Updates in Robotic Head and Neck Reconstructive Surgery.

The use of robotics in head and neck surgery has drastically increased over the past two decades. Transoral robotic surgery has revolutionized the surgical approach to the upper aerodigestive tract including the oropharynx and supraglottic larynx. The expanded use and improving technology of robotics have allowed for new approaches in both the ablative and reconstructive aspects of head and neck surgery. Here, we discuss the recent updates in robotics in head and neck surgery and future directions the field may turn.

Internal dosimetric analyser to assist routine, confirmatory and special radiobioassays.

The IAEA Radiation Safety Technical Services Laboratory has developed and validated an Internal Dosimetric Analyser (IDA) software tool to facilitate access to dosimetric data and perform calculations related to individual monitoring for intakes of radionuclides and occupational radiation protection. IDA serves to correlate measurements from routine, confirmatory and special internal monitoring with data obtained from the Occupational Intakes of Radionuclides series of recommendations published by the International Commission on Radiological Protection. The purpose of IDA is to keep the internal dosimetry data in the background and allow the dosimetrist to make the necessary calculations to be able to decide (1) whether the bioassay method and monitoring period are appropriate for routine, confirmatory or special monitoring; (2) whether the method and period will allow the recording level to be detected; (3) whether previous intakes are contributing to the current measurement; and (4) whether measurement uncertainties affect the dose assessment.

Experiences in transitioning a testing laboratoryto the new ISO/IEC 17025:2017 standard.

Since its inception, the international quality standard ISO/IEC 17025 has been revised twice. The most recent edition adopted a new structure to align with other conformity assessment and quality management standards, harmonized the terminology with the International Vocabulary of Metrology and introduced the concept of risk-based thinking. This paper disseminates the experience of the IAEA Radiation Safety Technical Services Laboratory in successful transition and re-accreditation to ISO/IEC 17025:2017. It covers all stages of the transition cycle: from conducting a gap analysis between the existing quality system and the requirements in the revised standard, updating the corresponding quality documents, developing training and communication plans for laboratory personnel, to monitoring the changes and improving the system through auditing, management review and participation in proficiency testing schemes. Lessons learned about building operational resilience and maintaining a business continuity management system to prepare for, respond to, and recover from disruptions are considered.

Novel Machine Learning Model to Predict Interval of Oral Cancer Recurrence for Surveillance Stratification.

OBJECTIVE(S): We aimed to develop a machine learning (ML) model to accurately predict the timing of oral squamous cell carcinoma (OSCC) recurrence across four 1-year intervals. METHODS: Patients with surgically treated OSCC between 2012-2018 were retrospectively identified from the Yale-New Haven Health system tumor registry. Patients with known recurrence or minimum follow-up of 24 months from surgery were included. Patients were classified into one of five levels: four 1-year intervals and one level for no recurrence (within 4 years of surgery). Three sets of data inputs (comprehensive, feature selection, nomogram) were combined with 4 ML architectures (logistic regression, decision tree (DT), support vector machine (SVM), artificial neural network classifiers) yielding 12 models in total. Models were primarily evaluated using mean absolute error (MAE), lower values indicating better prediction of 1-year interval recurrence. Secondary outcomes included accuracy, weighted precision, and weighted recall. RESULTS: 389 patients met inclusion criteria: 102 (26.2%) recurred within 48 months of surgery. Median follow-up time was 25 months (IQR: 15-37.5) for patients with recurrence and 44 months (IQR: 32-57) for patients without recurrence. MAE of 0.654% and 80.8% accuracy were achieved on a 15-variable feature selection input by 2 ML models: DT and SVM classifiers. CONCLUSIONS: To our knowledge, this is the first study to leverage multiclass ML models to predict time to OSCC recurrence. We developed a model using feature selection data input that reliably predicted recurrence within 1-year intervals. Precise modeling of recurrence timing has the potential to personalize surveillance protocols in the future to enhance early detection and reduce extraneous healthcare costs. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1652-1659, 2023.

Correlations of Radiographic and Endoscopic Observations in Subglottic Stenosis.

OBJECTIVE(S): Subglottic stenosis (SGS) represents a constellation of diverse pathologic processes that ultimately lead to narrowing of the subglottic region and can produce significant morbidity. Existing endoscopic and radiographic assessments may not be consistent in practice. METHODS: Severity of stenosis was evaluated and reported using the Cotton-Myer classification system from 33 endoscopic procedures from 32 unique subjects. Radiographic imaging within the preceding 3 month period was subsequently reviewed and narrowing was measured by a blinded radiologist. Degree of stenosis was reported as a percentage in 30 out of 33 endoscopic evaluations and subsequently compared to radiographically determined percentage of stenosis. Statistical analyzes were conducted to evaluate concordance between endoscopic and radiographic assessments. RESULTS: About 45.5% (15/33) of the evaluations were in agreement using Cotton-Myer scoring, while 27.3% (9/33) were discrepant by 1 grade and 27.3% (9/33) by 2 grades. Correlation of degree of stenosis as a percentage using Spearman (coefficient: 0.233, P-value: .214) and Pearson (coefficient: 0.138, P-value: .466) methods demonstrated very weak relationships. Radiographic scoring did not predict endoscopic classification to a significant degree using mixed effects regression. CONCLUSIONS: Radiographic and endoscopic grading of subglottic stenosis may not be reliably concordant in practice.

Global Genome Demethylation Causes Transcription-Associated DNA Double Strand Breaks in HPV-Associated Head and Neck Cancer Cells.

High levels of DNA methylation at CpG loci are associated with transcriptional repression of tumor suppressor genes and dysregulation of DNA repair genes. Human papilloma virus (HPV)-associated head and neck squamous cell carcinomas (HNSCC) have high levels of DNA methylation and methylation has been associated with dampening of an innate immune response in virally infected cells. We have been exploring demethylation as a potential treatment in HPV+ HNSCC and recently reported results of a window clinical trial showing that HNSCCs are particularly sensitive to demethylating agent 5-azacytidine (5-aza). Mechanistically, sensitivity is partially due to downregulation of HPV genes expression and restoration of tumor suppressors p53 and Rb. Here, for the first time, we show that 5-azaC treatment of HPV+ HNSCC induces replication and transcription-associated DNA double strand breaks (DSBs) that occur preferentially at demethylated genomic DNA. Blocking replication or transcription prevented formation of DNA DSBs and reduced sensitivity of HPV-positive head and neck cancer cells to 5-azaC, demonstrating that both replication and active transcription are required for formation of DSBs associated with 5-azaC.

The role of vitamin D in head and neck cancer.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) describes a set of malignancies of the head and neck that continue to inflict considerable morbidity and mortality. Because HNSCC often presents at an advanced stage, patients frequently undergo intensive multi-modal therapy with an intent to cure. Vitamin D is a precursor to the biologically active hormone calcitriol which governs bone and calcium physiology that is obtained from diet and UV-B exposure. Vitamin D is known to have pleiotropic effects on health and disease. In this review, we examine the role of vitamin D in cancer with emphasis on HNSCC and discuss potential avenues for further research that might better elucidate the role of vitamin D in the management of HNSCC. REVIEW METHODS: A review of MEDLINE database indexed literature concerning the role and biology of vitamin D in HNSCC was conducted, with special consideration of recently published work and research involving immunobiology and HNSCC. CONCLUSIONS: The available evidence suggests that vitamin D may play a role in protecting against HNSCC, particularly in persons who smoke, although conflicting and limited data exists. Promising initial work encourages the pursuit of further study. IMPLICATIONS FOR PRACTICE: The significant morbidity and mortality that HNSCC brings warrants continued research in available and safe interventions that improve patient outcomes. With the rise of immunotherapy as an effective modality for treatment, continued research of vitamin D as an adjunct in the treatment of HNSCC is supported.

The role of bile reflux and its related NF-κB activated pathway in progression of hypopharyngeal squamous cell cancer.

BACKGROUND: Prognosis for hypopharyngeal cancer is usually poor, and recurrence is common. Identifying new factors or related mechanisms that promote its progression may have clinical implications. Although, recent studies support bile reflux in hypopharyngeal carcinogenesis, it remains to be explored how bile and its related NF-κB activated pathway may further affects its progression in already established hypopharyngeal cancer. METHODS: Hypopharyngeal squamous cell carcinoma (HSCC) cell lines, FaDu and UMSCC11A, both negative for HPV, were repetitively exposed to bile acids (400 µM) at variable pH points (4.0, 5.5 and 7.0). Immunofluorescence, western blotting, luciferase assay, and qPCR were used to detect NF-κB activation, bcl-2 overexpression and gene expression. RESULTS: Bile at strongly acidic pH (4.0) potentiated the activation of NF-κB and its related mRNA phenotype in HSCC cells. IL-6, TNF-α, and BCL2 were found among the highest overexpressed genes as was previously found in HSCCs excised from patients with documented biliary reflux. An enhanced transcriptional activity of EGFR, RELA, STAT3, and WNT5Α and higher survival rates were observed in HSCC cells exposed to acidic bile compared to those exposed to bile at weakly acidic or neutral pH. CONCLUSION: Our novel findings support the observation that bile reflux has the potential for actively influencing the progression of hypopharyngeal cancer, mediated by NF-κB. In patients with hypopharyngeal cancer and known gastroesophageal reflux disease, antacid therapy may exert a role in furthering control of disease recurrence and progression.

Pediatric thyroidectomies: A surgical subspecialty comparison.

OBJECTIVE: This study aims to establish the typical population, safety, and outcomes of pediatric thyroidectomies, specifically identifying surgical complication rates. Furthermore, the study compares management and complication differences between the two specialties that most often manage these patients - Pediatric General Surgery and Otolaryngology. METHODS: National Surgical Quality Improvement Program - Pediatrics (NSQIP-P) data between the years of 2012 and 2016 was reviewed and analyzed for patient characteristics, perioperative course and outcomes. Sub-group analysis was used to compare groups based on surgeon sub-specialty: Otolaryngology or Pediatric General Surgery. RESULTS: The study identified 516 cases pediatric patients operated on by Pediatric Otolaryngology (229; 44.4%) and Pediatric General Surgery (287; 55.6%). Overall, rates of surgical and medical adverse events were low (1.2% and 0.7%, respectively). Upon univariate analysis, there were no differences between specialties in surgical adverse events (p = 1.000), medical adverse events (p = 0.196), reoperation (p = 0.505), or readmission (p = 0.262). Indication for surgery differed between specialties, with benign neoplasm more common in the Pediatric Otolaryngology group (48.9% vs. 35.2%), and thyrotoxicosis more common in the Pediatric General Surgery group (43.9% vs. 23.1%) (p < 0.001). Compared to cases done by Otolaryngology, Pediatric General Surgery was independently associated with a shorter operative time (B: -31.583 min [95% CI: -42.802 to -20.364]; p < 0.001). CONCLUSION: Thyroidectomy in the pediatric population is a safe procedure with no differences in adverse outcomes noted when comparing Pediatric General Surgeons to Pediatric Otolaryngologists. Pediatric General Surgeons were observed to have a significantly shorter operative time.

Thirty-day morbidity and mortality following otologic/neurotologic surgery: Analysis of the national surgical quality improvement program.

OBJECTIVES/HYPOTHESIS: To determine the rate and timing of, as well as risk factors for, postoperative morbidity and mortality following otologic and neurotologic surgery. STUDY DESIGN: Retrospective cohort study. METHODS: A total of 1,381 patients were identified in the American College of Surgeons National Surgical Quality Improvement Program for the years 2005 to 2010. Simple summary statistics, χ2 , and multivariable logistic regression were performed. RESULTS: Lateral skull base/neurotologic tumor resection (LSB) was done in 35.9%, and middle ear/mastoid procedures (MEM) were performed in 63.5%. The overall adverse event rate was 10.4%, although it was significantly higher for LSB (24.2%) and lower for MEM (2.6%). The overall mortality rate was 1.4%. Complications occurred postdischarge in 40.4% of cases. The outpatient setting (odds ratio [OR]: 0.31, 95% confidence interval [CI]: 0.15-0.65) and undergoing MEM (OR: 0.23, 95% CI: 0.12-0.47) were associated with lower risk of experiencing a complication. Impaired functional status (OR: 10.45, 95% CI: 3.65-29.89) was associated with postoperative mortality. An open wound preoperatively was associated with multiple causes of postoperative morbidity. CONCLUSIONS: Patients undergoing approaches to the skull base and neurotologic tumor resections had the higher adverse event rate. Open wounds were predictive of several postoperative complications, and poor functional status was associated with mortality. Patients with significant comorbidities should be evaluated early on in their postoperative course to prevent readmission as well as major morbidity and mortality. LEVEL OF EVIDENCE: 2b. Laryngoscope, 128:1431-1437, 2018.

Demethylation Therapy as a Targeted Treatment for Human Papillomavirus-Associated Head and Neck Cancer.

Purpose: DNA methylation in human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) may have importance for continuous expression of HPV oncogenes, tumor cell proliferation, and survival. Here, we determined activity of a global DNA-demethylating agent, 5-azacytidine (5-aza), against HPV+ HNSCC in preclinical models and explored it as a targeted therapy in a window trial enrolling patients with HPV+ HNSCC.Experimental Design: Sensitivity of HNSCC cells to 5-aza treatment was determined, and then 5-aza activity was tested in vivo using xenografted tumors in a mouse model. Finally, tumor samples from patients enrolled in a window clinical trial were analyzed to identify activity of 5-aza therapy in patients with HPV+ HNSCC.Results: Clinical trial and experimental data show that 5-aza induced growth inhibition and cell death in HPV+ HNSCC. 5-aza reduced expression of HPV genes, stabilized p53, and induced p53-dependent apoptosis in HNSCC cells and tumors. 5-aza repressed expression and activity of matrix metalloproteinases (MMP) in HPV+ HNSCC, activated IFN response in some HPV+ head and neck cancer cells, and inhibited the ability of HPV+ xenografted tumors to invade mouse blood vessels.Conclusions: 5-aza may provide effective therapy for HPV-associated HNSCC as an alternative or complement to standard cytotoxic therapy. Clin Cancer Res; 23(23); 7276-87. ©2017 AACR.

Time-of-day influences on respiratory sequelae following maximal electroshock-induced seizures in mice.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in refractory epilepsy patients. Although specific mechanisms underlying SUDEP are not well understood, evidence suggests most SUDEP occurs due to seizure-induced respiratory arrest. SUDEP also tends to happen at night. Although this may be due to circumstances in which humans find themselves at night, such as being alone without supervision or sleeping prone, or to independent influences of sleep state, there are a number of reasons why the night (i.e., circadian influences) could be an independent risk factor for SUDEP. We explored this possibility. Adult male WT mice were instrumented for EEG, EMG, and EKG recording and subjected to maximal electroshock (MES) seizures during wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep during the nighttime/dark phase. These data were compared with data collected following seizures induced during the daytime/light phase. Seizures induced during the nighttime were similar in severity and duration to those induced during the daytime; however, seizures induced during the nighttime were associated with a lesser degree of respiratory dysregulation and postictal EEG suppression. Seizures induced during REM sleep during the nighttime were universally fatal, as is seen when seizures are induced during REM during the daytime. Taken together, these data implicate a role for time of day in influencing the physiological consequences of seizures that may contribute to seizure-induced death.NEW & NOTEWORTHY Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. SUDEP frequently occurs during the night, which has been attributed to an effect of sleep. We have shown that sleep state does indeed influence survival following a seizure. That SUDEP occurs during the night could also implicate a circadian influence. In this study we found that time of day independently affects the physiological consequences of seizures.

Comparing 30-Day Morbidity and Mortality in Pediatric and Adult Otologic Surgery.

Objective To determine differences in timing and rate of postoperative adverse events among pediatric and adult populations undergoing specific otologic procedures. Study Design Administrative database study. Setting Multi-institutional database. Subjects and Methods The National Surgical Quality Improvement Program (NSQIP) and NSQIP-Pediatric (NSQIP-P) were used to extract data from 819 adults (years 2005-2010) and 7020 children (years 2012-2014) undergoing tympanoplasty and (tympano)mastoidectomy, respectively. Simple summary statistics, χ2, and multivariable logistic regression analyses were performed. Results There were no significant differences in overall adverse event rates between adults (2.9%) and children (2.3%) ( P = .233). Adults experienced infectious complications more frequently than did children (0.4% vs 0.0%, P = .002). Postdischarge complications accounted for 83.7% of all complications. Children treated by pediatric otolaryngologists had higher readmission rates (odds ratio [OR], 2.80; 95% confidence interval [CI], 1.20-3.60; P = .002). Tympanomastoidectomy was associated with higher odds of reoperation (OR, 1.02; 95% CI, 1.01-1.03; P < .001), as was undergoing a concurrent procedure that did not include myringotomy (OR, 3.38; 95% CI, 1.47-7.79; P = .004). Conclusion Both adult and pediatric otologic surgery are safe, with patients experiencing similarly low complication rates. Most adverse events occur after discharge.

TRAF3/CYLD mutations identify a distinct subset of human papillomavirus-associated head and neck squamous cell carcinoma.

BACKGROUND: The incidence of human papillomavirus (HPV)-associated (HPV-positive) head and neck squamous cell carcinoma (HNSCC) of the oropharynx has dramatically increased over the last decade and continues to rise. Newly diagnosed HPV-positive HNSCCs in the United States currently outnumber any other HPV-associated cancers, including cervical cancer. Despite introduction of the HPV vaccine, the epidemic of HPV-positive HNSCC is expected to continue for approximately 60 years. Compared with patients who have tobacco-associated HNSCC, those who have HPV-positive HNSCC have better overall survival and response to treatment. Current treatment, including chemotherapy and radiation therapy, is associated with lifelong morbidity, and there are limited treatments and no curative options for patients who develop recurrent metastatic disease. Therapeutic de-escalation (decreased radiation dose) is being tested through clinical trials; however, those studies select patients based solely on tumor and patient smoking characteristics. Mechanisms of HPV-driven carcinogenesis in HNSCC are not well understood, which limits new therapeutic strategies and hinders the appropriate selection of patients for de-escalation therapy. METHODS: The authors analyzed HNSCC data from The Cancer Genome Atlas to identify molecular characteristics that correlate with outcomes and integration status of the HPV genome. RESULTS: The current investigations identified a subset of HPV-positive HNSCCs with mutations in the genes TRAF3 (tumor necrosis factor receptor-associated factor 3) and CYLD (cylindromatosis lysine 63 deubiquitinase). Defects in TRAF3 and CYLD correlated with the activation of transcriptional factor nuclear factor κB, episomal HPV status of tumors, and improved patient survival. CONCLUSIONS: Defects in TRAF3/CYLD were accompanied with the activation of nuclear factor κB signaling and maintenance of episomal HPV in tumors, suggesting that these mutations may support an alternative mechanism of HPV tumorigenesis in head and neck tumors. Cancer 2017;123:1778-1790. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Selective antitumor activity of roscovitine in head and neck cancer.

Radiation and chemotherapy that are commonly used to treat human cancers damage cellular DNA. DNA damage appears to be more toxic to cancer cells than normal cells, most likely due to deregulated checkpoint activation and/or deficiency in DNA repair pathways that are characteristics of many tumors. However, unwanted side effects arise as a result of DNA damage to normal cells during the treatment.Here, we show that roscovitine, a cyclin-dependent kinase (CDK) inhibitor that inhibits CDK-1, CDK-2, CDK-5, CDK-7, and CDK-9 due to competitive binding to the ATP site on the kinases, causes significant DNA damage followed by p53-dependent cell death in human papilloma virus (HPV)-positive, but not in HPV-negative, head and neck cancer cells. Since HPV positivity was a molecular marker for increased sensitivity of cells to roscovitine, we reasoned that systemic roscovitine administration would not be toxic to healthy HPV-negative tissue. Indeed, low roscovitine doses significantly inhibited the growth of HPV-associated xenografted tumors in mice without causing any detectable side effects.Given that inhibition of CDKs has been shown to inhibit replication of several viruses, we suggest that roscovitine treatment may represent a selective and safe targeted therapeutic option against HPV-positive head and neck cancer.

Influence of vigilance state on physiological consequences of seizures and seizure-induced death in mice.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. SUDEP occurs more commonly during nighttime sleep. The details of why SUDEP occurs at night are not well understood. Understanding why SUDEP occurs at night during sleep might help to better understand why SUDEP occurs at all and hasten development of preventive strategies. Here we aimed to understand circumstances causing seizures that occur during sleep to result in death. Groups of 12 adult male mice were instrumented for EEG, EMG, and EKG recording and subjected to seizure induction via maximal electroshock (MES) during wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Seizure inductions were performed with concomitant EEG, EMG, and EKG recording and breathing assessment via whole body plethysmography. Seizures induced via MES during sleep were associated with more profound respiratory suppression and were more likely to result in death. Despite REM sleep being a time when seizures do not typically occur spontaneously, when seizures were forced to occur during REM sleep, they were invariably fatal in this model. An examination of baseline breathing revealed that mice that died following a seizure had increased baseline respiratory rate variability compared with those that did not die. These data demonstrate that sleep, especially REM sleep, can be a dangerous time for a seizure to occur. These data also demonstrate that there may be baseline respiratory abnormalities that can predict which individuals have higher risk for seizure-induced death.

Severe epistaxis due to aberrant vasculature in a patient with STAT-1 mutation.

BACKGROUND: Signal transducer and activator 1 (STAT-1) mutations are rare and have been implicated in combined immunodeficiency, enhanced tumorigenesis, and vascular defects. METHODS: A 60-year-old woman with a novel STAT-1 mutation and resulting immunodeficiency, squamous cell carcinoma, and vascular disease presented with profuse epistaxis secondary to rupture of an aberrant artery that she developed in part because of this mutation. After unsuccessful posterior packing, embolization was initiated but subsequently aborted because of a bovine origin carotid artery and a history of multiple carotid dissections. RESULTS: After repeat posterior packing, hemostasis was achieved. No additional episodes of epistaxis occurred in the subsequent 13 months. CONCLUSION: Vascular anomalies can present challenges in epistaxis management. In patients with conditions known to cause vascular anomalies, it is critical to obtain vascular imaging before intervention.

Serotonin neurones have anti-convulsant effects and reduce seizure-induced mortality.

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. Defects in central control of breathing are important contributors to the pathophysiology of SUDEP, and serotonin (5-HT) system dysfunction may be involved. Here we examined the effect of 5-HT neurone elimination or 5-HT reduction on seizure risk and seizure-induced mortality. Adult Lmx1b(f/f/p) mice, which lack >99% of 5-HT neurones in the CNS, and littermate controls (Lmx1b(f/f)) were subjected to acute seizure induction by maximal electroshock (MES) or pilocarpine, variably including electroencephalography, electrocardiography, plethysmography, mechanical ventilation or pharmacological therapy. Lmx1b(f/f/p) mice had a lower seizure threshold and increased seizure-induced mortality. Breathing ceased during most seizures without recovery, whereas cardiac activity persisted for up to 9 min before terminal arrest. The mortality rate of mice of both genotypes was reduced by mechanical ventilation during the seizure or 5-HT2A receptor agonist pretreatment. The selective serotonin reuptake inhibitor citalopram reduced mortality of Lmx1b(f/f) but not of Lmx1b(f/f/p) mice. In C57BL/6N mice, reduction of 5-HT synthesis with para-chlorophenylalanine increased MES-induced seizure severity but not mortality. We conclude that 5-HT neurones raise seizure threshold and decrease seizure-related mortality. Death ensued from respiratory failure, followed by terminal asystole. Given that SUDEP often occurs in association with generalised seizures, some mechanisms causing death in our model might be shared with those leading to SUDEP. This model may help determine the relationship between seizures, 5-HT system dysfunction, breathing and death, which may lead to novel ways to prevent SUDEP.

NUNDO: a numerical model of a human torso phantom and its application to effective dose equivalent calculations for astronauts at the ISS.

The health effects of cosmic radiation on astronauts need to be precisely quantified and controlled. This task is important not only in perspective of the increasing human presence at the International Space Station (ISS), but also for the preparation of safe human missions beyond low earth orbit. From a radiation protection point of view, the baseline quantity for radiation risk assessment in space is the effective dose equivalent. The present work reports the first successful attempt of the experimental determination of the effective dose equivalent in space, both for extra-vehicular activity (EVA) and intra-vehicular activity (IVA). This was achieved using the anthropomorphic torso phantom RANDO(®) equipped with more than 6,000 passive thermoluminescent detectors and plastic nuclear track detectors, which have been exposed to cosmic radiation inside the European Space Agency MATROSHKA facility both outside and inside the ISS. In order to calculate the effective dose equivalent, a numerical model of the RANDO(®) phantom, based on computer tomography scans of the actual phantom, was developed. It was found that the effective dose equivalent rate during an EVA approaches 700 µSv/d, while during an IVA about 20 % lower values were observed. It is shown that the individual dose based on a personal dosimeter reading for an astronaut during IVA results in an overestimate of the effective dose equivalent of about 15 %, whereas under an EVA conditions the overestimate is more than 200 %. A personal dosemeter can therefore deliver quite good exposure records during IVA, but may overestimate the effective dose equivalent received during an EVA considerably.

The MATROSHKA experiment: results and comparison from extravehicular activity (MTR-1) and intravehicular activity (MTR-2A/2B) exposure.

Astronauts working and living in space are exposed to considerably higher doses and different qualities of ionizing radiation than people on Earth. The multilateral MATROSHKA (MTR) experiment, coordinated by the German Aerospace Center, represents the most comprehensive effort to date in radiation protection dosimetry in space using an anthropomorphic upper-torso phantom used for radiotherapy treatment planning. The anthropomorphic upper-torso phantom maps the radiation distribution as a simulated human body installed outside (MTR-1) and inside different compartments (MTR-2A: Pirs; MTR-2B: Zvezda) of the Russian Segment of the International Space Station. Thermoluminescence dosimeters arranged in a 2.54 cm orthogonal grid, at the site of vital organs and on the surface of the phantom allow for visualization of the absorbed dose distribution with superior spatial resolution. These results should help improve the estimation of radiation risks for long-term human space exploration and support benchmarking of radiation transport codes.