The host galaxy and late-time evolution of the superluminous supernova PTF12dam

Superluminous supernovae (SLSNe) of Type Ic have a tendency to occur in faint host galaxies which are likely to have low mass and low metallicity. PTF12dam is one of the closest and best-studied superluminous explosions that has a broad and slowly fading light curve similar to SN 2007bi. Here we present new photometry and spectroscopy for PTF12dam from 200-500 d (rest frame) after peak and a detailed analysis of the host galaxy (SDSS J142446.21+461348.6 at z = 0.107). Using deep templates and image subtraction we show that the light curve can be fit with a magnetar model if escape of high-energy gamma rays is taken into account. The full bolometric light curve from -53 to +399 d (with respect to peak) cannot be fit satisfactorily with the pair-instability models. An alternative model of interaction with a dense circumstellar material (CSM) produces a good fit to the data although this requires a very large mass (˜13 M⊙) of hydrogen-free CSM. The host galaxy is a compact dwarf (physical size ˜1.9 kpc) and with Mg = -19.33 ± 0.10, it is the brightest nearby SLSN Ic host discovered so far. The host is a low-mass system (2.8 × 108 M⊙) with a star formation rate (5.0 M⊙ yr-1), which implies a very high specific star formation rate (17.9 Gyr-1). The remarkably strong nebular emission provide detections of the [O III] λ4363 and [O II] λλ7320, 7330auroral lines and an accurate oxygen abundance of 12 + log (O/H) = 8.05 ± 0.09. We show here that they are at the extreme end of the metallicity distribution of dwarf galaxies and propose that low metallicity is a requirement to produce these rare and peculiar SNe.

Effect of high-pressure processing on the shelf life, safety and organoleptic characteristics of lasagne ready meals during storage at refrigeration and abuse temperature

The effect of different pressure levels (500 and 600. MPa for 1. min at ambient temperature) on lasagne ready meal as a means of increasing the safety and shelf life during storage at refrigeration (4. °C) and abuse temperature (8. °C) was investigated. High-pressure processing (500 and 600. MPa for 1. min) was able to significantly reduce the total aerobic and lactic acid bacteria counts and prolong the microbiological shelf life of lasagne at both refrigeration and abuse temperatures. Pressure at 600. MPa was a useful tool to reduce the safety risks associated with Staphylococcus aureus and Listeria monocytogenes. However, abuse storage temperature facilitated the recovery of L. monocytogenes towards the end of storage. Organoleptic evaluation revealed that HPP did not negatively influence the quality attributes of lasagne and prolonged its organoleptic shelf life. HPP treatment can serve as a useful additional step to enhance safety and increase the shelf life of multicomponent ready meals, such as lasagne. Industrial relevance: The ready meals sector of the food industry has been experiencing increasing growth in the past years. This comprehensive study explored the effects of HPP on a very popular multicomponent ready meal i.e., lasagne after treatment and during storage. The results showed that HPP can be successfully applied to lasagne ready meals to decrease the risk from S. aureus and L. monocytogenes and also significantly prolong its shelf life without affecting its organoleptic properties. The utilisation of HPP by the industry can significantly increase safety and also provide the opportunity for this product to reach markets further away.

Low-dose aspirin and survival from lung cancer: a population-based cohort study

Background
Preclinical evidence suggests that aspirin may inhibit lung cancer progression. In a large cohort of lung cancer patients, we investigated whether low-dose aspirin use was associated with a reduction in the risk of lung cancer-specific mortality.

Methods
We identified lung cancer patients from English cancer registries diagnosed between 1998 to 2009 from the National Cancer Data Repository. Medication usage was obtained from linkages to the UK Clinical Practice Research Datalink and lung cancer-specific deaths were identified from Office of National Statistics mortality data. Hazard ratios (HR) and 95 % confidence intervals (CI) for the association between low-dose aspirin use (before and after diagnosis) and risk of lung cancer-specific mortality were calculated using Cox regression models.

Results
A total of 14,735 lung cancer patients were identified during the study period. In analysis of 3,635 lung cancer patients, there was no suggestion of an association between low-dose aspirin use after diagnosis and cancer-specific mortality (adjusted HR = 0.96, 95 % CI: 0.85, 1.09). Similarly, no association was evident for low-dose aspirin use before diagnosis and cancer-specific mortality (adjusted HR = 1.00, 95 % CI: 0.95, 1.05). Associations were comparable by duration of use and for all-cause mortality.

Conclusion
Overall, we found little evidence of a protective association between low-dose aspirin use and cancer-specific mortality in a large population-based lung cancer cohort.

Naturally-occurring TGR5 agonists modulating glucagon-like peptide-1 biosynthesis and secretion

Selective GLP-1 secretagogues represent a novel potential therapy for type 2 diabetes mellitus. This study examined the GLP-1 secretory activity of the ethnomedicinal plant, Fagonia cretica, which is postulated to possess anti-diabetic activity. After extraction and fractionation extracts and purified compounds were tested for GLP-1 and GIP secretory activity in STC-1 pGIP/neo cells. Intracellular levels of incretin hormones and their gene expression were also determined. Crude F. cretica extracts stimulated both GLP-1 and GIP secretion, increased cellular hormone content, and upregulated gene expression of proglucagon, GIP and prohormone convertase. However, ethyl acetate partitioning significantly enriched GLP-1 secretory activity and this fraction underwent bioactivity-guided fractionation. Three isolated compounds were potent and selective GLP-1 secretagogues: quinovic acid (QA) and two QA derivatives, QA-3β-O-β-D-glycopyranoside and QA-3β-O-β-D-glucopyranosyl-(28→1)-β-D-glucopyranosyl ester. All QA compounds activated the TGR5 receptor and increased intracellular incretin levels and gene expression. QA derivatives were more potent GLP-1 secretagogues than QA. This is the first time that QA and its naturally-occurring derivatives have been shown to activate TGR5 and stimulate GLP-1 secretion. These data provide a plausible mechanism for the ethnomedicinal use of F. cretica and may assist in the ongoing development of selective GLP-1 agonists.

The effect of pantethine and ultraviolet-B radiation on the development of lenticular opacity in the emory mouse.

PURPOSE: Few studies have examined the impact of long-term treatments or exposures on the development of cataract in maturity-onset animal models. We studied the effect of treatment with D-pantethine and exposure to ultraviolet-B (UVB) radiation on the development of lenticular opacity in the Emory mouse. METHODS: A total of 164 Emory mice were randomized by litter at weaning to exposure to UVB light at 12 mJ/cm(2) for 6 hr/day (UV) or usual room light (A), and within litter, were further randomized to bi-weekly intra-peritoneal injections of 0.8 g/kg pantethine (T) or no treatment (C). Retro illumination lens photos were taken at 2, 4, 6, 8, and 10 months after weaning, and graded in masked fashion. The animals were sacrificed at 10 months and the lenses analyzed for total pantethine and total cysteamine. RESULTS: Lens pantethine and cysteamine levels were significantly (P < 0.001) higher for the T as compared to C litters. Mean cataract grade increased monotonically over time for all four groups. Unadjusted mean grade for the AT group at 8 (1.32) and 10 (1.86) months appeared lower than for the other groups (AC: 2.17, 2.39; UVC: 1.77, 2.40; UVT: 1.88, 2.37). However, the mean grade for the pantethine-treated litters did not differ significantly from the untreated litters except at 2 months (when untreated litters had significantly lower grades), when adjusting for UV treatment, gender and litter effect. No significant difference in cataract score existed between UV-exposed and ambient litters. Mortality was higher among pantethine-treated (hazard ratio = 1.8, p = 0.05) and UV-exposed animals (hazard ratio = 1.8, p = 0. 03) than among the untreated and unexposed litters. CONCLUSION: Significantly increased lens levels of pantethine are achieved with long-term intra-peritoneal dosing. The impact of pantethine on the progression of lenticular opacity in the Emory mouse is less than has been reported in other models. This level of chronic UVB exposure appeared to have no effect on the development of cataract in this model.

Responsiveness of dark-adaptation threshold to vitamin A and beta-carotene supplementation in pregnant and lactating women in Nepal.

BACKGROUND: Impaired dark adaptation occurs commonly in vitamin A deficiency. OBJECTIVE: We sought to examine the responsiveness of dark-adaptation threshold to vitamin A and beta-carotene supplementation in Nepali women. DESIGN: The dark-adapted pupillary response was tested in 298 pregnant women aged 15-45 y in a placebo-controlled trial of vitamin A and beta-carotene; 131 of these women were also tested at 3 mo postpartum. Results were compared with those for 100 nonpregnant US women of similar age. The amount of light required for pupillary constriction was recorded after bleaching and dark adaptation. RESULTS: Pregnant women receiving vitamin A had better dark-adaptation thresholds (-1.24 log cd/m(2)) than did those receiving placebo (-1.11 log cd/m(2); P: = 0. 03) or beta-carotene (-1.13 log cd/m(2); P: = 0.05) (t tests with Bonferroni correction). Dark-adaptation threshold was associated with serum retinol concentration in pregnant women receiving placebo (P: = 0.001) and in those receiving beta-carotene (P: = 0.003) but not in those receiving vitamin A. Among women receiving placebo, mean dark-adaptation thresholds were better during the first trimester (-1.23 log cd/m(2)) than during the second and third trimesters (-1.03 log cd/m(2); P: = 0.02, t test). The mean threshold of nonpregnant US women (-1.35 log cd/m(2)) was better than that of all 3 Nepali groups (P: < 0.001, t test, for all 3 groups). CONCLUSIONS: During pregnancy, pupillary dark adaptation was strongly associated with serum retinol concentration and improved significantly in response to vitamin A supplementation. This noninvasive testing technique is a valid indicator of population vitamin A status in women of reproductive age.

Early assessment of visual acuity after cataract surgery in rural Indonesia.

BACKGROUND: The accuracy and impact on service uptake of early examination after cataract surgery is not known. DESIGN:   Prospective cohort study. PARTICIPANTS: Cataract patients in rural Indonesia. METHODS: Visual acuity was measured preoperatively, 1day, 1-3, 4-6 and >12weeks after surgery, and 6-8months postoperatively at an outreach examination. Acceptance of second-eye surgery and spectacles was evaluated. MAIN OUTCOME MEASURE: Presenting visual acuity in the operated eye. RESULTS: Among 241 subjects (extracapsular surgery 84%), examinations at 1day, 1-3, 4-6 and >12weeks and 6-8months were completed for 100% (241), 90.9% (219), 67.6% (163), 22.0% (53) and 80.0% (193), respectively. Among subjects at the final examination (mean age 65.8±10.6years, 51.8% male), 73.6% had bilateral preoperative presenting visual acuity≤6/60. By 4-6weeks, the proportion with good (≥6/18) or poor (≤6/60) visual acuity did not differ significantly from the final examination. Among 49 persons accepting free second-eye surgery, 69.4% (34) and 16.3% (8) returned to clinic at 4-6 and >12weeks, respectively. Among 131 patients (67.9%) paying US$7 for glasses, 94 (71.8%) and 30 (22.9%) attended 4- to 6- and >12-week examinations, respectively. CONCLUSION: Even with large-incision surgery, early assessment of postoperative vision is representative of final vision, and may help deliver postoperative services to more of those needing them. © 2011 The Authors. Clinical and Experimental Ophthalmology © 2011 Royal Australian and New Zealand College of Ophthalmologists.

Italian Canzone d'autore and Greek Entechno tragoudi: a comparative overview

‘Canzone d’autore’ is the name that a vast community of Italian music critics, authors, per-formers, producers agreed upon in the mid-1970s, to describe the Italian singer-songwriter genre. Singer-songwriters, who had been missing from Italian popular music – with very few exceptions – until the late 1950s, had become increasingly popular after 1958, and were dubbed ‘cantautori’ in 1960. The term, which propagated to Spain, Catalonia, and Latin Amer-ica, is still in use, but ‘canzone d’autore’ superseded it as a genre label, highlighting the con-nections between authorship and artistic value, implied in the already established notion of ‘Cinéma d’auteur’ from which it was derived.

The expression ‘entechno laiko tragoudi’ (‘art-folk song’) was coined in Greece by Mikis The-odorakis in the 1950s, to describe a new music genre combining the urban-folk musical idi-om with lyrics coming from high-art poetry. Although the origins of the genre are tied to the work of composers like Theodorakis and Hatzidakis who did not perform as singers, from the 1970s onwards entechno became the privileged field of new generations of Greek singer-songwriters. Dropping ‘laiko’ (folk) from its label, entechno expanded its musical influences outside the urban-folk repertory and transformed into the more all-encompassing contempo-rary ‘art song’.

Transcending epithelial and intracellular biological barriers; a prototype DNA delivery device

Microneedle technology provides the opportunity for the delivery of DNA therapeutics by a non-invasive, patient acceptable route. To deliver DNA successfully requires consideration of both extra and intracellular biological barriers. In this study we present a novel two tier platform; i) a peptide delivery system, termed RALA, that is able to wrap the DNA into nanoparticles, protect the DNA from degradation, enter cells, disrupt endosomes and deliver the DNA to the nucleus of cells ii) a microneedle (MN) patch that will house the nanoparticles within the polymer matrix, breach the skin's stratum corneum barrier and dissolve upon contact with skin interstitial fluid thus releasing the nanoparticles into the skin. Our data demonstrates that the RALA is essential for preventing DNA degradation within the poly(vinylpyrrolidone) (PVP) polymer matrix. In fact the RALA/DNA nanoparticles (NPs) retained functionality when in the MN arrays after 28days and over a range of temperatures. Furthermore the physical strength and structure of the MNs was not compromised when loaded with the NPs. Finally we demonstrated the effectiveness of our MN-NP platform in vitro and in vivo, with systemic gene expression in highly vascularised regions. Taken together this 'smart-system' technology could be applied to a wide range of genetic therapies.