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In 2009, the U.S. Preventive Services Task Force updated recommended mammography screening frequency from annual to biennial for average-risk women aged 50-74 years. The association between estimated breast cancer risk and mammography screening frequency was evaluated.A single-center retrospective cohort study was conducted among racially/ethnically diverse women, aged 50-74 years, who underwent screening mammography from 2014 to 2018. Data on age, race/ethnicity, first-degree family history of breast cancer, previous benign breast biopsies, and mammographic density were extracted from the electronic health record to calculate Breast Cancer Surveillance Consortium 5-year risk of invasive breast cancer, with a 5-year risk ≥1.67% defined as high risk. Multivariable analyses were conducted to determine the association between breast cancer risk factors and mammography screening frequency (annual versus biennial). Data were analyzed from 2020 to 2022.Among 12,929 women with a mean age of 61±6.9 years, 82.7% underwent annual screening mammography, and 30.7% met high-risk criteria for breast cancer. Hispanic women were more likely to screen annually than non-Hispanic Whites (85.0% vs 79.8%, respectively), despite fewer meeting high-risk criteria. In multivariable analyses adjusting for breast cancer risk factors, high- versus low/average-risk women (OR=1.17; 95% CI=1.04, 1.32) and Hispanic versus non-Hispanic White women (OR=1.46; 95% CI=1.29, 1.65) were more likely to undergo annual mammography.A majority of women continue to undergo annual screening mammography despite only a minority meeting high-risk criteria, and Hispanic women were more likely to screen annually despite lower overall breast cancer risk. Future studies should focus on the implementation of risk-stratified breast cancer screening strategies.

The Arctic is experiencing rapid climate change. This research documents changes to tundra vegetation near Atqasuk and Utqiaġvik, Alaska. At each location, 30 plots were sampled annually from 2010 to 2019 using a point frame. For every encounter, we recorded the height and classified it into eight groupings (deciduous shrubs, evergreen shrubs, forbs, graminoids, bryophytes, lichens, litter, and standing dead vegetation); for vascular plants we also identified the species. We found an increase in plant stature and cover over time, consistent with regional warming. Graminoid cover and height increased at both sites, with a 5-fold increase in cover in Atqasuk. At Atqasuk, the cover and height of shrubs and forbs increased. Species diversity decreased at both the sites. Year was generally the strongest predictor of vegetation change, suggesting a cumulative change over time; however, soil moisture and soil temperature were also predictors of vegetation change. We anticipate that plants in the region will continue to grow taller as the region warms, resulting in greater plant cover, especially of graminoids and shrubs. The increase in plant cover and accumulation of litter may negatively impact non-vascular plants. Continued changes in community structure will impact energy balance and carbon cycling and may have regional and global consequences.

The Arctic is warming twice as fast as the rest of the globe. Graminoid, deciduous shrub, and evergreen shrub cover has increased in some regions, but not others. To better understand why plant responses vary across regions, we compared change in plant cover over time with nine functional traits of 12 dominant species in three regions of northern Alaska (Utqiaġvik, Atqasuk, and Toolik Lake). Cover was measured three times from 2008 to 2018. Repeated-measures analysis of variance (ANOVA) found that one species — Carex aquatilis — showed significant change in cover over time, increasing by 12.7% at Atqasuk. Canonical correspondence analysis suggested a relationship between shifts in species cover and traits, but Pearson and Spearman rank correlations did not find a significant trend for any trait when analyzed individually. Investigation of community-weighted means (CWMs) for each trait revealed no significant changes over time for any trait in any region. By comparison, estimated ecosystem values for several traits important to ecosystem functioning showed consistent increases over time in two regions (Utqiaġvik and Atqasuk). Our results indicate that vascular plant community composition and function have remained consistent over time; however, documented increases in total plant cover have important implications for ecosystem functioning.

Increases in shrub growth and canopy cover are well documented community responses to climate warming in the Arctic. An important consequence of larger deciduous shrubs is shading of prostrate plant species, many of which are important sources of nectar and berries. Here, we present the impact of a shading experiment on two prostrate shrubs, Vaccinium vitis-idaea L. and Arctous alpina L., in northern Alaska over two growing seasons. We implemented three levels of shading (no shade, 40% shade, and 80% shade) in dry heath and moist acidic tundra. Plots were monitored for soil moisture content, surface temperature, normalized difference vegetation index (NDVI), and flowering. Shading was shown to, on average, lower surface temperature (0.7 °C to 5.3 °C) and increase soil moisture content (0.5% to 5.6%) in both communities. Both species- and plot-level NDVI values were delayed in timing of peak values (7 to 13 days) and decreased at the highest shading. Flower abundance of both species was lower in shaded plots and peak flowering was delayed (3 to 8 days) compared with controls. Changes in timing may result in phenological mismatches and can impact other trophic levels in the Arctic as both the flowers and resulting berries are important food sources for animals.

Succinate dehydrogenase inhibitors (SDHIs) fungicides are used to control Asian soybean rust (Phakopsora pachyrhizi), and the SdhC-I86F mutation is related to pathogen resistance. The objective of this study was to determine whether fitness penalties are associated with SDHI resistance (SdhC-I86F mutation) in P. pachyrhizi populations. Moreover, the study investigated whether the SdhC-I86F mutation remained stable after the fungus propagation both in the absence and presence of fungicide. The populations used in this study presented mutations for all genes analyzed (Cyp51, Cytb, and SdhC), except for a wild-type population (WTSdhC) found with no SdhC-I86F mutation. The frequencies of the SdhC-I86F mutant populations were stable after 36 generations in the absence of fungicide. However, in the case of the WTSdhC population, the SdhC-I86F mutation was further detected after one generation of the fungus in the presence of the SDHI fungicide, according to the results of a detached leaf assay. Three tests were performed to evaluate fitness components and sensitivity to fungicides (half maximal effective concentration). SdhC-I86F mutant populations were more sensitive to osmotic and oxidative stress than the WTSdhC population; however, the sensitivity to ultraviolet radiation was similar for both populations. All mutated populations were less sensitive than the WTSdhC when using SDHI (azoxystrobin + benzovindiflupyr), but more sensitive to mancozeb. The presence of fitness penalties, the mutation stability, and the sensitivity to mancozeb presented by the SdhC-I86F mutant populations can be relevant to the management of the disease in the field.

Background Intensive care unit (ICU) sedation guidelines recommend targeting a light sedation level, but light sedation has no accepted definition, and inconsistent levels have been proposed. Objective To determine Sedation-Agitation Scale and Richmond Agitation-Sedation Scale scores that best describe patients’ ability to follow voice commands. Methods This prospective, observational pilot study enrolled a convenience sample of ICU patients receiving mechanical ventilation. Pairs of trained investigators evaluated scores on the Sedation-Agitation Scale and Richmond Agitation-Sedation Scale and ability to follow commands before and up to 2 hours after sedation lightening in a blind, independent, simultaneous fashion. Positive predictive values (PPVs) and likelihood ratios (LRs) of Sedation-Agitation Scale and Richmond Agitation-Sedation Scale scores associated with light sedation (ability to follow at least 3 commands) were calculated. Results Ninety-six assessments (50 before and 46 after lightening of sedation) were performed in medical ICU patients. Scores best associated with ability to follow at least 3 commands were Sedation-Agitation Scale score of 4 (PPV, 0.88; 95% CI, 0.70-0.98; LR, 14.0) and Richmond Agitation-Sedation Scale score of −1 (PPV, 0.81; 95% CI, 0.61-0.93; LR, 10.7), superior to previously recommended thresholds of Sedation-Agitation Scale score of 3 (PPV, 0.62; 95% CI, 0.48-0.75; LR, 3.1) and Richmond Agitation-Sedation Scale score of −3 (PPV, 0.52; 95% CI, 0.39-0.64; LR, 2.0). Conclusions The level of sedation most associated with the ability to follow commands appears higher than previously recommended. Further study is needed regarding the effects of sedation level on ICU patients’ ability to follow commands and assessment of delirium, pain, and patient preferences.

BACKGROUND AND AIM: Humans with inborn errors of immunity (IEI), or primary immunodeficiencies, may be associated with a potential risk factor for early-onset gastrointestinal (GI) cancer. METHODS: We systematically reviewed all cases with clinical diagnoses of both an IEI and a GI cancer in three databases (MEDLINE, SCOPUS, and EMBASE). In total, 76 publications satisfying our inclusion criteria were identified, and data for 149 cases were analyzed. We also searched our institutional cancer registry for such cases. RESULTS: We identified 149 patients with both an IEI and a GI cancer, 95 presented gastric cancer, 13 small bowel cancer, 35 colorectal cancer, and 6 had an unspecified cancer or cancer at another site. Gastric and colon adenocarcinomas were the most common. For both gastric and colorectal cancers, age at onset was significantly earlier in patients with IEIs than in the general population, based on the SEER database. Common variable immunodeficiency (CVID) was the most common IEI associated with gastrointestinal cancer. About 12% of patients had molecular genetic diagnoses, the three most frequently implicated genes being ATM, CARMIL2, and CTLA4. Impaired humoral immunity and Epstein–Barr virus (EBV) infection were frequently reported as factors potentially underlying early-onset GI cancers in patients with IEIs. We identified one patient with CVID and early-onset gastric adenocarcinoma, recurrent diarrhea, and gastrointestinal CMV infection from a retrospective survey. CONCLUSION: Patients with IEIs should be considered at risk of early-onset GI cancers and should therefore undergo cancer screening at an earlier age.

Prior research suggests that anhedonia symptoms related to posttraumatic stress disorder (PTSD; i.e., diminished interest, detachment from others, and difficulty experiencing positive emotions) are consistently associated with a higher degree of impairment in psychosocial functioning beyond that associated with other PTSD symptoms. Unfortunately, much of this research has used cross-sectional study designs; relied upon outdated DSM diagnostic criteria; and failed to control for potentially confounding variables, such as the presence of co-occurring depression. This study used data from Waves 2 and 4 (n = 1,649) of the Veterans' After-Discharge Longitudinal Registry (Project VALOR), a longitudinal dataset of U.S. Army and Marine veterans. As measured using the Inventory of Psychosocial Functioning, Wave 4 psychosocial functioning was regressed on seven PTSD symptom factors at Wave 2 (i.e., intrusions, avoidance, negative affect, anhedonia, externalizing behaviors, anxious arousal, and dysphoric arousal) and potential Wave 2 confounds. The Anhedonia factor, β = .123, most strongly predicted later psychosocial functional impairment beyond the impact of other PTSD symptom factors, βs = -.076-.046. Clinical implications of these findings are also discussed.

Mesoporous silica particles (MSPs) are emerging as an interesting option to reduce calorific uptake as a treatment for obesity and other metabolic conditions. However, their further development under the pharmaceutical regulatory framework is hindered by poor understanding of the mechanisms by which they exert their effects. In the current study the interaction of MSPs with the lipid digestion process is investigated, specifically interactions with lipase enzymes and lipid digestion products as a key contributing factor to lipid absorption and calorific intake. The impact of exposing lipase to MSPs on the enzyme activity was assessed directly using the tributyrin digestion test. The extent of interaction of digestion products with MSPs was studied using selectively radiolabeled bile components and lipids, while the impact on in vivo absorption of lipids was studied by incorporation of radiolabelled lipid (triolein) into milk and administration with and without particles. The studies showed that particles that inhibited lipase activity also tended to interact more extensively with lipid digestion products. In vitro X-ray scattering studies revealed the interaction of some MSPs with lipid digestion products through changes in lipid self-assembly during digestion. The MSPs led to reduced lipid absorption in vivo compared to the control particles and MSP-free milk. While the specific properties of the MSPs that drive the differences between the behavior of MSPs during lipid digestion remain elusive, the studies highlight that interactions with the lipid digestion and absorption pathways are a likely mechanism for reducing calorific uptake.

We evaluated the number of CD26 expressing cells in peripheral blood of patients with COVID-19 within 72 h of admission and on day 4 and day 7 after enrollment. The majority of CD26 expressing cells were presented by CD3

Supplementary Figure 1 from Genetic Polymorphisms in Adaptive Immunity Genes and Childhood Acute Lymphoblastic Leukemia

Supplementary Table 2 from Genetic Polymorphisms in Adaptive Immunity Genes and Childhood Acute Lymphoblastic Leukemia

Supplementary Figure 2 from Genetic Polymorphisms in Adaptive Immunity Genes and Childhood Acute Lymphoblastic Leukemia

Supplementary Table 1 from Genetic Polymorphisms in Adaptive Immunity Genes and Childhood Acute Lymphoblastic Leukemia

Background: Childhood acute lymphoblastic leukemia (ALL) has been hypothesized to have an infection- and immune-related etiology. The lack of immune priming in early childhood may result in abnormal immune responses to infections later in life and increase ALL risk.Methods: The current analyses examined the association between childhood ALL and 208 single-nucleotide polymorphisms (SNP) of 29 adaptive immune function genes among 377 ALL cases and 448 healthy controls. Single SNPs were analyzed with a log-additive approach using logistic regression models adjusted for sex, age, Hispanic ethnicity, and race. Sliding window haplotype analyses were done with haplotypes consisting of 2 to 6 SNPs.Results: Of the 208 SNPs, only rs583911 of IL12A, which encodes a critical modulator of T-cell development, remained significant after accounting for multiple testing (odds ratio for each copy of the variant G allele, 1.52; 95% confidence interval, 1.25-1.85; P = 2.9 × 10−5). This increased risk was stronger among firstborn children of all ethnicities and among non-Hispanic children with less day care attendance, consistent with the hypothesis about the role of early immune modulation in the development of childhood ALL. Haplotype analyses identified additional regions of CD28, FCGR2, GATA3, IL2RA, STAT4, and STAT6 associated with childhood ALL.Conclusion: Polymorphisms of genes on the adaptive immunity pathway are associated with childhood ALL risk.Impact: Results of this study support an immune-related etiology of childhood ALL. Further confirmation is required to detect functional variants in the significant genomic regions identified in this study, in particular for IL12A. Cancer Epidemiol Biomarkers Prev; 19(9); 2152–63. ©2010 AACR.

Metazoan parasite species composition changes with an increase in geographical distance, but not their functional traits. We compared the performance of the taxonomy and functional traits of metazoan parasites as bioindicators of chemical pollution along the continental shelf of the South Gulf of Mexico (sGOM). Parasites were obtained from Syacium gunteri and Syacium papillosum, together with hydrocarbons, heavy metals and physicochemical variables from water and sediments during 12 oceanographic cruises. We compared regions without oil extraction: Veracruz-Tamaulipas (VT) and Yucatan shelf (YS) and one with it, north-western end of YS to Coatzacoalcos, Veracruz (NYV). In addition to taxonomy, the trait-based approach community-weighted means (CWM) was performed. Species richness was compared between regions using rarefaction curves, and the taxonomic and trait composition between regions were compared using multivariate analyses. The relationships between taxonomy, traits and environmental variables were tested using BIOENV. We identified 57 species and body tegument, transmission, feeding mode, life stage and attachment organs as informative traits. By rarefaction, VT and YS had higher species richness than NYV for both hosts, but there were questionable values due to the small fish sample size. Except for YS, significant parasite community variability was detected by PERMANOVA using taxonomy and CWM for all regions, hosts and interactions. The same group of larval species was detected by SIMPER for regions and hosts, suggesting low functional turnover. BIOENV showed that polyaromatic hydrocarbons explained most of the variability. Taxonomy and functional traits produced similar explained variance, but the latter saved time analysis and financial resources.

PURPOSEImplementation of routine financial screening is a critical step toward mitigating financial toxicity. We evaluated the feasibility, sustainability, and acceptability of systematic financial screening in the outpatient breast oncology clinic at a large, urban cancer center.METHODSWe developed and implemented a stakeholder-informed process to systematically screen for financial hardship and worry. A 2-item assessment in English or Spanish was administered to patients through the electronic medical record portal or using paper forms. We evaluated completion rates and mode of completion. Through feedback from patients, clinicians, and staff, we identified strategies to improve completion rates and acceptability.RESULTSFrom March, 2021, to February, 2022, 3,500 patients were seen in the breast oncology clinic. Of them, 39% (n = 1,349) responded to the screening items, either by paper or portal, 12% (n = 437) preferred not to answer, and the remaining 49% (n = 1,714) did not have data in their electronic health record, meaning they were not offered screening or did not complete the paper forms. Young adults (18-39 years) were more likely to respond compared with patients 70 years or older (61% v 30%, P < .01). English-preferring patients were more likely to complete the screening compared with those who preferred Spanish (46% v 28%, P < .01). Non-Hispanic White patients were more likely to respond compared with Non-Hispanic Black patients and with Hispanic patients (46% v 39% v 32%, P < .01). Strategies to improve completion rates included partnering with staff to facilitate paper form administration, optimizing patient engagement with the portal, and clearly communicating the purpose of the screening.CONCLUSIONSystematic financial screening is feasible, and electronic data capture facilitates successful implementation. However, inclusive procedures that address language and technology preferences are needed to optimize screening.

Human parechovirus (HPeV) is an increasingly recognised cause of severe illness and central nervous system infection in infants. Medium- to long-term neurodevelopmental outcomes post-HPeV infection remain unknown. This study aims to assess neurodevelopmental outcomes for children hospitalised as infants with HPeV infection in their second and third years of life.This prospective cohort study followed children hospitalised with HPeV in Brisbane, Queensland during the 2017/2018 outbreak. Serial application of Ages and Stages Questionnaire (ASQ) was used to assess developmental progress in the second and third years of life. Data from clinical follow-up, audiology and neuroradiology were included.In the second year of life, 63% (n = 29) of children showed some or significant concerns for developmental delay. This had largely been ameliorated by the third year of life when only 30% (n = 14) reported developmental concerns. Prematurity and apnoeas were associated with developmental concerns at 27-36 months of age. Communication was the most common domain of concern.The majority of infants hospitalised with HPeV infection in 2017-2018 showed normalisation of developmental progress by 27-36 months of age. Further investigation into more subtle neurological impairments in later childhood is required. These results can help guide clinicians in counselling parents during the acute illness and in planning appropriate follow-up.

Wind damage from cyclones can devastate the forest canopy, altering environmental conditions in the understory that affect seedling growth and plant community regeneration. To investigate the impact of hurricane‐induced increases in light and soil nutrients as a result of canopy defoliation, we conducted a two‐way factorial light and nutrient manipulation in a shadehouse experiment. We measured seedling growth of the dominant canopy species in the four Everglades forest communities: pine rocklands (Pinus elliottii var densa), cypress domes (Taxodium distichum), hardwood hammocks, and tree islands (Quercus virginiana and Bursera simaruba). Light levels were full sun and 50% shade, and nutrient levels coupled with an additional set of individuals that were subjected to a treatment mimicking the sudden effects of canopy opening from hurricane‐induced defoliation and the corresponding nutrient pulse. Seedlings were measured weekly for height growth and photosynthesis, with seedlings being harvested after 16 weeks for biomass, leaf area, and leaf tissue N and 13C isotope ratio. Growth rates and biomass accumulation responded more to differences in soil nutrients than differences in light availability, with largest individuals being in the high nutrient treatments. For B. simaruba and P. elliottii, the highest photosynthetic rates occurred in the high light, high nutrient treatment, while T. distichum and Q. virginiana photosynthetic rates were highest in low light, high nutrient treatment. Tissue biomass allocation patterns remained similar across treatments, except for Q. virginiana, which altered above‐ and belowground biomass allocation to increase capture of limiting soil and light resources. In response to the hurricane simulation treatment, height growth increased rapidly for Q. virginiana and B. simaruba, with nonsignificant increases for the other two species. We show here that ultimately, hurricane‐adapted, tropical species may be more likely to recolonize the forest canopy following a large‐scale hurricane disturbance., Wind damage associated with cyclones can devastate the forest canopy, strongly altering environmental conditions in the understory that affect seedling growth and canopy regeneration. To investigate the impact of hurricane‐induced increases in light and soil nutrients as a result of canopy defoliation, we conducted a two‐way factorial light and nutrient manipulation in a shadehouse. Ultimately, the ability of a species to recolonize hurricane damaged canopies may shift community dominance to more hurricane‐adapted species.

Telescopes measuring cosmic microwave background (CMB) polarization on large angular scales require exquisite control of systematic errors to ensure the fidelity of the cosmological results. In particular, far-sidelobe contamination from wide angle scattering is a potentially prominent source of systematic error for large aperture microwave telescopes. Here we describe and demonstrate a ray-tracing-based modeling technique to predict far sidelobes for a Three Mirror Anistigmat (TMA) telescope designed to observe the CMB from the South Pole. Those sidelobes are produced by light scattered in the receiver optics subsequently interacting with the walls of the surrounding telescope enclosure. After comparing simulated sidelobe maps and angular power spectra for different enclosure wall treatments, we propose a highly scattering surface that would provide more than an order of magnitude reduction in the degree-scale far-sidelobe contrast compared to a typical reflective surface. We conclude by discussing the fabrication of a prototype scattering wall panel and presenting measurements of its angular scattering profile., 14 pages, 8 figures

The outer membrane (OM) is the defining feature of gram-negative bacteria and is an essential organelle. Accordingly, OM assembly pathways and their essential protein components are conserved throughout all gram-negative species. Lipoprotein trafficking lies at the heart of OM assembly since it supplies several different biogenesis machines with essential lipoproteins. The Escherichia coli Lol trafficking pathway relies on an inner membrane LolCDE transporter that transfers newly made lipoproteins to the chaperone LolA, which rapidly traffics lipoproteins across the periplasm to LolB for insertion into the OM. Strikingly, many gram-negative species (like Caulobacter vibrioides ) do not produce LolB, yet essential lipoproteins are still trafficked to the OM. How the final step of trafficking occurs in these organisms has remained a long-standing mystery. We demonstrate that LolA from C. vibrioides can complement the deletion of both LolA and LolB in E. coli , revealing that this protein possesses both chaperone and insertion activities. Moreover, we define the region of C. vibrioides LolA that is responsible for its bifunctionality. This knowledge enabled us to convert E. coli LolA into a similarly bifunctional protein, capable of chaperone and insertion activities. We propose that a bifunctional LolA eliminates the need for LolB. Our findings provide an explanation for why some gram-negative species have retained an essential LolA yet completely lack a dedicated LolB protein.

The decision-to-delivery interval is a widely used term at non-elective caesarean section. While the definition may appear self-evident, there is no universally agreed consensus about when this period begins and ends. We reviewed the literature for original research utilising the terms 'decision-to-delivery', 'decision-to-incision' or 'incision-to-delivery' and examined definitions used for decision, delivery, incision, as well as any additional time intervals that were assessed. Our analysis demonstrated an inconsistent non-standardised approach to defining these intervals, which might have clinical practice and medicolegal ramifications. We propose that the decision-to-delivery interval should be defined as follows: the interval between the time at which the senior obstetrician makes the decision that a caesarean section is required and the time at which the fetus (or first fetus in the case of multiples) is delivered. The decision time should ideally be recorded contemporaneously in the medical notes or partogram.

Primary cilia are microtubule based sensory organelles important for receiving and processing cellular signals. Recent studies have shown that cilia also release extracellular vesicles (EVs). Because EVs have been shown to exert various physiological functions, these findings have the potential to alter our understanding of how primary cilia regulate specific signalling pathways. So far the focus has been on lgEVs budding directly from the ciliary membrane. An association between cilia and MVB-derived smEVs has not yet been described. We show that ciliary mutant mammalian cells demonstrate increased secretion of small EVs (smEVs) and a change in EV composition. Characterisation of smEV cargo identified signalling molecules that are differentially loaded upon ciliary dysfunction. Furthermore, we show that these smEVs are biologically active and modulate the WNT response in recipient cells. These results provide us with insights into smEV-dependent ciliary signalling mechanisms which might underly ciliopathy disease pathogenesis., Extracellular vesicles (EV) are known to be released from the primary cilium, but the role ciliary proteins play in EV biogenesis remains unexplored. Here, the authors demonstrate increased secretion of small EVs with altered cargo composition from cells with known ciliarelated mutations. Wnt related molecules made up a majority of altered cargo