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Introduction: As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. Methods: In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. Results: Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p = 0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. Conclusion: Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes.

Mass photometry (MP) was used to investigate the assembly of myristoylated full-length HIV-1 Gag (myr-Gag) and vRNA 5’ UTR fragment in a supported lipid bilayer (SLB) model system. The MP trajectories demonstrated that Gag trimerization on the membrane is a key step of early Gag assembly in the presence of vRNA. Growth of myr-Gag oligomers requires vRNA, occuring by addition of 1 or 2 monomers at a time from solution. These data support a model where formation of the Gag hexamers characteristic of the immature capsid lattice occurs by a gradual edge expansion, following a trimeric nucleation event. These dynamic single molecule data involving protein, RNA, and lipid components together, provide novel and fundamental insights into the initiation of virus capsid assembly.

A wholly mapped ocean is one of the foundational goals of the United Nations Decade of Ocean Science for Sustainable Development. This multifaceted initiative aims to reverse the cycle of decline in ocean health and facilitate improved conditions for sustainable ocean development worldwide. Meeting this goal will require significant innovations in marine geodesy and survey. The following commentary details how innovations in satellite postioning, satellite imaging technology, remote operations, autonomous vehicles and robotics, and analytics and cloud automation are helping to provide safer, more efficient, cost-effective and sustainable marine survey and mapping solutions in support of the Ocean Decade. Real-world innovation examples from Geo-data specialist company Fugro are provided.

BACKGROUND: Preterm infants are at risk of lung atelectasis due to various anatomical and physiological immaturities, placing them at high risk of respiratory failure and associated harms. Nasal continuous positive airway pressure (CPAP) is a positive pressure applied to the airways via the nares. It helps prevent atelectasis and supports adequate gas exchange in spontaneously breathing infants. Nasal CPAP is used in the care of preterm infants around the world. Despite its common use, the appropriate pressure levels to apply during nasal CPAP use remain uncertain. OBJECTIVES: To assess the effects of 'low' (≤ 5 cm H(2)O) versus 'moderate‐high' (> 5 cm H(2)O) initial nasal CPAP pressure levels in preterm infants receiving CPAP either: 1) for initial respiratory support after birth and neonatal resuscitation or 2) following mechanical ventilation and endotracheal extubation. SEARCH METHODS: We ran a comprehensive search on 6 November 2020 in the following databases: CENTRAL via CRS Web and MEDLINE via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi‐randomized trials. SELECTION CRITERIA: We included RCTs, quasi‐RCTs, cluster‐RCTs and cross‐over RCTs randomizing preterm infants of gestational age < 37 weeks or birth weight < 2500 grams within the first 28 days of life to different nasal CPAP levels. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal to collect and analyze data. We used the GRADE approach to assess the certainty of the evidence for the prespecified primary outcomes. MAIN RESULTS: Eleven trials met inclusion criteria of the review. Four trials were parallel‐group RCTs reporting our prespecified primary or secondary outcomes. Two trials randomized 316 infants to low versus moderate‐high nasal CPAP for initial respiratory support, and two trials randomized 117 infants to low versus moderate‐high nasal CPAP following endotracheal extubation. The remaining seven studies were cross‐over trials reporting short‐term physiological outcomes. The most common potential sources of bias were absent or unclear blinding of personnel and assessors and uncertain selective reporting. Nasal CPAP for initial respiratory support after birth and neonatal resuscitation None of the six primary outcomes prespecified for inclusion in the summary of findings was eligible for meta‐analysis. No trials reported on moderate‐severe neurodevelopmental impairment at 18 to 26 months. The remaining five outcomes were reported in a single trial. On the basis of this trial, we are uncertain whether low or moderate‐high nasal CPAP levels improve the outcomes of: death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (PMA) (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.56 to 1.85; 1 trial, 271 participants); mortality by hospital discharge (RR 1.04, 95% CI 0.51 to 2.12; 1 trial, 271 participants); BPD at 28 days of age (RR 1.10, 95% CI 0.56 to 2.17; 1 trial, 271 participants); BPD at 36 weeks' PMA (RR 0.80, 95% CI 0.25 to 2.57; 1 trial, 271 participants), and treatment failure or need for mechanical ventilation (RR 1.00, 95% CI 0.63 to 1.57; 1 trial, 271 participants). We assessed the certainty of the evidence as very low for all five outcomes due to risk of bias, a lack of consistency across multiple studies, and imprecise effect estimates. Nasal CPAP following mechanical ventilation and endotracheal extubation One of the six primary outcomes prespecified for inclusion in the summary of findings was eligible for meta‐analysis. On the basis of these data, we are uncertain whether low or moderate‐high nasal CPAP levels improve the outcome of treatment failure or need for mechanical ventilation (RR 1.52, 95% CI 0.92 to 2.50; 2 trials, 117 participants; I(2) = 17%; risk difference 0.15, 95% CI −0.02 to 0.32; number needed to treat for an additional beneficial outcome 7, 95% CI −50 to 3). We assessed the certainty of the evidence as very low due to risk of bias, inconsistency across the studies, and imprecise effect estimates. No trials reported on moderate‐severe neurodevelopmental impairment at 18 to 26 months or BPD at 28 days of age. The remaining three outcomes were reported in a single trial. On the basis of this trial, we are uncertain whether low or moderate‐high nasal CPAP levels improve the outcomes of: death or BPD at 36 weeks' PMA (RR 0.87, 95% CI 0.51 to 1.49; 1 trial, 93 participants); mortality by hospital discharge (RR 2.94, 95% CI 0.12 to 70.30; 1 trial, 93 participants), and BPD at 36 weeks' PMA (RR 0.87, 95% CI 0.51 to 1.49; 1 trial, 93 participants). We assessed the certainty of the evidence as very low for all three outcomes due to risk of bias, a lack of consistency across multiple studies, and imprecise effect estimates. AUTHORS' CONCLUSIONS: There are insufficient data from randomized trials to guide nasal CPAP level selection in preterm infants, whether provided as initial respiratory support or following extubation from invasive mechanical ventilation. We are uncertain as to whether low or moderate‐high nasal CPAP levels improve morbidity and mortality in preterm infants. Well‐designed trials evaluating this important aspect of a commonly used neonatal therapy are needed.

Xenograft cancer studies using rag2Δ/Δ, il2rga−/− zebrafish allow facile, single-cell imaging of T cell–mediated tumor killing by CAR T cell, BiTE, and APEC immunotherapies and identified EGFR-targeted immunotherapies as an effective treatment for rhabdomyosarcoma muscle cancers., T cell immunotherapies have revolutionized treatment for a subset of cancers. Yet, a major hurdle has been the lack of facile and predicative preclinical animal models that permit dynamic visualization of T cell immune responses at single-cell resolution in vivo. Here, optically clear immunocompromised zebrafish were engrafted with fluorescent-labeled human cancers along with chimeric antigen receptor T (CAR T) cells, bispecific T cell engagers (BiTEs), and antibody peptide epitope conjugates (APECs), allowing real-time single-cell visualization of T cell–based immunotherapies in vivo. This work uncovered important differences in the kinetics of T cell infiltration, tumor cell engagement, and killing between these immunotherapies and established early endpoint analysis to predict therapy responses. We also established EGFR-targeted immunotherapies as a powerful approach to kill rhabdomyosarcoma muscle cancers, providing strong preclinical rationale for assessing a wider array of T cell immunotherapies in this disease.

What use is technology if no one uses it? This question underscores the critical interaction between people and the technology, highlighting the importance of understanding the underlying psychological factors that influence technology uptake. This study focuses on the corporate decision-makers who are the “gatekeepers” to the introduction of new technologies by their organizations. The offshore oil and gas industry has been characterized as reluctant to adopt new technology. Our thematic analysis of an interview study with 37 innovation technology stakeholders from this sector identified a set of six categories encompassing 15 psychological factors that influence the organizational decision-maker. The categories were labeled personality, attitudes, motivations, cognitive factors, social factors, and organizational factors set in a Psychological Technology Adoption Framework. This is the first attempt to focus exclusively on the main psychological factors that relate to this key decision-maker in the adoption of new technology. With further development, this preliminary psychological technology adoption framework can be used to develop interventions that support the successful technology uptake in the oil and gas business and similar industries.

Psychoanalytic training has been an object of controversy for many years. Arguments have been intense about the details, sometimes called "requirements", and particularly over whether or not training institutes should have routine external validation. We describe these arguments and present preliminary conclusions about the core challenges psychoanalytic trainings face using a unique set of detailed observations collected during structured "conversations" inside nine European institutes. We conclude that whether a psychoanalytic training is "working" is not a matter of compliance with requirements. Rather, it is an issue of how candidates, training analysts, supervisors and committee members, confront within and between each other the consequences of the unconscious dynamics that psychoanalytic training must inevitably create. Institutional psychoanalytic capacity is to take itself as the object. Consequentially, we propose that training committees that seek to claim that their psychoanalytic training is genuinely and safely producing psychoanalysts would be ones that institute routine procedures to show to themselves, transparently, how they attend to the dynamics just mentioned and how they take a neutral inquisitive stance towards them. Fear of oversight, we suggest, is a symptom of deeper anxieties. They can be faced by creating an appropriate setting. Properly conducted visits from outsiders are welcomed.

IntroductionThe ‘Developmental Origins of Health and Disease’ hypothesis suggests that a healthy trajectory of growth and development in pregnancy and early childhood is necessary for optimal health, development and lifetime well-being. The purpose of this paper is to present the protocol for a randomised controlled trial evaluating a preconception-early childhood telephone-based intervention with tailored e-health resources for women and their partners to optimise growth and development among children in Canada: a Healthy Life Trajectory Initiative (HeLTI Canada). The primary objective of HeLTI Canada is to determine whether a 4-phase ‘preconception to early childhood’ lifecourse intervention can reduce the rate of child overweight and obesity. Secondary objectives include improved child: (1) growth trajectories; (2) cardiometabolic risk factors; (3) health behaviours, including nutrition, physical activity, sedentary behaviour and sleep; and (4) development and school readiness at age 5 years.Method and analysisA randomised controlled multicentre trial will be conducted in two of Canada’s highly populous provinces—Alberta and Ontario—with 786 nulliparous (15%) and 4444 primiparous (85%) women, their partners and, when possible, the first ‘sibling child.’ The intervention is telephone-based collaborative care delivered by experienced public health nurses trained in healthy conversation skills that includes detailed risk assessments, individualised structured management plans, scheduled follow-up calls, and access to a web-based app with individualised, evidence-based resources. An ‘index child’ conceived after randomisation will be followed until age 5 years and assessed for the primary and secondary outcomes. Pregnancy, infancy (age 2 years) and parental outcomes across time will also be assessed.Ethics and disseminationThe study has received approval from Clinical Trials Ontario (CTO 1776). The findings will be published in peer-reviewed journals and disseminated to policymakers at local, national and international agencies. Findings will also be shared with study participants and their communities.Trial registration numberISRCTN13308752; Pre-results.

This chapter explores the importance of seafloor mapping to the new blue economy and the private sector’s role in making these critical datasets more accessible worldwide. It starts by decribing a general lack of good bathymetry data globally, and notes how this deficiency inhibits sustainable ocean development. Multibeam echosounder technology is presented as an ideal tool for acquiring high-resolution bathymetry, along with ancillary data sets that serve multiple other needs. Innovations to enable faster, safer, more cost-effective, and more sustainable multibeam data acquisition and delivery are explored, including remote operations, autonmous vehicle and robotic technologies, and artificial intelligence and cloud processing. These innovations are also examined in the context of a changing workforce. The article closes with a call for private sector engagement in two global ocean science initiatives that support a wholly mapped ocean: The Nippon Foundation-GEBCO Seabed 2030 Project and the United Nations Decade of Ocean Science for Sustainable Development.

The results of an investigation into the impact of in situ H2 plasma exposure on the electrical properties of the p/n-In0.3 Ga0.7 Sb-Al2O3 interface are presented. Samples were processed using a clustered inductively coupled plasma reactive ion etching and atomic layer deposition tool. Metal oxide semiconductor capacitors were fabricated subsequent to H2 plasma processing and Al2O3 deposition, and the corresponding capacitance-voltage and conductance-voltage measurements were analyzed quantitatively via the simulation of an equivalent circuit model. Interface state ( D it) and border trap ( N bt) densities were extracted for samples subjected to the optimal process, with a minimum Dit of 1.73 × 10 12 eV−1 cm−2 located at ∼110 meV below the conduction band edge and peak N bt approximately aligned with the valence and conduction band edges of 3 × 10 19 cm−3 and 6.5 × 10 19 cm−3, respectively. Analysis of the inversion response in terms of the extraction of the activation energy of minority carriers in inversion (p-type) and the observation of characteristics that pertain to minority carriers being supplied from an external inversion region (n-type) unequivocally demonstrate that the Fermi level is unpinned and that genuine surface inversion is observed for both doping polarities.

Background Reduction in postpartum length of stay has been advocated within a context of reducing health care system costs and maintaining quality of care. We assessed trends in postpartum length of stay for vaginal and cesarean deliveries at an academic hospital, The Ottawa Hospital, before and after the implementation in 2014 of a novel community-based postpartum outpatient clinic, the Monarch Centre. Methods The Monarch Centre model of postpartum care consists of prebooked appointments at the postpartum clinic, scheduled within 48 hours of hospital discharge. Clients receive maternal assessment including mood screening and care, neonatal care, laboratory testing including infant total serum bilirubin level, and breast-feeding assessment and support. Family physicians, lactation consultants and registered nurses are available for consultation at the appointment, and there is coordination with institutional care, community partners and primary care providers. We used interrupted time-series regression models to assess trends in postpartum length of stay at The Ottawa Hospital between January 2012 and December 2016. Results There were 16 023 deliveries with 16 515 babies born over the study period. The mean postpartum length of stay was 46 hours (66 h for cesarean deliveries and 37 h for vaginal deliveries). Eighteen months after implementation of the centre, the average length of stay following a cesarean birth had decreased by 20 hours, a relative reduction of 27% (95% confidence interval [CI] 9.5 to 30.4); for vaginal deliveries, length of stay was reduced by 6 hours, a relative reduction of 18% (95% CI 5.2 to 31.1), and by 12 hours among typical cases (relative reduction 28%, 95% CI 19.2 to 36.6). There was a decrease in the proportion of women with a length of stay exceeding 48 hours after centre implementation. An increase in the rate of 30-day readmission from 1.1% to 1.9% was observed among babies. Interpretation A strong association was found between implementation of a community-based multidisciplinary postpartum clinic and declines in postpartum length of stay. This alternative model of postpartum care is safe, has the potential for reducing provider costs and should be considered for further implementation at provincial and national levels.

This volume of papers by Otto Kernberg covers a wide range of topics. They span 30 years of his work and a number of them voice his criticisms of psychoanalytic education. Kernberg is a highly perc...

The centre of Ghana development is land that plays a vital role. This article focused mainly on the rapid land degradation and deforestation due to bush fires, poorly managed grazing, farming and agricultural conversion, current forest/woodland governance systems and major policy gaps that were identified. A combination of methods used included: Extensive study of secondary literature/reports/programmes/write-ups (from 1999-2004), key informant interview: a one-on-one interview with Government Officials, 7 responsible for forest management, Forestry, Commission and Traditional Institutions (men-10, women-5), elders-6, and functionaries-4 living in the community, phased assertion. The study recommend Forest Management System needs to be evolved that includes the management and development of sacred groves, shrines, sacred bodies and natures, and totems; associated with indigenous agricultural practices and seeds, indigenous agro-ecological management practices, indigenous tree and vegetation management practices, indigenous livelihood developments and human activity systems which are both enhancing and militating against biodiversity conservation and development encourage and systematically develop traditionally protect areas/plants/animals (TPAs). Attention should be paid to conservation of: 1) sacred groves; 2) burial grounds and spiritual lands; 3) sacred water bodies and fauna; 4) totemic animals; 5) traditional cultural practices; 6) farming systems; 7) traditional crop varieties; 8) home gardens; 9) graze-lands and rest lands; 10) wild fruits supply systems.

Multibeam echosounder (MBES) technology has been constantly evolving since its commercial introduction in the late 1970s. The early systems were large and designed to efficiently acquire bathymetric data in deep water. As the underlying sonar technologies improved and computing power increased, systems became smaller and capable of operating on a wider range of vessels over a broader range of depths. Modern deep seafloor exploration, and our present understanding of the geomorphological and biophysical processes that shape it, are closely linked to advances in multibeam echosounder technology. Low- to mid-frequency (12–30 kHz) acoustic waves generated by MBES sonars can penetrate kilometers of water column and remotely measure the deep seafloor and shallow subsurface. Reflectivity measurements of the seafloor and water column can also be extracted from MBES datasets, but until the last decade of the 20th century, only the bathymetric swath data was being utilized. In the 1990s, scientists began taking advantage of the multibeam acoustic wave's reflected energy, or backscatter, to interpret information on seafloor geometry (slope), physical characteristics (hardness and roughness), and intrinsic properties, such as composition, surficial and volumetric scattering. Analyzing the geophysical signature of reflected acoustic beams has proven an effective quantitative and qualitative tool to remotely characterize the lithologic composition and geologic nature of the seafloor. Analyzing seafloor backscatter and most recently, backscatter intensities in the water column, has been used for a wide range of applications, including fisheries research, marine biomass assessment, benthic habitat mapping, geological classification, subsea engineering and geohazard mitigation, and hydrocarbon seep studies. This presentation will briefly look at the evolution of MBES technology before focusing on how modern MBES surveys, using the latest generation technology, can deliver a comprehensive characterization of the seafloor and the waters above, as opposed to bathymetry data alone. With The Nippon Foundation-GEBCO Seabed 2030 Project now underway, and planning for the United Nations (UN) Decade of Ocean Science for Sustainable Development having recently commenced, modern MBES technology will play a critical role in bridging ocean bathymetry and ocean observation to improve our understanding of the ocean, its seafloor and its processes. One of the key R&D priorities of the Decade is a comprehensive map (digital atlas) of the ocean. Modern multibeam surveys will support not only bathymetric mapping, but also physical, biological, chemical, geologic, ecosystem, cultural and resource mapping of the world's oceans. Such an approach can feed both Seabed 2030 and the Decade to deliver, as the UN has so eloquently stated, “the ocean we want for the future we need.”

Innovation is critical to the future success of the oil and gas industry. Yet, the sector has a reputation for being conservative and reluctant to adopt new technology with companies sometimes referred to as "fast followers". Compared to other sectors, O&G has a set of unique characteristics that has the potential to hinder technology adoption. Research in other industries indicates that there is a range of sector, organizational and psychological factors that can hinder the introduction of new technologies. Evidence from O&G industry bodies indicate that the psychological factors play a key role in technology adoption; not surprisingly, as workers, managers, investors and regulators can all have a powerful influence on an organisation's receptivity to new technology. The psychological factors do not appear to be well understood but may include risk aversion (Wood Review, 2014), lack of ownership and leadership around technology (OGTC, 2018), and an attitude of reluctance to change (Oil and Gas Authority, 2018). This new research project is designed to examine how the particular attributes of the upstream oil and gas industry on the United Kingdom Continental Shelf interact with the underlying psychological processes that govern adoption and deployment decisions. The presentation will first outline what can be learned from about the psychological factors that influence technology innovation and adoption from the broader consumer behaviour and human factors literatures. Then the preliminary results of an interview study with stakeholders involved in technology innovation and adoption on the UKCS, will be reported. Roles include senior managers, innovation leads, and end users from a spectrum of established and new comer companies. A summary of the key themes identified will be discussed including personality (e.g. innovativeness), attitude (e.g. risk aversion), cognitive (e.g. risk perception), social (subjective norms) and organisational level factors (e.g. leadership and organisational culture). These results are being used to develop a preliminary framework of the psychological factors that influence technology adoption in O&G and to produce tools and guidelines on how to support the introduction of new technologies.

Innovation is critical to the future success of the oil and gas industry (Wood, 2014), particularly when addressing the challenges that the industry is facing. However, the sector has a reputation for being conservative, insular in its collaborative efforts and reluctant to adopt new technology. As a way of addressing this, the TechX programme at the Oil & Gas Technology Centre has launched TechX Ventures in July 2018 – a partnership with Deep Science Ventures (DSV) – that combines deep science with engineering to create the next generation of start-up companies with technologies that will position the oil and gas industry for a sustainable future in a low carbon economy. The start of the programme was a workshop held with industry, academia and the scientific community, to identify areas where new thinking and technology could open up significant opportunities. Three challenge themes were developed, each of which became an opportunity areas for DSV to address. These are: Carbon negative operations - Effective, large scale, affordable carbon capture and storage solutions are essential to meet global emissions targets. TechX Ventures seeks to create new technologies that will allow the capture of carbon at source, safe storage and conversion to other useful products such as graphene and hydrogen. Automated oil and gas - Oil and gas is playing catch-up with other industries, such as automotive and aerospace, when it comes to adopting robotics, automation and artificial intelligence. TechX Ventures aims to apply recent advances in these areas to North Sea operations to improve safety, enhance production efficiency and automate the decommissioning process. Energy movement/storage - Extracting, transporting, storing and using oil and gas presents many challenges. TechX Ventures wants to revolutionise the movement and storage of energy from well to customer by creating technologies which convert the reserves to electrical energy at source, store and transport electrical energy and convert currently wasteful processes e.g. gas flaring to electrical energy. As part of the TechX Ventures programme, DSV recruited thirty scientists and engineering experts from across the world to tackle the opportunity areas and at the end of the nine-month programme a total of six new start-up companies with new intellectual property were created and invested in by DSV. Of these six, two were selected to join the coveted TechX Pioneer accelerator programme run by OGTC in Aberdeen. These companies are called Eltera and Optic Earth.

Advances in genomic medicine have elucidated an increasing number of genetic etiologies for patients with common variable immunodeficiency (CVID). However, there is heterogeneity in clinical and immunophenotypic presentations and a limited understanding of the underlying pathophysiology of many cases. The primary defects in CVID may extend beyond the adaptive immune system, and the combined defect in both the myeloid and lymphoid compartments suggests the mechanism may involve bone marrow output and earlier progenitors. Using the methylation profile of the human androgen receptor (AR) gene as a surrogate epigenetic marker for bone marrow clonality, we examined the hematopoietic compartments of patients with CVID. Our data show that clonal hematopoiesis is common among patients with adult-onset CVID who do not have associated noninfectious complications. Nonblood tissues did not show a skewed AR methylation status, supporting a model of an acquired clonal hematopoietic event. Attenuation of memory B cell differentiation into long-lived plasma cells (CD20–CD27+CD38+CD138+) was associated with marked changes in the postdifferentiation methylation profile, demonstrating the functional consequence of clonal hematopoiesis on humoral immunity in these patients. This study sheds light on a potential etiology of a subset of patients with CVID, and the findings suggest that it is a stage of an acquired lymphocyte maturation disorder., Clonal hematopoiesis is common among a subset of patients with common variable immunodeficiency (CVID), suggesting that CVID may be a stage of lymphoid dysplasia.

Infantile hepatic haemangioendothelioma (IHH) is the commonest benign vascular tumour occurring in the first six-months of life. Medical treatment is first-line but a transcatheter arterial embolization (TAE) was also used in this preterm neonatal case; this is an innovative procedure used to reduce hepatic shunting by occluding the feeding vessels. Case report A 2.09 kg male infant was delivered at 31+3weeks by emergency C-section. There were antenatal concerns regarding ascites and dilated bowel loops and at delivery he was noted to have hydrops. He required intubation and high frequency oscillatory ventilation. Extensive bruising and active bleeding from multiple sites was noted, so the massive blood transfusion protocol was initiated. An ejection systolic murmur was heard and he had hepatomegaly. Initial blood-work showed anaemia and disseminated intravascular coagulopathy. Thrombocytopenia was likely from Kasabach-Merritt syndrome (KMS). He also had deranged liver enzymes, jaundice and an acute kidney injury. AFP, thyroid function tests and urinary VMA were reassuring. Echocardiography demonstrated a small PDA and moderately impaired biventricular function. Abdominal ultrasound showed a mixed lesion involving both liver lobes, measuring 8.2×5.7 cm with dilated hepatic veins and ascites. MRI was not possible due to his unstable clinical condition. A large number of blood products were required including recombinant factor 7. Regular vitamin K and broad-spectrum antibiotics were initiated. Propranolol and dexamethasone were commenced to try to shrink the lesion. On day 3 of life he had embolization of his AVM, this was a novel procedure and involved accessing the coeliac axis via the umbilical artery and releasing micro-particles.Satisfactory devascularisation was achieved. Despite this innovative technique, he deteriorated secondary to high-output CCF, pulmonary oedema, anuria and hepatic failure.It was apparent to his parents and the multidisciplinary team that he would not survive and life-sustaining care was withdrawn on day 6. Discussion It is clear that a multidisciplinary approach is required for the best treatment options. Corticosteroids (prednisolone) and propranolol are commonly prescribed and lesions unresponsive (15% cases) have been treated with antiangiogenic agents such as IFN-alpha, sirolimus, vincristine and cyclophosphamide.Invasive measures like hepatic artery ligation or embolization may be tried in complicated cases. Surgical therapy is recommended for uni-lobe lesions, masses with low potential for regression or in suspected malignancy. In summary, this case always had a poor prognosis as it was multifocal, had intra-hepatic shunting and was complicated by CCF and haemorrhage. Unfortunately TAE wasn’t successful on this occasion but sub-speciality involvement was greatly appreciated.

Several cancer immunotherapy approaches, such as immune checkpoint blockade and adoptive T-cell therapy, boost T-cell activity against the tumor, but these strategies are not effective in the absence of T cells specific for displayed tumor antigens. Here we outline an immunotherapy in which endogenous T cells specific for a noncancer antigen are retargeted to attack tumors. The approach relies on the use of antibody-peptide epitope conjugates (APECs) to deliver suitable antigens to the tumor surface for presention by HLA-I. To retarget cytomegalovirus (CMV)-specific CD8+ T cells against tumors, we used APECs containing CMV-derived epitopes conjugated to tumor-targeting antibodies via metalloprotease-sensitive linkers. These APECs redirect pre-existing CMV immunity against tumor cells in vitro and in mouse cancer models. In vitro, APECs activated specifically CMV-reactive effector T cells whereas a bispecific T-cell engager activated both effector and regulatory T cells. Our approach may provide an effective alternative in cancers that are not amenable to checkpoint inhibitors or other immunotherapies.

BACKGROUND: Conventional mechanical ventilation (CMV) is a common therapy for neonatal respiratory failure. While CMV facilitates gas exchange, it may simultaneously injure the lungs. Positive end‐expiratory pressure (PEEP) has received less attention than other ventilation parameters when considering this benefit–risk balance. While an appropriate PEEP level may result in clinical benefits, both inappropriately low or high levels may cause harm. An appropriate PEEP level may also be best achieved by an individualized approach. OBJECTIVES: 1. To compare the effects of PEEP levels in preterm infants requiring CMV for respiratory distress syndrome (RDS). We compare both: zero end‐expiratory pressure (ZEEP) (0 cm H(2)O) versus any PEEP and low (< 5 cm H(2)O) vs high (≥ 5 cm H(2)O) PEEP. 2. To compare the effects of PEEP levels in preterm infants requiring CMV for bronchopulmonary dysplasia (BPD). We compare both: ZEEP (0 cm H(2)O) vs any PEEP and low (< 5 cm H(2)O) versus high (≥ 5 cm H(2)O) PEEP. 3. To compare the effects of different methods for individualizing PEEP to an optimal level in preterm newborn infants requiring CMV for RDS. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials, MEDLINE via PubMed, Embase, and CINAHL to 14 February 2018. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi‐randomized trials. SELECTION CRITERIA: We included all randomized or quasi‐randomized controlled trials studying preterm infants born at less than 37 weeks' gestational age, requiring CMV and undergoing randomization to either different PEEP levels (RDS or BPD); or, two or more alternative methods for individualizing PEEP levels (RDS only). We included cross‐over trials but limited outcomes to those from the first cross‐over period. DATA COLLECTION AND ANALYSIS: We performed data collection and analysis according to the recommendations of the Cochrane Neonatal Review Group. We used the GRADE approach to assess the quality of evidence for prespecified key clinically relevant outcomes. MAIN RESULTS: Four trials met the inclusion criteria. Two cross‐over trials with 28 participants compared different PEEP levels in infants with RDS. Meta‐analysis was limited to short‐term measures of pulmonary gas exchange and showed no differences between low and high PEEP. We identified no trials comparing PEEP levels in infants with BPD. Two trials enrolling 44 participants compared different methods for individualizing PEEP in infants with RDS. Both trials compared an oxygenation‐guided lung‐recruitment maneuver (LRM) with gradual PEEP level titrations for individualizing PEEP to routine care (control). Meta‐analysis showed no difference between LRM and control on mortality by hospital discharge (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.17 to 5.77); there was no statistically significant difference on BPD, with an effect estimate favoring LRM (RR 0.25, 95% CI 0.03 to 2.07); and a statistically significant difference favoring LRM for the outcome of duration of ventilatory support (mean difference –1.06 days, 95% CI –1.85 to –0.26; moderate heterogeneity, I(2) = 67%). Short‐term oxygenation measures also favored LRM. We graded the quality of the evidence as low for all key outcomes due to risk of bias and imprecision of the effect estimates. AUTHORS' CONCLUSIONS: There continues to be insufficient evidence to guide PEEP level selection for preterm infants on CMV for RDS or BPD. Low‐quality data suggests that selecting PEEP levels through the application of an oxygenation‐guided LRM may result in clinical benefit. Well‐conducted randomized trials, particularly to further evaluate the potential benefits of oxygenation‐guided LRMs, are needed.

The Pseudomonas syringae acetyltransferase HopZ1a is delivered directly into host cells by the type III secretion system to promote bacterial growth. However, in the model plant host Arabidopsis thaliana, HopZ1a activity results in an effector-triggered immune response (ETI) that limits bacterial proliferation. HopZ1a-triggered immunity requires the nucleotide-binding, leucine-rich repeat domain (NLR) protein, ZAR1, and the ZED1 pseudokinase. Here we demonstrate that HopZ1a can acetylate members of a family of ‘receptor-like cytoplasmic kinases’ (RLCK family VII; also known as PBS1-like kinases, or PBLs) and promote their interaction with ZED1 and ZAR1 to form a ZAR1/ZED1/PBL ternary complex. Interactions between ZED1 and PBL kinases are determined by the pseudokinase features of ZED1, and mutants designed to restore ZED1 kinase motifs can (1) bind to PBLs, (2) recruit ZAR1, and (3) trigger immunity in planta, all independently of HopZ1a. Our results suggest that interactions between these two RLCK families are promoted by perturbations of structural features that distinguish active from inactive kinase domain conformations. We propose that effector-induced interactions between ZED1/ZRK pseudokinases (RLCK family XII) and PBL kinases (RLCK family VII) provide a sensitive mechanism for detecting perturbations of either kinase family and activating ZAR1-mediated ETI.AUTHOR SUMMARYAll plants must ward off potentially infectious microbes, and those grown in large-scale crop operations are especially vulnerable to the rapid spread of disease by successful pathogens. Although many bacteria and fungi can supress plant immune responses by producing specialized virulence proteins called ‘effectors’, these effectors can also trigger immune responses that render plants resistant to infection. We studied the molecular mechanisms underlying one such effector-triggered immune response elicited by the bacterial effector HopZ1a in the model plant host Arabidopsis thaliana. We have shown that HopZ1a promotes binding between a ZED1, a ‘pseudokinase’ required for HopZ1a-triggered immunity, and several ‘true kinases’ (known as PBLs) that are likely targets of HopZ1a activity in planta. HopZ1a-induced ZED1-PBL interactions also recruit ZAR1, an Arabidopsis ‘resistance protein’ previously implicated in HopZ1a-triggered immunity. Importantly, ZED1 mutants that restore degenerate kinase motifs can bridge interactions between PBLs and ZAR1 (independently of HopZ1a) and trigger immunity in planta. Our results suggest that equilibria between active and inactive kinase domain conformations regulate ZED1-PBL interactions and formation of ternary complexes with ZAR1. Improved models describing molecular interactions between immunity determinants, effectors and effector targets will inform efforts to exploit natural diversity for development of crops with enhanced disease resistance.

The world's oceans are critical to sustaining life, controlling climate, and providing economic wealth. Despite this fact, our understanding of the ocean and its seafloor processes is limited, in part because we lack accurate ocean mapping data. The situation is dramatic in the Arctic, where the physical environment is changing rapidly and where the vast majority of the 15,588,000-square-kilometer Arctic Ocean remains unmapped using modern survey methods. Given current and anticipated increases in vessel traffic, resource exploration and development, and impacts of climate change on coastal areas, the need for bathymetric data in the region is becoming increasingly urgent. The Nippon Foundation-GEBCO Seabed 2030 Project promises a solution for the Arctic's growing data demand. Launched in 2017, the project aims to produce a definitive and publicly available high-resolution map of the world's ocean floor by 2030. To achieve these goals, the program is advancing three strategies. First, existing data must be identified and the remaining gaps mapped. For the Arctic, apart from the ice covered central basin, an appreciable volume of bathymetric data already exists, but the national governments and private sector companies who hold these data will need to make them available to Seabed 2030, even if at decimated levels. Second, the project looks to crowd sourced bathymetry as an important means of acquiring new datasets. Vessels operating in or passing through Arctic waters can log and contribute bathymetric data from their movements. Finally, even if existing data and crowd sourced bathymetry data contributions are made, there will undoubtedly be a need for a coordinated Arctic Ocean basin mapping campaign by a combination of government, scientific, and private industry survey vessels to fill the remaining gaps in coverage. This paper will review the need for bathymetric data in the Arctic, the potential for the Seabed 2030 project to deliver these data, and the methods that will be used to ensure its success. It will also discuss the anticipated impacts of Seabed 2030 on Arctic resource development.

People have the power to make an innovation a success or a failure. Corporate decision makers act as both facilitators and barriers to the introduction of technologies into their organisations. Psychological factors clearly have an impact on their decisions and acceptance behaviours, but these have not been fully explored. Consequently, an understanding of these factors is essential for organisations who wish to accelerate technology adoption as well as for innovators who face numerous barriers when introducing their new products to the industrial market. The upstream oil and gas (O&G) industry has been characterised as reluctant to adopt new technology. The analysis of three technology introduction case studies in the UK offshore O&G sector (including interviews with 22 personnel involved in developing and commercially buying new technology) confirmed the influence of 15 psychological factors on organisational technology adoption decision making. These have been organized into a framework (P-TAF) consisting of six categories of psychological constructs, namely: personality, attitudes, motivation, social, cognitive, and organisational factors. With further development, this preliminary framework can be used to develop interventions that support the successful technology uptake in O&G and in other sectors experiencing resistance to the introduction of new technology.

This article presents the principles and findings of developing a new participatory assessment of development (PADev) evaluation approach that was codesigned with Dutch nongovernmental organizations (NGOs) and northern and southern research institutes over a period of 4 years in the context of rural development in Ghana and Burkina Faso. Although participatory approaches in development evaluations have become widely accepted since the 1990s, the PADev approach is different by taking the principles of holism and local knowledge as starting points for its methodological elaboration. The PADev approach is found to have an added value for assessing the differentiated effects of development interventions across different subgroups in a community through intersubjectivity. Moreover, if PADev is taken up by a multitude of stakeholders, including the intended beneficiaries of development interventions and development stakeholders, it can contribute to a process of local history writing, knowledge sharing, capacity development, and providing input into community action plans and the strategies of community-based organizations and NGOs.

Land issues have the potential to, and actually do generate a lot of conflicts and controversies in rural communities. In Northern Ghana, certain dilemmas, animated controversies, and conflicts about land rights, the resolution of which sometimes leads relatively innocuous compromise later manifest in several negative ramifications. For women in particular, the above negativities associated with land are even more pronounce and more protracted. This research adopted a case study approach to conduct this survey. The specific techniques used for data collection and analysis include: stratified group discussions, focus group discussions, key informant interview, phased assertion (confrontational dialogue), and critical arena analysis. The major findings include the fact that both men and women stated that land allocation to women is a regular affair now. It is the aspect of outright long-term ownership and user rights that are still very restricted. Since women do not sacrifice to the land her role in land sacrifices will be problematic. Women would prefer to acquire such formalized rights in their husbands’ homes, with the understanding that they could pass rights so acquired to their sons. Because of the intricate nature of land and the complications therein, and for the avoidance of perpetual conflicts, the women opted for increasing user-rights rather than ownership or controls of land. The concept of ownership, in their local language, was very nebulous to the women. Some were quick to state that they never wanted to own land. The study thus recommended that the socio-cultural values and practices in the area were inimical to any reforms to mainstream women in land issues. An extensive education and re-education of communities, linked with exposing them to best practices elsewhere are recommended. An endogenous development approach is recommended for such an education. There is a need to strengthen dialogue between women and men on issues of land. When men appreciate the benefits of making land available to women it facilitates the ease of giving out land. Economic empowerment of women is also recommended as a way of making land more accessible to women. The women contend that when they have money or wealth in the form of livestock, these assets make it easier for them to either rent land or engage in some form of traditional land tenure arrangement to acquire land for farming purposes.