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OBJECTIVES/GOALS: Antibiotic treatment sets the stage for intestinal domination by Candida albicanswhich is necessary for development of invasive disease, but the resources driving this bloom remain poorly defined. We sought to determine these factors in order to design novel prophylaxis strategies for reducing gastrointestinal (GI) colonization. METHODS/STUDY POPULATION: We initially developed a generalizable framework, termed metabolic footprinting to determine the metabolites C. albicanspreferentially uses in the mouse GI tract. After identifying the metabolites C. albicansutilizes, we usedin vitro growth assays in the presence and absence of oxygen to validate out metabolomics findings. We next determined if a probiotic E. coli that utilizes oxygen would reduce C. albicanscolonization compared to a mutant E. coli that could not respire oxygen. Finding that oxygen was a necessary resource, we utilized germ-free mice to determine if Clostridiaspp. known to reduce GI oxygen would prevent C. albicanscolonization. Lastly, we sought to see if 5-aminosalicylic acid (5-ASA) could prevent C. albicanscolonization. RESULTS/ANTICIPATED RESULTS: We found that C. albicans preferentially utilizes simple carbohydrates including fructo-oligosaccharides (e.g., 1-kestose), disaccharides (e.g., β-gentiobiose), and alcoholic sugars (e.g., sorbitol) and is able to grow in vitro on minimal media supplemented with either of these nutrients. However, in the hypoxic environment that is found in the “healthy” colon, C. albicans cannot utilize these nutrients. We next found that pre-colonization in a mouse model with a probiotic E. coli significantly reduced C. albicanscolonization, but the mutant E. coli had no effect on colonization. We next showed that Clostridia supplementation restored GI hypoxia and reduced C. albicanscolonization. Remarkably, we found that 5-ASA significantly reduced GI colonization of C. albicans. DISCUSSION/SIGNIFICANCE: We have shown that C. albicans requires oxygen to colonize the GI tract. Importantly, we found that 5-ASA can prevent an antibiotic mediated bloom of C. albicans by restoring GI hypoxia, which warrants additional studies to determine if 5-ASA can be used as an adjunctive prophylactic treatment in high risk patients.
Suicide is the second leading cause of death in 12- to 17-year-old adolescents in the USA. Research on biological mechanisms contributing to self-harm risk that could be targeted in treatment could help to prevent suicide and self-harm episodes.
Aims
We aimed to evaluate whether markers of inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP), predict self-harm over 3 months within a sample selected for elevated suicide/self-harm risk at project entry.
Method
Fifty-one adolescents aged 12–19 years selected for elevated suicide/self-harm risk completed three clinical interviews about suicide attempts and non-suicidal self-injury, 3 months apart. At baseline and 3 months, youth also provided blood samples, from which we assayed levels of IL-6 and CRP.
Results
Using generalised mixed models, we found that greater levels of IL-6 predicted more self-harm episodes (odds ratio [OR] = 3.3, 95% CI: 1.1, 10.0) and specifically, non-suicidal self-injury (OR = 3.5, 95% CI: 1.1, 11.2), over 3 months.
Conclusions
The study findings increase our understanding of whether and how inflammation may be implicated in risk of self-harm. IL-6 may be a viable biological marker of short-term risk for self-harm.
The reading the mind in the eyes test (RMET) – which assesses the theory of mind component of social cognition – is often used to compare social cognition between patients with schizophrenia and healthy controls. There is, however, no systematic review integrating the results of these studies. We identified 198 studies published before July 2020 that administered RMET to patients with schizophrenia or healthy controls from three English-language and two Chinese-language databases. These studies included 41 separate samples of patients with schizophrenia (total n = 1836) and 197 separate samples of healthy controls (total n = 23 675). The pooled RMET score was 19.76 (95% CI 18.91–20.60) in patients and 25.53 (95% CI 25.19–25.87) in controls (z = 12.41, p < 0.001). After excluding small-sample outlier studies, this difference in RMET performance was greater in studies using non-English v. English versions of RMET (Chi [Q] = 8.54, p < 0.001). Meta-regression analyses found a negative association of age with RMET score and a positive association of years of schooling with RMET score in both patients and controls. A secondary meta-analysis using a spline construction of 180 healthy control samples identified a non-monotonic relationship between age and RMET score – RMET scores increased with age before 31 and decreased with age after 31. These results indicate that patients with schizophrenia have substantial deficits in theory of mind compared with healthy controls, supporting the construct validity of RMET as a measure of social cognition. The different results for English versus non-English versions of RMET and the non-monotonic relationship between age and RMET score highlight the importance of the language of administration of RMET and the possibility that the relationship of aging with theory of mind is different from the relationship of aging with other types of cognitive functioning.
An alternative surgical approach for hypoplastic left heart syndrome is the Hybrid pathway, which delays the risk of acute kidney injury outside of the newborn period. We sought to determine the incidence, and associated morbidity, of acute kidney injury after the comprehensive stage 2 and the cumulative incidence after the first two operations in the Hybrid pathway.
Design:
A single centre, retrospective study was conducted of hypoplastic left heart patients completing the second-stage palliation in the Hybrid pathway from 2009 to 2018. Acute kidney injury was defined utilising Kidney Diseases Improving Global Outcomes criteria. Perioperative and post-operative characteristics were analysed.
Results:
Sixty-one patients were included in the study cohort. The incidence of acute kidney injury was 63.9%, with 36.1% developing severe injury. Cumulatively after the Hybrid Stage 1 and comprehensive stage 2 procedures, 69% developed acute kidney injury with 36% developing severe injury. The presence of post-operative acute kidney injury was not associated with an increase in 30-day mortality (acute kidney injury 7.7% versus none 9.1%; p = > 0.9). There was a significantly longer median duration of intubation among those with acute kidney injury (acute kidney injury 32 (8, 155) hours vs. no injury 9 (0, 94) hours; p = 0.018).
Conclusions:
Acute kidney injury after the comprehensive stage two procedure is common and accounts for most of the kidney injury in the first two operations of the Hybrid pathway. No difference in mortality was detected between those with acute kidney injury and those without, although there may be an increase in morbidity.
Evidence clearly indicates that the nutritional and non-nutritional environment and level of physical activity during the early-life period from preconception through infancy has a lifelong impact on the child’s health. However this message must be communicated effectively to parents and other stakeholders such as grandparents, health professionals, policymakers and the wider community in order for positive change to occur. This systematic review explores how both awareness and understanding of the long-term effects of the early-life environment have been measured in various populations and whether any patterns are evident. Ten articles were retrieved via a search of Embase, Medline and Scopus databases for peer-reviewed studies designed to assess participants’ knowledge of the links between early-life exposures and adult health. Eligible articles spanned a wide range of countries, population groups and research methods. Three common themes were identified using thematic analysis: 1. a tendency for researchers to conflate participant understanding of the issue (the WHY) with a knowledge of key phrases and nutrition guidelines (the WHAT); 2. bias in both researchers and participants towards short-term thinking due to difficulty conceptualising long-term risk; and 3. challenges in comprehending the complexity of the evidence resulting in oversimplification and the overemphasis of maternal factors. Taken together these findings underscore the importance of a multi-level, whole-of-society approach to communicating the evidence, with the goal of influencing policy decisions as well as building a foundation of community support for parents and prospective parents to create a healthy early-life environment for the long-term wellbeing of all.
Three machine learning techniques (multilayer perceptron, random forest and Gaussian process) provide fast surrogate models for lower hybrid current drive (LHCD) simulations. A single GENRAY/CQL3D simulation without radial diffusion of fast electrons requires several minutes of wall-clock time to complete, which is acceptable for many purposes, but too slow for integrated modelling and real-time control applications. The machine learning models use a database of more than 16 000 GENRAY/CQL3D simulations for training, validation and testing. Latin hypercube sampling methods ensure that the database covers the range of nine input parameters ($n_{e0}$, $T_{e0}$, $I_p$, $B_t$, $R_0$, $n_{\|}$, $Z_{{\rm eff}}$, $V_{{\rm loop}}$ and $P_{{\rm LHCD}}$) with sufficient density in all regions of parameter space. The surrogate models reduce the inference time from minutes to $\sim$ms with high accuracy across the input parameter space.
We report the experimental results of the commissioning phase in the 10 PW laser beamline of the Shanghai Superintense Ultrafast Laser Facility (SULF). The peak power reaches 2.4 PW on target without the last amplifying during the experiment. The laser energy of 72 ± 9 J is directed to a focal spot of approximately 6 μm diameter (full width at half maximum) in 30 fs pulse duration, yielding a focused peak intensity around 2.0 × 1021 W/cm2. The first laser-proton acceleration experiment is performed using plain copper and plastic targets. High-energy proton beams with maximum cut-off energy up to 62.5 MeV are achieved using copper foils at the optimum target thickness of 4 μm via target normal sheath acceleration. For plastic targets of tens of nanometers thick, the proton cut-off energy is approximately 20 MeV, showing ring-like or filamented density distributions. These experimental results reflect the capabilities of the SULF-10 PW beamline, for example, both ultrahigh intensity and relatively good beam contrast. Further optimization for these key parameters is underway, where peak laser intensities of 1022–1023 W/cm2 are anticipated to support various experiments on extreme field physics.
In Japan, schistosomiasis was endemic in Yamanashi Prefecture and a few other hotspot areas where the Miya’iri snail lived. The parasite’s lifecycle relied on the intermediary Miya’iri snail as well as the human host. Parasite eggs passed into the agrarian environment through untreated night soil used as fertiliser or through the culture of open defecation in rural Japan. Manmade rice fields and irrigation ditches, night soil covered paddies and highly refined growing seasons put people in flooded rice paddies to intensively work the land in the spring and summer. The disease was equally dependent on human intervention in the natural world as it was on the natural world intervening in the human body. It is important to stress the role of both the environment and culture in disease causation. This study posits that we view the pre- and post-war national mobilisation to remake the environmental and reform the culture of the rural sector to align with public health mandates and notions of hygienic modernity as a case of total prevention.
Variable camber flap technology can adjust the spanwise circulation distribution, thereby reducing the induced drag. Therefore, the concept of variable camber flap is introduced into the design of propeller aircraft wing, and the design for drag reduction of propeller aircraft is carried out. The numerical simulation of the propeller aircraft is carried out by using the actuator disc method with non-uniform distribution of radial and circumferential loads. Through the unsteady simulation of a single propeller, the aerodynamic load on a periodic propeller is extracted as a boundary condition to the steady simulation of the full aircraft. The load extracted by the actuator disc is compared with the unsteady simulation result, which verifies the reliability of the method. The design for drag reduction at cruise and climb design conditions are respectively carried out with the variable camber flap technology. The variable camber cruise configuration is evaluated at both the begin and end cruise conditions. The results show that, after the flaps deflecting at a small angle according to the circulation distribution, the camber distribution of the wing is adjusted to make the circulation distribution closer to the elliptical circulation distribution. At the design cruise condition, the drag coefficient is reduced by 1.4 counts, and the lift-drag ratio increase by 0.1. At both begin and end cruise conditions, the drag coefficient decreases by 1 count, and the lift-drag ratio increases by 0.07. At the design climb condition, the drag coefficient decreases by 1 count, and the lift-to-drag ratio increases by 0.09.
The commercial Computational Fluid Dynamics (CFD) software STAR-CCM+ was used to simulate the flow and breakup characteristics of a Liquid Jet Injected into the gaseous Crossflow (LJIC) under real engine operating conditions. The reasonable calculation domain geometry and flow boundary conditions were obtained based on a civil aviation engine performance model similar to the Leap-1B engine which was developed using the GasTurb software and the preliminary design results of its low-emission combustor. The Volume of Fluid (VOF) model was applied to simulate the breakup feature of the near field of LJIC. The numerical method was validated and calibrated through comparison with the public test data at atmospheric conditions. The results showed that the numerical method can capture most of the jet breakup structure and predict the jet trajectory with an error not exceeding ±5%. The verified numerical method was applied to simulate the breakup of LJIC at the real engine operating condition. The breakup mode of LJIC was shown to be surface shear breakup at elevated condition. The trajectory of the liquid jet showed good agreement with Ragucci’s empirical correlation.
Research into associations between early life nutritional exposures and vulnerability to adult non-communicable disease (NCD) highlights the importance of maternal diet. A booklet outlining evidence-based dietary guidelines for the first 1000 days of life was first published in 2016 by early life nutrition experts for distribution to pregnant women in Australia and New Zealand. First-time New Zealand mothers’ (n=9) perceptions of the booklet and its relevance for the future health of their child were explored via semi-structured focus groups and interviews. Recruitment took place via social media channels and antenatal classes around Auckland. Three major themes were identified using thematic analysis: 1. A difference in the ways mothers related to the booklet depending on their apparent level of health literacy and communication preferences; 2. A tendency for women to outsource decision-making to nutrition ‘rules’, rather than interpreting information to suit personal circumstances; 3. Intense pressure to comply, resulting in feelings of shame or guilt when the ‘rules’ were not followed. In this study, first-time mums expressed feeling under pressure to ‘get it right’ and identified a desire for more support from healthcare providers and society. Nutrition education is essential; however, a booklet should provide a starting point for conversation rather than a stand-alone list of recommendations. Further exploration is needed to develop a resource that can be used by health professionals working alongside women and their partners to support healthy child development.
Acute kidney injury leads to worse outcomes following paediatric cardiac surgery. There is a lack of literature focusing on acute kidney injury after the Hybrid stage 1 palliation for single ventricle physiology. Patients undergoing the Hybrid Stage 1, as a primary option, may have a lower incidence of kidney injury than previously reported. When present, kidney injury may increase the risk of post-operative morbidity and mortality.
Methods:
A retrospective, single centre review was conducted in patients with hypoplastic left heart syndrome who underwent Hybrid Stage 1 from 2008 to 2018. Acute kidney injury was defined as a dichotomous yes (meeting any injury criteria) or no (no injury) utilising two different criteria utilised in paediatrics. The impact of kidney injury on perioperative characteristics and 30-day mortality was analysed.
Results:
The incidence of acute kidney injury is 13.4–20.7%, with a severe injury rate of 2.4%. Patients without a prenatal diagnosis of hypoplastic left heart syndrome have a higher incidence of kidney injury than those prenatally diagnosed, (40% versus 14.5%, p = 0.024). Patients with acute kidney injury have a significantly higher incidence of 30-day mortality, 27.3%, compared to without, 5.6% (p = 0.047).
Discussion:
The incidence of severe acute kidney injury after the Hybrid Stage 1 palliation is low. A prenatal diagnosis may be associated with a lower incidence of kidney injury following the Hybrid Stage 1. Though uncommon, severe acute kidney injury following Hybrid Stage 1 may be associated with higher 30-day mortality.
To describe the pattern of transmission of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) during 2 nosocomial outbreaks of coronavirus disease 2019 (COVID-19) with regard to the possibility of airborne transmission.
Design:
Contact investigations with active case finding were used to assess the pattern of spread from 2 COVID-19 index patients.
Setting:
A community hospital and university medical center in the United States, in February and March, 2020, early in the COVID-19 pandemic.
Patients:
Two index patients and 421 exposed healthcare workers.
Methods:
Exposed healthcare workers (HCWs) were identified by analyzing the electronic medical record (EMR) and conducting active case finding in combination with structured interviews. Healthcare coworkers (HCWs) were tested for COVID-19 by obtaining oropharyngeal/nasopharyngeal specimens, and RT-PCR testing was used to detect SARS-CoV-2.
Results:
Two separate index patients were admitted in February and March 2020, without initial suspicion for COVID-19 and without contact or droplet precautions in place; both patients underwent several aerosol-generating procedures in this context. In total, 421 HCWs were exposed in total, and the results of the case contact investigations identified 8 secondary infections in HCWs. In all 8 cases, the HCWs had close contact with the index patients without sufficient personal protective equipment. Importantly, despite multiple aerosol-generating procedures, there was no evidence of airborne transmission.
Conclusion:
These observations suggest that, at least in a healthcare setting, most SARS-CoV-2 transmission is likely to take place during close contact with infected patients through respiratory droplets, rather than by long-distance airborne transmission.
An experiment was conducted to determine the effects of supplementing different amounts of daidzein in a diet on the growth performance, blood biochemical parameters and meat quality of finishing beef cattle. Thirty finishing Xianan steers were distributed in three groups equilibrated by weight and fed three different dietary treatments (concentrate ratio = 80%): (1) control; (2) 500 mg/kg daidzein and (3) 1000 mg/kg daidzein, respectively. Steers were slaughtered after an 80-day feeding trial. Results showed that daidzein supplementation had no effect on the final body weight, average daily gain and feed conversion rate of steers. Steers fed with 1000 mg/kg daidzein had greater dry matter intake than those fed with control diets. Compared with the control group, the 1000 mg/kg daidzein group had a higher fat thickness, lower shear force and lightness. The pH, drip loss, cooking loss, redness (a*), yellowness (b*), moisture, ash, crude protein and intramuscular fat of the Longissimus dorsi muscle were unaffected by daidzein supplementation. Compared with the control group, the 1000 mg/kg daidzein group significantly increased the serum concentrations of insulin, free fatty acid and Glutamic-pyruvic transaminase. The 500 mg/kg daidzein group significantly increased the serum concentration of tetraiodothyronine compared with the control group. Supplemental daidzein did not affect the blood antioxidant ability and blood immune parameters in serum. In conclusion, daidzein supplementation above 500 mg/day modifies feed intake and metabolic and hormonal profile, with positive and negative effects on meat quality.
We introduce CRYSTAL, a multi-agent AI system for crystal-structure phase mapping. CRYSTAL is the first system that can automatically generate a portfolio of physically meaningful phase diagrams for expert-user exploration and selection. CRYSTAL outperforms previous methods to solve the example Pd-Rh-Ta phase diagram, enabling the discovery of a mixed-intermetallic methanol oxidation electrocatalyst. The integration of multiple data-knowledge sources and learning and reasoning algorithms, combined with the exploitation of problem decompositions, relaxations, and parallelism, empowers AI to supersede human scientific data interpretation capabilities and enable otherwise inaccessible scientific discovery in materials science and beyond.
Evidence in support of the Developmental Origins of Health and Disease (DOHaD) hypothesis has reached the level where it can appropriately be used to inform practice. DOHaD informed interventions supporting primary noncommunicable disease risk reduction should target the pre- and periconceptional periods, pregnancy, lactation, childhood and adolescence. Such interventions are dependent on a health workforce (including dietitians, nurses, midwives, doctors, and nutrition teachers), that has a deep understanding of DOHaD concepts. This study assessed development of awareness of DOHaD concepts during undergraduate health professional training programs. Using a cross-sectional design, a standardized questionnaire was completed by Year 1–4 undergraduate students studying nutrition in Japan (n=309) and Year 1–3 nursing students in New Zealand (n=151). On entry to undergraduate study, most students had no awareness of the terms ‘DOHaD’ or ‘First 1000 Days’. While awareness reached 60% by Year 3 in courses that included DOHaD-related teaching, this remains inadequate. More than 95% of Year 1 undergraduates in both countries demonstrated an appreciation of associations between maternal nutrition and fetal health. However, awareness of associations between parental health status and/or nutritional environment and later-life health was low. While levels of awareness increased across program years, overall awareness was less than optimal. These results indicate evidence of some focus on DOHaD-related content in curricula. We argue that DOHaD principles should be one pillar around which health training curricula are built. This study indicates a need for the DOHaD community to engage with faculties in curriculum development.
In modern Japan, beriberi (or thiamin deficiency) became a public health problem that cut across all social boundaries, afflicting even the Meiji Emperor. During an age of empire building for the Japanese nation, incidence rates in the military ranged from 30 percent in peacetime to 90 percent during war. Doctors and public health officials called beriberi a "national disease" because it festered within the bodies of the people and threatened the health of the empire. Nevertheless, they could not agree over what caused the disease, attributing it to a diet deficiency or a microbe.
InBeriberi in Modern Japan, Alexander R. Bay examines the debates over the etiology of this "national disease" during the late nineteenth and early twentieth centuries. Etiological consensus came after World War I, but the struggle at the national level to direct beriberi prevention continued, peaking during wartime mobilization. War served as the context within which scientific knowledge of beriberi and its prevention was made. The story of beriberi research is not simply about the march toward the inevitable discovery of "the beriberi vitamin," but rather the history of the role of medicine in state-making and empire-building in modern Japan.
Alexander Bay is assistant professor of history at Chapman University.
In this paper, the occurrence of the stimulated Raman scattering (SRS) and its effects on stimulated Brillouin scattering (SBS) pulse compression in FC-40 are investigated. As the experimental medium, the characteristics of FC-40 are suitable for pulse compression. Firstly, the frequency shifts and the threshold of SRS in FC-40 are studied with a mode-locked laser system as pump source, without taking the SBS effect into account. On the basis of the experimental results, the competition between SRS and SBS as well as its effect on pulse compression is investigated. Results show that SRS gets higher gain and grows rapidly with the increase of the laser intensity by pump effect, which will result in decreasing of SBS energy reflection.
The present study investigated alteration of brain resting-state activity induced by antidepressant treatment and attempted to investigate whether treatment efficacy can be predicted at an early stage of pharmacological treatment.
Method
Forty-eight first-episode medication-free patients diagnosed with major depression received treatment with escitalopram. Resting-state functional magnetic resonance imaging was administered prior to treatment, 5 h after the first dose, during the course of pharmacological treatment (week 4) and at endpoint (week 8). Resting-state activity was evaluated in the course of the 8-week treatment and in relation to clinical improvement.
Results
Escitalopram dynamically modified resting-state activity in depression during the treatment. After 5 h the antidepressant induced a significant decrease in the signal in the occipital cortex and an increase in the dorsolateral and dorsomedial prefrontal cortices and middle cingulate cortex. Furthermore, while remitters demonstrated more obvious changes following treatment, these were more modest in non-responders suggesting possible tonic and dynamic differences in the serotonergic system. Changes after 5 h in the caudate, occipital and temporal cortices were the best predictor of clinical remission at endpoint.
Conclusions
This study revealed the possibility of using the measurement of resting-state neural changes a few hours after acute administration of antidepressant to identify individuals likely to remit after a few weeks of treatment.