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Single-scan NMR spectroscopy at arbitrary dimensions.

Multidimensional nuclear magnetic resonance (NMR) provides one of the foremost analytical tools available to elucidate the structure and dynamics of complex molecules in their native states. Executing this kind of experiment generally requires collecting an n-dimensional time-domain signal S, from which the spectrum arises via an appropriate Fourier analysis of its various time variables. This time-domain signal is actually measured directly only along one of the time axes, while the effects introduced by the remaining time variables are monitored via a parametric incrementation of their values throughout independent experiments. Two-dimensional (2D) NMR experiments thus usually require longer acquisition times than unidimensional experiments, 3D NMR is orders-of-magnitude more time consuming than 2D spectroscopy, etc. Very recently, we proposed and demonstrated an approach whereby data acquisition in 2D NMR can be parallelized, enabling the collection of complete 2D spectral sets within a single transient. The present paper discusses the extension of this 2D NMR methodology to an arbitrary number of dimensions. The principles of the ensuing ultrafast n-dimensional NMR approach are described, and a variety of homo- and heteronuclear 3D and 4D NMR spectra collected within a fraction of a second are presented.

Journal Article↗

Validity and completeness of registration of surgically treated malignant gynaecological diseases in the Danish National Hospital Registry.

BACKGROUND: The increasing tendency to acquire data by linkage to registries not designed for research has introduced a problem into epidemiological research. The data is often crude or possibly incomplete and, in some cases, it has been proposed to use these registries in the routine acquisition of data for existing epidemiological research registries. This study estimates the validity and completeness of the registration of surgically treated malignant gynaecological diseases in the Danish National Hospital Registry 1977-88. METHODS: Completeness was estimated by the method of independent case ascertainment, by comparison with the registration of surgically treated gynaecological cancer cases registered in the Danish Cancer Registry. The validity of the diagnoses was analysed by comparison with the recoding of discharge summaries describing the admission of a 5% random sample. RESULTS: The completeness of registration was 87% overall. Ovarian cancer, cervical cancer and cancer of the uterus were registered with a positive predictive value (PPV) of 89-90%. DISCUSSION: The results of the study emphasise the need to consider the validation of Danish Hospital Registry data before linkage and analysis. In epidemiological cancer research the Danish Cancer Registry is the better alternative when information on malignant tumours is needed.

Denmark↗

Factors related to adaptive behavior changes among profoundly mentally retarded, physically disabled persons.

Changes in adaptive competence over a 1-year period of profoundly mentally retarded, physically disabled persons living in a moderately sized residential facility or in small community programs were examined. No evidence was found to indicate that habilitative growth was greater for residents in the small community programs. Indeed, residents of the moderately sized facility showed evidence of skill acquisition whereas community residents declined slightly in adaptive skill. Within community programs, presence of a relevant goal was positively related to change in independent living skills, and clients with musculoskeletal impairments tended to regress in motor and eating skills. These data suggest that client characteristics and habilitative program content are significant predictors of client growth, and size of the residence is probably not as important for delivery of effective services.

Activities of Daily Living↗

Correlation of myocardial Doppler velocity response to exercise with independent evidence of myocardial ischemia by dual-isotope single-photon emission computed tomography.

Myocardial Doppler velocity (MDV) imaging may provide an objective correlate of ischemia, thereby reducing the expertise needed for interpreting stress echocardiography and improving its reproducibility. This study sought to independently validate the results of exercise MDV imaging with single-photon emission computed tomography (SPECT) perfusion imaging in 116 patients (age 60+/-12 years, 28 women) referred for exercise SPECT for diagnostic or prognostic assessment of coronary artery disease. Two-dimensional echocardiography was performed with simultaneous color MDV data acquisition before and after exercise treadmill testing. MDV data were processed off-line to display myocardial velocity profiles in each segment at rest and peak exercise. SPECT was analyzed using a 16-segment model and segments were classified as normal or showing resting or stress defects. Resting defects within segments showing normal function were attributed to attenuation. Color MDV data were compared with SPECT results, and a multivariate analysis (including exercise and SPECT results) was performed to identify the determinants of the exercise MDV response. Patients exercised maximally (peak rate-pressure product 27.6+/-6.1x10(3), and SPECT was abnormal in 33 patients. Of the 1,333 left ventricular segments evaluable by SPECT and MDV, 1,217 segments were classified as normal, 43 showed a stress defect, and 73 a rest defect. Segmental comparison of thallium findings and MDV showed that segments with a rest defect had a lower velocity at rest and stress than normal segments (p<0.001). Segments with a stress defect had a marked reduction in peak exercise velocity and less increment in velocity than normal segments. Heart rate, functional capacity, and presence of abnormally perfused segments were independent predictors of myocardial velocity at peak exercise. Thus, color MDV correlates with independent evidence of ischemia, although it is also influenced by exercise capacity and left ventricular function. This technique may permit a feasible approach to quantitation of exercise echocardiography.

Blood Flow Velocity↗

Quantifying IOHDR brachytherapy underdosage resulting from an incomplete scatter environment.

PURPOSE: Most brachytherapy planning systems are based on a dose calculation algorithm that assumes an infinite scatter environment surrounding the target volume and applicator. Dosimetric errors from this assumption are negligible. However, in intraoperative high-dose-rate brachytherapy (IOHDR) where treatment catheters are typically laid either directly on a tumor bed or within applicators that may have little or no scatter material above them, the lack of scatter from one side of the applicator can result in underdosage during treatment. This study was carried out to investigate the magnitude of this underdosage. METHODS: IOHDR treatment geometries were simulated using a solid water phantom beneath an applicator with varying amounts of bolus material on the top and sides of the applicator to account for missing tissue. Treatment plans were developed for 3 different treatment surface areas (4 x 4, 7 x 7, 12 x 12 cm(2)), each with prescription points located at 3 distances (0.5 cm, 1.0 cm, and 1.5 cm) from the source dwell positions. Ionization measurements were made with a liquid-filled ionization chamber linear array with a dedicated electrometer and data acquisition system. RESULTS: Measurements showed that the magnitude of the underdosage varies from about 8% to 13% of the prescription dose as the prescription depth is increased from 0.5 cm to 1.5 cm. This treatment error was found to be independent of the irradiated area and strongly dependent on the prescription distance. Furthermore, for a given prescription depth, measurements in planes parallel to an applicator at distances up to 4.0 cm from the applicator plane showed that the dose delivery error is equal in magnitude throughout the target volume. CONCLUSION: This study demonstrates the magnitude of underdosage in IOHDR treatments delivered in a geometry that may not result in a full scatter environment around the applicator. This implies that the target volume and, specifically, the prescription depth (tumor bed) may get a dose significantly less than prescribed. It might be clinically relevant to correct for this inaccuracy.

Algorithms↗

Vector Doppler imaging of a spinning disc ultrasound Doppler phantom.

Vector Doppler methods are used to obtain angle independent in-plane velocity information. Velocity magnitude as well as direction are reconstructed from regular steered colour flow and from split-aperture Doppler acquisitions. Spatially resolved in-plane velocity was obtained through Doppler colour flow mode and subsequent data triangulation. A depth-invariant constant Doppler angle was achieved by using a depth expanding transmit-receive Doppler aperture. Velocities of up to 50 cm s(-1) and 360 degrees vector velocity directions were measured. This was achieved by creating a spinning solid disc phantom. Such a phantom was built to allow underwater mounting and spinning of a solid disc-shaped ultrasound phantom (maximum velocity of 50 cm s-1). Doppler triangulation was realised by steered Doppler and by a split-aperture approach. Results of both imaging methods are shown. Split-aperture results showed errors of less then 10% for velocity magnitude estimation and less then 2.5 degrees for directional information.

Humans↗

A population-based study of sexually transmitted disease incidence and risk factors in human immunodeficiency virus-infected people.

BACKGROUND AND OBJECTIVES: The Minnesota Department of Health conducts active surveillance for cases of human immunodeficiency virus (HIV) infection and passive surveillance for gonorrhea, Chlamydia trachomatis infection, and syphilis. The authors linked two computerized surveillance databases to assess gonorrhea incidence and risk factors for sexually transmitted disease (STD) acquisition among people with known HIV infection. STUDY DESIGN: People diagnosed with adolescent/adult HIV infection before 1993 and still alive as of December 31, 1994 were compared to people diagnosed with gonorrhea, chlamydial infection, or primary/secondary syphilis in 1993 or 1994. Records were matched on name, date of birth, and gender. The incidence of reported gonorrhea was calculated and risk factors for STD acquisition were examined. RESULTS: Thirty (1.3%) of 2,315 HIV-infected people were diagnosed with one or more STDs after HIV diagnosis (median interval: 3 years). There were 31 episodes of gonorrhea, seven episodes of chlamydial infection, and one episode of secondary syphilis. The gonorrhea incidence among HIV-infected people was high compared to the general population in Minnesota, even after stratifying by gender, age, and county of residence. STD acquisition was independently associated with female gender (odds ratio [OR] = 3.8; 95% confidence interval [CI] = 1.7, 8.3) and residence in Hennepin County (OR = 2.9; 95% CI = 1.2, 7.1), the most populous county in Minnesota. CONCLUSIONS: Linkage of STD and HIV surveillance data is useful as a sentinel for high-risk sexual behavior among HIV-infected people, and it can help identify individuals who require additional interventions to prevent HIV transmission. State and local health departments should consider linking these data sources to assess trends and allocate resources.

Adolescent↗

A novel regulatory pathway of sulfate uptake in Arabidopsis roots: implication of CRE1/WOL/AHK4-mediated cytokinin-dependent regulation.

Cytokinin is an adenine derivative plant hormone that generally regulates plant cell division and differentiation in conjunction with auxin. We report that a major cue for the negative regulation of sulfur acquisition is executed by cytokinin response 1 (CRE1)/wooden leg (WOL)/Arabidopsis histidine kinase 4 (AHK4) cytokinin receptor in Arabidopsis root. We constructed a green fluorescent protein (GFP) reporter system that generally displays the expression of the high-affinity sulfate transporter SULTR1;2 in Arabidopsis roots. GFP under the control of SULTR1;2 promoter showed typical sulfur responses that correlate with the changes in SULTR1;2 mRNA levels; accumulation of GFP was induced by sulfur limitation (-S), but was repressed in the presence of reduced sulfur compounds. Among the plant hormones tested, cytokinin significantly downregulated the expression of SULTR1;2. SULTR1;1 conducting sulfate uptake in sultr1;2 mutant was similarly downregulated by cytokinin. Downregulation of SULTR1;1 and SULTR1;2 by cytokinin correlated with the decrease in sulfate uptake activities in roots. The effect of cytokinin on sulfate uptake was moderated in the cre1-1 mutant, providing genetic evidence for involvement of CRE1/WOL/AHK4 in the negative regulation of high-affinity sulfate transporters. These data demonstrated the physiological importance of the cytokinin-dependent regulatory pathway in acquisition of sulfate in roots. Our results suggested that two different modes of regulation, represented as the -S induction and the cytokinin-dependent repression of sulfate transporters, independently control the uptake of sulfate in Arabidopsis roots.

Arabidopsis↗

Impaired distensibility of the left ventricle after stiffening of the right ventricle.

Acute and chronic alterations of right ventricular (RV) wall properties can change left ventricular (LV) performance. We investigated whether and how stiffening of the RV free wall alters LV diastolic distensibility. We used cross-circulated isolated hearts, in which the LV and RV were independently controllable. Stiffness of the RV free wall was altered by intramuscular injections of glutaraldehyde into the RV free wall after right coronary artery ligation. We measured circumferential and longitudinal regional lengths in the septum and LV free wall. During data acquisition, RV volume was held constant. After the RV free wall was stiffened by glutaraldehyde, the LV diastolic pressure-volume relation shifted upward and became steeper. Importantly, stiffening of the RV free wall increased the diastolic regional area in the septum and LV free wall under constant LV volume. The augmented regional dimensions may result in enhanced regional tension under constant LV volume and may be related to the observed increase in LV diastolic intracavitary pressure. The impaired LV diastolic distensibility by stiffening of the RV free wall may be at least partly explained by myocardial stretch, probably due to LV deformation.

Animals↗

Responses to chemical cues from animal and plant foods by actively foraging insectivorous and omnivorous scincine lizards.

If tongue-flicking is important to lizards to sample chemical cues permitting identification of foods, tongue-flicking and subsequent feeding responses should be adjusted to match diet. This hypothesis can be examined for plant foods because most lizards are insectivores, but herbivory/omnivory has evolved independently in many lizard taxa. Here we present experimental data on chemosensory responses to chemical cues from animal prey and palatable plants by three species of the scincine lizards. When tested with chemical stimuli presented on cotton swabs, the insectivorous Eumeces fasciatus responded strongly to prey chemicals but not to chemicals from plants palatable to omnivorous lizards or to pungent or odorless control stimuli. Two omnivorous species, E. schneideri and Scincus mitranus, responded more strongly to chemical cues from both prey and food plants than to the control chemicals. All available data for actively foraging lizards, including these skinks, show that they are capable of prey chemical discrimination, and insectivores do not exhibit elevated tongue-flicking or biting responses to chemical cues from palatable plants. In all of the several species of herbivores/omnivores tested, the lizards show elevated responses to both animal and plant chemicals. We suggest two independent origins of both omnivory and plant chemical discrimination that may account for the evolution of diet and food chemical discriminations in the eight species of skinks studied, five of which are omnivores. All data are consistent with the hypothesis that acquisition of omnivory is accompanied by acquisition of plant chemical discrimination, but data on a broad diversity of taxa are needed for a definitive comparative test of the evolutionary hypothesis. J. Exp. Zool. 287:327-339, 2000.

Animals↗

Field programmable gate array in a fast 256-channel data acquisition system.

We describe an FPGA (Field Programmable Gate Array) controlled fast data acquisition system with 256 channels suitable for high resolution electrocardiographic (ECG), electrogastrographic (EGG) and late potential (LP) recordings. The A/D converter provides 800ns conversion time with 12 bits. The S11W, a 16 bit, parallel, I/O interface, is used to connect the data acquisition device to a portable SPARC-compatible computer. With only one A/D converter, we have achieved 2 kHz sampling rate for each channel and more than 1MB/s overall by using an overlapping delay technique. Channel parameters can be selected independently from one of eight gains ranging from 50 to 10,000, and one of three filters ("ECG" 0.05-120Hz, "EGG" 0.001-1Hz and "LP" 60-1kHz). There are eight programmable sampling frequencies from 2Hz to 2kHz. The system is fully battery operated and protected from the defibrillation high voltages to meet the safety requirements. The acquisition system can be widely used in medical research and clinical applications.

Analog-Digital Conversion↗

Magnetic resonance phase velocity mapping through NiTi stents in a flow phantom model.

PURPOSE: To assess constant and pulsatile flow velocity within the lumen of a peripheral NiTi stent using phase velocity mapping for comparison with independent assessments of flow velocity in a phantom model. MATERIALS AND METHODS: A 9 x 20-mm stent installed in flexible tubing was placed in a phantom filled with stationary fluid. Constant and pulsatile flow (produced by a pump programmed to produce a simulation of the carotid artery flow) was assessed using phase velocity mapping at 4.1 T (for constant flow) and at 1.5 T (for pulsatile flow). In all cases 256 x 256 gradient echo phase velocity maps were acquired. For the pulsatile flow condition, cine images with acquisition gated to the pump cycle were acquired with 40 msec temporal resolution across the simulated cardiac cycle. Computed flow volume rates were compared with fluid volume collection for the constant flow model, and with ultrasonic Doppler flow meter measurements for the pulsatile model. RESULTS: The data showed that volume flow rate assessments by phase velocity mapping agreed with independent measurements within 10% to 15%. CONCLUSION: Phase velocity mapping of the lumen of peripheral size NiTi stents is possible in an in vitro model.

Alloys↗

Individual differences in the onset of tense marking: a growth-curve analysis.

The purpose of this study was to explore individual differences in children's tense onset growth trajectories and to determine whether any within- or between-child predictors could account for these differences. Twenty-two children with expressive vocabulary abilities in the low-average to below-average range participated. Sixteen children were at risk for specific language impairment (SLI), and 6 children had low-average language abilities. Spontaneous language samples, obtained at 3-month intervals between 2;0 and 3;0, were analyzed to examine change in a cumulative productivity score for 5 tense morphemes: third person singular present, past tense, copula BE, auxiliary BE, and auxiliary DO. Hierarchical linear modeling was used to model intercept and linear growth at 30 months and quadratic growth overall. A growth model that included mean length of utterance (MLU) and MLU growth better explained within-child productivity score growth trajectories than a parallel model with vocabulary and vocabulary growth. Significant linear growth in productivity scores remained even after a control for MLU was in place. When between-child predictors were added in the final conditional model, only positive family history approached statistical significance, improving the overall estimation of the model's growth parameters. The findings support theoretical models of language acquisition that claim relative independence of tense marking from other more general aspects of vocabulary development and sentence length. The trends for family history are also consistent with proposals implicating faulty genetic mechanisms underlying developmental language disorders. Systematic use of familial risk data is recommended in future investigations examining the relationship between late-talking children and children at risk for SLI.

Age Factors↗

Analysis of human breast adenocarcinoma MCF7 resistance to tumor necrosis factor-induced cell death. Lack of correlation between JNK activation and ceramide pathway.

Considerable progress has been made in the understanding of tumor necrosis factor (TNF) signaling; however, the molecular and biochemical basis of tumor resistance to the cytotoxic action of TNF are still not definitively identified yet. Although a role of c-Jun N-terminal kinase (JNK) pathway has been suggested as an effector in TNF signaling, its exact relative contribution and its interaction with ceramide pathway and tumor resistance to TNF remain unknown. The relationship between JNK activation and human breast adenocarcinoma MCF7 resistance acquisition to the cytotoxic action of TNF was therefore investigated. We demonstrate that TNF triggers JNK activation in both TNF-sensitive MCF7 cells and its resistant derivative, RA1/1001. In addition, when MCF7 cells were stably transfected with mitogen-activated protein kinase kinase 4 (MKK4) dominant-negative cDNA or transiently transfected with a dominant-negative c-Jun mutant (TAM 67), their susceptibility to the cytotoxic action of TNF remains comparable with control cells. We also demonstrated that JNK activation does not require ceramide generation since in MCF7 cells transfected with a dominant-negative derivative of FADD (FADD-DN), which are resistant to the cytotoxic action of TNF, TNF induced JNK activation in the absence of ceramide generation. Furthermore, our data indicate that exogenous permeable synthetic ceramide C-6 induced the killing of MCF7 cells transfected with MKK4 dominant-negative cDNA. These results provide strong evidence indicating that tumor acquisition of resistance to the cytotoxic action of TNF may occur either independently or at a level downstream of JNK activation and suggest that JNK activation is not linked to ceramide pathway in TNF-mediated apoptosis.

Adenocarcinoma↗

Electrical impedance tomography. An improved design of voltmeter for semi-parallel data acquisition.

The design and implementation of high performance differential voltmeters for semi-parallel data acquisition are described. The general requirements and specific conditions encountered in electrical impedance tomography (EIT) for accurate measurements are analysed. The major parameters are common-mode rejection and bandwidth. A specific implementation of the voltmeters, with separate DC supplies and independent signal references, is described. This arrangement, in which each voltmeter follows the input signal, automatically cancels any common-mode voltage present at the input. The signal is fed to the remainder of the instrumentation through a transformer. The use of a reduced number of components contributes to the minimisation of the inter-channel variations. Furthermore, the geometrical distribution of the voltmeters around the object minimises the length of electrode wires, also reducing the input capacitance. The number of modular voltmeters and DC/DC converters is 32. The common-mode rejection of these voltmeters is greater than 72 dB in the frequency range 3.6-560 kHz. In conclusion, the proposed solution ensures a minimisation of common-mode errors and enables the use of a 250 kHz frequency.

Electric Conductivity↗

Macroprolactinemia as a diagnostic pitfall in hyperprolactinemia: a systematic review and quantitative synthesis.

CONTEXT: Macroprolactinemia is a well-recognized cause of hyperprolactinemia and an important diagnostic pitfall in endocrine practice. However, interpretation of published quantitative prolactin data remains sparse as studies vary in confirmation method, assay platform, polyethylene glycol (PEG) recovery cutoff, and reporting of prolactin measurement. EVIDENCE ACQUISITION: PubMed, Embase, Scopus, Web of Science, the Cochrane Library, and Google Scholar were systematically searched. Eligible studies reported macroprolactinemia-specific quantitative prolactin data in patients with confirmed macroprolactinemia defined by PEG precipitation, gel filtration chromatography (GFC), or both. Two reviewers independently performed study selection, data extraction, and quality assessment. Findings were summarized using study-level descriptive synthesis. The review was prospectively registered in PROSPERO and conducted in accordance with PRISMA 2020 guidelines. EVIDENCE SYNTHESIS: Forty-five studies encompassing 2853 macroprolactinemia cases from 21 413 screened patients with hyperprolactinemia across 22 countries were included. Among 33 studies eligible for primary quantitative analysis, the median study-level central total prolactin attributed to macroprolactinemia was 61.4 ng/mL ([IQR] 42.0-80.0; range 28.1-137.6), and the median study-level post-PEG monomeric prolactin was 11.7 ng/mL (IQR 8.3-13.2; range 4.0-17.0)). The median study-level maximum total prolactin was 264.5 ng/mL (IQR 97.0-425.5; range 81.8-663.0); extreme elevations were attributable to coexisting prolactinomas. CONCLUSION: In confirmed macroprolactinemia, total prolactin elevation is typically moderate, and post-PEG monomeric prolactin is usually within or near the normal range. The post-PEG monomeric prolactin value, rather than percent recovery alone, is the most informative parameter for distinguishing isolated macroprolactinemia from coexisting true hyperprolactinemia. These quantitative benchmarks may help clinicians to avoid unnecessary investigation or treatment.

Humans↗

The instability of the neural crest phenotypes: Schwann cells can differentiate into myofibroblasts.

In the vertebrate embryo, the neural crest cells (NCCs) that migrate out from the neural primordium yield multiple phenotypes, including melanocytes, peripheral neurones and glia and, in the head, cartilage, bone, connective cells and myofibroblasts / vascular smooth muscle cells (SMCs). The differentiation of pluripotent NCCs is mainly directed by local growth factors. Even at postmigratory stages, NC-derived cells exhibit some fate plasticity. Thus, we reported earlier that pigment cells and Schwann cells are able in vitro to interconvert in the presence of endothelin 3 (ET3). Here, we further investigated the capacity of Schwann cells to reprogram their phenotype. We show that purified quail Schwann cells in dissociated cultures produce alpha smooth muscle actin ((alpha)SMA)-expressing myofibroblasts through the generation of a pluripotent progeny. This transdifferentiation took place independently of ET3, but was promoted by transforming growth factor beta1 (TGF(beta)1). Moreover, when implanted into chick embryos, the Schwann cells were found to contribute with host cephalic NCCs to perivascular SMCs. These data provided the first evidence for the acquisition of an NC-derived mesenchymal fate by Schwann cells and further demonstrate that the differentiation state of NC-derived cells is unstable and capable of reprogramming. The high plasticity of Schwann cells evidenced here also suggests that, as in the CNS, glial cells of the PNS may function as NC stem cells in particular circumstances such as repair.

Animals↗

A fermentation system designed to independently evaluate mixing and/or oxygen tension effects in microbial processes: development, application and performance.

In order to evaluate the independent effects of hydrodynamic conditions and/or oxygen tension on culture physiology and productivity, a fermentation system designed to control dissolved oxygen at constant power drawn (P/V) was developed. The system included a fully instrumented 14 l bioreactor coupled to a PC for data acquisition and control. Power drawn was measured (using a commercial torquemeter coupled to the shaft) and maintained constant by varying the agitation speed; while gas blending was used to control dissolved oxygen concentration. To validate the system, rheological-complex fermentations involving xanthan gum production and filamentous fungal cultivation (using Xanthomonas campestris and Trichoderma harzianum) were developed. In both cases, and despite the changing environmental conditions (due to increased broth viscosities and microbial respiration), both variables were controlled at the desired set points. Through such a system, a rigorous evaluation of the hydrodynamic conditions and/or oxygen tension on culture physiology and productivity is now feasible.

Bioreactors↗