It is well known that sexual selection is the main driving force of substantial diversity of genitalia found in animals. However, how it facilitates the diversity is still largely unknown, because genital morpho/physical features and motions/functional morphology of the structures in sexual intercourse are not linked for the vast majority of organisms. Here we showed the presence of material gradient and numerically studied an effect of stiffness gradient of the beetle penis during its propulsion through the female duct. We found that stiffness gradient on the penis essentially affects its propulsion. Microscopic investigation suggests the possibility that the tip of the hyper-elongated penis is softer than the rest of it, and our numerical model confirms that this type of distribution of stiffness gradient aids in faster propulsion than other types. This result indicates that previously ignored physical properties of genital materials are of crucial importance in evolutionary studies of genitalia. Male and female genitalia evolve more quickly and yield remarkable diversity in comparison with other characters12344678910111213141251820Knowledge of how male and female genital properties affect physical interaction during sexual intercourse is essential in the evolutionary studies of genital structures. Since natural selection does not act directly on shapes, but rather influences shapes indirectly through functions, links between genital morpho-physical features and their functional significance are critically important to understand evolutionary mechanisms of diversification. Nevertheless biomechanics which challenges comprehensive understanding of kinematics and dynamics of movements in relation to the structural features have been largely ignored in this field, but recently this topic started to contribute more to our knowledge due to modern experimental techniques, elaborate modeling tools, and by increasing number of interdisciplinary studies152223242526Hereby we numerically modeled hyper-elongated male and female genitalia especially focusing on physical properties observed in cassidine beetles, to gain insights about how genital features affect penile propulsion that is an initial and vital process of male and female physical interactions during copulation. In these beetles, the male penises represent an elongated cuticular flagellum, transferring sperm, and female genitalia where the flagellum is inserted represent a partly cuticular and helical spermathecal duct including some reversal turnset al.In order to test this hypothesis, we analyzed the autofluorescence composition of the genitalia based on the differences of different biopolymers using confocal laser scanning microscopyThe confocal laser scanning microscopy analysis revealed a gradient in the autofluorescence composition along the flagellum . Except We hereby applied the previous numerical modelj, which is produced by the phase shift around every knot j.Results of the simulations for the flagellum with uniform and gradient of rigidity  and 4 arA correlation between maxima of the absolute tip velocity along the female duct and positions of the knots is presented in The CLSM results of the present study indicate longitudinal gradient in the material composition of the flagellum and the absence of such a longitudinal gradient in the female spermathecal duct. According to Michels and Gorb3225et al.The flagellum that is equally stiff along its length results in a greater deformation between the original and penetrated positions of the female duct . It meanIn our previous studyet al.There are several sophisticated experimental studies investigating driving and stabilizing mechanisms of hyper-elongation713152834Cassida rubiginosa (Chrysomelidae) were collected in Jena (Germany) in May 2014 and in June 2015, kept in plastic jars with fresh leaves of thistles Cirsium spp., (Asteraceae) and grew to the next generation of adults. The shape and measurements of the male flagellum and female spermathecal duct of this species had reported in Filippov et al.The autofluorescence composition of the flagellum was investigated with the confocal laser scanning microscope Zeiss LSM 700 . For this purpose, beetles et al.Here we have developed further a numerical model previously proposed in Filippov N (up to N = 105) of elastically connected discrete segments. In the present study, we needed more accurate calculation than before and created more segments in comparison with the previous modeldr ≤ 1 μm defined by a total length of the system L = 10 mm measured from the microscopic images for our model beetle, Cassida rubiginosa.The flagellum was numerically constructed from a big number dr.The flagellum model is provided with strong longitudinal stiffness k⊥ = const is much weaker k⊥ varies from segment to segment. From preliminary experiments we expect that k⊥ should be a nonlinear function, which is almost constant at the beginning and quickly falls down near the end. For definiteness we apply:Like in the previous modelg determine general rigidity and a rigidity gradient along the flagellum. In particular, at g = 0, large/small constant g = 0.99, then the tip of the flagellum is 100 times softer than its base. Using different combinations of the parameters, we analyzed four different variants of the system: constantly soft, constantly hard, almost constantly soft with the hard end, and almost constantly hard with the soft end. To reproduce the two last cases, we had used exponent α = 5.Here parameters Female duct along the coordinate Lx/30; λ = Lx/40, 0.1Lx < A0 < 0.5Lx and 0.2Lx < λ0 < 0.4Lx. It has secondary structure with some number Nknots of knot points at positions Xn, where direction of spiral rotation changes to a reverse one. The phase rotations were caused by the phase function φ(X) defined as a sum of step-like functions n = ±1 for mutually opposite phase rotations around even and odd nods, respectively.with the parameters R = Y0 = A0 cos (2πX/λ0) = 0 and limited ourselves by the straight spiraled-duct only. Such spirals having four knots Nknots = 4 and different combinations of the flagellum rigidities are shown in zj(xj),yj(xj)} of the male flagellum by the returning forces:K.The female spermathecal duct is not only helical but also convolutedg = 0.99 and g = −99 and for For reflecting a probable uniform stiffness which is suggested by CLSM images, we fixed everywhere below, i.e. a general flagellum rigidity The presence of liquid inside the channel was taken into account by introducing a proportional to the velocity How to cite this article: Filippov, A. E. et al. Stiffness gradient of the beetle penis facilitates propulsion in the spiraled female spermathecal duct. Sci. Rep.6, 27608; doi: 10.1038/srep27608 (2016).


In the paper titled “Does Urinary Bladder Shape Affect Urinary Flow Rate in Men with Lower Urinary Tract Symptoms?” we should add an author who has contributed to our study for the images: Murat Çınar, Department of Biomedical Engineering, Faculty of Engineering and Architecture, Izmir Katip Celebi University, 35620 Izmir, Turkey.In addition we should here correct the affiliation of one of the authors named Ömer Karal and the postal code in the affiliation of the author Mahmut Pekedis.


To investigate the association between frequency of visiting shops and noticing of tobacco point‐of‐sale (PoS) displays and the development of susceptibility to smoking, or smoking uptake, in secondary school students.Two surveys of a school based cohort study carried out in 2011 and 2012.Nottinghamshire, UK.A total of 2270 children aged 11–16 years from eight schools in Nottinghamshire.We investigated changes in susceptibility to smoking and smoking status in relation to frequency of visiting shops and noticing PoS displays and number of tobacco brands recognized, controlling for a range of potential confounders. Susceptibility to smoking was defined using a set of three questions covering intentions to try smoking, to smoke within the next year and likelihood of smoking if a best friend offered a cigarette. For the analysis we used multinomial logistic regression.Among non‐susceptible never smokers, noticing PoS displays more frequently was associated independently with an increased risk of becoming susceptible to smoking , but was not associated with smoking uptake. Recognizing a higher number of brands among non‐susceptible never smokers doubled the risk of becoming susceptible to smoking and of becoming a smoker, but this did not have a significant effect on transition to smoking among susceptible never smokers. Frequency of noticing tobacco PoS displays was not associated significantly with smoking uptake among those who were susceptible never smokers at baseline.Noticing tobacco point‐of‐sale displays more often and recognizing a higher number of tobacco brands is associated with an increased risk of becoming susceptible to smoking among adolescents in the United Kingdom, and recognizing a higher number of brands is associated positively with an increased risk of smoking uptake. Smoking is the largest preventable cause of death in industrialized countries, and in the United Kingdom accounts for more than 100 000 deaths every year Of the many causes of smoking initiation in adolescence, exposure to tobacco advertising and promotion are important, as they are entirely preventable In England, open PoS displays are being prohibited in two stages, starting with large shops such as supermarkets from April 2012, and in smaller retailers, which occur typically in the locality of schools and are the main source of children's exposure to PoS displays In March 2011, we carried out a cross‐sectional study of smoking and PoS display exposure in students attending 11 secondary schools in Nottingham All students whose parents did not decline consent were invited to complete a paper‐based questionnaire, under teacher supervision, during the school day. The questionnaire collected data on age, sex, postcode [from which quintiles of the Index of Multiple Deprivation (IMD) were derived as an area‐level measure of socio‐economic status We measured the frequency of visiting small shops and supermarkets by asking students how often they go to each of these categories of shops , and merging these responses into a binary variable—fewer than two or three times a week, or two or three times a week or more—to avoid categories with small numbers. We measured frequency of noticing tobacco PoS displays by asking students whether, when going to shops, they noticed cigarettes on display every time, most times, sometimes, hardly ever or never. We merged these categories into a binary variable comprising sometimes or less, and most or every time to avoid categories with small numbers. We examined the brands of cigarettes and hand‐rolling tobacco that students recognized by listing the most popular brands  susceptibility to smoking in 2012 among students who were non‐susceptible never smokers in 2011; (2) ever smoking in 2012 among students who were non‐susceptible never smokers in 2011; (3) non‐susceptibility to smoking in 2012 among students who were susceptible never smokers in 2011 and (4) ever smoking in 2012 among students who were susceptible never smokers in 2011. Our main exposure variables were frequency of visiting shops in 2011, noticing of tobacco PoS displays in 2011 and number of brands recognized in 2011, with adjustment for suspected confounders using data from 2011. Additionally, we used two combined exposure variables to estimate joint effects: frequency of visiting shops combined with frequency of noticing PoS displays, and frequency of noticing tobacco PoS displays combined with number of brands recognized. Students with missing values for outcome variables were excluded from the analysis, but those with missing exposure data were included, coding missing values as a separate category, to maximize study power.P‐values with significance levels set at 0.01. The students who responded to our survey are clustered within classes and schools, and thus we needed to account for this non‐independence in our analysis. However, the small total number of students (particularly baseline susceptible never smokers), and students per cluster, meant that we could not fit a multi‐level model. Therefore, for all models we used a clustered sandwich estimator to produce robust 99% confidence intervals around our point estimates of effect to account for the clustering.We used multinomial logistic regression to obtain relative risk ratios (RRRs) for changes in smoking and susceptibility status relative to no change between 2011 and 2012 in children who are exposed frequently to PoS displays, noticed PoS displays more often and recalled higher number of brands, compared to children who did not report these exposures. We also investigated the association between the combined exposure variables and changes in smoking status. We first built two unadjusted multinomial models, one restricted to those who were non‐susceptible never smokers at baseline and a second restricted to those who were susceptible never smokers at baseline, and then adjusted these models for potential confounding variables that were found to be significant at univariable level. Likelihood ratio tests were used to determine which of these confounding variables should be included in the final models. Given the large number of statistical tests carried out, we present 99% confidence intervals (CIs) for each measure of association, as well as exact It is possible that the inclusion of parental, sibling and friend smoking as confounding variables may lead to over‐adjustment, as these variables may themselves be related to exposure to tobacco marketing. Therefore, as a sensitivity analysis we built adjusted models where these variables were not considered as potential confounders.Data were analysed using Stata 13 .We received questionnaires from 4302 students  from the eight schools surveyed in 2012, of whom 3672 were in school years 8–11 and hence potentially also participants in the 2011 survey Of the non‐susceptible never smokers in 2011, 313 (19.9%) became susceptible never smokers in 2012 and 111 (7.0%) became ever smokers. Of the 494 susceptible never smokers in 2011, 224 (45.3%) did not change status, while 128 (25.9%) became non‐susceptible never smokers and 142 (28.7%) progressed to being a smoker. Other characteristics of the students included in the analysis are presented in Table Among those who were non‐susceptible never smokers in 2011, the univariable RRRs of becoming susceptible to smoking in 2012 compared to remaining non‐susceptible were significantly higher among students with parents who smoked, or with more friends who smoked, among those with lower perceived levels of academic performance and higher levels of rebelliousness, those who visited shops more frequently and noticed cigarettes on PoS displays more often, and those who recognized a higher number of brands . There was no association between frequency of visiting shops and noticing PoS displays and progression to smoking among baseline non‐susceptible never smokers.After adjustment for confounding variables, non‐susceptible never smokers at baseline who visited shops and noticed PoS displays more frequently, and who recognized more brands, were more likely to become susceptible than respondents without these exposures Table . Non‐susBased on 99% CIs there were no significant associations between frequency of visiting shops, noticing displays and brand recognition and changes in smoking status among students who were susceptible never smokers at baseline.P = 0.002).When frequency of visiting shops was combined with frequency of noticing PoS displays, increases in the risk of non‐susceptible never smokers becoming susceptible were seen across all categories compared to those who both visit shops and notice PoS displays infrequently. Non‐susceptible never smokers who noticed PoS displays most or every time, and who recognized at least one brand, were approximately three times more likely to become susceptible compared to those who infrequently noticed PoS displays and recognized no brands. Non‐susceptible never smokers who noticed PoS displays most or every time and who recognized more than five brands were more likely to have progressed to smoking by 2012 .The results of sensitivity analyses excluding from the list of potential confounders parental, sibling and friend smoking which may, themselves, be related to tobacco marketing, are presented as Supporting information (Table S1). Here, the previously significant associations between noticing point of sale displays and changes in smoking status among baseline non‐susceptible never smokers (to both susceptible never smokers and ever smokers) are now non‐significant. However, susceptible never smokers in 2011 who recognized more than five brands were now significantly more likely to have progressed to smoking in 2012, with a 99% CI that excludes the possibility of no association .Supporting info itemClick here for additional data file.


Hum Brain Mapp 37:1254–1270, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.Attentional and executive dysfunction contribute to cognitive impairment in both Lewy body dementia and Alzheimer's disease. Using functional MRI, we examined the neural correlates of three components of attention  in 23 patients with Alzheimer's disease, 32 patients with Lewy body dementia (19 with dementia with Lewy bodies and 13 with Parkinson's disease with dementia), and 23 healthy controls using a modified Attention Network Test. Although the functional MRI demonstrated a similar fronto‐parieto‐occipital network activation in all groups, Alzheimer's disease and Lewy body dementia patients had greater activation of this network for incongruent and more difficult trials, which were also accompanied by slower reaction times. There was no recruitment of additional brain regions or, conversely, regional deficits in brain activation. The default mode network, however, displayed diverging activity patterns in the dementia groups. The Alzheimer's disease group had limited task related deactivations of the default mode network, whereas patients with Lewy body dementia showed heightened deactivation to all trials, which might be an attempt to allocate neural resources to impaired attentional networks. We posit that, despite a common endpoint of attention‐executive disturbances in both dementias, the pathophysiological basis of these is very different between these diseases.  ANTattention network testCAMCOGCambridge cognitive examinationDMNdefault mode networkLBDLewy body dementiaMCImild cognitive impairmentMMSEmini‐mental state examinationNPIneuropsychiatric inventoryROIregion of interestRTreaction timesUPDRSunified Parkinson's disease rating scaleLewy body dementia (LBD) includes both dementia with Lewy bodies and Parkinson's disease dementia, and is a major cause of dementia after Alzheimer's disease, representing 10%–15% of all late onset dementia cases [Vann Jones and O'Brien, Deficits in attention and executive functioning are a common feature across a range of different neurodegenerative dementias [Bosboom et al., Posner and colleagues [Fan et al., The three domains of attention described by Posner and colleagues can be delineated by the attention network test (ANT) [Fan et al., Our study aim, therefore, was to investigate the neural correlates of different subcomponents of attentional function using a version of the ANT in LBD and Alzheimer's disease in comparison to each other and a healthy aged control group using functional magnetic resonance imaging (fMRI). We attempted to identify how attention brain regions were altered in people with dementia, and to determine to what extent this varied between these dementia subtypes. In particular, given the extensive literature associating dysfunction of the DMN with neurodegeneration [Buckner et al., We hypothesized that we would find less task related deactivation of the DMN in Alzheimer's disease as demonstrated by previous studies [Rombouts et al., Study participants were recruited between September 2010 and January 2014 prospectively from people aged over 60 with mild to moderate dementia with a Mini‐Mental State Examination (MMSE) score >12 from a local community‐dwelling population of participants who had been referred to local old age psychiatry and neurology services. Healthy controls were selected from friends and spouses of participants included in this and previous studies. The study was approved by the local ethics committee.Diagnosis of probable dementia with Lewy bodies, Parkinson's disease with dementia or Alzheimer's disease was made independently by two experienced clinicians using the revised International Consensus Guidelines for dementia with Lewy bodies [McKeith et al., Control participants in the study demonstrated no evidence of dementia (from history and score >80 on CAMCOG). Exclusion criteria for all participants included contra‐indications for MR imaging, moderate to severe visual impairment, previous history of alcohol or substance misuse, significant neurological or psychiatric history, moderate to severe cerebral small vessel disease, focal brain lesions on brain imaging or the presence of other severe or unstable medical illness.Before undergoing a scanning session and formal in‐scan testing with the ANT, participants were familiarized with the task, and it was verified that they could perform it correctly (task accuracy > 70%). All LBD patients were scanned whilst taking their usual anti‐parkinsonian medications and in an “on” motor state.The task was based on the ANT [Fan et al., Visual stimuli were back‐projected on to a screen at the foot of the scanner, and participants viewed the stimuli via a mirror positioned above their eyes. All participants had measurement of their best near visual acuity on Landolt broken rings and fMRI compatible goggles with lenses that ranged from −4.0 to 4.0 diopters (0.5 increment) were used to correct any refractive errors that participants had.http://www.vislab.ucl.ac.uk/cogent_2000.php)Participants looked at a screen with a central cross hair, and three grey boxes Fig. . For eac2; TR = 8.3 ms; TE= 4.6 ms; flip angle = 8°; SENSE factor = 2). fMRI data were collected with a gradient‐echo (GE) echo planar imaging (EPI) sequence  192 × 192 mm2 64 × 64 matrix size, flip angle 90°, 27 slices, slice thickness 3 mm, slice gap 1 mm) with 156 volumes (five minutes). We collected between four and six runs of fMRI data whilst participants performed the attention task. We excluded those runs with < 2/3 correct responses as performance per run worse than this was not significantly different from chance.Participants were scanned on a 3T whole body MR scanner , with body coil transmission and eight channel head coil receiver. Images acquired included a standard whole brain structural scan  for all image analysis. For each participant, the T1 anatomical image was segmented and spatially normalised in SPM using the default parameters. We then used the DARTEL [Ashburner, 3. The normalized images were then smoothed with a 8 × 8 × 8 mm3 FWHM  Gaussian kernel. A high pass filter of 128 seconds was used, and serial correlations were removed with SPM's AR(1) model.We used SPM8  in SPM was used to conduct a whole‐brain analysis of the fMRI data. We created a design matrix using an impulse function with onset time of the events . Missed targets and incorrectly responded to targets were combined as an extra column in the design matrix. These events were convolved with the canonical haemodynamic response function (HRF), and the first derivative of the HRF was also included to model variation in onset latency.P < 0.001 and a clusterwise familywise error (FWE) corrected threshold of P < 0.05 were interpreted.The six parameters from the motion correction for each functional run were included in the design matrix as covariates of no interest. The regressors were fitted to the fMRI data to produce beta estimates for each regressor. Individual subject and second level (random effects) group analyses were conducted. Contrasts were as the behavioral analysis, except inverted . Only effects surviving an uncorrected voxelwise threshold of P <0.05, and the voxels surviving this threshold were manually divided into distinct anatomical regions to define the activation ROIs . For the DMN, we thresholded the congruent > incongruent voxelwise analysis at P < 0.001 uncorrected, and created two ROIs  from the thresholded voxels. We investigated deactivations in the DMN by examination of the blood‐oxygen‐level dependent (BOLD) signal during the targets compared to baseline in all participants within the two DMN ROIs  which are integral to this network.Regions of interest (ROIs) were defined from the incongruent vs congruent contrast over all participants. The whole group incongruent > congruent voxelwise statistics were thresholded at FWE http://marsbar.sourceforge.net/) to extract mean values for the BOLD contrast for the comparisons.In order to investigate the magnitude of the BOLD signal during task related deactivations, we utilised the MarsBaR SPM toolbox  excessive motion on MRI , scanning stopped before sufficient functional scans completed , and insufficiently accurate task performance . This left 23 controls (21 with six runs and 2 with five runs of fMRI data), 23 Alzheimer's disease , 19 dementia with Lewy bodies , and 13 Parkinson's disease with dementia .l‐Dopa equivalent doses  of the dementia with Lewy bodies patients), and had higher scores for the Cornell depression scale, the total neuropsychiatric inventory, and the MAYO and CAF than dementia with Lewy bodies patients (Supporting Information Table S1). However, there were no significant differences between these two groups in cognitive performance on the MMSE, CAMCOG, FAS, or visuospatial tests.Those with Parkinson's disease and dementia had a significantly higher UPDRS motor score, were on higher P = 0.03) over all ROIs and target/cue comparisons. Results from the combined dementia with Lewy bodies and Parkinson's disease with dementia patients group are presented in the rest of the paper as a single LBD group (n = 32).Since previous studies have found a similar profile of attentional and executive function between dementia with Lewy bodies, and Parkinson's disease with dementia patients [Ballard et al., Table The minimum number of trials responded to was 74%, with a minimum of 71% of all trials being correctly responded to. Table P =0.004), which was not significant in either dementia group, though there were no significant group differences in alerting. There was an orienting effect of similar magnitude in all groups, with responses following the directional cue being significantly faster than to the neutral cue. There was also evidence of an executive‐conflict effect, with congruent RT < easy incongruent RT < hard incongruent RT in all groups, though the difference between the easy and hard incongruent conditions was smaller for the controls than the dementia patients. Although the LBD were overall slower than the Alzheimer's disease patients, there were no significant differences between the dementia groups in alerting, orienting or executive‐conflict behavioural effects.Responses were fastest in controls, then Alzheimer's disease, and slowest in LBD across all cue and target types Table . In the P = 0.001 uncorrected) between any groups. For the orienting  we did not see any significant increases in activation in any group. However, there was a small bilateral medial occipital region in all groups where activity was greater for neutral vs directional cues, although this cluster was only significant in the Alzheimer's disease group. There were no significant differences between any groups.Figure P = 0.016; directional cue, P = 0.025; Supporting Information Fig. S2), and frontal deactivation to neutral cue (P = 0.009), whilst LBD had only frontal deactivation to the neutral cue (P = 0.021). The Alzheimer's disease group showed a degree of deactivation, but this was not significant for any cue.We used the frontal and parietal DMN ROIs to investigate deactivation following the cues relative to no cue. The control group had significant parietal deactivation to both cues , but not to the neutral or directional cues (Supporting Information Table S6). The LBD group, in contrast, had strong DMN deactivation  to the target following both cues and no‐cues and the Alzheimer's disease group demonstrated deactivation following the cues only in the frontal DMN For the DMN regions, the controls demonstrated a significant target deactivation following the no‐cue condition  response vs those with a correct response. For this analysis, we included those participants with at least 15 invalid responses ; there were no controls, 10 Alzheimer's disease and 21 LBD in this analysis. Supporting Information Table S7 shows the BOLD response for the invalid vs valid responses. For both Alzheimer's disease and LBD, there is more activity for invalid responses, in most regions of the task positive network, and deactivation for the LBD group in the DMN. There were no significant difference between Alzheimer's disease and LBD groups in any region.In the present study we sought to compare the alerting, orienting and executive networks of attention [Fan et al., We investigated the effect of cueing in two ways. Firstly, we examined how brain activation changed directly on presentation of a cue vs no cue. Secondly, we examined the effect of the cue on target response from an fMRI BOLD perspective during target presentation in response to each cue type given evidences supporting cue‐target interactions in the ANT [MacLeod et al., We found a strong behavioral alerting effect in controls, but no effect of alerting in either dementia group, which is in line with previous studies showing reduced alerting effects in dementia. Possibly the lack of alerting is because of impaired interactions of the noradrenergic system in the brainstem with frontoparietal regions [Fernandez‐Duque and Black, However, the brain activation during target processing was differentially influenced by the alerting effect in all three groups Fig. . In contIn Alzheimer's disease, presentation of the neutral cue compared with no cue led to decreased frontoparietal activation as well as deactivation of only the anterior DMN during target presentation. Many studies have found reduced task related deactivation in the DMN in Alzheimer's disease [Celone et al., In LBD patients, in contrast to Alzheimer's disease patients and controls, target activations following the cues tended to be higher than following no cue, and this was significantly so in the parietal region. This enhanced activation may be a compensatory attempt, as observed in other studies in related conditions such as Parkinson's disease [Helmich et al., Both dementia groups and controls benefited from the orienting effect in terms of task speed. In Alzheimer's disease, these findings are supported by a number of behavioral studies showing normal [Festa‐Martino, However despite the faster responses following the orienting cue, our study did not show any specific orienting effect on brain activation in either controls or LBD and only a small occipital activation in Alzheimer's disease, contradicting prior evidence which showed a subtle involvement of frontoparietal brain regions [Fan et al., Examining the activation to target following the directional vs neutral cue, we found reduced occipital activity in Alzheimer's disease which was also almost significant for the control group , suggesting that the cue, by drawing attention to the target location, leads to less visual search. On the other hand, in LBD, orienting led to increased activation of the insula on ROI analysis during target presentation. The insula is regarded to play a role in cognitive control activating task positive networks [Sidlauskaite et al., We were able to demonstrate variation in RT with executive function demands in all groups. The error rate was consistently low in controls in both conditions, whereas it significantly increased in LBD and Alzheimer's disease when an incongruent target was presented. In terms of brain activity, all three groups had similar fronto‐occipito‐parietal activations to the targets, which were broadly similar to previous studies [Liu et al., These findings contrast with our a priori hypothesis of finding regional deficits, particularly in LBD. However, there is an increasing evidence base to suggest that large scale neocortical network alterations may be more pertinent to clinical and cognitive symptoms in LBD rather than specific regional nodes [Peraza et al., We looked specifically at the role of the DMN during executive function by plotting its BOLD activation during different conditions. In agreement with a number of previous studies [Browndyke et al., Intriguingly the DMN demonstrated strong deactivation during both congruent and incongruent tasks in LBD. Previous studies have found mixed results regarding the DMN in dementia with Lewy bodies, although there is a tendency for it to demonstrate less impairment than in Alzheimer's disease [Franciotti et al., The strong deactivation, however was not accompanied by a comparable increase in activation of the fronto‐parietal networks with task difficulty. We hypothesize therefore that it is not a failure to deactivate the DMN that leads to inattention, which has been suggested to occur in young healthy controls [Weissman et al., A number of limitations to our study need to be considered. Firstly, as we only used visual stimuli in our study, our findings are potentially confounded by the greater tendency for visuo‐perceptual deficits in LBD as evidenced with our angle discrimination task. Indeed, in response to our executive task, there was a tendency for the LBD patients to have more occipital activation compared with controls which could suggest inefficiencies in visual processing in this group. However this activation increase was relatively subtle and could have been driven by the longer attendence of the LBD patients to the target stimuli i.e. reflecting impaired top‐down attentional processing rather than aberrant bottom‐up visual processing. Further fMRI studies with tasks differentially weighted on attention and visual complexity may help address this question.Another limitation was the effect of concurrent psychotropic medication. Cholinergic drugs are reported to improve attentional function in controls and dementia [Bentley et al., The LBD group had relatively few PDD subjects, since the recruited subjects in that group had more difficulty with motion in the scanner and performing the task, as well as some unrelated technical difficulties. This may have biased the LBD group toward a less motor predominant phenotype. DLB have also been reported to have more AD‐like amyloid pathology [Petrou et al., Depression can influence attention and cortical network activity, [Kertzman et al., Finally, we did not examine dynamic interactions and connectivity between different regions in our present study, although our findings suggest a dynamic interplay between task‐positive and task‐negative regions in LBD and Alzheimer's disease during task performance. We also focussed our present analyses on cortical activity; however the pathophysiological role of key subcortical structures which provide corticopetal efferents to these neocortical networks such as the thalamus [Delli Pizzi et al., We found increased frontoparietal activation in LBD and Alzheimer's disease during attentional‐executive function in relation to task demand, with no regionally specific deficits nor recruitment of additional brain regions. Both the LBD and Alzheimer's disease patients had equally reduced performance compared to controls on the task. Despite these similarities; however, the dementia groups differed in the dynamic changes of the DMN. While in the LBD group we found a significantly increased DMN deactivation during target presentation, which was modulated by the task demand, the Alzheimer's disease group demonstrated limited task related deactivations in DMN regions. This has implications in the design of future clinical trials targeting attentional‐executive dysfunction in these disorders, suggesting that different therapeutic approaches may be needed in LBD compared with Alzheimer's to optimize outcomes.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.Supporting InformationClick here for additional data file.


Simultaneous multislice imaging (SMS) using parallel image reconstruction has rapidly advanced to become a major imaging technique. The primary benefit is an acceleration in data acquisition that is equal to the number of simultaneously excited slices. Unlike in‐plane parallel imaging this can have only a marginal intrinsic signal‐to‐noise ratio penalty, and the full acceleration is attainable at fixed echo time, as is required for many echo planar imaging applications. Furthermore, for some implementations SMS techniques can reduce radiofrequency (RF) power deposition. In this review the current state of the art of SMS imaging is presented. In the Introduction, a historical overview is given of the history of SMS excitation in MRI. The following section on RF pulses gives both the theoretical background and practical application. The section on encoding and reconstruction shows how the collapsed multislice images can be disentangled by means of the transmitter pulse phase, gradient pulses, and most importantly using multichannel receiver coils. The relationship between classic parallel imaging techniques and SMS reconstruction methods is explored. The subsequent section describes the practical implementation, including the acquisition of reference data, and slice cross‐talk. Published applications of SMS imaging are then reviewed, and the article concludes with an outlook and perspective of SMS imaging. Magn Reson Med 75:63–81, 2016. © 2015 The Authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc. on behalf of International Society of Medicine in Resonance. N slices, the imaging experiment must be repeated N times, with a different phase pattern for each excited slice. The use of such add/subtract schemes makes the experiment vulnerable to the effects of motion and other system instabilities; furthermore, the acquisition durations become quite long. The use of Hadamard encoding was thus more attractive for spectroscopy than imaging, as the extra acquisitions necessitated generally would not exceed the number of averages required to achieve sufficient sensitivity The possible advantages of simultaneously exciting and imaging several slices were realized early in the development of MRI An important development, that indeed foreshadowed many of those made in recent years, was the introduction of the POMP technique [phase offset multiplanar volume imaging N slices resulted in an increase in sensitivity of √N relative to the sequential acquisition of data from the same number of slices, but in no net reduction in acquisition time. Furthermore, it was inherent to the summation principle of the RF pulses used, that the power deposition would increase linearly with the number of excited slices, and if the pulses had identical phase then the peak power would increase with 2N. The peak power could, however, be reduced by finding an optimum phase variation between the pulses In both Hadamard and POMP imaging it was clear that the simultaneous detection of signals from z‐axis, which is necessary to accelerate axial acquisitions; and the lack of an obvious application. Despite this relative lack of initial interest, important progress was made during these years, and special attention should be given to the CAIPIRINHA  technique The revolution in imaging acquisition brought about by the introduction of parallel imaging techniques For most pulse sequences, the accelerations achievable by implementing standard parallel imaging and SMS imaging are similar, but the implementation of SMS is more demanding as higher power RF pulses have to be incorporated into the imaging sequence. A significant advantage of SMS is that it does not directly cause a reduction in sensitivity, whereas this is inherent to the reduction in the number of phase‐encoding steps acquired in standard parallel imaging methods. For echo planar imaging (EPI) in particular, the benefits of SMS are qualitatively different than for standard parallel imaging. The latter reduces the duration of the EPI readout; hence, both the distortion and the SNR are correspondingly reduced. SMS leads to a reduction in acquisition time by a factor N, with no impact on distortion or SNR. Although an earlier abstract had demonstrated the combination of EPI with SMS In this review, we shall give a comprehensive and detailed explanation of current techniques for performing SMS imaging, in so doing we build upon a previous related review A(t) is the standard complex RF waveform that in conjunction with the slice selective gradient determines the slice profile , and P(t) is an additional phase modulation function that determines the slice position (Δω) and its phase (φ) at TE = 0 according to:P(t) resulting in a multiband pulse that excites the desired slices in the presence of a common slice selective gradient.A(t) remains unchanged in most common situations where the same flip angle and slice profile are desired for each slice, which will be assumed for the remainder of this section. However, this is not a general requirement, and in principle N arbitrary waveforms at arbitrary slice positions can be added up by complex summation to form a multiband pulse, as long as each pulse individually is consistent with the chosen slice selection gradient. Slice and transmit channel dependent pulse shapes n(t)A play an important role in parallel transmission (pTX) SMS excitation which will be discussed below.A slice selective complex RF pulse can be described as the product of two functions:MB(t)RF is prone to exceed peak amplitude capabilities of the RF amplifier and the total power in the pulse may exceed specific absorption rate (SAR) limits. Increasing the duration of the RF pulse—while keeping the flip angle and bandwidth‐time‐product (BWTP) constant to ensure identical slice profiles—will reduce both SAR and peak amplitude. Unfortunately, the amount of stretching needed for high MB factors can have serious implications with respect to sequence timing, robustness against off‐resonance effects (due to reduced bandwidth) and non‐negligible T2* decay during the pulse. Alternative strategies are discussed below, starting with methods to reduce peak amplitude without affecting SAR, followed by methods that achieve time‐averaged power reduction.There are two major technical challenges with MB RF pulse design. MB(t)RF is governed by the amplitudes of both A(t) and n(t)ΣP. In practice, however, n(t)ΣP will be oscillating at such a high frequency compared with the modulations in A(t) that one can approximate max(|MB(t)RF|) to be equal to max(|n(t)ΣP|) × max(|A(t)|).Strictly speaking, the peak amplitude of φ is identical for all slices, max(|n(t)ΣP|) simply scales with N. Lower peak amplitudes can be achieved by allowing the phase of each slice to vary N, max(|n(t)ΣP|) approaches its theoretical lower bound of sqrt(N) and that for acceleration factors in the range of four to eight the theoretical optimum is exceeded by 24 or 14%, respectively If An alternative strategy to reduce peak amplitude in spin‐echo imaging was recently proposed by Auerbach et al A method closely related to the time‐shifting strategy is that of “root‐flipping” for MB RF pulses using a SLR design approach N. This can be shown using Parseval's theorem:MB(t)RF, if the number of slices in image space is altered P that do not create overlapping slices, but this requirement is generally met in SMS applications.The methods described above aim to reduce the peak amplitude so as to allow the RF pulses to be produced by the amplifiers without clipping. However, with high multiband factors and/or high flip angles, power deposition in the body becomes the main limitation. Irrespective of the manipulations outlined above, the power of multiband pulses scales with how we traverse excitation k‐space, or—put another way—how the k‐space trajectory is mapped onto the time domain.Parseval's theorem then appears to put quite a hard limitation on power reduction, because there is not much leeway in how we want to distribute our slices. The crucial degree of freedom, however, is given by ° refocusing pulses with moderate multiband factors (MB < 4) at 3 Tesla (T), still allows an acceptable slice profile and high effective bandwidth‐time product The true RF power is determined by the power integral of the RF over time. By varying the slice selection gradient with time, the k‐space representation of the RF pulse is no longer mapped linearly to the time domain, and power can be reduced without modifying the slice profile. This is the principle of VERSE Norris et al proposed the use of periodic excitation profiles for SMS imaging to reduce RF power in a method called PINS 0 inhomogeneities. Although this is not ideal, it should be put in perspective: virtually all EPI studies to date have suffered from distortion in the phase‐encoding direction to a much larger extent without it being prohibitively bad.The bandwidth of a PINS pulse is of limited magnitude: the bandwidth of an RF pulse is proportional to the average slice selection gradient amplitude. With PINS, the gradient blips are typically small while being interleaved with periods of no gradient at all when an RF sub‐pulse is transmitted. The BW of a PINS pulse can be readily calculated from Eq. This leaves the question when to use PINS and when to use a conventional, higher BWTP (VERSE) multiband pulse. This depends on the application, with PINS being most useful if the multiband factor is high and/or slices are relatively thick with respect to the slice period. PINS is least useful in the opposite case when the slices are thin relative to their spacing as Eq. PINS produces periodic slice profiles meaning that in theory the slice FOV is infinitely large. This can create difficulties in cleanly reconstructing all the slices; however, there are several strategies available for avoiding these. As PINS is primarily used in high‐power applications like spin‐echo, one can simply use conventional SMS excitation pulses to limit the FOV and only apply PINS to the refocusing pulses that need power reduction most. If PINS is needed for excitation as well, a sagittal orientation can be a solution when imaging the brain, as the additional slices then fall outside the head. Finally, one can opt to exploit limited coil coverage by trying to position the unwanted slices outside the range of either the transmit or receive arrays.To improve the BWTP and power performance of PINS for refocusing pulses in a spin‐echo sequence, Eichner et al have proposed a hybrid technique dubbed multi‐PINS The slices affected by the multiband pulse will receive the summed flip angle of both techniques, whereas the remaining periodic slices will only receive the flip angle imposed by the PINS pulse. Like PINS, multi‐PINS is mostly used in a spin‐echo sequence for the refocusing pulse, while excitation is performed with a conventional multiband pulse . In SMS imaging, this is still possible albeit with a small caveat: the number of stacks  needs to be an odd number There are three ways in which SMS spatial encoding can be accomplished: RF phase encoding, gradient phase encoding and coil encoding. In practice, modern SMS acquisitions will use a combination of coil encoding with either RF encoding or gradient encoding to resolve the slice direction . The in‐plane direction is sampled with readout and phase encode gradients as in a regular 2D slice‐selective acquisition. Furthermore, it is generally the objective to acquire the simultaneously excited slices in such a way that they appear shifted with respect to each other, which aids the subsequent reconstruction as discussed later in this section. For clarity, we first introduce the various relative slice shift approaches and then demonstrate how they can complement the slice‐encoding method for efficient SMS acquisitions.N slices were accommodated into one large FOV without overlap . This required the FOV to be a factor N larger than the single slice FOV and each slice to be shifted by a unique integer multiple of the FOV. This was achieved with a factor of N more phase encoding steps at N times tighter sampling distance of 1/N⋅Δk, while using alternating RF‐pulses with phases ϕnk=2π⋅(k−1)⋅(n−1) /(2N) with n and k running from 1 to N. RF encoding is directly applicable to standard “one‐line‐per‐excitation” sequences such as GRE or SE.According to the Fourier shift theorem, an image slice can be shifted to different locations in the FOV along the phase encoding direction by imposing a corresponding phase gradient on the acquisition k‐space. One can achieve this by applying a phase gradient to the RF pulse. For multiband excitations, shifts between simultaneously excited slices can be accomplished by applying individual phase cycling patterns to each frequency band. The number of different multiband RF pulses that are required will depend on the number of simultaneous slices and the desired shifts between them as demonstrated in Figure FOVz is then given by the number of simultaneously excited slices times the distance between them, represented in k‐space by a kz phase encode increment kz=1/FOVz=1/(N⋅gap), and the number of “voxels”; i.e., kz‐planes is equal to N. The 3D perspective of slice encoding is equivalent to a 2D perspective with shifted slices kz ‐phase encoding across the slices.Simultaneously excited slices can be resolved by conventional gradient phase encoding along the slice direction. This is in direct analogy to three‐dimensional (3D) imaging where a thick slab is excited and phase encoded along the slice direction. This perspective can be taken by recognizing that a MB pulse also excites magnetization in 3D space, which naturally gives rise to the notion of a 3D k‐space kz direction Coil encoding is also known as parallel MRI (pMRI) and is an integral part of modern clinical MRI. Coil encoding almost always accompanies gradient encoding, and by replacing some of the (time consuming) conventional gradient encoding allows a substantial acceleration. In the same way, coil encoding can replace some or all of the RF or gradient slice encoding in SMS acquisitions. Larkman et al The limitations of coil encoding have led to the concept of CAIPIRINHA ky,  kz), as can be seen by reference to Figure Thus, by using suitable shift patterns, the degree of coil sensitivity encoding can be shared arbitrarily between the two directions  aliased pixels are usually sufficiently far apart that the coil sensitivity variations make it possible to separate them, the situation in an SMS experiment can be much more challenging: consider for example an axial SMS brain scan with three simultaneously excited slices and 120 mm coverage along the slice direction: aliased pixels are then only 40 mm apart. In standard sequential MS with a phase encoding FOV of typically 220 mm and R = 3 acceleration along the PE direction, the separation of aliased pixels is much greater (∼70 mm), approximately a factor of 2 compared with the SMS acquisition. Even today, most coil arrays may not provide enough sensitivity variation along the slice direction to compensate for this, which inevitably results in high g‐factor noise in the reconstructed slices.N along the phase encoding direction and shifting the individual slices such that the distance between aliased pixels is N*FOV/R. The procedure is shown in Figure R = 2. This “extended FOV” concept allows an arbitrary number of slices with integer undersampling factor R to be reconstructed with standard 1D SENSE. Another approach has been taken recently by using the 3D nature of the acquisition using adapted 2D SENSE CAIPIRINHA K, which when applied to multiple measured k‐space locations from all coils within a certain k‐space region, generates multiple nonacquired k‐space data for all the coils within this k‐space region. In the case of regular integer undersampling, these weights apply everywhere in k‐space and can thus be used to reconstruct all the missing data points in all coils. This convolution process in k‐space can also be formulated in the image space Jl represented in the full FOV with the GRAPPA weights Kkl transformed into image space by means of inverse 2D Fourier transformation.K and corresponding weights in image space K can be efficiently derived from a fully sampled low resolution reference k‐space also referred to as autocalibration signals (ACS). To this end, all the kernel replicas available within the ACS data are assembled into matrices i and j according to the missing data points and measured data points, respectively. The GRAPPA weights in k‐space are then derived by, e.g., least‐squares fitting.GRAPPA The first GRAPPA based algorithm capable of reconstructing accelerated SMS data was the SENSE‐GRAPPA hybrid described by Blaimer et al In case of CAIPIRINHA SMS acquisitions with slice shifts, the same procedure as described above for SENSE can be applied to rearrange the reference data for SENSE‐GRAPPA reconstruction. While the slices can be separated, for certain MB factors/acceleration factors, sharp transitions of the shifted slice may appear in the full extended FOV that can cause high artifact levels in the transition region, as demonstrated in Setsompop et al This limitation when simply adopting SENSE‐GRAPPA to SMS reconstruction led to the development of several alternative reconstruction approaches allowing GRAPPA to be used in combination with SMS‐CAIPIRINHA: (a) SENSE‐GRAPPA hybrid with “virtual” acceleration factors; (b) slice‐GRAPPA using slice specific reconstruction kernels; and (c) direct GRAPPA in 3D k‐space recognizing the 3D nature of the SMS acquisition.R* along the phase encoding direction in an extended FOV, here denoted by FOV*, collapses to the actual SMS‐CAIPIRINHA aliasing pattern; (b) the individual slice shifts in the large FOV* are represented by linear phase ramps across the large FOV k‐space; and (c) all the slices appear without overlap within the extended FOV*. The procedure for meeting these conditions is described for an exemplary situation in Figure The g‐factor noise enhancement in SENSE‐GRAPPA in conjunction with CAIPIRINHA shifts described in Setsompop et al As in the simple SENSE‐GRAPPA hybrid, the reconstructed slices appear unaliased in the extended FOV. This concept allows reconstruction of accelerated SMS acquisitions with arbitrary numbers of slices and both slice and in‐plane undersampling, by using standard 1D GRAPPA. Alternatively, as has been shown recently, the slices can also be distributed along the read‐out direction with each slice carrying the corresponding individual CAIPIRINHA shifts along the phase encoding direction Kz are slice‐specific GRAPPA weights in the image domain which when applied to the aliased image to extract the signals originating only from the corresponding slice z. The k‐space weights Kz can be calibrated from the multislice ACS fromjs are the individual slice specific convolution kernels derived from the single slice k‐spaces that may or may not contain slice‐specific FOV shifts. However, the main drawback of this slice specific reconstruction process is that it is limited to the separation of slices. In‐plane undersampling requires a separate reconstruction step. The analogue reconstruction procedure for two slices and R = 4 is sketched in Figure Another way to reconstruct SMS‐CAIPIRINHA data with GRAPPA is the slice‐GRAPPA (SG) method Kz themselves which ideally pass only the slice z and cancel the contribution of all other slices. Thus, undesired residual signal contributions from other slices directly characterize the slice leakage. In addition, this property can be used to constrain the weights calibration such that contributions of all other slices are blocked when reconstructing a slice, known as split slice‐GRAPPA (SP‐SG). With the explicit constraint that the application of weights to reconstruct a specific slice cancels the contribution of all the other slices (jsKz=0 for s≠z) the appropriate split‐slice GRAPPA reconstruction weights are:An interesting property of the slice‐GRAPPA approach lies in the ability to quantify the so‐called slice‐leakage artifact “L”‐factor. This was introduced by Moeller et al A further option for SMS‐CAIPIRINHA reconstruction with GRAPPA becomes evident when recognizing the 3D nature of the SMS acquisition The question as to which of the presented methods/implementations is best suited to which imaging situation is difficult to answer and in many cases will dependent on the application or the preference of the observer. To our knowledge, at the time of this writing, a thorough quantitative comparison of the reconstruction performance is lacking, although to be expected at some future stage.The CAIPIRINHA sampling considered so far aims for a controlled but coherent signal aliasing that maximizes the coil's ability to separate overlapping voxels. The use of FOV shifts causes characteristic aliasing patterns, hence, potentially sharp discontinuities in the reconstruction related noise enhancement. Some authors have recently advocated forms of less coherent aliasing, by pseudorandom RF phase cycle patterns in abdominal GRE acquisitions Non‐Cartesian SMS acquisition schemes have also been proposed. One such method is radial CAIPIRINHA Setsompop and colleagues recently extended this concept to SMS imaging under the name wave‐CAIPI This section discusses several practical aspects of the implementation and use of SMS acquisitions.N compared with single slice acquisition as N times more spins are simultaneously excited. Consequently, N slices can be simultaneously acquired  without any SNR penalty other than g‐factor reconstruction noise. As the use of SMS typically involves reductions in the repetition time well below the T1 of the tissue of interest, the available longitudinal steady state magnetization for signal formation will, however, be somewhat lower. SNR optimal acquisitions of short‐TR SMS EPI, therefore, require excitations at the Ernst angle, which has the beneficial side effect that RF peak power and SAR can be considerably reduced. Also in this regard, SMS has some of the favorable properties of 3D sampling.SMS acquisitions share the SNR benefits of 3D sampling that arise due to Fourier averaging. This improves SNR efficiency by Gradient and RF phase encoding for effecting slice shifts in controlled aliasing are mathematically equivalent as discussed in the previous section, however, their applicability depends on the type of sequence. RF phase encoding is not feasible in echo‐train sequences that acquire multiple or all k‐space lines per excitation, which will, therefore, all carry the same phase. In single‐shot EPI or RARE/TSE sequences, any phase pattern between lines can, however, be achieved by the application of gradient blips between successive lines along the readout. Use of RF encoding in a single‐shot RARE type sequence is in principle possible by using the appropriate slice specific phase cycles by means of the refocusing pulses, but this is somewhat impractical, and more importantly, it will be incompatible with the Carr‐Purcell‐Meiboom‐Gill condition. For segmented echo train sequences, there is some potential for RF encoding but with limited flexibility, by cycling the RF phase between EPI segments A further practical consideration is that the phase imposed by an RF pulse has no spatial dependence, whereas a z‐gradient blip always imposes a phase that is linearly proportional to the blip moment and distance away from the isocenter; therefore, there will be a constant shift between equidistant neighboring slices, while RF encoding in principle allows for any arbitrary individual phase schedule to be given to the simultaneous slices. For constant interslice shifts, it is always possible to replace RF encoding by gradient blips, and in many cases this may be easier to implement in the sequence code. It is self‐evident that more complex 3D aliasing patterns, e.g., due to spiral or wave‐CAIPI readouts can only be achieved by the use of gradients.A further consideration is that the gradient blips will cause some through slice dephasing. This may generally be neglected for the typical slice thicknesses used in 2D imaging, but may be a consideration if SMS is applied to multislab 3D acquisitions.Just as standard pMRI, SMS acquisitions require reference data to successfully separate the simultaneous slice signals. In applications that acquire many volumes in a time series , the reference data for slice reconstruction usually consists of a separate fully‐sampled multiple slice scan. In this situation, a high quality reference dataset can be obtained using the same acquisition sequence and readout module because it only takes up a small fraction of the total scan time. For structural (single volume) slice‐accelerated imaging, the acquisition of a fully sampled reference dataset with the same sequence is not an option. A practical way to acquire single‐slice reference data quickly, and without dead time and SNR loss due to magnetization preparation such as inversion recovery, is the use of FLASH calibration scans, as the reconstruction algorithms described in Section 3 are either independent of or very robust against differences in contrast between the imaging and calibration data EPI acquisitions are prone to N/2 Nyquist ghosting artifacts, due to eddy current delays in the alternating readout gradients leading to nonalignment of the odd and even k‐space lines. Similar to the problematic interaction of residual N/2 ghosting with in‐plane acceleration factors that are multiples of two, this causes challenges for SMS reconstruction, where the Nyquist ghosting resembles, and hence becomes inseparable from, the intended effect of CAIPI slice shifts by FOV/2. The particular challenge for SMS is that ghosting cannot be fully corrected for, before unaliasing the slices, because the degree of N/2 ghosting varies by slice due to the spatial dependence of the eddy currents. As a solution, it was proposed in Setsompop et al For EPI calibration scans in case of in‐plane acceleration, it is desirable to match the echo‐spacing or the imaging and calibration scan for them to have the same phase evolutions and point spread (distortion). If this is not the case, the GRAPPA kernel or coil sensitivity profiles derived from the calibration data may not result in a clean reconstruction, causing residual artifacts particularly in regions of large B0 inhomogeneity. In a typical implementation, this is achieved by acquiring the ACS data in a segmented manner , at a TR time interval so as to remain in the steady state. A major concern here is motion or breathing occurring during such segmented reference acquisition, which can have a serious effect on the quality of the subsequent reconstruction. This has been addressed by using the FLEET technique (fast low‐angle excitation echo‐planar technique) Similar to in‐plane pMRI, imperfect SMS reconstruction results in residual aliasing artifacts. In the context of SMS imaging, residual aliasing often originates from different slices and thus is sometimes referred to as “slice leakage.” This has received much attention especially in the context of EPI, because residual aliasing in SMS fMRI data is more apparent than in in‐plane accelerated scans. Any temporal disparity within a calibration dataset for slice and in‐plane unfolding can significantly reduce the quality of parallel imaging reconstructions as shown in the context of in‐plane acceleration by Polimeni et al Finally, the impact of residual aliasing depends on the application. In anatomical imaging, residual in‐plane aliasing that originates from the same imaging plane is typically easy to interpret, and is unlikely to cause misinterpretations. SMS imaging, however, is currently most commonly used for (resting state) fMRI and diffusion imaging of the brain. These methods analyze data for connections across the entire brain and spurious correlations due to residual aliasing can easily be mistaken for long‐range connectivity.The computational demand of SMS reconstructions is still an obstacle to some applications such as real‐time fMRI, and high‐resolution EPI acquisitions with high in‐plane and/or slice acceleration factors often suffer considerable reconstruction delays on standard vendor reconstruction hardware. This is being addressed by code optimization, GPU implementations, and use of high‐end hardware. In particular, the use of coil compression now plays an important role in effectively reducing the number of channels, thereby drastically lowering computational demand. This can be achieved by PCA approaches, or by explicitly exploiting the spatially varying coil sensitivities along the nonundersampled (the readout) encoding direction in Cartesian acquisitions However, it remains important to take the computational burden into account when implementing SMS reconstruction. If implementation on the scanner for online reconstruction cannot easily be achieved, researchers might consider interfacing with external computational resources such as the Gadgetron framework http://www.humanconnectome.org) gave a boost to the acquisition techniques for fMRI and DTI, and has facilitated the development and dissemination of SMS acquisition within the neuroimaging community. While the availability of SMS implementations is still limited and the process of sequence‐ and reconstruction implementation often needs to be done in‐house, mature SMS EPI customer solutions for the dominant commercial platforms can be obtained from some research labs under sharing agreements, or as a third party commercial software add‐on.To the authors' knowledge, no product implementations of SMS are being offered by the MRI vendors at the time of writing. However, the early phase of the Human Connectome project  In addition, the increase in the  degrees‐of‐freedom allows the application of advanced analysis strategies such as temporal independent component analysis or ICA A detailed assessment of the benefits for fMRI of using SMS is not straightforward as many parameters influence performance. One would have to include the benefits of the excitation of a larger volume (as mentioned in the Introduction section) and the larger number of time points, which are counteracted by the noise introduced during reconstruction as already described in the section Reconstruction Methods. Furthermore, a reduced magnetization is available due to the much shorter TR compared with tissue T1 even if the optimal flip angle (Ernst angle) is used, which impacts the image SNR. To what extend this reduces the temporal SNR in fMRI acquisitions depends on the relative contribution of physiological noise: typical fMRI acquisitions are physiological noise dominated, allowing rather high MB acceleration factors The SMS approach is particularly interesting for SE‐EPI in fMRI, as this is an inherently slow method that needs a much longer TE (approximately two‐fold) compared with GE for optimal SE BOLD contrast Most modern diffusion weighted imaging is performed with DW‐EPI. It was, hence, one of the core beneficiaries alongside fMRI from the advent of SMS imaging To reduce peak power, it has been proposed to split the refocusing pulse into two sequential but overlapping pulses This review has attempted to provide a comprehensive snapshot of the state of the art of SMS methodology, with particular emphasis on SMS excitation, reconstruction, and applications. Much of the material presented will remain valid and relevant, but as SMS is anticipated to be a dynamic and rapidly developing field for some time, further important developments can be expected. With vendors rapidly adopting the technique, its establishment in routine clinical application in the near future seems certain. A series of first studies on SMS cardiac imaging has shown great promise for applications below the neck It was not until it was proven beneficial for fMRI in 2010 The recent literature has indicated that parallel‐transmit technology will play an increasingly important role, especially at ultrahigh field strengths. A further aspect of practical relevance will remain the refinement of suitable reference scans for calibrating the reconstruction, as the quality and integrity of the calibration data are essential especially for highly undersampled scans.In conclusion, SMS imaging can offer both significantly accelerated data acquisition, and reduced RF‐power deposition for a broad range of MRI applications. Its position as a cornerstone of modern MRI seems assured.


Although health policy makers call for the transformation of health care organizations to health literacy responsive ones, there is limited evidence on the care experiences of patients with limited health literacy skills (HL) in respect to health care quality. We explored if HL and patient-reported experiences regarding access to care and support in care-coordination in primary care organizations (PCO) have an impact on patients satisfaction with the care received by their personal general practitioner (GP).A nationwide representative survey was administered in a random sample of 1125 German adults. Binary logistic regression analyses were performed to determine whether HL and perceived access to and coordination of care were associated with satisfaction with care received in primary care adjusting for demographics and health status.β= 1.858; 2.032 p < 0.001) frequent support in care coordination by the general practitioner  as well as sufficient HL  were independent predictors of a higher satisfaction with care received in the general practice.In the unadjusted as well as adjusted model, better accessibility of the primary care practice (German adults with sufficient HL and positive experiences regarding care coordination and access to care are more satisfied with care received by their personal general practitioner. This result is from major importance for primary care organizations intending to transform their processes and structures to respond to the health literacy needs of their patients more effectively. The principles of equality and quality in health care provision are becoming the tipping points of health policy agendas worldwide , 2. The In our study, we will fill this research gap by performing a nationwide representative survey among the German adult population to explore if health literacy skills and patient-reported experiences in regard to access to care and support in care-coordination in the primary care setting have an impact on patients overall satisfaction with the care received by their personal general practitioner (GP).N = 1125) out of the overall sample members that could be contacted (N = 10.300). Since the survey was non-medical, there was no ethical approval required from the Ethical Review Board of the Medical Faculty of the University of Cologne, Germany. Participation in the survey was voluntary. Written informed consent was obtained from every participant before the questionnaire was answered. Confidentiality was maintained by data coding to eliminate the identification of data with personal information.The study involves computer-assisted telephone interviews with a nationally representative random sample of adults aged 18 and older living in Germany. Data was derived from the 2013 Commonwealth Fund International Health Policy Survey. The sample was contacted from February to May 2013 by random-digit dialing of both landlines and mobile phones covering whole Germany. Up to eight calls were made to establish contact. The responders were 11.0 %, defined as completed interviews , migration status and insurance type (public/private). Educational attainment was categorized according to the International Standard Classification of Education (ISCED) organizing educational attainment in three levels  . MigratiSelf-rated health status was assessed using one item asking “In general, how would you describe your own health?”. The item was answered on a five point Likert scale ranging from “poor” to “excellent”. In addition, a more objective indicator was added asking if someone was diagnosed suffering from a chronic condition such as diabetes, coronary artery disease, hypertension, asthma, or a depression. For the analysis self-rated health status  as well as was number of chronic conditions  were analyzed as binary outcomes.Health literacy was measured using a one-item screener retrieved from the Brief Health Literacy Screen (BHLS), a verbally administered self-report measure of functional health literacy. The screener item was developed by Chew and colleagues and has been validated against widely used measures of health literacy , 31 acroPerceived satisfaction with the care received by the general practitioner was measured using the item “How do you rate the overall medical care received in the last 12 months by your general practitioner?”. Response was assessed on a five point Likert scale ranging from “1 = poor” to “5 = excellent”. The item was analyzed as a binary outcome .Perceived accessibility of the general practice was assessed using the item “When you call your regular doctor’s office with a medical concern during regular practice hours, how often do you get an answer that same day?”. Response was assessed on a five point Likert scale ranging from “always” to “never”. The item was analyzed as a binary outcome .Perceived support in care coordination was measured using the item “How often does your regular doctor or someone in your doctor’s practice help coordinate or arrange the care you receive from other doctors and places?”. Response was assessed on a five point Likert scale ranging from “always” to “never”. The item was analyzed as a binary outcome .p < 0.05.Demographic data was analyzed using means, frequencies, and cross tabulations to calculate descriptive statistics. Associations between the outcome  and predictor variables  were examined by conducting bivariate analysis using chi-squared tests for independence. The main study hypothesis was examined by applying binary logistic regression analyses. The dichotomized item assessing the satisfaction with the care received by the general practitioner served as the dependent variable. We compared an unadjusted model with a sequential model that controlled for age, gender, educational attainment, migration status, self-rated health and number of chronic conditions. Missing values for a variable were not included in analysis using that variable. Data was analyzed with SPSS version 21. Statistical significance was assessed as Table p < 0.001). Sufficient health literacy skills were also related to reporting satisfaction with the care received by the GP (p < 0.05).As presented in Table p < 0.01) received in the general practice.Table Although patient satisfaction with health care is recognized as an important dimension of health care quality  insightsOur findings support the notion that prompt access to care as well as comprehensive care coordination are key elements of high performing primary care organizations, subsequently having an impact on patient experiences with health care . Prior sWhile there has been extensive research on patient reported experiences on provider related determinants of care quality , patientOur finding that health literacy plays a significant role alongside provider related care factors has considerable implications for the future development of primary care organizations. Therefore, primary care organizations aiming to deliver care in a way that patient satisfaction is improved need to address the issue of limited health literacy by transforming there organizational processes and structures according to the respective needs of patients , 15 to iThis national study has several strengths that should be mentioned. First, it includes representative data of the German adult population obtained by generating a random sample. Second, it uses survey items developed in a scientifically rigorous process. Additionally the measurement approach to assess the outcome variable by asking to “think of care received by the personal GP in the last 12 months” is deemed appropriate since nearly all respondents had a personal GP they consulted on a regular basis.The study limitations include the use of self-reported data to assess health care quality. Although this approach is a valuable way to assess the quality of care, objective measures are preferable . In addiGerman adults with sufficient health literacy skills and positive experiences regarding care coordination and access to care are more satisfied with care received by their personal general practitioner. This result is from major importance for primary care organizations intending to transform their processes and structures to respond to the health literacy needs of their patients more effectively. In addition, it highlights the need for the establishment of new care models and frameworks in primary care aliening the current approaches with novel techniques that address the health literacy needs of populations in need for care.


Bolsa Família Program, the Brazilian conditional cash transfer program (Bolsa Família Program). The aim of this study was to examine the oral health care and promotion provided by the Family Health Teams to children and caregivers covered by the Bolsa Família Program. Data was collected through interviews with three groups of participants: 1) dentists working for the Family Health Program; 2) Family Health Program professionals supervising the Bolsa Família Program health conditionalities (Bolsa Família Program supervisors); and 3) parents/caregivers of children covered by the Bolsa Família Program. A pretested questionnaire included sociodemographic, Bolsa Família Program, oral health promotion, dental prevention and dental treatment questions. The results showed that most dentists performed no systematic efforts to promote oral health care to children covered by the Bolsa Família Program  or to their parents/caregivers . Many dentists (33.8%) did not provide oral health care to children covered by the Bolsa Família Program because they felt it was beyond their responsibilities. Nearly all Bolsa Família Program supervisors  supported the inclusion of oral health care in the health conditionality of the Bolsa Família Program, but 82.4% (n = 61) stated they did not promote oral health activities to children covered by the Bolsa Família Program. Children in the routine care setting were more often referred to dentists than children covered by the Bolsa Familia Program (p≤0.001). Parents/caregivers  agreed that oral health care is important and 99.5% (n = 382) would like their children to be seen regularly. Conclusions: No collaboration was observed between the Bolsa Família Program and the Family Health Program with regard to the provision of oral health care. Making oral health care a Bolsa Família Program conditionality may reduce oral health care inequalities for extreme poor children under seven in Brazil.Over the last decade, there has been a great improvement in the oral health of Brazilians. However, such a trend was not observed among five-year-old children. Dental caries are determined by the interplay between biological and behavioral factors that are shaped by broader socioeconomic determinants. It is well established that dental disease is concentrated in socially disadvantaged populations. To reduce social and health inequalities, the Brazilian government created Family Health Program (ESF), and the  The field of dentistry has over the past century witnessed numerous advances in research and biomedical technology, leading to improvements in health and overall well-being worldwide . HoweverThe prevalence of dental caries is strongly shaped by the social determinants of health. In general, socioeconomically disadvantaged communities present higher levels of dental caries,  in part The burden of dental disease is highly concentrated in socially disadvantaged populations, especially in the Northeast of Brazil, one of the poorest regions of the country ,7. DentaEstratégia Saúde da Família—ESF), and the Bolsa Família Program (PBF), the Brazilian Conditional Cash Transfer (CCT) Program. The Family Health Program is the primary health care strategy implemented by the Brazilian universal health care system,  were performed on: 1) the willingness to include oral health conditionality in the Bolsa Família Program by sociodemographics; 2) the development of oral health promotion activities by sociodemographics. Additionally, we assessed if there were differences regarding provision of oral health care among dentists who only work at Family Health Program and those who work a third shift elsewhere .Data were analyzed using the software SPSS 20.0 . The study protocol was previously approved by the research ethics committee of the Ceará State University (UECE). All participants gave their informed written consent. Univariate descriptive statistics on sociodemographics, provision of oral health care, knowledge of the Bolsa Família Program supervisors and 384 parents/caregivers). The dentists were aged 38.1±7.3 years on average (range:30–61); most were female  and most were specialists , with Family Health as the most frequently reported specialty . Many  had worked for the Family Health Program for over 10 years. Over half the dentists  did not work exclusively for the Family Health Program  or their parents/caregivers  , the infrastructure, human resources and dental supplies required for such actions were not available in the workplace (Approximately 83% (n = 61) of the dentists considered the PBF important for childrenʼs health. Most were aware of  and agreed with  the PBF conditionalities . The vas;n = 55) . Many deorkplace .Bolsa Família Program supervisors were predominantly nurses  and female . The average age in this group was 41.9±9.2 years (range:28–65)  agreed with the inclusion of oral health care in the conditionality of the Bolsa Família Program , but 63.7% (n = 47) reported referring children covered by the Bolsa Família Program under seven years old for dental care. However, children in the routine care setting were more often referred than children covered by the Bolsa Família Program  (e:28–65) . Nearly  Program , but 82.p≤0.001) .Bolsa Família Program . Practically all parents/caregivers  agreed that oral health care is important and 99.7% (n = 383) would like their children to be seen regularly by a dentist (Parents/caregivers were aged 33.7±9.5 years on average (range:16–69) and approximately one third  were not married. Many  were elementary school dropouts. Almost all were women  and 85.1% (n = 327) identified themselves as the mother of the child covered by the  Program . Most pa dentist .Bolsa Família Program are not in school yet, do not attend pre-school, and therefore would be out of reach of these programs. In addition, only 25.7% of dentists reported developing these activities outside the school and kindergarten,  and an even lower proportion of dentists (6.8%) reported developing oral health promotion activities with children covered by the Bolsa Família Program  targeting all children are some of the Family Oral Health team duties, very few dentists include such activities in their work routine. Only 43% of dentists interviewed reported that they developed school-based oral health promotion activities. It is important to note that most children covered by the  Program .Bolsa Família Program was deemed desirable by 88.8% (n = 341) of the interviewed parents/caregivers  performed no systematic efforts to provide oral health promotion or prevention to parents/caregivers of children covered by the Bolsa Família Program. Many of the dentists  mentioned lack of integration between the Bolsa Família Program and the Family Health Program as the main reason for not developing oral health promotion or prevention activities. Many of the Bolsa Família Program supervisors stated they had never thought about it   and ;n = 26) .Bolsa Família Program are important” and “oral health care should be made a Bolsa Família Program conditionality” . The variables “agree with the existence of health-related conditionalities” and “agree with the inclusion of oral health care in the conditionality of the Bolsa Família Program” were significantly related (p = 0.002), but no relation was observed between the variables “believes that the infrastructure of the health care facility is appropriate for oral health services” and “agrees with the inclusion of oral health care in the conditionality of the Bolsa Família Program” (p = 0.361). When comparing dentists sorking exclusively for the Family Health Program to those working a third shift elsewhere , a significant difference  was found regarding “taking advantage of regular visits to the health unit by children covered by the Bolsa Família Program to provide them with oral health care ”, where those who also work elsewhere, are more likely to perform such care than those who only work at the Family Health Program. When comparing orthodontists and/or cosmetic dentists with all other dentists working for Family Health Program, it was noted that the former were less likely to perform health promotion and preventive activities for children outside daycare , as well as seem to know less about BF conditionalities  than the latter.When testing for correlations between the variables in the dentist group, a significant relationship was noted between the variables “oral health care check-ups for children covered by the Bolsa Família Program. Studies have shown that the positive results of the Bolsa Família Program are to some extent associated with compliance to the Bolsa Família health conditionality, which is conducted by Family Health Program teams in the public primary health care facilities [Bolsa Família become considerably less effective [Bolsa Família Program. The present study is an attempt to fill this gap.This is the first study to evaluate the provision of oral health care by the Family Health Program to children under seven years old covered by the cilities , 25. In cilities , the quaffective . Howeverffective . As for Bolsa Família Program [Bolsa Família Program (4.77) is almost twice the average for Northeastern Brazil, which displays the country’s worst oral health indicators [et al. [Bolsa Família Program also had the lowest levels of attendance to dental services [Children growing up in extreme poverty are generally at greater risk of developing chronic conditions such as stunting and dental caries and are more likely to suffer lifelong limitations imposed by such conditions . The con Program . For exarogram 4.7 is almo [et al.  who founservices . On the services , 30.Bolsa Família Program. While working a third shift was associated with increased engagement in oral health promotion activities, having an orthodontics and/or cosmetic dentistry specialty was associated with a lower engagement in oral health promotion activities. These results point out to the need of implementing continuing education programs for dentists that are not engaging in oral health promotion activities. This initiative could help dentists promote oral health, and improve the dental care currently provided for the community. It should be noted that dentists working for the Family Health Program generally do not perceive children covered by the Bolsa Família Program as a specific risk group, as such children often receive treatment through school campaigns and other initiatives without being identified as Bolsa Família Program recipients. The same pattern was observed for Bolsa Família Program supervisors. The latter provided more health promotion and prevention care, and referred more children for dental treatment in the routine care setting than when the children were identified as beneficiaries of the Bolsa Família Program.Our study found that the proportion of dentists including oral health promotion activities in their daily routine is very low. This proportion is even lower among dentists specifically targeting beneficiaries of the Bolsa Família Program should receive comprehensive oral health care, due to both their age  and socioeconomic vulnerability, these children were not prioritized in the family health dentists' work routine. This represents a missed opportunity to promote the oral health for this vulnerable group. The childrenʼs regular attendance of Public Primary Health Care facilities as part of the conditionality of the Bolsa Família Program may be used to increase access to oral health care. In addition, a change in priorities would make these children more accessible to Family Health Program professionals since many children under seven years are not enrolled in kindergarten or preschool and therefore do not benefit from Family Health Program-sponsored campaigns in public schools, when those are performed.Our results showed that although most dentists agreed that children under seven years covered by the Bolsa Família Program, and being aware of the opportunity for referral provided by the children’s regular contact with Family Health Program professionals, dentists made little or no effort to promote or provide oral health care to this risk group. One of the reasons given by a significant number of dentists and Bolsa Família Program supervisors was that they saw no close connection between the Family Health Program and the Bolsa Família Program and many had never considered giving special attention to this risk group. This finding reveals serious flaws in the working and planning processes of the Family Health Program when viewed in light of the tenets of the National Primary Health Care Policy (PNAB) [It is rather intriguing that, despite recognizing the urgent oral health care needs of children covered by the y (PNAB)  and the y (PNAB)  set fortBrazilian primary care is supported by the pillars of universality, accessibility, bonding, continuity, integration, accountability, humanization, equity and social participation. Brazil’s National Primary Health Care Policy fosters individual and collective health actions with the purpose of developing integrated care capable of positively impacting citizens’ health status, autonomy and social determinants of health towards greater equity .In accordance with the Brazilian’s National Oral Health Care and National Primary Health Care Policy’s guidelines, oral health teams should i) plan and provide effective oral health care  for all individuals, families and risk groups, ii) coordinate and participate in campaigns and projects of oral health promotion and prevention, and iii) collaborate with other Family Health Program professionals in the building of a multidisciplinary framework of integrated health care ,32. EarlBolsa Família Program, this outlook is obscured by an overemphasis on bureaucratic aspects and a lack of awareness of the essential social and political role of the Bolsa Família Program. The authors added that, on part of the Family Health Program, health-related Bolsa Família Program conditionalities translate into little more than the collection of statistical indicators, such as weight, height, vaccination status and breastfeeding indices. Many Family Health Program professionals do not think of the Bolsa Família Program as a potential key instrument for the promotion of health, let alone oral health. As for the latter, professional motivation and government pressure have been insufficient to explore the potential for this type of intervention and municipal agencies lack clear guidelines for the supervision of oral health promotion, prevention and treatment of children under seven covered by the Bolsa Família Program. Although the guidelines of the Bolsa Familia Program [The guidelines expounded above point to a Public Primary Health Care system centered on population health care needs. However, according to Ramos and Cuervo , at the  Program  recommenet al. [According to Adato et al. , though Bolsa Família Program are unlikely to receive regular oral health check-ups unless oral care is made a Bolsa Família Program conditionality and thus agreed with this proposal. However, the interviewees did not seem to be aware that the provision of oral health care to vulnerable groups  has always been a mandate of the Family Health Program. This raises the question of whether the inclusion of oral care in the conditionality of the PBF will bring about the desired change, and whether dental care is the only form of health service neglected by Family Health Program teams. The authors believe that, while desirable, the inclusion of dental care in the conditionality of the Bolsa Família Program may not solve the problem, but might instead strengthen the tendency to rely solely on rules and regulations to change behaviors and realities. Better results would likely be achieved by focusing efforts on the improvement of Public Primary Health Care infrastructure, continuing hands-on professional training, humanization and the ability to identify and satisfy population health care needs.Most of the interviewees expressed the belief that children covered by the Bolsa Família Program as a risk group, thus a priority, goes against their job description. Our findings not only confirm the relevance of including pediatric oral health care in the conditionality of the Bolsa Família Program, making the health care system more equitable, but, more importantly, allow to infer that significant changes in currently counterproductive processes and behaviors are unlikely to happen without continuing professional training of Family Health Program professionals in addition to an acute awareness of local population health care needs.Considering the formal commission of the Family Health Program to provide primary health care—including oral care—to the Brazilian population as a whole and the emphasis of the National Oral Health Care and National Primary Health Care Policys guidelines on population-based care, failure to identify children under seven years of age covered by the Conditionality in Conditional Cash Transfer Programs has the aim of helping the assisted population to develop human/social capital . HoweverEstratégia Saúde da Família) and the Bolsa Família Program (Programa Bolsa Família) with regard to the provision of oral health care for children under seven at public primary health care facilities in Fortaleza. No systematic oral health promotion and prevention initiatives were specifically directed at children covered by the Bolsa Família Program or their parents/caregivers.In this study, no collaboration was observed between the Family Health Program  inclusion of oral health care for children under seven years of age as a Bolsa Família Program conditionality; ii) improvements in Family Health Program organization and infrastructure (including human resources and supplies) to reflect National Primary Health Care Policy guidelines; iii) continued training of Family Health Program professionals to capacitate them towards the needs of children covered by the Bolsa Família Program, as well as ways to improve children oral health; iv) creation of coordination programs, at all public administrative levels , to enhance the interaction between Bolsa Família and Family Health Programs towards actions aimed at Bolsa Família Program families—allowing optimization of resources and better health outcomes for the population; and v) enforcement of working and planning processes in accordance with the National Primary Health Care Policy (PNAB) and the National Oral Health Care Policy (PNSB) guidelines.However, considering the protective effect of preventive and restorative oral health care in children, as well as the well-documented potentiating effect of intersectorality on health care outcomes in general, a closer interaction between the