Body mass index and weight change during adulthood are associated with increased mortality from liver cancer: the JACC Study.

BACKGROUND: We investigated the association of baseline body mass index (BMI) and weight change since age 20 years with liver cancer mortality among Japanese. METHODS: The data were obtained from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). A total of 31 018 Japanese men and 41 455 Japanese women aged 40 to 79 years who had no history of cancer were followed from 1988 through 2009. RESULTS: During a median 19-year follow-up, 527 deaths from liver cancer (338 men, 189 women) were documented. There was no association between baseline BMI and liver cancer mortality among men or men with history of liver disease. Men without history of liver disease had multivariable hazard ratios (HR) of 1.95 (95%CI, 1.07-3.54) for BMI less than 18.5 kg/m(2) and 1.65 (1.05-2.60) for BMI of 25 kg/m(2) or higher, as compared with a BMI of 21.0 to 22.9 kg/m(2). BMI was positively associated with liver cancer mortality among women and women with history of liver disease. Weight change since age 20 years was positively associated with liver cancer mortality among women regardless of history of liver disease. Women with history of liver disease had a multivariable HRs of 1.96 (1.05-3.66) for weight gain of 5.0 to 9.9 kg and 2.31 (1.18-4.49) for weight gain of 10 kg or more, as compared with weight change of -4.9 to 4.9 kg. CONCLUSIONS: Both underweight (BMI <18.5 kg/m(2)) and overweight (BMI ≥25 kg/m(2)) among men without history of liver disease, and weight gain after age 20 (weight change ≥5 kg) among women with history of liver disease, were associated with increased mortality from liver cancer.

Cohort profile of the Japan Collaborative Cohort Study at final follow-up.

The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) was established in the late 1980s to evaluate the risk impact of lifestyle factors and levels of serum components on human health. During the 20-year follow-up period, the results of the study have been published in almost 200 original articles in peer-reviewed English-language journals. However, continued follow-up of the study subjects became difficult because of the retirements of principal researchers, city mergers throughout Japan in the year 2000, and reduced funding. Thus, we decided to terminate the JACC Study follow-up at the end of 2009. As a final point of interest, we reviewed the population registry information of survivors. A total of 207 (0.19%) subjects were ineligible, leaving 110 585 eligible participants (46 395 men and 64 190 women). Moreover, errors in coding date of birth and sex were found in 356 (0.32%) and 59 (0.05%) cases, respectively, during routine follow-up and final review. Although such errors were unexpected, their impact is believed to be negligible because of the small numbers relative to the large total study population. Here, we describe the final cohort profile at the end of the JACC Study along with selected characteristics of the participants and their status at the final follow-up. Although follow-up of the JACC Study participants is finished, we will continue to analyze and publish study results.

Interest in dietary pattern, social capital, and psychological distress: a cross-sectional study in a rural Japanese community.

BACKGROUND: Among life-style factors affecting mental health, dietary habits are becoming a public health concern in their relation to psychological distress and social capital. We examined associations between interest in dietary pattern, social capital, and psychological distress with a population-based cross-sectional study in rural Japan. METHODS: A total of 16,996 residents of a rural town in northern Japan aged 30-79 years participated in this questionnaire survey. The questionnaire gathered data about socio-demographic variables, psychological distress, issues related to dietary habits, including interest in dietary pattern, and the social capital factors of reciprocity and sense of community belonging. Factors related to psychological distress were analyzed by using multiple logistic regression analysis. RESULTS: A high interest in dietary pattern was significantly associated with a high level of social capital. In addition, an association between interest in dietary pattern and frequencies of intake of vegetables and fruits was confirmed. The multiple logistic regression analyses showed significant associations between interest in dietary pattern, social capital, frequency of intake of vegetables, and psychological distress after adjusting for socio-demographic variables. Low interest in dietary pattern was positively associated with psychological distress after adjusting for socio-demographic variables (OR = 2.18; 95%CI: 1.69-2.81). Low levels of both reciprocity and sense of community belonging were associated with psychological distress after adjusting for socio-demographic variables (OR = 3.46 with 95%CI of 2.10-5.71 for reciprocity, and OR = 7.42 with 95%CI of 4.64-11.87 for sense of community belonging). CONCLUSION: Low interest in dietary pattern, low frequency of intake of vegetables, and low levels of social capital were significantly associated with psychological distress after adjusting for socio-demographic variables.

Impact of obesity on plasma B-type natriuretic peptide levels in Japanese community-based subjects.

The plasma B-type natriuretic peptide (BNP) concentration was recently shown to be inversely correlated with body mass index (BMI). However, very few attempts have been made to associate abdominal obesity and BNP in the Japanese general population. Here, we conducted a cross-sectional study, and examined 339 male and 429 female residents without heart disease in a rural Japanese community who received an annual health checkup in 2006. BNP was inversely associated with both BMI and abdominal circumference (AC) in the age-adjusted regression analysis (p < 0.05). Following adjustment for traditional risk factors, multiple regression analysis revealed that BNP was negatively correlated with AC (p < 0.05), but not BMI. Although metabolic syndrome was not associated with BNP levels, AC had an influence on low BNP levels in the multiple regression analysis using both AC and BMI concurrently (p < 0.05 for AC and p > 0.60 for BMI). These effects were more prominent in men than in women. Collectively, plasma BNP levels are inversely related with obesity, as measured by AC, in Japanese community-based subjects.

Association between psychological distress and a sense of contribution to society in the workplace.

BACKGROUND: Globally, mental health promotion related to psychological distress in the workplace has become a great concern, and a focus of much research attention. However, a sense of contribution to society and sense of bonding with the workplace have not been examined in relation to psychological distress. Thus, the purpose of this study is to examine whether these two factors are associated with psychological distress. METHODS: We conducted a cross-sectional survey of 1137 full-time employees who worked in systems engineering, sales, or administration at a Japanese company. Participant's sense of contribution to society, sense of bonding with the workplace, psychological distress, and qualitative job stress (quantitative and qualitative workloads, job-control latitude, and support from supervisors, co-workers and family) were assessed with a questionnaire. We performed multiple logistic regression analyses to examine associations between psychological distress and sense of contribution to society and of bonding with the workplace. RESULTS: A high sense of contribution to society was significantly associated with a high sense of bonding with the workplace (Spearman's ρ = 0.47, p < 0.01). A sense of contribution to society was negatively associated with psychological distress after adjusting for job stress factors (OR = 2.05, 95% CI 0.99-4.23) or sociodemographic characteristics of participants (OR = 2.92, 1.53-5.59). After adjusting for job stress factors as well as sociodemographic characteristics, the association became weaker. A sense of bonding with the workplace was negatively associated with psychological distress after adjusting for sociodemographic characteristics (OR = 2.49, 1.29-4.79). However, this association was not observed after adjusting for job stress factors. CONCLUSIONS: Psychological distress in the workplace was associated with sense of contribution to society. Therefore, workplace mental health promotion should consider the workers' sense of contribution to society.

[Recommendation for revision of the General Principles of Suicide Prevention Policy].

Since the promulgation of the Basic Act for Suicide Prevention, suicide prevention in Japan has developed rapidly. In order to further reinforce such activities, it is necessary to balance universal, selective, and indicated prevention. For the revision of the General Principles of Suicide Prevention Policy, the Center for Suicide Prevention announced this recommendation with 29 societies. We hope that it will promote suicide prevention in Japan and lead to expansion of the suicide prevention network by academic organizations, NGOs, as well as local and central government.

Suicide Prevention Program with Cooperation from Senior Volunteers, Governments, and Schools: A Study of the Intervention Effects of "Educational Lessons Regarding SOS Output" Focusing on Junior High School Students.

As a suicide countermeasure for young people, implementing "SOS output education" that provides young people with opportunities and approaches to seeking support with community cooperation can be expected to reduce lifelong suicide risk. We implemented an "SOS output education" for junior high school students with cooperation from educators, government staff, and older people working as community volunteers. A total of 188 students were allocated to an intervention group and a waiting group. Outcome assessments were implemented at three points in time: before the program (Time 1), after the program (Time 2), and three months after the program (Time 3). Results showed that the number of people with worries increased in the intervention group compared with the waiting group between Time 1 and Time 2. There was also an increase in people with "reliable adults" between Time 1 and Time 3, and people with "adults who you can talk to at any time" increased between Time 2 and Time 3 in the intervention group. By implementing the SOS output education program with community cooperation, an increase was observed in the intervention group in terms of support-seeking awareness and the number of people with reliable adults and with adults who they can talk to at any time.

History of blood transfusion before 1990 is associated with increased risk for cancer mortality independently of liver disease: a prospective long-term follow-up study.

OBJECTIVES: The aim of this work is to investigate the association between transfusion history and cancer mortality in a prospective follow-up study. METHODS: We conducted a prospective cohort study in four areas of Akita Prefecture, Japan, in 10,451 individuals (4,401 men and 6,050 women, aged 40-79 years) without history of cancer. The subjects were followed until 31 December 2003 and the number of deaths from cancer was recorded. RESULTS: After mean follow-up of 12.76 years (140,259 person-years), 520 individuals (333 men and 187 women) died of cancer. History of blood transfusion before 1990 was mildly but significantly associated with overall cancer mortality (hazard ratio = 1.75, 95% confidence interval: 1.32-2.18) and nonliver cancer mortality (HR = 1.68, 95% CI: 1.25-2.26). This significant association remained unchanged after excluding deaths that occurred within 5 years of baseline for overall cancer mortality (HR = 1.47, 95% CI: 1.04-2.09) and for nonliver cancer mortality (HR = 1.43, 95% CI: 1.00-2.04). The significant association for nonliver cancer mortality was confirmed in subjects with no smoking history and/or alcohol consumption (HR = 2.01, 95% CI: 1.35-3.00). Site-specific analysis showed a possible association between transfusion history and death from pancreatic cancer. CONCLUSIONS: History of blood transfusion before 1990 was found to be associated with increased risk for cancer mortality and was independent of liver diseases. The mechanism of the association between blood transfusion and cancer mortality warrants further research.

Inter-individual difference in pupil size correlates to suppression of melatonin by exposure to light.

There are large inter-individual differences in pupil size and suppression of melatonin by exposure to light. It has been reported that melatonin suppression by exposure to light increases when pupils are pharmacologically dilated. However, the correlation between normal inter-individual difference in pupil size and melatonin suppression by exposure to light is not clear. Twenty-three healthy male subjects (22.6+/-2.7 years old) were exposed to light (1000 lx) for 2 h at night. The starting time of exposure to light was set to the ascending phase of melatonin concentration of each subject. Pupil area and saliva melatonin concentration were measured before exposure to light under dim light (15 lx) and during exposure to light. There were large inter-individual differences in melatonin suppression and pupil area. The mean and standard deviation of percentage of melatonin suppression 2 h after exposure to light was 57.2+/-22.1%. The mean and standard deviation of pupil areas before and 2 h after exposure to light were 30.7+/-7.9 mm2 and 15.9+/-4.8 mm2, respectively. The percentage of melatonin suppression by light was positively correlated with pupil area during light exposure (r=0.525, p<0.02). Interestingly, it was also correlated with pupil area measured before exposure to light, under dim light (15 lx) (r=0.658, p<0.001). These results suggest that inter-individual difference in pupil area positively correlates with melatonin suppression by light and that pupil area under dim light is a predictor of inter-individual differences in melatonin suppression by light.

Effect of having a sense of purpose in life on the risk of death from cardiovascular diseases.

BACKGROUND: Many studies have focused on disease causality, but few of them deal with health-promoting factors. Thus, we examined the effect of having a sense of purpose in life (ikigai) on mortality from cardiovascular disease (CVD). METHODS: In 1988, we conducted a prospective cohort study of 2,959 Japanese subjects, ranging in age from 40 to 74 years, and followed them till the end of 2003. The level of their sense of purpose in life was evaluated by a self-administered questionnaire. After excluding those with a history of heart disease, stroke, or malignant tumor, 1,618 subjects (832 men and 786 women) who had completed the questionnaire were used in the analyses with Cox's proportional hazards model. RESULTS: During the average 13.3 years of follow up, 249 deaths (172 men and 77 women) occurred as a result of all causes: 32 from heart disease, 31 from stroke, 63 from CVD, and 104 from malignant tumors. The adjusted hazard ratios for death in men with a strong sense of purpose in life, as compared with those with a low sense of purpose, were 0.28 (95% confidence interval: 0.10-0.84) for stroke, 0.56 (0.28-1.10) for CVD, and 0.62 (0.45-0.86) as a result of all causes. In women, no significant relationship was found between having a sense of purpose in life and mortality; this was possibly because the smaller number of deaths reduced the statistical significance. CONCLUSION: We found that in men, having a sense of purpose in life affected the risk of death as a result of all causes, stroke, and CVD.

Attitudes towards those bereaved by a suicide: a population-based, cross-sectional study in rural Japan.

BACKGROUND: Family or friends bereaved by suicide are at risk of experiencing complications because of attitudes regarding suicide. It is important that individuals close to those grieving after a death by suicide demonstrate adequate knowledge and compassionate attitudes. To this end, we examined the factors that contribute to attitudes toward persons bereaved by the suicide of a family member or friend, and perceptions of suicide prevention and the promotion of mental health. METHODS: A total of 5154 residents of a rural town in northern Japan aged 30-69 years completed a cross-sectional questionnaire. The questionnaire gathered data about demographic variables, depressive symptoms, and issues related to suicide including personal experience of an acquaintance's suicide, attitudes towards those bereaved by suicide, and perceptions regarding suicide prevention. Factors related to these attitudes and perceptions were analysed using logistic regression models. RESULTS: Overall, 67.5% of respondents demonstrated appropriate attitudes towards those bereaved by suicide; 30.4% of responses were undetermined, and 2.1% were inappropriate. Undetermined attitudes were associated with male gender (adjusted OR 1.42, 95%CI = 1.26-1.61), younger age (2.64, 2.12-3.29), lower education level (1.32, 1.07-1.62), greater severity of depression (3.81, 2.80-5.20), and lack of personal experience of an acquaintance's suicide (1.39, 1.22-1.57). Inappropriate attitudes were associated with male gender (adjusted OR 1.98, 95%CI = 1.33-2.94), lower education level (2.55 1.34-4.83), and greater severity of depression (6.93, 3.52-13.67). Overall, 16.0% demonstrated passive thoughts regarding suicide prevention and the promotion of mental health in the community, and were associated with male gender (1.22, 1.04-1.42), younger age (2.72, 2.03-3.65), lower education level (1.32, 1.02-1.71), and greater severity of depression (4.94, 3.58-6.82). CONCLUSION: Factors that contributed to undetermined attitudes included male gender, younger age, lower education level, greater severity of depression, and lack of personal experience of an acquaintance's suicide. Passive thoughts regarding suicide prevention and the promotion of mental health were associated with male gender, younger age, lower education level, and greater severity of depression.

A community intervention trial of multimodal suicide prevention program in Japan: a novel multimodal community intervention program to prevent suicide and suicide attempt in Japan, NOCOMIT-J.

BACKGROUND: To respond to the rapid surge in the incidence of suicide in Japan, which appears to be an ongoing trend, the Japanese Multimodal Intervention Trials for Suicide Prevention (J-MISP) have launched a multimodal community-based suicide prevention program, NOCOMIT-J. The primary aim of this study is to examine whether NOCOMIT-J is effective in reducing suicidal behavior in the community. METHODS/DESIGN: This study is a community intervention trial involving seven intervention regions with accompanying control regions, all with populations of statistically sufficient size. The program focuses on building social support networks in the public health system for suicide prevention and mental health promotion, intending to reinforce human relationships in the community. The intervention program components includes a primary prevention measures of awareness campaign for the public and key personnel, secondary prevention measures for screening of, and assisting, high-risk individuals, after-care for individuals bereaved by suicide, and other measures. The intervention started in July 2006, and will continue for 3.5 years. Participants are Japanese and foreign residents living in the intervention and control regions (a total of population of 2,120,000 individuals). DISCUSSION: The present study is designed to evaluate the effectiveness of the community-based suicide prevention program in the seven participating areas. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000460.

Less exposure to daily ambient light in winter increases sensitivity of melatonin to light suppression.

This study was carried out to examine the seasonal difference in the magnitude of the suppression of melatonin secretion induced by exposure to light in the late evening. The study was carried out in Akita (39 degrees North, 140 degrees East), in the northern part of Japan, where the duration of sunshine in winter is the shortest. Ten healthy male university students (mean age: 21.9+/-1.2 yrs) volunteered to participate twice in the study in winter (from January to February) and summer (from June to July) 2004. According to Japanese meteorological data, the duration of sunshine in Akita in the winter (50.5 h/month) is approximately one-third of that in summer (159.7 h/month). Beginning one week prior to the start of the experiment, the level of daily ambient light to which each subject was exposed was recorded every minute using a small light sensor that was attached to the subject's wrist. In the first experiment, saliva samples were collected every hour over a period of 24 h in a dark experimental room (<15 lux) to determine peak salivary melatonin concentration. The second experiment was conducted after the first experiment to determine the percentage of melatonin suppression induced by exposure to light. The starting time of exposure to light was set 2 h before the time of peak salivary melatonin concentration detected in the first experiment. The subjects were exposed to light (1000 lux) for 2 h using white fluorescent lamps (4200 K). The percentage of suppression of melatonin by light was calculated on the basis of the melatonin concentration determined before the start of exposure to light. The percentage of suppression of melatonin 2 h after the start of exposure to light was significantly greater in winter (66.6+/-18.4%) than summer (37.2+/-33.2%), p<0.01). The integrated level of daily ambient light from rising time to bedtime in summer was approximately twice that in winter. The results suggest that the increase in suppression of melatonin by light in winter is caused by less exposure to daily ambient light.

A decrease in suicide rates in Japanese rural towns after community-based intervention by the health promotion approach.

A community-based intervention study for suicide prevention was conducted in six towns (total population 43,964) in Akita Prefecture of Japan according to a quasi-experimental design to reduce suicide rates in rural towns. Public awareness raising activities using a health promotion approach emphasizing the empowerment of residents and civic participation were conducted. The welfare measures of promoting a sense of purpose among senior citizens and creating a community network were also taken. As a result, the suicide rate per 100,000 in the intervention towns decreased from 70.8 before intervention (1999) to 34.1 after intervention (2004). The suicide rate per 100,000 in the control towns was 47.8 before intervention and 49.1 after intervention.

Association of menstrual and reproductive factors with pancreatic cancer risk in women: findings of the Japan Collaborative Cohort Study for Evaluation of Cancer Risk.

BACKGROUND: The etiology of pancreatic cancer remains largely unknown. We examined the association of pancreatic cancer deaths with menstrual and reproductive factors in a cohort study involving Japanese women. METHODS: A total of 63,273 women were followed up for mortality from 1988 to 1999. Information on menstrual and reproductive factors was obtained by a questionnaire survey at baseline. Cox proportional-hazards models were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for death from pancreatic cancer in relation to menstrual and reproductive factors. RESULTS: During 631,401 person-years of follow-up, 154 women died from pancreatic cancer. Parity was not significantly associated with the risk of death from pancreatic cancer; the RR was 0.80 (95% CI, 0.31-2.11) for women with six or more births compared with women with zero or one birth. We found no significant overall association with other reproductive factors, including pregnancy, age at first birth, and menopause. The risk appeared to increase with increasing age at menarche; the RR was 1.49 (95% CI, 0.95-2.34) for women who had menarche after 16 years of age compared to those who had menarche before they were 15 years old. CONCLUSIONS: Our prospective data indicate that menstrual and reproductive factors are not associated with the risk of death from pancreatic cancer among Japanese women.

Factors associated with the reproductive health risk behavior of high school students in the Republic of the Marshall Islands.

This study revealed factors associated with reproductive health risk behavior among high school students in the Republic of the Marshall Islands. The survey was conducted among high school students from grades 9 through 12 at 2 schools in Majuro, the capital of the Marshall Islands. The questions asked inquired about knowledge, attitude, and behavior related to reproductive health, experience of sexual acts and pregnancy. Multiple logistic regression analysis was performed to assess the association between risk behavior and knowledge, attitude, and other factors. Data obtained from 433 students were used in the analysis. Factors significantly associated with reproductive health risk behavior among both the boys and the girls were a negative attitude toward condom use (odds ratio of the risk group to the low-risk group: boys, 19.54; girls 4.10), not considering receiving public health information and services as a human right (8.10, 3.96), and not knowing where to go for consultation about questions and concerns related to sex (3.32, 4.73). A factor associated with risk behavior in boys alone was acceptance of sexual acts without love (8.46), and factors in girls alone were insufficient knowledge concerning routes of infection by sexually transmitted diseases (6.75) and lack of future life plans (5.00). Neither age nor sex education was a significant predictor. In conclusion, considering reproductive health not to be a personal right was associated with the risk behavior of high school students in the Marshall Islands in regard to reproductive health.

[An evaluation of teaching objectives for seminars and clerkship of social medicine in medical schools in Japan].

OBJECTIVES: The purpose of this study was to evaluate the curriculum of seminars and clerkship for social medicine in medical schools in Japan, with special reference to teaching objectives. METHODS: A survey was conducted in December, 2002 by sending questionnaires to all the member departments of the Conference for Hygiene and Public Health Teaching in Medical Schools in Japan. Teaching objectives for seminars and clerkship of social medicine stated in their curricula were analyzed by frequencies of key words related to learner's "Knowledge, Attitude, and Behavior". Also, five professors of public health independently rated the stated teaching objectives using nine evaluation criteria divided into three levels and mean ratings were obtained. RESULTS: Although 80% of the schools described their General Instructional Objectives (GIOs), only 63% of the universities stated Specific Behavioral Objectives (SBOs). Evaluation of the contents of the descriptions revealed that, although many courses described the GIOs with the student as subjective, only a small number of courses mentioned "Attitude and Behavior" in SBO. Also, many courses did not make any apparent distinction between GIOs and SBOs. CONCLUSIONS: Practical training is a crucial component in medical education and seminars and clerkship play an important role in teaching social medicine to medical students. However, the present study revealed that many medical schools in Japan do not have adequately defined teaching objectives. Improvement of the curricula in courses of social medicine is required with particular reference to specific behavioral objectives and goals for seminars and clerkship.

Leisure-time activities and psychological distress in a suburban community in Japan.

OBJECTIVE: There is a wide range of leisure-time activities and previous research indicates that some of these are associated with lower psychological distress. The aim of this study was to assess whether leisure-time activities were associated with psychological distress. METHODS: A population-based questionnaire survey was conducted in 2009 in a suburban area of northern Japan using complete enumeration. Of 16,996 residents aged 30-79 years who received the questionnaire, 14,261 (83.9%) responded and 9908 (58.3%) responses were eligible for analysis. The relationship between psychological distress and physical, artistic, outdoor, and volunteer leisure-time activities was assessed separately and simultaneously by sex. RESULTS: The percentage of reported psychological distress was 2.8% for men and 3.9% for women. Each category of leisure-time activity was related to psychological distress separately. The simultaneous analyses revealed that engaging in regular outdoor leisure activity was associated with less psychological distress in both men (odds ratio [OR] = 0.38; 95% confidence intervals [CI]: 0.23, 0.63, p < 0.001) and women (OR = 0.39; 95% CI: 0.25, 0.59, p < 0.001). Engaging in regular physical activity was associated with less psychological distress in women (OR = 0.09; 95% CI: 0.01, 0.68, p = 0.019). Volunteer work and art activities were not associated with psychological distress in either men or women. CONCLUSION: Greater engagement in outdoor leisure activity and physical activity was significantly associated with a lower likelihood of psychological distress. The results from the present study indicate that engaging in leisure-time activities, especially in outdoor leisure and physical activities, may be an effective means of promoting public health.

Effects of VDT tasks with a bright display at night on melatonin, core temperature, heart rate, and sleepiness.

The effects of performing video display terminal (VDT) tasks with a bright display (BD) at night on nocturnal salivary melatonin concentration, rectal temperature, heart rate, and sleepiness were examined. Seven healthy male adults performed exciting VDT tasks with a BD and a dark display (DD) and boring VDT tasks with a BD and a DD from 2300 to 0200. The light intensities of the BD and DD were 45 and 15 lx at each subject's eye level, respectively. The exciting VDT task with both BD and DD significantly suppressed the nocturnal decrease in rectal temperature and heart rate and the nocturnal increase in sleepiness. The BD significantly suppressed the nocturnal decrease in rectal temperature during both exciting and boring VDT tasks. The nocturnal salivary melatonin concentration was significantly suppressed by the combination of the exciting task and BD. The results suggest that performing an exciting VDT task with a BD suppresses the nocturnal changes in melatonin concentration and other physiological indicators of human biological clocks.