A seven-planet resonant chain in TRAPPIST-1

The TRAPPIST-1 system is the first transiting planet system found orbiting an ultra-cool dwarf star1. At least seven planets similar to Earth in radius were previously found to transit this host star2. Subsequently, TRAPPIST-1 was observed as part of the K2 mission and, with these new data, we report the measurement of an 18.77 d orbital period for the outermost transiting planet, TRAPPIST-1h, which was unconstrained until now. This value matches our theoretical expectations based on Laplace relations3 and places TRAPPIST-1h as the seventh member of a complex chain, with three-body resonances linking every member. We find that TRAPPIST-1h has a radius of 0.727 R⊕ and an equilibrium temperature of 169 K. We have also measured the rotational period of the star at 3.3 d and detected a number of flares consistent with a low-activity, middle-aged, late M dwarf

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Hemodynamic impact of isobaric levobupivacaine versus hyperbaric bupivacaine for subarachnoid anesthesia in patients aged 65 and older undergoing hip surgery

BackgroundThe altered hemodynamics, and therefore the arterial hypotension is the most prevalent adverse effect after subarachnoid anesthesia. The objective of the study was to determine the exact role of local anesthetic selection underlying spinal anesthesia-induced hypotension in the elderly patient. We conducted a descriptive, observational pilot study to assess the hemodynamic impact of subarachnoid anesthesia with isobaric levobupivacaine versus hyperbaric bupivacaine for hip fracture surgery.DescriptionHundred twenty ASA status I-IV patients aged 65 and older undergoing hip fracture surgery were enrolled. The primary objective of our study was to compare hemodynamic effects based on systolic blood pressure (SBP) and dyastolic blood pressure (DBP) values, heart rate (HR) and hemoglobin (Hb) and respiratory effects based on partial oxygen saturation (SpO2%) values. The secondary objective was to assess potential adverse events with the use of levobupivacaine versus bupivacaine. Assessments were performed preoperatively, at 30 minutes into surgery, at the end of anesthesia and at 48 hours and 6 months after surgery.Among intraoperative events, the incidence of hypotension was statistically significantly higher (p <0.05) in group BUPI (38.3%) compared to group LEVO (13.3%). There was a decrease (p <0.05) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 30 minutes intraoperatively (19% in group BUPI versus 17% in group LEVO). SpO2% increased at 30 minutes after anesthesia onset (1% in group BUPI versus 1.5% in group LEVO). Heart rate (HR) decreased at 30 minutes after anesthesia onset (5% in group BUPI versus 9% in group L). Hemoglobin (Hb) decreased from time of operating room (OR) admission to the end of anesthesia (9.3% in group BUPI versus 12.5% in group LEVO). The incidence of red blood cell (RBC) transfusion was 13.3% in group BUPI versus 31.7% in group LEVO, this difference was statistically significant. Among postoperative events, the incidence of congestive heart failure (CHF) was significantly higher in group BUPI (8,3%). At 6 months after anesthesia, no differences were found.ConclusionsGiven the hemodynamic stability and lower incidence of intraoperative hypotension observed, levobupivacaine could be the agent of choice for subarachnoid anesthesia in elderly patients

Refining the transit-timing and photometric analysis of TRAPPIST-1: Masses, Radii, densities, dynamics, and ephemerides

We have collected transit times for the TRAPPIST-1 system with the Spitzer Space Telescope over four years. We add to these ground-based, HST and K2 transit time measurements, and revisit an N-body dynamical analysis of the seven-planet system using our complete set of times from which we refine the mass ratios of the planets to the star. We next carry out a photodynamical analysis of the Spitzer light curves to derive the density of the host star and the planet densities. We find that all seven planets' densities may be described with a single rocky mass-radius relation which is depleted in iron relative to Earth, with Fe 21 wt% versus 32 wt% for Earth, and otherwise Earth-like in composition. Alternatively, the planets may have an Earth-like composition, but enhanced in light elements, such as a surface water layer or a core-free structure with oxidized iron in the mantle. We measure planet masses to a precision of 3-5%, equivalent to a radial-velocity (RV) precision of 2.5 cm/sec, or two orders of magnitude more precise than current RV capabilities. We find the eccentricities of the planets are very small; the orbits are extremely coplanar; and the system is stable on 10 Myr timescales. We find evidence of infrequent timing outliers which we cannot explain with an eighth planet; we instead account for the outliers using a robust likelihood function. We forecast JWST timing observations, and speculate on possible implications of the planet densities for the formation, migration and evolution of the planet system

Treatment and Intervention for Opiate Dependence in the United Kingdom:Lessons from Triumph and Failure

The history of opiate treatment in the United Kingdom (UK) since the early 1980s is a rich source of learning about the benefits and pitfalls of drug treatment policy. We present five possible lessons to be learnt about how factors outside the clinic, including government, charities and researchers can influence treatment and outcomes. First, do not let a crisis go to waste. The philosophical shift from abstinence to harm reduction in the 1980s, in response to an HIV outbreak in injecting users, facilitated expansion in addiction services and made a harm reduction approach more acceptable. Second, studies of drug-related deaths can lead to advances in care. By elucidating the pattern of mortality, and designing interventions to address the causes, researchers have improved patient safety in certain contexts, though significant investment in Scotland has not arrested rising mortality. Third, collection of longitudinal data and its use to inform clinical guidelines, as pursued from the mid-1990s, can form an enduring evidence base and shape policy, sometimes in unintended ways. Fourth, beware of the presentation of harm reduction and recovery as in conflict. At the least, this reduces patient choice, and at worst, it has caused some services to be redesigned in a manner that jeopardises patient safety. Fifth, the relationship between the third and state sectors must be carefully nurtured. In the UK, early collaboration has been replaced by competition, driven by changes in funding, to the detriment of service provision

Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains

The ISWI family of ATP-dependent chromatin remodelers represses transcription by changing nucleosome positioning. The interactions with extranucleosomal DNA and the requirement of a minimal length of extranucleosomal DNA by ISWI mediate the spacing of nucleosomes. ISW2 from Saccharomyces cerevisiae, a member of the ISWI family, has a conserved domain called SLIDE (SANT-like ISWI domain), whose binding to extranucleosomal DNA ~19 bp from the edge of nucleosomes is required for efficiently pushing DNA into nucleosomes and maintaining the unidirectional movement of nucleosomes, as reported here. Loss of SLIDE binding does not perturb ATPase domain binding to the SHL2 site of nucleosomes or its initial movement of DNA inside of nucleosomes. ISW2 has therefore two distinct roles in mobilizing nucleosomes, with the ATPase domain translocating and moving DNA inside nucleosomes, and the SLIDE domain facilitating the entry of linker DNA into nucleosomes

Effects of low power laser irradiation on bone healing in animals: a meta-analysis

<p>Abstract</p> <p>Purpose</p> <p>The meta-analysis was performed to identify animal research defining the effects of low power laser irradiation on biomechanical indicators of bone regeneration and the impact of dosage.</p> <p>Methods</p> <p>We searched five electronic databases (MEDLINE, EMBASE, PubMed, CINAHL, and Cochrane Database of Randomised Clinical Trials) for studies in the area of laser and bone healing published from 1966 to October 2008. Included studies had to investigate fracture healing in any animal model, using any type of low power laser irradiation, and use at least one quantitative biomechanical measures of bone strength. There were 880 abstracts related to the laser irradiation and bone issues (healing, surgery and assessment). Five studies met our inclusion criteria and were critically appraised by two raters independently using a structured tool designed for rating the quality of animal research studies. After full text review, two articles were deemed ineligible for meta-analysis because of the type of injury method and biomechanical variables used, leaving three studies for meta-analysis. Maximum bone tolerance force before the point of fracture during the biomechanical test, 4 weeks after bone deficiency was our main biomechanical bone properties for the Meta analysis.</p> <p>Results</p> <p>Studies indicate that low power laser irradiation can enhance biomechanical properties of bone during fracture healing in animal models. Maximum bone tolerance was statistically improved following low level laser irradiation (average random effect size 0.726, 95% CI 0.08 - 1.37, p 0.028). While conclusions are limited by the low number of studies, there is concordance across limited evidence that laser improves the strength of bone tissue during the healing process in animal models.</p

Neck dissection and post-operative chemotherapy with dimethyl triazeno imidazole carboxamide and cisplatin protocol are useful for oral mucosal melanoma

<p>Abstract</p> <p>Background</p> <p>Oral mucosal melanoma (OMM) is a clinically rare disease with poor prognosis. Various treatment methods have been investigated with the aim of improving the prognosis. This study aimed to analyze the data of a single institution in the management of OMM.</p> <p>Methods</p> <p>A total of 78 consecutive OMM patients were included in this retrospective study. The intraoral lesion was treated either by cryotherapy, surgery or both; the neck was treated by neck dissection or observation; post-operative chemotherapy with dimethyl triazeno imidazole carboxamide and cisplatin was performed in some patients. The Kaplan-Meier method was used for statistical analysis.</p> <p>Results</p> <p>Among the 78 patients, there were 50 males and 28 females with an average age of 53.8 years (ranging from 27 to 85 years). The most common sites of OMM were the hard palate and gingiva. The main cause of death in OMM was distant metastasis. No significant difference was found between the intraoral/cervical lesion recurrence/post-operative distant metastasis and the intraoral lesion site/biopsy method/treatment method. The metastasis rate of cervical lymph node was high in the OMM patients, even in the patients with clinically negative necks. Cervical lesion recurrence was correlated with N stage and intraoral lesion recurrence. The survival period was longer in the patients with T3 staging, clinical stage III disease, with post-operative chemotherapy and without post-operative distant metastasis when compared to those patients with T4a staging, clinical stage IV disease, without post-operative chemotherapy and with post-operative distant metastasis.</p> <p>Conclusions</p> <p>Radical surgery including wide intraoral resection and neck dissection is recommended for OMM patients. Post-operative chemotherapy may also be beneficial for both primary and recurrent OMM patients.</p

Intercalation of small molecules into DNA in chromatin is primarily controlled by superhelical constraint

The restricted access of regulatory factors to their binding sites on DNA wrapped around the nucleosomes is generally interpreted in terms of molecular shielding exerted by nucleosomal structure and internucleosomal interactions. Binding of proteins to DNA often includes intercalation of hydrophobic amino acids into the DNA. To assess the role of constrained superhelicity in limiting these interactions, we studied the binding of small molecule intercalators to chromatin in close to native conditions by laser scanning cytometry. We demonstrate that the nucleosome-constrained superhelical configuration of DNA is the main barrier to intercalation. As a result, intercalating compounds are virtually excluded from the nucleosome-occupied regions of the chromatin. Binding of intercalators to extranucleosomal regions is limited to a smaller degree, in line with the existence of net supercoiling in the regions comprising linker and nucleosome free DNA. Its relaxation by inducing as few as a single nick per ~50 kb increases intercalation in the entire chromatin loop, demonstrating the possibility for long-distance effects of regulatory potential