Marine plastic debris emits a keystone infochemical for olfactory foraging seabirds.

Plastic debris is ingested by hundreds of species of organisms, from zooplankton to baleen whales, but how such a diversity of consumers can mistake plastic for their natural prey is largely unknown. The sensory mechanisms underlying plastic detection and consumption have rarely been examined within the context of sensory signals driving marine food web dynamics. We demonstrate experimentally that marine-seasoned microplastics produce a dimethyl sulfide (DMS) signature that is also a keystone odorant for natural trophic interactions. We further demonstrate a positive relationship between DMS responsiveness and plastic ingestion frequency using procellariiform seabirds as a model taxonomic group. Together, these results suggest that plastic debris emits the scent of a marine infochemical, creating an olfactory trap for susceptible marine wildlife

A clinical evaluation of the Ciba toric and Hydron toric soft contact lenses

Two currently available brands of soft toric contact lenses were evaluated in a clinical setting. The study was designed to assess the overall effectiveness of the Ciba TORISOFT and the American Hydton soft toric contact lens. Each lens was judged, based on manufacturer quality control, visual acuity, how well the eye physiology adapts to the lens, how comfortable the lens is, and the durability of the lens. The Hydron Toric and the Torisoft lenses both utilize front surface toricity. The Rydron lens makes use of a prism ballast and inferior truncation for stability, while the Torisoft incorporates thin zones at 90° and 270° and no truncation to orient the lens properly. The American Hydron is constructed with an aspheric back surface in an attempt to conform to the topography of the cornea and immediately surrounding sclera. The Torisoft makes use of a spherical back surface. At the writting of this paper patients in the study have been wearing the lenses anywhere from two weeks to three months. Presently 91% of the twenty lenses initially fit are still being worn. Further data on these lenses is forthcoming in Part II of this study. Initially both lenses have shown a high level of success in all areas of investigation

Statistical methods used to combine the effective reproduction number, R(t), and other related measures of COVID-19 in the UK

In the COVID-19 pandemic, a range of epidemiological models have been used to predict the number of new daily infections, $I$, daily rate of exponential growth, $r$, and effective reproduction number, $R(t)$. These models differ in their approaches (e.g. mechanistic or empirical) and/or assumptions about spatial or age mixing, and some capture uncertainty in scientific understanding of disease dynamics, and/or have different simplifying assumptions. Combining estimates from multiple models to better understand the variation of these outcome measures is important to help inform decision making. We incorporate estimates of these outcome measures from a number of candidate models for specific UK nations/regions using meta analysis. Random effects models have been implemented to accommodate differing modelling approaches and assumptions between candidate models. Restricted maximum likelihood (REML) is used to estimate the heterogeneity variance parameter, with two approaches to calculate the confidence interval for the combined effect: standard Wald-type intervals and the Knapp and Hartung (KNHA) method. Approaches using REML alone and REML+KNHA provided similar ranges of variation for $R(t)$ and $r$. However, differences were observed when combining estimates on $I$, with the REML+KNHA approach providing more conservative confidence intervals. This is likely due to the limited number of candidate models contributing estimates for this outcome measure, coupled with the large variability observed between model estimates. Utilising these meta-analysis techniques has allowed for statistically robust combined estimates to be calculated for key COVID-19 outcome measures, allowing an overall assessment of the current response measures with associated uncertainty. This in turn allows timely and informed decision making based on all available information

Seizure first aid training for people with epilepsy attending emergency departments and their significant others: the SAFE intervention and feasibility RCT

Background No seizure first aid training intervention exists for people with epilepsy who regularly attend emergency departments and their significant others, despite such an intervention’s potential to reduce clinically unnecessary and costly visits. Objectives The objectives were to (1) develop Seizure first Aid training For Epilepsy (SAFE) by adapting a broader intervention and (2) determine the feasibility and optimal design of a definitive randomised controlled trial to test SAFE’s efficacy. Design The study involved (1) the development of an intervention informed by a co-design approach with qualitative feedback and (2) a pilot randomised controlled trial with follow-ups at 3, 6 and 12 months and assessments of treatment fidelity and the cost of SAFE’s delivery. Setting The setting was (1) third-sector patient support groups and professional health-care organisations and (2) three NHS emergency departments in England. Participants Participants were (1) people with epilepsy who had visited emergency departments in the prior 2 years, their significant others and emergency department, paramedic, general practice, commissioning, neurology and nursing representatives and (2) people with epilepsy aged ≥ 16 years who had been diagnosed for ≥ 1 year and who had made two or more emergency department visits in the prior 12 months, and one of their significant others. Emergency departments identified ostensibly eligible people with epilepsy from attendance records and patients confirmed their eligibility. Interventions Participants in the pilot randomised controlled trial were randomly allocated 1 : 1 to SAFE plus treatment as usual or to treatment as usual only. Main outcome measures Consent rate and availability of routine data on emergency department use at 12 months were the main outcome measures. Other measures of interest included eligibility rate, ease with which people with epilepsy could be identified and routine data secured, availability of self-reported emergency department data, self-reported emergency department data’s comparability with routine data, SAFE’s effect on emergency department use, and emergency department use in the treatment as usual arm, which could be used in sample size calculations. Results (1) Nine health-care professionals and 23 service users provided feedback that generated an intervention considered to be NHS feasible and well positioned to achieve its purpose. (2) The consent rate was 12.5%, with 53 people with epilepsy and 38 significant others recruited. The eligibility rate was 10.6%. Identifying people with epilepsy from attendance records was resource intensive for emergency department staff. Those recruited felt more stigmatised because of epilepsy than the wider epilepsy population. Routine data on emergency department use at 12 months were secured for 94.1% of people with epilepsy, but the application process took 8.5 months. Self-reported emergency department data were available for 66.7% of people with epilepsy, and people with epilepsy self-reported more emergency department visits than were captured in routine data. Most participants (76.9%) randomised to SAFE received the intervention. The intervention was delivered with high fidelity. No related serious adverse events occurred. Emergency department use at 12 months was lower in the SAFE plus treatment as usual arm than in the treatment as usual only arm, but not significantly so. Calculations indicated that a definitive trial would need ≈ 674 people with epilepsy and ≈ 39 emergency department sites. Limitations Contrary to patient statements on recruitment, routine data secured at the pilot trial’s end indicated that ≈ 40% may not have satisfied the inclusion criterion of two or more emergency department visits. Conclusions An intervention was successfully developed, a pilot randomised controlled trial conducted and outcome data secured for most participants. The consent rate did not satisfy a predetermined ‘stop/go’ level of ≥ 20%. The time that emergency department staff needed to identify eligible people with epilepsy is unlikely to be replicable. A definitive trial is currently not feasible. Future work Research to more easily identify and recruit people from the target population is required. Trial registration Current Controlled Trials ISRCTN13871327. Funding This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 39. See the NIHR Journals Library website for further project information

Severe radiographic knee osteoarthritis – does Kellgren and Lawrence grade 4 represent end stage disease? – the MOST study

SummaryObjectiveTo determine what MRI-detectable osteoarthritis features that are not visualized on radiography demonstrate progression longitudinally in Kellgren and Lawrence (KL) grade 4 knees.MethodsWe studied subjects from the Multicenter Osteoarthritis Study who had KL grade 4 knees at baseline and had baseline and 30-month MRI. Cartilage damage, bone marrow lesions (BMLs), meniscal damage, synovitis (signal changes in Hoffa fat pad), and effusion (fluid equivalent signal in the joint cavity) were semiquantitatively scored using the Whole Organ MRI Score (WORMS) system in five subregions of the medial and lateral tibiofemoral (TF) compartments. Analysis was performed for the compartment showing bone-on-bone appearance (“index”) on radiograph and also for the other TF compartment of the same knee. Synovitis and effusion were assessed for the whole knee. Changes in scores at follow-up were noted for each feature. For cartilage and BML, within-grade changes were also recorded.Results140 subjects (164 knees) were included (50% women, mean age 66.0 ± 8.6 years, mean BMI 30.4 ± 5.1 kg/m2). Longitudinally, 51 index compartments (34%) showed an increase in the sum of cartilage scores from all subregions. In the other compartment, 25% showed an increase in the sum score for cartilage damage. For BMLs in the index compartment, 50 knees (33%) showed an increase in maximum score and 32 (21%) showed a decrease. Meniscal status mostly remained stable. Effusion worsened in 36 knees (25%) and improved in 13 knees (9%). Synovitis worsened in 14 knees (10%) and improved in six knees (4%).ConclusionIn KL grade 4 knees, MRI-detected cartilage loss and fluctuation of BMLs, effusion, and synovitis occurred frequently over a 30-month period

Patella malalignment, pain and patellofemoral progression: the Health ABC Study

SummaryObjectivePatellofemoral (PF) joint osteoarthritis (OA) is strongly correlated with lower extremity disability and knee pain. Risk factors for pain and structural progression in PF OA are poorly understood. Our objective was to determine the association between patella malalignment and its relation to pain severity, and PF OA disease progression.MethodsWe conducted an analysis of data from the Health ABC knee OA study. Health ABC is a community based, multi-center cohort study of 3075 Caucasian and Black men and women aged 70–79 at enrollment. Weight bearing skyline knee X-rays were obtained in a subset (595) of subjects, with and without knee pain, at year 2 and year 5 (mean follow-up 36 months). Films were read paired, and PF osteophytes (OST) and joint space narrowing (JSN) were scored on a 0–3 scale using the Osteoarthritis Research Society International atlas. We defined progression of PF OA as any increase in JSN score. Three measures of patella malalignment were made: sulcus angle; patella tilt angle; and patella subluxation medially or laterally (bisect offset). Knee symptoms were assessed using a knee specific Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain subscale. We assessed the relationship between baseline patella malalignment and pain severity (linear regression for WOMAC) and compartment specific PF OA progression (logistic regression for dichotomous outcomes). We classified continuous measures of patella alignment into quartile groups. We performed multivariable adjusted logistic regression models, including age, gender and body mass index (BMI) to assess the relation of baseline patella alignment to the occurrence of PF JSN progression using generalized estimating equations (GEE).ResultsThe subjects had a mean age 73.6 (SD 2.9), BMI 28.8 (SD 4.9), 40.3% male, and 46% were Black. Medial displacement of the patella predisposed to medial JSN progression; odds for each quartile 1, 1.2, 1.2, 2.2 (P for trend=0.03), whilst protecting from lateral JSN progression; odds for each quartile 1, 0.7, 0.6, 0.4 (P for trend=0.0004). Increasing patella tilt protected from medial JSN progression; odds for each quartile 1, 0.8, 0.5, 0.2 (P<0.0001) and trended to increasing pain severity (P=0.09).ConclusionPatella malalignment is associated with PF disease progression. Medial displacement and tilt of the patella predisposes to medial JSN progression, whilst lateral displacement is predictive of lateral JSN progression. The influence of patella malalignment has important implications since it is potentially modifiable through footwear, taping and/or knee bracing

Inhaled mannitol for cystic fibrosis.

BackgroundSeveral agents are used to clear secretions from the airways of people with cystic fibrosis. Mannitol increases mucociliary clearance, but its exact mechanism of action is unknown. The dry powder formulation of mannitol may be more convenient and easier to use compared with established agents which require delivery via a nebuliser. Phase III trials of inhaled dry powder mannitol for the treatment of cystic fibrosis have been completed and it is now available in Australia and some countries in Europe. This is an update of a previous review.ObjectivesTo assess whether inhaled dry powder mannitol is well tolerated, whether it improves the quality of life and respiratory function in people with cystic fibrosis and which adverse events are associated with the treatment.Search methodsWe searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic databases, handsearching relevant journals and abstracts from conferences. Date of last search: 12 December 2019.Selection criteriaAll randomised controlled studies comparing mannitol with placebo, active inhaled comparators (for example, hypertonic saline or dornase alfa) or with no treatment.Data collection and analysisAuthors independently assessed studies for inclusion, carried out data extraction and assessed the risk of bias in included studies. The quality of the evidence was assessed using GRADE.Main resultsSix studies (reported in 36 unique publications) were included with a total of 784 participants. Duration of treatment in the included studies ranged from 12 days to six months, with open-label treatment for an additional six months in two of the studies. Five studies compared mannitol with control (a very low dose of mannitol or non-respirable mannitol) and the final study compared mannitol to dornase alfa alone and to mannitol plus dornase alfa. Two large studies had a similar parallel design and provided data for 600 participants, which could be pooled where data for a particular outcome and time point were available. The remaining studies had much smaller sample sizes (ranging from 22 to 95) and data could not be pooled due to differences in design, interventions and population. Pooled evidence from the two large parallel studies was judged to be of low to moderate quality and from the smaller studies was judged to be of low to very low quality. In all studies, there was an initial test to see if participants tolerated mannitol, with only those who could tolerate the drug being randomised; therefore, the study results are not applicable to the cystic fibrosis population as a whole. While the published papers did not provide all the data required for our analysis, additional unpublished data were provided by the drug's manufacturer and the author of one of the studies. Pooling the large parallel studies comparing mannitol to control, up to and including six months, lung function (forced expiratory volume at one second) measured in both mL and % predicted was significantly improved in the mannitol group compared to the control group (moderate-quality evidence). Beneficial results were observed in these studies in adults and in both concomitant dornase alfa users and non-users in these studies. In the smaller studies, statistically significant improvements in lung function were also observed in the mannitol groups compared to the non-respirable mannitol groups; however, we judged this evidence to be of low to very low quality. For the comparisons of mannitol and control, we found no consistent differences in health-related quality of life in any of the domains except for burden of treatment, which was less for mannitol up to four months in the two pooled studies of a similar design; this difference was not maintained at six months. It should be noted that the tool used to measure health-related quality of life was not designed to assess mucolytics and pooling of the age-appropriate tools (as done in some of the included studies) may not be valid so results were judged to be low to very low quality and should be interpreted with caution. Cough, haemoptysis, bronchospasm, pharyngolaryngeal pain and post-tussive vomiting were the most commonly reported side effects in both treatment groups. Where rates of adverse events could be compared, statistically no significant differences were found between mannitol and control groups; although some of these events may have clinical relevance for people with CF. For the comparisons of mannitol to dornase alfa alone and to mannitol plus dornase alfa, very low-quality evidence from a 12-week cross-over study of 28 participants showed no statistically significant differences in the recorded domains of health-related quality of life or measures of lung function. Cough was the most common side effect in the mannitol alone arm but there was no occurrence of cough in the dornase alfa alone arm and the most commonly reported reason of withdrawal from the mannitol plus dornase alfa arm was pulmonary exacerbations. In terms of secondary outcomes of the review (pulmonary exacerbations, hospitalisations, symptoms, sputum microbiology), evidence provided by the included studies was more limited. For all comparisons, no consistent statistically significant and clinically meaningful differences were observed between mannitol and control treatments (including dornase alfa).Authors' conclusionsThere is moderate-quality evidence to show that treatment with mannitol over a six-month period is associated with an improvement in some measures of lung function in people with cystic fibrosis compared to control. There is low to very low-quality evidence suggesting no difference in quality of life for participants taking mannitol compared to control. This review provides very low-quality evidence suggesting no difference in lung function or quality of life comparing mannitol to dornase alfa alone and to mannitol plus dornase alfa. The clinical implications from this review suggest that mannitol could be considered as a treatment in cystic fibrosis; but further research is required in order to establish who may benefit most and whether this benefit is sustained in the longer term. Furthermore, studies comparing its efficacy against other (established) mucolytic therapies need to be undertaken before it can be considered for mainstream practice