A new clinical index scale for measuring secondary alveolar bone grafting success based on canine eruption.

Objectives: To develop a reproducible, reliable clinical index of alveolar bone grafting (ABG) outcome based on the eruption position of the cleft canine tooth and determine the association between eruption position and radiographic outcome at 6 months post-grafting.

Methods: Children with complete, non-syndromic, unilateral/bilateral cleft lip and palate in the West of Scotland were identified. Post-ABG radiographic outcome (Kindelan index) and canine eruption position in children with a cleft of the alveolus who had undergone ABG were documented.

Discovery of a highly potent, selective, orally bioavailable inhibitor of KAT6A/B histone acetyltransferases with efficacy against KAT6A-high ER+ breast cancer.

KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate histone H3K23 and exert an oncogenic role in several tumor types including breast cancer where KAT6A is frequently amplified/overexpressed. However, pharmacologic targeting of KAT6A to achieve therapeutic benefit has been a challenge. Here we describe identification of a highly potent, selective, and orally bioavailable KAT6A/KAT6B inhibitor CTx-648 (PF-9363), derived from a benzisoxazole series, which demonstrates anti-tumor activity in correlation with H3K23Ac inhibition in KAT6A over-expressing breast cancer.

Idiopathic Fistula in an Unrepaired Submucous Cleft Palate.

Palatal fistulae are a recognised complication in individuals who have undergone surgical repair of a cleft palate, however, congenital or idiopathic palatal fistulae are rare. This report discusses the presentation and treatment of a 16-year-old female with a submucous cleft palate, who presented with a recent onset change in speech and evidence of a new palatal fistula. There was no history of recent infection or known trauma, and the patient had not undergone any previous palatal surgery.

The Simons Observatory: A large-diameter truss for a refracting telescope cooled to 1 K.

We present the design and measured performance of a new carbon fiber strut design that is used in a cryogenically cooled truss for the Simons Observatory small aperture telescope. The truss consists of two aluminum 6061 rings separated by 24 struts. Each strut consists of a central carbon fiber tube fitted with two aluminum end caps.

The Cleft Lip Education with Augmented Reality (CLEAR) VR Phase 2 Trial: A Pilot Randomized Crossover Trial of a Novel Patient Information Leaflet.

Background: The Cleft Lip Education with Augmented Reality (CLEAR) project centers around the use of augmented reality (AR) in patient leaflets, as a visual means to overcome the "health literacy" gap. This trial followed Virtual Reality (VR CORE) guidelines for VR Phase 2 (Pilot) trials.

Methods: Participants included families of children treated for Cleft Lip and Palate at the Royal Hospital for Children, Glasgow.

Five-year prospective fistula audit in a single center. TIG training negates consultant learning curve, but surgeons should beware the mid-range palatal defect.

The aim of primary palatoplasty is to achieve optimum speech with minimal morbidity. Symptomatic fistulae are well-recognised complications of palatoplasty and may require additional surgical intervention, increasing the burden of care. Our aims were to better understand fistula experience in our unit and compare fistula rates between an established consultant and a newly appointed training interface group (TIG) trained consultant.

Preclinical small molecule WEHI-7326 overcomes drug resistance and elicits response in patient-derived xenograft models of human treatment-refractory tumors.

Targeting cell division by chemotherapy is a highly effective strategy to treat a wide range of cancers. However, there are limitations of many standard-of-care chemotherapies: undesirable drug toxicity, side-effects, resistance and high cost. New small molecules which kill a wide range of cancer subtypes, with good therapeutic window in vivo, have the potential to complement the current arsenal of anti-cancer agents and deliver improved safety profiles for cancer patients.

The Simons Observatory: metamaterial microwave absorber and its cryogenic applications.

Controlling stray light at millimeter wavelengths requires special optical design and selection of absorptive materials that should be compatible with cryogenic operating environments. While a wide selection of absorptive materials exists, these typically exhibit high indices of refraction and reflect/scatter a significant fraction of light before absorption. For many lower index materials such as commercial microwave absorbers, their applications in cryogenic environments are challenging.

The Simons Observatory: modeling optical systematics in the Large Aperture Telescope.

We present geometrical and physical optics simulation results for the Simons Observatory Large Aperture Telescope. This work was developed as part of the general design process for the telescope, allowing us to evaluate the impact of various design choices on performance metrics and potential systematic effects. The primary goal of the simulations was to evaluate the final design of the reflectors and the cold optics that are now being built.

Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are an established treatment in estrogen receptor-positive breast cancer and are currently in clinical development in melanoma, a tumor that exhibits high rates of CDK4 activation. We analyzed melanoma cells with acquired resistance to the CDK4/6 inhibitor palbociclib and demonstrate that the activity of PRMT5, a protein arginine methyltransferase and indirect target of CDK4, is essential for CDK4/6 inhibitor sensitivity. By indirectly suppressing PRMT5 activity, palbociclib alters the pre-mRNA splicing of MDM4, a negative regulator of p53, leading to decreased MDM4 protein expression and subsequent p53 activation.

Highly fluorescent and HDAC6 selective scriptaid analogues.

Fluorescent scriptaid analogues with excellent HDAC6 selectivity (HDAC1/6 > 500) and potency (HDAC6 IC < 5 nM) have been synthesised and evaluated. The highly fluorescent nature of the compounds (up to Φ = 0.83 in DMSO and 0.

Secondary Alveolar Bone Grafting (CLEFTSiS) 2007-2010.

Objective To determine whether alveolar bone graft outcomes for unilateral and bilateral cleft lip and palate patients have continued to improve since the reorganization of cleft services in Scotland in 2000. Design Retrospective analysis of postoperative anterior occlusal radiographs. Patients and Participants Eighty-one of 106 patients who were eligible for alveolar bone grafting between 2007 and 2010 had suitable postoperative radiographs available.

Evidence of lensing of the cosmic microwave background by dark matter halos.

We present evidence of the gravitational lensing of the cosmic microwave background by 10(13) solar mass dark matter halos. Lensing convergence maps from the Atacama Cosmology Telescope Polarimeter (ACTPol) are stacked at the positions of around 12 000 optically selected CMASS galaxies from the SDSS-III/BOSS survey. The mean lensing signal is consistent with simulated dark matter halo profiles and is favored over a null signal at 3.

A fluorescent histone deacetylase (HDAC) inhibitor for cellular imaging.

Fluorescence microscopy studies using 4-morpholinoscriptaid (4MS) demonstrated rapid cellular uptake of this scriptaid analogue into the cytoplasm but no nuclear penetration. As 4MS and scriptaid have the same in vitro activity against HDACs and KASUMI-1 cells; 4MS exemplifies a rational approach to subtly modify ‘profluorogenic’ substrates for intracellular studies.

Secondary Alveolar Bone Grafting (CLEFTSiS) 2007-2010.

Objective :  To determine whether alveolar bone graft outcomes for unilateral and bilateral cleft lip and palate patients have continued to improve since the reorganization of cleft services in Scotland in 2000. Design :  Retrospective analysis of postoperative anterior occlusal radiographs. Patients and Participants :  Eighty-one of 106 patients who were eligible for alveolar bone grafting between 2007 and 2010 had suitable postoperative radiographs available.

Adopting a Sustainable Community of Practice Model when Developing a Service to Support Patients with Epidermolysis Bullosa (EB): A Stakeholder-Centered Approach.

Objectives: Epidermolysis bullosa (EB) is a rare, genetic skin condition that is complicated, distressing, and painful and permeates every aspect of patients' lives. Support services are essential for meeting the primary needs of patients and families living with EB; however, provision is challenged by many complex issues. In collaboration with the patient organization DEBRA Ireland, this research conducted an in-depth analysis of Irish healthcare support services for EB, with a view to moving towards an improved and sustainable care pathway.

LIM kinase inhibition reduces breast cancer growth and invasiveness but systemic inhibition does not reduce metastasis in mice.

Metastasis is the major cause of morbidity and mortality in cancer patients. An understanding of the genes that regulate metastasis and development of therapies to target these genes is needed urgently. Since members of the LIM kinase (LIMK) family are key regulators of the actin cytoskeleton and are involved in cell motility and invasion, LIMK is considered to be a good therapeutic target for metastatic disease.

Cleft lip and palate in Scotland: a survey.

The aim of the survey was to assess midwives' experiences and knowledge of cleft lip and/or palate (CL+/-P), confidence in supporting the families and giving feeding advice, and to identify areas for input from the cleft team. In order to do so, questionnaires were sent to maternity units across Scotland. The results were as follows: 206 questionnaires were returned (42 per cent response rate).

Evidence of galaxy cluster motions with the kinematic Sunyaev-Zel'dovich effect.

Using high-resolution microwave sky maps made by the Atacama Cosmology Telescope, we for the first time present strong evidence for motions of galaxy clusters and groups via microwave background temperature distortions due to the kinematic Sunyaev-Zel'dovich effect. Galaxy clusters are identified by their constituent luminous galaxies observed by the Baryon Oscillation Spectroscopic Survey, part of the Sloan Digital Sky Survey III. We measure the mean pairwise momentum of clusters, with a probability of the signal being due to random errors of 0.

Reducing the need for general anaesthesia in children: use of LAT gel in treating facial lacerations.

Facial lacerations in children are common emergencies that often require debridement and closure under general anaesthesia because of poor cooperation by the patient. General anaesthesia in children is not without risk so any technique that avoids its use is beneficial. LAT gel (lidocaine, adrenaline, and tetracaine) is a topical anaesthetic, which is ideal for suturing facial lacerations in children.