A new primary dental care service compared with standard care for child and family to reduce the re-occurrence of childhood dental caries (Dental RECUR): study protocol for a randomised controlled trial

Background: In England and Scotland, dental extraction is the single highest cause of planned admission to the hospital for children under 11 years. Traditional dental services have had limited success in reducing this disease burden. Interventions based on motivational interviewing have been shown to impact positively dental health behaviours and could facilitate the prevention of re-occurrence of dental caries in this high-risk population. The objective of the study is to evaluate whether a new, dental nurse-led service, delivered using a brief negotiated interview based on motivational interviewing, is a more cost-effective service than treatment as usual, in reducing the re-occurrence of dental decay in young children with previous dental extractions. Methods/Design: This 2-year, two-arm, multicentre, randomised controlled trial will include 224 child participants, initially aged 5 to 7 years, who are scheduled to have one or more primary teeth extracted for dental caries under general anaesthesia (GA), relative analgesia (RA: inhalation sedation) or local anaesthesia (LA). The trial will be conducted in University Dental Hospitals, Secondary Care Centres or other providers of dental extraction services across the United Kingdom. The intervention will include a brief negotiated interview (based on the principles of motivational interviewing) delivered between enrolment and 6 weeks post-extraction, followed by directed prevention in primary dental care. Participants will be followed up for 2 years. The main outcome measure will be the dental caries experienced by 2 years post-enrolment at the level of dentine involvement on any tooth in either dentition, which had been caries-free at the baseline assessment. Discussion: The participants are a hard-to-reach group in which secondary prevention is a challenge. Lack of engagement with dental care makes the children and their families scheduled for extraction particularly difficult to recruit to an RCT. Variations in service delivery between sites have also added to the challenges in implementing the Dental RECUR protocol during the recruitment phase. Trial registration: ISRCTN24958829 (date of registration: 27 September 2013), Current protocol version: 5.0

Anticipatory governance for social-ecological resilience

Anticipation is increasingly central to urgent contemporary debates, from climate change to the global economic crisis. Anticipatory practices are coming to the forefront of political, organizational, and citizens’ society. Research into anticipation, however, has not kept pace with public demand for insights into anticipatory practices, their risks and uses. Where research exists, it is deeply fragmented. This paper seeks to identify how anticipation is defined and understood in the literature and to explore the role of anticipatory practice to address individual, social, and global challenges. We use a resilience lens to examine these questions. We illustrate how varying forms of anticipatory governance are enhanced by multi-scale regional networks and technologies and by the agency of individuals, drawing from an empirical case study on regional water governance of Malaren, Sweden. Finally, we discuss how an anticipatory approach can inform adaptive institutions, decision making, strategy formation, and societal resilience

Similarity of Traveling-Wave Delays in the Hearing Organs of Humans and Other Tetrapods

Transduction of sound in mammalian ears is mediated by basilar-membrane waves exhibiting delays that increase systematically with distance from the cochlear base. Most contemporary accounts of such “traveling-wave” delays in humans have ignored postmortem basilar-membrane measurements in favor of indirect in vivo estimates derived from brainstem-evoked responses, compound action potentials, and otoacoustic emissions. Here, we show that those indirect delay estimates are either flawed or inadequately calibrated. In particular, we argue against assertions based on indirect estimates that basilar-membrane delays are much longer in humans than in experimental animals. We also estimate in vivo basilar-membrane delays in humans by correcting postmortem measurements in humans according to the effects of death on basilar-membrane vibrations in other mammalian species. The estimated in vivo basilar-membrane delays in humans are similar to delays in the hearing organs of other tetrapods, including those in which basilar membranes do not sustain traveling waves or that lack basilar membranes altogether

In Vitro Surfactant Structure-Toxicity Relationships: Implications for Surfactant Use in Sexually Transmitted Infection Prophylaxis and Contraception

Background The need for woman-controlled, cheap, safe, effective, easy-to-use and easy-to-store topical applications for prophylaxis against sexually transmitted infections (STIs) makes surfactant-containing formulations an interesting option that requires a more fundamental knowledge concerning surfactant toxicology and structure-activity relationships. Methodology/Principal Findings We report in vitro effects of surfactant concentration, exposure time and structure on the viability of mammalian cell types typically encountered in the vagina, namely, fully polarized and confluent epithelial cells, confluent but non-polarized epithelial-like cells, dendritic cells, and human sperm. Representatives of the different families of commercially available surfactants – nonionic (Triton X-100 and monolaurin), zwitterionic (DDPS), anionic (SDS), and cationic (CnTAB (n = 10 to 16), C12PB, and C12BZK) – were examined. Triton X-100, monolaurin, DDPS and SDS were toxic to all cell types at concentrations around their critical micelle concentration (CMC) suggesting a non-selective mode of action involving cell membrane destabilization and/or destruction. All cationic surfactants were toxic at concentrations far below their CMC and showed significant differences in their toxicity toward polarized as compared with non-polarized cells. Their toxicity was also dependent on the chemical nature of the polar head group. Our results suggest an intracellular locus of action for cationic surfactants and show that their structure-activity relationships could be profitably exploited for STI prophylaxis in vaginal gel formulations. The therapeutic indices comparing polarized epithelial cell toxicity to sperm toxicity for all surfactants examined, except C12PB and C12BZK, does not justify their use as contraceptive agents. C12PB and C12BZK are shown to have a narrow therapeutic index recommending caution in their use in contraceptive formulations. Conclusions/Significance Our results contribute to understanding the mechanisms involved in surfactant toxicity, have a predictive value with regard to their safety, and may be used to design more effective and less harmful surfactants for use in topical applications for STI prophylaxis.Foundation for Science and Technology of the Portuguese Ministry of Science and Higher Educatio

Clinical chronobiology: a timely consideration in critical care medicine

A fundamental aspect of human physiology is its cyclical nature over a 24-h period, a feature conserved across most life on Earth. Organisms compartmentalise processes with respect to time in order to promote survival, in a manner that mirrors the rotation of the planet and accompanying diurnal cycles of light and darkness. The influence of circadian rhythms can no longer be overlooked in clinical settings; this review provides intensivists with an up-to-date understanding of the burgeoning field of chronobiology, and suggests ways to incorporate these concepts into daily practice to improve patient outcomes. We outline the function of molecular clocks in remote tissues, which adjust cellular and global physiological function according to the time of day, and the potential clinical advantages to keeping in time with them. We highlight the consequences of "chronopathology", when this harmony is lost, and the risk factors for this condition in critically ill patients. We introduce the concept of "chronofitness" as a new target in the treatment of critical illness: preserving the internal synchronisation of clocks in different tissues, as well as external synchronisation with the environment. We describe methods for monitoring circadian rhythms in a clinical setting, and how this technology may be used for identifying optimal time windows for interventions, or to alert the physician to a critical deterioration of circadian rhythmicity. We suggest a chronobiological approach to critical illness, involving multicomponent strategies to promote chronofitness (chronobundles), and further investment in the development of personalised, time-based treatment for critically ill patients

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society

Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO’s second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h95%0=3.47×10−25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering