BACKGROUND

The International Classification of Functioning (ICF) has acquired a central role in the WHO Family of International Classifications and it has been extensively adopted as the reference framework for health-related functioning (HrF). This review aims to provide a description of the ICF/HrF to contextualise ICF/HrF in relation to other approaches to health functioning and to describe its application in policy and legislation with a special focus on Spain.

METHODS

Narrative review based on the scientific literature and prior expert knowledge.

RESULTS

ICF is both a coding system and a conceptual framework of HrF, which is framed as a unidimensional, bipolar and asymmetric construct with a negative pole (disability) and a positive pole (good functioning) with higher complexity. Other models of HrF include health promotion, quality of life and activities of daily living (ADL). The curtailed taxonomy of ICF and its unclear distinction from other approaches have had significant implications for research, policy and legislation, as illustrated by the case of the legislation and services for functional dependency in Spain and other examples.

CONCLUSIONS

The ICF model of functioning is more comprehensive and usable than previous alternatives, but a full taxonomy of the HrF construct is needed to avoid further confusions in this field. This should also comprise harmonization with other classifications of the WHO Family of International Classifications and other models of health functioning.

OBJECTIVE

To determine if perfusion per unit tissue volume of retinal nerve fibre layer and optic nerve head in the inferior sector is lower than in the superior sector.

METHODS

Heidelberg retinal tomogram (HRT) for topographic measurement of optic nerve head and retinal nerve fibre layer and Heidelberg retinal flowmeter (HRF) for retinal blood flow were performed on 19 normal healthy subjects. Measurements from the superior and inferior sectors were compared. The perfusion/nerve fibre ratio (PNR); the blood flow per unit retinal nerve fibre tissue volume, was calculated in each sector with a formula; HRF flow measurements divided by HRT measurements.

RESULTS

Retinal nerve fibre layer thickness in the inferior retina was significantly higher than in the superior retina (p<0.05). There were, however, no differences in retinal blood flow between the superior and inferior retinal sectors. The PNR in the inferior sector were significantly lower than in the superior sector (p=0.047 for HRF mean flow/rim volume and p = 0.0282 for HRF 75th percentile flow/rim volume).

CONCLUSIONS

The inferior sector of retinal nerve fibre layer and optic nerve head may have lower blood flow per unit nerve tissue volume compared to the superior sector. This result suggests that the inferior sector is more vulnerable to elevated intraocular pressure (IOP) and ischaemic insults in glaucomatous optic neuropathy.

OBJECTIVE

To evaluate the impact of data quality on the localization of brain activation in functional magnetic resonance imaging (fMRI) and to explore whether the temporal contrast-to-noise-ratio (CNR) provides a quantitative parameter to estimate fMRI quality.

METHODS

We investigated two methods for defining the CNR by comparing them on a single-run, single session, as well as on a group-wise basis. The CNRs of healthy subjects and a group of patients with brain lesions were calculated using two different strategies: one based on a general linear model (GLM) analysis (CNR_SPM), and one that acts as an adaptive low-pass filter and assumes that the high-frequency components contain the temporal noise (CNR_SG). Runs with low CNR were identified as outliers using a common exclusion criterion (2 x standard deviation (SD)).

RESULTS

The results of the two CNR methods are highly correlated. Both between and within subjects and patients the CNR showed quite large variations, but the average CNR did not differ between a group of healthy subjects and a patient group. In total, seven of 213 runs (3.3% of all runs) had to be excluded when CNR_SG was used, and 14 of 213 (6.6%) runs had to be excluded when CNR_SPM was used.

CONCLUSIONS

Calculating the CNR using an adaptive low-pass filter gives similar results to a GLM-based approach and could be advantageous for cases in which the hemodynamic response function (HRF) differs significantly from common assumptions. The CNR can be used to identify and exclude runs with suboptimal CNR, and to identify sessions with insufficient data quality. The CNR may serve as a quantitative and intuitive parameter to assess the performance and quality of clinical fMRI investigations, including information on both functional performance (contrast) and data quality (noise caused by the system and physiology).

OBJECTIVE

To assess the diurnal variation in bulbar conjunctival redness, conjunctival temperature, and conjunctival blood flow.

METHODS

Bulbar redness was quantified by CIE u' chromaticity using a SpectraScan PR650 spectrophotometer. Conjunctival temperature was measured using a Tasco-Thi 500 infrared thermometer. Measurements of conjunctival blood flow were obtained using a modified Heidelberg Retinal Flowmeter (HRF). Measurements on 10 subjects were made on a periodic basis over the day and on waking.

RESULTS

For each factor measured a cyclical pattern was observed, with highest values on waking, a reduction in values towards mid-day, and then a gradual increase over the remainder of the day. There was a significant effect of time for redness, temperature, and conjunctival blood flow (p < 0.001 for all three variables), with no significant difference in the cyclical pattern between eyes being observed (p = NS).

CONCLUSIONS

Diurnal bulbar redness, temperature, and conjunctival blood flow variation may be objectively quantified and all three are lowest during the middle of the day and maximal at the start of the day. This information should be considered when undertaking studies in which redness, temperature, and ocular surface blood flow are important outcome variables and time of day is a potential confounding factor.

The gypsy moth (Lymantria dispar) is nonpermissive for Autographa californica nucleopolyhedrovirus (AcNPV) infection. We previously isolated a gene, host range factor 1 (hrf-1), from L. dispar nucleopolyhedrovirus that promotes AcNPV replication in Ld652Y cells, a nonpermissive L. dispar cell line (S. M. Thiem, X. Du, M. E. Quentin, and M. M. Berner, J. Virol. 70:2221-2229, 1996). In the present study, we investigated the ability of hrf-1 to alter the larval host range of AcNPV. Bioassays using recombinant AcNPV bearing hrf-1 were conducted with insect larvae by use of oral infection. AcNPV bearing hrf-1 was infectious for neonate L. dispar larvae, with a 50% lethal concentration of 1.2 x 10(5) polyhedral inclusion bodies/ml of diet, which is similar to that of wild-type AcNPV for permissive hosts. AcNPV can kill neonate L. dispar larvae at high doses, but it does not kill third-instar larvae. However, electron microscopy studies of AcNPV-inoculated third-instar larvae revealed virus replication in the midgut cells. PCR analyses indicated that the virus was AcNPV. These results suggest that the block for AcNPV infection of L. dispar larvae is its inability to spread systematically from primary infection sites in the midgut epithelium and that this barrier is leaky in neonates. hrf-1 allows AcNPV to overcome this barrier. AcNPV recombinants bearing hrf-1 were also significantly more infectious for Helicoverpa zea, a resistant species, suggesting that the blocks for AcNPV infection of L. dispar and H. zea larvae may be similar.

Antigenic relationships among 20 strains of haemorrhagic fever with renal syndrome (HFRS) viruses isolated in Korea, China, U.S.S.R., Finland, Japan and U.S.A. were examined with rat immune sera, patient sera, eight monoclonal antibodies against the SR-11 strain and 10 monoclonal antibodies against the 76-118 strain. Antigen analyses by indirect immunofluorescent antibody and immune adherence haemagglutination tests using polyclonal and monoclonal antibodies demonstrated that HRFS viruses may be divided into four serotypes, i.e. Apodemus (Type 1), Rattus (Type 2), Clethrionomys (Type 3) and Microtus (Type 4). Further, it was demonstrated that Type 1 could be divided into three subtypes and Type 3 into two subtypes. The two sets of monoclonal antibodies were useful for identification of the antigenic types of viruses isolated from patients in endemic areas.

BACKGROUND

We have previously shown that the human recombinant histamine releasing factor (HrHRF) caused histamine release from a subset of basophils from donors with allergy, and this release seemed to be dependent on the presence of a certain type of IgE, termed IgE+. IgE molecules that did not support HrHRF-induced histamine release were termed IgE-. However, subsequently we demonstrated that HrHRF primes anti-IgE-antibody-induced histamine release from all basophils, irrespective of the type of IgE on the cell surface.

OBJECTIVE

Because these data suggested that HrHRF does not exert its biologic effects by binding to IgE, but rather that it interacted with a surface receptor on the basophil, we wanted to obtain functional evidence that HrHRF did or did not bind to the IgE molecule.

METHODS

The rat basophilic leukemia cell line (RBL-SX38), which has been transfected to express a functional human FcepsilonRI (alpha-, beta-, and gamma-chains of the receptor) in addition to the normal rat FcepsilonRI, was used. The presence of the human FcepsilonRI receptor enables these cells to be sensitized with human IgE. Cells were passively sensitized with 1000 ng/mL human IgE+ or 1000 ng/mL human IgE- for 60 minutes at 37 degrees C. Unsensitized cells served as a control. After the cells were washed, 1 x l0(5) cells were stimulated in the presence of 1 mmol/L Ca2+ with 0.1 microg/mL anti-IgE, 40 microg/mL HrHRF, or 40 microg/mL mouse recombinant HRF (MrHRF), which has 96% homology to HrHRF.

RESULTS

Mean anti-IgE-induced histamine release was 33% +/- 15%, and there was no difference between IgE+ sensitization (32% +/- 12%) and IgE- sensitization (34% +/- 18%). However, in contrast to human basophil experiments, neither HrHRF (0% +/- 0%) nor MrHRF (3% +/- 5%) caused histamine release in RBL cells sensitized with IgE+. In addition, priming the transfected RBL-SX38 cells or the parental cell line, RBL-2H3 cells, with HrHRF or MrHRF did not increase anti-IgE-induced histamine release.

CONCLUSIONS

The results indicate that HrHRF does not bind to IgE, either IgE+ or IgE-. Therefore it appears likely that rHRF signals through its own specific receptor, which is not expressed or functional on RBL-SX38 or RBL-2H3 cells, but which seems to be expressed on basophils of atopic and nonatopic donors.

Simultaneous transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) may advance the understanding of neurophysiological mechanisms of TMS. However, it remains unclear if TMS induces fMRI signal changes consistent with the standard hemodynamic response function (HRF) in both local and remote regions. To address this issue, we delivered single-pulse TMS to the left M1 during simultaneous recoding of electromyography and time-resolved fMRI in 36 healthy participants. First, we examined the time-course of fMRI signals during supra- and subthreshold single-pulse TMS in comparison with those during voluntary right hand movement and electrical stimulation to the right median nerve (MNS). All conditions yielded comparable time-courses of fMRI signals, showing that HRF would generally provide reasonable estimates for TMS-evoked activity in the motor areas. However, a clear undershoot following the signal peak was observed only during subthreshold TMS in the left M1, suggesting a small but meaningful difference between the locally and remotely TMS-evoked activities. Second, we compared the spatial distribution of activity across the conditions. Suprathreshold TMS-evoked activity overlapped not only with voluntary movement-related activity but also partially with MNS-induced activity, yielding overlapped areas of activity around the stimulated M1. The present study has provided the first experimental evidence that motor area activity during suprathreshold TMS likely includes activity for processing of muscle afferents. A method should be developed to control the effects of muscle afferents for fair interpretation of TMS-induced motor area activity during suprathreshold TMS to M1.

The operculo-insular cortex has been recently pointed out to be the main area of the pain matrix to be involved in the integration of pain intensity. This fMRI study specified the pattern of response to laser stimuli by focusing on this cortical area, by optimizing the temporal sampling and by investigating pain-related differences in the amplitudes and latencies of the BOLD responses. Canonical and temporal derivative hemodynamic response function (HRF) and finite impulse response (FIR) modeling provided consistent results. Amplitude of BOLD response discriminated painful from non-painful conditions in posterior and mid-insular cortices, bilaterally. Pain conditions were characterized by a shortened latency (as compared to non-painful conditions) in the anterior insula. In the functional organization of the insula, these results suggest a double dissociation that can be summarized as the 'where' and the 'when' of the BOLD response to pain. These results suggest that differences in the amplitude of the BOLD activity in the posterior and in the mid-insular cortices as well as shortened latency of the response in the anterior insula deal with discriminative processes related to painful conditions.

High-field gradient-echo (GE) BOLD fMRI enables very high resolution imaging, and has great potential for detailed investigations of brain function. However, as spatial resolution increases, confounds due to signal from non-capillary vessels increasingly impact the fidelity of GE BOLD fMRI signals. Here we report on an assessment of the microvascular weighting of the GE BOLD response across the cortical depth in human cortex using spin-echo fMRI which is thought to be dominated by microvasculature (albeit not completely). BOLD responses were measured with a hemodynamic impulse response (HRF) obtained from the spin-echo (SE) and gradient-echo (GE) BOLD contrast using very short stimuli (0.25 s) and a fast event-related functional paradigm. We show that the onset (≈ 1.25 s) and the rising slope of the GE and SE HRFs are strikingly similar for voxels in deep gray matter presumably containing the most metabolically demanding neurons (layers III-IV). This finding provides a strong indication that the onset of the GE HRF in deep gray matter is predominantly associated with microvasculature.

We have previously purified and partially characterized histamine releasing factors (HRF), which were derived from a mixture of human mononuclear cells and platelets. We now report the effect of IL-8 upon HRF-, connective tissue activating peptide III (CTAP III)-, and IL-3-induced histamine release from human basophils. We determined that IL-8 itself, at concentrations between 10(-7) to 10(-11) M, does not release histamine from basophils, although positive results are observed in two of 26 subjects at 10(-7) M. Unfractionated (crude) HRF released histamine in 25 of 26 donors, in the range of 6.7% to 100% of total basophil histamine stores. When basophils were preincubated with IL-8 (10(-7) to 10(-11) M) for 5 min, followed by a 40-min incubation with HRF, histamine release was significantly inhibited in 20 of 25 donors. Inhibition was observed at as little as 10(-11) M IL-8, with maximal inhibition being attained at 10(-9) M. HRF-containing supernatants contain a mixture of different histamine-releasing moieties. To better define which factor(s) may be inhibited by IL-8, fractionated supernatants, purified CTAP III, and IL-3 were studied. Histamine release produced by two different HRF-containing chromatographic fractions (HRFvoid and HRFpeak 2) and purified CTAP-III (5 micrograms/ml) was inhibited by IL-8 in 10 of 12 donors, three of three donors, and seven of 10 donors, respectively. IL-3 (5000 U/ml)-dependent histamine release was inhibited by IL-8 in all subjects tested. In contrast, histamine release by anti-IgE and FMLP was not affected by IL-8. Thus, IL-8 appears to be an inhibitor of cytokine-like molecules that induce histamine release and may represent the previously described 8-kDa histamine release inhibitory factor present in mononuclear cell supernatants.

We have purified and further characterized a histamine releasing factor (HRF) derived from human mononuclear cells using gel-filtration HPLC, reverse-phase HPLC, anion exchange chromatography, and elution from SDS gels after electrophoresis. Considerable heterogeneity is seen, far exceeding that published in prior reports. Gel filtration HPLC yielded a major peak at molecular weight 30,000 and minor peaks at 50,000 and 12,000. Reverse-phase HPLC gave one major fraction in the void volume and an eluted peak at 50-60% acetonitrile. Accell QMA anion exchange HPLC revealed three peaks of activity; one in the void volume similar to that published previously using QAE-Sephadex, and peaks that eluted at 0.5 and 0.8 M ammonium acetate, respectively. Electroelution following SDS-PAGE yielded peaks at MW 12,000 and 15-17,000 plus variable peaks at 25-27,000, 31-34,000, and 80-90,000 D. Using a combination of the aforementioned procedures, we have purified molecular species of HRF at 41,000 and 17,000 D to apparent homogeneity, as judged by SDS PAGE and autoradiography. Since human interleukin 3 and granulocyte-macrophage colony-stimulating factor possess histamine-releasing capability, it is clear that multiple cytokines can share this activity. However, the major HRF we isolate from human mononuclear cells appears, thus far, to be unique.

OBJECTIVE

We aimed to investigate patterns of electroencephalography-correlated functional MRI (EEG-fMRI) and subtle structural abnormalities in patients with mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (MTLE-HS) or normal MRI (MTLE-NL).

METHODS

We evaluated EEG-fMRI acquisition of the 25 patients with diagnosis of MTLE who had interictal epileptiform discharges (IEDs) in the intra-MRI EEG: 13 MTLE-HS and 12 MTLE-NL. fMRI was performed using echo-planar images in a 3T MRI coupled with EEG acquired with 64 MRI-compatible electrodes. In the first level analyses, the time of the IEDs ipsilateral to the epileptogenic zone was used as the paradigm, and four contrasts maps were built according to the variation of the hemodynamic response function (HRF) peaks (0, +3, +5, and +7 s). Second level group analyses were performed combining the contrast maps of MTLE-HS or MTLE-NL patients with each different HRF obtained at the first level. Areas of gray matter atrophy were evaluated with voxel-based morphometry (VBM) in both groups.

RESULTS

MTLE-HS and MTLE-NL had IED-related positive BOLD (posBOLD) detected in the ipsilateral anterior temporal lobe and insula. However, only MTLE-HS had significant posBOLD on contralateral hippocampus and anterior cingulate, whereas MTLE-NL had areas of posBOLD on ipsilateral frontal lobe. Both groups had significant IED-related negBOLD responses in areas of the default mode network (DMN), such as posterior cingulate and precuneus. There was no overlap of both posBOLD and negBOLD and areas of atrophy detected by VBM.

CONCLUSIONS

Similar IEDs have different patterns of hemodynamic responses in sub-groups of MTLE. In both MTLE-HS and MTLE-NL, there is a possible suppression of the DMN related to IEDs, as demonstrated by the negBOLD in these areas. The brain areas involved in the interictal related hemodynamic network are not the regions with the most significant gray matter atrophy in MTLE with or without MRI signs of HS.

Previously, we demonstrated a negative correlation between histamine release to histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) and protein levels of SHIP-1 in human basophils. The present study was conducted to investigate whether suppressing SHIP-1 using small interfering (si)RNA technology would alter the releasability of culture-derived mast cells and basophils, as determined by HRF/TCTP histamine release. Frozen CD34+ cells were obtained from the Fred Hutchinson Cancer Research Center (Seattle, WA, USA). Cells were grown in StemPro-34 medium containing cytokines: mast cells with IL-6 and stem cell factor (100 ng/ml each) for 6-8 weeks and basophils with IL-3 (6.7 ng/ml) for 2-3 weeks. siRNA transfections were performed during Week 6 for mast cells and Week 2 for basophils with siRNA for SHIP-1 or a negative control siRNA. Changes in SHIP-1 expression were determined by Western blot. The functional knockdown was measured by HRF/TCTP-induced histamine release. siRNA knockdown of SHIP-1 in mast cells ranged from 31% to 82%, mean 65 +/- 12%, compared with control (n=4). Histamine release to HRF/TCTP was increased only slightly in two experiments. SHIP-1 knockdown in basophils ranged from 34% to 69%, mean 51.8 +/- 7% (n=4). Histamine release to HRF/TCTP in these basophils was dependent on the amount of SHIP knockdown. Mast cells and basophils derived from CD34+ precursor cells represent suitable models for transfection studies. Reducing SHIP-1 protein in cultured mast cells and in cultured basophils increases releasability of the cells.

BACKGROUND

EEG-fMRI of interictal epileptiform discharges (IEDs) usually assumes a fixed hemodynamic response function (HRF). This study investigates HRF variability with respect to IED amplitude fluctuations using independent component analysis (ICA), with the goal of improving the specificity of EEG-fMRI analyses.

METHODS

We selected EEG-fMRI data from 10 focal epilepsy patients with a good quality EEG. IED amplitudes were calculated in an average reference montage. The fMRI data were decomposed by ICA and a deconvolution method identified IED-related components by detecting time courses with a significant HRF time-locked to the IEDs (F-test, p<0.05). Individual HRF amplitudes were then calculated for each IED. Components with a significant HRF/IED amplitude correlation (Spearman test, p<0.05) were compared to the presumed epileptogenic focus and to results of a general linear model (GLM) analysis.

RESULTS

In 7 patients, at least one IED-related component was concordant with the focus, but many IED-related components were at distant locations. When considering only components with a significant HRF/IED amplitude correlation, distant components could be discarded, significantly increasing the relative proportion of activated voxels in the focus (p=0.02). In the 3 patients without concordant IED-related components, no HRF/IED amplitude correlations were detected inside the brain. Integrating IED-related amplitudes in the GLM significantly improved fMRI signal modeling in the epileptogenic focus in 4 patients (p<0.05).

CONCLUSIONS

Activations in the epileptogenic focus appear to show significant correlations between HRF and IED amplitudes, unlike distant responses. These correlations could be integrated in the analysis to increase the specificity of EEG-fMRI studies in epilepsy.

The hantavirus strain Vranica was previously reported to have been isolated from a bank vole in Bosnia-Hercegovina and associated with the occurrence of hemorrhagic fever with renal syndrome (HRFS) in humans. The complete cDNA nucleotide sequences of the small (S) and medium (M) genomic RNA segments of this virus were determined. Major open reading frames were found in the S and M segment between nucleotide positions 43 and 1341 coding for a polypeptide of 433 amino acid residues and between nucleotide positions 41 and 3,484 coding for 1,148 amino acid residues, respectively. The analysis and the alignment of the nucleotide and the derived amino acid sequences with known sequences of other hantavirus strains demonstrate that Vranica resembles Swedish strains and represents a new virus subtype of the Puumala serotype distinct from the subtypes represented by virus strains CG18-20 and Sotkamo.

Information on health-seeking behavior and utilization of health facilities in slums of Addis Ababa is scarce, impeding the implementation of effective interventions. The purpose of this study is to assess the status of health facilities utilization and predictors for health-seeking behavior of mothers/caregivers of under-five children with acute diarrhea in slums of Addis Ababa, Ethiopia.

A community-based cross-sectional study design was employed in five rounds of surveys in seven kebeles in slums of Addis Ababa among 472 mothers/caregivers of 472 under-five children with acute diarrhea in reference to Andersen's behavioral model. Data were entered into EpiData Version 3.1 and analyzed using STATA Version 14.0. Descriptive statistics were used to examine patterns of health facilities utilization and multivariable logistic regression analysis was applied to identify predictors associated with health-seeking behavior.

Most mothers/caregivers (70.8%) sought care either at home (14.2%) or health facilities (56.6%), whereas 29.2% reported that they did not seek any care. Of those who consulted health facilities, government health facilities (76.9%) were more utilized than private (18.0%) and informal (5.1%) health facilities. Nearly all (93.9%) of the mothers/caregivers using government health facilities used health centers, and of those who took their children to private health facilities (60.9%) used clinics and 26.1% used pharmacies/drug vendors. Mothers/caregivers visiting health facilities obtained mainly oral rehydration salt (ORS) (39.8%) and home-recommended fluids (HRF) (40.3%), but few of them (11.9%) obtained ORS plus zinc supplementation. Predisposing factors of literacy of mothers/caregivers (adjusted odds ratio (AOR) = 2.4; 95% CI 1.4-4.1) and occupation (AOR = 2.6; 95% CI 1.5-4.6), the enabling factors of households monthly income of 50 United States Dollars (US$) and above (AOR = 2.9; 95% CI 1.5-5.6) and availability of nearest health facilities within 15 min walking distance (AOR = 3.3; 95% CI 1.7-6.6), and the need factors of recognizing danger signs of fever (AOR = 4.3; 95% CI 2.4-7.6) and vomiting (AOR = 3.3; 95% CI 1.8-5.9) were significantly associated with health-seeking behavior.

Increasing the proximity of health facilities in slums and health education and socioeconomic development programs targeting illiterate mothers/caregivers and poor households may promote and increase health-seeking behavior and the accessibility of health facilities for the treatment of acute diarrhea in under-five children in Addis Ababa slums.

Accurate estimates of the BOLD hemodynamic response function (HRF) are crucial for the interpretation and analysis of event-related functional MRI data. To date, however, there have been no comprehensive measurements of the HRF in white matter (WM) despite increasing evidence that BOLD signals in WM change after a stimulus. We performed an event-related cognitive task (Stroop color-word interference) to measure the HRF in selected human WM pathways. The task was chosen in order to produce robust, distributed centers of activity throughout the cortex. To measure the HRF in WM, fiber tracts were reconstructed between each pair of activated cortical areas. We observed clear task-specific HRFs with reduced magnitudes, delayed onsets and prolonged initial dips in WM tracts compared with activated grey matter, thus calling for significant changes to current standard models for accurately characterizing the HRFs in WM and for modifications of standard methods of analysis of functional imaging data.

In this work, we present an extensive description and evaluation of our method for blood vessel segmentation in fundus images based on a discriminatively trained fully connected conditional random field model.

Standard segmentation priors such as a Potts model or total variation usually fail when dealing with thin and elongated structures. We overcome this difficulty by using a conditional random field model with more expressive potentials, taking advantage of recent results enabling inference of fully connected models almost in real time. Parameters of the method are learned automatically using a structured output support vector machine, a supervised technique widely used for structured prediction in a number of machine learning applications.

Our method, trained with state of the art features, is evaluated both quantitatively and qualitatively on four publicly available datasets: DRIVE, STARE, CHASEDB1, and HRF. Additionally, a quantitative comparison with respect to other strategies is included.

The experimental results show that this approach outperforms other techniques when evaluated in terms of sensitivity, F1-score, G-mean, and Matthews correlation coefficient. Additionally, it was observed that the fully connected model is able to better distinguish the desired structures than the local neighborhood-based approach.

Results suggest that this method is suitable for the task of segmenting elongated structures, a feature that can be exploited to contribute with other medical and biological applications.

OBJECTIVE

This exploratory study examined the notion of Seefeldt's (1980) hypothesized motor skill "proficiency barrier" related to composite levels of health-related physical fitness (HRF) in young adults.

METHODS

A motor skill competence (MSC) index composed of maximum throwing and kicking speed and jumping distance in 187 young adults aged 18 to 25 years old was evaluated against a composite index of 5 health-related fitness (HRF) test scores. MSC (high, moderate, and low) and HRF indexes (good, fair, and poor) were categorized according to normative fitness percentile ranges. 2 separate 3-way chi-square analyses were conducted to determine the probabilities of skill predicting fitness and fitness predicting skill.

RESULTS

Most correlations among HRF and MSC variables by gender demonstrated low-to-moderate positive correlations in both men (12/15; r = .23-.58) and women (14/15; r = .21-.53). Chi-square analyses for the total sample, using composite indexes, demonstrated statistically significant predictive models, chi2(1, N = 187) = 66.99, p < .001, Cramer's V = .42. Only 3.1% of low-skilled (2 of 65) individuals were classified as having a "good" HRF. Only 1 participant (out of 65) who demonstrated high MSC was classified as having "poor" HRF (1.5%).

CONCLUSIONS

Although individual correlations among individual MSC and HRF measures were low to moderate, these data provide indirect evidence for the possibility of a motor skill "proficiency barrier" as indicated by low composite HRF levels. This study may generate future research to address the proficiency barrier hypothesis in youth as well as adults.

Measurements from hydroxyl radical footprinting (HRF) provide rich information about the solvent accessibility of amino acid side chains of a protein. Traditional HRF data analyses focus on comparing the difference in the modification/footprinting rate of a specific site to infer structural changes across two protein states, e.g., between a free and ligand-bound state. However, the rate information itself is not fully used for the purpose of comparing different protein sites within a protein on an absolute scale. To provide such a cross-site comparison, we present a new, to our knowledge, data analysis algorithm to convert the measured footprinting rate constant to a protection factor (PF) by taking into account the known intrinsic reactivity of amino acid side chain. To examine the extent to which PFs can be used for structural interpretation, this PF analysis is applied to three model systems where radiolytic footprinting data are reported in the literature. By visualizing structures colored with the PF values for individual peptides, a rational view of the structural features of various protein sites regarding their solvent accessibility is revealed, where high-PF regions are buried and low-PF regions are more exposed to the solvent. Furthermore, a detailed analysis correlating solvent accessibility and local structural contacts for gelsolin shows a statistically significant agreement between PF values and various structure measures, demonstrating that the PFs derived from this PF analysis readily explain fundamental HRF rate measurements. We also tested this PF analysis on alternative, chemical-based HRF data, showing improved correlations of structural properties of a model protein barstar compared to examining HRF rate data alone. Together, this PF analysis not only permits a novel, to our knowledge, approach of mapping protein structures by using footprinting data, but also elevates the use of HRF measurements from a qualitative, cross-state comparison to a quantitative, cross-site assessment of protein structures in the context of individual conformational states of interest.

OBJECTIVE

To study antenatal risk factors and inflammatory responses during hypoxic respiratory failure (HRF) in infants of very low gestational age (VLGA, ≤32.0 weeks).

METHODS

Of a cohort of 765 VLGA infants, 144 required mechanical ventilation. Airway specimens from these patients were prospectively studied. Infants who developed HRF (oxygenation index >25) with echocardiographic diagnosis of pulmonary hypertension were treated with inhaled nitric oxide (iNO). Three gestation comparison groups were formed on the basis of specific antenatal complications: prolonged preterm rupture of membranes (PPROM), spontaneous preterm birth, and preeclampsia. Chest radiographs were studied and airway specimens were analyzed for concentrations of tumor necrosis factor-α, interleukin (IL)-6, IL-8, IL-10, IL-12p70, IL-1β, and nitrite + nitrate over 4 days.

RESULTS

Seventeen (2.2% of all VLGA infants) developed HRF. In all 17 cases, PPROM complicated the antenatal course; these infants responded to iNO, regardless of infection or PPROM. The chest radiographs of HRF and non-HRF PPROM infants were similar. Airway proinflammatory cytokines and nitrite + nitrate levels were low in infants with HRF, but they increased during iNO treatment and remained elevated after discontinuation of iNO. Each of the 3 comparison groups had different and characteristic patterns of airway cytokines and nitrite + nitrate levels.

CONCLUSIONS

Seven percent of VLGA infants with preterm rupture of membranes and 15% of those with PPROM developed HRF, characterized by pulmonary hypertension that acutely responds to iNO. These infants may have a transient deficiency in the inflammatory response, including a defect in nitric oxide generation in airspaces.

OBJECTIVE

To determine the clinical utility of SNAP score versus the highest oxygen index (OI) in first 24 hours of admission in predicting outcome of HRF.

METHODS

All admissions (1991 to 1999)>> or =36 weeks gestation, ventilated for>> or =12 hours with FiO(2>> or =0.50, without congenital anomalies were reviewed. Primary outcome measure was survival (without ECMO) versus ECMO and/or death.

RESULTS

From 184 infants with HRF, 148 survived (without ECMO) versus 36 died and/or received ECMO. SNAP score and highest OI were similar in predicting outcome of HRF (area under ROC curve: 0.813+/-0.037 versus 0.814+/-0.041; P=0.72). Death and/or ECMO requirement were best predicted by a SNAP score of 19 (Sensitivity 75.0%, Specificity 71%) or an OI of 28 (Sensitivity 75.0%, Specificity 76.4%).

CONCLUSIONS

Although both, the SNAP score and highest OI, are useful and similar in predicting outcome of HRF, OI is preferable because of its ease of use. We believe the predictive value of these parameters should be evaluated in a multicenter setting.

UNASSIGNED

The purpose of this study was to evaluate the correlation between quantity of intraretinal hyperreflective foci (HRF) in the eye with intermediate AMD and progression to late AMD.

UNASSIGNED

Volume optical coherence tomography (OCT) scans from 114 eyes of 114 patients were retrospectively reviewed. <em>HRF</em> were assessed both qualitatively and quantitatively. Five sequential en face slabs from midretina were thresholded to isolate the <em>HRF</em>. These five slabs were recombined, and <em>HRF</em> area was measured in the whole 6 × 6-mm image (<em>HRF</em>TOT) and within the central 3-mm (<em>HRF</em>3mm) and 5-mm (<em>HRF</em>5mm) regions. These measurements were correlated with the development of late AMD (defined as choroidal neovascularization [CNV] and/or complete RPE and photoreceptor atrophy [cRORA]) after 1 year of follow-up.

UNASSIGNED

HRF area in all three regions showed significant correlations with progression to late AMD: R = 0.610 for HRFHRFHRFTOT (all P < 0.001). Correlations remained significant with progression to cRORA alone, though not for progression to CNV alone. While qualitative assessment of HRF (i.e., presence of HRF: yes or no) also showed a significant correlation with progression to late AMD (R = 0.454, P < 0.001) and atrophy alone (R = 0.445, P < 0.001), they were weaker than by HRF quantification.

UNASSIGNED

The area of HRF from en face OCT in eyes with intermediate AMD correlates with the 1-year risk of progression to late AMD, and in particular with the development of atrophy.