Accommodative intraocular lens versus standard monofocal intraocular lens implantation in cataract surgery.

BACKGROUND: Following cataract surgery and intraocular lens (IOL) implantation, loss of accommodation or postoperative presbyopia occurs and remains a challenge. Standard monofocal IOLs correct only distance vision; patients require spectacles for near vision. Accommodative IOLs have been designed to overcome loss of accommodation after cataract surgery. OBJECTIVES: To define (a) the extent to which accommodative IOLs improve unaided near visual function, in comparison with monofocal IOLs; (b) the extent of compromise to unaided distance visual acuity; c) whether a higher rate of additional complications is associated the use of accommodative IOLs. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 9), Ovid MEDLINE, Ovid MEDLINE in-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily Update, Ovid OLDMEDLINE (January 1946 to October 2013), EMBASE (January 1980 to October 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrial.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 10 October 2013. SELECTION CRITERIA: We include randomised controlled trials (RCTs) which compared implantation of accommodative IOLs to implantation of monofocal IOLs in cataract surgery. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results, assessed risk of bias and extracted data. All included trials used the 1CU accommodative IOL (HumanOptics, Erlangen, Germany) for their intervention group. One trial had an additional arm with the AT-45 Crystalens accommodative IOL (Eyeonics Vision). We performed a separate analysis comparing 1CU and AT-45 IOL. MAIN RESULTS: We included four RCTs, including 229 participants (256 eyes), conducted in Germany, Italy and the UK. The age range of participants was 21 to 87 years. All studies included people who had bilateral cataracts with no pre-existing ocular pathologies. We judged all studies to be at high risk of performance bias. We graded two studies with high risk of detection bias and one study with high risk of selection bias.Participants who received the accommodative IOLs achieved better distance-corrected near visual acuity (DCNVA) at six months (mean difference (MD) -3.10 Jaeger units; 95% confidence intervals (CI) -3.36 to -2.83, 2 studies, 106 people, 136 eyes, moderate quality evidence). Better DCNVA was seen in the accommodative lens group at 12 to 18 months in the three trials that reported this time point but considerable heterogeneity of effect was seen, ranging from 1.3 (95% CI 0.98 to 1.68; 20 people, 40 eyes) to 6 (95% CI 4.15 to 7.85; 51 people, 51 eyes) Jaeger units and 0.12 (95% CI 0.05 to 0.19; 40 people, binocular) logMAR improvement (low quality evidence). The relative effect of the lenses on corrected distant visual acuity (CDVA) was less certain. At six months there was a standardised mean difference of -0.04 standard deviations (95% CI -0.37 to 0.30, 2 studies, 106 people, 136 eyes, low quality evidence). At long-term follow-up there was heterogeneity of effect with 18-month data in two studies showing that CDVA was better in the monofocal group (MD 0.12 logMAR; 95% CI 0.07 to 0.16, 2 studies, 70 people,100 eyes) and one study which reported data at 12 months finding similar CDVA in the two groups (-0.02 logMAR units, 95% CI -0.06 to 0.02, 51 people) (low quality evidence).The relative effect of the lenses on reading speed and spectacle independence was uncertain, The average reading speed was 11.6 words per minute more in the accommodative lens group but the 95% confidence intervals ranged from 12.2 words less to 35.4 words more (1 study, 40 people, low quality evidence). People with accommodative lenses were more likely to be spectacle-independent but the estimate was very uncertain (risk ratio (RR) 8.18; 95% CI 0.47 to 142.62, 1 study, 40 people, very low quality evidence).More cases of posterior capsule opacification (PCO) were seen in accommodative lenses but the effect of the lenses on PCO was uncertain (Peto odds ratio (OR) 2.12; 95% CI 0.45 to 10.02, 91 people, 2 studies, low quality evidence). People in the accommodative lens group were more likely to require laser capsulotomy (Peto OR 7.96; 95% CI 2.49 to 25.45, 2 studies, 60 people, 80 eyes, low quality evidence). Glare was reported less frequently with accommodative lenses but the relative effect of the lenses on glare was uncertain (RR any glare 0.78; 95% CI 0.32 to 1.90, 1 study, 40 people, and RR moderate/severe glare 0.45; 95% CI 0.04 to 4.60, low quality evidence). AUTHORS' CONCLUSIONS: There is moderate-quality evidence that study participants who received accommodative IOLs had a small gain in near visual acuity after six months. There is some evidence that distance visual acuity with accommodative lenses may be worse after 12 months but due to low quality of evidence and heterogeneity of effect, the evidence for this is not clear-cut. People receiving accommodative lenses had more PCO which may be associated with poorer distance vision. However, the effect of the lenses on PCO was uncertain.Further research is required to improve the understanding of how accommodative IOLs may affect near visual function, and whether they provide any durable gains. Additional trials, with longer follow-up, comparing different accommodative IOLs, multifocal IOLs and monofocal IOLs, would help map out their relative efficacy, and associated late complications. Research is needed on control over capsular fibrosis postimplantation.Risks of bias, heterogeneity of outcome measures and study designs used, and the dominance of one design of accommodative lens in existing trials (the HumanOptics 1CU) mean that these results should be interpreted with caution. They may not be applicable to other accommodative IOL designs

Human COQ9 Rescues a coq9 Yeast Mutant by Enhancing Coenzyme Q Biosynthesis from 4-Hydroxybenzoic Acid and Stabilizing the CoQ-Synthome

Coq9 is required for the stability of a mitochondrial multi-subunit complex, termed the CoQ-synthome, and the deamination step of Q intermediates that derive from para-aminobenzoic acid (pABA) in yeast. In human, mutations in the COQ9 gene cause neonatal-onset primary Q10 deficiency. In this study, we determined whether expression of human COQ9 could complement yeast coq9 point or null mutants. We found that expression of human COQ9 rescues the growth of the temperature-sensitive yeast mutant, coq9-ts19, on a non-fermentable carbon source and increases the content of Q6, by enhancing Q biosynthesis from 4-hydroxybenzoic acid (4HB). To study the mechanism for the rescue by human COQ9, we determined the steady-state levels of yeast Coq polypeptides in the mitochondria of the temperature-sensitive yeast coq9 mutant expressing human COQ9. We show that the expression of human COQ9 significantly increased steady-state levels of yeast Coq4, Coq6, Coq7, and Coq9 at permissive temperature. Human COQ9 polypeptide levels persisted at non-permissive temperature. A small amount of the human COQ9 co-purified with tagged Coq6, Coq6-CNAP, indicating that human COQ9 interacts with the yeast Q-biosynthetic complex. These findings suggest that human COQ9 rescues the yeast coq9 temperature-sensitive mutant by stabilizing the CoQ-synthome and increasing Q biosynthesis from 4HB. This finding provides a powerful approach to studying the function of human COQ9 using yeast as a model

To respond or not to respond - a personal perspective of intestinal tolerance

For many years, the intestine was one of the poor relations of the immunology world, being a realm inhabited mostly by specialists and those interested in unusual phenomena. However, this has changed dramatically in recent years with the realization of how important the microbiota is in shaping immune function throughout the body, and almost every major immunology institution now includes the intestine as an area of interest. One of the most important aspects of the intestinal immune system is how it discriminates carefully between harmless and harmful antigens, in particular, its ability to generate active tolerance to materials such as commensal bacteria and food proteins. This phenomenon has been recognized for more than 100 years, and it is essential for preventing inflammatory disease in the intestine, but its basis remains enigmatic. Here, I discuss the progress that has been made in understanding oral tolerance during my 40 years in the field and highlight the topics that will be the focus of future research

Bird pollination of Canary Island endemic plants

The Canary Islands are home to a guild of endemic, threatened bird pollinated plants. Previous work has suggested that these plants evolved floral traits as adaptations to pollination by flower specialist sunbirds, but subsequently they appear to be have co-opted passerine birds as sub-optimal pollinators. To test this idea we carried out a quantitative study of the pollination biology of three of the bird pollinated plants, Canarina canariensis (Campanulaceae), Isoplexis canariensis (Veronicaceae) and Lotus berthelotii (Fabaceae), on the island of Tenerife. Using colour vision models, we predicted the detectability of flowers to bird and bee pollinators. We measured pollinator visitation rates, nectar standing crops, as well as seed set and pollen removal and deposition. These data showed that the plants are effectively pollinated by non-flower specialist passerine birds that only occasionally visit flowers. The large nectar standing crops and extended flower longevities (>10days) of Canarina and Isoplexis suggests that they have evolved bird pollination system that effectively exploits these low frequency non-specialist pollen vectors and is in no way suboptimal. Seed set in two of the three species was high, and was significantly reduced or zero in flowers where pollinator access was restricted. In L. berthelotii, however, no fruit set was observed, probably because the plants were self incompatible horticultural clones of a single genet. We also show that, while all three species are easily detectable for birds, the orange Canarina and the red Lotus (but less so the yellow-orange Isoplexis) should be difficult to detect for insect pollinators without specialised red receptors, such as bumblebees. Contrary to expectations if we accept that the flowers are primarily adapted to sunbird pollination, the chiffchaff (Phylloscopus canariensis) was an effective pollinator of these species

Internationally recruited nurses from India and the Philippines in the United Kingdom: the decision to emigrate

Background: The United Kingdom has recruited nurses from countries with a reported surplus in their nursing workforce, such as India and the Philippines. However, little is known about the decision to emigrate made by nurses from these countries. One theory suggests that individuals weigh the benefits and costs of migration: the push and pull factors. This paper challenges the restricted economic focus of this predominant theory and compares the diverse motivations of nurses from different countries as well as those of nurses with previous migratory experience and first-time migrants. Methods: This research was undertaken in a National Health Service acute trust in London by means of a qualitative interpretative approach. Data were collected through face-to-face longitudinal and cross-sectional interviews with internationally recruited nurses from India (n = 6) and the Philippines (n = 15); and analysis of their narratives was used to generate data about their expectations and experiences. Data were analysed by means of a framework approach that allowed for intra-case and cross-case analysis. Results: From an individual perspective, nurses in this study reported economic reasons as the main trigger for migration in the first instance. Yet this doesn't entirely explain the decision to move from previous migratory destinations ( e. g. Saudi Arabia) where economic needs are already fulfilled. In these cases migration is influenced by professional and social aspirations that highlight the influence of the cultural environment - specifically some religious and gender-related issues. Family support and support from migratory networks in the country of origin and destination were also important elements conducive to and supportive of migration. Nurses from India report coming to the United Kingdom to stay, while Filipina nurses come as temporary migrants sending remittances to support their families in the Philippines. Conclusion: This study shows the diverse motivations of nurses from different countries and with different migratory backgrounds and provides evidence that factors other than economic factors influence nurses' decision to emigrate. This information can help developing countries increase retention of this essential and often scarce resource and can also help the United Kingdom's National Health Service to improve the experience of internationally recruited nurses and therefore increase their retention in the United Kingdom

Human Analogue Safe Haven Effect of the Owner : Behavioural and Heart Rate Response to Stressful Social Stimuli in Dogs

The secure base and safe haven effects of the attachment figure are central features of the human attachment theory. Recently, conclusive evidence for human analogue attachment behaviours in dogs has been provided, however, the owner’s security-providing role in danger has not been directly supported. We investigated the relationship between the behavioural and cardiac response in dogs (N = 30) while being approached by a threatening stranger in separation vs. in the presence of the owner, presented in a balanced order. Non-invasive telemetric measures of heart rate (HR) and heart rate variability (HRV) data during the threatening approaches was compared to periods before and after the encounters. Dogs that showed distress vocalisation during separation (N = 18) and that growled or barked at the stranger during the threatening approach (N = 17) were defined as behaviourally reactive in the given situation. While characteristic stress vocalisations were emitted during separations, the absence of the owner did not have an effect on dogs’ mean HR, but significantly increased the HRV. The threatening approach increased dogs’ mean HR, with a parallel decrease in the HRV, particularly in dogs that were behaviourally reactive to the encounter. Importantly, the HR increase was significantly less pronounced when dogs faced the stranger in the presence of the owner. Moreover, the test order, whether the dog encountered the stranger first with or without its owner, also proved important: HR increase associated with the encounter in separation seemed to be attenuated in dogs that faced the stranger first in the presence of their owner. We provided evidence for human analogue safe haven effect of the owner in a potentially dangerous situation. Similarly to parents of infants, owners can provide a buffer against stress in dogs, which can even reduce the effect of a subsequent encounter with the same threatening stimuli later when the owner is not present

Short-term acclimation in adults does not predict offspring acclimation potential to hypoxia

Abstract The prevalence of hypoxic areas in coastal waters is predicted to increase and lead to reduced biodiversity. While the adult stages of many estuarine invertebrates can cope with short periods of hypoxia, it remains unclear whether that ability is present if animals are bred and reared under chronic hypoxia. We firstly investigated the effect of moderate, short-term environmental hypoxia (40% air saturation for one week) on metabolic performance in adults of an estuarine amphipod, and the fitness consequences of prolonged exposure. We then reared the offspring of hypoxia-exposed parents under hypoxia, and assessed their oxyregulatory ability under declining oxygen tensions as juveniles and adults. Adults from the parental generation were able to acclimate their metabolism to hypoxia after one week, employing mechanisms typically associated with prolonged exposure. Their progeny, however, did not develop the adult pattern of respiratory regulation when reared under chronic hypoxia, but instead exhibited a poorer oxyregulatory ability than their parents. We conclude that species apparently hypoxia-tolerant when tested in short-term experiments, could be physiologically compromised as adults if they develop under hypoxia. Consequently, we propose that the increased prevalence of hypoxia in coastal regions will have marked effects in some species currently considered hypoxia tolerant

Panel 4 : Report of the Microbiology Panel

Objective. To perform a comprehensive review of the literature from July 2011 until June 2015 on the virology and bacteriology of otitis media in children. Data Sources. PubMed database of the National Library of Medicine. Review Methods. Two subpanels comprising experts in the virology and bacteriology of otitis media were created. Each panel reviewed the relevant literature in the fields of virology and bacteriology and generated draft reviews. These initial reviews were distributed to all panel members prior to meeting together at the Post-symposium Research Conference of the 18th International Symposium on Recent Advances in Otitis Media, National Harbor, Maryland, in June 2015. A final draft was created, circulated, and approved by all panel members. Conclusions. Excellent progress has been made in the past 4 years in advancing our understanding of the microbiology of otitis media. Numerous advances were made in basic laboratory studies, in animal models of otitis media, in better understanding the epidemiology of disease, and in clinical practice. Implications for Practice. (1) Many viruses cause acute otitis media without bacterial coinfection, and such cases do not require antibiotic treatment. (2) When respiratory syncytial virus, metapneumovirus, and influenza virus peak in the community, practitioners can expect to see an increase in clinical otitis media cases. (3) Biomarkers that predict which children with upper respiratory tract infections will develop otitis media may be available in the future. (4) Compounds that target newly identified bacterial virulence determinants may be available as future treatment options for children with otitis media.Peer reviewe

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

Bottom-up effects of plant diversity on multitrophic interactions in a biodiversity experiment

Biodiversity is rapidly declining1, and this may negatively affect ecosystem processes, including economically important ecosystem services. Previous studies have shown that biodiversity has positive effects on organisms and processes4 across trophic levels. However, only a few studies have so far incorporated an explicit food-web perspective. In an eight-year biodiversity experiment, we studied an unprecedented range of above- and below-ground organisms and multitrophic interactions. A multitrophic data set originating from a single long-term experiment allows mechanistic insights that would not be gained from meta-analysis of different experiments. Here we show that plant diversity effects dampen with increasing trophic level and degree of omnivory. This was true both for abundance and species richness of organisms. Furthermore, we present comprehensive above-ground/below-ground biodiversity food webs. Both above ground and below ground, herbivores responded more strongly to changes in plant diversity than did carnivores or omnivores. Density and richness of carnivorous taxa was independent of vegetation structure. Below-ground responses to plant diversity were consistently weaker than above-ground responses. Responses to increasing plant diversity were generally positive, but were negative for biological invasion, pathogen infestation and hyperparasitism. Our results suggest that plant diversity has strong bottom-up effects on multitrophic interaction networks, with particularly strong effects on lower trophic levels. Effects on higher trophic levels are indirectly mediated through bottom-up trophic cascades