Current practices in marine systematic conservation planning: protocol for a global scoping review.

Background: Systematic Conservation Planning (SCP) involves a series of steps to identify conservation areas and develop management strategies, incorporating feedbacks, revisions, and iterations at any stage. It is a valuable tool in facilitating the effective implementation of Ecosystem-Based Marine Spatial Planning (EB-MSP). However, few efforts have been carried out to summarize information on methods, trends, and progress in SCP in the designation of Marine Protected Areas (MPAs). The present work aims at providing the protocol to perform a scoping review (ScR) to assess the contribution of SCP to the design of effective MPA networks, identifying both the development of good practices and the presence of gaps of knowledge in terms of criteria for their implementation. Protocol: The ScR will follow the Joanna Briggs Institute (JBI) methodology. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for ScRs supported the definition of this protocol. The three databases Web of Science, Scopus, and Google Scholar will be used for the bibliographic search. Inclusion criteria will be as follows: studies applying SCP in the marine realms worldwide, assessing its contribution to the design of MPA networks. Both peer-reviewed and grey literature will be considered for eligibility. No search limitations will be applied regarding publications' year, stage, subject area and source type. Studies in English, French, German, Greek, Italian, and Spanish will be reviewed. Grey literature will be sourced from pre-print archives, institutional websites and other web-based search engines. The Covidence software will be used for the process of documents selection and data extraction. The findings of the ScR will be presented through tables, graphs, and maps, accompanied by a narrative summary of the outcomes. Conclusions: This comprehensive approach will provide a visual representation of the data, enhancing the understanding and interpretation of the results.

Promoting informed prostate cancer screening decision-making for African American men in a community-based setting.

PURPOSE: Current screening guidelines for prostate cancer (PCa) encourage men to make individual screening decisions after consulting with their primary care provider to weigh the risks and benefits of undergoing prostate specific antigen (PSA) testing, but many men at high risk of PCa diagnosis (notably African American men) are more likely to be uninsured and lack a primary care provider. An academic-community partnership redesigned its community-based screening program to ensure access to services for African American men, incorporating a session with a trained clinical educator in community settings, designed to increase knowledge and promote informed decision-making regarding PSA testing. This study evaluated effects of the intervention on decision-making outcomes. METHODS: To evaluate program efficacy, 88 men completed pre- and post-test surveys assessing outcomes of interest. RESULTS: Participants' knowledge, beliefs, attitudes, anxiety levels, and self-efficacy all improved from pre- to post-test at a statistically significant level. Most notably participants' awareness that PCa is often not life-threatening, and watchful waiting is a reasonable treatment option increased after the encounter. More than half of the study sample felt they had received enough knowledge to make an informed decision about whether the PSA test was right for them. CONCLUSION: Our findings show the program had positive effects on men's ability to make informed decisions about PCa screening and demonstrate that educational outreach programs with an emphasis on informed decision-making can effectively balance screening guidelines with the needs of underserved populations in community settings to improve outcomes.

Multiple imputation with missing data indicators.

Multiple imputation is a well-established general technique for analyzing data with missing values. A convenient way to implement multiple imputation is sequential regression multiple imputation, also called chained equations multiple imputation. In this approach, we impute missing values using regression models for each variable, conditional on the other variables in the data. This approach, however, assumes that the missingness mechanism is missing at random, and it is not well-justified under not-at-random missingness without additional modification. In this paper, we describe how we can generalize the sequential regression multiple imputation imputation procedure to handle missingness not at random in the setting where missingness may depend on other variables that are also missing but not on the missing variable itself, conditioning on fully observed variables. We provide algebraic justification for several generalizations of standard sequential regression multiple imputation using Taylor series and other approximations of the target imputation distribution under missingness not at random. Resulting regression model approximations include indicators for missingness, interactions, or other functions of the missingness not at random missingness model and observed data. In a simulation study, we demonstrate that the proposed sequential regression multiple imputation modifications result in reduced bias in the final analysis compared to standard sequential regression multiple imputation, with an approximation strategy involving inclusion of an offset in the imputation model performing the best overall. The method is illustrated in a breast cancer study, where the goal is to estimate the prevalence of a specific genetic pathogenic variant.

High incidence of early onset preeclampsia is probably the rule and not the exception worldwide. 20th anniversary of the reunion workshop. A summary.

The 11th workshop on Immunology of preeclampsia in Reunion 2018 celebrated its 20th candle In this paper we try to summarize the main tracks of reflections during these two decades. First, of course, the advances in immunology of reproduction in the field of preeclampsia, which was poorly developed 2 decades ago when we first started in 1998. But, this workshop has not been dedicated only to immunology. Second, one of the main reflections has always been, workshop after workshop: "why does preeclampsia exists in humans?" in an evolutionary view, as we have no established natural animal models in the other some 4500 other mammal species. Third, besides the reflections on the biological plausibility of preeclampsia-disease-of-first-pregnancies-at-a-level-of-a-couple (primipaternity rather than primigravidity), i.e. immunology, paternal-maternal conflict, we had to face an apparent conundrum: the human species should have disappeared (almost 40-50% incidence of hypertensive disorders of pregnancy in couples conceiving within the first 4 months of sexual cohabitation). We report then the dialogues we were obliged to have with zoologists who themselves had no clues on our apparent "extravagant sexuality" and strange reproduction (ridiculous low fertility rate of the human female: 25%). Fourth, debates on the main difference between early onset ("rather immunological") and late onset PE ("rather maternal vascular predispositions"). Further, the debate of why high income countries report 90% of their PE being LOP, while other countries describe epidemiologically very high incidences of EOP. Finally, and always present at all workshops, the physiopathology of the reversible systemic maternal vascular inflammation.

Happiness among South African private sector physiotherapists.

BACKGROUND: Happiness of people can affect their daily functioning and work performance. There is limited research assessing the happiness levels of various disciplines within the health care industry. This article is the first attempt to evaluate the happiness levels of private sector physiotherapists in South Africa. OBJECTIVES: Research in happiness and physiotherapy studies are two research areas that are not associated with one another in a global perspective. The objective of this study was to assess the happiness levels of private sector physiotherapists in South Africa. METHODS: A hypothesised model was statistically tested using a quantitative questionnaire, which was completed online. The target population of this study were all private sector physiotherapists who are members of the South African Society of Physiotherapy. A total of 395 respondents participated in the study. RESULTS: This study confirmed that factors such as influence, social relations, life balance, optimism, work and leisure are all positively associated with the happiness levels of private sector physiotherapists in South Africa. These variables are recommended as key focus areas for physiotherapy practice owners to address, in order to positively affect the happiness levels of all people in their workplace. CONCLUSION: The study concludes the following: if happiness becomes a priority, then owners of physiotherapy practices need to generate a workforce who are more productive, demonstrate greater collaboration with colleagues and patients, are more positively energised, are less absent and are more loyal to the practice. CLINICAL IMPLICATIONS: The contribution of this study is that it highlights the importance of managing staff in private physiotherapy practices in a holistic manner.

Amelioration of mechanism-based inactivation of CYP3A4 by a H-PGDS inhibitor.

This work describes the rational amelioration of mechanism-based inactivation (MBI) of Cytochrome P450 (CYP) 3A4 in a human hematopoietic prostaglandin D synthase (hH-PGDS) inhibitor (cpd 1). We utilized metabolism reports in order to check if patterns in the metabolism of 1 and similar compounds by CYP3A4 could be deciphered. Then we used structure based design, first modifying the CYP3A4 crystal structure (pdb code: 4NY4) by adding an oxyferryl moiety to the heme, followed by validating the modified structure to obtain the 1' and 4 position oxidation products of midazolam and then recapitulating the metabolism patterns deciphered previously for 1 and analogs. We checked if the pattern deciphered could lead to a putative reactive moiety. Finally we used the docking pose of 1 into this model of the modified CYP3A4 crystal structure to guide transformation of 1 into MBI-free H-PGDS inhibitors.

Circulating TFH cells, serological memory, and tissue compartmentalization shape human influenza-specific B cell immunity.

Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (TFH) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5-CXCR3+ antibody-secreting B cell population, CD21hiCD27+ memory B cells, and CD21loCD27+ B cells. Activation of circulating TFH cells correlated with the development of both CD21lo and CD21hi memory B cells. However, preexisting antibodies could limit increases in serum antibody titers. IIV had no marked effect on CD8+, mucosal-associated invariant T, γδ T, and natural killer cell activation. In addition, vaccine-induced B cells were not maintained in peripheral blood at 1 year after vaccination. We provide a dissection of rHA-specific B cells across seven human tissue compartments, showing that influenza-specific memory (CD21hiCD27+) B cells primarily reside within secondary lymphoid tissues and the lungs. Our study suggests that a rational design of universal vaccines needs to consider circulating TFH cells, preexisting serological memory, and tissue compartmentalization for effective B cell immunity, as well as to improve targeting cellular T cell immunity.

Resuspension of house dust and allergens during walking and vacuum cleaning.

Conventional wisdom has been that hard, resilient surfaces resuspend fewer particles than carpeted surfaces, however, exceptions to this have been demonstrated and uncertainty remains about the factors that lead to this resuspension, notably, the effect of vacuum cleaning on either increasing or reducing resuspension from flooring. The purpose of this study was to determine how resuspension of house dust by aerodynamic size or particle type, including cat allergen and bacterial endotoxin, is affected by flooring, dust loading, embedding dust, and walking/cleaning activities. House dust was blown in and allowed to settle in a walk-in chamber after overnight deposition followed by walking or a vacuum cleaning procedure. Using an aerosol particle sizer and large-volume air samplers at different heights in the chamber, concentrations of airborne particles, resuspension rates, and fractions were computed for four types of flooring conditions during six walking activities. Carpeting resulted in significantly more airborne cat allergen and airborne endotoxin than a laminate floor. Height does have an effect on measured allergen over carpet and this is apparent with concentrations at the infant and adult air samplers. Walking on laminate flooring resuspends less house dust than walking on an equally dusty carpeted floor, where dust is entirely on the surface of the carpet. However, vacuum cleaning a laminate floor resuspended more dust than vacuum cleaning carpets, at large particle sizes of 5 µm and 10 µm. Activities following a deep cleaning of hard resilient or a carpeted surface is likely to leave no differences in resuspended particles between them.

RNA-seq reveals conservation of function among the yolk sacs of human, mouse, and chicken.

The yolk sac is phylogenetically the oldest of the extraembryonic membranes. The human embryo retains a yolk sac, which goes through primary and secondary phases of development, but its importance is controversial. Although it is known to synthesize proteins, its transport functions are widely considered vestigial. Here, we report RNA-sequencing (RNA-seq) data for the human and murine yolk sacs and compare those data with data for the chicken. We also relate the human RNA-seq data to proteomic data for the coelomic fluid bathing the yolk sac. Conservation of transcriptomes across the species indicates that the human secondary yolk sac likely performs key functions early in development, particularly uptake and processing of macro- and micronutrients, many of which are found in coelomic fluid. More generally, our findings shed light on evolutionary mechanisms that give rise to complex structures such as the placenta. We identify genetic modules that are conserved across mammals and birds, suggesting these modules are part of the core amniote genetic repertoire and are the building blocks for both oviparous and viviparous reproductive modes. We propose that although a choriovitelline placenta is never established physically in the human, the placental villi, the exocoelomic cavity, and the secondary yolk sac function together as a physiological equivalent.

The Integrin LFA-1 Controls T Follicular Helper Cell Generation and Maintenance.

T follicular helper (Tfh) cells are a CD4+ T cell subset critical for long-lived humoral immunity. We hypothesized that integrins play a decisive role in Tfh cell biology. Here we show that Tfh cells expressed a highly active form of leukocyte function-associated antigen-1 (LFA-1) that was required for their survival within the germinal center niche. In addition, LFA-1 promoted expression of Bcl-6, a transcriptional repressor critical for Tfh cell differentiation, and inhibition of LFA-1 abolished Tfh cell generation and prevented protective humoral immunity to intestinal helminth infection. Furthermore, we demonstrated that expression of Talin-1, an adaptor protein that regulates LFA-1 affinity, dictated Tfh versus Th2 effector cell differentiation. Collectively, our results define unique functions for LFA-1 in the Tfh cell effector program and suggest that integrin activity is important in lineage decision-making events in the adaptive immune system.

Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.

Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2). Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections.

Oxidative stress and the evolutionary origins of preeclampsia.

In this speculative paper, I consider the relationship between oxidative stress and the evolution of placentation in eutherian mammals. I argue that epitheliochorial placentation, in which fetal tissues remain separated from maternal blood throughout gestation, has evolved as a protective mechanism against oxidative stress arising from pregnancy, particularly in species with unusually long gestation periods and unusually large placentas. Human beings comprise an unusual species that has the life history characteristics of an epitheliochorial species, but exhibits hemochorial placentation, in which fetal tissues come into direct contact with maternal blood. I argue that the risk of preeclampsia has arisen as a consequence of the failure of human beings to evolve epitheliochorial placentation.

Margin to tumor thickness ratio - A predictor of local recurrence and survival in oral squamous cell carcinoma.

OBJECTIVES: To assess whether small oral squamous cell carcinomas (OSCC) require the same margin clearance as large tumors. We evaluated the association between the ratio of the closest margin to tumor size (MSR) and tumor thickness (MTR) with local control and survival. METHODS AND METHODS: The clinicopathologic and follow up data were obtained for 501 OSCC patients who had surgical resection with curative intent at our institution. MTR and MSR were computed and their associations with local control and survival were assessed using multivariable Cox-regression model. Survival curves were generated using the Kaplan-Meier method. RESULTS: MTR was a better predictor of disease control than MSR. MTR was a predictor of local failure (p=0.033) and disease specific death (p=0.038) after adjusting for perineural invasion, lymphovascular involvement, nodal status, and radiotherapy. A threshold MTR value of 0.3 was identified, above which the risk of local recurrence was low. CONCLUSION: The ratio of margin to tumor thickness was an independent predictor for local recurrence and disease specific death in this cohort. A MTR>0.3 can serve as a useful tool for adjuvant therapy planning as it combines tumor thickness and margin clearance, two well established prognostic factors. The minimum safe margin can be calculated by multiplying the tumor thickness by 0.3. Further prospective studies in other institutions are warranted to confirm the prognostic utility of MTR and assess the generalizability of our threshold values.

Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals.

The relationship between phenotypic variation arising through individual development and phenotypic variation arising through diversification of species has long been a central question in evolutionary biology. Among humans, reduced placental invasion into endometrial tissues is associated with diseases of pregnancy, especially pre-eclampsia, and reduced placental invasiveness has also evolved, convergently, in at least 10 lineages of eutherian mammals. We tested the hypothesis that a common genetic basis underlies both reduced placental invasion arising through a developmental process in human placental disease and reduced placental invasion found as a derived trait in the diversification of Euarchontoglires (rodents, lagomorphs, tree shrews, colugos and primates). Based on whole-genome analyses across 18 taxa, we identified 1254 genes as having evolved adaptively across all three lineages exhibiting independent evolutionary transitions towards reduced placental invasion. These genes showed strong evidence of enrichment for associations with pre-eclampsia, based on genetic-association studies, gene-expression analyses and gene ontology. We further used in silico prediction to identify a subset of 199 genes that are likely targets of natural selection during transitions in placental invasiveness and which are predicted to also underlie human placental disorders. Our results indicate that abnormal ontogenies can recapitulate major phylogenetic shifts in mammalian evolution, identify new candidate genes for involvement in pre-eclampsia, imply that study of species with less-invasive placentation will provide useful insights into the regulation of placental invasion and pre-eclampsia, and recommend a novel comparative functional-evolutionary approach to the study of genetically based human disease and mammalian diversification.

Identical inferences about correlated evolution arise from ancestral state reconstruction and independent contrasts.

Inferences about the evolution of continuous traits based on reconstruction of ancestral states have often been considered more error-prone than analysis of independent contrasts. Here we show that both methods in fact yield identical estimators for the correlation coefficient and regression gradient of correlated traits, indicating that reconstructed ancestral states are a valid source of information about correlated evolution. We show that the independent contrast associated with a pair of sibling nodes on a phylogenetic tree can be expressed in terms of the maximum likelihood ancestral state function at those nodes and their common parent. This expression gives rise to novel formulae for independent contrasts for any model of evolution admitting of a local likelihood function. We thus derive new formulae for independent contrasts applicable to traits evolving under directional drift, and use simulated data to show that these directional contrasts provide better estimates of evolutionary model parameters than standard independent contrasts, when traits in fact evolve with a directional tendency.

Head and neck multidisciplinary team meetings: Effect on patient management.

BACKGROUND: The purpose of this study was for us to present our findings on the prospectively audited impact of head and neck multidisciplinary team meetings on patient management. METHODS: We collected clinical data, the pre-multidisciplinary team meeting treatment plan, the post-multidisciplinary team meeting treatment plans, and follow-up data from all patients discussed at a weekly multidisciplinary team meeting and we recorded the changes in management. RESULTS: One hundred seventy-two patients were discussed in 39 meetings. In 52 patients (30%), changes in management were documented of which 20 (67%) were major. Changes were statistically more likely when the referring physician was a medical or radiation oncologist, when the initial treatment plan did not include surgery, and when the histology was neither mucosal squamous cell cancer nor a skin malignancy. Compliance to the multidisciplinary team meeting treatment recommendation was 84% for all patients and 70% for patients with changes in their treatment recommendation. CONCLUSION: Head and neck multidisciplinary team meetings changed management in almost a third of the cases.

Inferring ancestral states without assuming neutrality or gradualism using a stable model of continuous character evolution.

BACKGROUND: The value of a continuous character evolving on a phylogenetic tree is commonly modelled as the location of a particle moving under one-dimensional Brownian motion with constant rate. The Brownian motion model is best suited to characters evolving under neutral drift or tracking an optimum that drifts neutrally. We present a generalization of the Brownian motion model which relaxes assumptions of neutrality and gradualism by considering increments to evolving characters to be drawn from a heavy-tailed stable distribution (of which the normal distribution is a specialized form). RESULTS: We describe Markov chain Monte Carlo methods for fitting the model to biological data paying special attention to ancestral state reconstruction, and study the performance of the model in comparison with a selection of existing comparative methods, using both simulated data and a database of body mass in 1,679 mammalian species. We discuss hypothesis testing and model selection. The stable model outperforms Brownian and Ornstein-Uhlenbeck approaches under simulations in which traits evolve with occasional large "jumps" in their value, but does not perform markedly worse for traits evolving under a truly Brownian process. CONCLUSIONS: The stable model is well suited to a stochastic process with a volatile rate of change in which biological characters undergo a mixture of neutral drift and occasional evolutionary events of large magnitude.

Outcomes of pediatric low-grade gliomas treated with radiation therapy: a single-institution study.

Radiation therapy is often considered the treatment of choice for low-grade gliomas. However, given the long-term effects of radiation on the developing brain, the appropriate use of radiation therapy in pediatric patients remains controversial. The purpose of this study was to evaluate progression-free survival (PFS) of pediatric low-grade glioma patients treated with radiation therapy. Data were obtained through a retrospective chart review of patients treated between 1991 and 2008 from a single tertiary care center in the midwest. The study population consisted of 17 patients, of whom 8 (47%) had tumor recurrence after radiation therapy. The median follow-up time was 8.2 years, with a range of 2.3 to 17.2 years. The median age at diagnosis was 5.4 years, and the median age at radiation therapy was 9.4 years. The 3- and the 10-year PFS were 69%± 11.7% and 46%± 13.3%, respectively. A significant difference in PFS was seen when comparing brainstem tumors with hypothalamic/optic pathway tumors (P=0.019). Differences in PFS based on the age at diagnosis, the extent of initial surgery, and indication for radiation therapy were not significant. A larger multicenter study is needed to better assess PFS in these patients.

Evolution in health and medicine Sackler colloquium: Comparative genomics of autism and schizophrenia.

We used data from studies of copy-number variants (CNVs), single-gene associations, growth-signaling pathways, and intermediate phenotypes associated with brain growth to evaluate four alternative hypotheses for the genomic and developmental relationships between autism and schizophrenia: (i) autism subsumed in schizophrenia, (ii) independence, (iii) diametric, and (iv) partial overlap. Data from CNVs provides statistical support for the hypothesis that autism and schizophrenia are associated with reciprocal variants, such that at four loci, deletions predispose to one disorder, whereas duplications predispose to the other. Data from single-gene studies are inconsistent with a hypothesis based on independence, in that autism and schizophrenia share associated genes more often than expected by chance. However, differentiation between the partial overlap and diametric hypotheses using these data is precluded by limited overlap in the specific genetic markers analyzed in both autism and schizophrenia. Evidence from the effects of risk variants on growth-signaling pathways shows that autism-spectrum conditions tend to be associated with up-regulation of pathways due to loss of function mutations in negative regulators, whereas schizophrenia is associated with reduced pathway activation. Finally, data from studies of head and brain size phenotypes indicate that autism is commonly associated with developmentally-enhanced brain growth, whereas schizophrenia is characterized, on average, by reduced brain growth. These convergent lines of evidence appear most compatible with the hypothesis that autism and schizophrenia represent diametric conditions with regard to their genomic underpinnings, neurodevelopmental bases, and phenotypic manifestations as reflecting under-development versus dysregulated over-development of the human social brain.

Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha.

OBJECTIVE: To evaluate the safety and efficacy of a chimeric monoclonal antibody to tumor necrosis factor alpha (TNF alpha) in the treatment of patients with rheumatoid arthritis (RA). METHODS: Twenty patients with active RA were treated with 20 mg/kg of anti-TNF alpha in an open phase I/II trial lasting 8 weeks. RESULTS: The treatment was well tolerated, with no serious adverse events. Significant improvements were seen in the Ritchie Articular Index, which fell from a median of 28 at study entry to a median of 6 by week 6 (P < 0.001), the swollen joint count, which fell from 18 to 5 (P < 0.001) over the same period, and in the other major clinical assessments. Serum C-reactive protein levels fell from a median of 39.5 mg/liter at study entry to 8 mg/liter at week 6 (P < 0.001), and significant decreases were also seen in serum amyloid A and interleukin-6 levels. CONCLUSION: Treatment with anti-TNF alpha was safe and well tolerated and resulted in significant clinical and laboratory improvements. These preliminary results support the hypothesis that TNF alpha is an important regulator in RA, and suggest that it may be a useful new therapeutic target in this disease.