UK Neovascular Age-Related Macular Degeneration Database. Report 6: time to retreatment after a pause in therapy. Outcomes from 92 976 intravitreal ranibizumab injections.

BACKGROUND/AIMS: To study the time to retreatment in eyes with neovascular age-related macular degeneration (nAMD) that had been treatment-free for intervals of 3 months, 6 months, 9 months and 12 months during the maintenance phase of ranibizumab therapy within the UK National Health Service. METHODS: In this multicentre national nAMD database study, structured data were collected from 14 centres (involving 12 951 eyes receiving 92 976 ranibizumab injections). Patients were treated with three fixed, monthly injections in a loading phase of treatment, followed by a pro re nata retreatment regimen in a maintenance phase. Eyes with a treatment-free interval (TFI) of 3 months, 6 months, 9 months or 12 months in the maintenance phase were identified and the time to retreatment after these TFIs was determined. RESULTS: The time to retreatment for the 20th and 50th centiles was 0.58/2.54 months after a 3-month TFI, 2.07/9.62 months after a 6-month TFI, 3.69/15.84 months after a 9-month TFI and 5.90/22.49 months after a 12-month TFI. Following a TFI of 3 months, 6 months, 9 months and 12 months, 68%, 44%, 31% and 21% of eyes required retreatments after an additional 6 months of follow-up, respectively. Similarly, after 12 months of follow-up, 77%, 56%, 43% and 34% of these eyes required retreatment. CONCLUSIONS: This study provides times to retreatment in eyes with nAMD that have been treatment-free for intervals of 3-12 months and demonstrates the likelihood of repeat therapy within the next year, even after a TFI of 12 months. These outcomes can help plan appropriate follow-up intervals for patients who have been treatment-free for intervals of up to 12 months

Optimisation of CdTe electrodeposition voltage for development of CdS/CdTe solar cells

Cadmium telluride (CdTe) thin films have been deposited on glass/conducting glass (FTO) substrates using low-cost two electrode system and aqueous electrodeposition method. The glass/FTO substrates were used to grow the CdTe layers at different deposition voltages. The structural, electrical, optical and morphological properties of the resulting films have been characterized using X-ray diffraction (XRD), Photoelectrochemical (PEC) cell measurements, optical absorption spectroscopy and Scanning Electron Microscopy (SEM). The XRD results indicate that at voltages less than or higher than 1.576 V, crystallinity is poor due to presence of two phases. When CdTe is grown at 1.576 V, the composition is stoichiometric, and the (111) peak has the highest intensity in the XRD diffractogram indicating a high degree of crystallinity. SEM studies showed that all layers had pin-holes and gaps between the grains. These openings seem to be more common in the samples grown at voltages away from the stoichiometric voltage (1.576 V). The linear I–V curves of glass/FTO/CdS/CdTe/Au structures fabricated using stoichiometric CdTe showed efficiency of 10.1 % under AM 1.5 illuminatio

The Radially Swollen 4 Separase Mutation of Arabidopsis thaliana Blocks Chromosome Disjunction and Disrupts the Radial Microtubule System in Meiocytes

The caspase-family protease, separase, is required at the onset of anaphase to cleave the cohesin complex that joins replicated sister chromatids. However, in various eukaryotes, separase has acquired additional and distinct functions. A single amino-acid substitution in separase is responsible for phenotypes of the Arabidopsis thaliana mutant, radially swollen 4 (rsw4). This is a conditional mutant, resembling the wild type at the permissive temperature (∼20°C) and expressing mutant phenotypes at the restrictive temperature (∼30°C). Root cells in rsw4 at the restrictive temperature undergo non-disjunction and other indications of the loss of separase function. To determine to what extent separase activity remains at 30°C, we examined the effect of the mutation on meiosis, where the effects of loss of separase activity through RNA interference are known; and in addition, we examined female gametophyte development. Here, we report that, at the restrictive temperature, replicated chromosomes in rsw4 meiocytes typically fail to disjoin and the cohesin complex remains at centromeres after metaphase. Meiotic spindles appear normal in rsw4 male meiocytes; however the mutation disrupts the radial microtubule system, which is replaced by asymmetric arrays. Surprisingly, female gametophyte development was relatively insensitive to loss of separase activity, through either rsw4 or RNAi. These effects confirm that phenotypes in rsw4 result from loss of separase activity and establish a role for separase in regulating cell polarization following male meiosis

Gγ1, a Downstream Target for the hmgcr-Isoprenoid Biosynthetic Pathway, Is Required for Releasing the Hedgehog Ligand and Directing Germ Cell Migration

The isoprenoid biosynthetic pathway leading from the production of mevalonate by HMGCoA reductase (Hmgcr) to the geranylation of the G protein subunit, Gγ1, plays an important role in cardiac development in the fly. Hmgcr has also been implicated in the release of the signaling molecule Hedgehog (Hh) from hh expressing cells and in the production of an attractant that directs primordial germ cells to migrate to the somatic gonadal precursor cells (SGPs). The studies reported here indicate that this same hmgcr→Gγ1 pathway provides a novel post-translational mechanism for modulating the range and activity of the Hh signal produced by hh expressing cells. We show that, like hmgcr, gγ1 and quemao (which encodes the enzyme, geranylgeranyl diphosphate synthetase, that produces the substrate for geranylation of Gγ1) are components of the hh signaling pathway and are required for the efficient release of the Hh ligand from hh expressing cells. We also show that the hmgcr→Gγ1 pathway is linked to production of the germ cell attractant by the SGPs through its ability to enhance the potency of the Hh signal. We show that germ cell migration is disrupted by the loss or gain of gγ1 activity, by trans-heterozygous combinations between gγ1 and either hmgcr or hh mutations, and by ectopic expression of dominant negative Gγ1 proteins that cannot be geranylated

Fluoxetine reverses the memory impairment and reduction in proliferation and survival of hippocampal cells caused by methotrexate chemotherapy

RATIONALE: Adjuvant cancer chemotherapy can cause long-lasting, cognitive deficits. It is postulated that these impairments are due to these drugs targeting neural precursors within the adult hippocampus, the loss of which has been associated with memory impairment. OBJECTIVES: The present study investigates the effects of the chemotherapy, methotrexate (MTX) on spatial working memory and the proliferation and survival of the neural precursors involved in hippocampal neurogenesis, and the possible neuroprotective properties of the antidepressant fluoxetine. METHODS: Male Lister hooded rats were administered MTX (75 mg/kg, two i.v. doses a week apart) followed by leucovorin rescue (i.p. 18 h after MTX at 6 mg/kg and at 26, 42 and 50 h at 3 mg/kg) and/or fluoxetine (10 mg/kg/day in drinking water for 40 days). Memory was tested using the novel location recognition (NLR) test. Using markers, cell proliferation (Ki67) and survival (bromodeoxyuridine/BrdU), in the dentate gyrus were quantified. RESULTS: MTX-treated rats showed a cognitive deficit in the NLR task compared with the vehicle and fluoxetine-treated groups. Cognitive ability was restored in the group receiving both MTX and fluoxetine. MTX reduced both the number of proliferating cells in the SGZ and their survival. This was prevented by the co-administration of fluoxetine, which alone increased cell numbers. CONCLUSIONS: These results demonstrate that MTX induces an impairment in spatial working memory and has a negative long-term effect on hippocampal neurogenesis, which is counteracted by the co-administration of fluoxetine. If translatable to patients, this finding has the potential to prevent the chemotherapy-induced cognitive deficits experienced by many cancer survivors

A pilot randomized controlled trial comparing bismuth iodine paraffin paste external ear pack and no ear pack after middle ear surgery

© 2013, The Author(s). To pilot a substantive randomized control trial comparing post-operative external ear canal pack with no ear pack after middle ear surgery, 32 adults undergoing primary posterior bony canal wall preserving middle ear surgery were randomized to have either a bismuth iodoform paraffin paste pack or no ear pack post-operatively. Outcome measures included clinician- and patient-recorded visual analogue scale scores for ear signs and symptoms at 3weeks and 3months and audiometric findings at 3months post-operatively. There was no statistically significant inter-group difference in 3-week clinician and patient cumulative scores for ear signs and symptoms. There was also no significant difference in graft take rate, appearance of ear canals and audiometric results in either group at 3months. No difference in ear symptoms, clinician findings or hearing was demonstrated between patients with a post-operative pack compared to those without a pack following middle ear surgery in this pilot study

Simulating the midlatitude atmospheric circulation: what might we gain from high-resolution modeling of air-sea interactions?

Purpose of Review. To provide a snapshot of the current research on the oceanic forcing of the atmospheric circulation in midlatitudes and a concise update on previous review papers. Recent findings. Atmospheric models used for seasonal and longer timescales predictions are starting to resolve motions so far only studied in conjunction with weather forecasts. These phenomena have horizontal scales of ~ 10–100 km which coincide with energetic scales in the ocean circulation. Evidence has been presented that, as a result of this matching of scale, oceanic forcing of the atmosphere was enhanced in models with 10–100 km grid size, especially at upper tropospheric levels. The robustness of these results and their underlying mechanisms are however unclear. Summary. Despite indications that higher resolution atmospheric models respond more strongly to sea surface temperature anomalies, their responses are still generally weaker than those estimated empirically from observations. Coarse atmospheric models (grid size greater than 100 km) will miss important signals arising from future changes in ocean circulation unless new parameterizations are developed