Characterisation of enterovirus 71 replication kinetics in human colorectal cell line, HT29

Hand, Foot and Mouth Disease (HFMD), a contagious viral disease that commonly affects infants and children with blisters and flu like symptoms, is caused by a group of enteroviruses such as Enterovirus 71 (EV71) and coxsackievirus A16 (CA16). However some HFMD caused by EV71 may further develop into severe neurological complications such as encephalitis and meningitis. The route of transmission was postulated that the virus transmit from one person to another through direct contact of vesicular fluid or droplet from the infected or via faecal-oral route. To this end, this study utilised a human colorectal adenocarcinoma cell line (HT29) with epithelioid morphology as an in vitro model for the investigation of EV71 replication kinetics. Using qPCR, viral RNA was first detected in HT29 cells as early as 12 h post infection (hpi) while viral protein was first detected at 48 hpi. A significant change in HT29 cells’ morphology was also observed after 48 hpi. Furthermore HT29 cell viability also significantly decreased at 72 hpi. Together, data from this study demonstrated that co-culture of HT29 with EV71 is a useful in vitro model to study the pathogenesis of EV71

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.

Prevalence of chronic ocular diseases in a genetic isolate : the Norfolk Island Eye Study (NIES)

Purpose: Over 40% of the permanent population of Norfolk Island possesses a unique genetic admixture dating to Pitcairn Island in the late 18 th century, with descendents having varying degrees of combined Polynesian and European ancestry. We conducted a population-based study to determine the prevalence and causes of blindness and low vision on Norfolk Island. Methods: All permanent residents of Norfolk Island aged ≥ 15 years were invited to participate. Participants completed a structured questionnaire/interview and underwent a comprehensive ophthalmic examination including slit-lamp biomicroscopy. Results: We recruited 781 people aged ≥ 15, equal to 62% of the permanent population, 44% of whom could trace their ancestry to Pitcairn Island. No one was bilaterally blind. Prevalence of unilateral blindness (visual acuity [VA] < 6/60) in those aged ≥ 40 was 1.5%. Blindness was more common in females (P=0.049) and less common in people with Pitcairn Island ancestry (P<0.001). The most common causes of unilateral blindness were age-related macular degeneration (AMD), amblyopia, and glaucoma. Five people had low vision (Best-Corrected VA < 6/18 in better eye), with 4 (80%) due to AMD. People with Pitcairn Island ancestry had a lower prevalence of AMD (P<0.001) but a similar prevalence of glaucoma to those without Pitcairn Island ancestry. Conclusions: The prevalence of blindness and visual impairment in this isolated Australian territory is low, especially amongst those with Pitcairn Island ancestry. AMD was the most common cause of unilateral blindness and low vision. The distribution of chronic ocular diseases on Norfolk Island is similar to mainland Australian estimates.

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.

A pre-post evaluation of an ambulatory nutrition support service for malnourished patients post hospital discharge: a pilot study

Introduction Malnutrition is common among hospitalised patients, with poor follow-up of nutrition support post-discharge. Published studies on the efficacy of ambulatory nutrition support (ANS) for malnourished patients post-discharge are scarce. The aims of this study were to evaluate the rate of dietetics follow-up of malnourished patients post-discharge, before (2008) and after (2010) implementation of a new ANS service, and to evaluate nutritional outcomes post-implementation. Materials and Methods Consecutive samples of 261 (2008) and 163 (2010) adult inpatients referred to dietetics and assessed as malnourished using Subjective Global Assessment (SGA) were enrolled. All subjects received inpatient nutrition intervention and dietetic outpatient clinic follow-up appointments. For the 2010 cohort, ANS was initiated to provide telephone follow-up and home visits for patients who failed to attend the outpatient clinic. Subjective Global Assessment, body weight, quality of life (EQ-5D VAS) and handgrip strength were measured at baseline and five months post-discharge. Paired t-test was used to compare pre- and post-intervention results. Results In 2008, only 15% of patients returned for follow-up with a dietitian within four months post-discharge. After implementation of ANS in 2010, the follow-up rate was 100%. Mean weight improved from 44.0 ± 8.5kg to 46.3 ± 9.6kg, EQ-5D VAS from 61.2 ± 19.8 to 71.6 ± 17.4 and handgrip strength from 15.1 ± 7.1 kg force to 17.5 ± 8.5 kg force; p<0.001 for all. Seventy-four percent of patients improved in SGA score. Conclusion Ambulatory nutrition support resulted in significant improvements in follow-up rate, nutritional status and quality of life of malnourished patients post-discharge.

Evaluation of an ambulatory nutrition support service for malnourished patients post hospital discharge

Introduction Malnutrition is common among hospitalised patients, with poor follow-up of nutrition support post-discharge. Published studies on the efficacy of ambulatory nutrition support (ANS) for malnourished patients post-discharge are scarce. The aims of this study were to evaluate the rate of dietetics follow-up of malnourished patients post-discharge, before (2008) and after (2010) implementation of a new ANS service, and to evaluate nutritional outcomes post-implementation. Materials and Methods Consecutive samples of 261 (2008) and 163 (2010) adult inpatients referred to dietetics and assessed as malnourished using Subjective Global Assessment (SGA) were enrolled. All subjects received inpatient nutrition intervention and dietetic outpatient clinic follow-up appointments. For the 2010 cohort, ANS was initiated to provide telephone follow-up and home visits for patients who failed to attend the outpatient clinic. Subjective Global Assessment, body weight, quality of life (EQ-5D VAS) and handgrip strength were measured at baseline and five months post-discharge. Paired t-test was used to compare pre- and post-intervention results. Results In 2008, only 15% of patients returned for follow-up with a dietitian within four months post-discharge. After implementation of ANS in 2010, the follow-up rate was 100%. Mean weight improved from 44.0 ± 8.5kg to 46.3 ± 9.6kg, EQ-5D VAS from 61.2 ± 19.8 to 71.6 ± 17.4 and handgrip strength from 15.1 ± 7.1 kg force to 17.5 ± 8.5 kg force; p<0.001 for all. Seventy-four percent of patients improved in SGA score. Conclusion Ambulatory nutrition support resulted in significant improvements in follow-up rate, nutritional status and quality of life of malnourished patients post-discharge.

A randomised, concentration-controlled, comparison of standard (5-day) vs. prolonged (15-day) infusions of etoposide phosphate in small-cell lung cancer

Purpose: This randomised trial was designed to investigate the activity and toxicity of continuous infusion etoposide phosphate (EP), targeting a plasma etoposide concentration of either 3 μg/ml for five days (5d) or 1 μg/ml for 15 days (15d), in previously untreated SCLC patients with extensive disease. Patients and methods: EP was used as a single agent. Plasma etoposide concentration was monitored on days 2 and 4 in patients receiving 5d EP and on days 2, 5, 8 and 11 in patients receiving 15d EP, with infusion modification to ensure target concentrations were achieved. Treatment was repeated every 21 days for up to six cycles, with a 25% reduction in target concentration in patients with toxicity. Results: The study has closed early after entry of 29 patients (14 with 5d EP, 15 with 15d EP). Objective responses were seen in seven of 12 (58%, confidence interval (CI): 27%-85%) evaluable patients after 5d EP, and two of 14 (14%, CI: 4%42%) evaluable patients after 15d EP (P = 0.038). Grade 3 or 4 neutropenia or leucopenia during the first cycle of treatment was observed in six of 12 patients after 5d EP and 0/14 patients after 15d EP (P = 0.004), with median nadir WBC count of 2.6 x 109/1 after 5d and 5.0 x 109/1 after 15d EP (P = 0.017). Only one of 49 cycles of 15d EP was associated with grade 3 or worse haematological toxicity, compared to 14 of 61 cycles of 5d EP. Conclusions: Although the number of patients entered into this trial was small, the low activity seen at 1 μg/ml in the 15d arm suggests that this concentration is below the therapeutic window in this setting. Further concentration- controlled studies with prolonged EP infusions are required.

Molecular biomarkers in non-small-cell lung cancer : a retrospective analysis of data from the phase 3 FLEX study

Background: Findings from the phase 3 FLEX study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival, compared with cisplatin and vinorelbine alone, in the first-line treatment of EGFR-expressing, advanced non-small-cell lung cancer (NSCLC). We investigated whether candidate biomarkers were predictive for the efficacy of chemotherapy plus cetuximab in this setting. Methods: Genomic DNA extracted from formalin-fixed paraffin-embedded (FFPE) tumour tissue of patients enrolled in the FLEX study was screened for KRAS codon 12 and 13 and EGFR kinase domain mutations with PCR-based assays. In FFPE tissue sections, EGFR copy number was assessed by dual-colour fluorescence in-situ hybridisation and PTEN expression by immunohistochemistry. Treatment outcome was investigated according to biomarker status in all available samples from patients in the intention-to-treat population. The primary endpoint in the FLEX study was overall survival. The FLEX study, which is ongoing but not recruiting participants, is registered with ClinicalTrials.gov, number NCT00148798. Findings: KRAS mutations were detected in 75 of 395 (19%) tumours and activating EGFR mutations in 64 of 436 (15%). EGFR copy number was scored as increased in 102 of 279 (37%) tumours and PTEN expression as negative in 107 of 303 (35%). Comparisons of treatment outcome between the two groups (chemotherapy plus cetuximab vs chemotherapy alone) according to biomarker status provided no indication that these biomarkers were of predictive value. Activating EGFR mutations were identified as indicators of good prognosis, with patients in both treatment groups whose tumours carried such mutations having improved survival compared with those whose tumours did not (chemotherapy plus cetuximab: median 17·5 months [95% CI 11·7-23·4] vs 8·5 months [7·1-10·8], hazard ratio [HR] 0·52 [0·32-0·84], p=0·0063; chemotherapy alone: 23·8 months [15·2-not reached] vs 10·0 months [8·7-11·0], HR 0·35 [0·21-0·59], p<0·0001). Expression of PTEN seemed to be a potential indicator of good prognosis, with patients whose tumours expressed PTEN having improved survival compared with those whose tumours did not, although this finding was not significant (chemotherapy plus cetuximab: median 11·4 months [8·6-13·6] vs 6·8 months [5·9-12·7], HR 0·80 [0·55-1·16], p=0·24; chemotherapy alone: 11·0 months [9·2-12·6] vs 9·3 months [7·6-11·9], HR 0·77 [0·54-1·10], p=0·16). Interpretation: The efficacy of chemotherapy plus cetuximab in the first-line treatment of advanced NSCLC seems to be independent of each of the biomarkers assessed. Funding: Merck KGaA. © 2011 Elsevier Ltd.

Geologic map of the Valley Mountain 15’ quadrangle, San Bernardino and Riverside Counties, California: U.S. Geological Survey Geologic Quadrangle Map GQ–1767, scale 1:62,500

The Valley Mountain 15’ quadrangle straddles the Pinto Mountain Fault, which bounds the eastern Transverse Ranges in the south against the Mojave Desert province in the north. The Pinto Mountains, part of the eastern Transverse Ranges in the south part of the quadrangle expose a series of Paleoproterozoic gneisses and granite and the Proterozoic quartzite of Pinto Mountain. Early Triassic quartz monzonite intruded the gneisses and was ductiley deformed prior to voluminous Jurassic intrusion of diorite, granodiorite, quartz monzonite, and granite plutons. The Jurassic rocks include part of the Bullion Mountains Intrusive Suite, which crops out prominently at Valley Mountain and in the Bullion Mountains, as well as in the Pinto Mountains. Jurassic plutons in the southwest part of the quadrangle are deeply denuded from midcrustal emplacement levels in contrast to supracrustal Jurassic limestone and volcanic rocks exposed in the northeast. Dikes inferred to be part of the Jurassic Independence Dike Swarm intrude the Jurassic plutons and Proterozoic rocks. Late Cretaceous intrusion of the Cadiz Valley Batholith in the northeast caused contact metamorphism of adjacent Jurassic plutonic rocks...

Child sexual abuse in China : a meta-analysis of 27 studies

Objective: To examine whether Chinese studies of child sexual abuse (CSA) in the general population show lower prevalence rates than other international studies, and whether certain features of these studies may help to account for variation in estimates. Methods: A meta-analysis and meta-regression were conducted on 27 studies found in the English and Chinese language peer reviewed journals that involved general populations of students or residents, estimated CSA prior to age 18, and specified rates for males or females individually. Results: Estimates for Chinese females were lower than the international composites. For total CSA for females, the Chinese pooled estimate was 15.3% (95% CI = 12.6–18.0) based on the meta-analysis of 24 studies, lower than the international estimate (Stoltenborgh, van IJzendoorn, Euser, & Bakermans-Kranenburg, 2011) but not significantly. For contact CSA for females, the pooled estimate was 9.5% (95% CI = 7.5–11.5), based on 16 studies, significantly lower than the international prevalence. For penetrative CSA for females, the pooled estimate was 1% (95% CI = 0.7–1.3), based on 15 studies, significantly lower than the international estimate of 15.1%. Chinese men reported significantly less penetrative CSA but significantly more total CSA than international estimates; while contact CSA reported by Chinese and international males appeared to be roughly equivalent. Chinese CSA prevalence estimates were lower in studies from urban areas and non-mainland areas (Hong Kong and Taiwan), and in surveys with larger and probability samples, multiple sites, face-to-face interview method and when using less widely used instruments. Conclusions: The findings to date justify further research into possible cultural and sociological reasons for lower risk of contact and penetrative sexual abuse of girls and less penetrative abuse of boys in China. Future research should examine sociological explanations, including patterns of supervision, sexual socialization and attitudes related to male sexual prowess. Practice implications: The findings suggest that future general population studies in China should use well validated instruments, avoid face-to-face interview formats and be careful to maintain methodological standards when sampling large populations over multiple sites.

Replacement of healthcare-associated MRSA by community-associated MRSA in Queensland : confirmation by genotyping

Objective To describe the changing prevalence of healthcare- and community-associated MRSA. Methods Susceptibility phenotypes of MRSA were observed from 2000 to 2012 using routine susceptibility data. Phenotypic definitions of major clones were validated by genotyping isolates from a nested period prevalence survey in 2011. Results The predominant healthcare-associated (AUS-2/3 like) MRSA phenotype decreased from 42 to 14 isolates per million occasions of service in outpatients (P < 0.0001) and from 650 to 75 isolates per million accrued patient days in inpatients (P 0.0005), while the respective rates of the healthcare-related EMRSA-15 like phenotype increased from 1 to 19 in outpatients (P < 0.0001) and from 11 to 83 in inpatients (P < 0.0001) and those of the community-associated MRSA phenotype increased from 17 to 296 in outpatients (P < 0.0001) and from 71 to 486 in inpatients (P < 0.0001). When compared with single nucleotide polymorphism genotyping the AUS-2/3 like phenotype had a sensitivity and positive predictive value (PPV) for CC239 of 1 and 0.791 respectively, while the EMRSA-15 like phenotype had a sensitivity and PPV for CC22 of 0.903 and 0.774. PVL-positive CA-MRSA, predominantly ST93 and CC30, accounted for 60.8% of MRSA, while PVL-negative CA-MRSA, mainly CC5 and CC1, accounted for 21.4%. Conclusions The initially dominant healthcare-associated MRSA clone has been progressively replaced, mainly by four community-associated lineages.

Elucidating the host–pathogen interaction between human colorectal cells and invading Enterovirus 71 using transcriptomics profiling

Enterovirus 71 (EV71) is one of the main etiological agents for Hand, Foot and Mouth Disease (HFMD) and has been shown to be associated with severe clinical manifestation. Currently, there is no antiviral therapeutic for the treatment of HFMD patients owing to a lack of understanding of EV71 pathogenesis. This study seeks to elucidate the transcriptomic changes that result from EV71 infection. Human whole genome microarray was employed to monitor changes in genomic profiles between infected and uninfected cells. The results reveal altered expression of human genes involved in critical pathways including the immune response and the stress response. Together, data from this study provide valuable insights into the host–pathogen interaction between human colorectal cells and EV71.

The visibility of disaster deaths in news images : a comparison of newspapers from 15 countries

The extent to which newspapers display graphic images of death has rarely been studied in relation to the degree of the visibility of bodies, nor do many comparative analyses exist. This has led to a narrow understanding of how and why audiences are exposed to human suffering around the world. In examining newspaper images of the dead from the 2010 Haiti earthquake across 15 countries, this study develops a graphic image content scale to measure such visualizations. It finds significant differences in graphic images across the studied sample, both in terms of the amount of images and the degree of visibility of death. The study argues that major sociocultural influences, such as different religious traditions and societal levels of violence are part of the reason for the differences.

Benchmarking the standard of environmental management practised in marinas

Most existing marinas are boat parking/storing and servicing facilities that have been built over a long period of time for the convenience of local boat owners.

Editorial

The Scientific Social Planning Committee was in a fantastic position to design this programme, with over 270 abstracts representing a broad range of nutrition and dietetics areas, translating evidence to practice. When reviewing the abstract submissions, clear themes emerged, including those related to the nutrition and dietetics workforce and how to deliver effective outcomes that make meaningful differences to people's lives, while also equitable and sustainable. These papers challenge us to reflect on ourselves as health professionals, including our knowledge, how confident we are in what we do and what bias we may bring to the table when dealing with health issues, for example, in relation to weight management...