Population data-based federated machine learning improves automated echocardiographic quantification of cardiac structure and function: the Automatisierte Vermessung der Echokardiographie project.

Aims: Machine-learning (ML)-based automated measurement of echocardiography images emerges as an option to reduce observer variability. The objective of the study is to improve the accuracy of a pre-existing automated reading tool ('original detector') by federated ML-based re-training. Methods and results: Automatisierte Vermessung der Echokardiographie was based on the echocardiography images of n = 4965 participants of the population-based Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression Cohort Study. We implemented federated ML: echocardiography images were read by the Academic Core Lab Ultrasound-based Cardiovascular Imaging at the University Hospital Würzburg (UKW). A random algorithm selected 3226 participants for re-training of the original detector. According to data protection rules, the generation of ground truth and ML training cycles took place within the UKW network. Only non-personal training weights were exchanged with the external cooperation partner for the refinement of ML algorithms. Both the original detectors as the re-trained detector were then applied to the echocardiograms of n = 563 participants not used for training. With regard to the human referent, the re-trained detector revealed (i) superior accuracy when contrasted with the original detector's performance as it arrived at significantly smaller mean differences in all but one parameter, and a (ii) smaller absolute difference between measurements when compared with a group of different human observers. Conclusion: Population data-based ML in a federated ML set-up was feasible. The re-trained detector exhibited a much lower measurement variability than human readers. This gain in accuracy and precision strengthens the confidence in automated echocardiographic readings, which carries large potential for applications in various settings.

Determinants and reference values of the 6-min walk distance in the general population-results of the population-based STAAB cohort study.

AIMS: The 6-min walk test is an inexpensive, safe, and easy tool to assess functional capacity in patients with cardiopulmonary diseases including heart failure (HF). There is a lack of reference values, which are a prerequisite for the interpretation of test results in patients. Furthermore, determinants independent of the respective disease need to be considered when interpreting the 6-min walk distance (6MWD). METHODS: The prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigates a representative sample of residents of the City of Würzburg, Germany, aged 30 to 79 years, without a history of HF. Participants underwent detailed clinical and echocardiographic phenotyping as well as a standardized assessment of the 6MWD using a 15-m hallway. RESULTS: In a sample of 2762 participants (51% women, mean age 58 ± 11 years), we identified age and height, but not sex, as determinants of the 6MWD. While a worse metabolic profile showed a negative association with the 6MWD, a better systolic and diastolic function showed a positive association with 6MWD. From a subgroup of 681 individuals without any cardiovascular risk factors (60% women, mean age 52 ± 10 years), we computed age- and height-specific reference percentiles. CONCLUSION: In a representative sample of the general population free from HF, we identified determinants of the 6MWD implying objective physical fitness associated with metabolic health as well as with cardiac structure and function. Furthermore, we derived reference percentiles applicable when using a 15-m hallway.

Heart rate variability, interoceptive accuracy and functional connectivity in middle-aged and older patients with depression.

BACKGROUND AND OBJECTIVE: Major depressive disorder (MDD) is associated with increased cardiac morbidity. Reduced heart rate variability (HRV) as well as lower interoceptive accuracy (IAc) have been observed in MDD as possible sympathomimetic mechanisms related to insula activity. The salience network (SN) anchored by the insula has been posited as a crucial functional network for cardiac sensations and the default mode network (DMN) for MDD. This study aimed to investigate the relation between insula-centered and depression-related brain networks, IAc and HRV in patients with depression as a possible mechanism by which MDD increases cardiac morbidity. METHODS: 30 depressed inpatients and 30 healthy subjects (derived from the population-based "Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression" cohort study, STAAB) all over 50 years were examined. HRV and IAc were assessed via electrocardiogram and a heartbeat perception task prior to a 3 T resting-state functional magnetic resonance imaging. Seed-to-voxel resting-state functional connectivity (FC) analysis was conducted with six seeds in the insula and two seeds in the DMN. RESULTS: Depressed patients on the one hand showed decreased FC between insula cortex and frontal as well occipital cortical brain regions compared to controls. Depressed patients on the other hand exhibited higher FC between the medial prefrontal cortex and the insula cortex compared to controls. However, depressed patients did not differ in HRV nor in IAc compared to controls. CONCLUSION: Thus, differences in insula-related brain networks in depression in our study were not mirrored by differences in HRV and IAc. Future research is needed to define the mechanism by which depression increases cardiac morbidity.

Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism-the Find-AF 2 study-rationale and design.

BACKGROUND: Atrial fibrillation (AF) is one of the most frequent causes of stroke. Several randomized trials have shown that prolonged monitoring increases the detection of AF, but the effect on reducing recurrent cardioembolism, ie, ischemic stroke and systemic embolism, remains unknown. We aim to evaluate whether a risk-adapted, intensified heart rhythm monitoring with consequent guideline conform treatment, which implies initiation of oral anticoagulation (OAC), leads to a reduction of recurrent cardioembolism. METHODS: Find-AF 2 is a randomized, controlled, open-label parallel multicenter trial with blinded endpoint assessment. 5,200 patients ≥ 60 years of age with symptomatic ischemic stroke within the last 30 days and without known AF will be included at 52 study centers with a specialized stroke unit in Germany. Patients without AF in an additional 24-hour Holter ECG after the qualifying event will be randomized in a 1:1 fashion to either enhanced, prolonged and intensified ECG-monitoring (intervention arm) or standard of care monitoring (control arm). In the intervention arm, patients with a high risk of underlying AF will receive continuous rhythm monitoring using an implantable cardiac monitor (ICM) whereas those without high risk of underlying AF will receive repeated 7-day Holter ECGs. The duration of rhythm monitoring within the control arm is up to the discretion of the participating centers and is allowed for up to 7 days. Patients will be followed for at least 24 months. The primary efficacy endpoint is the time until recurrent ischemic stroke or systemic embolism occur. CONCLUSIONS: The Find-AF 2 trial aims to demonstrate that enhanced, prolonged and intensified rhythm monitoring results in a more effective prevention of recurrent ischemic stroke and systemic embolism compared to usual care.

Deep phenotyping as a contribution to personalized depression therapy: the GEParD and DaCFail protocols.

Depressive patients suffer from a complex of symptoms of varying intensity compromising their mood, emotions, self-concept, neurocognition, and somatic function. Due to a mosaic of aetiologies involved in developing depression, such as somatic, neurobiological, (epi-)genetic factors, or adverse life events, patients often experience recurrent depressive episodes. About 20-30% of these patients develop difficult-to-treat depression. Here, we describe the design of the GEParD (Genetics and Epigenetics of Pharmaco- and Psychotherapy in acute and recurrent Depression) cohort and the DaCFail (Depression-associated Cardiac Failure) case-control protocol. Both protocols intended to investigate the incremental utility of multimodal biomarkers including cardiovascular and (epi-)genetic markers, functional brain and heart imaging when evaluating the response to antidepressive therapy using comprehensive psychometry. From 2012 to 2020, 346 depressed patients (mean age 45 years) were recruited to the prospective, observational GEParD cohort protocol. Between 2016 and 2020, the DaCFail case-control protocol was initiated integrating four study subgroups to focus on heart-brain interactions and stress systems in patients > 50 years with depression and heart failure, respectively. For DaCFail, 120 depressed patients (mean age 60 years, group 1 + 2), of which 115 also completed GEParD, and 95 non-depressed controls (mean age 66 years) were recruited. The latter comprised 47 patients with heart failure (group 3) and 48 healthy subjects (group 4) of a population-based control group derived from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study. Our hypothesis-driven, exploratory study design may serve as an exemplary roadmap for a standardized, reproducible investigation of personalized antidepressant therapy in an inpatient setting with focus on heart comorbidities in future multicentre studies.

The Population Comparison Index: An Intuitive Measure to Calibrate the Extent of Impairments in Patient Cohorts in Relation to Healthy and Diseased Populations.

We assume that a specific health constraint, e.g., a certain aspect of bodily function or quality of life that is measured by a variable X, is absent (or irrelevant) in a healthy reference population (Ref0), and it is materially present and precisely measured in a diseased reference population (Ref1). We further assume that some amount of this constraint of interest is suspected to be present in a population under study (SP). In order to quantify this issue, we propose the introduction of an intuitive measure, the population comparison index (PCI), that relates the mean value of X in population SP to the mean values of X in populations Ref0 and Ref1. This measure is defined as PCI[X] = (mean[X|SP] - mean[X|Ref0])/(mean[X|Ref1] - mean[X|Ref0]) × 100[%], where mean[X|.] is the average value of X in the respective group of individuals. For interpretation, PCI[X] ≈ 0 indicates that the values of X in the population SP are similar to those in population Ref0, and hence, the impairment measured by X is not materially present in the individuals in population SP. On the other hand, PCI[X] ≈ 100 means that the individuals in SP exhibit values of X comparable to those occurring in Ref1, i.e., the constraint of interest is equally present in populations SP and Ref1. A value of 0 < PCI[X] < 100 indicates that a certain percentage of the constraint is present in SP, and it is more than in Ref0 but less than in Ref1. A value of PCI[X] > 100 means that population SP is even more affected by the constraint than population Ref1.

Generalised anxiety and panic symptoms in the German National Cohort (NAKO).

OBJECTIVES: Anxiety disorders (AD) are common in the general population, leading to high emotional distress and disability. The German National Cohort (NAKO) is a population-based mega-cohort study, examining participants in 16 German regions. The present study includes data of the first 101,667 participants and investigates the frequency and severity of generalised anxiety symptoms and panic attacks (PA). METHODS: The Generalised Anxiety Disorder Symptoms Scale (GAD-7) and the first part of the Patient Health Questionnaire Panic Disorder (PHQ-PD) were filled out by NAKO participants (93,002). We examined the correlation of GAD-7 and PHQ-PD with demographic variables, stress (PHQ-Stress), depression (PHQ-9) and childhood trauma (CTS). RESULTS: The total proportion of prior lifetime diagnoses of AD in the NAKO cohort reached 7.8%. Panic attacks were reported by 6.0% and possible/probable current GAD symptoms in 5.2% of the examined participants. Higher anxiety severity was associated with female sex, lower education level, German as a foreign language and younger age as well as high perceived stress and depression. CONCLUSIONS: Clinically relevant GAD symptoms as well as panic attacks are frequent in the NAKO and are associated with sociodemographic factors, and high anxiety symptoms are accompanied by pronounced stress and depression levels.

The assessment of cognitive function in the German National Cohort (NAKO) - Associations of demographics and psychiatric symptoms with cognitive test performance.

OBJECTIVES: To describe the cognitive test battery of the German National Cohort (NAKO), a population-based mega cohort of 205,000 randomly selected participants, and to examine associations with demographic variables and selected psychiatric and neurological conditions. METHODS: Initial data from 96,401 participants providing data on the cognitive performance measured by a brief cognitive test battery (12-word list recall task, semantic fluency, Stroop test, digit span backwards) was examined. Test results were summarised in cognitive domain scores using exploratory and confirmatory factor analyses. Associations with sociodemographic and psychiatric factors were analysed using linear regression and generalised additive models. RESULTS: Cognitive test results were best represented by two domain scores reflecting memory and executive functions. Lower cognitive functions were associated with increasing age and male sex. Higher education and absence of childhood trauma were associated with better cognitive function. Moderate to severe levels of anxiety and depression, and a history of stroke, were related to lower cognitive function with a stronger effect on executive function as compared to memory. Some associations with cognition differed by German language proficiency. CONCLUSIONS: The NAKO cognitive test battery and the derived cognitive domain scores for memory and executive function are sensitive measures of cognition.

Impact of cardiovascular risk factors on myocardial work-insights from the STAAB cohort study.

Myocardial work is a new echocardiography-based diagnostic tool, which allows to quantify left ventricular performance based on pressure-strain loops, and has been validated against invasively derived pressure-volume measurements. Myocardial work is described by its components (global constructive work [GCW], global wasted work [GWW]) and indices (global work index [GWI], global work efficiency [GWE]). Applying this innovative concept, we characterized the prevalence and severity of subclinical left ventricular compromise in the general population and estimated its association with cardiovascular (CV) risk factors. Within the Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study we comprehensively phenotyped a representative sample of the population of Würzburg, Germany, aged 30-79 years. Indices of myocardial work were determined in 1929 individuals (49.3% female, mean age 54 ± 12 years). In multivariable analysis, hypertension was associated with a mild increase in GCW, but a profound increase in GWW, resulting in higher GWI and lower GWE. All other CV risk factors were associated with lower GCW and GWI, but not with GWW. The association of hypertension and obesity with GWI was stronger in women. We conclude that traditional CV risk factors impact selectively and gender-specifically on left ventricular myocardial performance, independent of systolic blood pressure. Quantifying active systolic and diastolic compromise by derivation of myocardial work advances our understanding of pathophysiological processes in health and cardiac disease.

DIPS (Dystonia Image-based Programming of Stimulation: a prospective, randomized, double-blind crossover trial).

INTRODUCTION: Deep brain stimulation of the internal globus pallidus is an effective treatment for dystonia. However, there is a large variability in clinical outcome with up to 25% non-responders even in highly selected primary dystonia patients. In a large cohort of patients we recently demonstrated that the variable clinical outcomes of pallidal DBS for dystonia may result to a large degree by the exact location and stimulation volume within the pallidal region. Here we test a novel approach of programing based on these insights: we first defined probabilistic maps of anti-dystonic effects by aggregating individual electrode locations and volumes of tissue activated of > 80 patients collected in a multicentre effort. We subsequently modified the algorithms to be able to test all possible stimulation settings of de novo patients in silico based on the expected clinical outcome and thus potentially predict the best possible stimulation parameters for the individual patients. METHODS: Within the framework of a BMBF-funded study, this concept of a computer-based prediction of optimal stimulation parameters for patients with dystonia will be tested in a randomized, controlled crossover study. The main parameter for clinical efficacy and primary endpoint is based on the blinded physician rating of dystonia severity reflected by Clinical Dystonia Rating Scales for both interventions (best clinical settings and model predicted settings) after 4 weeks of continuous stimulation. The primary endpoint is defined as "successful treatment with model predicted settings" (yes or no). The value is "yes" if the motor symptoms with model predicted settings are equal or better (tolerance 5% of absolute difference in percentages) to clinical settings. Secondary endpoints will include measures of quality of life, calculated energy consumption of the neurostimulation system and physician time for programming. PERSPECTIVE: We envision, that computer-guided deep brain stimulation programming in silico might provide optimal stimulation settings for patients with dystonia without the burden of months of programming sessions. The study protocol is designed to evaluate which programming method is more effective in controlling motor symptom severity and improving quality of life in dystonia (best clinical settings and model predicted settings). Trial registration Registered with ClinicalTrials.gov on Oct 27, 2021 (NCT05097001).

[Seroprevalence of COVID-19 and Psychosocial Effects in the General Population: Results of the STAAB-COVID-One Program]. / Seroprävalenz von COVID-19 und psychosoziale Auswirkungen in der Allgemeinbevölkerung: Ergebnisse des STAAB-COVID-One Programms.

BACKGROUND: Research of SARS-CoV-2 has so far largely focused on symptomatic cases. The STAAB-COVID study therefore examined the seroprevalence of COVID-19 in the general population and the psychosocial effects of the pandemic. METHODS: From June-October 2020, a sub-study was conducted within the "Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB)" cohort study. 4,860 study participants identified from a representative age-stratified sample of Würzburg residents were asked to provide a blood sample and to fill in a questionnaire. All participants also received an offer to take part in a point prevalence assessment (nasal swab taken from the participant at the beginning of November 2020). RESULTS: A total of 3,034 subjects took part in the STAAB-COVID program (response rate 62%). Antibodies against SARS-CoV-2 were detected in 33 participants (1.1%; 95% confidence interval 0.7-1.5%). Higher values on the GAD-7 anxiety scale were associated with lower rates of SARS-CoV-2 antibodies (Odds Ratio=0.78 for each+1 point in GAD-7; 95% confidence interval 0.65-0.95). Within this rather anxious group of subjects, however, the rate of cancellation of medical appointments was also increased (Odds Ratio=1.13 for each+1 point in GAD-7; 95% confidence interval 1.10-1.16). An acute infection was detected in six of a total of 2,451 participants in the point prevalence assessment (0.24%; 95% confidence interval 0.09-0.53%). CONCLUSION: Between the first and second COVID-19 waves in Germany, we found a low level of SARS-CoV-2 contamination in the city of Würzburg. A more anxious personality was associated with a lower seroprevalence. Conducting the study was largely facilitated by the existing cohort study.

Functional versus morphological assessment of vascular age in patients with coronary heart disease.

Communicating cardiovascular risk based on individual vascular age (VA) is a well acknowledged concept in patient education and disease prevention. VA may be derived functionally, e.g. by measurement of pulse wave velocity (PWV), or morphologically, e.g. by assessment of carotid intima-media thickness (cIMT). The purpose of this study was to investigate whether both approaches produce similar results. Within the context of the German subset of the EUROASPIRE IV survey, 501 patients with coronary heart disease underwent (a) oscillometric PWV measurement at the aortic, carotid-femoral and brachial-ankle site (PWVao, PWVcf, PWVba) and derivation of the aortic augmentation index (AIao); (b) bilateral cIMT assessment by high-resolution ultrasound at three sites (common, bulb, internal). Respective VA was calculated using published equations. According to VA derived from PWV, most patients exhibited values below chronological age indicating a counterintuitive healthier-than-anticipated vascular status: for VAPWVao in 68% of patients; for VAAIao in 52% of patients. By contrast, VA derived from cIMT delivered opposite results: e.g. according to VAtotal-cIMT accelerated vascular aging in 75% of patients. To strengthen the concept of VA, further efforts are needed to better standardise the current approaches to estimate VA and, thereby, to improve comparability and clinical utility.

Prevalence and determinants of the precursor stages of heart failure: results from the population-based STAAB cohort study.

AIMS: Prevention of heart failure relies on the early identification and control of risk factors. We aimed to identify the frequency and characteristics of individuals at risk of heart failure in the general population. METHODS AND RESULTS: We report cross-sectional data from the prospective Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of residents of Würzburg, Germany. Sampling was stratified 1:1 for sex and 10:27:27:27:10 for age groups of 30-39/40-49/50-59/60-69/70-79 years. Heart failure precursor stages were defined according to American College of Cardiology/American Heart Association: stage A (risk factors for heart failure), stage B (asymptomatic cardiac dysfunction). The main results were internally validated in the second half of the participants. The derivation sample comprised 2473 participants (51% women) with a distribution of 10%/28%/25%/27%/10% in respective age groups. Stages A and B were prevalent in 42% and 17% of subjects, respectively. Of stage B subjects, 31% had no risk factor qualifying for stage A (group 'B-not-A'). Compared to individuals in stage B with A criteria, B-not-A were younger, more often women, and had left ventricular dilation as the predominant B qualifying criterion (all P < 0.001). These results were confirmed in the validation sample (n = 2492). CONCLUSION: We identified a hitherto undescribed group of asymptomatic individuals with cardiac dysfunction predisposing to heart failure, who lacked established heart failure risk factors and therefore would have been missed by conventional primary prevention. Further studies need to replicate this finding in independent cohorts and characterise their genetic and -omic profile and the inception of clinically overt heart failure in subjects of group B-not-A.

Left Ventricular Remodeling and Myocardial Work: Results From the Population-Based STAAB Cohort Study.

Introduction: Left ventricular (LV) dilatation and LV hypertrophy are acknowledged precursors of myocardial dysfunction and ultimately of heart failure, but the implications of abnormal LV geometry on myocardial function are not well-understood. Non-invasive LV myocardial work (MyW) assessment based on echocardiography-derived pressure-strain loops offers the opportunity to study detailed myocardial function in larger cohorts. We aimed to assess the relationship of LV geometry with MyW indices in general population free from heart failure. Methods and Results: We report cross-sectional baseline data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort study investigating a representative sample of the general population of Würzburg, Germany, aged 30-79 years. MyW analysis was performed in 1,926 individuals who were in sinus rhythm and free from valvular disease (49.3% female, 54 ± 12 years). In multivariable regression, higher LV volume was associated with higher global wasted work (GWW) (+0.5 mmHg% per mL/m2, p < 0.001) and lower global work efficiency (GWE) (-0.02% per mL/m2, p < 0.01), while higher LV mass was associated with higher GWW (+0.45 mmHg% per g/m2, p < 0.001) and global constructive work (GCW) (+2.05 mmHg% per g/m2, p < 0.01) and lower GWE (-0.015% per g/m2, p < 0.001). This was dominated by the blood pressure level and also observed in participants with normal LV geometry and concomitant hypertension. Conclusion: Abnormal LV geometric profiles were associated with a higher amount of wasted work, which translated into reduced work efficiency. The pattern of a disproportionate increase in GWW with higher LV mass might be an early sign of hypertensive heart disease.

Physicians' lifestyle advice on primary and secondary cardiovascular disease prevention in Germany: A comparison between the STAAB cohort study and the German subset of EUROASPIRE IV.

BACKGROUND: We assessed prevalence and determinants in appropriate physician-led lifestyle advice (PLA) in a population-based sample of individuals without cardiovascular disease (CVD) compared with a sample of CVD patients. METHODS: PLA was assessed via questionnaire in a subsample of the population-based Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) cohort free of CVD (primary prevention sample) and the German subset of the fourth EUROASPIRE survey (EUROASPIRE-IV) comprising CVD patients (secondary prevention sample). PLA was fulfilled if the participant reported having ever been told by a physician to: stop smoking (current/former smokers), reduce weight (overweight/obese participants), increase physical activity (physically inactive participants) or keep to a healthy diet (all participants). Factors associated with receiving at least 50% of the PLA were identified using logistic regression. RESULTS: Information on PLA was available in 665 STAAB participants (55 ± 11; 55% females) and in 536 EUROASPIRE-IV patients (67 ± 9; 18% females). Except for smoking, appropriate PLA was more frequently given in the secondary compared with the primary prevention sample. Determinants associated with appropriate PLA in primary prevention were: diabetes mellitus (odds ratio (OR) 4.54; 95% confidence interval (CI) 1.88-10.95), hyperlipidaemia (OR 3.12; 95% CI 2.06-4.73) and hypertension (OR 1.74; 95% CI 1.15-2.62); in secondary prevention: age (OR per year 0.96; 95% CI 0.93-0.98) and diabetes mellitus (OR 2.33; 95% CI 1.20-4.54). CONCLUSIONS: In primary prevention, PLA was mainly determined by the presence of vascular risk factors, whereas in secondary prevention the level of PLA was higher in general, but the association between CVD risk factors and PLA was less pronounced.

Musical Intervals in Infants' Spontaneous Crying over the First 4 Months of Life.

INTRODUCTION: Perception and memorizing of melody and rhythm start about the third trimester of gestation. Infants have astonishing musical predispositions, and melody contour is most salient for them. OBJECTIVE: To longitudinally analyse melody contour of spontaneous crying of healthy infants and to identify melodic intervals. The aim was 3-fold: (1) to answer the question whether spontaneous crying of healthy infants regularly exhibits melodic intervals across the observation period, (2) to investigate whether interval events become more complex with age and (3) to analyse interval size distribution. METHODS: Weekly cry recordings of 12 healthy infants (6 females) over the first 4 months of life were analysed (6,130 cry utterances) using frequency spectrograms and pitch analyses (PRAAT). A preselection of utterances containing a well-identifiable, noise-free and undisturbed melodic contour was applied to identify and measure melodic intervals in the final subset of 3,114 utterances. Age-dependent frequency of occurrence of melodic intervals was statistically analysed using generalized estimating equations. RESULTS: 85.3% of all preselected melody contours (n = 3,114) either contained single rising or falling melodic intervals or complex events as combinations of both. In total 6,814 melodic intervals were measured. A significant increase in interval occurrence was found characterized by a non-linear age effect (3 developmental phases). Complex events were found to significantly increase linearly with age. In both calculations, no sex effect was found. Interval size distribution showed a maximum of the minor second as the prevailing musical interval in infants' crying over the first 4 months of life. CONCLUSION: Melodic intervals seem to be a regular phenomenon of spontaneous crying of healthy infants. They are suggested to be a further candidate for developing an early risk marker of vocal control in infants. Subsequent studies are needed to compare healthy infants and infants at risk for respiratory-laryngeal dysfunction to investigate the diagnostic value of the occurrence of melodic intervals and their age-depending complexification.

Myocardial work - correlation patterns and reference values from the population-based STAAB cohort study.

BACKGROUND: Recently, myocardial work analysis as an echocardiographic tool to non-invasively determine LV work has been introduced and validated against invasive measurements. Based on systolic blood pressure and speckle-tracking derived longitudinal strain (GLS) during systole and isovolumic relaxation, it is considered less load-dependent than LV ejection fraction (LVEF) or GLS and to integrate information on LV active systolic and diastolic work. OBJECTIVES: We aimed to establish reference values for global constructive (GCW) and global wasted work (GWW) as well as of global work index (GWI) and global work efficiency (GWE) across a wide age range and to assess the association with standard echocardiography parameters to estimate the potential additional information provided by myocardial work (MyW). METHODS: The Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study carefully characterized a representative sample of the population of the City of Würzburg, Germany, aged 30-79 years. We performed myocardial work analysis using the standardized, quality-controlled transthoracic echocardiograms of all individuals lacking any cardiovascular risk factor. RESULTS: Out of 4965 participants, 779 (49±10 years, 59% women) were eligible for the present analysis. Levels of GCW, GWW, and GWE were independent of sex and body mass index, and were stable until the age of 45 years. Thereafter, we observed an upward shift to further stable values of GCW and a linear increase of GWW with advancing age, resulting in lower GWE. Age-adjusted percentiles for GCW, GWW, GWI, and GWE were derived. Higher levels of blood pressure or LV mass were associated with higher GCW, GWI, and GWW, resulting in lower GWE; higher LVEF correlated with higher GCW and GWI, but lower GWW. Higher E/e´ correlated with higher GWW, higher e´ with lower GWW. CONCLUSIONS: Derived from a large sample of apparently healthy individuals from a population based-cohort, we provide age-adjusted reference values for myocardial work indices, applicable for either sex. Weak correlations with common echocardiographic parameters suggest MyW indices to potentially provide additional information, which has to be evaluated in diseased patient cohorts.

Consumption of Lactobacillus reuteri-containing lozenges improves periodontal health in navy sailors at sea: A randomized controlled trial.

BACKGROUND: The objective of this trial was to evaluate whether the regular consumption of probiotics may improve the known deterioration of periodontal health in navy sailors during deployments at sea. METHODS: 72 healthy sailors of a naval ship on a practicing mission at sea were recruited and randomly provided with a blinded supply of lozenges to be consumed twice daily for the following 42 days containing either the probiotic strains Lactobacillus reuteri (DSM 17938 and L. reuteri (ATTC PTA 5289) (test n = 36) or no probiotics (placebo n = 36). At baseline, at day 14 and day 42 bleeding on probing (primary outcome), gingival index, plaque control record, probing attachment level, and probing pocket depth were assessed at the Ramfjord teeth. RESULTS: At baseline there were no significant differences between the groups. At day 14 and day 42 test group scores of all assessed parameters were significantly improved (P < 0.001) compared to baseline and to the placebo group which by contrast showed a significant (P < 0.001) deterioration of all parameters at the end of the study. CONCLUSIONS: The consumption of probiotic L. reuteri-lozenges is an efficacious measure to improve and maintain periodontal health in situations with waning efficacy of personal oral hygiene.

Comparison of three methods to estimate dental age in children.

OBJECTIVES: In 1973, Demirjian and colleagues introduced a staging for tooth mineralization. Staging of the teeth of the left mandible generates a dental maturity score and an estimate of dental age. An update of this method was published in 2001 by Willems and colleagues. The London Atlas (2008) is another method used to assess dental age. This study compared the precision of these three methods for forensic age estimation. MATERIALS AND METHODS: A total of 500 panoramic images of 251 boys and 249 girls aged 6-16 years had dental maturity evaluated by the same observer using the London Atlas and the methods of Demirjian and Willems. Individuals with syndromes potentially affecting dental maturation were excluded. The three methods were compared with respect to their precision in estimating chronological age. RESULTS: Age estimates using Willems' method were significantly more precise than those obtained using Demirjian's method, while estimates obtained using the London Atlas method were comparable with both the others. The highest precision was obtained using the average of age estimates from Willems' method and the London Atlas. CONCLUSIONS: To estimate age in individuals suspected of being below 16 years of age, we suggest first applying the London Atlas then computing age from the Demirjian stages of particular teeth using Willems' method, and finally using the average age estimate of both methods. CLINICAL RELEVANCE: Combining the London Atlas and Willems' scoring method provides more precise estimates of dental age than the current practice of applying a single preferred method.