The health and well-being of older women living alone in the United Kingdom and beyond: a scoping review.

In the United Kingdom (UK), women are more likely to live alone in later life. Social factors such as household composition have been shown to affect health and wellbeing as we age. The health and well-being of older women who live alone are of interest to researchers, care providers, health organizations, and policymakers. This article contributes to the literature by detailing a scoping review, establishing the current evidence in this field. The purpose and context of the review are given. The methodology and resulting data are described. Gaps in the literature and implications for practice and research are given.

Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial.

BACKGROUND: This multicentre, randomised, double-blinded, placebo-controlled, phase II/III trial aimed to evaluate an oral THC:CBD (tetrahydrocannabinol:cannabidiol) cannabis extract for prevention of refractory chemotherapy-induced nausea and vomiting (CINV). Here we report the phase II component results. PATIENTS AND METHODS: Eligible patients experienced CINV during moderate-to-high emetogenic intravenous chemotherapy despite guideline-consistent antiemetic prophylaxis. Study treatment consisted of one cycle of 1-4 self-titrated capsules of oral THC 2.5 mg/CBD 2.5 mg (TN-TC11M) three times daily, from days -1 to 5, and 1 cycle of matching placebo in a crossover design, then blinded patient preference for a third cycle. The primary end point was the proportion of participants with complete response during 0-120 h from chemotherapy. A total of 80 participants provided 80% power to detect a 20% absolute improvement with a two-sided P value of 0.1. RESULTS: A total of 81 participants were randomised; 72 completing two cycles were included in the efficacy analyses and 78 not withdrawing consent were included in safety analyses. Median age was 55 years (range 29-80 years); 78% were female. Complete response was improved with THC:CBD from 14% to 25% (relative risk 1.77, 90% confidence interval 1.12-2.79, P = 0.041), with similar effects on absence of emesis, use of rescue medications, absence of significant nausea, and summary scores for the Functional Living Index-Emesis (FLIE). Thirty-one percent experienced moderate or severe cannabinoid-related adverse events such as sedation, dizziness, or disorientation, but 83% of participants preferred cannabis to placebo. No serious adverse events were attributed to THC:CBD. CONCLUSION: The addition of oral THC:CBD to standard antiemetics was associated with less nausea and vomiting but additional side-effects. Most participants preferred THC:CBD to placebo. Based on these promising results, we plan to recruit an additional 170 participants to complete accrual for the definitive, phase III, parallel group analysis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12616001036404; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=370473&isReview=true.

Testicular tissue cryopreservation: 8 years of experience from a coordinated network of academic centers.

STUDY QUESTION: Is it feasible to disseminate testicular tissue cryopreservation with a standardized protocol through a coordinated network of centers and provide centralized processing/freezing for centers that do not have those capabilities? SUMMARY ANSWER: Centralized processing and freezing of testicular tissue from multiple sites is feasible and accelerates recruitment, providing the statistical power to make inferences that may inform fertility preservation practice. WHAT IS KNOWN ALREADY: Several centers in the USA and abroad are preserving testicular biopsies for patients who cannot preserve sperm in anticipation that cell- or tissue-based therapies can be used in the future to generate sperm and offspring. STUDY DESIGN, SIZE, DURATION: Testicular tissue samples from 189 patients were cryopreserved between January 2011 and November 2018. Medical diagnosis, previous chemotherapy exposure, tissue weight, and presence of germ cells were recorded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human testicular tissue samples were obtained from patients undergoing treatments likely to cause infertility. Twenty five percent of the patient's tissue was donated to research and 75% was stored for patient's future use. The tissue was weighed, and research tissue was fixed for histological analysis with Periodic acid-Schiff hematoxylin staining and/or immunofluorescence staining for DEAD-box helicase 4, and/or undifferentiated embryonic cell transcription factor 1. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of fertility preservation patients was 7.9 (SD = 5) years and ranged from 5 months to 34 years. The average amount of tissue collected was 411.3 (SD = 837.3) mg and ranged from 14.4 mg-6880.2 mg. Malignancies (n = 118) were the most common indication for testicular tissue freezing, followed by blood disorders (n = 45) and other conditions (n = 26). Thirty nine percent (n = 74) of patients had initiated their chemotherapy prior to undergoing testicular biopsy. Of the 189 patients recruited to date, 137 have been analyzed for the presence of germ cells and germ cells were confirmed in 132. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive study of testicular tissues obtained from patients who were at risk of infertility. The function of spermatogonia in those biopsies could not be tested by transplantation due limited sample size. WIDER IMPLICATIONS OF THE FINDINGS: Patients and/or guardians are willing to pursue an experimental fertility preservation procedure when no alternatives are available. Our coordinated network of centers found that many patients request fertility preservation after initiating gonadotoxic therapies. This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of those spermatogonia was not tested. STUDY FUNDING/COMPETING INTEREST(S): Support for the research was from the Eunice Kennedy Shriver National Institute for Child Health and Human Development grants HD061289 and HD092084, the Scaife Foundation, the Richard King Mellon Foundation, the Departments of Ob/Gyn & Reproductive Sciences and Urology of the University of Pittsburgh Medical Center, United States-Israel Binational Science Foundation (BSF), and the Kahn Foundation. The authors declare that they do not have competing financial interests.

Localised grey matter atrophy in multiple sclerosis is network-based: a coordinate-based meta-analysis.

AIM: To test the network degeneration hypothesis in multiple sclerosis (MS) with a two-stage coordinate-based meta-analysis by: (1) characterising regional selectivity of grey matter (GM) atrophy and (2) testing for functional connectivity involving these regions. MATERIALS AND METHODS: Meta-analytic sources included 33 journal articles (1,666 MS patients and 1,269 healthy controls) with coordinate-based results from voxel-based morphometry analysis demonstrating GM atrophy. Mass univariate and multivariate coordinate-based meta-analyses were performed to identify a convergent pattern of GM atrophy and determine inter-regional co-activation (as a surrogate of functional connectivity), with anatomical likelihood estimation and functional meta-analytic connectivity modelling, respectively. RESULTS: Localised GM atrophy was demonstrated in the thalamus, putamen, caudate, sensorimotor cortex, insula, superior temporal gyrus, and cingulate gyrus. This convergent pattern of atrophy displayed significant inter-regional functional co-activations. CONCLUSION: In MS, GM atrophy was regionally selective, and these regions were functionally connected. The meta-analytic model-based results of this study are intended to guide future development of quantitative neuroimaging markers for diagnosis, evaluating disease progression, and monitoring treatment response.

Definition and characterization of an extended multiple-demand network.

Neuroimaging evidence suggests that executive functions (EF) depend on brain regions that are not closely tied to specific cognitive demands but rather to a wide range of behaviors. A multiple-demand (MD) system has been proposed, consisting of regions showing conjoint activation across multiple demands. Additionally, a number of studies defining networks specific to certain cognitive tasks suggest that the MD system may be composed of a number of sub-networks each subserving specific roles within the system. We here provide a robust definition of an extended MDN (eMDN) based on task-dependent and task-independent functional connectivity analyses seeded from regions previously shown to be convergently recruited across neuroimaging studies probing working memory, attention and inhibition, i.e., the proposed key components of EF. Additionally, we investigated potential sub-networks within the eMDN based on their connectional and functional similarities. We propose an eMDN network consisting of a core whose integrity should be crucial to performance of most operations that are considered higher cognitive or EF. This then recruits additional areas depending on specific demands.

BrainMap VBM: An environment for structural meta-analysis.

The BrainMap database is a community resource that curates peer-reviewed, coordinate-based human neuroimaging literature. By pairing the results of neuroimaging studies with their relevant meta-data, BrainMap facilitates coordinate-based meta-analysis (CBMA) of the neuroimaging literature en masse or at the level of experimental paradigm, clinical disease, or anatomic location. Initially dedicated to the functional, task-activation literature, BrainMap is now expanding to include voxel-based morphometry (VBM) studies in a separate sector, titled: BrainMap VBM. VBM is a whole-brain, voxel-wise method that measures significant structural differences between or within groups which are reported as standardized, peak x-y-z coordinates. Here we describe BrainMap VBM, including the meta-data structure, current data volume, and automated reverse inference functions (region-to-disease profile) of this new community resource. CBMA offers a robust methodology for retaining true-positive and excluding false-positive findings across studies in the VBM literature. As with BrainMap's functional database, BrainMap VBM may be synthesized en masse or at the level of clinical disease or anatomic location. As a use-case scenario for BrainMap VBM, we illustrate a trans-diagnostic data-mining procedure wherein we explore the underlying network structure of 2,002 experiments representing over 53,000 subjects through independent components analysis (ICA). To reduce data-redundancy effects inherent to any database, we demonstrate two data-filtering approaches that proved helpful to ICA. Finally, we apply hierarchical clustering analysis (HCA) to measure network- and disease-specificity. This procedure distinguished psychiatric from neurological diseases. We invite the neuroscientific community to further exploit BrainMap VBM with other modeling approaches.

Characterisation of meta-analytical functional connectivity in progressive supranuclear palsy.

AIM: To characterise the meta-analytical functional connectivity patterns in progressive supranuclear palsy (PSP) and compare them to idiopathic Parkinson's disease (IPD). MATERIALS AND METHODS: It was previously reported that PSP and IPD showed distinct regions of brain atrophy based on voxel-based morphometry (VBM) meta-analysis. Using these regions as seeds, healthy control data were referenced to create and statistically compare meta-analytical functional connectivity maps of PSP and IPD. RESULTS: Some overlap was noted between the two diseases, including within the thalamus, striatum, and prefrontal cortex; however, the PSP seeds demonstrated more extensive functional co-activity throughout the brain, particularly within the midbrain, precentral gyrus, parietal cortex, basal ganglia, and cerebellum. CONCLUSION: These findings may help guide future longitudinal studies in the development of new functional imaging biomarkers for diagnosis and assessing treatment response.

Implementation errors in the GingerALE Software: Description and recommendations.

Neuroscience imaging is a burgeoning, highly sophisticated field the growth of which has been fostered by grant-funded, freely distributed software libraries that perform voxel-wise analyses in anatomically standardized three-dimensional space on multi-subject, whole-brain, primary datasets. Despite the ongoing advances made using these non-commercial computational tools, the replicability of individual studies is an acknowledged limitation. Coordinate-based meta-analysis offers a practical solution to this limitation and, consequently, plays an important role in filtering and consolidating the enormous corpus of functional and structural neuroimaging results reported in the peer-reviewed literature. In both primary data and meta-analytic neuroimaging analyses, correction for multiple comparisons is a complex but critical step for ensuring statistical rigor. Reports of errors in multiple-comparison corrections in primary-data analyses have recently appeared. Here, we report two such errors in GingerALE, a widely used, US National Institutes of Health (NIH)-funded, freely distributed software package for coordinate-based meta-analysis. These errors have given rise to published reports with more liberal statistical inferences than were specified by the authors. The intent of this technical report is threefold. First, we inform authors who used GingerALE of these errors so that they can take appropriate actions including re-analyses and corrective publications. Second, we seek to exemplify and promote an open approach to error management. Third, we discuss the implications of these and similar errors in a scientific environment dependent on third-party software. Hum Brain Mapp 38:7-11, 2017. © 2016 Wiley Periodicals, Inc.

Double-blind randomized controlled trial of letrozole versus clomiphene citrate in subfertile women with polycystic ovarian syndrome.

STUDY QUESTION: Would letrozole as a primary ovulation induction agent generate better pregnancy rates than clomiphene citrate (CC) in subfertile women with anovulatory polycystic ovarian syndrome (PCOS)? SUMMARY ANSWER: Participants receiving letrozole as a primary treatment achieved a significantly (P = 0.022) higher clinical pregnancy rate per patient (61.2%) compared to CC (43.0%). WHAT IS KNOWN ALREADY: According to a recent Cochrane systematic review (2014), letrozole appears to improve live-birth (LB) and pregnancy rates in anovulatory women with PCOS, compared to CC. However, the review concluded that the quality of evidence was low due to poor reporting of study methods and possible publication bias. STUDY DESIGN, SIZE, DURATION: This double-blind randomized controlled trial (RCT) included 159 participants between April 2007 and June 2014. Subjects were randomly allocated to either CC (n = 79) or letrozole (n = 80) in a 1:1 ratio. Both drugs were encapsulated to look identical. Randomization was performed in mixed blocks and stratified by patients' BMI (<30 and 30-35 kg/m2). PARTICIPANTS/MATERIALS, SETTING, METHODS: The trial included subfertile women diagnosed with PCOS. Treatment started with one tablet (CC 50 mg, letrozole 2.5 mg) increasing to two in non-responders and continuing until pregnancy or for up to six ovulatory cycles. Non-responders were crossed over to the other treatment after a 6-week break. Cycles were initially monitored with ultrasound follicle tracking then mid-luteal serum progesterone measurement in subsequent cycles. MAIN RESULTS AND THE ROLE OF CHANCE: Amongst the 159 participants included in the intention-to-treat analysis, four women conceived before treatment and six were lost-to-follow-up. The remaining 149 participants (74 on CC and 75 on letrozole) completed at least the first treatment. Women receiving letrozole achieved a significantly (P = 0.022; absolute difference [95% confidence interval] 18% [3-33%]) higher pregnancy rate (61.%) than those on CC (43%). The median number of treatment cycles received until pregnancy was significantly (log rank P = 0.038) smaller with letrozole (4[3-5] cycles) compared to CC (6[4-7] cycles). LB rates were not statistically (P = 0.089) different between the two groups, although there was a trend towards higher rates on letrozole (48.8%) compared to CC (35.4%). After the crossover, pregnancy and LB rates on letrozole (n = 45; 28.9 and 24.4%, respectively) were not statistically (P = 0.539 and P = 0.601) different from CC (n = 31; 22.6 and 19.4%). LIMITATIONS, REASONS FOR CAUTION: One possible limitation of this trial may be the exclusion of PCOS women with BMI > 35 kg/m2, which would limit the applicability of the results in this subgroup of PCOS. However, this group of women are generally excluded from treatment in the majority of fertility centres, especially in Europe, due to the associated challenges and risks. WIDER IMPLICATIONS OF THE FINDINGS: The results of this trial are consistent with the recent Cochrane systematic review. However, with its robust design, the current RCT provides more valid and compelling evidence for the superiority of letrozole over CC as a primary ovulation induction agent in PCOS women with 40% increase in pregnancy rates and with a shorter time-to-pregnancy. Furthermore, the participants in this RCT are a good representation of subfertile PCOS population receiving fertility treatment in Europe and worldwide. The results are therefore globally generalizable for clinical practice. STUDY FUNDING/COMPETING INTEREST(S): This RCT was mainly funded by the R&D Funding Scheme of Derby Hospitals NHS Foundation Trust. The study also received funds from School of Medicine, University of Nottingham. The Trust R&D department was involved in the development of the protocol and the running of the trial. The trial was sponsored and monitored by the University of Nottingham. The authors have no conflicts of interest. TRIAL REGISTRATION NUMBER: www.Clinicaltrials.gov: NCT00478504. TRIAL REGISTRATION DATE: Registration was verified on 23/05/2007. DATE OF FIRST PATIENT'S ENROLMENT: 25/04/2007.

Developing and validating a new national remote health advice syndromic surveillance system in England.

Background: Public Health England (PHE) coordinates a suite of real-time national syndromic surveillance systems monitoring general practice, emergency department and remote health advice data. We describe the development and informal evaluation of a new syndromic surveillance system using NHS 111 remote health advice data. Methods: NHS 111 syndromic indicators were monitored daily at national and local level. Statistical models were applied to daily data to identify significant exceedances; statistical baselines were developed for each syndrome and area using a multi-level hierarchical mixed effects model. Results: Between November 2013 and October 2014, there were on average 19 095 NHS 111 calls each weekday and 43 084 each weekend day in the PHE dataset. There was a predominance of females using the service (57%); highest percentage of calls received was in the age group 1-4 years (14%). This system was used to monitor respiratory and gastrointestinal infections over the winter of 2013-14, the potential public health impact of severe flooding across parts of southern England and poor air quality episodes across England in April 2014. Conclusions: This new system complements and supplements the existing PHE syndromic surveillance systems and is now integrated into the routine daily processes that form this national syndromic surveillance service.

The symptom phenotype of oncology outpatients remains relatively stable from prior to through 1 week following chemotherapy.

Some oncology outpatients experience a higher number of and more severe symptoms during chemotherapy (CTX). However, little is known about whether this high risk phenotype persists over time. Latent transition analysis (LTA) was used to examine the probability that patients remained in the same symptom class when assessed prior to the administration of and following their next dose of CTX. For the patients whose class membership remained consistent, differences in demographic and clinical characteristics, and quality of life (QOL) were evaluated. The Memorial Symptom Assessment Scale (MSAS) was used to evaluate symptom burden. LTA was used to identify subgroups of patients with distinct symptom experiences based on the occurrence of the MSAS symptoms. Of the 906 patients evaluated, 83.9% were classified in the same symptom occurrence class at both assessments. Of these 760 patients, 25.0% were classified as Low-Low, 44.1% as Moderate-Moderate and 30.9% as High-High. Compared to the Low-Low class, the other two classes were younger, more likely to be women and to report child care responsibilities, and had a lower functional status and a higher comorbidity scores. The two higher classes reported lower QOL scores. The use of LTA could assist clinicians to identify higher risk patients and initiate more aggressive interventions.

Meta-connectomics: human brain network and connectivity meta-analyses.

Abnormal brain connectivity or network dysfunction has been suggested as a paradigm to understand several psychiatric disorders. We here review the use of novel meta-analytic approaches in neuroscience that go beyond a summary description of existing results by applying network analysis methods to previously published studies and/or publicly accessible databases. We define this strategy of combining connectivity with other brain characteristics as 'meta-connectomics'. For example, we show how network analysis of task-based neuroimaging studies has been used to infer functional co-activation from primary data on regional activations. This approach has been able to relate cognition to functional network topology, demonstrating that the brain is composed of cognitively specialized functional subnetworks or modules, linked by a rich club of cognitively generalized regions that mediate many inter-modular connections. Another major application of meta-connectomics has been efforts to link meta-analytic maps of disorder-related abnormalities or MRI 'lesions' to the complex topology of the normative connectome. This work has highlighted the general importance of network hubs as hotspots for concentration of cortical grey-matter deficits in schizophrenia, Alzheimer's disease and other disorders. Finally, we show how by incorporating cellular and transcriptional data on individual nodes with network models of the connectome, studies have begun to elucidate the microscopic mechanisms underpinning the macroscopic organization of whole-brain networks. We argue that meta-connectomics is an exciting field, providing robust and integrative insights into brain organization that will likely play an important future role in consolidating network models of psychiatric disorders.

Meta-analytic connectivity and behavioral parcellation of the human cerebellum.

The cerebellum historically has been thought to mediate motor and sensory signals between the body and cerebral cortex, yet cerebellar lesions are also associated with altered cognitive behavioral performance. Neuroimaging evidence indicates that the cerebellum contributes to a wide range of cognitive, perceptual, and motor functions. Here, we used the BrainMap database to investigate whole-brainco-activation patterns between cerebellar structures and regions of the cerebral cortex, as well as associations with behavioral tasks. Hierarchical clustering was performed to meta-analytically identify cerebellar structures with similar cortical co-activation, and independently, with similar correlations to specific behavioral tasks. Strong correspondences were observed in these separate but parallel analyses of meta-analytic connectivity and behavioral metadata. We recovered differential zones of cerebellar co-activation that are reflected across the literature. Furthermore, the behaviors and tasks associated with the different cerebellar zones provide insight into the specialized function of the cerebellum, relating to high-order cognition, emotion, perception, interoception, and action. Taken together, these task-basedmeta-analytic results implicate distinct zones of the cerebellum as critically involved in the monitoring and mediation of psychological responses to internal and external stimuli.

Neural architecture underlying classification of face perception paradigms.

We present a novel strategy for deriving a classification system of functional neuroimaging paradigms that relies on hierarchical clustering of experiments archived in the BrainMap database. The goal of our proof-of-concept application was to examine the underlying neural architecture of the face perception literature from a meta-analytic perspective, as these studies include a wide range of tasks. Task-based results exhibiting similar activation patterns were grouped as similar, while tasks activating different brain networks were classified as functionally distinct. We identified four sub-classes of face tasks: (1) Visuospatial Attention and Visuomotor Coordination to Faces, (2) Perception and Recognition of Faces, (3) Social Processing and Episodic Recall of Faces, and (4) Face Naming and Lexical Retrieval. Interpretation of these sub-classes supports an extension of a well-known model of face perception to include a core system for visual analysis and extended systems for personal information, emotion, and salience processing. Overall, these results demonstrate that a large-scale data mining approach can inform the evolution of theoretical cognitive models by probing the range of behavioral manipulations across experimental tasks.

Co-activation based parcellation of the human frontal pole.

Historically, the human frontal pole (FP) has been considered as a single architectonic area. Brodmann's area 10 is located in the frontal lobe with known contributions in the execution of various higher order cognitive processes. However, recent cytoarchitectural studies of the FP in humans have shown that this portion of cortex contains two distinct cytoarchitectonic regions. Since architectonic differences are accompanied by differential connectivity and functions, the frontal pole qualifies as a candidate region for exploratory parcellation into functionally discrete sub-regions. We investigated whether this functional heterogeneity is reflected in distinct segregations within cytoarchitectonically defined FP-areas using meta-analytic co-activation based parcellation (CBP). The CBP method examined the co-activation patterns of all voxels within the FP as reported in functional neuroimaging studies archived in the BrainMap database. Voxels within the FP were subsequently clustered into sub-regions based on the similarity of their respective meta-analytically derived co-activation maps. Performing this CBP analysis on the FP via k-means clustering produced a distinct 3-cluster parcellation for each hemisphere corresponding to previously identified cytoarchitectural differences. Post-hoc functional characterization of clusters via BrainMap metadata revealed that lateral regions of the FP mapped to memory and emotion domains, while the dorso- and ventromedial clusters were associated broadly with emotion and social cognition processes. Furthermore, the dorsomedial regions contain an emphasis on theory of mind and affective related paradigms whereas ventromedial regions couple with reward tasks. Results from this study support previous segregations of the FP and provide meta-analytic contributions to the ongoing discussion of elucidating functional architecture within human FP.

Statistical controversies in clinical research: scientific and ethical problems with adaptive randomization in comparative clinical trials.

BACKGROUND: In recent years, various outcome adaptive randomization (AR) methods have been used to conduct comparative clinical trials. Rather than randomizing patients equally between treatments, outcome AR uses the accumulating data to unbalance the randomization probabilities in favor of the treatment arm that currently is superior empirically. This is motivated by the idea that, on average, more patients in the trial will be given the treatment that is truly superior, so AR is ethically more desirable than equal randomization. AR remains controversial, however, and some of its properties are not well understood by the clinical trials community. MATERIALS AND METHODS: Computer simulation was used to evaluate properties of a 200-patient clinical trial conducted using one of four Bayesian AR methods and compare them to an equally randomized group sequential design. RESULTS: Outcome AR has several undesirable properties. These include a high probability of a sample size imbalance in the wrong direction, which might be surprising to nonstatisticians, wherein many more patients are assigned to the inferior treatment arm, the opposite of the intended effect. Compared with an equally randomized design, outcome AR produces less reliable final inferences, including a greatly overestimated actual treatment effect difference and smaller power to detect a treatment difference. This estimation bias becomes much larger if the prognosis of the accrued patients either improves or worsens systematically during the trial. CONCLUSIONS: AR produces inferential problems that decrease potential benefit to future patients, and may decrease benefit to patients enrolled in the trial. These problems should be weighed against its putative ethical benefit. For randomized comparative trials to obtain confirmatory comparisons, designs with fixed randomization probabilities and group sequential decision rules appear to be preferable to AR, scientifically, and ethically.

Incidental primary breast cancer detected on PET-CT.

The purpose of this study is to determine the incidence of primary breast cancer (PBC) detected on (18) F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) in patients with a known diagnosis of non-mammary malignancies. A database search was performed to identify patients with non-mammary malignancies who had undergone staging with FDG PET-CT at a single institution between September 2005 and September 2011 and with the word "breast" reported in the PET-CT dictation. Additional breast imaging studies, clinical data, and the final histopathology of the breast lesions were correlated with the PET-CT images. Of 1951 patients who underwent PET/CT, 440 incidental breast lesions were identified in 438 patients. Of these 440 lesions, 195 (45 %) were benign, 160 (37 %) malignant, and 85 (19 %) missing data. A total of 25 PBCs were diagnosed; with a median size of 1.8 cm (range 0.8-10.7 cm); and a median SUVmax of 4.4 (range 1.7-17.6). There were 19 invasive ductal cancers, 1 invasive lobular cancer, 2 papillary cancers, 1 tubular cancer, 1 sarcomatoid cancer, and 1 ductal carcinoma in situ. Eight patients had regional nodal disease. Mammography revealed the PBC in 19 of 23 tumors (83 %), sonography in 22 of 23 (96 %). Six percent (25 of 440) of incidental breast lesions identified on FDG PET-CT represent PBCs; more than half were at an early stage and potentially curable.

Access to surgical upper extremity care for people with tetraplegia: an international perspective.

STUDY DESIGN: Survey. OBJECTIVES: To determine whether upper extremity reconstruction in patients with tetraplegia is underutilized internationally and, if so, what are the barriers to care. SETTING: International-attendees of a meeting in Paris, France. METHODS: One hundred and seventy attendees at the Tetrahand meeting in Paris in 2010 were sent a 13-question survey to determine the access and utilization of upper limb reconstruction in tetraplegic patients in their practice. RESULTS: Respondents ranged the globe including North America, South America, Europe, Asia and Australia. Fifty-nine percent of respondents had been practicing for more than 10 years. Sixty-four percent of respondents felt that at least 25% of people with tetraplegia would be candidates for surgery. Yet the majority of respondents found that <15% of potential patients underwent upper extremity reconstruction. Throughout the world direct patient referral was the main avenue of surgeons meeting patients with peer networking a distant second. Designated as the top three barriers to this care were lack of knowledge of surgical options by patients, lack of desire for surgery and poor referral patterns to appropriate upper extremity surgeons. CONCLUSION: The results of this survey, of a worldwide audience, indicate that many of the same barriers to care exist regardless of the patient's address. This was a preliminary opinion survey and thus the results are subjective. However, these results provide a roadmap to improving access to care by improving patient education and interdisciplinary physician communication.

Neural network of cognitive emotion regulation--an ALE meta-analysis and MACM analysis.

Cognitive regulation of emotions is a fundamental prerequisite for intact social functioning which impacts on both well being and psychopathology. The neural underpinnings of this process have been studied intensively in recent years, without, however, a general consensus. We here quantitatively summarize the published literature on cognitive emotion regulation using activation likelihood estimation in fMRI and PET (23 studies/479 subjects). In addition, we assessed the particular functional contribution of identified regions and their interactions using quantitative functional inference and meta-analytic connectivity modeling, respectively. In doing so, we developed a model for the core brain network involved in emotion regulation of emotional reactivity. According to this, the superior temporal gyrus, angular gyrus and (pre) supplementary motor area should be involved in execution of regulation initiated by frontal areas. The dorsolateral prefrontal cortex may be related to regulation of cognitive processes such as attention, while the ventrolateral prefrontal cortex may not necessarily reflect the regulatory process per se, but signals salience and therefore the need to regulate. We also identified a cluster in the anterior middle cingulate cortex as a region, which is anatomically and functionally in an ideal position to influence behavior and subcortical structures related to affect generation. Hence this area may play a central, integrative role in emotion regulation. By focusing on regions commonly active across multiple studies, this proposed model should provide important a priori information for the assessment of dysregulated emotion regulation in psychiatric disorders.

Cytoarchitecture, probability maps and functions of the human frontal pole.

The frontal pole has more expanded than any other part in the human brain as compared to our ancestors. It plays an important role for specifically human behavior and cognitive abilities, e.g. action selection (Kovach et al., 2012). Evidence about divergent functions of its medial and lateral part has been provided, both in the healthy brain and in psychiatric disorders. The anatomical correlates of such functional segregation, however, are still unknown due to a lack of stereotaxic, microstructural maps obtained in a representative sample of brains. Here we show that the human frontopolar cortex consists of two cytoarchitectonically and functionally distinct areas: lateral frontopolar area 1 (Fp1) and medial frontopolar area 2 (Fp2). Based on observer-independent mapping in serial, cell-body stained sections of 10 brains, three-dimensional, probabilistic maps of areas Fp1 and Fp2 were created. They show, for each position of the reference space, the probability with which each area was found in a particular voxel. Applying these maps as seed regions for a meta-analysis revealed that Fp1 and Fp2 differentially contribute to functional networks: Fp1 was involved in cognition, working memory and perception, whereas Fp2 was part of brain networks underlying affective processing and social cognition. The present study thus disclosed cortical correlates of a functional segregation of the human frontopolar cortex. The probabilistic maps provide a sound anatomical basis for interpreting neuroimaging data in the living human brain, and open new perspectives for analyzing structure-function relationships in the prefrontal cortex. The new data will also serve as a starting point for further comparative studies between human and non-human primate brains. This allows finding similarities and differences in the organizational principles of the frontal lobe during evolution as neurobiological basis for our behavior and cognitive abilities.