Non-linear QED approach for betatron radiation in a laser wakefield accelerator.

Laser plasma-based accelerators provide an excellent source of collimated, bright, and adequately coherent betatron-type x-ray pulses with potential applications in science and industry. So far the laser plasma-based betatron radiation has been described within the concept of classical Liénard-Wiechert potentials incorporated in particle-in-cell simulations, a computing power-demanding approach, especially for the case of multi-petawatt lasers. In this work, we describe the laser plasma-based generation of betatron radiation at the most fundamental level of quantum mechanics. In our approach, photon emission from the relativistic electrons in the plasma bubble is described within a nonlinear quantum electrodynamics (QED) framework. The reported QED-based betatron radiation results are in excellent agreement with similar results using Liénard-Wiechert potentials, as well as in very good agreement with betatron radiation measurements, obtained with multi-10-TW lasers interacting with He and multielectron N[Formula: see text] gas targets. Furthermore, our QED approach results in a dramatic reduction of the computational runtime demands, making it a favorable tool for designing betatron radiation experiments, especially in multi-petawatt laser facilities.

Risk-Based Screening Tools to Optimise HIV Testing Services: a Systematic Review.

PURPOSE OF REVIEW: Effective ways to diagnose the remaining people living with HIV who do not know their status are a global priority. We reviewed the use of risk-based tools, a set of criteria to identify individuals who would not otherwise be tested (screen in) or excluded people from testing (screen out). RECENT FINDINGS: Recent studies suggest that there may be value in risk-based tools to improve testing efficiency (i.e. identifying those who need to be tested). However, there has not been any systematic reviews to synthesize these studies. We identified 18,238 citations, and 71 were included. The risk-based tools identified were most commonly from high-income (51%) and low HIV (<5%) prevalence countries (73%). The majority were for "screening in" (70%), with the highest performance tools related to identifying MSM with acute HIV. Screening in tools may be helpful in settings where it is not feasible or recommended to offer testing routinely. Caution is needed for screening out tools, where there is a trade-off between reducing costs of testing with missing cases of people living with HIV.

Parametrizing the genioplasty: a biomechanical virtual study on soft tissue behavior.

PURPOSE: Sliding genioplasty is used to surgically correct a retruded or misaligned chin: in this procedure, an osteotomy is performed and the bony segment is repositioned. In this study we investigate the effect of surgical parameters (bony segment movement, osteotomy design) on postop soft tissue changes in a patient cohort. METHODS: Seven patients were retrospectively recruited. Cone beam computed tomography data were obtained and soft tissue and bone shape reconstructions were performed. 3D models were created and surgical cuts were replicated according to postop scans. Each model was imported in ANSYS 2019R1 (Ansys Inc, USA) for simulation: the effect of variation in osteotomy plane as well as extent of bony segment movement were assessed by means of design of experiment: surgical parameters were varied in a surgically acceptable range and the soft tissue predictions were evaluated as displacement output of five craniometric landmarks. RESULTS: Simulation results show the overall changes of the lower third of the face are sensitive to changes in horizontal and vertical displacement of the bony segment as well as segment rotation. No significant changes in the soft tissue response were to attribute to the osteotomy design. CONCLUSIONS: Our results are consistent with experimental findings reported in the literature: when planning genioplasty in orthognathic surgery, particular focus on the segment movement (horizontal translation, vertical translation and rotation), rather than on the design of the osteotomy itself, should be considered.

Treatment outcomes of laryngectomy compared to non-surgical management of T3 laryngeal carcinomas: a 10-year multicentre audit of 179 patients in the northeast of England.

OBJECTIVE: Wide-ranging outcomes have been reported for surgical and non-surgical management of T3 laryngeal carcinomas. This study compared the outcomes of T3 tumours treated with laryngectomy or (chemo)radiotherapy in the northeast of England. METHODS: The outcomes of T3 laryngeal carcinoma treatment at three centres (2007-2016) were retrospectively analysed using descriptive statistics and survival curves. RESULTS: Of 179 T3 laryngeal carcinomas, 68 were treated with laryngectomies, 57 with chemoradiotherapy and 32 with radiotherapy. There was no significant five-year survival difference between treatment with laryngectomy (34.1 per cent) and chemoradiotherapy (48.6 per cent) (p = 0.184). The five-year overall survival rate for radiotherapy (12.5 per cent) was significantly inferior compared to laryngectomy and chemoradiotherapy (p = 0.003 and p < 0.001, respectively). The recurrence rates were 22.1 per cent for laryngectomy, 17.5 per cent for chemoradiotherapy and 50 per cent for radiotherapy. There were significant differences in recurrence rates when laryngectomy (p = 0.005) and chemoradiotherapy (p = 0.001) were compared to radiotherapy. CONCLUSION: Laryngectomy and chemoradiotherapy had significantly higher five-year overall survival and lower recurrence rates compared with radiotherapy alone. Laryngectomy should be considered in patients unsuitable for chemotherapy, as it may convey a significant survival advantage over radiotherapy alone.

Does the gene matter? Genotype-phenotype and genotype-outcome associations in congenital melanocytic naevi.

BACKGROUND: Genotype-phenotype studies can identify subgroups of patients with specific clinical features or differing outcomes, which can help shape management. OBJECTIVES: To characterize the frequency of different causative genotypes in congenital melanocytic naevi (CMN), and to investigate genotype-phenotype and genotype-outcome associations. METHODS: We conducted a large cohort study in which we undertook MC1R genotyping from blood, and high-sensitivity genotyping of NRAS and BRAF hotspots in 156 naevus biopsies from 134 patients with CMN [male 40%; multiple CMN 76%; projected adult size (PAS) > 20 cm, 59%]. RESULTS: Mosaic NRAS mutations were detected in 68%, mutually exclusive with BRAF mutations in 7%, with double wild-type in 25%. Two separate naevi were sequenced in five of seven patients with BRAF mutations, confirming clonality. Five of seven patients with BRAF mutations had a dramatic multinodular phenotype, with characteristic histology distinct from classical proliferative nodules. NRAS mutation was the commonest in all sizes of CMN, but was particularly common in naevi with PAS > 60 cm, implying more tolerance to that mutation early in embryogenesis. Facial features were less common in double wild-type patients. Importantly, the incidence of congenital neurological disease, and apparently of melanoma, was not altered by genotype; no cases of melanoma were seen in BRAF-mutant multiple CMN, however, this genotype is rare. CONCLUSIONS: CMN of all sizes are most commonly caused by mutations in NRAS. BRAF is confirmed as a much rarer cause of multiple CMN, and appears to be commonly associated with a multinodular phenotype. Genotype in this cohort was not associated with differences in incidence of neurological disease in childhood. However, genotyping should be undertaken in suspected melanoma, for guidance of treatment. What's already known about this topic? Multiple congenital melanocytic naevi (CMN) have been shown to be caused by NRAS mosaic mutations in 70-80% of cases, by BRAF mosaicism in one case report and by inference in some previous cases. There has been debate about genotypic association with different sizes of CMN, and no data on genotype-outcome. What does this study add? NRAS mosaicism was found in 68%, BRAF in 7% and double wild-type in 25% of cases of CMN. NRAS was the commonest mutation in all sizes of CMN, but was nearly universal in projected adult size > 60 cm. BRAF is often associated with a distinct multinodular clinical/histological phenotype. Adverse outcomes did not differ between genotypes on current numbers.

Factors influencing patient decision-making between simple mastectomy and surgical alternatives.

Background: Despite similar survival rates, breast-conserving therapy (BCT) remains a distant second choice after simple mastectomy for patients with early-stage breast cancer in Singapore. Uptake of reconstruction after mastectomy is also low (18 per cent). The aim of this study was to explore the factors influencing a patient's choice for mastectomy when eligible for BCT, and why patients decline reconstruction after mastectomy. Methods: Patients from the National Cancer Centre Singapore, who were eligible for BCT but chose mastectomy without reconstruction, between December 2014 and December 2015 were included. An interviewer-administered questionnaire focusing on patients' reasons for choosing mastectomy over BCT and not opting for immediate breast reconstruction after mastectomy was used. Tumour characteristics were retrieved from medical records. Spearman's rank correlation coefficient, Mann-Whitney U and Kruskal-Wallis tests were used to analyse the correlation between the patient's self-rated influential factors and variables. Statistical significance was taken as P < 0·050. Results: Ninety-one patients were included (90·1 per cent response rate). The main reasons for choosing mastectomy over BCT were: fear of cancer recurrence (considered very important in 74 per cent), the perception that health outweighs breast retention (49 per cent) and the possibility of second surgery for margins (40 per cent). Key factors for rejecting immediate reconstruction after mastectomy were: patient-perceived 'old age' (very important in 53 per cent), concern about two sites of surgery (42 per cent) and financial cost (29 per cent). Given a second chance, 19·8 per cent of patients would undergo BCT instead of mastectomy. Conclusion: This study has identified the considerations that women in Singapore have when deciding on breast cancer surgery. Some perceptions need to be addressed for women to make a fully informed decision, especially as one-fifth regret their initial choice.

Three-dimensional soft tissue prediction in orthognathic surgery: a clinical comparison of Dolphin, ProPlan CMF, and probabilistic finite element modelling.

Three-dimensional surgical planning is used widely in orthognathic surgery. Although numerous computer programs exist, the accuracy of soft tissue prediction remains uncertain. The purpose of this study was to compare the prediction accuracy of Dolphin, ProPlan CMF, and a probabilistic finite element method (PFEM). Seven patients (mean age 18years; five female) who had undergone Le Fort I osteotomy with preoperative and 1-year postoperative cone beam computed tomography (CBCT) were included. The three programs were used for soft tissue prediction using planned and postoperative maxillary position, and these were compared to postoperative CBCT. Accurate predictions were obtained with each program, indicated by root mean square distances: RMSDolphin=1.8±0.8mm, RMSProPlan=1.2±0.4mm, and RMSPFEM=1.3±0.4mm. Dolphin utilizes a landmark-based algorithm allowing for patient-specific bone-to-soft tissue ratios, which works well for cephalometric radiographs but has limited three-dimensional accuracy, whilst ProPlan and PFEM provide better three-dimensional predictions with continuous displacements. Patient or population-specific material properties can be defined in PFEM, while no soft tissue parameters are adjustable in ProPlan. Important clinical considerations are the topological differences between predictions due to the three algorithms, the non-negligible influence of the mismatch between planned and postoperative maxillary position, and the learning curve associated with sophisticated programs like PFEM.

A 24-month cost and outcome analysis comparing traditional fronto-orbital advancment and remodeling with endoscopic strip craniectomy and molding helmet in the management of unicoronal craniosynostosis: A retrospective bi-institutional review.

INTRODUCTION: Endoscopic strip craniectomy with helmeting (ESCH) has been shown to be a safe and efficacious alternative to fronto-orbital remodeling (FOR) for selected children with craniosynostosis. In addition to clinical factors, there may be economic benefits from the use of ESCH instead of FOR. METHODS: A retrospective review of 23 patients with nonsyndromic unicoronal craniosynostosis (UCS) treated with FOR was carried out at Great Ormond Street Hospital (GOSH) for Children in London, UK. Secondary data were used for the ESCH cohort from a paper published by Jimenez and Barone (2013). Data were collected on surgical time, transfusion rates, length of hospital stay, adverse event rates, reintervention rates, and overall costs. Costs were categorized and then assigned to the appropriate data sets. RESULTS: The mean age of patients undergoing FOR (vs. ESCH) was 17.4 mo (vs. 3.1 mo) with a mean surgical time of 234 min (vs. 55 min), mean transfusion volume of 221.6 mL (vs. 80.0 mL), mean transfusion rate of 14/23 (vs. 2/115), and a total immediate overnight stay of 3.13 days (vs. 97% next-day discharge). The FOR group had a higher adverse event rate (5/23 vs. 4/115, p=<0.005) and a higher number requiring extraocular muscle surgery (4/23 vs. 7/109, p=0.16). There was a substantial difference in overall costs between the two groups. Total variance cost for the FOR group was £7436.5 vs. £4951.35, representing a cost difference of £2485.15 over the 24-month study period. CONCLUSION: ESCH, in comparison to FOR, appears as a more economical method in the management of USC patients, as well as having clinical benefits including reduced adverse event rate and improved ophthalmic outcomes.

Lactobacilli modulated AMPK activity and prevented telomere shortening in ageing rats.

This study aimed to evaluate the anti-ageing effects of different strains of lactobacilli putative probiotics on an ageing rat model as induced by D-galactose and a high fat diet. Male Sprague-Dawley rats were fed with high fat diet (54% kcal fat) and injected with D-galactose daily for 12 weeks to induce ageing. The effects of putative probiotic strains on age-related impairment such as telomere length, plasma lipid peroxidation, hepatic 5'adenosine monophosphate-activated protein kinase (AMPK) expression, as well as endurance performance were evaluated. Administration of statin, Lactobacillus plantarum DR7 (LP-DR7), Lactobacillus fermentum DR9 (LF-DR9), and Lactobacillus reuteri 8513d (LR-8513d) significantly reduced the shortening of telomere and increased the expression of AMPK subunit-α1 (P<0.05). Plasma lipid peroxidation was lower (P<0.05) in groups administered with statin and LF-DR9 as compared to the control. AMPK subunit-α2 was elevated in rats administered with LP-DR7 as compared to the control (P<0.05). Using an in vivo ageing rat model, the current study has illustrated the potentials of lactobacilli putative probiotics in alleviation of age-related impairment in a strain-dependent manner.

Asymptomatic and symptomatic urethral gonorrhoea in men who have sex with men attending a sexual health service.

OBJECTIVES: Guidelines regarding whether men who have sex with men (MSM) without symptoms of urethritis should be screened for urethral gonorrhoea differ between countries. We examined the rate of asymptomatic urethral gonorrhoea in MSM using sensitive nucleic acid amplification testing. METHODS: This study was conducted on consecutive MSM attending the Melbourne Sexual Health Centre between July 2015 and May 2016 for sexually transmitted infections screening. Gonorrhoea testing with the Aptima Combo 2 (AC2) assay was performed on all urine specimens obtained from MSM, whether symptoms of urethritis were present or not. Men were classified as having: typical discharge if they reported symptoms suggesting purulent discharge; other symptoms if they reported other symptoms of urethritis; and no symptoms if they reported no urethral symptoms. RESULTS: During the study period, there were 7941 clinic visits by 5947 individual MSM with 7090 urine specimens obtained from 5497 individual MSM tested with the AC2 assay. Urethral gonorrhoea was detected in 242 urine specimens from 228 individual MSM. The majority (189/242, 78%, 95% CI 73-83) reported typical discharge, 27/242 (11%, 95% CI 8-16) reported other urethral symptoms, and 26/242 (11%, 95% CI 7-15) reported no symptoms on the day of presentation and testing. Among men with urethral gonorrhoea, the proportions with concurrent pharyngeal or rectal gonorrhoea were 32% (134/210) and 64% (74/235), respectively. The mean interval between last reported sexual contact and onset of typical urethral discharge, where present, was 3.9 days. CONCLUSION: The findings from our study lend support to guidelines that recommend screening asymptomatic MSM for urethral gonorrhoea.

Female genital cosmetic surgery: a cross-sectional survey exploring knowledge, attitude and practice of general practitioners.

OBJECTIVE: To explore general practitioner's (GP) knowledge, attitudes and practice regarding female genital cosmetic surgery (FGCS) in Australia. DESIGN: Cross-sectional survey. SETTING: Australia. SAMPLE: GPs who attended a women's health seminar and GPs who subscribed to a non-governmental, national health professional organisation database that provides education to primary care professionals. METHOD: A national online survey of GPs was conducted for the 10-week period, starting 1 week prior and 2 months after a Women's Health seminar was held in Perth on 8 August 2015. 31 questions prompted GPs' knowledge, attitudes and practice in managing patients asking about FGCS. RESULTS: The survey was fully completed by 443 GPs; 54% had seen patients requesting FGCS. Overall, 75% (95% CI 71% to 79%) of GPs rated their knowledge of FGCS as inadequate and 97% (95% CI 94% to 99%) had been asked by women of all ages about genital normality. Of those who had seen patients requesting FGCS, nearly half (44%, 95% CI 38% to 51%) reported they had insufficient knowledge of risks of FGCS procedures and 35% (95% CI 29% to 41%) reported seeing females younger than 18 years of age requesting FGCS. Just over half (56%, 95% CI 51% to 60%) of the GPs felt that women should be counselled before making a referral for FGCS. More than half the GPs suspected psychological disturbances in their patients requesting FGCS such as depression, anxiety, relationship difficulties and body dysmorphic disorder. CONCLUSIONS: GPs see women of all ages presenting with genital anatomy concerns and in those who request FGCS, GPs often suspected a range of mental health difficulties. GPs require greater education to support their patients who request FGCS.

A smoking cessation programme for current and recent ex-smokers following diagnosis of a potentially curable cancer.

BACKGROUND: Cancer patients who quit smoking have improved survival rates. The time of diagnosis provides a 'teachable moment' when healthcare providers can offer smoking-cessation treatment. AIMS: To assess the impact on quit rates of a tailored smoking-cessation intervention for patients diagnosed with a potentially curable cancer. METHODS: A prospective, one-arm cohort study of current smokers and recent quitters (<30 days) who had commenced treatment for a potentially curable cancer was performed. Intervention involved an initial motivational interview, regular follow up and pharmacotherapy when appropriate. Quit rates were measured at 1, 3, 6 and 12 months by self-reported abstinence and biochemical confirmation. The primary end point was prolonged abstinence at 12 months. Changes in quality of life parameters and distress were also assessed. RESULTS: Seventy-one patients were recruited, with a median age of 56 years. Forty-one patients (58%) had a smoking-related cancer. The prolonged abstinence rate at 12 months was 24% (95% confidence interval 14-36%). Factors associated with successful quitting included being in the preparation or action phase of readiness to change at study entry (P = 0.012) and having complications of treatment requiring hospitalisation (P = 0.024). Between baseline and 12 months, quitters reported improvement in self-control (P < 0.001) and reduced levels of distress (P = 0.03) compared to non-quitters. CONCLUSION: Patients who continue to smoke after being diagnosed with cancer require intensive support to quit. An individualised behavioural and pharmacological intervention can be successful in helping patients quit smoking, with quality of life improvements seen amongst successful quitters. Population measures to stop people starting smoking remain essential.

Effect of cell-seeded hydroxyapatite scaffolds on rabbit radius bone regeneration.

Highly porous hydroxyapatite (HA) scaffolds were developed as bone graft substitutes using a template coating process, characterized, and seeded with bone marrow-derived mesenchymal stem cells (BMSCs). To test the hypothesis that cell-seeded HA scaffolds improve bone regeneration, HA scaffolds without cell seeding (HA-empty), HA scaffolds with 1.5 × 10(4) BMSCs (HA-low), and HA scaffolds with 1.5 × 10(6) BMSCs (HA-high) were implanted in a 10-mm rabbit radius segmental defect model for 4 and 8 weeks. Three different fluorochromes were administered at 2, 4, and 6 weeks after implantation to identify differences in temporal bone growth patterns. It was observed from fluorescence histomorphometry analyses that an increased rate of bone infiltration occurred from 0 to 2 weeks (p < 0.05) of implantation for the HA-high group (2.9 ± 0.5 mm) as compared with HA-empty (1.8 ± 0.8 mm) and HA-low (1.3 ± 0.2 mm) groups. No significant differences in bone formation within the scaffold or callus formation was observed between all groups after 4 weeks, with a significant increase in bone regenerated for all groups from 4 to 8 weeks (28.4% across groups). Although there was no difference in bone formation within scaffolds, callus formation was significantly higher in HA-empty scaffolds (100.9 ± 14.1 mm(3) ) when compared with HA-low (57.8 ± 7.3 mm(3) ; p ≤ 0.003) and HA-high (69.2 ± 10.4 mm(3) ; p ≤ 0.02) after 8 weeks. These data highlight the need for a better understanding of the parameters critical to the success of cell-seeded HA scaffolds for bone regeneration.

A review and update on the current status of stem cell therapy and the retina.

INTRODUCTION OR BACKGROUND: Many diseases of the retina result in irreversible visual loss. Stem cell (SC) therapy is a rapidly developing field and represents a novel approach to replace non-functioning neuro-retinal cells. SOURCES OF DATA: A systematic computerized literature search was conducted on PubMed (http://www.ncbi.nlm.nih.gov/pubmed/). AREAS OF AGREEMENT: The use of stem cells (SCs) in animal models of retinal diseases has resulted in improvement in visual function and performance. SC therapy represents an exciting prospect in restoring vision. Areas of controversy The use of human embryonic SCs raises ethical concerns. GROWING POINTS: Human trials using SCs in retinal diseases have recently been approved. AREAS TIMELY FOR DEVELOPING RESEARCH: The success of SCs in retinal therapy depends not only on implanted cell survival, but also on how well SCs migrate, integrate and form synapses. Further research will be needed to overcome these hurdles.

Trans-scleral dye injection during vitreous surgery to identify clinically undetectable retinal breaks causing retinal detachment.

BACKGROUND/AIMS: Finding all retinal breaks is a critical step in rhegmatogenous retinal detachment (RRD) surgery in order to prevent persistent/recurrent retinal detachment (RD). We describe a technique of trans-scleral dye injection into the subretinal fluid under the detached retina in the context of recurrent/persistent RD in vitrectomized eyes, in order to determine the location of clinically unidentified (occult) retinal breaks causing RD. METHODS: Retrospective consecutive single-surgeon case-series analysis of patients presenting with a repeat RRD after having been treated with pars plana vitrectomy (PPV) as the method of primary RRD repair. Trans-scleral injection of subretinal vision blue (TSVB) was used to help identify retinal breaks during repeat vitrectomy. OUTCOME MEASURES: successful detection of a break; location of breaks; persistent retinal attachment; final visual acuity (VA); complications. RESULTS: There were 395 cases of RRD during the 3-year period reviewed. TSVB was used for eight instances in seven eyes. All eight instances were repeat RRD. TSVB facilitated occult break detection in 7/8 instances of use. Breaks were at or adjacent to the previous cryo site in three instances. Persistent retinal attachment was achieved in 5/7 cases. Final VA increased in 5/7 cases. There was no evidence of complications as a result of TSVB injection. CONCLUSIONS: TSVB coupled with indentation to vent a plume of dye through an occult break during vitreous surgery is a relatively simple technique that may facilitate the identification of occult retinal breaks and help achieve anatomical success and functional success.