Melanopsin mediated post-illumination pupil response in early age-related macular degeneration

Purpose To determine whether melanopsin expressing intrinsically photosensitive Retinal Ganglion Cell (ipRGC) inputs to the pupil light reflex (PLR) are affected in early age-related macular degeneration (AMD). Methods The PLR was measured in 40 participants (20 early AMD and 20 age-matched controls) using a custom-built Maxwellian-view pupillometer. Sinusoidal stimuli (0.5 Hz, 11.9 s duration, 35.6° diameter) were presented to the study eye and the consensual pupil response was measured for stimuli with high melanopsin excitation (464nm; blue) and with low melanopsin excitation (638 nm; red) that biased activation to the outer retina. Two melanopsin PLR metrics were quantified: the Phase Amplitude Percentage (PAP) during the sinusoidal stimulus presentation and the Post-Illumination Pupil Response (PIPR). The PLR during stimulus presentation was analyzed using latency to constriction, transient pupil response and maximum pupil constriction metrics. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves. Results The blue PIPR was significantly less sustained in the early AMD group (p<0.001). The red PIPR was not significantly different between groups (p>0.05). The PAP and blue stimulus constriction amplitude were significantly lower in the early AMD group (p < 0.05). There was no significant difference between groups in the latency or transient amplitude for both stimuli (p>0.05). ROC analysis showed excellent diagnostic accuracy for the blue PIPR metrics (AUC>0.9). Conclusions This is the initial report that the melanopsin controlled PIPR is dysfunctional in early AMD. The non-invasive, objective measurement of the ipRGC controlled PIPR has excellent diagnostic accuracy for early AMD.

Effect of age and refractive error on the melanopsin mediated Post-Illumination Pupil Response (PIPR)

Melanopsin containing intrinsically photosensitive Retinal Ganglion cells (ipRGCs) mediate the pupil light reflex (PLR) during light onset and at light offset (the post-illumination pupil response, PIPR). Recent evidence shows that the PLR and PIPR can provide non-invasive, objective markers of age-related retinal and optic nerve disease, however there is no consensus on the effects of healthy ageing or refractive error on the ipRGC mediated pupil function. Here we isolated melanopsin contributions to the pupil control pathway in 59 human participants with no ocular pathology across a range of ages and refractive errors. We show that there is no effect of age or refractive error on ipRGC inputs to the human pupil control pathway. The stability of the ipRGC mediated pupil response across the human lifespan provides a functional correlate of their robustness observed during ageing in rodent models.

Melanopsin ganglion cell function in early age-related macular degeneration

Purpose Melanopsin-expressing retinal ganglion cells (mRGCs) have non-image forming functions including mediation of the pupil light reflex (PLR). There is limited knowledge about mRGC function in retinal disease. Initial retinal changes in age-related macular degeneration (AMD) occur in the paracentral region where mRGCs have their highest density, making them vulnerable during disease onset. In this cross-sectional clinical study, we measured the PLR to determine if mRGC function is altered in early stages of macular degeneration. Methods Pupil responses were measured in 8 early AMD patients (AREDS 2001 classification; mean age 72.6 ± 7.2 years, 5M, and 3F) and 12 healthy control participants (mean age 66.6 ± 6.1 years, 8M and 4F) using a custom-built Maxwellian-view pupillometer. Stimuli were 0.5 Hz sinewaves (10 s duration, 35.6° diameter) of short wavelength light (464nm, blue; retinal irradiance = 14.5 log quanta.cm-2.s-1) to produce high melanopsin excitation and of long wavelength light (638nm, red; retinal irradiance = 14.9 log quanta.cm-2.s-1), to bias activation to outer retina and provide a control. Baseline pupil diameter was determined during a 10 s pre-stimulus period. The post illumination pupil response (PIPR) was recorded for 40 s. The 6 s PIPR and maximum pupil constriction were expressed as percentage baseline (M ± SD). Results The blue PIPR was significantly less sustained (p<0.01) in the early AMD group (75.49 ± 7.88%) than the control group (58.28 ± 9.05%). The red PIPR was not significantly different (p>0.05) between the early AMD (84.79 ± 4.03%) and control groups (82.01 ± 5.86%). Maximum constriction amplitude in the early AMD group for blue (43.67 ± 6.35%) and red (48.64 ± 6.49%) stimuli were not significantly different to the control group for blue (39.94 ± 3.66%) and red (44.98 ± 3.15%) stimuli (p>0.05). Conclusions These results are suggestive of inner retinal mRGC deficits in early AMD. This non-invasive, objective measure of pupil responses may provide a new method for quantifying mRGC function and monitoring AMD progression.

Modelling growth rate of Penaeus monodon Fabricius in intensively managed ponds: effects of temperature, pond age and stocking density

Records of shrimp growth and water quality made during 12 crops from each of 48 ponds, over a period of 6.5 years, were provided by a Queensland, Australia, commercial shrimp farm, These data were analysed with a new growth model derived from the Gompertz model. The results indicate that water temperature, mortality and pond age significantly affect growth rates. After 180 days, shrimp reach 34 g at constant 30 degrees C, but only 15 g after the same amount of time at 20 degrees C. Mortality, through thinning the density of shrimp in the ponds, increased the growth rate, but the effect is small. With continual production, growth rates at first remained steady, then appeared to decrease for the sixth and seventh crop, after which they have increased steadily with each crop. It appears that conservative pond management, together with a gradual improvement in husbandry techniques, particularly feed management, brought about this change. This has encouraging implications for the long-term sustainability of the farming methods used. The growth model can be used to predict productivity, and hence, profitability, of new aquaculture locations or new production strategies.

Age-related alterations of immunoreactive pancreatic cationic trypsinogen in sera from cystic fibrosis patients with and without pancreatic insufficiency

Serum immunoreactive cationic trypsinogen levels were determined in 99 control subjects and 381 cystic fibrosis (CF) patients. To evaluate the status of the exocrine pancreas all CF patients had previously undergone fecal fat balance studies and/or pancreatic stimulation tests. Three hundred fourteen CF patients had fat malabsorption and/or had inadequate pancreatic enzyme secretion (pancreatic insufficiency) requiring oral pancreatic enzyme supplements with meals. Sixty-seven CF patients did not have fat malabsorption and/or had adequate enzyme secretion (pancreatic sufficiency) and were not receiving pancreatic enzyme supplements with meals. Mean serum trypsinogen in 99 control subjects was 31.4 ± 14.8 /µg/hter (± 2 SD) and levels did not vary with age or sex. In CF infants (< 2 yr) with pancreatic insufficiency, mean serum trypsinogen was significantly above the non-CF values (p < 0.001). Ninety-one percent of the CF infants had elevated levels. Serum trypsinogen values in the pancreatic insuffi ient group declined steeply up to 5 years, reaching subnormal values by age 6. An equation was developed which described these age-related changes very accurately. Only six CF patients with pancreatic insufficiency had serum trypsinogen levels above the 95% confidence limits of this equation. In contrast, there was no age related decline in serum trypsinogen among the CF group with pancreatic sufficiency. Under 7 yr, serum trypsinogen failed to distinguish the two groups. In those over 7 yr of age, however, serum trypsinogen was significantly higher than the CF group with pancreatic insufficiency (p < 0.001), and 93% had values within or above the control range. In conclusion, serum trypsinogen appears to be a useful screening test for CF in infancy. Between 2 and 7 yr of age this test is of little diagnostic value. After 7 yr of age, serum trypsinogen can reliably distinguish between CF patients with and without pancreatic insufficiency.

Age-related alterations in immunoreactive pancreatic lipase and cationic trypsinogen in young children with cystic fibrosis

Serum immunoreactive pancreatic lipase and cationic trypsinogen are elevated in young infants with cystic fibrosis (CF) and may be useful neonatal screening tests for CF. We compared lipase measured by a recently developed ELISA immunoassay with trypsinogen measured by radioimmunoassay in 70 children (ages 0.1 to 9.9 years) with CF who had various degrees of pancreatic dysfunction and in 79 similarly aged children without CF (controls). In the control children, lipase activity increased with advancing age, whereas trypsinogen showed no age-related trend. Lipase and trypsinogen were significantly elevated in the infants with CF who were younger than 1 year, irrespective of pancreatic function (trypsinogen, P<0.001; lipase, P<0.05). Sensitivities in detecting CF were 76% and 90% for lipase and trypsinogen, respectively. After the first year of life, lipase and trypsinogen values declined toward normal, the rate of decline of lipase being greater than that of trypsinogen; 67% of lipase values were within or below the normal range by 3 years, whereas 67% of trypsinogen values continued to be elevated. We conclude that trypsinogen is an excellent screening test for CF in young infants regardless of pancreatic function, and that the addition of a serum pancreatic lipase determination does not improve the accuracy of trypsinogen as a screening test for cystic fibrosis.

Motivation or demotivation of health workers providing maternal health services in rural areas in Vietnam: findings from a mixed-methods study

Background Motivation is an important driver for health professionals to maintain professional competencies, continue in a workforce and contribute to work tasks. While there is some research about motivation in health workers in low to middle income countries, maternal morbidity and mortality remains high in many low and middle income countries and this can be improved by improving the quality of maternal services and the training and skills maintenance of maternal health workers. This study examines the impact of motivation on maintenance of professional competence among maternal health workers in Vietnam using mixed methods. Methods The study consisted of a survey using a self-administered questionnaire of 240 health workers in 5 districts across two Vietnamese provinces and in-depth interviews with 43 health workers and health managers at the commune, district and provincial level to explore external factors that influenced motivation. The questionnaire includes a 23 item motivation instrument based on Kenyan health context, modified for Vietnamese language and culture. Results The 240 responses represented an estimated 95% of the target sample. Multivariate analysis showed that three factors contributed to the motivation of health workers: access to training (β = -0.14, p=0.03), ability to perform key tasks (β = 0.22, p=0.001), and shift schedule (β = -0.13, p=0.05). Motivation was higher in health workers self-identifying as competent or enabled to provide more care activities. Motivation was lower in those who worked more frequent night shifts and those who had received training in the last 12 months. The interviews identified that the latter was because they felt the training was irrelevant to them, and in some cases, they do not have opportunity to practice their learnt skills. The qualitative data also showed other factors relating to service context and organisational management practices contributed to motivation. Conclusions The study demonstrates the importance of understanding the motivations of health workers and the factors that contribute to this and may contribute to more effective management of the health workforce in low and middle income countries.

Awareness and attitudes toward age-restricted communities in Finland

The average population age has been increasing for decades. In the U.S., the history of retirement communities in some states is relatively long, reaching back to the 1920s. In Finland, with one of the fastest-growing elderly population and highest total dependency ratios, seniors housing is a relatively new market within the residential housing business. Some studies have reported that only a small percentage of seniors are willing to move into age-restricted communities in Finland. This study analyzes awareness and attitudes of Finnish people toward age-restricted housing for seniors and toward seniors living in these communities. The results show that the majority of Finns were undecided if “senior houses” were the same as assisted living facilities. The respondents associated age-restricted communities with institutional housing for lonely elderly people with illnesses. The results of this study will help investors and developers understand how potential customers see age-restricted housing for seniors. Also, managers of senior houses can use the results for clarifying the idea of senior houses.

The Connor-Davidson Resilience Scale (CD-RISC): Dimensionality and age-related measurement invariance with Australian cricketers

Objective This study explored the dimensionality and measurement invariance of the 25-item Connor-Davidson Resilience Scale (CD-RISC; Connor & Davidson, 2003) across samples of adult (n = 321; aged 20–36) and adolescent (n = 199; aged 12–18) Australian cricketers. Design Cross-sectional, self-report survey Methods An online, multi-section questionnaire. Results Confirmatory factor and item level analyses supported the psychometric superiority of a revised 10-item, unidimensional model of resilience over the original 25-item, five-factor measurement model. Positive and moderate correlations with hardiness as well as negative and moderate correlations with burnout components were evidenced thereby providing support for the convergent validity of the unidimensional model. Measurement invariance analyses of the unidimensional model across the two age-group samples supported configural (i.e., same factor structure across groups), metric (i.e., same pattern of factor loadings across the groups), and partial scalar invariance (i.e., mostly the same intercepts across the groups). Conclusion Evidence for a psychometrically sound measure of resilient qualities of the individual provides an important foundation upon which researchers can identify the antecedents to and outcomes of resilience in sport contexts.

Country of Origin and Internet Publication: Applying the Berne Convention in the Digital Age

Historically, determining the country of origin of a published work presented few challenges, because works were generally published physically – whether in print or otherwise – in a distinct location or few locations. However, publishing opportunities presented by new technologies mean that we now live in a world of simultaneous publication – works that are first published online are published simultaneously to every country in world in which there is Internet connectivity. While this is certainly advantageous for the dissemination and impact of information and creative works, it creates potential complications under the Berne Convention for the Protection of Literary and Artistic Works (“Berne Convention”), an international intellectual property agreement to which most countries in the world now subscribe. Under the Berne Convention’s national treatment provisions, rights accorded to foreign copyright works may not be subject to any formality, such as registration requirements (although member countries are free to impose formalities in relation to domestic copyright works). In Kernel Records Oy v. Timothy Mosley p/k/a Timbaland, et al. however, the Florida Southern District Court of the United States ruled that first publication of a work on the Internet via an Australian website constituted “simultaneous publication all over the world,” and therefore rendered the work a “United States work” under the definition in section 101 of the U.S. Copyright Act, subjecting the work to registration formality under section 411. This ruling is in sharp contrast with an earlier decision delivered by the Delaware District Court in Håkan Moberg v. 33T LLC, et al. which arrived at an opposite conclusion. The conflicting rulings of the U.S. courts reveal the problems posed by new forms of publishing online and demonstrate a compelling need for further harmonization between the Berne Convention, domestic laws and the practical realities of digital publishing. In this chapter, we argue that even if a work first published online can be considered to be simultaneously published all over the world it does not follow that any country can assert itself as the “country of origin” of the work for the purpose of imposing domestic copyright formalities. More specifically, we argue that the meaning of “United States work” under the U.S. Copyright Act should be interpreted in line with the presumption against extraterritorial application of domestic law to limit its application to only those works with a real and substantial connection to the United States. There are gaps in the Berne Convention’s articulation of “country of origin” which provide scope for judicial interpretation, at a national level, of the most pragmatic way forward in reconciling the goals of the Berne Convention with the practical requirements of domestic law. We believe that the uncertainties arising under the Berne Convention created by new forms of online publishing can be resolved at a national level by the sensible application of principles of statutory interpretation by the courts. While at the international level we may need a clearer consensus on what amounts to “simultaneous publication” in the digital age, state practice may mean that we do not yet need to explore textual changes to the Berne Convention.

Understanding the roles of social and tangible technologies in maintaining social interaction, habits and independence into old age

The research offers a deeper understanding of how objects currently facilitate social interaction and physical activity for older adults living independently. It uses this awareness to develop, from a human perspective, considerations for the design of internet connected objects that provide novel ways of maintaining contact with loved ones. The research found that people invest emotional attachment to objects and objects foster emotional responses in people. Objects can facilitate feeling connected to another however the relationship is a result of time and repeated interaction. Recreating this connection/relationship digitally is not as simple as attaching a hyperlink.

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 x 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-kappaB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.

Loci affecting gamma-glutamyl transferase in adults and adolescents show age x SNP interaction and cardiometabolic disease associations

Serum gamma-glutamyl transferase (GGT) activity is a marker of liver disease which is also prospectively associated with the risk of all-cause mortality, cardiovascular disease, type 2 diabetes and cancers. We have discovered novel loci affecting GGT in a genome-wide association study (rs1497406 in an intergenic region of chromosome 1, P = 3.9 x 10(-8); rs944002 in C14orf73 on chromosome 14, P = 4.7 x 10(-13); rs340005 in RORA on chromosome 15, P = 2.4 x 10(-8)), and a highly significant heterogeneity between adult and adolescent results at the GGT1 locus on chromosome 22 (maximum P(HET) = 5.6 x 10(-12) at rs6519520). Pathway analysis of significant and suggestive single-nucleotide polymorphism associations showed significant overlap between genes affecting GGT and those affecting common metabolic and inflammatory diseases, and identified the hepatic nuclear factor (HNF) family as controllers of a network of genes affecting GGT. Our results reinforce the disease associations of GGT and demonstrate that control by the GGT1 locus varies with age.

Amber teething necklaces – medical marvel or maternal myth?

BACKGROUND: Baltic amber-bead necklaces or bracelets are commonly used for managing teething symptoms in infants. The effectiveness of these beads is claimed to be from succinic acid release (a compound with analgesic and anti-inflammatory properties), which is then absorbed through the skin. AIM: To investigate whether Baltic amber teething necklaces purchased in Australia contained succinic acid, and to quantify succinic acid release from the beads. METHODS: Infrared spectroscopy was used to confirm that the teething necklaces were made of Baltic amber. The amount of succinic acid contained within the beads was quantified, and succinic acid release from intact beads was measured in phosphate buffered saline (PBS) pH 5.5 or octanol to simulate aqueous or oily skin environments. RESULTS: Each necklace (33 beads in length) contained 19.17±4.89 mg of succinic acid (mean±se). Over a 6-month period, no succinic acid was detected in PBS, while 0.13±0.09 mg of succinic acid per necklace was released in octanol. Only one replicate of amber beads in octanol released succinic acid, and they had fragmented, with shards free-floating in the solvent. DISCUSSION: It is likely succinic acid was only detected because the beads were breaking down in octanol, which does not occur when worn around the neck of a child. Furthermore, the hydrophilic properties of succinic acid would not favour its absorption across hydrophobic layers of the skin and into the bloodstream. CONCLUSION: While the teething necklaces do contain small quantities of succinic acid, it is highly unlikely to be released from intact beads.