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From November, 1973, through June, 1978, 428 operations in 425 patients were performed for replacement of aortic, mitral, or aortic plus mitral valves, utilizing 277 Hancock and 180 Carpentier-Edwards bioprostheses. Actuarially determined survival at 36 months was similar for all three groups and compared favorably with our experience with the Björk-Shiley prosthesis. Certain patient-related variables influencing late survival were identified by multivariate analysis and included previous operation for congenital heart disease, coronary artery bypass grafting in nonaortic valve replacement, race (black), age at operation, and New York Heart Association Functional Class. A small but definite incidence of thromboembolism occurred in all three groups, again similar to our experience with the Björk-Shiley prosthesis. Multivariate analysis identified four factors influencing risk of thromboembolism: previous cardiac operation, age, double-valve replacement, and rhythm at discharge. Valve degeneraation occurred, primarily in children and young adults. Over the medium term, the porcine bioprosthesis compared favorably with mechanical prostheses in terms of survival, function, and thromboembolism. Certain patient-related variables affecting survival may be modified by earlier surgical intervention.

Objective Identifying optimal strategies for managing patients of any age with varying risk of acute rheumatic fever (ARF) attending for an apparently uncomplicated acute sore throat, also clarifying the role of point-of-care testing (POCT) for presence of group A beta-haemolytic Streptococcus (GABHS) in these settings.Design We compared outcomes of adhering to nine different strategies for managing these patients in primary healthcare.Setting and participants The nine strategies, similar to guidelines from several countries, were tested against two validation data sets being constructs from seven prior studies.Main outcome measures The proportion of patients requiring a POCT, prescribed antibiotics, prescribed antibiotics having GABHS and finally having GABHS not prescribed antibiotics, if different strategies had been adhered to.Results In a scenario with high risk of ARF, adhering to existing guidelines would risk many patients ill from GABHS left without antibiotics. Hence, using a POCT on all of these patients minimised their risk. For low-risk patients, it is reasonable to only consider antibiotics if the patient has more than low pain levels despite adequate analgesia, 3–4 Centor scores (or 2–3 FeverPAIN scores or 3–4 McIsaac scores) and a POCT confirming the presence of GABHS. This would require testing only 10%–15% of patients and prescribing antibiotics to only 3.5%–6.6%.Conclusions Patients with high or low risk for ARF needs to be managed very differently. POCT can play an important role in safely targeting the use of antibiotics for patients with an apparently uncomplicated acute sore throat.

IntroductionAdvances in multiparametric MRI (mpMRI) combining anatomic and functional imaging can accurately identify foci of adenocarcinoma within the prostate, offering the possibility of partial gland therapy. We performed tandem prospective pilot trials to investigate the feasibility of focal prostate SBRT (f-SBRT) based on correlating diagnostic mpMRI and biopsies with confirmatory pathology in treatment planning.Materials and MethodsPatients with pathologic focal Gleason 6–7 disease and a corresponding PIRADS 4–5 lesion on mpMRI underwent targeted and comprehensive biopsies using MRI/ultrasound fusion under electromagnetic sensor navigation. After rigorous analysis for imaging biopsy concordance, five of 18 patients were eligible to proceed to f-SBRT. Chi-squared test was used for differences from expected outcomes, and concordance was estimated with binomial distribution theory and Wilson’s method.ResultsSix patients had Gleason 6 and 12 had Gleason 3 + 4 disease (mean PSA: 5.8 ng/ml, range: 2.2–8.4). Absolute concordance was 43.8% (95% CI: 0.20, 0.64). Patterns of discordance included additional sites of ipsilateral disease, bilateral disease, and negative target. Five were upstaged to a new NCCN risk category necessitating treatment escalation. The five patients with concordant pathology completed three-fraction f-SBRT with sparing of the surrounding normal structures (including contralateral neurovascular bundle), with no reported grade 2+ toxicities and favorable PSA responses (mean: 41% decrease).ConclusionsOn our pilot trials of f-SBRT planning using rigorous imaging and pathology concordance, image-guided confirmatory biopsies frequently revealed additional disease, suggesting the need for caution in partial-gland therapy. For truly focal disease, f-SBRT provided excellent dosimetry, minimal toxicity, and encouraging biochemical response. Clinical Trial Registration: www.clinicaltrials.gov, NCT02681614; NCT02163317.

Background Exercise-induced muscle damage (EIMD) results in transient muscle inflammation, strength loss, muscle soreness and may cause subsequent exercise avoidance. Omega-3 (n-3) supplementation may minimise EIMD via its anti-inflammatory properties, however, its efficacy remains unclear. Methods Healthy males (n = 14, 25.07 ± 4.05 years) were randomised to 3 g/day n-3 supplementation (N-3, n = 7) or placebo (PLA, n = 7). Following 4 weeks supplementation, a downhill running protocol (60 min, 65% V̇O2max, − 10% gradient) was performed. Creatine kinase (CK), interleukin (IL)-6 and tumour necrosis factor (TNF)-α, perceived muscle soreness, maximal voluntary isometric contraction (MVIC) and peak power were quantified pre, post, and 24, 48 and 72 h post-EIMD. Results Muscle soreness was significantly lower in N-3 vs PLA group at 24 h post-EIMD (p = 0.034). IL-6 was increased in PLA (p = 0.009) but not in N-3 (p = 0.434) following EIMD, however, no significant differences were noted between groups. Peak power was significantly suppressed in PLA relative to pre-EIMD but not in N-3 group at 24 h post-EIMD. However, no significant difference in peak power output was observed between groups. MVIC, CK and TNF-α were altered by EIMD but did not differ between groups. Conclusion N-3 supplementation for 4 weeks may successfully attenuate minor aspects of EIMD. Whilst not improving performance, these findings may have relevance to soreness-associated exercise avoidance.

For over 50 years instructor humor has been recognized as a way to positively impact student cognitive and affective learning. However, no study has explored humor exclusively in the context of college science courses, which have the reputation of being difficult and boring. The majority of studies that explore humor have assumed that students perceive instructor humor to be funny, yet students likely perceive some instructor humor as unfunny or offensive. Further, evidence suggests that women perceive certain subjects to be more offensive than men, yet we do not know what impact this may have on the experience of women in the classroom. To address these gaps in the literature, we surveyed students across 25 different college science courses about their perceptions of instructor humor in college science classes, which yielded 1637 student responses. Open-coding methods were used to analyze student responses to a question about why students appreciate humor. Multinomial regression was used to identify whether there are gender differences in the extent to which funny, unfunny, and offensive humor influenced student attention to course content, instructor relatability, and student sense of belonging. Logistic regression was used to examine gender differences in what subjects students find funny and offensive when joked about by college science instructors. Nearly 99% of students reported that they appreciate instructor humor and reported that it positively changes the classroom atmosphere, improves student experiences during class, and enhances the student-instructor relationship. We found that funny humor tends to increase student attention to course content, instructor relatability, and student sense of belonging. Conversely, offensive humor tends to decrease instructor relatability and student sense of belonging. Lastly, we identified subjects that males were more likely to find funny and females were more likely to find offensive if a college science instructor were to joke about them.

Current operational forecasts of solar eruptions are made by human experts using a combination of qualitative shape-based classification systems and historical data about flaring frequencies. In the past decade, there has been a great deal of interest in crafting machine-learning (ML) flare-prediction methods to extract underlying patterns from a training set – e.g. a set of solar magnetogram images, each characterized by features derived from the magnetic field and labeled as to whether it was an eruption precursor. These patterns, captured by various methods (neural nets, support vector machines, etc.), can then be used to classify new images. A major challenge with any ML method is the featurization of the data: pre-processing the raw images to extract higher-level properties, such as characteristics of the magnetic field, that can streamline the training and use of these methods. It is key to choose features that are informative, from the standpoint of the task at hand. To date, the majority of ML-based solar eruption methods have used physics-based magnetic and electric field features such as the total unsigned magnetic flux, the gradients of the fields, the vertical current density, etc. In this paper, we extend the relevant feature set to include characteristics of the magnetic field that are based purely on the geometry and topology of 2D magnetogram images and show that this improves the prediction accuracy of a neural-net based flare-prediction method.

In non-stationary environments, there is a conflict between exploiting currently favored options and gaining information by exploring lesser-known options that in the past have proven less rewarding. Optimal decision making in such tasks requires considering future states of the environment (i.e., planning) and properly updating beliefs about the state of environment after observing outcomes associated with choices. Optimal belief-updating is reflective in that beliefs can change without directly observing environmental change. For example, after ten seconds elapse, one might correctly believe that a traffic light last observed to be red is now more likely to be green. To understand human decision-making when rewards associated with choice options change over time, we develop a variant of the classic bandit task that is both rich enough to encompass relevant phenomena and sufficiently tractable to allow for ideal actor analysis of sequential choice behavior. We evaluate whether people update beliefs about the state of environment in a reflexive (i.e., only in response to observed changes in reward structure) or reflective manner. In contrast to purely "random" accounts of exploratory behavior, model-based analyses of the subjects’ choices and latencies indicate that people are reflective belief-updaters. However, unlike the Ideal Actor model, our analyses indicate that people's choice behavior does not reflect consideration of future environmental states. Thus, although people update beliefs in a reflective manner consistent with the ideal actor, they do not engage in optimal long-term planning, but instead myopically choose the option on every trial that is believed to have the highest immediate payoff.

Abstract Background The emigration of skilled nurses from the Philippines is an ongoing phenomenon that has impacted the quality and quantity of the nursing workforce, while strengthening the domestic economy through remittances. This study examines how the development of brain drain-responsive policies is driven by the effects of nurse migration and how such efforts aim to achieve mind-shifts among nurses, governing and regulatory bodies, and public and private institutions in the Philippines and worldwide. Methods Interviews and focus group discussions were conducted to elicit exploratory perspectives on the policy response to nurse brain drain. Interviews with key informants from the nursing, labour and immigration sectors explored key themes behind the development of policies and programmes that respond to nurse migration. Focus group discussions were held with practising nurses to understand policy recipients’ perspectives on nurse migration and policy. Results Using the qualitative data, a thematic framework was created to conceptualize participants’ perceptions of how nurse migration has driven the policy development process. The framework demonstrates that policymakers have recognised the complexity of the brain drain phenomenon and are crafting dynamic policies and programmes that work to shift domestic and global mindsets on nurse training, employment and recruitment. Conclusions Development of responsive policy to Filipino nurse brain drain offers a glimpse into a domestic response to an increasingly prominent global issue. As a major source of professionals migrating abroad for employment, the Philippines has formalised efforts to manage nurse migration. Accordingly, the Philippine paradigm, summarised by the thematic framework presented in this paper, may act as an example for other countries that are experiencing similar shifts in healthcare worker employment due to migration.

Abstract Background Leadership is widely regarded as central to effective health-care systems, and resources are increasingly devoted to the cultivation of strong health-care leadership. Nevertheless, the literature regarding leadership capacity building has been developed primarily in the context of high-income settings. Less research has been done on leadership in low-income settings, including sub-Saharan Africa, particularly in health care, with attention to historical, political and sociocultural context. We sought to characterize the experiences of individuals in key health-care leadership roles in sub-Saharan Africa. Methods We conducted a qualitative study using in-person interviews with individuals (n = 17) in health-care leadership roles in four countries in sub-Saharan Africa: the Federal Democratic Republic of Ethiopia, the Republic of Ghana, the Republic of Liberia and the Republic of Rwanda. Individuals were identified by their country’s minister of health as key leaders in the health sector and were nominated to serve as delegates to a global health leadership conference in June 2010, at Yale University in the United States. Interviews were audio recorded and professionally transcribed. Data analysis was performed by a five-person multidisciplinary team using the constant comparative method, facilitated by ATLAS.ti 5.0 software. Results Five key themes emerged as important to participants in their leadership roles: having an aspirational, value-based vision for improving the future health of the country, being self-aware and having the ability to identify and use complementary skills of others, tending to relationships, using data in decision making, and sustaining a commitment to learning. Conclusions Current models of leadership capacity building address the need for core technical and management competencies. While these competencies are important, skills relevant to managing relationships are also critical in the sub-Saharan African context. Developing such skills may require more time and a deeper level of engagement and collaboration than is typically invested in efforts to strengthen health systems.

Abstract Background Although rates of maternal and neonatal mortality have decreased in many countries over the last two decades, they remain unacceptably high, particularly in sub-Saharan Africa. Nevertheless, we know little about the quality of facility-based maternal and newborn care in low-income countries and little about the association between quality of care and health worker training, supervision, and incentives in these settings. We therefore sought to examine the quality of facility-based maternal and newborn health care by describing the implementation of recommended practices for maternal and newborn care among health care facilities. We also aimed to determine whether increased training, supervision, and incentives for health workers were associated with implementing these recommended practices. We chose to study these aims in the Republic of Rwanda, where rates of maternal and newborn mortality are high and where substantial attention is currently focused on strengthening health workforce capacity and quality. Methods We used data from the 2007 Rwanda Service Provision Assessment. Using observations from 455 facilities and interviews from 1357 providers, we generated descriptive statistics to describe the use of recommended practices and frequencies of provider training, supervision, and incentives in the areas of antenatal, delivery, and newborn care. We then constructed multivariable regression models to examine the associations between using recommended practices and health provider training, supervision, and incentives. Results Use of recommended practices varied widely, and very few facilities performed all recommended practices. Furthermore, in most areas of care, less than 25% of providers reported having had any pre-service or in-service training in the last 3 years. Contrary to our hypotheses, we found no evidence that training, supervision, or incentives were consistently associated with using recommended practices. Conclusion Our findings highlight the need to improve facility-based maternal and newborn care in Rwanda and suggest that current approaches to workforce training, supervision, and incentives may not be adequate for improving these critical practices.

Abstract Background A powerful approach to understanding complex processes such as aging is to use model organisms amenable to genetic manipulation, and to seek relevant phenotypes to measure. Caenorhabditis elegans is particularly suited to studies of aging, since numerous single-gene mutations have been identified that affect its lifespan; it possesses an innate immune system employing evolutionarily conserved signaling pathways affecting longevity. As worms age, bacteria accumulate in the intestinal tract. However, quantitative relationships between worm genotype, lifespan, and intestinal lumen bacterial load have not been examined. We hypothesized that gut immunity is less efficient in older animals, leading to enhanced bacterial accumulation, reducing longevity. To address this question, we evaluated the ability of worms to control bacterial accumulation as a functional marker of intestinal immunity. Results We show that as adult worms age, several C. elegans genotypes show diminished capacity to control intestinal bacterial accumulation. We provide evidence that intestinal bacterial load, regulated by gut immunity, is an important causative factor of lifespan determination; the effects are specified by bacterial strain, worm genotype, and biologic age, all acting in concert. Conclusions In total, these studies focus attention on the worm intestine as a locus that influences longevity in the presence of an accumulating bacterial population. Further studies defining the interplay between bacterial species and host immunity in C. elegans may provide insights into the general mechanisms of aging and age-related diseases.

Abstract Introduction Roma, the largest minority group in Europe, face widespread racism and health disadvantage. Using qualitative data from Serbia and Macedonia, our objective was to develop a conceptual framework showing how three levels of racism--personal, internalized, and institutional--affect access to maternal health care among Romani women. Methods Eight focus groups of Romani women aged 14-44 (n = 71), as well as in-depth semi-structured interviews with gynecologists (n = 8) and key informants from NGOs and state institutions (n = 11) were conducted on maternal health care seeking, experiences during care, and perceived health care discrimination. Transcripts were coded, and analyzed using a grounded theory approach. Themes were categorized into domains. Results Twenty-two emergent themes identified barriers that reflected how racism affects access to maternal health care. The domains into which the themes were classified were perceptions and interactions with health system, psychological factors, social environment and resources, lack of health system accountability, financial needs, and exclusion from education. Conclusions The experiences of Romani women demonstrate psychosocial and structural pathways by which racism and discrimination affect access to prenatal and maternity care. Interventions to address maternal health inequalities should target barriers within all three levels of racism.

Abstract Background As low- and middle-income countries experience economic development, ensuring quality of health care delivery is a central component of health reform. Nevertheless, health reforms in low- and middle-income countries have focused more on access to services rather than the quality of these services, and reporting on quality has been limited. In the present study, we sought to examine the prevalence and regional variation in key management practices in Egyptian health facilities within three domains: supervision of the facility from the Ministry of Health and Population (MOHP), managerial processes, and patient and community involvement in care. Methods We conducted a cross-sectional analysis of data from 559 facilities surveyed with the Egyptian Service Provision Assessment (ESPA) survey in 2004, the most recent such survey in Egypt. We registered on the Measure Demographic and Health Survey (DHS) website http://legacy.measuredhs.com/login.cfm to gain access to the survey data. From the ESPA sampled 559 MOHP facilities, we excluded a total of 79 facilities because they did not offer facility-based 24-hour care or have at least one physician working in the facility, resulting in a final sample of 480 facilities. The final sample included 76 general service hospitals, 307 rural health units, and 97 maternal and child health and urban health units (MCH/urban units). We used standard frequency analyses to describe facility characteristics and tested the statistical significance of regional differences using chi-square statistics. Results Nearly all facilities reported having external supervision within the 6 months preceding the interview. In contrast, key facility-level managerial processes, such as having routine and documented management meetings and applying quality assurance approaches, were uncommon. Involvement of communities and patients was also reported in a minority of facilities. Hospitals and health units located in Urban Egypt compared with more rural parts of Egypt were significantly more likely to have management committees that met at least monthly, to keep official records of the meetings, and to have an approach for reviewing quality assurance activities. Conclusions Although the data precede the recent reform efforts of the MOHP, they provide a baseline against which future progress can be measured. Targeted efforts to improve facility-level management are critical to supporting quality improvement initiatives directed at improving the quality of health care throughout the country.

Abstract Introduction Capacity-building programs are vital for healthcare workforce development in low- and middle-income countries. In addition to increasing human capital, participation in such programs may lead to new professional networks and access to social capital. Although network development and social capital generation were not explicit program goals, we took advantage of a natural experiment and studied the social networks that developed in the first year of an executive-education Master of Hospital and Healthcare Administration (MHA) program in Jimma, Ethiopia. Case description We conducted a sociometric network analysis, which included all program participants and supporters (formally affiliated educators and mentors). We studied two networks: the Trainee Network (all 25 trainees) and the Trainee-Supporter Network (25 trainees and 38 supporters). The independent variable of interest was out-degree, the number of program-related connections reported by each respondent. We assessed social capital exchange in terms of resource exchange, both informational and functional. Contingency table analysis for relational data was used to evaluate the relationship between out-degree and informational and functional exchange. Discussion and evaluation Both networks demonstrated growth and inclusion of most or all network members. In the Trainee Network, those with the highest level of out-degree had the highest reports of informational exchange, χ2 (1, N = 23) = 123.61, p < 0.01. We did not find a statistically significant relationship between out-degree and functional exchange in this network, χ2(1, N = 23) = 26.11, p > 0.05. In the Trainee-Supporter Network, trainees with the highest level of out-degree had the highest reports of informational exchange, χ2 (1, N = 23) = 74.93, p < 0.05. The same pattern held for functional exchange, χ2 (1, N = 23) = 81.31, p < 0.01. Conclusions We found substantial and productive development of social networks in the first year of a healthcare management capacity-building program. Environmental constraints, such as limited access to information and communication technologies, or challenges with transportation and logistics, may limit the ability of some participants to engage in the networks fully. This work suggests that intentional social network development may be an important opportunity for capacity-building programs as healthcare systems improve their ability to manage resources and tackle emerging problems.

Abstract Background Management training is fundamental to developing human resources for health. Particularly as Liberia revives its health delivery system, facility and county health team managers are central to progress. Nevertheless, such management skills are rarely prioritized in health training, and sustained capacity building in this area is limited. We describe a health management delivery program in which a north and south institution collaborated to integrate classroom and field-based training in health management and to transfer the capacity for sustained management development in Liberia. Methods We developed and implemented a 6-month training program in health management skills (i.e. strategic problem solving, financial management, human resource management and leadership) delivered by Yale University and Mother Patern College from Liberia, with support from the Clinton HIV/AIDS Initiative. Over three 6-month cycles, responsibility for course instruction was transferred from the north institution to the south institution. A self-administered survey was conducted of all participants completing the course to measure changes in self-rated management skills, the degree to which the course was helpful and met its stated objectives, and faculty members' responsiveness to participant needs as the transfer process occurred. Results Respondents (n = 93, response rate 95.9%) reported substantial improvement in self-reported management skills, and rated the helpfulness of the course and the degree to which the course met its objectives highly. Levels of improvement and course ratings were similar over the three cohorts as the course was transferred to the south institution. We suggest a framework of five elements for implementing successful management training programs that can be transferred and sustained in resource-limited settings, including: 1) use a short-course format focusing on four key skill areas with practical tools; 2) include didactic training, on-site projects, and on-site mentoring; 3) collaborate with an in-country academic institution, willing and able to scale-up and maintain the training; 4) provide training for the in-country academic faculty; and 5) secure Ministry-level support to ensure participation. Conclusion Our findings demonstrate key elements for scaling up and replicating educational initiatives that address management skills essential for long-term health systems strengthening in resource-poor settings.

Abstract Background Despite decades of efforts to improve quality of health care, poor performance persists in many aspects of care. Less than 1% of the enormous national investment in medical research is focused on improving health care delivery. Furthermore, when effective innovations in clinical care are discovered, uptake of these innovations is often delayed and incomplete. In this paper, we build on the established principle of 'positive deviance' to propose an approach to identifying practices that improve health care quality. Methods We synthesize existing literature on positive deviance, describe major alternative approaches, propose benefits and limitations of a positive deviance approach for research directed toward improving quality of health care, and describe an application of this approach in improving hospital care for patients with acute myocardial infarction. Results The positive deviance approach, as adapted for use in health care, presumes that the knowledge about 'what works' is available in existing organizations that demonstrate consistently exceptional performance. Steps in this approach: identify 'positive deviants,' i.e., organizations that consistently demonstrate exceptionally high performance in the area of interest (e.g., proper medication use, timeliness of care); study the organizations in-depth using qualitative methods to generate hypotheses about practices that allow organizations to achieve top performance; test hypotheses statistically in larger, representative samples of organizations; and work in partnership with key stakeholders, including potential adopters, to disseminate the evidence about newly characterized best practices. The approach is particularly appropriate in situations where organizations can be ranked reliably based on valid performance measures, where there is substantial natural variation in performance within an industry, when openness about practices to achieve exceptional performance exists, and where there is an engaged constituency to promote uptake of discovered practices. Conclusion The identification and examination of health care organizations that demonstrate positive deviance provides an opportunity to characterize and disseminate strategies for improving quality.

Abstract Background Less than half of U.S. hospitals meet guidelines for prompt treatment of ST-segment elevation myocardial infarction (STEMI). The Door-to-Balloon (D2B) Alliance is a collaborative effort of more than 900 hospitals committed to implementing a set of evidence-based strategies for reducing D2B time. This study presents data on (1) the prevalence of evidence-based strategies in U.S. hospitals that participated in the D2B Alliance and (2) identifies key hospital characteristics associated with their use. Methods We conducted a cross-sectional study of U.S. hospitals that joined the D2B Alliance through a Web-based survey about their current practices for patients with STEMI who received primary percutaneous coronary intervention (PCI). We used multivariate logistic regression to identify hospital characteristics associated with use of each strategy. Results Of the 915 U.S. hospitals enrolled in the D2B Alliance as of June 2007, 797 (87%) completed the survey. Only 30.4% of responding hospitals reported employing at least 4 of the 5 key strategies (emergency medicine activates catheterization laboratory, single-call activation, expectation that catheterization team is available in the laboratory within 20–30 minutes after page, prompt data feedback on D2B times, use of pre-hospital electrocardiograms to activate the laboratory while the patient is en route to the hospital); 9.3% employed none of the strategies. There was no clear pattern of correlation between hospital characteristics and reported strategies. Conclusion As of 2007, many hospitals had implemented few of the key strategies to reduce D2B time, suggesting substantial opportunity to improve care for patients with STEMI.

Fulvia fulva and Dothistroma septosporum are closely related apoplastic pathogens with similar lifestyles but different hosts: F. fulva is a pathogen of tomato, whilst D. septosporum is a pathogen of pine trees. In 2012, the first genome sequences of these pathogens were published, with F. fulva and D. septosporum having highly fragmented and near-complete assemblies, respectively. Since then, significant advances have been made in unravelling their genome architectures. For instance, the genome of F. fulva has now been assembled into 14 chromosomes, 13 of which have synteny with the 14 chromosomes of D. septosporum, suggesting these pathogens are even more closely related than originally thought. Considerable advances have also been made in the identification and functional characterization of virulence factors (e.g., effector proteins and secondary metabolites) from these pathogens, thereby providing new insights into how they promote host colonization or activate plant defence responses. For example, it has now been established that effector proteins from both F. fulva and D. septosporum interact with cell-surface immune receptors and co-receptors to activate the plant immune system. Progress has also been made in understanding how F. fulva and D. septosporum have evolved with their host plants, whilst intensive research into pandemics of Dothistroma needle blight in the Northern Hemisphere has shed light on the origins, migration, and genetic diversity of the global D. septosporum population. In this review, we specifically summarize advances made in our understanding of the F. fulva-tomato and D. septosporum-pine pathosystems over the last 10 years., (© 2023 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

Phytophthora species are notorious plant pathogens, with some causing devastating tree diseases that threaten the survival of their host species. One such example is Phytophthora agathidicida , the causal agent of kauri dieback - a root and trunk rot disease that kills the ancient, iconic and culturally significant tree species, Agathis australis (New Zealand kauri). A deeper understanding of how Phytophthora pathogens infect their hosts and cause disease is critical for the development of effective treatments. Such an understanding can be gained by interrogating pathogen genomes for effector genes, which are involved in virulence or pathogenicity. Although genome sequencing has become more affordable, the complete assembly of Phytophthora genomes has been problematic, particularly for those with a high abundance of repetitive sequences. Therefore, effector genes located in repetitive regions could be truncated or missed in a fragmented genome assembly. Using a combination of long-read PacBio sequences, chromatin conformation capture (Hi-C) and Illumina short reads, we assembled the P. agathidicida genome into ten complete chromosomes, with a genome size of 57 Mb including 34% repeats. This is the first Phytophthora genome assembled to chromosome level and it reveals a high level of syntenic conservation with the complete genome of Peronospora effusa , the only other completely assembled genome sequence of an oomycete. All P. agathidicida chromosomes have clearly defined centromeres and contain candidate effector genes such as RXLRs and CRNs, but in different proportions, reflecting the presence of gene family clusters. Candidate effector genes are predominantly found in gene-poor, repeat-rich regions of the genome, and in some cases showed a high degree of duplication. Analysis of candidate RXLR effector genes that occur in multicopy gene families indicated half of them were not expressed in planta . Candidate CRN effector gene families showed evidence of transposon-mediated recombination leading to new combinations of protein domains, both within and between chromosomes. Further analysis of this complete genome assembly will help inform new methods of disease control against P. agathidicida and other Phytophthora species, ultimately helping decipher how Phytophthora pathogens have evolved to shape their effector repertoires and how they might adapt in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cox, Guo, Winter, Sen, Cauldron, Shiller, Bradley, Ganley, Gerth, Lacey, McDougal, Panda, Williams, Grunwald, Mesarich and Bradshaw.)

During host colonization, plant-associated microbes, including fungi and oomycetes, deliver a collection of glycoside hydrolases (GHs) to their cell surfaces and surrounding extracellular environments. The number and type of GHs secreted by each organism is typically associated with their lifestyle or mode of nutrient acquisition. Secreted GHs of plant-associated fungi and oomycetes serve a number of different functions, with many of them acting as virulence factors (effectors) to promote microbial host colonization. Specific functions involve, for example, nutrient acquisition, the detoxification of antimicrobial compounds, the manipulation of plant microbiota, and the suppression or prevention of plant immune responses. In contrast, secreted GHs of plant-associated fungi and oomycetes can also activate the plant immune system, either by acting as microbe-associated molecular patterns (MAMPs), or through the release of damage-associated molecular patterns (DAMPs) as a consequence of their enzymatic activity. In this review, we highlight the critical roles that secreted GHs from plant-associated fungi and oomycetes play in plant-microbe interactions, provide an overview of existing knowledge gaps and summarize future directions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bradley, Ökmen, Doehlemann, Henrissat, Bradshaw and Mesarich.)

The polymeric coating used in metal packaging such as cans for foods and beverages may contain residual amounts of monomers used in the production of the coating, as well as unreacted linear and cyclic oligomers. Traditionally, although designed for use with plastic food contact materials, food simulants have been used to determine the migration of monomers from coatings into foodstuffs. More recently, food simulants have also been used to determine oligomeric species migrating from can coatings. In the work reported here, the migration of both monomers and oligomers from polyester-based can coatings into food simulants and foodstuffs, some of which were towards the end of their shelf-life, is compared. The concentrations of monomers and selected oligomers in canned foods at the end of their shelf life were found to be significantly lower than those in food simulants, which in turn was lower than those in the extraction solvent acetonitrile.

Objectives: To document the existence of primary pancreatic secretinoma in patients with watery diarrhea syndrome (WDS) and achlorhydria and establish secretin as a diarrheogenic hormone., Background: Vasoactive intestinal peptide (VIP) has been widely accepted as the main mediator of WDS. However, in 1968, Zollinger et al reported 2 female patients with pancreatic neuroendocrine tumors, WDS, and achlorhydria. During surgery on the first, a 24-year-old patient, they noticed distended duodenum filled with fluid and a dilated gallbladder containing dilute bile with high bicarbonate concentration. After excision of the tumor, WDS ceased and gastric acid secretion returned. The second, a 47-year-old, patient's metastatic tumor extract given intravenously in dogs, produced significantly increased pancreatic and biliary fluid rich in bicarbonate. They suggested a secretin-like hormone of islet cell origin explains WDS and achlorhydria. These observations, however, predated radioimmunoassay, immunohistochemical staining, and other molecular studies., Methods: The first patient's tumor tissue was investigated for secretin and VIP. Using both immunohistochemistry and laser microdissection and pressure catapulting technique for RNA isolation and subsequent reverse transcription polymerase chain reaction, the expression levels of secretin, and VIP were measured., Results: Immunoreactive secretin and its mRNA were predominantly found in the tumor tissue whereas VIP and its mRNA were scarce., Conclusions: The findings strongly support that the WDS and achlorhydria in this patient may have been caused by secretin as originally proposed in 1968 and that secretin may act as a diarrheogenic hormone.

Fenton's reagent was used to isolate microplastics from organic-rich wastewater. The catalytic reaction did not affect microplastic chemistry or size, enabling its use as a pre-treatment method for focal plane array-based micro-FT-IR imaging. Compared with previously described microplastic treatment methods, Fenton's reagent offers a considerable reduction in sample preparation times.

Sexual risk reduction interventions are often ineffective for women who drink alcohol. The present study examines whether an alcohol-related sexual risk reduction intervention successfully trains women to increase assertive communication behaviors and decrease aggressive communication behaviors. Women demonstrated their communication skills during interactive role-plays with male role-play partners. Young, unmarried, and nonpregnant African American women (N = 228, ages 18-24) reporting unprotected vaginal or anal sex and greater than three alcoholic drinks in the past 90 days were randomly assigned to a control, a sexual risk reduction, or a sexual and alcohol risk reduction (NLITEN) condition. Women in the NLITEN condition significantly increased assertive communication behavior compared to women in the control condition, yet use of aggressive communicative behaviors was unchanged. These data suggest assertive communication training is an efficacious component of a sexual and alcohol risk reduction intervention. Public health practitioners and health educators may benefit from group motivational enhancement therapy (GMET) training and adding a GMET module to existing sexual health risk reduction interventions. Future research should examine GMET's efficacy in combination with other evidence-based interventions within other populations and examine talking over and interrupting one's sexual partner as an assertive communication behavior within sexual health contexts., Competing Interests: Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2016 Society for Public Health Education.)

Long-term, sublethal methylmercury exposure can cause reproductive depression, immune suppression, endocrine disruption and other problems in birds. We used two biomarkers to detect oxidative stress in livers of zebra finches (Taeniopygia guttata) developmentally exposed to sublethal levels of dietary methylmercury (0.0, 0.3, 0.6, 1.2, or 2.4 μg/g wet weight in diet). Our findings indicate that young adult finches exposed to environmentally relevant concentrations of mercury in ovo and through their diets, exhibited oxidative stress in their livers. We measured the ratio of the antioxidant glutathione in its reduced form (GSH) versus its oxidized form (GSSG) and the activity of the superoxide dismutase (SOD) enzyme suite. Blood total mercury served as a proxy for liver mercury concentration, and was on average 8.4 times the dietary dose (e.g., birds consuming 0.6 μg/g had blood mercury levels of ~5 μg/g on a wet weight basis). Consistent with what is known from large, aquatic bird species, there was a significant, negative relationship between GSH/GSSG ratios and tissue mercury concentrations, which is indicative of oxidative stress. This relationship was driven by a significant increase in the oxidized glutathione in the livers of birds with higher blood mercury levels. SOD activity was also found to have a significant, negative relationship with blood mercury.

Although songbirds accumulate mercury at rates equivalent to better-studied aquatic avian species, effects of mercury bioaccumulation in songbirds remain understudied. Little is known about the effects of mercury on endocrine physiology, but recent evidence indicates that mercury may disrupt the function of the hypothalamic-pituitary-adrenal axis. Both field-based correlational studies and a recent dosing experiment suggest that mercury exposure alters levels of the primary avian stress hormone, CORT. We sampled zebra finches that had been dosed with 0, 0.5, or 1.0 ppm dietary methylmercury for baseline CORT twice; once during pairing and once after successfully fledging young. Circulating levels of CORT were not significantly affected by mercury exposure. However, our findings indicate potentially important differences in CORT responses between the sexes when exposed to environmentally relevant doses of mercury across the nesting cycle.

Mercury can disrupt the endocrine systems of mammals and fish, but little is known about its effects on avian hormones. The authors employed an experimental manipulation to show that methylmercury suppresses the stress-induced corticosterone response in birds, an effect previously unreported in the literature. Corticosterone regulates many normal metabolic processes, such as the maintenance of proper blood glucose levels during stressful daily fasting; an inability to increase corticosterone levels in response to stressors renders a bird less able to face a wide array of environmental challenges. The authors studied reproductively mature zebra finches that had been exposed to 0.0 µg/g, 0.3 µg/g, 0.6 µg/g, 1.2 µg/g, or 2.4 µg/g (wet wt) dietary methylmercury throughout their life (i.e., from the egg onward). In contrast to some field studies, the present study found no significant change in baseline plasma corticosterone concentrations attributable to chronic methylmercury exposure. However, a comparison between the baseline corticosterone levels and levels after 30 min of handling stress revealed that the ability of birds to mount a stress response was reduced with increasing blood total mercury concentration. These results are consistent with adrenal corticoid disruption caused by chronic mercury exposure and mirror a similar study on free-living nestling songbirds exposed to environmental mercury., (© 2014 SETAC.)

Four samples of paper and board (P/B) of a type used for packaging dry foods were subjected to migration tests using mushrooms, apples, potatoes and bananas, and using the polymeric powder Tenax as a food simulant. The P/B samples contained only low levels of diisopropylnaphthalene (DiPN) and diisobutyl phthalate (DiBP) and so the experiments were conducted after impregnating the P/B with added model substances. These were o-xylene, acetophenone, dodecane, benzophenone, DiPN and DiBP. Migration levels depended strongly on the nature of the substance and on the nature of the food and much less on the characteristics of the P/B, except insofar as they affected the contact area - flexible papers giving more extensive contact with the food than thick rigid board. Migration into Tenax was at least a factor of 10 higher than migration into the fresh fruit and vegetables. The food samples were placed in contact with the P/B and then overwrapped loosely with aluminium foil and so this correction factor will tend to be conservative compared with a more open storage of the packed foods. Washing, peeling or cooking the fruits and vegetables after contact with the P/B had a surprisingly small effect on contaminant levels in general, and no one processing step was effective in giving a significant reduction of all the types of chemicals studied. This was because either they had penetrated into the food (so resisting peeling), or were not freely water-soluble (so resisting washing) or were not particularly volatile (so resisting loss by evaporation during cooking).

Foods may be irradiated in their final packaging and this process may affect the composition of the packaging and in turn affect the migration of substances into food. Headspace and liquid injection GC-MS and HPLC with time-of-flight MS have been used to identify and estimate levels of radiolytic products in irradiated finished plastic packaging materials. Fifteen retail packaging materials were studied. Investigations were carried out into the effect of different irradiation types (gamma and electron beam), irradiation doses (1, 3, 7 and 10 kGy) and dose rates (5 kGy s(-1) for electron beam and 0.4 and 1.85 kGy h(-1) for gamma) on the radiolytic products. Any differences seen in comparing the two ionising radiation types were attributed largely to the very different dose rates; for electron beam a 10 kGy dose was delivered in just 2 s whereas using gamma it took 5.4 h. Differences were also seen when comparing the same samples irradiated at different doses. Some substances were not affected by irradiation, others decreased in concentration and others were formed upon increasing doses of irradiation. These results confirm that irradiation-induced changes do occur in substances with the potential to migrate and that the safety of the finished packaging material following irradiation should be assessed.

In this study, processed natural rubber latex was degraded in outdoor aquatic microcosms, under a number of treatment scenarios for 200 days. The analytical strategy adopted aimed to characterise a range of volatile, semi-volatile and non-volatile substances. Zinc, was shown to migrate from the latex into solution and increase in concentration over time. Dissolved compounds for which predicted formulas were generated largely consisted of oxygen containing compounds, and are potential oxidised polyisoprene oligomers of various chain lengths. A classification of samples based on principal component analysis showed a clear separation of the degraded latex samples from the representative controls. This technique identified an increase in the complexity of the substances produced and showed that these substances undergo further degradation and transformation processes. A number of volatile substances were also identified indicating the atmosphere to be a potential receiving environmental compartment for polymer degradates. Overall, the results show that complex mixtures of substances are produced when polymer-based materials degrade under environmental conditions.

Following use polymer materials may be released to the natural environment distributed to various environmental compartments and may undergo a variety of mechanical and chemical weathering processes. This study characterised the degradation of a latex polymer of different thicknesses under a range of environmental conditions in outdoor microcosms. Samples were immersed in either demineralised water, artificial freshwater and marine water media and exposed for a period of 200-250 days with exposure starting at different times of the year. Effects of pH, agitation and the exclusion of light on degradation were also studied. At the end of the exposure period, recovery of polymer material ≥ 1.6 μm ranged from a low of 22.04% (± 16.35, for the freshwater treatment at pH5.5) to a high of 97.73% (± 0.38, for the exclusion of light treatment). The disappearance of the bulk material corresponded to an increase in nanoparticles and dissolved organic material in the test media. Modelled degradation kinetics were characterised by multi-phasic degradation patterns and the results indicated degradation rate is affected by light intensity and polymer thickness. Mass balance analysis indicates that losses of volatile materials to the air compartment may also be occurring., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Phthalates are ubiquitous in the environment and thus exposure to these compounds can occur in various forms. Foods are one source of such exposure. There are only a limited number of studies that describe the levels of phthalates (diesters, monoesters and phthalic acid) in foods and assess the exposure from this source. In this study the levels of selected phthalate diesters, phthalate monoesters and phthalic acid in total diet study (TDS) samples are determined and the resulting exposure estimated. The methodology for the determination of phthalic acid and nine phthalate monoesters (mono-isopropyl phthalate, mono-n-butyl phthalate, mono-isobutyl phthalate, mono-benzyl phthalate, mono-cyclohexyl phthalate, mono-n-pentyl phthalate, mono-(2-ethylhexyl) phthalate, mono-n-octyl phthalate and mono-isononyl phthalate) in foods is described. In this method phthalate monoesters and phthalic acid are extracted from the foodstuffs with a mixture of acidified acetonitrile and dichloromethane. The method uses isotope-labelled phthalic acid and phthalate monoester internal standards and is appropriate for quantitative determination in the concentration range of 5-100 µg kg⁻¹. The method was validated in-house and its broad applicability demonstrated by the analysis of high-fat, high-carbohydrate and high-protein foodstuffs as well as combinations of all three major food constituents. The methodology used for 15 major phthalate diesters has been reported elsewhere. Phthalic acid was the most prevalent phthalate, being detected in 17 food groups. The highest concentration measured was di-(2-ethylhexyl) phthalate in fish (789 µg kg⁻¹). Low levels of mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate were detected in several of the TDS animal-based food groups and the highest concentrations measured corresponded with the most abundant diesters (di-n-butyl phthalate and di-(2-ethylhexyl) phthalate). The UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT) considered the levels found and concluded that they did not indicate a risk to human health from dietary exposure alone.