Petrogenesis and Geodynamic Significance of Xenolithic Eclogites

Kimberlite-borne xenolithic eclogites, typically occurring in or near cratons, have long been recognized as remnants of Precambrian subducted oceanic crust that have undergone partial melting to yield granitoids similar to the Archaean continental crust. While some eclogitized oceanic crust was emplaced into cratonic lithospheres, the majority was deeply subducted to form lithologic and geochemical heterogeneities in the convecting mantle. If we accept that most xenolithic eclogites originally formed at Earth's surface, then their geodynamic significance encompasses four tectonic environments: (a) spreading ridges, where precursors formed by partial melting of convecting mantle and subsequent melt differentiation; (b) subduction zones, where oceanic crust was metamorphosed and interacted with other slab lithologies; (c) the cratonic mantle lithosphere, where the eclogite source was variably modified subsequent to emplacement in Mesoarchaean to Palaeoproterozoic time; and (d) the convecting mantle, into which the vast majority of subduction-modified oceanic crust not captured in the cratonic lithosphere was recycled

Bullying Panel

This panel is set to push the boundaries of typical bullying prevention and propose fresh ideas for solutions in schools. Bullying prevention is one of the most pressing topics in education today. With many instances of school violence linked to bullying, schools are actively seeking practical solutions that can curtail this epidemic

The PVC element of Photorhabdus asymbiotica virulence cassettes deliver protein effectors directly into target eukaryotic cells

Photorhabdus is a highly effective insect pathogen and symbiont of insecticidal nematodes. To exert its potent insecticidal effects, it elaborates a myriad of toxins and small molecule effectors. Among these, the Photorhabdus Virulence Cassettes (PVCs) represent an elegant self-contained delivery mechanism for diverse protein toxins. Importantly, these self-contained nanosyringes overcome host cell membrane barriers, and act independently, at a distance from the bacteria itself. In this study, we demonstrate that Pnf, a PVC needle complex associated toxin, is a Rho-GTPase, which acts via deamidation and transglutamination to disrupt the cytoskeleton. TEM and Western blots have shown a physical association between Pnf and its cognate PVC delivery mechanism. We demonstrate that for Pnf to exert its effect, translocation across the cell membrane is absolutely essential

Why does bee health matter? The science surrounding honey bee health concerns and what we can do about it

CAST Commentary; QTA2017-1 June 201

A dynamic network of proteins facilitate cell envelope biogenesis in gram-negative bacteria

Bacteria must maintain the ability to modify and repair the peptidoglycan layer without jeopardising its essential functions in cell shape, cellular integrity and intermolecular interactions. A range of new experimental techniques is bringing an advanced understanding of how bacteria regulate and achieve peptidoglycan synthesis, particularly in respect of the central role played by complexes of Sporulation, Elongation or Division (SEDs) and class B penicillin-binding proteins required for cell division, growth and shape. In this review we highlight relationships implicated by a bioinformatic approach between the outer membrane, cytoskeletal components, periplasmic control proteins, and cell elongation/division proteins to provide further perspective on the interactions of these cell division, growth and shape complexes. We detail the network of protein interactions that assist in the formation of peptidoglycan and highlight the increasingly dynamic and connected set of protein machinery and macrostructures that assist in creating the cell envelope layers in Gram-negative bacteria

Substrate and Stereochemical Control of Peptidoglycan Cross-Linking by Transpeptidation by Escherichia coli PBP1B

Penicillin binding proteins (PBPs) catalyzing transpeptidation reactions that stabilize the peptidoglycan component of the bacterial cell wall are the targets of β-lactams, the most clinically successful antibiotics to date. However, PBP-transpeptidation enzymology has evaded detailed analysis, because of the historical unavailability of kinetically competent assays with physiologically relevant substrates and the previously unappreciated contribution of protein cofactors to PBP activity. By re-engineering peptidoglycan synthesis, we have constructed a continuous spectrophotometric assay for transpeptidation of native or near native peptidoglycan precursors and fragments by Escherichia coli PBP1B, allowing us to (a) identify recognition elements of transpeptidase substrates, (b) reveal a novel mechanism of stereochemical editing within peptidoglycan transpeptidation, (c) assess the impact of peptidoglycan substrates on β-lactam targeting of transpeptidation, and (d) demonstrate that both substrates have to be bound before transpeptidation occurs. The results allow characterization of high molecular weight PBPs as enzymes and not merely the targets of β-lactam acylation

Torture and the UK’s “war on asylum”: medical power and the culture of disbelief

When the now ‘iconic’ images of shackled, humiliated and dehumanised detainees in the Abu Ghraib prison complex in Iraq were broadcast globally, in the mid-2000s, the relationship between medical power and torture in the “war on terror” was also thrust sharply into focus. Graphic images of coalition troops photographing and posing in front of hooded, naked prisoners forced into a “human pyramid”, and of people made to wear animal collars, indicated a regime in which degradation had a defining role. The photograph of a soldier gloating over the corpse of a man who had died as a result of torture was just one picture of a network of interrogation camps in which detention by coalition forces could be fatal. Yet if there were any expectations that the presence of medical personnel may have checked this violence, these were shattered by the fact that clinicians – in some cases at least – were integral to its practice. «It is now beyond doubt that Armed Forces physicians, psychologists, and medics were active and passive partners in the systematic neglect and abuse of war on terror prisoners», wrote Steven Miles in 2009 (Miles 2009, X). And as he continued, this involved providing interrogators «with medical information to use in setting the nature and degree of physical and psychological abuse during interrogations». It involved monitoring «interrogations to devise ways to break prisoners down or to keep them alive». It involved pathologists holding back death certificates and autopsy reports in order to minimise the number of fatalities or cover up torture-related deaths as deaths by natural causes (Ibid). Procedures including «cramped confinement, dietary manipulation, sleep deprivation, and waterboarding» were among the practices that were «at times (…) legally sanctioned due to medical supervision» in the context of the “war on terror”, according to Hoffman (2011, 1535). He continued to suggest that doctors are not just important to «modern torture methods», they are «irreplaceable». In this context, the “war on terror” is no aberration. As the revolutionary psychoanalyst and philosopher Frantz Fanon documented in 1959, for example, certain medical practitioners had an integral role in the military occupation of Algeria, and «There are, for instance, psychiatrists … known to numerous prisoners», he suggested, «who have given electric shock treatments to the accused and have questioned them during the waking phase, which is characterized by a certain confusion, a relaxation of resistance, a disappearance of the person's defences.» (Fanon 1959/1965, 138). Indeed, in his analysis of the Algerian revolution, he discussed how resistance to and struggles over the meanings of medical power were integral to the revolution itself. However, while the role of medical power in the practice of torture has been subjected to sustained critique in the context of the “war on terror”, what follows examines the relationship between medical power and torture in the context of what has been depicted – metaphorically – as another (although to some extents related) “war”: the “war” on asylum. According to the UNHCR (2017, 3), between 5 and 35 per cent of those asylum seekers who have been granted refugee status have survived torture. And focusing on the UK as a case study, this chapter examines the institutional and legal structures prohibiting torture and inhuman and degrading treatment, particularly as they apply to those subject to immigration control in this context. But further, it also examines the ideological and political conditions within which claims by those seeking asylum that they have been subjected to torture prior to arrival can be (and have been) ignored, downplayed and denied. It examines how medical expertise has frequently been undermined in the asylum process when this expertise is utilised to add weight to asylum seekers’ claims to have experienced torture. It examines how there have been attempts to narrow the definition of torture in ways which exclude people from the protections to which torture survivors are entitled. But it also explores the ways in which segments of the medical profession have been complicit in riding roughshod over existing safeguards to prevent further harm to those who have experienced torture, thus potentially compounding its effects. In particular, it examines claims that in certain contexts clinicians have administered dangerous “care” in order to ensure the removal of people from the UK, despite them claiming that they – or their family members – face serious harm and persecution on arrival as a result of this. In a historical discussion of medical involvement in torture, Giovanni Maio (2001, 1609) has noted that from its earliest incarnations one of the features of torture has been its use as an «oppressive instrument used in the preservation of power». Furthermore, whilst methods of torture have certainly «developed», and continue to do so, he argues, this «function» of torture is «especially relevant today». This chapter argues that the (mis)treatment of those in the UK who say they have been tortured, preserves and is bound up with a particular manifestation of state power: the aims, rationale and dictates of immigration control. Its claims are perhaps much more mundane than the forms of direct medical complicity in torture alluded to above. But they are nonetheless important. For it is argued that the acts of omission and commission documented in this chapter expose the tensions between the rights of certain “categories” of migrants to be afforded adequate clinical care on the one hand, and the goals and aims of immigration control itself on the other. This poses profound questions about the functions of clinical care and the ethical duties, responsibilities and obligations of clinicians, it is suggested. But as this chapter also crucially explores, this is a form of power that many within the medical profession have historically challenged, and continue to do so

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes