Paramagnetic-iterative relaxation matrix approach: extracting PRE-restraints from NOESY spectra for 3D structure elucidation of biomolecules.

Paramagnetic relaxation enhancement (PRE) can be used to determine long-range distance restraints in biomolecules. The PREs are typically determined by analysis of intensity differences in HSQC experiments of paramagnetic and diamagnetic spin labels. However, this approach requires both isotope- and spin-labelling. Herein, we report a novel method to evaluate NOESY intensities in the presence of a paramagnetic moiety to determine PRE restraints. The advantage of our approach over HSQC-based approaches is the increased number of available signals without the need for isotope labelling. NOESY intensities affected by a paramagnetic center were evaluated during a structure calculation within the paramagnetic iterative relaxation matrix approach (P-IRMA). We applied P-IRMA to a 14-mer RNA with a known NMR solution structure, which allowed us to assess the quality of the PRE restraints. To this end, three different spin labels have been attached at different positions of the 14-mer to test the influence of flexibility on the structure calculation. Structural disturbances introduced by the spin label have been evaluated by chemical shift analysis. Furthermore, the impact of P-IRMA on the quality of the structure bundles were tested by intentionally leaving out available diamagnetic restraints. Our analyses show that P-IRMA is a powerful tool to refine RNA structures for systems that are insufficiently described by using only diamagnetic restraints.

Photo-physical properties of 2-(1-ethynylpyrene)-adenosine: influence of hydrogen bonding on excited state properties.

The photo-physical properties of 2-(1-ethynylpyrene)-adenosine (PyA), a fluorescent probe for RNA dynamics, were examined by solvation studies. The excited-state dynamics display the influence of the vicinity on the spectral features. Combining improved transient absorption and streak camera measurements along with a new analysis method provide a detailed molecular picture of the photophysics. After intramolecular vibrational energy redistribution (IVR), two distinct states are observed. Solvent class (protic/aprotic) and permittivity strongly affect the properties of these states and their population ratio. As a result their emission spectrum is altered, while the fluorescence quantum yield and the overall lifetime remain nearly unchanged. Consequently, the hitherto existing model of the photophysics is herein refined and extended. The findings can serve as basis for improving the information content of measurements with PyA as a label in RNA.

Role of the Renner-Teller effect after core hole excitation in the dissociation dynamics of carbon dioxide dication.

The fragmentation of the doubly-charged carbon dioxide molecule is studied after photoexcitation to the C 1s(1)2π(u) and O 1s(1)2π(u) states using a multicoincidence ion-imaging technique. The bent component of the Renner-Teller split states populated in the 1s→ π* resonant excitation at both the carbon and oxygen 1s ionization edges opens pathways to potential surfaces in highly bent geometries in the dication. Evidence for a complete deformation of the molecule is found in the coincident detection of C(+) and O(2)(+) ions. The distinct alignment of this fragmentation channel indicates rapid deformation and subsequent fragmentation. Investigation of the complete atomization dynamics in the dication leading to asymmetric charge separation shows that the primary dissociation mechanisms, sequential, concerted, and asynchronous concerted, are correlated to specific fragment kinetic energies. The study shows that the bond angle in fragmentation can extend below 20°.

Improvement of lipid production in the marine strains Alexandrium minutum and Heterosigma akashiwo by utilizing abiotic parameters.

Two different strains of microalgae, one raphidophyte and one dinoflagellate, were tested under different abiotic conditions with the goal of enhancing lipid production. Whereas aeration was crucial for biomass production, nitrogen deficiency and temperature were found to be the main abiotic parameters inducing the high-level cellular accumulation of neutral lipids. Net neutral lipid production and especially triacylglycerol (TAG) per cell were higher in microalgae (>200% in Alexandrium minutum, and 30% in Heterosigma akashiwo) under treatment conditions (25°C; 330 µM NaNO(3)) than under control conditions (20°C; 880 µM NaNO(3)). For both algal species, oil production (free fatty acids plus TAG fraction) was also higher under treatment conditions (57 mg L(-1) in A. minutum and 323 mg L(-1) in H. akashiwo). Despite the increased production and accumulation of lipids in microalgae, the different conditions did not significantly change the fatty acids profiles of the species analyzed. These profiles consisted of saturated fatty acids (SAFA) and polyunsaturated fatty acids (PUFA) in significant proportions. However, during the stationary phase, the concentrations per cell of some PUFAs, especially arachidonic acid (C20:4n6), were higher in treated than in control algae. These results suggest that the adjustment of abiotic parameters is a suitable and one of the cheapest alternatives to obtain sufficient quantities of microalgal biomass, with high oil content and minimal changes in the fatty acid profile of the strains under consideration.

How often is a low Apgar score the result of substandard care during labour?

OBJECTIVE: To increase our knowledge of the occurrence of substandard care during labour. DESIGN: A population-based case-control study. SETTING: Stockholm County. POPULATION: Infants born in the period 2004-2006 in Stockholm County. METHODS: Cases and controls were identified from the Swedish Medical Birth Register, had a gestational age of +/-33 complete weeks, had planned for a vaginal delivery, and had a normal cardiotocographic (CTG) recording on admission. We compared 313 infants with an Apgar score of < 7 at 5 minutes of age with 313 randomly selected controls with a full Apgar score, matched for year of birth. MAIN OUTCOME MEASURE: Substandard care during labour. RESULTS: We found that 62% of cases and 36% of controls were subject to some form of substandard care during labour. In half of the cases and in 12% of the controls, CTG was abnormal for > or = 45 minutes before birth. Fetal blood sampling was not performed in 79% of both cases and controls, when indicated.Oxytocin was provided without signs of uterine inertia in 20% of both cases and controls. Uterine contractions were hyperstimulated by oxytocin in 29% of cases and in 9% of controls, and the dose of oxytocin was increased despite abnormal CTG in 19% and 6% of cases and controls, respectively. Assuming that substandard care is a risk factor for low Apgar score, we estimate that up to 42% of the cases could be prevented by avoiding substandard care. CONCLUSIONS: There was substandard care during labour of two thirds of infants with a low Apgar score. The main reasons for substandard care were related to misinterpretation of CTG, not acting on an abnormal CTG in a timely fashion and incautious use of oxytocin.

How often is a low Apgar score the result of substandard care during labour?

Please cite this paper as: Berglund S, Pettersson H, Cnattingius S, Grunewald C. How often is a low Apgar score the result of substandard care during labour? BJOG 2010;117:968-978. Objective To increase our knowledge of the occurrence of substandard care during labour. Design A population-based case-control study. Setting Stockholm County. Population Infants born in the period 2004-2006 in Stockholm County. Methods Cases and controls were identified from the Swedish Medical Birth Register, had a gestational age of >/=33 complete weeks, had planned for a vaginal delivery, and had a normal cardiotocographic (CTG) recording on admission. We compared 313 infants with an Apgar score of <7 at 5 minutes of age with 313 randomly selected controls with a full Apgar score, matched for year of birth. Main outcome measure Substandard care during labour. Results We found that 62% of cases and 36% of controls were subject to some form of substandard care during labour. In half of the cases and in 12% of the controls, CTG was abnormal for >/=45 minutes before birth. Fetal blood sampling was not performed in 79% of both cases and controls, when indicated. Oxytocin was provided without signs of uterine inertia in 20% of both cases and controls. Uterine contractions were hyperstimulated by oxytocin in 29% of cases and in 9% of controls, and the dose of oxytocin was increased despite abnormal CTG in 19% and 6% of cases and controls, respectively. Assuming that substandard care is a risk factor for low Apgar score, we estimate that up to 42% of the cases could be prevented by avoiding substandard care. Conclusions There was substandard care during labour of two-thirds of infants with a low Apgar score. The main reasons for substandard care were related to misinterpretation of CTG, not acting on an abnormal CTG in a timely fashion and incautious use of oxytocin.

A novel two-phase bioprocess for the production of Arthrospira (Spirulina) maxima LJGR1 at pilot plant scale during different seasons and for phycocyanin induction under controlled conditions.

A two-phase outdoor cultivation bioprocess for Arthrospira maxima LJGR1 combined with phycocyanin induction in concentrated cultures under controlled conditions was evaluated using a modified low-cost Zarrouk medium. Growth was monitored during 4 cycles in 2018 and 4 cycles in 2019. Biomass was harvested and concentrated using membrane technology at the end of each cycle for further phycocyanin induction using blue LED light (controlled conditions, 24 h). The highest biomass productivity was observed during spring and summer cycles (13.63-18.97 gDWm-2 d-1); during mid-fall and mid-end fall, a decrease was observed (9.93-7.76 gDWm-2 d-1). Under favorable growth conditions, phycocyanin induction was successful. However, during cycles with unfavorable growth condition, phycocyanin induction was not observed. Reactive-grade phycocyanin (3.72 ± 0.14) was recovered and purified using microfiltration and ultrafiltration technologies.

Severe asphyxia due to delivery-related malpractice in Sweden 1990-2005.

OBJECTIVE: To describe possible causes of delivery-related severe asphyxia due to malpractice. DESIGN AND SETTING: A nationwide descriptive study in Sweden. POPULATION: All women asking for financial compensation because of suspected medical malpractice in connection with childbirth during 1990-2005. METHOD: We included infants with a gestational age of >or=33 completed gestational weeks, a planned vaginal onset of delivery, reactive cardiotocography at admission for labour and severe asphyxia-related outcomes presumably due to malpractice. As asphyxia-related outcomes, we included cases of neonatal death and infants with diagnosed encephalopathy before the age of 28 days. MAIN OUTCOME MEASURE: Severe asphyxia due to malpractice during labour. RESULTS: A total of 472 case records were scrutinised. One hundred and seventy-seven infants were considered to suffer from severe asphyxia due to malpractice around labour. The most common events of malpractice in connection with delivery were neglecting to supervise fetal wellbeing in 173 cases (98%), neglecting signs of fetal asphyxia in 126 cases (71%), including incautious use of oxytocin in 126 cases (71%) and choosing a nonoptimal mode of delivery in 92 cases (52%). CONCLUSION: There is a great need and a challenge to improve cooperation and to create security barriers within our labour units. The most common cause of malpractice is that stated guidelines for fetal surveillance are not followed. Midwives and obstetricians need to improve their shared understanding of how to act in cases of imminent fetal asphyxia and how to choose a timely and optimal mode of delivery.

Hemiextinction induced by transcranial magnetic stimulation over the right temporo-parietal junction.

Whereas it is widely accepted that the parietal cortex is crucial for visual attention, the role of the temporal cortex and the temporo-parietal junction (TPJ) is less clear. There are clinical reports of patients with lesions in different posterior temporal areas which exhibit contralateral visual neglect but this syndrome seems to be less frequent than in patients with parietal lesions. In a previous study, we could show that single-pulse transcranial magnetic stimulation (TMS) over the right inferior parietal cortex is capable to induce both neglect-like and extinction-like impairments of performance in normal subjects. In the present study, we used this method to examine the functional role of the superior temporal gyrus (STG) and the TPJ of the right hemisphere for visuo-spatial attention. Healthy volunteers were asked to detect small dots appearing for 40 ms unilaterally on right or left side or bilaterally on a computer screen. TMS was applied over the TPJ or STG. TMS over the TPJ induced an extinction-like behavioral pattern to the contralateral hemifield. TMS over the STG had no effect. The results demonstrate a functional involvement of the TPJ in visuo-attentional processing of competing stimuli in both hemifields. This region is part of the cortical network mediating stimulus-driven attention which is relevant for processing of competing stimuli.

Long-term dinoflagellate culture performance in a commercial photobioreactor: Amphidinium carterae case.

The aim of this work was to study the culture performance of a dinoflagellate in a commercial photobioreactor. The results obtained during this long-term experiment allow to confirm that Amphidinium carterae is a promising dinoflagellate that can be exploited successfully in closed systems, in semi-continuous mode in indoor and outdoor environments. The average results in an indoor 5cm light-path 320L photobioreactor were, in terms of specific growth rate (0.29d(-1)), duplication time (3.1d(-1)) and dry biomass productivity (78mgL(-1)d(-1)). Specific compounds production was found including ω3 and ω6 fatty acids and, pigments (Peridinin, ß-carotene). These promising results, besides unique characteristics found during the exploitation period such as resistance to mechanical stress, self-control of contaminant organisms, and quick cells aggregation when the culture is not in turbulence conditions, makes A. carterae one of the new target species suitable for commercially exploitation on an industrial scale.

Obstetric complications and the risk of schizophrenia: a longitudinal study of a national birth cohort.

BACKGROUND: Numerous epidemiological studies found an increased risk of schizophrenia among persons exposed to various obstetric complications. The underlying mechanisms are unknown. OBJECTIVE: To study specific risk factors, as well as sets of risk factors, representing 3 different etiologic mechanisms: (1) malnutrition during fetal life; (2) extreme prematurity; and (3) hypoxia or ischemia. METHODS: In this longitudinal cohort study, information in the National Birth Register was linked to the National Inpatient Register. We followed up 507516 children born between 1973 and 1977 with regard to a diagnosis of schizophrenia between 1987 and 1995 (238 cases). By record linkage, we also had access to data on psychiatric illness in the mother. Occurrence of schizophrenia was measured by the Mantel-Haenszel test and logistic regression. RESULTS: A number of specific risk factors were associated with an increased risk of schizophrenia. The relative risk (95% confidence interval) for preeclampsia was 2.5 (1.4-4.5); vacuum extraction, 1.7 (1.1-2.6); and malformations, 2.4 (1.2-5.1). In logistic regression models, we found that indicators of all 3 etiologic mechanisms were associated with increased point estimates of schizophrenia, although at lower risk levels. Preeclampsia, an indicator of fetal malnutrition, was the only risk factor with statistically significant increased risk after control for all potentially confounding factors. CONCLUSION: This study supports the theory of an association between obstetric complications and schizophrenia. Although preeclampsia was the strongest individual risk factor, there was evidence of increased risk associated with all 3 etiologic mechanisms.

Evaluation of batch and semi-continuous culture of Porphyridium purpureum in a photobioreactor in high latitudes using Fourier Transform Infrared spectroscopy for monitoring biomass composition and metabolites production.

The culture strategy (batch or semi-continuous) was evaluated for biomass and metabolite formation in Porphyridium purpureum cultures in higher latitudes (>50° N). FTIR was used technology to characterise macromolecule biomass composition and the quality of the metabolites produced. Semi-continuous culture was found to be the most feasible strategy to develop microalgal biomass production facilities in higher latitudes, due to their average results in terms of growth rate (0.27 day(-1)), duplication time (2.5-4 days), maximum cell density achieved (1.43*10(7) cells m L(-1)), biomass productivity of 47.04 mg L(-1) day(-1) and an exopolysaccharides production of 2.1 g L(-1). FTIR technology applied to microalgal production is a valuable and reliable tool to determine on a daily basis not just the evolution of macromolecules composition (lipids, carbohydrates and proteins) but also for the characterisation of the metabolites produced such as phycoerythrin or exopolysaccharides in P. purpureum cultures.

Transplacental passage of isradipine in the treatment of pregnancy-induced hypertension.

The aim of this study was to assess the concentration of isradipine in maternal and fetal plasma, and in amniotic fluid under steady-state conditions. Eight women were treated with 5-mg isradipine tablets twice daily and eight women were given slow-release isradipine capsules (SRO) twice daily for hypertension in pregnancy. Blood and amniotic fluid sampling for analysis of drug concentration was performed at delivery. In the isradipine tablet group, maternal and fetal plasma levels were 788 +/- 701 pg/mL (mean +/- SD) and 270 +/- 90 pg/mL, respectively. The corresponding levels in the SRO-treated group were 463 +/- 217 pg/mL and 185 +/- 95 pg/mL, respectively. In the amniotic fluid, the concentration was 74 +/- 42 pg/mL in the tablet group and 45 +/- 14 pg/mL in the SRO group. Therefore, isradipine passes the placental barrier, but its concentration is considerably lower in the fetal compartments.

Effects of nitroglycerin on the uterine and umbilical circulation in severe preeclampsia.

OBJECTIVE: To determine the effects of nitroglycerin on placental circulation in severe preeclampsia. METHODS: Twelve women with severe preeclampsia were examined. Uterine and umbilical artery pulsatility indices (PI) were assessed by pulsed Doppler ultrasound before and after infusion of nitroglycerin, starting at 0.25 micrograms/kg per minute with stepwise dosage increases until a diastolic blood pressure (BP) of 100 mmHg was achieved. Blood pressure and heart rate were recorded every 5 minutes. Blood was sampled for analysis of the second messenger of nitric oxide, cyclic guanosine monophosphate (cGMP), before and at the end of the infusion. RESULTS: During the infusion, the mean systolic BP decreased from 161 (95% confidence interval [CI] 154-169) to 138 mmHg (95% CI 131-146), and the diastolic pressure decreased from 116 (95% CI 111-122) to 103 (95% CI 96-110) mmHg (P < .01). The PI of the uterine artery did not change significantly (1.23 [95% CI 1.01-1.61]) versus 1.30 [95% CI 1.01-1.88]), whereas umbilical artery PI decreased significantly (P < .01), from 1.35 (95% CI 1.09-1.73) to 1.20 (95% CI 1.05-1.40), with a more pronounced decrease in patients with high basal values. Cyclic GMP remained essentially unchanged (6.4 [95% CI 5.4-7.7] versus 5.5 [4.7-6.6] nmol/L). CONCLUSION: The reduction in the PI of the umbilical artery during nitroglycerin-induced BP reduction implies vasodilation in the umbilical circulation. The absence of an increase in cGMP does not support the view that the nitroglycerin effect is reflected by the plasma concentration of cGMP.

Possible improvement in uteroplacental blood flow during atrial natriuretic peptide infusion in preeclampsia.

OBJECTIVE: To study the effects of low doses of the hormone atrial natriuretic peptide (ANP) on uteroplacental blood flow in patients with preeclampsia. METHODS: Eleven women with preeclampsia were infused intravenously with ANP (10 ng/kg/minute). Uteroplacental blood flow index was measured using dynamic placental scintigraphy with indium-113m. Regional blood flows were assessed by pulsed Doppler ultrasound and expressed as pulsatility index (PI). Hemodynamic measurements and blood sampling for peripheral venous plasma analysis of cyclic guanosine monophosphate (cGMP), an ANP second messenger, were performed before and after 30 minutes of infusion. Nonparametric statistics were used. RESULTS: The uteroplacental blood flow index increased by 28% (-2 to 58%; mean and 95% confidence interval). The Doppler findings were unaffected. Mean arterial blood pressure decreased from 112 (108-117) to 108 (103-114) mmHg (P < .01). Cyclic GMP increased significantly from 9.2 (6.2-12.3) to 17.4 (12.3-22.6) nmol/L (P < .01). Subjects exhibiting a substantial increase in uteroplacental blood flow index (25% or more) demonstrated a significantly greater cGMP response (P < .01) than those who did not (6% or less increase). CONCLUSION: A tendency to an increased uteroplacental blood flow index combined with minor blood pressure reduction after ANP infusion suggest the possibility of uteroplacental vasodilatation.

Atrial natriuretic peptide concentrations and hemodynamic effects of acute plasma volume expansion in normal pregnancy and preeclampsia.

Plasma atrial natriuretic peptide (ANP) and circulatory responses were studied during rapid plasma volume expansion with crystalloid solutions. Sixteen women with preeclampsia and 16 healthy controls in the third trimester were compared. Basal mean (+/- standard error of the mean) ANP levels were not significantly higher in the preeclamptics than in controls (13.6 +/- 3.5 versus 6.4 +/- 1.1 pmol/L; not significant), but the increment following volume expansion was more pronounced (12.9 +/- 2.6 versus 6.1 +/- 2.3 pmol/L; P less than .05). The mean plasma volume expansion was less in the preeclamptic group (6.1 +/- 0.8 versus 9.3 +/- 1.1%; P less than .05), reflecting a higher capillary permeability in this disease. Left ventricular posterior-wall thickness in diastole was increased in the preeclamptics under basal conditions as compared with the controls (9.8 +/- 0.3 versus 8.9 +/- 0.3 mm; P less than .05), as was the thickness of the interventricular septum in systole (14.3 +/- 0.5 versus 12.3 +/- 0.6 mm; P less than .05). Systemic vascular resistance was higher in the preeclamptic group (19.7 +/- 0.8 versus 15.1 +/- 1.1 peripheral resistance units; P less than .01). In the controls, cardiac output increased by 23 +/- 4% and systemic vascular resistance decreased by 17 +/- 3%. The preeclamptic women reacted in a similar way. Our results indicate that preeclampsia is associated with an enhanced ANP response despite a less pronounced increase in plasma volume during acute fluid challenge.

Evaluation of a noninvasive transcranial Doppler and blood pressure-based method for the assessment of cerebral perfusion pressure in pregnant women.

OBJECTIVE: We have developed a Doppler method for the estimation of cerebral perfusion pressure (CPP) using noninvasive techniques. Our objective was to evaluate our new method in pregnant women. METHODS AND MATERIALS: Laboring women with a lumbar epidural in situ had transcranial Doppler interrogation of the maternal middle cerebral artery (MCA) to measure systolic, diastolic, and mean velocities. A pressure transducer was connected to the epidural catheter and pressure was recorded. Systolic (SBP), diastolic (DBP), and mean (MAP) blood pressure were taken with a Dinamap monitor. Doppler estimated CPP (mm Hg) = [V(mean)/(V(mean) - V(diastolic)](MAP - DBP) and directly measured CPP = MAP - Epidural pressure data were plotted on a Bland-Altman graph with limits of agreement. The mean difference (the mean of the sum of both positive and negative differences) and absolute difference (the mean of the sum of the absolute differences) were calculated. In addition, linear and polynomial regression analyses were performed. RESULTS: Twenty laboring women were studied. All had normal pregnancies. The mean maternal age was 28 +/- 7 years and the mean gestational age was 39 +/- 2 weeks. The mean maternal MAP was 77 +/- 12 mm Hg. The Bland-Altman plot showed a mean difference of 2.2 mm Hg at a mean CPP of 65 +/- 12 mm Hg; with a standard deviation of 4.8 mm Hg, the absolute difference was 3.9 +/- 3.0 mm Hg at a mean CPP of 65 +/- 12 mm Hg. The regression analysis showed an r = 0.92, r(2) = 0.86, and p < 0.0001. CONCLUSIONS: Our formula allows the estimation of CPP using a simple calculation and noninvasively acquired data. This method may be of use for frequent, easy, and accurate CPP and intracranial pressure estimation and may, as such, have significant research and clinical applications.

Successful EXIT (ex utero intrapartum treatment) procedure in a fetus diagnosed prenatally with congenital high-airway obstruction syndrome due to laryngeal atresia.

Congenital high-airway obstruction syndrome (CHAOS) is due to rare malformations and has been reported previously in only few cases. If the diagnosis can be made prenatally, the ex utero intrapartum treatment (EXIT) procedure may be life-saving. A healthy 28-year old nulli-para was referred because of isolated ascites found at gestational week 16 during routine ultrasound scan. Repeated scans showed overdistended hyperechogenic lungs with inverted diaphragm and a dilated trachea, which was interpreted as a CHAOS resulting from laryngeal atresia. The ascites eventually disappeared. An EXIT procedure was performed at 35 weeks of gestation. Anesthesia of the mother was induced with thiopental, succinylcholine and fentanyl followed by intubation, and maintained with isoflurane and nitrous oxide. A low abdominal midline incision was performed followed by a low transverse incision of the uterus. The fetal head, right arm and shoulder were delivered and intramuscular anesthesia was administered to the fetus. Immediate laryngoscopy confirmed the diagnosis and a tracheostomy was therefore performed. Surfactant was given after a few minutes of ventilation. Compliance improved and when the fetus was easy to ventilate, it was delivered. The baby is developing normally at 18 months of age. Surgical correction of the malformation will be performed after two years of age. It is concluded that some fetuses with a prenatal diagnosis of CHAOS can benefit from the EXIT procedure at delivery. This necessitates a multidisciplinary management team.

[Obstetric Doppler--justified i high-risk pregnancies]. / Obstetrisk Doppler--motiverat för gravida i högriskgrupp.

Doppler ultrasound is a well established technique for evaluating impedance to blood flow. A review of current literature in the field yields convincing support for the use of obstetric Doppler ultrasonography in the management of high-risk pregnancies. By measuring the pulsatility index of Doppler blood flow velocity waveforms in the umbilical and uterine arteries, it is possible to obtain accurate information on the placental circulation. Meta-analysis of 12 randomised studies showed perinatal mortality to have been significantly reduced as a result of Doppler measurements of umbilical artery blood flow in high-risk pregnancies. However, every technique has its limitations, and it should be borne in mind that even if fetal hypoxia is often revealed by an abnormal Doppler ultrasound result before the cardiotocography pattern becomes abnormal, it is nonetheless a late sign. It is concluded in the article that Doppler ultrasonography needs to be combined with other methods, such as the measurement of biochemical markers, to ensure satisfactory fetal monitoring.