The depression in visual impairment trial (DEPVIT): trial design and protocol

<b>Background</b> The prevalence of depression in people with a visual disability is high but screening for depression and referral for treatment is not yet an integral part of visual rehabilitation service provision. One reason for this may be that there is no good evidence about the effectiveness of treatments in this patient group. This study is the first to evaluate the effect of depression treatments on people with a visual impairment and co morbid depression.<p></p> <b>Methods/design</b> The study is an exploratory, multicentre, individually randomised waiting list controlled trial. Participants will be randomised to receive Problem Solving Therapy (PST), a ‘referral to the GP’ requesting treatment according to the NICE’s ‘stepped care’ recommendations or the waiting list arm of the trial. The primary outcome measure is change (from randomisation) in depressive symptoms as measured by the Beck’s Depression Inventory (BDI-II) at 6 months. Secondary outcomes include change in depressive symptoms at 3 months, change in visual function as measured with the near vision subscale of the VFQ-48 and 7 item NEI-VFQ at 3 and 6 months, change in generic health related quality of life (EQ5D), the costs associated with PST, estimates of incremental cost effectiveness, and recruitment rate estimation.<p></p> <b>Discussion</b> Depression is prevalent in people with disabling visual impairment. This exploratory study will establish depression screening and referral for treatment in visual rehabilitation clinics in the UK. It will be the first to explore the efficacy of PST and the effectiveness of NICE’s ‘stepped care’ approach to the treatment of depression in people with a visual impairment.<p></p&gt

Foreigners vs. Natives: Bank Lending Technologies and Loan Pricing

Can distance-related information asymmetries in credit markets be overcome with contract design and credit scoring models? To answer this question, we explore differences in foreign and domestic banks’ credit contract terms and pricing models. Using a sample of firms that borrow from both domestic and foreign banks in the same month, we show that foreign banks are more likely to demand collateral and grant shorter maturity loans than domestic banks. Foreign banks also base their pricing on internal credit ratings and collateral pledges, while domestic banks price according to the length, depth and breadth of their relationship with a firm. These findings confirm that foreign banks can overcome informational disadvantages using contract design and credit scoring models. However, we also show that there are limitations, with foreign banks facing higher default rates and lower returns on lending if not using collateral and short maturity as disciplining tools

Dietary and animal strategies to reduce the environmental impact of pastoral dairy systems result in altered nutraceutical profiles in milk

The objective of this study was to evaluate and provide further insights into how dairy cows genetically divergent for milk urea N breeding values [MUNBV, high (2.21 ± 0.21) vs. low (−1.16 ± 0.21); µ ± SEM], consuming either fresh cut Plantain (Plantago lanceolata L., PL) or Ryegrass (Lolium perenne L., RG) herbage, impacted the nutraceutical profile of whole milk by investigating amino and fatty acid composition and applying metabolomic profiling techniques. Both diet and MUNBV, and their interaction term, were found to affect the relative abundance of alanine, glycine, histidine, and phenylalanine in the milk (p < 0.05), but their minor absolute differences (up to ~0.13%) would not be considered biologically relevant. Differences were also detected in the fatty acid profile based on MUNBV and diet (p < 0.05) with low MUNBV cows having a greater content of total unsaturated fatty acids (+16%) compared to high MUNBV cows and cows consuming PL having greater content of polyunsaturated fatty acids (+92%), omega 3 (+101%) and 6 (+113%) compared to RG. Differences in the metabolomic profile of the milk were also detected for both MUNBV and dietary treatments. Low MUNBV cows were found to have greater abundances of choline phosphate, phosphorylethanolamine, N-acetylglucosamine 1-phosphate, and 2-dimethylaminoethanol (p < 0.05). High MUNBV cows had a greater abundance of methionine sulfoxide, malate, 1,5-anhydroglucitol (1,5-AG), glycerate, arabitol/xylitol, 3-hydroxy-3-methylglutarate, 5-hydroxylysine and cystine (p < 0.05). Large differences (p < 0.05) were also detected as a result of diet with PL diets having greater abundances of the phytochemicals 4-acetylcatechol sulfate, 4-methylcatechol sulfate, and p-cresol glucuronide whilst RG diets had greater abundances of 2,6-dihydroxybenzoic acid, 2-acetamidophenol sulfate, and 2-hydroxyhippurate. The results of this study indicate the potential to alter the nutraceutical value of milk from dietary and genetic strategies that have been previously demonstrated to reduce environmental impact

A diverse diet as an alternative to ryegrass can improve the total antioxidant status of dams at lambing

The objective of this experiment was to determine if providing ewes in the final trimester of pregnancy with choice from diverse diet components would reduce markers of oxidative and metabolic stress in ewes and improve lamb birth weights relative to ewes offered only one forage species, repetitively. Fifty-four, twin bearing Coopworth ewes [initial live weight (LW) = 69.82 ± 1.16 kg] were blocked by weight onto iso-energetic diets with either choice from taxonomically diverse plants [DIV; spatially separated strips of ryegrass (Lolium perenne L.), chicory (Cichorium intybus L.), plantain (Plantago lanceolata L.), red clover (Trifolium pratense L.), and alfalfa (Medicago sativa L.)] or a ryegrass only diet (RYE) for the final third of gestation. The ewes offered the DIV diet birthed 8.9% heavier lambs (5.64 ± 0.20 kg) than RYE ewes (5.18 ± 0.20 kg; P = 0.03). In addition, the DIV ewes had greater (P < 0.01) glutathione peroxidase and total antioxidant status, and lower (P = 0.01) plasma non-esterified fatty acid concentrations than the RYE fed ewes 24 h after lambing. The results indicate that the DIV diet can improve antioxidant status and reduce some markers of oxidative and metabolic stress at lambing compared to a conventional RYE diet

Health-state utilities in a prisoner population : a cross-sectional survey

Background: Health-state utilities for prisoners have not been described. Methods: We used data from a 1996 cross-sectional survey of Australian prisoners (n = 734). Respondent-level SF-36 data was transformed into utility scores by both the SF-6D and Nichol's method. Socio-demographic and clinical predictors of SF-6D utility were assessed in univariate analyses and a multivariate general linear model. Results: The overall mean SF-6D utility was 0.725 (SD 0.119). When subdivided by various medical conditions, prisoner SF-6D utilities ranged from 0.620 for angina to 0.764 for those with none/mild depressive symptoms. Utilities derived by the Nichol's method were higher than SF-6D scores, often by more than 0.1. In multivariate analysis, significant independent predictors of worse utility included female gender, increasing age, increasing number of comorbidities and more severe depressive symptoms. Conclusion: The utilities presented may prove useful for future economic and decision models evaluating prison-based health programs

An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo.

BACKGROUND: Restraining or slowing ageing hallmarks at the cellular level have been proposed as a route to increased organismal lifespan and healthspan. Consequently, there is great interest in anti-ageing drug discovery. However, this currently requires laborious and lengthy longevity analysis. Here, we present a novel screening readout for the expedited discovery of compounds that restrain ageing of cell populations in vitro and enable extension of in vivo lifespan. METHODS: Using Illumina methylation arrays, we monitored DNA methylation changes accompanying long-term passaging of adult primary human cells in culture. This enabled us to develop, test, and validate the CellPopAge Clock, an epigenetic clock with underlying algorithm, unique among existing epigenetic clocks for its design to detect anti-ageing compounds in vitro. Additionally, we measured markers of senescence and performed longevity experiments in vivo in Drosophila, to further validate our approach to discover novel anti-ageing compounds. Finally, we bench mark our epigenetic clock with other available epigenetic clocks to consolidate its usefulness and specialisation for primary cells in culture. RESULTS: We developed a novel epigenetic clock, the CellPopAge Clock, to accurately monitor the age of a population of adult human primary cells. We find that the CellPopAge Clock can detect decelerated passage-based ageing of human primary cells treated with rapamycin or trametinib, well-established longevity drugs. We then utilise the CellPopAge Clock as a screening tool for the identification of compounds which decelerate ageing of cell populations, uncovering novel anti-ageing drugs, torin2 and dactolisib (BEZ-235). We demonstrate that delayed epigenetic ageing in human primary cells treated with anti-ageing compounds is accompanied by a reduction in senescence and ageing biomarkers. Finally, we extend our screening platform in vivo by taking advantage of a specially formulated holidic medium for increased drug bioavailability in Drosophila. We show that the novel anti-ageing drugs, torin2 and dactolisib (BEZ-235), increase longevity in vivo. CONCLUSIONS: Our method expands the scope of CpG methylation profiling to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, and in vivo, providing a novel accelerated discovery platform to test sought after anti-ageing compounds and geroprotectors

Nitrogen balance of dairy cows divergent for milk urea nitrogen breeding values consuming either plantain or perennial ryegrass

Inefficient nitrogen (N) use from pastoral dairy production systems has resulted in environmental degradation, as a result of excessive concentrations of urinary N excretion leaching into waterways and N₂O emissions from urination events into the atmosphere. The objectives of this study were to measure and evaluate the total N balance of lactating dairy cows selected for milk urea N concentration breeding values (MUNBVs) consuming either a 100% perennial ryegrass (Lolium perenne L.) or 100% plantain (Plantago lanceolata L.) diet. Sixteen multiparous lactating HolsteinFriesian × Jersey cows divergent for MUNBV were housed in metabolism crates for 72 h, where intake and excretions were collected and measured. No effect of MUNBV was detected for total N excretion; however, different excretion characteristics were detected, per urination event. Low MUNBV cows had a 28% reduction in the concentration of urinary urea nitrogen (g/event) compared to high MUNBV cows when consuming a ryegrass diet. Cows consuming plantain regardless of their MUNBV value had a 62% and 48% reduction in urinary urea nitrogen (g/event) compared to high and low MUNBV cows consuming ryegrass, respectively. Cows consuming plantain also partitioned more N into faeces. These results suggest that breeding for low MUNBV cows on ryegrass diets and the use of a plantain diet will reduce urinary urea nitrogen loading rates and therefore estimated nitrate leaching values, thus reducing the environmental impact of pastoral dairy production systems

Lingual haemangiosarcoma in a crossbred dog

An eight-year-old, male neutered, crossbred dog was presented for investigation of a lingual mass of four months duration. Oral examination revealed a 7 cm × 5 cm soft, fluctuant mass at the caudal aspect of the tongue. Ultrasound examination of the mass demonstrated mixed echogenicity, with cavitations containing hypoechoic and anechoic regions. Lingual haemangiosarcoma was diagnosed on histopathological examination of multiple biopsy samples, with confirmation of the vascular endothelial origin of tumour cells by positive immunolabelling for factor VIII-related antigen

The co-evolution of technological promises, modelling, policies and climate change targets

The nature and framing of climate targets in international politics has changed substantially since their early expressions in the 1980s. Here, we describe their evolution in five phases-from 'climate stabilization' to specific 'temperature outcomes'-co-evolving with wider climate politics and policy, modelling methods and scenarios, and technological promises (from nuclear power to carbon removal). We argue that this co-evolution has enabled policy prevarication, leaving mitigation poorly delivered, yet the technological promises often remain buried in the models used to inform policy. We conclude with a call to recognise and break this pattern to unleash more effective and just climate policy. This Perspective maps the history of climate targets and shows how the international goal of avoiding dangerous climate change has been reinterpreted in the light of new modelling methods and technological promises, ultimately enabling policy prevarication and limiting mitigation

Rumen function and grazing behavior of early-lactation dairy cows supplemented with fodder beet

Fodder beet (FB) is a source of readily fermentable carbohydrate that can mitigate early spring herbage deficits and correct the negative energy balance experienced during early lactation in pastoral dairy systems of New Zealand. However, the low-fiber and high-soluble carbohydrate content of both FB bulb and spring herbage are factors that promote subacute ruminal acidosis, impairing rumen function and limiting the marginal milk production response to supplement. In a crossover experiment, 8 Holstein Friesian × Jersey early-lactation dairy cows were used to test the effect of supplementing 16 kg of dry matter (DM) of a grazed perennial ryegrass herbage with 6 kg of DM/d of FB bulb (FBH) versus herbage only (HO) on changes in rumen function and grazing behavior. Following 20 d of adaptation to diets, DM disappearance (%) of FB bulb (FBH cows only) and herbage were measured in sacco, separately. Cows were fasted overnight, and the ruminal contents were bailed the following morning (~0930 h) again to determine the pool size of volatile fatty acids, ammonia, and particle size of digesta, as well as to estimate the rate of ruminal outflow and degradation of neutral detergent fiber. The FBH diet did not alter DM intake, milk yield, or milk solid (fat + protein) production compared with HO. Supplementation of herbage with FB reduced ruminal pH compared with HO between ~0800 h and 1300 h each day. During each period, 1 cow experienced severe subacute ruminal acidosis (pH 180 min/d) during final adaptation to the target FB allocation. The FBH diet reduced the ruminal pool of acetate and ammonia, but increased the ruminal pool of butyrate and lactate compared with HO. When fed FB, rumination and grazing time increased and grazing intensity declined compared with cows fed HO. Despite increased rumination, the comminution of large particles declined 28% between the first and second rumen bailing when cows were fed FB, and in sacco DM disappearance of perennial ryegrass declined 18% compared with cows fed HO. These results indicate that grazing dairy cows supplemented with FB (40% of daily intake) increase rumination and mastication intensity to counteract reduced ruminal degradation of ryegrass herbage due to low ruminal fluid pH