Biomedical subjects

Yoav Benjamini

Publications and source records attributed to Yoav Benjamini.

17 recordsLinked to original sources

PubMed2006

Coordination of steering in a free-trotting quadruped.

Typically, locomotion has been studied by restricting the animal's path and/or speed, focusing on stride and step kinematics. Here we incorporate measurements of the legs and trunk in the support and swing phases, during trotting with various speeds and curvatures. This paradigm releases the animal from the confines of the treadmill and runway into the open space. The diagonal step, a new unit of locomotion, is defined by regarding the line between the two supporting diagonal legs as a frame of reference for the description of the dynamics of the virtual line between the two swinging diagonal legs. This analysis reveals that during free trotting the mouse uses three types of steps: fixating, opening, and closing steps. During progression along a straight path, the mouse uses fixating steps, in which the swinging diagonal maintains a fixed direction, landing on the supporting foreleg; during progression along a curved path the mouse uses opening and closing steps alternately. If two steps of the same type are performed sequentially, they engender an abrupt change of direction. Our results reveal how steering with the swinging diagonal, while using a virtually bipedal gait, engenders the whole repertoire of free-trotting behavior.

Animals↗

PubMed2006

Cluster-based analysis of FMRI data.

We propose a method for the statistical analysis of fMRI data that tests cluster units rather than voxel units for activation. The advantages of this analysis over previous ones are both conceptual and statistical. Recognizing that the fundamental units of interest are the spatially contiguous clusters of voxels that are activated together, we set out to approximate these cluster units from the data by a clustering algorithm especially tailored for fMRI data. Testing the cluster units has a two-fold statistical advantage over testing each voxel separately: the signal to noise ratio within the unit tested is higher, and the number of hypotheses tests compared is smaller. We suggest controlling FDR on clusters, i.e., the proportion of clusters rejected erroneously out of all clusters rejected and explain the meaning of controlling this error rate. We introduce the powerful adaptive procedure to control the FDR on clusters. We apply our cluster-based analysis (CBA) to both an event-related and a block design fMRI vision experiment and demonstrate its increased power over voxel-by-voxel analysis in these examples as well as in simulations.

Algorithms↗

PubMed2006

Combined application of behavior genetics and microarray analysis to identify regional expression themes and gene-behavior associations.

In this report we link candidate genes to complex behavioral phenotypes by using a behavior genetics approach. Gene expression signatures were generated for the prefrontal cortex, ventral striatum, temporal lobe, periaqueductal gray, and cerebellum in eight inbred strains from priority group A of the Mouse Phenome Project. Bioinformatic analysis of regionally enriched genes that were conserved across all strains revealed both functional and structural specialization of particular brain regions. For example, genes encoding proteins with demonstrated anti-apoptotic function were over-represented in the cerebellum, whereas genes coding for proteins associated with learning and memory were enriched in the ventral striatum, as defined by the Expression Analysis Systematic Explorer (EASE) application. Association of regional gene expression with behavioral phenotypes was exploited to identify candidate behavioral genes. Phenotypes that were investigated included anxiety, drug-naive and ethanol-induced distance traveled across a grid floor, and seizure susceptibility. Several genes within the glutamatergic signaling pathway (i.e., NMDA/glutamate receptor subunit 2C, calmodulin, solute carrier family 1 member 2, and glutamine synthetase) were identified in a phenotype-dependent and region-specific manner. In addition to supporting evidence in the literature, many of the genes that were identified could be mapped in silico to surrogate behavior-related quantitative trait loci. The approaches and data set described herein serve as a valuable resource to investigate the genetic underpinning of complex behaviors.

Alcoholism↗

PubMed2006

Extrinsic and intrinsic systems in the posterior cortex of the human brain revealed during natural sensory stimulation.

When exposing subjects to a continuous segment of an audiovisual movie, a large expanse of human cortex, especially in the posterior half of the cerebral cortex, shows stimulus-driven activity. However, embedded within this widespread activity, there are cortical regions whose activity is dissociated from the external stimulation. These regions are intercorrelated among themselves, forming a functional network, which largely overlaps with cortical areas previously shown to be deactivated by task-oriented paradigms. Moreover, the network of areas whose neuronal dynamics are associated with external inputs and the network of areas that appears to be intrinsically driven complement each other, providing coverage of most of the posterior cortex. Thus, we propose that naturalistic stimuli reveal a fundamental neuroanatomical partition of the human posterior cortex into 2 global networks: an "extrinsic" system, comprising areas associated with the processing of external inputs, and an "intrinsic" system, largely overlapping with the task-negative, default-mode network, comprising areas associated with--as yet not fully understood--intrinsically oriented functions.

Acoustic Stimulation↗

PubMed2005

Quantitative trait Loci analysis using the false discovery rate.

False discovery rate control has become an essential tool in any study that has a very large multiplicity problem. False discovery rate-controlling procedures have also been found to be very effective in QTL analysis, ensuring reproducible results with few falsely discovered linkages and offering increased power to discover QTL, although their acceptance has been slower than in microarray analysis, for example. The reason is partly because the methodological aspects of applying the false discovery rate to QTL mapping are not well developed. Our aim in this work is to lay a solid foundation for the use of the false discovery rate in QTL mapping. We review the false discovery rate criterion, the appropriate interpretation of the FDR, and alternative formulations of the FDR that appeared in the statistical and genetics literature. We discuss important features of the FDR approach, some stemming from new developments in FDR theory and methodology, which deem it especially useful in linkage analysis. We review false discovery rate-controlling procedures--the BH, the resampling procedure, and the adaptive two-stage procedure-and discuss the validity of these procedures in single- and multiple-trait QTL mapping. Finally we argue that the control of the false discovery rate has an important role in suggesting, indicating the significance of, and confirming QTL and present guidelines for its use.

Chromosome Mapping↗

PubMed2005

Genotype-environment interactions in mouse behavior: a way out of the problem.

In behavior genetics, behavioral patterns of mouse genotypes, such as inbred strains, crosses, and knockouts, are characterized and compared to associate them with particular gene loci. Such genotype differences, however, are usually established in single-laboratory experiments, and questions have been raised regarding the replicability of the results in other laboratories. A recent multilaboratory experiment found significant laboratory effects and genotype x laboratory interactions even after rigorous standardization, raising the concern that results are idiosyncratic to a particular laboratory. This finding may be regarded by some critics as a serious shortcoming in behavior genetics. A different strategy is offered here: (i) recognize that even after investing much effort in identifying and eliminating causes for laboratory differences, genotype x laboratory interaction is an unavoidable fact of life. (ii) Incorporate this understanding into the statistical analysis of multilaboratory experiments using the mixed model. Such a statistical approach sets a higher benchmark for finding significant genotype differences. (iii) Develop behavioral assays and endpoints that are able to discriminate genetic differences even over the background of the interaction. (iv) Use the publicly available multilaboratory results in single-laboratory experiments. We use software-based strategy for exploring exploration (see) to analyze the open-field behavior in eight genotypes across three laboratories. Our results demonstrate that replicable behavioral measures can be practically established. Even though we address the replicability problem in behavioral genetics, our strategy is also applicable in other areas where concern about replicability has been raised.

Analysis of Variance↗

PubMed2004

New replicable anxiety-related measures of wall vs center behavior of mice in the open field.

Anxiety is a widely studied psychiatric disorder and is thought to be a complex and multidimensional phenomenon. Sensitive behavioral discrimination of animal models of anxiety is crucial for the elucidation of the behavioral components of anxiety and the physiological processes that mediate them. Commonly used behavior paradigms of anxiety usually include only a few automatically collected measures; these do not exhaust the behavioral richness exhibited by animals, thus perhaps missing important differences between preparations. The aim of the present study was to expand the repertoire of automatically collected measures in a classical test of anxiety: behavior in relation to the wall in the open field. We present an algorithm, based on the Software for the Exploration of Exploration strategy, which automatically partitions the mouse path into intrinsically defined patterns of movement near the wall and in the center. These patterns are used to design new end points, which provide an articulated description of various aspects of behavior near the wall and in the center. Sixteen new end points were designed with data from C57BL/6J and DBA/2J mice tested in three laboratories. The strain differences in all end points were evaluated on another data set to assess their validity and were found to remain stable. Ten of the sixteen end points were found to discriminate between the two strains in a replicable manner. The entire set of end points can be used on various genetic and pharmacological models of anxiety with good prospects of providing fine discrimination in a replicable manner.

Algorithms↗

PubMed2004

The dynamics of spatial behavior: how can robust smoothing techniques help?

A variety of setups and paradigms are used in the neurosciences for automatically tracking the location of an animal in an experiment and for extracting features of interest out of it. Many of these features, however, are critically sensitive to the unavoidable noise and artifacts of tracking. Here, we examine the relevant properties of several smoothing methods and suggest a combination of methods for retrieving locations and velocities and recognizing arrests from time series of coordinates of an animal's center of gravity. We accomplish these by using robust nonparametric methods, such as Running Median (RM) and locally weighted regression methods. The smoothed data may, subsequently, be segmented to obtain discrete behavioral units with proven ethological relevance. New parameters such as the length, duration, maximal speed, and acceleration of these units provide a wealth of measures for, e.g., mouse behavioral phenotyping, studies on spatial orientation in vertebrates and invertebrates, and studies on rodent hippocampal function. This methodology may have implications for many tests of spatial behavior.

Algorithms↗

PubMed2004

Photodynamic therapy for age-related macular degeneration in a clinical setting: visual results and angiographic patterns.

PURPOSE: To evaluate the visual outcome of patients with subfoveal choroidal neovascularization due to age-related macular degeneration, who received photodynamic therapy (PTD) in a clinical setting and to identify potential predictive visual and angiographic factors. DESIGN: Interventional case series. METHODS: The study included 74 patients with subfoveal choroidal neovascularization who underwent PDT from January 2000 to March 2001 and completed at least 1 year follow-up. All patients received verteporfin PDT and were followed clinically, with fluorescein angiography (74 eyes), and with indocyanine green angiography (65 eyes). A review of the medical records and angiograms was performed. RESULTS: Mean follow-up was 15.6 months. Patients received a mean of 3.4 treatments per year. Sixty-six percent lost less than 3 Snellen lines of visual acuity. Three patients (4%) experienced profound visual acuity loss to finger counting. Final visual acuity was positively correlated with lesion size and visual acuity at presentation. Visual outcome was worse in the presence of cystoid macular edema. On indocyanine green angiography, a round hypofluorescent spot was seen at the site of the PDT, with maintenance of medium and large choroidal vessels. CONCLUSION: Smaller lesion size and better visual acuity at presentation were good predictive signs, whereas cystoid macular edema was found to be a poor prognostic sign for visual outcome following PDT.

Aged↗

PubMed2004

Intraocular pressure variations after diode laser photocoagulation for threshold retinopathy of prematurity.

PURPOSE: To investigate the intraocular pressure (IOP) variations occurring after indirect diode laser photocoagulation for threshold retinopathy of prematurity. DESIGN: Prospective, nonrandomized, comparative study. PARTICIPANTS: A study group-21 consecutive premature babies (42 eyes) undergoing diode laser photocoagulation for retinopathy of prematurity-and control groups-32 premature babies (64 eyes) undergoing retinal examination with or without scleral indentation. INTERVENTION: Intraocular pressure was measured with a portable electronic tonometer before, immediately after, and 1, 2, and 3 days after diode laser photocoagulation in the study group; before retinal examination in control group 1; and before and after retinal examination with scleral indentation in control group 2. MAIN OUTCOME MEASURE: Intraocular pressure after diode laser photocoagulation for threshold retinopathy of prematurity. RESULTS: Mean IOP in the study group rose from 15 mmHg (standard deviation [SD] = 4.1) before coagulation to 33.2 mmHg (SD = 7.8; range, 20-50) immediately after, and then dropped to 22.2 (SD = 5.2), 16.5 (SD = 3), and 14.5 mmHg (SD = 2.1) 1, 2, and 3 days later, respectively. All the changes were statistically significant at P<0.0001, except for the difference between days 2 and 3 (P = 0.096). Mean baseline IOPs were 16.3 mmHg (SD = 3.7) in control group 1 and 15.7 mmHg (SD = 2.3) in control group 2 (P = 0.84 between control group 1 and study group, and P = 0.32 between control group 2 and the study group). At termination of the retinal examination with scleral indentation (control group 2), IOP measured 15.1 mmHg (SD = 2.2) (P = 0.49 compared with baseline). CONCLUSIONS: Intraocular pressure may be significantly elevated after diode laser photocoagulation for retinopathy of prematurity. The mechanism and long-term clinical implications of this observation should be investigated.

Female↗

PubMed2004

Association of neovascular age-related macular degeneration and hyperhomocysteinemia.

PURPOSE: To assess the relationship between plasma homocysteine levels and exudative neovascular age-related macular degeneration (AMD). DESIGN: Cross-sectional study. METHODS: A prospective comparative cross-sectional study was conducted in outpatient ophthalmology clinics in a university-affiliated medical institution. The cohort consisted of 59 patients (25 male, 34 female) with a mean age of 78 years (standard deviation [SD] = 8.4) with neovascular AMD who were candidates for photodynamic treatment. Patients were compared for plasma homocysteine levels with 58 patients who had dry AMD (24 male, 34 female) with a mean age of 76.3 years (SD = 8.4) and with a control group of 56 age-matched subjects (27 male, 29 female), with a mean age of 77.3 years (SD = 8.2). A 3-ml venous blood sample was obtained from each participant after an 8-hour fast. Levels of plasma homocysteine were measured by high performance liquid chromatography. The main outcome measure was hyperhomocysteinemia, defined as a plasma homocysteine level above 15 micromol/l. RESULTS: Homocysteine levels were higher by 27.9% in the neovascular AMD than in the dry AMD group, and by 21.9% than in the control group (P <.02). Hyperhomocysteinemia was found in 44.1% of the study group, in 22.4% of the dry AMD group, and in 21.4% of the control group (P =.011). CONCLUSIONS: This study suggests an association between an elevated plasma level of homocysteine and exudative neovascular AMD but not dry AMD.

Aged↗

PubMed2003

Identifying differentially expressed genes using false discovery rate controlling procedures.

MOTIVATION: DNA microarrays have recently been used for the purpose of monitoring expression levels of thousands of genes simultaneously and identifying those genes that are differentially expressed. The probability that a false identification (type I error) is committed can increase sharply when the number of tested genes gets large. Correlation between the test statistics attributed to gene co-regulation and dependency in the measurement errors of the gene expression levels further complicates the problem. In this paper we address this very large multiplicity problem by adopting the false discovery rate (FDR) controlling approach. In order to address the dependency problem, we present three resampling-based FDR controlling procedures, that account for the test statistics distribution, and compare their performance to that of the naïve application of the linear step-up procedure in Benjamini and Hochberg (1995). The procedures are studied using simulated microarray data, and their performance is examined relative to their ease of implementation. RESULTS: Comparative simulation analysis shows that all four FDR controlling procedures control the FDR at the desired level, and retain substantially more power then the family-wise error rate controlling procedures. In terms of power, using resampling of the marginal distribution of each test statistics substantially improves the performance over the naïve one. The highest power is achieved, at the expense of a more sophisticated algorithm, by the resampling-based procedures that resample the joint distribution of the test statistics and estimate the level of FDR control. AVAILABILITY: An R program that adjusts p-values using FDR controlling procedures is freely available over the Internet at www.math.tau.ac.il/~ybenja.

Algorithms↗

PubMed2003

SEE locomotor behavior test discriminates C57BL/6J and DBA/2J mouse inbred strains across laboratories and protocol conditions.

Conventional tests of behavioral phenotyping frequently have difficulties differentiating certain genotypes and replicating these differences across laboratories and protocol conditions. This study explores the hypothesis that automated tests can be designed to quantify ethologically relevant behavior patterns that more readily characterize heritable and replicable phenotypes. It used SEE (Strategy for the Exploration of Exploration) to phenotype the locomotor behavior of the C57BL/6 and DBA/2 mouse inbred strains across 3 laboratories. The 2 genotypes differed in 15 different measures of behavior, none of which had a significant genotype-laboratory interaction. Within the same laboratory, most of these differences were replicated in additional experiments despite the test photoperiod phase being changed and saline being injected. Results suggest that well-designed tests may considerably enhance replicability across laboratories.

Animals↗

PubMed2002

Tactile corneal reflex development in full-term babies.

OBJECTIVE: To evaluate the development of the tactile corneal reflex in healthy full-term babies. DESIGN: Prospective longitudinal comparative case series. PARTICIPANTS: One hundred and ninety-one babies aged 1 to 3 days examined in the nursery, and 200 babies aged 1 to 12 weeks examined in an orthopedic outpatient clinic. METHODS: The tactile corneal reflex was evaluated by three ophthalmologists using the Cochet-Bonnet esthesiometer. MAIN OUTCOME MEASURES: The probability of the presence of the tactile corneal reflex was calculated in relation to gestational age, postpartum age, postconceptional age, and birth weight. RESULTS: The proportion of children with tactile corneal reflex was expressed in a linear logistic model. We found that 10% of the babies had tactile corneal reflex in at least one eye at 2 days of age, 25% at 1 week, 50% at 3.5 weeks, 75% at 6 weeks, and 100% at 12 weeks. The postpartum age had a greater impact on the development of the tactile corneal reflex than the gestational age. The birth weight also had a statistically significant influence (P = 0.005, Wald's test). CONCLUSIONS: The tactile corneal reflex is present in only a minority of newborns and develops during the first 3 months of life. These results demonstrate that the tactile corneal reflex has a longitudinal neurologic development and is part of the normal neurologic maturation process.

Aging↗

PubMed2002

Serum creatine kinase levels in untreated hospitalized adolescents during acute psychosis.

OBJECTIVE: Psychosis-associated creatine kinase (CK)-emia (PACK) is a common and pronounced laboratory abnormality that accompanies adult psychotic conditions. Adult PACK is a relatively consistent individual trait. The authors investigated whether psychotic adolescents also present with such PACK characteristics. METHOD: Participants were 127 newly admitted, drug-free, psychotic Israeli adolescents. Measures were baseline psychotic severity, serum creatine kinase (CK0), lactate dehydrogenase (LDH0), glutamate oxaloacetate transaminase (SGOT0), white blood cell count (WBC0), urine myoglobulin, and the repeated CK (RepCK) measurements taken during recurrent psychotic episodes. RESULTS: Schizophrenia was the prevalent diagnosis (53%). CK0 levels did not correlate with the severity of the psychotic symptoms. Twenty-one percent of patients had a CK0 level >1,000 IU/L. CK0 and RepCK levels were higher in males than in females (p < or = .001) and in Jewish Sephardi patients than in Ashkenazi patients (p < .007). There was no difference by diagnosis. Logarithmic (Ln) CK0 correlated with RepCK, SGOT0, LDH0, and WBC0 (r = +0.32-0.74, p < .001) but correlated inversely with serum cholesterol0 (r = -0.36, p = .002) in males. Even prominent PACK was not associated with myoglobinuria. These findings remained significant among the younger patients (aged <18 years). In males from this subgroup, LnCK0 also correlated with age (p < .007) but not with weight. CONCLUSIONS: In psychotic adolescents, PACK is common, is more prevalent among males, is independent of diagnosis, is influenced by ethnicity, and tends to recur.

Adolescent↗

PubMed2002

High serum creatinine kinase level: possible risk factor for neuroleptic malignant syndrome.

High creatinine kinase (CK) levels and leukocytosis are known to be associated with neuroleptic malignant syndrome (NMS). The authors sought to determine if their presence during non-NMS psychotic episodes is predictive of the later development of NMS. Sixteen psychotic inpatients who met the criteria for NMS were included. For statistical comparison, two control groups were formed by matching each study patient with two non-NMS patients for age, gender, ethnicity, and year and ward of hospitalization (n = 32). The maximal individual serum levels of CK, lactate dehydrogenase (LDH), serum glutamic oxaloacetic transaminase (SGOT), and white blood cell count (WBC) during all non-NMS psychotic episodes (Brief Psychiatric Rating Scale 40) were averaged. To normalize the distribution, the individual averages were transformed to natural logarithms (Ln). Mean Ln (average [CK]) in the patients with NMS was found to be 6.46 +/- 0.91 IU/L, and in the non-NMS patients, 5.24 +/- 0.90 IU/L (actual serum CK levels, 911 +/- 747 IU/L and 343 +/- 620 IU/L, respectively). This difference was statistically significant (F [2,15] = 10.5, p < 0.0001). In addition, CK levels above the upper limit of normal were noted in 76% of psychotic episodes in the patients with NMS and in only 30% of psychotic episodes in the non-NMS patients (p < 0.0001). There was no significant difference between the NMS and non-NMS groups in Ln(LDH), Ln(SGOT), or Ln(WBC) (F [2,15] = 1.4, 2.1, and 0.9, respectively). The authors concluded that high serum CK level during non-NMS psychotic episodes seems to be a risk factor for future NMS. Therefore, CK measurement may be justified on admission of acutely psychotic patients who have other risk factors and a history of psychosis-associated CKemia.

Adult↗

PubMedDate not supplied

Combined pars plana vitrectomy and cataract surgery: outcome of phacoemulsification versus manual extracapsular cataract extraction through a sclerocorneal tunnel.

BACKGROUND AND OBJECTIVE: To compare the results of combined pars plana vitrectomy and cataract extraction with intraocular lens implantation by phacoemulsification versus manual extracapsular cataract extraction through a sclerocorneal tunnel. PATIENTS AND METHODS: Retrospective chart review of all patients who underwent combined pars plana vitrectomy with intraocular lens implantation and phacoemulsification or extracapsular cataract extraction through a sclerocorneal tunnel between March 1992 and July 2002. RESULTS: Fifty-four eyes of 51 patients were evaluated. Mean age was 69.68 +/- 9.11 years, and mean follow-up was 9 months. Phacoemulsification was performed in 35 cases (64%) and manual extraction in 19 cases (36%). Visual acuity improved from mean logarithm of the minimal angle of resolution 1.69 +/- 0.54 before surgery to 1.22 +/- 0.76 after surgery. There was a greater improvement of visual acuity in the phacoemulsification group (0.59 +/- 0.67) than in the extracapsular cataract extraction group (0.22 +/- 0.68) (P = .06). Final visual acuity was correlated to the vitreoretinal pathology. Ultrasound biomicroscopy showed well-positioned foldable or rigid intraocular lens in the bag or in the sulcus. CONCLUSION: Combined cataract extraction by phacoemulsification or extracapsular cataract extraction through sclerocorneal tunnel and pars plana vitrectomy are safe and effective procedures.

Adult↗