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OBJECTIVES/GOALS: The goal of this study is to develop a multi-centered Translational Studio model that can help in the development of quality translational studies using resources from four different institutional partners (University of Texas Medical Branch, Texas Southern University, University of Houston Clear Lake and Houston Methodist). METHODS/STUDY POPULATION: We conducted two rounds of four Futures Workshops for a total participation of 28 stakeholders from four different partners. Future Workshops were used to critique, envision, and articulate novel “futures” that can be achieved at least partly through design practices (Muller, 2002). In the first round of workshops, we asked participants about their institutions’ strengths, weaknesses, resources and investigator needs regarding the Studio. In the second round we asked about different studio models, pros and cons of each model and guiding principles for a studio. Alongside a pragmatic content analysis, multi-stage deductive and inductive qualitative analyses were used to understand people’s views on the future of a multi-institutional Clinical Trials Studio. RESULTS/ANTICIPATED RESULTS: The first-round workshops’ analysis described peoples’ goals for what the studio should be. The future desired studio was described as guide, matchmaker, initiator and advocate. The second-round workshops’ analysis discussed the pros and cons of a variety of possible models including, centralized, decentralized, and topic-specific (and allowed other suggestions) while also describing principles for the guidance of a studio. Here the analysis showed people wanted certain characteristics for the studio (i.e. effective, efficient, locally-responsive, consistent, etc.). They also prescribed four principles that a studio should be guided by: non-hierarchical partnership, user-centeredness, respect/collegiality, and sharing. DISCUSSION/SIGNIFICANCE: The future workshops were useful in developing a shared multi-institutional Clinical Trials Studio model that is planned to be deployed in 2025. Participants valued a studio that was both directly supportive to participants and played a role in creating or advocating for institutional resources and policy for research.
In the Basilicata region, located in southern Italy and known for hosting among the first occurrences of the Acheulean culture in southwestern Europe, the Lower Paleolithic site of Loreto at Venosa is located less than a kilometer from the emblematic site of Notarchirico and less than 25 km from Cimitero di Atella. The Loreto site has not been studied as thoroughly as the two other sites and, although geological investigations have been carried out in the Venosa basin, no direct numerical dating has ever been published for the three archaeological levels brought to light during the excavation campaigns. We present a multi-method geochronological approach combining ESR/U-series, ESR, and 40Ar/39Ar permitting to refine the age of the most ancient archaeological level (A) of the Loreto site. These data allow us to propose an MIS 13 age for this level, in accordance with previous hypotheses based on geological and paleontological data. We also propose a technical review of the lithic tools preserved in the collection of the National Archaeological Museum of Venosa to integrate Loreto in the evolution scheme of the European Acheulean techno-complex emergence and diffusion.
This study aimed to determine which social network, demographic, and health-indicator variables were able to predict the development of high nutrition risk in Canadian adults at midlife and beyond, using data from the Canadian Longitudinal Study on Aging. Multivariable binomial logistic regression was used to examine the predictors of the development of high nutrition risk at follow-up, 3 years after baseline. At baseline, 35.0 per cent of participants were at high nutrition risk and 42.2 per cent were at high risk at follow-up. Lower levels of social support, lower social participation, depression, and poor self-rated healthy aging were associated with the development of high nutrition risk at follow-up. Individuals showing these factors should be screened proactively for nutrition risk.
To evaluate the impact of a diagnostic stewardship intervention on Clostridioides difficile healthcare-associated infections (HAI).
Design:
Quality improvement study.
Setting:
Two urban acute care hospitals.
Interventions:
All inpatient stool testing for C. difficile required review and approval prior to specimen processing in the laboratory. An infection preventionist reviewed all orders daily through chart review and conversations with nursing; orders meeting clinical criteria for testing were approved, orders not meeting clinical criteria were discussed with the ordering provider. The proportion of completed tests meeting clinical criteria for testing and the primary outcome of C. difficile HAI were compared before and after the intervention.
Results:
The frequency of completed C. difficile orders not meeting criteria was lower [146 (7.5%) of 1,958] in the intervention period (January 10, 2022–October 14, 2022) than in the sampled 3-month preintervention period [26 (21.0%) of 124; P < .001]. C. difficile HAI rates were 8.80 per 10,000 patient days prior to the intervention (March 1, 2021–January 9, 2022) and 7.69 per 10,000 patient days during the intervention period (incidence rate ratio, 0.87; 95% confidence interval, 0.73–1.05; P = .13).
Conclusions:
A stringent order-approval process reduced clinically nonindicated testing for C. difficile but did not significantly decrease HAIs.
Fossils are more and more used in phylogenetic evolutionary studies either for clade calibration, or as terminals in a dataset including morphological characters. The strength of these methodological advances relies however on the quality and completeness of the fossil record. For crickets (Insecta, Orthoptera, Gryllidea), few ancient (pre-Cenozoic) well-preserved fossils are known, except for isolated wings often classified in purely fossil groups and a few fossils found in Cretaceous amber. Here, we present two remarkable fossils from mid-Cretaceous amber of France, that were imaged using X-ray synchrotron microtomography and exhibit an exquisite preservation allowing description with a precision similar to that of extant taxa. Palaeonemobius occidentalis Laurent and Desutter-Grandcolas, gen. nov., sp. nov. and Picogryllus carentonensis Josse and Desutter-Grandcolas, gen. nov., sp. nov. are the oldest representatives of the Nemobiinae and Podoscirtinae subfamilies of the Trigonidiidae and Oecanthidae families respectively. P. carentonensis Josse and Desutter-Grandcolas, gen. nov., sp. nov. is also the smallest adult male with a full stridulatory apparatus ever documented in crickets (body length 3.3 mm), and the first taxon of the cricket clade for which male genitalia can be partly described. We discuss the significance of Cretaceous fossils of crickets for future evolutionary studies of this clade.
Childhood maltreatment can result in lifelong psychological and physical sequelae, including coronary artery disease (CAD). Mechanisms leading to increased risk of illness may involve emotional dysregulation and shortened leukocyte telomere length (LTL).
Methods
To evaluate whether (1) childhood maltreatment is associated with shorter LTL among older adults with CAD or other chronic illnesses; (2) sex and/or CAD status influence these results; and (3) symptoms of anxiety, depression, and stress moderate or mediate the association between childhood maltreatment and LTL, men and women (N = 1247; aged 65 ± 7.2 years) with and without CAD completed validated questionnaires on childhood maltreatment, symptoms of depression, anxiety, and perceived stress. LTL was measured using quantitative polymerase chain reaction. Analyses included bivariate correlations, hierarchical regressions, and moderation/mediation analyses, controlling for sociodemographic and lifestyle variables.
Results
Childhood maltreatment was associated with significantly shorter LTL (r = −0.059, p = 0.038, b = −0.016, p = 0.005). This relation was not moderated by depression, anxiety, nor perceived stress, though there was mitigated evidence for absence of a maltreatment-LTL relation in men with CAD. Stress perception (but not anxiety or depression) partially mediated the relation between childhood maltreatment and LTL [Indirect effect, b = −0.0041, s.e. = 0.002, 95% CI (−0.0085 to −0.0002)].
Conclusions
Childhood maltreatment was associated with accelerated biological aging independently of patient characteristics. Emotional dysregulation resulting in chronic stress may contribute to this process. Whether stress management or other interventions may help prevent or slow premature aging in those who have suffered maltreatment requires study.
The coronavirus disease 2019 (COVID-19) pandemic might affect mental health. Data from population-representative panel surveys with multiple waves including pre-COVID data investigating risk and protective factors are still rare.
Methods
In a stratified random sample of the German household population (n = 6684), we conducted survey-weighted multiple linear regressions to determine the association of various psychological risk and protective factors assessed between 2015 and 2020 with changes in psychological distress [(PD; measured via Patient Health Questionnaire for Depression and Anxiety (PHQ-4)] from pre-pandemic (average of 2016 and 2019) to peri-pandemic (both 2020 and 2021) time points. Control analyses on PD change between two pre-pandemic time points (2016 and 2019) were conducted. Regularized regressions were computed to inform on which factors were statistically most influential in the multicollinear setting.
Results
PHQ-4 scores in 2020 (M = 2.45) and 2021 (M = 2.21) were elevated compared to 2019 (M = 1.79). Several risk factors (catastrophizing, neuroticism, and asking for instrumental support) and protective factors (perceived stress recovery, positive reappraisal, and optimism) were identified for the peri-pandemic outcomes. Control analyses revealed that in pre-pandemic times, neuroticism and optimism were predominantly related to PD changes. Regularized regression mostly confirmed the results and highlighted perceived stress recovery as most consistent influential protective factor across peri-pandemic outcomes.
Conclusions
We identified several psychological risk and protective factors related to PD outcomes during the COVID-19 pandemic. A comparison of pre-pandemic data stresses the relevance of longitudinal assessments to potentially reconcile contradictory findings. Implications and suggestions for targeted prevention and intervention programs during highly stressful times such as pandemics are discussed.
Background: Identification of hospitalized patients with enteric multidrug-resistant organism (MDRO) carriage, combined with implementation of targeted infection control interventions, may help reduce MDRO transmission. However, the optimal surveillance approach has not been defined. We sought to determine whether daily serial rectal surveillance for MDROs detects more incident cases (acquisition) of MDRO colonization in medical intensive care unit (MICU) patients than admission and discharge surveillance alone. Methods: Prospective longitudinal observational single-center study from January 11, 2017, to January 11, 2018. Inclusion criteria were ≥3 consecutive MICU days and ≥2 rectal or stool swabs per MICU admission. Daily rectal or stool swabs were collected from patients and cultured for MDROs, including vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Enterobacterales (CRE), third-generation cephalosporin-resistant Enterobacterales (3GCR), and extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E) (as a subset of 3GCR). MDRO detection at any time during the MICU stay was used to calculate prevalent colonization. Incident colonization (acquisition) was defined as new detection of an MDRO after at least 1 prior negative swab. We then determined the proportion of prevalent and incident cases detected by daily testing that were also detected when only first swabs (admission) and last swabs (discharge) were tested. Data were analyzed using SAS version 9.4 software. Results: In total, 939 MICU stays of 842 patients were analyzed. Patient characteristics were median age 64 years (interquartile range [IQR], 51–74), median MICU length of stay 5 days (IQR, 3–8), median number of samples per admission 3 (IQR, 2–5), and median Charlson index 4 (IQR, 2–7). Prevalent colonization with any MDRO was detected by daily swabbing in 401 stays (42.7%). Compared to daily serial swabbing, an admission- and discharge-only approach detected ≥86% of MDRO cases (ie, overall prevalent MDRO colonization). Detection of incident MDRO colonization by an admission- or discharge-only approach would have detected fewer cases than daily swabbing (Figure 1); ≥34% of total MDRO acquisitions would have been missed. Conclusions: Testing patients upon admission and discharge to an MICU may fail to detect MDRO acquisition in more than one-third of patients, thereby reducing the effectiveness of MDRO control programs that are targeted against known MDRO carriers. The poor performance of a single discharge swab may be due to intermittent or low-level MDRO shedding, inadequate sampling, or transient MDRO colonization. Additional research is needed to determine the optimal surveillance approach of enteric MDRO carriage.
Isolated chronic granulomatous meningitis remains a diagnostic challenge for the physician. Symptoms are often nonspecific and ancillary tests have low-sensitivity rates, which may delay targeted treatment and lead to increased morbidity and mortality. Here, we discuss the challenges in diagnosing and treating patients with chronic meningitis by reporting two cases of previously healthy patients who presented with granulomatous meningitis on brain biopsy.
High dietary phosphorus (P), particularly soluble salts, may contribute to chronic kidney disease development in cats. The aim of the present study was to assess the safety of P supplied at 1 g/1000 kcal (4184kJ) from a highly soluble P salt in P-rich dry format feline diets. Seventy-five healthy adult cats (n 25/group) were fed either a low P control (1·4 g/1000 kcal [4184kJ]; Ca:P ratio 0·97) or one of two test diets with 4 g/1000 kcal (4184 kJ); Ca:P 1·04 or 5 g/1000 kcal (4184kJ); Ca:P 1·27, both incorporating 1 g/1000 kcal (4184 kJ) sodium tripolyphosphate (STPP) – for a period of 30 weeks in a randomised parallel-group study. Health markers in blood and urine, glomerular filtration rate, renal ultrasound and bone density were assessed at baseline and at regular time points. At the end of the test period, responses following transition to a commercial diet (total P – 2·34 g/1000 kcal [4184kJ], Ca:P 1·3) for a 4-week washout period were also assessed. No adverse effects on general, kidney or bone (skeletal) function and health were observed. P and Ca balance, some serum biochemistry parameters and regulatory hormones were increased in cats fed test diets from week 2 onwards (P ≤ 0·05). Data from the washout period suggest that increased serum creatinine and urea values observed in the two test diet groups were influenced by dietary differences during the test period, and not indicative of changes in renal function. The present data suggest no observed adverse effect level for feline diets containing 1 g P/1000 kcal (4184 kJ) from STPP and total P level of up to 5 g/1000 kcal (4184 kJ) when fed for 30 weeks.
Recent European Society of Parenteral and Enteral Nutrition guidelines highlighted the interest of prevention, diagnosis and treatment of malnutrition in the management of coronavirus disease 19 (COVID-19) patients. The aim of our study was to evaluate the prevalence of malnutrition in patients hospitalised for COVID-19. In a prospective observational cohort study malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition (GLIM) two-step approach. Patients were divided into two groups according to the diagnosis of malnutrition. Covariate selection for the multivariate analysis was based on P <0·2 in univariate analysis, with a logistic regression model and a backward elimination procedure. A partitioning of the population was realised. Eighty patients were prospectively enrolled. Thirty patients (37·5 %) had criteria for malnutrition. The need for intensive care unit admission (n 46, 57·5 %) was similar in the two groups. Three patients who died (3·75 %) were malnourished. Multivariate analysis exhibited that low BMI (OR 0·83, 95 % CI 0·73, 0·96, P = 0·0083), dyslipidaemia (OR 29·45, 95 % CI 3·12, 277·73, P = 0·0031), oral intake reduction <50 % (OR 3·169, 95 % CI 1·04, 9·64, P = 0·0422) and glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration; CKD-EPI) at admission (OR 0·979, 95 % CI 0·96, 0·998, P = 0·0297) were associated with the occurrence of malnutrition. We demonstrate the existence of a high prevalence of malnutrition in a general cohort of COVID-19 inpatients according to GLIM criteria. Nutritional support in COVID-19 care seems an essential element.
The anticlerical violence of the Spanish Civil War has received significant scholarly attention in recent years. However, there has been relatively little focus on the iconoclasm, even though the destruction of objects was easily the most common form of anticlerical violence. Nor has the effect of iconoclastic violence on those who treasured or venerated these objects been examined. This article looks at the emotional significance of the material artefacts that came under attack during the Civil War. It argues that, while some objects were treated simply as the material of which they were made, most provoked more complex interactions. In contrast to most earlier episodes of iconoclasm, these also left a visual record, which shows how the memory of the violence was shaped not only by textual accounts but also by photographs that memorialised and aestheticised it.
Background: Cultivation of targeted pathogens has been long recognized as a gold standard for healthcare surveillance. However, there is an emergent need to characterize all viable microorganisms in healthcare facilities to understand the role that both clinical and nonclinical microorganisms play in healthcare-associated infections. Metagenomic sequencing allows detection of entire microbial communities, in contrast to targeted identification by cultivation. Widespread application of metagenomic sequencing has been impeded in part because the sensitivity and specificity are unknown, which inhibits our ability to interpret results for risk assessment. To assess the impact of sample preparation methods on sensitivity and specificity, we compared several pretreatment steps followed by metagenomic sequencing, and we performed culture-based analyses. Methods: We collected 120 surface swabs from the medical intensive care unit at Rush University Medical Center, which we aggregated to create a representative microbiome sample. We then subjected aliquots to different processing methods (DNA extraction methods, internal standard addition, propidium monoazide (PMA) treatment, and whole-cell serial filtration). We evaluated the effects of these methods based on DNA yields and metagenomic sequencing outcomes. We also compared the metagenomic results to the microbial identifications obtained by cultivation using environmental microbiology methods and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results: Our results demonstrate that bead-beating and heat lysis followed by liquid-liquid extraction is the optimal method for the identification of low-biomass surface-associated microbes, as opposed to widely used column-based and magnetic bead-based methods. For low-biomass surface-associated samples, ~590,000 reads per sample are sufficient for ≍90% coverage in metagenomic sequencing (Fig. 1). The ZymoBIOMICS microbial community standard is not appropriate for methods assessing membrane integrity. For the identification of putatively viable microorganisms, PMA treatment is promising, although elimination of signals from nonviable organisms will reduce the overall detectable signal. Combining PMA-treated metagenomic sequencing with cultivation yields the most comprehensive results, particularly for low-abundance taxa, despite high sequencing coverage (Fig. 2). To distribute more detection resources to bacteria, our target domain, we tried whole-cell filtration prior to extraction, attempting to isolate bacterial cells from eukaryotic cells and other particles. For low-biomass surface-associated samples, the sample loss and the difficulties in performing filtration outweigh the slight increase of bacterial signal. Conclusions: Despite optimization, we observed certain blind spots in both cultivation and metagenomic sequencing. This information is essential for informed risk assessment. Further research is needed to identify additional limitations to ensure that results from metagenomic sequencing can be interpreted in the context of healthcare-acquired infection prevention.
Funding: This work was supported by the Centers for Disease Control and Prevention (BAA FY2018-OADS-01 Contract 02915).
Terrestrial laser scanning (TLS) provides a means of rapid and highly accurate survey of archaeological excavations and structures at landscape scales, and is particularly valuable for documenting tidal environments. Here, the authors use TLS to record tidal fixed fishing structures and a tide mill within the Léguer Estuary at Le Yaudet, in north-west France. As part of a comprehensive resource-exploitation system, the early medieval (sixth to eighth centuries AD) structures lie within, and exploit different parts of, the tidal frame. The results are used to quantify production within an estuarine landscape associated with seignorial or monastic control of environmental resources.
Resistant dextrins are glucose polymers with atypical linkages making them non-digestible in the upper part of the gastrointestinal tract. NUTRIOSE® is slightly digested in the small intestine and then, progressively fermented in the colon. The objective of this study is to investigate the beneficial effects resulting from the colonic fermentation of NUTRIOSE® and the underlying mechanism of action in rats.
Materials & Methods:
This experiment was conducted according to the French Regulations for Animal Experimentation and authorized under the project Number 00619.01. After acclimatisation on maintaining diet, 20 Sprague-Dawley rats were blocked by body weight and randomly split into 2 groups. The control group was given a fibre-free diet where corn starch was used to replace fibre and the experimental group was supplemented with 10% NUTRIOSE®. Feces were collected for enzymatic activities measurement. Caecal contents were collected so as caecal cell walls and colon biopsies for gene expression analysis.
Results:
The significant increases in caecal content weight (p < 0.001) fecal activity of saccharolytic enzymes (p < 0.05) and the decrease in caecal pH (p < 0.001) after the supplementation of NUTRIOSE® suggested its fermentation in the colon and caecum. It is also known from literature that NUTRIOSE® fermentation leads to higher levels of short chain fatty acids including higher levels of propionate and butyrate. This enhanced fermentation induced several positive impacts in the colon such as an increased caecal wall weight (p < 0.001) demonstrating beneficial effect on colon epithelial cells, an up-regulation of genes involved in membrane integrity (occludin (p = 0.01), ZO-1(p = 0.01)), and a positive impact on genes involved in inflammation (Tnf-α (p = 0.03), FOXP3 (p = 0.01)). The present study demonstrated the positive effects of NUTRIOSE® supplementation on glucose metabolism through the up-regulation of PEPCK in the colon (p < 0.001). This effect may also be mediated by the up-regulation of the GPR41 receptor in the colon (p < 0.001) and probably activated by butyrate.
Conclusions:
All together, these results confirmed that NUTRIOSE® is well fermented in the colon and that these fermentations may be associated with beneficial impacts on colonic epithelial integrity, inflammation and neoglucogenesis. Here we demonstrate a putative mechanism of action of NUTRIOSE® to improve the colonic health which is through the production of butyrate and the resulting activation of GPR41 receptor. Thus, this study helps us to understand the physiological impact of NUTRIOSE® fermentation in colon to produce several health benefits as observed in clinical studies.
Any civil war leaves a legacy of partisanship. Divisions persist over time and may be particularly bitter when, as in Spain, a culture of victory survives long after the end of hostilities. Any attempt at reconciliation was postponed, leading to an unusually bifurcated historiography, framed by a perennial interest into who, at base, was responsible for the outbreak of the civil war. The parameters of this debate were set in the 1970s, most notably in works by Stanley Payne and Paul Preston. It has continued in various guises since then, most recently revived by a generation of Spanish scholars, such as Fernando del Rey Reguillo, who have added case studies and new levels of detail, while leaving the terms of the debate more or less unchanged. Of course the historiographical panorama can change, often in tandem with the historical context, as several contributions to this roundtable make clear, notably those of Vjeran Pavlaković, Helen Graham and Giuliana Chamedes. However, the framing of the Spanish Civil War is still essentially moral: who bore responsibility for the outbreak of war, who was to blame for the defeat of the republic and, as a consequence, the conduct of the repression. One result has been to assimilate the history of the civil war with that of the Second Republic; another is a historiography that is largely political in tone and focus.
With the rise of information technology, an increasing proportion of public African archives are being digitized and made accessible on the internet. The same is being done to a certain extent with private archives too. As much as the new technologies are raising enthusiasm, they have prompted discussion among researchers and archivists, on subjects ranging from matters of intellectual property to sovereignty and governance. Digital archiving disrupts archival norms and practices, opening up a field of reflection relatively little explored by historians. This article therefore seeks to reflect on the digital turn of African archives as a subject for study in its own right, located at the crossroads of political and economic interests.
Among 300 advanced cancer patients with potential urinary tract infection (UTI), 19 had symptomatic UTI. Among remaining patients (n = 281), 21% had asymptomatic bacteriuria or candiduria, and 14% received inappropriate therapy for 279 antimicrobial days. Bacteriuria or candiduria predicted antimicrobial therapy. At 10,000 to <100,000 CFU/mL, the incidence rate ratio [IRR] was 16.9 (95% confidence interval [CI], 6.0–47.2), and at ≥100,000 CFU/mL, the IRR was 27.9 (95% CI, 10.9–71.2).