Wind speed variability over the Canary Islands, 1948-2014: focusing on trend differences at the land-ocean interface and below-above the trade-wind inversion layer

This study simultaneously examines wind speed trends at the land?ocean interface, and below?above the trade-wind inversion layer in the Canary Islands and the surrounding Eastern North Atlantic Ocean: a key region for quantifying the variability of trade-winds and its response to large-scale atmospheric circulation changes. Two homogenized data sources are used: (1) observed wind speed from nine land-based stations (1981?2014), including one mountain weather station (Izaña) located above the trade-wind inversion layer; and (2) simulated wind speed from two atmospheric hindcasts over ocean (i.e., SeaWind I at 30 km for 1948?2014; and SeaWind II at 15 km for 1989?2014). The results revealed a widespread significant negative trend of trade-winds over ocean for 1948?2014, whereas no significant trends were detected for 1989?2014. For this recent period wind speed over land and ocean displayed the same multi-decadal variability and a distinct seasonal trend pattern with a strengthening (late spring and summer; significant in May and August) and weakening (winter?spring?autumn; significant in April and September) of trade-winds. Above the inversion layer at Izaña, we found a predominance of significant positive trends, indicating a decoupled variability and opposite wind speed trends when compared to those reported in boundary layer. The analysis of the Trade Wind Index (TWI), the North Atlantic Oscillation Index (NAOI) and the Eastern Atlantic Index (EAI) demonstrated significant correlations with the wind speed variability, revealing that the correlation patterns of the three indices showed a spatio-temporal complementarity in shaping wind speed trends across the Eastern North Atlantic.C. A. -M. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 703733 (STILLING project). This research was also supported by the Research Projects: Swedish BECC, MERGE, VR (2014–5320), PCIN-2015-220, CGL2014-52135-C03-01 and Red de variabilidad y cambio climático RECLIM (CGL2014-517221-REDT). M.M is indebted to the Spanish Government for funding through the “Ramón y Cajal” program and supported by Grant PORTIO (BIA2015-70644-R

Nitric oxide orchestrates metabolic rewiring in M1 macrophages by targeting aconitase 2 and pyruvate dehydrogenase.

Profound metabolic changes are characteristic of macrophages during classical activation and have been implicated in this phenotype. Here we demonstrate that nitric oxide (NO) produced by murine macrophages is responsible for TCA cycle alterations and citrate accumulation associated with polarization. 13C tracing and mitochondrial respiration experiments map NO-mediated suppression of metabolism to mitochondrial aconitase (ACO2). Moreover, we find that inflammatory macrophages reroute pyruvate away from pyruvate dehydrogenase (PDH) in an NO-dependent and hypoxia-inducible factor 1α (Hif1α)-independent manner, thereby promoting glutamine-based anaplerosis. Ultimately, NO accumulation leads to suppression and loss of mitochondrial electron transport chain (ETC) complexes. Our data reveal that macrophages metabolic rewiring, in vitro and in vivo, is dependent on NO targeting specific pathways, resulting in reduced production of inflammatory mediators. Our findings require modification to current models of macrophage biology and demonstrate that reprogramming of metabolism should be considered a result rather than a mediator of inflammatory polarization

Nationwide randomised trial evaluating elective neck dissection for early stage oral cancer (SEND study) with meta-analysis and concurrent real-world cohort

BACKGROUND: Guidelines remain unclear over whether patients with early stage oral cancer without overt neck disease benefit from upfront elective neck dissection (END), particularly those with the smallest tumours. // METHODS: We conducted a randomised trial of patients with stage T1/T2 N0 disease, who had their mouth tumour resected either with or without END. Data were also collected from a concurrent cohort of patients who had their preferred surgery. Endpoints included overall survival (OS) and disease-free survival (DFS). We conducted a meta-analysis of all six randomised trials. // RESULTS: Two hundred fifty randomised and 346 observational cohort patients were studied (27 hospitals). Occult neck disease was found in 19.1% (T1) and 34.7% (T2) patients respectively. Five-year intention-to-treat hazard ratios (HR) were: OS HR = 0.71 (p = 0.18), and DFS HR = 0.66 (p = 0.04). Corresponding per-protocol results were: OS HR = 0.59 (p = 0.054), and DFS HR = 0.56 (p = 0.007). END was effective for small tumours. END patients experienced more facial/neck nerve damage; QoL was largely unaffected. The observational cohort supported the randomised findings. The meta-analysis produced HR OS 0.64 and DFS 0.54 (p < 0.001). // CONCLUSION: SEND and the cumulative evidence show that within a generalisable setting oral cancer patients who have an upfront END have a lower risk of death/recurrence, even with small tumours. // CLINICAL TRIAL REGISTRATION: NIHR UK Clinical Research Network database ID number: UKCRN 2069 (registered on 17/02/2006), ISCRTN number: 65018995, ClinicalTrials.gov Identifier: NCT00571883

Materialising architecture for social care: brick walls and compromises in design for later life.

This article reports on an ethnography of architectural projects for later life social care in the UK. Informed by recent debates in material studies and ‘materialities of care’ we offer an analysis of a care home project that is sensitive to architectural materials that are not normally associated with care and wellbeing. Although the care home design project we focus on in this article was never built, we found that design discussions relating to both a curved brick wall and bricks more generally were significant to its architectural ‘making’. The curved wall and the bricks were used by the architects to encode quality and values of care into their design. This was explicit in the design narrative that was core to a successful tender submitted by a consortium comprising architects, developers, contractors, and a care provider to a local authority who commissioned the care home. However, as the project developed, initial consensus for the design features fractured. Using a materialised analysis, we document the tussles generated by the curved wall and the bricks and argue that mundane building materials can be important to, and yet marginalised within, the relations inherent within an ‘architectural care assemblage.’ During the design process we saw how decisions about materials are contentious and they act as a catalyst of negotiations that compromise ‘materialities of care.

Building the capacity to solve complex health challenges in Sub-Saharan Africa : CARTA’s multidisciplinary PhD training

Objectives: To develop a curriculum (Joint Advanced Seminars- JAS) that produced PhD fellows who understood that health is an outcome of multiple determinants within complex environments and that approaches from a range of disciplines is required to address health and development within the Consortium for Advanced Research Training in Africa. We sought to attract PhD fellows, supervisors and teaching faculty from a range of disciplines into the program. Methods: Multidisciplinary teams developed the JAS curriculum. CARTA PhD fellowships were open to academics in consortium member institutions, irrespective of primary discipline, interested in doing a PhD in public and population health. Supervisors and JAS faculty were recruited from CARTA institutions. We use routine JAS evaluation data (closed and open ended questions) collected from PhD fellows at every JAS, a survey of one CARTA cohort and an external evaluation of CARTA to assess the impact of the JAS curriculum on learning. Results: We describe our pedagogic approach arguing its centrality to an appreciation of multiple disciplines and illustrate how it promotes working in multidisciplinary ways. CARTA has attracted PhD fellows, supervisors and JAS teaching faculty from across a range of disciplines. Evaluations indicate PhD fellows have a greater appreciation of how disciplines other than their own are important to understand health and its determinants and an appreciation and capacity to employ mixed methods research. Conclusions: In the short-term, we have been effective in promoting an understanding of multidisciplinarity resulting in fellows using methods from beyond their discipline of origin. This curriculum has international application

'High'-School: The Relationship between Early Marijuana Use and Educational Outcomes

We use unique survey data linked to nearly a decade of administrative welfare data to examine the relationship between early marijuana use (at age 14 or younger) and young people's educational outcomes. We find evidence that early marijuana use is related to educational penalties that are compounded by high-intensity use and are larger for young people living in families with a history of welfare receipt. The relationships between marijuana use and both high school completion and achieving a university entrance score appear to stem from selectivity into the use of marijuana. In contrast, early marijuana use is associated with significantly lower university entrance score for those who obtain one and we provide evidence that this effect is unlikely to be driven by selection. Collectively, these findings point to a more nuanced view of the relationship between adolescent marijuana use and educational outcomes than is suggested by the existing literature

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

A therapy for suppressing canonical and noncanonical SARS-CoV-2 viral entry and an intrinsic intrapulmonary inflammatory response

The prevalence of "long COVID" is just one of the conundrums highlighting how little we know about the lung's response to viral infection, particularly to syndromecoronavirus-2 (SARS-CoV-2), for which the lung is the point of entry. We used an in vitro human lung system to enable a prospective, unbiased, sequential single-cell level analysis of pulmonary cell responses to infection by multiple SARS-CoV-2 strains. Starting with human induced pluripotent stem cells and emulating lung organogenesis, we generated and infected three-dimensional, multi-cell-type-containing lung organoids (LOs) and gained several unexpected insights. First, SARS-CoV-2 tropism is much broader than previously believed: Many lung cell types are infectable, if not through a canonical receptor-mediated route (e.g., via Angiotensin-converting encyme 2(ACE2)) then via a noncanonical "backdoor" route (via macropinocytosis, a form of endocytosis). Food and Drug Administration (FDA)-approved endocytosis blockers can abrogate such entry, suggesting adjunctive therapies. Regardless of the route of entry, the virus triggers a lung-autonomous, pulmonary epithelial cell-intrinsic, innate immune response involving interferons and cytokine/chemokine production in the absence of hematopoietic derivatives. The virus can spread rapidly throughout human LOs resulting in mitochondrial apoptosis mediated by the prosurvival protein Bcl-xL. This host cytopathic response to the virus may help explain persistent inflammatory signatures in a dysfunctional pulmonary environment of long COVID. The host response to the virus is, in significant part, dependent on pulmonary Surfactant Protein-B, which plays an unanticipated role in signal transduction, viral resistance, dampening of systemic inflammatory cytokine production, and minimizing apoptosis. Exogenous surfactant, in fact, can be broadly therapeutic

Diamonds, gold and crime displacement: Hatton Garden, and the evolution of organised crime in the UK

The 2015 Hatton Garden Heist was described as the ‘largest burglary in English legal history’. However, the global attention that this spectacular crime attracted to ‘The Garden’ tended to concentrate upon the value of the stolen goods and the vintage of the burglars. What has been ignored is how the burglary shone a spotlight into Hatton Garden itself, as an area with a unique ‘upperworld’ commercial profile and skills cluster that we identify as an incubator and facilitator for organised crime. The Garden is the UK’s foremost jewellery production and retail centre and this paper seeks to explore how Hatton Garden’s businesses integrated with a fluid criminal population to transition, through hosting lucrative (and bureaucratically complex) VAT gold frauds from 1980 to the early 1990s, to become a major base for sophisticated acquisitive criminal activities. Based on extensive interviews over a thirty year period, evidence from a personal research archive and public records, this paper details a cultural community with a unique criminal profile due to the particularities of its geographical location, ethnic composition, trading culture, skills base and international connections. The processes and structures that facilitate criminal markets are largely under-researched (Antonopoulos et al. 2015: 11), and this paper considers how elements of Hatton Garden’s ‘upperworld’ businesses integrated with project criminals, displaced by policing strategies, to effect this transition