Establishing an Integrative Oncology Service: Essential Aspects of Program Development.

PURPOSE OF REVIEW: Over the last 2 decades, integrative oncology (IO) has seen exponential growth within cancer care. It aims to combine evidence-based complementary therapies with conventional treatments to improve the well-being and quality of life for individuals dealing with cancer. The proliferation of integrative medicine programs in major cancer centers globally reflects varying approaches shaped by cultural, demographic, and resource-based factors. RECENT FINDINGS: Drawing upon the expertise of leaders in IO from the Society for Integrative Oncology (SIO) Clinical Practice Committee, this manuscript serves as a practical guide for establishing an IO practice. Collating insights from diverse professionals, including oncologists, integrative oncologists, supportive care physicians, researchers, and clinicians, the paper aims to provide a comprehensive roadmap for initiating and advancing IO services. The primary objective is to bridge the gap between conventional cancer care and complementary therapies, fostering a patient-centric approach to address the multifaceted challenges encountered by individuals with cancer. This paper delineates several key sections elucidating different aspects of IO practice. It delves into the core components necessary for an IO service's foundation, outlines the initial medical consultation process, and presents crucial tools essential for successful consultations. By consolidating insights and expertise, this manuscript seeks to facilitate the integration of IO into mainstream cancer care, ultimately enhancing patient outcomes and experiences.

Infradian Rhythms in Cerebrovascular Oxygenation and Blood Volume in Humans at Rest: A 5-Year Study.

BACKGROUND: All parameters of human physiology show chronobiological variability. While circadian (cycle length ~ 24 h) rhythms of the neuronal, hemodynamic and metabolic aspects of human brain activity are increasingly being explored, infradian (cycle length > 24 h) rhythms are largely unexplored. AIM: We investigated if cerebrovascular oxygen saturation (StO2) and blood volume ([tHb]) values measured over many years in many subjects during resting show infradian rhythmicity. SUBJECTS AND METHODS:  Absolute StO2 and [tHb] values (median over a 5 min resting-phase while sitting) were measured in 220 healthy subjects (age: 24.7 ± 3.6 years, 87 males, 133 females) 2-4 times on different days over the right and left frontal lobe (FL) and occipital lobe (OL) by employing frequency-domain NIRS as part of different systemic physiology augmented functional near-infrared spectroscopy, SPA-fNIRS, studies. The data set consisted of 708 single measurements performed over a timespan of 5 years (2017-2021). General additive models (GAM) and cosinor modelling were used to analyze the data. RESULTS:  The GAM analysis revealed (i) a non-linear trend in the StO2 and [tHb] values over the 5-year span, (ii) a circannual (cycle length ~ 12 months) rhythm in StO2 at the FL (amplitude (A): 3.4%, acrophase (φ): June) and OL (A: 1.5%, φ: May) as well as in [tHb] at the OL (A: 1.2 µM, bathyphase (θ): June), and (iii) a circasemiannual (cycle length ~ 6 months) rhythm in [tHb] at the FL (A: 2.7 µM, φ: March and September, respectively). Furthermore, the circannual oscillations of StO2 (at the FL) and [tHb] (at the OL) were statistically significantly correlated with the day length, outdoor temperature, humidity and air pressure. DISCUSSION AND CONCLUSION:  We conclude that absolute values of StO2 and [tHb] show chronobiological variability on the group-level with a long-term nonlinear trend as well as circannual/circasemiannual rhythmicity. These rhythms need to be taken into account when defining reference values for StO2 and [tHb] and may correlate with the variability of cerebrovascular disease incidents over the year.

Accuracy of Tissue Oxygen Saturation Measurements of a Textile-Based NIRS Sensor.

Pressure injuries (PI) are dangerous tissue lesions that heal very slowly and pose a high risk of serious infections. They are caused by pressure applied to the tissue, which stops blood circulation and therefore induces hypoxia, i.e., low tissue oxygen saturation (StO2). PI cause severe suffering and are expensive to treat. Hence it is essential to prevent them with a device that detects a dangerous situation, e.g., by measuring StO2 using near-infrared spectroscopy (NIRS). For such a device to be wearable without causing PI, it must not introduce pressure points itself. This can be achieved by integrating optical fibers into a textile to transport light to and from the tissue.The aim of this paper is to investigate the accuracy of StO2 measurements using a NIRS device based only on textile-integrated optical fibers.Bundles of fibers were stitched into a textile in such a way that loops of <1 mm diameters were formed at the stitching locations. Detection points (DPs) on the fabric consisted of 8 fibers with 3 loops each. Emission points (EPs) were made from 4 fibers with 3 loops each. All fiber ends of a DP were connected to an avalanche photodiode. One end of each fiber belonging to an EP was connected to an LED (740 nm, 810 nm, or 880 nm; 290, 560, or 610 mW).To verify the accuracy of this textile-based sensor, we placed it on a subject's forearm and compared the derived StO2 during arterial occlusion to the values of a gold-standard NIRS device (ISS Imagent), which was placed on the forearm too.We found that our textile-based sensor repeatedly measured StO2 values over a range of 40% with a deviation of <10% from the reference device.By showing the ability to measure StO2 using textile-integrated optical fibers accurately, we have reached a significant milestone on our way to building a wearable device to monitor tissue health and prevent PI.

Differences Between Good, Moderate and Poor Performers of a Verbal Fluency Task under Blue Light Exposure: An SPA-fNIRS Study.

Individuals have different performance levels for cognitive tasks. Are these performance levels reflected in physiological parameters? The aim of this study was to address this question by systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS). We aimed to investigate whether different verbal fluency task (VFT) performances under blue light exposure were associated with different changes in cerebrovascular oxygenation and systemic physiological activity. The VFT performance of 32 healthy subjects (17 female, 15 male, age: 25.5 ± 4.3 years) was investigated under blue light exposure (120 lux). The VFT, which contained letter and category fluency tasks, lasted 9 min. There were rest periods without light exposure before and after the VFT for 8 min and 15 min, respectively. Based on their number of correct responses, subjects were classified into three groups, i.e., good, moderate, and poor performers. During the entire experiment, we simultaneously measured changes in cerebral and systemic physiological parameters using the SPA-fNIRS approach. We found that the better the subject's performance was, the smaller the task-evoked changes in cerebrovascular hemodynamics and oxygenation in the prefrontal cortex. Performance-dependent changes were also evident for skin conductance, arterial oxygen saturation and mean arterial pressure. This is the first VFT study that applies the comprehensive SPA-fNIRS approach to determine the relationship between task performance and changes in cerebral oxygenation and systemic physiology. Our study shows that these parameters are indeed related and the performance is reflected in the task-evoked cerebrovascular and systemic physiological changes.

A Prospective Observational Pilot Study on the Effects of the Activity-Based Stress Release Program on the Mental State and Autonomic Nervous System in Psychiatric Patients.

BACKGROUND: In our pilot study, we investigated the psychological (well-being and personal coping strategies) and physiological (assessed by heart rate variability (HRV)) effects of the newly developed activity-based stress release (ABSR) program for people with depressive disorders, also in combination with burnout symptoms and/or anxiety disorders. METHODS: A single-arm prospective observational study was carried out. Twenty participants diagnosed with depression and burnout or anxiety disorders were invited to participate in the 8-week ABSR program. All participants filled in two questionnaires (the multidimensional mental state questionnaire and the Ehrenfeld inventory on coping style) before, directly after and 2 months after the 8-week ABSR program. In addition, all participants were offered a 24-hour Holter ECG measurement before, directly after and 2 months after the 8-week ABSR program to measure HRV. RESULTS: Calmness and serenity showed a statistically significant improvement after the 8-week ABSR program. However, complete questionnaire sets were not available from all of the participants. In the four individuals who had agreed to a 24-hour Holter ECG, the overall HRV and parasympathetic activity increased. CONCLUSIONS: The ABSR program is an encouraging novel therapeutic approach: A significant improvement in calmness and serenity was observed after ABSR. A larger and controlled trial of this treatment option in depression and burnout is recommended. It should be further investigated how ABSR affects task-evoked and resting brain activity, and what effects it has on the cardiovascular system in general (better blood flow and normalization of activity are to be expected).

Individual Pharmacotherapy Management (IPM) - I: a group-matched retrospective controlled clinical study on prevention of complicating delirium in the elderly trauma patients and identification of associated factors.

BACKGROUND: Delirium is one of the most frequent complications in hospitalized elderly patients with additional costs such as prolongation of hospital stays and institutionalization, with risk of reduced functional recovery, long-term cognitive impairment, and increased morbidity and mortality. We analyzed the effect of individual pharmacotherapy management (IPM) in the University Hospital Halle in geriatric trauma patients on complicating delirium and aimed to identify associated factors. METHODS: In a retrospective controlled clinical study of 404 hospitalized trauma patients ≥70 years we compared the IPM intervention group (IG) with a control group (CG) before IPM implementation. Delirium was recorded from the hospital discharge letter. The medication review and data records included baseline data, all medications, diagnoses, electrocardiogram (ECG), laboratory and vital parameters during hospitalization. The IPM internist and the senior trauma physician guaranteed personnel and structural continuity in the implementation of the interdisciplinary patient rounds. RESULTS: There was a highly matched congruence between CG and IG in terms of age, gender, residency, BMI, most diagnoses, and injury patterns to compare the two groups. The total number of medications per patient was 11.1 ± 4.9 (CG) versus 10.4 ± 3.6 (IG). Our targeted IPM focus on 6 frontline aspects with reduction of antipsychotics, anticholinergic burden, benzodiazepines, serotonergic opioids, elimination of pharmacokinetic and pharmacodynamic drug interactions and overdosage reduced complicating delirium from 5% to almost zero at 0.5%. The association of IPM with a significant 10-fold reduction, OR = 0.09 [95% CI 0.01-0.7], in univariable regression, maintained of clinical relevance in multivariable regression OR = 0.1 [95% CI 0.01-1.1]. Factors most strongly associated with complicating delirium in univariable regression were cognitive dysfunction, nursing home residency, muscle relaxants, antiparkinsonian agents, xanthines, transient disorientation documented in the fall risk scale, antibiotic-requiring infections, antifungals, antipsychotics, and intensive care stay, the two latter maintaining significance in multivariable regression. CONCLUSIONS: IPM is associated with a highly effective prevention of complicating delirium in the elderly trauma patients. For patient safety it should be integrated as an essential preventative contribution. The associated factors help identify patients at risk.

Changes in Cerebral Oxygenation and Systemic Physiology During a Verbal Fluency Task: Differences Between Men and Women.

BACKGROUND: Sex differences in behavioural performance of a cognitive task have been repeatedly reported in the literature. Whether such differences are also relevant for evoked cerebral haemodynamic and oxygenation responses as well as systemic physiological changes is a topic of ongoing investigations. AIM: We investigated whether changes in cerebral oxygenation and systemic physiological activity are sex-dependent during a verbal fluency task (VFT). SUBJECTS AND METHODS: VFT performance and changes in cerebral oxygenation and systemic physiology were investigated in 32 healthy right-handed adults (17 females, 15 males, age: 25.5 ± 4.3 years). The total duration of the VFT was 9 min. During this phase, subjects were also exposed to blue light (peak wavelength: 450 nm, illuminance: 120 lux). Before and after the VFT, subjects were in darkness. In this study, we used the systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) approach. Absolute concentration changes of oxyhaemoglobin ([O2Hb]), deoxyhaemoglobin ([HHb]), total haemoglobin ([tHb]), as well as tissue oxygen saturation (StO2) were measured bilaterally over the prefrontal cortex (PFC) and visual cortex (VC). Systemic physiological parameters were also recorded in parallel (e.g., end-tidal CO2, heart rate, respiration rate, skin conductance). RESULTS: We found that: (i) Females were better VFT performers in comparison to males. (ii) Changes in [O2Hb] and [HHb] in the VC were higher for males compared to females during the VFT under blue light exposure. (iii) Lower and higher StO2 changes were detected for males compared to females in the PFC and VC, respectively. (iv) Sex-dependent changes were also evident for end-tidal CO2, heart rate, respiration rate, and pulse-respiration quotient. CONCLUSIONS: Our study showed that sex differences are not only observed in task performance but also in the magnitudes of changes in cerebral and physiological parameters. The findings of the current study emphasise that sex differences in brain activation and systemic physiological activity need to be considered when interpreting functional neuroimaging data. These findings offer a broad range of implications for educational purposes and facilitate a better understanding of the effects of sex on behavioural performance as well as human physiology.

Frontal Cerebral Oxygenation in Humans at Rest: A Mirror Symmetry in the Correlation with Cardiorespiratory Activity.

BACKGROUND: Although several studies published reference values for frontal cerebral tissue oxygen saturation (StO2) measured with near-infrared spectroscopy (NIRS) based cerebral oximetry, a detailed investigation, whether and which factors from systemic physiology are related to the individual StO2 values, is missing. AIM: We investigated how the state of the cardiorespiratory system is linked to StO2 values at rest. SUBJECTS AND METHODS: Absolute StO2 values (median over a 5 min resting-phase while sitting) were obtained from 126 healthy subjects (age: 24.0 ± 0.2 years, 45 males, 81 females) over the left and right prefrontal cortex (PFC) by employing frequency-domain NIRS as part of a systemic physiology augmented functional near-infrared spectroscopy (SPA-fNIRS) study. In addition, heart rate (HR) and respiration rate (RR) were measured, and the pulse respiration quotient (PRQ) was determined (PRQ = HR/RR). General additive models (GAM) were used to analyse the data. RESULTS: The GAM analysis revealed a specific relationship between the overall PFC StO2 values (mean over right and left PFC) and the variables HR and RR: HR was positively correlated with mean StO2, while RR showed no correlation. In the mirror case, RR was negatively linearly correlated with the frontal cerebral oxygenation asymmetry (FCOA), which was not correlated with HR. The right PFC StO2 was not linked to the RR, whereas the left PFC StO2 was. Positive correlations of the PRQ with the mean PFC StO2 as well as the FCOA were also found. GAM modelling revealed that the individual FCOA values are explained to a large extent (deviance explained: 88.8%) by the individual mean PFC StO2 and PRQ. We conclude that (i) the state of the cardiorespiratory system is significantly correlated with StO2 values and (ii) there is a mirror symmetry with regard to the impact of cardiorespiratory parameters on the mean PFC StO2 and FCOA.

In Vitro Validation of a New Tissue Oximeter Using Visible Light.

There is a clinical need to measure local tissue oxygen saturation (StO2), oxy-, deoxy- and total haemoglobin concentration ([O2Hb], [HHb], [tHb]) in human tissue. The aim was to validate an oximeter called OxyVLS applying visible light spectroscopy (VLS) to determine these parameters without needing to assume a reduced scattering coefficient (µ's). This problem is solved by appropriate calibrations. Compared to near-infrared spectroscopy (NIRS), OxyVLS determines the oxygenation in a much smaller more superficial volume of tissue, which is useful in many clinical cases. OxyVLS was validated in liquid phantoms with known StO2, [tHb], and µ's and compared to frequency domain NIRS as a reliable reference. OxyVLS showed a high accuracy for all the mentioned parameters and was even able to measure µ's. Thus, OxyVLS was successfully tested in vitro.

Long-Term Blue Light Exposure Changes Frontal and Occipital Cerebral Hemodynamics: Not All Subjects React the Same.

BACKGROUND: In modern society, we are increasingly exposed to numerous sources of blue light, including screens (e.g., TVs, computers, laptops, smartphones, tablets) and light from fluorescent and LED lamps. Due to this wide range of applications, the effects of blue light exposure (BLE) on the human physiology need to be thoroughly studied. AIM: To investigate the impact of long-term BLE on frontal and occipital human cerebral hemodynamics and oxygenation using functional near-infrared spectroscopy (fNIRS) neuroimaging. MATERIALS AND METHODS: 32 healthy right-handed subjects (20 females, 12 males; age: 23.8 ± 2.2 years) were exposed to blue LED light for 15 minutes. Before (baseline, 8 min) and after (recovery, 10 min) the BLE, subjects were in darkness. We measured the concentration changes of oxyhemoglobin ([O2Hb]) and deoxyhemoglobin ([HHb]) at the prefrontal cortex (PFC) and visual cortex (VC) by fNIRS during the experiment. Subjects were then classified into different groups based on their hemodynamic response pattern of [O2Hb] at the PFC and VC during BLE. RESULTS: On the group level (32 subjects), we found an increase in [O2Hb] and a decrease in [HHb] at both cortices during BLE. Evoked changes of [O2Hb] were higher at the VC compared to the PFC. Eight different hemodynamic response patterns were detected in the subgroup analysis, while an increase of [O2Hb] in both cortices was the most common pattern (8 out of 32 cases, 25%) during BLE. DISCUSSION AND CONCLUSION: Our study showed that the hemodynamic and oxygenation changes at the PFC and VC during BLE (i) were generally higher in the VC compared to the PFC, (ii) showed an intersubject variability with respect to their magnitudes and shapes, and (iii) can be classified into eight groups. We conclude that blue light affects humans differently. It is essential to consider this when assessing the impact of the BLE on society.

Right-Left Asymmetry of Prefrontal Cerebral Oxygenation: Does it Depend on Systemic Physiological Activity, Absolute Tissue Oxygenation or Hemoglobin Concentration?

BACKGROUND: We have repeatedly observed a right-left asymmetry (RLA) of prefrontal cerebral oxygenation of subjects during the resting state. AIM: To clarify if the RLA is a reliably observable phenomenon at the group level and whether it is associated with systemic physiology, absolute tissue oxygen saturation (StO2) or total hemoglobin concentration ([tHb]). MATERIAL AND METHODS: StO2 and [tHb] values at the right and left prefrontal cortex (PFC) were calculated for two 5- min resting phases based on data from 76 single measurements (24 healthy adults, aged 22.0 ± 6.4 years). StO2 and [tHb] were measured with an ISS OxiplexTS frequency domain near-infrared spectroscopy device. In addition, end-tidal CO2 (PETCO2), heart rate (HR), respiration rate (RR) and the pulse-respiration quotient (PRQ = HR/RR) were measured and analyzed for the two phases. RESULTS: On the group level it was found that i) StO2 was higher at the right compared to the left PFC (for both phases), ii) RLA of StO2 (∆StO2 = StO2 (right)-StO2 (left) was independent of PETCO2, HR and PRQ, and iii) ∆StO2 was associated with absolute StO2 and [tHb] values (positively and negatively, respectively). DISCUSSION AND CONCLUSION: This study shows that i) RLA of StO2 at the PFC is a real phenomenon, and that ii) ∆StO2 at the group level does not depend on PETCO2, HR, RR or PRQ, but on absolute StO2 and [tHb]. We conclude that the RLA is a real effect, independent of systemic physiology, and most likely reflects genuine properties of the brain, i.e. different activity states of the two hemispheres.

Effect of person-centred care on antipsychotic drug use in nursing homes (EPCentCare): a cluster-randomised controlled trial.

BACKGROUND: antipsychotic drugs are regularly prescribed as first-line treatment for neuropsychiatric symptoms in persons with dementia although guidelines clearly prioritise non-pharmacological interventions. OBJECTIVE: we investigated a person-centred care approach, which has been successfully evaluated in nursing homes in the UK, and adapted it to German conditions. DESIGN: a 2-armed 12-month cluster-randomised controlled trial. SETTING: nursing homes in East, North and West Germany. METHODS: all prescribing physicians from both study arms received medication reviews for individual patients and were offered access to 2 h of continuing medical education. Nursing homes in the intervention group received educational interventions on person-centred care and a continuous supervision programme. Primary outcome: proportion of residents receiving at least one antipsychotic prescription after 12 months of follow-up. Secondary outcomes: quality of life, agitated behaviour, falls and fall-related medical attention, a health economics evaluation and a process evaluation. RESULTS: the study was conducted in 37 nursing homes with n = 1,153 residents (intervention group: n = 493; control group: n = 660). The proportion of residents with at least one antipsychotic medication changed after 12 months from 44.6% to 44.8% in the intervention group and from 39.8 to 33.3% in the control group. After 12 months, the difference in the prevalence was 11.4% between the intervention and control groups (95% confidence interval: 0.9-21.9; P = 0.033); odds ratio: 1.621 (95% confidence interval: 1.038-2.532). CONCLUSIONS: the implementation of a proven person-centred care approach adapted to national conditions did not reduce antipsychotic prescriptions in German nursing homes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02295462.

Impact of Changes in Systemic Physiology on fNIRS/NIRS Signals: Analysis Based on Oblique Subspace Projections Decomposition.

Measurements of cerebral and muscle oxygenation (StO2) and perfusion ([tHb]) with functional near-infrared spectroscopy (fNIRS) and near infrared spectroscopy (NIRS), respectively, can be influenced by changes in systemic physiology. The aim of our study was to apply the oblique subspace projections signal decomposition (OSPSD) to find the contribution from systemic physiology, i.e. heart rate (HR), electrocardiography (ECG)-derived respiration (EDR) and partial pressure of carbon dioxide (pCO2) to StO2 and [tHb] signals measured on the prefrontal cortex (PFC) and calf muscle. OSPSD was applied to two datasets (n1 = 42, n2 = 79 measurements) from two fNIRS/NIRS speech studies. We found that (i) all StO2 and [tHb] signals contained components related to changes in systemic physiology, (ii) the contribution from systemic physiology varied strongly between subjects, and (iii) changes in systemic physiology generally influenced fNIRS signals on the left and right PFC to a similar degree.

Absolute Values of Optical Properties (µa, µÎ„s, µeff and DPF) of Human Head Tissue: Dependence on Head Region and Individual.

BACKGROUND: Absolute optical properties (i.e., the absorption coefficient, µa, and the reduced scattering coefficient, [Formula: see text]) of head tissue can be measured with frequency-domain near-infrared spectroscopy (FD-NIRS). AIM: We investigated how the absolute optical properties depend on the individual subject and the head region. MATERIALS AND METHODS: The data set used for the analysis comprised 31 single FD-NIRS measurements of 14 healthy subjects (9 men, 5 women, aged 33.4 ± 10.5 years). From an 8-min measurement (resting-state; FD-NIRS device: Imagent, ISS Inc.; bilateral over the prefrontal cortex, PFC, and visual cortex, VC) median values were calculated for µa and [Formula: see text] as well as the effective attenuation coefficient (µeff) and the differential pathlength factor (DPF). The measurement was done for each subject one to three times with at least 24 h between the measurements. RESULTS: (i) A Bayesian ANOVA analysis revealed that head region and subject were the most significant main effects on µa, [Formula: see text] and µeff, as well as DPF, respectively. (ii) At the VC, µa, [Formula: see text] and µeff had higher values compared to the PFC. (iii) The differences in the optical properties between PFC and VC were age-dependent. (iv) All optical properties also were age-dependent. This was strongest for the properties of the PFC compared to the VC. DISCUSSION AND CONCLUSION: Our analysis demonstrates that all optical head tissue properties (µa, [Formula: see text], µeff and DPF) were dependent on the head region, individual subject and age. The optical properties of the head are like a 'fingerprint' for the individual subject. Assuming constant optical properties for the whole head should be carefully reconsidered.

Long-Term Changes in Optical Properties (µa, µ's, µeff and DPF) of Human Head Tissue During Functional Neuroimaging Experiments.

Frequency-domain near-infrared spectroscopy (FD-NIRS) enables to measure absolute optical properties (i.e. the absorption coefficient, µa, and the reduced scattering coefficient, [Formula: see text]) of the brain tissue. The aim of this study was to investigate how the optical properties changed during the course of a functional NIRS experiment. The analyzed dataset comprised of FD-NIRS measurements of 14 healthy subjects (9 males, 5 females, aged: 33.4 ± 10.5 years, range: 24-57 years old). Each measurement lasted 33 min, i.e. 8 min baseline in darkness, 10 min intermittent light stimulation, and 15 min recovery in darkness. Optical tissue properties were obtained bilaterally over the prefrontal cortex (PFC) and visual cortex (VC) with FD-NIRS (Imagent, ISS Inc., USA). Changes in µa and [Formula: see text] were directly measured and two parameters were calculated, i.e. the differential pathlength factor (DPF) and the effective attenuation coefficient (µeff). Differences in the behavior of the optical changes were observed when comparing group-averaged data versus single datasets: no clear overall trend was presented in the group data, whereas a clear long-term trend was visible in almost all of the single measurements. Interestingly, the changes in [Formula: see text] statistically significantly correlated with µa, positively in the PFC and negatively in the VC. Our analysis demonstrates that all optical brain tissue properties (µa, [Formula: see text], µeff and DPF) change during these functional neuroimaging experiments. The change in [Formula: see text] is not random but follows a trend, which depends on the single experiment and measurement location. The change in the scattering properties of the brain tissue during a functional experiment is not negligible. The assumption [Formula: see text] ≈ const during an experiment is valid for group-averaged data but not for data from single experiments.

Synchronized Oscillations of Arterial Oxygen Saturation, Cerebral Tissue Oxygenation and Heart Rate in Preterm Neonates: Investigation of Long-Term Measurements with Multiple Einstein's Cross Wavelet Analysis.

BACKGROUND: In preterm neonates, the cardiovascular and cerebral vascular control is immature, making the brain vulnerable to an increased incidence of hypoxic and hyperoxic episodes. AIM: The aim of the study was to apply the recently developed multiple Einstein's cross wavelet analysis (MECWA) to quantify the coupling of fluctuations of peripherally measured arterial oxygen saturation (SpO2), cerebral tissue oxygen saturation (StO2) and heart rate (HR). METHODS: Two long-term measurements on preterm neonates with a gestational age at birth of 26.4 and 26.8 weeks and a postnatal age of 2.1 and 3.9 weeks were analyzed. MECWA was applied to SpO2, StO2 and HR. RESULTS: MECWA showed that the fluctuations of SpO2, StO2 and HR were synchronized in the low-frequency range with periods of ~1 h and ~0.5 h. The amplitudes of the synchronization frequencies were dependent on the individual neonate. DISCUSSION: MECWA is a useful novel tool to assess the coupling of physiological signals. The parameters determined by MECWA seem to be related to the chronobiological processes, as well as constant regulations of the cardiovascular and cerebral perfusion state. CONCLUSION: MECWA was able to identify long-term synchronization of the cardiovascular and cerebral perfusion state in preterm neonates with periods of ~1 h and ~0.5 h.

Modelling confounding effects from extracerebral contamination and systemic factors on functional near-infrared spectroscopy.

Haemodynamics-based neuroimaging is widely used to study brain function. Regional blood flow changes characteristic of neurovascular coupling provide an important marker of neuronal activation. However, changes in systemic physiological parameters such as blood pressure and concentration of CO2 can also affect regional blood flow and may confound haemodynamics-based neuroimaging. Measurements with functional near-infrared spectroscopy (fNIRS) may additionally be confounded by blood flow and oxygenation changes in extracerebral tissue layers. Here we investigate these confounds using an extended version of an existing computational model of cerebral physiology, 'BrainSignals'. Our results show that confounding from systemic physiological factors is able to produce misleading haemodynamic responses in both positive and negative directions. By applying the model to data from previous fNIRS studies, we demonstrate that such potentially deceptive responses can indeed occur in at least some experimental scenarios. It is therefore important to record the major potential confounders in the course of fNIRS experiments. Our model may then allow the observed behaviour to be attributed among the potential causes and hence reduce identification errors.

The use of plant-based bioassays in homeopathic basic research.

OBJECTIVES: The objective was to evaluate homeopathic basic research studies that use plant-based bioassays. With this in view, a compilation was made of the findings of three systematic literature reviews covering plant-based bioassays in the three fields of healthy, abiotically, or biotically stressed plants. This compilation focused on investigations using advanced experimental methods and detailed descriptions, also with the aim of supporting the design of future experiments. METHODS: Publications included had to report on studies into the effects of homeopathic preparations on whole plants, seeds, plant parts and cells. Outcomes had to be measured by established procedures and statistically evaluated. A Manuscript Information Score (MIS) was applied using predefined criteria to identify publications with sufficient information for adequate interpretation (MIS ≥ 5). Additional evaluation focused on the use of adequate controls to investigate specific effects of homeopathic preparations, and on the use of systematic negative control (SNC) experiments to ensure the stability of the bioassay. Only a fraction of the studies reported here were performed with 'ultra high' dilutions, whereas other studies were performed with moderate or high dilutions. RESULTS: A total of 157 publications were identified, describing a total of 167 experimental studies. 84 studies included statistics and 48 had a MIS ≥ 5, thus allowing adequate interpretation. 29 studies had adequate controls to identify specific effects of homeopathic preparations, and reported significant effects of decimal and centesimal homeopathic potencies, including dilution levels beyond Avogadro's number. 10 studies reported use of SNC experiments, yielding evidence for the stability of the experimental set-up. CONCLUSION: Plant models appear to be a useful approach for investigating basic research questions relating to homeopathic preparations, but more independent replication trials are needed in order to verify the results found in single experiments. Adequate controls and SNC experiments should be implemented on a routine basis to exclude false-positive results.

A review on continuous wave functional near-infrared spectroscopy and imaging instrumentation and methodology.

This year marks the 20th anniversary of functional near-infrared spectroscopy and imaging (fNIRS/fNIRI). As the vast majority of commercial instruments developed until now are based on continuous wave technology, the aim of this publication is to review the current state of instrumentation and methodology of continuous wave fNIRI. For this purpose we provide an overview of the commercially available instruments and address instrumental aspects such as light sources, detectors and sensor arrangements. Methodological aspects, algorithms to calculate the concentrations of oxy- and deoxyhemoglobin and approaches for data analysis are also reviewed. From the single-location measurements of the early years, instrumentation has progressed to imaging initially in two dimensions (topography) and then three (tomography). The methods of analysis have also changed tremendously, from the simple modified Beer-Lambert law to sophisticated image reconstruction and data analysis methods used today. Due to these advances, fNIRI has become a modality that is widely used in neuroscience research and several manufacturers provide commercial instrumentation. It seems likely that fNIRI will become a clinical tool in the foreseeable future, which will enable diagnosis in single subjects.

The Alexander Technique and musicians: a systematic review of controlled trials.

BACKGROUND: Musculoskeletal disorders, stress and performance anxiety are common in musicians. Therefore, some use the Alexander Technique (AT), a psycho-physical method that helps to release unnecessary muscle tension and re-educates non-beneficial movement patterns through intentional inhibition of unwanted habitual behaviours. According to a recent review AT sessions may be effective for chronic back pain. This review aimed to evaluate the evidence for the effectiveness of AT sessions on musicians' performance, anxiety, respiratory function and posture. METHODS: The following electronic databases were searched up to February 2014 for relevant publications: PUBMED, Google Scholar, CINAHL, EMBASE, AMED, PsycINFO and RILM. The search criteria were "Alexander Technique" AND "music*". References were searched, and experts and societies of AT or musicians' medicine contacted for further publications. RESULTS: 237 citations were assessed. 12 studies were included for further analysis, 5 of which were randomised controlled trials (RCTs), 5 controlled but not randomised (CTs), and 2 mixed methods studies. Main outcome measures in RCTs and CTs were music performance, respiratory function, performance anxiety, body use and posture. Music performance was judged by external experts and found to be improved by AT in 1 of 3 RCTs; in 1 RCT comparing neurofeedback (NF) to AT, only NF caused improvements. Respiratory function was investigated in 2 RCTs, but not improved by AT training. Performance anxiety was mostly assessed by questionnaires and decreased by AT in 2 of 2 RCTs and in 2 of 2 CTs. CONCLUSIONS: A variety of outcome measures has been used to investigate the effectiveness of AT sessions in musicians. Evidence from RCTs and CTs suggests that AT sessions may improve performance anxiety in musicians. Effects on music performance, respiratory function and posture yet remain inconclusive. Future trials with well-established study designs are warranted to further and more reliably explore the potential of AT in the interest of musicians.