The intrinsic stiffness of human trabecular meshwork cells increases with senescence.

Dysfunction of the human trabecular meshwork (HTM) plays a central role in the age-associated disease glaucoma, a leading cause of irreversible blindness. The etiology remains poorly understood but cellular senescence, increased stiffness of the tissue, and the expression of Wnt antagonists such as secreted frizzled related protein-1 (SFRP1) have been implicated. However, it is not known if senescence is causally linked to either stiffness or SFRP1 expression. In this study, we utilized in vitro HTM senescence to determine the effect on cellular stiffening and SFRP1 expression. Stiffness of cultured cells was measured using atomic force microscopy and the morphology of the cytoskeleton was determined using immunofluorescent analysis. SFRP1 expression was measured using qPCR and immunofluorescent analysis. Senescent cell stiffness increased 1.88±0.14 or 2.57±0.14 fold in the presence or absence of serum, respectively. This was accompanied by increased vimentin expression, stress fiber formation, and SFRP1 expression. In aggregate, these data demonstrate that senescence may be a causal factor in HTM stiffening and elevated SFRP1 expression, and contribute towards disease progression. These findings provide insight into the etiology of glaucoma and, more broadly, suggest a causal link between senescence and altered tissue biomechanics in aging-associated diseases

Construction of an instrument for the measurement of educational philosophy

Thesis (M.Ed.)--Boston Universit

The tear ferning test: a simple clinical technique to evaluate the ocular tear film

This is the peer reviewed version of the following article: Masmali, A. M., Purslow, C., & Murphy, P. J. (2014). The tear ferning test: a simple clinical technique to evaluate the ocular tear film: The tear ferning test. Clinical and Experimental Optometry, 97(5), 399–406., which has been published in final form at https://doi.org/10.1111/cxo.12160. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.A healthy tear film is very important for many major functions of the ocular surface. Dry eye disease is a significant clinical problem that needs to be solved but the poor correlation between clinical signs and reported symptoms makes it difficult for the clinician to apply a scientific basis to his clinical management. The problem is compounded by the difficulties of evaluating the tear film due to its transparency, small volume and complex composition. Practical insight into tear film composition would be very useful to the clinician for patient diagnosis and treatment but detailed analysis is restricted to expensive, laboratory-based systems. There is a pressing need for a simple test. The tear ferning test is a laboratory test but it has the potential to be applied in the clinic setting to investigate the tear film in a simple way. Drying a small sample of tear fluid onto a clean, glass microscope slide produces a characteristic crystallisation pattern, described as a ‘tear fern’. This test is currently not widely used because of some limitations that need to be overcome but several studies have demonstrated its potential. Such limitations need to be resolved so that tear ferning could be used in the clinic setting to assess the tear film

Development of a new grading scale for tear ferning

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.clae.2013.09.011" © 2014. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Purpose: This paper reports on the development of a new tear ferning (TF) subjective grading scale, and compares it with the Rolando scale. Method: TF patterns obtained from tear film samples collected from normal and dry eye subjects in previous studies were collated into a large image library. From this library, 60 images were selected to represent the full range of possible TF patterns, and a further sub-set of 15 images was chosen for analysis. Twenty-five optometrists were asked to rank the images in increasing order between extreme anchors on a scale of TF patterns. Interim statistical analysis of this ranking found 7 homogeneous sub-sets, where the image rankings overlapped for a group of images. A representative image (typically the mean) from each group was then adopted as the grade standard. Using this new 7-point grading scale, 25 optometrists were asked to grade the entire 60 image library at two sessions: once using the 4-point Rolando scale and once using the new 7-point scale, applying 0.25 grade unit interpolation. Results: Statistical analysis found that for the larger image set, the Rolando scale produced 3 homogeneous sub-sets, and the 7-point scale produced 5 homogeneous sub-sets. With this refinement, a new 5-point TF scale (Grades 0–4) was obtained. Conclusions: The Rolando grading scale lacks discrimination between its Type I and II grades, reducing its reliability. The new 5-point grading scale is able to differentiate between TF patterns, and may provide additional support for the use of TF for both researcher and clinician

The host galaxies of strong CaII QSO absorption systems at z<0.5

We present new imaging and spectroscopic observations of the fields of five QSOs with very strong intervening CaII absorption systems at redshifts z<0.5 selected from the Sloan Digital Sky Survey. Recent studies of these very rare absorbers indicate that they may be related to damped Lyman alpha systems (DLAs). In all five cases we identify a galaxy at the redshift of the CaII system with impact parameters up to ~24 kpc. In four out of five cases the galaxies are luminous (L ~L*), metal-rich (Z ~Zsun), massive (velocity dispersion, sigma ~100 km/s) spirals. Their star formation rates, deduced from Halpha emission, are high, in the range SFR = 0.3 - 30 Msun/yr. In our analysis, we paid particular attention to correcting the observed emission line fluxes for stellar absorption and dust extinction. We show that these effects are important for a correct SFR estimate; their neglect in previous low-z studies of DLA-selected galaxies has probably led to an underestimate of the star formation activity in at least some DLA hosts. We discuss possible links between CaII-selected galaxies and DLAs and outline future observations which will help clarify the relationship between these different classes of QSO absorbers.Comment: Accepted for publication in MNRAS, 14 pages, 9 figures. Version with full resolution images available at http://www.ast.cam.ac.uk/~bjz/papers/Zych_etal_2007a.pd

Dose-response modelling of resistance exercise across outcome domains in strength and conditioning: a meta-analysis.

Resistance exercise is the most common training modality included within strength and conditioning (S&C) practice. Understanding dose-response relationships between resistance training and a range of outcomes relevant to physical and sporting performance is of primary importance for quality S&C prescription. The aim of this meta-analysis was to use contemporary modelling techniques to investigate resistance-only and resistance-dominant training interventions, and explore relationships between training variables (frequency, volume, intensity), participant characteristics (training status, sex) and improvements across a range of outcome domains including maximum strength, power, vertical jump, change of direction, and sprinting performance. Data were obtained from a database of training studies conducted between 1962-2018, which comprised healthy trained or untrained adults engaged in resistance-only or resistance-dominant interventions. Studies were not required to include a control group. Standardized mean difference effect sizes were calculated and interventions categorized according to a range of training variables describing frequency (number of sessions per week), volume (number of sets and repetitions performed), overall intensity (intensity of effort and load, categorised as low, medium, or high), and intensity of load (represented as % 1RM prescribed). Contemporary modelling techniques including Bayesian mixed effects meta-analytic models were fitted to investigate linear and non-linear dose-responses with models compared based on predictive accuracy. Data from a total of 295 studies comprising 535 groups and 6710 participants were included with analyses conducted on time points ≤26 weeks. The best performing model included: duration from baseline, average number of sets, and the main and interaction effects between outcome domain and intensity of load (%1RM) expressed non-linearly. Model performance was not improved by the inclusion of participant training status or sex. The current meta-analysis represents the most comprehensive investigation of dose-response relationships across a range of outcome domains commonly targeted within strength and conditioning to date. Results demonstrate the magnitude of improvements are predominantly influenced by training intensity of load and the outcome measured. When considering the effects of intensity as a %1RM, profiles differ across outcome domains with maximum strength likely to be maximised with the heaviest loads, vertical jump performance likely to be maximised with relatively light loads (~30%1RM), and power likely to be maximised with low to moderate loads (40-70% 1RM)