Harnessing Big Data to Support the Conservation and Rehabilitation of Mangrove Forests Globally

Mangrove forests are found on sheltered coastlines in tropical, subtropical, and some warm temperate regions. These forests support unique biodiversity and provide a range of benefits to coastal communities, but as a result of large-scale conversion for aquaculture, agriculture, and urbanization, mangroves are considered increasingly threatened ecosystems. Scientific advances have led to accurate and comprehensive global datasets on mangrove extent, structure, and condition, and these can support evaluation of ecosystem services and stimulate greater conservation and rehabilitation efforts. To increase the utility and uptake of these products, in this Perspective we provide an overview of these recent and forthcoming global datasets and explore the challenges of translating these new analyses into policy action and on the ground conservation. We describe a new platform for visualizing and disseminating these datasets to the global science community, non-governmental organizations, government officials, and rehabilitation practitioners and highlight future directions and collaborations to increase the uptake and impact of largescale mangrove research

Pathogenic variants in MT-ATP6: A UK-based Mitochondrial Disease Cohort Study

Distinct clinical syndromes have been associated with pathogenic MT-ATP6 variants. In this cohort study, we identified 125 individuals (60 families) including 88 clinically affected individuals and 37 asymptomatic carriers. Thirty-one individuals presented with Leigh syndrome and seven with Neuropathy Ataxia Retinitis Pigmentosa. The remaining 50 patients presented with variable non-syndromic features including ataxia, neuropathy and learning disability. We confirmed maternal inheritance in 39 families, and demonstrated tissue segregation patterns and phenotypic threshold are variant-dependent. Our findings suggest that MT-ATP6-related mitochondrial disease is best conceptualised as a spectrum disorder and should be routinely included in genetic ataxia and neuropathy gene panels. This article is protected by copyright. All rights reserved

Treating implicit trauma: a quasi-experimental study comparing the EMDR Therapy Standard Protocol with a ‘Blind 2 Therapist’ version within a trauma capacity building project in Northern Iraq

Psychological trauma is a silent epidemic which presents as a global public health issue, often in the form of post- traumatic stress disorder (PTSD). Eye Movement Desensitisation and Reprocessing (EMDR) Therapy is an empirically supported treatment intervention for PTSD and has been used as part of trauma-capacity building, particularly in low- and middle-income countries (LMIC). For some survivor’s, their trauma experiences cannot be spoken of: they may be alluded to, suggested and though not directly expressed. There are several factors as to why these implicit trauma experiences are ‘unspoken’, for example, when the trauma involves a deep-rooted sense of shame or guilt, a distorted sense of over-responsibility or when to speak of the trauma engenders fear of retribution, reprisal and consequence. This paper will explore the effectiveness of using two protocol variations of EMDR Therapy—standard versus a ‘Blind 2 Therapist’ protocol version as part of a quasi-experimental study which took place in Northern Iraq. The study contains two projects and subsequently tested several hypotheses regarding safety, effectiveness, efficiency and relevance of the ‘Blind 2 Therapist’ protocol within EMDR Therapy. Results indicated support for the B2T protocol intervention with various trauma populations including Yezidi survivors of Islamic State of Iraq and the Levant (ISIL)—also known as Daesh

Adolescent pregnancies in the Amazon Basin of Ecuador: a rights and gender approach to adolescents' sexual and reproductive health

In the Andean region of Latin America over one million adolescent girls get pregnant every year. Adolescent pregnancy (AP) has been associated with adverse health and social outcomes, but it has also been favorably viewed as a pathway to adulthood. AP can also be conceptualized as a marker of inequity, since it disproportionately affects girls from the poorest households and those who have not been able to attend school

Bone Marrow Stromal Cells Modulate Mouse ENT1 Activity and Protect Leukemia Cells from Cytarabine Induced Apoptosis

BACKGROUND: Despite a high response rate to chemotherapy, the majority of patients with acute myeloid leukemia (AML) are destined to relapse due to residual disease in the bone marrow (BM). The tumor microenvironment is increasingly being recognized as a critical factor in mediating cancer cell survival and drug resistance. In this study, we propose to identify mechanisms involved in the chemoprotection conferred by the BM stroma to leukemia cells. METHODS: Using a leukemia mouse model and a human leukemia cell line, we studied the interaction of leukemia cells with the BM microenvironment. We evaluated in vivo and in vitro leukemia cell chemoprotection to different cytotoxic agents mediated by the BM stroma. Leukemia cell apoptosis was assessed by flow cytometry and western blotting. The activity of the equilibrative nucleoside transporter 1 (ENT1), responsible for cytarabine cell incorporation, was investigated by measuring transport and intracellular accumulation of (3)H-adenosine. RESULTS: Leukemia cell mobilization from the bone marrow into peripheral blood in vivo using a CXCR4 inhibitor induced chemo-sensitization of leukemia cells to cytarabine, which translated into a prolonged survival advantage in our mouse leukemia model. In vitro, the BM stromal cells secreted a soluble factor that mediated significant chemoprotection to leukemia cells from cytarabine induced apoptosis. Furthermore, the BM stromal cell supernatant induced a 50% reduction of the ENT1 activity in leukemia cells, reducing the incorporation of cytarabine. No protection was observed when radiation or other cytotoxic agents such as etoposide, cisplatin and 5-fluorouracil were used. CONCLUSION: The BM stroma secretes a soluble factor that significantly protects leukemia cells from cytarabine-induced apoptosis and blocks ENT1 activity. Strategies that modify the chemo-protective effects mediated by the BM microenvironment may enhance the benefit of conventional chemotherapy for patients with AML

Cullin3-KLHL15 ubiquitin ligase mediates CtIP protein turnover to fine-tune DNA-end resection

Human CtIP is a decisive factor in DNA double-strand break repair pathway choice by enabling DNA-end resection, the first step that differentiates homologous recombination (HR) from non-homologous end-joining (NHEJ). To coordinate appropriate and timely execution of DNA-end resection, CtIP function is tightly controlled by multiple protein-protein interactions and post-translational modifications. Here, we identify the Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as a new interaction partner of CtIP and show that KLHL15 promotes CtIP protein turnover via the ubiquitin-proteasome pathway. A tripeptide motif (FRY) conserved across vertebrate CtIP proteins is essential for KLHL15-binding; its mutation blocks KLHL15-dependent CtIP ubiquitination and degradation. Consequently, DNA-end resection is strongly attenuated in cells overexpressing KLHL15 but amplified in cells either expressing a CtIP-FRY mutant or lacking KLHL15, thus impacting the balance between HR and NHEJ. Collectively, our findings underline the key importance and high complexity of CtIP modulation for genome integrity

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Modeling working memory: An interference model of complex span

This article introduces a new computational model for the complex-span task, the most popular task for studying working memory. SOB-CS is a two-layer neural network that associates distributed item representations with distributed, overlapping position markers. Memory capacity limits are explained by interference from a superposition of associations. Concurrent processing interferes with memory through involuntary encoding of distractors. Free time in-between distractors is used to remove irrelevant representations, thereby reducing interference. The model accounts for benchmark findings in four areas: (1) effects of processing pace, processing difficulty, and number of processing steps; (2) effects of serial position and error patterns; (3) effects of different kinds of item-distractor similarity; and (4) correlations between span tasks. The model makes several new predictions in these areas, which were confirmed experimentally

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone