Efficient total variation algorithm for fetal brain MRI reconstruction.

Fetal MRI reconstruction aims at finding a high-resolution image given a small set of low-resolution images. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has considered several regularization terms s.a. Dirichlet/Laplacian energy, Total Variation (TV)- based energies and more recently non-local means. Although TV energies are quite attractive because of their ability in edge preservation, standard explicit steepest gradient techniques have been applied to optimize fetal-based TV energies. The main contribution of this work lies in the introduction of a well-posed TV algorithm from the point of view of convex optimization. Specifically, our proposed TV optimization algorithm or fetal reconstruction is optimal w.r.t. the asymptotic and iterative convergence speeds O(1/n2) and O(1/√ε), while existing techniques are in O(1/n2) and O(1/√ε). We apply our algorithm to (1) clinical newborn data, considered as ground truth, and (2) clinical fetal acquisitions. Our algorithm compares favorably with the literature in terms of speed and accuracy.

An efficient total variation algorithm for super-resolution in fetal brain MRI with adaptive regularization.

Although fetal anatomy can be adequately viewed in new multi-slice MR images, many critical limitations remain for quantitative data analysis. To this end, several research groups have recently developed advanced image processing methods, often denoted by super-resolution (SR) techniques, to reconstruct from a set of clinical low-resolution (LR) images, a high-resolution (HR) motion-free volume. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has been quite attracted by Total Variation energies because of their ability in edge preserving but only standard explicit steepest gradient techniques have been applied for optimization. In a preliminary work, it has been shown that novel fast convex optimization techniques could be successfully applied to design an efficient Total Variation optimization algorithm for the super-resolution problem. In this work, two major contributions are presented. Firstly, we will briefly review the Bayesian and Variational dual formulations of current state-of-the-art methods dedicated to fetal MRI reconstruction. Secondly, we present an extensive quantitative evaluation of our SR algorithm previously introduced on both simulated fetal and real clinical data (with both normal and pathological subjects). Specifically, we study the robustness of regularization terms in front of residual registration errors and we also present a novel strategy for automatically select the weight of the regularization as regards the data fidelity term. Our results show that our TV implementation is highly robust in front of motion artifacts and that it offers the best trade-off between speed and accuracy for fetal MRI recovery as in comparison with state-of-the art methods.

Efficient total variation algorithm for fetal MRI reconstruction

Fetal MRI reconstruction aims at finding a high-resolution image given a small set of low-resolution images. It is usually modeled as an inverse problem where the regularization term plays a central role in the reconstruction quality. Literature has considered several regularization terms s.a. Dirichlet/Laplacian energy [1], Total Variation (TV)based energies [2,3] and more recently non-local means [4]. Although TV energies are quite attractive because of their ability in edge preservation, standard explicit steepest gradient techniques have been applied to optimize fetal-based TV energies. The main contribution of this work lies in the introduction of a well-posed TV algorithm from the point of view of convex optimization. Specifically, our proposed TV optimization algorithm for fetal reconstruction is optimal w.r.t. the asymptotic and iterative convergence speeds O(1/n(2)) and O(1/root epsilon), while existing techniques are in O(1/n) and O(1/epsilon). We apply our algorithm to (1) clinical newborn data, considered as ground truth, and (2) clinical fetal acquisitions. Our algorithm compares favorably with the literature in terms of speed and accuracy.

The circadian rhythm of the perinatal mortality rate in Switzerland.

The authors examine the relation between the perinatal mortality rate (PMR), birth weight in four categories, and hour of birth throughout the week in Switzerland, using data on 672,013 births and 5,764 perinatal deaths recorded between 1979 and 1987. From Monday to Friday, the PMR follows a circadian rhythm with a regular increase from early morning to evening, with a peak for babies born between 7 and 8 p.m. This pattern of variation has two main components: The circadian rhythms for the proportion of births in the four weight categories and the PMR circadian rhythm for babies weighing more than 2.5 kg. According to a cosinor model, which describes about 40% of the total variation in the PMR, the most important determinants are changes in the proportions of births: Low birth weight increases toward the afternoon and night. Mechanisms underlying the weight-specific timing of birth are discussed, including time selection of birth according to obstetric risks, the direct effect of neonatal and obstetric care, and chronobiologic behavior.

The circadian rhythm of the perinatal mortality rate in Switzerland.

The authors examine the relation between the perinatal mortality rate (PMR), birth weight in four categories, and hour of birth throughout the week in Switzerland, using data on 672,013 births and 5,764 perinatal deaths recorded between 1979 and 1987. From Monday to Friday, the PMR follows a circadian rhythm with a regular increase from early morning to evening, with a peak for babies born between 7 and 8 p.m. This pattern of variation has two main components: The circadian rhythms for the proportion of births in the four weight categories and the PMR circadian rhythm for babies weighing more than 2.5 kg. According to a cosinor model, which describes about 40% of the total variation in the PMR, the most important determinants are changes in the proportions of births: Low birth weight increases toward the afternoon and night. Mechanisms underlying the weight-specific timing of birth are discussed, including time selection of birth according to obstetric risks, the direct effect of neonatal and obstetric care, and chronobiologic behavior.

Sparse image reconstruction on the sphere: implications of a new sampling theorem.

We study the impact of sampling theorems on the fidelity of sparse image reconstruction on the sphere. We discuss how a reduction in the number of samples required to represent all information content of a band-limited signal acts to improve the fidelity of sparse image reconstruction, through both the dimensionality and sparsity of signals. To demonstrate this result, we consider a simple inpainting problem on the sphere and consider images sparse in the magnitude of their gradient. We develop a framework for total variation inpainting on the sphere, including fast methods to render the inpainting problem computationally feasible at high resolution. Recently a new sampling theorem on the sphere was developed, reducing the required number of samples by a factor of two for equiangular sampling schemes. Through numerical simulations, we verify the enhanced fidelity of sparse image reconstruction due to the more efficient sampling of the sphere provided by the new sampling theorem.

Variation in novel exons (RACEfrags) of the MECP2 gene in Rett syndrome patients and controls.

The study of transcription using genomic tiling arrays has lead to the identification of numerous additional exons. One example is the MECP2 gene on the X chromosome; using 5'RACE and RT-PCR in human tissues and cell lines, we have found more than 70 novel exons (RACEfrags) connecting to at least one annotated exon.. We sequenced all MECP2-connected exons and flanking sequences in 3 groups: 46 patients with the Rett syndrome and without mutations in the currently annotated exons of the MECP2 and CDKL5 genes; 32 patients with the Rett syndrome and identified mutations in the MECP2 gene; 100 control individuals from the same geoethnic group. Approximately 13 kb were sequenced per sample, (2.4 Mb of DNA resequencing). A total of 75 individuals had novel rare variants (mostly private variants) but no statistically significant difference was found among the 3 groups. These results suggest that variants in the newly discovered exons may not contribute to Rett syndrome. Interestingly however, there are about twice more variants in the novel exons than in the flanking sequences (44 vs. 21 for approximately 1.3 Mb sequenced for each class of sequences, p=0.0025). Thus the evolutionary forces that shape these novel exons may be different than those of neighboring sequences.

Total hemoglobin mass--a new parameter to detect blood doping?

PURPOSE: All kinds of blood manipulations aim to increase the total hemoglobin mass (tHb-mass). To establish tHb-mass as an effective screening parameter for detecting blood doping, the knowledge of its normal variation over time is necessary. The aim of the present study, therefore, was to determine the intraindividual variance of tHb-mass in elite athletes during a training year emphasizing off, training, and race seasons at sea level. METHODS: tHb-mass and hemoglobin concentration ([Hb]) were determined in 24 endurance athletes five times during a year and were compared with a control group (n = 6). An analysis of covariance was used to test the effects of training phases, age, gender, competition level, body mass, and training volume. Three error models, based on 1) a total percentage error of measurement, 2) the combination of a typical percentage error (TE) of analytical origin with an absolute SD of biological origin, and 3) between-subject and within-subject variance components as obtained by an analysis of variance, were tested. RESULTS: In addition to the expected influence of performance status, the main results were that the effects of training volume (P = 0.20) and training phases (P = 0.81) on tHb-mass were not significant. We found that within-subject variations mainly have an analytical origin (TE approximately 1.4%) and a very small SD (7.5 g) of biological origin. CONCLUSION: tHb-mass shows very low individual oscillations during a training year (<6%), and these oscillations are below the expected changes in tHb-mass due to Herythropoetin (EPO) application or blood infusion (approximately 10%). The high stability of tHb-mass over a period of 1 year suggests that it should be included in an athlete's biological passport and analyzed by recently developed probabilistic inference techniques that define subject-based reference ranges.

Undertreatment of acute pain (oligoanalgesia) and medical practice variation in prehospital analgesia of adult trauma patients: a 10 yr retrospective study.

BACKGROUND: Prehospital oligoanalgesia is prevalent among trauma victims, even when the emergency medical services team includes a physician. We investigated if not only patients' characteristics but physicians' practice variations contributed to prehospital oligoanalgesia. METHODS: Patient records of conscious adult trauma victims transported by our air rescue helicopter service over 10 yr were reviewed retrospectively. Oligoanalgesia was defined as a numeric rating scale (NRS) >3 at hospital admission. Multilevel logistic regression analysis was used to predict oligoanalgesia, accounting first for patient case-mix, and then physician-level clustering. The intraclass correlation was expressed as the median odds ratio (MOR). RESULTS: A total of 1202 patients and 77 physicians were included in the study. NRS at the scene was 6.9 (1.9). The prevalence of oligoanalgesia was 43%. Physicians had a median of 5.7 yr (inter-quartile range: 4.2-7.5) of post-graduate training and 27% were female. In our multilevel analysis, significant predictors of oligoanalgesia were: no analgesia [odds ratio (OR) 8.8], National Advisory Committee for Aeronautics V on site (OR 4.4), NRS on site (OR 1.5 per additional NRS unit >4), female physician (OR 2.0), and years of post-graduate experience [>4.0 to ≤5.0 (OR 1.3), >3.0 to ≤4.0 (OR 1.6), >2.0 to ≤3.0 (OR 2.6), and ≤2.0 yr (OR 16.7)]. The MOR was 2.6, and was statistically significant. CONCLUSIONS: Physicians' practice variations contributed to oligoanalgesia, a factor often overlooked in analyses of prehospital pain management. Further exploration of the sources of these variations may provide innovative targets for quality improvement programmes to achieve consistent pain relief for trauma victims.

Between-year variation in population sex ratio increases with complexity of the breeding system in Hymenoptera.

While adaptive adjustment of sex ratio in the function of colony kin structure and food availability commonly occurs in social Hymenoptera, long-term studies have revealed substantial unexplained between-year variation in sex ratio at the population level. In order to identify factors that contribute to increased between-year variation in population sex ratio, we conducted a comparative analysis across 47 Hymenoptera species differing in their breeding system. We found that between-year variation in population sex ratio steadily increased as one moved from solitary species, to primitively eusocial species, to single-queen eusocial species, to multiple-queen eusocial species. Specifically, between-year variation in population sex ratio was low (6.6% of total possible variation) in solitary species, which is consistent with the view that in solitary species, sex ratio can vary only in response to fluctuations in ecological factors such as food availability. In contrast, we found significantly higher (19.5%) between-year variation in population sex ratio in multiple-queen eusocial species, which supports the view that in these species, sex ratio can also fluctuate in response to temporal changes in social factors such as queen number and queen-worker control over sex ratio, as well as factors influencing caste determination. The simultaneous adjustment of sex ratio in response to temporal fluctuations in ecological and social factors seems to preclude the existence of a single sex ratio optimum. The absence of such an optimum may reflect an additional cost associated with the evolution of complex breeding systems in Hymenoptera societies.

Investigating the genetic variation underlying episodicity in major depressive disorder: Suggestive evidence for a bipolar contribution.

BACKGROUND: Highly recurrent major depressive disorder (MDD) has reportedly increased risk of shifting to bipolar disorder; high recurrence frequency has, therefore, featured as evidence of 'soft bipolarity'. We aimed to investigate the genetic underpinnings of total depressive episode count in recurrent MDD. METHODS: Our primary sample included 1966 MDD cases with negative family history of bipolar disorder from the RADIANT studies. Total episode count was adjusted for gender, age, MDD duration, study and center before being tested for association with genotype in two separate genome-wide analyses (GWAS), in the full set and in a subset of 1364 cases with positive family history of MDD (FH+). We also calculated polygenic scores from the Psychiatric Genomics Consortium MDD and bipolar disorder studies. RESULTS: Episodicity (especially intermediate episode counts) was an independent index of MDD familial aggregation, replicating previous reports. The GWAS produced no genome-wide significant findings. The strongest signals were detected in the full set at MAGI1 (p=5.1×10(-7)), previously associated with bipolar disorder, and in the FH+ subset at STIM1 (p=3.9×10(-6) after imputation), a calcium channel signaling gene. However, these findings failed to replicate in an independent Munich cohort. In the full set polygenic profile analyses, MDD polygenes predicted episodicity better than bipolar polygenes; however, in the FH+ subset, both polygenic scores performed similarly. LIMITATIONS: Episode count was self-reported and, therefore, subject to recall bias. CONCLUSIONS: Our findings lend preliminary support to the hypothesis that highly recurrent MDD with FH+ is part of a 'soft bipolar spectrum' but await replication in larger cohorts.

Extent of resection in glioblastoma - variation between molecular risk groups in rtog-0525

Whether maximal surgical resection of glioblastoma improves patient survival has been controversial, as it is difficult to perform an unbiased assessment of extent of resection (EOR) independent of other patient-specific prognostic factors. Recently, glioblastoma has been sub-classified into 4 distinct molecular risk groups (RGs), which have been validated as prognostic biomarkers in the randomized clinical trial of temozolomide dosing in glioblastoma: the Radiation Therapy Oncology Group 0525 (RTOG-0525) trial. We sought to perform exploratory analyses examining gross total resection (GTR) versus sub-total resection (STR) within these RGs in RTOG-0525 patients. Across all randomized patients, n ¼ 354 had STR and n ¼ 450 had GTR as determined by neurosurgeon operative report. GTR was not significantly associated with survival across the overall study group. A total of 725 patients had sufficient tissue for determination of molecular RG. There were no significant differences in percentage of GTR between each of the 4 RGs (P ¼ 0.64). In exploratory subgroup analyses, GTR was associated with improved survival only for patients with tumors from RG4. Hazard ratios (95% confidence intervals) were 0.52 (0.08-2.07) for RG1 (n ¼ 28, 68% GTR), 1.74 (0.75-4.05) for RG2 (n ¼ 39, 56% GTR), 1.09 (0.84-1.42) for RG3 (n ¼ 284, 56% GTR), and 1.26 (1.01-1.56) for RG4 (n ¼ 374, 55% GTR). In univariate analysis within RG4, GTR was associated with a median survival of 14.6 months vs 12.7 months for STR (P ¼ 0.0352. In a Cox model adjusting for age, KPS, and neurologic function (NF), surgery remained an independent factor within RG4: GTR (P ¼ 0.0331), age (P ¼ 0.0014), KPS (P ¼ .3289), and NF (P ¼ 0.3804). There are important cautions in the interpretation of these data, including lack of MRI confirmation of EOR, and inclusion of a range of STR (from biopsy to near-total resection). However, these exploratory results raise the possibility that upfront characterization of tumor molecular profile may allow for personalized therapeutic strategies to improve outcomes for patients with glioblastoma.

International variation in management of screen-detected ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) incidence has grown with the implementation of screening and its detection varies across International Cancer Screening Network (ICSN) countries. The aim of this survey is to describe the management of screen-detected DCIS in ICSN countries and to evaluate the potential for treatment related morbidity. METHODS: We sought screen-detected DCIS data from the ICSN countries identified during 2004-2008. We adopted standardised data collection forms and analysis and explored DCIS diagnosis and treatment processes ranging from pre-operative diagnosis to type of surgery and radiotherapy. RESULTS: Twelve countries contributed data from a total of 15 screening programmes, all from Europe except the United States of America and Japan. Among women aged 50-69years, 7,176,050 screening tests and 5324 screen-detected DCIS were reported. From 21% to 93% of DCIS had a pre-operative diagnosis (PO); 67-90% of DCIS received breast conservation surgery (BCS), and in 41-100% of the cases this was followed by radiotherapy; 6.4-59% received sentinel lymph node biopsy (SLNB) only and 0.8-49% axillary dissection (ALND) with 0.6% (range by programmes 0-8.1%) being node positive. Among BCS patients 35% received SLNB only and 4.8% received ALND. Starting in 2006, PO and SLNB use increased while ALND remained stable. SLNB and ALND were associated with larger size and higher grade DCIS lesions. CONCLUSIONS: Variation in DCIS management among screened women is wide and includes lymph node surgery beyond what is currently recommended. This indicates the presence of varying levels of overtreatment and the potential for its reduction.

Geographic variation in the frequency of isolation and fluconazole and voriconazole susceptibilities of Candida glabrata: an assessment from the ARTEMIS DISK Global Antifungal Surveillance Program.

Geographic differences in frequency and azole resistance among Candida glabrata may impact empiric antifungal therapy choice. We examined geographic variation in isolation and azole susceptibility of C. glabrata. We examined 23 305 clinical isolates of C. glabrata during ARTEMIS DISK global surveillance. Susceptibility testing to fluconazole and voriconazole was assessed by disk diffusion, and the results were grouped by geographic location: North America (NA) (2470 isolates), Latin America (LA) (2039), Europe (EU) (12 439), Africa and the Middle East (AME) (728), and Asia-Pacific (AP) (5629). Overall, C. glabrata accounted for 11.6% of 201 653 isolates of Candida and varied as a proportion of all Candida isolated from 7.4% in LA to 21.1% in NA. Decreased susceptibility (S) to fluconazole was observed in all geographic regions and ranged from 62.8% in AME to 76.7% in LA. Variation in fluconazole susceptibility was observed within each region: AP (range, 50-100% S), AME (48-86.9%), EU (44.8-88%), LA (43-92%), and NA (74.5-91.6%). Voriconazole was more active than fluconazole (range, 82.3-84.2% S) with similar regional variation. Among 22 sentinel sites participating in ARTEMIS from 2001 through 2007 (84 140 total isolates, 8163 C. glabrata), the frequency of C. glabrata isolation increased in 14 sites and the frequency of fluconazole resistance (R) increased in 11 sites over the 7-year period of study. The sites with the highest cumulative rates of fluconazole R were in Poland (22% R), the Czech Republic (27% R), Venezuela (27% R), and Greece (33% R). C. glabrata was most often isolated from blood, normally sterile body fluids and urine. There is substantial geographic and institutional variation in both frequency of isolation and azole resistance among C. glabrata. Prompt species identification and fluconazole susceptibility testing are necessary to optimize therapy for invasive candidiasis.

Altitudinal variation in haemosporidian parasite distribution in great tit populations.

BACKGROUND: One of the major issues concerning disease ecology and conservation is knowledge of the factors that influence the distribution of parasites and consequently disease outbreaks. This study aimed to investigate avian haemosporidian composition and the distribution of these parasites in three altitudinally separated great tit (Parus major) populations in western Switzerland over a three-year period. The objectives were to determine the lineage diversity of parasites occuring across the study populations and to investigate whether altitudinal gradients govern the distribution of haemosporidian parasites by lineage. METHODS: In this study molecular approaches (PCR and sequencing) were used to detect avian blood parasites (Plasmodium sp., Haemoproteus sp. and Leucocytozoon sp.) in populations of adult great tits caught on their nests during three consecutive breeding seasons. RESULTS: High levels of parasite prevalence (88-96%) were found across all of the study populations with no significant altitude effect. Altitude did, however, govern the distribution of parasites belonging to different genera, with Plasmodium parasites being more prevalent at lower altitudes, Leucocytozoon parasites more at high altitude and Haemoproteus parasite prevalence increasing with altitude. A total of 27 haemosporidian parasite lineages were recorded across all study sites, with diversity showing a positive correlation to altitude. Parasites belonging to lineage SGS1 (P. relictum) and PARUS4 and PARUS19 (Leucocytozoon sp.) dominated lower altitudes. SW2 (P. polare) was the second most prevalent lineage of parasite detected overall and these parasites were responsible for 68% of infections at intermediate altitude, but were only documented at this one study site. CONCLUSIONS: Avian haemosporidian parasites are not homogeneously distributed across host populations, but differ by altitude. This difference is most probably brought about by environmental factors influencing vector prevalence and distribution. The high occurrence of co-infection by different genera of parasites might have pronounced effects on host fitness and should consequently be investigated more rigorously.