Antiproton induced DNA damage : proton like in flight, carbon-ion light near rest

Biological validation of new radiotherapy modalities is essential to understand their therapeutic potential. Antiprotons have been proposed for cancer therapy due to enhanced dose deposition provided by antiproton-nucleon annihilation. We assessed cellular DNA damage and relative biological effectiveness (RBE) of a clinically relevant antiproton beam. Despite a modest LET (~19 keV/μm), antiproton spread out Bragg peak (SOBP) irradiation caused significant residual γ-H2AX foci compared to X-ray, proton and antiproton plateau irradiation. RBE of ~1.48 in the SOBP and ~1 in the plateau were measured and used for a qualitative effective dose curve comparison with proton and carbon-ions. Foci in the antiproton SOBP were larger and more structured compared to X-rays, protons and carbon-ions. This is likely due to overlapping particle tracks near the annihilation vertex, creating spatially correlated DNA lesions. No biological effects were observed at 28–42 mm away from the primary beam suggesting minimal risk from long-range secondary particles.

Supporting the development of inclusive products : the effects of everyday ambient illumination levels and contrast on older adults' near visual acuity

Current older adult capability data-sets fail to account for the effects of everyday environmental conditions on capability. This article details a study that investigates the effects of everyday ambient illumination conditions (overcast, 6000 lx; in-house lighting, 150 lx and street lighting, 7.5 lx) and contrast (90%, 70%, 50% and 30%) on the near visual acuity (VA) of older adults (n= 38, 65-87 years). VA was measured at a 1-m viewing distance using logarithm of minimum angle of resolution (LogMAR) acuity charts. Results from the study showed that for all contrast levels tested, VA decreased by 0.2 log units between the overcast and street lighting conditions. On average, in overcast conditions, participants could detect detail around 1.6 times smaller on the LogMAR charts compared with street lighting. VA also significantly decreased when contrast was reduced from 70% to 50%, and from 50% to 30% in each of the ambient illumination conditions. Practitioner summary: This article presents an experimental study that investigates the impact of everyday ambient illumination levels and contrast on older adults' VA. Results show that both factors have a significant effect on their VA. Findings suggest that environmental conditions need to be accounted for in older adult capability data-sets/designs.

Cerebral cortex activation mapping upon electrical muscle stimulation by 32-channel time-domain functional near-infrared spectroscopy

The application of different EMS current thresholds on muscle activates not only the muscle but also peripheral sensory axons that send proprioceptive and pain signals to the cerebral cortex. A 32-channel time-domain fNIRS instrument was employed to map regional cortical activities under varied EMS current intensities applied on the right wrist extensor muscle. Eight healthy volunteers underwent four EMS at different current thresholds based on their individual maximal tolerated intensity (MTI), i.e., 10 % < 50 % < 100 % < over 100 % MTI. Time courses of the absolute oxygenated and deoxygenated hemoglobin concentrations primarily over the bilateral sensorimotor cortical (SMC) regions were extrapolated, and cortical activation maps were determined by general linear model using the NIRS-SPM software. The stimulation-induced wrist extension paradigm significantly increased activation of the contralateral SMC region according to the EMS intensities, while the ipsilateral SMC region showed no significant changes. This could be due in part to a nociceptive response to the higher EMS current intensities and result also from increased sensorimotor integration in these cortical regions.

In vitro models for investigating keratinocyte responses to ultraviolet B radiation

This thesis describes the use of 2- and 3-dimensional cell-based models for studying how skin cells respond to ultraviolet radiation. These methods were used to investigate skin damage and repair after exposure to radiation in the context of skin cancer development. Interactions between different skin cell types were demonstrated as being significant in protecting against ultraviolet radiation-induced skin damage. This has important implications in understanding how skin cancers occur, as well as in the development of new strategies to prevent and treat them.

The effect of MC1R variants and sunscreen on the response of human melanocytes in vivo to ultraviolet radiation and implications for melanoma.

We conducted a clinical trial to compare the molecular and cellular responses of human melanocytes and keratinocytes in vivo to solar-simulated ultraviolet radiation (SSUVR) in 57 Caucasian participants grouped according to MC1R genotype. We found that, on average, the density of epidermal melanocytes 14 days after exposure to 2 minimal erythemal dose (MED) SSUVR was twofold higher than baseline (unirradiated) skin. However, the change in epidermal melanocyte counts among people carrying germline MC1R variants (97% increase) was significantly less than those with wild-type MC1R (164% increase; P = 0.01). We also found that sunscreen applied to the skin before exposure to 2 MED SSUVR completely blocked the effects of DNA damage, p53 induction, and cellular proliferation in both melanocytes and keratinocytes.

The association between pterygium and conjunctival ultraviolet autofluorescence : The Norfolk Island Eye Study

Purpose: To investigate the association between conjunctival ultraviolet autofluorescence (UVAF), a biomarker of ocular ultraviolet radiation (UVR) exposure, and prevalent pterygium. Methods: We conducted a cross-sectional study on Norfolk Island, South Pacific. All permanent residents aged ‡15 were invited to participate. Participants completed a sun exposure questionnaire and underwent autorefraction and slit lamp biomicroscope examination. Area of conjunctival UVAF (sum of temporal ⁄ nasal area in right and left eyes) was determined using computerized methods. Multivariate logistic and linear regression models were used to estimate the associations with pterygia and UVAF, respectively. Results: Of 641 participants, 70 people (10.9%) had pterygium in one or both eyes, and prevalence was higher in males (15.0% versus 7.7%, p = 0.003). Significant independent associations with pterygium in any eye were UVAF (per 10 mm2) [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.16–1.28, p = 0.002], tanning skin phenotype (OR 2.17,1.20–3.92, p = 0.010) and spending more than three-quarters of the day outside (OR 2.22, 1.20–4.09, p = 0.011). Increasing quartile of UVAF was associated with increased risk of pterygium following adjustment of age, sex and time outdoors (pTrend = 0.002). Independent associations with increasing UVAF (per 10 mm2) were decreasing age, time outdoors, skin type and male gender (all p < 0.001). UVAF area correlated well with the duration of outdoor activity (pTrend < 0.001). Conclusion: Pterygium occurs in approximately one-tenth of Norfolk Islanders. Increasing conjunctival UVAF is associated with prevalent pterygia, confirming earlier epidemiological, laboratory and ray-tracing studies that pterygia are associated with UVR. Protection from the sun should be encouraged to reduce the prevalence of pterygium in the community.

Reliability and validity of conjunctival ultraviolet autofluorescence measurement

BACKGROUND: Conjunctival ultraviolet autofluorescence (UVAF) photography was developed to detect and characterise pre-clinical sunlight-induced UV damage. The reliability of this measurement and its relationship to outdoor activity are currently unknown. METHODS: 599 people aged 16-85 years in the cross-sectional Norfolk Island Eye Study were included in the validation study. 196 UVAF individual photographs (49 people) and 60 UVAF photographs (15 people) of Norfolk Island Eye Study participants were used for intra- and inter-observer reliability assessment, respectively. Conjunctival UVAF was measured using UV photography. UVAF area was calculated using computerised methods by one grader on two occasions (intra-observer analysis) or two graders (inter-observer analysis). Outdoor activity category, during summer and winter separately, was determined with a UV questionnaire. Total UVAF equalled the area measured in four conjunctival areas (nasal/temporal conjunctiva of right and left eyes). RESULTS: Intra-observer (ρ_c=0.988, 95% CI 0.967 to 0.996, p<0.001), and inter-observer concordance correlation coefficients (ρ_c=0.924, 95% CI 0.870 to 0.956, p<0.001) of total UVAF exceeded 0.900. When grouped according to 10 mm(2) total UVAF increments, intra- and inter-observer reliability was very good (κ=0.81) and good (κ=0.71), respectively. Increasing time outdoors was strongly with increasing total UVAF in summer and winter (p(trend) <0.001). CONCLUSION: Intra- and inter-observer reliability of conjunctival UVAF is high. In this population, UVAF correlates strongly with the authors' survey-based assessment of time spent outdoors.

Distribution of conjunctival ultraviolet autoflourescence in a population-based study : the Norfolk Island Eye Study

OBJECTIVE: The objective of this study was to describe the distribution of conjunctival ultraviolet autofluorescence (UVAF) in an adult population. METHODS: We conducted a cross-sectional, population-based study in the genetic isolate of Norfolk Island, South Pacific Ocean. In all, 641 people, aged 15 to 89 years, were recruited. UVAF and standard (control) photographs were taken of the nasal and temporal interpalpebral regions bilaterally. Differences between the groups for non-normally distributed continuous variables were assessed using the Wilcoxon-Mann-Whitney ranksum test. Trends across categories were assessed using Cuzick's non-parametric test for trend or Kendall's rank correlation τ. RESULTS: Conjunctival UVAF is a non-parametric trait with a positively skewed distribution. Median amount of conjunctival UVAF per person (sum of four measurements; right nasal/temporal and left nasal/temporal) was 28.2 mm(2) (interquartile range 14.5-48.2). There was an inverse, linear relationship between UVAF and advancing age (P<0.001). Males had a higher sum of UVAF compared with females (34.4 mm(2) vs 23.2 mm(2), P<0.0001). There were no statistically significant differences in area of UVAF between right and left eyes or between nasal and temporal regions. CONCLUSION: We have provided the first quantifiable estimates of conjunctival UVAF in an adult population. Further data are required to provide information about the natural history of UVAF and to characterise other potential disease associations with UVAF. UVR protective strategies should be emphasised at an early age to prevent the long-term adverse effects on health associated with excess UVR.

Feasibility of ranking articular cartilage conditions with non-destructive near-infrared spectroscopy with extension to the Mankin grading system

Grading osteoarthritic tissue has, until now, been a laboratory process confined to research activities. This thesis establishes a scientific protocol that extends osteoarthritic tissue ranking to surgical practice. The innovative protocol, which now incorporates the structural degeneration of collagen, enhances the traditional Modified Mankin ranking system, enabling its application to real time decision during surgery. Because it is fast and without time consuming laboratory process, it would potentially enable the cataloguing of tissues in osteoarthritic joints in all compartments of diseased joints during surgery for epistemological study and insight into the manifestation of osteoarthritis across age, gender, occupation, physical activities and race.

Raman, infrared and near-infrared spectroscopic characterization of the herderite-hydroxylherderite mineral series

Natural single-crystal specimens of the herderite-hydroxylherderite series from Brazil, with general formula CaBePO4(F,OH), were investigated by electron microprobe, Raman, infrared and near-infrared spectroscopies. The minerals occur as secondary products in granitic pegmatites. Herderite and hydroxylherderite minerals show extensive solid solution formation. The Raman spectra of hydroxylherderite are characterized by bands at around 985 and 998 cm-1, assigned to ν1 symmetric stretching mode of the HOPO33- and PO43- units. Raman bands at around 1085, 1128 and 1138 cm-1 are attributed to both the HOP and PO antisymmetric stretching vibrations. The set of Raman bands observed at 563, 568, 577, 598, 616 and 633 cm-1 are assigned to the ν4 out of plane bending modes of the PO4 and H2PO4 units. The OH Raman stretching vibrations of hydroxylherderite were observed ranging from 3626 cm-1 to 3609 cm-1. The infrared stretching vibrations of hydroxylherderites were observed between 3606 cm-1 and 3599 cm-1. By using a Libowitzky type function, hydrogen bond distances based upon the OH stretching bands were calculated. Characteristic NIR bands at around 6961 and 7054 cm-1 were assigned to the first overtone of the fundamental, whilst NIR bands at 10194 and 10329 cm-1 are assigned to the second overtone of the fundamental OH stretching vibration. Insight into the structure of the herderite-hydroxylherderite series is assessed by vibrational spectroscopy.

Mid- and near-infrared spectroscopic investigation of homogeneous cation distribution in MgxZnyAl(x+y)/2-layered double hydroxide (LDH)

In this report, a detailed FTIR fitting analysis was used to recognize Mg, Zn and Al homogeneous distribution in MgxZnyAl(x+y)/2-Layered double hydroxide (LDH) hydroxyl layer. In detail, OH-Mg2Al:OH-Mg3 ratios decreased from 95.2:4.8 (MIR) and 94.2:5.8 (NIR) to 58.9:41.1 (MIR) and 61.8:38.2 (NIR), when Mg:Al increased from 2.2:1.0 to 4.1:1.0 in MgAl-LDHs. These fitting results were similar with theoretical calculations of 94.3:5.7 and 59.0:41.0. In a further analysis of MgxZnyAl(x+y)/2-LDHs, OH bonded Zn2Mg, Zn2Al, MgZnAl, Mg2Al and Mg2Zn peaks were identified at 3420, 3430, 3445–3450, 3454 and 3545 cm-1, respectively. With the decrease of Mg:Zn from 3:1 to 1:3, metal-hydroxyl bands changed from OH-Mg2Al and MgZnAl (with a ratio of 49.4:50.6) to OH-MgZnAl and Zn2Al (with a ratio of 55.0:45.0). They were also similar with theoretical calculations of 47.6:52.4 and 54.6:45.4. As a result, these results show that there is an ordered cation distribution in MgxZnyAl(x+y)/2-LDH, and FTIR is feasible in recognizing this structure.

Optical and biomechanical factors, associated with near work and myopia

Near work may play an important role in the development of myopia in the younger population. The prevalence of myopia has also been found to be higher in occupations that involve substantial near work tasks, for example in microscopists and textile workers. When nearwork is performed, it typically involves accommodation, convergence and downward gaze. A number of previous studies have examined the effects of accommodation and convergence on changes in the optics and biometrics of the eye in primary gaze. However, little is known about the influence of accommodation on the eye in downward gaze. This thesis is primarily concerned with investigating the changes in the eye during near work in downward gaze under natural viewing conditions. To measure wavefront aberrations in downward gaze under natural viewing conditions, we modified a commercial Shack-Hartmann wavefront sensor by adding a relay lens system to allow on-axis ocular aberration measurements in primary gaze and downward gaze, with binocular fixation. Measurements with the modified wavefront sensor in primary and downward gaze were validated against a conventional aberrometer using both a model eye and in 9 human subjects. We then conducted an experiment to investigate changes in ocular aberrations associated with accommodation in downward gaze over 10 mins in groups of both myopes (n = 14) and emmetropes (n =12) using the modified Shack-Hartmann wavefront sensor. During the distance accommodation task, small but significant changes in refractive power (myopic shift) and higher order aberrations were observed in downward gaze compared to primary gaze. Accommodation caused greater changes in higher order aberrations (in particular coma and spherical aberration) in downward gaze than primary gaze, and there was evidence that the changes in certain aberrations with accommodation over time were different in downward gaze compared to primary gaze. There were no obvious systematic differences in higher order aberrations between refractive error groups during accommodation or downward gaze for fixed pupils. However, myopes exhibited a significantly greater change in higher order aberrations (in particular spherical aberration) than emmetropes for natural pupils after 10 mins of a near task (5 D accommodation) in downward gaze. These findings indicated that ocular aberrations change from primary to downward gaze, particularly with accommodation. To understand the mechanism underlying these changes in greater detail, we then extended this work to examine the characteristics of the corneal optics, internal optics, anterior biometrics and axial length of the eye during a near task, in downward gaze, over 10 mins. Twenty young adult subjects (10 emmetropes and 10 myopes) participated in this study. To measure corneal topography and ocular biometrics in downward gaze, a rotating Scheimpflug camera and an optical biometer were inclined on a custom built, height and tilt adjustable table. We found that both corneal optics and internal optics change with downward gaze, resulting in a myopic shift (~0.10 D) in the spherical power of the eye. The changes in corneal optics appear to be due to eyelid pressure on the anterior surface of the cornea, whereas the changes in the internal optics (an increase in axial length and a decrease in anterior chamber depth) may be associated with movement of the crystalline lens, under the action of gravity, and the influence of altered biomechanical forces from the extraocular muscles on the globe with downward gaze. Changes in axial length with accommodation were significantly greater in downward gaze than primary gaze (p < 0.05), indicating an increased effect of the mechanical forces from the ciliary muscle and extraocular muscles. A subsequent study was conducted to investigate the changes in anterior biometrics, axial length and choroidal thickness in nine cardinal gaze directions under the actions of the extraocular muscles. Ocular biometry measurements were obtained from 30 young adults (10 emmetropes, 10 low myopes and 10 moderate myopes) through a rotating prism with 15° deviation, along the foveal axis, using a non-contact optical biometer in each of nine different cardinal directions of gaze, over 5 mins. There was a significant influence of gaze angle and time on axial length (both p < 0.001), with the greatest axial elongation (+18 ± 8 μm) occurring with infero-nasal gaze (p < 0.001) and a slight decrease in axial length in superior gaze (−12 ± 17 μm) compared with primary gaze (p < 0.001). There was a significant correlation between refractive error (spherical equivalent refraction) and the mean change in axial length in the infero-nasal gaze direction (Pearson's R2 = 0.71, p < 0.001). To further investigate the relative effect of gravity and extraocular muscle force on the axial length, we measured axial length in 15° and 25° downward gaze with the biometer inclined on a tilting table that allowed gaze shifts to occur with either full head turn but no eye turn (reflects the effect of gravity), or full eye turn with no head turn (reflects the effect of extraocular muscle forces). We observed a significant axial elongation in 15° and 25° downward gaze in the full eye turn condition. However, axial length did not change significantly in downward gaze over 5 mins (p > 0.05) in the full head turn condition. The elongation of the axial length in downward gaze appears to be due to the influence of the extraocular muscles, since the effect was not present when head turn was used instead of eye turn. The findings of these experiments collectively show the dynamic characteristics of the optics and biometrics of the eye in downward gaze during a near task, over time. These were small but significant differences between myopic and emmetropic eyes in both the optical and biomechanical changes associated with shifts of gaze direction. These differences between myopes and emmetropes could arise as a consequence of excessive eye growth associated with myopia. However the potentially additive effects of repeated or long lasting near work activities employing infero-nasal gaze could also act to promote elongation of the eye due to optical and/or biomechanical stimuli.

Application of near infrared (NIR) spectroscopy for determining the thickness of articular cartilage

The determination of the characteristics of articular cartilage such as thickness, stiffness and swelling, especially in the form that can facilitate real-time decisions and diagnostics is still a matter for research and development. This paper correlates near infrared spectroscopy with mechanically measured cartilage thickness to establish a fast, non-destructive, repeatable and precise protocol for determining this tissue property. Statistical correlation was conducted between the thickness of bovine cartilage specimens (n = 97) and regions of their near infrared spectra. Nine regions were established along the full absorption spectrum of each sample and were correlated with the thickness using partial least squares (PLS) regression multivariate analysis. The coefficient of determination (R2) varied between 53 and 93%, with the most predictive region (R2 = 93.1%, p < 0.0001) for cartilage thickness lying in the region (wavenumber) 5350–8850 cm−1. Our results demonstrate that the thickness of articular cartilage can be measured spectroscopically using NIR light. This protocol is potentially beneficial to clinical practice and surgical procedures in the treatment of joint disease such as osteoarthritis.

Rapid nutrient determination of sugarcane milling by-products using near infrared spectroscopy

This thesis investigates the use of near infrared (NIR) spectroscopic methods for rapid measurement of nutrient elements in mill mud and mill ash. Adoption of NIR-based analyses for carbon, nitrogen, phosphorus, potassium and silicon will allow Australian sugarcane farmers to comply with recent legislative changes, and act within recommended precision farming frameworks. For these analyses, NIR spectroscopic methods surpass several facets of traditional wet chemistry techniques, dramatically reducing costs, required expertise and chemical exposure, while increasing throughput and access to data. Further, this technology can be applied in various modes, including laboratory, at-line and on-line installations, allowing targeted measurement.