Homogenization of an ensemble of interacting resonant scatterers

We study theoretically the concept of homogenization in optics using an ensemble of randomly distributed resonant stationary atoms with density $\rho$. The ensemble is dense enough for the usual condition for homogenization, viz. $\rho\lambda^3 \gg 1$, to be reached. Introducing the coherent and incoherent scattered powers, we define two criteria to define the homogenization regime. We find that when the excitation field is tuned in a broad frequency range around the resonance, none of the criteria for homogenization is fulfilled, meaning that the condition $\rho\lambda^3\gg 1$ is not sufficient to characterize the homogenized regime around the atomic resonance. We interpret these results as a consequence of the light-induced dipole-dipole interactions between the atoms, which implies a description of scattering in terms of collective modes rather than as a sequence of individual scattering events. Finally, we show that, although homogenization can never be reached for a dense ensemble of randomly positioned laser-cooled atoms around resonance, it becomes possible if one introduces spatial correlations in the positions of the atoms or non-radiative losses, such as would be the case for organic molecules or quantum dots coupled to a phonon bath.Comment: 9 pages, 5 figures. Corrected mistakes in reference

A Combination of Metabolomics and Machine Learning Results in the Identification of a New Cyst Nematode Hatching Factor

Potato Cyst Nematodes (PCNs) are an economically important pest for potato growers. A crucial event in the life cycle of the nematode is hatching, after which the juvenile will move toward the host root and infect it. The hatching of PCNs is induced by known and unknown compounds in the root exudates of host plant species, called hatching factors (HFs, induce hatching independently), such as solanoeclepin A (solA), or hatching stimulants (HSs, enhance hatching activity of HFs). Unraveling the identity of unknown HSs and HFs and their natural variation is important for the selection of cultivars that produce low amounts of HFs and HSs, thus contributing to more sustainable agriculture. In this study, we used a new approach aimed at the identification of new HFs and HSs for PCNs in potato. Hereto, root exudates of a series of different potato cultivars were analyzed for their PCN hatch-inducing activity and their solA content. The exudates were also analyzed using untargeted metabolomics, and subsequently the data were integrated using machine learning, specifically random forest feature selection, and Pearson’s correlation testing. As expected, solA highly correlates with hatching. Furthermore, this resulted in the discovery of a number of metabolite features present in the root exudate that correlate with hatching and solA content, and one of these is a compound of m/z 526.18 that predicts hatching even better than solA with both data methods. This compound’s involvement in hatch stimulation was confirmed by the fractionation of three representative root exudates and hatching assays with the resulting fractions. Moreover, the compound shares mass fragmentation similarity with solA, and we therefore assume it has a similar structure. With this work, we show that potato likely produces a solA analogue, and we contribute to unraveling the hatch-inducing cocktail exuded by plant roots

Impact of acute otitis media clinical practice guidelines on antibiotic and analgesic prescriptions: a systematic review

BACKGROUND: Clinical practice guidelines focusing on judicious use of antibiotics for childhood acute otitis media (AOM) have been introduced in many countries around the world. OBJECTIVE: To systematically review the effects of these guidelines on the prescription of antibiotics and analgesics for children with AOM. METHODS: Systematic searches of PubMed, Embase and Cochrane Library from inception to 6 June 2017 using broad search terms. Studies specifically aimed at evaluating the effects of introduction of national AOM practice guidelines on type of antibiotic and/or analgesic prescriptions were included, irrespective of design, setting or language. The Risk Of Bias In Non-randomized Studies of Interventions tool was used to assess risk of bias. RESULTS: Of 411 unique records retrieved, seven studies conducted in six different countries (France, Italy, Spain, Sweden, UK and USA (twice)) compared data before and after guideline introduction. All studies had an observational design, using longitudinal data of children aged under 15 years (n=200-4.6 million) from either routine care, insurance databases or electronic surveys. Risk of bias of all studies was judged serious to critical.Of the five studies reporting on antibiotic prescription rates, three showed a decline of 5%-12% up to 3 years after guideline introduction and two found no or negligible effect. In one US study, the initial 9% decline decreased to 5% after 4-6 years. The recommended first choice antibiotic was prescribed more frequently (9%-58% increase) after guideline introduction in four out of five studies reporting on this outcome. Analgesic prescription rates for AOM were reported in one US study and increased from 14% to 24% after guideline introduction. CONCLUSION: Based upon what is published, the effects of introduction of national clinical practice guidelines on antibiotic and analgesic prescribing for children with AOM seem modest at the most. REGISTRATION: PROSPERO: CRD42016050976

Aural toilet (ear cleaning) for chronic suppurative otitis media

BACKGROUND: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection (involving more than one micro-organism) of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Aural toileting is a term describing a number of processes for manually cleaning the ear. Techniques used may include dry mopping (with cotton wool or tissue paper), suction clearance (typically under a microscope) or irrigation (using manual or automated syringing). Dry mopping may be effective in removing mucopurulent discharge. Compared to irrigation or microsuction it is less effective in removing epithelial debris or thick pus. Aural toileting can be used alone or in addition to other treatments for CSOM, such as antibiotics or topical antiseptics. OBJECTIVES: To assess the effects of aural toilet procedures for people with CSOM. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL via the Cochrane Register of Studies); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 16 March 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with at least a one-week follow-up involving people (adults and children) who had chronic ear discharge of unknown cause or CSOM, where the ear discharge had continued for more than two weeks. We included any aural toileting method as the intervention, at any frequency and for any duration. The comparisons were aural toileting compared with a) placebo or no intervention, and b) any other aural toileting method. We analysed trials in which background treatments were used in both arms (e.g. topical antiseptics or topical antibiotics) separately. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methodological procedures. We used GRADE to assess the certainty of the evidence for each outcome. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not), measured at between one week and up to two weeks, two weeks to up to four weeks, and after four weeks; health-related quality of life using a validated instrument; and ear pain (otalgia) or discomfort or local irritation. Secondary outcomes were hearing, serious complications, and the adverse events of ear bleeding and dizziness/vertigo/balance problems. MAIN RESULTS: We included three studies with a total of 431 participants (465 ears), reporting on two comparisons. Two studies included only children with CSOM in the community (351 participants) and the other study (80 participants) included children and adults with chronic ear discharge for at least six weeks. None of the included studies reported the outcomes of health-related quality of life, ear pain or the adverse event of ear bleeding. Daily aural toileting (dry mopping) versus no treatment Two studies (351 children; 370 ears) compared daily dry mopping with no treatment. Neither study presented results for resolution of ear discharge at between one and up to two weeks or between two to four weeks. For resolution of ear discharge after four weeks, one study reported the results per person. We are very uncertain whether there is a difference at 16 weeks (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.60 to 1.72; 1 study; 217 participants) because the certainty of the evidence is very low. No results were reported for the adverse events of dizziness, vertigo or balance problems. Only one study reported serious complications, but it was not clear which group these patients were from, or whether the complications occurred pre- or post-treatment. One study reported hearing, but the results were presented by treatment outcome rather than by treatment group so it is not possible to determine whether there is a difference between the two groups. Daily aural toileting versus single aural toileting on top of topical ciprofloxacin One study (80 participants; 95 ears) compared daily aural toileting (suction) with administration of topical antibiotic (ciprofloxacin) ear drops in a clinic, to a single aural toileting (suction) episode followed by daily self-administered topical antibiotic drops, in participants of all ages. We are unsure whether there is a difference in resolution of ear discharge at between one and up to two weeks (RR 1.09, 95% CI 0.91 to 1.30; 1 study; 80 participants) because the certainty of the evidence is very low. There were no results reported for resolution of ear discharge at between two to four weeks. The results for resolution of ear discharge after four weeks were presented by ear, not person, and could not be adjusted to by person. One patient in the group with single aural toileting and self administration of topical antibiotic ear drops reported the adverse event of dizziness, which the authors attributed to the use of cold topical ciprofloxacin. It is very uncertain whether there is a difference between the groups (RR 0.33, 95% CI 0.01 to 7.95; 1 study; 80 participants, very low-certainty). No results were reported for the other adverse events of vertigo or balance problems, or for serious complications. The authors only reported qualitatively that there was no difference between the two groups in hearing results (very low-certainty). AUTHORS' CONCLUSIONS: We are very uncertain whether or not treatment with aural toileting is effective in resolving ear discharge in people with CSOM, due to a lack of data and the poor quality of the available evidence. We also remain uncertain about other outcomes, including adverse events, as these were not well reported. Similarly, we are very uncertain whether daily suction clearance, followed by antibiotic ear drops administered at a clinic, is better than a single episode of suction clearance followed by self-administration of topical antibiotic ear drops

Larotrectinib efficacy and safety in TRK fusion cancer: An expanded clinical dataset showing consistency in an age and tumor agnostic approach

Background: TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19thFeb 2018. Methods: Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials (NCT02122913, NCT02637687, and NCT02576431) were eligible.Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed using RECIST version 1.1. Results: As of Feb 2018, by independent review, 6 PRs in the PAS deepened to CRs. The median duration of response (DoR) and progression-free survival in the PAS had still not been reached, with 12.9 months median follow-up. At 1 year, 69% of responses were ongoing, 58% of patients remained progression-free and 90% of patients were alive. An additional 19 children and 25 adults (age range, 0.1-78 years) with TRK fusion cancer were enrolled after the PAS, and included cancers of the salivary gland, thyroid, lung, colon, melanoma, sarcoma, GIST and congenital mesoblastic nephroma. In 35 evaluable patients, the ORR by investigator assessment was 74% (5 CR, 21 PR, 6 SD, 2 PD, 1 not determined). In these patients, with median follow-up of 5.5 months, median DoR had not yet been reached, and 88% of responses were ongoing at 6 months, consistent with the PAS. Adverse events (AEs) were predominantly grade 1, with dizziness, increased AST/ALT, fatigue, nausea and constipation the most common AEs reported in ≥ 10% of patients. No AE of grade 3 or 4 related to larotrectinib occurred in more than 5% of patients. Conclusions: TRK fusions are detected in a broad range of tumor types. Larotrectinib is an effective age- and tumor-agnostic treatment for TRK fusion cancer with a positive safety profile. Screening patients for NTRK gene fusions in solid- and brain tumors should be actively considered

Prognostic factors for outcomes of idiopathic sudden sensorineural hearing loss: protocol for the SeaSHeL national prospective cohort study

INTRODUCTION: The mainstay of treatment for idiopathic sudden sensorineural hearing loss (SSNHL) includes oral steroids, intratympanic steroid injections or a combination of both. The National Institute for Health and Care Excellence, in their recent hearing loss guidelines, highlighted the paucity of evidence assessing the comparative effectiveness of these treatments; and the National Institute for Health Research (NIHR) Health Technology Assessment Programme has since released a commissioned call for a trial to identify the most effective route of administration of steroids as a first-line treatment for idiopathic SSNHL. For such trials to be run effectively, reliable information is needed on patients with SSNHL: where they present, numbers, demographics, treatment pathways, as well as outcomes. This study will collect these data in a nationwide cohort study of patients presenting with SSNHL across 97 National Health Service (NHS) trusts. The study will be delivered through ear, nose and throat (ENT) trainee networks, the NIHR Clinical Research Network (CRN) Audiology Champions and the NIHR CRN. Importantly, this study will also provide a dataset to develop a prognostic model to predict recovery for patients with idiopathic SSNHL. The study objectives are to: (1) map the patient pathway and identify the characteristics of adult patients presenting to NHS ENT and hearing services with SSNHL, (2) develop a prognostic model to predict recovery for patients with idiopathic SSNHL and (3) establish the impact of idiopathic SSNHL on patients' quality of life (QoL). METHODS AND ANALYSIS: Study design: national multicentre prospective cohort study across 97 NHS trusts. INCLUSION CRITERIA: adult patients presenting to NHS ENT and hearing services with SSNHL. OUTCOMES: change in auditory function; change in QoL score. ANALYSIS: multivariable prognostic model, using prespecified candidate predictors. Mean change in QoL scores will be calculated from initial presentation to follow-up. ETHICS AND DISSEMINATION: Health Research Authority and NHS Research Ethics Committee approved the study. Publication will be on behalf of study sites and collaborators. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04108598)

The polymer phase of the TDAE-C60_{60} organic ferromagnet

The high-pressure Electron Spin Resonance (ESR) measurements were preformed on TDAE-C$_{60}$ single crystals and stability of the polymeric phase was established in the $P - T$ parameter space. At 7 kbar the system undergoes a ferromagnetic to paramagnetic phase transition due to the pressure-induced polymerization. The polymeric phase remains stable after the pressure release. The depolymerization of the pressure-induced phase was observed at the temperature of 520 K. Below room temperature, the polymeric phase behaves as a simple Curie-type insulator with one unpaired electron spin per chemical formula. The TDAE$^+$ donor-related unpaired electron spins, formerly ESR-silent, become active above the temperature of 320 K and the Curie-Weiss behavior is re-established.Comment: Submitted to Phys. Rev.

A meta-analytic review of stand-alone interventions to improve body image

Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions