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PURPOSE: To perform a meta-analysis on how the admissions of stroke and transient ischemic attack (TIA) changed during the Corona Virus infection-19 (COVID-19) pandemic and evaluate if the effect was depending on stroke severity. METHODS: Observational cohort studies comparing the number of stroke and/or TIA admissions during a period of the pandemic compared to a period before the pandemic were identified in PubMed and Embase. After excluding studies with overlapping populations and studies without satisfactory case ascertainment, data was extracted and meta-analyzed. FINDINGS: A total of 59 studies were included. During the pandemic, there was a decrease in admissions of ischemic stroke (admission rate ratio (ARR) = 0.77, 95% confidence interval (CI): 0.72, 0.82), intracerebral hemorrhage (ARR = 0.79, 95% CI: 0.70, 0.90) and TIA (ARR = 0.66, 95% CI: 0.58, 0.75). Albeit admission rates of both mild (ARR = 0.61, 95% CI: 0.49, 0.77) and severe (ARR = 0.82, 95% CI = 0.71, 0.95) strokes decreased, milder strokes decreased more (proportion ratio (PR) = 0.76, 95% CI: 0.65, 0.89). DISCUSSION: Potential causes for the admission reduction could be strict prioritizations within the health care, patients' fear of acquiring COVID-19, or decreased access to health care due to lockdowns. CONCLUSION: During the COVID-19 pandemic, there was a reduction in admissions of stroke and TIA, possibly caused by reluctance to seek medical care.

Introduction: Atrial fibrillation (AF) is a major risk factor for ischaemic stroke and transient ischaemic attack (TIA), and AF detection can be challenged by asymptomatic and paroxysmal presentation. Long-term ECG monitoring after ischaemic stroke or TIA is recommended by all major societies in cardiology and cerebrovascular medicine as a secondary prophylactic measure. However, data on stroke reduction are lacking, and the recommendations show significant diversity. Methods and analysis: AF SPICE is a multicentre, national, investigator-initiated, randomised, parallel-group, register-based trial comparing extended ECG monitoring versus standard ECG monitoring in patients admitted with ischaemic stroke or TIA, with a composite endpoint of stroke, all-cause-mortality and intracerebral bleeding. Patients aged ≥70 years without previous AF will be randomised 1:1 to control (standard ECG monitoring) or intervention (extended ECG monitoring). In the control arm, patients will undergo 48±24 hours (ie, a range of 24-72 hours) of continuous ECG monitoring according to national recommendations. In the intervention arm, patients will undergo 14+14 days of continuous ECG monitoring 3 months apart using an ECG patch device, which will provide an easy-accessed, well-tolerated 14-day continuous ECG recording. All ECG patch recordings will be read in a core facility. In cases of AF detection, oral anticoagulation will be recommended if not contraindicated. A pilot phase has been concluded in 2022, which will transcend into the main trial during 2023-2026, including approximately 30 stroke units. The sample size was calculated to be 3262 patients. The primary outcome will be collected from register data during a 36-month follow-up. Ethics and dissemination: Ethical approval has been provided by the Swedish Ethical Review Authority, reference 2021-02770. The trial will be conducted according to the ethical principles of the Declaration of Helsinki and national regulatory standards.

Purpose Testosterone analysis in hair allows for retrospective evaluation of endogenous testosterone concentrations, but studies devoted to investigating confounders in hair testosterone analysis have hitherto been scarce. The current study examined the stability of testosterone concentrations between two hair samples collected three months apart and investigated two potential confounding factors: natural hair colour and cosmetic hair treatments. Methods Testosterone was analysed with an in-house radioimmunoassay with a limit of detection adequate for the purpose. Results The testosterone concentrations from the two samplings, at baseline and three months later, had an intra-individual correlation of moderate strength (rho = 0.378, p<0.001, n = 146). Hair treatment, such as colouring or bleaching, seemed to increase testosterone concentrations (p = 0.051, n = 191, and in a paired analysis in a subset of the cohort p = 0.005, n = 24), while no effect of natural colour in untreated hair (p = 0.133) could be detected. Conclusion The current results suggest that cosmetic hair treatments need to be considered in hair testosterone analyses and demonstrate the utility of a radioimmunoassay to reliably measure testosterone concentrations in small hair samples in women.

Testosterone is thought to be incorporated in growing hair strands so that specific hair segments reflect average free hormone concentrations from the corresponding time period. However, the exact mechanisms of hormone integration in scalp hair have not yet been established and it is not known how testosterone is stored in the hair segments over time. The aim of this study was to investigate the stability of testosterone concentrations in hair as it grows and to determine if segmental hair analysis can be used as a retrospective testosterone diary. Thirty men and 40 women provided two hair samples and 16 saliva samples during a period of three months. Hair growth between the two samplings was measured. Hair samples were cut into 10 mm segments resulting in three segments from the first sampling and six segments from the second sampling. Hair samples were pulverised and extracted with methanol. Hair testosterone concentrations were analysed using an in-house radioimmunoassay. Salivary testosterone was analysed using a commercial enzyme-linked immunosorbent assay (Demeditec). The results demonstrated that there is a degree of segmental hormone conservation over time (rho = 0.405-0.461, p < 0.001, n = 66-67), but also highlighted three potential confounders. Firstly, testosterone concentrations were higher in distal hair segments (mean concentration ratio most distal by most scalp-near was 1.55, SD 0.70), which may be due to continuous hormone integration from sebum and changes in hair matrix composition. Secondly, more frequent hair washing stunted the increase in testosterone concentrations in distal segments (rho = -0.404, p = < 0.001, n = 66). And lastly, intra- and inter- individual variability in hair growth rate influenced the temporal resolution along the hair, although mean growth rate was indeed 30.0 mm for three months. In a multiple regression model the biological sex, natural hair colour, and relationship status were significant explanatory variable

Comment on “Reperfusion Treatments in Disabling Versus Nondisabling Mild Stroke due to Anterior Circulation Vessel Occlusion.” Schwarz et al. Stroke. 2023;54:743–750.

Introduction: Cardiovascular events and infections are common in the acute phase after stroke. It has been suggested that these complications may be associated with excessive sympathetic activation due to the stroke, and that beta-adrenergic antagonists (beta-blockers) therefore may be beneficial. Aim: The aim of the current meta-analysis was to investigate the association between beta-blocker treatment in acute stroke and the three outcomes: mortality, functional outcome and post-stroke infections. Methods: A literature search was performed using the keywords stroke, cerebrovascular disorders, adrenergic beta-antagonists, treatment outcome and mortality. Randomized clinical trials and observational studies were eligible for data extraction. Heterogeneity was investigated using I-2 statistics. Random effect model was used when heterogeneity presented among studies; otherwise, a fixed-effect model was used. Publication bias was assessed using Eggers test and by visually inspecting funnel plots. Results: A total of 20 studies were eligible for at least one of the three outcomes. Two of the included studies were randomized controlled trials and 18 were observational studies. Quality assessments indicated that the risk of bias was moderate. The meta-analysis found no significant association between treatment with beta-blockers and any of the three outcomes. The studies analyzed for the outcomes mortality and infection were heterogeneous, while studies analyzed for functional outcome were homogeneous. The articles analyzed for mortality showed signs of publication bias. Conclusion: The lack of significant effects in the current meta-analysis, comprising more than 100,000 patients, does not support the proposed beneficial effects of beta-blockers in the acute phase of stroke.

Rationale and aims: The Quality of Dyadic Relationships is a self-assessment scale used to evaluate various aspects of relationship quality. Psychometric evaluation by the developers of the instrument has led to a nontested amended version. Further psychometric testing is thus warranted, and the aim of this study was to evaluate homogeneity, construct validity (in terms of concurrent, discriminant and known-groups validity) and any floor and ceiling effects of the Quality of Dyadic Relationships. Methods: Forty-seven cohabitant couples (47 women with a mean age of 30.0 years and 47 men with a mean age of 31.5 years) answered the Quality of Dyadic Relationships, the Relationship Assessment Scale (to test concurrent validity) and the Perceived Stress Scale (to test discriminant validity). Homogeneity (internal consistency) was calculated by Cronbach's alpha. Concurrent and discriminant validity were estimated as correlations between Quality of Dyadic Relationships and the other instruments. Assessment of known-groups validity was based on the variables of parental status and gender. Floor and ceiling effects were evaluated according to frequency distribution. Results: The overall homogeneity was good with acceptable Cronbach's alpha values (alpha > 0.70) for all subscales but dyadic sexuality. Concurrent validity and discriminant validity were found. Known-groups validity was indicated by significant differences between individuals with different parental status on the total QDR index, where the ones without children scored higher. No difference between the genders was found. No significant floor effects were found, but a significant ceiling effect was found in the subscale dyadic sensuality, with 27.7% of respondents scoring maximum. Conclusion: In all, the QDR showed promising psychometric properties and may be used for screening and follow-up purposes. However, it can benefit from further development, as suggested by the ceiling effect in the subscale dyadic sen, Funding Agencies:Region Östergötland Region Örebro Örebro University

Extensive research has been devoted to developing methods for assessing core body temperature, and to determine which method is most accurate. A number of wireless dermal thermometers for home use are presently available, but their relation to core body temperature and suitability for use in clinical research has hitherto not been assessed. The current study aimed to evaluate such thermometers by comparing them to the results of a rectal thermometer. Four wireless dermal thermometers for home use (FeverSmart, iThermonitor, Quest Temp Sitter, and Thermochron iButton) were applied to 15 patients during 24 h, and rectal temperature was measured at four occasions. Pearson correlation revealed moderate correlation for the Feversmart (r = 0.75), iThermonitor (r = 0.79), and Thermochron iButton (r = 0.71) systems. The Quest Temp Sitter system malfunctioned repeatedly, and the correlation (r = 0.29) for this method should therefore be assessed with caution. All dermal thermometers rendered lower average temperatures than Terumo c405 (Feversmart -0.70 ± 0.65 °C; iThermonitor -0.77 ± 0.53 °C, Quest Temp Sitter -1.18 ± 0.66 °C, and Thermochron iButton -0.87 ± 0.65 °C). Sensitivity of the dermal thermometers for detecting core temperatures ≥38.0 °C was low, ranging from 0.33 to 0.6, but improved to 0.60 to 0.80 after adjusting temperatures by the methods' average deviation from rectal temperature. The results from the dermal thermometers tested here showed an insufficient correlation to core temperature to be used for core temperature monitoring in clinical research and practice. Unfortunately, other options for non-invasive temperature measurements are few. The two thermometers with the least unsatisfactory performance profile in our evaluations were the Feversmart and iThermonitor systems., Funding Agency:Region Örebro Län

Background: It has not yet been established whether men in heterosexual relationships adapt their hormone levels to their female partner's menstrual cycle to allocate reproductive resources to the period when the female is actually fertile. Aim: This prospective observational study tested the hypothesis that some males have peaks in testosterone or acne (a possible biomarker for androgen activity) near their partners' ovulation, whereas other males display the opposite pattern. Methods: 48 couples supplied menstrual cycle data, male salivary samples, and a protocol of daily activities for 120 days. Daily saliva samples were analyzed for testosterone concentrations by enzyme-linked immunosorbent assay. The main hypothesis was tested by analyzing whether each individual male's testosterone/acne response to ovulation (either an increase or a decrease in comparison to the individual's average levels) was stable over time. To do this, we analyzed the Spearman correlation between individually normalized periovulatory testosterone and acne during the first half of the study versus the second half of the study. Outcomes: Correlation between each male individual's periovulatory testosterone and acne patterns during the first half of the study versus the second half of the study. Results: No predictability in the male individuals' testosterone (Spearman's rho = -0.018, P = .905) or acne (Spearman's rho = -0.036, P = .862) levels during ovulation was found. Clinical translation: The study being "negative," there is no obvious translational potential in the results. Strengths and limitations: The main strength of this study lies in the excellent compliance of the study participants and the large number of sampling timepoints over several menstrual cycles, thereby allowing each male individual to be his own control subject. A limitation is that samples were only obtained in the morning; however, including later timepoints would have introduced a number of confounders and would a, Funding Agencies:Linköping University Region Östergötland Örebro University Region Örebro län Forskningskommitten

The pathogenesis of acne vulgaris has only been partially elucidated. Various hormones, especially androgens, are likely to play a role, but results of studies are still inconclusive. The objective of the current study was to investigate whether day to day variation in salivary testosterone correlates with acne in males. Saliva samples were collected for 120 consecutive days from each of the 40 males. Salivary testosterone concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Facial acne lesions were assessed on a daily basis by photography by the participating males. Potential confounders’ (sexual intercourse, masturbation, physical exercise and disease) were also registered every day by the participants. A significant but weak association between salivary testosterone and acne was found (n = 4602, r = 0.031, P = 0.034). Elevated testosterone concentrations were associated with an increase in acne, but when testosterone concentrations were above twice the individual average, acne lesions paradoxically decreased. The current results indicate that daily fluctuations in salivary testosterone levels in males are associated with acne patterns, but the weak correlation suggests that the effect is too small to be of clinical significance. The analysis in the current study was complicated by a large number of days on which the participants had no acne, as well as the seemingly non-monotonic relation between testosterone and acne. This may indicate that the actual relation is stronger than concluded here.

Background: Growing evidence indicates that elevated body temperature after stroke is associated with unfavorable outcome. The aim of the current study was to investigate which factors predict temperature elevation within 48 h of stroke onset. Specifically, we hypothesized that temperature elevation would be associated with stroke symptom severity and that hemorrhagic stroke would cause a more pronounced temperature increase compared to ischemic stroke. Methods: The medical records of 400 stroke patients were retrospectively reviewed. Multiple linear regression analysis was used to determine which factors were associated with elevated body temperature. Results: Several factors were significantly associated with peak body temperature (the highest recorded body temperature) within 48 h of stroke onset: stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS) (regression coefficient; (RC) 0.022), female gender (RC 0.157), tympanic/non-rectal temperature reading (RC -0.265), swallowing difficulties (RC 0.335), intubation (RC 0.470), antipyretic treatment (RC 0.563), and C-reactive protein amp;gt; 50 or signs of infection at admission (RC 0.298). Contrary to our expectations, patients with intracerebral hemorrhage did not have higher peak body temperatures than patients with ischemic stroke. Conclusions: In conclusion, temperature elevation within the first 48 h of stroke onset is common, can be partially predicted using information at admission and is strongly associated with stroke severity. The strong association with stroke severity may, at least partly, explain the previously described association between post-stroke temperature elevation and unfavorable outcome., Funding Agencies|Orebro County Council (Region Orebro lan)

The concentrations of testosterone deposited in hair during hair growth may provide a retrospective reflection of the concentrations of bioactive testosterone in plasma. The objective of this study was to develop a radioimmunoassay with a sufficiently low limit of detection to measure the testosterone-like immunoreactivity in smaller hair samples (5 mg) than used in earlier studies, and to compare three different extraction procedures. The competitive radioimmunoassay consisted of a polyclonal antiserum (immunogen testosterone-7 alpha-BSA) and a radioligand synthesised from testosterone-3-CMO-histamine. The within-assay and total coefficients of variation in the working range was 3% and 4.5%, respectively. The limit of detection was 0.87 pg/mL, which is equivalent to 0.12 pg/mg testosterone in 5 mg of hair. The concentration of testosterone-like immunoreactivity in hair samples was 1.23 (SD 0.47) pg/mg in women and 2.67 (SD 0.58) pg/mg in men (pulverised hair). Significantly improved precision was found when pulverised hair was used compared to non-pulverised hair. Our data indicate that pulverisation of the hair prior to hormone extraction is crucial. Detection limits fit for the intended purpose are achievable with 5 mg samples of hair., Funding Agencies|County Council of Ostergotland

INTRODUCTION: Measuring testosterone concentrations is of interest both in clinical situations and for research, the latter expanding rapidly during recent years. An increased demand for convenient methods has prompted a number of companies to develop enzyme-linked immunosorbent assay (ELISA) kits to measure testosterone concentrations in saliva. However, the inter-comparability of kits from different manufacturers have yet to be determined. AIM OF STUDY: The aim of this study was to compare commercially available ELISA kits from four different manufacturers (Salimetrics, IBL, DRG and Demeditec). METHODS: Saliva was collected from 50 participants (25 men and 25 women). Each sample was analysed by the four ELISA kits. RESULTS: The correlations between the ELISA kits from Demeditec, DRG and Salimetrics were moderate to high with r-values > .77; however, proportional errors between the methods calls for caution. The ELISA kit from IBL malfunctioned and no results from this kit was obtained. CONCLUSIONS: Results from studies using the ELISA kits from Demeditec, DRG and Salimetrics are generally comparable; however, translation using the formulae presented in the current study could increase the accuracy of these comparisons., Funding Agencies:Linköping University Östergötland County Örebro University Region Örebro län Forskningskommitten

Background: In the absence of active management, the stroke risk after a transient ischemic attack (TIA) may be high. Almost 10 years ago, the results of the EXPRESS and SOS-TIA studies called for a more rapid management of TIA patients. The purpose of this study was to investigate the other stroke risks in the longer term, after the implementation of a more active approach to TIA. We also wanted to assess the predictive value of the ABCD2 score in this context. Methods: Riksstroke is the national stroke registry in Sweden. Data from Riksstroke's TIA module, and the national cause-of-death register, for the years 2011 and 2012 were used in this study. Stroke occurrence was monitored via Riksstroke. Cox's regression was used for risk evaluation. The predictive value of the ABCD2 score was assessed by calculating the area under the receiver operating characteristics curve. Results: A total of 15,068 TIA episodes occurred in 14,102 patients. The follow-up time varied between 0 and 819 days, with an average of 417 days. The mortality for all TIA patients during the follow-up time was 7.1%. Of the unique patients, 545 had one or more strokes (3.9%), corresponding to 34 events per 1,000 person years. Significant risk factors for stroke were: age, previous TIA, atrial fibrillation (AF), oral anticoagulant (OAC) treatment, hypertension treatment, and the ABCD2 items speech impairment, unilateral weakness, and diabetes mellitus. The ABCD2 score correlated with a subsequent stroke, but its predictive value was low. Conclusion: The risk of stroke is low after the acute phase of a TIA, probably lower than in previous studies. This may be due to better secondary prevention in recent years. Several risk factors predict stroke, notably hypertensive treatment, which may be inadequate; and AF, where OACs may be under-used. It is difficult to identify the role of the ABCD2 score in clinical practice.

The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17β-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n=40 per group) were randomized into three groups, subcutaneously administered different doses of 17β-estradiol and subjected to transient middle cerebral artery occlusion. The modifi ed sticky tape test was performed after 24 h and the rats were subsequently sacrifi ced for infarct size measurements. In contrast to our hypothesis, a signifi cant negative correlation between 17β-estradiol dose and infarct size was found (p=0.018). Thus, no support was found for the hypothesis that 17β-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the fi ndings indicate that the higher the dose of 17β-estradiol, the smaller the infarct.

Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specific pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters' impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models., Funding Agency:County Council of Östergötland, Sweden

Background and Purpose: Stroke incidence may be on the decline in high-income countries. There may have been a shift from severe forms of cerebrovascular disease to less severe forms. No study regarding transient ischemic attack (TIA) incidence has been performed in Sweden since the 1980s. Methods: We used 2011 and 2012 data from the Swedish stroke register. A large proportion of Sweden's 72 hospitals took part in the TIA register, meaning that 63 (2011) and 66 (2012) percent of the entire population were studied. Results: The number of TIA-cases was 13,880. The number of first ever TIA cases was 9098, 4,675 in men, and 4,423 in women, comprising 66% of all TIAs. The crude overall IR for first ever TIA was 74 per 100,000. The age- and sex-standardized IRs were 73 per 100,000 when standardized to the European population of 2013, and 47 per 100,000 when standardized to the European population 1976. Conclusions: The TIA incidence in Sweden is high, and no decline is seen when compared with previous studies. Better prevention may have caused a shift from severe forms of cerebrovascular disease to less severe forms. Fordemographic reasons, the health services will most likely face an increasing number of TIA patients in the coming years.

This corrects the article Development of Salivary Cortisol Circadian Rhythm and Reference Intervals in Full-Term Infants DO1:10.1371/journal.pone.0129502

Background: The elevated body swing test (EBST) is a behavioral test used to evaluate experimental stroke in rodents. The basic idea is that when the animal is suspended vertically by the tail, it will swing its head laterally to the left or right depending on lesion side. In a previous study from our lab using the EBST after middle cerebral artery occlusion (MCAo), rats swung contralateral to the infarct day 1 post-MCAo, but ipsilateral day 3 post-MCAo. This shift was unexpected and prompted us to perform the present study. First, the literature was systematically reviewed to elucidate whether a similar shift had been noticed before, and if consensus existed regarding swing direction. Secondly, an experiment was conducted to systematically investigate the suggested behavior. Eighty-three adult male and female Sprague-Dawley rats were subjected to MCAo or sham surgery and the EBST was performed up to 7 days after the lesion. Results: Both experimentally and through systematic literature review, the present study shows that the direction of biased swing activity in the EBST for rodents after cerebral ischemia can differ and even shift over time in some situations. The EBST curve for females was significantly different from that of males after the same occlusion time (p = 0.023). Conclusions: This study highlights the importance of adequate reporting of behavioral tests for lateralization and it is concluded that the EBST cannot be recommended as a test for motor asymmetry after MCAo in rats., Funding Agency:Region Östergötland/Linköping University, Sweden

Background: In 2010, the Swedish Stroke Register (Riksstroke; RS) established a module for transient ischemic attacks (RS-TIA). We report a diagnostic validation study of patients included in RS-TIA. Methods: During the first year, 7,825 patients were registered at 59 out of 74 Swedish hospitals. A time-based TIA definition was applied. A sample of 180 patients (30 patients each from 6 hospitals), with a similar distribution of age and sex as in RS-TIA, was prepared. Two independent observers assessed medical records for quality of documentation and assigned a diagnosis of likely, possible, unlikely TIA or ischennic stroke, according to pre-specified criteria. Results:The 2 observers agreed in 77% of cases that the event was a likely or possible TIA, in 3% that the event was an ischemic stroke, and in 2% that the event was an unlikely TIA. The observers disagreed in 8% of patients on TIA vs. ischennic stroke, and in 11% on a vascular vs. non-vascular cause. Quality of documentation was fair. Conclusions: There was interobserver agreement on diagnosis of TIA in the majority of patients included in RS-TIA. Diagnostic accuracy may be further improved by more systematic documentation of symptoms and signs., Funding Agency:Swedish Stroke-Riksförbundet

Background: Cortisol concentrations in plasma display a circadian rhythm in adults and children older than one year. Earlier studies report divergent results regarding when cortisol circadian rhythm is established. The present study aims to investigate at what age infants develop a circadian rhythm, as well as the possible influences of behavioral regularity and daily life trauma on when the rhythm is established. Furthermore, we determine age-related reference intervals for cortisol concentrations in saliva during the first year of life. Methods: 130 healthy full-term infants were included in a prospective, longitudinal study with saliva sampling on two consecutive days, in the morning (07:30-09:30), noon (10:00-12:00) and evening (19:30-21:30), each month from birth until the infant was twelve months old. Information about development of behavioral regularity and potential exposure to trauma was obtained from the parents through the Baby Behavior Questionnaire and the Life Incidence of Traumatic Events checklist. Results: A significant group-level circadian rhythm of salivary cortisol secretion was established at one month, and remained throughout the first year of life, although there was considerable individual variability. No correlation was found between development of cortisol circadian rhythm and the results from either the Baby Behavior Questionnaire or the Life Incidence of Traumatic Events checklist. The study presents salivary cortisol reference intervals for infants during the first twelve months of life. Conclusions: Cortisol circadian rhythm in infants is already established by one month of age, earlier than previous studies have shown. The current study also provides first year age-related reference intervals for salivary cortisol levels in healthy, full-term infants., The erratum to this article is published in PLoS ONE, 2016, 11:3.