The Use of a Scoring System to Guide Thromboprophylaxis in a High-Risk Pregnant Population

Guidelines for thromboprophylaxis in pregnancy are usually based upon clinical observations and expert opinion. For optimal impact, their use must be attended by consistency in the advice given to women. In this observational study, we evaluated the performance of a scoring system, used as a guide for clinicians administering dalteparin to pregnant women at increased risk of venous thromboembolism. The work included 47 women treated with dalteparin prior to adoption of the scoring system and 58 women treated with dalteparin after its adoption. The indication for thromboprophylaxis was recorded in each case together with details of the regimen employed, obstetric, and haematological outcomes. The main outcome measure was to determine whether consistency improved after adoption of the scoring system. We also recorded the occurrence of any new venous thromboembolism, haemorrhage, the use of regional anaesthesia during labour, evidence of allergy, and thrombocytopenia. We found that use of the scoring system improved the consistency of advice and increased the mean duration of thromboprophylaxis. None of the subjects suffered venous thromboembolism after assessment using the scoring system. There was no increase in obstetric or anaesthetic morbidity when dalteparin was given antenatally period and no evidence of heparin-induced thrombocytopenia

The historical vanishing of the Blazhko effect of RR Lyr from GEOS and Kepler surveys

RR Lyr is one of the most studied variable stars. Its light curve has been regularly monitored since the discovery of the periodic variability in 1899. Analysis of all observed maxima allows us to identify two primary pulsation states defined as pulsation over a long (P0 longer than 0.56684 d) and a short (P0 shorter than 0.56682 d) primary pulsation period. These states alternate with intervals of 13-16 yr, and are well defined after 1943. The 40.8 d periodical modulations of the amplitude and the period (i.e. Blazhko effect) were noticed in 1916. We provide homogeneous determinations of the Blazhko period in the different primary pulsation states. The Blazhko period does not follow the variations of P0 and suddenly diminished from 40.8 d to around 39.0 d in 1975. The monitoring of these periodicities deserved and deserves a continuous and intensive observational effort. For this purpose we have built dedicated, transportable and autonomous small instruments, Very Tiny Telescopes (VTTs), to observe the times of maximum brightness of RR Lyr. As immediate results the VTTs recorded the last change of P0 state in mid-2009 and extended the time coverage of the Kepler observations, thus recording a maximum O-C amplitude of the Blazhko effect at the end of 2008, followed by the historically smallest O-C amplitude in late 2013. This decrease is still ongoing and VTT instruments are ready to monitor the expected increase in the next few years.Comment: 10 pages, 6 figures. Accepted for publication in MNRAS. Contents of appendix B may be requested to first autho

Graph-based ship traffic partitioning for intelligent maritime surveillance in complex port waters

Maritime Situational Awareness (MSA) is a critical component of intelligent maritime traffic surveillance. However, it becomes increasingly challenging to gain MSA accurately given the growing complexity of ship traffic patterns due to multi-ship interactions possibly involving classical manned ships and emerging autonomous ships. This study proposes a new traffic partitioning methodology to realise the optimal maritime traffic partition in complex waters. The methodology combines conflict criticality and spatial distance to generate conflict-connected and spatially compact traffic clusters, thereby improving the interpretability of traffic patterns and supporting ship anti-collision risk management. First, a composite similarity measure is designed using a probabilistic conflict detection approach and a newly formulated maritime traffic route network learned through maritime knowledge mining. Then, an extended graph-based clustering framework is used to produce balanced traffic clusters with high intra-connections but low inter-connections. The proposed methodology is thoroughly demonstrated and tested using Automatic Identification System (AIS) trajectory data in the Ningbo-Zhoushan Port. The experimental results show that the proposed methodology 1) has effective performance in decomposing the traffic complexity, 2) can assist in identifying high-risk/density traffic clusters, and 3) is sufficiently generic to handle various traffic scenarios in complex geographical waters. Therefore, this study makes significant contributions to intelligent maritime surveillance and provides a theoretical foundation for promoting maritime anti-collision risk management for the future mixed traffic of both manned and autonomous ships

Why do some women choose to freebirth in the UK? An interpretative phenomenological study

Background Freebirthing or unassisted birth is the active choice made by a woman to birth without a trained professional present, even where there is access to maternity provision. This is a radical childbirth choice, which has potential morbidity and mortality risks for mother and baby. While a number of studies have explored women’s freebirth experiences, there has been no research undertaken in the UK. The aim of this study was to explore and identify what influenced women’s decision to freebirth in a UK context. Methods An interpretive phenomenological approach was adopted. Advertisements were posted on freebirth websites, and ten women participated in the study by completing a narrative (n = 9) and/or taking part in an in-depth interview (n = 10). Data analysis was carried out using interpretative methods informed by Heidegger and Gadamer’s hermeneutic-phenomenological concepts. Results Three main themes emerged from the data. Contextualising herstory describes how the participants’ backgrounds (personal and/or childbirth related) influenced their decision making. Diverging paths of decision making provides more detailed insights into how and why women’s different backgrounds and experiences of childbirth and maternity care influenced their decision to freebirth. Converging path of decision making, outlines the commonalities in women’s narratives in terms of how they sought to validate their decision to freebirth, such as through self-directed research, enlisting the support of others and conceptualising risk. Conclusion The UK based midwifery philosophy of woman-centred care that tailors care to individual needs is not always carried out, leaving women to feel disillusioned, unsafe and opting out of any form of professionalised care for their births. Maternity services need to provide support for women who have experienced a previous traumatic birth. Midwives also need to help restore relationships with women, and co-create birth plans that enable women to be active agents in their birthing decisions even if they challenge normative practices. The fact that women choose to freebirth in order to create a calm, quiet birthing space that is free from clinical interruptions and that enhances the physiology of labour, should be a key consideration

Phosphodiesterase 10A Upregulation Contributes to Pulmonary Vascular Remodeling

Phosphodiesterases (PDEs) modulate the cellular proliferation involved in the pathophysiology of pulmonary hypertension (PH) by hydrolyzing cAMP and cGMP. The present study was designed to determine whether any of the recently identified PDEs (PDE7-PDE11) contribute to progressive pulmonary vascular remodeling in PH. All in vitro experiments were performed with lung tissue or pulmonary arterial smooth muscle cells (PASMCs) obtained from control rats or monocrotaline (MCT)-induced pulmonary hypertensive (MCT-PH) rats, and we examined the effects of the PDE10 inhibitor papaverine (Pap) and specific small interfering RNA (siRNA). In addition, papaverine was administrated to MCT-induced PH rats from day 21 to day 35 by continuous intravenous infusion to examine the in vivo effects of PDE10A inhibition. We found that PDE10A was predominantly present in the lung vasculature, and the mRNA, protein, and activity levels of PDE10A were all significantly increased in MCT PASMCs compared with control PASMCs. Papaverine and PDE10A siRNA induced an accumulation of intracellular cAMP, activated cAMP response element binding protein and attenuated PASMC proliferation. Intravenous infusion of papaverine in MCT-PH rats resulted in a 40%–50% attenuation of the effects on pulmonary hypertensive hemodynamic parameters and pulmonary vascular remodeling. The present study is the first to demonstrate a central role of PDE10A in progressive pulmonary vascular remodeling, and the results suggest a novel therapeutic approach for the treatment of PH

Human Epidermal Neural Crest Stem Cells (hEPI-NCSC)—Characterization and Directed Differentiation into Osteocytes and Melanocytes

Here we describe the isolation, characterisation and ex-vivo expansion of human epidermal neural crest stem cells (hEPI-NCSC) and we provide protocols for their directed differentiation into osteocytes and melanocytes. hEPI-NCSC are neural crest-derived multipotent stem cells that persist into adulthood in the bulge of hair follicles. Multipotency and self-renewal were determined by in vitro clonal analyses. hEPI-NCSC generate all major neural crest derivatives, including bone/cartilage cells, neurons, Schwann cells, myofibroblasts and melanocytes. Furthermore, hEPI-NCSC express additional neural crest stem cell markers and global stem cell genes. To variable degrees and in a donor-dependent manner, hEPI-NCSC express the six essential pluripotency genes C-MYC, KLF4, SOX2, LIN28, OCT-4/POU5F1 and NANOG. hEPI-NCSC can be expanded ex vivo into millions of stem cells that remain mulitpotent and continue to express stem cell genes. The novelty of hEPI-NCSC lies in the combination of their highly desirable traits. hEPI-NCSC are embryonic remnants in a postnatal location, the bulge of hair follicles. Therefore they are readily accessible in the hairy skin by minimal invasive procedure. hEPI-NCSC are multipotent somatic stem cells that can be isolated reproducibly and with high yield. By taking advantage of their migratory ability, hEPI-NCSC can be isolated as a highly pure population of stem cells. hEPI-NCSC can undergo robust ex vivo expansion and directed differentiation. As somatic stem cells, hEPI-NCSC are conducive to autologous transplantation, which avoids graft rejection. Together, these traits make hEPI-NCSC novel and attractive candidates for future cell-based therapies and regenerative medicine

Sildenafil, a phosphodiesterase type 5 inhibitor, enhances the antidepressant activity of amitriptyline but not desipramine, in the forced swim test in mice

The cholinergic theory of depression highlights the involvement of muscarinic acetylcholine receptors in the neurobiology of mood disorders. The present study was designed to investigate the effect of sildenafil, a phosphodiesterase type 5 inhibitor which exhibits cholinomimetic properties, alone and in combination with scopolamine in the forced swim test in mice. Moreover, we assessed the ability of sildenafil to modify the antidepressant activity of two tricyclic antidepressants with distinct cholinolytic activity, amitriptyline and desipramine. Swim sessions were conducted by placing mice in glass cylinders filled with water for 6 min and the duration of behavioral immobility during the last 4 min of the test was evaluated. Locomotor activity was measured with photoresistor actimeters. To evaluate the potential pharmacokinetic interaction between amitriptyline and sildenafil, brain and serum concentrations of amitriptyline were determined by HPLC. Sildenafil (1.25–20 mg/kg) as well as scopolamine (0.5 mg/kg) and its combination with sildenafil (1.25 mg/kg) did not affect the total immobility time duration. However, joint administration of scopolamine with sildenafil at doses of 2.5 and 5 mg/kg significantly reduced immobility time as compared to control group. Moreover, co-administration of scopolamine with sildenafil at the highest dose (5 mg/kg) significantly decreased immobility time as compared to scopolamine-treated group. Sildenafil (1.25, 2.5 and 5 mg/kg) significantly enhanced the antidepressant activity of amitriptyline (5 mg/kg). No changes in anti-immobility action of desipramine (20 mg/kg) in combination with sildenafil (5, 10 and 20 mg/kg) were observed. Sildenafil did not affect amitriptyline level in both brain and serum. In conclusion, the present study suggests that sildenafil may enhance the activity of antidepressant drugs which exhibit cholinolytic activity

A simplified (modified) Duke Activity Status Index (M-DASI) to characterise functional capacity: A secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) study

Background Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity. Methods In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg −1 min −1 and peak oxygen consumption (VO 2 peak) >16 ml kg −1 min −1, cut-points that represent a reduced risk of postoperative complications. Results Five questions were identified to have dominance in predicting AT>11 ml kg −1 min −1 and VO 2 peak>16 ml.kg −1min −1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg −1.min −1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO 2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO 2 peak>16 ml.kg −1.min −1 and VO 2 peak<16 ml.kg −1.min −1. Conclusions The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management

Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study.

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability