Monomeric Bistability and the Role of Autoloops in Gene Regulation

Genetic toggle switches are widespread in gene regulatory networks (GRN). Bistability, namely the ability to choose among two different stable states, is an essential feature of switching and memory devices. Cells have many regulatory circuits able to provide bistability that endow a cell with efficient and reliable switching between different physiological modes of operation. It is often assumed that negative feedbacks with cooperative binding (i.e. the formation of dimers or multimers) are a prerequisite for bistability. Here we analyze the relation between bistability in GRN under monomeric regulation and the role of autoloops under a deterministic setting. Using a simple geometric argument, we show analytically that bistability can also emerge without multimeric regulation, provided that at least one regulatory autoloop is present

Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)

Objective- To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods- This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results- Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group. Conclusions- The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma

UK Environmental Change Network (ECN) common breeding birds data 1971-2007

Bird species data from the UK Environmental Change Network (ECN) lowland terrestrial sites. These data were collected, using the British Trust for Ornithology (BTO)'s Common Bird Census methodology (CBC), at ECN's lowland terrestrial sites using a standard protocol. This protocol was abandoned in favour of the Breeding Bird Survey (Rennie et al (2017) UK Environmental Change Network (ECN) bird data: 1995-2015 https://doi.org/10.5285/5886c3ba-1fa5-49c0-8da8-40e69a10d2b5) in 1999; however, some sites continued to follow this protocol for a number of years after 1999 to allow comparison with the Breeding Bird Survey data. The CBC uses a mapping method in which a series of visits are made to all parts of a defined plot during the breeding season and contacts with birds by sight or sound are recorded on large-scale maps. Information from the series of visits is combined to estimate the number of territories found. Annual data are recorded but the date ranges available are variable for each site. ECN is the UK’s long-term environmental monitoring programme. It is a multi-agency programme sponsored by a consortium of fourteen government departments and agencies. These organisations contribute to the programme through funding either site monitoring and/or network co-ordination activities. These organisations are: Agri-Food and Biosciences Institute, Biotechnology and Biological Sciences Research Council, Cyfoeth Naturiol Cymru - Natural Resources Wales, Defence Science & Technology Laboratory, Department for Environment, Food and Rural Affairs, Environment Agency, Forestry Commission, Llywodraeth Cymru - Welsh Government, Natural England, Natural Environment Research Council, Northern Ireland Environment Agency, Scottish Environment Protection Agency, Scottish Government and Scottish Natural Heritage

Physicians' working conditions and job satisfaction: does hospital ownership in Germany make a difference?

<p>Abstract</p> <p>Background</p> <p>A growing number of German hospitals have been privatized with the intention of increasing cost effectiveness and improving the quality of health care. Numerous studies investigated what possible qualitative and economic consequences these changes issues might have on patient care.</p> <p>However, little is known about how this privatization trend relates to physicians' working conditions and job satisfaction. It was anticipated that different working conditions would be associated with different types of hospital ownership. To that end, this study's purpose is to compare how physicians, working for both public and privatized hospitals, rate their respective psychosocial working conditions and job satisfaction.</p> <p>Methods</p> <p>The study was designed as a cross-sectional comparison using questionnaire data from 203 physicians working at German hospitals of different ownership types (private for-profit, public and private nonprofit).</p> <p>Results</p> <p>The present study shows that several aspects of physicians' perceived working conditions differ significantly depending on hospital ownership. However, results also indicated that physicians' job satisfaction does not vary between different types of hospital ownership. Finally, it was demonstrated that job demands and resources are associated with job satisfaction, while type of ownership is not.</p> <p>Conclusion</p> <p>This study represents one of a few studies that investigate the effect of hospital ownership on physicians work situation and demonstrated that the type of ownership is a potential factor accounting for differences in working conditions. The findings provide an informative basis to find solutions improving physicians' work at German hospitals.</p

UK Environmental Change Network (ECN) stream water discharge data: 1993-2015

Stream water discharge data from the UK Environmental Change Network (ECN) terrestrial sites. The data (stage and discharge) are collected by loggers at ECN's terrestrial sites (where a stream is present) using a standard protocol. They represent continuous 15-minute records from 1993 to 2015. The sites at which these data are collected are: Glensaugh, Moor House - Upper Teesdale, Sourhope, Wytham and Y Wyddfa (Snowdon). ECN is the UK's long-term environmental monitoring programme. It is a multi-agency programme sponsored by a consortium of fourteen government departments and agencies. These organisations contribute to the programme through funding either site monitoring and/or network co-ordination activities. These organisations are: Agri-Food and Biosciences Institute, Biotechnology and Biological Sciences Research Council, Cyfoeth Naturiol Cymru - Natural Resources Wales, Defence Science & Technology Laboratory, Department for Environment, Food and Rural Affairs, Environment Agency, Forestry Commission, Llywodraeth Cymru - Welsh Government, Natural England, Natural Environment Research Council, Northern Ireland Environment Agency, Scottish Environment Protection Agency, Scottish Government and Scottish Natural Heritage

UK Environmental Change Network (ECN) coarse grain vegetation data: 1993-2012

Coarse grain vegetation data from the UK Environmental Change Network (ECN) terrestrial sites. These data are collected at all of ECN's terrestrial sites using a standard protocol (see supporting documentation). In this protocol, 50 2m x 2m plots are randomly selected within each vegetation type on the site - species presence is recorded in 40cm x 40 cm cells randomly selected within these plots. They represent continuous records every nine years from 1993 to 2012. ECN is the UK’s long-term environmental monitoring programme. It is a multi-agency programme sponsored by a consortium of fourteen government departments and agencies. These organisations contribute to the programme through funding either site monitoring and/or network co-ordination activities. These organisations are: Agri-Food and Biosciences Institute, Biotechnology and Biological Sciences Research Council, Cyfoeth Naturiol Cymru - Natural Resources Wales, Defence Science & Technology Laboratory, Department for Environment, Food and Rural Affairs, Environment Agency, Forestry Commission, Llywodraeth Cymru - Welsh Government, Natural England, Natural Environment Research Council, Northern Ireland Environment Agency, Scottish Environment Protection Agency, Scottish Government and Scottish Natural Heritage