The TRUFFLE study; fetal monitoring indications for delivery in 310 IUGR infants with 2 year's outcome delivered before 32 weeks of gestation.

OBJECTIVE: In the TRUFFLE study on outcome of early fetal growth restriction women were allocated to three timing of delivery plans according to antenatal monitoring strategies based on reduced computerized cardiotocographic heart rate short term variation (c-CTG STV) , early Ductus Venosus (DV p95) or late DV (DV noA) changes. However, many infants were per protocol delivered because of 'safety net' criteria, or for maternal indications, or 'other fetal indications' or after 32 weeks of gestation when the protocol was not applied anymore. It was the objective of the present post-hoc sub-analysis to investigate the indications for delivery in relation to outcome at 2 years in infants delivered before 32 weeks, to come to a further refinement of management proposals. METHODS: we included all 310 cases of the TRUFFLE study with known outcome at 2 years corrected age and 7 perinatal and infant deaths, apart from 7 cases with an inevitable death. Data were analyzed according to the randomization allocation and specified for the intervention indication. RESULTS: overall only 32% of fetuses born alive were delivered according to the specified monitoring parameter for indication for delivery. 38% were delivered because of safety net criteria, 15% because of other fetal reasons and 15% because of maternal reasons. In the c-CTG arm 51% of infants were delivered because of reduced STV. In the DV p95 arm 34% were delivered because of an abnormal DV and in the DV no A wave arm only 10% of cases were delivered accordingly. The majority of fetuses in the DV arms delivered for safety net criteria were delivered because of spontaneous decelerations. Two year's intact survival was highest in the combined DV arms as compared to the c-CTG arm (p = 0.05 when life born, p = 0.21 including fetal death), with no difference between the DV arms. Poorer outcome in the c-CTG arm was restricted to fetuses delivered because of decelerations in the safety net subgroup. Infants delivered because of maternal reasons had the highest birth weight and a non-significant higher intact survival. CONCLUSIONS: In this sub-analysis of fetuses delivered before 32 weeks the majority of infants were delivered for other reasons than according to the allocated CTG or DV monitoring strategy. Since in the DV arms CTG criteria were used as safety net criteria, but in the c-CTG arms no DV safety net criteria were applied, we speculate that the slightly poorer outcome in the CTG arm might be explained by absence of DV data. Optimal timing of delivery of the early IUGR fetus may therefore best be achieved by monitoring them longitudinally with DV and CTG monitoring

How to monitor pregnancies complicated by fetal growth restriction and delivery below 32 weeks: a post-hoc sensitivity analysis of the TRUFFLE-study.

OBJECTIVES: In the recent TRUFFLE study it appeared that, in pregnancies complicated by fetal growth restriction (FGR) between 26 and 32 weeks, monitoring of the ductus venosus (DV) combined with computerised cardiotocography (cCTG) as a trigger for delivery, increased the chance of infant survival without neurological impairment. However, concerns in interpretation were raised as DV monitoring appeared associated with a non-significant increase in fetal death, and part of the infants were delivered after 32 weeks, after which the study protocol was no longer applied. This secondary sensitivity analysis focuses on women who delivered before 32 completed weeks, and analyses fetal death cases in detail. METHODS: We analysed the monitoring data of 317 women who delivered before 32 weeks, excluding women with absent infant outcome data or inevitable perinatal death. The association of the last monitoring data before delivery and infant outcome was assessed by multivariable analysis. RESULTS: The primary outcome (two year survival without neurological impairment) occurred more often in the two DV groups (both 83%) than in the CTG-STV group (77%), however the difference was not statistically significant (p = 0.21). Nevertheless, in surviving infants 93% was free of neurological impairment in the DV groups versus 85% in the CTG-STV group (p = 0.049). All fetal deaths (n = 7) occurred in women allocated to DV monitoring, which explains this difference. Assessment of the monitoring parameters that were obtained shortly before fetal death in these 7 cases showed an abnormal CTG in only one. Multivariable regression analysis of factors at study entry demonstrated that higher gestational age, larger estimated fetal weight 50th percentile ratio and lower U/C ratio were significantly associated with the (normal) primary outcome. Allocation to the DV groups had a smaller effect, but remained in the model (p < 0.1). Assessment of the last monitoring data before delivery showed that in the CTG-STV group abnormal fetal arterial Doppler was significantly associated with adverse outcome. In contrast, in the DV groups an abnormal DV was the only fetal monitoring parameter that was associated with adverse infant outcome, while fetal arterial Doppler, STV below CTG-group cut-off or recurrent fetal heart rate decelerations were not. CONCLUSIONS: In accordance with the results of the overall TRUFFLE study of the monitoring-intervention management of very early severe FGR we found that the difference in the proportion of infants surviving without neuroimpairment (the primary endpoint) was non-significant when comparing timing of delivery with or without changes in the DV waveform. However, the uneven distribution of fetal deaths towards the DV groups was likely by chance, and among surviving children neurological outcomes were better. Before 32 weeks, delaying delivery until abnormalities in DVPI or STV and/or recurrent decelerations occur, as defined by the study protocol, is therefore probably safe and possibly benefits long-term outcome

Effects of antenatal betamethasone on fetal Doppler indices and short term fetal heart rate variation in early growth restricted fetuses

Purpose To investigate the effects of the antenatal administration of betamethasone on fetal Doppler and short term fetal heart rate variation (CTG-STV) in early growth restricted (FGR) fetuses.Materials and Methods Post hoc analysis of data derived from the TRUFFLE study, a prospective, multicenter, randomized management trial of severe early onset FGR. Repeat Doppler and CTG-STV measurements between the last recording within 48 hours before the first dose of betamethasone (base-line value) and for 10 days after were evaluated. Multilevel analysis was performed to analyze the longitudinal course of the umbilico-cerebral ratio (UC ratio), the ductus venosus pulsatility index (DVPIV) and CTG-STV.Results We included 115 fetuses. A significant increase from baseline in CTG-STV was found on day + 1 (p = 0.019) but no difference thereafter. The DVPIV was not significantly different from baseline in any of the 10 days following the first dose of betamethasone (p = 0.167). Multilevel analysis revealed that, over 10 days, the time elapsed from antenatal administration of betamethasone was significantly associated with a decrease in CTG-STV (p = 0.045) and an increase in the DVPIV (p = 0.001) and UC ratio (p < 0.001).Conclusion Although steroid administration in early FGR has a minimal effect on increasing CTG-STV one day afterwards, the effects on Doppler parameters were extremely slight with regression coefficients of small magnitude suggesting no clinical significance, and were most likely related to the deterioration with time in FGR. Hence, arterial and venous Doppler assessment of fetal health remains informative following antenatal steroid administration to accelerate fetal lung maturation.Developmen

Recovery to Preinterventional Functioning, Return-to-Work, and Life Satisfaction After Treatment of Unruptured Aneurysms

Background and Purpose—The eventual goal of preventive treatment of unruptured intracranial aneurysms is to increase the number of life years with high life satisfaction. Insight in the time with reduced functioning, working capacity, and life satisfaction after aneurysm treatment is pivotal to balance the pros and cons of preventive aneurysm occlusion. Methods—We sent a questionnaire on time-to-recovery to preintervention functioning and return-to-work and life satisfaction to patients treated for an unruptured aneurysm between 2000 and 2013. Changes in life satisfaction before treatment, during recovery, and at follow-up were assessed with Wilcoxon signed-rank tests. Results—The questionnaire was sent to 159 patients of whom 110 (69%) responded. The mean follow-up time after aneurysm treatment was 6 years (SD 4). Fifty-four patients had endovascular and 56 had microsurgical occlusion. Complete recovery to preintervention functioning was reported by 81% (95% confidence interval [CI], 74–88) of patients, with a median time-to-recovery of 3 months (range 0–48). Complete work recovery was reported by 78% (95% CI, 66–87) of patients. The proportion of patients with high life satisfaction reduced from 76% (95% CI, 67–84) before treatment to 52% (95% CI, 43–61) during the period of recovery (P<0.01) and restored largely at long-term follow-up (67% [95% CI, 59–76], P=0.08). Conclusion—Life satisfaction is significantly reduced during the period of recovery after treatment of unruptured aneurysms. In the long-term, ≈1 out of 5 patients reports incomplete recovery. These treatment effects should be kept in mind when considering preventive aneurysm treatment. Prospective studies are needed to better compare these losses in patients treated for unruptured aneurysms with those who had subarachnoid hemorrhage

External Validation of the HATCH (Hemorrhage, Age, Treatment, Clinical State, Hydrocephalus) Score for Prediction of Functional Outcome After Subarachnoid Hemorrhage.

The Hemorrhage, Age, Treatment, Clinical State, Hydrocephalus (HATCH) Score has previously shown to predict functional outcome in aneurysmal subarachnoid hemorrhage (aSAH). To validate the HATCH score. This is a pooled cohort study including prospective collected data on 761 patients with aSAH from 4 different hospitals. The HATCH score for prediction of functional outcome was validated using calibration and discrimination analysis (area under the curve). HATCH score model performance was compared with the World Federation of Neurosurgical Societies and Barrow Neurological Institute score. At the follow-up of at least 6 months, favorable (Glasgow Outcome Score 4-5) and unfavorable functional outcomes (Glasgow Outcome Score 1-3) were observed in 512 (73%) and 189 (27%) patients, respectively. A higher HATCH score was associated with an increased risk of unfavorable outcome with a score of 1 showing a risk of 1.3% and a score of 12 yielding a risk of 67%. External validation showed a calibration intercept of -0.07 and slope of 0.60 with a Brier score of 0.157 indicating good model calibration and accuracy. With an area under the curve of 0.81 (95% CI 0.77-0.84), the HATCH score demonstrated superior discriminative ability to detect favorable outcome at follow-up compared with the World Federation of Neurosurgical Societies and Barrow Neurological Institute score with 0.72 (95% CI 0.67-0.75) and 0.63 (95% CI 0.59-0.68), respectively. This multicenter external validation analysis confirms the HATCH score to be a strong independent predictor for functional outcome. Its incorporation into daily practice may be of benefit for goal-directed patient care in aSAH

Scientific background document in support of the development of a CCAMLR MPA in the Weddell Sea (Antarctica) – Version 2016 -Part A: General context of the establishment of MPAs and background information on the Weddell Sea MPA planning area-

The authors present to the Working Group on Ecosystem Monitoring and Management (WG EMM) the scientific background and justification for the development of a marine protected area (MPA) in the Weddell Sea planning area. In accordance with the recommendations by WG-EMM-14 (SC-CAMLR-XXIII, Annex 6), this was done in three separate documents (Part A-C). WG-EMM-16/01 (Part A) sets out the general context of the establishment of CCAMLR-MPAs and provides the background information on the Weddell Sea MPA (WSMPA) planning area; WG-EMM-16/02 (Part B) informs on the data retrieval process and WG-EMM-16/03 (Part C) describes the methods and the results of the scientific analyses as well as the development of the objectives and finally of the borders for the WSMPA. Earlier versions of Parts A-C were already presented at the meetings of EMM and SC-CAMLR in 2015. The Scientific Committee did recognise that the body of science of the background documents (SC-CAMLR-XXXIV/BG/15, BG/16, BG/17) provides the necessary foundation for developing a WSMPA proposal (SC-CAMLR-XXXIV, § 5.11). Here, the authors present the final version of Part A to WG EMM. Part A has undergone final editorial corrections in the 2015/16 intersessional period and contains (i) a synopsis in terms of the establishment of MPAs (chapter 1); (ii) a description of the boundaries of the WSMPA planning area (chapter 2); (iii) a comprehensive, yet succinct, general description of the Weddell Sea ecosystem (chapter 3); (iv) and finally a guidance regarding the future work beyond the development of the scientific basis for the evaluation of a WSMPA (chapter 4)

Cytogenetic analysis on Pterophyllum scalare

Cytogenetic studies were carried out on eighteen wild specimens of Pterophyllum scalare from Jari River, in Pará state, and the results were compared to literature. Mitotic chromosomes were obtained from kidney cells and the analysis was done using: C-banding, Ag-NOR staining, Chromomycin A3/DAPI sequential staining and fluorochrome in situ hybridization with human telomere probes. All individuals showed a chromosome number of 2n = 48 (12 M/SM and 36 ST/A) and FN = 60. No differences were detected between male and female karyotypes, indicating the absence of morphologically differentiated mitotic sexual chromosomes. Constitutive heterochromatin blocks were located at the centromeric and pericentromeric regions of all chromosomes. The largest submetacentric pair showed a differential staining on their short arms. Only two NOR bearing chromosomes were detected, and the stainings were observed at the distal region of the short arm of the largest chromosome pair, matching the secondary constriction. Chromomycin A3, stained the NOR and the centromeres of some chromosomes. DAPI-bands were observed at the centromeric regions of all chromosomes. Telomere sequences hybridised only at the terminal regions. © 2006 Taylor and Francis Group, LLC

The terrestrial carbon cycle: implications for the Kyoto Protocol

The Kyoto Protocol achieved a significant breakthrough by including terrestrial carbon sources and sinks into a legally binding emissions reduction framework. The effectiveness of the portocol can be improved by adopting a full carbon budget. Terrestrial carbon sinks are part of an active biological cycle and can offset fossil fuel emissions only temporarily, from decades to a century. They can thus buy time to address anthropogenic perturbation emissions