320 medicated IUDs were removed from 292 women by means of the dynamometer. This instrument indicates the highest retention force (HRF) in newtons (N). Ages of the women ranged from 17-50 years. The IUDs were fitted in nulligravidae (56%), nulliparous with 1 or more abortions (13%), primiparous (18%), and multiparous (13%) women. The IUDs used were the ML Cu 250-standard, 7 Cu 200, T Cu 200-adapted, with a shortened transversal arm of 15-30 mm and T Cu 200 standard. With the low expulsion rate, the ML Cu 250-standard IUD needed 5.8-5.4N and the 7 Cu 200 3.8-2.6N. The adapted T Cu 200 IUD needed 2.6-1.6N, i.e., about 1N more thant the T Cu 200-standard with an HRF of 1.7-1.0N. As the dynamomoeter only indicated the highest retention force, a retentiograph was devised to demonstrate the different retention forces and phases of the various IUDs by characteristic curves. The possible connections between retention and expulsion of IUDs are discussed. The retention forces of the different IUDs compared are congruent with the published expulsion rates. The retentiograph showed new patterns to test IUDs before they demonstrate side effects in vitro.

Understanding the spatiotemporal features of the hemodynamic response function (HRF) to brain stimulation is essential for the correct application of neuroimaging methods to study brain function. Here, we investigated the spatiotemporal evolution of the blood oxygen level-dependent (BOLD) and cerebral blood volume (CBV) HRF in conscious, awake marmosets (Callithrix jacchus), a New World non-human primate with a lissencephalic brain and with growing use in biomedical research. The marmosets were acclimatized to head fixation and placed in a 7-T magnetic resonance imaging (MRI) scanner. Somatosensory stimulation (333-μs pulses; amplitude, 2 mA; 64 Hz) was delivered bilaterally via pairs of contact electrodes. A block design paradigm was used in which the stimulus duration increased in pseudo-random order from a single pulse up to 256 electrical pulses (4 s). For CBV measurements, 30 mg/kg of ultrasmall superparamagnetic ironoxide particles (USPIO) injected intravenously, were used. Robust BOLD and CBV HRFs were obtained in the primary somatosensory cortex (S1), secondary somatosensory cortex (S2) and caudate at all stimulus conditions. In particular, BOLD and CBV responses to a single 333-μs-long stimulus were reliably measured, and the CBV HRF presented shorter onset time and time to peak than the BOLD HRF. Both the size of the regions of activation and the peak amplitude of the HRFs grew quickly with increasing stimulus duration, and saturated for stimulus durations greater than 1 s. Onset times in S1 and S2 were faster than in caudate. Finally, the fine spatiotemporal features of the HRF in awake marmosets were similar to those obtained in humans, indicating that the continued refinement of awake non-human primate models is essential to maximize the applicability of animal functional MRI studies to the investigation of human brain function.

Early de-oxygenation (initial dip) is an indicator of the primal cortical activity source in functional neuro-imaging. In this study, initial dip's existence and its estimation in relation to the differential pathlength factor (DPF) and data drift were investigated in detail. An efficient algorithm for estimation of drift in fNIRS data is proposed. The results favor the shifting of the fNIRS signal to a transformed coordinate system to infer correct information. Additionally, in this study, the effect of the DPF on initial dip was comprehensively analyzed. Four different cases of initial dip existence were treated, and the resultant characteristics of the hemodynamic response function (HRF) for DPF variation corresponding to particular near-infrared (NIR) wavelengths were summarized. A unique neuro-activation model and its iterative optimization solution that can estimate drift in fNIRS data and determine the best possible fit of HRF with free parameters were developed and herein proposed. The results were verified on simulated data sets. The algorithm is applied to free available datasets in addition to six healthy subjects those were experimented using fNIRS and observations and analysis regarding shape of HRF were summarized as well. A comparison with standard GLM is also discussed and effects of activity strength parameters have also been analyzed.

We introduce a model describing real-time grating formation in holographic photopolymers, under the assumption that the diffusion of free monomers is much faster than the grating formation. This model, which combines polymerization kinetics with results from coupled-wave theory, indicates that the grating formation time depends sublinearly on the average holographic recording intensity, and the beam intensity ratio controls the grating index modulation at saturation. We validate the model by comparing its predictions with the results of experiments in which DuPont HRF-150X001 photopolymer was used.

OBJECTIVE

To study whether nebulized nitroprusside (neb-NP) improves oxygenation in term infants with hypoxic respiratory failure (HRF).

METHODS

We studied 22 newborn term infants (gestational age, 39.7+/-0.4 weeks [mean+/-SEM]; birth weight, 3.6+/-0.1 kg) with hypoxia (Pao2<100 mm Hg) during mechanical ventilation (Fio2=1.0). Sodium nitroprusside (5 mg followed by 25 mg) was nebulized into the inspiratory arm of the ventilator circuit. Vital signs and arterial blood gas values were recorded after 20 minutes at each dose and before and after initiation of inhaled nitric oxide (iNO).

RESULTS

Pao2 increased significantly with 5 mg neb-NP (from 64.6+/-5.6 to 90.1+/-15.3 mm Hg, P=.04) and with 25 mg neb-NP (113.2+/-20.4 mm Hg, P=.009). Differences between mean Pao2 at 5 mg versus 25 mg neb-NP were also statistically significant (P=.03). When comparing the effect of neb-NP to iNO, the treatment-induced increases in Pao2 were similar (52.1+/-18.7 vs 62.2+/-18.2 mm Hg, respectively, P=not significant).

CONCLUSIONS

Neb-NP causes a dose-dependent increase in oxygenation in term infants with HRF, similar in magnitude to iNO* Neb-NP may be beneficial in infants with HRF when iNO is not readily available.

OBJECTIVE

We evaluated the efficacy of surfactant therapy and assisted ventilation on morbidity and mortality of neonates with birth weight (BW) ⩾1500 g and hypoxemic respiratory failure (HRF).

METHODS

We retrospectively analyzed 5650 patients with BW ⩾1500 g for incidence, management and outcome of HRF, defined as acute hypoxemia requiring mechanical ventilation and/or nasal continuous positive airway pressure ⩾24 h. The patients were allocated into groups of moderate preterm (1735, 30.7%), late preterm (1431, 25.4%), early term (ETM, 986, 17.5%), full term (1390, 24.6%) and post term (79, 1.4%), with gestational age ⩽33, 34 to 36, 37 to 38, 39 to 41 and ⩾42 weeks, respectively.

RESULTS

In the five groups, 66.9, 42, 21.6, 12.8 and 5.1% had respiratory distress syndrome (RDS). For pneumonia/sepsis and meconium aspiration syndrome (MAS), the proportion was 13.8%, 25.4%, 38.0%, 52.5% and 76.0%, respectively. Surfactant was given to 21.9% (n=1238) of HRF and 51.2% (n=1108) of RDS. Survival rates of RDS were 82.2%, 87.8%, 84.5%, 77.1% and 75.0%, respectively (numbers needed to treat was 8 to 11 for surfactant benefit). Overall mortality rate of HRF was 21%, or 17.9%, 14.7%, 25.6%, 28.9% and 39.2%, respectively. Mortalities of MAS and pneumonia/sepsis were 29.4 and 27.6%. Relative risk of death was associated with initial disease severity, female gender, mechanical ventilation and congenital anomalies by multivariate logistic regression analysis.

CONCLUSIONS

Surfactant was effective for infants with RDS and BW ⩾1500 g, and different incidences and outcome of HRF among GA groups reflected standard of perinatal and respiratory care in emerging neonatal intensive care unit network.

OBJECTIVE

To evaluate whether hemodynamic refractory effects provoked by repeated visual stimulation can be detected and quantified at the single-subject level using a recently described hemodynamic response function (HRF) fitting algorithm.

METHODS

Hemodynamic refractory effects were induced with an easily applicable functional MRI (fMRI) paradigm. A fitting method with inverse logit (IL) functions was applied to quantify net HRFs at the single-subject level with three interstimulus intervals (ISI; 1, 2, and 6 s). The model yielded amplitude, latencies, and width for each HRF.

RESULTS

HRF fitting was possible in 44 of 51 healthy volunteers, with excellent goodness-of-fit (R(2) = 0.9745 ± 0.0241). Refractory effects were most pronounced for the 1-s ISI (P < 0.001) and had nearly disappeared for the 6-s ISI.

CONCLUSIONS

Quantifying refractory effects in individuals was possible in 86.3% of normal subjects using the IL fitting algorithm. This setup may be suitable to explore such effects in individual patients.

Pain is a complex experience that is thought to emerge from the activity of multiple brain areas, some of which are inconsistently detected using traditional fMRI analysis. One hypothesis is that the traditional analysis of pain-related cerebral responses, by relying on the correlation of a predictor and the canonical hemodynamic response function (HRF)- the general linear model (GLM)- may under-detect the activity of those areas involved in stimulus processing that do not present a canonical HRF. In this study, we employed an innovative data-driven processing approach- an inter-run synchronization (IRS) analysis- that has the advantage of not establishing any pre-determined predictor definition. With this method we were able to evidence the involvement of several brain regions that are not usually found when using predictor-based analysis. These areas are synchronized during the administration of mechanical punctate stimuli and are characterized by a BOLD response different from the canonical HRF. This finding opens to new approaches in the study of pain imaging.

Functional Magnetic Resonance Imaging (fMRI), measuring Blood Oxygen Level-Dependent (BOLD), is a widely used tool to reveal spatiotemporal pattern of neural activity in human brain. Standard analysis of fMRI data relies on a general linear model and the model is constructed by convolving the task stimuli with a hypothesized hemodynamic response function (HRF). To capture possible phase shifts in the observed BOLD response, the informed basis functions including canonical HRF and its temporal derivative, have been proposed to extend the hypothesized hemodynamic response in order to obtain a good fitting model. Different t contrasts are constructed from the estimated model parameters for detecting the neural activity between different task conditions. However, the estimated model parameters corresponding to the orthogonal basis functions have different physical meanings. It remains unclear how to combine the neural features detected by the two basis functions and construct t contrasts for further analyses. In this paper, we have proposed a novel method for representing multiple basis functions in complex domain to model the task-driven fMRI data. Using this method, we can treat each pair of model parameters, corresponding respectively to canonical HRF and its temporal derivative, as one complex number for each task condition. Using the specific rule we have defined, we can conveniently perform arithmetical operations on the estimated model parameters and generate different t contrasts. We validate this method using the fMRI data acquired from twenty-two healthy participants who underwent an auditory stimulation task.

Modeling the Hemodynamic Response Function (HRF) is a critical step in fMRI studies of brain activity, and it is often desirable to estimate HRF parameters with physiological interpretability. A biophysically informed model of the HRF can be described by a non-linear time-invariant dynamic system. However, the identification of this dynamic system may leave much uncertainty on the exact values of the parameters. Moreover, the high noise levels in the data may hinder the model estimation task. In this context, the estimation of the HRF may be seen as a problem of model falsification or invalidation, where we are interested in distinguishing among a set of eligible models of dynamic systems. Here, we propose a systematic tool to determine the distinguishability among a set of physiologically plausible HRF models. The concept of absolutely input-distinguishable systems is introduced and applied to a biophysically informed HRF model, by exploiting the structure of the underlying non-linear dynamic system. A strategy to model uncertainty in the input time-delay and magnitude is developed and its impact on the distinguishability of two physiologically plausible HRF models is assessed, in terms of the maximum noise amplitude above which it is not possible to guarantee the falsification of one model in relation to another. Finally, a methodology is proposed for the choice of the input sequence, or experimental paradigm, that maximizes the distinguishability of the HRF models under investigation. The proposed approach may be used to evaluate the performance of HRF model estimation techniques from fMRI data.

Functional magnetic resonance imaging (fMRI) often relies on a hemodynamic response function (HRF), the stereotypical blood oxygen level dependent (BOLD) response elicited by a brief (<4s) stimulus. Early measurements of the HRF used coarse spatial resolutions (≥3mm voxels) that would generally include contributions from white matter, gray matter, and the extra-pial compartment (the space between the pial surface and skull including pial blood vessels) within each voxel. To resolve these contributions, high-resolution fMRI (0.9-mm voxels) was performed at 3T in early visual cortex and its apposed white-matter and extra-pial compartments. The results characterized the depth dependence of the HRF and its reliability during nine fMRI sessions. Significant HRFs were observed in white-matter and extra-pial compartments as well as in gray matter. White-matter HRFs were faster and weaker than in the gray matter, while extra-pial HRFs were comparatively slower and stronger. Depth trends of the HRF peak amplitude were stable throughout a broad depth range that included all three compartments for each session. Across sessions, however, the depth trend of HRF peak amplitudes was stable only in the white matter and deep-intermediate gray matter, while there were strong session-to-session variations in the superficial gray matter and the extra-pial compartment. Thus, high-resolution fMRI can resolve significant and dynamically distinct HRFs in gray matter, white matter, and extra-pial compartments.

OBJECTIVE

To investigate the safety and efficacy of low-concentration inhaled nitric oxide (NO) in the treatment of hypoxic respiratory failure (HRF) among premature infants.

METHODS

Sixty premature infants (gestational age ≤ 34 weeks) with HRF were randomized into NO and control groups between 2012 and 2013, with 30 cases in each group. Both groups received nasal continuous positive airway pressure (nCPAP) or mechanical ventilation. NO inhalation was continued for at least 7 days or until weaning in the NO group. The general conditions, blood gas results, complications, and clinical outcomes of the two groups were analyzed.

RESULTS

The NO group showed significantly more improvement in blood gas results than the control group after 12 hours of treatment (P<0.05). After that, the change in oxygenation status over time showed no significant difference between the two groups (P>0.05). There were no significant differences in total time of assisted ventilation and duration of oxygen therapy between the two groups (P>0.05). The incidence of bronchopulmonary dysplasia (BPD), patent ductus arteriosus, necrotizing enterocolitis, retinopathy of prematurity, and pneumothorax in infants showed no significant differences between the NO and control groups (P>0.05), but the incidence of IVH and mortality were significantly lower in the NO group than in the control group (7% vs 17%, P<0.05; 3% vs 13%, P<0.05).

CONCLUSIONS

NO inhalation may improve oxygenation status and reduce the mortality in premature infants with HRF, but it cannot reduce the incidence of BPD and the total time of mechanical ventilation or nCPAP and duration of oxygen therapy. NO therapy may have a brain-protective effect for premature infants with HRF and does not increase clinical complications.

This paper proposes a new approach for the selection of a biophysical model describing the haemodynamic response function (HRF) measured in BOLD-fMRI data, based on model falsification techniques. Specifically, the novel method of Multiple Model Set-Valued Observers (MMSVOs) is introduced. The observers consider that the initial state lives in a set, the linear time-varying dynamic system obtained from a bilinear approximation of the nonlinear HRF model about the nominal input signal is uncertain, and the output measurements are corrupted by bounded noise. It is shown, both theoretically and through simulation, that the proposed method is able to successfully distinguish the correct HRF model among a set of physiologically plausible alternatives. Moreover, the feasibility of the technique is demonstrated by its application to an empirical dataset. In summary, the results obtained clearly indicate that the proposed methodology is potentially well-suited to be used in the modeling of BOLD-fMRI data.

In this paper, we propose a musculoskeletal model of walker-assisted FES-activated paraplegic walking for the generation of muscle stimulation patterns and characterization of the causal relationships between muscle excitations, multi-joint movement, and handle reaction force (HRF). The model consists of the lower extremities, trunk, hands, and a walker. The simulation of walking is performed using particle swarm optimization to minimize the tracking errors from the desired trajectories for the lower extremity joints, to reduce the stimulations of the muscle groups acting around the hip, knee, and ankle joints, and to minimize the HRF. The results of the simulation studies using data recorded from healthy subjects performing walker-assisted walking indicate that the model-generated muscle stimulation patterns are in agreement with the EMG patterns that have been reported in the literature. The experimental results on two paraplegic subjects demonstrate that the proposed methodology can improve walking performance, reduce HRF, and increase walking speed when compared to the conventional FES-activated paraplegic walking.

This paper proposes a methodology for estimating Neural Response Functions (NRFs) from fMRI data. These NRFs describe non-linear relationships between experimental stimuli and neuronal population responses. The method is based on a two-stage model comprising an NRF and a Hemodynamic Response Function (HRF) that are simultaneously fitted to fMRI data using a Bayesian optimization algorithm. This algorithm also produces a model evidence score, providing a formal model comparison method for evaluating alternative NRFs. The HRF is characterized using previously established "Balloon" and BOLD signal models. We illustrate the method with two example applications based on fMRI studies of the auditory system. In the first, we estimate the time constants of repetition suppression and facilitation, and in the second we estimate the parameters of population receptive fields in a tonotopic mapping study.

Physiologic or pathologically induced periods of exposure to relatively low levels of oxygen during pregnancy affect the expression and function of certain genes in the placenta. In this study, the differential display technique was utilized to identify genes that are regulated in cultured cytotrophoblast cells by exposure to low levels of oxygen. Using this approach, four genes, which have been designated HRF-1, HRF-2, HRF-6, and HRF-8, were cloned and partially characterized. Northern blot analysis showed that clones HRF-1 and HRF-2 were downregulated in response to exposure to low levels of oxygen, whereas expression of HRF-6 and HRF-8 was increased. DNA sequencing and sequence analysis revealed that HRF-1 may represent an alternatively spliced or tissue-specific form of the Kruppel family zinc finger protein znfp104 gene. Clone HRF-2 showed a high degree of identity with exons 9, 10 and 11 of N33, a gene that is located within a homozygously deleted region of metastatic prostate cancer. Clones HRF-6 and HRF-8 did not exhibit significant sequence identity with known sequences in GenBank and may represent novel genes. None of these genes have previously been shown to be present in trophoblast cells, nor have their expressions been shown to be regulated by oxygen. This study demonstrates that the differential display technique is a novel and effective method to analyse oxygen-mediated changes in gene expression in trophoblast cells.

OBJECTIVE

To describe the clinical characteristics and radiographic findings of horizontal root fractures (HRF) in posterior teeth without a history of dental trauma.

METHODS

A total 24 patients and 31 HRF cases in 28 posterior teeth were collected from 2006 to 2015. Clinical examinations and radiographic imaging were evaluated. Value of confidence intervals of the proportions was calculated for data presentation.

RESULTS

The number of males (54%) was similar to females (46%). The patients were predominantly between 50 and 70 years of age (75%). Most HRF cases were found in nonendodontically treated teeth (79%), without crown and bridge restorations (82%), and maxillary molars (54%). Many roots of maxillary molars had developed HRF, and the probability was nearly equal. Fractured teeth usually presented with periodontal and apical bone loss, and most patients (92%) were diagnosed with full mouth chronic periodontitis. Tooth wear was another common clinical feature amongst these patients.

CONCLUSIONS

HRF in posterior teeth without dental trauma occurred mainly in patients aged between 50 and 70, in nonendodontically treated teeth, teeth with attrition but without crown and bridge restorations, maxillary molars and with periodontal and periapical bony destruction. Periodontal condition, occlusal wear and patients' age at diagnosis were the possible related factors. HRF in posterior teeth without dental trauma is a diagnostic challenge and even misdiagnosed. A thorough clinical examination, radiographic analysis and recognition of the clinical characteristics are helpful in the early diagnosis and treatment of HRF.

A convenient way to analyze BOLD fMRI data consists of modeling the whole brain as a stationary, linear system characterized by its transfer function: the Hemodynamic Response Function (HRF). HRF estimation, though of the greatest interest, is still under investigation, for the problem is ill-conditioned. In this paper, we recall the most general Bayesian model for HRF estimation and show how it can beneficially be translated in terms of graphical models, leading to (i) a clear and efficient representation of all structural and functional relationships entailed by the model, and (ii) a straightforward numerical scheme to approximate the joint posterior distribution, allowing for estimation of the HRF, as well as all other model parameters. We finally apply this novel technique on both simulations and real data.

The extent to which health-related physical fitness (HRF) attenuates age differences in psychomotor speed as a function of task complexity was examined in a sample of 48 men. Physiological measures were used to assign participants to fitness group (n1-4- = 12): young less fit (mean age = 25.83 years), young fitter (mean age = 25.08 years), old less fit (mean age = 71.83 years), old fitter (mean age = 66.75 years). A serial choice reaction time (RT) task was used in which three conditions of two, four, or eight choices were administered. RTs for the choice and motor components of the task were recorded separately. A significant Age x HRF interaction was found in relation to choice RT but not motor time; older less fit individuals underperformed older fitter participants, and younger adults regardless of fitness level. This interaction remained significant having statistically controlled for motor function, suggesting benefits to central processing. The strength of this interaction did not increase as a function of task complexity. The findings suggest an association between HRF and psychomotor speed, and support the view that physically active lifestyles should be encouraged among older adults.

An adaptive spatial filtering method is proposed that takes into account contextual information in fMRI activation detection. This filter replaces the time series of each voxel with a weighted average of time series of a small neighborhood around it. The filter coefficients at each voxel are derived so as to maximize a test statistic designed to indicate the presence of activation. This statistic is the ratio of the energy of the filtered time series in a signal subspace to the energy of the residuals. It is shown that the filter coefficients and the maximum energy ratio can be found through a generalized eigenproblem. This approach equates the filter coefficients to the elements of an eigenvector corresponding to the largest eigenvalue of a specific matrix, while the largest eigenvalue itself becomes the maximum energy ratio that can be used as a statistic for detecting activation. The distribution of this statistic under the null hypothesis is derived by a nonparametric permutation technique in the wavelet domain. Also, in this paper we introduce a new set of basis vectors that define the signal subspace. The space spanned by these basis vectors covers a wide range of possible hemodynamic response functions (HRF) and is applicable to both event related and block design fMRI signal analysis. This approach circumvents the need for a priori assumptions about the exact shape of the HRF. Resting-state experimental fMRI data were used to assess the specificity of the method, showing that the actual false-alarm rate of the proposed method is equal or less than its expected value. Analysis of simulated data and motor task fMRI datasets from six volunteers using the method proposed here showed an improved sensitivity as compared to a conventional test with a similar statistic applied to spatially smoothed data.

Homologous restriction factor (HRF) has been shown to inhibit complement-mediated lysis in a species-restrictive manner. Human HRF is able to block lysis by human complement but not by complement from other species. HRF has also been found in the membrane of lymphokine-activated killer (LAK) cells. When this HRF is inserted into sheep erythrocyte membranes, it is able to protect the erythrocyte from LAK cell lysis. In this report, we show that while HRF can inhibit human complement but not rat complement-mediated hemolysis, it is able to inhibit LAK cell lysis by both human and rat LAK cells. HRF is therefore a more general protective protein than has been previously thought.

BACKGROUND

A fixed hemodynamic response function (HRF) is commonly used for functional magnetic resonance imaging (fMRI) analysis. However, HRF may vary from region to region and subject to subject. We investigated the effect of locally estimated HRF (in functionally homogenous parcels) on activation detection sensitivity in a heroin cue reactivity study.

METHODS

We proposed a novel exploratory method for brain parcellation based on a probabilistic model to segregate the brain into spatially connected and functionally homogeneous components. Then, we estimated HRF and detected activated regions in response to an experimental task in each parcel using a joint detection estimation (JDE) method. We compared the proposed JDE method with the general linear model (GLM) that uses a fixed HRF and is implemented in FEAT (as a part of FMRIB Software Library, version 4.1).

RESULTS

1) Regions detected by JDE are larger than those detected by fixed HRF, 2) In group analysis, JDE found areas of activation not detected by fixed HRF. It detected drug craving a priori "regions-of-interest" in the limbic lobe (anterior cingulate cortex [ACC], posterior cingulate cortex [PCC] and cingulate gyrus), basal ganglia, especially striatum (putamen and head of caudate), and cerebellum in addition to the areas detected by the fixed HRF method, 3) JDE obtained higher Z-values of local maxima compared to those obtained by fixed HRF.

CONCLUSIONS

In our study of heroin cue reactivity, our proposed method (that estimates HRF locally) outperformed the conventional GLM that uses a fixed HRF.