Operationalizing ambiguity in sustainability science: embracing the elephant in the room.

Ambiguity is often recognized as an intrinsic aspect of addressing complex sustainability challenges. Nevertheless, in the practice of transdisciplinary sustainability research, ambiguity is often an 'elephant in the room' to be either side-stepped or reduced rather than explicitly mobilized in pursuit of solutions. These responses threaten the salience and legitimacy of sustainability science by masking the pluralism of real-world sustainability challenges and how research renders certain frames visible and invisible. Critical systems thinking (CST) emerged from the efforts of operational researchers to address theoretical and practical aspects of ambiguity. By adapting key concepts, frameworks, and lessons from CST literature and case studies, this paper aims to establish (1) an expansive conceptualization of ambiguity and (2) recommendations for operationalizing ambiguity as a valuable means of addressing sustainability challenges. We conceptualize ambiguity as an emergent feature of the simultaneous and interacting boundary processes associated with being, knowing, and intervening in complex systems, and propose Reflexive Boundary Critique (RBC) as a novel framework to help navigate these boundary processes. Our characterization of ambiguity acknowledges the boundary of a researcher's subjective orientation and its influence on how ambiguity is exposed and mediated in research (being), characterizes knowledge as produced through the process of making boundary judgments, generating a partial, contextual, and provisional frame (knowing), and situates a researcher as part of the complexity they seek to understand, rendering any boundary process as a form of intervention that reinforces or marginalizes certain frames and, in turn, influences action (intervening). Our recommendations for sustainability scientists to operationalize ambiguity include (1) nurturing the reflexive capacities of transdisciplinary researchers to navigate persistent ambiguity (e.g., using our proposed framework of RBC), and (2) grappling with the potential for and consequences of theoretical incommensurability and discordant pluralism. Our findings can help sustainability scientists give shape to and embrace ambiguity as a fundamental part of rigorous sustainability science.

Staged treatment of placenta accreta spectrum: A combined surgical and radiological approach.

BACKGROUND: Placenta accreta spectrum (PAS) is a rare but serious complication of pregnancy. AIMS: The aim of this study was to determine maternal and neonatal outcomes following a combined surgical and interventional radiology (IR) approach to managing PAS, and the risks associated with this technique. METHODS AND MATERIALS: Retrospective cohort study of all cases of PAS in a tertiary maternity centre between January 2001 and July 2020. Women who underwent caesarean hysterectomy for histologically confirmed PAS with a staged surgical and IR approach were compared with those who underwent caesarean hysterectomy without IR. Maternal, neonatal outcomes, surgical and radiological complications were assessed. RESULTS: Forty-six women were included in the study, and 30/46 (65.2%) underwent the staged surgical and IR approach. Women in the staged group had less overall blood loss (1794 mL vs 3713 mL; P < 0.001), less requirement for blood transfusion (40% vs 75%; P < 0.001), and a lower mean volume of packed red cells transfused (2.5 vs 6.1 units). Anaesthetic and operative times were longer for the staged group (468 vs 189 min: 272 vs 141 min P < 0.001), respectively. There were no differences in rates of neonatal or maternal complications between the two groups. CONCLUSION: This study demonstrates that a staged procedure combining surgery and IR for PAS results in a considerable reduction in blood loss, need for transfusion, and units of packed red cells transfused compared with surgery alone. The staged procedure required significantly longer anaesthetic and operative times; however, there were no differences in maternal and neonatal morbidity.

Interventional radiology in obstetric patients: A population-based record linkage study of use and outcomes.

INTRODUCTION: Interventional radiology (IR) is a technique for controlling hemorrhage and preserving fertility for women with serious obstetric conditions such as placenta accreta spectrum (PAS) or postpartum hemorrhage. This study examined maternal, pregnancy and hospital characteristics and outcomes for women receiving IR in pregnancy and postpartum. MATERIAL AND METHODS: A population-based record linkage study was conducted, including all women who gave birth in hospital in New South Wales or the major tertiary hospital in the neighboring Australian Capital Territory, Australia, between 2003 and 2019. Data were obtained from birth and hospital records. Characteristics and outcomes of women who underwent IR in pregnancy or postpartum are described. Outcomes following IR were compared in a high-risk cohort of women: those with PAS who had a planned cesarean with hysterectomy. Women were grouped by those who did and those who did did not have IR and were matched using propensity score and other factors. RESULTS: We identified IR in 236 pregnancies of 1 584 708 (15.0 per 100 000), including 208 in the delivery and 26 in a postpartum admission. Two-thirds of women receiving IR in the birth admission received a transfusion of red cells or blood products, 28% underwent hysterectomy and 12.5% were readmitted within 6 weeks. Other complications included: severe maternal morbidity (29.8%), genitourinary tract trauma/repair (17.3%) and deep vein thrombosis/pulmonary embolism (4.3%). Outcomes for women with PAS who underwent planned cesarean with hysterectomy were similar for those who did and did not receive IR, with a small reduction in transfusion requirement for those who received IR. CONCLUSIONS: Interventional radiology is infrequently used in pregnant women. In our study it was performed at a limited number of hospitals, largely tertiary centers, with the level of adverse outcomes reflecting use in a high-risk population. For women with PAS undergoing planned cesarean with hysterectomy, most outcomes were similar for those receiving IR and those not receiving IR, but IR may reduce bleeding.

Utility of adjuvant whole abdominal radiation therapy in ovarian clear cell cancer (OCCC): a pragmatic cohort study of women with classic immuno-phenotypic signature.

BACKGROUND: To evaluate the initial experience and clinical utility of first-line adjuvant intensity-modulated whole abdominal radiation therapy (WART) in women with ovarian clear cell cancer (OCCC) referred to an academic center. METHODS: Progression-free and overall survival was analyzed in a pragmatic observational cohort study of histologically pure OCCC patients over-expressing HNF-1ß treated between 2013 and end-December 2018. An in-house intensity-modulated WART program was developed from a published pre-clinical model. Radiation dose-volume data was curated to American Association of Physics in Medicine (AAPM) Task Group 263 recommendations. A dedicated database prospectively recorded presenting characteristics and outcomes in a standardized fashion. RESULTS: Five women with FIGO (2018) stage IA to IIIA2 OCCC were treated with first-line WART. Median age was 58 years (range 47-68 years). At diagnosis CA-125 was elevated in 4 cases (median 56 kU/L: range 18.4-370 kU/L) before primary de-bulking surgery. Severe premorbid endometriosis was documented in 3 patients. At a median follow-up of 77 months (range 16-83 mo.), all patients remain alive and progression-free on clinical, biochemical (CA-125), and 18Fluoro-deoxyglucose (FDG) PET/CT re-evaluation. Late radiation toxicity was significant (G3) in 1 case who required a limited bowel resection and chronic nutritional support at 9 months post-WART; 2 further patients had asymptomatic (G2) osteoporotic fragility fractures of axial skeleton at 12 months post-radiation treated with anti-resorptive agents (denosumab). CONCLUSIONS: The clinical utility of intensity-modulated WART in OCCC over-expressing HNF-1ß was suggested in this small observational cohort study. The hypothesis that HNF-1ß is a portent of platinum-resistance and an important predictive biomarker in OCCC needs further confirmation. Curating multi-institutional cohort studies utilizing WART by means of "Big Data" may improve OCCC care standards in the future.

Intrapartum fetal blood sampling performed at early cervical dilatation and delivery outcomes.

BACKGROUND: Intrapartum fetal blood sampling (FBS) is a fetal well-being diagnostic test for cardiotocogram abnormalities. AIM: The aim of this study was to determine whether women who had their first FBS at <4 cm cervical dilation had an increased risk of operative delivery (caesarean section, instrumental delivery) compared to those women who had their first FBS ≥ 4 cm dilation. MATERIALS AND METHODS: Retrospective cohort study involving labouring women who underwent FBS in a tertiary centre between 2015 and 2017. Women who had their first FBS at <4 cm dilation were compared to those who had their first FBS at ≥4 cm. The primary outcome was operative delivery (caesarean, instrumental delivery); secondary outcomes were neonatal complications. Univariate logistic regression was used to assess the association between degree of cervical dilation at first FBS and study outcomes. RESULTS: Among 591 women, 39 (6.6%) had their first FBS at <4 cm cervical dilation. Women in the ≥4 cm group were less likely to have a total of ≥2 FBS (P = 0.003). There was no difference in the primary outcome between the two groups. Women who had the first FBS at <4 cm dilation were twice as likely to have a caesarean section delivery (odds ratio 2.06, 95% confidence interval 1.06-3.98), although 41% had a vaginal birth (instrumental and spontaneous). There were no differences in rates of resuscitation or admission to nursery between groups. CONCLUSION: Women who had their first FBS < 4cm cervical dilation were twice as likely to have a caesarean section compared to women who had their first FBS ≥ 4 cm. However, 41% had a vaginal birth, and there were no differences in fetal outcomes.

Pelvic girdle pain in pregnancy.

BACKGROUND: Pelvic girdle pain (PGP) in pregnancy is a common condition that can cause significant physical disability and has an important psychosocial impact on pregnant women and their families. It is often under-reported and poorly managed by obstetric caregivers, and this can result in poorer outcomes, reduced quality of life and chronic pain. OBJECTIVE: The objective of this article is to discuss the practical assessment and management of PGP in pregnancy. DISCUSSION: Conservative management that includes activity modification, pelvic support garments, management of acute exacerbations, physiotherapy and exercise programs can alleviate symptoms and prevent progression of symptoms. General practitioners are an integral part of the multidisciplinary team to help manage PGP.

Unusual association between cardiac, skeletal, urogenital and renal abnormalities.

We present a 33-year-old woman with an array of congenital abnormalities. She has been diagnosed with polycystic kidney disease (PCKD) with no detectable mutations in PKD1 or PKD2, spina bifida occulta, thoracic skeletal abnormalities, a uterus didelphys and a patent foramen ovale (PFO). There are several associations reported in the literature that include abnormalities similar to the patient's, but none describe her presentation in its entirety. The MURCS association is characterised by (MU)llerian duct aplasia, (R)enal dysplasia and (C)ervical (S)omite anomalies and goes some way in explaining these condition. Patients with both MURCS and PCKD have not been described in current literature. Through this report, we hope to bring a potential diagnosis to light and provide the patient with an improved understanding of her health.

Rethinking Social Barriers to Effective Adaptive Management.

Adaptive management is an approach to environmental management based on learning-by-doing, where complexity, uncertainty, and incomplete knowledge are acknowledged and management actions are treated as experiments. However, while adaptive management has received significant uptake in theory, it remains elusively difficult to enact in practice. Proponents have blamed social barriers and have called for social science contributions. We address this gap by adopting a qualitative approach to explore the development of an ecological monitoring program within an adaptive management framework in a public land management organization in Australia. We ask what practices are used to enact the monitoring program and how do they shape learning? We elicit a rich narrative through extensive interviews with a key individual, and analyze the narrative using thematic analysis. We discuss our results in relation to the concept of 'knowledge work' and Westley's (2002) framework for interpreting the strategies of adaptive managers-'managing through, in, out and up.' We find that enacting the program is conditioned by distinct and sometimes competing logics-scientific logics prioritizing experimentation and learning, public logics emphasizing accountability and legitimacy, and corporate logics demanding efficiency and effectiveness. In this context, implementing adaptive management entails practices of translation to negotiate tensions between objective and situated knowledge, external experts and organizational staff, and collegiate and hierarchical norms. Our contribution embraces the 'doing' of learning-by-doing and marks a shift from conceptualizing the social as an external barrier to adaptive management to be removed to an approach that situates adaptive management as social knowledge practice.

A method of 'speed coefficients' for biochemical model reduction applied to the NF-κB system.

The relationship between components of biochemical network and the resulting dynamics of the overall system is a key focus of computational biology. However, as these networks and resulting mathematical models are inherently complex and non-linear, the understanding of this relationship becomes challenging. Among many approaches, model reduction methods provide an avenue to extract components responsible for the key dynamical features of the system. Unfortunately, these approaches often require intuition to apply. In this manuscript we propose a practical algorithm for the reduction of biochemical reaction systems using fast-slow asymptotics. This method allows the ranking of system variables according to how quickly they approach their momentary steady state, thus selecting the fastest for a steady state approximation. We applied this method to derive models of the Nuclear Factor kappa B network, a key regulator of the immune response that exhibits oscillatory dynamics. Analyses with respect to two specific solutions, which corresponded to different experimental conditions identified different components of the system that were responsible for the respective dynamics. This is an important demonstration of how reduction methods that provide approximations around a specific steady state, could be utilised in order to gain a better understanding of network topology in a broader context.

Lower limb elevation: useful and effective technique of exsanguination prior to knee arthroscopy.

The use of a Rhys-Davies (R-D) mechanical exsanguinator prior to the application of tourniquet is routine clinical practice in knee arthroscopy. However, this technique has been reported to cause injuries and is contraindicated in conditions like malignancy and latex allergy. Lower limb elevation alone has also been described as a technique of exsanguination. We conducted a prospective audit of two groups of patients (25 each) undergoing routine knee arthroscopy comparing the practice of mechanical exsanguination (R-D) with lower limb elevation technique. Average total operative times of the two groups were similar (R-D exsanguinator-23 min, limb elevation-21 min, n.s). Time interval between tourniquet inflation and skin incision was significantly lower in limb elevation technique (R-D exsanguinator-5 min, limb elevation-0.2 min, P < 0.001). Limb elevation technique of exsanguination helps avoid the risks associated with mechanical exsanguination and may potentially reduce the non-operative tourniquet application time.

Multiparameter quantitative computer-assisted tomography assessment of unicompartmental knee arthroplasties.

BACKGROUND: Unicompartmental knee arthroplasty is a popular alternative to total knee replacement in selected patients. Component alignment has not yet been described by computer-assisted tomography (CAT) imaging techniques; these have been developed for total knee arthroplasty analysis. The aims of this study were to report two new technologies; a new unicompartmental knee arthroplasty system was radiographically assessed with a new CAT scan protocol. METHODS: In a consecutive cohort study, 60 knees were analysed by the 'UniCAT Protocol'. Patients were implanted with a unicompartmental knee arthroplasty system that uses a unique ligament tensor for femoral component alignment. The uniCAT protocol requires a long anteroposterior and lateral scout scan to measure limb alignment and component orientation. A spiral computer-assisted tomography at the knee is used to measure component rotation. The total scan time was 20 s with a calculated unshielded radiation dose of 1 mSv or less. RESULTS: The mechanical axis had a mean of 2.7 degrees varus. Femoral components were implanted with a mean of 0.37 degrees valgus and 1.3 degrees flexion. Tibial components were implanted with a mean 3.47 degrees varus and 5.1 degrees posterior slope. Femoral components were externally rotated a mean of 3.36 degrees, tibial components were externally rotated 6.59 degrees from the posterior tibia and 5.68 degrees from the transepicondylar axis. CONCLUSION: The UniCAT protocol uses less radiation than whole-limb spiral scans and is a method that can be used with all modern computer-assisted tomography machines. The coronal and sagital alignment results compare favourably with previous published reports without computer-assisted tomography. Component rotation has not previously been reported and its implications are yet to be defined.

Alpha-tocopheryl phosphate: a novel, natural form of vitamin E.

We have detected alpha-tocopheryl phosphate in biological tissues including liver and adipose tissue, as well as in a variety of foods, suggesting a ubiquitous presence in animal and plant tissue. Alpha-tocopheryl phosphate is a water-soluble molecule that is resistant to both acid and alkaline hydrolysis, making it undetectable using standard assays for vitamin E. A new method was therefore developed to allow the extraction of both alpha-tocopheryl phosphate and alpha-tocopherol from a single specimen. We used ESMS to detect endogenous alpha-tocopheryl phosphate in biological samples that also contained alpha-tocopherol. Due to the significance of these findings, further proof was required to unequivocally demonstrate the presence of endogenous alpha-tocopheryl phosphate in biological samples. Four independent methods of analysis were examined: HPLC, LCMS, LCMS/MS, and GCMS. Alpha-tocopherol phosphate was identified in all instances by comparison between standard alpha-tocopheryl phosphate and extracts of biological tissues. The results show that alpha-tocopheryl phosphate is a natural form of vitamin E. The discovery of endogenous alpha-tocopheryl phosphate has implications for the expanding knowledge of the roles of alpha-tocopherol in biological systems.

Buckle fractures of the distal radius are safely treated in a soft bandage: a randomized prospective trial of bandage versus plaster cast.

To show that the treatment of buckle fractures of the distal radius in children in a soft bandage is an effective and safe method of treatment, a randomized prospective trial was undertaken. Patients entered the trial after diagnosis in the accident and emergency department. Allocation to either plaster cast or bandage was random. Bandage patients were seen each week. Plaster cast patients were seen at 4 weeks. Measurements were taken at all visits. Patient questionnaires were completed at the end of treatment. Thirty-nine patients completed the study. Eighteen were allocated to bandage, 21 to plaster cast. Those in bandage showed an excellent range of movement by the first week. Results were highly positive for treatment in bandage, with no reported adverse effects and a highly desirable result for the patient. The authors would suggest a change in treatment policy for such fractures.

Modulation of cell proliferation and gene expression by alpha-tocopheryl phosphates: relevance to atherosclerosis and inflammation.

The effect of a mixture of alpha-tocopheryl phosphate and di-alpha-tocopheryl phosphate (TPm) was studied in vitro on two cell lines, RASMC (from rat aortic smooth muscle) and human THP-1 monocytic leukaemia cells. Inhibition of cell proliferation by TPm was shown in both lines and occurred with TPm at concentrations lower than those at which alpha-tocopherol was equally inhibitory. TPm led in non-stimulated THP-1 cells to inhibition of CD36 mRNA and protein expression, to inhibition of oxidized low density lipoprotein surface binding and oxLDL uptake. In non-stimulated THP-1 cells, alpha-tocopherol had only very weak effects on these events. Contrary to alpha-tocopherol, TPm was cytotoxic to THP-1 cells at high concentrations. Thus, TPm is able to inhibit the major aggravating elements involved in the progression of atherosclerosis. The higher potency of TPm may be due to a better uptake of the molecule and to its intracellular hydrolysis, providing more alpha-tocopherol to sensitive sites. Alternatively, a direct effect of the phosphate ester on specific cell targets may be considered.

Modulation of cell proliferation and gene expression by alpha-tocopheryl phosphates: relevance to atherosclerosis and inflammation.

The effect of a mixture of alpha-tocopheryl phosphate plus di-alpha-tocopheryl phosphate (TPm) was studied in vitro on two cell lines, RASMC (from rat aortic smooth muscle) and human THP-1 monocytic leukemia cells. Inhibition of cell proliferation by TPm was shown in both lines and occurred with TPm at concentrations lower than those at which alpha-tocopherol was equally inhibitory. TPm led in nonstimulated THP-1 cells to inhibition of CD36 mRNA and protein expression, to inhibition of oxidized low-density lipoprotein surface binding and oxLDL uptake. In nonstimulated THP-1 cells, alpha-tocopherol had only very weak effects on these events.