Subretinal pigment epithelial deposition of Drusen components including hydroxyapatite in a primary cell culture model

Purpose: Extracellular deposits containing hydroxyapatite, lipids, proteins, and trace metals that form between the basal lamina of the RPE and the inner collagenous layer of Bruch's membrane are hallmarks of early AMD. We examined whether cultured RPE cells could produce extracellular deposits containing all of these molecular components. Methods: Retinal pigment epithelium cells isolated from freshly enucleated porcine eyes were cultured on Transwell membranes for up to 6 months. Deposit composition and structure were characterized using light, fluorescence, and electron microscopy; synchrotron x-ray diffraction and x-ray fluorescence; secondary ion mass spectroscopy; and immunohistochemistry. Results: Apparently functional primary RPE cells, when cultured on 10-μm-thick inserts with 0.4-μm-diameter pores, can produce sub-RPE deposits that contain hydroxyapatite, lipids, proteins, and trace elements, without outer segment supplementation, by 12 weeks. Conclusions: The data suggest that sub-RPE deposit formation is initiated, and probably regulated, by the RPE, as well as the loss of permeability of the Bruch's membrane and choriocapillaris complex associated with age and early AMD. This cell culture model of early AMD lesions provides a novel system for testing new therapeutic interventions against sub-RPE deposit formation, an event occurring well in advance of the onset of vision loss

A Systematic Literature Review with Meta-Analyses of Within- and Between-Day Differences in Objectively Measured Physical Activity in School-Aged Children

Background: Targeting specific time periods of the day or week may enhance physical activity (PA) interventions in youth. The most prudent time segments to target are currently unclear.  Objectives: To systematically review the literature describing differences in young people’s objectively measured PA on weekdays vs. weekends, in school vs. out of school, weekends vs. out of school and lesson time vs. break time.  Methods: Electronic databases were searched for English-language, cross-sectional studies of school-aged children (4–18 years) reporting time-segment-specific accelerometer-measured PA from 01/1990 to 01/2013. We meta-analysed standardised mean differences (SMD) between time segments for mean accelerometer counts per minute (TPA) and minutes in moderate-to-vigorous PA (MVPA). SMD is reported in units of standard deviation; 0.2, 0.5 and 0.8 represent small, moderate and large effects. Heterogeneity was explored using meta-regression (potential effect modifiers: age, sex and study setting).  Results: Of the 54 included studies, 37 were eligible for meta-analyses. Children were more active on weekdays than weekends [pooled SMD (95 % CI) TPA 0.14 (0.08; 0.20), MVPA 0.42 (0.35; 0.49)]. On school days, TPA was lower in school than out of school; however, marginally more MVPA was accumulated in school [TPA −0.24 (−0.40; −0.08), MVPA 0.17 (−0.03; 0.38)]. TPA was slightly lower on weekends than out of school on school days, but a greater absolute volume of MVPA was performed on weekends [TPA −0.10 (−0.19; −0.01), MVPA 1.02 (0.82; 1.23)]. Heterogeneity between studies was high (I2 73.3–96.3 %), with 20.3–53.1 % of variance between studies attributable to potential moderating factors.  Conclusions: School-aged children are more active on weekdays than weekend days. The outcome measure influences the conclusions for other comparisons. Findings support the tailoring of intervention strategies to specific time periods

Measurement of the tau lepton lifetime with the three-dimensional impact parameter method.

A new method is presented for the measurement of the mean $\tau$ lepton lifetime using events in which $\tau$'s are pair-produced and both $\tau$'s decay to hadrons and $\nu_\tau$. Based on the correlation between the two $\tau$'s produced at a symmetric $e^+ e^-$ collider, the 3DIP method relies on the three-dimensional information from a double-sided vertex detector and on kinematic constraints for the precise measurement of the $\tau$ decay angles. Using the data collected from 1992 to 1994 with the ALEPH detector at LEP, a $\tau$ lifetime of $288.0 \pm 3.1 \pm 1.3$\fs is obtained from the sample in which both $\tau$'s decay to one charged track, and $292.8 \pm 5.6 \pm 3.0$\fs from the sample in which one $\tau$ decays to one prong and the other to three prongs. The results show small statistical correlations with those derived from other methods. When combined with the previously published ALEPH measurements, the resulting $\tau$ lifetime is $291.2 \pm 2.0 \pm 1.2$\fs

Characterization of multinucleated giant cells in synovium and subchondral bone in knee osteoarthritis and rheumatoid arthritis

Background: Multinucleated giant cells have been noticed in diverse arthritic conditions since their first description in rheumatoid synovium. However, their role in the pathogenesis of osteoarthritis (OA) or rheumatoid arthritis (RA) still remains broadly unknown. We aimed to study the presence and characteristics of multinucleated giant cells (MGC) both in synovium and in subchondral bone tissues of patients with OA or RA. Methods: Knee synovial and subchondral bone samples were from age-matched patients undergoing total joint replacement for OA or RA, or non-arthritic post mortem (PM) controls. OA synovium was stratified by histological inflammation grade using index tissue sections. Synovitis was assessed by Krenn score. Histological studies employed specific antibodies against macrophage markers or cathepsin K, or TRAP enzymatic assay. Results: Inflamed OA and RA synovia displayed more multinucleated giant cells than did non-inflamed OA and PM synovia. There was a significant association between MGC numbers and synovitis severity. A TRAP negative/cathepsin K negative Langhans-like subtype was predominant in OA, whereas both Langhans-like and TRAP-positive/ cathepsin K negative foreign-body-like subtypes were most commonly detected in RA. Plasma-like and foam-like subtypes also were observed in OA and RA synovia, and the latter was found surrounding adipocytes. TRAP positive/ cathepsin K positive osteoclasts were only identified adjacent to subchondral bone surfaces. TRAP positive osteoclasts were significantly increased in subchondral bone in OA and RA compared to PM controls. Conclusions: Multinucleated giant cells are associated with synovitis severity, and subchondral osteoclast numbers are increased in OA, as well as in RA. Further research targeting multinucleated giant cells is warranted to elucidate their contributions to the symptoms and joint damage associated with arthritis

Determination of sin2 θeff w using jet charge measurements in hadronic Z decays

The electroweak mixing angle is determined with high precision from measurements of the mean difference between forward and backward hemisphere charges in hadronic decays of the Z. A data sample of 2.5 million hadronic Z decays recorded over the period 1990 to 1994 in the ALEPH detector at LEP is used. The mean charge separation between event hemispheres containing the original quark and antiquark is measured for bb̄ and cc̄ events in subsamples selected by their long lifetimes or using fast D*'s. The corresponding average charge separation for light quarks is measured in an inclusive sample from the anticorrelation between charges of opposite hemispheres and agrees with predictions of hadronisation models with a precision of 2%. It is shown that differences between light quark charge separations and the measured average can be determined using hadronisation models, with systematic uncertainties constrained by measurements of inclusive production of kaons, protons and A's. The separations are used to measure the electroweak mixing angle precisely as sin2 θeff w = 0.2322 ± 0.0008(exp. stat.) ±0.0007(exp. syst.) ± 0.0008(sep.). The first two errors are due to purely experimental sources whereas the third stems from uncertainties in the quark charge separations

Measurement of the tau lepton lifetime with the three-dimensional impact parameter method.

A new method is presented for the measurement of the mean $\tau$ lepton lifetime using events in which $\tau$'s are pair-produced and both $\tau$'s decay to hadrons and $\nu_\tau$. Based on the correlation between the two $\tau$'s produced at a symmetric $e^+ e^-$ collider, the 3DIP method relies on the three-dimensional information from a double-sided vertex detector and on kinematic constraints for the precise measurement of the $\tau$ decay angles. Using the data collected from 1992 to 1994 with the ALEPH detector at LEP, a $\tau$ lifetime of $288.0 \pm 3.1 \pm 1.3$\fs is obtained from the sample in which both $\tau$'s decay to one charged track, and $292.8 \pm 5.6 \pm 3.0$\fs from the sample in which one $\tau$ decays to one prong and the other to three prongs. The results show small statistical correlations with those derived from other methods. When combined with the previously published ALEPH measurements, the resulting $\tau$ lifetime is $291.2 \pm 2.0 \pm 1.2$\fs

Measurement of the tau lepton lifetime with the three-dimensional impact parameter method.

A new method is presented for the measurement of the mean $\tau$ lepton lifetime using events in which $\tau$'s are pair-produced and both $\tau$'s decay to hadrons and $\nu_\tau$. Based on the correlation between the two $\tau$'s produced at a symmetric $e^+ e^-$ collider, the 3DIP method relies on the three-dimensional information from a double-sided vertex detector and on kinematic constraints for the precise measurement of the $\tau$ decay angles. Using the data collected from 1992 to 1994 with the ALEPH detector at LEP, a $\tau$ lifetime of $288.0 \pm 3.1 \pm 1.3$\fs is obtained from the sample in which both $\tau$'s decay to one charged track, and $292.8 \pm 5.6 \pm 3.0$\fs from the sample in which one $\tau$ decays to one prong and the other to three prongs. The results show small statistical correlations with those derived from other methods. When combined with the previously published ALEPH measurements, the resulting $\tau$ lifetime is $291.2 \pm 2.0 \pm 1.2$\fs

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

Evaluation of test statistics in split-mouth clinical trials

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65787/1/j.1600-0765.1988.tb01616.x.pd