Structured illumination microscopy using micro-pixellated light-emitting diodes

Structured illumination is a flexible and economical method of obtaining optical sectioning in wide-field microscopy [1]. In this technique the illumination system is modified to project a single-spatial frequency grid pattern onto the sample [2, 3]. The pattern can only be resolved in the focal plane and by recording images for different transverse grid positions (or phases) an image of the in-focus parts of the object can be calculated. Light emitting diodes (LEDs) are becoming increasingly popular for lighting and illumination systems due to their low cost, small dimensions, low coherence, uniform illumination, high efficiency and long lifetime. These properties, together with recent developments in high brightness, ultraviolet operation and microstructured emitter design offer great potential for LEDs as light sources for microscopy. In this paper we demonstrate a novel structured illumination microscope using a blue micro-structured light emitting diode as the illumination source. The system is potentially very compact and has no-moving-parts

Genetic Assimilation and Canalisation in the Baldwin Effect

The Baldwin Effect indicates that individually learned behaviours acquired during an organism’s lifetime can influence the evolutionary path taken by a population, without any direct Lamarckian transfer of traits from phenotype to genotype. Several computational studies modelling this effect have included complications that restrict its applicability. Here we present a simplified model that is used to reveal the essential mechanisms and highlight several conceptual issues that have not been clearly defined in prior literature. In particular, we suggest that canalisation and genetic assimilation, often conflated in previous studies, are separate concepts and the former is actually not required for non-heritable phenotypic variation to guide genetic variation. Additionally, learning, often considered to be essential for the Baldwin Effect, can be replaced with a more general phenotypic plasticity model. These simplifications potentially permit the Baldwin Effect to operate in much more general circumstances

Understanding the pain experience in hip and knee osteoarthritis – an OARSI/OMERACT initiative

SummaryObjectiveTo examine the pain experience of people with hip or knee osteoarthritis (OA), particularly changes over time and most distressing features.MethodFocus groups in individuals aged 40+ years with painful hip or knee OA obtained detailed descriptions of OA pain from early to late disease. A modified Patient Generated Index (PGI) was used to assess the features of OA pain that participants found most distressing. Content analysis was performed to examine response patterns; descriptive statistics were used to summarize PGI responses.ResultsMean age of the 143 participants (52 hip OA; 91 knee OA) was 69.5 years (47–92 years); 60.8% were female and 93.7% Caucasian. Participants described two distinct types of pain – a dull, aching pain, which became more constant over time, punctuated increasingly with short episodes of a more intense, often unpredictable, emotionally draining pain. The latter, but not the former, resulted in significant avoidance of social and recreational activities. From PGI responses, distressing pain features were: the pain itself (particularly intense and unpredictable pain) and the pain's impact on mobility, mood and sleep.ConclusionsTwo distinct pain types were identified. Intermittent intense pain, particularly when unpredictable, had the greatest impact on quality of life

Investigating an unusually large 28-day oscillation in mesospheric temperature over Antarctica using ground-based and satellite measurements

The Utah State University (USU) Advanced Mesospheric Temperature Mapper (AMTM) was deployed at the Amundsen‐Scott South Pole Station in 2010 to measure OH temperature at ~87 km as part of an international network to study the mesospheric dynamics over Antarctica. During the austral winter of 2014, an unusually large amplitude ~28‐day oscillation in mesospheric temperature was observed for ~100 days from the South Pole Station. This study investigates the characteristics and global structure of this exceptional planetary‐scale wave event utilizing ground‐based mesospheric OH temperature measurements from two Antarctic stations (South Pole and Rothera) together with satellite temperature measurements from the Microwave Limb Sounder (MLS) on the Aura satellite, and the Solar Occultation For Ice Experiment (SOFIE) on the Aeronomy of Ice in the Mesosphere (AIM) satellite. Our analyses have revealed that this large oscillation is a winter time, high latitude phenomenon, exhibiting a coherent zonal wave #1 structure below 80 km altitude. At higher altitudes, the wave was confined in longitude between 180‐360°E. The amplitude of this oscillation reached ~15 K at 85 km and it was observed to grow with altitude as it extended from the stratosphere into the lower thermosphere in the southern hemisphere. The satellite data further established the existence of this oscillation in the northern hemisphere during the boreal winter time. The main characteristics and global structure of this event as observed in temperature are consistent with the predicted 28‐day Rossby Wave (1,4) mode

Full 0ℏω0\hbar\omega shell model calculation of the binding energies of the 1f7/21f_{7/2} nuclei

Binding energies and other global properties of nuclei in the middle of the $pf$ shell, such as M1, E2 and Gamow-Teller sum rules, have been obtained using a new Shell Model code (NATHAN) written in quasi-spin formalism and using a $j-j$-coupled basis. An extensive comparison is made with the recently available Shell Model Monte Carlo results using the effective interaction KB3. The binding energies for -nearly- all the $1f_{7/2}$ nuclei are compared with the measured (and extrapolated) results.Comment: 7 page

Improving adherence to acute low back pain guideline recommendations with chiropractors and physiotherapists: the ALIGN cluster randomised controlled trial

Background Acute low back pain is a common condition, has high burden, and there are evidence-to-practice gaps in the chiropractic and physiotherapy setting for imaging and giving advice to stay active. The aim of this cluster randomised trial was to estimate the effects of a theory- and evidence-based implementation intervention to increase chiropractors’ and physiotherapists’ adherence to a guideline for acute low back pain compared with the comparator (passive dissemination of the guideline). In particular, the primary aim of the intervention was to reduce inappropriate imaging referral and improve patient low back pain outcomes, and to determine whether this intervention was cost-effective. Methods Physiotherapy and chiropractic practices in the state of Victoria, Australia, comprising at least one practising clinician who provided care to patients with acute low back pain, were invited to participate. Patients attending these practices were included if they had acute non-specific low back pain (duration less than 3 months), were 18 years of age or older, and were able to understand and read English. Practices were randomly assigned either to a tailored, multi-faceted intervention based on the guideline (interactive educational symposium plus academic detailing) or passive dissemination of the guideline (comparator). A statistician independent of the study team undertook stratified randomisation using computer-generated random numbers; four strata were defined by professional group and the rural or metropolitan location of the practice. Investigators not involved in intervention delivery were blinded to allocation. Primary outcomes were X-ray referral self-reported by clinicians using a checklist and patient low back pain-specific disability (at 3 months). Results A total of 104 practices (43 chiropractors, 85 physiotherapists; 755 patients) were assigned to the intervention and 106 practices (45 chiropractors, 97 physiotherapists; 603 patients) to the comparator; 449 patients were available for the patient-level primary outcome. There was no important difference in the odds of patients being referred for X-ray (adjusted (Adj) OR: 1.40; 95% CI 0.51, 3.87; Adj risk difference (RD): 0.01; 95% CI − 0.02, 0.04) or patient low back pain-specific disability (Adj mean difference: 0.37; 95% CI − 0.48, 1.21, scale 0–24). The intervention did lead to improvement for some key secondary outcomes, including giving advice to stay active (Adj OR: 1.96; 95% CI 1.20, 3.22; Adj RD: 0.10; 95% CI 0.01, 0.19) and intending to adhere to the guideline recommendations (e.g. intention to refer for X-ray: Adj OR: 0.27; 95% CI 0.17, 0.44; intention to give advice to stay active: Adj OR: 2.37; 95% CI 1.51, 3.74). Conclusions Intervention group clinicians were more likely to give advice to stay active and to intend to adhere to the guideline recommendations about X-ray referral. The intervention did not change the primary study outcomes, with no important differences in X-ray referral and patient disability between groups, implying that hypothesised reductions in health service utilisation and/or productivity gains are unlikely to offset the direct costs of the intervention. We report these results with the caveat that we enrolled less patients into the trial than our determined sample size. We cannot recommend this intervention as a cost-effective use of resources

Higher serum immunoglobulin G3 levels may predict the development of multiple sclerosis in individuals with Clinically Isolated Syndrome

Clinically isolated syndrome (CIS) is a first episode of neurological symptoms that may precede a diagnosis of multiple sclerosis (MS). Therefore, studying individuals with CIS may lead to breakthroughs in understanding the development and pathogenesis of MS. In this study, serum levels of immunoglobulin (Ig)G, IgA, IgM, and IgG1–4 were measured in 20 people with CIS and compared with those in 10 healthy controls (HC) and 8 people with MS. Serum Ig levels in individuals with CIS were compared with (a) the time to their conversion from CIS to MS, (b) serum levels of antibodies to Epstein–Barr virus, (c) frequencies of T regulatory (Treg), T follicular regulatory (Tfr), and B cell subsets, and (d) Treg/Tfr expression of Helios. Serum IgG, IgM, and IgG2 levels were significantly lower in people with CIS than HC, and IgG, IgM, and IgG1 levels were significantly lower in people with CIS than MS. After adjusting for age, sex, and serum 25(OH) vitamin D3 [25(OH)D] levels, CIS was associated with lower serum levels of IgG and IgG2 compared with HC (p = 0.001 and p < 0.001, respectively). People with MS had lower IgG2 levels (p < 0.001) and IgG2 proportions (%IgG; p = 0.007) compared with HC. After adjusting for age, sex, and 25(OH)D, these outcomes remained, in addition to lower serum IgA levels (p = 0.01) and increased IgG3 levels (p = 0.053) in people with MS compared with HC. Furthermore, serum from people with MS had increased proportions of IgG1 and IgG3 (p = 0.03 and p = 0.02, respectively), decreased proportions of IgG2 (p = 0.007), and greater ratios of “upstream” to “downstream” IgG subclasses (p = 0.001) compared with HC. Serum IgG3 proportions (%IgG) from people with CIS correlated with the frequency of plasmablasts in peripheral blood (p = 0.02). Expression of Helios by Treg and Tfr cell subsets from individuals with CIS correlated with levels of serum IgG2 and IgG4. IgG3 levels and proportions of IgG3 (%IgG) in serum at CIS diagnosis were inversely correlated with the time until conversion to MS (p = 0.018 and p < 0.001, respectively), suggesting they may be useful prognostic markers of individuals with CIS who rapidly convert to MS