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1.  Incidence of cancer among Nordic airline pilots over five decades: occupational cohort study 
BMJ : British Medical Journal  2002;325(7364):567.
Objective
To assess the incidence of cancer among male airline pilots in the Nordic countries, with special reference to risk related to cosmic radiation.
Design
Retrospective cohort study, with follow up of cancer incidence through the national cancer registries.
Setting
Denmark, Finland, Iceland, Norway, and Sweden.
Participants
10 032 male airline pilots, with an average follow up of 17 years.
Main outcome measures
Standardised incidence ratios, with expected numbers based on national cancer incidence rates; dose-response analysis using Poisson regression.
Results
466 cases of cancer were diagnosed compared with 456 expected. The only significantly increased standardised incidence ratios were for skin cancer: melanoma 2.3 (95% confidence interval 1.7 to 3.0), non-melanoma 2.1 (1.7 to 2.8), basal cell carcinoma 2.5 (1.9 to 3.2). The relative risk of skin cancers increased with the estimated radiation dose. The relative risk of prostate cancer increased with increasing number of flight hours in long distance aircraft.
Conclusions
This study does not indicate a marked increase in cancer risk attributable to cosmic radiation, although some influence of cosmic radiation on skin cancer cannot be entirely excluded. The suggestion of an association between number of long distance flights (possibly related to circadian hormonal disturbances) and prostate cancer needs to be confirmed.
What is already known on this topicAirline pilots are occupationally exposed to cosmic radiation and other potentially carcinogenic elementsIn the studies published so far, dose-response patterns have not been characterisedWhat this study addsNo marked risk of cancer attributable to cosmic radiation is observed in airline pilotsA threefold excess of skin cancers is seen among pilots with longer careers, but the influence of recreational exposure to ultraviolet light cannot be quantifiedA slight increase in risk of prostate cancer with increasing number of long haul flights suggests a need for more studies on the effects of circadian hormonal disturbances
PMCID: PMC124549  PMID: 12228131
2.  Incidence of cancer among commercial airline pilots 
OBJECTIVES—To describe the cancer pattern in a cohort of commercial pilots by follow up through the Icelandic Cancer Registry.
METHODS—This is a retrospective cohort study of 458 pilots with emphasis on subcohort working for an airline operating on international routes. A computerised file of the cohort was record linked to the Cancer Registry by making use of personal identification numbers. Expected numbers of cancer cases were calculated on the basis of number of person-years and incidences of cancer at specific sites for men provided by the Cancer Registry. Numbers of separate analyses were made according to different exposure variables.
RESULTS—The standardised incidence ratio (SIR) for all cancers was 0.97 (95% confidence interval (95% CI) 0.62 to 1.46) in the total cohort and 1.16 (95% CI 0.70 to 1.81) among those operating on international routes. The SIR for malignant melanoma of the skin was 10.20, 95% CI 3.29 to 23.81 in the total cohort and 15.63, 95% CI 5.04 to 36.46 in the restricted cohort. Analyses according to number of block-hours and radiation dose showed that malignant melanomas were found in the subgroups with highest exposure estimates, the SIRs were 13.04 and 28.57 respectively. The SIR was 25.00 for malignant melanoma among those who had been flying over five time zones.
CONCLUSIONS—The study shows a high occurrence of malignant melanoma among pilots. It is open to discussion what role exposure of cosmic radiation, numbers of block-hours flown, or lifestyle factors—such as possible excessive sunbathing—play in the aetiology of cancer among pilots. This calls for further and more powerful studies. The excess of malignant melanoma among those flying over five time zones suggests that the importance of disturbance of the circadian rhythm should be taken into consideration in future studies.


Keywords: cancer registry; malignant melanoma of the skin; cosmic radiation; block-hours; time zones
doi:10.1136/oem.57.3.175
PMCID: PMC1739925  PMID: 10810099
3.  Increased frequency of chromosome translocations in airline pilots with long-term flying experience 
Background
Chromosome translocations are an established biomarker of cumulative exposure to external ionising radiation. Airline pilots are exposed to cosmic ionising radiation, but few flight crew studies have examined translocations in relation to flight experience.
Methods
We determined the frequency of translocations in the peripheral blood lymphocytes of 83 airline pilots and 50 comparison subjects (mean age 47 and 46 years, respectively). Translocations were scored in an average of 1039 cell equivalents (CE) per subject using fluorescence in situ hybridisation (FISH) whole chromo-some painting and expressed per 100 CE. Negative binomial regression models were used to assess the relationship between translocation frequency and exposure status and flight years, adjusting for age, diagnostic x ray procedures, and military flying.
Results
There was no significant difference in the adjusted mean translocation frequency of pilots and comparison subjects (0.37 (SE 0.04) vs 0.38 (SE 0.06) translocations/100 CE, respectively). However, among pilots, the adjusted translocation frequency was significantly associated with flight years (p = 0.01) with rate ratios of 1.06 (95% CI 1.01 to 1.11) and 1.81 (95% CI 1.16 to 2.82) for a 1- and 10-year incremental increase in flight years, respectively. The adjusted rate ratio for pilots in the highest compared to the lowest quartile of flight years was 2.59 (95% CI 1.26 to 5.33).
Conclusions
This data suggests that pilots with long-term flying experience may be exposed to biologically significant doses of ionising radiation. Epidemiological studies with longer follow-up of larger cohorts of pilots with a wide range of radiation exposure levels are needed to clarify the relationship between cosmic radiation exposure and cancer risk.
doi:10.1136/oem.2008.038901
PMCID: PMC2608721  PMID: 19074211
4.  Incidence of cancer among Finnish airline cabin attendants, 1967-92. 
BMJ : British Medical Journal  1995;311(7006):649-652.
OBJECTIVE--To assess whether occupational exposure among commercial airline cabin attendants are associated with risk of cancer. DESIGN--Record linkage study. SETTING--Finland. SUBJECTS-1577 female and 187 male cabin attendants who had worked for the Finnish airline companies. MAIN OUTCOME MEASURE--Standardised incidence ratio; expected number of cases based on national cancer incidences. RESULTS--A significant excess of breast cancer (standardised incidence ratio 1.87 (95% confidence interval 1.15 to 2.23)) and bone cancer (15.10 (1.82 to 54.40)) was found among female workers. The risk of breast cancer was most prominent 15 years after recruitment. Risks of leukaemia (3.57 (0.43 to 12.9)) and skin melanoma (2.11 (0.43 to 6.15) were not significantly raised. Among men, one lymphoma and one Kaposi's sarcoma were found (expected number of cases 1.6). CONCLUSIONS--Although the lifestyle of cabin attendants is different from that of the reference population--for example, in terms of social status and parity--concentration of the excess risks to primary sites sensitive to radiation suggests that ionising radiation during flights may add to the cancer risk of all flight personnel. Otherwise the lifestyle of cabin attendants did not seem to affect their risks of cancer. Estimates of the effect of reproductive risk factors only partly explained the increased risk of breast cancer. If present estimates of health hazards due to radiation are also valid for cosmic radiation, then the radiation doses of cabin attendants seem too small to account entirely for the observed excess risk.
PMCID: PMC2551425  PMID: 7549630
5.  Predictors of skin cancer in commercial airline pilots 
Background Skin cancers among commercial airline pilots have been reported to occur at increased rates in pilot populations worldwide. The reasons for these increases are unclear, but postulated factors include ionizing radiation, circadian disruption and leisure sun exposure.
Aims To investigate the potential association of these occupational and lifestyle factors, as well as medical history and skin type, with non-melanoma skin cancer in pilots.
Methods Data were collected using a confidential Internet survey administered in collaboration with the Air Line Pilots Association International to all active pilots in four US commercial airlines. Pilots with non-melanoma skin cancer were compared to those without using multivariable analysis.
Results The response rate was 19%. Among pilots flying <20 years prior to diagnosis, factors associated with increased odds of non-melanoma skin cancer were at-risk skin type, childhood sunburns and family history of non-melanoma skin cancer. Off-duty sunscreen use and family history of melanoma were protective. Among pilots with ≥20 years flight time prior to diagnosis, childhood sunburns and family history of non-melanoma skin cancer persisted as risk factors, with the addition of flight time at high latitude.
Conclusions Further investigation regarding the potential health impact of long-term flying at high latitudes is recommended. Additionally, occupational health programmes for pilots should stress awareness of and protection against established risk factors for non-melanoma skin cancer.
doi:10.1093/occmed/kqp058
PMCID: PMC2729324  PMID: 19465434
Aviation; epidemiological studies; skin cancer
6.  Empirical Evidence for the Effect of Airline Travel on Inter-Regional Influenza Spread in the United States 
PLoS Medicine  2006;3(10):e401.
Background
The influence of air travel on influenza spread has been the subject of numerous investigations using simulation, but very little empirical evidence has been provided. Understanding the role of airline travel in large-scale influenza spread is especially important given the mounting threat of an influenza pandemic. Several recent simulation studies have concluded that air travel restrictions may not have a significant impact on the course of a pandemic. Here, we assess, with empirical data, the role of airline volume on the yearly inter-regional spread of influenza in the United States.
Methods and Findings
We measured rate of inter-regional spread and timing of influenza in the United States for nine seasons, from 1996 to 2005 using weekly influenza and pneumonia mortality from the Centers for Disease Control and Prevention. Seasonality was characterized by band-pass filtering. We found that domestic airline travel volume in November (mostly surrounding the Thanksgiving holiday) predicts the rate of influenza spread (r2 = 0.60; p = 0.014). We also found that international airline travel influences the timing of influenza mortality (r2 = 0.59; p = 0.016). The flight ban in the US after the terrorist attack on September 11, 2001, and the subsequent depression of the air travel market, provided a natural experiment for the evaluation of flight restrictions; the decrease in air travel was associated with a delayed and prolonged influenza season.
Conclusions
We provide the first empirical evidence for the role of airline travel in long-range dissemination of influenza. Our results suggest an important influence of international air travel on the timing of influenza introduction, as well as an influence of domestic air travel on the rate of inter-regional influenza spread in the US. Pandemic preparedness strategies should account for a possible benefit of airline travel restrictions on influenza spread.
Influenza timing and spread in the US from 1996 to 2005 was influenced by the volume of domestic and international air travel. The flight ban after September 11, 2001, was associated with a delayed and prolonged influenza season.
Editors' Summary
Background.
In both the northern and southern hemispheres, influenza epidemics occur annually during the winter “flu season.” Although the disease maps out a remarkably similar pattern in most years, little is known about the specific mechanisms by which geographic spread occurs. Given the perennial possibility of influenza global epidemics (pandemics) such as occurred in 1918, 1957, and 1969, as well as the more recent, localized outbreaks of avian influenza (“bird flu”) in which a high proportion of affected people have died, we need to understand how influenza spreads in order to limit the destructive impact of future pandemics.
Why Was This Study Done?
In theory, airline travel might be expected to play a role in the spread of influenza across large distances. If so, reducing or restricting air travel might be an appropriate public health intervention in the early stages of an influenza pandemic. This study was performed to identify specific effects of air travel on the annual spread of influenza in the United States.
What Did the Researchers Do and Find?
The researchers analyzed weekly government records on deaths from influenza and pneumonia in cities from nine regions of the US during the nine influenza seasons between 1996 and 2005. For each year, they determined the time it took for the epidemic to spread across the US and the date of the national peak in influenza deaths. They then used government estimates of passenger air travel to explore any connection with the timing of the annual flu epidemics.
The analysis found that the usual time for an influenza epidemic to reach peak levels across the US was approximately two weeks, and that the national peak date fell within two days of the average date, February 17, in five of the nine seasons. In general, influenza was found to spread more slowly during years when the number of domestic air travelers, particularly during November, was lower. Also, the peak of the influenza season was found to come later during years when the number of international air travelers, particularly in September, was lower. These results, based on reported deaths from pneumonia or influenza, were corroborated using data from an influenza virus surveillance program, and could not be explained by variations in winter temperatures or by different types of influenza virus circulating in different years.
Of note, the peak date of the US influenza season following September 11, 2001, was delayed by 13 days to March 2, consistent with marked reductions in airline travel following the terrorist attack, and then returned to February 17 over the subsequent two influenza seasons as international airline travel returned to its previous levels. In contrast, the investigators found no delay in the 2001–2002 influenza season in France, where flight restrictions were not imposed.
What Do These Findings Mean?
While this study does not demonstrate that travel restriction would be effective in altering the course of a flu pandemic, it does provides evidence that air travel plays a significant role in the annual spread of influenza in the United States. Although other factors, related or unrelated to the decrease in air travel after September 11, may have affected the course of the 2001–2002 influenza season, the general findings across several years suggest that air travel affects both the peak date and the rate of spread of influenza. These findings merit consideration in the process of preparing for the next influenza pandemic.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030401.
World Health Organization: influenza pandemic preparedness page
US Department of Health and Human Services: avian and pandemic flu information site
Wikipedia page on influenza pandemic (note: Wikipedia is a free Internet encyclopedia that anyone can edit)
doi:10.1371/journal.pmed.0030401
PMCID: PMC1564183  PMID: 16968115
7.  Breast cancer risk among Finnish cabin attendants: a nested case-control study 
Background: Earlier studies have found increased breast cancer risk among female cabin crew. This has been suggested to reflect lifestyle factors (for example, age at first birth), other confounding factors (for example, age at menarche), or occupational factors such as exposure to cosmic radiation and circadian rhythm alterations due to repeated jet lag.
Aims: To assess the contribution of occupational versus lifestyle and other factors to breast cancer risk among cabin attendants in Finland.
Methods: A standardised self-administered questionnaire on demographic, occupational, and lifestyle factors was given to 1041 cabin attendants. A total of 27 breast cancer cases and 517 non-cases completed the questionnaire. Breast cancer diagnoses were confirmed through the Finnish Cancer Registry. Exposure to cosmic radiation was estimated based on self-reported flight history and timetables. A conditional logistic regression model was used for analysis.
Results: In the univariate analysis, family history of breast cancer (OR = 2.67, 95% CI: 1.00 to 7.08) was the strongest determinant of breast cancer. Of occupational exposures, sleep rhythm disruptions (OR = 1.72, 95% CI: 0.70 to 4.27) were positively related and disruption of menstrual cycles (OR = 0.71, 95% CI: 0.26 to 1.96) negatively related to breast cancer. However, both associations were statistically non-significant. Cumulative radiation dose (OR = 0.99, 95% CI: 0.83 to 1.19) showed no effect on breast cancer.
Conclusions: Results suggest that breast cancer risk among Finnish cabin attendants is related to well established risk factors of breast cancer, such as family history of breast cancer. There was no clear evidence that the three occupational factors studied affected breast cancer risk among Finnish flight attendants.
doi:10.1136/oem.2004.014738
PMCID: PMC1741059  PMID: 15961626
8.  Development and evaluation of an intervention aiming to reduce fatigue in airline pilots: design of a randomised controlled trial 
BMC Public Health  2013;13:776.
Background
A considerable percentage of flight crew reports to be fatigued regularly. This is partly caused by irregular and long working hours and the crossing of time zones. It has been shown that persistent fatigue can lead to health problems, impaired performance during work, and a decreased work-private life balance. It is hypothesized that an intervention consisting of tailored advice regarding exposure to daylight, optimising sleep, physical activity, and nutrition will lead to a reduction of fatigue in airline pilots compared to a control group, which receives a minimal intervention with standard available information.
Methods/design
The study population will consist of pilots of a large airline company. All pilots who posses a smartphone or tablet, and who are not on sick leave for more than four weeks at the moment of recruitment, will be eligible for participation.
In a two-armed randomised controlled trial, participants will be allocated to an intervention group that will receive the tailored advice to optimise exposure to daylight, sleep, physical activity and nutrition, and a control group that will receive standard available information. The intervention will be applied using a smartphone application and a website, and will be tailored on flight- and participant-specific characteristics. The primary outcome of the study is perceived fatigue. Secondary outcomes are need for recovery, duration and quality of sleep, dietary and physical activity behaviours, work-private life balance, general health, and sickness absence. A process evaluation will be conducted as well. Outcomes will be measured at baseline and at three and six months after baseline.
Discussion
This paper describes the development of an intervention for airline pilots, consisting of tailored advice (on exposure to daylight and sleep-, physical activity, and nutrition) applied into a smartphone application. Further, the paper describes the design of the randomised controlled trial evaluating the effect of the intervention on fatigue, health and sickness absence. If proven effective, the intervention can be applied as a new and practical tool in fatigue management. Results are expected at the end of 2013.
Trial registration
Netherlands Trial Register: NTR2722
doi:10.1186/1471-2458-13-776
PMCID: PMC3765738  PMID: 23971514
Flight crew; Pilots; Irregular working hours; Fatigue; Intervention; Tailored advice; Implementation; Smartphone application; mHealth
9.  The Absolute Risk of Venous Thrombosis after Air Travel: A Cohort Study of 8,755 Employees of International Organisations 
PLoS Medicine  2007;4(9):e290.
Background
The risk of venous thrombosis is approximately 2- to 4-fold increased after air travel, but the absolute risk is unknown. The objective of this study was to assess the absolute risk of venous thrombosis after air travel.
Methods and Findings
We conducted a cohort study among employees of large international companies and organisations, who were followed between 1 January 2000 and 31 December 2005. The occurrence of symptomatic venous thrombosis was linked to exposure to air travel, as assessed by travel records provided by the companies and organisations. A long-haul flight was defined as a flight of at least 4 h and participants were considered exposed for a postflight period of 8 wk. A total of 8,755 employees were followed during a total follow-up time of 38,910 person-years (PY). The total time employees were exposed to a long-haul flight was 6,872 PY. In the follow-up period, 53 thromboses occurred, 22 of which within 8 wk of a long-haul flight, yielding an incidence rate of 3.2/1,000 PY, as compared to 1.0/1,000 PY in individuals not exposed to air travel (incidence rate ratio 3.2, 95% confidence interval 1.8–5.6). This rate was equivalent to a risk of one event per 4,656 long-haul flights. The risk increased with exposure to more flights within a short time frame and with increasing duration of flights. The incidence was highest in the first 2 wk after travel and gradually decreased to baseline after 8 wk. The risk was particularly high in employees under age 30 y, women who used oral contraceptives, and individuals who were particularly short, tall, or overweight.
Conclusions
The risk of symptomatic venous thrombosis after air travel is moderately increased on average, and rises with increasing exposure and in high-risk groups.
In a cohort study of 8,755 employees of large international organizations followed for 38,910 person-years, Suzanne Cannegieter and colleagues find a risk of one thrombosis per 4,656 long-haul flights.
Editors' Summary
Background.
Blood normally flows smoothly throughout the human body, supplying the brain and other vital organs with oxygen and nutrients. When an injury occurs, proteins called clotting factors make the blood gel or coagulate at the injury site. The resultant blood clot (thrombus) plugs the wound and prevents blood loss. Sometimes, however, a thrombus forms inside an uninjured blood vessel and partly or completely blocks the blood flow. A clot inside one of the veins (vessels that take blood to the heart) deep within the body is called a deep vein thrombosis (DVT). Symptoms of DVT (which usually occurs in the deep veins of the leg) include pain, swelling, and redness in one leg. DVT is usually treated with heparin and warfarin, two anticoagulant drugs that stop the blood clot growing. If left untreated, part of the clot (an embolus) can break off and travel to the lungs, where it can cause a life-threatening condition called pulmonary embolism (PE). Fortunately, DVT and PE are rare but having an inherited blood clotting disorder, taking an oral contraceptive, and some types of surgery are all risk factors for them. In addition, long-haul plane travel increases the risk of DVT and PE, known collectively as venous thrombosis (VT) 2- to 4-fold, in part because the enforced immobilization during flights slows down blood flow.
Why Was This Study Done?
Although the link between air travel and VT was first noticed in the 1950s, exactly how many people will develop DVT and PE (the absolute risk of developing VT) after a long flight remains unknown. This information is needed so that travelers can be given advice about their actual risk and can make informed decisions about trying to reduce that risk by, for example, taking small doses of anticoagulant medicine before a flight. In this study, the researchers have determined the absolute risk of VT during and after long-haul air travel in a large group of business travelers.
What Did the Researchers Do and Find?
The researchers enrolled almost 9,000 employees from several international companies and organizations and followed them for an average of 4.4 years. The details of flights taken by each employee were obtained from company records, and employees completed a Web-based questionnaire about whether they had developed VT and what risk factors they had for the condition. Out of 53 thrombi that occurred during the study, 22 occurred within eight weeks of a long-haul flight (a flight of more than four hours). From this and data on the total time employees spent on long-haul flights, the researchers calculated that these flights tripled the risk of developing VT, and that the absolute risk (the probability of something occurring in a certain time period) of a VT occurring shortly after such travel was one event per 4,656 flights. They also calculated that the risk of VT was increased by exposure to more flights during a short period and to longer flights and was greatest in the first two weeks after a flight. In addition, the risk of VT was particularly high in young employees, women taking oral contraceptives, and people who were short, tall or overweight.
What Do These Findings Mean?
The main finding of this study is that the absolute risk of VT after of a long-haul flight is low—only one passenger out of nearly 5,000 is likely to develop VT because of flying. However, the study included only healthy people without previous VT whose average age was 40 years, so the absolute risk of VT after long-haul flights might be higher in the general traveling population. Even so, this finding strongly suggests that prophylactic (preventative) use of anticoagulants by all long-haul travelers may not be justified because these drugs have potentially dangerous side effects (for example, they can cause uncontrolled bleeding). Subgroups of travelers with additional risk factors for VT might, however, benefit from the use of this and other prophylactic measures, but randomized trials are needed to find out who would benefit most from which prophylactic measure.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040290.
MedlinePlus encyclopedia pages on blood clots, deep vein thrombosis, and pulmonary embolism (in English and Spanish)
Information from the US National Heart Lung and Blood Institute on deep vein thrombosis, including an animation of how DVT causes pulmonary embolisms
Information for patients from the UK National Health Service Direct health encyclopedia on deep vein thrombosis (in several languages)
Information for travelers on DVT from the US Centers for Disease Control and Prevention and from the UK National Travel Health Network and Centre
This study came out of the WHO Research Into Global Hazards of Travel (WRIGHT) project, and WHO's WRIGHT project on Air Travel and Venous Thromboembolism, of which his study forms a part, has a Web site
doi:10.1371/journal.pmed.0040290
PMCID: PMC1989755  PMID: 17896862
10.  Study of dose distribution in a human body in international space station compartments with the tissue-equivalent spherical phantom 
Journal of Radiation Research  2014;55(Suppl 1):i61.
Space radiation is known to be key hazard of manned space mission. To estimate accurately radiation health risk detailed study of dose distribution inside human body by means of human phantom is conducted. In the space experiment MATROSHKA-R, the tissue-equivalent spherical phantom (32 kg mass, 35 cm diameter and 10 cm central spherical cave) made in Russia has been used on board the ISS for more than 8 years. Owing to the specially chosen phantom shape and size, the chord length distributions of the detector locations are attributed to self-shielding properties of the critical organs in a real human body. If compared with the anthropomorphic phantom Rando used inside and outside the ISS, the spherical phantom has lower mass, smaller size and requires less crew time for the detector installation/retrieval; its tissue-equivalent properties are closer to the standard human body tissue than the Rando-phantom material. Originally the spherical phantom was installed in the star board crew cabin of the ISS Service Module, then in the Piers-1, MIM-2 and MIM-1 modules of the ISS Russian segment, and finally in JAXA Kibo module. Total duration of the detector exposure is more than 1700 days in 8 sessions.
In the first phase of the experiment with the spherical phantom, the dose measurements were realized with only passive detectors (thermoluminescent and solid-state track detectors). The detectors are placed inside the phantom along the axes of 20 containers and on the phantom outer surface in 32 pockets of the phantom jacket. After each session the passive detectors are returned to the ground. The results obtained show the dose difference on the phantom surface as much as a factor of 2, the highest dose being observed close to the outer wall of the compartment, and the lowest dose being in the opposite location along the phantom diameter. Maximum dose rate measured in the phantom is obviously due to the galactic cosmic ray (GCR) and Earth' radiation belt contribution on the ISS trajectory. Minimum dose rate is caused mainly by the strongly penetrating GCR particles and is observed behind more than 5 g/cm2 tissue shielding. Critical organ doses, mean-tissue and effective doses of a crew member in the ISS compartments are also estimated with the spherical phantom data. The estimated effective dose rate is found to be from 10 to 15% lower than the averaged dose on the phantom surface as dependent on the attitude of the critical organs.
The spherical phantom proved its effectiveness to measure the critical organ doses together with the effective dose in-flight and if supplied with active dosimeters can be recommended for future exploratory manned missions to monitor continuously the effective dose.
doi:10.1093/jrr/rrt220
PMCID: PMC3941517
space radiation; spherical phantom; passive and active detectors; effective dose
11.  In-flight automated external defibrillator use and consultation patterns 
Background
Limited information exists about the in-flight use and outcomes associated with automatic external defibrillators (AED) on commercial airlines.
Methods
We collected self-reported cases of AED use to an airline consultation service from three US airlines between May 2004 and March 2009. We reviewed all available data files, related consult forms, and recordings. For each case, demographics, initial rhythm, shock delivery/success, survival to admission, and ground medical consultation use were obtained. Success was defined as the return of a perfusing rhythm. Initial rhythms were classified as: sinus, heart block, SVT, atrial fibrillation/flutter, asystole, PEA and VF/VT.
Results
There were a total of 169 AED applications with 40 cardiac arrests. The mean ages were 58 years (SD 15) and 63 years (SD 12) respectively; both populations were 64% male. AEDs were applied for monitoring in 129 (76%) cases with initial rhythms of: sinus 114 (88%); atrial fibrillation/flutter 7 (5%); complete heart block 4 (3%); and SVT 4 (3%). Presenting rhythms among the cardiac arrest population were: asystole 16 (40%); ventricular fibrillation/ventricular tachycardia 10 (25%); and PEA 14 (35%). Fourteen patients were defibrillated including nine of the 10 patients with initial VF/VT and five for the presence of VF/VT after resuscitation for initial PEA/asystole. Defibrillation was advised but not performed in the remaining case of initial VF/VT and no medical consult was obtained. All five successful defibrillations occurred in patients with initial VF/VT. There were 6 (15%; 95% CI 3–27%) survivors with 5 occurring after successful defibrillation for initial VF/VT and one with return of a perfusing rhythm after CPR for a junctional rhythm. Survival in those with VF/VT was 5/10 (50%; 95% CI 14–86%). Medications were delivered twice. The median time to first shock was 19 (IQR 12–24) seconds from AED application. Medical consultation was obtained in 56 (33%) of the 169 AED cases and 14 (35%) of the cardiac arrests.
Conclusion
AEDs resulted in 50% survival among those with VT/VF in-flight and 14% overall survival for cardiac arrest. Survival is poor among patients presenting with non-shockable rhythms. AEDs are used extensively for in-flight monitoring with significant rhythms identified. Ground medical consultation is sought in only one-third of AED uses and cardiac arrests.
doi:10.3109/10903120903572319
PMCID: PMC2881954  PMID: 20128705
12.  Pilot Alcohol Violations Reported in U.S. Newspapers, 1990–2006 
Introduction
Alcohol violations by airline pilots are rare yet remain a public concern. Such incidents often generate widespread news coverage. This study examines the frequency and characteristics of alcohol violation incidents involving airline pilots reported in U.S. newspapers.
Methods
The database of Lexis-Nexis™, which contains full-text articles for over 350 newspapers, was searched to identify alcohol violation incidents involving airline pilots in the U.S. between January 1990 and June 2006. Information pertaining to the pilot, flight, blood alcohol concentration (BAC), and consequence was ascertained for each incident based on the newspaper coverage.
Results
During the study period, newspapers reported on a total of 13 incidents of alcohol violations involving 17 pilots. All but two of the incidents occurred during January 2002 through June 2006. The majority (85%) of the incidents were first identified by airport personnel, such as security screeners, based on suspicion of alcohol use by the pilot. Subsequent alcohol testing revealed a mean BAC of 90 mg/dL (ranging from 10 mg · dL−1 to 182 mg · dL−1). Of the 17 pilots, 6 were known to be prosecuted criminally, including 5 who were sentenced to jail terms.
Discussion
Incidents of alcohol violations by airline pilots reported in U.S. newspapers have increased in recent years. This increase is likely due in part to increased detection resulting from enhanced aviation security and enforcement following the September 2001 terrorist attacks.
PMCID: PMC2730652  PMID: 17183928
alcohol; aviation; pilots
13.  Prevalence of risk factors for breast cancer in German airline cabin crew: a cross-sectional study 
Background
Many epidemiological studies point to an increased risk of breast cancer among female airline cabin crew. Possible causes include occupational factors (e.g. cosmic radiation exposure, chronodisruption), as well as lifestyle and reproductive factors.
Aims
To investigate the frequency of various risk factors in German flight attendants which are recognised to be associated with breast cancer.
Methods
2708 current and former female cabin crew were randomly selected by a flight attendants’ union and mailed a questionnaire; 1311 responded (48% response). Descriptive statistics were used to compare the distribution of breast cancer risk factors with general German population data.
Results
On average, cabin crew were 3.0 cm (95% CI 2.7-3.3) taller than the comparison group, while their body mass index was 2.5 kg/m2 (95% CI 2.4-2.6) lower. We found less use of hormone replacement therapy, but longer average use of oral contraceptives. Nulliparity among respondents aged 45+ was 57% (95% CI 54%-60%) compared to 16%. Average age at first birth was 32.1 years (95% CI 31.7-32.4) vs. 25.5 years. The birth rate was 0.62 (95% CI 0.58-0.67), less than half the population average of 1.34. Alcohol consumption was considerably higher, whereas cabin crew tended to smoke less and performed more physical exercise.
Conclusion
We found important differences in terms of anthropometric, gynaecological, reproductive and lifestyle factors. Some of these differences (e.g. higher nulliparity, alcohol consumption, taller size) could contribute to a higher breast cancer risk, whereas others could lead to a reduction (e.g. increased physical exercise, lower BMI, less HRT use).
doi:10.1186/1745-6673-9-27
PMCID: PMC4110375  PMID: 25067940
Breast cancer; Cabin crew; Flight attendants; Germany
14.  Oxidative Lung Damage Resulting from Repeated Exposure to Radiation and Hyperoxia Associated with Space Exploration 
Background
Spaceflight missions may require crewmembers to conduct Extravehicular Activities (EVA) for repair, maintenance or scientific purposes. Pre-breathe protocols in preparation for an EVA entail 100% hyperoxia exposure that may last for a few hours (5-8 hours), and may be repeated 2-3 times weekly. Each EVA is associated with additional challenges such as low levels of total body cosmic/galactic radiation exposure that may present a threat to crewmember health and therefore, pose a threat to the success of the mission. We have developed a murine model of combined, hyperoxia and radiation exposure (double-hit) in the context of evaluating countermeasures to oxidative lung damage associated with space flight. In the current study, our objective was to characterize the early and chronic effects of repeated single and double-hit challenge on lung tissue using a novel murine model of repeated exposure to low-level total body radiation and hyperoxia. This is the first study of its kind evaluating lung damage relevant to space exploration in a rodent model.
Methods
Mouse cohorts (n=5-15/group) were exposed to repeated: a) normoxia; b) >95% O2 (O2); c) 0.25Gy single fraction gamma radiation (IR); or d) a combination of O2 and IR (O2+IR) given 3 times per week for 4 weeks. Lungs were evaluated for oxidative damage, active TGFβ1 levels, cell apoptosis, inflammation, injury, and fibrosis at 1, 2, 4, 8, 12, 16, and 20 weeks post-initiation of exposure.
Results
Mouse cohorts exposed to all challenge conditions displayed decreased bodyweight compared to untreated controls at 4 and 8 weeks post-challenge initiation. Chronic oxidative lung damage to lipids (malondialdehyde levels), DNA (TUNEL, cleaved Caspase 3, cleaved PARP positivity) leading to apoptotic cell death and to proteins (nitrotyrosine levels) was elevated all treatment groups. Importantly, significant systemic oxidative stress was also noted at the late phase in mouse plasma, BAL fluid, and urine. Importantly, however, late oxidative damage across all parameters that we measured was significantly higher than controls in all cohorts but was exacerbated by the combined exposure to O2 and IR. Additionally, impaired levels of arterial blood oxygenation were noted in all exposure cohorts. Significant but transient elevation of lung tissue fibrosis (p<0.05), determined by lung hydroxyproline content, was detected as early as 2 week in mice exposed to challenge conditions and persisted for 4-8 weeks only. Interestingly, active TGFβ1 levels in +BAL fluid was also transiently elevated during the exposure time only (1-4 weeks). Inflammation and lung edema/lung injury was also significantly elevated in all groups at both early and late time points, especially the double-hit group.
Conclusion
We have characterized significant, early and chronic lung changes consistent with oxidative tissue damage in our murine model of repeated radiation and hyperoxia exposure relevant to space travel. Lung tissue changes, detectable several months after the original exposure, include significant oxidative lung damage (lipid peroxidation, DNA damage and protein nitrosative stress) and increased pulmonary fibrosis. These findings, along with increased oxidative stress in diverse body fluids and the observed decreases in blood oxygenation levels in all challenge conditions (whether single or in combination), lead us to conclude that in our model of repeated exposure to oxidative stressors, chronic tissue changes are detected that persist even months after the exposure to the stressor has ended. This data will provide useful information in the design of countermeasures to tissue oxidative damage associated with space exploration.
PMCID: PMC3866035  PMID: 24358450
Apoptosis; Bronchoalveolar lavage; Caspase 3; Double-hit; Extravehicular activity; Hyperoxia; Inflammation; Lung fibrosis; Lung injury; Mouse model; Nitrotyrosine; Oxidative stress; PARP; Radiation pneumonopathy; Space exploration; TGF-β1; Total body irradiation; TUNEL
15.  Influences of early shift work on the diurnal cortisol rhythm, mood and sleep: Within-subject variation in male airline pilots 
Psychoneuroendocrinology  2013;38(4):533-541.
Summary
We aimed to investigate how early and late work shifts influenced the diurnal cortisol rhythm using a within-subjects study design. Participants were 30 healthy male non-smoking pilots, mean age 39.4, employed by a short-haul airline. The standard rotating shift pattern consisted of 5 early shifts (starting before 0600 h), followed by 3 rest days, 5 late shifts (starting after 1200 h) and 4 rest days. Pilots sampled saliva and completed subjective mood ratings in a logbook 6 times over the day on two consecutive early shift days, two late days and two rest days. Sampling was scheduled at waking, waking + 30 m, waking + 2.5 h, waking + 8 h, waking + 12 h and bedtime. Waking time, sleep duration, sleep quality and working hours were also recorded. Cortisol responses were analysed with repeated measures analysis of variance with shift condition (early, late, rest) and sample time (1–6) as within-subject factors. Early shifts were associated with a higher cortisol increase in response to awakening (CARi), a greater total cortisol output over the day (AUCG) and a slower rate of decline over the day than late shifts or rest days. Early shifts were also associated with shorter sleep duration but co-varying for sleep duration did not alter the effects of shift on the cortisol rhythm. Both types of work shift were associated with more stress, tiredness and lower happiness than rest days, but statistical adjustment for mood ratings did not alter the findings. Early shift days were associated with significantly higher levels of circulating cortisol during waking hours than late shifts or rest days.
doi:10.1016/j.psyneuen.2012.07.012
PMCID: PMC3608033  PMID: 22877997
Shift work; Cortisol; Hpa axis; Time of waking; Sleep
16.  R3DE: Radiation Risk Radiometer-Dosimeter on the International Space Station—Optical Radiation Data Recorded During 18 Months of EXPOSE-E Exposure to Open Space 
Astrobiology  2012;12(5):393-402.
Abstract
Radiation Risk Radiometer-Dosimeter E (R3DE) served as a device for measuring ionizing and non-ionizing radiation as well as cosmic radiation reaching biological samples located on the EXPOSE platform EXPOSE-E. The duration of the mission was almost 1.5 years (2008–2009). With four channels, R3DE detected the wavelength ranges of photosynthetically active radiation (PAR, 400–700 nm), UVA (315–400 nm), UVB (280–315 nm), and UVC (<280 nm). In addition, the temperature was recorded. Cosmic ionizing radiation was assessed with a 256-channel spectrometer dosimeter (see separate report in this issue). The light and UV sensors of the device were calibrated with spectral measurement data obtained by the Solar Radiation and Climate Experiment (SORCE) satellite as standard. The data were corrected with respect to the cosine error of the diodes. Measurement frequency was 0.1 Hz. Due to errors in data transmission or temporary termination of EXPOSE power, not all data could be acquired. Radiation was not constant during the mission. At regular intervals of about 2 months, low or almost no radiation was encountered. The radiation dose during the mission was 1823.98 MJ m−2 for PAR, 269.03 MJ m−2 for UVA, 45.73 MJ m−2 for UVB, or 18.28 MJ m−2 for UVC. Registered sunshine duration during the mission was about 152 days (about 27% of mission time).The surface of EXPOSE was most likely turned away from the Sun for considerably longer. R3DE played a crucial role on EXPOSE-EuTEF (EuTEF, European Technology Exposure Facility), because evaluation of the astrobiology experiments depended on reliability of the data collected by the device. Observed effects in the samples were weighted by radiation doses measured by R3DE. Key Words: ISS—EXPOSE-E—R3DE—Radiation measurement—PAR—UV radiation. Astrobiology 12, 393–402.
doi:10.1089/ast.2011.0743
PMCID: PMC3371263  PMID: 22680686
17.  Gene Expression Signatures That Predict Radiation Exposure in Mice and Humans 
PLoS Medicine  2007;4(4):e106.
Background
The capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation.
Methods and Findings
We have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, ranging from 50 cGy to 1,000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from nonirradiated samples with an accuracy of 90%, sensitivity of 85%, and specificity of 94%. We further demonstrate that a radiation profile developed in the mouse can correctly distinguish PB samples from irradiated and nonirradiated human patients with an accuracy of 77%, sensitivity of 82%, and specificity of 75%. Taken together, these data demonstrate that molecular profiles can be generated that are highly predictive of different levels of radiation exposure in mice and humans.
Conclusions
We suggest that this approach, with additional refinement, could provide a method to assess the effects of various environmental inputs into biological phenotypes as well as providing a more practical application of a rapid molecular screening test for the diagnosis of radiation exposure.
John Chute and colleagues report that gene expression patterns in peripheral blood mononuclear cells from mice and humans reflect prior radiation exposure.
Editors' Summary
Background.
Everyone living on earth is constantly exposed to low levels of ionizing radiation—energy in the form of waves or particles that is powerful enough to strip electrons out of atoms and to break chemical bonds in important biomolecules. These low levels of ionizing radiation come from radioactive chemicals in the ground and cosmic rays, for example, and are relatively harmless. Occasionally, though, individuals are exposed to larger amounts of ionizing radiation, often as a result of medical tests and treatments but sometimes through the accidental or deliberate release of radioactive chemicals. These larger doses, which permanently damage or kill cells, can cause radiation sickness, a condition characterized by bone marrow failure, gut problems, susceptibility to bacterial infections, and other symptoms that develop days or months after exposure to ionizing radiation. Particularly large doses can be lethal but even moderate doses can increase an individual's risk of developing cancer later in life.
Why Was This Study Done?
Some of the effects of ionizing radiation can be reduced if suitable treatment is started immediately after exposure. Unfortunately, it takes several days to estimate the amount of ionizing radiation to which an individual has been exposed. It would be useful to measure personal exposures more quickly, especially in emergency situations where ideally doctors would be able to distinguish rapidly and accurately between the “worried well” and exposed individuals. As cells respond to irradiation by altering the expression of some genes, the researchers in this study investigated whether gene expression profiling (a molecular biology technique that catalogues all the genes expressed by a cell) can be used to define a set of gene expression changes—called a metagene—that differentiates between irradiated and non-irradiated cells.
What Did the Researchers Do and Find?
The researchers exposed mice to no ionizing radiation, a low dose that causes no medical problems, an intermediate dose that damages blood cells, or a lethal dose. Six hours later, they isolated blood cells from the mice, and catalogued which genes each sample expressed. Using this information, the researchers identified and validated metagenes that accurately distinguished between blood samples from non-irradiated and irradiated animals and between samples from animals exposed to different radiation doses. The researchers then developed a metagene for human radiation exposure using blood samples taken from patients before and after total body irradiation given as part of their medical treatment. This metagene correctly identified 18 of 20 pre-irradiation samples and 17 of 20 post-irradiation samples. Finally, the researchers tested whether the radiation metagenes developed in mice could distinguish between samples taken from irradiated and non-irradiated people. Although the high-dose mouse metagene correctly identified all of the samples from healthy donors as being non-irradiated, it correctly identified only two-thirds of the pre-irradiated samples from patients.
What Do These Findings Mean?
These findings indicate that metagenes can be generated that recognize different levels of radiation exposure in mice and people. In the mouse study a metagene was identified that correctly identified in all cases whether a sample came from a non-irradiated mouse or an animal exposed to the lowest dose of radiation. This result suggests that it might be possible to use a metagene to identify exposed individuals among thousands of “worried well” after a radiation emergency. First, however, the mouse and human metagenes identified here need to be refined to improve their accuracy and then validated in more people. The current high-dose mouse metagene may be bad at identifying non-irradiated patients, for example, because of gene expression changes that are a result of the patients' underlying disease or previous medical treatments. By studying additional patients, it might be possible to improve the accuracy of the metagene by taking these radiation-independent changes into account. Finally and more generally, these findings suggest that the metagene approach could be used to monitor people's exposure to other dangerous environmental agents.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040106.
US Environmental Protection Agency offers information on understanding radiation and factsheets on ionizing radiation
MedlinePlus provides links to information on radiation exposure and pages on radiation sickness
US Centers for Disease Control and Prevention has information on emergency preparedness and response to radiation emergencies
Wikipedia has pages on ionizing radiation, radiation poisoning, and expression profiling (note that Wikipedia is a free online encyclopedia that anyone can edit)
doi:10.1371/journal.pmed.0040106
PMCID: PMC1845155  PMID: 17407386
18.  Radiation-associated cardiovascular risks for future deep-space missions 
Journal of Radiation Research  2014;55(Suppl 1):i37-i39.
Background: During the future Moon and Mars missions, astronauts will be exposed to space radiation (IR) for extended time. The majority of space flight-associated risks identified for the cardiovascular (CV) system to date were determined shortly after low Earth orbit (LEO) short- and long-duration space flights that include: serious cardiac dysrhythmias, compromised orthostatic CV response and manifestation of previously asymptomatic CV disease. Further ground-based experiments using a surrogate model of microgravity supported the space flight data for significant cardiac remodeling due to prolonged exposure to microgravity. These symptoms were determined to be a consequence of adaptation to microgravity that could be ameliorated by a post-mission exercise program, and were not identified as risk factors that were causatively related to space IR. Long-term degenerative effects of cosmic IR during and after space flights on CV system are unknown.
It was suggested that due to GCR, each cell in an astronaut's body will be traversed by 1H every 3 days, helium (2He) nuclei every few weeks and high charge and energy (HZE) nuclei (e.g. 28Si, 56Fe) every few months. Despite the fact that only 1% of GCR is composed of ions heavier than helium, ∼41% of the IR dose-equivalent is predicted to be HZE particles with 13% being from 56Fe particles, only. During an exploration-class space mission to Mars, astronauts will not have access to comprehensive healthcare services for a period of at least 2–3 years. Since the majority of experienced astronauts are middle-aged (average age is 46, and the range is 33–58 years), they are at risk for developing serious CV events which could be life-threatening for the astronaut and mission-threatening for NASA. Therefore, it is important to evaluate the effects and potential CV risks caused by space IR. We hypothesized that: (i) low-dose space IR-induced biological responses may be long-lasting and are IR type-dependent; (ii) IR may increase CV risks in the aging heart (IR + AGING model) and affect the heart recovery after an adverse CV event, such as acute myocardial infarct (IR + AGING + AMI model).
Methods: Eight- to 9-month-old C57BL/6N male mice were IR once with proton (1H) 50 cGy, 1 GeV/n or iron (56Fe) 15 cGy, 1 GeV/n. We evaluated IR-induced biological tissue responses—underlying molecular mechanisms, calcium handling, signal transduction, gene expression and cardiac fibrosis. Cardiac function was assessed by echocardiography (ECHO) and hemodynamic measurements (HEMO) as detailed in Fig. 1. AMI was induced by ligation of left anterior descending coronary artery 1 and 3 months post-IR as detailed in Fig. 2.Fig. 1.Radiation + aging model. Fig. 2.Radiation + aging model + adverse CV event model.
Results: In the IR + AGING model, cardiac function was not different among the control and 1H-IR group, whereas left ventricular end-diastolic pressure (LVEDP) was significantly increased in 56Fe mice 1 and 3 months post-IR. There was a small but statistically significant (P < 0.04) improvement of ejection fraction % (EF%) in 1H-IR vs control mice. One month post-IR, compared with control, 1H- and 56Fe-IR hearts had a significant up-regulation of sarcolemmal Na+–Ca2+ exchanger (NCX) (∼200% P<0.007), sarco(endo)plasmic reticulum calcium-ATPase (SERCA2a, >200% increases, P < 0.02) and 400% decreases in p-p38 MAPK (P < 0.05), suggesting activation of compensatory mechanisms in [Ca2+]i handling in these hearts. By 3 months, compared with control, 1H- and 56Fe-IR hearts had 200–500% (P < 0.02) decreases in SERCA2a and more than 200% decreases in p-Creb-1 (P < 0.02), suggesting reduced capacity in intracellular [Ca2+]i handling. These data suggest that dysfunction in [Ca2+]i handling combined with LVEDP increase after 56Fe-IR may arise from the excessive demand on the heart due to prolonged activation of compensatory mechanisms that lead to changes in SERCA2a and p-Creb1 levels. This may represent a possible intracellular mechanism of heart failure in development in 56Fe-IR hearts.
In the IR + AGING + AMI model, no mortality was observed among three different groups 1 or 3 months post-IR and up to 28 days post-AMI. However, 1 month post-IR and 28 days post-AMI, the infarct size was significantly smaller in 56Fe-IR (p < 0.003) and 1H-IR (p = n.s.) vs control-IR mice, suggesting that at 1 month, 56Fe-IR primes the heart to recover better after AMI. In contrast, 3 months post AMI, 1H-AMI mice had a better cardiac functional recovery compared with control-AMI and 56Fe-AMI mice. The ejection fraction (EF%) was most decreased in 56Fe-AMI mice (56Fe-AMI vs 1H-AMI: 18 vs 48%, P < 0.007, ∼65–70% pre-AMI EF% for all groups). There was a 2- to 4-fold increase in LVEDP in 56Fe-AMI vs 1H-AMI (P < 0.04), suggesting that 56Fe-AMI hearts developed cardiac de-compensation. Western blots showed that 3 days post-AMI, compared with control- and 1H-IR-AMI mice, 56Fe-IR-AMI hearts had a 4- to 7-fold (P < 0.04) decreases in p-Akt (Thr308), p-Erk1/2 (P < 0.007) and ∼2-fold (P < 0.01) increase in phosphorylated ribosomal protein S6 kinase (p-S6k, a readout for mTORC1 pathway activation), suggesting decreased survival and angiogenesis signaling and decreased autophagy in these hearts. Seven days post-AMI, the levels of p-pErk1/2 were comparable between all three treatment conditions. However, in 56Fe-IR-AMI hearts, the p-Akt (Thr308) levels remained 4-fold decreased. Additionally, here was a 3-fold (P<0.05) decrease in p-S6k levels and >10-fold increase in p-p38 MAPK level in 56Fe vs control and 1H-IR-AMI hearts, suggesting continuous decreases in the survival, proliferation and angiogenesis signaling (p-Akt and p-S6k) and increase in the apoptotic signaling (p-p38 MAPK) up to Day 7 post-AMI in 56Fe-IR-AMI mice.
In summary, our results revealed that by 1 and 3 months post-IR in IR + AGING, 56Fe-IR but not 1H-IR mice had worse cardiac function. Further, a single 1H-IR 3 months prior to AMI improved, whereas 56Fe-IR worsened, recovery from AMI recovery. Our data in the IR + AGING and IR + AGING + AMI groups strongly suggest that low-dose HZE particle IR (56Fe) have long-lasting negative effect on heart homeostasis during normal aging, and present a significant CV risk for recovery after adverse CV event, such as AMI.
doi:10.1093/jrr/rrt202
PMCID: PMC3941505
HZE; iron; proton; low-dose; cardiovascular risks; Ca2+
19.  Genotoxicity of charged particles of importance in space flight using murine kidney epithelial cells 
Journal of Radiation Research  2014;55(Suppl 1):i77-i78.
Ionizing radiation presents significant challenges for human space flight including an increased cancer risk. High-energy heavy ions in the galactic cosmic radiation can produce qualitative and quantitative differences in biological effects when compared with sparsely ionizing radiations. Mutations are induced by charged particle exposure and are integral to the formation and/or progression of human cancers. Most cancer-associated mutations occur on autosomal chromosomes, and most solid cancers occur in epithelial tissues. Here, a combined in vitro/in vivo approach was used to evaluate cell killing and the induction of mutations at a model autosomal locus, Aprt, in mouse kidney epithelium. For in vitro exposures, Aprt heterozygous kidney cells (clones 1a, 4a or 6a) were used from C57BL/6×DBA/2 mice. Additional experiments were performed using whole body irradiation of mice with the same genotype. Both males and females were irradiated in approximately equal numbers. Irradiations were performed at the NASA Space Radiation Laboratories at Brookhaven National Laboratory. For in vitro studies, cells from primary kidney clones were irradiated and seeded at limiting dilution immediately post-irradiation to determine the toxicity of the treatment. The irradiated kidney cells were also seeded in mutation assays within 1 week post-irradiation to determine the Aprt mutant fraction at the earliest time post-exposure. This work was complemented by studies wherein mice were exposed to the same ions with kidneys harvested several months post-irradiation to determine the residual toxicity and the Aprt mutant fraction. Our previous studies focused on sparsely ionizing 1 GeV protons (LET = 0.24 keV/µm) and densely ionizing 1 GeV/amu Fe ions (LET = 151 keV/µm). Our most recent studies have included work with Si ions (240 MeV/amu for in vitro studies, LET = 78 keV/µm; 263 MeV/amu initial energy for in vivo studies to achieve 78 keV/µm near the midline of the animal) and O ions (250 MeV/amu in vitro studies only, LET = 25 keV/µm). Toxicity for the cultured kidney cells in vitro follows this pattern: Fe > Si > O > protons when the results are expressed per unit dose. D0 values were 92 cGy for Fe ions, 103 cGy for Si ions, 192 cGy for O ions and 340 cGy for protons. With regard to the induction of Aprt mutations, Fe ions were more mutagenic than protons. Si ions were also quite mutagenic with evidence for a linear dose–response for Aprt mutations in kidney cells exposed in vitro or in kidneys harvested from mice irradiated several months earlier. These results are consistent with the linear dose–response data obtained previously for Aprt mutation induction following Fe ion exposure in vitro or in vivo, but the results for Si ions differ from the curvilinear dose–response data we recently published following similar exposures to energetic protons [ 1, 2]. Our most recent studies examined the molecular characteristics of Si ion-induced Aprt mutants following in vitro exposure. A dose of 160 cGy was used to collect 58 Aprt kidney cell mutants. Mutational events were classified as follows based on PCR-based analyses of polymorphic markers along mouse chromosome 8: intragenic events, apparent mitotic recombination, interstitial deletions of Aprt only, multilocus deletions, discontinuous loss of heterozygosity or whole chromosome loss. The results for this group of mutants will be compared against our previous studies on Aprt mutants arising after exposure to sparsely ionizing 1 GeV protons or densely ionizing 1 GeV/amu Fe ions. Additional studies are ongoing to define mutational spectra following Si ion exposure to kidney epithelium in vivo.
Clinical Trial Registration number: not applicable.
doi:10.1093/jrr/rrt191
PMCID: PMC3941538
charged particles; heavy ions; mutation; cell killing; epithelium
20.  56Fe ion irradiation enhances angiogenesis and other inter-cellular determinants of carcinogenesis risk 
Journal of Radiation Research  2014;55(Suppl 1):i124-i126.
In the assessment of radiogenic cancer risk from space flight, it is imperative to consider effects not only on the creation of cancer cells (initiation) but also on cell–cell interactions that play an important and often decisive role in the promotion and progression phases. Autopsy results confirm that most adults carry fully malignant tumors that are held in check at a small size and will never become symptomatic [ 1, 2]. This introduces the possibility that cosmic radiation may significantly influence cancer risk through alteration of the bottleneck inter-tissue interactions responsible for maintaining this dormant state. One such bottleneck is the growth limitation imposed by the failure of the tumor to induce blood vessels (angiogenesis). Other deciding events are the ability of a tumor to proliferate and invade. We have previously shown that proton radiation, the most prevalent radiation in space, has a suppressive effect on all three of these functional responses. It down-regulates angiogenic genes like VEGF and HIF-1α and impairs cell invasion and tumor growth [ 3]. We decided to test these responses after 56Fe irradiation, an HZE radiation type present in the cosmic environment with presumably high carcinogenic potential [ 4].
Human microvascular endothelial cells (HMVEC) and normal human dermal fibroblast (NHDF) cells were irradiated with different doses of 56Fe ion radiation (1 GeV/n) at Brookhaven National Laboratory and RNA was extracted 6 h later. Genomic-wide array analysis was done on the isolated RNA through the Agilent Platform. It was observed that several pro-angiogenic genes like VEGF, IL-6 and HIF-1α were significantly up-regulated after treatment with 56Fe ion radiation (Fig.  1). These results were also confirmed at the mRNA and protein levels with the human and murine lung cancer lines, A549 and LLC, respectively. Additional verification of modulation of these key genes was also observed when lungs of C57BL/6 mice treated with 56Fe ion radiation showed an increase in VEGF and MMP9 mRNA and protein expression 6 h post-irradiation (Fig.  2). Cell invasion was shown to be increased by 56Fe ion radiation in various cell types, including fibroblast, tumor and endothelial progenitor cells. 56Fe ion irradiation also modulated functional processes crucial to angiogenesis. It enhanced the ability of untargeted (bystander) endothelial cells to invade and proliferate in response to factors produced by targeted fibroblast or cancer cells in vitro. Results also carry over to in vivo. C57BL/6 mice exposed to whole-body irradiation with 0.2 Gy dose of 56Fe and injected subcutaneously with LLC tumor cells showed a significant augmentation in tumor growth and growth rate in the irradiated group. Additionally, nude mice exposed to whole-body 56Fe radiation and injected intravenously with A549 cancer cells 3 h post-irradiation demonstrated a significant enhancement in lung colonization capacity when compared with the sham-irradiated control mice injected.
These results together suggest cell and tissue-level responses to 56Fe irradiation may act to overcome major cancer progression-level bottlenecks including those related to angiogenesis, cell proliferation and invasion. This is of significant concern for cancer risk estimations pertinent to NASA as achieving these cancer hallmark processes can make the difference between a radiation-induced cancer cell progressing to a clinically detectable cancer in astronauts or not. In conclusion, we demonstrate a strong radiation quality dependence for space radiation carcinogenesis risk manifested through influences on intercellular interactions in the progression phase of carcinogenesis. Fig. 1.Heatmaps of selected differentially regulated major angiogenesis genes after proton and 56Fe ion radiation in HMVECs and NHDF. Cells were treated with either 0, 0.5, 1 or 2 Gy of proton radiation or 0, 0.2, 0.4 or 1 Gy of 56Fe ion dose. Among the major regulated genes were VEGF, HIF-1A and IL-6; they were down-regulated by proton radiation and up-regulated by iron radiation. Fig. 2.Immunofluorescence images of lungs of C57BL/6 mice treated with 0, 0.2 or 1 Gy of 56Fe ion dose and stained 6 h later. Pro-angiogenic factors VEGF and MMP9 were increased in mice that received the 56Fe ion treatment.
doi:10.1093/jrr/rrt180
PMCID: PMC3941549
21.  The self-reported health of U.S. flight attendants compared to the general population 
Environmental Health  2014;13:13.
Background
Few studies have examined the broad health effects of occupational exposures in flight attendants apart from disease-specific morbidity and mortality studies. We describe the health status of flight attendants and compare it to the U.S. population. In addition, we explore whether the prevalence of major health conditions in flight attendants is associated with length of exposure to the aircraft environment using job tenure as a proxy.
Methods
We surveyed flight attendants from two domestic U.S. airlines in 2007 and compared the prevalence of their health conditions to contemporaneous cohorts in the National Health and Nutrition Survey (NHANES), 2005-2006 and 2007-2008. We weighted the prevalence of flight attendant conditions to match the age distribution in the NHANES and compared the two populations stratified by gender using the Standardized Prevalence Ratio (SPR). For leading health conditions in flight attendants, we analyzed the association between job tenure and health outcomes in logistic regression models.
Results
Compared to the NHANES population (n =5,713), flight attendants (n = 4,011) had about a 3-fold increase in the age-adjusted prevalence of chronic bronchitis despite considerably lower levels of smoking. In addition, the prevalence of cardiac disease in female flight attendants was 3.5 times greater than the general population while their prevalence of hypertension and being overweight was significantly lower. Flight attendants reported 2 to 5.7 times more sleep disorders, depression, and fatigue, than the general population. Female flight attendants reported 34% more reproductive cancers. Health conditions that increased with longer job tenure as a flight attendant were chronic bronchitis, heart disease in females, skin cancer, hearing loss, depression and anxiety, even after adjusting for age, gender, body mass index (BMI), education, and smoking.
Conclusions
This study found higher rates of specific diseases in flight attendants than the general population. Longer tenure appears to explain some of the higher disease prevalence. Conclusions are limited by the cross-sectional design and recall bias. Further study is needed to determine the source of risk and to elucidate specific exposure-disease relationships over time.
doi:10.1186/1476-069X-13-13
PMCID: PMC4007523  PMID: 24612632
Flight attendant health; Occupational diseases in airliner cabin crew; Flight attendant jobs; Chronic bronchitis; Depression; Fatigue; Sleep disorders; Hearing loss; Heart disease; Cancer; Second-hand tobacco smoke exposure
22.  Calculating Radiation Exposures during Use of 14C-Labeled Nutrients, Food Components, and Biopharmaceuticals To Quantify Metabolic Behavior in Humans 
14C has long been used as a tracer for quantifying the in vivo human metabolism of food components, biopharmaceuticals, and nutrients. Minute amounts (≤1 × 10 −18 mol) of 14C can be measured with high-throughput 14C-accelerator mass spectrometry (HT 14C-AMS) in isolated chemical extracts of biological, biomedical, and environmental samples. Availability of in vivo human data sets using a 14C tracer would enable current concepts of the metabolic behavior of food components, biopharmaceuticals, or nutrients to be organized into models suitable for quantitative hypothesis testing and determination of metabolic parameters. In vivo models are important for specification of intake levels for food components, biopharmaceuticals, and nutrients. Accurate estimation of the radiation exposure from ingested 14C is an essential component of the experimental design. Therefore, this paper illustrates the calculation involved in determining the radiation exposure from a minute dose of orally administered 14C-β-carotene, 14C-α-tocopherol, 14C-lutein, and 14C-folic acid from four prior experiments. The administered doses ranged from 36 to 100 nCi, and radiation exposure ranged from 0.12 to 5.2 μSv to whole body and from 0.2 to 3.4 μSv to liver with consideration of tissue weighting factor and fractional nutrient. In comparison, radiation exposure experienced during a 4 h airline flight across the United States at 37000 ft was 20 μSv.
doi:10.1021/jf100113c
PMCID: PMC2857889  PMID: 20349979
14C tracer; radiation exposure calculation; in vivo in human; accelerator mass spectrometry (AMS)
23.  Time Profile of Cosmic Radiation Exposure During the EXPOSE-E Mission: The R3DE Instrument 
Astrobiology  2012;12(5):403-411.
Abstract
The aim of this paper is to present the time profile of cosmic radiation exposure obtained by the Radiation Risk Radiometer-Dosimeter during the EXPOSE-E mission in the European Technology Exposure Facility on the International Space Station's Columbus module. Another aim is to make the obtained results available to other EXPOSE-E teams for use in their data analysis. Radiation Risk Radiometer-Dosimeter is a low-mass and small-dimension automatic device that measures solar radiation in four channels and cosmic ionizing radiation as well. The main results of the present study include the following: (1) three different radiation sources were detected and quantified—galactic cosmic rays (GCR), energetic protons from the South Atlantic Anomaly (SAA) region of the inner radiation belt, and energetic electrons from the outer radiation belt (ORB); (2) the highest daily averaged absorbed dose rate of 426 μGy d−1 came from SAA protons; (3) GCR delivered a much smaller daily absorbed dose rate of 91.1 μGy d−1, and the ORB source delivered only 8.6 μGy d−1. The analysis of the UV and temperature data is a subject of another article (Schuster et al., 2012). Key Words: Ionizing radiation—R3D—ISS. Astrobiology 12, 403–411.
doi:10.1089/ast.2011.0759
PMCID: PMC3371259  PMID: 22680687
24.  Stretching and Joint Mobilization Exercises Reduce Call-Center Operators’ Musculoskeletal Discomfort and Fatigue 
Clinics  2010;65(7):657-662.
AIM:
We sought to evaluate musculoskeletal discomfort and mental and physical fatigue in the call-center workers of an airline company before and after a supervised exercise program compared with rest breaks during the work shift.
INTRODUCTION:
This was a longitudinal pilot study conducted in a flight-booking call-center for an airline in São Paulo, Brazil. Occupational health activities are recommended to decrease the negative effects of the call-center working conditions. In practice, exercise programs are commonly recommended for computer workers, but their effects have not been studied in call-center operators.
METHODS:
Sixty-four call-center operators participated in this study. Thirty-two subjects were placed into the experimental group and attended a 10-min daily exercise session for 2 months. Conversely, 32 participants were placed into the control group and took a 10-min daily rest break during the same period. Each subject was evaluated once a week by means of the Corlett-Bishop body map with a visual analog discomfort scale and the Chalder fatigue questionnaire.
RESULTS:
Musculoskeletal discomfort decreased in both groups, but the reduction was only statistically significant for the spine and buttocks (p=0.04) and the sum of the segments (p=0.01) in the experimental group. In addition, the experimental group showed significant differences in the level of mental fatigue, especially in questions related to memory Rienzo, #181ff and tiredness (p=0.001).
CONCLUSIONS:
Our preliminary results demonstrate that appropriately designed and supervised exercise programs may be more efficient than rest breaks in decreasing discomfort and fatigue levels in call-center operators.
doi:10.1590/S1807-59322010000700003
PMCID: PMC2910853  PMID: 20668622
Exercise therapy; Occupational disorders; Computer terminal; Computer users; Work rest
25.  A comparison approach to explain risks related to X-ray imaging for scoliosis, 2012 SOSORT award winner 
Scoliosis  2013;8:11.
Background
X-ray imaging is frequently used as diagnostic approach for scoliosis in children and adolescents. X-ray procedures are considered as justified only when expected benefits exceed related risks. While benefits are well known to physicians, radiological risk awareness can be vague, impeding an optimal communication with patients’ parents and possibly leading to discomfort and anxiety. Objective of the study is the suggestion of a risk comparison approach for better communicating the radiological risks related to X-ray investigation of scoliosis.
Methods
Starting point of the analysis is the Linear Non-Threshold (LNT) assumption for radiation stochastic effect, which states that for effective doses (E, Sievert – Sv) below 100 mSv, the probability of future stochastic damage is linearly related to E: absorbing two E’s in separate moments results in the addition of the risks related to each E. This allows to add E from different sources to calculate a cumulative risk of health detriment. Medline (Pubmed) was systematically searched in order to determine the average E delivered during X-ray investigation of scoliosis. Subsequently, the major natural sources of radiation were considered. The average yearly E due to natural sources was compared with E due to the imaging of the vertebral column.
Results
E’s due to X-ray scoliosis examinations show a large variability: under 7 years of age, 0.03-0.54 mSv; 7–12 years, 0.11-0.80 mSv; 13–18 years, 0.17-1.09 mSv. Overall, 65% of the world population is expected to be exposed to an annual E between 1 and 3 mSv. More in detail, worldwide the total annual average E due to natural sources is 2.4 mSv (range 1–10), of which half originates from Radon exposure. Other sources are cosmic rays and ingestion and inhalation of radionuclides. For example, one flight between Europe and America accounts for 0.030-0.045 mSv because of exposure to cosmic rays.
Conclusions
X-rays are carcinogenic and exposures to them always need to be justified and optimized in order to minimize the risks of health effects. However, the human body is continuously struck by radiations coming from natural sources. A useful element of comparison to evaluate E due to medical exposures in scoliosis can be then provided by the amount of E coming from natural sources. This comparison approach can play a role in the relationship between physicians and patients’ parents and lead to an improved awareness in patients’ parents.
doi:10.1186/1748-7161-8-11
PMCID: PMC3710473  PMID: 23819852

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