Network modeling suggests HIV infection phenocopies PI3K-AKT pathway mutations to enhance HPV-associated cervical cancer

Women coinfected with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV) are six times as likely to develop invasive cervical carcinoma compared to those without HIV. Unlike other HIV-associated cancers, the risk of cervical cancer development does not change when HPV/HIV coinfected women begin antiretroviral therapy, suggesting HIV-associated immune suppression is not a key driver of cervical cancer development in coinfected women. Here, we investigated whether the persistent secretion of inflammatory factors in HIV-positive patients on antiretroviral therapy could enhance cancer signaling in HPV-infected cervical cells via endocrine mechanisms. We integrated previously reported HIV-induced secreted inflammatory factors (Hi-SIFs), HIV and HPV virus-human protein interactions, and cervical cancer patient genomic data using network propagation to understand the pathways underlying disease development in HPV/HIV coinfection. Our results pinpointed the PI3K-AKT signaling pathway to be enriched at the interface between Hi-SIFs and HPV-host molecular networks, in alignment with PI3K pathway mutations being prominent drivers of HPV-associated, but HIV independent, cervical cancer development. Furthermore, we experimentally stimulated cervical cells with 14 Hi-SIFs to assess their ability to activate PI3K-AKT signaling. Strikingly, we found 8 factors (CD14, CXCL11, CXCL9, CXCL13, CXCL17, AHSG, CCL18, and MMP-1) to significantly upregulate AKT phosphorylation (pAKT-S473) relative to a phosphate buffered saline control. Our findings suggest that Hi-SIFs cooperate with HPV infection in cervical cells to over-activate PI3K-AKT signaling, effectively phenocopying PI3K-AKT pathway mutations, resulting in enhanced cervical cancer development in coinfected women. Our insights could support the design of therapeutic interventions targeting the PI3K-AKT pathway or neutralizing Hi-SIFs in HPV/HIV coinfected cervical cancer patients

Risk of Injection-Site Abscess among Infants Receiving a Preservative-Free, Two-Dose Vial Formulation of Pneumococcal Conjugate Vaccine in Kenya.

There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10). We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants) were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance) and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance). Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator). A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose). The risk ratio for abscess following injection with the second (41 per 100,000) vs first (33 per 100,000) vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37-4.06). The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12-8.56) and 0.27 (95% CI 0.14-0.54) when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study

'Overnight, things changed. Suddenly, we were in it': a qualitative study exploring how surgical teams mitigated risks of COVID-19.

OBJECTIVES: COVID-19 presents a risk of infection and transmission for operating theatre teams. Guidelines to protect patients and staff emerged and changed rapidly based on expert opinion and limited evidence. This paper presents the experiences and innovations developed by international surgical teams during the early stages of the pandemic to attempt to mitigate risk. DESIGN: In-depth, semistructured interviews were audio recorded, transcribed and analysed thematically using methods of constant comparison. PARTICIPANTS: 43 participants, including surgeons from a range of specialties (primarily general surgery, otolaryngology, neurosurgery, cardiothoracic and ophthalmology), anaesthetists and those in nursing roles. SETTING: The UK, Italy, Spain, the USA, China and New Zealand between March and May 2020. RESULTS: Surgical teams sought to mitigate COVID-19 risks by modifying their current practice with an abundance of strategies and innovations. Communication and teamwork played an integral role in how teams adapted, although participants reflected on the challenges of having to improvise in real time. Uncertainties remained about optimal surgical practice and there were significant tensions where teams were forced to balance what was best for patients while contemplating their own safety. CONCLUSIONS: The perceptions of risks during a pandemic such as COVID-19 can be complex and context dependent. Management of these risks in surgery must be driven by evidence-based practice resulting from a pragmatic and novel approach to collation of global evidence. The context of surgery has changed dramatically, and surgical teams have developed a plethora of innovations. There is an urgent need for high-quality evidence to inform surgical practice that optimises the safety of both patients and healthcare professionals as the COVID-19 pandemic unfolds

Integrated assessment and valuation of ecosystem services - Guidelines and experiences

EU FP7 OpenNESS project deliverable D33 & D4

Body composition at birth and its relationship with neonatal anthropometric ratios: the newborn body composition study of the INTERGROWTH-21(st) project.

Background We aimed to describe newborn body composition and identify which anthropometric ratio (weight/length; BMI; or ponderal index, PI) best predicts fat mass (FM) and fat-free mass (FFM). Methods Air-displacement plethysmography (PEA POD) was used to estimate FM, FFM, and body fat percentage (BF%). Associations between FFM, FM, and BF% and weight/length, BMI, and PI were evaluated in 1,019 newborns using multivariate regression analysis. Charts for FM, FFM, and BF% were generated using a prescriptive subsample (n=247). Standards for the best-predicting anthropometric ratio were calculated utilizing the same population used for the INTERGROWTH-21(st) Newborn Size Standards (n=20,479). Results FFM and FM increased consistently during late pregnancy. Differential FM, BF%, and FFM patterns were observed for those born preterm (34(+0)-36(+6) weeks' gestation) and with impaired intrauterine growth. Weight/length by gestational age (GA) was a better predictor of FFM and FM (adjusted R(2)=0.92 and 0.71, respectively) than BMI or PI, independent of sex, GA, and timing of measurement. Results were almost identical when only preterm newborns were studied. We present sex-specific centiles for weight/length ratio for GA. Conclusions Weight/length best predicts newborn FFM and FM. There are differential FM, FFM, and BF% patterns by sex, GA, and size at birth

Stakeholders' perspectives on the operationalisation of the ecosystem service concept : Results from 27 case studies

The ecosystem service (ES) concept is becoming mainstream in policy and planning, but operational influence on practice is seldom reported. Here, we report the practitioners' perspectives on the practical implementation of the ES concept in 27 case studies. A standardised anonymous survey (n = 246), was used, focusing on the science-practice interaction process, perceived impact and expected use of the case study assessments. Operationalisation of the concept was shown to achieve a gradual change in practices: 13% of the case studies reported a change in action (e.g. management or policy change), and a further 40% anticipated that a change would result from the work. To a large extent the impact was attributed to a well conducted science-practice interaction process (>70%). The main reported advantages of the concept included: increased concept awareness and communication; enhanced participation and collaboration; production of comprehensive science-based knowledge; and production of spatially referenced knowledge for input to planning (91% indicated they had acquired new knowledge). The limitations were mostly case-specific and centred on methodology, data, and challenges with result implementation. The survey highlighted the crucial role of communication, participation and collaboration across different stakeholders, to implement the ES concept and enhance the democratisation of nature and landscape planning. (C) 2017 Published by Elsevier B.V.Peer reviewe

Comprehensive transcriptome of the maize stalk borer, Busseola fusca, from multiple tissue types, developmental stages, and parasitoid wasp exposures

International audienc