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Noise is a consistent problem for x-ray transmission images of High-Energy-Density (HED) experiments because it can significantly affect the accuracy of inferring quantitative physical properties from these images. We consider experiments that use x-ray area backlighting to image a thin layer of opaque material within a physics package to observe its hydrodynamic evolution. The spatial variance of the x-ray transmission across the system due to changing opacity serves as an analog for measuring density in this evolving layer. The noise in these images adds nonphysical variations in measured intensity, which can significantly reduce the accuracy of our inferred densities, particularly at small spatial scales. Denoising these images is thus necessary to improve our quantitative analysis, but any denoising method also affects the underlying information in the image. In this paper, we present a method for denoising HED x-ray images via a deep convolutional neural network model with a modified DenseNet architecture. In our denoising framework, we estimate the noise present in the real (data) images of interest and apply the inferred noise distribution to a set of natural images. These synthetic noisy images are then used to train a neural network model to recognize and remove noise of that character. We show that our trained denoiser network significantly reduces the noise in our experimental images while retaining important physical features.

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Cyanobacterial harmful algal blooms (cyanoHABs) occur in fresh water globally. These can degrade water quality and produce toxins, resulting in ecological and economic damages. Thus, short-term management methods (i.e., algaecides) are necessary to rapidly mitigate the negative impacts of cyanoHABs. In this study, we assess the efficacy of a hydrogen peroxide-based algaecide (PAK® 27) on a Microcystis dominated bloom which occurred within the Pahokee Marina on Lake Okeechobee, Florida, USA. We observed a significant reduction in chlorophyll a (96.81%), phycocyanin (93.17%), and Microcystis cell counts (99.92%), and a substantial reduction in microcystins (86.7%) 48 h after treatment (HAT). Additionally, there was a significant shift in bacterial community structure 48 HAT, which coincided with an increase in the relative abundance of photosynthetic protists. These results indicate that hydrogen peroxide-based algaecides are an effective treatment method for cyanoHAB control and highlight their effects on non-target microorganisms (i.e., bacteria and protists).

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OBJECTIVES: Blood-based multi-cancer early detection (MCED) tests are now commercially available. However, there are currently no consensus guidelines available for head and neck cancer (HNC) providers to direct work up or surveillance for patients with a positive MCED test. We seek to describe cases of patients with positive MCED tests suggesting HNC and provide insights for their evaluation. METHODS: Retrospective chart review of patients referred to Otolaryngology with an MCED result suggesting HNC. Patients enrolled in prospective MCED clinical trials were excluded. Cancer diagnoses were confirmed via frozen-section pathology. RESULTS: Five patients were included (mean age: 69.2 years, range 50-87; 4 male) with MCED-identified-high-risk for HNC or lymphoma. Only patient was symptomatic. After physical exam and follow-up head and neck imaging, circulating tumor HPV DNA testing, two patients were diagnosed with p16 + oropharyngeal squamous cell carcinomas and underwent appropriate therapy. A third patient had no evidence of head and neck cancer but was diagnosed with sarcoma of the thigh. The remaining two patients had no evidence of malignancy after in-depth workup. CONCLUSIONS: In this retrospective study, 2 of 5 patients referred to Otolaryngology with a positive MCED result were diagnosed with HPV + oropharyngeal squamous cell carcinoma. We recommend that positive HNC MCED work up include thorough head and neck examination with flexible laryngoscopy and focused CT or MRI imaging. Given the potential for inaccurate MCED tissue of origin classification, PET/CT may be useful in specific situations. For a patient with no cancer identified, development of clear guidelines is warranted.

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Shallow lakes are typically dominated by macrophytes, which have important functional roles regulating trophic conditions and creating biological habitat. Macrophytes have been shown to strongly influence water chemistry and shape microbial communities in shallow lakes. In Florida, many large, shallow lakes are dominated by alien invasive, submersed macrophytes, such as hydrilla (Hydrilla verticillata [L.F.] Royle) and are intensively managed to reduce infestations and contain the spread of these alien invasive macrophytes. In this study, we investigated the effects of large (40 ha) herbicidal and mechanical control treatments on a large lake located in Central Florida that resulted in the reduction of Hydrilla and concomitant changes in water chemistry and microbial communities (both bacteria and protists [microbial eukaryotes]). We observed a considerable decrease in macrophyte coverage associated with plant control treatments as well as a temporal change in macrophyte coverage in Lake Tohopekaliga. We found that changes in macrophyte coverage, regardless of treatment type, significantly affected the water chemistry of the lake, resulting in a sharp increase of chlorophyll a concentration as well as an increase in turbidity with the decrease of macrophyte coverage. Moreover, the decline in macrophytes led to decreases in microbial community diversity with over-representation of phototrophic functional groups. Specifically, we observed an increase in cyanobacteria with the decrease in macrophyte coverage. Our study highlights the advantages and disadvantages of macrophyte control. Although there was an initial decrease in macrophyte coverage associated with the chemical and mechanical control of aquatic plants, after a few months, we found a considerable increase in coverage. In addition, the increase of cyanobacterial relative abundance demonstrates the possible consequences of aquatic plant control such as cyanobacterial blooms if there is a continued decline of macrophytes.

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Background: Objective measurement of where observers direct their attention to faces when searching for signs of facial plastic surgery (FPS) is currently lacking. Objective: To compare where laypersons direct their attention on facial photographs using eye-tracking software when they are asked to (1) search for signs of aesthetic facial surgery or (2) allowed to gaze without direction (free-gaze). Methods: Naïve observers either free-gazed or examined faces for signs of FPS (FPS-prompted) for 10 s per face while their gaze was recorded by an eye-tracking system. Faces had no known history or signs/stigmata of FPS and were selected from the FACES and CFD databases with a diverse demographic distribution. Gaze times in nine facial subregions were analyzed using mixed-effects linear regression. Results: In FPS-prompted observers (n = 50, mean age 32.7 ± 11.3 years, 23/50 (46%) female), the nose, mouth, cheeks, and forehead experienced the most substantial increases (p < 0.001) and a high percentage of overall gaze time (17.9%, 12.5%, 12.0%, 9.6%, respectively) compared to free-gazing observers [n = 57, 35.5 ± 13.9 years, 31/57 (54%) female]. Conclusions: Observers direct attention differently on a face when searching for signs of plastic surgery with increased attention on the nose, mouth, cheeks, and forehead.

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BACKGROUND: Based in part on the results of randomized controlled trials (RCTs) that suggest a beneficial effect over alternative treatment options, the use of platelet-rich plasma (PRP) for the management of knee osteoarthritis (OA) is widespread and increasing. However, the extent to which these studies are vulnerable to slight variations in the outcomes of patients remains unknown. PURPOSE: To evaluate the statistical fragility of conclusions from RCTs that reported outcomes of patients with knee OA who were treated with PRP versus alternative nonoperative management strategies. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 2. METHODS: All RCTs comparing PRP with alternative nonoperative treatment options for knee OA were identified. The fragility index (FI) and reverse FI were applied to assess the robustness of conclusions regarding the efficacy of PRP for knee OA. Meta-analyses were performed to determine the minimum number of patients from ≥1 trials included in the meta-analysis for which a modification on the event status would change the statistical significance of the pooled treatment effect. RESULTS: In total, this analysis included outcomes from 1993 patients with a mean ± SD age of 58.0 ± 3.8 years. The mean number of events required to reverse significance of individual RCTs (FI) was 4.57 ± 5.85. Based on random-effects meta-analyses, PRP demonstrated a significantly higher rate of successful outcomes when compared with hyaluronic acid (P = .002; odds ratio [OR], 2.19; 95% CI, 1.33-3.62), as well as higher rates of patient-reported symptom relief (P = .019; OR, 1.55; 95% CI, 1.07-2.24), not requiring a reintervention after the initial injection treatment (P = .002; OR, 2.17; 95% CI, 1.33-3.53), and achieving the minimal clinically important difference (MCID) for pain improvement (P = .007; OR, 6.19; 95% CI, 1.63-23.42) when compared with all alternative nonoperative treatments. Overall, the mean number of events per meta-analysis required to change the statistical significance of the pooled treatment effect was 8.67 ± 4.50. CONCLUSION: Conclusions drawn from individual RCTs evaluating PRP for knee OA demonstrated slight robustness. On meta-analysis, PRP demonstrated a significant advantage over hyaluronic acid as well as improved symptom relief, lower rates of reintervention, and more frequent achievement of the MCID for pain improvement when compared with alternative nonoperative treatment options. Statistically significant pooled treatment effects evaluating PRP for knee OA are more robust than approximately half of all comparable meta-analyses in medicine and health care. Future RCTs and meta-analyses should consider reporting FIs and fragility quotients to facilitate interpretation of results in their proper context.

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PURPOSE: To perform a systematic review of the literature to evaluate (1) activity level and knee function, (2) reoperation and failure rates, and (3) risk factors for reoperation and failure of autologous osteochondral transfer (AOT) at long-term follow-up. METHODS: A comprehensive review of the long-term outcomes of AOT was performed. Studies reported on activity-based outcomes (Tegner Activity Scale) and clinical outcomes (Lysholm score and International Knee Documentation Committee score). Reoperation and failure rates as defined by the publishing authors were recorded for each study. Modified Coleman Methodology Scores were calculated to assess study methodological quality. RESULTS: Twelve studies with a total of 495 patients and an average age of 32.5 years at the time of surgery and a mean follow-up of 15.1 years (range, 10.4-18.0 years) were included. The mean defect size was 3.2 cm2 (range, 1.9-6.9 cm2). The mean duration of symptoms before surgery was 5.1 years. Return to sport rates ranged from 86% to 100%. Conversion to arthroplasty rates ranged from 0% to 16%. The average preoperative International Knee Documentation Committee scores ranged from 32.9 to 36.8, and the average postoperative International Knee Documentation Committee scores at final follow-up ranged from 66.3 to 77.3. The average preoperative Lysholm scores ranged from 44.5 to 56.0 and the average postoperative Lysholm scores ranged from 70.0 to 96.5. The average preoperative Tegner scores ranged from 2.5 to 3.0, and the average postoperative scores ranged from 4.1 to 7.0. CONCLUSIONS: AOT of the knee resulted in high rates of return to sport with correspondingly low rates of conversion to arthroplasty at long-term follow-up. In addition, AOT demonstrated significant improvements in long-term patient-reported outcomes from baseline. LEVEL OF EVIDENCE: Level IV, systematic review of Level I-IV studies.

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This paper describes coinage-metal-doped InP quantum dots (QDs) as a platform for enhanced electron transfer to molecular acceptors relative to undoped QDs. A synthetic strategy is developed to prepare doped InP/ZnSe QDs. First-principles DFT calculations show that Ag+ and Cu+ dopants localize photoexcited holes while leaving electrons delocalized. This charge carrier wave function modulation is leveraged to enhance electron transfer to molecular acceptors by up to an order of magnitude. Examination of photoluminescence quenching data suggests that larger electron acceptors, such as anthraquinone and methyl viologen, bind to the QD surface in two ways: by direct adsorption to the surface and by adsorption following displacement of a weakly bound surface cation-ligand complex. Reactions with larger acceptors show the greatest increases in electron transfer between doped and undoped quantum dots, while smaller acceptors show smaller enhancements. Specifically, benzoquinone shows the smallest, followed by naphthoquinone and then methyl viologen and anthraquinone. These results demonstrate the benefits of dopant-induced excited-state carrier localization on photoinduced charge transfer and highlight design principles for improved implementation of quantum dots in photoredox catalysis.

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BACKGROUND: Septoplasty is used to correct nasal obstruction from nasal septum deviation. However, the long-term efficacy of septoplasty is unclear, and no literature reviews have examined long-term outcomes of septoplasty with or without turbinate modification. This systematic review aimed to evaluate the long-term efficacy of septoplasty with or without turbinate modification in improving nasal obstruction. DATA SOURCES: PubMed, EMBASE, Cochrane CENTRAL. METHODS: A systematic review of the literature was conducted using the aforementioned databases. Studies reporting outcomes 12+ months after functional septoplasty with or without turbinate surgery for nasal obstruction were included. Septorhinoplasties, concurrent sinus surgery, pediatric studies, and studies where septoplasty was performed for indications other than nasal obstruction were excluded. RESULTS: After screening, 35 studies with 4,432 patients were included. Mean weighted post-operative follow-up time was 29.1 months (range 12-120 months). All studies reported significant improvement in subjective and objective outcomes at long-term follow-up compared to baseline. When comparing short-term (<12 months) to long-term (≥12 months) outcomes, four studies noticed that subjective outcomes worsened slightly over time, but no study found a significant change in objective outcomes over time. In addition, 23 studies reported patient satisfaction and/or improvement rates, with 75.4% (2,348/3,113) of patients expressing satisfaction/improvement at an average of 27.0 months after surgery. CONCLUSIONS: Overall, septoplasty with or without turbinate modification shows significant improvement in obstructive symptoms at long-term follow-up per both objective and subjective measures. Whether outcomes may worsen slightly over time remains indeterminate based on mixed results in the literature. LEVEL OF EVIDENCE: N/A Laryngoscope, 2023.

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Capture-recapture (CRC) surveys are used to estimate the size of a population whose members cannot be enumerated directly. CRC surveys have been used to estimate the number of Coronavirus Disease 2019 (COVID-19) infections, people who use drugs, sex workers, conflict casualties, and trafficking victims. When k-capture samples are obtained, counts of unit captures in subsets of samples are represented naturally by a 2k contingency table in which one element-the number of individuals appearing in none of the samples-remains unobserved. In the absence of additional assumptions, the population size is not identifiable (i.e., point identified). Stringent assumptions about the dependence between samples are often used to achieve point identification. However, real-world CRC surveys often use convenience samples in which the assumed dependence cannot be guaranteed, and population size estimates under these assumptions may lack empirical credibility. In this work, we apply the theory of partial identification to show that weak assumptions or qualitative knowledge about the nature of dependence between samples can be used to characterize a nontrivial confidence set for the true population size. We construct confidence sets under bounds on pairwise capture probabilities using two methods: test inversion bootstrap confidence intervals and profile likelihood confidence intervals. Simulation results demonstrate well-calibrated confidence sets for each method. In an extensive real-world study, we apply the new methodology to the problem of using heterogeneous survey data to estimate the number of people who inject drugs in Brussels, Belgium.

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Benthic cyanobacterial mats (BCMs) are natural phenomena in marine environments. Reports of BCMs occurring across coastal marine environments have increased, partly driven by nutrient loading and climate change; thus, there is a need to understand the diversity involved in the proliferations and potential toxicity of the BCMs. Furthermore, marine cyanobacterial mats are observed growing on and affecting the health of corals with one specific cyanobacterial genus, Roseofilum, dominating the microbial mats associated with black band disease (BBD), a destructive polymicrobial disease that affects corals. To explore the diversity of Roseofilum, cyanobacterial mats from various marine habitats were sampled, and individual isolates were identified based on morphology, 16S rRNA gene phylogenies, 16S-23S ITS rRNA region sequence dissimilarities, and phylogenomics. Four novel species of Roseofilum were isolated from benthic marine mats, three from the coasts of Florida, United States (R. capinflatum sp. nov., R. casamattae sp. nov., and R. acuticapitatum sp. nov.) and one from the coast of France (R. halophilum sp. nov.). Our analyses revealed that Roseofilum associated with coral BBD and those not associated with corals but rather from coastal benthic mats are systematically distinct based on both phylogenetic and phylogenomic analyses. Enzyme-linked immunosorbent assay (ELISA) and LC-MS data indicated that microcystin production was found in one of the four species.

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Lake Okeechobee is a large eutrophic, shallow, subtropical lake in south Florida, United States. Due to decades of nutrient loading and phosphorus rich sediments, the lake is eutrophic and frequently experiences cyanobacterial harmful algal blooms (cyanoHABs). In the past, surveys of the phytoplankton community structure in the lake have been conducted by morphological studies, whereas molecular based studies have been seldom employed. With increased frequency of cyanoHABs in Lake Okeechobee (e.g., 2016 and 2018 Microcystis-dominated blooms), it is imperative to determine the diversity of cyanobacterial taxa that exist within the lake and the limnological parameters that drive bloom-forming genera. A spatiotemporal study of the lake was conducted over the course of 1 year to characterize the (cyano)bacterial community structure, using 16S rRNA metabarcoding, with coincident collection of limnological parameters (e.g., nutrients, water temperature, major ions), and cyanotoxins. The objectives of this study were to elucidate spatiotemporal trends of community structure, identify drivers of community structure, and examine cyanobacteria-bacterial relationships within the lake. Results indicated that cyanobacterial communities within the lake were significantly different between the wet and dry season, but not between periods of nitrogen limitation and co-nutrient limitation. Throughout the year, the lake was primarily dominated by the picocyanobacterium Cyanobium. The bloom-forming genera Cuspidothrix, Dolichospermum, Microcystis, and Raphidiopsis were highly abundant throughout the lake and had disparate nutrient requirements and niches within the lake. Anatoxin-a, microcystins, and nodularins were detected throughout the lake across both seasons. There were no correlated (cyano)bacteria shared between the common bloom-forming cyanobacteria Dolichospermum, Microcystis, and Raphidiopsis. This study is the first of its kind to use molecular based methods to assess the cyanobacterial community structure within the lake. These data greatly improve our understanding of the cyanobacterial community structure within the lake and the physiochemical parameters which may drive the bloom-forming taxa within Lake Okeechobee.

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Here, we report the draft genome sequences of nine bacterial species isolated from eutrophic waters associated with cyanobacterial harmful algal blooms with cyanocidal potential.

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Cyanobacteria are photosynthetic bacteria that occupy various habitats across the globe, playing critical roles in many of Earth's biogeochemical cycles both in both aquatic and terrestrial systems. Despite their well-known significance, their taxonomy remains problematic and is the subject of much research. Taxonomic issues of Cyanobacteria have consequently led to inaccurate curation within known reference databases, ultimately leading to problematic taxonomic assignment during diversity studies. Recent advances in sequencing technologies have increased our ability to characterize and understand microbial communities, leading to the generation of thousands of sequences that require taxonomic assignment. We herein propose CyanoSeq (https://zenodo.org/record/7569105), a database of cyanobacterial 16S rRNA gene sequences with curated taxonomy. The taxonomy of CyanoSeq is based on the current state of cyanobacterial taxonomy, with ranks from the domain to genus level. Files are provided for use with common naive Bayes taxonomic classifiers, such as those included in DADA2 or the QIIME2 platform. Additionally, FASTA files are provided for creation of de novo phylogenetic trees with (near) full-length 16S rRNA gene sequences to determine the phylogenetic relationship of cyanobacterial strains and/or ASV/OTUs. The database currently consists of 5410 cyanobacterial 16S rRNA gene sequences along with 123 Chloroplast, Bacterial, and Vampirovibrionia (formally Melainabacteria) sequences.

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PURPOSE: Since 2012 fentanyl-detected fatal overdoses have risen from 4% of all fatal overdoses in Connecticut to 82% in 2019. We aimed to investigate the geographic and temporal trends in fentanyl-detected deaths in Connecticut during 2009-2019. METHODS: Data on the dates and locations of accidental/undetermined opioid-detected fatalities were obtained from Connecticut Office of the Chief Medical Examiner. Using a Bayesian space-time binomial model, we estimated spatiotemporal trends in the proportion of fentanyl-detected deaths. RESULTS: During 2009-2019, a total of 6,632 opioid deaths were identified. Among these, 3234 (49%) were fentanyl-detected. The modeled spatial patterns suggested that opioid deaths in northeastern Connecticut had higher probability of being fentanyl-detected, while New Haven and its neighboring towns and the southwestern region of Connecticut, primarily Greenwich, had a lower risk. Model estimates also suggested fentanyl-detected deaths gradually overtook the preceding non-fentanyl opioid-detected deaths across Connecticut. The estimated temporal trend showed the probability of fentanyl involvement increased substantially since 2014. CONCLUSIONS: Our findings suggest that geographic variation exists in the probability of fentanyl-detected deaths, and areas at heightened risk are identified. Further studies are warranted to explore potential factors contributing to the geographic heterogeneity and continuing dispersion of fentanyl-detected deaths in Connecticut.

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BACKGROUND AND OBJECTIVES: Published data comparing peritoneal metastases from appendiceal cancers (pAC) and colorectal cancers (pCRC) remain sparse. We compared pAC and pCRC using comprehensive tumor profiling (CTP). METHODS: CTP was performed, including next-generation sequencing and analysis of copy number variation (CNV), microsatellite instability (MSI) and tumor mutational burden (TMB). RESULTS: One hundred thirty-six pAC and 348 pCRC samples underwent CTP. The cohorts' age and gender were similar. pCRC demonstrated increased pathogenic variants (PATHs) in APC (48% vs. 3%, p < 0.01), ARID1A (12% vs. 2%, p < 0.01), BRAF (12% vs. 2%, p < 0.01), FBXW7 (7% vs. 2%, p < 0.01), KRAS (52% vs. 41%, p < 0.05), PIK3CA (15% vs. 2%, p < 0.01), and TP53 (53% vs. 23%, p < 0.01), and decreased PATHs in GNAS (8% vs. 31%, p < 0.01). There was no difference in CNV, fusion rate, or MSI. Median TMB was higher in pCRC (5.8 vs. 5.0 mutations per megabase, p = 0.0007). Rates of TMB-high tumors were similar (pAC 2.1% vs. pCRC 9.0%, p = 0.1957). pCRC had significantly more TMB-high tumors at lower thresholds. CONCLUSIONS: Despite a reduced overall TMB, pAC demonstrated mutations distinct from those seen in pCRC. These may serve as discrete biomarkers for future study.

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INTRODUCTION: Randomized controlled trials are used to estimate the causal effect of a treatment on a health outcome of interest in a patient population. Often the specified treatment in a randomized controlled trial is a medical intervention-such as a drug or procedure-experienced directly by the patient. Sometimes the "treatment" in a randomized controlled trial is a target-such as a goal biomarker measurement-that the patient's physician attempts to reach using available medications or procedures. Large randomized controlled trials of biomarker targets are common in clinical research, and trials have been conducted to compare targets in the management of hypertension, diabetes, anemia, and acute respiratory distress syndrome. However, different randomized controlled trials intended to evaluate the same biomarker targets have produced conflicting recommendations, and meta-analyses that aggregate results of trials of biomarker targets have been inconclusive. METHODS: We use causal reasoning to explain why randomized controlled trials of biomarker targets can arrive at conflicting or misleading conclusions. We describe four key threats to the validity of trials of targets: (1) intention-to-treat analysis can be misleading when a direct effect of target assignment on the outcome exists due to lack of blinding; (2) incomparability in results across trials of targets; (3) time-varying adaptive treatment strategies; and (4) Goodhart's law, "when a measure becomes a target, it ceases to be a good measure." RESULTS: We illustrate these findings using evidence from 15 randomized controlled trials of blood pressure targets for management of hypertension. Randomized trials of blood pressure targets exhibit substantial variation in the trial patient populations and antihypertensives used to achieve the blood pressure targets assigned in the trials. The trials did not compare or account for time-varying treatment strategies used to reach the randomized targets. Possible "off-target" effects of antihypertensive medications needed to reach lower blood pressure targets may explain the absence of a clear benefit from intensive blood pressure control. DISCUSSION: Researchers should critically assess meta-analyses of trials of targets for variation in the types, distributions, and off-target effects of therapies studied. Trial investigators should release detailed information about the biomarker targets compared in new randomized trials, as well as confounders, treatments delivered, and outcomes. New randomized controlled trials should experimentally compare treatment algorithms incorporating biomarkers, rather than targets alone. Causal inference methodology that adjusts for time-varying confounding should be used to compare time-varying treatment strategies in observational settings.

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Peer-driven interventions can be effective in reducing HIV injection risk behaviors among people who inject drugs (PWID). We employed a causal mediation framework to examine the mediating role of recall of intervention knowledge in the relationship between a peer-driven intervention and subsequent self-reported HIV injection-related risk behavior among PWID in the HIV Prevention Trials Network (HPTN) 037 study. For each intervention network, the index participant received training at baseline to become a peer educator, while non-index participants and all participants in the control networks received only HIV testing and counseling; recall of intervention knowledge was measured at the 6-month visit for each participant, and each participant was followed to ascertain HIV injection-related risk behaviors at the 12-month visit. We used inverse probability weighting to fit marginal structural models to estimate the total effect (TE) and controlled direct effect (CDE) of the intervention on the outcome. The proportion eliminated (PE) by intervening to remove mediation by the recall of intervention knowledge was computed. There were 385 participants (47% in intervention networks) included in the analysis. The TE and CDE risk ratios for the intervention were 0.47 [95% confidence interval (CI): 0.28, 0.78] and 0.73 (95% CI: 0.26, 2.06) and the PE was 49%. Compared to participants in the control networks, the peer-driven intervention reduced the risk of HIV injection-related risk behavior by 53%. The mediating role of recall of intervention knowledge accounted for less than 50% of the total effect of the intervention, suggesting that other potential causal pathways between the intervention and the outcome, such as motivation and skill, self-efficacy, social norms and behavior modeling, should be considered in future studies.

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Land use disrupts the ecosystem functioning of freshwater systems and significantly affects trophic state. Consequently, biodiversity is severely affected by changes to the ecosystem. Microbial eukaryotes (i.e., protists) play an essential role in ecosystem functioning, contributing to biogeochemical processes, nutrient cycling, and food webs. Protist composition is a useful biological quality parameter for monitoring aquatic ecosystems and determining aquatic system health. In this study, we investigated the effects of land usage and trophic state on the communities of microbial eukaryotes in the New River (Belize, C.A.). Land use and trophic state both significantly affected protist community compositions, with impacted and mesotrophic sampled sites having higher biodiversity when compared to other sites. Autotrophic organisms dominated indirectly impacted and eutrophic sites, while impacted and mesotrophic sites had proportional ratios of autotrophic and heterotrophic organisms. Our study highlights the significant effects of trophic gradients on protistan community composition, even at the local scales.

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Randomized trials of infectious disease interventions, such as vaccines, often focus on groups of connected or potentially interacting individuals. When the pathogen of interest is transmissible between study subjects, interference may occur: individual infection outcomes may depend on treatments received by others. Epidemiologists have defined the primary parameter of interest-called the "susceptibility effect"-as a contrast in infection risk under treatment versus no treatment, while holding exposure to infectiousness constant. A related quantity-the "direct effect"-is defined as an unconditional contrast between the infection risk under treatment versus no treatment. The purpose of this paper is to show that under a widely recommended randomization design, the direct effect may fail to recover the sign of the true susceptibility effect of the intervention in a randomized trial when outcomes are contagious. The analytical approach uses structural features of infectious disease transmission to define the susceptibility effect. A new probabilistic coupling argument reveals stochastic dominance relations between potential infection outcomes under different treatment allocations. The results suggest that estimating the direct effect under randomization may provide misleading conclusions about the effect of an intervention-such as a vaccine-when outcomes are contagious. Investigators who estimate the direct effect may wrongly conclude an intervention that protects treated individuals from infection is harmful, or that a harmful treatment is beneficial.

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