute amount of drug released was higher.

Improved Limits on Scattering of Weakly Interacting Massive Particles from Reanalysis of 2013 LUX Data.

We present constraints on weakly interacting massive particles (WIMP)-nucleus scattering from the 2013 data of the Large Underground Xenon dark matter experiment, including 1.4×10^{4} kg day of search exposure. This new analysis incorporates several advances: single-photon calibration at the scintillation wavelength, improved event-reconstruction algorithms, a revised background model including events originating on the detector walls in an enlarged fiducial volume, and new calibrations from decays of an injected tritium ß source and from kinematically constrained nuclear recoils down to 1.1 keV. Sensitivity, especially to low-mass WIMPs, is enhanced compared to our previous results which modeled the signal only above a 3 keV minimum energy. Under standard dark matter halo assumptions and in the mass range above 4 GeV c^{-2}, these new results give the most stringent direct limits on the spin-independent WIMP-nucleon cross section. The 90% C.L. upper limit has a minimum of 0.6 zb at 33 GeV c^{-2} WIMP mass.

Results on the Spin-Dependent Scattering of Weakly Interacting Massive Particles on Nucleons from the Run 3 Data of the LUX Experiment.

We present experimental constraints on the spin-dependent WIMP (weakly interacting massive particle)-nucleon elastic cross sections from LUX data acquired in 2013. LUX is a dual-phase xenon time projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota), which is designed to observe the recoil signature of galactic WIMPs scattering from xenon nuclei. A profile likelihood ratio analysis of 1.4×10^{4} kg day of fiducial exposure allows 90% C.L. upper limits to be set on the WIMP-neutron (WIMP-proton) cross section of σ_{n}=9.4×10^{-41} cm^{2} (σ_{p}=2.9×10^{-39} cm^{2}) at 33 GeV/c^{2}. The spin-dependent WIMP-neutron limit is the most sensitive constraint to date.

A Single Dose of the Anti-Resorptive Peptide Human Calcitonin Paradoxically Augments Particle- and Endotoxin-Mediated Pro-Inflammatory Cytokine Production In Vitro.

The peptide hormone calcitonin (CT) is known to inhibit bone resorption and has previously been shown also to prevent particle-induced osteolysis, the leading cause of revision arthroplasty. In the present study, the influence of human CT on the initial inflammatory response to particulate wear debris or bacterial endotoxins, ultimately leading to osteoclast-mediated bone resorption, was analysed in human THP-1 macrophage-like cells. The cells were activated with either ultra-high molecular weight polyethylene (UHMWPE) particles or bacterial lipopolysaccharides (LPS) in order to simulate an osteolysis-associated inflammatory response. The cells were simultaneously treated with human CT (10(-9) M). Cytokine production of tumour necrosis factor (TNF)-α was quantified on both RNA and protein levels while interleukins (IL)-1ß and IL-6 were measured as secreted protein only. Stimulation of the cells with either particles or LPS led to a dose- and time-dependent increase of TNF-α mRNA production and protein secretion of TNF-α, IL-1ß, and IL-6. Application of CT mostly enhanced cytokine production as elicited by UHMWPE particles while a pronounced transient inhibitory effect on LPS-induced inflammation became evident at 24 h of incubation. Human CT displayed ambivalent effects on the wear- and LPS-induced production of pro-inflammatory cytokines. Thereby, the peptide primarily upregulated particle-induced inflammation while LPS-induced cytokine secretion was temporarily attenuated in a distinct manner. It needs to be evaluated whether the pro- or anti-inflammatory action of CT contributes to its known anti-resorptive effects. Thus, the therapeutic potential of the peptide in the treatment of either particle- or endotoxin-mediated bone resorption could be determined.

Precision Measurement of the p(e,e

New results are reported from a measurement of π^{0} electroproduction near threshold using the p(e,e^{'}p)π^{0} reaction. The experiment was designed to determine precisely the energy dependence of s- and p-wave electromagnetic multipoles as a stringent test of the predictions of chiral perturbation theory (ChPT). The data were taken with an electron beam energy of 1192 MeV using a two-spectrometer setup in Hall A at Jefferson Lab. For the first time, complete coverage of the ϕ_{π}^{*} and θ_{π}^{*} angles in the pπ^{0} center of mass was obtained for invariant energies above threshold from 0.5 up to 15 MeV. The 4-momentum transfer Q^{2} coverage ranges from 0.05 to 0.155 (GeV/c)^{2} in fine steps. A simple phenomenological analysis of our data shows strong disagreement with p-wave predictions from ChPT for Q^{2}>0.07 (GeV/c)^{2}, while the s-wave predictions are in reasonable agreement.

Measurements of double-polarized compton scattering asymmetries and extraction of the proton spin polarizabilities.

The spin polarizabilities of the nucleon describe how the spin of the nucleon responds to an incident polarized photon. The most model-independent way to extract the nucleon spin polarizabilities is through polarized Compton scattering. Double-polarized Compton scattering asymmetries on the proton were measured in the Δ(1232) region using circularly polarized incident photons and a transversely polarized proton target at the Mainz Microtron. Fits to asymmetry data were performed using a dispersion model calculation and a baryon chiral perturbation theory calculation, and a separation of all four proton spin polarizabilities in the multipole basis was achieved. The analysis based on a dispersion model calculation yields γ(E1E1)=-3.5±1.2, γ(M1M1)=3.16±0.85, γ(E1M2)=-0.7±1.2, and γ(M1E2)=1.99±0.29, in units of 10(-4) fm(4).

The relationship between challenging behaviours, mood and interest/pleasure in adults with severe and profound intellectual disabilities.

BACKGROUND: We investigated whether current mood and interest/pleasure ratings in adults with moderate to profound intellectual disabilities were predictive of challenging behaviour [self-injurious behaviour (SIB), aggressive/destructive behaviour and stereotypic behaviour] and vice versa. METHOD: In this combined cross-sectional and longitudinal study, staff members of a Hungarian residential facility completed translated versions of the Behaviour Problems Inventory-Short Form (BPI-S), the Challenging Behaviour Interview (CBI) and the Mood, Interest and Pleasure Questionnaire-Short Form (MIPQ-S) for 50 participants at two time points, approximately 4 to 5 months apart. RESULTS: Bivariate correlations from data concurrently assessed at Time-1 showed significant linear relationships between the SIB (both frequency and severity scores) and Interest/Pleasure sub-scales, and the Aggressive/Destructive Behaviour (severity scores) and the MIPQ-S Mood sub-scales (unadjusted for multiple correlations). All of these effects were found with the BPI-S data, but not with the CBI. Multiple regression analyses revealed that (1) low interest/pleasure assessed at Time-1 predicted high SIB (frequency and severity) at Time-2. (2) Interest/pleasure was not predictive of aggressive or stereotypic behaviour. (3) Mood at Time-1 did not predict any of the three types of behaviour problems at Time-2. (4) In reverse, high SIB (frequency and severity) at Time-1 predicted low interest/pleasure ratings at Time-2. (5) Surprisingly, frequent aggressive/destructive behaviour predicted high interest/pleasure. (6) Stereotypic behaviour scores at Time-1 did not predict interest/pleasure ratings at Time-2. Again, all of these effects were only found with the BPI-S data, but not with the CBI. Internal consistency, test-retest reliability and concurrent validity of the Hungarian versions of all three questionnaires had generally satisfactory outcomes. DISCUSSION: The fact that increasingly frequent and severe SIB was predicted by declining measures of interest/pleasure is consistent with previous studies. Contrary to those earlier studies, however, we found that SIB was not predicted by mood and that aggressive/destructive behaviour actually predicted future elevated mood. Implications for future research regarding the directional relationship between affective states such as mood and interest and pleasure, on the one hand, and challenging behaviour, on the other, were discussed.

Ultrashort pulsed neutron source.

We report on a novel compact laser-driven neutron source with an unprecedented short pulse duration (<50 ps) and high peak flux (>10(18) n/cm(2)/s), an order of magnitude higher than any existing source. In our experiments, high-energy electron jets are generated from thin (<3 µm) plastic targets irradiated by a petawatt laser. These intense electron beams are employed to generate neutrons from a metal converter. Our method opens venues for enhancing neutron radiography contrast and for creating astrophysical conditions of heavy element synthesis in the laboratory.

First measurement of the ionization yield of nuclear recoils in liquid argon.

This Letter details a measurement of the ionization yield (Q(y)) of 6.7 keV(40)Ar atoms stopping in a liquid argon detector. The Q(y) of 3.6-6.3 detected e(-)/keV, for applied electric fields in the range 240-2130 V/cm, is encouraging for the use of this detector medium to search for the signals from hypothetical dark matter particle interactions and from coherent elastic neutrino-nucleus scattering. A significant dependence of Q(y) on the applied electric field is observed and explained in the context of ion recombination.

Measurement of the transverse target and beam-target asymmetries in η meson photoproduction at MAMI.

We present new data for the transverse target asymmetry T and the very first data for the beam-target asymmetry F in the γ[over →]p[over →]→ηp reaction up to a center-of-mass energy of W=1.9 GeV. The data were obtained with the Crystal-Ball/TAPS detector setup at the Glasgow tagged photon facility of the Mainz Microtron MAMI. All existing model predictions fail to reproduce the new data indicating a significant impact on our understanding of the underlying dynamics of η meson photoproduction. The peculiar nodal structure observed in existing T data close to threshold is not confirmed.

First results from the LUX dark matter experiment at the Sanford underground research facility.

The Large Underground Xenon (LUX) experiment is a dual-phase xenon time-projection chamber operating at the Sanford Underground Research Facility (Lead, South Dakota). The LUX cryostat was filled for the first time in the underground laboratory in February 2013. We report results of the first WIMP search data set, taken during the period from April to August 2013, presenting the analysis of 85.3 live days of data with a fiducial volume of 118 kg. A profile-likelihood analysis technique shows our data to be consistent with the background-only hypothesis, allowing 90% confidence limits to be set on spin-independent WIMP-nucleon elastic scattering with a minimum upper limit on the cross section of 7.6 × 10(-46) cm(2) at a WIMP mass of 33 GeV/c(2). We find that the LUX data are in disagreement with low-mass WIMP signal interpretations of the results from several recent direct detection experiments.

Evaluating the impact of anatomical and physiological variability on human equivalent doses using PBPK models.

Addressing human anatomical and physiological variability is a crucial component of human health risk assessment of chemicals. Experts have recommended probabilistic chemical risk assessment paradigms in which distributional adjustment factors are used to account for various sources of uncertainty and variability, including variability in the pharmacokinetic behavior of a given substance in different humans. In practice, convenient assumptions about the distribution forms of adjustment factors and human equivalent doses (HEDs) are often used. Parameters such as tissue volumes and blood flows are likewise often assumed to be lognormally or normally distributed without evaluating empirical data for consistency with these forms. In this work, we performed dosimetric extrapolations using physiologically based pharmacokinetic (PBPK) models for dichloromethane (DCM) and chloroform that incorporate uncertainty and variability to determine if the HEDs associated with such extrapolations are approximately lognormal and how they depend on the underlying distribution shapes chosen to represent model parameters. We accounted for uncertainty and variability in PBPK model parameters by randomly drawing their values from a variety of distribution types. We then performed reverse dosimetry to calculate HEDs based on animal points of departure (PODs) for each set of sampled parameters. Corresponding samples of HEDs were tested to determine the impact of input parameter distributions on their central tendencies, extreme percentiles, and degree of conformance to lognormality. This work demonstrates that the measurable attributes of human variability should be considered more carefully and that generalized assumptions about parameter distribution shapes may lead to inaccurate estimates of extreme percentiles of HEDs.