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Leukemia and lymphoma are cancers affecting children, adolescents, and young adults and may affect reproductive outcomes and maternal metabolism. We evaluated for metabolic changes in newborns of mothers with a history of these cancers.A cross-sectional study was conducted on California births from 2007 to 2011 with linked maternal hospital discharge records, birth certificate, and newborn screening metabolites. History of leukemia or lymphoma was determined using ICD-9-CM codes from hospital discharge data and newborn metabolite data from the newborn screening program.A total of 2,068,038 women without cancer history and 906 with history of leukemia or lymphoma were included. After adjusting for differences in maternal age, infant sex, age at metabolite collection, gestational age, and birthweight, among newborns born to women with history of leukemia/lymphoma, several acylcarnitines were significantly (The varied metabolite levels suggest history of leukemia or lymphoma has metabolic impact on newborn offspring, which may have implications for future metabolic consequences such as necrotizing enterocolitis and urea cycle enzyme disorders in children born to mothers with a history of leukemia or lymphoma.

We used a computational model of the active zone (AZ) in the mammalian neuromuscular junction to investigate Lambert-Eaton myasthenic syndrome (LEMS) pathophysiology. This model suggests that disruptions in presynaptic active zone organization and protein content (particularly synaptotagmin), beyond the simple removal of presynaptic calcium channels, play an important role in LEMS pathophysiology.

First pioneered in 2010, Fish Cam provides the opportunity for students to engage in novel behavioral research without the need for extensive materials or for leaving the classroom. Fish Cam utilizes a robust behavioral paradigm, shoaling behavior in fish, and enables students to collect information from simple, easy-to-understand observations, allowing for student-led experimental design, data collection, analysis, and discussions on the scientific process. In these ways Fish Cam removes the cost and time-intensive aspects of doing this sort of work in the classroom. Shoaling behavior, which is well represented in the scientific literature, refers to social aggregations of fish. Almost all species of fish form shoals, and this process is easy to study under laboratory conditions. An evolutionary adaptation, shoaling provides individuals better access to resources and decreases the risk of predation. In its initial launch, Fish Cam was highly successful as a learning tool but suffered from difficulties associated with delivering the information online in 2010. Now, with the rapid development of online communication tools associated with the COVID-19 pandemic, we have the second iteration of Fish Cam. The flexibility of new delivery platforms enables partner organizations to view experiments and adapt the experience to their specific educational goals. Here we present an overview of Fish Cam, including lesson plans, a description of shoaling behavior in fish, and the results of Fish Cam studies run in the fall of 2020.

This study reports a new methodology for right heart imaging by ultrasound in mice under right ventricular (RV) pressure overload. Pulmonary artery constriction (PAC) or sham surgeries were performed on C57BL/6 male mice at 8 weeks of age. Ultrasound imaging was conducted at 2, 4 and 8 weeks post-surgery using both classical and advanced ultrasound imaging modalities including ECG-based kilohertz visualization, anatomical M-mode and strain imaging. Based on pulsed Doppler, the PAC group demonstrated dramatically enhanced pressure gradient in the main pulmonary artery (MPA) as compared to the sham group. By applying advanced imaging modalities in novel short axis views of the ventricles, the PAC group demonstrated increased thickness of RV free wall, enlarged RV chamber and reduced RV fractional shortening compared to the sham group. The PAC group also showed prolonged RV contraction, asynchronous inter-play between RV and left ventricle (LV), and passive leftward motion of the inter-ventricular septum (IVS) at early diastole. Consequently, the PAC group exhibited prolongation of LV isovolumic relaxation time, without change in LV wall thickness or systolic function. Significant correlations were found between the maximal pressure gradient in MPA measured by Doppler and the RV systolic pressure by catheterization, as well as the morphological and functional parameters of RV by ultrasound.

Hepatitis E virus (HEV) is an emerging viral disease known to cause acute viral hepatitis globally. Various genotypes of HEV have been identified that produce genotype specific lesions depending on the HEV targeted population. Pregnant or immunosuppressed individuals develop significantly more severe hepatitis E in comparison to the general population. In the last 40 years, we discovered that the tropism of HEV is not restricted to the liver, and virus replication was demonstrated in multiple organs. Out of the 10 body systems described in humans, HEV produces lesions causing a broad range of extrahepatic clinical manifestations in each of them. Affected body systems include nervous and musculoskeletal, cardiovascular, digestive, endocrine, integumentary, renal, respiratory, immune, and reproductive systems producing systemic lesions. All extrahepatic signs are caused by either direct HEV replication in these tissues, or indirectly by various immune mediated mechanisms. Extrahepatic replication features of HEV allowed it to cross the placental barrier, blood–brain barrier (BBB), and blood–testis barrier (BTB) that do not typically grant entry to viruses in general. Thus, in this review, we summarized the extrahepatic replication sites of HEV, listed the body systems where HEV invaded, and described multiple animal models including immunocompetent and immunosuppressed that were used to study the extrahepatic replication sites of HEV.

Background: Demographic diversity among clinical trials is required for representing the real-world populations intended for treatment and disease prevention. Moreover, genetic and environmental differences between ethnic and racial groups necessitate appropriately powered trials for relevant subgroups. We investigate the racial and ethnic demographic diversity of US-based participants in GSK-sponsored interventional trials. We also assess the evaluation of demographic diversity against US Census and epidemiologic data. Methods: GSK-sponsored interventional phase I–IV clinical trials conducted from 2002 to 2019 across three areas were analyzed: pharmaceutical (includes therapeutic medicines except for vaccines and human immunodeficiency virus (HIV)), vaccine (includes prophylactic and therapeutic vaccines), and ViiV (includes HIV therapies). A total of 1005 global trials encompassing 460,707 global participants were identified, of which 495 had US-based sites with a total of 108,261 (23.5% of global) US participants (pharmaceutical, n = 357 trials; vaccine, n = 45 trials; and ViiV, n = 93 trials). We evaluated how GSK US-based trial recruitment compares with US Census (in line with previously published studies from other groups) and with epidemiologic data. Results: GSK participant data for race and ethnicity combined across areas were generally similar to US Census levels (e.g. GSK versus census: White, 76.5% versus 76.3%; Black or African American, 15.1% versus 13.4%; Asian, 1.8% versus 5.9%; Hispanic or Latino, 14.0% versus 18.5%; Non-Hispanic White, 63.5% versus 60.1%). However, this was not the case for the individual pharmaceutical, vaccine, and ViiV data sets; least represented groups were Asian individuals for pharmaceutical and ViiV trials and American Indian or Alaskan Native individuals for vaccine trials (6.2%, 11.8%, and 11.1% of trials met/exceeded census level representation, respectively). The percentage of trials reaching/exceeding census levels also varied per trial phase for race and ethnicity. Furthermore, disparities in the percentage of trials reaching/exceeding census levels versus epidemiology-based prevalence levels have revealed opportunities to improve industry success metrics; in HIV trials, the proportion of Black or African American individuals (35.1%) exceeded census (13.4%) but not epidemiologic levels (55.3%). Conclusion: Further work is required to achieve demographic diversity across clinical trials. We conclude that US Census data are an inappropriate universal benchmark. A shift to epidemiology benchmarking will enable the consideration of global participants into US analyses for highly intrinsic (i.e. influenced by ancestry) diseases and more firm requirements for US-based participants into US analyses for extrinsic (i.e. influenced by location or culture) diseases. Benchmarking in line with epidemiologic data will allow us to set better trial enrollment goals, with the aim of conducting more demographically balanced, diverse, and representative clinical trials and enabling a better understanding of drug safety and efficacy per demographic group.

Alcohol use disorders can be driven by negative reinforcement. Alterations of the microtubule cytoskeleton have been associated with mood regulation in the context of depression. Notably, MAP4343, a pregnenolone derivative known to promote tubulin assembly, has antidepressant properties. In the present study, we tested the hypothesis that MAP4343 may reduce excessive alcohol drinking in a mouse model of alcohol dependence by normalizing affect during withdrawal. Adult male C57BL/6J mice were given limited access to voluntary alcohol drinking and ethanol intake escalation was induced by chronic intermittent ethanol (CIE) vapor inhalation. Chronic, but not acute, administration of MAP4343 reduced ethanol intake and this effect was more pronounced in CIE-exposed mice. There was a complex interaction between the effects of MAP4343 and alcohol on affective behaviors. In the elevated plus maze, chronic MAP4343 tended to increase open-arm exploration in alcohol-naive mice but reduced it in alcohol-withdrawn mice. In the tail suspension test, chronic MAP4343 reduced immobility selectively in Air-exposed alcohol-drinking mice. Finally, chronic MAP4343 countered the plasma corticosterone reduction induced by CIE. Parallel analysis of tubulin post-translational modifications revealed lower α-tubulin acetylation in the medial prefrontal cortex of CIE-withdrawn mice. Altogether, these data support the relevance of microtubules as a therapeutic target for the treatment of AUD.

Teachers often encourage students to use test-taking strategies during reading comprehension assessments, but these strategies are not always evidence-based. One common strategy involves teaching students to read the questions before reading an associated passage. Research findings comparing the passage-first (PF) and questions-first (QF) strategies are mixed. The present study employed eye-tracking technology to record 84 third- and fourth-grade participants' eye movements (EMs) as they read a passage and responded to multiple-choice (MC) questions using PF and QF strategies in a within-subject design. Although there were no significant differences between groups in accuracy on MC questions, EM measures revealed that the PF condition was superior to the QF condition for elementary readers in terms of efficiency in reading and responding to questions. These findings suggest that the PF strategy supports a more comprehensive understanding of the text. Ultimately, within the PF condition, students required less time to obtain the same accuracy outcomes they attained when reading in the QF condition. School psychologists can improve reading comprehension instruction by encouraging the importance of teaching children to gain meaning from the text rather than search the passage for answers to MC questions. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Efforts to mentor undergraduates in research require time, energy, and resources but can yield significant benefits. A review of education research on undergraduate research is presented followed by a case study of how technical and educational principles from the literature have been implemented and practiced in a new underwater acoustics lab. This case study involves the students who have joined this lab over its first three years. The results highlight the importance of several key factors that mentors can implement to improve their students' research experience. In order to meet the steep learning curve that new students face, faculty mentors should establish a culture of research (i.e., well established norms, expectations, and practices associated with being a part of a research group) through clear expectations, open communication, and student-led peer mentorship supported by carefully selected or designed resources (i.e., scaffolding). This paper seeks to share these education research resources with the acoustics community while providing a case study for review as a specific application of these key principles into an acoustics laboratory setting.

Objectives. To understand the frequency, magnitude, geography, and characteristics of tuberculosis outbreaks in US state prisons. Methods. Using data from the National Tuberculosis Surveillance System, we identified all cases of tuberculosis during 2011 to 2019 that were reported as occurring among individuals incarcerated in a state prison at the time of diagnosis. We used whole-genome sequencing to define 3 or more cases within 2 single nucleotide polymorphisms within 3 years as clustered; we classified clusters with 6 or more cases during a 3-year period as tuberculosis outbreaks. Results. During 2011 to 2019, 566 tuberculosis cases occurred in 41 state prison systems (a median of 3 cases per state). A total of 19 tuberculosis genotype clusters comprising 134 cases were identified in 6 state prison systems; these clusters included a subset of 5 outbreaks in 2 states. Two Alabama outbreaks during 2011 to 2017 totaled 20 cases; 3 Texas outbreaks during 2014 to 2019 totaled 51 cases. Conclusions. Only Alabama and Texas reported outbreaks during the 9-year period; only Texas state prisons had ongoing transmission in 2019. Effective interventions are needed to stop tuberculosis outbreaks in Texas state prisons. (Am J Public Health. 2022;112(8):1170–1179. https://doi.org/10.2105/AJPH.2022.306864 )

It is necessary to analyze the whole-body kinematics (including joint locations and joint angles) to assess risks of fatal and musculoskeletal injuries in occupational tasks. Human pose estimation has gotten more attention in recent years as a method to minimize the errors in determining joint locations. However, the joint angles are not often estimated, nor is the quality of joint angle estimation assessed. In this paper, we presented an end-to-end approach on direct joint angle estimation from multi-view images. Our method leveraged the volumetric pose representation and mapped the rotation representation to a continuous space where each rotation was uniquely represented. We also presented a new kinematic dataset in the domain of residential roofing with a data processing pipeline to generate necessary annotations for the supervised training procedure on direct joint angle estimation. We achieved a mean angle error of $7.19^\circ$ on the new Roofing dataset and $8.41^\circ$ on the Human3.6M dataset, paving the way for employment of on-site kinematic analysis using multi-view images.

Significant genetic variability exits within sheep breeds for gastrointestinal nematode (GIN) resistance. There-fore, selection may be an important tool to combat anthelmintic resistance in GIN populations. To better un-derstand the effect of selection based on the fecal egg count (FEC) estimated breeding value (EBV) on lamb GIN resistance in a pasture-based system, a divergent mating scheme was established. Over two years, Katahdin rams with exceptionally high (High FEC; n = 5) or low (Low FEC, n = 5) FEC EBV were mated to random groups of Katahdin ewes at the Southwest Virginia Agricultural Research and Extension Center (Glade Spring, VA). Lambs were born mid-March and managed as one contemporary group (Weaning: June 4). In Year 1 (YR1), FEC was collected on all lambs June 26 with no prior anthelmintic treatment. In Year 2 (YR2), beginning at 60 days of age, body weights and FAMACHA scores were collected weekly and FEC biweekly. Anthelmintic administration occurred based on FAMACHA >= 3 in YR2. Lamb survival determination excluded first 7 days of age. Statistical analysis was performed using SAS (SAS Institute, Cary, NC) with fixed effects of sire type. Lamb FEC EBV cor-responded to sire type validating the mating scheme. Lamb FEC was similar and variable prior to and shortly after weaning. After this point, High FEC-sired lambs had greater FEC compared to Low FEC-sired lambs (P < 0.05) and anthelmintic treatment corresponded to FEC EBV type (P < 0.05). In YR1, death losses were greater for High FEC-sired lambs (P < 0.05) and those lambs that died had greater FEC EBV than those that survived (P < 0.05). In YR2, post-weaning FEC EBV difference between High FEC-sired lambs that survived to 120 days of age and those that died was significant (73% vs. 138%, P < 0.01). Therefore, selection for improved GIN resistance using FEC EBV is effective and the FEC EBV is also associated with lamb survival in a pasture-based system. USDA NIFA [OREI 59-6020-7-004] Published version Funding USDA NIFA OREI 59-6020-7-004.

We detail the the REACH radiometric system designed to enable measurements of the 21-cm neutral hydrogen line. Included is the radiometer architecture and end-to-end system simulations as well as a discussion of the challenges intrinsic to highly-calibratable system development. Following this, we share laboratory results based on the calculation of noise wave parameters utilising an over-constrained least squares approach demonstrating a calibration RMSE of 80 mK for five hours of integration on a custom-made source with comparable impedance to that of the antenna used in the field. This paper therefore documents the state of the calibrator and data analysis in December 2022 in Cambridge before shipping to South Africa., 30 pages, 19 figures

In this paper, we are concerned with efficiently solving the sequences of regularized linear least squares problems associated with employing Tikhonov-type regularization with regularization operators designed to enforce edge recovery. An optimal regularization parameter, which balances the fidelity to the data with the edge-enforcing constraint term, is typically not known a priori. This adds to the total number of regularized linear least squares problems that must be solved before the final image can be recovered. Therefore, in this paper, we determine effective multigrid preconditioners for these sequences of systems. We focus our approach on the sequences that arise as a result of the edge-preserving method introduced in [6], where we can exploit an interpretation of the regularization term as a diffusion operator; however, our methods are also applicable in other edge-preserving settings, such as iteratively reweighted least squares problems. Particular attention is paid to the selection of components of the multigrid preconditioner in order to achieve robustness for different ranges of the regularization parameter value. In addition, we present a parameter culling approach that, when used with the L-curve heuristic, reduces the total number of solves required. We demonstrate our preconditioning and parameter culling routines on examples in computed tomography and image deblurring.

Awkward kneeling in sloped shingle installation operations exposes roofers to knee musculoskeletal disorder (MSD) risks. To address the varying levels of risk associated with different phases of shingle installation, this research investigated utilizing machine learning to automatically classify seven distinct phases in a typical shingle installation task. The classification process relied on analyzing knee kinematics data and roof slope information. Nine participants were recruited and performed simulated shingle installation tasks while kneeling on a sloped wooden platform. The knee kinematics data were collected using an optical motion capture system. Three supervised machine learning classification methods (i.e., k-nearest neighbors (KNNs), decision tree (DT), and random forest (RF)) were selected for evaluation. The KNN classifier provided the best performance for overall accuracy. The results substantiated the feasibility of applying machine learning in classifying shingle installation phases from workers’ knee joint rotation and roof slope angles, which may help facilitate method and tool development for automated knee MSD risk surveillance and assessment among roofers.

11β-Hydroxysteroid dehydrogenase 1 (11βHSD1) is a drug target to attenuate adverse effects of chronic glucocorticoid excess. It catalyses intracellular regeneration of active glucocorticoids in tissues including brain, liver and adipose tissue (coupled to hexose-6-phosphate dehydrogenase, H6PDH). 11βHSD1 activity in individual tissues is thought to contribute significantly to glucocorticoid levels at those sites, but its local contribution versus glucocorticoid delivery via the circulation is unknown. Here, we hypothesised that hepatic 11βHSD1 would contribute significantly to the circulating pool. This was studied in mice with Cre-mediated disruption of Hsd11b1 in liver (Alac-Cre) versus adipose tissue (aP2-Cre) or whole-body disruption of H6pdh. Regeneration of [9,12,12-2 46 H3]-cortisol (d3F) from [9,12,12-2 47 H3]-cortisone (d3E), measuring 11βHSD1 reductase activity was assessed at steady state following infusion of [9,11,12,12-2 48 H4]-cortisol (d4F) in male mice. Concentrations of steroids in plasma and amounts in liver, adipose tissue and brain were measured using mass spectrometry interfaced with matrix assisted laser desorption ionisation or liquid chromatography. Amounts of d3F were higher in liver, compared with brain and adipose tissue. Rates of appearance of d3F were ~6-fold slower in H6pdh-/- 52 mice, showing the importance of whole-body 11βHSD1 reductase activity. Disruption of liver 11βHSD1 reduced amounts of d3F in liver (by ~36%), without changes elsewhere. In contrast disruption of 11βHSD1 in adipose tissue reduced rates of appearance of circulating d3F (by ~67%) and also reduced regeneration of d3F in liver and brain (both by ~30%). Thus, the contribution of hepatic 11βHSD1 to circulating glucocorticoid levels and amounts in other tissues is less than that of adipose tissue.

Global guidelines for the management of high-cardiovascular-risk patients include aggressive goals for low-density lipoprotein cholesterol (LDL-C). Statin therapy alone is often insufficient to reach goals and nonstatin options have limitations. Here, we tested the lipid-lowering effects of the cholesteryl ester transfer protein (CETP) inhibitor drug obicetrapib in a randomized, double-blind, placebo-controlled trial in dyslipidaemic patients (n = 120, median LDL-C 88 mg dl−1) with background high-intensity statin treatment (NCT04753606). Over the course of 8 weeks, treatment with 5 mg or 10 mg obicetrapib resulted in a significant decrease as compared with placebo in median LDL-C concentration (by up to 51%; P < 0.0001), the primary trial outcome. As compared with placebo, obicetrapib treatment also significantly (P < 0.0001) decreased apolipoprotein B (by up to 30%) and non-high-density lipoprotein cholesterol (non-HDL-C) concentration (by up to 44%), and significantly (P < 0.0001) increased HDL-C concentration (by up to 165%; the secondary trial outcomes) and had an acceptable safety profile. These results support the potential of obicetrapib to address an unmet medical need for high-cardiovascular-risk patients.

The purpose of this study was to evaluate the epidemiology and perioperative complications of different reconstructive strategies to correct cleft nasal deformity, with particular attention paid to type and timing of cartilage grafting.Retrospective cohort study was conducted of cleft rhinoplasty performed between 2012 and 2017 in North America utilizing the American College of Surgeons National Surgical Quality Improvement Program- Pediatric hospital network. Medical/surgical complications, reoperations, and readmissions within 30 days postoperatively were analyzed with appropriate statistics.During the study interval, 3317 pediatric patients underwent cleft rhinoplasty, with 8.0% involving the use of cartilage grafts. Ear cartilage was significantly more commonly used for intermediate repair, whereas rib cartilage was more commonly used for late repair (P=0.006). Overall, rhinoplasties with ear cartilage grafts had shorter procedure durations than those without cartilage grafts (P=0.005), whereas those with rib cartilage grafts had increased procedure duration (P0.001). The use of cartilage grafts was not associated with increased complications in either intermediate or late cleft rhinoplasty. Patients with bilateral clefts were more likely to undergo rhinoplasty with cartilage grafts overall (P=0.047) and with cartilage grafts for late reconstruction (P=0.039).Ear cartilage is most frequently utilized for intermediate repair, whereas rib cartilage is most frequently utilized for late repair during cleft rhinoplasty. Ear cartilage grafts are associated with significantly decreased procedure duration, whereas rib cartilage grafts are associated with significantly increased procedure duration. Not surprisingly, cleft rhinoplasty is relatively safe, with a 2% overall short-term complication rate.

Numerosity and privileges of occurrence of various types of interjections (primary conventional, primary non-conventional, secondary, and onomatopoeic) were investigated in three different literary readings of Winnie-the-Pooh (Milne 1926), in one reading of Ulysses (Joyce 1960), and in an artistic performance by actors (the film The third man, Korda, Selznik, & Reed 1949). The spoken corpora, based on printed texts as source, consisted of 667 interjections. Ameka’s (1992 b, 1994) hypothesis that, parallel to their independence from ambient grammar, interjections would also be isolated temporally by preceding and following pauses, was not confirmed; for the entire corpus, only 39% of all interjections were thus isolated. However, an alternative hypothesis, that interjections serve an initializing function, was confirmed: Altogether, 77% of the interjections were found to be initializing, i.e., were preceded by a pause, introduced a speaking turn, introduced an utterance, and/or introduced a citation. Primary conventional interjections constituted the majority of interjections (overall 56%), but only two of these were common to all the corpora (oh and ah). By far the highest percentage (28 %) of primary non- conventional interjections occurred in the artistic performance of The third man. None of these occurred in either the novel or the screenplay of The third man, unlike the primary non-conventional interjections throughout the text of the literary readings. Functions of interjections are discussed in terms of Goffman’s (1981: 226) animators (literary readers, 26% of whose spoken interjections were added to those in the printed text) and principals (actors, 79% of whose spoken interjections were added to those in the printed text), in terms of literacy and orality, and in terms of the emotional stance and perspective of a speaker at the very moment of utterance.

Interesting recent trends are apparent in the setting of shoulder and elbow pathology. There is an increase in utilization of shoulder arthroplasty for osteoarthritis and post traumatic arthritis. At the same time, there remain limited options for osteoarthritis of the elbow particularly in the young and or active patient. This manuscript details surgical options for osteoarthritis at the elbow and shoulder.

Facial proportionality and symmetry are positively associated with perceived levels of facial attractiveness.The aims of this study were to confirm and extend the association of proportionality with perceived levels of attractiveness and character traits and determine differences in attractiveness and character ratings between "anomalous" and "typical" faces using a large dataset.Ratings of 597 unique individuals from the Chicago Face Database were used. A formula was developed as a proxy of relative horizontal proportionality, where a proportionality score of "0" indicated perfect proportionality and more negative scores indicated less proportionality. Faces were categorized as "anomalous" or "typical" by 2 independent reviewers based on physical features.Across the ratings for all faces, Spearman correlations revealed greater proportionality was associated with attractiveness ( ρ = 0.292, P0.001) and trustworthiness ( ρ = 0.193, P0.001), while lesser proportionality was associated with impressions of anger (ρ = 0.132, P = 0.001), dominance (ρ = 0.259, P0.001), and threateningness ( ρ = 0.234, P0.001). Mann-Whitney U tests revealed the typical cohort had significantly higher levels of proportionality (-13.98 versus -15.14, P = 0.030) and ratings of attractiveness (3.39 versus 2.99, P0.001) and trustworthiness (3.48 versus 3.35, P0.001).This study demonstrated that facial proportionality is not only significantly associated with higher ratings of attractiveness, but also associated with judgements of trustworthiness. Proportionality plays a role in evoking negative attributions of personality characteristics to people with facial anomalies.

Antimicrobial resistance (AR) is a serious global problem due to the overuse of antimicrobials in human, animal, and agriculture sectors. There is intense research to control the dissemination of AR, but little is known regarding the environmental drivers influencing its spread. Although AR genes (ARGs) are detected in many different environments, the risk associated with the spread of these genes to microbial pathogens is unknown. Recreational microbial exposure risks are likely to be greater in water bodies receiving discharge from human and animal waste in comparison to less disturbed aquatic environments. Given this scenario, research practitioners are encouraged to consider an ecological context to assess the effect of environmental ARGs on public health. Here, we use a stratified, probabilistic survey of nearly 2000 sites to determine national patterns of the anthropogenic indicator class I integron Integrase gene (

The goal of this study was to describe the 10-year evolution of the authors' surgical technique and institutional perioperative outcomes using posterior vault distraction osteogenesis (PVDO) in patients with syndromic and multisuture craniosynostosis.The authors performed a retrospective cohort study of patients who underwent PVDO for treatment of syndromic and multisuture craniosynostosis at a single institution over a 10-year period. Demographic data, perioperative outcomes, distraction patterns, and complications were analyzed. Outcomes of patients in the first 5 years (early cohort) were compared with those of the latter 5 years (late cohort).One hundred ten patients underwent a total of 118 PVDO procedures. Patients with a syndromic diagnosis represented 83.6 percent of the cohort ( n = 92) and were significantly younger than patients with a nonsyndromic diagnosis at the time of first PVDO (median [25th percentile, 75th percentile] 14.1 [6.6, 40.1] versus 42.7 [15.2, 59.6] months; p = 0.014). Mean distraction distance in the anterior-posterior direction was 30.8 mm (SD, 7.4). Compared with the early cohort, PVDO in the late cohort had faster median operative times (144.0 [123.0, 189.0] minutes versus 161.0 [138.0, 199.0] minutes; p = 0.038), lower estimated blood loss as a percentage of blood volume (28.5 [20.6, 45.3] versus 50.0 [31.1, 95.8]; p0.001), and lower blood replacement as percentage of blood volume (39.5 [23.8, 59.1] versus 56.3 [37.8, 110.1]; p = 0.009).This 10-year experience with PVDO demonstrates continued overall safety and efficacy with improved perioperative outcomes over time. Although PVDO has become the authors' first line of expansion in syndromic craniosynostosis, shortcomings such as need for device removal, infection concerns, and potential for cerebrospinal fluid leak merit attention by the craniofacial community.Therapeutic, III.

IntroductionToxoplasma gondii induces a strong CD8 T cell response characterized by the secretion of IFNγ that promotes host survival during infection. The initiation of CD8 T cell IFNγ responses in vitro differs widely between clonal lineage strains of T. gondii, in which type I strains are low inducers, while types II and III strains are high inducers. We hypothesized this phenotype is due to a polymorphic “Regulator Of CD8 T cell Response” (ROCTR).MethodsTherefore, we screened F1 progeny from genetic crosses between the clonal lineage strains to identify ROCTR. Naïve antigen-specific CD8 T cells (T57) isolated from transnuclear mice, which are specific for the endogenous and vacuolar TGD057 antigen, were measured for their ability to become activated, transcribe Ifng and produce IFNγ in response to T. gondii infected macrophages.ResultsGenetic mapping returned four non-interacting quantitative trait loci (QTL) with small effect on T. gondii chromosomes (chr) VIIb-VIII, X and XII. These loci encompass multiple gene candidates highlighted by ROP16 (chrVIIb-VIII), GRA35 (chrX), TgNSM (chrX), and a pair of uncharacterized NTPases (chrXII), whose locus we report to be significantly truncated in the type I RH background. Although none of the chromosome X and XII candidates bore evidence for regulating CD8 T cell IFNγ responses, type I variants of ROP16 lowered Ifng transcription early after T cell activation. During our search for ROCTR, we also noted the parasitophorous vacuole membrane (PVM) targeting factor for dense granules (GRAs), GRA43, repressed the response suggesting PVM-associated GRAs are important for CD8 T cell activation. Furthermore, RIPK3 expression in macrophages was an absolute requirement for CD8 T cell IFNγ differentiation implicating the necroptosis pathway in T cell immunity to T. gondii.DiscussionCollectively, our data suggest that while CD8 T cell IFNγ production to T. gondii strains vary dramatically, it is not controlled by a single polymorphism with strong effect. However, early in the differentiation process, polymorphisms in ROP16 can regulate commitment of responding CD8 T cells to IFNγ production which may have bearing on immunity to T. gondii.