Pesticide impacts on insect pollinators: Current knowledge and future research challenges.

With the need to intensify agriculture to meet growing food demand, there has been significant rise in pesticide use to protect crops, but at different rates in different world regions. In 2016, the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) global assessment on pollinators, pollination and food production identified pesticides as one of the major drivers of pollinator decline.. This assessment highlighted that studies on the effects of pesticides on pollinating insects have been limited to only a few species, primarily from developed countries. Given the worldwide variation in the scale of intensive agricultural practices, pesticide application intensities are likely to vary regionally and consequently the associated risks for insect pollinators. We provide the first long-term, global analysis of inter-regional trends in the use of different classes of pesticide between 1995 and 2020 (FAOSTAT) and a review of literature since the IPBES pollination assessment (2016). All three pesticide classes use rates varied greatly with some countries seeing increased use by 3000 to 4000 % between 1995 and 2020, while for most countries, growth roughly doubled. We present forecast models to predict regional trends of different pesticides up to 2030. Use of all three pesticide classes is to increase in Africa and South America. Herbicide use is to increase in North America and Central Asia. Fungicide use is to increase across all Asian regions. In each of the respective regions, we also examined the number of studies since 2016 in relation to pesticide use trends over the past twenty-five years. Additionally, we present a comprehensive update on the status of knowledge on pesticide impacts on different pollinating insects from literature published during 2016-2022. Finally, we outline several research challenges and knowledge gaps with respect to pesticides and highlight some regional and international conservation efforts and initiatives that address pesticide reduction and/or elimination.

Rumen-protected choline and methionine during the periparturient period affect choline metabolites, amino acids, and hepatic expression of genes associated with one-carbon and lipid metabolism.

Feeding supplemental choline and Met during the periparturient period can have positive effects on cow performance; however, the mechanisms by which these nutrients affect performance and metabolism are unclear. The objective of this experiment was to determine if providing rumen-protected choline, rumen-protected Met, or both during the periparturient period modifies the choline metabolitic profile of plasma and milk, plasma AA, and hepatic mRNA expression of genes associated with choline, Met, and lipid metabolism. Cows (25 primiparous, 29 multiparous) were blocked by expected calving date and parity and randomly assigned to 1 of 4 treatments: control (no rumen-protected choline or rumen-protected Met); CHO (13 g/d choline ion); MET (9 g/d DL-methionine prepartum; 13.5 g/d DL-methionine, postpartum); or CHO + MET. Treatments were applied daily as a top dress from ∼21 d prepartum through 35 d in milk (DIM). On the day of treatment enrollment (d -19 ± 2 relative to calving), blood samples were collected for covariate measurements. At 7 and 14 DIM, samples of blood and milk were collected for analysis of choline metabolites, including 16 species of phosphatidylcholine (PC) and 4 species of lysophosphatidylcholine (LPC). Blood was also analyzed for AA concentrations. Liver samples collected from multiparous cows on the day of treatment enrollment and at 7 DIM were used for gene expression analysis. There was no consistent effect of CHO or MET on milk or plasma free choline, betaine, sphingomyelin, or glycerophosphocholine. However, CHO increased milk secretion of total LPC irrespective of MET for multiparous cows and in absence of MET for primiparous cows. Furthermore, CHO increased or tended to increase milk secretion of LPC 16:0, LPC 18:1, and LPC 18:0 for primi- and multiparous cows, although the response varied with MET supplementation. Feeding CHO also increased plasma concentrations of LPC 16:0 and LPC 18:1 in absence of MET for multiparous cows. Although milk secretion of total PC was unaffected, CHO and MET increased secretion of 6 and 5 individual PC species for multiparous cows, respectively. Plasma concentrations of total PC and individual PC species were unaffected by CHO or MET for multiparous cows, but MET reduced total PC and 11 PC species during wk 2 postpartum for primiparous cows. Feeding MET consistently increased plasma Met concentrations for both primi- and multiparous cows. Additionally, MET decreased plasma serine concentrations during wk 2 postpartum and increased plasma phenylalanine in absence of CHO for multiparous cows. In absence of MET, CHO tended to increase hepatic mRNA levels of betaine-homocysteine methyltransferase and phosphate cytidylyltransferase 1 choline, α, but tended to decrease expression of 3-hydroxy-3-methylglutaryl-coenzyme A synthase 2 and peroxisome proliferator activated receptor α irrespective of MET. Although shifts in the milk and plasma PC profile were subtle and inconsistent between primi- and multiparous cows, gene expression results suggest that supplemental choline plays a probable role in promoting the cytidine diphosphate-choline and betaine-homocysteine S-methyltransferase pathways. However, interactive effects suggest that this response depends on Met availability, which may explain the inconsistent results observed among studies when supplemental choline is fed.

Production responses to rumen-protected choline and methionine supplemented during the periparturient period differ for primi- and multiparous cows.

The objective of this experiment was to examine production performance responses to feeding rumen-protected choline (RPC) or methionine (RPM), or both, during the periparturient period. Fifty-four Holstein cows (25 primiparous, 29 multiparous) were used in a randomized block design experiment with a 2 × 2 factorial treatment structure. Cows were blocked by expected calving date and parity and assigned to 1 of 4 treatments: CON (no RPC or RPM); RPC (13.0 g/d of choline ion); RPM (9 g/d of dl-methionine prepartum; 13.5 g/d of dl-methionine postpartum); or RPC + RPM. Treatments were applied once daily as a top-dress from 3 wk before through 5 wk after calving. Dry matter intake and milk production were recorded daily, and milk samples were obtained once weekly. Data were analyzed for primi- and multiparous cows separately, using a repeated-measures mixed model that included random effects of cow and block and fixed effects of RPC, RPM, week, and their interactions; week served as the repeated effect. Initial BW and previous lactation milk yield were included as covariates in the statistical model for multiparous cows. Feeding RPC without RPM increased milk yield for multiparous cows by 8.7 kg/d, but this increase was not observed when RPC was fed with RPM. In multiparous cows, feeding RPM increased milk fat concentration and tended to increase milk fat yield. Because of this, RPM increased fat-corrected milk (FCM) by 2.8 kg/d at wk 2 postpartum, and this increase was sustained through wk 5 postpartum. In contrast, RPM did not affect overall milk fat yield and concentration for primiparous cows. Feeding RPC increased milk yield for primiparous cows by 3.5 kg/d irrespective of RPM inclusion, which is contrary to observations in multiparous cows, where RPC increased milk yield only in the absence of RPM. These results indicate that responses to RPC during the periparturient period may be dependent upon supply of methionine. Our observations also demonstrate that primi- and multiparous cows respond differently to RPC and RPM supplemented individually or simultaneously during the periparturient period. This variation in response could have been mediated by putative differences in choline and methionine requirements of primiparous versus multiparous cows, or by differences in the levels of milk production between the 2 groups (36 vs. 25 kg of FCM/d). However, cows in this study did not experience severe negative energy balance (mean nadirs of -6.6 and -5.0 Mcal/d for multiparous and primiparous cows, respectively), which likely affected their responses to RPC and RPM.

Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield.

How insects promote crop pollination remains poorly understood in terms of the contribution of functional trait differences between species. We used meta-analyses to test for correlations between community abundance, species richness and functional trait metrics with oilseed rape yield, a globally important crop. While overall abundance is consistently important in predicting yield, functional divergence between species traits also showed a positive correlation. This result supports the complementarity hypothesis that pollination function is maintained by non-overlapping trait distributions. In artificially constructed communities (mesocosms), species richness is positively correlated with yield, although this effect is not seen under field conditions. As traits of the dominant species do not predict yield above that attributed to the effect of abundance alone, we find no evidence in support of the mass ratio hypothesis. Management practices increasing not just pollinator abundance, but also functional divergence, could benefit oilseed rape agriculture.

The decline in digestive efficiency of US dairy cows from 1970 to 2014.

Since the year 1970, US milk production per cow has more than doubled, in part because of large increases in feed intake. It is well established that increasing feed intake reduces diet digestibility in dairy cattle. Our objective was to determine whether the digestive efficiency of US dairy cows had also changed. We assembled a data set consisting of diet digestibility measured either by total collection of feces or by use of indigestible neutral detergent fiber (NDF) in lactating dairy cow studies published in the Journal of Dairy Science from July 1970 to July 2014. The data set contained 575 treatment means from 154 individual research trials conducted at 26 US institutions. Based on regression analysis, mean milk yield and dry matter intake (DMI) between 1970 and 2014 increased by 19.7 and 10.3 kg/d, respectively. Temporal effects on digestibility [dry matter (DM), crude protein (CP), and NDF] were determined using the regression model Yi = YEAR1970i + CPi + NDFi + ei, where YEAR1970i is the publication year minus 1970, CPi and NDFi are diet constituents (% of diet DM) that were included to account for their known effects on digestibility, and ei is the residual error. Dry matter digestibility decreased 0.07 percentage units/yr for a total reduction of 3.08 percentage units since 1970. Furthermore, CP and NDF digestibilities decreased 0.04 and 0.17 percentage units/yr, respectively. To account for the potential effect of feed intake on digestibility, DMI as a percentage of body weight was added to the regression model. With DMI as a percentage of body weight in the model, temporal changes in DM, CP, and NDF digestibilities were no longer significant. This suggested that the apparent decline in DM digestibility could be mostly accounted for by simultaneous increases in level of feed intake. Despite lower apparent digestive efficiency, the modern dairy cow has greater production efficiency than the 1970s dairy cow because she produces more milk per unit of feed consumed and digested.

Relationship between residual feed intake and digestibility for lactating Holstein cows fed high and low starch diets.

We determined if differences in digestibility among cows explained variation in residual feed intake (RFI) in 4 crossover design experiments. Lactating Holstein cows (n=109; 120±30d in milk; mean ± SD) were fed diets high (HS) or low (LS) in starch. The HS diets were 30% (±1.8%) starch and 27% (±1.2%) neutral detergent fiber (NDF); LS diets were 14% (±2.2%) starch and 40% (±5.3%) NDF. Each experiment consisted of two 28-d treatment periods, with apparent total-tract digestibility measured using indigestible NDF as an internal marker during the last 5d of each period. Individual cow dry matter (DM) intake and milk yield were recorded daily, body weight was measured 3 to 5 times per week, and milk components were analyzed 2 d/wk. Individual DM intake was regressed on milk energy output, metabolic body weight, body energy gain, and fixed effects of parity, experiment, cohort (a group of cows that received treatments in the same sequence) nested within experiment, and diet nested within cohort and experiment, with the residual being RFI. High RFI cows ate more than expected and were deemed less efficient. Residual feed intake correlated negatively with digestibility of starch for both HS (r=-0.31) and LS (r=-0.23) diets, and with digestibilities of DM (r=-0.30) and NDF (r=-0.23) for LS diets but was not correlated with DM or NDF digestibility for HS diets. For each cohort within an experiment, cows were classified as high RFI (HRFI; >0.5 SD), medium RFI (MRFI; ±0.5 SD), and low RFI (LRFI; <-0.5 SD). Digestibility of DM was similar (~66%) among HRFI and LRFI for HS diets but greater for LRFI when fed LS diets (64 vs. 62%). For LS diets, digestibility of DM could account for up to 31% of the differences among HRFI and LRFI for apparent diet energy density, as determined from individual cow performance, indicating that digestibility explains some of the between-animal differences for the ability to convert gross energy into net energy. Some of the differences in digestibility between HRFI and LRFI were expected because cows with high RFI eat at a greater multiple of maintenance, and greater intake is associated with increased passage rate and digestibility depression. Based on these data, we conclude that a cow's digestive ability explains none of the variation in RFI for cows eating high starch diets but 9 to 31% of the variation in RFI when cows are fed low starch diets. Perhaps differences in other metabolic processes, such as tissue turnover, heat production, or others related to maintenance, can account for more variation in RFI than digestibility.

Apple Pollination: Demand Depends on Variety and Supply Depends on Pollinator Identity.

Insect pollination underpins apple production but the extent to which different pollinator guilds supply this service, particularly across different apple varieties, is unknown. Such information is essential if appropriate orchard management practices are to be targeted and proportional to the potential benefits pollinator species may provide. Here we use a novel combination of pollinator effectiveness assays (floral visit effectiveness), orchard field surveys (flower visitation rate) and pollinator dependence manipulations (pollinator exclusion experiments) to quantify the supply of pollination services provided by four different pollinator guilds to the production of four commercial varieties of apple. We show that not all pollinators are equally effective at pollinating apples, with hoverflies being less effective than solitary bees and bumblebees, and the relative abundance of different pollinator guilds visiting apple flowers of different varieties varies significantly. Based on this, the taxa specific economic benefits to UK apple production have been established. The contribution of insect pollinators to the economic output in all varieties was estimated to be £92.1M across the UK, with contributions varying widely across taxa: solitary bees (£51.4M), honeybees (£21.4M), bumblebees (£18.6M) and hoverflies (£0.7M). This research highlights the differences in the economic benefits of four insect pollinator guilds to four major apple varieties in the UK. This information is essential to underpin appropriate investment in pollination services management and provides a model that can be used in other entomolophilous crops to improve our understanding of crop pollination ecology.

Susceptibility of Faba Bean (Vicia faba L.) to Heat Stress During Floral Development and Anthesis.

Experiments were conducted over 2 years to quantify the response of faba bean (Vicia faba L.) to heat stress. Potted winter faba bean plants (cv. Wizard) were exposed to temperature treatments (18/10; 22/14; 26/18; 30/22; 34/26 °C day/night) for 5 days during floral development and anthesis. Developmental stages of all flowers were scored prior to stress, plants were grown in exclusion from insect pollinators to prevent pollen movement between flowers, and yield was harvested at an individual pod scale, enabling effects of heat stress to be investigated at a high resolution. Susceptibility to stress differed between floral stages; flowers were most affected during initial green-bud stages. Yield and pollen germination of flowers present before stress showed threshold relationships to stress, with lethal temperatures (t50) ˜28 °C and ~32 °C, while whole plant yield showed a linear negative relationship to stress with high plasticity in yield allocation, such that yield lost at lower nodes was partially compensated at higher nodal positions. Faba bean has many beneficial attributes for sustainable modern cropping systems but these results suggest that yield will be limited by projected climate change, necessitating the development of heat tolerant cultivars, or improved resilience by other mechanisms such as earlier flowering times.

Effects of partly replacing dietary starch with fiber and fat on milk production and energy partitioning.

The effects of partly replacing dietary starch with fiber and fat to provide a diet with similar net energy for lactation (NEL) density on yields of milk and milk components and on energy partitioning were evaluated in a crossover design experiment. Holstein cows (n = 32; 109 ± 22 d in milk, mean ± standard deviation) were randomly assigned to treatment sequence. Treatments were a high-starch diet containing 33% corn grain (mixture of dry ground and high-moisture corn; HS) or a high-fiber, high-fat diet containing 2.5% palmitic acid-enriched fatty acid (FA) supplement (HFF). Diets contained corn silage, alfalfa silage, and wheat straw as forage sources; HS contained 32% starch, 3.2% FA, and 25% neutral detergent fiber, whereas HFF contained 16% starch, 5.4% FA, and 33% neutral detergent fiber. Compared with HS, the HFF treatment reduced milk yield, milk protein concentration, and milk protein yield, but increased milk fat concentration, milk fat yield, milk energy output, and milk to feed ratio (energy-corrected milk/dry matter intake). The HFF treatment reduced the yield of de novo synthesized (< 16-carbon) milk FA and increased the yield of 16-carbon milk FA. Yield of preformed (> 16-carbon) milk FA was not different. The HFF treatment increased plasma concentrations of triglycerides and nonesterified fatty acids, but decreased plasma concentration of insulin. Compared with HS, the HFF treatment reduced body weight gain, change in body condition score, and fat thickness over the rump and rib. Calculated body energy gain, as a fraction of NEL use, was less for HFF than HS, whereas milk energy as a fraction of NEL use was increased for HFF. We concluded that the 2 treatments resulted in similar apparent NEL densities and intakes, but the HS treatment partitioned more energy toward body gain whereas the HFF treatment partitioned more energy toward milk. A high-fiber, high-fat diet might diminish the incidence of over conditioning in mid-lactation cows while maintaining high milk production.

Residual feed intake is repeatable for lactating Holstein dairy cows fed high and low starch diets.

Residual feed intake (RFI) is a tool to quantify feed efficiency in livestock and is commonly used to assess feed efficiency independent of production level, body weight (BW), or BW change. Lactating Holstein cows (n=109; 44 primiparous and 65 multiparous), averaging (mean ± standard deviation, SD) 665±77kg of BW, 42±9kg of milk/d, and 120±30 d postpartum, were fed diets of high (HI) or low (LO) starch content in 4 crossover experiments with two 28-d treatment periods. The LO diets were ~40% neutral detergent fiber (NDF) and ~14% starch and the HI diets were ~26% NDF and ~30% starch. Individual dry matter intake (DMI) of a cow was modeled as a function of milk energy output, metabolic BW, body energy change, and fixed effects of parity, experiment, cohort nested within experiment, and diet nested within cohort and experiment; RFI for each cow was the residual error term. Cows were classified as high (>0.5 SD of the mean), medium (±0.5 SD of the mean), or low (<-0.5 SD of the mean) RFI. On average, for the linear model used to determine RFI for individual cows, each unit increase in milk energy output, metabolic BW, or body energy gain was associated with 0.35, 0.09, or 0.05kg increase in DMI, respectively. When compared with LO diets, HI diets increased energy partitioning to body energy gain and tended to increase DMI. The correlation between RFI when cows were fed HI diets and RFI when cows were fed LO diets was 0.73 and was similar across each parity and experiment. Fifty-six percent of cows maintained the same RFI classification (high, medium, or low RFI) and only 4 of 109 cows changed from high RFI to low RFI or vice versa when diets were changed. Milk:feed, income over feed cost, and DMI were also highly repeatable (r=0.72, 0.84, and 0.92, respectively). We achieved significant changes in milk yield and component concentration as well as energy partitioning between HI and LO diets and still determined RFI to be repeatable across diets. We conclude that RFI is reasonably repeatable for a wide range of dietary starch levels fed to mid-lactation cows, so that cows that have low RFI when fed high corn diets will likely also have low RFI when fed diets high in nonforage fiber sources.

Milk production responses to a change in dietary starch concentration vary by production level in dairy cattle.

The effects of dietary starch concentration on yield of milk and milk components were evaluated in a crossover design experiment. Holstein cows (n=32; 115±22 d in milk) with a wide range in milk yield (28 to 62kg/d) were assigned randomly within level of milk yield to a treatment sequence. Treatments were diets containing 30% dry ground corn (CG) or 30% soyhulls (SH) on a DM basis. Diets containing corn silage and alfalfa silage were formulated to contain 16% crude protein, 24% forage neutral detergent fiber, and either 27 or 44% neutral detergent fiber and 30 or 12% starch for CG and SH, respectively. Cows were fed a diet intermediate to the treatments during a preliminary 14-d period. Treatment periods were 28 d with measurements taken throughout the period for energy calculations and the final 5 d used for data and sample collection for production variables. Compared with SH, CG increased dry matter intake, and yields of milk, milk protein, milk fat, and energy-corrected milk, as well as milk protein concentration. Treatment did not affect milk fat concentration. Yield of de novo synthesized and preformed milk fatty acids increased with CG. Treatment interacted with level of preliminary milk production for several response variables (yields of milk, milk protein, milk fat, energy-corrected milk, and 3.5% fat-corrected milk). Compared with SH, the CG treatment increased energy-corrected milk in higher-producing cows with a lesser response to CG as milk yield decreased. The CG treatment increased milk:feed compared with the SH treatment, but not body weight or body condition score. In conclusion, higher-producing cows benefited from the high-starch diet, and lower-producing cows were able to maintain production when most of the starch was replaced with nonforage fiber.

Avoiding a bad apple: Insect pollination enhances fruit quality and economic value.

Insect pollination is important for food production globally and apples are one of the major fruit crops which are reliant on this ecosystem service. It is fundamentally important that the full range of benefits of insect pollination to crop production are understood, if the costs of interventions aiming to enhance pollination are to be compared against the costs of the interventions themselves. Most previous studies have simply assessed the benefits of pollination to crop yield and ignored quality benefits and how these translate through to economic values. In the present study we examine the influence of insect pollination services on farmgate output of two important UK apple varieties; Gala and Cox. Using field experiments, we quantify the influence of insect pollination on yield and importantly quality and whether either may be limited by sub-optimal insect pollination. Using an expanded bioeconomic model we value insect pollination to UK apple production and establish the potential for improvement through pollination service management. We show that insects are essential in the production of both varieties of apple in the UK and contribute a total of £36.7 million per annum, over £6 million more than the value calculated using more conventional dependence ratio methods. Insect pollination not only affects the quantity of production but can also have marked impacts on the quality of apples, influencing size, shape and effecting their classification for market. These effects are variety specific however. Due to the influence of pollination on both yield and quality in Gala, there is potential for insect pollination services to improve UK output by up to £5.7 million per annum. Our research shows that continued pollinator decline could have serious financial implications for the apple industry but there is considerable scope through management of wild pollinators or using managed pollinator augmentation, to improve the quality of production. Furthermore, we show that it is critically important to consider all production parameters including quality, varietal differences and management costs when valuing the pollination service of any crop so investment in pollinator management can be proportional to its contribution.

The identity of crop pollinators helps target conservation for improved ecosystem services.

Insect pollinated mass flowering crops are becoming more widespread and there is a need to understand which insects are primarily responsible for the pollination of these crops so conservation measures can be appropriately targeted in the face of pollinator declines. This study used field surveys in conjunction with cage manipulations to identify the relative contributions of different pollinator taxa to the pollination of two widespread flowering crops, field beans and oilseed rape. Flower visiting pollinator communities observed in the field were distinct for each crop; while field beans were visited primarily by a few bumblebee species, multiple pollinator taxa visited oilseed, and the composition of this pollinator community was highly variable spatially and temporally. Neither pollinator community, however, appears to be meeting the demands of crops in our study regions. Cage manipulations showed that multiple taxa can effectively pollinate both oilseed and field beans, but bumblebees are particularly effective bean pollinators. Combining field observations and cage manipulations demonstrated that the pollination demands of these two mass flowering crops are highly contrasting, one would benefit from management to increase the abundance of some key taxa, whilst for the other, boosting overall pollinator abundance and diversity would be more appropriate. Our findings highlight the need for crop specific mitigation strategies that are targeted at conserving specific pollinator taxa (or group of taxa) that are both active and capable of crop pollination in order to reduce pollination deficits and meet the demands of future crop production.

Costing conservation: an expert appraisal of the pollinator habitat benefits of England's entry level stewardship.

Pollination services provided by insects play a key role in English crop production and wider ecology. Despite growing evidence of the negative effects of habitat loss on pollinator populations, limited policy support is available to reverse this pressure. One measure that may provide beneficial habitat to pollinators is England's entry level stewardship agri-environment scheme. This study uses a novel expert survey to develop weights for a range of models which adjust the balance of Entry Level Stewardship options within the current area of spending. The annual costs of establishing and maintaining these option compositions were estimated at £59.3-£12.4 M above current expenditure. Although this produced substantial reduction in private cost:benefit ratios, the benefits of the scheme to pollinator habitat rose by 7-140 %; significantly increasing the public cost:benefit ratio. This study demonstrates that the scheme has significant untapped potential to provide good quality habitat for pollinators across England, even within existing expenditure. The findings should open debate on the costs and benefits of specific entry level stewardship management options and how these can be enhanced to benefit both participants and biodiversity more equitably.

Establishment of a cross-European field site network in the ALARM project for assessing large-scale changes in biodiversity.

The field site network (FSN) plays a central role in conducting joint research within all Assessing Large-scale Risks for biodiversity with tested Methods (ALARM) modules and provides a mechanism for integrating research on different topics in ALARM on the same site for measuring multiple impacts on biodiversity. The network covers most European climates and biogeographic regions, from Mediterranean through central European and boreal to subarctic. The project links databases with the European-wide field site network FSN, including geographic information system (GIS)-based information to characterise the test location for ALARM researchers for joint on-site research. Maps are provided in a standardised way and merged with other site-specific information. The application of GIS for these field sites and the information management promotes the use of the FSN for research and to disseminate the results. We conclude that ALARM FSN sites together with other research sites in Europe jointly could be used as a future backbone for research proposals.

Transplant psychiatry.

Transplant units increasingly recognise a need for assistance from psychiatrists and psychologists in the assessment and management of potential transplant recipients and live donors. This arises from the various known associations between mental disorder and the need for transplantation; the intensifying requirement to select carefully among the potential recipients and donors of scarce human organs; and the drive to maximise transplant outcomes by optimising all aspects of treatment after surgery. There is good evidence that careful, protocol-guided selection among potential candidates for transplantation with alcoholic liver disease helps ensure outcomes at least as good as for other forms of liver disease. The evidence base in other areas is less robust, but the principles guiding the psychiatric assessment are broadly the same. There is an increasing need for psychiatric assessment of potential live organ donors, in order to minimise the risks they run, and in the case of altruistic donation this is now mandatory in UK law.

Knowledge about the Scottish Mental Health Act in a general hospital setting.

BACKGROUND: Clinical experience suggests that non-psychiatrists' knowledge of mental health legislation in relation to emergency detention is inadequate. However, most non-psychiatrists will use this legislation at some point in their career. METHODOLOGY: A questionnaire about emergency detention legislation was circulated to non-psychiatric medical staff to test their knowledge of the provisions relevant to the general hospital. RESULTS: Two hundred and seventy four medical staff replied (a response rate of 82%). Results showed that an understanding of detention procedures and applicability were markedly deficient, irrespective of grade, specialty or experience. CONCLUSION: The results indicate a need for increased education and awareness about emergency detention legislation especially in view of the implementation of the Mental Health (Scotland) Act (2003).

Molecular basis of antagonism between K70E and K65R tenofovir-associated mutations in HIV-1 reverse transcriptase.

The K70E mutation in HIV-1 reverse transcriptase was observed in 10% of virologic non-responders of the abacavir/lamivudine/tenofovir arm of ESS30009, alone, or in mixtures with K65R by population sequencing. Clonal analysis of six ESS30009 K70E isolates failed to identify double mutants carrying K65R+K70E. Site-directed K70E mutants had a replication capacity of 97+/-29%, but only 2.4+/-0.9% for K65R+K70E and 0.01% for K65R+K70E+M184V mutants. K65R+K70E phenotypic fold changes for abacavir, lamivudine and tenofovir were comparable to reported values for K65R alone. In molecular dynamic simulations, the epsilon-amino group of K65 was positioned 2.7+/-0.1A from the gamma-phosphate of the dTTP ligand and stabilized the triphosphate. In the R65 mutant, this distance increased to 4.2+/-0.4A and the interaction energy with the ligand was less favorable, but the K70 epsilon-amino group was repositioned closer to the gamma-phosphate and had a more favorable interaction energy. In the double mutant, E70 could not stabilize the gamma-phosphate, resulting in a more severe defect. The net effect of the atomic-level changes in the double mutant may be to destabilize the pyrophosphate leaving group of the ligand, more severely affecting the catalytic rate of the polymerization reaction than the R65 single mutation.

Analgesic and anti-inflammatory effectiveness of nepafenac 0.1% for cataract surgery.

BACKGROUND: To compare nepafenac 0.1% with placebo and ketorolac 0.5% for prevention and treatment of ocular pain and inflammation after cataract surgery. METHODS: In a multi-center, randomized, placebo- and active-controlled, double-masked clinical trial, 227 patients with cataract were randomized to receive nepafenac 0.1%, ketorolac 0.5%, or placebo TID beginning 1 day pre-operatively and continuing for 21 days postoperatively. At each postoperative visit, cure rates and clinical success rates (