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.

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.

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.

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.

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.

Biomass and lipid production of dinoflagellates and raphidophytes in indoor and outdoor photobioreactors.

The principal fatty acids from the lipid profiles of two autochthonous dinoflagellates (Alexandrium minutum and Karlodinium veneficum) and one raphidophyte (Heterosigma akashiwo) maintained in bubble column photobioreactors under outdoor culture conditions are described for the first time. The biomass production, lipid content and lipid productivity of these three species were determined and the results compared to those obtained when the strains were cultured indoors. Under the latter condition, the biotic values did not significantly differ among species, whereas under outdoor conditions, differences in both duplication time and fatty acids content were observed. Specifically, A. minutum had higher biomass productivity (0.35 g·L⁻¹ day⁻¹), lipid productivity (80.7 mg lipid·L⁻¹ day⁻¹) and lipid concentration (252 mg lipid·L⁻¹) at harvest time (stationary phase) in outdoor conditions. In all three strains, the growth rate and physiological response to the light and temperature fluctuations of outdoor conditions greatly impacted the production parameters. Nonetheless, the species could be successfully grown in an outdoor photobioreactor and were of sufficient robustness to enable the establishment of long-term cultures yielding consistent biomass and lipid production.

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°.

The impact of a computer assisted learning programme on the ability to interpret cardiotochography. A before and after study.

OBJECTIVE: To evaluate if a computer assisted learning programme could bring about a higher degree of individuals who correctly classified cardiotochography (CTG) recordings in a non-selected population of midwives and physicians. STUDY DESIGN: A before and after study. SETTING: Södersjukhuset, Stockholm, Sweden. SUBJECTS: One hundred and thirty midwives and 49 physicians at the maternity unit, September 2009-April 2010. A computer assisted learning programme for interpreting CTG patterns has been created. All 179 individuals included made the first interpretation and the 135 individuals also completing the education made the second interpretation. A third randomly selected interpretation was performed immediately following the second; permitting two participants to classify a CTG together. Comparison between the before and after-test was based on the Fisher exact test. MAIN OUTCOME MEASURE: The proportion of individuals who correctly classified CTGs before and after the training. RESULTS: Sixty four percentage of the individuals classified the CTGs correctly before and 66% after the training (P=0.76). There was no difference between the two professional groups. Normal CTGs were correctly identified by 36% of the individuals before and in 80% after the training (P=0.065). Corresponding figures for pathological CTGs were 83% and 85% (P=1.00), respectively. CONCLUSION: We found no improvement in the proportion of individuals who classified CTGs correctly after the completion of a computer assisted learning programme in fetal monitoring. The baseline level of competence was higher than expected.

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.

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.

Miscarriage after a normal scan at 12-14 gestational weeks in women at low risk of carrying a fetus with chromosomal anomaly according to nuchal translucency screening.

OBJECTIVES: To estimate the risk of second-trimester miscarriage in women with low risk of carrying a fetus with chromosomal abnormality, according to nuchal translucency (NT) screening, and to determine whether NT thickness or other factors affect the risk. METHODS: The study population comprised 14 278 singleton pregnancies with a risk of Down syndrome < 1:250 at NT scan, and where no fetal karyotyping was performed < 25 weeks. Risk factors for miscarriage were investigated by logistic regression. RESULTS: The median risk of Down syndrome was 1 : 3138 (range 1 : 9651-1 : 251) and median NT was 1.7 (range 0.4-3.0) mm. The miscarriage rate was 0.5% (77/14 278; 95% CI 0.4-0.6). After having controlled for maternal age, we found the number of previous deliveries and miscarriages to independently predict miscarriage: odds ratio (OR) for each previous delivery 1.48, 95% CI 1.22-1.94, P < 0.0001; OR for each previous miscarriage 1.34, 95% CI 1.07-1.68, P = 0.01. Excluding women with any previous miscarriage and adjusting for parity, we found a U-shaped relationship between maternal age and miscarriage (P = 0.04). CONCLUSION: In singleton pregnancies with estimated risk of Down syndrome < 1:250 according to NT screening at 12-14 weeks, the spontaneous fetal loss rate before 25 weeks is likely to be around 0.5%. NT thickness up to 3 mm does not seem to affect the risk of miscarriage in such pregnancies. Instead, the risk seems to increase with number of previous miscarriages and deliveries, and possibly the risk is highest in the youngest and oldest women.

By how much does increased nuchal translucency increase the risk of adverse pregnancy outcome in chromosomally normal fetuses? A study of 16,260 fetuses derived from an unselected pregnant population.

OBJECTIVE: In this study we aimed to estimate the magnitude of a possible increase in risk of adverse outcome in fetuses with normal karyotype and increased nuchal translucency (NT), and to determine how well NT measurements can distinguish between fetuses with normal and adverse outcome. METHODS: We studied 16,260 consecutive fetuses with normal karyotype derived from an unselected pregnant population. The following cut-offs for increased risk of adverse outcome were chosen a priori: NT > or = 95th percentile, > or = 3 mm, > or = 3.5 mm, and > or = 4.5 mm. The positive and negative likelihood ratios (+LR, - LR) of the risk cut-offs with regard to fetal malformation, miscarriage, perinatal death, termination of pregnancy and total adverse outcome were calculated, and receiver-operating characteristics (ROC) curves were drawn. RESULTS: The total rate of adverse outcome was 2.7%. + LR and - LR of NT > or = 3.0 mm were: for lethal or severe malformation, + LR 15.0 (95% CI 7.0-28.6), - LR 0.89 (95% CI 0.81-0.95); for malformation of at least intermediate severity, + LR 8.1 (95% CI 4.3-14.0), - LR 0.95 (95% CI 0.92-0.97); for termination of pregnancy, + LR 41.6 (95% CI 17.1-86.6), - LR 0.67 (95% CI 0.41-0.85); for any adverse outcome, + LR 6.4 (95% CI 3.4-11), - LR 0.96 (95% CI 0.94-0.98). The odds for these adverse outcomes increased with increasing NT. NT > or = 3 mm did not significantly increase the risk of miscarriage or perinatal death. Areas under ROC curves for NT were small, with 95% CI below or only slightly above 0.5. CONCLUSION: Our likelihood ratios can be used to calculate the individual risk of unfavorable outcome, but NT screening cannot reliably distinguish between normal and adverse outcome in fetuses with normal karyotype.

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.

Detection of malformations in chromosomally normal fetuses by routine ultrasound at 12 or 18 weeks of gestation-a randomised controlled trial in 39,572 pregnancies.

OBJECTIVE: To compare the antenatal detection rate of malformations in chromosomally normal fetuses between a strategy of offering one routine ultrasound examination at 12 gestational weeks (gws) and a strategy of offering one routine examination at 18 gws. DESIGN: Randomised controlled trial. SETTING: Multicentre trial including eight hospitals. POPULATION: A total of 39,572 unselected pregnant women. METHODS: Women were randomised either to one routine ultrasound scan at 12 (12-14) gws including nuchal translucency (NT) measurement or to one routine scan at 18 (15-22) gws. Anomaly screening was performed in both groups following a check-list. A repeat scan was offered in the 12-week scan group if the fetal anatomy could not be adequately seen at 12-14 gws or if NT was >or=3.5 mm in a fetus with normal or unknown chromosomes. MAIN OUTCOME MEASURES: Antenatal detection rate of malformed fetuses. RESULTS: The antenatal detection rate of fetuses with a major malformation was 38% (66/176) in the 12-week scan group and 47% (72/152) in the 18-week scan group (P= 0.06). The corresponding figures for detection at <22 gws were 30% (53/176) and 40% (61/152) (P= 0.07). In the 12-week scan group, 69% of fetuses with a lethal anomaly were detected at a scan at 12-14 gws. CONCLUSIONS: None of the two strategies for prenatal diagnosis is clearly superior to the other. The 12-week strategy has the advantage that most lethal malformations will be detected at <15 gws, enabling earlier pregnancy termination. The 18-week strategy seems to be associated with a slightly higher detection rate of major malformations, although the difference was not statistically significant.

Routine ultrasound examination at 12 or 18 gestational weeks for prenatal detection of major congenital heart malformations? A randomised controlled trial comprising 36,299 fetuses.

OBJECTIVE: To compare the rate of prenatal diagnosis of heart malformations between two policies of screening for heart malformations. DESIGN: Randomised controlled trial. SETTING: Six university hospitals, two district general hospitals. SAMPLE: A total of 39 572 unselected pregnancies randomised to either policy. METHODS: The 12-week policy implied one routine scan at 12 weeks including measurement of nuchal translucency (NT), and the 18-week policy implied one routine scan at 18 weeks. Fetal anatomy was scrutinised using the same check-list in both groups, and in both groups, indications for fetal echocardiography were ultrasound findings of any fetal anomaly, including abnormal four-chamber view, or other risk factors for heart malformation. In the 12-week scan group, NT >or=3.5 mm was also an indication for fetal echocardiography. MAIN OUTCOME MEASURE: Prenatal diagnosis of major congenital heart malformation. RESULTS: In the 12-week scan group, 7 (11%) of 61 major heart malformations were prenatally diagnosed versus 9 (15%) of 60 in the 18-week scan group (P= 0.60). In four (6.6%) women in the 12-week scan group, the routine scan was the starting point for investigations resulting in a prenatal diagnosis versus in 9 (15%) women in the 18-week scan group (P=0.15). The diagnosis was made

Is measurement of nuchal translucency thickness a useful screening tool for heart defects? A study of 16,383 fetuses.

OBJECTIVE: To determine the performance of nuchal translucency thickness (NT) measurement as a screening method for congenital heart defects (CHD) among fetuses with normal karyotype. METHODS: An NT measurement was made in 16 383 consecutive euploid fetuses derived from an unselected pregnant population. The cut-offs for increased risk of heart defects, chosen a priori and tested prospectively, were: NT >or= 95th centile for crown-rump length, NT >or= 3 mm, and NT >or= 3.5 mm. The sensitivity and false-positive rate (FPR; 1 minus specificity) of the risk cut-offs and their positive and negative likelihood ratios (+LR and -LR) with regard to CHD were calculated. RESULTS: Among the 16 383 fetuses with an NT measurement there were 127 cases with a diagnosis of heart defect confirmed by cardiac investigations after birth or at autopsy. Of these, 55 defects were defined as major, of which 52 were isolated (no other defects or chromosomal aberrations), corresponding to a prevalence of major heart defects in chromosomally normal fetuses/newborns of 3.3/1000. The sensitivity, FPR, +LR and -LR for NT >or= 95th centile with regard to an isolated major heart defect were: 13.5%, 2.6%, 5.2 and 0.9, respectively. For NT >or= 3.0 mm these values were: 9.6%, 0.8%, 12.0 and 0.9, and for NT >or= 3.5 mm they were: 5.8%, 0.3%, 19.3 and 0.9. CONCLUSIONS: NT measurement is a poor screening method for isolated major CHD. A method with a much higher detection rate and with a reasonably low FPR is needed. However, increased NT indicates increased risk of fetal heart defect, and women carrying fetuses with increased NT should be offered fetal echocardiography in the second trimester.