The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] ¼ 0.99, 95% confidence interval [CI] ¼ 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc¼ 0.79, 95% CI ¼ 0.69 to 0.91; HRc¼ 0.70, 95% CI ¼ 0.59 to 0.82; HRc¼ 0.50, 95% CI ¼ 0.40 to 0.63, for 2, 3, and 4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend ¼ .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] ¼ 1.69, 95% CI ¼ 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc ¼ 1.33, 95% CI ¼ 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc¼ 0.72, 95% CI ¼ 0.54 to 0.98). Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Fluid modelling of Stimulated Raman Scattering accounting for trapped particles benchmarked against fully kinetic simulations

International audienceA new fluid model describing backward stimulated Raman scattering (SRS) is presented based on parametric three-wave coupling in multidimensional geometry. It takes into account kinetic effects in the description of the plasma wave via a non linear frequency shift due to trapped electrons. The model is valid in the regime of hot and weakly inhomogeneous plasmas under conditions relevant for inertial confinement fusion with the plasma parameter k L λ De 0.25 (k L standing for the plasma wave number and λ De for the Debye length). Benchmarks of the model have been performed against the Maxwell-particle-in-cell (PIC) code Emi2D in order to calibrate the adjustable parameters controlling the non linear frequency shift. Two major configurations have been tested, one in a homogeneous plasma, with the onset of laser pump depletion and the other in an inhomogeneous plasma, producing auto-resonant growth. Good agreement between fluid and PIC simulations has been found for both configurations, in particular for the growth of SRS, and further on in time for the average backscatter level. The model is a promising tool to be implemented in multi-dimensional laser-plasma interaction packages coupled to hydrodynamics codes in order to compute SRS in mm-size volumes, usually inaccessible with PIC codes

Yoongoorrookoo:The emergence of ancestral personhood

Since the momentous release of the Montecristi Constitution of Ecuador in 2008, which recognised Nature, or Pacha Mama, as a subject of rights, the rights of Nature movement across the world has gained exponential momentum, with numerous jurisdictions worldwide now recognising some form of legal subjectivity vested upon Nature. In particular, since 2017, river personhood has dominated news headlines around the world as one of the most recognisable forms of Nature’s novel subjectivity. The emergence of legal personhood for nature, however, has been far from uncontroversial, and numerous critiques have been advanced against the use of such a legal category – traditionally applied to humans and their abstract creations (such as States and corporations) – to the natural world, resulting in numerous calls for an alternative category of legal personhood (one that some rights of Nature advocates have termed an ‘environmental person’). Against the backdrop of this emerging debate, this paper acknowledges the work undertaken by the Martuwarra Fitzroy River Council (Martuwarra Council), which was established in 2018 in the Kimberley region of Western Australia by six independent Indigenous nations to preserve, promote and protect their ancestral River from ongoing destructive ‘development’. The Council believes it is time to recognise the pre-existing and continuing legal authority of Indigenous law, or ‘First Law’, in relation to the River, in order to preserve its integrity through a process of legal decolonisation. First Law differs markedly from its colonial counterpart, as its principles are not articulated in terms of rules, policies and procedures, but rather through stories. This paper, therefore, begins with a dialogical translation of one First Law story relating to Yoongoorrookoo, 1 1 Nyikina elders Rosie Mulligan, Madeline Yanamarra, and Jeannie Warbie, as well as emerging Nyikina leaders, over the past three years have used multiple mediums to translate the stories of Senior Nyikina elder, Joe Nangan: Edwards & Nangan (1976). Furthermore, Anne Poelina, Nyikina leader and Chair of the Martuwarra Council, is working directly with Traditional Owners to privilege the voice and standing of Martuwarra. the ancestral serpent being, 2 2 Yoongoorrookoo is the Nyikina name of the Serpent, which is known by other names by other language groups of the Martuwarra/Fitzroy River catchment as described in the National Heritage listing assessment of the Martuwarra: ‘Martuwarra encompasses four contiguous and distinctive freshwater-based Aboriginal cultural domains, focused upon the tradition of the Rainbow Serpent, as exemplified by the religious traditions of Galaroo, Woonyoomboo-Yoongoorroonkoo, Wanjina- Wunggurr, and the jila-kalpurtu cultural systems. A song line known as Warloongarriy (Walungarri) serves to unite Aboriginal people and their Rainbow Serpent traditions along the Fitzroy River as part of one regional ritual complex, called Warloongarriy Law or “River Law”’ (Australian Government (date unknown), p 168). to create a semantic bridge between two apparently distant legal worldviews. A dialogical comparative analysis is then followed to posit and explore the concept of an ‘ancestral person’ as a novel comparative tool that may be able not only to capture the idea of Nature as a legal subject, but also complex Indigenous worldviews that see Nature–in this case instantiated in the Martuwarra–as an ancestral being enmeshed in a relationship of interdependence and guardianship between the human and the nonhuman world. To instantiate and embody such relationships, the paper directly, and somewhat provocatively, acknowledges the River itself, the Martuwarra RiverOfLife, as the primary participant in such dialogue, an embodied non-human co-author who began a conversation then left to human writers to continue

Reducing Health Risk Behaviors and Improving Depression in Adolescents: A Randomized Controlled Trial in Primary Care Clinics

ObjectivePrimary care (PC) is a major service delivery setting that can provide preventive behavioral health care to youths. To explore the hypothesis that reducing health risk behaviors (HRBs) would lower depressive symptoms, and that health risk and depression can be efficiently targeted together in PC, this study (1) evaluates an intervention designed to reduce HRBs among adolescent PC patients with depressive symptoms and (2) examines prospective links between HRBs and depressive symptoms.MethodA Randomized controlled trial was conducted comparing a behavioral health intervention with enhanced Usual PC (UC+). Participants were 187 adolescents (ages 13-18 years) with past-year depression, assessed at baseline, 6 months, and 12 months. Primary outcome was the Health Risk Behavior Index (HRBI), a composite score indexing smoking, substance use, unsafe sex, and obesity risk. Secondary/exploratory outcomes were an index of the first three most correlated behaviors (HRBI-S), each HRB, depressive symptoms, and satisfaction with mental health care.ResultsOutcomes were similar at 6 and 12 months, with no significant between-group differences. HRBI, HRBI-S, and depressive symptoms decreased, and satisfaction with mental health care increased across time in both groups. HRBI, HRBI-S, and smoking predicted later severe depression. Conversely, severe depression predicted later HRBI-S and substance use.ConclusionsUC+ and the behavioral health intervention yielded similar benefits in reducing HRBs and depressive symptoms. Findings underscore the bidirectional links between depression and HRBs, supporting the importance of monitoring for HRBs and depression in PC to allow for effective intervention in both areas

Model collaboration for the improved assessment of biomass supply, demand, and impacts

Existing assessments of biomass supply and demand and their impacts face various types of limitations and uncertainties, partly due to the type of tools and methods applied (e.g., partial representation of sectors, lack of geographical details, and aggregated representation of technologies involved). Improved collaboration between existing modeling approaches may provide new, more comprehensive insights, especially into issues that involve multiple economic sectors, different temporal and spatial scales, or various impact categories. Model collaboration consists of aligning and harmonizing input data and scenarios, model comparison and/or model linkage. Improved collaboration between existing modeling approaches can help assess (i) the causes of differences and similarities in model output, which is important for interpreting the results for policy-making and (ii) the linkages, feedbacks, and trade-offs between different systems and impacts (e.g., economic and natural), which is key to a more comprehensive understanding of the impacts of biomass supply and demand. But, full consistency or integration in assumptions, structure, solution algorithms, dynamics and feedbacks can be difficult to achieve. And, if it is done, it frequently implies a trade-off in terms of resolution (spatial, temporal, and structural) and/or computation. Three key research areas are selected to illustrate how model collaboration can provide additional ways for tackling some of the shortcomings and uncertainties in the assessment of biomass supply and demand and their impacts. These research areas are livestock production, agricultural residues, and greenhouse gas emissions from land-use change. Describing how model collaboration might look like in these examples, we show how improved model collaboration can strengthen our ability to project biomass supply, demand, and impacts. This in turn can aid in improving the information for policy-makers and in taking better-informed decisions

The Congolobe project, a multidisciplinary study of Congo deep-sea fan lobe complex: Overview of methods, strategies, observations and sampling

The presently active region of the Congo deep-sea fan (around 330 000 km2), called the terminal lobes or lobe complex, covers an area of 2500 km2 at 4700–5100 m water depth and 750–800 km offshore. It is a unique sedimentary area in the world ocean fed by a submarine canyon and a channel-levee system which presently deliver large amounts of organic carbon originating from the Congo River by turbidity currents. This particularity is due to the deep incision of the shelf by the Congo canyon, up to 30 km into the estuary, which funnels the Congo River sediments into the deep-sea. The connection between the river and the canyon is unique for major world rivers. In 2011, two cruises (WACS leg 2 and Congolobe) were conducted to simultaneously investigate the geology, organic and inorganic geochemistry, and micro- and macro-biology of the terminal lobes of the Congo deep-sea fan. Using this multidisciplinary approach, the morpho-sedimentary features of the lobes were characterized along with the origin and reactivity of organic matter, the recycling and burial of biogenic compounds, the diversity and function of bacterial and archaeal communities within the sediment, and the biodiversity and functioning of the faunal assemblages on the seafloor. Six different sites were selected for this study: Four distributed along the active channel from the lobe complex entrance to the outer rim of the sediment deposition zone, and two positioned cross-axis and at increasing distance from the active channel, thus providing a gradient in turbidite particle delivery and sediment age. This paper aims to provide the general context of this multidisciplinary study. It describes the general features of the site and the overall sampling strategy and provides the initial habitat observations to guide the other in-depth investigations presented in this special issue. Detailed bathymetry of each sampling site using 0.1 m to 1 m resolution multibeam obtained with a remotely operated vehicle (ROV) shows progressive widening and smoothing of the channel-levees with increasing depth and reveals a complex morphology with channel bifurcations, erosional features and massive deposits. Dense ecosystems surveyed in the study area gather high density clusters of two large-sized species of symbiotic Vesicomyidae bivalves and microbial mats. These assemblages, which are rarely observed in sedimentary zones, resemble those based on chemosynthesis at cold-seep sites, such as the active pockmarks encountered along the Congo margin, and share with these sites the dominant vesicomyid species Christineconcha regab. Sedimentation rates estimated in the lobe complex range between 0.5 and 10 cm yr−1, which is 2-3 orders of magnitude higher than values generally encountered at abyssal depths. The bathymetry, faunal assemblages and sedimentation rates make the Congo lobe complex a highly peculiar deep-sea habitat driven by high inputs of terrigenous material delivered by the Congo channel-levee system