Effectiveness of adenoidectomy in children with recurrent upper respiratory tract infections: open randomised controlled trial

Objective To assess the effectiveness of adenoidectomy in children with recurrent upper respiratory tract infections

Take the Monkey and Run

The common marmoset (Callithrix jacchus) is a small, New World primate that is used extensively in biomedical and behavioral research. This short-lived primate, with its small body size, ease of handling, and docile temperament, has emerged as a valuable model for aging and neurodegenerative research. A growing body of research has indicated exercise, aerobic exercise especially, imparts beneficial effects to normal aging. Understanding the mechanisms underlying these positive effects of exercise, and the degree to which exercise has neurotherapeutic effects, is an important research focus. Thus, developing techniques to engage marmosets in aerobic exercise would have great advantages

Outpatient antibiotic use in Dutch infants after 10-valent pneumococcal vaccine introduction: a time-series analysis.

This population-based cohort study assesses the impact of switching from a 7-valent pneumococcal conjugate vaccine (PCV) to a 10-valent PCV on outpatient antibiotic use in Dutch infants, and whether geographical vaccination coverage modifies this association

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

Coherent scattering of near-resonant light by a dense microscopic cold atomic cloud

We measure the coherent scattering of light by a cloud of laser-cooled atoms with a size comparable to the wavelength of light. By interfering a laser beam tuned near an atomic resonance with the field scattered by the atoms, we observe a resonance with a redshift, a broadening, and a saturation of the extinction for increasing atom numbers. We attribute these features to enhanced light-induced dipole-dipole interactions in a cold, dense atomic ensemble that result in a failure of standard predictions such as the “cooperative Lamb shift”. The description of the atomic cloud by a mean-field model based on the Lorentz-Lorenz formula that ignores scattering events where light is scattered recurrently by the same atom and by a microscopic discrete dipole model that incorporates these effects lead to progressively closer agreement with the observations, despite remaining difference

Evaluation of the Serotonergic Genes htr1A, htr1B, htr2A, and slc6A4 in Aggressive Behavior of Golden Retriever Dogs

Aggressive behavior displays a high heritability in our study group of Golden Retriever dogs. Alterations in brain serotonin metabolism have been described in aggressive dogs before. Here, we evaluate whether four genes of the canine serotonergic system, coding for the serotonin receptors 1A, 1B, and 2A, and the serotonin transporter, could play a major role in aggression in Golden Retrievers. We performed mutation screens, linkage analysis, an association study, and a quantitative genetic analysis. There was no systematic difference between the coding DNA sequence of the candidate genes in aggressive and non-aggressive Golden Retrievers. An affecteds-only parametric linkage analysis revealed no strong major locus effect on human-directed aggression related to the candidate genes. An analysis of 41 single nucleotide polymorphisms (SNPs) in the 1 Mb regions flanking the genes in 49 unrelated human-directed aggressive and 49 unrelated non-aggressive dogs did not show association of SNP alleles, genotypes, or haplotypes with aggression at the candidate loci. We completed our analyses with a study of the effect of variation in the candidate genes on a collection of aggression-related phenotypic measures. The effects of the candidate gene haplotypes were estimated using the Restricted Maximum Likelihood method, with the haplotypes included as fixed effects in a linear animal model. We observed no effect of the candidate gene haplotypes on a range of aggression-related phenotypes, thus extending our conclusions to several types of aggressive behavior. We conclude that it is unlikely that these genes play a major role in the variation in aggression in the Golden Retrievers that we studied. Smaller phenotypic effects of these loci could not be ruled out with our sample size.Organismic and Evolutionary Biolog

From Spinning Silk to Spreading Saliva: Mouthpart Remodeling in Manduca sexta (Lepidoptera: Sphingidae)

As a model organism, the tobacco hornworm Manduca sexta (Linnaeus 1763) has contributed much to our knowledge of developmental processes in insects, and major developmental changes between different larval instars are generally well understood. Second and later instars of M. sexta do not produce silk, and their spinneret and accessory labial glands (=Lyonet’s glands), structures thought to be key players in silk production in other lepidopterans, are highly reduced. To our knowledge, mouthparts and labial gland morphology of the silk-producing first instar have never been described. In this study, we compared the mouthpart morphology and transcriptome profile of first and later instars of M. sexta to determine whether the loss of silk production correlates with changes in the structure of the spinneret and the labial glands, and with changes in expression of silk-related genes. We found that the first instar, unlike later instars, has a typical, silk-producing spinneret with a tube-like spigot and well developed Lyonet’s glands. Moreover, three known silk protein genes are highly expressed in the first instar but exhibit little to no expression in the embryo or later instars. Thus, the changes in morphology and gene expression presented here, coinciding with changes in larval behavior from silk production to saliva spreading, further our understanding of the developmental processes underlying this transition in this model organism

Optimising pain management in children with acute otitis media through a primary care-based multifaceted educational intervention: study protocol for a cluster randomised controlled trial.

Whilst current guidelines highlight the importance of pain management for children with acute otitis media (AOM), there is evidence to suggest that this is not implemented in everyday practice. We have developed a primary care-based multifaceted educational intervention to optimise pain management in children with AOM, and we trial its clinical and cost effectiveness

Far-infrared study of the Jahn-Teller distorted C60 monoanion in C60 tetraphenylphosphoniumiodide

We report high-resolution far-infrared transmission measurements on C(60)-tetraphenylphosphoniumiodide as a function of temperature. In the spectral region investigated (20-650 cm(-1)), we assign intramolecular modes of the C(60) monoanion and identify low-frequency combination modes. The well-known F(1u)(1) and F(1u)(2) modes are split into doublers at room temperature, indicating a D(5d) or D(3d) distorted ball. This result is consistent with a dynamic Jahn-Teller effect in the strong-coupling limit or with a static distortion stabilized by low-symmetry perturbations. The appearance of silent odd modes is in keeping with symmetry reduction of the hall, while activation of even modes is attributed to interband electron-phonon coupling and orientational disorder in the fulleride salt. Temperature dependences reveal a weak transition in the region 125-150 K in both C(60)(-) and counterion modes, indicating a bulk, rather than solely molecular, effect. Anomalous softening (with decreasing temperature) in several modes may correlate with the radial character of those vibrations. [S0163-1829(98)03245-7]

Addressing resistance to antibiotics in systematic reviews of antibiotic interventions

Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews