Mouse embryo culture induces changes in postnatal phenotype including raised systolic blood pressure

A key factor in the use of assisted reproductive technologies (ART) for diverse species is the safety of procedures for long-term health. By using a mouse model, we have investigated the effect of in vitro culture and embryo transfer (ET) of superovulated embryos on postnatal growth and physiological activity compared with that of embryos developing in vivo. Embryo culture from two-cell to blastocyst stages in T6 medium either with or without a protein source reduced blastocyst trophectoderm and inner cell mass cell number compared with that of embryos developing in vivo. Embryo culture and ET had minimal effects on postnatal growth when compared with in vivo development with an equivalent litter size. However, embryo culture, and to a lesser extent ET, led to an enhanced systolic blood pressure at 21 weeks compared with in vivo development independent of litter size, maternal origin, or body weight. Moreover, activity of enzymatic regulators of cardiovascular and metabolic physiology, namely, serum angiotensin-converting enzyme and the gluconeogenesis controller, hepatic phosphoeno/pyruvate carboxykinase, were significantly elevated in response to embryo culture and/or ET in female offspring at 27 weeks, independent of maternal factors and postnatal growth. These animal data indicate that postnatal physiological criteria important in cardiovascular and metabolic health may be more sensitive to routine ART procedures than growth. © 2007 by The National Academy of Sciences of the USA.

Communication between the nucleotide binding domains of P-glycoprotein occurs via conformational changes that involve residue 508

Our aim is to provide molecular understanding of the mechanisms underlying the (i) interaction between the two nucleotide binding domains (NBDs) and (ii) coupling between NBDs and transmembrane domains within P-glycoprotein (Pgp) during a transport cycle. To facilitate this, we have introduced a number of unique cysteine residues at surface exposed positions (E393C, S452C, I500C, N508C, and K578C) in the N-terminal NBD of Pgp, which had previously been engineered to remove endogenous cysteines. Positions of the mutations were designed using a model based on crystallographic features of prokaryotic NBDs. The single cysteine mutants were expressed in insect cells using recombinant baculovirus and the proteins purified by metal affinity chromatography by virtue of a polyhistidine tag. None of the introduced cysteine residues perturbed the function of Pgp as judged by the characteristics of drug stimulated ATP hydrolysis. The role of residues at each of the introduced sites in the catalytic cycle of Pgp was investigated by the effect of covalent conjugation with N-ethyl-maleimide (NEM). All but one mutation (K578C) was accessible to labeling with [3H]-NEM. However, perturbation of ATPase activity was only observed for the derivitized N508C isoform. The principle functional manifestation was a marked inhibition of the "basal" rate of ATP hydrolysis. Neither the extent nor potency to which a range of drugs could affect the ATPase activity were altered in the NEM conjugated N508C isoform. The results imply that the accessibility of residue 508, located in the alpha-helical subdomain of NBD1 in Pgp, is altered by the conformational changes that occur during ATP hydrolysis.

Postgraduate training offered to primary care pharmacists by schools of pharmacy - changes over the last five years

Poster session - A review of the postgraduate training courses offered by the 15 schools of pharmacy within Britain was undertaken - The training currently on offer was compared with that offered by the same schools of pharmacy five years ago - It was found that although the numbers of training courses offered by the 15 schools had significantly increased, the orientation of the courses remained more or less as it was five years ago - The increases in the number of courses had not reflected the increased roles that pharmacists currently have and are hoping to undertake in the future - Any new training offered will need to reflect a wider “modernising and managing NHS organisations” agenda

Can the Q Link Ally,® a form of sympathetic resonance technology (SRT™), sttenuate scute mobile phone-related changes to neural function?

OBJECTIVES: Exposure to active mobile phones (MP) has been shown to affect human neural function as shown by the electroencephalogram (EEG). Although it has not been determined whether such effects are harmful, a number of devices have been developed that attempt to minimize these MP-related effects. One such device, the Q Link Ally® (QL; Clarus Products, International, L.L.C., San Rafael, CA), is argued to affect the human organism in such a way as to attenuate the effect of MPs. The present pilot study was designed to determine whether there is any indication that QL does alter MP-related effects on the human EEG. DESIGN: Twenty-four (24) subjects participated in a single-blind, fully counterbalanced crossover design in which subjects' resting EEG and phase-locked neural responses to auditory stimuli were assessed under conditions of either active MP or active MP plus QL. RESULTS: The addition of QL to the MP condition increased resting EEG in the gamma range and did so as a function of exposure duration, and it attenuated MP-related effects in the delta and alpha range (at trend-level). The addition of the QL also affected phase-locked neural responses, with a laterality reversal in the alpha range and an alteration to changes over time in the delta range, a reduction of the MP-related beta decrease over time at fronto-posterior sites, and a global reduction in the gamma range that increased as a function of exposure duration. No unambiguous relations were found between these changes and either performance or psychologic state. CONCLUSIONS: This pilot study suggests that the addition of the QL to active MP-exposure does affect neural function in humans, altering both resting EEG patterns and the evoked neural response to auditory stimuli, and that there is a tendency for some MP-related changes to the EEG to be attenuated by the QL.

Spectrum of morphological and visual changes due to vitreomacular interface disorders encountered in a large consecutive cohort of patients

Aim: Identify the incidence of vitreomacular traction (VMT) and frequency of reduced vision in the absence of other coexisting macular pathology using a pragmatic classification system for VMT in a population of patients referred to the hospital eye service. Methods: A detailed survey of consecutive optical coherence tomography (OCT) scans was done in a high-throughput ocular imaging service to ascertain cases of vitreomacular adhesion (VMA) and VMT using a departmental classification system. Analysis was done on the stages of traction, visual acuity, and association with other macular conditions. Results: In total, 4384 OCT scan episodes of 2223 patients were performed. Two hundred and fourteen eyes had VMA/VMT, with 112 eyes having coexisting macular pathology. Of 102 patients without coexisting pathology, 57 patients had VMT grade between 2 and 8, with a negative correlation between VMT grade and number of Snellen lines (r= -0.61717). There was a distinct cutoff in visual function when VMT grade was higher than 4 with the presence of cysts and sub retinal separation and breaks in the retinal layers. Conclusions: VMT is a common encounter often associated with other coexisting macular pathology. We estimated an incidence rate of 0.01% of VMT cases with reduced vision and without coexisting macular pathology that may potentially benefit from intervention. Grading of VMT to select eyes with cyst formation as well as hole formation may be useful for targeting patients who are at higher risk of visual loss from VMT.

Profit, productivity and price performance changes in the water and sewerage industry:an empirical application for England and Wales

This paper aims to analyse the impact of regulation in the financial performance of the Water and Sewerage companies (WaSCs) in England and Wales over the period 1991–2008. In doing so, a panel index approach is applied across WaSCs over time to decompose unit-specific index number-based profitability growth as a function of the profitability, productivity and price performance growth achieved by benchmark firms, and the catch up to the benchmark firm achieved by less productive firms. The results indicated that after 2000 there is a steady decline in average price performance, while productivity improves resulting in a relatively stable economic profitability. It is suggested that the English and Welsh water regulator is now more focused on passing productivity benefits to consumers, and maintaining stable profitability than it was in earlier regulatory periods. This technique is of great interest for regulators to evaluate the effectiveness of regulation and companies to identify the determinants of profit change and improve future performance, even if sample sizes are limited.

CLAE to move to online format

Editorial: The 2015 BCLA annual conference was another fantastic affair. It was the first time the conference was held in the beautiful city of Liverpool. The venue was great and the programme was excellent. The venue overlooked the River Mersey and many of the hotels were local boutique hotels. I stayed in one which was formerly the offices of White Star Liners—where the RMS Titanic was originally registered. The hotel decor was consistent with its historic significance. The BCLA gala dinner was held in the hugely impressive Anglican Cathedral with entertainment from a Beatles tribute band. That will certainly be a hard act to follow at the next conference in 2017. Brian Tompkins took the reigns as the new BCLA president. Professor Fiona Stapleton was the recipient of the BCLA Gold Medal Award. The winner of the poster competition was Dorota Szczesna-Iskander with a poster entitled ‘Dry Contact lens poor wettability and visual performance’. Second place was Renee Reeder with her poster entitled ‘Abnormal Rosacea as a differential diagnosis in corneal scarring’. And third place was Maria Jesus Gonzalez-Garcia with her poster entitled ‘Dry Effect of the Environmental Conditions on Tear Inflammatory Mediators Concentration in Contact Lens Wearers’. The photographic competition winner was Professor Wolfgang Sickenberger from Jena in Germany. The Editorial Panel of CLAE met at the BCLA conference for their first biannual meeting. The journal metrics were discussed. In terms of number of submissions of new papers CLAE seems to have plateaued after seeing a rapid growth in the number of submissions over the last few years. The increase over the last few years could be attributed to the fact that CLAE was awarded an impact factor for the first time in 2012. This year it seems that impact factors across nearly all ophthalmic related journals has dropped. This could in part be due to the fact that last year was a ‘Research Exercise Framework (REF) year for UK universities, where they are judged on quality of their research output. The next REF is in 2020 so we may see changes nearing that time. Looking at article downloads, there seems to be a continued rise in figures. Currently CLAE attracts around 85,000 downloads per year (this is an increase of around 10,000 per year for the last few years) and the 2015 prediction is 120,000! With this in mind and with other contributing factors too, the BCLA has decided to move to online delivery of CLAE to its members starting from issue 5 of 2015. Some members do like to flick through the pages of a hard copy of the journal so members will still have the option of receiving a hard copy through the post but the default journal delivery method will now be online. The BCLA office will send various alerts and content details to members email addresses. To access CLAE online you will need to log in via the BCLA web page, currently you then click on ‘Resources’ and then under ‘Free and Discounted Publications’ you will see CLAE. This actually takes you to CLAE’s own webpage (www.contactlensjournal.com) but you need to log in via the BCLA web page. The BCLA plans to change these weblinks so that from the BCLA web page you can link to the journal website much more easily and you have the choice of going directly into the general website for CLAE or straight to the current issue. In 2016 you will see an even easier way of accessing CLAE online as the BCLA will launch a CLAE application for mobile devices where the journal can be downloaded as a ‘flick-book’. This is a great way of bringing CLAE into the modern era where people access their information in newer ways. For many the BCLA conference was part of a very busy conference week as it was preceded by the International Association of Contact Lens Educators’ (IACLE) Third World Congress, held in Manchester on the 4 days before the BCLA conference. The first and second IACE World Congresses were held in Waterloo, Canada in 1994 and 2000 respectively and hosted by Professor Des Fonn. Professor Fonn was the recipient of the first ever IACLE lifetime achievement award. The Third IACLE World Congress saw more than 100 contact lens educators and industry representatives from around 30 countries gather in the UK for the four-day event, hosted by The University of Manchester. Delegates gained hands-on experience of innovations in teaching, such as learning delivery systems, the use of iPads in the classroom and for creating ePub content, and augmented and virtual reality technologies. IACLE members around the world also took part via a live online broadcast. The Third IACLE World Congress was made possible by the generous support of Sponsors Alcon, CooperVision and Johnson & Johnson Vision Care., for more information look at the IACLE web page (www.iacle.org).

Relationship between changes in postprandial glucagon, patient characteristics, and response to lixisenatide as add-on to oral antidiabetics

Background and aims: Lixisenatide, a once-daily prandial glucagon-like peptide-1 receptor agonist, reduces postprandial (PP) glycaemic excursions and HbA 1c . We report an exploratory analysis of the GetGoal-M and S trials in patients with type 2 diabetes mellitus (T2DM) with different changes in PP glucagon levels in response to lixisenatide treatment. Materials and methods: Patients (n=423) were stratified by their change in 2 hour PP glucagon level between baseline evaluation and Week 24 of treat - ment with lixisenatide as add-on to oral antidiabetics (OADs) into groups of Greater Change (GC; n=213) or Smaller Change (SC; n=210) in plasma glucagon levels (median change -23.57 ng/L). ANOVA and Chi-squared tests were used for the comparison of continuous and categorical variables, respec - tively. Baseline and endpoint continuous measurements in each group were compared using paired t -tests. Results: Mean change from baseline in 2 hour PP glucagon levels for the GC vs SC groups was -47.19 vs -0.59 ng/L (p<0.0001), respectively. Patients in the GC group had a shorter mean duration of diabetes (7.3 vs 9.0 years; p=0.0036) and lesser OAD use (4.5 vs 5.7 years; p=0.0092) than those in the SC group. Patients in the GC group had a greater mean reduction in HbA 1c (-1.10 vs -0.67%; p<0.0001), fasting plasma glucose (FPG; -25.20 vs -9.30 mg/dL [p<0.0001]), PP plasma glucose (PPG; -129.40 vs -78.22 mg/dL [p<0.0001]), and a greater drop in weight (-2.27 vs -1.17 kg; p=0.0002) and body mass index (-0.84 vs -0.44 kg/m 2 ; p=0.0002) than those in the SC group. More patients in the GC group also achieved composite endpoints, including HbA 1c <7% with no symptomatic hypoglycaemia and no weight gain (40.38 vs 19.52%; p<0.0001), than in the SC group. Conclusion: Greater reductions in PP glucagon associated with lixisenatide as add-on to OADs in patients with T2DM are also associated with greater reductions in HbA1c, FPG, PPG, and greater weight loss, highlighting the importance of glucagon suppression on therapeutic response. Clinical Trial Registration Number: NCT00712673; NCT00713830 Supported by: Sanof

Mobility changes in older age: neuropsychological, neurophysiological and cognitive predictors of successful adaptation in a real world scenario

The aims of this thesis were to investigate the neuropsychological, neurophysiological, and cognitive contributors to mobility changes with increasing age. In a series of studies with adults aged 45-88 years, unsafe pedestrian behaviour and falls were investigated in relation to i) cognitive functions (including response time variability, executive function, and visual attention tests), ii) mobility assessments (including gait and balance and using motion capture cameras), iii) motor initiation and pedestrian road crossing behavior (using a simulated pedestrian road scene), iv) neuronal and functional brain changes (using a computer based crossing task with magnetoencephalography), and v) quality of life questionnaires (including fear of falling and restricted range of travel). Older adults are more likely to be fatally injured at the far-side of the road compared to the near-side of the road, however, the underlying mobility and cognitive processes related to lane-specific (i.e. near-side or far-side) pedestrian crossing errors in older adults is currently unknown. The first study explored cognitive, motor initiation, and mobility predictors of unsafe pedestrian crossing behaviours. The purpose of the first study (Chapter 2) was to determine whether collisions at the near-side and far-side would be differentially predicted by mobility indices (such as walking speed and postural sway), motor initiation, and cognitive function (including spatial planning, visual attention, and within participant variability) with increasing age. The results suggest that near-side unsafe pedestrian crossing errors are related to processing speed, whereas far-side errors are related to spatial planning difficulties. Both near-side and far-side crossing errors were related to walking speed and motor initiation measures (specifically motor initiation variability). The salient mobility predictors of unsafe pedestrian crossings determined in the above study were examined in Chapter 3 in conjunction with the presence of a history of falls. The purpose of this study was to determine the extent to which walking speed (indicated as a salient predictor of unsafe crossings and start-up delay in Chapter 2), and previous falls can be predicted and explained by age-related changes in mobility and cognitive function changes (specifically within participant variability and spatial ability). 53.2% of walking speed variance was found to be predicted by self-rated mobility score, sit-to-stand time, motor initiation, and within participant variability. Although a significant model was not found to predict fall history variance, postural sway and attentional set shifting ability was found to be strongly related to the occurrence of falls within the last year. Next in Chapter 4, unsafe pedestrian crossing behaviour and pedestrian predictors (both mobility and cognitive measures) from Chapter 2 were explored in terms of increasing hemispheric laterality of attentional functions and inter-hemispheric oscillatory beta power changes associated with increasing age. Elevated beta (15-35 Hz) power in the motor cortex prior to movement, and reduced beta power post-movement has been linked to age-related changes in mobility. In addition, increasing recruitment of both hemispheres has been shown to occur and be beneficial to perform similarly to younger adults in cognitive tasks (Cabeza, Anderson, Locantore, & McIntosh, 2002). It has been hypothesised that changes in hemispheric neural beta power may explain the presence of more pedestrian errors at the farside of the road in older adults. The purpose of the study was to determine whether changes in age-related cortical oscillatory beta power and hemispheric laterality are linked to unsafe pedestrian behaviour in older adults. Results indicated that pedestrian errors at the near-side are linked to hemispheric bilateralisation, and neural overcompensation post-movement, 4 whereas far-side unsafe errors are linked to not employing neural compensation methods (hemispheric bilateralisation). Finally, in Chapter 5, fear of falling, life space mobility, and quality of life in old age were examined to determine their relationships with cognition, mobility (including fall history and pedestrian behaviour), and motor initiation. In addition to death and injury, mobility decline (such as pedestrian errors in Chapter 2, and falls in Chapter 3) and cognition can negatively affect quality of life and result in activity avoidance. Further, number of falls in Chapter 3 was not significantly linked to mobility and cognition alone, and may be further explained by a fear of falling. The objective of the above study (Study 2, Chapter 3) was to determine the role of mobility and cognition on fear of falling and life space mobility, and the impact on quality of life measures. Results indicated that missing safe pedestrian crossing gaps (potentially indicating crossing anxiety) and mobility decline were consistent predictors of fear of falling, reduced life space mobility, and quality of life variance. Social community (total number of close family and friends) was also linked to life space mobility and quality of life. Lower cognitive functions (particularly processing speed and reaction time) were found to predict variance in fear of falling and quality of life in old age. Overall, the findings indicated that mobility decline (particularly walking speed or walking difficulty), processing speed, and intra-individual variability in attention (including motor initiation variability) are salient predictors of participant safety (mainly pedestrian crossing errors) and wellbeing with increasing age. More research is required to produce a significant model to explain the number of falls.

Observing population changes of thrips (Thysanoptera) species damaging forced pepper and their natural enemies

By the strengthening of environmental protection and food safety efforts in Hungary, integrated and especially biological pest control methods should increasingly put forward, for which a solid knowledge on the life course and efficiency of natural enemies applied against certain pests is necessary. Pepper has distinguished significance in domestic vegetable forcing, and the profitability of production is determined primarily by the efficiency of the control of thrips pests. This is why we attached great importance to study what results may be expected by introducing arthropod predators (Amblyseius cucumeris, Orius laevigatus) to control thrips species under domestic conditions on rock wool in a long vegetation period pepper culture. We also liked to find out what kind of role the cultivars play in the change of phytophagous and zoophagous populations. The A. cucumeris predatory mite introduced in late January proved to be effective in controlling thrips pests until mid-April. Despite repeated introductions, the predatory bug O. laevigatus (Heteroptera: Anthocoridae) did not proliferate. Among the three pepper cultivars (Hó, Keceli, Titán) grown at Ráckeve, thrips species proliferated in the highest number on cultivar ‘Hó’, while the population of predatory mites was lowest on the cultivar ‘Titán’, compared to the other two cultivars.

Tree Islands in Everglades Landscapes: Current Status, Historical Changes, and Hydrologic Impacts on Population Dynamics and Moisture Relations, First Annual Report

In 2005 we initiated a project designed to better understand tree island structure and function in the Everglades and the wetlands bordering it. Focus was on the raised portions at the upstream end of the islands, where tropical hardwood species adapted to well-drained conditions usually are the most prominent component of the vegetation. The study design is hierarchical, with four levels; in general, a large number of sites is to be surveyed once for a limited set of parameters, and increasingly small sets of islands are to be sampled more intensively, more frequently, and for more aspects of ecosystem function. During the first year of the 3-year study, we completed surveys of 41 Level 1 (i.e., the least intensive level) islands, and established permanent plots in two and three islands of Levels 2 and 4 intensity, respectively. Tree species richness and structural complexity was highest in Shark Slough “hammocks”, while islands in Northeast Shark Slough and Water Conservation Area 3B, which receive heavy human use, were simpler, more park-like communities. Initial monitoring of soil moisture in Level 4 hammocks indicated considerable local variation, presumably associated with antecedent rainfall and current water levels in the adjacent marsh. Tree islands throughout the study area were impacted significantly by Hurricanes Katrina and Wilma in 2005, but appear to be recovering rapidly. As the project continues to include more islands and repeated measurements, we expect to develop a better grasp of tree island dynamics across the Everglades ecosystem, especially with respect to moisture relations and water levels in the adjacent marsh. The detailed progress report which follows is also available online at http://www.fiu.edu/~serp1/projects/treeislands/tree_islands_2005_annual_report.pd

An empirical analysis of the global audit market: International Financial Reporting Standards-related changes and differences within the Big 4 global networks

Ongoing debates within the professional and academic communities have raised a number of questions specific to the international audit market. This dissertation consists of three related essays that address such issues. First, I examine whether the propensity to switch between auditors of different sizes (i.e., Big 4 versus non-Big 4) changes as adoption of International Financial Reporting Standards (IFRS) becomes a more common phenomenon, arguing that smaller auditors have an opportunity to invest in necessary skills and training needed to enter this market. Findings suggest that clients are relatively less (more) likely to switch to (away from) a Big 4 auditor if the client's adoption of IFRS occurs in more recent years. ^ In the second essay, I draw on these inferences and test whether the change in audit fees in the year of IFRS adoption changes over time. As the market becomes less concentrated, larger auditors becomes less able to demand a premium for their services. Consistent with my arguments, results suggest that the change in audit service fees declines over time, although this effect seems concentrated among the Big 4. I also find that this effect is partially attributable to a differential effect of the auditors' experience in pricing audit services related to IFRS based on the period in which adoption occurs. The results of these two essays offer important implications to policy debates on the costs and benefits of IFRS adoption. ^ In the third essay, I differentiate Big 4 auditors into three classifications—Parent firms, Brand Name affiliates, and Local affiliates—and test for differences in audit fee premiums (relative to non-Big 4 auditors) and audit quality. Results suggest that there is significant heterogeneity between the three classifications based on both of these characteristics, which is an important consideration for future research. Overall, this dissertation provides additional insights into a variety of aspects of the global audit market.^

A primary care web-based intervention modelling experiment replicated behaviour changes seen in earlier paper-based experiment

Acknowledgements and funding We would like to thank the GPs who took part in this study. We would also like to thank Marie Pitkethly and Gail Morrison for their help and support in recruiting GPs to the study. WIME was funded by the Chief Scientist Office, grant number CZH/4/610. The Health Services Research Unit, University of Aberdeen, is core funded by the Chief Scientist Office of the Scottish Government Health Directorates.

Education and Self-Cultivation: Foundational Changes for Existential Flourishing

The strained relationship between pedagogy and self-cultivation is often overlooked in favour of more pressing and profitable concerns within educational institutions. However, the end of education is not a well-paying job. It is often thought that education will produce a certain type of learned individual. Students are entered into educational institutions from a very young age and spend most of their youth within them, subsequently forming a part of themselves, their self-identify and agency, through these institutions. A significant amount of trust is placed in the hands of educators not only to impart information about various subject matters but to teach students how to think. This, however, is a difficult task which cannot be completely accomplished; thinking is a skill which an educator can promote but only the individual can cultivate. If self-cultivation is not the end of pedagogical practice and education, there is something deeply contradictory between the theoretical and practical values and aims of educational institutions.This thesis will address the problems caused by the neglect of self-cultivation within the pedagogical practices of contemporary educational institutions. I argue that self-cultivation, existential learning and flourishing should be the focus of these institutions. Educational institutions can make alternative efforts not only to improve the learning environment for these students but to prepare them to cope with existential questions. By acknowledging and focusing on the significance of self-cultivation, educational institutions can and should make efforts not only to teach useful, marketable skills and information but to also nurture the agency and mental well-being of the student him- or herself. My hope is that this thesis will be the first step towards answering a larger concern: How can educational institutions alleviate the struggles of students, particularly the seemingly growing number who are suffering from depression, by appealing to notions of self-cultivation?

The hypoxia that developed in a microtidal estuary following an extreme storm produced dramatic changes in the benthos

Runoff from an extreme storm on 22 March 2010 led, during the next 3 months, to the formation of a pronounced halocline and underlying hypoxia in the upper reaches of the microtidal Swan–Canning Estuary. Benthic macroinvertebrates were sampled between January 2010 and October 2011 at five sites along 10 km of this region. By mid-April, the number of species, total density, Simpson’s evenness index and taxonomic distinctness had declined markedly, crustaceans had disappeared and the densities of annelids and molluscs had declined slightly. These faunal attributes (except Simpson’s index) and species composition did not recover until after the end of the hypoxia. The survival of annelids and loss of crustaceans in this period reflects different sensitivities of these taxa to severe environmental stress. The results emphasise that microtidal estuaries with long residence times are highly vulnerable to the effects of environmental perturbations, particularly during warmer periods of the year.