Population divergence in heat and drought responses of a coastal plant: from metabolic phenotypes to plant morphology and growth.

Studying intraspecific variation in multistress responses is central for predicting and managing the population dynamics of wild plant species under rapid global change. Yet, it remains a challenging goal in this field to integrate knowledge on the complex biochemical underpinnings for the targeted 'non-model' species. Here, we studied divergence in combined drought and heat responses among Northern and Southern European populations of the dune plant Cakile maritima, by combining comprehensive plant phenotyping with metabolic profiling via FT-ICR-MS and UPLC-TQ-MS/MS. We observed pronounced constitutive divergence in growth phenology, leaf functional traits, and defence chemistry (glucosinolates and alkaloids) among population origins. Most importantly, the magnitude of growth reduction under drought was partly weaker in southern plants and associated with divergence in plastic growth responses (leaf abscission) and the modulation of primary and specialized metabolites with known central functions not only in plant abiotic but also in biotic stress responses. Our study indicates that divergent selection has shaped the constitutive and drought-/heat-induced expression of numerous morphological and biochemical functional traits to mediate higher abiotic stress resistance in southern Cakile populations, and highlights that metabolomics can be a powerful tool to explore the underlying mechanisms of local adaptation in 'non-model' species.

Preventive care recommendations to promote health equity.

BACKGROUND: Avoidable disparities in health outcomes persist in Canada despite substantial investments in a publicly funded health care system that includes preventive services. Our objective was to provide preventive care recommendations that promote health equity by prioritizing effective interventions for people experiencing disadvantages. METHODS: The guideline was developed by a primary care provider-patient panel, with input from a patient-partner panel with diverse lived experiences. After selecting priority topics, we searched for systematic reviews and recent randomized controlled trials of screening and other relevant studies of screening accuracy and management efficacy. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach to develop recommendations and followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) reporting guidance. We managed competing interests using the Guideline International Network principles. The recommendations were externally reviewed by content experts and circulated for endorsement by national stakeholders. RECOMMENDATIONS: We developed 15 screening and other preventive care recommendations and 1 policy recommendation on improving access to primary care. We recommend prioritized outreach for colorectal cancer screening starting at age 45 years and for cardiovascular disease risk assessment, to help address inequities and promote health. Specific interventions that should be rolled out in ways that address inequities include human papillomavirus (HPV) self-testing, HIV self-testing and interferon-γ release assays for tuberculosis infection. Screening for depression, substance use, intimate partner violence and poverty should help connect people experiencing specific disadvantages with proven interventions. We recommend automatic connection to primary care for people experiencing disadvantages. INTERPRETATION: Proven preventive care interventions can address health inequities if people experiencing disadvantages are prioritized. Clinicians, health care organizations and governments should take evidence-based actions and track progress in promoting health equity across Canada.

Sphingolipids in Atherosclerosis: Chimeras in Structure and Function.

Atherosclerosis-a systemic inflammatory disease-is the number one cause of mortality and morbidity worldwide. As such, the prevention of disease progression is of global interest in order to reduce annual deaths at a significant scale. Atherosclerosis is characterized by plaque formation in the arteries, resulting in vascular events such as ischemic stroke or myocardial infarction. A better understanding of the underlying pathophysiological processes at the cellular and molecular level is indispensable to identify novel therapeutic targets that may alleviate disease initiation or progression. Sphingolipids-a lipid class named after the chimeric creature sphinx-are considered to play a critical and, metaphorically, equally chimeric regulatory role in atherogenesis. Previous studies identified six common sphingolipids, namely dihydroceramide (DhCer), ceramide (Cer), sphingosine-1-phosphate (S1P), sphingomyelin (SM), lactosylceramide (LacCer), and glucosylceramide (GluCer) in carotid plaques, and demonstrated their potential as inducers of plaque inflammation. In this review, we point out their specific roles in atherosclerosis by focusing on different cell types, carrier molecules, enzymes, and receptors involved in atherogenesis. Whereas we assume mainly atheroprotective effects for GluCer and LacCer, the sphingolipids DhCer, Cer, SM and S1P mediate chimeric functions. Initial studies demonstrate the successful use of interventions in the sphingolipid pathway to prevent atherosclerosis. However, as atherosclerosis is a multifactorial disease with a variety of underlying cellular processes, it is imperative for future research to emphasize the circumstances in which sphingolipids exert protective or progressive functions and to evaluate their therapeutic benefits in a spatiotemporal manner.

Combustion of crude oil during in-situ burning can introduce polycyclic aromatic compounds (PACs) into small-scale freshwater systems.

In-situ burning (ISB) is the controlled combustion of an oil slick to remove large quantities of spilled oil from the aquatic environment. Prior to employing ISB as a remediation technique, an oil slick must often be corralled by physical or chemical means to achieve a sufficient thickness (typically >1 mm) for ignition. While ISB is an effective means to remove oil mass, less is known about the potential for ISB to mobilize polycyclic aromatic compounds (PACs) into the aquatic environment. The PACs are primary contaminants of concern in crude oil due to their environmental persistence and toxicity. We examined the potential for ISB to mobilize PACs into underlying waters in a series of small-scale burns conducted across a gradient of oil slick thicknesses (0-7 mm). Concentrations of PACs in underlying waters were evaluated and compared to reference conditions using an equivalent gradient of oil slick thicknesses that were not ignited. At thinner slick thicknesses (i.e. 0 - 4 mm) ISB enhanced the mobilization of total PACs, likely a result of heat transfer to underlying waters; this effect increased as slick thickness increased. Among thicker slicks (i.e. 4 - 7 mm), pyrogenic PACs became more prevalent and greater concentrations of 4-ring PACs were detected in underlying waters. The potential for PAC mobilization needs to be considered in scenarios where ISB may be the only viable oil spill remediation option (e.g. wetlands, marshes, or where oil is entrained) and in shallow systems susceptible to temperature changes.

Effects of Environmentally Relevant Residual Levels of Diluted Bitumen on Wild Fathead Minnows (Pimephales promelas).

Transportation of crude oil across North America's boreal ecozone creates the potential for spills in freshwater where less is known about the sensitivity of resident fish than for marine systems. The sensitivity of wild fathead minnows (FHM) to residual concentrations (ppb range) of the water accommodated fraction (WAF) of diluted bitumen (dilbit) was assessed by exposing them for 21 days followed by a 14 days depuration. Target concentrations were well below detection limits for GC-MS, but were estimated by dilution factor (1:100,000 and 1:1,000,000 WAF:water) to contain less than 0.0003 µg/L of polycyclic aromatic compounds. Confinement and handling stress caused by transfer of wild fish into tanks much smaller than their natural range resulted in mortality and lower body condition among all groups, but interactive effects of oil exposures still resulted in females with smaller cortical alveolar oocytes, and males with larger testicular lobe lumen sizes. Additional studies examining the compounded effects of stress and environmentally relevant oil exposures in wild fishes are needed.

In ovo exposure to brominated flame retardants Part II: Assessment of effects of TBBPA-BDBPE and BTBPE on hatching success, morphometric and physiological endpoints in American kestrels.

Tetrabromobisphenol A bis(2,3-dibromopropyl ether) (TBBPA-BDBPE) and 1,2-bis(2,4,6-tribromophenoxy)ethane (BTPBE) are both brominated flame retardants (BFRs) that have been detected in birds; however, their potential biological effects are largely unknown. We assessed the effects of embryonic exposure to TBBPA-BDBPE and BTBPE in a model avian predator, the American kestrel (Falco sparverius). Fertile eggs from a captive population of kestrels were injected on embryonic day 5 (ED5) with a vehicle control or one of three doses within the range of concentrations that have been detected in biota (nominal concentrations of 0, 10, 50 or 100 ng/g egg; measured concentrations 0, 3.0, 13.7 or 33.5 ng TBBPA-BDBPE/g egg and 0, 5.3, 26.8 or 58.1 ng BTBPE/g egg). Eggs were artificially incubated until hatching (ED28), at which point blood and tissues were collected to measure morphological and physiological endpoints, including organ somatic indices, circulating and glandular thyroid hormone concentrations, thyroid gland histology, hepatic deiodinase activity, and markers of oxidative stress. Neither compound had any effects on embryo survival through 90% of the incubation period or on hatching success, body mass, organ size, or oxidative stress of hatchlings. There was evidence of sex-specific effects in the thyroid system responses to the BTBPE exposures, with type 2 deiodinase (D2) activity decreasing at higher doses in female, but not in male hatchlings, suggesting that females may be more sensitive to BTBPE. However, there were no effects of TBBPA-BDBPE on the thyroid system in kestrels. For the BTPBE study, a subset of high-dose eggs was collected throughout the incubation period to measure changes in BTBPE concentrations. There was no decrease in BTBPE over the incubation period, suggesting that BTBPE is slowly metabolized by kestrel embryos throughout their ∼28-d development. These two compounds, therefore, do not appear to be particularly toxic to embryos of the American kestrel.

Describing a Process for Creating a Patient Visible Quality Educational Display to Increase Patient Engagement in Radiation Oncology Throughout the Canadian Maritimes Provinces.

Here, we report the process for creating a patient visible quality educational display to highlight the collaborative quality working practices of Radiation Oncology clinicians and staff in the main Radiotherapy Centers throughout three Canadian provinces. These processes are often not visible to patients yet they speak directly to the standards of care delivered at these centers. The Canadian Partnership for Quality Radiotherapy (CPQR) Quality Assurance Guidelines for Canadian Radiation Treatment Programs guided this process. The display slides created were approved by the local Radiation Oncology departmental leadership for each participating medical center as well as patient focus groups and revised with feedback from both perspectives. Of 27 patients/families who evaluated the resulting educational patient display, 70% expressed high engagement in the information presented, and 81% felt the display will be of interest to patients receiving radiotherapy treatment. Patients/families surveyed reported that the displayed content made them feel more informed and more comfortable with their treatments. Survey data from this project indicates that increasing transparency and deepening patient education about the quality working practices behind radiotherapy treatments has the potential to empower patients receiving radiotherapy and increase their confidence in the care they are receiving.

Recommandations pour des soins préventifs pour promouvoir l'équité en matière de santé.

CONTEXTE: Malgré des investissements importants dans un système de soins de santé public qui comprend des services préventifs, on continue d'observer des disparités évitables en matière de santé au Canada. L'équipe avait pour objectif de formuler des recommandations pour des soins de santé préventifs qui puissent améliorer l'équité en matière de santé par la priorisation des interventions efficaces à l'intention des groupes défavorisés. MÉTHODES: La ligne directrice a été élaborée par un comité composé de spécialistes en soins primaires et de membres de la patientèle, avec la contribution d'un groupe de patientes-et patientspartenaires ayant vécu diverses expériences. Après avoir sélectionné les sujets à prioriser, nous avons recensé les revues systématiques, les essais randomisés et contrôlés récents sur les méthodes de dépistage et d'autres études pertinentes sur l'efficacité du dépistage et de la prise en charge. Nous avons utilisé l'approche GRADE (Grading of Recommendations, Assessment, Development and Evaluation) pour formuler les recommandations et avons suivi le guide AGREE II (Appraisal of Guidelines for Research and Evaluation) pour rédiger le rapport. Il en a été de même avec les principes du Guidelines International Network pour la gestion des intérêts concurrents. Les recommandations ont été passées en revue par un comité externe d'experts en contenu avant d'être distribuées à des intervenants à l'échelle nationale pour approbation. RECOMMANDATIONS: Nous avons formulé 15 recommandations concernant le dépistage et d'autres soins préventifs et 1 recommandation de nature politique visant à améliorer l'accès aux soins primaires. Ainsi, nous recommandons de prioriser une stratégie de communication pour le dépistage du cancer colorectal à partir de l'âge de 45 ans et pour l'évaluation du risque de maladie cardiovasculaire pour lutter contre les iniquités en matière de santé et promouvoir la santé. Les interventions particulières qui devraient être déployées pour lutter contre les iniquités comprennent l'autodépistage du virus du papillome humain (VPH) et du VIH, et le test de libération de l'interféron γ pour l'infection tuberculeuse. Le dépistage de la dépression, de la toxicomanie, de la violence conjugale et de la pauvreté devrait également permettre aux personnes touchées d'accéder plus facilement à des interventions éprouvées. Nous recommandons une prise de contact systématique avec des professionnels de la santé en soins primaires pour les personnes défavorisées. INTERPRÉTATION: Les interventions préventives éprouvées peuvent aider à combattre les iniquités en matière de santé si la priorité est accordée aux personnes défavorisées. Les médecins, les organisations de santé et les gouvernements devraient adopter des mesures fondées sur des données probantes et en faire le suivi s'ils veulent promouvoir l'équité en matière de santé partout au Canada.

Inhaling Benzene, Toluene, Nitrogen Dioxide, and Sulfur Dioxide, Disrupts Thyroid Function in Captive American Kestrels (Falco sparverius).

Research investigating the effects of air contaminants on biota has been limited to date. Captive adult female American kestrels (Falco sparverius) were exposed to a mixture of benzene (0.6 ppm), toluene (1 ppm), nitrogen dioxide (NO2; 2 ppm) and sulfur dioxide (SO2; 5.6 ppm), in a whole-body inhalation chamber. Thyroid axis responses to meet metabolic demands were examined through thyroid histology, plasma thyroxine (T4), and triiodothyronine (T3), and hepatic outer ring deiodination (T4-ORD). Plasma free (F) T3 and T4 were measured at baseline, and at 9 days and 18 days of exposure, whereas total (T) T3 and TT4, thyroid histology and hepatic T4-ORD were determined at the final 18 day exposure. Inhalation of these contaminants significantly suppressed plasma FT4 and TT4, and depleted follicular colloid and increased epithelial cell height at 18 days, and significantly altered the temporal pattern of plasma FT4. Significant histological changes in the follicular colloid:epithelial cell height ratio indicated sustained T4 production and release by the thyroid glands. There was no effect on plasma FT3, TT3, or hepatic T4-ORD. We hypothesize that contaminant-related activation of the hypothalamus-pituitary-thyroid axis in the kestrels increased elimination of plasma T4 through Phase II enzymes. Further research is required to test this hypothesis in wild birds.

Investigating endocrine and physiological parameters of captive American kestrels exposed by diet to selected organophosphate flame retardants.

Organophosphate triesters are high production volume additive flame retardants (OPFRs) and plasticizers. Shown to accumulate in abiotic and biotic environmental compartments, little is known about the risks they pose. Captive adult male American kestrels (Falco sparverius) were fed the same dose (22 ng OPFR/g kestrel/d) daily (21 d) of tris(2-butoxyethyl) phosphate (TBOEP), tris(2-chloroethyl) phosphate (TCEP), tris(2-chloroisopropyl) phosphate (TCIPP), or tris(1,2-dichloro-2-propyl) phosphate (TDCIPP). Concentrations were undetected in tissues (renal, hepatic), suggesting rapid metabolism. There were no changes in glutathione status, indicators of hepatic oxidative status, or the cholinergic system (i.e., cerebrum, plasma cholinesterases; cerebrum muscarinic, nicotinic receptors). Modest changes occurred in hepatocyte integrity and function (clinical chemistry). Significant effects on plasma free triiodothyronine (FT3) concentrations occurred with exposure to TBOEP, TCEP, TCIPP, and TDCIPP; TBOEP and TCEP had additional overall effects on free thyroxine (FT4), whereas TDCIPP also influenced total thyroxine (TT4). Relative increases (32%-96%) in circulating FT3, TT3, FT4, and/or TT4 were variable with each OPFR at 7 d exposure, but limited thereafter, which was likely maintained through decreased thyroid gland activity and increased hepatic deiodinase activity. The observed physiological and endocrine effects occurred at environmentally relevant concentrations and suggest parent OPFRs or metabolites may have been present despite rapid degradation.

[Elderly patients in psychotherapy--results of an inquiry of psychotherapists]. / Ältere Patienten in der psychotherapeutischen Praxis--Ergebnisse einer Befragung von Psychotherapeuten.

The elderly patients were underrepresented in outpatient psychotherapy, is returned in the clinical literature on the reluctance and skepticism of psychotherapists. In the study presented here, psychotherapists were asked how they perceive the elderly, the attitudes they have towards them and what factors it depends on how many older people a psychotherapist treats. Total confirmed that psychotherapists also create a very positive attitude towards older people of the day. Of particular impact in terms of how many older people treated a psychotherapist, have experience and knowledge in the age of psychotherapy. Overall, there are a number of references for arguing that the clinical field of treating the elderly gradually gains more contours.

Evaluation of Children's Anxiety Level in Relation to a Dental Visit/Treatment and Their Parents' Dental Fear.

The patients' fear of the dentist plays an important role in the everyday life of a dentist. The anxiety level of children in relation to dental treatment/visits and to their parents' dental fear was evaluated in three different centers. Assessments of a modified CFSS-DS (mCFSS-DS) were performed by questionnaire with 60 children and their parents. Children's dmft/DMFT scores, age and gender were evaluated in relation to the parents' perception of their child's anxiety levels. For statistical evaluation, Kruskal-Wallis and Wilcoxon tests as well as Spearman's correlation coefficient (Spearman) were used. The significance level was set at 0.05. There were no significant differences regarding children's mCFSS-DS between the three centers (p = 0.398, Kruskal-Wallis). The parents' mCFSS-DS scores correlated significantly with their children's mCFSS-DS scores (p = 0.004, Spearman). However, the mean mCFSS-DS score of the children was significantly higher than the mean score of parents' perception of their child's anxiety (p = 0.000, Wilcoxon). The age of the child had an influence on the mCFSS-DS score (p = 0.02, Kruskal-Wallis) but neither the children's gender (p = 0.170, Kruskal-Wallis), nor the dmft/DMFT showed an impact (p < 0.725, Spearman). Although a positive correlation was found between the results of the children's and parents' questionnaire, many parents underestimated the anxiety level of their children.

RNA metabarcoding helps reveal zooplankton community response to environmental stressors.

DNA metabarcoding can provide a high-throughput and rapid method for characterizing responses of communities to environmental stressors. However, within bulk samples, DNA metabarcoding hardly distinguishes live from the dead organisms. Here, both DNA and RNA metabarcoding were applied and compared in experimental freshwater mesocosms conducted for assessment of ecotoxicological responses of zooplankton communities to remediation treatment until 38 days post oil-spill. Furthermore, a novel indicator of normalized vitality (NV), sequence counts of RNA metabarcoding normalized by that of DNA metabarcoding, was developed for assessment of ecological responses. DNA and RNA metabarcoding detected similar taxa richness and rank of relative abundances. Both DNA and RNA metabarcoding demonstrated slight shifts in measured α-diversities in response to treatments. NV presented relatively greater magnitudes of differential responses of community compositions to treatments compared to DNA or RNA metabarcoding. NV declined from the start of the experiment (3 days pre-spill) to the end (38 days post-spill). NV also differed between Rotifer and Arthropoda, possibly due to differential life histories and sizes of organisms. NV could be a useful indicator for characterizing ecological responses to anthropogenic influence; however, the biology of target organisms and subsequent RNA production need to be considered.

Responses of Wild Finescale Dace (Phoxinus neogaeus) to Experimental Spills of Cold Lake Blend Diluted Bitumen at the International Institute for Sustainable Development-Experimental Lakes Area, Northwestern Ontario.

Pipelines carrying diluted bitumen (dilbit) traverse North America and may result in dilbit release into sensitive freshwater ecosystems. To better understand the potential effects of a freshwater oil release, the Boreal-lake Oil Release Experiment by Additions to Limnocorrals project at the International Institute for Sustainable Development-Experimental Lakes Area (Ontario, Canada) modeled seven dilbit spills contained within a 10-m diameter of littoral limnocorrals in a boreal lake. Wild finescale dace (Phoxinus neogaeus) were released in the limnocorrals 21 days after oil addition and remained there for 70 days. Dilbit volumes covered a large range representing a regression of real spill sizes and total polycyclic aromatic compounds (TPAC) between 167 ng L-1 day-1 and 1989 ng L-1 day-1 . We report the effects of chronic exposure on reproductive potential as well as physiological responses in the gallbladder and liver. In exposures >1000 ng L-1 day-1 , there was a significant decrease in fish retrieval, culminating in zero recapture from the three highest treatments. Among the fish from the limnocorrals with lower levels of TPAC (<500 ng L-1 day-1 ), effects were inconsistent. Gallbladder bile fluorescence for a naphthalene metabolite was significantly different in fish from the oil-exposed limnocorrals when compared to the lake and reference corral, indicating that fish in these lower exposures were interacting with dilbit-derived polycyclic aromatic compounds. There were no significant differences in condition factor, somatic indices, or hepatocyte volume indices. There were also no significant changes in the development of testes or ovaries of exposed dace. The results from the present study may serve to orient policymakers and emergency responders to the range of TPAC exposures that may not significantly affect wild fish. Environ Toxicol Chem 2022;41:2745-2757. © 2022 SETAC.

Thyroid disruption and oxidative stress in American kestrels following embryonic exposure to the alternative flame retardants, EHTBB and TBPH.

Brominated flame retardant chemicals, such as 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB) (CAS #: 183658-27-7) and bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (TBPH) (CAS #: 26040-51-7), have been detected in avian tissues and eggs from remote regions. Exposure to EHTBB and TBPH has been shown to cause oxidative stress and altered thyroid function in rodents and fish, yet no controlled studies have examined potential adverse effects of exposure in birds. Because flame retardants have been detected in wild raptors, we used American kestrels (Falco sparverius) as a model raptor to determine whether in ovo exposure to EHTBB or TBPH affected growth, hatching success, oxidative stress, or thyroid function. We exposed kestrel embryos to nominal concentrations (10, 50, or 100 ng g-1 egg weight) of EHTBB and TBPH via egg-injection on embryonic day 5. Embryonic exposure (~23 d) to EHTBB increased thyroid gland mass, reduced glandular colloid and total thyroxine (T4) in hatchling males and females, whereas deiodinase enzyme activity increased in males but decreased in females. Hatchlings exposed to TBPH in ovo exhibited reduced colloid and increased oxidative stress. Although exposure to EHTBB and TBPH caused several physiological effects (e.g., heart and brain mass), only exposure to 50 ng g-1 EHTBB appeared to reduce hatching success. Our results suggest these flame retardants may be hazardous for predatory birds. Future research should evaluate long-term survival and fitness consequences in birds exposed to these chemicals.

Comparison of common acute respiratory infection case definitions for identification of hospitalized influenza cases at a population-based surveillance site in Egypt.

BACKGROUND: Multiple case definitions are used to identify hospitalized patients with community-acquired acute respiratory infections (ARI). We evaluated several commonly used hospitalized ARI case definitions to identify influenza cases. METHODS: The study included all patients from a population-based surveillance site in Damanhour, Egypt hospitalized for a broad set of criteria consistent with community acquired ARIs. Naso- and oropharyngeal (NP/OP) swabs were tested for influenza using RT-PCR. Sensitivity, specificity and PPV for influenza identification was compared between the 2014 WHO Severe Acute Respiratory Infection (SARI) definition (fever ≥38°C and cough with onset within 10 days), the 2011 WHO SARI definition (fever ≥38°C and cough with onset within 7 days), the 2006 PAHO SARI definition, the International Emerging Infections Program (IEIP) pneumonia case definition, and the International Management of Childhood Illness (IMCI) case definitions for moderate and severe pneumonia. RESULTS: From June 2009-December 2012, 5768 NP/OP swabs were obtained from 6113 hospitalized ARI patients; 799 (13.9%) were influenza positive. The 2014 WHO SARI case definition captured the greatest number of ARI patients, influenza positive patients and ARI deaths compared to the other case definitions examined. Sensitivity for influenza detection was highest for the 2014 WHO SARI definition with 88.6%, compared to the 2011 WHO SARI (78.2%) the 2006 PAHO SARI (15.8%) the IEIP pneumonia (61.0%) and the IMCI moderate and severe pneumonia (33.8% and 38.9%) case definitions (IMCI applies to <5 only). CONCLUSIONS: Our results support use of the 2014 WHO SARI definition for identifying influenza positive hospitalized SARI cases as it captures the highest proportion of ARI deaths and influenza positive cases. Routine use of this case definition for hospital-based surveillance will provide a solid, globally comparable foundation on which to build needed response efforts for novel pandemic viruses.

Evidence for the need of educational programs for cervical screening in rural Tanzania.

The Ocean Road Cancer Institute (ORCI) in Tanzania sees about 3,000 new cancer patients annually, 47% of whom have advanced cervical cancer. We interviewed 98 women from the screening clinic and 49 women from the new cancer treatment clinic about their education, income, occupation, residence, medical history, and knowledge about cancer. Women in the screening clinic had higher socioeconomic levels, as shown by more education and employment than women in the new-patient clinic. Patients from the screening clinic were also younger, lived in near ORCI, and had better knowledge of cancer than women from the new-patient treatment clinic. Educational programs focused on the importance of cervical screening in rural remote areas of Tanzania may have a positive impact on the early detection and identification of patients at early disease stages.

AutoPEWS: Automating Pediatric Early Warning Score Calculation Improves Accuracy Without Sacrificing Predictive Ability.

INTRODUCTION: Pediatric early warning scores (PEWS) identify hospitalized children at risk for deterioration. Manual calculation is prone to human error. Electronic health records (EHRs) enable automated calculation, removing human error. This study's objective was to compare the accuracy of automated EHR-based PEWS calculation (AutoPEWS) to manual calculation and evaluate the non-inferiority of AutoPEWS in predicting deterioration. METHODS: We performed a retrospective cohort study inclusive of non-intensive care unit inpatients at a freestanding children's hospital over 4.5 months in Fall 2018. AutoPEWS mapped the historical manual PEWS scoring rubric to frequently used EHR documentation. We determined accuracy by comparing the expected respiratory subset score based on the current respiratory rate to the actual respiratory score of AutoPEWS and the manual PEWS. The agreement was determined using kappa statistics. We used predicted probabilities from a generalized linear mixed model to calculate areas under the curve for each combination of scores (AutoPEWS, manual) and deterioration outcome (rapid response team activation, unplanned intensive care unit transfer, critical deterioration event). We compared the adjusted difference in areas under the curves between the scores. Non-inferiority was defined as a difference of <0.05. RESULTS: There were 23,514 total PEWS representative of 5,384 patients. AutoPEWS respiratory scores were 99.97% accurate, while the manual PEWS respiratory scores were 86% accurate. AutoPEWS were higher overall than the manual PEWS (mean 0.65 versus 0.34). They showed a fair-to-good agreement (weighted kappa 0.42). Non-inferiority of AutoPEWS compared with the manual PEWS was demonstrated for all deterioration outcomes. CONCLUSIONS: Automation of PEWS calculation improved accuracy without sacrificing predictive ability.

Report from the 2018 consensus conference on immunomodulating agents in thoracic transplantation: Access, formulations, generics, therapeutic drug monitoring, and special populations.

In 2009, the International Society for Heart and Lung Transplantation recognized the importance and challenges surrounding generic drug immunosuppression. As experience with generics has expanded and comfort has increased, substantial issues have arisen since that time with other aspects of immunomodulation that have not been addressed, such as access to medicines, alternative immunosuppression formulations, additional generics, implications on therapeutic drug monitoring, and implications for special populations such as pediatrics and older adults. The aim of this consensus document is to address critically each of these concerns, expand on the challenges and barriers, and provide therapeutic considerations for practitioners who manage patients who need to undergo or have undergone cardiothoracic transplantation.