Experimentally increased snow depth affects high Arctic microarthropods inconsistently over two consecutive winters.

Climate change induced alterations to winter conditions may affect decomposer organisms controlling the vast carbon stores in northern soils. Soil microarthropods are particularly abundant decomposers in Arctic ecosystems. We studied whether increased snow depth affected microarthropods, and if effects were consistent over two consecutive winters. We sampled Collembola and soil mites from a snow accumulation experiment at Svalbard in early summer and used soil microclimatic data to explore to which aspects of winter climate microarthropods are most sensitive. Community densities differed substantially between years and increased snow depth had inconsistent effects. Deeper snow hardly affected microarthropods in 2015, but decreased densities and altered relative abundances of microarthropods and Collembola species after a milder winter in 2016. Although increased snow depth increased soil temperatures by 3.2 °C throughout the snow cover periods, the best microclimatic predictors of microarthropod density changes were spring soil temperature and snowmelt day. Our study shows that extrapolation of observations of decomposer responses to altered winter climate conditions to future scenarios should be avoided when communities are only sampled on a single occasion, since effects of longer-term gradual changes in winter climate may be obscured by inter-annual weather variability and natural variability in population sizes.

Spatiotemporal kinetics of the SRP pathway in live E. coli cells.

Mechanistic details of the signal recognition particle (SRP)-mediated insertion of membrane proteins have been described from decades of in vitro biochemical studies. However, the dynamics of the pathway inside the living cell remain obscure. By combining in vivo single-molecule tracking with numerical modeling and simulated microscopy, we have constructed a quantitative reaction-diffusion model of the SRP cycle. Our results suggest that the SRP-ribosome complex finds its target, the membrane-bound translocon, through a combination of three-dimensional (3D) and 2D diffusional search, together taking on average 750 ms. During this time, the nascent peptide is expected to be elongated only 12 or 13 amino acids, which explains why, in Escherichia coli, no translation arrest is needed to prevent incorrect folding of the polypeptide in the cytosol. We also found that a remarkably high proportion (75%) of SRP bindings to ribosomes occur in the cytosol, suggesting that the majority of target ribosomes bind SRP before reaching the membrane. In combination with the average SRP cycling time, 2.2 s, this result further shows that the SRP pathway is capable of targeting all substrate ribosomes to translocons.

Direct measurements of mRNA translation kinetics in living cells.

Ribosome mediated mRNA translation is central to life. The cycle of translation, however, has been characterized mostly using reconstituted systems, with only few techniques applicable for studies in the living cell. Here we describe a live-cell ribosome-labeling method, which allows us to characterize the whole processes of finding and translating an mRNA, using single-molecule tracking techniques. We find that more than 90% of both bacterial ribosomal subunits are engaged in translation at any particular time, and that the 30S and 50S ribosomal subunits spend the same average time bound to an mRNA, revealing that 30S re-initiation on poly-cistronic mRNAs is not prevalent in E. coli. Instead, our results are best explained by substantial 70S re-initiation of translation of poly-cistronic mRNAs, which is further corroborated by experiments with translation initiation inhibitors. Finally, we find that a variety of previously described orthogonal ribosomes, with altered anti-Shine-Dalgarno sequences, show significant binding to endogenous mRNAs.

Seasonal Fluctuations in Iron Cycling in Thawing Permafrost Peatlands.

In permafrost peatlands, up to 20% of total organic carbon (OC) is bound to reactive iron (Fe) minerals in the active layer overlying intact permafrost, potentially protecting OC from microbial degradation and transformation into greenhouse gases (GHG) such as CO2 and CH4. During the summer, shifts in runoff and soil moisture influence redox conditions and therefore the balance of Fe oxidation and reduction. Whether reactive iron minerals could act as a stable sink for carbon or whether they are continuously dissolved and reprecipitated during redox shifts remains unknown. We deployed bags of synthetic ferrihydrite (FH)-coated sand in the active layer along a permafrost thaw gradient in Stordalen mire (Abisko, Sweden) over the summer (June to September) to capture changes in redox conditions and quantify the formation and dissolution of reactive Fe(III) (oxyhydr)oxides. We found that the bags accumulated Fe(III) under constant oxic conditions in areas overlying intact permafrost over the full summer season. In contrast, in fully thawed areas, conditions were continuously anoxic, and by late summer, 50.4 ± 12.8% of the original Fe(III) (oxyhydr)oxides were lost via dissolution. Periodic redox shifts (from 0 to +300 mV) were observed over the summer season in the partially thawed areas. This resulted in the dissolution and loss of 47.2 ± 20.3% of initial Fe(III) (oxyhydr)oxides when conditions are wetter and more reduced, and new formation of Fe(III) minerals (33.7 ± 8.6% gain in comparison to initial Fe) in the late summer under more dry and oxic conditions, which also led to the sequestration of Fe-bound organic carbon. Our data suggest that there is seasonal turnover of iron minerals in partially thawed permafrost peatlands, but that a fraction of the Fe pool remains stable even under continuously anoxic conditions.

Radiotherapy as Elective Treatment of the Node-negative Neck in Oral Squamous Cell Cancer.

BACKGROUND/AIM: Previous studies of node-negative oral squamous cell carcinoma have shown a benefit of elective neck dissection compared to observation. Evidence for radiotherapy as single-modality elective treatment of the node-negative neck is so far lacking. PATIENTS AND METHODS: In a retrospective material of 420 early-stage oral cancers from 2000 to 2016, overall survival, disease-free survival, and regional relapse-free survival were calculated with the Kaplan-Meier method. RESULTS: At five years, overall survival was 59.7%, disease-specific survival was 77.2%, and regional relapse-free survival was 83.5%. Among those with adjuvant treatment of the neck after surgery of T1-T2 tumours during 2009-2016, regional relapse-free survival at five years was 85.7% for elective radiotherapy of the neck and 87.4% for elective neck dissection. CONCLUSION: Elective radiotherapy to the neck with a modern technique and adequate dose might be an alternative to neck dissection for patients with early-stage oral squamous cell cancer.

Cardiac involvement in critically ill and mechanically ventilated patients with COVID-19 - a prospective, observational echocardiographic study.

INTRODUCTION: In this prospective, observational study, we have evaluated right (RV) and left (LV) ventricular function with echocardiography and correlated it to the levels of biomarkers, hs-TNT, NT-pro-BNP, D-dimer and fibrinogen. In a subgroup, we have evaluated the effect of inhaled milrinone on RV afterload and function. METHODS: Thirty-one ICU patients with COVID-19 in need of mechanical ventilation and norepinephrine infusion were prospectively included. Hemodynamic and respiratory variables were measured at the time of the echocardiographic examination and biomarkers were obtained on arrival at the ICU and then followed up routinely. Eight patients received inhaled aerosolized milrinone at a dose of 2.5 mg/hour. RESULTS: The most common echocardiographic pattern was RV dilation with or without systolic dysfunction, which was found in 62% of patients. Pulmonary acceleration time was abnormal in 55% and indices of RV systolic function, such as fractional area of change, RV strain, were abnormal in 30% and 31% of patients respectively. A cardiac index of < 2.5 l/min*m2 was seen in 58% of the patients. Left ventricular ejection fraction and global left ventricular strain were impaired in 10% and 16% respectively. The correlation between echocardiographic variables and cardiac biomarkers was poor. RV afterload correlated well to the levels of D-dimer. Milrinone inhalation did not improve RV function or afterload. CONCLUSION: RV dysfunction was the most common finding. The poor correlation to cardiac biomarkers argues against extensive myocardial involvement. The lack of improvement in RV function after milrinone inhalation suggests that the most likely cause of RV dysfunction is increased RV afterload caused by pulmonary thrombosis/embolism.

High-dose-rate brachytherapy as monotherapy for low- and intermediate-risk prostate cancer: long-term experience of Swedish single-center.

PURPOSE: Until now, most long-term results for brachytherapy only has been published for low-dose-rate (LDR) seeds. Due to radiobiology reasons, high-dose-rate (HDR) mono-brachytherapy is of growing interest. The aim of the study was to report long-term biochemical control rate and toxicities with HDR monotherapy. MATERIAL AND METHODS: This was a retrospective single-institution experience, including 229 men, clinically staged T1c-T2b, Gleason 3 + 3 (prostate specific antigen (PSA) ≤ 15), or Gleason 3 + 4 (PSA ≤ 10), consecutively treated between 2004 and 2012 with HDR brachytherapy alone, using three different fractionation schedules of 92-95 Gy (EQD(2), α/ß = 3). Group 4F (n = 19) had a single implant of 9.5 Gy in four fractions over 2 days. Group 3F (n = 107) had three separate implants of 11 Gy over 4 weeks. Group 2F (n = 103) had two implants of 14 Gy over 2 weeks. No adjuvant hormonal therapy was allowed. RESULTS: For 4F, 3F, and 2F study groups, median follow-up was 10.2, 7.1, and 6.1 years, respectively, and biochemical failure rate was 10.5%, 4.7%, and 14.6%, respectively. Early and late side effects were followed with common terminology criteria version 2.0 and patient-reported questionnaires. There were a temporary acute urethral toxicity increase, 1-2 grades over baseline lower urinary tract symptoms (LUTS), which usually recovered. About 1/3 of the patients had a remaining one grade over baseline LUTS. Severe grade 3-4 toxicity were only found in 3.5% of patients. No rectal toxicity was observed. Erectile dysfunction (ED) was depending on age and erectile function before treatment. In patients without ED before the treatment, we found a complete ED in 21% of men at the last follow-up. CONCLUSIONS: In the present study, HDR mono-brachytherapy was found to be an effective treatment, with mild long-term side effects difficult to differentiate from aging effects. There were no significant differences in PSA regression, PSA failure rate, and toxicity between the different fraction schedules.

The missing pieces for better future predictions in subarctic ecosystems: A Torneträsk case study.

Arctic and subarctic ecosystems are experiencing substantial changes in hydrology, vegetation, permafrost conditions, and carbon cycling, in response to climatic change and other anthropogenic drivers, and these changes are likely to continue over this century. The total magnitude of these changes results from multiple interactions among these drivers. Field measurements can address the overall responses to different changing drivers, but are less capable of quantifying the interactions among them. Currently, a comprehensive assessment of the drivers of ecosystem changes, and the magnitude of their direct and indirect impacts on subarctic ecosystems, is missing. The Torneträsk area, in the Swedish subarctic, has an unrivalled history of environmental observation over 100 years, and is one of the most studied sites in the Arctic. In this study, we summarize and rank the drivers of ecosystem change in the Torneträsk area, and propose research priorities identified, by expert assessment, to improve predictions of ecosystem changes. The research priorities identified include understanding impacts on ecosystems brought on by altered frequency and intensity of winter warming events, evapotranspiration rates, rainfall, duration of snow cover and lake-ice, changed soil moisture, and droughts. This case study can help us understand the ongoing ecosystem changes occurring in the Torneträsk area, and contribute to improve predictions of future ecosystem changes at a larger scale. This understanding will provide the basis for the future mitigation and adaptation plans needed in a changing climate.

Mutational Pathways and Trade-Offs Between HisA and TrpF Functions: Implications for Evolution via Gene Duplication and Divergence.

When a new activity evolves by changes in a pre-existing enzyme this is likely to reduce the original activity, generating a functional trade-off. The properties of this trade-off will affect the continued evolution of both functions. If the trade-off is strong, gene duplication and subsequent divergence would be favored whereas if the trade-off is weak a bi-functional enzyme could evolve that performs both functions. We previously showed that when a bi-functional HisA enzyme was evolved under selection for both HisA and TrpF functions, evolution mainly proceeded via duplication-divergence and specialization, implying that the trade-off is strong between these two functions. Here, we examined this hypothesis by identifying the mutational pathways (i.e., the mutational landscape) in the Salmonella enterica HisA enzyme that conferred a TrpF-like activity, and examining the trade-offs between the original and new activity. For the HisA enzyme there are many different paths toward the new TrpF function, each with its own unique trade-off. A total of 16 single mutations resulted in HisA enzyme variants that acquired TrpF activity and only three of them maintained HisA activity. Twelve mutants were evolved further toward increased TrpF activity and during evolution toward improved TrpF activity the original HisA activity was completely lost in all lineages. We propose that, aside from various relevant ecological factors, two main genetic factors influence whether evolution of a new function proceeds via duplication - divergence (specialization) or by evolution of a generalist: (i) the relative mutation supply of the two pathways and (ii) the shape of the trade-off curve between the native and new function.

Selection for novel metabolic capabilities in Salmonella enterica.

Bacteria are known to display extensive metabolic diversity and many studies have shown that they can use an extensive repertoire of small molecules as carbon- and energy sources. However, it is less clear to what extent a bacterium can expand its existing metabolic capabilities by acquiring mutations that, for example, rewire its metabolic pathways. To investigate this capability and potential for evolution of novel phenotypes, we sampled large populations of mutagenized Salmonella enterica to select very rare mutants that can grow on minimal media containing 124 low molecular weight compounds as sole carbon sources. We found mutants growing on 18 of these novel carbon sources, and identified the causal mutations that allowed growth for four of them. Mutations that relieve physiological constraints or increase expression of existing pathways were found to be important contributors to the novel phenotypes. For the remaining 14 novel phenotypes, whole genome sequencing of independent mutants and genetic analysis suggested that these novel metabolic phenotypes result from a combination of multiple mutations. This work, by virtue of identifying the genetic and mechanistic basis for new metabolic capabilities, sheds light on the properties of adaptive landscapes underlying the evolution of novel phenotypes.

Validation of a Clinical Cancer Register at the Head and Neck Oncology Center in Örebro.

BACKGROUND: This was a validation study of a regional register of oral cancer in Örebro, Sweden. The purpose was to assess the rate of errors in baseline, and treatment, and the completeness and accuracy of data on recurrences. MATERIALS AND METHODS: A total of 653 cases with squamous cell cancer in the oral cavity were identified from the register. A randomized sample of 73 (11%) was selected, and a set of relevant data was compared to medical records. RESULTS: Data on patient and tumour characteristics showed high accuracy, with 98% correct data and more than 99% of treatment data were correct. Follow-up data had a higher rate of errors, with 23% of recurrences not recorded, 13.6% misclassified, and 9.1% of cases showing errors in timing of the recurrence. CONCLUSION: data concerning patients, tumour status, and treatment in the Regional Head and Neck Register in Örebro are highly accurate. However, the follow-up data contain a higher rate of errors, that must be taken into consideration when evaluating outcome after treatment.

Dissolved organic carbon in streams within a subarctic catchment analysed using a GIS/remote sensing approach.

Climate change projections show that temperature and precipitation increases can alter the exchange of greenhouse gases between the atmosphere and high latitude landscapes, including their freshwaters. Dissolved organic carbon (DOC) plays an important role in greenhouse gas emissions, but the impact of catchment productivity on DOC release to subarctic waters remains poorly known, especially at regional scales. We test the hypothesis that increased terrestrial productivity, as indicated by the normalized difference vegetation index (NDVI), generates higher stream DOC concentrations in the Stordalen catchment in subarctic Sweden. Furthermore, we aimed to determine the degree to which other generic catchment properties (elevation, slope) explain DOC concentration, and whether or not land cover variables representing the local vegetation type (e.g., mire, forest) need to be included to obtain adequate predictive models for DOC delivered into rivers. We show that the land cover type, especially the proportion of mire, played a dominant role in the catchment's release of DOC, while NDVI, slope, and elevation were supporting predictor variables. The NDVI as a single predictor showed weak and inconsistent relationships to DOC concentrations in recipient waters, yet NDVI was a significant positive regulator of DOC in multiple regression models that included land cover variables. Our study illustrates that vegetation type exerts primary control in DOC regulation in Stordalen, while productivity (NDVI) is of secondary importance. Thus, predictive multiple linear regression models for DOC can be utilized combining these different types of explanatory variables.

Dose escalation to 84 Gy with concurrent chemotherapy in stage III NSCLC appears excessively toxic: Results from a prematurely terminated randomized phase II trial.

OBJECTIVES: Concurrent chemoradiotherapy is the mainstay treatment for NSCLC stage III disease. To investigate whether radiation dose escalation based on individual normal tissue constraints can improve outcome, the Swedish lung cancer study group launched this randomized phase II trial. MATERIALS AND METHODS: NSCLC patients with stage III disease, good performance status (0-1) and adequate lung function (FEV1 > 1.0 L and CO diffusion capacity > 40%) received three cycles of cisplatin (75 mg/m2 day 1) and vinorelbine (25 mg/m2 day 1 and 8) every third week. Radiotherapy started concurrently with the second cycle, with either 2 Gy daily, 5 days a week, to 68 Gy (A) or escalated therapy (B) based on constraints to the spinal cord, esophagus and lungs up to 84 Gy by adding an extra fraction of 2 Gy per week. RESULTS: A pre-planned safety analysis revealed excessive toxicity and decreased survival in the escalated arm, and the study was stopped. Thirty-six patients were included during 2011-2013 (56% male, 78% with adenocarcinoma, 64% with PS 0 and 53% with stage IIIB). The median progression-free survival (PFS) and overall survival (OS) were 11 and 17 months in arm B compared to the encouraging results of 28 and 45 months in the standard arm. The 1- and 3-year survival rates were 56% and 33% (B) and 72% and 56% (A), respectively. There were seven toxicity-related deaths due to esophageal perforations and pneumonitis: five in the escalated group and two with standard treatment. CONCLUSION: Dose-escalated concurrent chemoradiotherapy to 84 Gy to primary tumor and nodal disease is hazardous, with a high risk of excessive toxicity, whereas modern standard dose chemoradiotherapy with proper staging given in the control arm shows a promising outcome with a median survival of 45 months and a 3-year survival of 56% (NCT01664663).

Emissions from thaw ponds largely offset the carbon sink of northern permafrost wetlands.

Northern regions have received considerable attention not only because the effects of climate change are amplified at high latitudes but also because this region holds vast amounts of carbon (C) stored in permafrost. These carbon stocks are vulnerable to warming temperatures and increased permafrost thaw and the breakdown and release of soil C in the form of carbon dioxide (CO2) and methane (CH4). The majority of research has focused on quantifying and upscaling the effects of thaw on CO2 and CH4 emissions from terrestrial systems. However, small ponds formed in permafrost wetlands following thawing have been recognized as hotspots for C emissions. Here, we examined the importance of small ponds for C fluxes in two permafrost wetland ecosystems in northern Sweden. Detailed flux estimates of thaw ponds during the growing season show that ponds emit, on average (±SD), 279 ± 415 and 7 ± 11 mmol C m-2 d-1 of CO2 and CH4, respectively. Importantly, addition of pond emissions to the total C budget of the wetland decreases the C sink by ~39%. Our results emphasize the need for integrated research linking C cycling on land and in water in order to make correct assessments of contemporary C balances.

Engineering a palette of eukaryotic chromoproteins for bacterial synthetic biology.

BACKGROUND: Coral reefs are colored by eukaryotic chromoproteins (CPs) that are homologous to green fluorescent protein. CPs differ from fluorescent proteins (FPs) by intensely absorbing visible light to give strong colors in ambient light. This endows CPs with certain advantages over FPs, such as instrument-free detection uncomplicated by ultra-violet light damage or background fluorescence, efficient Förster resonance energy transfer (FRET) quenching, and photoacoustic imaging. Thus, CPs have found utility as genetic markers and in teaching, and are attractive for potential cell biosensor applications in the field. Most near-term applications of CPs require expression in a different domain of life: bacteria. However, it is unclear which of the eukaryotic CP genes might be suitable and how best to assay them. RESULTS: Here, taking advantage of codon optimization programs in 12 cases, we engineered 14 CP sequences (meffRed, eforRed, asPink, spisPink, scOrange, fwYellow, amilGFP, amajLime, cjBlue, meffBlue, aeBlue, amilCP, tsPurple and gfasPurple) into a palette of Escherichia coli BioBrick plasmids. BioBricks comply with synthetic biology's most widely used, simplified, cloning standard. Differences in color intensities, maturation times and fitness costs of expression were compared under the same conditions, and visible readout of gene expression was quantitated. A surprisingly large variation in cellular fitness costs was found, resulting in loss of color in some overnight liquid cultures of certain high-copy-plasmid-borne CPs, and cautioning the use of multiple CPs as markers in competition assays. We solved these two problems by integrating pairs of these genes into the chromosome and by engineering versions of the same CP with very different colors. CONCLUSION: Availability of 14 engineered CP genes compared in E. coli, together with chromosomal mutants suitable for competition assays, should simplify and expand CP study and applications. There was no single plasmid-borne CP that combined all of the most desirable features of intense color, fast maturation and low fitness cost, so this study should help direct future engineering efforts.

Genetic Adaptation to Growth Under Laboratory Conditions in Escherichia coli and Salmonella enterica.

Experimental evolution under controlled laboratory conditions is becoming increasingly important to address various evolutionary questions, including, for example, the dynamics and mechanisms of genetic adaptation to different growth and stress conditions. In such experiments, mutations typically appear that increase the fitness under the conditions tested (medium adaptation), but that are not necessarily of interest for the specific research question. Here, we have identified mutations that appeared during serial passage of E. coli and S. enterica in four different and commonly used laboratory media and measured the relative competitive fitness and maximum growth rate of 111 genetically re-constituted strains, carrying different single and multiple mutations. Little overlap was found between the mutations that were selected in the two species and the different media, implying that adaptation occurs via different genetic pathways. Furthermore, we show that commonly occurring adaptive mutations can generate undesired genetic variation in a population and reduce the accuracy of competition experiments. However, by introducing media adaptation mutations with large effects into the parental strain that was used for the evolution experiment, the variation (standard deviation) was decreased 10-fold, and it was possible to measure fitness differences between two competitors as small as |s| < 0.001.

Experimental Determination and Prediction of the Fitness Effects of Random Point Mutations in the Biosynthetic Enzyme HisA.

The distribution of fitness effects of mutations is a factor of fundamental importance in evolutionary biology. We determined the distribution of fitness effects of 510 mutants that each carried between 1 and 10 mutations (synonymous and nonsynonymous) in the hisA gene, encoding an essential enzyme in the l-histidine biosynthesis pathway of Salmonella enterica. For the full set of mutants, the distribution was bimodal with many apparently neutral mutations and many lethal mutations. For a subset of 81 single, nonsynonymous mutants most mutations appeared neutral at high expression levels, whereas at low expression levels only a few mutations were neutral. Furthermore, we examined how the magnitude of the observed fitness effects was correlated to several measures of biophysical properties and phylogenetic conservation.We conclude that for HisA: (i) The effect of mutations can be masked by high expression levels, such that mutations that are deleterious to the function of the protein can still be neutral with regard to organism fitness if the protein is expressed at a sufficiently high level; (ii) the shape of the fitness distribution is dependent on the extent to which the protein is rate-limiting for growth; (iii) negative epistatic interactions, on an average, amplified the combined effect of nonsynonymous mutations; and (iv) no single sequence-based predictor could confidently predict the fitness effects of mutations in HisA, but a combination of multiple predictors could predict the effect with a SD of 0.04 resulting in 80% of the mutations predicted within 12% of their observed selection coefficients.

Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization.

Small molecule neurotransmitters are essential for the function of the nervous system, and neurotransmitter imbalances are often connected to neurological disorders. The ability to quantify such imbalances is important to provide insights into the biochemical mechanisms underlying the disorder. This proof-of-principle study presents online quantification of small molecule neurotransmitters, specifically acetylcholine, γ-aminobutyric acid (GABA) and glutamate, in rat brain tissue sections using nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging. By incorporating deuterated internal standards in the nano-DESI solvent we show identification, accurate mapping, and quantification of these small neurotransmitters in rat brain tissue without introducing any additional sample preparation steps. We find that GABA is about twice as abundant in the medial septum-diagonal band complex (MSDB) as in the cortex, while glutamate is about twice as abundant in the cortex as compared to the MSDB. The study shows that nano-DESI is well suited for imaging of small molecule neurotransmitters in health and disease.

Differences in health related quality of life in the randomised ARTSCAN study; accelerated vs. conventional radiotherapy for head and neck cancer. A five year follow up.

BACKGROUND AND PURPOSE: Health related quality of life (HRQoL) was assessed in the randomised, prospective ARTSCAN study comparing conventional radiotherapy (CF) with accelerated radiotherapy (AF) for head and neck cancer. MATERIAL AND METHODS: 750 patients with squamous cell carcinoma (of any grade and stage) in the oral cavity, oro-, or hypopharynx or larynx (except T1-2, N0 glottic carcinoma) without distant metastases were randomised to either conventional fractionation (2 Gy/day, 5 days/week in 49 days, total dose 68 Gy) or accelerated fractionation (1.1+2.0 Gy/day, 5 days/week in 35 days, total dose 68 Gy). HRQoL was assessed with EORTC QLQ-C30, QLQ-H&N35 and HADS at baseline, at end of radiotherapy (eRT) and at 3 and 6 months and 1, 2 and 5 years after start of treatment. RESULTS: The AF group reported HRQoL was significantly lower at eRT and at 3 months for most symptoms, scales and functions. Few significant differences were noted between the groups at 6 months and 5 years. Scores related to functional oral intake never reached baseline. CONCLUSION: In comparison to CF, AF has a stronger adverse effect on HRQoL in the acute phase.