Stabilization of Liner Implosions via a Dynamic Screw Pinch.

Magnetically driven implosions are susceptible to magnetohydrodynamic instabilities, including the magneto-Rayleigh-Taylor instability (MRTI). To reduce MRTI growth in solid-metal liner implosions, the use of a dynamic screw pinch (DSP) has been proposed [P. F. Schmit et al., Phys. Rev. Lett. 117, 205001 (2016)PRLTAO0031-900710.1103/PhysRevLett.117.205001]. In a DSP configuration, a helical return-current structure surrounds the liner, resulting in a helical magnetic field that drives the implosion. Here, we present the first experimental tests of a solid-metal liner implosion driven by a DSP. Using the 1-MA, 100-200-ns COBRA pulsed-power driver, we tested three DSP cases (with peak axial magnetic fields of 2 T, 14 T, and 20 T) and a standard z-pinch (SZP) case (with a straight return-current structure and thus zero axial field). The liners had an initial radius of 3.2 mm and were made from 650-nm-thick aluminum foil. Images collected during the experiments reveal that helical MRTI modes developed in the DSP cases, while nonhelical (azimuthally symmetric) MRTI modes developed in the SZP case. Additionally, the MRTI amplitudes for the 14-T and 20-T DSP cases were smaller than in the SZP case. Specifically, when the liner had imploded to half of its initial radius, the MRTI amplitudes for the SZP case and for the 14-T and 20-T DSP cases were, respectively, 1.1±0.3 mm, 0.7±0.2 mm, and 0.3±0.1 mm. Relative to the SZP, the stabilization obtained using the DSP agrees reasonably well with theoretical estimates.

The α2,3-selective potentiator of GABAA receptors, KRM-II-81, reduces nociceptive-associated behaviors induced by formalin and spinal nerve ligation in rats.

Clinical evidence indicates that positive allosteric modulators (PAMs) of GABAA receptors have analgesic benefit in addition to efficacy in anxiety disorders. However, the utility of GABAA receptor PAMs as analgesics is compromised by the central nervous system side effects of non-selective potentiators. A selective potentiator of GABAA receptors associated with α2/3 subunits, KRM-II-81(5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)oxazole), has demonstrated anxiolytic, anticonvulsant, and antinociceptive effects in rodents with reduced motoric side effects. The present study evaluated the potential of KRM-II-81 as a novel analgesic. Oral administration of KRM-II-81 attenuated formalin-induced flinching; in contrast, diazepam was not active. KRM-II-81 attenuated nociceptive-associated behaviors engendered by chronic spinal nerve ligation (L5/L6). Diazepam decreased locomotion of rats at the dose tested in the formalin assay (10 mg/kg) whereas KRM-II-81 produced small decreases that were not dose-dependent (10-100 mg/kg). Plasma and brain levels of KRM-II-81 were used to demonstrate selectivity for α2/3- over α1-associated GABAA receptors and to define the degree of engagement of these receptors. Plasma and brain concentrations of KRM-II-81 were positively-associated with analgesic efficacy. GABA currents from isolated rat dorsal-root ganglion cultures were potentiated by KRM-II-81 with an ED50 of 32 nM. Measures of respiratory depression were reduced by alprazolam whereas KRM-II-81 was either inactive or produced effects with lower potency and efficacy. These findings add to the growing body of data supporting the idea that α2/3-selective GABAA receptor PAMs will have efficacy and tolerability as pain medications including those for neuropathic pain. Given their predicted anxiolytic effects, α2/3-selective GABAA receptor PAMs offer an additional inroad into the management of pain.

Childhood neighborhood context and adult substance use problems: the role of socio-economic status at the age of 30 years.

OBJECTIVES: To examine whether the (a) childhood neighborhood context predicts alcohol use disorder, nicotine dependence, and cannabis use disorder symptoms at the age of 39 years; and (b) socio-economic status during young adulthood mediates these relationships. Gender differences were also examined. STUDY DESIGN: The Seattle Social Development Project is a prospective longitudinal study of 808 individuals followed up from ages 10 to 39 years in Seattle, Washington, United States. The sample was gender balanced (51% were men). METHODS: Alcohol, nicotine, and cannabis use disorder symptoms were assessed using the Diagnostic and Statistical Manual of Mental Disorders IV-based Diagnostic Interview Schedule. Childhood neighborhood data consisted of 10 neighborhood-level variables from the 1990 national census, which were consolidated using principal component analyses. Two components with eigenvalues greater than 1 were extracted-neighborhood disadvantage and neighborhood stability. Educational attainment and employment status represented socio-economic status during young adulthood. Covariates included baseline symptoms of psychopathology, baseline substance use, gender, ethnicity, and childhood socio-economic status at the family level. Negative binomial regression was used as the primary modeling strategy. Six models for each outcome measure were estimated. The first three models examined associations between two neighborhood components and each substance use outcome measure. Next, we tested the second research question by adding unemployment and college graduate indicators at the age of 30 years as potential mediators underlying the link between the childhood neighborhood context and three substance use measures. RESULTS: Study findings revealed that childhood neighborhood stability significantly reduced alcohol and cannabis use disorder symptoms nearly 3 decades later. Path analyses suggested that socio-economic status during the transition to adulthood did not influence these relationships but rather had independent effects on problematic nicotine and cannabis use. Furthermore, the effects of childhood neighborhood factors on problematic nicotine use were stronger for men. CONCLUSIONS: Neighborhood characteristics during childhood may be important factors for alcohol and cannabis use disorder symptoms among adults and nicotine dependence disorder symptoms among men. Prevention efforts that address community stability and disadvantage can and should start in childhood, with a focus on intervention targets that might gain salience later in life to discourage the development and persistence of problematic substance use in adulthood.

Bioisosteres of ethyl 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo [1,5-a][1,4]diazepine-3-carboxylate (HZ-166) as novel alpha 2,3 selective potentiators of GABAA receptors: Improved bioavailability enhances anticonvulsant efficacy.

HZ-166 has previously been characterized as an α2,3-selective GABAA receptor modulator with anticonvulsant, anxiolytic, and anti-nociceptive properties but reduced motor effects. We discovered a series of ester bioisosteres with reduced metabolic liabilities, leading to improved efficacy as anxiolytic-like compounds in rats. In the present study, we evaluated the anticonvulsant effects KRM-II-81 across several rodent models. In some models we also evaluated key structural analogs. KRM-II-81 suppressed hyper-excitation in a network of cultured cortical neurons without affecting the basal neuronal activity. KRM-II-81 was active against electroshock-induced convulsions in mice, pentylenetetrazole (PTZ)-induced convulsions in rats, elevations in PTZ-seizure thresholds, and amygdala-kindled seizures in rats with efficacies greater than that of diazepam. KRM-II-81 was also active in the 6 Hz seizure model in mice. Structural analogs of KRM-II-81 but not the ester, HZ-166, were active in all models in which they were evaluated. We further evaluated KRM-II-81 in human cortical epileptic tissue where it was found to significantly-attenuate picrotoxin- and AP-4-induced increases in firing rate across an electrode array. These molecules generally had a wider margin of separation in potencies to produce anticonvulsant effects vs. motor impairment on an inverted screen test than did diazepam. Ester bioisosters of HZ-166 are thus presented as novel agents for the potential treatment of epilepsy acting via selective positive allosteric amplification of GABAA signaling through α2/α3-containing GABA receptors. The in vivo data from the present study can serve as a guide to dosing parameters that predict engagement of central GABAA receptors.

Socioeconomic deprivation and the burden of head and neck cancer-Regional variations of incidence and mortality in Merseyside and Cheshire, North West, England.

OBJECTIVES: The aim of this longitudinal study was to examine the distribution of head and neck cancer (HANC) disease burden across the region comparing it to national trends. DESIGN: We undertook a retrospective study of routine data combining it with indicators of deprivation and lifestyle at small geographical areas within the 9 Local Authorities (LAs) of Merseyside and Cheshire Network (MCCN) for head and neck cancers. Data from the North West of England and England were used as comparator regions. SETTING: This research was undertaken by the Cheshire and Merseyside Public Health Collaborative, UK. PARTICIPANTS: The Merseyside and Cheshire region serves a population of 2.2 million. Routine data allowed us to identify HANC patients diagnosed with cancers coded ICD C00-C14 and C30-C32 within 3 cohorts 1998-2000, 2008-2010 and 2009-2011 for our analysis. MAIN OUTCOME MEASURES: Directly age-standardised incidence rates and directly age-standardised mortality rates in the LAs and comparator regions were measured. Lifestyle and deprivation indicators were plotted against them and measured by Pearson's correlation coefficients. RESULTS: The incidence of head and neck cancer has increased across the region from 1998-2000 to 2008-2010 with a peak incidence for Liverpool males at 35/100 000 population. Certain Middle Super Output Areas contribute disproportionately to the significant effect of incidence and mortality within LAs. Income deprivation had the strongest correlation with incidence (r = .59) and mortality (r = .53) of head and neck cancer. CONCLUSION: Our study emphasises notable geographical variations within the region which need to be addressed through public health measures.

The cost of oropharyngeal cancer in England: A retrospective hospital data analysis.

OBJECTIVES: To estimate the total costs of treating head and neck cancers, specifically oropharyngeal, laryngeal and oral cavity cancer, in secondary care facilities in England during the period 2006/2007 to 2010/2011. DESIGN: Patient records were extracted from an English hospital database to estimate the number of patients treated for oropharyngeal, laryngeal and oral cavity cancer in England. Identified resource use was linked to published United Kingdom cost estimates to quantify the reimbursement of treatment through the Payment by Results system. SETTING: Retrospective hospital data analysis. PARTICIPANTS: From the hospital data, patient records of patients treated for oropharyngeal, laryngeal and oral cavity cancer were selected. MAIN OUTCOME MEASURES: Annual total costs of treatment, stratified by inpatient and outpatient setting and by male and female patients. RESULTS: From 2006/2007 to 2010/2011, total costs of treatment across the three head and neck cancer sites were estimated to be approximately £309 million, with 90% attributable to inpatient care (bundled costs). Oropharyngeal cancer accounted for 37% of total costs. Costs and patient numbers increased over time, largely due to a rise in oropharyngeal cancer, where total costs increased from £17.21 million to £30.32 million, with over 1400 (52%) more inpatients treated in 2010/11 compared to 2006/07. CONCLUSIONS: In 4 years, the number of patients with oropharyngeal cancer receiving some form of inpatient care increased by more than half, and associated costs increased by three quarters. This reinforces the case for prevention and early detection strategies to help contain this epidemiological and economic burden.

Beta-blockers in hospitalised patients with cirrhosis and ascites: mortality and factors determining discontinuation and reinitiation.

BACKGROUND: It has been suggested that beta-blockers may increase mortality in patients with cirrhosis and refractory ascites but the effect of beta-blockers discontinuation or reinitiation has not been examined. AIMS: To compare, in hospitalised patients with cirrhosis and ascites, the effect of BB on survival and to examine the effect/predictors of beta-blockers discontinuation and reinitiation. METHODS: Sub-analysis of NACSELD (North American consortium for the study of end-stage liver disease, database containing prospective data on hospitalised patients with cirrhosis) data from 7 centres enrolling >100 patients with ascites. Data on BB discontinuation and reinitiation were collected by chart review. RESULTS: Seven hundred and sixteen patients, 307 (43%) on beta-blockers at admission and 366 (51%) with refractory ascites, were followed to death or hospital discharge. Beta-blocker use was associated with a lower white blood cell count at admission. Beta-blocker use in hospitalised patients with ascites was not associated with a higher mortality, even in those with refractory ascites. No significant changes in mean arterial pressure (MAP) were observed between groups. Discontinuation of beta-blockers (49%) was driven by low MAP, infection and acute kidney injury at time of discontinuation but was not associated with a higher mortality. Beta-blocker reinitiation occurred in 40% prior to discharge and was mainly driven by an increase in MAP. CONCLUSIONS: Beta-blocker use is safe in patients with cirrhosis and ascites (including those with refractory ascites) provided beta-blockers are discontinued in the presence of a low MAP and reinitiated once MAP reincreases. A potentially beneficial anti-inflammatory effect of beta-blockers is suggested.

Chronic exposure to dim artificial light at night decreases fecundity and adult survival in Drosophila melanogaster.

The presence of artificial light at night is expanding in geographical range and increasing in intensity to such an extent that species living in urban environments may never experience natural darkness. The negative ecological consequences of artificial night lighting have been identified in several key life history traits across multiple taxa (albeit with a strong vertebrate focus); comparable data for invertebrates is lacking. In this study, we explored the effect of chronic exposure to different night-time lighting intensities on growth, reproduction and survival in Drosophila melanogaster. We reared three generations of flies under identical daytime light conditions (2600lx) and one of four ecologically relevant ALAN treatments (0, 1, 10 or 100lx), then explored variation in oviposition, number of eggs produced, juvenile growth and survival and adult survival. We found that, in the presence of light at night (1, 10 and 100lx treatments), the probability of a female commencing oviposition and the number of eggs laid was significantly reduced. This did not translate into differences at the juvenile phase: juvenile development times and the probability of eclosing as an adult were comparable across all treatments. However, we demonstrate for the first time a direct link between chronic exposure to light at night (greater than 1lx) and adult survival. Our data highlight that ALAN has the capacity to cause dramatic shifts in multiple life history traits at both the individual and population level. Such shifts are likely to be species-specific, however a more in depth understanding of the broad-scale impact of ALAN and the relevant mechanisms driving biological change is urgently required as we move into an increasing brightly lit future.

Further evaluation of the potential anxiolytic activity of imidazo[1,5-a][1,4]diazepin agents selective for α2/3-containing GABAA receptors.

Positive allosteric modulators of GABAA receptors transduce a host of beneficial effects including anxiolytic actions. We have recently shown that bioavailability and anxiolytic-like activity can be improved by eliminating the ester functionality in imidazo[1,5-a][1,4]diazepines. In the present series of experiments, we further substantiate the value of heterocyle replacement of the ester for potential treatment of anxiety. None of three esters was active in a Vogel conflict test in rats that detects anxiolytic drugs like diazepam. Compounds 7 and 8, ester bioisosters, were selective for alpha 2 and 3 over alpha 1-containing GABAA receptors but also had modest efficacy at GABAA alpha 5-containing receptors. Compound 7 was efficacious and potent in this anxiolytic-detecting assay without affecting non-punished responding. The efficacies of the esters and of compound 7 were predicted from their efficacies as anticonvulsants against the GABAA antagonist pentylenetetrazole (PTZ). In contrast, the related structural analog, compound 8, did not produce anxiolytic-like effects in rats despite anticonvulsant efficacy. These data thus support the following conclusions: 1) ancillary pharmacological actions of compound 8 might be responsible for its lack of anxiolytic-like efficacy despite its efficacy as an anticonvulsant 2) esters of imidazo[1,5-a][1,4]diazepines do not demonstrate anxiolytic-like effects in rats due to their low bioavailability and 3) replacement of the ester function with suitable heterocycles markedly improves bioavailability and engenders molecules with the opportunity to have potent and efficacious effects in vivo that correspond to human anxiolytic actions.

Laryngeal cancer: United Kingdom National Multidisciplinary guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Significantly new data have been published on laryngeal cancer management since the last edition of the guidelines. This paper discusses the evidence base pertaining to the management of laryngeal cancer and provides updated recommendations on management for this group of patients receiving cancer care. Recommendations • Radiotherapy (RT) and transoral laser microsurgery (TLM) are accepted treatment options for T1a-T2a glottic carcinoma. (R) • Open partial surgery may have a role in the management of selected tumours. (R) • Radiotherapy, TLM and transoral robotic surgery are reasonable treatment options for T1-T2 supraglottic carcinoma. (R) • Supraglottic laryngectomy may have a role in the management of selected tumours. (R) • Most patients with T2b-T3 glottic cancers are suitable for non-surgical larynx preservation therapies. (R) • Concurrent chemoradiotherapy should be regarded as the standard of care for non-surgical management. (R) • Subject to the availability of appropriate surgical expertise and multi-disciplinary rehabilitation services, TLM or open partial surgical procedures ± post-operative RT, may be also be appropriate in selected cases. (R) • In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-operative RT) is recommended to at least lymph node levels II, III and IV bilaterally. In node positive disease, it is recommended that lymph node levels II-V should be treated on the involved side. If level II nodes are involved, then elective irradiation of ipsilateral level Ib nodes may be considered. (R) • Most patients with T3 supraglottic cancers are suitable for non-surgical larynx preservation therapies. (R) • Concurrent chemoradiotherapy should be regarded as the standard of care for non-surgical management. (R) • Subject to the availability of appropriate surgical expertise and multi-disciplinary rehabilitation services, TLM or open partial surgical procedures ± post-operative RT, may also be appropriate in selected cases. (R) • In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-operative RT) is recommended to at least lymph node levels II, III and IV bilaterally. In node positive disease, lymph node levels II-V should be treated on the involved side. (R) • As per the PET-Neck clinical trial, patients with N2 or N3 neck disease who undergo treatment with chemoradiotherapy to their laryngeal primary and experience a complete response with a subsequent negative post-treatment positron emission tomography combined with computed tomography (PET-CT) scan do not require an elective neck dissection. In contrast, patients who have a partial response to treatment or have increased uptake on a post-treatment PET-CT scan should have a neck dissection. (R) • Larynx preservation with concurrent chemoradiotherapy should be considered for T4 tumours, unless there is tumour invasion through cartilage into the soft tissues of the neck, in which case total laryngectomy yields better outcomes. (R) • In the absence of clinical or radiological evidence of nodal disease, elective treatment (RT or surgery ± post-operative RT) is recommended to bilateral lymph node levels II, III, IV, V and VI. (R).

Pathology-based staging for HPV-positive squamous carcinoma of the oropharynx.

OBJECTIVE: The rapid worldwide rise in incidence of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has generated studies confirming this disease as an entity distinct from traditional OPSCC. Based on pathology, surgical studies have revealed prognosticators specific to HPV-positive OPSCC. The current AJCC/UICC staging and pathologic nodal (pN)-classification do not differentiate for survival, demonstrating the need for new, HPV-specific OPSCC staging. The objective of this study was to define a pathologic staging system specific to HPV-positive OPSCC. METHODS: Data were assembled from a surgically-managed, p16-positive OPSCC cohort (any T, any N, M0) of 704 patients from five cancer centers. Analysis was performed for (a) the AJCC/UICC pathologic staging, (b) newly published clinical staging for non-surgically managed HPV-positive OPSCC, and (c) a novel, pathology-based, "HPVpath" staging system that combines features of the primary tumor and nodal metastases. RESULTS: A combination of AJCC/UICC pT-classification and pathology-confirmed metastatic node count (⩽4 versus ⩾5) yielded three groups: stages I (pT1-T2, ⩽4 nodes), II (pT1-T2, ⩾5 nodes; pT3-T4, ⩽4 nodes), and III (pT3-T4, ⩾5 nodes), with incrementally worse prognosis (Kaplan-Meier overall survival of 90%, 84% and 48% respectively). Existing AJCC/UICC pathologic staging lacked prognostic definition. Newly published HPV-specific clinical stagings from non-surgically managed patients, although prognostic, showed lower precision for this surgically managed cohort. CONCLUSIONS: Three loco-regional "HPVpath" stages are identifiable for HPV-positive OPSCC, based on a combination of AJCC/UICC primary tumor pT-classification and metastatic node count. A workable, pathologic staging system is feasible to establish prognosis and guide adjuvant therapy decisions in surgically-managed HPV-positive OPSCC.

Mechanisms linking high school graduation to health disparities in young adulthood: a longitudinal analysis of the role of health behaviours, psychosocial stressors, and health insurance.

OBJECTIVES: This study examined three competing mechanisms in the link between educational attainment and health among young adults: (a) a health behaviour mechanism; (b) a psychosocial stressor mechanism; and (c) a health insurance mechanism. The central research question was the pervasiveness and specificity of these mechanisms in the link between low educational attainment and health outcomes during young adulthood. STUDY DESIGN: A prospective longitudinal study was conducted with 808 men and women followed to age 33 years in the USA. METHODS: Health outcomes included major depressive disorder, obesity, chronic health conditions, and self-rated health. The focal predictor was educational attainment at age 21. The roles of the health behaviour mechanism (heavy episodic drinking, cigarette smoking, and meeting physical activity guidelines), the psychosocial stressor mechanism (stressful life events, perceived financial stress, and lack of control at work), and having health insurance (either through their employer or union or via family members) in the link between education and varying health outcomes were assessed using path analyses. RESULTS: Lack of health insurance emerged as a statistically significant explanatory factor underlying the association of education with depression and self-rated health. Health behaviours, specifically smoking and physical activity, were statistically significant intervening factors for obesity and self-rated health. CONCLUSIONS: The processes linking educational attainment to health inequalities begin unfolding during young adulthood. The salience of different mechanisms is specific to a health outcome rather than pervasive across multiple health outcomes. Public health policies with a broad spectrum of components, particularly focussing on smoking, physical activity, and lack of health insurance, are recommended to promote educational equalities in multiple health outcomes among young adults.

Health related quality of life following the treatment of oropharyngeal cancer by transoral laser.

In 2006, our Institution changed the treatment strategy for small volume primary oropharyngeal tumours to transoral laser microsurgery (TOLM). The main aim of this cohort study was to report the health related quality of life (HRQOL) at around 2 years following TOLM in consecutive patients treated from July 2006 through April 2013. The University of Washington Quality of Life (UW-QOL) questionnaire was administered annually up to Spring 2014 and adjusting for mortality the overall response rate was 71 % (108/153). Tonsil primary site characterised 60 % (98) of patients, base of tongue 25 % (40), soft palate 13 % (21) and others 2 %, (3). Most patients had TOLM, neck dissection and adjuvant radiotherapy, with 21 % (34) of tumours at stage 1 or 2, 25 % (40) at stage 3 and 54 % (88) at stage 4. Kaplan-Meier estimates of overall survival were 94 % at 1 year, 88 % at 2 years and 68 % at 5 years after TOLM. Three-quarters (76 %) reported their overall QOL as being good, very good or outstanding, and by domain a clear majority of patients (range 57-94 %, median 79 %) reported none or only minor problems, most notably for swallowing, chewing and speech. The main dysfunction was in saliva (39 %). In conclusion, the outcomes in TOLM for oropharyngeal squamous cell carcinoma are very encouraging. The data supports the current treatment strategy in the Unit. Further outcomes research is required to help refine patient selection to help optimise the survival and HRQOL benefit of TOLM.

Transoral Surgery or Radiotherapy for Oropharyngeal Carcinoma - Is It Either Or ?

The management of oropharyngeal carcinoma represents an increasing clinical challenge, because of its rising incidence, particularly in younger patients as a result of human papillomavirus (HPV) infection, and because significant technological advances have occurred in radiotherapy and surgery over the last 10 years that have increased treatment options for patients, with little robust evidence yet of their relative merits. As a result, there is a lack of clinical consensus on the optimum treatment modality, reflected in wide variation in practice between different cancer networks across the UK. Here, we consider the evidence base for minimally invasive transoral surgery and for intensity-modulated radiotherapy-based primary treatment for oropharyngeal cancer, in terms of both oncological and functional outcomes. Management strategies for HPV-positive and HPV-negative disease, and for different stages of the disease, are considered. There is currently an unparalleled opportunity to shape the future management of oropharyngeal cancer, which is dependent on recruiting patients to ongoing clinical trials, in order to build an evidence base to support a clinical consensus on the optimal treatment strategies. It appears likely that future evidence-based decision-making will use both primary radiotherapy and primary surgical treatment modalities to maximise patient benefit.

Injection of botulinum toxin for the treatment of post-laryngectomy pharyngoesophageal spasm-related disorders.

Introduction Pharyngoesophageal spasm (PES) can cause dysphagia, central valve leak (CVL), and dypshonia in post-laryngectomy patients. Botulinum toxin has been used effectively for the treatment of PES, but data regarding patient-reported outcomes and efficacy for CVL are limited. We evaluated the results of botox injection for PES spasm using subjective and objective measures. Methods Data were collected prospectively (February 2010 to August 2013) on 13 patients undergoing botox injection for PES as identified by video fluoroscopy. We collected digital voice recordings, air-pressure measurements (APMs) for speech, and quality of life (QoL) data before and after the procedure: University of Washington QoL questionnaire (UW-QoL), MD Anderson Swallowing Inventory (MDADI) and the Voice Handicap Index (VHI-30). Results APMs for a sustained vowel decreased by 18% after botox injection, whereas maximum phonatory times increased by 63% (mean increase, 8 to 13 seconds). Sustained vowel amplitude decreased (mean, 87db to 83db) with an associated reduction in sustained vowel frequency (117Hz to 77Hz). MDADI scores improved by 10.2% overall, and UW-QoL scores showed an improvement in score of 7.6%. Mean scores for VHI-30 deteriorated by 2% overall but, when considering only those patients experiencing dysphonia, an improvement of 9.4% was seen. There was an overall net reduction for the CVL cohort of 12 speech valves in the year after injection. Conclusions Our series confirm the safety and objective efficacy of botox injection for PES. QoL measurements were less convincing, and this disparity between subjective and objective measurements must be considered when treating such patients.

Upper airway obstruction in a patient with Ehlers-Danlos syndrome.

We report a case of recurrent airway obstruction episodes resulting from laryngeal hypermobility in a patient with Ehlers-Danlos syndrome. A 44-year-old woman, with known Ehlers-Danlos syndrome, presented with recent onset of episodes of upper airway obstruction due to hypermobility of her larynx. A suitable conservative management strategy proved elusive and the patient finally underwent a thyrohyoidopexy. The patient remains symptom free nine months after the procedure. This is the first report of spontaneous life threatening upper airway obstruction due to hypermobility of the suprahyoid suspensory soft tissues in Ehlers-Danlos syndrome.

Circulating and disseminated tumour cells in head and neck cancer.

BACKGROUND: Multimodal treatment options in head and neck squamous cell carcinoma have allowed for greater control of locoregional disease, but this has not translated into a significant overall survival advantage for patients. This is partially because these treatment modalities have no influence over the rate of development of distant metastases. OBJECTIVE: This article summarises the current methods of detecting circulating and disseminated tumour cells. It also discusses how these cells can offer prognostic value in head and neck squamous cell carcinoma, and considers questions posed by the identification of these cells. METHODS: A literature search of relevant journal articles was performed using ScienceDirect and PubMed databases, and a general article search was conducted using the online search engine Google. RESULTS AND CONCLUSION: The evidence presented in this article indicates that circulating tumour cells and disseminated tumour cells may be clinically useful as prognostic markers or in the assessment of response to treatment in head and neck squamous cell carcinoma.

Incidental head and neck findings on 18F-fluoro-deoxy-glucose positron emission tomography computed tomography.

OBJECTIVE: The overlapping risk factors for lung and head and neck cancer present a definite risk of synchronous malignant pathology. This is the first study to specifically review incidental positron emission tomography computed tomography findings in the head and neck region in lung carcinoma patients. METHODS: A retrospective review was performed of all lung cancer patients who underwent positron emission tomography computed tomography imaging over a five-year period (January 2008 - December 2012), identified from the Liverpool thoracic multidisciplinary team database. RESULTS: Six hundred and nine patients underwent positron emission tomography computed tomography imaging over this period. In 76 (12.5 per cent) scans, incidental regions of avid 18F-fluoro-deoxy-glucose uptake were reported in the head and neck region. In the 28 patients who were fully investigated, there were 4 incidental findings of malignancy. CONCLUSION: In lung cancer patients undergoing investigative positron emission tomography computed tomography scanning, a significant number will also present with areas of clinically significant 18F-fluoro-deoxy-glucose uptake in the head and neck region. Of these, at least 5 per cent may have an undiagnosed malignancy.