The case for resequencing studies of Arabidopsis thaliana accessions: mining the dark matter of natural genetic variation.

Ultra-high-throughput sequencing (UHTS) techniques are evolving rapidly and may soon become an affordable and routine tool for sequencing plant DNA, even in smaller plant biology labs. Here we review recent insights into intraspecific genome variation gained from UHTS, which offers a glimpse of the rather unexpected levels of structural variability among Arabidopsis thaliana accessions. The challenges that will need to be addressed to efficiently assemble and exploit this information are also discussed.

Toll-Interacting Protein Modulates Gut Flora Composition, Epithelial Barrier Integrity and Susceptibility to Colitis

Toll-like receptor ( TLR) s ignals are key to maintaining hostmicrobial i nteractions. T he T oll-interacting-protein (Tollip) is a ubiquitously-expressed inhibitor of inflammasome a nd TLR signaling. W e hypothesized that T ollip might control g ut homeostasis. G enetic ablation of T ollip d id not lead to spontaneous colitis b ut h ad d ramatic c onsequences on t he intestinal expression of the α-defensin cryptidin 4 and the C-type lectin R EGIIIβ. These c hanges were associated with intestinal dysbiosis a nd e nhanced colonization b y segmented filamentous bacteria - a k ey p ro-inflammatory component of the microbiota. Tollip deficiency increased susceptibility to dextran sulfate sodium (DSS) colitis and aggravated chronic Th17-driven colitis in IL-10-/- mice. Flora d epletion w ith a ntibiotics in T ollip-/- mice w as not sufficient to restore DSS colitis susceptibility and deletion of Tollip in n on-hematopoietic c ells using bone-marrow chimeras w as sufficient to increase s usceptibility t o DSS colitis. After D SS administration, we o bserved several e pithelial defects i n Tollip-/- mice including early tight junctions disruption, increased epithelial apoptosis, and increased intestinal permeability. Overall, our data show that T ollip significantly impacts intestinal h omeostasis by controlling b acterial ecology and intestinal r esponse to chemical and immunological stresses.

Exposure of highway maintenance workers to fine particulate matter and noise

In this study, we assessed the mixed exposure of highway maintenance workers to airborne particles, noise, and gaseous co-pollutants. The aim was to provide a better understanding of the workers' exposure to facilitate the evaluation of short-term effects on cardiovascular health endpoints. To quantify the workers' exposure, we monitored 18 subjects during 50 non-consecutive work shifts. Exposure assessment was based on personal and work site measurements and included fine particulate matter (PM2.5), particle number concentration (PNC), noise (Leq), and the gaseous co-pollutants: carbon monoxide, nitrogen dioxide, and ozone. Mean work shift PM2.5 concentrations (gravimetric measurements) ranged from 20.3 to 321 μg m(-3) (mean 62 μg m(-3)) and PNC were between 1.6×10(4) and 4.1×10(5) particles cm(-3) (8.9×10(4) particles cm(-3)). Noise levels were generally high with Leq over work shifts from 73.3 to 96.0 dB(A); the averaged Leq over all work shifts was 87.2 dB(A). The highest exposure to fine and ultrafine particles was measured during grass mowing and lumbering when motorized brush cutters and chain saws were used. Highest noise levels, caused by pneumatic hammers, were measured during paving and guardrail repair. We found moderate Spearman correlations between PNC and PM2.5 (r = 0.56); PNC, PM2.5, and CO (r = 0.60 and r = 0.50) as well as PNC and noise (r = 0.50). Variability and correlation of parameters were influenced by work activities that included equipment causing combined air pollutant and noise emissions (e.g. brush cutters and chain saws). We conclude that highway maintenance workers are frequently exposed to elevated airborne particle and noise levels compared with the average population. This elevated exposure is a consequence of the permanent proximity to highway traffic with additional peak exposures caused by emissions of the work-related equipment.

Which clinical signs predict hypoxaemia in young Senegalese children with acute lower respiratory tract disease?

BACKGROUND: Acute lower respiratory tract diseases are an important cause of mortality in children in resource-limited settings. In the absence of pulse oximetry, clinicians rely on clinical signs to detect hypoxaemia. OBJECTIVE: To assess the diagnostic value of clinical signs of hypoxaemia in children aged 2 months to 5 years with acute lower respiratory tract disease. METHODS: Seventy children with a history of cough and signs of respiratory distress were enrolled. Three experienced physicians recorded clinical signs and oxygen saturation by pulse oximetry. Hypoxaemia was defined as oxygen saturation <90%. Clinical predictors of hypoxaemia were evaluated using adjusted diagnostic odds ratios (aDOR). RESULTS: There was a 43% prevalence of hypoxaemia. An initial visual impression of poor general status [aDOR 20·0, 95% CI 3·8-106], severe chest-indrawing (aDOR 9·8, 95% CI 1·5-65), audible grunting (aDOR 6·9, 95% CI 1·4-25) and cyanosis (aDOR 26·5, 95% CI 1·1-677) were significant predictors of hypoxaemia. CONCLUSION: In children under 5 years of age, several simple clinical signs are reliable predictors of hypoxaemia. These should be included in diagnostic guidelines.

Hypernatrémie: une question d'eau [Hypernatremia: a matter of water]

Hypernatremia is defined as a serum sodium concentration above the upper laboratory reference range, usually > 145 mmol/l. It is a common electrolyte disorder in the very young and the very old patient. Hospitalization itself is a risk factor for developing hypernatremia. Free water deficit is the main cause of this condition. It induces hyperosmolality and an intracellular dehydration. Clinical manifestations are mostly neurological but non-specific. A blood sample analysis is needed to establish the diagnosis. Hypernatremia is associated with a high mortality and morbidity. Treatment consists of correcting the underlying cause and the volume deficit. A brief review of this condition is proposed.

Traitement des infections urinaires simples: impact des résistances antibiotiques croissantes dans la communauté [Uncomplicated urinary tract infections: impact of increasing antibiotic resistance in the community].

Uncomplicated urinary tract infections are commonly encountered in primary care and frequently lead to empirical antibiotic prescriptions. The development of antibiotic resistance in the community explains treatment failures observed with commonly-prescribed drugs such as quinolones and co-trimoxazole. This article describes the epidemiology of antibiotic resistance among pathogens causing uncomplicated urinary tract infections and the consequences in terms of recommendations for empirical antibiotic therapy.

Compartmentalized secretory leukocyte protease inhibitor expression and hormone responses along the reproductive tract of postmenopausal women

Immunity and hormonal responses in the reproductive tissues of postmenopausal women are poorly understood. Secretory leukocyte protease inhibitor (SLPI), a multifunctional antimicrobial protein expressed at mucosal surfaces, is thought to play a key role in infectious and inflammatory contexts. The aim of this study was to measure SLPI production along the female reproductive tract in postmenopausal women with and without hormonal treatment. We additionally quantified estrogen receptor alpha (ERα) and progesterone receptor A (PRA) in these tissues. Expression of SLPI was decreased in the vagina and ectocervix of women under hormonal treatment. Endocervical ERα mRNA expression was increased while this did not reach significance at the protein level. SLPI expression in the endometrium was not influenced by hormonal treatment. We observed attenuated ERα expression in the cervix and endometrium of hormonally treated women, whereas vaginal expression was increased. PRA expression was augmented in the cervix and endometrium and unchanged in the vagina. Taken together, our results indicate that hormonal responses and receptor expression are differentially regulated in vaginal tissue compared with the cervix and endometrium.

Multi-modal assessment of long-term erythropoietin treatment after neonatal hypoxic-ischemic injury in rat brain.

Erythropoietin (EPO) has been recognized as a neuroprotective agent. In animal models of neonatal brain injury, exogenous EPO has been shown to reduce lesion size, improve structure and function. Experimental studies have focused on short course treatment after injury. Timing, dose and length of treatment in preterm brain damage remain to be defined. We have evaluated the effects of high dose and long-term EPO treatment in hypoxic-ischemic (HI) injury in 3 days old (P3) rat pups using histopathology, magnetic resonance imaging (MRI) and spectroscopy (MRS) as well as functional assessment with somatosensory-evoked potentials (SEP). After HI, rat pups were assessed by MRI for initial damage and were randomized to receive EPO or vehicle. At the end of treatment period (P25) the size of resulting cortical damage and white matter (WM) microstructure integrity were assessed by MRI and cortical metabolism by MRS. Whisker elicited SEP were recorded to evaluate somatosensory function. Brains were collected for neuropathological assessment. The EPO treated animals did not show significant decrease of the HI induced cortical loss at P25. WM microstructure measured by diffusion tensor imaging was improved and SEP response in the injured cortex was recovered in the EPO treated animals compared to vehicle treated animals. In addition, the metabolic profile was less altered in the EPO group. Long-term treatment with high dose EPO after HI injury in the very immature rat brain induced recovery of WM microstructure and connectivity as well as somatosensory cortical function despite no effects on volume of cortical damage. This indicates that long-term high-dose EPO induces recovery of structural and functional connectivity despite persisting gross anatomical cortical alteration resulting from HI.

Paleoenvironmental evolution of the Helvetic shallow-water carbonate platform near the Barremian-Aptian boundary, and its relationship with paleoceanographic and paleoclimatic change in the Tethys

Abstract:During my doctoral research, I focused on deciphering the interactions between sea-level and climate change during the Late Barremian-Early Aptian, their expression in the Tethys basin and in the Helvetic carbonate platform. The research highlights are summarized here in three points: In the Helvetic Alps, the transition between the Lower Schrattenkalk (Upper Barremian) and the Rawil Member (Lowermost Aptian) is characterized by a change from a predominantly photozoan to a heterozoan carbonate-producing system, which coincides in time with a general increase in detrital and nutrient input. The clay mineral record shows the appearance of kaolinite within the Rawil Member, whereas this mineral is absent from the uppermost Lower and lowermost Upper Schrattenkalk Members. This indicates the installation of a warmer and more humid climate during this time period. A negative peak in 513C is recorded at the top of the Lower Schrattenkalk Member, and correlates with the well-known negative excursion of -l%o occurring in other basins and dated as latest Barremian, thus confirming a latest Barremian and earliest Aptian age for the Lower Schrattenkalk and Rawil Members, respectively. Furthermore, a sequence stratigraphie framework has been defined for the Rawil Member, based on both the ecology of faunal and floral assemblages, and their palaeoenvironmental interpretation, as well as on the stacking pattern of limestone beds observed during field prospection. The presence of a sequence boundary is postulated near the top of the Lower Schrattenkalk Member, which is correlated with the earliest Aptian SbAl defined in Vercors (France). The SbAl is characterized by a maximum of proximal assemblages and by the disappearance of several benthic foraminiferal species. Within the Rawil Member itself, the stacking pattern and microfacies trends are interpreted to represent the TST of the first Aptian sequence. With regards to the pelagic setting in the Tethyan realm, I investigated the Gorgo a Cerbara section (central Italy). There, thin organic-rich layers occur episodically in pelagic carbonates of the upper Barremian portion of the Maiolica Formation. They are associated with high Corg:Ptot ratios, which indicate the presence of intermittent dysoxic to anoxic conditions. Coarse correlations are also observed between TOC, Ρ and biogenic silica contents, indicating links between Ρ availability, productivity, and organic matter preservation. The corresponding 813Ccarb and δ180 records remain, however, quite stable, indicating that these brief periods of enhanced TOC preservation did not have sufficient impact on the marine carbon household to deviate 6,3C records, and are probably not the consequence of major climate change. On the other hand, organic-rich layers become more frequent around the Barremian-Aptian boundary in both pelagic and hemi-pelagic environments (Gorgo a Cerbara and La Bédoule, France), which are correlated with negative excursions in 6l3Ccarb and 613Corg records. During the earliest Aptian, at Gorgo a Cerbara, the frequency of organic-rich intervals progressively increases and redox-sensitive trace-element enrichments become more frequent, until the highest TOC-enriched level just below the "Livello Selli", indicator of Oceanic Anoxic Event la (OAEla). The latter is associated with the well-known negative spike in 613Ccarb and S,3Corg records, a diminution in the δ,80 record interpreted as the consequence of a wanning interval, an important peak in Ρ accumulation and high Cor::Ptot ratios indicating the prevalence of anoxic conditions. The Selli Level (OAEla) documents a general cooling phase and coincides with maximum RSTE enrichments as well as high Corg:Ptot ratios, which confirm the importance of anoxic conditions during OAE1 a at this site.During the Early Aptian, environmental change on the platform is expressed by orbitolinids proliferation that may be induced by both climate change and sea-level rise. In the basin, the successive black shales horizons from the Late Barremian until the OAE la are interpreted as the progressive impact of palaeoenvironmental change probably linked to the formation of the Ontong- Java plate-basalt plateau.RésuméCe travail de thèse a permis d'investiguer les interactions entre les variations du niveau marin et les changements climatiques sur la plate-forme helvétique ainsi qu'en domaine pélagique à la limite Barrémien-Aptien (Crétacé).Dans les Alpes helvétiques, la limite Barrémien-Aptien est marquée par la transition du Schrattenkalk inférieur, caractérisé par des carbonates photozaires, au Membre de Rawil caractérisé par des carbonates héterozoaires. Cette transition est marquée par une arrivée massive d'éléments détritiques et un apport de nutriments ayant entraîné la prolifération de foraminifères agglutinés tels que les orbitolines. L'analyse des minéraux argileux indique l'apparition de la kaolinite durant le Membre de Rawil, interprétée comme l'installation d'un climat plus chaud et humide. Un pic négatif en 513C est enregistré au sommet du Schrattenkalk inférieur correspond à l'excursion négative de -1%0 bien connue en domaine pélagique et datée comme Barrémien terminal. Cette corrélation apporte un contrôle chronostratigraphique supplémentaire permettant de dater le Schrattenkalk inférieur du Barrémien sup. et le Membre de Rawil de l'Aptien inf. D'autre part, une étude stratigraphique, basée sur des observations de terrain et sur l'interprétation d'assemblages floristiques et faunistiques en terme de paléoenvironnement a permis de mettre en évidence une limite de séquence au sommet du Schrattenkalk inf., corrélable avec la SbAl définie dans le Vercors. Durant la mise en place du Membre de Rawil, l'évolution des microfaciès est interprétée comme le « Transgressive System Tract » de la première séquence aptienne.En domaine pélagique, de minces couches riches en matière organique (MO) apparaissent dès le Barrémien sup. dans la coupe de Gorgo a Cerbara (Italie). Elles sont associées à un ratio C:P élevé indiquant des conditions épisodiquement dysoxiques à anoxiques. De plus, une corrélation nette entre Carbone Organique Total (TOC), phosphore (P) et silice biogénique est observée correspondant à un lien entre Ρ disponible, productivité et préservation de la MO. Pourtant, dans le même temps, le ÔI3C et le δ1βΟ restent constants indiquant des conditions environnementales stables et un cycle du carbone non perturbé par la préservation de MO qui ne serait pas la conséquence d'un changement climatique global mais juste d'un effet local.Ala limite Barrémien-Aptien, en domaine hémi-pélagique (La Bédoule, France) et pélagique (Gorgo a Cerbara), les couches riches en MO sont plus fréquentes et plus épaisses, elles se sont déposées en même temps qu'un pic négatif en 513CCARB et ô13Coib probablement dû à un épisode volcanique. A l'Aptien inf. le TOC des niveaux riches en MO augmente progressivement en même temps que la teneur en éléments traces jusqu'au dernier enrichissement avant l'événement anoxique océanique la (OAE la) correspondant au « niveau critique inf. », indiquant des conditions anoxiques moins restreintes. Celui-ci est également caractérisé par le fameux pic négatif en Ô13C (C3), une diminution du δ180 interprétée comme un réchauffement, par un pic en Ρ et un ratio C:P élevé. L'OAE 1 a, quant à lui, enregistre un refroidissement et coïncide avec le maximum en éléments traces ainsi qu'un fort ratio C:P mettant en valeur l'importance des conditions anoxiques pendant 1ΌΑΕ la dans cette coupe alors qu'aucune perturbation n'est enregistrés à La Bédoule probablement à cause de conditions paléogéographiques locales.Durant l'Aptien inf., les changements environnementaux sur la plate-forme se marquent par la prolifération d'orbitolines due à un changement climatique et une hausse du niveau marin. En domaine profond, la succession de niveaux riches en MO du Barrémien sup. jusqu'à l'OAE la documente l'impact progressif de changements paléoenvironnementaux, probablement liés à la formation du plateau d'Ontong Java à l'ouest de l'océan Pacifique.

Does gender really matter in cathlab

Purpose: Results of some PCI clinical trials indicated more procedure related complications and worse clinical outcomes in women than men, but due to a lower representation of female patients this question still remains open. We aimed toinvestigate characteristics and early and late clinical outcomes in female patients as compared to male when treated in a real life setting with a new generation DES.Methods: Among 3069 consecutive patients treated with Nobori DES, and enrolled in NOBORI 2 study, 675 were female. The primary endpoint of the study is target lesion failure (TLF), a composite of cardiac death, MI and target lesion revascularization (TLR) at 12 months. Data are entered in an electronic database; all adverse events are adjudicated by an independent clinical event committee and independent corelabs analyse all angiograms.Results: Compared to male patients, female patients were significantly older (68±10 vs ± 63±11 years; p<0.001), had higher incidence of diabetes (37% vs 27%; p<0.001) and hypertension (75% vs 66%; p<0.001), but lower frequency of previous MI, PCI/CABG and smoking history. Lesion characteristics were similar in two genders, except for lesions located at bifurcation which were more frequent inmale patients (22% vs 15% inmale and female patients respectively; p<0.001). Majority of QCA assessed parameters were similar with the exception for RVD, post-procedure MLD in-segment and %DS in-stent which were significantly lower in female patients (p<0.05 for all). In table 1 results at 6 months follow-up are presented and at the time of presentation 1 year results will be available. Table 1. Clinical results at 6 months follow-up Male (n=2394) Female (n=675) P value Cardiac Death 12 (0.5%) 5 (0.7%) 0.5550 MI 5 (2.1%) 4 (1.3%) 0.5089 TLR rate 17 (0.7%) 13 (1.9%) 0.0124 TLF rate 44 (1.8%) 17 (2.5%) 0.2745 Stent Thrombosis 12 (0.5%) 6 (0.9%) 0.2548Conclusions: Results indicate that there are differences in the demographics and risk factors in female and male patient's population. The frequency of adverse events at 6 months is low in both populations, showing trend toward slightly higher rate in female patients, particularly for target lesion revascularization.

High proportion of healthcare-associated urinary tract infection in the absence of prior exposure to urinary catheter: a cross-sectional study.

BACKGROUND: Exposure to urinary catheters is considered the most important risk factor for healthcare-associated urinary tract infection (UTI) and is associated with significant morbidity and substantial extra-costs. In this study, we assessed the impact of urinary catheterisation (UC) on symptomatic healthcare-associated UTI among hospitalized patients. METHODS: A nationwide period prevalence survey of healthcare-associated infections was conducted during 1 May to 30 June 2004 in 49 Swiss hospitals and included 8169 adult patients (4313 female; 52.8%) hospitalised in medical, surgical, intermediate, and intensive care wards. Additional data were collected on exposure to UC to investigate factors associated with UTI among hospitalised adult patients exposed and non-exposed to UC. RESULTS: 1917 (23.5%) patients were exposed to UC within the week prior to survey day; 126 (126/8169; 1.5%) developed UTI. Exposure to UC preceded UTI only in 73 cases (58%). By multivariate logistic regression analysis, UTI was independently associated with exposure to UC (odds ratio [OR], 3.9 [95% CI, 2.6-5.9]), female gender (OR, 2.1 [95% CI, 1.4-3.1]), an American Society of Anesthesiologists' score > 2 points (OR, 3.2 [95% CI, 1.1-9.4], and prolonged hospital stay >20 days (OR, 1.9 [95% CI, 1.4-3.2]. Further analysis showed that the only significant factor for UTI with exposure to UC use was prolonged hospital stay >40 days (OR, 2.9 [95% CI, 1.3-6.1], while female gender only showed a tendency (OR, 1.6 [95% CI, 1.0-2.7]. In the absence of exposure to UC, the only significant risk factor for UTI was female gender (OR, 3.3 [95% CI, 1.7-6.5]). CONCLUSIONS: Exposure to UC was the most important risk factor for symptomatic healthcare-associated UTI, but only concerned about half of all patients with UTI. Further investigation is warranted to improve overall infection control strategies for UTI.

Ubiquitination of the Epstein-Barr virus-encoded latent membrane protein 1 depends on the integrity of the TRAF binding site.

The latent membrane protein 1 (LMP1) encoded by the Epstein-Barr virus functions as a constitutively activated receptor of the tumor necrosis factor receptor family. LMP1 is a short-lived protein that is ubiquitinated and degraded by the proteasome. We have previously shown that LMP1 recruits the adapter protein tumor necrosis factor receptor-associated factor 3 (TRAF3) to lipid rafts. To test if TRAFs are involved in LMP1's ubiquitination, we have mutated the LMP1 CTAR1 site that has been identified as a TRAF binding site. We show that the CTAR1 mutant (CTAR1(-)) is expressed after transfection at a similar level to wild-type LMP1, and behaves as wild-type LMP1 with respect to membrane localization. However, CTAR1(-) does not bind TRAF3. We demonstrate that ubiquitination of CTAR1(-) is significantly reduced when compared to wild-type LMP1. In addition, the expression of wild-type LMP1 induces the ubiquitination, an effect that is significantly reduced when the CTAR1(-) is expressed. Taken together, our results suggest that TRAF proteins are involved in the ubiquitination of LMP1, and that their binding to LMP1 may facilitate their own ubiquitination.

Thalamic connectivity in patients with essential tremor treated with MR imaging-guided focused ultrasound: in vivo fiber tracking by using diffusion-tensor MR imaging.

PURPOSE: To use diffusion-tensor (DT) magnetic resonance (MR) imaging in patients with essential tremor who were treated with transcranial MR imaging-guided focused ultrasound lesion inducement to identify the structural connectivity of the ventralis intermedius nucleus of the thalamus and determine how DT imaging changes correlated with tremor changes after lesion inducement. MATERIALS AND METHODS: With institutional review board approval, and with prospective informed consent, 15 patients with medication-refractory essential tremor were enrolled in a HIPAA-compliant pilot study and were treated with transcranial MR imaging-guided focused ultrasound surgery targeting the ventralis intermedius nucleus of the thalamus contralateral to their dominant hand. Fourteen patients were ultimately included. DT MR imaging studies at 3.0 T were performed preoperatively and 24 hours, 1 week, 1 month, and 3 months after the procedure. Fractional anisotropy (FA) maps were calculated from the DT imaging data sets for all time points in all patients. Voxels where FA consistently decreased over time were identified, and FA change in these voxels was correlated with clinical changes in tremor over the same period by using Pearson correlation. RESULTS: Ipsilateral brain structures that showed prespecified negative correlation values of FA over time of -0.5 or less included the pre- and postcentral subcortical white matter in the hand knob area; the region of the corticospinal tract in the centrum semiovale, in the posterior limb of the internal capsule, and in the cerebral peduncle; the thalamus; the region of the red nucleus; the location of the central tegmental tract; and the region of the inferior olive. The contralateral middle cerebellar peduncle and bilateral portions of the superior vermis also showed persistent decrease in FA over time. There was strong correlation between decrease in FA and clinical improvement in hand tremor 3 months after lesion inducement (P < .001). CONCLUSION: DT MR imaging after MR imaging-guided focused ultrasound thalamotomy depicts changes in specific brain structures. The magnitude of the DT imaging changes after thalamic lesion inducement correlates with the degree of clinical improvement in essential tremor.

Global tractography with embedded anatomical priors for quantitative connectivity analysis.

Tractography algorithms provide us with the ability to non-invasively reconstruct fiber pathways in the white matter (WM) by exploiting the directional information described with diffusion magnetic resonance. These methods could be divided into two major classes, local and global. Local methods reconstruct each fiber tract iteratively by considering only directional information at the voxel level and its neighborhood. Global methods, on the other hand, reconstruct all the fiber tracts of the whole brain simultaneously by solving a global energy minimization problem. The latter have shown improvements compared to previous techniques but these algorithms still suffer from an important shortcoming that is crucial in the context of brain connectivity analyses. As no anatomical priors are usually considered during the reconstruction process, the recovered fiber tracts are not guaranteed to connect cortical regions and, as a matter of fact, most of them stop prematurely in the WM; this violates important properties of neural connections, which are known to originate in the gray matter (GM) and develop in the WM. Hence, this shortcoming poses serious limitations for the use of these techniques for the assessment of the structural connectivity between brain regions and, de facto, it can potentially bias any subsequent analysis. Moreover, the estimated tracts are not quantitative, every fiber contributes with the same weight toward the predicted diffusion signal. In this work, we propose a novel approach for global tractography that is specifically designed for connectivity analysis applications which: (i) explicitly enforces anatomical priors of the tracts in the optimization and (ii) considers the effective contribution of each of them, i.e., volume, to the acquired diffusion magnetic resonance imaging (MRI) image. We evaluated our approach on both a realistic diffusion MRI phantom and in vivo data, and also compared its performance to existing tractography algorithms.