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Technology-delivered cognitive behavioral therapy (CBT) has enabled more people to access effective, affordable mental health care. This study provides an overview of the most common types of technology-delivered CBT, including Internet-delivered, smartphone app, and telehealth CBT, as well as their evidence for the treatment of a range of mental health conditions. We discuss gaps in the existing evidence and future directions in the field for the use of technology CBT interventions., Competing Interests: Disclosure J.M. Newby receives funding from the HCF Research Foundation, Australia, the Australian National Health and Medical Research Council (grant: 2008839), and Australian Medical Research Future Fund. These funding sources had no role in the content or the decision to publish this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

During embryonic development, lymphatic endothelial cell (LEC) precursors are distinguished from blood endothelial cells by the expression of Prospero-related homeobox 1 (Prox1), which is essential for lymphatic vasculature formation in mouse and zebrafish. Prox1 expression initiation precedes LEC sprouting and migration, serving as the marker of specified LECs. Despite its crucial role in lymphatic development, Prox1 upstream regulation in LECs remains to be uncovered. SOX18 and COUP-TFII are thought to regulate Prox1 in mice by binding its promoter region. However, the specific regulation of Prox1 expression in LECs remains to be studied in detail. Here, we used evolutionary conservation and chromatin accessibility to identify enhancers located in the proximity of zebrafish prox1a active in developing LECs. We confirmed the functional role of the identified sequences through CRISPR/Cas9 mutagenesis of a lymphatic valve enhancer. The deletion of this region results in impaired valve morphology and function. Overall, our results reveal an intricate control of prox1a expression through a collection of enhancers. Ray-finned fish-specific distal enhancers drive pan-lymphatic expression, whereas vertebrate-conserved proximal enhancers refine expression in functionally distinct subsets of lymphatic endothelium., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Nicotine delivery and subjective effects are determinants of the ability of potentially less harmful tobacco products such as heated tobacco products (HTPs) to support adult smokers in switching away from cigarettes, and therefore to support tobacco harm reduction. This open-label, randomised, crossover, clinical study in 24 healthy adult smokers study assessed nicotine pharmacokinetics and subjective effects of the Pulze Heated Tobacco System (HTS; Pulze HTP device and three iD stick variants-Intense American Blend, Regular American Blend and Regular Menthol) compared with subjects' usual brand cigarettes (UBC). C max and AUC t were highest for UBC and significantly lower for each Pulze HTS variant. C max and AUC t were significantly higher for Intense American Blend compared with Regular American Blend, while AUC t was significantly higher for Intense American Blend compared with Regular Menthol. Median T max was lowest (i.e., nicotine delivery was fastest) for subjects' usual brand cigarettes and similar across the iD stick variants, although no between-product differences were statistically significant. All study products reduced urges to smoke; this effect was greatest for cigarettes although this was not statistically significant. Product evaluation scores for each Pulze HTS variant in the domains of 'satisfaction', 'psychological reward' and 'relief' were similar, and lower than those for UBC. These data demonstrate that the Pulze HTS effectively delivers nicotine and generates positive subjective effects, including satisfaction and reduced urge to smoke. This supports the conclusion that the Pulze HTS may be an acceptable alternative to cigarettes for adult smokers while having a lower abuse liability than cigarettes., (© 2023. The Author(s).)

During development, the lymphatic vasculature forms as a second network derived chiefly from blood vessels. The transdifferentiation of embryonic venous endothelial cells (VECs) into lymphatic endothelial cells (LECs) is a key step in this process. Specification, differentiation and maintenance of LEC fate are all driven by the transcription factor Prox1, yet the downstream mechanisms remain to be elucidated. We here present a single-cell transcriptomic atlas of lymphangiogenesis in zebrafish, revealing new markers and hallmarks of LEC differentiation over four developmental stages. We further profile single-cell transcriptomic and chromatin accessibility changes in zygotic prox1a mutants that are undergoing a LEC-VEC fate shift. Using maternal and zygotic prox1a/prox1b mutants, we determine the earliest transcriptomic changes directed by Prox1 during LEC specification. This work altogether reveals new downstream targets and regulatory regions of the genome controlled by Prox1 and presents evidence that Prox1 specifies LEC fate primarily by limiting blood vascular and haematopoietic fate. This extensive single-cell resource provides new mechanistic insights into the enigmatic role of Prox1 and the control of LEC differentiation in development., (© 2023 The Authors.)

Tobacco harm reduction (THR) involves providing adult smokers with potentially reduced harm modes of nicotine delivery as alternatives to smoking combustible cigarettes. Heated tobacco products (HTPs) form a category with THR potential due to their ability to deliver nicotine and flavours through heating, not burning, tobacco. By eliminating burning, heated tobacco does not produce smoke but an aerosol which contains fewer and lower levels of harmful chemicals compared to cigarette smoke. In this study we assessed the in vitro toxicological profiles of two prototype HTPs' aerosols compared to the 1R6F reference cigarette using the 3D human (bronchial) MucilAir™ model. To increase consumer relevance, whole aerosol/smoke exposures were delivered repeatedly across a 28 day period (16, 32, or 48 puffs per exposure). Cytotoxicity (LDH secretion), histology (Alcian Blue/H&E; Muc5AC; FoxJ1 staining), cilia active area and beat frequency and inflammatory marker (IL-6; IL-8; MMP-1; MMP-3; MMP-9; TNFα) levels were assessed. Diluted 1R6F smoke consistently induced greater and earlier effects compared to the prototype HTP aerosols across the endpoints, and in a puff dependent manner. Although some significant changes across the endpoints were induced by exposure to the HTPs, these were substantially less pronounced and less frequently observed, with apparent adaptive responses occurring over the experimental period. Furthermore, these differences between the two product categories were observed at a greater dilution (and generally lower nicotine delivery range) for 1R6F (1R6F smoke diluted 1/14, HTP aerosols diluted 1/2, with air). Overall, the findings demonstrate the THR potential of the prototype HTPs through demonstrated substantial reductions in toxicological outcomes in in vitro 3D human lung models., Competing Interests: Authors FC, EM, LC, GO’C, LS and MS were employed by the company Imperial Brands PLC. Authors SP, RW, ES, JB, KR, SO and TN were employed by the company Reemtsma Cigarettenfabriken GmbH, a subsidiary of Imperial Brands PLC., (Copyright © 2023 Chapman, Pour, Wieczorek, Trelles Sticken, Budde, Röwer, Otte, Mason, Czekala, Nahde, O’Connell, Simms and Stevenson.)

Study Objectives: Insomnia and anxiety are highly prevalent and frequently co-occur. Given limited therapeutic resources and time constraints, the aim of this study was to compare which treatment-internet cognitive behavioral therapy (CBT) for insomnia or internet CBT for anxiety-leads to the best outcomes in individuals with comorbid insomnia and anxiety., Methods: 120 participants with comorbid insomnia and clinical anxiety (as defined by scores above the clinical cutoff on the insomnia severity index (ISI) and the generalized anxiety disorder 7-item scale (GAD-7)) were randomized to receive internet-based cognitive behavioral therapy (iCBT) for insomnia or iCBT for anxiety. The primary outcome measures were the ISI and the generalized anxiety disorder 7-item scale. Primary outcome measures were assessed before treatment, at mid-treatment, at post-treatment, and 3 months after treatment. Secondary outcome measures assessed depression symptoms, distress, and sleep diary parameters., Results: Participants in both groups experienced large reductions in symptoms of insomnia, anxiety, depression, and distress, as well as improvements in sleep efficiency and total sleep time. Improvements were maintained at follow-up. Crucially, at the end of treatment, the insomnia treatment was more effective in reducing symptoms of insomnia than the anxiety treatment, and equally effective in reducing symptoms of anxiety. Treatment gains were maintained at 3-month follow-up, however, there were no differences between groups at that time point., Conclusions: These results suggest that in the common case of a patient presenting with comorbid insomnia and anxiety, treatment for insomnia may be the most efficient treatment strategy., Trial Registration: The trial was registered with the Australian and New Zealand Clinical Trials Registry, https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12618001141235. Trial ID: ACTRN12618001141235. Trial name: a comparison of internet-based CBT for insomnia versus internet-based CBT for anxiety in a comorbid sample., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study aimed to compare the aerosol chemistry and in vitro toxicological profiles of two prototype Heated Tobacco Product (p-HTP) variants to the 1R6F Reference Cigarette. In the neutral red uptake screen the p-HTPs were 37-39-fold less potent than 1R6F, in the micronucleus assay, responses to the p-HTPs were 8-22-fold less, and in the Ames test mutagenicity was weak or removed compared to 1R6F. The cardiovascular scratch wound assay revealed 58-fold greater wound healing impairment following exposure to 1R6F smoke extracts than the p-HTPs. Furthermore, in seven cell stress-related high content screening endpoints (cell count, cytochrome c release, mitochondrial membrane potential, GSH depletion, NFkB translocation, phosphorylation of c-jun and phosphorylation of H2AX), at 4 and 24 h, responses were substantially greater to 1R6F smoke extracts at comparable nicotine levels. The reduced in vitro effects of the p-HTPs were attributed to substantial reductions (90-97%) in selected HPHCs measured compared to in 1R6F smoke. The multiple endpoint in vitro assessment approach provides greater mechanistic insight and the first reported toxicological characterisation of these p-HTPs in the literature. Overall, the findings contribute to the growing weight of evidence that HTPs may offer a reduced harm mode of nicotine delivery to adult smokers., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fiona Chapman reports a relationship with Imperial Brands plc that includes: employment. Edgar Trelles Sticken reports a relationship with Imperial Brands plc that includes: employment. Roman Wieczorek reports a relationship with Imperial Brands plc that includes: employment. Sarah Jean Pour reports a relationship with Imperial Brands plc that includes: employment. Ole Dethloff reports a relationship with Imperial Brands plc that includes: employment. Jessica Budde reports a relationship with Imperial Brands plc that includes: employment. Kathryn Rudd reports a relationship with Imperial Brands plc that includes: employment. Elizabeth Mason reports a relationship with Imperial Brands plc that includes: employment. Lukasz Czekala reports a relationship with Imperial Brands plc that includes: employment. Fan Yu reports a relationship with Imperial Brands plc that includes: employment. Liam Simms reports a relationship with Imperial Brands plc that includes: employment. Thomas Nahde reports a relationship with Imperial Brands plc that includes: employment. Grant O'Connell reports a relationship with Imperial Brands plc that includes: employment. Matthew Stevenson reports a relationship with Imperial Brands plc that includes: employment., (Copyright © 2022. Published by Elsevier Ltd.)

Competing Interests: Conflict-of-Interest Disclosures: None to disclose.

Objectives: A key feature of blood-injection-injury (BII) phobia is activation of disgust responses, in addition to fear. Yet, standard treatments have largely neglected addressing disgust responses. The disorder is further complicated by fainting in 75% of sufferers. Moreover, treatments have been traditionally delivered in an individual format, which may not be as efficient as group treatment. The aim of this study was to develop a group-based programme for BII phobia, with components targeting fear, disgust, and fainting, to determine feasibility and effectiveness of such an intervention., Methods: Participants took part in an 8-session, group-based Cognitive Behavioural Therapy (CBT) programme for BII phobia (N = 40). The key outcome measure was the Multidimensional Blood/Injury Phobia Inventory, which assesses a range of phobic stimuli and responses (including fear, disgust, and fainting)., Results: There were significant improvements, with large effect sizes, across symptoms over the course of treatment. Participants with higher disgust sensitivity reported higher pre-treatment symptom severity and greater life interference than those with lower disgust scores. Despite this, neither pre-treatment disgust sensitivity nor fainting history impacted on treatment response. For the first time, however, we showed that greater reductions in disgust to BII stimuli were associated with greater overall symptom reductions, highlighting the importance of disgust in the treatment of this disorder, and potentially others., Conclusion: Despite the heterogeneous nature of BII phobia, this group-based, modified CBT intervention was effective in reducing a variety of phobic responses, including fear, disgust, and fainting., Practitioner Points: Disgust is a key maintaining factor in blood-injection-injury phobia, which clinicians should consider in their assessment and treatment of this disorder. There is little in the existing literature to guide clinicians in this regard. This study examined a novel group treatment for blood-injection-injury phobia which included strategies to target disgust, in addition to traditional CBT strategies to address fear and fainting. The treatment was feasible and acceptable. Symptoms of fear, disgust, and fainting reduced significantly over treatment. Changes in disgust symptoms were associated with overall symptom changes, however a control group is needed to determine the effects of individual treatment components and to make more robust conclusions about the benefits of this enhanced approach., (© 2021 The British Psychological Society.)

Background: Online communities such as Reddit can provide social support for those recovering from opioid use disorder. However, it is unclear whether and how advice-seekers differ from other users. Our research addresses this gap by identifying key characteristics of r/suboxone users that predict advice-seeking behavior. Objective: The objective of this analysis is to identify and describe advice-seekers on Reddit for buprenorphine-naloxone use using text annotation, social network analysis, and statistical modeling techniques. Methods: We collected 5258 posts and their comments from Reddit between 2014 and 2019. Among 202 posts which met our inclusion criteria, we annotated each post to determine which were advice-seeking (n = 137) or not advice-seeking (n = 65). We also annotated each posting user’s buprenorphine-naloxone use status (current versus formerly taking and, if currently taking, whether inducting or tapering versus other stages) and quantified their connectedness using social network analysis. To analyze the relationship between Reddit users’ advice-seeking and their social connectivity and medication use status, we constructed four models which varied in their inclusion of explanatory variables for social connectedness and buprenorphine use status. Results: The stepwise model containing “total degree” (p = 0.002), “using: inducting/tapering” (p < 0.001), and “using: other” (p = 0.01) outperformed all other models. Reddit users with fewer connections and who are currently using buprenorphine-naloxone are more likely to seek advice than those who are well-connected and no longer using the medication, respectively. Importantly, advice-seeking behavior is most accurately predicted using a combination of network characteristics and medication use status, rather than either factor alone. Conclusions: Our findings provide insights for the clinical care of people recovering from opioid use disorder and the nature of online medical advice-seeking overall. Clinicians should be especially attentive (e.g., through frequent follow-up) to patients who are inducting or tapering buprenorphine-naloxone or signal limited social support.

Objectives: The growth and development of smartphones and eHealth technologies have enabled the potential for extended care hospitals (e-hospitals) in China in order to facilitate the success of a primary healthcare centre (PHC)-based integrated delivery model. Although the adoption of e-hospitals is essential, few studies have directed their research towards understanding the perspectives of healthcare providers. This study aims to identify the current readiness of healthcare providers to adopt e-hospital technologies, determine the factors influencing this adoption and describe the perceived facilitators and barriers in regard to working at e-hospitals., Design: A cross-sectional study conducted in Sichuan, China, between June and September 2019., Settings: Information was collected from healthcare providers who have more than 3 years of work experience from a tertiary hospital, secondary hospital, PHCs and private hospital., Participants: 2298 medical professionals were included in this study., Outcome Measure: This study included a self-administered questionnaire that was used to assess participants' sociodemographic characteristics, online medical practices, willingness to use e-hospitals and perceived facilitators/barriers to working at e-hospitals. Multivariate regression analysis was performed in order to evaluate the independent factors associated with e-hospital work., Results: Overall, 86.3% had a positive response towards working at e-hospitals. Age (p<0.05), familiarity with e-hospitals (p<0.001) and prior work practices in online healthcare settings (p<0.001) were associated with participants' readiness to work at e-hospitals. Gender, education level, professional level, the tier of their affiliated hospital and workload were not statistically associated. Healthcare providers who had positive attitudes towards e-hospitals considered improved efficiency, patient satisfaction, communication among physicians, increased reputation and income, and alleviated workload to be advantages of adoption. The participants who were unwilling to work at e-hospitals perceived lack of time, insufficient authenticity/reliability and underdeveloped policies as potential barriers., Conclusion: Improving operative proficiency in electronic devices, accommodating to work schedules, increasing familiarity with e-hospitals and regulating practices will improve the readiness of healthcare providers to work at e-hospitals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To inform the World Health Organization's full value of vaccine assessment for group B Streptococcus (GBS) vaccines, a rapid literature appraisal was conducted to inform the operationalization of maternal GBS vaccination. We found limited published information on stakeholder perceptions of the public health importance of GBS disease and vaccination, and we therefore undertook a multicountry survey., Methods: An online survey was conducted in late 2019 to collect information on stakeholders' awareness of GBS disease and the priority accorded to vaccination. The survey was distributed by email to 395 representatives of national pediatric, gynecology, and obstetrics associations, national immunization technical advisory groups (NITAGs), national regulatory agencies, academia, and United Nations organizations., Results: Among 101 survey respondents from 66 countries, 36% were pediatricians, 25% obstetricians/gynecologists, 21% immunization specialists, and 18% other public health specialists. More than half (58%) of respondents reported being familiar with GBS disease as a public health problem; familiarity decreased by country income level. Knowledge of GBS disease was greatest in the Americas (68%) and Europe (66%) and lowest in Asia (13%-38%). Perception of GBS disease as a public health problem was highest among pediatricians (71%) and lowest among public health policy makers and NITAG members (30%) across country groupings. Approximately half of respondents (49%) considered the introduction of a GBS vaccine as a priority., Conclusions: The information obtained will inform the appropriate packaging and presentation of information to address stakeholder perceptions and promote evidence-based decision making on GBS vaccination., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Objective: To investigate vaccine hesitancy leading to underimmunization and a measles outbreak in Rwanda and to develop a conceptual, community-level model of behavioural factors., Methods: Local immunization systems in two Rwandan communities (one recently experienced a measles outbreak) were explored using systems thinking, human-centred design and behavioural frameworks. Data were collected between 2018 and 2020 from: discussions with 11 vaccination service providers (i.e. hospital and health centre staff); interviews with 161 children's caregivers at health centres; and nine validation interviews with health centre staff. Factors influencing vaccine hesitancy were categorized using the 3Cs framework: confidence, complacency and convenience. A conceptual model of vaccine hesitancy mechanisms with feedback loops was developed., Findings: A comparison of service providers' and caregivers' perspectives in both rural and peri-urban settings showed that similar factors strengthened vaccine uptake: (i) high trust in vaccines and service providers based on personal relationships with health centre staff; (ii) the connecting role of community health workers; and (iii) a strong sense of community. Factors identified as increasing vaccine hesitancy (e.g. service accessibility and inadequate follow-up) differed between service providers and caregivers and between settings. The conceptual model could be used to explain drivers of the recent measles outbreak and to guide interventions designed to increase vaccine uptake., Conclusion: The application of behavioural frameworks and systems thinking revealed vaccine hesitancy mechanisms in Rwandan communities that demonstrate the interrelationship between immunization services and caregivers' vaccination behaviour. Confidence-building social structures and context-dependent challenges that affect vaccine uptake were also identified., ((c) 2021 The authors; licensee World Health Organization.)

The development of a functional vasculature requires the coordinated control of cell fate, lineage differentiation and network growth. Cellular proliferation is spatiotemporally regulated in developing vessels, but how this is orchestrated in different lineages is unknown. Here, using a zebrafish genetic screen for lymphatic-deficient mutants, we uncover a mutant for the RNA helicase Ddx21. Ddx21 cell-autonomously regulates lymphatic vessel development. An established regulator of ribosomal RNA synthesis and ribosome biogenesis, Ddx21 is enriched in sprouting venous endothelial cells in response to Vegfc-Flt4 signalling. Ddx21 function is essential for Vegfc-Flt4-driven endothelial cell proliferation. In the absence of Ddx21, endothelial cells show reduced ribosome biogenesis, p53 and p21 upregulation and cell cycle arrest that blocks lymphangiogenesis. Thus, Ddx21 coordinates the lymphatic endothelial cell response to Vegfc-Flt4 signalling by balancing ribosome biogenesis and p53 function. This mechanism may be targetable in diseases of excessive lymphangiogenesis such as cancer metastasis or lymphatic malformation., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

A growing number of public health bodies, regulators and governments around the world consider electronic vapor products a lower risk alternative to conventional cigarettes. Of critical importance are rapid new approach methodologies to enable the screening of next generation products (NGPs) also known as next generation tobacco and nicotine products. In this study, the activity of conventional cigarette (3R4F) smoke and a range of NGP aerosols (heated tobacco product, hybrid product and electronic vapor product) captured in phosphate buffered saline, were screened by exposing a panel of human cell-based model systems using Biologically Multiplexed Activity Profiling (BioMAP® Diversity PLUS® Panel, Eurofins Discovery). Following exposure, the biological activity for a wide range of biomarkers in the BioMAP panel were compared to determine the presence of toxicity signatures that are associated with specific clinical findings. NGP aerosols were found to be weakly active in the BioMAP Diversity PLUS Panel (≤3/148 biomarkers) whereas significant activity was observed for 3R4F (22/148 biomarkers). Toxicity associated biomarker signatures for 3R4F included immunosuppression, skin irritation and thrombosis, with no toxicity signatures seen for the NGPs. BioMAP profiling could effectively be used to differentiate between complex mixtures of cigarette smoke or NGP aerosol extracts in a panel of human primary cell-based assays. Clinical validation of these results will be critical for confirming the utility of BioMAP for screening NGPs for potential adverse human effects., Competing Interests: Liam Simms, Elizabeth Mason, Fan Yu, Kathryn Rudd, Lukasz Czekala, Edgar Trelles Sticken, Oleg Brinster, Matthew Stevenson and Tanvir Walele were all current employees for Imperial Brands PLC at the time of submission. Imperial Brands PLC, who funded the work and was the sole sponsor of the project. Ellen L. Berg was the Eurofins Discovery contact who conducted the work and provided technical support to the project. None of the Imperial Brands personnel above have any known competing financial interests., (© 2021 The Author(s).)

Little is known about the prevalence and impact on treatment of comorbid personality disorders for adults undertaking online cognitive behaviour therapy (internet-delivered or internet-based cognitive behaviour therapy (iCBT)) for anxiety and depressive disorders. This study explored how common comorbid personality difficulties were in a large sample of consecutive patients (N = 1 132) seeking iCBT for their symptoms of anxiety and depression in routine care settings. Patients completed the Standardized Assessment of Personality-abbreviated Scale Self-Report prior to commencing an iCBT programme, as well as completing assessments of anxiety and depression symptom severity and psychological distress pre-iCBT and post-iCBT. Consistent with previous studies, a high proportion of the sample (62.6%) reported experiencing comorbid personality difficulties. However, comorbid personality difficulties were not significantly associated with poorer treatment adherence or higher post-treatment symptom severity or psychological distress (controlling for baseline symptom severity, demographic characteristics and treatment variables). Current findings support an inclusive approach to iCBT provision where comorbid personality difficulties do not appear to be a contraindication for treatment. © 2021 John Wiley & Sons, Ltd., (© 2021 John Wiley & Sons, Ltd.)

The formation of new blood vessel networks occurs via angiogenesis during development, tissue repair, and disease. Angiogenesis is regulated by intracellular endothelial signalling pathways, induced downstream of vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). A major challenge in understanding angiogenesis is interpreting how signalling events occur dynamically within endothelial cell populations during sprouting, proliferation, and migration. Extracellular signal-regulated kinase (Erk) is a central downstream effector of Vegf-signalling and reports the signalling that drives angiogenesis. We generated a vascular Erk biosensor transgenic line in zebrafish using a kinase translocation reporter that allows live-imaging of Erk-signalling dynamics. We demonstrate the utility of this line to live-image Erk activity during physiologically relevant angiogenic events. Further, we reveal dynamic and sequential endothelial cell Erk-signalling events following blood vessel wounding. Initial signalling is dependent upon Ca 2+ in the earliest responding endothelial cells, but is independent of Vegfr-signalling and local inflammation. The sustained regenerative response, however, involves a Vegfr-dependent mechanism that initiates concomitantly with the wound inflammatory response. This work reveals a highly dynamic sequence of signalling events in regenerative angiogenesis and validates a new resource for the study of vascular Erk-signalling in real-time., Competing Interests: KO, MK, DG, CS, EM, SP, HC, MS, NC, PM, MD, BH No competing interests declared, (© 2021, Okuda et al.)

This paper reports the genome sequences of bacteriophages isolated from soil samples using Microbacterium foliorum Phages Danno and Otwor (cluster EE) have genomes of 17,452 bp and 17,454 bp, respectively, and 25 predicted genes. The phage Scumberland (cluster EC) has a genome of 53,276 bp with 92 predicted genes., (Copyright © 2021 Markov et al.)

Competing Interests: Competing interests: None declared.

Prior to the addition of a maternal vaccine onto the National Immunization Programme, it is important for a country to evaluate their capacity and readiness. This checklist has been developed that is deliberately not restricted to any particular vaccine so it can be applied by national-level stakeholders during the decision-making stage for the introduction of any additional or new maternal vaccine. It is suggested that a team consisting of representatives from the Ministry of Health, including the National Immunization Programme (NIP) and Maternal, Newborn and Child Health (MNCH) programs complete and review the checklist together. This checklist enables countries to assess their capacity, strengths and weaknesses and identify a list of priorities to allow for smooth implementation of maternal vaccines.

Objective: To explore the association between early essential newborn care (EENC) policy, practice and environmental interventions and breastfeeding outcomes., Design: Cross-sectional observational study., Setting: 150 national, provincial and district hospitals implementing EENC in eight countries in East Asia and the Pacific., Participants: 1383 maternal interviews, chart reviews and environmental assessments during 2016 and 2017., Main Outcome Measures: Exclusive breastfeeding (EBF), that is, feeding only breastmilk without other food or fluids since birth and before discharge, and, early breastfeeding initiation, that is, during skin-to-skin contact (SSC) with the mother without separation., Results: Fifty-nine per cent of newborns initiated breastfeeding early and 83.5% were EBF. Duration of SSC showed a strong dose-response relationship with early breastfeeding initiation. SSC of at least 90 min was associated with 368.81 (95% CI 88.76 to 1532.38, p<0.001) times higher early breastfeeding. EBF was significantly associated with SSC duration of 30-59 min (OR 3.54, 95% CI 1.88 to 6.66, p<0.001), 60-89 min (OR 5.61, 95% CI 2.51 to 12.58, p<0.001) and at least 90 min (OR 3.78, 95% CI 2.12 to 6.74, p<0.001) regardless of delivery mode. Non-supine position (OR 2.80, 95% CI 1.90 to 4.11, p<0.001), rooming-in (OR 5.85, 95% CI 3.46 to 9.88, p<0.001), hospital breastfeeding policies (OR 2.82, 95% CI 1.97 to 4.02, p<0.001), quality improvement mechanisms (OR 1.63, 95% CI 1.07 to 2.49, p=0.02) and no formula products (OR 17.50, 95% CI 5.92 to 51.74, p<0.001) were associated with EBF., Conclusion: EENC policy, practice and environmental interventions were associated with breastfeeding outcomes. To maximise the likelihood of early and EBF, newborns, regardless of delivery mode, should receive immediate and uninterrupted SSC for at least 90 min., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: We present the integration of telemedicine into the healthcare system of West China Hospital of Sichuan University (WCH), one of the largest hospitals in the world with 4300 inpatient beds, as a means for maximising the efficiency of healthcare delivery during the COVID-19 pandemic., Methods: Implemented on 22 January 2020, the telemedicine technology allowed WCH providers to conduct teleconsultations, telerounds, teleradiology and tele-intensive care unit, which in culmination provided screening, triage and treatment for COVID-19 and other illnesses. To encourage its adoption, the government and the hospital publicised the platform on social media and waived fees., Discussion: From 1 February to 1 April 2020, 10557 online COVID-19 consultations were conducted for 6662 individuals; meanwhile, 32676 patients without COVID completed virtual follow-ups. We discuss that high-quality, secure, affordable and user-friendly telemedical platforms should be integrated into global healthcare systems to help decrease the transmission of the virus and protect healthcare providers from infection., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: As an innovative approach to providing web-based health care services from physical hospitals to patients at a distance, e-hospitals (ie, extended care hospitals through the internet) have been extensively developed in China. This closed health care delivery chain was developed by combining e-hospitals with physical hospitals; treatment begins with web-based consultation and registration, and then, patients are diagnosed and treated in a physical hospital. This approach is promising in its ability to improve accessibility, efficiency, and quality of health care. However, there is limited research on end users' acceptance of e-hospitals and the effectiveness of strategies aimed to prompt the adoption of e-hospitals in China., Objective: This study aimed to provide insights regarding the adoption of e-hospitals by investigating patients' willingness to use e-hospitals and analyzing the barriers and facilitators to the adoption of this technology., Methods: We used a pretested self-administered questionnaire and performed a cross-sectional analysis in 1032 patients across three hierarchical hospitals in West China from June to August 2019. Patients' sociodemographic characteristics, medical history, current disease status, proficiency with electronic devices, previous experience with web-based health services, willingness to use e-hospitals, and perceived facilitators and barriers were surveyed. Multiple significance tests were employed to examine disparities across four age groups, as well as those between patients who were willing to use e-hospitals and those who were not. Multivariate logistic regression was also performed to identify the potential predictors of willingness to use e-hospitals., Results: Overall, it was found that 65.6% (677/1032) of participants were willing to use e-hospitals. The significant predictors of willingness to use e-hospitals were employment status (P=.02), living with children (P<.001), education level (P=.046), information technology skills (P<.001), and prior experience with web-based health care services (P<.001), whereas age, income, medical insurance, and familiarity with e-hospitals were not predictors. Additionally, the prominent facilitators of e-hospitals were convenience (641/677, 94.7%) and accessibility to skilled medical experts (489/677, 72.2%). The most frequently perceived barrier varied among age groups; seniors most often reported their inability to operate technological devices as a barrier (144/166, 86.7%), whereas young participants most often reported that they avoided e-hospital services because they were accustomed to face-to-face consultation (39/52, 75%)., Conclusions: We identified the variables, facilitators, and barriers that play essential roles in the adoption of e-hospitals. Based on our findings, we suggest that efforts to increase the adoption of e-hospitals should focus on making target populations accustomed to web-based health care services while maximizing ease of use and providing assistance for technological inquiries., (©Peiyi Li, Yunmei Luo, Xuexin Yu, Jin Wen, Elizabeth Mason, Weimin Li, Mohammad S Jalali. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 11.06.2020.)

Archetypal human pluripotent stem cells (hPSC) are widely considered to be equivalent in developmental status to mouse epiblast stem cells, which correspond to pluripotent cells at a late post-implantation stage of embryogenesis. Heterogeneity within hPSC cultures complicates this interspecies comparison. Here we show that a subpopulation of archetypal hPSC enriched for high self-renewal capacity (ESR) has distinct properties relative to the bulk of the population, including a cell cycle with a very low G1 fraction and a metabolomic profile that reflects a combination of oxidative phosphorylation and glycolysis. ESR cells are pluripotent and capable of differentiation into primordial germ cell-like cells. Global DNA methylation levels in the ESR subpopulation are lower than those in mouse epiblast stem cells. Chromatin accessibility analysis revealed a unique set of open chromatin sites in ESR cells. RNA-seq at the subpopulation and single cell levels shows that, unlike mouse epiblast stem cells, the ESR subset of hPSC displays no lineage priming, and that it can be clearly distinguished from gastrulating and extraembryonic cell populations in the primate embryo. ESR hPSC correspond to an earlier stage of post-implantation development than mouse epiblast stem cells.

Background: There is widespread and some unexplained variation in induction of labour rates between hospitals. Some practice variation may stem from variability in clinical guidelines. This review aimed to identify to what extent induction of labour guidelines provide consistent recommendations in relation to reasons for, and timing of, induction of labour and ascertain whether inconsistencies can be explained by variability guideline quality., Method: We conducted a systematic search of national and international English-language guidelines published between 2008 and 2018. General induction of labour guidelines and condition-specific guidelines containing induction of labour recommendations were searched. Guidelines were reviewed and extracted independently by two reviewers. Guideline quality was assessed using the Appraisal of Guidelines for Research and Evaluation II Instrument., Findings: Forty nine guidelines of varying quality were included. Indications where guidelines had mostly consistent advice included prolonged pregnancy (induction between 41 and 42 weeks), preterm premature rupture of membranes, and term preeclampsia (induction when preeclampsia diagnosed ≥37 weeks). Guidelines were also consistent in agreeing on decreased fetal movements and oligohydramnios as valid indications for induction, although timing recommendations were absent or inconsistent. Common indications where there was little consensus on validity and/or timing of induction included gestational diabetes, fetal macrosomia, elevated maternal body mass index, and twin pregnancy., Conclusion: Substantial variation in clinical practice guidelines for indications for induction exists. As guidelines rated of similar quality presented conflicting recommendations, guideline variability was not explained by guideline quality. Guideline variability may partly account for unexplained variation in induction of labour rates., (Copyright © 2019 Australian College of Midwives. All rights reserved.)

Introduction: Randomised controlled trials have shown that internet-delivered cognitive behavioural treatment (iCBT) is an effective treatment for health anxiety, but the effectiveness of these programs in routine care has not been investigated. This study examined the effectiveness of iCBT for health anxiety symptoms in routine care settings in the community., Methods: Using an open-trial design, we investigated adherence to, and effectiveness of a 6-lesson iCBT program for health anxiety symptoms amongst individuals (n = 391, mean age 41 years, 64% female) who enrolled in the program either self-guided (n = 312) or under the supervision of community clinicians (general practitioners, psychologists and other allied health professionals) (n = 79). Primary outcome was health anxiety severity on the Short Health Anxiety Inventory (SHAI), and secondary outcomes were depression severity on the Patient Health Questionnaire 9-item (PHQ-9) (depression) and distress (Kessler-10: K-10)., Results: Adherence to the iCBT program was modest (45.6% in the clinician-supervised group, 33.0% in the unguided group), but within-subjects effect sizes were large (SHAI: g = 1.66, 95%CI: 1.45-1.88; PHQ-9: g = 1.12, 95%CI: 0.92-1.32; K-10: g = 1.35, 95%CI: 1.15-1.56)., Limitations: No control group, lack of follow-up data., Conclusions: iCBT is an effective treatment for health anxiety symptoms in routine care, but methods to increase adherence are needed to optimise benefits to participants. Randomised controlled effectiveness trials with long-term follow-up are needed., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2019. Published by Elsevier B.V.)

Background: There has been a worldwide rise in planned caesarean sections over recent decades, with significant variations in practice between hospitals and countries. Guidelines are known to influence clinical decision-making and, potentially, unwarranted clinical variation. The aim of this study was to review guidelines for recommendations in relation to the timing and indications for planned caesarean section as well as recommendations around the process of decision-making., Method: A systematic search of national and international English-language guidelines published between 2008 and 2018 was undertaken. Guidelines were reviewed, assessed in terms of quality and extracted independently by two reviewers., Findings: In total, 49 guidelines of varying quality were included. There was consistency between the guidelines in potential indications for caesarean section, although guidelines vary in terms of the level of detail. There was substantial variation in timing of birth, for example recommended timing of caesarean section for women with uncomplicated placenta praevia is between 36 and 39weeks depending on the guideline. Only 11 guidelines provided detailed guidance on shared decision-making. In general, national-level guidelines from Australia, and overseas, received higher quality ratings than regional guidelines., Conclusion: The majority of guidelines, regardless of their quality, provide very limited information to guide shared decision-making or the timing of planned caesarean section, two of the most vital aspects of guidance. National guidelines were generally of better quality than regional ones, suggesting these should be used as a template where possible and emphasis placed on improving national guidelines and minimising intra-country, regional, variability of guidelines., (Copyright © 2019 Australian College of Midwives. All rights reserved.)

Introduction: Maternal immunization (MI) with tetanus toxoid containing vaccine, is a safe and cost-effective way of preventing neonatal tetanus. Given the prospect of introducing new maternal vaccines in the near future, it is essential to identify and understand current policies, practices and unmet needs for introducing and/or scaling up MI in low-income and middle-income countries (LMICs)., Methods and Analysis: The Maternal Immunization and Antenatal Care Situation Analysis (MIACSA) is a mixed methods, cross-sectional study that will collect data in four phases: (1) a review of global databases for selected health indicators in 136 LMICs; (2) a structured online survey directed at Maternal, Newborn and Child Health and Expanded Programme on Immunization focal points in all 136 LMICs; (3) semistructured telephone interviews of 30 selected LMICs and (4) 10 week-long country visits, including key informant interviews, health facility visits and focus group discussions. The principal analyses will assess correlations between the various aspects of MI delivery strategies and proxy measures of health systems performance related to vaccine-preventable disease control. The primary outcome will be a typology of existing MI delivery models, and secondary outcomes will include country profiles of child and maternal health indicators, and a MI gaps and needs analysis., Ethics and Dissemination: The protocol was approved by the WHO Ethics Review Committee (ERC.0002908). The results will be made available in a project report and submitted for publication in peer-reviewed journals that will be shared broadly among global health decision-makers, researchers, product developers and country-level stakeholders., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

A subset of patients with gastric cancer have mutations in genes that participate in or regulate Wnt signaling at the level of ligand (Wnt) receptor (Fzd) binding. Moreover, increased Fzd expression is associated with poor clinical outcome. Despite these findings, there are no in vivo studies investigating the potential of targeting Wnt receptors for treating gastric cancer, and the specific Wnt receptor transmitting oncogenic Wnt signaling in gastric cancer is unknown. Here, we use inhibitors of Wnt/Fzd (OMP-18R5/vantictumab) and conditional gene deletion to test the therapeutic potential of targeting Wnt signaling in preclinical models of intestinal-type gastric cancer and ex vivo organoid cultures. Pharmacologic targeting of Fzd inhibited the growth of gastric adenomas in vivo . We identified Fzd7 to be the predominant Wnt receptor responsible for transmitting Wnt signaling in human gastric cancer cells and mouse models of gastric cancer, whereby Fzd7-deficient cells were retained in gastric adenomas but were unable to respond to Wnt signals and consequently failed to proliferate. Genetic deletion of Fzd7 or treatment with vantictumab was sufficient to inhibit the growth of gastric adenomas with or without mutations to Apc . Vantictumab is currently in phase Ib clinical trials for advanced pancreatic, lung, and breast cancer. Our data extend the scope of patients that may benefit from this therapeutic approach as we demonstrate that this drug will be effective in treating patients with gastric cancer regardless of APC mutation status. SIGNIFICANCE: The Wnt receptor Fzd7 plays an essential role in gastric tumorigenesis irrespective of Apc mutation status, therefore targeting Wnt/Fzd7 may be of therapeutic benefit to patients with gastric cancer., (©2019 American Association for Cancer Research.)

Introduction: The American Academy of Pediatrics recommends that adolescents be screened for mental health concerns and receive anticipatory guidance on stress management strategies., Methods: Eighty-six participants (50 participants in the intervention group; 36 participants in the control group) participated in the study. Intervention group participants received training in diaphragmatic breathing, progressive muscle relaxation, and use of no-cost/low-cost exercise options. Biofeedback was used to guide relaxation. Subjective distress and heart rate variability was measured before and after the intervention., Results: After the intervention, decreased levels of perceived stress and increased heart rate variability were reported compared with the control group., Discussion: This study show that an integrated care model in a primary care setting is feasible and effective at improving stress management., (Copyright © 2018 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the steps taken and results obtained by a rural primary care practice to effectively implement opioid prescribing guidelines., Patients and Methods: Between December 1, 2014, and May 30, 2017, a quality improvement project was undertaken. Elements included prescribing registries, a nurse coordinator, and an Opioid Use Review Panel. Clinic workflow was redesigned to more consistently incorporate these and other guideline recommendations into practice. The effect on opioid prescribing was measured as well as patient outcomes., Results: There were 462 patients meeting inclusion criteria before implementation. At the conclusion, 16 patients (3%) had died, 9 patients (2%) were no longer seeing clinicians participating in the project, and 2 patients (0.4%) had transitioned to hospice or long-term care facilities. Of the remaining 435 patients, 96 (22.1%; 95% CI, 18.4-26.2) had decreased prescribing below the threshold for inclusion or were no longer receiving opioid prescriptions. Originally, 64 patients (13.9%; 95% CI, 11.0-17.3) were using average daily doses equal to or greater than 90 morphine milligram equivalents. After implementation, 54 of 435 patients (12.4%; 95% CI, 9.6-15.8) were still using equal to or greater than 90 morphine milligram equivalents per day after accounting for death or loss to follow-up., Conclusion: A change in clinic process to implement guidelines for prescribing of chronic opioid therapy was completed. It was associated with a decrease in the number of patients using chronic opioid therapy, primarily at lower doses. This was accomplished in a rural practice with very limited resources in pain medicine, psychiatry, and addiction medicine.

Pregnant women and their babies are among the populations most vulnerable to untoward health outcomes. Yet current standards for evaluating health interventions cannot be met during pregnancy because of lack of adequate evidence. The situation is even more concerning in low-income and middle-income countries, where the need for effective interventions is the greatest. Meeting the Sustainable Development Goals for health will require strengthened attention to maternal and child health. In this paper we examine ongoing initiatives aimed at improving the assessment of maternal interventions. We review current methodologies to monitor outcomes of maternal interventions and identify where harmonisation is needed. Based on this analysis we identify settings where different minimal data sets should be considered taking into consideration the clinical realities. Stronger coordination mechanisms and a roadmap to support harmonised monitoring of maternal interventions across programmes and partners, working on improving pregnancy and early childhood health events, will greatly enhance ability to generate evidence-based policies., Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: All authors have completed the Unified Competing Interest form. We have read and understood BMJ policy on declaration of interests and declare no conflicts of interest. The authors alone are responsible for the views expressed in this article, which does not necessarily represent the views, decisions, or policies of the institutions with which the authors are affiliated.

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

The pathogenesis of many retinal degenerations, such as age-related macular degeneration (AMD), is punctuated by an ill-defined network of sterile inflammatory responses. The delineation of innate and adaptive immune milieu among the broad leukocyte infiltrate, and the gene networks, which construct these responses, are poorly described in the eye. Using photo-oxidative damage in a rodent model of subretinal inflammation, we employed a novel RNA-sequencing framework to map the global gene network signature of retinal leukocytes. This revealed a previously uncharted interplay of adaptive immunity during subretinal inflammation, including prolonged enrichment of myeloid and lymphocyte migration, antigen presentation, and the alternative arm of the complement cascade involving Factor B . We demonstrate Factor B -deficient mice are protected against macrophage infiltration and subretinal inflammation. Suppressing the drivers of retinal leukocyte proliferation, or their capacity to elicit complement responses, may help preserve retinal structure and function during sterile inflammation in diseases such as AMD.

Thirty patients aged 11 to 21 years presenting in an adolescent medicine clinic received a one-time stress management intervention. The intervention included psychoeducation on the effect stress has on the body and the positive benefits of exercise, diaphragmatic breathing, and progressive muscle relaxation. The intervention also included use of a biofeedback game to aid in relaxation. Analyses revealed an association between higher levels of internalizing symptoms and perceived stress. A clinically significant decrease in subjective distress was endorsed at post-intervention. Ninety-three percent of participants reported that the intervention was helpful and that they had the requisite knowledge to practice stress management strategies outside of the clinic. At a one-week follow-up, of the 23 participants who were able to be reached, 22 wanted to participate in additional training. Findings suggest that a one-time stress management intervention can be beneficial for patients and easily incorporated within a primary care setting.

Background: Hip osteoarthritis (OA) is common, painful, and disabling. Physical therapists have an important role in managing patients with hip OA; however, little is known about their current management approach and whether it aligns with clinical guideline recommendations., Objective: The objective of this study is to describe United Kingdom (UK) physical therapists' current management of patients with hip OA and to determine whether it aligns with clinical guidelines., Design: The design is a cross-section questionnaire., Methods: A questionnaire was mailed to 3126 physical therapists in the UK that explored physical therapists' self-reported management of a patient with hip OA using a case vignette and clinical management questions., Results: The response rate was 52.7% (n = 1646). In total, 1148 (69.7%) physical therapists had treated a patient with hip OA in the last 6 months and were included in the analyses. A treatment package was commonly provided incorporating advice, exercise (strength training 95.9%; general physical activity 85.4%), and other nonpharmacological modalities, predominantly manual therapy (69.6%), and gait retraining (66.4%). There were some differences in reported management between physical therapists based in the National Health Service (NHS) and non-NHS-based physical therapists, including fewer treatment sessions being provided by NHS-based therapists., Limitations: Limitations include the potential for nonresponder bias and, in clinical practice, physical therapists may manage patients with hip OA differently., Conclusion: UK-based physical therapists commonly provide a package of care for patients with hip OA that is broadly in line with current clinical guidelines, including advice, exercise, and other nonpharmacological treatments. There were some differences in clinical practice between NHS and non-NHS-based physical therapists, but whether these differences impact on clinical outcomes remains unknown.

Objective: To examine the efficacy of an Internet-delivered cognitive-behavioral therapy (iCBT) program for health anxiety compared to an active psychoeducation control group., Method: Individuals (N = 86, mean age: 30 years, 87% female) with a Diagnostic and Statistical Manual of Mental Disorders (5th ed.) diagnosis of illness anxiety disorder or somatic symptom disorder with health anxiety were randomized to either a 6-lesson clinician-guided iCBT program for health anxiety (n = 45) or an active control group who received anxiety psychoeducation, clinical support, and monitoring (control, n = 41) over a 12-week period., Results: Both groups experienced significant improvements between baseline and posttreatment on self-report measures of health anxiety, depression, general anxiety, and functional impairment. Intention-to-treat analyses indicated that the iCBT group experienced greater improvements in health anxiety on the Short Health Anxiety Inventory (SHAI) compared to controls (between-groups effect size = 1.39, 95% confidence interval [0.87, 1.93]), and a greater proportion of the iCBT group showed clinically reliable change on the SHAI (84% vs. 34% in the control group). Similarly, the iCBT group outperformed the control group on secondary measures of depression, generalized anxiety, functional impairment, maladaptive cognitions, body hypervigilance, safety behaviors and avoidance, and intolerance of uncertainty. Gains were maintained at 3-month follow-up in the iCBT group., Conclusion: iCBT for health anxiety is more effective than psychoeducation, clinical support, and monitoring, and presents an efficacious and accessible treatment option for people with health anxiety. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Clinician-guided internet-delivered cognitive behavioral therapy (iCBT) is an effective treatment for depression and anxiety disorders. However, few studies have examined the effectiveness of completely unguided iCBT. The current research investigated adherence to, and the effects of two brief unguided iCBT programs on depression and anxiety symptom severity, and psychological distress. Study 1 evaluated a four-lesson transdiagnostic iCBT program for anxiety and depression ( N  = 927). Study 2 then evaluated a three-lesson version of the same program ( N  = 5107) in order to determine whether reducing the duration of treatment would influence adherence and treatment effects. Cross-tabulations and independent t -tests were used to examine the extent to which users adhered and remitted with treatment. Linear mixed models were used to evaluate the effects of treatment in the entire sample, and stratified by gender and completer-type (e.g., users who completed some but not all lessons vs. those who completed all lessons of treatment). Among those who began treatment, 13.83% completed all four lessons in Study 1. Shortening the course to three lessons did not improve adherence (e.g., 13.11% in Study 2). In both studies, users, on average, experienced moderate to large effect size reductions in anxiety and depressive symptom severity, as well as psychological distress. This pattern of results was robust across gender and for those who did and did not complete treatment. Approximately two-thirds of those who completed treatment experienced remission. These data show that unguided iCBT programs, which have the capacity to attract large numbers of individuals with clinically significant symptoms of depression and anxiety, and psychological distress, can produce significant improvements in wellbeing.

Cognitive behavioural therapy (CBT) is an effective treatment for health anxiety, but more research is needed to evaluate accessible, low cost ways of delivering CBT. Internet CBT may be effective, but there are no iCBT programs available outside of Sweden. We developed the first English-language clinician-guided iCBT program for health anxiety and conducted an open pilot trial ( n  = 16) to examine its acceptability, and impact on health anxiety and comorbidity, disability, and the cognitive and behavioural factors thought to maintain the disorder (e.g., catastrophising, hypervigilance). 13/16 participants completed the program (81% adherence). We found large and significant reductions in health anxiety, depression, distress, anxiety and disability ( g's  > 1.0), dysfunctional cognitions, behaviours and body vigilance between pre- and post-treatment, which were maintained at 3-month follow-up. The results provide preliminary support for the use of iCBT for health anxiety. Randomised controlled efficacy trials are now needed to evaluate this program.

Mesenchymal stromal cells (MSC) are widely used for the study of mesenchymal tissue repair, and increasingly adopted for cell therapy, despite the lack of consensus on the identity of these cells. In part this is due to the lack of specificity of MSC markers. Distinguishing MSC from other stromal cells such as fibroblasts is particularly difficult using standard analysis of surface proteins, and there is an urgent need for improved classification approaches. Transcriptome profiling is commonly used to describe and compare different cell types; however, efforts to identify specific markers of rare cellular subsets may be confounded by the small sample sizes of most studies. Consequently, it is difficult to derive reproducible, and therefore useful markers. We addressed the question of MSC classification with a large integrative analysis of many public MSC datasets. We derived a sparse classifier (The Rohart MSC test) that accurately distinguished MSC from non-MSC samples with >97% accuracy on an internal training set of 635 samples from 41 studies derived on 10 different microarray platforms. The classifier was validated on an external test set of 1,291 samples from 65 studies derived on 15 different platforms, with >95% accuracy. The genes that contribute to the MSC classifier formed a protein-interaction network that included known MSC markers. Further evidence of the relevance of this new MSC panel came from the high number of Mendelian disorders associated with mutations in more than 65% of the network. These result in mesenchymal defects, particularly impacting on skeletal growth and function. The Rohart MSC test is a simple in silico test that accurately discriminates MSC from fibroblasts, other adult stem/progenitor cell types or differentiated stromal cells. It has been implemented in the www.stemformatics.org resource, to assist researchers wishing to benchmark their own MSC datasets or data from the public domain. The code is available from the CRAN repository and all data used to generate the MSC test is available to download via the Gene Expression Omnibus or the Stemformatics resource.

Global initiatives such as the Millennium Development Goals have led to major improvements in the health of women and children, and significant reductions in childhood mortality. Worldwide, maternal mortality has decreased by 45% and under-five mortality has fallen by over 50% over the past two decades [1]. However, improvements have not been achieved evenly across all ages; since 1990, under-five mortality has declined by ∼5% annually, but the average decrease in neonatal mortality is only ∼3% per year. Against this background, the Bill and Melinda Gates Foundation (BMGF) convened a meeting in Berlin on January 29-30, 2015 of global health stakeholders, representing funders, academia, regulatory agencies, non-governmental organizations, vaccine manufacturers, and Ministries of Health from Africa and Asia. The topic of discussion was the potential of maternal immunization (MI) to achieve further improvements in under-five morbidity and mortality rates in children, and particularly neonates and young infants, through targeting infectious diseases that are not preventable by other interventions in these age groups. The meeting focused on effective and appropriately priced MI vaccines against influenza, pertussis, and tetanus, as well as against respiratory syncytial virus, and the group B Streptococcus, for which no licensed vaccines currently exist. The primary goals of the BMGF 2015 convening were to bring together the global stakeholders in vaccine development, policy and delivery together with the Maternal, Newborn and Child Health (MNCH) community, to get recognition that MI is a strategy shared between these groups and so encourage increased collaboration, and obtain alignment on the next steps toward achieving a significant health impact through implementation of a MI program., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)