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This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It discusses the evidence base pertaining to the management of metastatic neck disease in the setting of an unknown primary and provides recommendations on the work up and management for this group of patients receiving cancer care.

Atmospheric new particle formation (NPF) and growth significantly influences the indirect aerosol-cloud effect within the polar climate system. In this work, the aerosol population is categorised via cluster analysis of aerosol number size distributions (9–915 nm, 65 bins) taken at Villum Research Station, Station Nord (VRS) in North Greenland during a 7 year record (2010–2016). Data are clustered at daily averaged resolution; in total, we classified six categories, five of which clearly describe the ultrafine aerosol population, one of which is linked to nucleation events (up to 39% during summer). Air mass trajectory analyses tie these frequent nucleation events to biogenic precursors released by open water and melting sea ice regions. NPF events in the studied regions seem not to be related to bird colonies from coastal zones. Our results show a negative correlation (r = −0.89) between NPF events and sea ice extent, suggesting the impact of ultrafine Arctic aerosols is likely to increase in the future, given the likely increased sea ice melting. Understanding the composition and the sources of Arctic aerosols requires further integrated studies with joint multi-component ocean-atmosphere observation and modelling.

The present work studies the dynamics of chaotic Rössler oscillators in a star network, where the central node or relay system is controlled by an external and similar system. Without the outer systems, the middle oscillator of the network is an amplified observer of the driver. Varying both amplification and coupling parameters leads the outer systems and the driver–relay to various behaviors. To perform the robustness of the synchronization between different blocks of our network, a certain amount of noise is introduced in all the external systems. This is done to deal with not only the noise amplitude but also the cumulative effects since the noise is introduced in all the outer systems. Later, a finite duration feedback (taken as a single interval) from the relay to the driver is considered to improve the synchronization domain between the driver and relay unit and to accelerate the coherent motion between outer systems. We analyze how synchronization works using the Hamiltonian formalism. We confirm our analysis through mathematical developments and numerical simulations.

Aerosols have a large potential to influence climate through their effects on the microphysics and optical properties of clouds and, hence, on the Earth's radiation budget. Aerosol–cloud interactions have been intensively studied in polluted air, but the possibility that the marine biosphere plays an important role in regulating cloud brightness in the pristine oceanic atmosphere remains largely unexplored. We used 9 yr of global satellite data and ocean climatologies to derive parameterizations of the temporal variability of (a) production fluxes of sulfur aerosols formed by the oxidation of the biogenic gas dimethylsulfide emitted from the sea surface; (b) production fluxes of secondary organic aerosols from biogenic organic volatiles; (c) emission fluxes of biogenic primary organic aerosols ejected by wind action on sea surface; and (d) emission fluxes of sea salt also lifted by the wind upon bubble bursting. Series of global monthly estimates of these fluxes were correlated to series of potential cloud condensation nuclei (CCN) numbers derived from satellite (MODIS). More detailed comparisons among weekly series of estimated fluxes and satellite-derived cloud droplet effective radius (re) data were conducted at locations spread among polluted and clean regions of the oceanic atmosphere. The outcome of the statistical analysis was that positive correlation to CCN numbers and negative correlation to re were common at mid and high latitude for sulfur and organic secondary aerosols, indicating both might be important in seeding cloud droplet activation. Conversely, primary aerosols (organic and sea salt) showed widespread positive correlations to CCN only at low latitudes. Correlations to re were more variable, non-significant or positive, suggesting that, despite contributing to large shares of the marine aerosol mass, primary aerosols are not widespread major drivers of the variability of cloud microphysics. Validation against ground measurements pointed out that the parameterizations used captured fairly well the variability of aerosol production fluxes in most cases, yet some caution is warranted because there is room for further improvement, particularly for primary organic aerosol. Uncertainties and synergies are discussed, and recommendations of research needs are given.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. In the absence of high-level evidence base for follow-up practices, the duration and frequency are often at the discretion of local centres. By reviewing the existing literature and collating experience from varying practices across the UK, this paper provides recommendations on the work up and management of lateral skull base cancer based on the existing evidence base for this rare condition.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Although much commoner in the eastern hemisphere, with an age-standardised incidence rate of 0.39 per 100 000 population, cancers of the nasopharynx form one of the rarer subsites in the head and neck.1 This paper provides recommendations on the work up and management of nasopharyngeal cancer based on the existing evidence base for this condition.

The coronavirus disease 2019 pandemic resulted in the cessation of elective surgery. The continued provision of complex head and neck cancer surgery was extremely variable, with some UK centres not performing any cancer surgery. During the pandemic, Guy's and St Thomas' NHS Foundation Trust received high numbers of coronavirus disease 2019 admissions. This paper presents our experience of elective complex major head and neck cancer surgery throughout the pandemic. A head and neck cancer surgery hub was set up that provided a co-ordinated managed care pathway for cancer patients during the pandemic; the Guy's Cancer Centre provided a separate, self-enclosed coronavirus-free environment within the hospital campus. Sixty-nine head and neck cancer patients were operated on in two months, and 13 patients had a microvascular free tissue transfer. Nosocomial infection with coronavirus disease 2019 was detected in two cases (3 per cent), neither required critical care unit admission. Both patients made a complete recovery and were discharged home. There were no deaths. Performing major head and neck surgery, including free flap surgery, is possible during the pandemic; however, significant changes to conventional practice are required to achieve desirable patient outcomes.

Vascular endothelial growth factor (VEGF) plays a key role in the development of both proliferative diabetic retinopathy (PDR) and diabetic macular oedema (DMO). In recent years, anti-VEGF agents have emerged as new approaches to the treatment of these devastating diabetic complications. Although Phase III studies in the diabetic population are needed, intravitreal anti-VEGF therapy is currently being used in clinical practice. Intravitreal injection is an effective means of delivering anti-VEGF drugs to the retina. However, this is an invasive procedure associated with potentially serious complications, such as endophthalmitis or retinal detachment, which may be significant for patients requiring serial treatment over many years. In addition, although delivered within the vitreous, anti-VEGF drugs could pass into the systemic circulation, which could potentially result in hypertension, proteinuria, increased cardiovascular events and impaired wound healing. Pegaptanib, ranibizumab and bevacizumab are the currently available anti-VEGF agents. Ranibizumab and bevacizumab block all VEGF isoforms, thus impairing both physiological and pathological neovascularisation. Pegaptanib only blocks the VEGF₁₆₅ isoform, and would therefore seem the best option for avoiding systemic adverse effects in diabetic patients, although this remains to be demonstrated in clinical trials. In this regard, head-to-head studies designed to evaluate not only the efficacy, but also the systemic adverse effects of these drugs in a high-risk population such as diabetic patients are warranted.

Aims/hypothesis The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride. Methods This randomised (using a telephone or web-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA₁c 7.5-10%) and combination therapy (7.0-10%) was conducted in 107 centres in 17 countries. The primary endpoint was HbA₁c. Patients were randomised (2:1:2) to liraglutide 1.8 mg once daily (n = 232), liraglutide placebo (n = 115) and open-label insulin glargine (n = 234), all in combination with metformin (1 g twice daily) and glimepiride (4 mg once daily). Investigators, participants and study monitors were blinded to the treatment status of the liraglutide and placebo groups at all times. Results The number of patients analysed as intention to treat were: liraglutide n = 230, placebo n = 114, insulin glargine n = 232. Liraglutide reduced HbA₁c significantly vs glargine (1.33% vs 1.09%; -0.24% difference, 95% CI 0.08, 0.39; p = 0.0015) and placebo (-1.09% difference, 95% CI 0.90, 1.28; p < 0.0001). There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p = 0.0001), and vs glargine (treatment difference -3.43 kg, 95% CI 4.00, 2.86; p < 0.0001). Liraglutide reduced systolic BP (-4.0 mmHg) vs glargine (+0.5 mmHg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine and placebo, respectively). A slightly higher number of adverse events (including nausea at 14%) were reported with liraglutide, but only 9.8% of participants in the group receiving liraglutide developed anti-liraglutide antibodies. Conclusions/interpretation Liraglutide added to metformin and sulfonylurea produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine. The difference vs insulin glargine in HbA₁c was within the predefined non-inferiority margin. Trial registration: ClinicalTrials.gov NCT00331851 Funding: The study was funded by Novo Nordisk A/S.

Numerous factors are considered to impact on the rate of complications during salvage total laryngectomy procedures. Neck dissection could be one of these factors. This study analysed the pattern of lymph node metastasis and rate of occult neck disease during salvage total laryngectomy as well as the impact of neck dissection on survival and complication rates. This was a retrospective analysis of a prospectively maintained laryngectomy database in two large tertiary teaching hospitals. The rate of occult neck disease was 11.1 per cent. Most cases with occult neck disease had rT disease. Patients with complications, advanced tumour stage and positive margins had a significant decrease in overall survival. Patients receiving elective neck dissection did not have any survival benefit. Positron emission tomography-computed tomography showed a very high specificity and negative predictive value. According to the low risk of occult neck disease when using contemporary imaging techniques as well as the lack of impact on survival, conservative management of the neck should be considered for crT -T recurrence.