Patient-centred measurement in ophthalmology – a paradigm shift

Ophthalmologists and researchers in ophthalmology understand what a rapidly evolving field ophthalmology is, and that to conduct good research it is essential to use the latest and best methods. In outcomes research, one modern initiative has been to conduct holistic measurement of outcomes inclusive of the patient's point of view; patient-centred outcome. This, of course, means including a questionnaire. However, the irony of trying to improve outcomes research by being inclusive of many measures is that the researcher may not be expert in all measures used. Certainly, few people conducting outcomes research in ophthalmology would claim to be questionnaire experts. Most tend to be experts in their ophthalmic subspecialty and probably simply choose a popular questionnaire that appears to fit their needs and think little more about it. Perhaps, unlike our own field, we assume that the field of questionnaire research is relatively stable. This is far from the case. The measurement of patient-centred outcomes with questionnaires is a rapidly evolving field. Indeed, over the last few years a paradigm shift has occurred in patient-centred measurement

Toll-Like Receptor 3 and Suppressor of Cytokine Signaling Proteins Regulate CXCR4 and CXCR7 Expression in Bone Marrow-Derived Human Multipotent Stromal Cells

The use of bone marrow-derived human multipotent stromal cells (hMSC) in cell-based therapies has dramatically increased in recent years, as researchers have exploited the ability of these cells to migrate to sites of tissue injury, inflammation, and tumors. Our group established that hMSC respond to "danger" signals--by-products of damaged, infected or inflamed tissues--via activation of Toll-like receptors (TLRs). However, little is known regarding downstream signaling mediated by TLRs in hMSC.We demonstrate that TLR3 stimulation activates a Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 1 pathway, and increases expression of suppressor of cytokine signaling (SOCS) 1 and SOCS3 in hMSC. Our studies suggest that each of these SOCS plays a distinct role in negatively regulating TLR3 and JAK/STAT signaling. TLR3-mediated interferon regulatory factor 1 (IRF1) expression was inhibited by SOCS3 overexpression in hMSC while SOCS1 overexpression reduced STAT1 activation. Furthermore, our study is the first to demonstrate that when TLR3 is activated in hMSC, expression of CXCR4 and CXCR7 is downregulated. SOCS3 overexpression inhibited internalization of both CXCR4 and CXCR7 following TLR3 stimulation. In contrast, SOCS1 overexpression only inhibited CXCR7 internalization.These results demonstrate that SOCS1 and SOCS3 each play a functionally distinct role in modulating TLR3, JAK/STAT, and CXCR4/CXCR7 signaling in hMSC and shed further light on the way hMSC respond to danger signals

Seasonal variations of the digestive tract of the Eurasian beaver castor fiber.

Forage availability for wild rodents varies with season. In turn, the composition of food can affect morphometric parameters of the digestive tract. This study was performed in Eurasian beavers (Castor fiber) whose population was close to extinction in most Eurasian countries, but has now increased. Due to the previous low number of studies, information about the effect of forage availability on the digestive tract morphology has previously been lacking. This study was performed using beavers captured from the natural environment during three seasons of different forage availability: winter, summer and autumn. It was found that the diet of the beaver varied during the year; in winter it was dominated by woody material consisting of willow shoots, whereas in summer the diet was primarily herbs, grass and leaves. Season also affected the mass of digested contents of the digestive tract. The digestive content increased in the caecum and colon in winter and autumn, when poor-quality food dominated the beaver's diet. The results indicated that the digestive tract parameters of beavers varied based on the composition of available forage

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021

Economic evaluation of point-of-care testing in the remote primary health care setting of Australia’s Northern Territory

Brooke A Spaeth,1 Billingsley Kaambwa,2 Mark DS Shephard,1 Rodney Omond3 1Flinders University International Centre for Point-of-Care Testing, Flinders University, Adelaide, SA, Australia; 2Health Economics Unit, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia; 3Primary Health Care Branch, Top End Health Service, Department of Health, Northern Territory Government, Darwin, NT, Australia Aim: To determine the cost-effectiveness of utilizing point-of-care testing (POCT) on the Abbott i-STAT device as a support tool to aid decisions regarding the emergency medical retrievals of patients at remote health centers in the Northern Territory (NT) of Australia.Methods: A decision analytic simulation model–based economic evaluation was conducted using data from patients presenting with three common acute conditions (chest pain, chronic renal failure due to missed dialysis session(s), and acute diarrhea) at six remote NT health centers from July to December 2015. The specific outcomes measured in this study were the number of unnecessary emergency medical retrieval prevented through POCT. Cost savings through prevented unnecessary medical retrievals for each presentation type were then determined and extrapolated to give per annum NT-wide estimates.Results: POCT prevented 60 unnecessary medical evacuations from a total of 200 patient cases meeting the selection criteria (48/147 for chest pain, 10/28 for missed dialysis, and 2/25 for acute diarrhea). The associated cost savings were AUD $4,674,$8,034, and $786 per patient translating to NT-wide savings of AUD$13.72 million, $6.45 million, and$1.57 million per annum (AUD $21.75 million in total) for chest pain, missed dialysis, and acute diarrhea presentations, respectively.Conclusion: This study demonstrated that POCT when used to aid decision making for acutely ill patients delivered significant cost savings for the NT health care system by preventing unnecessary emergency medical retrievals. Keywords: acute, remote health, primary care, retrieval, acute care, myocardial infarction, dialysis, dehydration, indigenous health, pathology testing, medical retrieval, cost-effectivenes

Quantifying wheelchair activity of children: A pilot study

Objective: The purpose of this study was to investigate mobility-related wheelchair activity of children in their community setting. Design: Mobility-related wheelchair activity data from 18 community-dwelling children (9 manual and 9 electric powered) were collected using custom-designed data logging devices. The children were between 8 and 17 yrs of age and independently used a wheelchair as their primary means of mobility. A data logging device was installed on their wheelchair for 7 days. However, because the device was attached and removed at different times of the day, the first and last days of the study period were not analyzed. Therefore, a total of 5 days of data were used to investigate wheelchair activity. Results: Overall, the children who used manual wheelchairs traveled on an average of 1602.31 m/day (SD, 976.78) at a speed of 0.67 m/sec (SD, 0.1 2), and the children who used electric-powered wheelchairs drove 1752.42 m/day (SD, 835.14) at a speed of 0.75 m/sec (SD, 0.35). It was also calculated that the average daily number of starts/stops per thousand meters the manual and electric-powered wheelchair users completed were 166.77 (SD, 64.32) and 112.53 (SD, 62.27), respectively. A comparison of mobility-related wheelchair activity revealed a significant (P = 0.008) difference in the average daily distance traveled between genders, with the boys traveling further than the girls. Conclusions: The mobility data obtained from the children wheelchair users suggest that one possible factor of variability among wheelchair activity is between genders. The data collected provide us with direction for future research in this area. Copyright © 2008 by Lippincott Williams & Wilkins