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Monitoring animal populations is essential to conservation, and complex monitoring goals require complex resources. Variable detection probabilities can create uncertainty in trends and abundances estimated from point count surveys (e.g. nest counts), as well as from more expensive monitoring methods such as line transect surveys (e.g. aerial surveys). Point count surveys in the form of nest counts are the most common form of sea turtle population monitoring, although in-water aerial surveys are also conducted. We used a loggerhead sea turtle Caretta caretta population model to generate stochastic ‘known’ populations from which we mimicked the information we would obtain from nest counts and from in-water aerial surveys. We subjected the populations to environmental or anthropogenic impacts and compared trends in each monitoring metric with the trend in simulated turtle population size in terms of adult equivalents. Over long time frames, either monitoring scheme performed equally well (mean population growth rates λ over 50 yr were within 1% of the growth rate estimated from simulated adult equivalents). Over shorter time frames, total adult females estimated from simulated nest counts generally tracked closer to adult equivalents than did abundance estimated from simulated aerial surveys; and λ for the nest count metric generally had a lower median absolute relative error. Aerial surveys added value if population impacts affected young turtles (which can take 20-30 yr to become nesters) or if impacts changed the population structure (e.g. changed the stable age distribution). For effective monitoring over short time frames, both monitoring schemes might be warranted.

Background: Sweat chloride (SC) concentrations in people with cystic fibrosis (PwCF) reflect relative CF transmembrane conductance regulator (CFTR) protein function, the primary CF defect. Populations with greater SC concentrations tend to have lesser CFTR function and more severe disease courses. CFTR modulator treatment can improve CFTR function within specific CF genotypes and is commonly associated with reduced SC concentration. However, SC concentrations do not necessarily fall to concentrations seen in the unaffected population, suggesting potential for better CFTR treatment outcomes. We characterized post-modulator SC concentration variability among CHEC-SC study participants by genotype and modulator., Methods: PwCF receiving commercially approved modulators for ≥90 days were enrolled for a single SC measurement. Clinical data were obtained from chart review and the CF Foundation Patient Registry (CFFPR). Variability of post-modulator SC concentrations was assessed by cumulative SC concentration frequencies., Results: Post-modulator SC concentrations (n = 3787) were collected from 3131 PwCF; most (n = 1769, 47 %) were collected after elexacaftor/tezacaftor/ivacaftor (ETI) treatment. Modulator use was associated with lower SC distributions, with post-ETI concentrations the lowest on average. Most post-ETI SC concentrations were <60 mmol/L (79 %); 26 % were <30 mmol/L. Post-ETI distributions varied by genotype. All genotypes containing at least one F508del allele had individuals with post-ETI SC ≥60 mmol/L, with the largest proportion being F508del/minimal function (31 %)., Conclusions: Post-modulator SC concentration heterogeneity was observed among all genotypes and modulators, including ETI. The presence of PwCF with post-modulator SC concentrations within the CF diagnostic range suggests room for additional treatment-associated CFTR restoration in this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

The blood-brain barrier (BBB) restricts the systemic delivery of messenger RNAs (mRNAs) into diseased neurons. Although leucocyte-derived extracellular vesicles (EVs) can cross the BBB at inflammatory sites, it is difficult to efficiently load long mRNAs into the EVs and to enhance their neuronal uptake. Here we show that the packaging of mRNA into leucocyte-derived EVs and the endocytosis of the EVs by neurons can be enhanced by engineering leucocytes to produce EVs that incorporate retrovirus-like mRNA-packaging capsids. We transfected immortalized and primary bone-marrow-derived leucocytes with DNA or RNA encoding the capsid-forming activity-regulated cytoskeleton-associated (Arc) protein as well as capsid-stabilizing Arc 5'-untranslated-region RNA elements. These engineered EVs inherit endothelial adhesion molecules from donor leukocytes, recruit endogenous enveloping proteins to their surface, cross the BBB, and enter the neurons in neuro-inflammatory sites. Produced from self-derived donor leukocytes, the EVs are immunologically inert, and enhanced the neuronal uptake of the packaged mRNA in a mouse model of low-grade chronic neuro-inflammation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

The murine Bordetella pertussis challenge model has been utilized in preclinical research for decades. Currently, inconsistent methodologies are employed by researchers across the globe, making it difficult to compare findings. The objective of this work was to utilize the CD-1 mouse model with two routes of challenge, intranasal and aerosol administration of B. pertussis, to understand the differences in disease manifestation elicited via each route. We observed that both routes of B. pertussis challenge result in dose-dependent colonization of the respiratory tract, but overall, intranasal challenge led to higher bacterial burden in the nasal lavage, trachea, and lung. Furthermore, high dose intranasal challenge results in induction of leukocytosis and pro-inflammatory cytokine responses compared to aerosol challenge. These data highlight crucial differences in B. pertussis challenge routes that should be considered during experimental design., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Weaver et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Hospital discharge is a highly critical and complex process that is prone to medical errors, poor communication, and ineffective synchronization of transitional teams. Improving safety during postacute care transitions has become a national focus. Simulation-based training is an underutilized method of instruction for medical resident transitions of care education., Methods: As an integral part of a transitions curriculum, 36 PGY 1 residents from internal medicine and transitional year residency programs underwent a discharge simulation utilizing a trained simulated participant (SP) and a lay caregiver. The objective of the training was to implement a simulation-based education intervention to improve transition practices and discharge communication in graduate medical education. A faculty observer used a case-specific discharge rubric to standardize feedback to the resident and observed the resident navigate the electronic medical record (EMR) for discharge orders. Pretest and posttest surveys assessing resident attitudes and confidence regarding specific areas of the discharge process were distributed to all participating residents for completion., Results: Thirty-six internal medicine and transitional year residents (100%) completed an observed discharge simulation with an SP and a separate encounter with the EMR discharge navigator. All 36 residents (100%) completed the pretest survey, and 23 (63%) completed the postsurvey evaluation. Postsurvey results showed residents agreed (92%, p < .05) that the simulation increased their confidence in safely discharging a patient., Discussion: Simulation encounters are an effective adjunct to postacute care transition education., (© 2023 Sizemore et al.)

Purpose: To develop and validate an algorithm to estimate probability of ever smoking using administrative claims., Methods: Using population-based samples of Medicare-aged individuals (121,278 Behavioral Risk Factor Surveillance System survey respondents and 207,885 Medicare beneficiaries), we developed a logistic regression model to predict probability of ever smoking from demographic and claims data. We applied the model in 1,657,266 additional Medicare beneficiaries and calculated area under the receiver operating characteristic curve (AUC) using presence or absence of a tobacco-specific diagnosis or procedure code as our "gold standard." We used these "gold standard" and lung/laryngeal cancer codes to over-ride predicted probability as 100%. We calculated Spearman's rho between probability from this full algorithm and smoking assessed in prior Parkinson disease studies, by substituting our observed and prior ("true") smoking-Parkinson disease odds ratios into the attenuation equation., Results: The predictive model contained 23 variables, including basic demographics, high alcohol consumption, asthma, cardiovascular disease and associated risk factors, selected cancers, and indicators of routine medical usage. The AUC was 67.6% (95% confidence interval 67.5%-67.7%) comparing smoking probability to tobacco-specific diagnosis or procedure codes. Spearman's rho for the full algorithm was 0.82., Conclusions: Ever smoking might be approximated in administrative data for use as a continuous, probabilistic variable in epidemiologic analyses., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Brad A. Racette and Susan Searles Nielsen report financial support was provided by the Paula and Rodger Riney Foundation. Susan Searles Nielsen, Brad A. Racette, and Alejandra Camacho-Soto report a relationship with Michael J Fox Foundation for Parkinson’s Research that includes: funding grants., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The mosquito midgut is an important site for bloodmeal regulation while also acting as a primary site for pathogen exposure within the mosquito. Recent studies show that exposure to dehydrating conditions alters mosquito bloodfeeding behaviors as well as post-feeding regulation, likely altering how pathogens interact with the mosquito. Unfortunately, few studies have explored the underlying dynamics between dehydration and bloodmeal utilization, and the overall impact on disease transmission dynamics remains veiled. In this study, we find that dehydration-based feeding in the yellow fever mosquito, Aedes aegypti , prompts alterations to midgut gene expression, as well as subsequent physiological factors involving water control and post-bloodfeeding (pbf) regulation. Altered expression of ion transporter genes and aquaporin 2 (AQP2) in the midgut of dehydrated mosquitoes as well as the rapid reequilibration of hemolymph osmolality after a bloodmeal indicate an ability to expedite fluid and ion processing. These alterations ultimately indicate that female A. aegypti employ mechanisms to ameliorate the detriments of dehydration by imbibing a bloodmeal, providing an effective avenue for rehydration. Continued research into bloodmeal utilization and the resulting effects on arthropod-borne transmission dynamics becomes increasingly important as drought prevalence is increased by climate change.

Background: Given future challenges in conducting large randomized, placebo controlled trials for future CF therapeutics development, we evaluated the potential for using external historical controls to either enrich or replace traditional concurrent placebo groups in CF trials., Methods: The study included data from sequentially completed, randomized, controlled clinical trials, EPIC and OPTIMIZE respectively, evaluating optimal antibiotic therapy to reduce the risk of pulmonary exacerbation in children with early Pseudomonas aeruginosa infection. The primary treatment effect in OPTIMIZE, the risk of pulmonary exacerbation associated with azithromycin, was re-estimated in alternative designs incorporating varying numbers of participants from the earlier trial (EPIC) as historical controls. Bias and precision of these estimates were characterized. Propensity scores were derived to adjust for baseline differences across study populations, and both Poisson and Cox regression were used to estimate treatment efficacy., Results: Replacing 86 OPTIMIZE placebo participants with 304 controls from EPIC to mimic a fully historically controlled trial resulted an 8% reduction in risk of pulmonary exacerbations (Hazard ratio (HR):0.92 95% CI 0.61, 1.34) when not adjusting for key baseline differences between study populations. After adjustment, a 37% decrease in risk of exacerbation (HR:0.63, 95% CI 0.50, 0.80) was estimated, comparable to the estimate from the original trial comparing the 86 placebo participants to 77 azithromycin participants on azithromycin (45%, HR:0.55, 95% CI: 0.34, 0.86). Other adjusted approaches provided similar estimates for the efficacy of azithromycin in reducing exacerbation risk: pooling all controls from both studies provided a HR of 0.60 (95% x`CI 0.46, 0.77) and augmenting half the OPTIMIZE placebo participants with EPIC controls gave a HR 0.63 (95% CI 0.48, 0.82)., Conclusions: The potential exists for future CF trials to utilize historical control data. Careful consideration of both the comparability of controls and of optimal methods can reduce the potential for biased estimation of treatment effects., Competing Interests: Conflict of Interest ASM, MW and GZRB received funding from the NIH during the conduct of this research. GZRB additionally received funding from the Cystic Fibrosis Foundation. BWR has received personal fees from Cystetic Medicines and Vetex Pharmaceuticals for serving as a member of Scientific Advisory Committees., (Copyright © 2021 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Mosquitoes readily lose water when exposed to any humidity less than that of near saturated air unless mitigated, leading to shifts in behavior, survival, distribution, and reproduction. In this study, we conducted a series of physiological experiments on two prominent species in the Culicinae subfamily: Culex pipiens, a vector of West Nile virus, and Aedes aegypti, a vector of yellow fever and Zika to examine the effects of dehydration. We exposed C. pipiens and A. aegypti to non-dehydrating conditions (saturated air), dehydrating conditions (air at a 0.89 kPa saturation vapor pressure deficit), several recovery conditions, as well as to bloodfeeding opportunities. We show that dehydrated mosquitoes increase bloodfeeding propensity, improve retention, and decrease excretion of a post-dehydration bloodmeal. In addition, mosquitoes that take a bloodmeal prior to dehydration exposure show increased survival over non-bloodfed counterparts. Dehydration-induced alterations in survival, reproduction, and bloodfeeding propensity of C. pipiens and A. aegypti resulted in marked changes to vectorial capacity. Ultimately, these results become increasingly important as drought intensifies in association with climate change and mosquitoes become more likely to experience arid periods., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Soybean cyst nematode (SCN), Heterodera glycines , is one of the most destructive soybean pests worldwide. Unlike many diseases, SCN doesn't show above ground evidence of disease until several weeks after infestation. Knowledge of Volatile Organic Compounds (VOCs) related to pests and pathogens of foliar tissue is extensive, however, information related to above ground VOCs in response to root damage is lacking. In temporal studies, gas chromatography-mass spectrometry analysis of VOCs from the foliar tissues of SCN infested plants yielded 107 VOCs, referred to as Common Plant Volatiles (CPVs), 33 with confirmed identities. Plants showed no significant stunting until 10 days after infestation. Total CPVs increased over time and were significantly higher from SCN infested plants compared to mock infested plants post 7 days after infestation (DAI). Hierarchical clustering analysis of expression ratios (SCN: Mock) across all time points revealed 5 groups, with the largest group containing VOCs elevated in response to SCN infestation. Linear projection of Principal Component Analysis clearly separated SCN infested from mock infested plants at time points 5, 7, 10 and 14 DAI. Elevated Styrene (CPV11), D-Limonene (CPV32), Tetradecane (CPV65), 2,6-Di-T-butyl-4-methylene-2,5-cyclohexadiene-1-one (CPV74), Butylated Hydroxytoluene (CPV76) and suppressed Ethylhexyl benzoate (CPV87) levels, were associated with SCN infestation prior to stunting. Our findings demonstrate that SCN infestation elevates the release of certain VOCs from foliage and that some are evident prior to symptom development. VOCs associated with SCN infestations prior to symptom development may be valuable for innovative diagnostic approaches., Competing Interests: MW was employed by BASF Plant Science. The remaining 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. The authors declare that this study received funding from BASF Plant Science. The funder had the following involvement in the study: MW contributed to plant propagation and infestation of plants with nematodes., (Copyright © 2021 Constantino, Oh, Şennik, Andersen, Warden, Oralkan and Dean.)

Objectives:: Real-world experience from a 6-month product familiarization programme (PFP) for 3-monthly paliperidone palmitate in schizophrenia maintenance treatment., Methods:: Prescribers completed an online questionnaire for each patient at enrolment with further questions at second dose (re-supply) stage and a second survey of their overall experience at the end., Results:: Ninety-four patients were enrolled and received a first dose and 23 received a second dose within the 6-month programme; 51.1% had been hospitalised for symptom relapse in the previous 2 years. Reasons for prescribing were convenience of 3-monthly dosing for patients (94.7%) and patient choice (54.6%). Prescribers followed-up at least once-monthly (69.6% cases) and indicated in 48.9% they would consider shared GP care. All patients were satisfied with symptom control and either maintained functioning or showed improvement. Clinicians felt confident with administration and identifying suitable patients and were all 'satisfied' or 'somewhat satisfied' with efficacy and tolerability. All felt patients' treatment goals were either 'met' (81.3%) or 'partly met' (18.7%) and none reported dissatisfaction with relapse prevention., Conclusions:: Convenient 3-monthly dosing was preferred by clinicians and patients, and symptoms were adequately managed. This has the potential to improve adherence and lead to better outcomes as patients only need four intramuscular doses per year.

Occupational manganese (Mn) exposure is associated with the development of parkinsonism; however, the mechanism of neurotoxicity is unknown. Brain positron emission tomography (PET) imaging provides a non-invasive method of assessing dopamineric neuronal function. 6-[ 18 F]fluoro-L-DOPA (FDOPA) PET reflects in-vivo nigrostriatal function, but results in Mn exposure are conflicting. The objective of this study was to investigate the association between Mn exposure secondary to occupational welding, FDOPA striatal uptake, and clinical parkinsonism as measured by Unified Parkinson Disease Rating Scale motor subscore 3 (UPDRS3) scores. FDOPA PET scans were acquired on 72 subjects (27 Mn-exposed welders, 14 other Mn-exposed workers, and 31 non-exposed subjects). We estimated cumulative welding exposure from detailed work histories, and a movement disorders specialist examined all subjects. Striatal volumes of interest were identified on aligned magnetic resonance imaging (MRI) for each subject. Specific striatal FDOPA uptake was calculated with a graphical analysis method. We used linear regression while adjusting for age to assess the association between welding exposure and FDOPA uptake in the caudate, anterior putamen, and posterior putamen. Compared to the non-exposed subjects, mean caudate FDOPA uptake was 0.0014min -1 (95% confidence interval [CI] 0.0008, 0.0020) lower in Mn-exposed welders and 0.0012min -1 (95% CI 0.0005, 0.0019) lower in other Mn-exposed workers (both p≤0.001). There was no clear dose-response association between caudate FDOPA uptake and Mn exposure or UPDRS3 scores. Mn-exposed welders and workers demonstrated lower caudate FDOPA uptake, indicating pre-synaptic dopaminergic dysfunction in Mn-exposed subjects that was not associated with clinical parkinsonism., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (-) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced. The main outcome was the percentage of cardiac marker studies performed within guidelines. Nonguideline orders dominated at baseline. Creatine kinase M and B isoenzyme testing in 7496 order sets failed to detect additional myocardial infarctions but was associated with 42 potentially preventable admissions/quarter. Interruptive computerized soft stops improved guideline compliance from 32.3% to 58% ( P < .001) in services not receiving peer leader intervention and to >80% ( P < .001) with peer leadership that featured dashboard feedback about test order performance. This successful experience was recapitulated in interrupted time series within 2 additional services within facility 1 and then in 2 external hospitals (including a critical access facility). Improvements have been sustained postintervention. Laboratory cost savings at the academic facility were estimated to be ≥US$635 000 per year. National collaborative data indicated that facility 1 improved its order patterns from fourth to first quartile compared to peer norms and imply that nonguideline orders persist elsewhere. This example illustrates how pathologists can provide leadership in assisting clinicians in changing laboratory ordering practices. We found that clinicians respond to local laboratory data about their own test performance and that evidence suggesting harm is more compelling to clinicians than evidence of cost savings. Our experience indicates that interventions done at an academic facility can be readily instituted by private practitioners at external facilities. The intervention data also supplement existing literature that electronic order interruptions are more successful when combined with modalities that rely on peer education combined with dashboard feedback about laboratory order performance. The findings may have implications for the role of the pathology laboratory in the ongoing pivot from quantity-based to value-based health care., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Providing optimal care to patients with recent-onset psychosis can improve outcomes and reduce relapse. However, there is a lack of consistency of the implementation of guidelines for such patients across the Asia-Pacific region. We determined a pragmatic set of recommendations for use on a day-to-day basis to help provide optimal care at this crucial stage of illness. The recommendations were developed over a series of meetings by an international faculty of 15 experts from the Asia-Pacific region, Europe, and South Africa. A structured search of the PubMed database was conducted. This was further developed based on the faculty's clinical experience and knowledge of the literature into 10 key aspects of optimal care for patients during the first five years of a diagnosis of a psychotic disorder, with particular relevance to the Asia-Pacific region. Several common principles emerged: adherence to antipsychotic medications is crucial; substance abuse, psychiatric and medical comorbidities should be addressed; psychosocial interventions play a pivotal role; and family members can play a vital role in overall patient care. By following these recommendations, clinicians may improve outcomes for patients with recent-onset psychosis., (© 2016 The Authors Asia-Pacific Psychiatry Published by John Wiley & Sons Australia, Ltd.)