In many applications of random-effects models to longitudinal data, such as heart rate variability (HRV) data, a normal-mixture distribution seems to be more appropriate than the normal distribution assumption. While the random-effects methodology is well developed for several distributions in the exponential family, the case of the normal-mixture has not been dealt with adequately in the literature. The models and the estimation methods that have been proposed in the past assume the conditional model (fixing the random-effects) to be normal and allow a mixture distribution for the random effects (Xu and Hedeker, 2001, Xu, 1995). The methods proposed in this dissertation assume the conditional model to be a normal-mixture while the random-effects are assumed to be normal. This is primarily to fit the HRV data, which seems to follow a normal-mixture within subjects. Another advantage of this model is that the estimation becomes much simpler through the use of an EM-algorithm. Existing methods and software such as the PROC MIXED in SAS are exploited to facilitate the estimation procedure.A simulation study is performed to examine the properties of the random-effects model with normal-mixture distribution and the estimation of the parameters using the EM-algorithm. The study shows that the estimates have similar properties to the usual normal random-effects models. The between subject variance parameter seems to require larger numbers of subjects to achieve reasonable accuracy, which is typical in all random-effects models.The HRV data is used to illustrate the random-effects normal-mixture method. These data consist of 9 subjects who completed a series of five speech tasks (Cacioppo et al., 2002). For each of the tasks, a series of RR-intervals was collected during baseline, preparation, and delivery periods. Information about their age and gender were also available. The random-effects mixture model presented in this dissertation treats the subjects as random and models age, gender, task, type, and task × type as fixed-effects. The analysis leads to the conclusion that all the fixed effects are statistically significant. The model further indicates a two-component normal-mixture with the same mixture proportion across individuals fit the data adequately.

La variabilité du rythme cardiaque « Heart Rate Variability (HRV) » consiste en des fluctuations perpétuelles du rythme cardiaque autour de sa fréquence moyenne. L’analyse de l’HRV constitue un biomarqueur du fonctionnement du système nerveux autonome (SNA), par l’intermédiaire de ses effets sur le cœur. De nombreuses études ont montré qu’une diminution de l’HRV est associée à un pronostic péjoratif, notamment dans le post infarctus et dans l’insuffisance cardiaque (IC). Nous nous sommes proposés d’élargir le champ d’investigation de l’HRV à de nouveaux domaines d’application, qu'il s'agisse de pathologies cardiaque ou extra cardiaque. Nous avons ciblé des contextes pathologiques dans lesquels le SNA joue un rôle important : 1-Accidents sur la Voie Publique (AVP) et le risque de développement d’un syndrome de stress post traumatique (PTSD). 2-Effet de la douleur et de l’analgésie péridurale sur l’HRV maternelle au cours de l’accouchement. 3-Lien avec les polymorphismes génétique des récepteurs bêta adrénergiques (β;-AR) chez des patients présentant une dysfonction ventriculaire gauche et implanté d’un défibrillateur automatique implantable (DAI) en prévention secondaire. L'analyse temporelle de l'HRV sur 24 heures est un facteur prédictif de survenue d'un PTSD et aussi de sa sévérité chez les victimes d'AVP. L'indice de variabilité est le meilleur paramètre prédictif de PTSD à 6 mois, avec une aire sous la courbe de 0.92 (IC 95% : 0.785; 1.046). Le seuil de 2.19% confère une sensibilité de 85,7 £ et une spécificité e 81.8 % pour prédire la survenue d'un PTSD. les valeurs prédictives positives et négatives sont de 75 % et 90 % respectivement. L'ANI, reflétant l'influence de la ventilation sur le rythme cardiaque, permet une mesure objective de la douleur chez les parturientes. Enfin, les patients ayant subi les substitutions Arg (pour Gly) en 16 et Gln (pour Glu) en 27 pour les récepteurs β2-AR, présentent une HRV plus faible que les patients ayant la forme sauvage du gène. / The heart rate variability (HRV) has arisen as a promising simple and non invasive biomarker of autonomic nervous system (ANS) function, through its effects on the heart. Multiple studies have shown that the decrease in the HRV is associated usually with poor prognosis. We proposed to further investigate the HRV in other domains of clinical application, including cardiac or extra-cardiac pathologies. In particular, the pathological contexts in which the ANS plays an important role :1-Traffic road accident (RTA) and the risk of development of post traumatic stress disorders (PTSD) in survivors.2-Effect of pain and of epidural analgesia on maternal HRV during childbirth.3-Genetic polymorphisms of beta adrenergic receptors (β-AR) in patients with left ventricular dysfunction and implanted with an implantable cardioverter defibrillator (ICD) for secondary prevention. At first, our study is the first to show that the temporal analysis of 24-h HRV is not only a predictive factor of the occurrence of PTSD but also its severity among victims of RTA AVP. The variability index was the best predictor of PTSD with the area under the receiver-operating curve for discriminating PTSD at 6 month at 0.92 (95% CI:0.785;1.046). Acut-off at 2.19% yielded a sensitivity of 85.7% and a specificity of 81.8% for PTSD. Positive and negative predictive values were respectively 75% and 90%. At next, we showed that the ANI, which reflects the influence of ventilation on heart rate, allows an objective measure of pain in conscious subjects? At last, we found that patients with the substitutions Arg (instead of Gly) at position 16 and Gln (instead of Glu) at position 27 for β2-AR have a lower HRV value than patients with wild type receptor.

Background: (Papers I and II) The objectives were to first determine incidence and contributing factors to cold-related injuries in northern Sweden, both those that led to hospitalization and those that led to fatality.  (Papers III and IV) A further aim was to assess post-cooling hand-rewarming responses and effects of training in a cold environment, both on fingertip rewarming and on function of the autonomic nervous system, to evaluate if there was adaptation related to prolonged occupational cold exposure. Methods:  In a retrospective analysis, cases of accidental cold-related injury with hospital admission in northern Sweden during 2000-2007 were analyzed (Paper I).  Cases of fatal hypothermia in the same region during 1992-2008 were analyzed (Paper II).  A cohort of volunteers was studied before and after many months of occupational cold exposure. Subject hand rewarming response was measured after a cold hand immersion provocation and categorized as slow, moderate or normal in rewarming speed.  This cold provocation and rewarming assessment was performed before and after their winter training.  (Paper III).  Heart rate variability (HRV) was analyzed from the same cold provocation/recovery sequences (Paper IV). Results:  (Paper I) For the 379 cases of hospitalization for cold-related injury, annual incidences for hypothermia, frostbite, and drowning were 3.4/100,000, 1.5/100,000, and 1.0/100,000 inhabitants, respectively.  Male gender was more frequent for all categories.  Annual frequencies for hypothermia hospitalizations increased during the study period.  Hypothermia degree and distribution of cases were 20 % mild (between 32 and 35ºC), 40% moderate (31.9 to 28ºC), and 24% severe (< 28ºC), while 12% had temperatures over 35.0ºC.  (Paper II) The 207 cases of fatal hypothermia showed an annual incidence of 1.35 per 100,000 inhabitants, 72% in rural areas, 93% outdoors, 40% found within 100 meters of a building.  Paradoxical undressing was documented in 30%.  Ethanol was detected in femoral vein blood in 43%. Contributing co-morbidity was common including heart disease, previous stroke, dementia, psychiatric disease, alcoholism, and recent trauma.  (Paper III) Post-training, baseline fingertip temperatures and cold recovery variables in terms of final rewarming fingertip temperature and vasodilation time increased significantly in moderate and slow rewarmers.  Cold-related injury (frostbite) during winter training occured disproportionately more often in slow rewarmers (4 of the 5 injuries).  (Paper IV) At ‘pre- winter-training’, normal rewarmers had higher power for low frequency and high frequency heart rate variability.  After cold acclimatization (post-training), normal rewarmers showed lower resting power values for the low frequency and high frequency heart rate variability components.  Conclusions: Hypothermia and cold injury continues to cause injury and hospitalization in the northern region of Sweden.  Assessment and management is not standardized across hospitals.  With the identification of groups at high risk for fatal hypothermia, it should be possible to reduce the incidence, particularly for highest risk subjects; rural, living alone, alcohol-imbibing, and psychiatric diagnosis-carrying citizens.  Long-term cold-weather training may affect hand rewarming patters after a cold provocation, and a warmer baseline hand temperature with faster rewarming after a cold provocation may be associated with less general risk for frostbite.  Heart rate variability results support the conclusion that cold adaptation in the autonomic nervous system occurred in both groups, though the biological significance of this is not yet clear.

Research indicates that learning how to regulate one’s emotions is critical to successful child development and is associated with adaptive social functioning and psychological adjustment (Dunn & Brown, 1994; Eisenberg, Fabes, Guthrie, & Reiser, 2000; Eisenberg, Fabes, & Murphy, 1996). Children’s emotion regulation abilities are thought to be influenced by both child (e.g., age, temperament) and parent characteristics (e.g., parenting behaviors, parental regulation; Eisenberg, Cumberland, & Spinrad, 1998). Resting heart rate variability (HRV) has emerged as a potentially important biomarker associated with emotion regulation (Porges, 2007; Thayer & Lane, 2000); however, there are still significant gaps in research. In particular, research indicates genetic correlates associated with HRV as well as an important role of parents in children’s emotion socialization, but research has yet to establish a strong link between parent and child HRV. Theoretically, parent and child HRV may be linked but only in specific contexts. For example, parent and child resting HRV may become more or less strongly related in the context of specific parenting behaviors, but research has yet to test this hypothesis. The present study examined the association between parenting behaviors and child resting HF-HRV (i.e., high frequency HRV), the links between parent and child resting HF-HRV, and potential moderating effects of parenting behaviors on the association in youth. Additional analyses examined associations between parent and child vagal regulation. Ninety-seven youth (11-17 years) and their caregivers (n = 81) participated in a physiological assessment and completed questionnaires assessing parenting behaviors. Results indicated that parent’s inconsistent discipline and corporal punishment were negatively associated with their child’s resting HF-HRV while positive parenting and parental involvement were positively associated. Furthermore, parent’s inconsistent discipline and parent’s involvement moderated the relationship between parent and child resting HF-HRV, such that in the context of high inconsistent discipline and high parental involvement, high parent resting HF-HRV was associated with low child resting HF-HRV. Findings add to the literature by providing evidence for the role of parenting behaviors in shaping the development of children’s HF-HRV and indicating that inconsistent discipline and parental involvement may affect the entrainment of HF-HRV in parents and their adolescent children.

Divorce is a stressor associated with long-term health risk, though the mechanisms of this effect are poorly understood. Cardiovascular reactivity is one biological pathway implicated as a predictor of poor long-term health after divorce. A sample of recently separated and divorced adults (N = 138) was assessed over an average of 7.5 months to explore whether individual differences in heart rate variability—assessed by respiratory sinus arrhythmia—operate in combination with subjective reports of separation-related distress to predict prospective changes in cardiovascular reactivity, as indexed by blood pressure reactivity. Participants with low resting respiratory sinus arrhythmia at baseline showed no association between divorce-related distress and later blood pressure reactivity, whereas participants with high respiratory sinus arrhythmia showed a positive association. In addition, within-person variation in respiratory sinus arrhythmia and between-persons variation in separation-related distress interacted to predict blood pressure reactivity at each laboratory visit. Individual differences in heart rate variability and subjective distress operate together to predict cardiovascular reactivity and may explain some of the long-term health risk associated with divorce.

Cette étude ergonomique a pour but l’analyse des processus de fatigue parmi différentes professions du milieu maritime. Quatre terrains d’étude en situation « naturelle » ont ainsi été investis : ceux de patrons de chalutiers pélagiques, de marins de navire océanographique, de skippers de course au large en solitaire, et de marins de dragues aspiratrices. Deux ordres de données ont été envisagés : celles ressortissant à la fatigue perçue et à la fatigue objectivée (fatigue « réelle », physiologique, de l’organisme). Du point de vue de la fatigue subjective perçue, notre méthode a consisté à croiser des observations ethnographiques avec des entretiens compréhensifs de type psychologique. Du point de vue de la fatigue physiologique, des mesures de la fréquence cardiaque sur l’intervalle R-R ont été réalisées (tests orthostatiques et enregistrements continus simultanément à l’activité). Nos résultats découlent alors de la confrontation de ces sources de données « objectives » et « subjectives ». Il s’avère d’une part, qu’à l’origine de la fatigue, les rythmes de travail tiennent un rôle prépondérant ; tout comme les contraintes appliquées au sommeil, et l’alternance de phases d’activité intenses et moins soutenues. D’autre part, la fatigue se manifeste par des troubles du sommeil, de la lassitude psychologique, et un « effet de cumul » (dont l’intensité est variable selon les métiers étudiés). De ce fait, les marins ont la possibilité de gérer leur fatigue par la répartition des périodes de sommeil, le repos à terre, et la prise de nourriture. Enfin, des pistes de conception sont suggérées afin d’adapter l’activité des marins en fonction des processus de fatigue analysés. / Our ergonomic approach analyzed the dynamics of the fatigue processes through different maritime professions. The data were collected in “natural” situations across four field studies: pelagic trawlers’ captains, oceanographical ship seamen, solo race’s yachtsmen, and pump dredger’s seamen. Two types of data must be distinguished: those issued from perceived fatigue and those from the ‘real’, physiological, fatigue of the organism. From a psychological point of view, our methodology combined direct observation with non-directive interviews. Concerning the physiological fatigue, measurements of the heart rate on interval R-R were carried out (stand-tests and continuous recordings simultaneously with activity). Our results issue from the confrontation of objective and subjective sources. First, the work rhythms are a preponderant cause of fatigue, with sleep strains, and alternation of activity. Then, fatigue shows sleep disorders, lassitude, and cumulative effect (of which intensity varies according to the professions). Thus, seamen can manage their fatigue with sleep periods repartition, recovery on the ground, and eating food. In addition, we point some solutions to adjust the activity of the seamen to their fatigue processes.

DIPLOMA THESIS: The impact of acupuncture on heart rate variability in patients with migraine SOCIAL AND CLINICAL PHARMACY DEPARTMENT, FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ, CHARLES UNIVERSITY IN PRAGUE AUTHOR: Kateřina Jehličková SUPERVISOR: PharmDr. Jitka Pokladníková, Ph.D. INTRODUCTION: Migraine is one of the most common diseases that affects up to 25% of human adult worldwide. The popularity of alternative therapeutic method is increasing, in this case namely acupuncture, currently between 11-46% globally, 4-9,9% respectively. OBJECTIVE: The primary goal of this work is to evaluate if acupuncture has any effect on HRV in patients with migraine. Secondary goal is to find out which psychosocial factors may influance HRV parameter changes. METHODOLOGY: HRV measurment was performed before acupuncture and after 12 weeks of acupuncture therapy. At first, results were processed in KUBIOS software which is specially designed for the study of heart rate variability and the needed parameters. Then the statistical analysis of a paired t-test (p=0,05) and linear regression (p=0,1) were done in SPSS software. MIDAS questionnaire (quality of life in patients with migraine), life satisfaction questionnaire (Satisfaction with Life Scale, SWLS) and The Symptom Checklist (SCL-90) were used to determine factors...

A obesidade é considerada atualmente um dos maiores problemas de saúde em humanos, sendo considerada endêmica entre adultos e crianças. Situação semelhante tem sido observada em medicina veterinária, como conseqüência de um desequilibrio energético que muitas vezes é resultado do tipo de manejo que os animais recebem. É caracterizada pelo acúmulo excessivo de gordura, superando 15% do peso ideal e culmina com várias modificações nas funções orgânicas. Em humanos, sabe-se que o excesso de peso gera alterações na hemodinâmica, no metabolismo, no estado inflamatório, gerando um aumento do volume circulatório, ativação do sistema nervoso simpático e hipertrofia ventricular e levando ao remodelamento cardíaco. As arritmias cardíacas têm sido descritas em indivíduos obesos, geralmente acompanhadas da hipertrofia ventricular esquerda ou da síndrome da apnéia do sono. A disfunção autonômica, avaliada pela redução da variabilidade da freqüência cardíaca, também é observada nos humanos obesos. Não foram encontradas arritmias em estudo com cães obesos no ECG de rotina. O Holter permite um registro contínuo da atividade elétrica cardíaca, enquanto o paciente continua com as suas atividades diárias normais, assim uma das suas principais indicações é a identificação de presença de arritmias que não são detectados pelo eletrocardiograma de curta duração. Desta forma, o objetivo do estudo foi avaliar, pelo método Holter, a presença de arritmias e, pela análise da variabilidade da freqüência cardíaca, avaliar o balanço autonômico em cães obesos. Para isto, foram selecionados 67 cães obesos com escore de condição corporal (ECC) 8 e 9 e 65 cães com peso ideal (ECC=5), pareados por raça/porte, gênero e idade. Os cães obesos não apresentaram alteração no eletrocardiograma de rotina e nem na mensuração da pressão arterial em relação ao grupo controle. No entanto, o grupo obeso, apresentou maior número de extrassístoles ventriculares, discreta hipertrofia de ventrículo esquerdo. Também foram observados menores valores nos parâmetros de variabilidade da freqüência cardíaca, indicando assim, uma disfunção autonômica. / Obesity is currently one of the major health problems in humans, and it is considered endemic among adults and children. A similar situation has been found in veterinary medicine, as a consequence of energy imbalance, resulting, most of the times from the management of these animals. It is characterized by excessive accumulation of fat, over 15% of ideal body weight, and culminates with various organic function modifications. In humans, it is known that body weight excess generates changes on hemodynamics, metabolism, inflammatory status, leading to increased circulatory volume, sympathetic nervous system activation, ventricular hypertrophy and leads to cardiac remodeling. Arrhythmias have been described in obese people, generally accompanied by ventricular hypertrophy or sleep apnea. The autonomic dysfunction, assessed by a decrease in heart rate variability, is also observed in humans. Arrhythmias were not observed in a previous study of routine ECG in obese dogs. Holter monitoring allows for the continuous registration of the electrical activity of the heart, while the patient continues the normal daily activities. Therefore, one of the main indications is the identification of the presence of arrhythmias that are not detected by the short duration ECG. The purpose of this study was to assess, by Holter method, the presence of cardiac arrhythmias, and by heart rate variability, to evaluate the autonomic balance in obese dogs. Sixty seven dogs, with a body condition score (BCS) of 8 and 9, and 65 dogs with ideal body (BCS= 5) weight were selected, matched for breed/size, gender and age. The obese dogs did not present changes on the routine ECG and blood pressure measurement, in relation to control group. Despite that, the obese group showed greater number of ventricular extra-systoles and mild left ventricular hypertrophy. There were also lower values of heart rate variability parameters, which indicate an autonomic dysfunction.

O objetivo do presente estudo foi verificar a possibilidade de identificação dos dois limiares metabólicos pelo comportamento da VFC. Para isso, 22 voluntários do gênero masculino [74,5 + 7,99kg, 177,0 + 8cm, 23,86 + 1,69 (índice de massa corporal) e 9,10 % de gordura], habituados à prática do ciclismo, realizaram teste ergométrico em bicicleta estacionária com carga inicial de 120W e incrementos de 30W a cada 3min, até a exaustão. Durante todo o teste foram feitos os registros da freqüência cardíaca (FC) e de sua variabilidade (VFC) e ao final de cada carga foram coletados 25µL de sangue para análise da concentração sangüínea de lactato. Aplicou-se um modelo matemático que ajustou a curva da VFC em três retas e o primeiro e segundo limiar de VFC foram identificados nas intersecções entre as retas. Para identificação do primeiro e segundo limiar de lactato, considerou-se as concentrações fixas de 2,0 e 3,5mM, respectivamente. A análise de variância para medidas repetidas indicou não haver diferenças significativas nas cargas em que os limiares de VFC e de lactato foram encontrados, mostrando que a metodologia proposta pode ser promissora. Entretanto a falta de correlação entre as variáveis indica que novos estudos necessitam ser realizados para confirmação desta possibilidade. / The purpose of this study was to verify the possibility of metabolic thresholds identifications through HRV. For that, 22 male volunteers [74,5 + 7,99kg, 177,0 + 8cm, 23,86 + 1,69 (body mass index) e 9,10 % fat], familiarized to cyclism practice, realized a cycloergometer test with initial load of 120W and 30W increases every 3min., until exhaustion. During all test, it was registered heart rate (HR) and its variability (HRV) and, at the end of each load, it was collected 25mL blood for lactate concentration analysis. It was applied a mathematical model to adjust HRV curve in three straight lines and first and second HRV thresholds were identified in intersections among the lines. For the identification of first and second lactate thresholds, it was considered 2,0 and 3,5mM fixed concentrations, respectively. Variance analysis for repeated measures indicated that there were no significant differences between loads in which HRV and lactate thresholds were found, showing that purposed methodology can be promissor. However, the lack of correlation between variables indicate that new studies must be made to confirm that possibility.

"As water covers over 75% surface area of the earth, humans have an innate desire to explore the underwater environment for various aims. Physiological responses are induced in humans and animals to adapt to different stresses imposed by the hyperbaric environment. When these stresses become overwhelming, certain hazards can occur to individuals in underwater or in similar hyperbaric environments, and they may include nitrogen narcosis, oxygen toxicity and decompression sickness (DCS). There are evidences showing that the autonomic nervous system (ANS) plays an important role in diving reflex and physiological responses to diving hazards. However, the assessment of the autonomic nervous activity during SCUBA dives and diving-related hazards are mostly absent from the literature. Thus, in order to evaluate the autonomic nervous alterations that may occur during diving, especially during DCS, the following three experiments were performed in this study: the simulated dives of human subjects in a hyperbaric chamber, the SCUBA diving performed in seawater and induced decompression sickness in a swine model. A novel algorithm developed in our lab, principal dynamic mode (PDM) analysis, is applied to the above data. It has been shown that the PDM is able to accurately separate the sympathetic and parasympathetic dynamics of the ANS, and subsequently it is able to obtain a better quantification of the autonomic nervous activity than a current golden-standard approach. Through the study, dominance of the parasympathetic modulation was found in both hyperbaric chamber and SCUBA diving conditions. And more stresses were present in real dives, compared to simulated dives in chamber. In the swine DCS model, we found neurological DCS and cardiopulmonary DCS resulted in different alterations in the ANS. Furthermore, tracking dynamics of the parasympathetic modulations via the PDM method may allow discrimination between cardiopulmonary DCS and neurological DCS, and has potential use as a marker for early diagnosis of cardiopulmonary DCS. "