Atypical Profiles Research Articles

Added value of 18F-florbetaben amyloid PET in the diagnostic workup of most complex patients with dementia in France: A naturalistic study

IntroductionAlthough some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting. MethodsThis multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials.gov: NCT02681172). ResultsTwo hundred five patients were enrolled with evaluable florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases. DiscussionHigh-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of florbetaben PET into current standard practices for the most complex dementia cases.

Speech perception in autism spectrum disorder: An activation likelihood estimation meta-analysis

Autism spectrum disorder (ASD) is often characterized by atypical language profiles and auditory and speech processing. These can contribute to aberrant language and social communication skills in ASD. The study of the neural basis of speech perception in ASD can serve as a potential neurobiological marker of ASD early on, but mixed results across studies renders it difficult to find a reliable neural characterization of speech processing in ASD. To this aim, the present study examined the functional neural basis of speech perception in ASD versus typical development (TD) using an activation likelihood estimation (ALE) meta-analysis of 18 qualifying studies. The present study included separate analyses for TD and ASD, which allowed us to examine patterns of within-group brain activation as well as both common and distinct patterns of brain activation across the ASD and TD groups. Overall, ASD and TD showed mostly common brain activation of speech processing in bilateral superior temporal gyrus (STG) and left inferior frontal gyrus (IFG). However, the results revealed trends for some distinct activation in the TD group showing additional activation in higher-order brain areas including left superior frontal gyrus (SFG), left medial frontal gyrus (MFG), and right IFG. These results provide a more reliable neural characterization of speech processing in ASD relative to previous single neuroimaging studies and motivate future work to investigate how these brain signatures relate to behavioral measures of speech processing in ASD.

Atypical profile problem in serological diagnosis of EBV

Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis. Burkitt's lymphoma, nasopharyngeal carcinoma and post-transplant lymphoproliferative diseases are also associated with EBV. Diagnosis is frequently based on detection of specific antibodies. Using three parameters (anti VCA-IgM, anti VCA-IgG and anti EBNA-1 IgG), it is possible to define infection status and diagnose acute or past infection. However, sometimes the detection of atypical serological profiles makes it difficult to interpret these results. This study aims to evaluate the serological profiles of patient sera suspected of EBV infection and to determine atypical profiles. Sera of 2749 patients were analyzed between January 2014 and August 2016, in the Dokuz Eylul University Hospital Central Laboratory and evaluated retrospectively. Serum samples were tested for EBV VCA IgM and EBV VCA IgG antibodies with immunofluorescence test (Euroimmun, Germany), EBNA-1 IgG antibodies with enzyme immunoassay (Euroimmun, Germany). Medical files of the patients with two or more samples and have an atypical profile were reviewed. Patients were grouped as no EBV infection, acute infection, past infection and atypical serologic profile according to three routine laboratory assays (VCA IgG, VCA IgM and EBNA-1 IgG). Out of 2794 subjects 1334 (48.5%) were female and 1415 (51.5%) were male, with mean age 30 (< 1-89 years, median value: 27). The distribution of the results was; 72.5% past infection, 10.9% absence of EBV infection and 5.2% acute infection and 11.4% showed atypical serologic profile. Among the atypical profiles, isolated VCA-IgG positivity was the most frequent pattern detected in 7.9% which is followed by 2.7% of the cases with all three markers positive and 0.8% with isolated EBNA-1 IgG positivity. Off the patients, 72.5% were seropositive for EBV and this result is consistent with the seroprevalence studies previously conducted in Turkey. The rate of atypical profiles was 11.4% which is close to the result (15%) of another study performed in Izmir. Nearly one third of the patients with atypical serological profile had an immune disorder and it was possible to reach a conclusion only among half of the patients during serological follow-up. This study points out that clinical diagnosis and serologic follow-up is important for the interpretation of the atypical profiles.

Male brain type women and female brain type men: Gender atypical cognitive profiles and their correlates

Gender differences exist in abilities, interests, and occupations. According to the Empathizing-Systemizing theory, the reason for all gender differences lies in the relative weights of two cognitive processes: women empathize more, which is useful in understanding people, while men systemize more, which means interpreting phenomena as rule-based systems. The terms “male and female brain type” refer to a heightened preference for one process over the other. We aimed to find out whether the gender atypical groups of male brain type women and female brain type men are more similar to the opposite sex than to their own in terms of a range of social, cognitive and personality variables. Female and male brain type groups were identified and compared within both genders in an online study (N=2983). The results show there are female brain type men and male brain type women, who are characterized by qualities more often associated with the opposite sex, and who have not been reached by prior research. Thus, these findings demonstrate that cognitive type is a more powerful predictor of certain characteristics than is biological sex.

MALDIrppa: quality control and robust analysis for mass spectrometry data.

This R package helps to implement a robust approach to deal with mass spectrometry (MS) data. It is aimed at alleviating reproducibility issues and pernicious effects of deviating signals on both data pre-processing and downstream data analysis. Based on robust statistical methods, it facilitates the identification and filtering of low-quality mass spectra and atypical peak profiles as well as monitoring and data handling through pre-processing, which extends existing computational tools for high-throughput data. MALDIrppa is implemented as a package for the R environment for data analysis and it is freely available to download from the CRAN repository at https://CRAN.R-project.org/package=MALDIrppa. javier.palarea@bioss.ac.uk.

TH1 signatures are present in the lower airways of children with severe asthma, regardless of allergic status

The pathogenesis of severe asthma in childhood remains poorly understood. We sought to construct the immunologic landscape in the airways of children with severe asthma. Comprehensive analysis of multiple cell types and mediators was performed by using flow cytometry and a multiplex assay with bronchoalveolar lavage (BAL) specimens (n=68) from 52 highly characterized allergic and nonallergic children (0.5-17years) with severe treatment-refractory asthma. Multiple relationships were tested by using linear mixed-effects modeling. Memory CCR5+ TH1 cells were enriched in BAL fluid versus blood, and pathogenic respiratory viruses and bacteria were readily detected. IFN-γ+IL-17+ and IFN-γ-IL-17+ subsets constituted secondary TH types, and BAL fluid CD8+ T cells were almost exclusively IFN-γ+. The TH17-associated mediators IL-23 and macrophage inflammatory protein 3α/CCL20 were highly expressed. Despite low TH2 numbers, TH2 cytokines were detected, and TH2 skewing correlated with total IgE levels. Type 2 innate lymphoid cells and basophils were scarce in BAL fluid. Levels of IL-5, IL-33, and IL-28A/IFN-λ2 were increased in multisensitized children and correlated with IgE levels to dust mite, ryegrass, and fungi but not cat, ragweed, or food sources. Additionally, levels of IL-5, but no other cytokine, increased with age and correlated with eosinophil numbers in BAL fluid and blood. Both plasmacytoid and IgE+FcεRI+ myeloid dendritic cells were present in BAL fluid. The lower airways of children with severe asthma display a dominant TH1 signature and atypical cytokine profiles that link to allergic status. Our findings deviate from established paradigms and warrant further assessment of the pathogenicity of TH1 cells in patients with severe asthma.

Does ethnicity and foveal morphology play a role in the spatial distribution of macular pigment?

SummaryWhile macular pigment optical density typically follows an exponential decline with eccentricity from the fovea, atypical profiles have also been described, including reports of increased prevalence of ring‐like and central dip profiles among non‐white ethnicities. However, classification of macular pigment (MP) profile phenotypes varies and is often based on subjective visualisation. We present data showing that compared to visual assessment, objective MP profiling (taking into account measurement repeatability) is a more reliable method that should be considered in future observational and interventional studies. We will also describe ethnic variations in MP spatial distribution (among white, black and South Asian individuals) in relation to variations in foveal architecture, including data regarding individual retinal layers, foveal width and pit slope taken from SD‐OCT images. Our data suggests that although ethnicity explains around 10% of the variance in MP profile, gender plays no significant role. In addition, although white subjects demonstrate thicker retinal layers than non‐whites, the significant differences in the amount and distribution of MP between ethnicities is not explained by variations in foveal morphology.

Level 2 Screening With the PDD Behavior Inventory: Subgroup Profiles and Implications for Differential Diagnosis

The PDD Behavior Inventory (PDDBI) has recently been shown, in a large multisite study, to discriminate well between autism spectrum disorder (ASD) and other groups when its scores were examined using a machine learning tool, Classification and Regression Trees (CART). Discrimination was good for toddlers, preschoolers, and school-age children; generalized across clinical diagnostic sites; and agreed well with Autism Diagnostic Observation Schedule (ADOS) classifications. Results also revealed three subtypes of ASD: minimally verbal, verbal, and atypical that differed in developmental history, behavior profiles, and biomedical findings. Seven subtypes of Not-ASD children were identified, two of which were relatively common. Three of the remaining five relatively rare Not-ASD subgroups had highly atypical profiles marked either by extreme aggressiveness or by extreme ritualistic behaviors. PDDBI profiles of these rare subgroups were not previously characterized. In this study, profiles of all CART subgroups based on parent and teacher PDDBIs are described, along with their implications for diagnosis and assessment.

Subcortical Brain and Behavior Phenotypes Differentiate Infants With Autism Versus Language Delay

BackgroundYounger siblings of children with autism spectrum disorder (ASD) are themselves at increased risk for ASD and other developmental concerns. It is unclear if infants who display developmental concerns, but are unaffected by ASD, share similar or dissimilar behavioral and brain phenotypes to infants with ASD. Most individuals with ASD exhibit heterogeneous difficulties with language, and their receptive-expressive language profiles are often atypical. Yet, little is known about the neurobiology that contributes to these language difficulties. MethodsIn this study, we used behavioral assessments and structural magnetic resonance imaging to investigate early brain structures and associations with later language skills. High-risk infants who were later diagnosed with ASD (n = 86) were compared with high-risk infants who showed signs of early language delay (n = 41) as well as with high- and low-risk infants who did not have ASD or language delay (n = 255 and 143, respectively). ResultsResults indicated that diminished language skills were evident at 12 months in infants with ASD and infants with early language delay. At 24 months of age, only the infants with ASD displayed atypical receptive-expressive language profiles. Associations between 12-month subcortical volumes and 24-month language skills were moderated by group status, indicating disordinal brain-behavior associations among infants with ASD and infants with language delay. ConclusionsThese results suggest that there are different brain mechanisms influencing language development in infants with ASD and infants with language delay, and that the two groups likely experience unique sets of genetic and environmental risk factors.

Variation of genomic islands and flanking fragments in Vibrio parahaemolyticus isolates from environmental and clinical sources in Taiwan

Vibrio parahaemolyticus is a halophilic foodborne pathogenic bacterium that causes gastroenteritis; it has become an issue of global concern since the emergence and spread of pandemic O3:K6 strains. This study evaluated the role of Vibrio pathogenicity island (VPaI)-associated fragments in the genetic variation and grouping of this pathogen. Distribution of some VPaI fragments and flanking fragments (VPaI-1, VPaI-4, VPaI-5, VPaI-6 and VPaI-7) was determined in a total of 53 V. parahaemolyticus isolates from environmental and clinical sources in Taiwan, and supported by the sequences of seven fragments of VPaI-4 and its flanking fragment VP2145. As determined from the distribution of these VPaI-associated fragments, the clinical pandemic isolates were closely related in a single cluster; the clinical nonpandemic isolates were grouped into several clusters, while the environmental isolates were comparatively highly diversified. The profiles of virulence-associated genes of environmental pathogenic isolates varied, and were closer to those of clinical nonpandemic isolates than those of pandemic isolates. Isolates with atypical profiles of the VPaI-associated fragments and virulence-associated genes were identified. Sequences of VP2145 exhibited a close phylogenetic relationship among these local isolates, which were distinct from most V. parahaemolyticus strains from other geographic regions. This investigation demonstrated the application of VPaI-associated fragments in studying the genetic variation and clustering of V. parahaemolyticus isolates from different sources.

Large-Eddy and Direct Numerical Simulations of the Bachalo-Johnson Flow with Shock-Induced Separation

The Bachalo-Johnson experiment on an axisymmetric bump has been a primary validation case for turbulence models in shock-boundary-layer interactions since the 1980’s. In the present work, Wall-Modelled Large-Eddy Simulations (WMLES) of this flow were conducted using Improved Delayed Detached-Eddy Simulation (IDDES) as the sub-grid-scale (SGS) and wall model, with a synthetic turbulence generator, expecting close enough agreement with experiment. However, the WMLES results are disappointing, even in terms of the shock position, even though the results from two grids with 4.7 × 108 and 1.6 × 109 cells respectively agree well with each other. This failure of grid refinement to warn of an inaccurate simulation is of great concern, and the reasons for it are explored. We then conducted a Direct Numerical Simulation (DNS) embedded in the LES over a reduced domain, with 8 × 109 grid cells. The DNS has a far more accurate shock position and overall pressure distribution. The skin friction in the favourable pressure gradient is also much higher than in the LES; thus, wide differences appear upstream of the shock wave, most probably caused by the rapid acceleration which leads to atypical shear-stress profiles. Other SGS models were tried, and performed worse than IDDES. The DNS essentially fulfils the initial expectations although in a reduced domain and provides data for turbulence-modelling studies, for instance by extracting an effective eddy viscosity from it. The most noticeable remaining disagreement with experiment is over the Reynolds shear stress.

HIV type 2 epidemic in Spain: challenges and missing opportunities.

: HIV type 2 (HIV-2) is a neglected virus despite estimates of 1-2 million people infected worldwide. HIV-2 is less efficiently transmitted than HIV-1 by sex and from mother to child. Although AIDS may develop in HIV-2 carriers, it takes longer than in HIV-1-infected patients. In contrast with HIV-1 infection, there is no global pandemic caused by HIV-2, as the virus is largely confined to West Africa. In a less extent and due to socioeconomic ties and wars, HIV-2 is prevalent in Portugal and its former colonies in Brazil, India, Mozambique and Angola. Globally, HIV-2 infections are steadily declining over time. A total of 338 cases of HIV-2 infection had been reported at the Spanish HIV-2 registry until December 2016, of whom 63% were men. Overall 72% were sub-Saharan Africans, whereas 16% were native Spaniards. Dual HIV-1 and HIV-2 coinfection was found in 9% of patients. Heterosexual contact was the most likely route of HIV-2 acquisition in more than 90% of cases. Roughly one-third presented with CD4 cell counts less than 200 cells/μl and/or AIDS clinical events. Plasma HIV-2 RNA was undetectable at baseline in 40% of patients. To date, one-third of HIV-2 carriers have received antiretroviral therapy, using integrase inhibitors 32 individuals. New diagnoses of HIV-2 in Spain have remained stable since 2010 with an average of 15 cases yearly. Illegal immigration from Northwestern African borders accounts for over 75% of new HIV-2 diagnoses. Given the relatively large community of West Africans already living in Spain and the continuous flux of immigration from endemic regions, HIV-2 infection either alone or as coinfection with HIV-1 should be excluded once in all HIV-seroreactive persons, especially when showing atypical HIV serological profiles, immunovirological disconnect (CD4 cell count loss despite undetectable HIV-1 viremia) and/or high epidemiological risks (birth in or sex partners from endemic regions).

The manual orienting response habituation to repeated tactile stimuli in preterm neonates: Discrimination of stimulus locations and interstimulus intervals.

Preterm infants frequently develop atypical sensory profiles, the tactile modality being particularly affected. However, there is a lack of recent investigation of neonatal tactile perception in a passive context, especially in preterms who are particularly exposed to this tactile stimuli. Our aims were to provide evidence of orienting responses (behavioral modifications directing subject's attention towards stimuli) and habituation to passive tactile stimuli in preterm neonates, to explore their ability to perceive spatial and temporal aspects of the stimulus, and to evaluate the effect of clinical factors on these abilities. We included 61 preterm neonates, born between 32 and 34 weeks of gestational age. At 35 weeks of corrected gestational age, we measured orienting responses (forearm, hand, and fingers movements) during vibrotactile stimulation of their hand and forearm; during a habituation and dishabituation paradigm, the dishabituation being either a location change or a pause in the stimulation sequence. Preterm newborns displayed a manual orienting response to vibrotactile stimuli which significantly decreased when the stimulus was repeated, regardless of the stimulated location on the limb. Habituation was delayed in subjects born at a younger gestational age, smaller birth weight, and having experienced more painful care procedures. Preterm neonates perceived changes in stimulus location and interstimulus time interval. Our findings provide insights on several aspects of the perception of repeated tactile stimuli by preterm neonates, and the first evidence of the early development of temporal processing abilities in the tactile modality. Future work will investigate the links between this ability and neurodevelopmental disorders.

Brain functional connectivity changes 7 years after Neonatal Arterial Ischemic Stroke (NAIS): A resting state fMRI study

Objective: Resting state fMRI (rs-fMRI) enables to study brain functional connectivity, i.e. the intrinsic functional architecture of brain networks at rest. NAIS is an exquisite model to study long-term plasticity after early focal lesions. We studied brain functional connectivity with rs-fMRI in school-age children after NAIS, focusing on language networks. Methods: From 100 newborns with NAIS followed until age 7 (n= 72, 2/3 boys, 85% MCA territory, 30% unilateral Cerebral Palsy, 49 % of atypical language profiles at N- EEL battery, without differences between left/right lesions, and with good global language performance), 38 patients and 29 age-matched controls underwent 3T rs- fMRI (exploitable in 32/26). After extended data preprocessing, we computed correlations (reflecting both direct and indirect connectivity) and partial correlations (direct connectivity only) within matrices of 64 bilateral homotopic regions grouped into 10 functional networks (the reference rs-fMRI functional atlas was derived from the controls data). Right lesions were flipped to the left side for group comparisons. Individual ROI volumes accounted for brain lesions, and statistics were corrected for multiple comparisons, FDR, p<0.05. Results: With both correlation and partial correlation, we found mostly reduced inter- hemispheric connectivity in the patient group as compared with controls (in motor, language and attentional networks). When restricting analysis to the language network, the reduction was strongest between homotopic inferior frontal and superior temporal regions (‘broca’ and ‘wernicke’). In the contralesional hemisphere, only intra- hemispheric correlations were increased mostly in the language network with stronger connections with the basal ganglia and motor network and within the visual occipital network. No connectivity difference could be evidenced between patients with either typical or atypical language. Conclusion: Rs-fMRI is useful to study the maturation of functional connectivity after NAIS, showing widespread reduction of inter-hemispheric connectivity and increased contralesional connectivity within the language network. The clinical correlates of this complex pattern remain to be fully understood.

A Two-Step Latent Profile Method for Identifying Invalid Respondents in Self-Reported Survey Data

ABSTRACTInsincere respondents can have an adverse impact on the validity of substantive inferences arising from self-administered questionnaires (SAQs). The current study introduces a new method for identifying potentially invalid respondents from their atypical response patterns. The two-step procedure involves generating a response inconsistency (RI) score for each participant and scale on the SAQ and subjecting the resulting scores to latent profile analysis to identify classes of atypical RI respondent profiles. The procedure can be implemented post–data collection and is illustrated through a survey of school climate that was administered to N = 52,102 high school students. Results of this screening procedure revealed high levels of specificity and expected levels of concordance when contrasted with the results of traditionally used methods of screening items and response time. Contrasts between valid and invalid respondents revealed similar patterns across the three screening procedures when compared across external measures of academics and risk behaviors.

Preserved search asymmetry in the detection of fearful faces among neutral faces in individuals with Williams syndrome revealed by measurement of both manual responses and eye tracking

BackgroundIndividuals with Williams syndrome (WS) exhibit an atypical social phenotype termed hypersociability. One theory accounting for hypersociability presumes an atypical function of the amygdala, which processes fear-related information. However, evidence is lacking regarding the detection mechanisms of fearful faces for individuals with WS. Here, we introduce a visual search paradigm to elucidate the mechanisms for detecting fearful faces by evaluating the search asymmetry; the reaction time when both the target and distractors were swapped was asymmetrical.MethodsEye movements reflect subtle atypical attentional properties, whereas, manual responses are unable to capture atypical attentional profiles toward faces in individuals with WS. Therefore, we measured both eye movements and manual responses of individuals with WS and typically developed children and adults in visual searching for a fearful face among neutral faces or a neutral face among fearful faces. Two task measures, namely reaction time and performance accuracy, were analyzed for each stimulus as well as gaze behavior and the initial fixation onset latency.ResultsOverall, reaction times in the WS group and the mentally age-matched control group were significantly longer than those in the chronologically age-matched group. We observed a search asymmetry effect in all groups: when a neutral target facial expression was presented among fearful faces, the reaction times were significantly prolonged in comparison with when a fearful target facial expression was displayed among neutral distractor faces. Furthermore, the first fixation onset latency of eye movement toward a target facial expression showed a similar tendency for manual responses.ConclusionsAlthough overall responses in detecting fearful faces for individuals with WS are slower than those for control groups, search asymmetry was observed. Therefore, cognitive mechanisms underlying the detection of fearful faces seem to be typical in individuals with WS. This finding is discussed with reference to the amygdala account explaining hypersociability in individuals with WS.

IRMPD Spectroscopy Sheds New (Infrared) Light on the Sulfate Pattern of Carbohydrates.

IR spectroscopy of gas-phase ions is proposed to resolve positional isomers of sulfated carbohydrates. Mass spectrometric fingerprints and gas-phase vibrational spectra in the near and mid-IR regions were obtained for sulfated monosaccharides, yielding unambiguous signatures of sulfated isomers. We report the first systematic exploration of the biologically relevant but notoriously challenging deprotonated state in the near IR region. Remarkably, anions displayed very atypical vibrational profiles, which challenge the well-established DFT (Density Functionnal Theory) modeling. The proposed approach was used to elucidate the sulfate patterns in glycosaminoglycans, a ubiquitous class of mammalian carbohydrates, which is regarded as a major challenge in carbohydrate structural analysis. Isomeric glycosaminoglycan disaccharides from heparin and chondroitin sources were resolved, highlighting the potential of infrared multiple photon dissociation spectroscopy as a novel structural tool for carbohydrates.

Atypical sensory profiles as core features of adult ADHD, irrespective of autistic symptoms

BackgroundAbnormal sensory sensitivity is a feature of autism-spectrum disorder (ASD), but is also reported in attention-deficit/hyperactivity disorder (ADHD). In many cases, ADHD and ASD are comorbid. This study investigated the prevalence of sensory hyper- and hyposensitivity among adults with ADHD, controlling for autistic symptoms. MethodOne hundred and sixteen adults diagnosed with ADHD completed the Adolescent/Adult Sensory Profile-NL (AASP-NL) and the Autism-spectrum Quotient (AQ) questionnaires. Prevalences of hyper- and hyposensitivity and autism-spectrum symptoms were compared to norm values. Multivariate binary logistic regressions were used to determine the association of autistic symptoms, age, gender, ADHD subtype, self-reported severity of ADHD symptoms, comorbid disorders, and use of medication on the sensory hypo- and hypersensitivity in adults with ADHD. ResultsAdults with ADHD had more autistic symptoms, and they had both more hyper- and hyposensitivity compared to norm groups. This was especially apparent in the Activity level and Auditory sensory modalities. Sensory hypo- and hypersensitivity were both related to an increased ADHD score, even showing a dose-response relationship, but not to any autistic symptom or comorbid disorder. As much as 43% of the females with ADHD reported sensory hypo- and/or hypersensitivity, compared to 22% of the men. ConclusionsSensory hypo- and hypersensitivity may be viewed as key features of adult ADHD, especially in females, regardless of any autistic symptoms. Future research should be directed at the implications of this sensory dysregulation for the understanding of the pathophysiology of (female) ADHD, and on the usefulness of assessment of atypical sensory profiles in the diagnostic procedure of ADHD in adults.

Plasma volume reduction and hematological fluctuations in high-level athletes after an increased training load.

The time course of plasma volume (PV) reduction following an increased training load period is unknown and was investigated. The accompanying fluctuations in [Hb] and OFF-hr score were analyzed in the Athlete Biological Passport. Further, whether fluctuations in plasma albumin, soluble transferrin receptors (sTfR), and pro-atrial natriuretic peptide (proANP) concentrations correlate with PV fluctuations was investigated. Eleven high-level competitive cyclists were investigated for 3weeks. After initial measurements in week 1, training load was increased ~250% in week 2 followed by a reversion to baseline training load in week 3. PV and hematological variables were determined frequently during all weeks. The higher training load in week 2 increased (P<.001) PV 10%, while [Hb] and OFF-hr score decreased ~6% (P<.01) and ~16% (P<.001), respectively. PV and [Hb] returned to baseline within 2 and 4days after week 2, respectively, while OFF-hr score remained reduced for 6days. Further, one and three atypical blood profiles of the ABP occurred during weeks 2 and 3, respectively. Individual changes in albumin, sTfR, and proANP only correlated weakly (R2 <.20) with PV fluctuations. In conclusion, PV and [Hb] fluctuations caused by an elevated training load period were reverted within 2 and 4days after returning to baseline training load, respectively, while OFF-hr remained altered for 6days. Furthermore, some atypical blood profiles were induced during and subsequent to the increased training load, demonstrating the importance of knowledge on naturally occurring hematological fluctuations. Finally, concentrations of albumin, sTfR, and proANP could not explain PV fluctuations.

New directions in hypnosis research: strategies for advancing the cognitive and clinical neuroscience of hypnosis.

This article summarizes key advances in hypnosis research during the past two decades, including (i) clinical research supporting the efficacy of hypnosis for managing a number of clinical symptoms and conditions, (ii) research supporting the role of various divisions in the anterior cingulate and prefrontal cortices in hypnotic responding, and (iii) an emerging finding that high hypnotic suggestibility is associated with atypical brain connectivity profiles. Key recommendations for a research agenda for the next decade include the recommendations that (i) laboratory hypnosis researchers should strongly consider how they assess hypnotic suggestibility in their studies, (ii) inclusion of study participants who score in the middle range of hypnotic suggestibility, and (iii) use of expanding research designs that more clearly delineate the roles of inductions and specific suggestions. Finally, we make two specific suggestions for helping to move the field forward including (i) the use of data sharing and (ii) redirecting resources away from contrasting state and nonstate positions toward studying (a) the efficacy of hypnotic treatments for clinical conditions influenced by central nervous system processes and (b) the neurophysiological underpinnings of hypnotic phenomena. As we learn more about the neurophysiological mechanisms underlying hypnosis and suggestion, we will strengthen our knowledge of both basic brain functions and a host of different psychological functions.