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ABSTRACT: Bovine viral diarrhea (BVD) is endemic in the United Kingdom and causes major economic losses. Control is largely voluntary for individual farmers and is likely to be influenced by psychosocial factors, such as altruism, trust, and psychological proximity (feeling close) to relevant “others,” such as farmers, veterinarians, the government, and their cows. These psychosocial factors (factors with both psychological and social aspects) are important determinants of how people make decisions related to their own health, many of which have not been studied in the context of infectious disease control by farmers. Farmer psychosocial profiles were investigated using multiple validated measures in an observational survey of 475 UK cattle farmers using the capability, opportunity, motivation-behavior (COM-B) framework. Farmers were clustered by their BVD control practices using latent class analysis. Farmers were split into 5 BVD control behavior classes, which were tested for associations with the psychosocial and COM-B factors using multinomial logistic regression, with doing nothing as the baseline class. Farmers who were controlling disease both for themselves and others were more likely to do something to control BVD (e.g., test, vaccinate). Farmers who did not trust other farmers, had high psychological capability (knowledge and understanding of how to control disease), and had high physical opportunity (time and money to control disease) were more likely to have a closed, separate herd and test. Farmers who did not trust other farmers were also more likely to undertake many prevention strategies with an open herd. Farmers with high automatic motivation (habits and emotions) and reflective motivation (decisions and goals) were more likely to vaccinate and test, alone or in combination with other controls. Farmers with high psychological proximity (feeling of closeness) to their veterinarian were more likely to undertake many prevention strategies in an open herd. Farmers with high psychological proximity to dairy farmers and low psychological proximity to beef farmers were more likely to keep their herd closed and separate and test or vaccinate and test. Farmers who had a lot of trust in other farmers and invested in them, rather than keeping everything for themselves, were more likely to be careful introducing new stock and test. In conclusion, farmer psychosocial factors were associated with strategies for BVD control in UK cattle farmers. Psychological proximity to veterinarians was a novel factor associated with proactive BVD control and was more important than the more extensively investigated trust. These findings highlight the importance of a close veterinarian-farmer relationship and are important for promoting effective BVD control by farmers, which has implications for successful nationwide BVD control and eradication schemes.

Seafood is the world’s most traded food commodity, and the international trade in seafood is promoted as a development strategy in low-income coastal communities across the globe. However, the seafood trade can drive negative social and environmental impacts in fishing communities, and whether the benefits of trade actually reach fishers is a subject of ongoing scholarship. Furthermore, scholars and policymakers have tended to treat fishing communities as homogeneous, assuming that trade policies will impact all members equally. Yet individual community members have different roles, statuses, and entitlements according to their intersecting identities, meaning that different fishers will be differently impacted by the seafood trade. In particular, women occupy different positions than men in seafood value chains and in fishing communities. There are also important within-group differences among men and among women depending on their nationality, marital status, and other identity markers. Through 205 surveys, 54 interviews, and ethnographic field methods conducted in fifteen rural Palauan fishing communities between November 2019 and March 2020, this case study of the sea cucumber trade in Palau brings together theories of gender, intersectionality, and access to answer the question, “How are the harms and benefits of the seafood trade distributed in fishing communities?” In this case, men benefited more than women from the export of sea cucumbers by leveraging access to technology; knowledge; and authority, and the trade depleted resources relied on primarily by women for their food security and livelihoods. An intersectional analysis revealed that marital status and nationality determined access among women, with married women having greater access than unmarried women and immigrant women having greater access than immigrant men, demonstrating the importance of intersectionality as an analytical tool.

Cassava (Manihot esculenta Crantz.) has been a vital staple and food security crop in Tanzania for several centuries, and it is likely that its resilience will play a key role in mitigating livelihood insecurities arising from climate change. The sector is dominated by smallholder farmers growing traditional landrace varieties. A recent surge in virus diseases and awareness in the commercial potential of cassava has prompted a drive to disseminate improved varieties in the country. These factors however also threaten the existence of landraces and associated farmer knowledge. It is important that the landraces are conserved and utilized as the adaptive gene complexes they harbor can drive breeding for improved varieties that meet agro-ecological adaptation as well as farmer and consumer needs, thereby improving adoption rates. Here we report on cassava germplasm collection missions and documentation of farmer knowledge in seven zones of Tanzania. A total of 277 unique landraces are identified through high-density genotyping. The large number of landraces is attributable to a mixed clonal/sexual reproductive system in which the soil seed bank and incorporation of seedlings plays an important role. A striking divergence in genetic relationships between the coastal regions and western regions is evident and explained by (i) independent introductions of cassava into the country, (ii) adaptation to prevailing agro-ecological conditions and (iii) farmer selections according to the intended use or market demands. The main uses of cassava with different product profiles are evident, including fresh consumption, flour production, dual purpose incorporating both these uses and longer-term food security. Each of these products have different trait requirements. Individual landraces were not widely distributed across the country with limited farmer-to-farmer diffusion with implications for seed systems.

BACKGROUND Surgery remains the frontline therapy for patients with localized clear cell renal cell carcinoma (ccRCC); however, 20%–40% recur. Angiogenesis inhibitors have improved survival in metastatic patients and may result in responses in the neoadjuvant setting. The impact of these agents on the tumor genetic heterogeneity or the immune milieu is largely unknown. This phase II study was designed to evaluate safety, response, and effect on tumor tissue of neoadjuvant pazopanib.METHODS ccRCC patients with localized disease received pazopanib (800 mg daily; median 8 weeks), followed by nephrectomy. Five tumors were examined for mutations by whole exome sequencing from samples collected before therapy and at nephrectomy. These samples underwent RNA sequencing; 17 samples were available for posttreatment assessment.RESULTS Twenty-one patients were enrolled. The overall response rate was 8 of 21 (38%). No patients with progressive disease. At 1-year, response-free survival and overall survival was 83% and 89%, respectively. The most frequent grade 3 toxicity was hypertension (33%, 7 of 21). Sequencing revealed strong concordance between pre- and posttreatment samples within individual tumors, suggesting tumors harbor stable core profiles. However, a reduction in private mutations followed treatment, suggesting a selective process favoring enrichment of driver mutations.CONCLUSION Neoadjuvant pazopanib is safe and active in ccRCC. Future genomic analyses may enable the segregation of driver and passenger mutations. Furthermore, tumor infiltrating immune cells persist during therapy, suggesting that pazopanib can be combined with immune checkpoint inhibitors without dampening the immune response.FUNDING Support was provided by Novartis and GlaxoSmithKline as part of an investigator-initiated study.

In Sub-Saharan Africa cassava (Manihot esculenta Crantz) is one of the most important food crops where more than 40% of the population relies on it as their staple carbohydrate source. Biotic constraints such as viral diseases, mainly Cassava Mosaic Disease (CMD) and Cassava Brown Streak Disease (CBSD), and arthropod pests, particularly Cassava Green Mite (CGM), are major constraints to the realization of cassava's full production potential in Africa. To address these problems, we aimed to map the quantitative trait loci (QTL) associated with resistance to CBSD foliar and root necrosis symptoms, foliar CMD and CGM symptoms in a full-sib mapping population derived from the genotypes AR40-6 and Albert. A high-density linkage map was constructed with 2,125 SNP markers using a genotyping-by-sequencing approach. For phenotyping, clonal evaluation trials were conducted with 120 F1 individuals for two consecutive field seasons using an alpha-lattice design at Chambezi and Naliendele, Tanzania. Previously identified QTL for resistance to CBSD foliar symptoms were corroborated, and a new putative QTL for CBSD root necrosis identified (qCBSDRNc14AR) from AR40-6. Two QTL were identified within the region of the previously recognized CMD2 locus from this population in which both parents are thought to possess the CMD2 locus. Interestingly, a minor but consistent QTL, qCGM18AR, for CGM resistance at 3 months after planting stage was also detected and co-localized with a previously identified SSR marker, NS346, linked with CGM resistance. Markers underlying these QTL may be used to increase efficiencies in cassava breeding programs.

Architectural and personal influences on neighboring behaviors were studied in a residential neighborhood using both qualitative informal conversations, and systematic recording of activity in the neighborhood׳s social space. This dual approach produced new insights into neighboring behaviors and social networks. It was discovered that the residents who participated in the social space were only a portion of the resident population. There was an additional neighborhood-based network whose neighboring was not conducted in the social space; instead it was maintained by direct house-to-house contact. It was also found that some individuals chose not to participate in any neighborhood social network. The social space was an effective neighboring venue for those residents who chose to use it, but did not attract commingling of groups. Contrary to an assumption in previous neighboring research, there are social groups which develop and maintain themselves without participation in a social space.

To describe the presence and distribution of tickborne bacteria and their vectors in Texas, USA, we screened ticks collected from humans during 2008–2014 for Rickettsia, Borrelia, and Ehrlichia spp. Thirteen tick species were identified, and 23% of ticks carried bacterial DNA from at least 1 of the 3 genera tested.

Although numerous studies of diversity have been conducted in cassava, there is no comprehensive assessment of global genetic diversity. Here we draw on previous studies and breeders' knowledge to select diversity sets from the International Institute of Tropical Agriculture (IITA) and the International Center for Tropical Agriculture (CIAT) genebanks and breeders' germplasm, as well as elite germplasm and landraces from eastern, southern and central (ESC) Africa to make a global assessment of diversity in cassava, using a SNP based GoldenGate (Illumina Inc.) assay. A synthesis of results from genetic distance and ADMIXTURE analysis essentially revealed four populations (i) South American germplasm characterised by relatively higher genetic diversity with hypothetical ancestral founder genotypes from Brazil, (ii) a smaller group of African introduction germplasm which is more distantly related to all other germplasm, (iii) West Africa germplasm dominated by IITA breeding lines, containing sources of cassava mosaic disease resistance, and IITA genebank accessions from West Africa, both characterised by slightly lower diversity, and (iv) a less cohesive group of African germplasm, termed 'Other', with moderate levels of diversity and a majority of germplasm from ESC Africa. This study highlights opportunities for heterosis breeding, purging of duplicates in genebanks and the need for conservation of ESC Africa landraces.

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Previous work suggests that to restore postural stability for individuals with lower-limb amputation, ankle-foot prostheses should be designed with a flat effective rocker shape for standing. However, most commercially available ankle-foot prostheses are designed with a curved effective rocker shape for walking. To address the demands of both standing and walking, we designed a novel bimodal ankle-foot prosthesis that can accommodate both functional modes using a rigid foot plate and an ankle that can lock and unlock. The primary objective of this study was to determine if the bimodal ankle-foot system could improve various aspects of standing balance (static, dynamic, and functional) and mobility in a group of Veterans with lower-limb amputation (n = 18). Standing balance was assessed while subjects completed a series of tests on a NeuroCom Clinical Research System (NeuroCom, a Division of Natus, Clackamas, OR), including a Sensory Organization Test, a Limits of Stability Test, and a modified Motor Control Test. Few statistically significant differences were observed between the locked and unlocked ankle conditions while subjects completed these tests. However, in the absence of visual feedback, the locked bimodal ankle appeared to improve static balance in a group of experienced lower-limb prosthesis users whose PLUS-M mobility rating was higher than approximately 73% of the sample population used to develop the PLUS-M survey. Given the statistically significant increase in mean equilibrium scores between the unlocked and locked conditions (p = 0.004), future testing of this system should focus on new amputees and lower mobility users (e.g., Medicare Functional Classification Level K1 and K2 prosthesis users). Furthermore, commercial implementation of the bimodal ankle-foot system should include a robust control system that can automatically switch between modes based on the user's activity.

We describe laboratory-confirmed influenza A pandemic (H1N1) 2009 in 17 hospitalized recipients of a hematopoietic stem cell transplant (HSCT) (8 allogeneic) and in 15 patients with malignancy treated at 6 Australian tertiary centers during winter 2009. Ten (31.3%) patients were admitted to intensive care, and 9 of them were HSCT recipients. All recipients of allogeneic HSCT with infection 4 days of oseltamivir therapy. Three of these 4 patients were critically ill. Oseltamivir resistance in 4 (13.3%) of 30 patients who were administered oseltamivir highlights the need for ongoing surveillance of such resistance and further research on optimal antiviral therapy in the immunocompromised.

Vascularization of the placenta is a critical developmental process that ensures fetal viability. Although the vascular health of the placenta affects both maternal and fetal well being, relatively little is known about the early stages of placental vascular development. The ubiquitin ligase Ankyrin repeat, SOCS box-containing 4 (ASB4) promotes embryonic stem cell differentiation to vascular lineages and is highly expressed early in placental development. The transcriptional regulator Inhibitor of DNA binding 2 (ID2) negatively regulates vascular differentiation during development and is a target of many ubiquitin ligases. Due to their overlapping spatiotemporal expression pattern in the placenta and contrasting effects on vascular differentiation, we investigated whether ASB4 regulates ID2 through its ligase activity in the placenta and whether this activity mediates vascular differentiation. In mouse placentas, ASB4 expression is restricted to a subset of cells that express both stem cell and endothelial markers. Placentas that lack Asb4 display immature vascular patterning and retain expression of placental progenitor markers, including ID2 expression. Using JAR placental cells, we determined that ASB4 ubiquitinates and represses ID2 expression in a proteasome-dependent fashion. Expression of ASB4 in JAR cells and primary isolated trophoblast stem cells promotes the expression of differentiation markers. In functional endothelial co-culture assays, JAR cells ectopically expressing ASB4 increased endothelial cell turnover and stabilized endothelial tube formation, both of which are hallmarks of vascular differentiation within the placenta. Co-transfection of a degradation-resistant Id2 mutant with Asb4 inhibits both differentiation and functional responses. Lastly, deletion of Asb4 in mice induces a pathology that phenocopies human pre-eclampsia, including hypertension and proteinuria in late-stage pregnant females. These results indicate that ASB4 mediates vascular differentiation in the placenta via its degradation of ID2.

Abstract Background Recruitment for clinical trials and large-scale studies is challenging, especially for patients with complex conditions like chronic pain. Email recruitment has the potential to increase efficiency, to reduce costs, and to improve access for underrepresented patient populations. The objective of this study was to examine the effectiveness, efficiency, and equitability of email versus postal mail recruitment for the Learning to Apply Mindfulness to Pain (LAMP) study, a three-site clinical trial of mindfulness-based interventions for chronic pain. Methods Patients with chronic pain diagnoses were recruited from three United States Department of Veterans Affairs (VA) facilities using the VA electronic health record (EHR). Recruitment materials were sent using either postal mail (n = 7986) or email (n = 19,333). Patients in the email recruitment group were also mailed introductory postcards before any emails. Mailing addresses and email addresses were obtained from the EHR. Effectiveness was measured by the response rate of patients who logged into the secure LAMP study website. Efficiency was measured by the number of days from when the recruitment materials were sent to when patients logged into the LAMP portal as well as the estimated costs of each recruitment approach. To assess equitability, we examined whether email recruitment was less effective for underrepresented populations, based on demographic information from the EHR. Results Effectiveness—unadjusted response rates were greater for email versus postal-mail recruitment (18.9% versus 6.3%), and adjusted response rates were over three times greater for email recruitment (RR = 3.5, 95% CI 3.1–3.8) based on a multivariable analysis controlling for age, gender, race, ethnicity, rurality, and site. Efficiency—email recruitment had a significantly lower mean response time (1 day versus 8 days) and a lower cost. Equity—email recruitment led to higher response rates for all subpopulations, including older, non-White, Hispanic, rural, and female Veterans. Conclusions Email recruitment is an effective, efficient, and equitable way to recruit VA patients to large-scale, chronic pain clinical trials. Trial registration Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.

Background: Although studies have documented higher rates of chronic pain among women Veterans compared to men Veterans, there remains a lack of comprehensive information about potential contributors to these disparities. Materials and Methods: This study examined gender differences in chronic pain and its contributors among 419 men and 392 women Veterans, enrolled in a mindfulness trial for chronic pain. We conducted descriptive analyses summarizing distributions of baseline measures, obtained by survey and through the electronic health record. Comparisons between genders were conducted using chi-square tests for categorical variables and t-tests for continuous measures. Results: Compared to men, women Veterans were more likely to have chronic overlapping pain conditions and had higher levels of pain interference and intensity. Women had higher prevalence of psychiatric and sleep disorder diagnoses, greater levels of depression, anxiety, post-traumatic stress disorder, fatigue, sleep disturbance, stress and pain catastrophizing, and lower levels of pain self-efficacy and participation in social roles and activities. However, women were less likely to smoke or have a substance abuse disorder and used more nonpharmacological pain treatment modalities. Conclusion: Among Veterans seeking treatment for chronic pain, women differed from men in their type of pain, had greater pain intensity and interference, and had greater prevalence and higher levels of many known biopsychosocial contributors to pain. Results point to the need for pain treatment that addresses the comprehensive needs of women Veterans. Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.

BackgroundPost-traumatic stress disorder (PTSD) and chronic pain are highly prevalent comorbid conditions. Veterans dually burdened by PTSD and chronic pain experience more severe outcomes compared to either disorder alone. Few studies have enrolled enough women Veterans to test gender differences in pain outcomes [catastrophizing, intensity, interference] by the severity of PTSD symptoms.AimExamine gender differences in the association between PTSD symptoms and pain outcomes among Veterans enrolled in a chronic pain clinical trial.MethodsParticipants were 421 men and 386 women Veterans with chronic pain who provided complete data on PTSD symptoms and pain outcomes. We used hierarchical linear regression models to examine gender differences in pain outcomes by PTSD symptoms.ResultsAdjusted multivariable models indicated that PTSD symptoms were associated with higher levels of pain catastrophizing (0.57, 95% CI [0.51, 0.63]), pain intensity (0.30, 95% CI [0.24, 0.37]), and pain interference (0.46, 95% CI [0.39, 0.52]). No evidence suggesting gender differences in this association were found in either the crude or adjusted models (all interaction p-valuesConclusionThese findings may reflect the underlying mutual maintenance of these conditions whereby the sensation of pain could trigger PTSD symptoms, particularly if the trauma and pain are associated with the same event. Clinical implications and opportunities testing relevant treatments that may benefit both chronic pain and PTSD are discussed.

Cassava (Manihot esculenta Crantz) is a food and industrial storage root crop with substantial potential to contribute to managing risk associated with climate change due to its inherent resilience and in providing a biodegradable option in manufacturing. In Africa, cassava production is challenged by two viral diseases, cassava brown streak disease (CBSD) and cassava mosaic disease. Here we detect quantitative trait loci (QTL) associated with CBSD in a biparental mapping population of a Tanzanian landrace, Nachinyaya and AR37-80, phenotyped in two locations over three years. The purpose was to use the information to ultimately facilitate either marker-assisted selection or adjust weightings in genomic selection to increase the efficiency of breeding. Results from this study were considered in relation to those from four other biparental populations, of similar genetic backgrounds, that were phenotyped and genotyped simultaneously. Further, we investigated the co-localization of QTL for CBSD resistance across populations and the genetic relationships of parents based on whole genome sequence information. Two QTL on chromosome 4 for resistance to CBSD foliar symptoms and one on each of chromosomes 11 and 18 for root necrosis were of interest. Of significance within the candidate genes underlying the QTL on chromosome 4 are Phenylalanine ammonia-lyase (PAL) and Cinnamoyl-CoA reductase (CCR) genes and three PEPR1-related kinases associated with the lignin pathway. In addition, a CCR gene was also underlying the root necrosis-resistant QTL on chromosome 11. Upregulation of key genes in the cassava lignification pathway from an earlier transcriptome study, including PAL and CCR, in a CBSD-resistant landrace compared to a susceptible landrace suggests a higher level of basal lignin deposition in the CBSD-resistant landrace. Earlier RNAscope®in situ hybridisation imaging experiments demonstrate that cassava brown streak virus (CBSV) is restricted to phloem vessels in CBSV-resistant varieties, and phloem unloading for replication in mesophyll cells is prevented. The results provide evidence for the involvement of the lignin pathway. In addition, five eukaryotic initiation factor (eIF) genes associated with plant virus resistance were found within the priority QTL regions.

Abstract Background Multisite practical clinical trials evaluate treatments in real-world practice. A multisite randomized Veterans Health Administration (VHA) cooperative study (CSP#555) published in 2011 compared the first long-acting injectable (LAI) second-generation antipsychotic (SGA), Risperidone Consta®, in veterans with a diagnosis of schizophrenia or schizoaffective disorder, to oral antipsychotics, with unexpected null results for effectiveness and cost-effectiveness. Whether null results of this type could change VHA practice has not been studied. Methods A longitudinal observational analysis was used to evaluate the impact of the trial findings on VHA clinical practices. National administrative data compared new starts on LAI risperidone during the 4 years before the publication of CSP#555 in 2011 to new starts on LAI risperidone during the 4 years after. Results Among 119,565 Veterans with the indicated diagnoses treated with antipsychotics from 2007 to 2015, the number and proportion of new starts on LAI risperidone declined significantly following the study publication, as did the total number of annual users and drug expenditures. However, data from 2007 to 2010 showed the decline in new starts actually preceded the publication of CSP#555. This change was likely explained by the increase in new starts, total use, and expenditures on a newer medicine, LAI paliperidone, a 4-week LAI treatment, in the 2 years prior to the publication of CSP#555. Conclusions The declining use of LAI risperidone likely primarily reflects the substitution of a longer-acting LAI SGA, paliperidone, that came to market 2 years before the study publication, a substitution that may have been reinforced by null CSP#555 study results for LAI risperidone.

BackgroundWheelchair users with a spinal cord injury (SCI) are at a high risk for developing pressure injuries (PIs). Performing weight shifts is a primary method of pressure management for PI prevention; however, individuals with SCI may lack confidence in their abilities to perform adequate pressure relief due to their lack of sensation. Real-time seat interface pressure mapping feedback may provide partial substitution for sensory feedback such that an individual’s confidence is improved. ObjectiveWe aim to examine how confidence for pressure management by wheelchair users with SCI was impacted by providing access to real-time, on-demand seat interface pressure mapping feedback. MethodsAdults with SCI (N=23) completed self-efficacy questions addressing confidence around 4 factors related to performing weight shifts in this longitudinal, repeated-measures study. We evaluated the impact of providing standard PI prevention education and access to live pressure map feedback on confidence levels for performing weight shifts. ResultsAccess to live pressure map feedback while learning how to perform weight shifts resulted in significantly higher confidence about moving far enough to relieve pressure at high-risk areas. Confidence for adhering to the recommended weight shift frequency and duration was not significantly impacted by in-clinic education or use of pressure map feedback. Confidence that performing weight shifts reduces PI risk increased most following education, with slight additional increase when pressure map feedback was added. ConclusionsAccess to live pressure mapping feedback improves confidence about performing weight shifts that relieve pressure when provided in the clinical setting and demonstrates potential for the same in the home. This preliminary exploration of a smartphone-based pressure mapping intervention highlights the value of access to continuous pressure mapping feedback to improve awareness and confidence for managing pressure. Trial RegistrationClinicalTrials.gov NCT03987243; https://clinicaltrials.gov/study/NCT03987243

Abstract Background With the advent of COVID-19, many healthcare workers (HWs) in Australia requested access to powered air purifying respirators (PAPR) for improved respiratory protection, comfort and visibility. The urgency of the response at our hospital required rapid deployment of innovative training to ensure the safe use of PAPRs, in particular, a video-feedback training option to prepare HWs for PAPR competency. Aim To explore the feasibility, acceptability, and utility of video-feedback in PAPR training and competency assessment. Methods Semi-structured interviews were conducted with 12 HWs, including clinicians from Intensive Care, Anaesthetics and Respiratory Medicine, at a large teaching hospital in Australia. Findings Participants believed that the use of video-feedback in PAPR training was feasible, acceptable and useful. They described a variety of benefits to learning and retention, from a variety of ways in which they engaged with the personal video-feedback. Participants also described the impact of reviewing personalised practice footage, compared to generic footage of an ideal performance. Conclusion By conceptualising video-feedback using a pedagogical approach, this study contributes to knowledge around optimising methods for training HWs in PPE use, particularly when introducing a new and complex PPE device during an infectious disease outbreak.

Background: First-line treatment of epithelial ovarian cancer (EOC) consists of a combination of cytoreductive surgery and platinum-based chemotherapy. Recently, targeted therapies such as bevacizumab have been shown to improve oncologic outcomes in a subset of a high-risk population. The objective of this study is to evaluate the patterns of practice and outcomes of first-line systemic treatment of advanced EOC, focusing on the adoption of bevacizumab. Methods: A population cohort study was conducted using administrative data in Ontario, Canada. Patients diagnosed with advanced stage non-mucinous EOC between 2014 and 2018 were identified. Datasets were linked to obtaining information on first-line treatment including surgery, systemic therapy, providers of care, systemic therapy facilities, and acute care utilization (emergency department (ED) visits and hospitalizations) during systemic treatment. Multivariate logistic regression was used to determine factors associated with systemic therapy utilization. Results: Among 3726 patients with advanced EOC, 2838 (76%) received chemotherapy: 1316 (47%) received neoadjuvant chemotherapy, 1060 (37%) underwent primary cytoreductive surgery followed by chemotherapy, and 462 (16%) received chemotherapy only. The median age was 67 (range: 20–100). Most chemotherapies were prescribed by gynecologic oncologists (60%) and in level 1 academic cancer centres (58%). Only 54 patients (3.1%) received bevacizumab in the first-line setting after its approval in Ontario in 2016. Bevacizumab was more likely to be administered by medical oncologists compared to gynecologic oncologists (OR 3.95, 95% CI 2.11–7.14). In total, 1561 (55%) and 1594 (56%) patients had at least one ED visit and/or hospitalization during systemic treatment, respectively. The most common reasons for ED visits were fever and bowel obstruction. Conclusion: Patterns of care for EOC in Ontario differed between care providers. The uptake of bevacizumab for first-line treatment of EOC was low. Acute care utilization related to EOC was high.

Abstract Background Reflex (automatic) BRCA1 and BRCA2 (BRCA1/2) genetic testing of tumour tissue is being completed for all newly diagnosed high-grade serous ovarian cancer (HGSOC) in the province of Ontario, Canada. The objective of this study was to measure the psychological impact of tumour genetic testing among individuals with a new diagnosis of HGSOC. Methods Participants had a new diagnosis of HGSOC and received reflex BRCA1/2 tumour genetic testing as a component of their care. Eligible individuals were recruited from two oncology centres in Toronto, Canada. One week after disclosure of tumour genetic test results, consenting participants were asked to complete a questionnaire that measured cancer-related distress, dispositional optimism, knowledge of hereditary breast/ovarian cancer, recall of tumour genetic test results, satisfaction, and the psychological impact of receiving tumour genetic test results. The Multidimensional Impact of Cancer Risk Assessment (MICRA) questionnaire was used to measure the psychological impact of tumour genetic testing. Results 76 individuals completed the study survey; 13 said they did not receive their tumour test results. Of the remaining 63 participants, the average MICRA score was 26.8 (SD = 16.3). Higher total MICRA scores were seen among those with children (p = 0.02), who received treatment with primary surgery (p = 0.02), and had higher reported cancer-related distress (p

Sentinel lymph node (SLN) mapping is becoming an acceptable alternative to full lymphadenectomy for evaluating lymphatic spread in clinical stage I endometrial cancer (EC). While the assessment of pelvic and para-aortic lymph nodes is part of the surgical staging of EC, there is a long-standing debate over the therapeutic value of full lymphadenectomy in this setting. Although lymphadenectomy offers critical information on lymphatic spread and prognosis, most patients will not derive oncologic benefit from this procedure as the majority of patients do not have lymph node involvement. SLN mapping offers prognostic information while simultaneously avoiding the morbidity associated with an extensive and often unnecessary lymphadenectomy. A key factor in the decision making when planning for EC surgery is the histologic subtype. Since the risk of lymphatic spread is less than 5% in low-grade EC, these patients might not benefit from lymph node assessment. Nonetheless, in high-grade EC, the risk for lymph node metastases is much higher (20–30%); therefore, it is crucial to determine the spread of disease both for determining prognosis and for tailoring the appropriate adjuvant treatment. Studies on the accuracy of SLN mapping in high-grade EC have shown a detection rate of over 90%. The available evidence supports adopting the SLN approach as an accurate method for surgical staging. However, there is a paucity of prospective data on the long-term oncologic outcome for patients undergoing SLN mapping in high-grade EC, and more trials are warranted to answer this question.

Anarchism is a fertile site for nurturing the sorts of encounters that feminists have called intersectionality. Anarchism and intersectionality share the goal of critically examining familiar as well as emergent flows of power and meaning, and understanding their relations to one another. This paper focuses on three compelling directions for anarchist studies: Indigenous anarchism, anarchism developing with new materialism, and anarchism emergent in radical book arts. Each thread has established roots while also moving in new directions. Anarchist encounters with Indigeneity, new materialism, and book arts resonate with each other: they can foster “a commitment to the particular” through which we can immerse ourselves in rich and dense worlds where specific Indigenous theories and practices, detailed encounters with non-human things, and particular artistic + intellectual productions of materials can emerge.

The beliefs teachers hold may provide information about their more or less evidence-informed reasoning about educational issues. However, gaining a clear picture of teachers’ beliefs has proven difficult. A promising line of inquiry uses scenario-based approaches to assess teachers’ enacted beliefs. Accordingly, we assessed 75 Norwegian pre-service teachers’ beliefs about student ability, sources of teaching knowledge, and teacher efficacy by analyzing their written responses to authentic classroom scenarios, with these responses also providing information about participants’ reasoning about the scenarios. While participants’ responses seemed to be evidence-informed in many ways, there were also indications of the opposite, such as limited consideration of educational research in pedagogical decision-making. The results contribute uniquely to an understanding of pre-service teachers’ beliefs and reasoning about educational issues. As such, they may help researchers and teacher educators to better understand the beliefs pre-service teachers hold, as well as to facilitate further development of these beliefs. Implications for future research and teacher education are discussed.

Metastatic urothelial carcinoma is generally incurable with current systemic therapies. Chromatin modifiers are frequently mutated in bladder cancer, with ARID1A-inactivating mutations present in about 20% of tumors. EZH2, a histone methyltransferase, acts as an oncogene that functionally opposes ARID1A. In addition, PI3K signaling is activated in more than 20% of bladder cancers. Using a combination of in vitro and in vivo data, including patient-derived xenografts, we show that ARID1A-mutant tumors were more sensitive to EZH2 inhibition than ARID1A WT tumors. Mechanistic studies revealed that (a) ARID1A deficiency results in a dependency on PI3K/AKT/mTOR signaling via upregulation of a noncanonical PI3K regulatory subunit, PIK3R3, and downregulation of MAPK signaling and (b) EZH2 inhibitor sensitivity is due to upregulation of PIK3IP1, a protein inhibitor of PI3K signaling. We show that PIK3IP1 inhibited PI3K signaling by inducing proteasomal degradation of PIK3R3. Furthermore, ARID1A-deficient bladder cancer was sensitive to combination therapies with EZH2 and PI3K inhibitors in a synergistic manner. Thus, our studies suggest that bladder cancers with ARID1A mutations can be treated with inhibitors of EZH2 and/or PI3K and revealed mechanistic insights into the role of noncanonical PI3K constituents in bladder cancer biology.

Objective: To provide recommendations on systemic therapy options in consolidation or maintenance therapy for women with newly diagnosed stage II, III, or IV epithelial ovary, fallopian tube, or primary peritoneal carcinoma including all histological types. Methods: Consistent with the Program in Evidence-based Program’s standardized approach, MEDLINE, EMBASE, PubMed, Cochrane Library, and PROSPERO (the international prospective register of systematic reviews) databases, and four relevant conferences were systematically searched. The Working Group drafted recommendations and revised them based on the comments from internal and external reviewers. Results: We have one recommendation for consolidation therapy and eight recommendations for maintenance therapy. Overall, consolidation therapy with chemotherapy should not be recommended in the target population. For maintenance therapy, we recommended olaparib (Recommendation), niraparib (Weak Recommendation), veliparib (Weak Recommendation), and bevacizumab (Weak Recommendation) for certain patients with newly diagnosed stage III–IV epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, respectively. We do not recommend some agents as maintenance therapy in four recommendations. We are unable to specify the patient population by histological types for different maintenance therapy recommendations. When new evidence that can impact the recommendations is available, the recommendations will be updated as soon as possible.

Abstract Background The prevalence of diabetes mellitus continues to inexorably rise in the United States and throughout the world. Lower limb amputations are a devastating comorbid complication of diabetes mellitus. Osteomyelitis increases the risk of amputation fourfold and commonly presages death. Antimicrobial therapy for diabetic foot osteomyelitis (DFO) varies greatly, indicating that high quality data are needed to inform clinical decision making. Several small trials have indicated that the addition of rifampin to backbone antimicrobial regimens for osteomyelitis outside the setting of the diabetic foot results in 28 to 42% higher cure rates. Methods/design This is a prospective, randomized, double-blind investigation of the addition of 6 weeks of rifampin, 600 mg daily, vs. matched placebo (riboflavin) to standard-of-care, backbone antimicrobial therapy for DFO. The study population are patients enrolled in Veteran Health Administration (VHA), ages ≥18 and ≤ 89 years with diabetes mellitus and definite or probable osteomyelitis of the foot for whom an extended course of oral or intravenous antibiotics is planned. The primary endpoint is amputation-free survival. The primary hypothesis is that using rifampin as adjunctive therapy will lower the hazard rate compared with the group that does not use rifampin as adjunctive therapy. The primary hypothesis will be tested by means of a two-sided log-rank test with a 5% significance level. The test has 90% power to detect a hazard ratio of 0.67 or lower with a total of 880 study participants followed on average for 1.8 years. Discussion VA INTREPID will test if a rifampin-adjunctive antibiotic regimen increases amputation-free survival in patients seeking care in the VHA with DFO. A positive finding and its adoption by clinicians would reduce lower extremity amputations and their associated physical and emotional impact and reduce mortality for Veterans and for the general population with diabetic foot osteomyelitis. Given that rifampin-adjunctive regimens are currently employed for therapy for the majority of DFO cases in Europe, and only in a small minority of cases in the United States, the trial results will impact therapeutic decisions, even if the null hypothesis is not rejected. Trial registration Registered January 6, 2017 at ClinicalTrials.gov, NCT03012529.

Cancer cells utilize vitamin folate to fulfill their excessive demand for nucleotides and amino acids. Dihydrofolate reductase (DHFR), an enzyme involved in folate metabolism converts dihydrofolate into tetrahydrofolate, which is required for the de novo synthesis of purines, and certain amino acids. DHFR inhibitors are used as a chemotherapeutic agent. Cancer sequencing analysis has identified additional enzymes in folate metabolism that are dysregulated in cancer. Methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L), one such enzyme is overexpressed in bladder cancer. MTHFD1L is a mitochondrial enzyme involved in the folate cycle by catalyzing the reaction of formyl-tetrahydrofolate to formate and tetrahydrofolate (THF). THF is crucial for de novo purine and thymidylate synthesis and is also involved in the regeneration of methionine. Cancer cells rely on purines derived from the de novo pathway for the nucleotides whereas normal cells favor the salvage pathway. In this study we examined MTHFD1L expression in bladder cancer. By using publicly available cancer transcriptome data analysis web-portal UALCAN, we found overexpression of MTHFD1L in bladder cancer and expression was associated with overall survival. RT-PCR and immunoblot analysis confirmed the overexpression of MTHFD1L in muscle invasive bladder cancer tissues compared to normal urothelium. Furthermore, our investigations suggested a critical role for MTHFD1L in bladder cancer cell proliferation, colony formation and invasion. Thus, in this study, we show the significance of the folate metabolic enzyme MTHFD1L in aggressive bladder cancers and suggest that being an enzyme, MTHFD1L serves as a valuable therapeutic target.

Abstract Background Lynch syndrome, a hereditary cancer syndrome, predisposes women to colorectal, endometrial, and ovarian cancer. Current guidelines recommend that women with Lynch syndrome undergo risk-reducing gynecological surgery to reduce their chances of developing endometrial or ovarian cancer. Little is known about how women with Lynch syndrome perceive gynecological cancer screening, or the psychosocial factors associated with screening attitudes and behaviour. Methods This study used a cross-sectional, quantitative design. Using self-report questionnaire data from a sample of women with Lynch syndrome (N = 50) who had not undergone risk-reducing surgery, the current study sought to: 1) describe the gynecological cancer screening behaviours of women with Lynch syndrome, as well participant-reported sources of information about Lynch syndrome; 2) examine the extent to which women believe gynecological cancer screening is effective and provides them with reassurance and; 3) assess to what extent relationships with one’s family physician were associated with gynecological cancer screening, perceptions about screening, and health self-efficacy. Data were analyzed using descriptive statistics and Spearman rank-ordered correlations. Results Data analyses showed that transvaginal ultrasound was the most common screening behaviour (57%) followed by pelvic ultrasound (47%). Only 22% of participants underwent endometrial biopsy. Patient-physician relationships were related to greater health self-efficacy to manage Lynch syndrome and greater perceived effectiveness of gynecological screening. However, health self-efficacy and better patient-physician relationships were not associated with increased engagement in gynecological cancer screening. Conclusions The data suggest that feeling efficacious about managing one’s Lynch syndrome and screening is related to positive interactions and communication with one’s family physician. While this is encouraging, future research should examine educating both family physicians and patients about current guidelines for Lynch syndrome gynecological screening recommendations.

At a Canadian cancer centre, rising patient volumes made it difficult to provide quality chemotherapy education to patients and families in the clinical setting. The gynecology oncology site identified several barriers to the provision of timely and comprehensive teaching. These barriers included receiving education after learning of a cancer diagnosis, the efficacy of written information, time constraints nurses experienced, and absence of standardized side effect management. This prompted an interdisciplinary team to review current teaching practices and engage the Patient Education Program to collaboratively develop strategies to overcome these challenges. This paper describes the development of a nurse-led chemotherapy education class tailored to patients with gynecologic cancers and focused on common chemotherapy treatment protocols. The purpose of the class was to help patients and caregivers know what to expect during their chemotherapy routine, lower anxiety, and to equip them with knowledge and skills to manage side effects of treatment.

L’augmentation du nombre de patients vus en clinique dans un centre de cancérologie du Canada est venue nuire à l’offre d’un enseignement de qualité sur la chimiothérapie pour les patients et leur famille. Le département de gynéco-oncologie a cerné plusieurs obstacles à la transmission d’un enseignement complet et opportun. Une fois le diagnostic de cancer tombé, l’accès à l’enseignement, l’efficacité de l’information transmise par écrit, les contraintes de temps des infirmières et l’absence d’uniformité dans la prise en charge des effets secondaires figurent parmi les obstacles relevés. Une équipe interdisciplinaire s’est donc rassemblée pour revoir les pratiques d’enseignement actuelles et se pencher sur le programme d’enseignement aux patients afin de développer, conjointement, des stratégies pour régler ces problèmes. Cet article décrit les étapes ayant mené à l’élaboration, par le personnel infirmier, d’une formation sur la chimiothérapie (protocoles courants) destinée aux patients atteints de cancers gynécologiques et visant à aider les patients et les soignants à mieux se préparer aux séances de chimiothérapie, à calmer l’anxiété et à savoir comment gérer les effets secondaires liés au traitement.

For an antibody to be a successful therapeutic many competing factors require optimization, including binding affinity, biophysical characteristics, and immunogenicity risk. Additional constraints may arise from the need to formulate antibodies at high concentrations (>150 mg/ml) to enable subcutaneous dosing with reasonable volume (ideally

ObjectiveObesity is a major risk factor for low-grade endometrial cancer. The surgical management of patients with obesity is challenging, and they may face unique barriers to accessing care. We completed a qualitative study to understand the experiences of low-grade endometrial cancer patients with morbid obesity, from symptom onset to diagnosis to surgery.DesignSemi-structured interviews were performed with endometrial cancer patients with morbid obesity (body mass index (BMI) >40 kg/m2) referred for primary surgery. Transcribed interviews were coded line-by-line and analysed using an interpretive descriptive approach that drew on labelling theory to understand patients’ experiences. Thematic sufficiency was confirmed after 15 interviews.SettingTwo tertiary care centres in Toronto, Ontario, Canada.ParticipantsFifteen endometrial cancer patients with a median age of 61 years (range: 50–74) and a median BMI of 50 kg/m2 (range: 44–70) were interviewed.ResultsThematic analysis identified that (1) both patients and providers lack knowledge on endometrial cancer and its presenting symptoms and risk factors; (2) patients with morbid obesity are subject to stigma and poor communication in the healthcare system and (3, 4) although clinical, administrative, financial, geographic and facility-related barriers exist, quality care for patients with morbid obesity is an achievable goal.ConclusionsImproved education on the prevention and identification of endometrial cancer is needed for both patients and providers. Delivery of cancer care to patients with morbid obesity may be improved through provider awareness of the impact of weight stigma and establishing streamlined care pathways at centres equipped to manage surgical complexity.

Type I interferon (IFN-I) has potent anti-tumor effects against urothelial carcinoma (UC) and may be an alternative treatment option for patients who do not respond to Bacillus Calmette-Guerin. However, the mechanisms that mediate the IFN-I-stimulated immune responses against UC have yet to be elucidated. Herein, we evaluated the anti-tumor mechanisms of IFN-I in UC in human patients and in mice. Patient tumors from a Phase I clinical trial with adenoviral interferon-α (Ad-IFNα/Syn3) showed increased expression of T cell and checkpoint markers following treatment with Ad-IFNα/Syn3 by RNAseq and immunohistochemistry analysis in 25% of patients. In mice, peritumoral injections of poly(I:C) into MB49 UC tumors was used to incite an IFN-driven inflammatory response that significantly inhibited tumor growth. IFN-I engaged both innate and adaptive cells, seen in increased intratumoral CD8 T cells, NK cells, and CD11b+Ly6G+ cells, but tumor inhibition was not reliant on any one immune cell type. Nonetheless, poly(I:C)-mediated tumor regression and change in the myeloid cell landscape was dependent on IL-6. Mice were also treated with poly(I:C) in combination with anti-PD-1 monoclonal antibody (mAb) to assess for additional benefit to tumor growth and animal survival. When used in combination with anti-PD-1 mAb, IFN-I stimulation prolonged survival, coinciding with inhibition of angiogenesis and enriched gene signatures of metabolism, extracellular matrix organization, and MAPK/AKT signaling. Altogether, these findings suggest IFN-I’s immune-driven antitumor response in UC is mediated by IL-6 and a collaboration of immune cells, and its use in combination with checkpoint blockade therapy can increase clinical benefit.

Background: The estimation of an effect size is an important step in designing an adequately powered, feasible clinical trial intended to change clinical practice. During the planning phase of VA Cooperative Study #590, “Double-Blind Placebo-Controlled Study of Lithium for Preventing Repeated Suicidal Self-Directed Violence in Patients with Depression or Bipolar Disorder (Li+),” it was not clear what effect size would be considered large enough to influence prescribing behavior among practicing clinicians. Methods: We conducted an online survey of VA psychiatrists to assess their interest in the study question, their clinical experience with lithium, and their opinion about what suicide reduction rate would change their prescribing habits. The 9-item survey was hosted on SurveyMonkey© and VA psychiatrists were individually emailed an invitation to complete an anonymous online survey. Three email waves were sent over three weeks. Results: Overall, 862 of 2713 VA psychiatrists (response rate = 31.8%) responded to the anonymous survey. 74% of the respondents would refer a patient to the proposed trial, 9% would not, and 17% were unsure. Presented with suicide reduction rates in 10% increments ranging from 10 to 100%, 61% of respondents indicated that they would use lithium if suicide attempts were reduced by at least 40%; 83% would use lithium if it reduced attempts by at least 50%. Conclusions: Even with the limitations of response bias and the reliability of responses on future prescribing behavior, a survey of potential users of a clinical trial's results offers a convenient, empirical method for determining and justifying clinically relevant effect sizes.

Malignant bowel obstruction (MBO) is a major complication in women with advanced gynecologic cancers which imposes a significant burden on patients, caregivers, and healthcare systems. Symptoms of MBO are challenging to palliate and result in progressive decompensation of already vulnerable patients with limited therapeutic options and a short prognosis. However, there is a paucity of guidelines or innovative approaches to improve the care of women who develop MBO. MBO is a complex clinical situation that requires a multidisciplinary approach to ensure the appropriate treatment modality and interprofessional care to optimally manage these patients. This review summarizes the current literature on the different approaches targeting MBO management including surgical intervention, chemotherapy, total parenteral nutrition, and pharmacological treatment. In addition, the impact of MBO management on patients’ quality of life (QOL) is examined. This article focuses on the challenges in developing evidence-based treatment guidelines for MBO and barriers in clinical trial design for MBO and proposes strategies to advance the MBO management. Collaboration is essential to design studies that may improve the overall care and quality of life for these patients. Prospective data are needed to inform clinical practice, establish a new benchmark for evidence-based MBO management, and better understand the biology of MBO.

Genetic mapping of quantitative trait loci (QTL) for resistance to cassava brown streak disease (CBSD), cassava mosaic disease (CMD), and cassava green mite (CGM) was performed using an F1 cross developed between the Tanzanian landrace, Kiroba, and a breeding line, AR37-80. The population was evaluated for two consecutive years in two sites in Tanzania. A genetic linkage map was derived from 106 F1 progeny and 1,974 SNP markers and spanned 18 chromosomes covering a distance of 1,698 cM. Fifteen significant QTL were identified; two are associated with CBSD root necrosis only, and were detected on chromosomes V and XII, while seven were associated with CBSD foliar symptoms only and were detected on chromosomes IV, VI, XVII, and XVIII. QTL on chromosomes 11 and 15 were associated with both CBSD foliar and root necrosis symptoms. Two QTL were found to be associated with CMD and were detected on chromosomes XII and XIV, while two were associated with CGM and were identified on chromosomes V and X. There are large Manihot glaziovii introgression regions in Kiroba on chromosomes I, XVII, and XVIII. The introgression segments on chromosomes XVII and XVIII overlap with QTL associated with CBSD foliar symptoms. The introgression region on chromosome I is of a different haplotype to the characteristic “Amani haplotype” found in the landrace Namikonga and others, and unlike some other genotypes, Kiroba does not have a large introgression block on chromosome IV. Kiroba is closely related to a sampled Tanzanian “tree cassava.” This supports the observation that some of the QTL associated with CBSD resistance in Kiroba are different to those observed in another variety, Namikonga.

Recent publications have emphasized the importance of a multidisciplinary strategy for maximum conservation and utilization of lung biopsy material for advanced testing, which may determine therapy. This paper quantifies the effect of a multidisciplinary strategy implemented to optimize and increase tissue volume in CT-guided transthoracic needle core lung biopsies. The strategy was three-pronged: (1) once there was confidence diagnostic tissue had been obtained and if safe for the patient, additional biopsy passes were performed to further increase volume of biopsy material, (2) biopsy material was placed in multiple cassettes for processing, and (3) all tissue ribbons were conserved when cutting blocks in the histology laboratory. This study quantifies the effects of strategies #1 and #2.This retrospective analysis comparing CT-guided lung biopsies from 2007 and 2012 (before and after multidisciplinary approach implementation) was performed at a single institution. Patient medical records were reviewed and main variables analyzed include biopsy sample size, radiologist, number of blocks submitted, diagnosis, and complications. The biopsy sample size measured was considered to be directly proportional to tissue volume in the block.Biopsy sample size increased 2.5 fold with the average total biopsy sample size increasing from 1.0 cm (0.9-1.1 cm) in 2007 to 2.5 cm (2.3-2.8 cm) in 2012 (P

Background: UK public health policy strongly advocates dietary change for the improvement of population health and emphasises the importance of individual empowerment to improve health. A new and evolving area in the promotion of dietary behavioural change is ‘e-learning’, the use of interactive electronic media to facilitate teaching and learning on a range of issues including health. The high level of accessibility, combined with emerging advances in computer processing power, data transmission and data storage, makes interactive e-learning a potentially powerful and cost-effective medium for improving dietary behaviour. Objective: This review aims to assess the effectiveness and cost-effectiveness of adaptive e-learning interventions for dietary behaviour change, and also to explore potential psychological mechanisms of action and components of effective interventions. Data sources: Electronic bibliographic databases (Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library, Dissertation Abstracts, EMBASE, Education Resources Information Center, Global Health, Health Economic Evaluations Database, Health Management Information Consortium, MEDLINE, PsycINFO and Web of Science) were searched for the period January 1990 to November 2009. Reference lists of included studies and previous reviews were also screened; authors were contacted and trial registers were searched. Review methods: Studies were included if they were randomised controlled trials, involving participants aged ≥ 13 years, which evaluated the effectiveness of interactive software programs for improving dietary behaviour. Primary outcomes were measures of dietary behaviours, including estimated intakes or changes in intake of energy, nutrients, dietary fibre, foods or food groups. Secondary outcome measures were clinical outcomes such as anthropometry or blood biochemistry. Psychological mediators of dietary behaviour change were also investigated. Two review authors independently screened results and extracted data from included studies, with any discrepancies settled by a third author. Where studies reported the same outcome, the results were pooled using a random-effects model, with weighted mean differences (WMDs), and 95% confidence intervals (CIs) were calculated. Cost-effectiveness was assessed in two ways: through a systematic literature review and by building a de novo decision model to assess the cost-effectiveness of a ‘generic’ e-learning device compared with dietary advice delivered by a health-care professional. Results: A total of 36,379 titles were initially identified by the electronic searches, of which 43 studies were eligible for inclusion in the review. All e-learning interventions were delivered in high-income countries. The most commonly used behavioural change techniques reported to have been used were goal setting; feedback on performance; information on consequences of behaviour in general; barrier identification/problem solving; prompting self-monitoring of behaviour; and instruction on how to perform the behaviour. There was substantial heterogeneity in the estimates of effect. E-learning interventions were associated with a WMD of +0.24 (95% CI 0.04 to 0.44) servings of fruit and vegetables per day; –0.78 g (95% CI –2.5 g to 0.95 g) total fat consumed per day; –0.24 g (95% CI –1.44 g to 0.96 g) saturated fat intake per day; –1.4% (95% CI –2.5% to –0.3%) of total energy consumed from fat per day; +1.45 g (95% CI –0.02 g to 2.92 g) dietary fibre per day; +4 kcal (95% CI –85 kcal to 93 kcal) daily energy intake; –0.1 kg/m2 (95% CI –0.7 kg/m2 to 0.4 kg/m2) change in body mass index. The base-case results from the E-Learning Economic Evaluation Model suggested that the incremental cost-effectiveness ratio was approximately £102,112 per quality-adjusted life-year (QALY). Expected value of perfect information (EVPI) analysis showed that although the individual-level EVPI was arguably negligible, the population-level value was between £37M and £170M at a willingness to pay of £20,000–30,000 per additional QALY. Limitations: The limitations of this review include potential reporting bias, incomplete retrieval of completed research studies and data extraction errors. Conclusion: The current clinical and economic evidence base suggests that e-learning devices designed to promote dietary behaviour change will not produce clinically significant changes in dietary behaviour and are at least as expensive as other individual behaviour change interventions. Future work recommendations: Despite the relatively high EVPI results from the cost-effectiveness modelling, further clinical trials of individual e-learning interventions should not be undertaken until theoretically informed work that addresses the question of which characteristics of the target population, target behaviour, content and delivery of the intervention are likely to lead to positive results, is completed. Funding: The National Institute for Health Research Health Technology Assessment programme.

Acute and chronic lung inflammation is associated with numerous important disease pathologies including asthma, chronic obstructive pulmonary disease and silicosis. Lung fibroblasts are a novel and important target of anti-inflammatory therapy, as they orchestrate, respond to, and amplify inflammatory cascades and are the key cell in the pathogenesis of lung fibrosis. Peroxisome proliferator-activated receptor gamma (PPARγ) ligands are small molecules that induce anti-inflammatory responses in a variety of tissues. Here, we report for the first time that PPARγ ligands have potent anti-inflammatory effects on human lung fibroblasts. 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid (CDDO) and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) inhibit production of the inflammatory mediators interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), COX-2, and prostaglandin (PG)E2 in primary human lung fibroblasts stimulated with either IL-1β or silica. The anti-inflammatory properties of these molecules are not blocked by the PPARγ antagonist GW9662 and thus are largely PPARγ independent. However, they are dependent on the presence of an electrophilic carbon. CDDO and 15d-PGJ2, but not rosiglitazone, inhibited NF-κB activity. These results demonstrate that CDDO and 15d-PGJ2 are potent attenuators of proinflammatory responses in lung fibroblasts and suggest that these molecules should be explored as the basis for novel, targeted anti-inflammatory therapies in the lung and other organs.

A User's Perspective on Electronic Data Archival: Tlie Importance of Standards