White matter integrity as a predictor of response to treatment in first episode psychosis

The integrity of brain white matter connections is central to a patient's ability to respond to pharmacological interventions. This study tested this hypothesis using a specific measure of white matter integrity, and examining its relationship to treatment response using a prospective design in patients within their first episode of psychosis. Diffusion tensor imaging data were acquired in 63 patients with first episode psychosis and 52 healthy control subjects (baseline). Response was assessed after 12 weeks and patients were classified as responders or non-responders according to treatment outcome. At this second time-point, they also underwent a second diffusion tensor imaging scan. Tract-based spatial statistics were used to assess fractional anisotropy as a marker of white matter integrity. At baseline, non-responders showed lower fractional anisotropy than both responders and healthy control subjects (P < 0.05; family-wise error-corrected), mainly in the uncinate, cingulum and corpus callosum, whereas responders were indistinguishable from healthy control subjects. After 12 weeks, there was an increase in fractional anisotropy in both responders and non-responders, positively correlated with antipsychotic exposure. This represents one of the largest, controlled investigations of white matter integrity and response to antipsychotic treatment early in psychosis. These data, together with earlier findings on cortical grey matter, suggest that grey and white matter integrity at the start of treatment is an important moderator of response to antipsychotics. These findings can inform patient stratification to anticipate care needs, and raise the possibility that antipsychotics may restore white matter integrity as part of the therapeutic response

Accelerating magnetic induction tomography‐based imaging through heterogeneous parallel computing

Magnetic Induction Tomography (MIT) is a non‐invasive imaging technique, which has applications in both industrial and clinical settings. In essence, it is capable of reconstructing the electromagnetic parameters of an object from measurements made on its surface. With the exploitation of parallelism, it is possible to achieve high quality inexpensive MIT images for biomedical applications on clinically relevant time scales. In this paper we investigate the performance of different parallel implementations of the forward eddy current problem, which is the main computational component of the inverse problem through which measured voltages are converted into images. We show that a heterogeneous parallel method that exploits multiple CPUs and GPUs can provide a high level of parallel scaling, leading to considerably improved runtimes. We also show how multiple GPUs can be used in conjunction with deal.II, a widely‐used open source finite element library

Multi-center MRI prediction models: Predicting sex and illness course in first episode psychosis patients.

Structural Magnetic Resonance Imaging (MRI) studies have attempted to use brain measures obtained at the first-episode of psychosis to predict subsequent outcome, with inconsistent results. Thus, there is a real need to validate the utility of brain measures in the prediction of outcome using large datasets, from independent samples, obtained with different protocols and from different MRI scanners. This study had three main aims: 1) to investigate whether structural MRI data from multiple centers can be combined to create a machine-learning model able to predict a strong biological variable like sex; 2) to replicate our previous finding that an MRI scan obtained at first episode significantly predicts subsequent illness course in other independent datasets; and finally, 3) to test whether these datasets can be combined to generate multicenter models with better accuracy in the prediction of illness course. The multi-center sample included brain structural MRI scans from 256 males and 133 females patients with first episode psychosis, acquired in five centers: University Medical Center Utrecht (The Netherlands) (n=67); Institute of Psychiatry, Psychology and Neuroscience, London (United Kingdom) (n=97); University of São Paulo (Brazil) (n=64); University of Cantabria, Santander (Spain) (n=107); and University of Melbourne (Australia) (n=54). All images were acquired on 1.5-Tesla scanners and all centers provided information on illness course during a follow-up period ranging 3 to 7years. We only included in the analyses of outcome prediction patients for whom illness course was categorized as either "continuous" (n=94) or "remitting" (n=118). Using structural brain scans from all centers, sex was predicted with significant accuracy (89%; p<0.001). In the single- or multi-center models, illness course could not be predicted with significant accuracy. However, when reducing heterogeneity by restricting the analyses to male patients only, classification accuracy improved in some samples. This study provides proof of concept that combining multi-center MRI data to create a well performing classification model is possible. However, to create complex multi-center models that perform accurately, each center should contribute a sample either large or homogeneous enough to first allow accurate classification within the single-center

B meson decay constants f(Bc), f(Bs) and f(B) from QCD sum rules

Finite energy QCD sum rules with Legendre polynomial integration kernels are used to determine the heavy meson decay constant f(Bc), and revisit f(B) and f(Bs). Results exhibit excellent stability in a wide range of values of the integration radius in the complex squared energy plane, and of the order of the Legendre polynomial. Results are f(Bc) = 528 +/- 19 MeV, f(B) = 186 +/- 14 MeV, and f(Bs) = 222 +/- 12 MeV

Analysis of the masses and decay constants of the heavy-light mesons with QCD sum rules

In this article, we calculate the contributions of the vacuum condensates up to dimension-6 including the $${\mathcal {O}}(\alpha _s)$$ corrections to the quark condensates in the operator product expansion, then we study the masses and decay constants of the pseudoscalar, scalar, vector, and axial-vector heavy-light mesons with the QCD sum rules in a systematic way. The masses of the observed mesons $$(D,D^*)$$, $$(D_s,D_s^*)$$, $$(D_0^*(2400),D_1(2430))$$, $$(D_{s0}^*(2317),D_{s1}(2460)),$$ $$(B,B^*)$$, $$(B_s,B_s^*)$$ can be well reproduced, while the predictions for the masses of $$(B^*_{0}, B_{1})$$ and $$(B^*_{s0}, B_{s1})$$ can be confronted with the experimental data in the future. We obtain the decay constants of the pseudoscalar, scalar, vector, and axial-vector heavy-light mesons, which have many phenomenological applications in studying the semi-leptonic and leptonic decays of the heavy-light mesons

Maternal Arterial Stiffness in Women Who Subsequently Develop Pre-Eclampsia

BACKGROUND/OBJECTIVES: Pre-eclampsia (PE) is associated with profound changes in the maternal cardiovascular system. The aim of the present study was to assess whether alterations in the maternal arterial stiffness precede the onset of PE in at risk women. METHODOLOGY/PRINCIPAL FINDINGS: This was a cross sectional study involving 70 pregnant women with normal and 70 women with abnormal uterine artery Doppler examination at 22-24 weeks of gestation. All women had their arterial stiffness (augmentation index and pulse wave velocity of the carotid-femoral and carotid-radial parts of the arterial tree) assessed by applanation tonometry in the second trimester of pregnancy, at the time of the uterine artery Doppler imaging. Among the 140 women participating in the study 29 developed PE (PE group) and 111 did not (non-PE group). Compared to the non-PE group, women that developed PE had higher central systolic (94.9 ± 8.6 mmHg vs 104.3 ± 11.1 mmHg; p  =  < 0.01) and diastolic (64.0 ± 6.0 vs 72.4 ± 9.1; p < 0.01) blood pressures. All the arterial stiffness indices were adjusted for possible confounders and expressed as multiples of the median (MoM) of the non-PE group. The adjusted median augmentation index was similar between the two groups (p  =  0.84). The adjusted median pulse wave velocities were higher in the PE group compared to the non-PE group (carotid-femoral: 1.10 ± 0.14 MoMs vs 0.99 ± 0.11 MoMs; p < 0.01 and carotid-radial: 1.08 ± 0.12 MoMs vs 1.0 ± 0.11 MoMs; p < 0.01). CONCLUSIONS/SIGNIFICANCE: Increased maternal arterial stiffness, as assessed by pulse wave velocity, predates the development of PE in at risk women

Functional sex differences in human primary auditory cortex

Background We used PET to study cortical activation during auditory stimulation and found sex differences in the human primary auditory cortex (PAC). Regional cerebral blood flow (rCBF) was measured in 10 male and 10 female volunteers while listening to sounds (music or white noise) and during a baseline (no auditory stimulation). Results and discussion We found a sex difference in activation of the left and right PAC when comparing music to noise. The PAC was more activated by music than by noise in both men and women. But this difference between the two stimuli was significantly higher in men than in women. To investigate whether this difference could be attributed to either music or noise, we compared both stimuli with the baseline and revealed that noise gave a significantly higher activation in the female PAC than in the male PAC. Moreover, the male group showed a deactivation in the right prefrontal cortex when comparing noise to the baseline, which was not present in the female group. Interestingly, the auditory and prefrontal regions are anatomically and functionally linked and the prefrontal cortex is known to be engaged in auditory tasks that involve sustained or selective auditory attention. Thus we hypothesize that differences in attention result in a different deactivation of the right prefrontal cortex, which in turn modulates the activation of the PAC and thus explains the sex differences found in the activation of the PAC. Conclusion Our results suggest that sex is an important factor in auditory brain studies

Gis1 and Rph1 Regulate Glycerol and Acetate Metabolism in Glucose Depleted Yeast Cells

Aging in organisms as diverse as yeast, nematodes, and mammals is delayed by caloric restriction, an effect mediated by the nutrient sensing TOR, RAS/cAMP, and AKT/Sch9 pathways. The transcription factor Gis1 functions downstream of these pathways in extending the lifespan of nutrient restricted yeast cells, but the mechanisms involved are still poorly understood. We have used gene expression microarrays to study the targets of Gis1 and the related protein Rph1 in different growth phases. Our results show that Gis1 and Rph1 act both as repressors and activators, on overlapping sets of genes as well as on distinct targets. Interestingly, both the activities and the target specificities of Gis1 and Rph1 depend on the growth phase. Thus, both proteins are associated with repression during exponential growth, targeting genes with STRE or PDS motifs in their promoters. After the diauxic shift, both become involved in activation, with Gis1 acting primarily on genes with PDS motifs, and Rph1 on genes with STRE motifs. Significantly, Gis1 and Rph1 control a number of genes involved in acetate and glycerol formation, metabolites that have been implicated in aging. Furthermore, several genes involved in acetyl-CoA metabolism are downregulated by Gis1

Seeing Emotion with Your Ears: Emotional Prosody Implicitly Guides Visual Attention to Faces

Interpersonal communication involves the processing of multimodal emotional cues, particularly facial expressions (visual modality) and emotional speech prosody (auditory modality) which can interact during information processing. Here, we investigated whether the implicit processing of emotional prosody systematically influences gaze behavior to facial expressions of emotion. We analyzed the eye movements of 31 participants as they scanned a visual array of four emotional faces portraying fear, anger, happiness, and neutrality, while listening to an emotionally-inflected pseudo-utterance (Someone migged the pazing) uttered in a congruent or incongruent tone. Participants heard the emotional utterance during the first 1250 milliseconds of a five-second visual array and then performed an immediate recall decision about the face they had just seen. The frequency and duration of first saccades and of total looks in three temporal windows ([0–1250 ms], [1250–2500 ms], [2500–5000 ms]) were analyzed according to the emotional content of faces and voices. Results showed that participants looked longer and more frequently at faces that matched the prosody in all three time windows (emotion congruency effect), although this effect was often emotion-specific (with greatest effects for fear). Effects of prosody on visual attention to faces persisted over time and could be detected long after the auditory information was no longer present. These data imply that emotional prosody is processed automatically during communication and that these cues play a critical role in how humans respond to related visual cues in the environment, such as facial expressions

Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer

Vascular endothelial growth factor (VEGF) is a key regulator of angiogenesis which drives endothelial cell survival, proliferation, and migration while increasing vascular permeability. Playing an important role in the physiology of normal ovaries, VEGF has also been implicated in the pathogenesis of ovarian cancer. Essentially by promoting tumor angiogenesis and enhancing vascular permeability, VEGF contributes to the development of peritoneal carcinomatosis associated with malignant ascites formation, the characteristic feature of advanced ovarian cancer at diagnosis. In both experimental and clinical studies, VEGF levels have been inversely correlated with survival. Moreover, VEGF inhibition has been shown to inhibit tumor growth and ascites production and to suppress tumor invasion and metastasis. These findings have laid the basis for the clinical evaluation of agents targeting VEGF signaling pathway in patients with ovarian cancer. In this review, we will focus on VEGF involvement in the pathophysiology of ovarian cancer and its contribution to the disease progression and dissemination