Clinical behaviour and mortality in idiopathic vs secondary nonspecific interstitial pneumonia.

RATIONALE: Nonspecific interstitial pneumonia (NSIP) is a subtype of interstitial lung disease which can either be idiopathic or secondary to other conditions. Idiopathic NSIP is a relatively rare entity and diagnosis should be considered carefully as it is mainly a diagnosis of exclusion. The aim of this retrospective study was to evaluate a cohort of NSIP patients with a view to identifying any clinical and mortality differences between idiopathic and secondary varieties. METHODS: We screened 700 patients from our interstitial lung disease database and identified 44 cases of NSIP retrospectively. Statistical analysis was conducted to evaluate if there was a difference in demographics such as gender and ethnicity, physiological parameters including forced vital capacity, diffusing capacity, average oxygen saturations, and immunology profile between two groups. Furthermore, a difference in mortality was evaluated between idiopathic and secondary NSIP. RESULTS: The data analysis showed that 63.6% (28 of 44) of patients had idiopathic NSIP versus 36.4% (16 of 44) of patients had secondary NSIP. Majority of the secondary NSIP patients had an underlying connective tissue disease. In the idiopathic variety, there was a male preponderance (64.2%, P = .02) which was statistically different compared to relatively equal gender divide in secondary NSIP which was statistically insignificant (male vs. female: 43.8% vs. 56.3%, respectively, P = .42). The mean age of the idiopathic group was 74 years compared to 64 years in the secondary group which was statistically different (P = .01). In both groups (idiopathic and secondary NSIP), more than two-thirds (68%) were of White British ethnicity. Immunology profile was similar across both groups with no statistical difference in IgM, IgG, or IgA levels. At the time of analysis, there were 17.9% deaths (5 of 28) in the idiopathic NSIP group versus 6.3% (1 of 16) in the secondary NSIP group but this was not statistically significant (P = .14). Similarly, there was no statistically significant difference in the forced vital capacity (P = .59), diffusing capacity (P = .88), and resting oxygen saturations (P = .28) between idiopathic and secondary NSIP varieties. CONCLUSION: Our analysis showed that there was a statistically significant difference in gender (male preponderance in idiopathic NSIP only) and mean age difference among both varieties. There were no statistically significant differences in the clinical features and outcomes including mortality, physiological, and immunological parameters between idiopathic and secondary NSIP. Idiopathic NSIP was more common than secondary NSIP and secondary NSIP is mostly due to underlying connective tissue disease.

Atom-resolved imaging with a silicon tip integrated into an on-chip scanning tunneling microscope.

Limited throughput is a shortcoming of the Scanning Tunneling Microscope (STM), particularly when used for atomically precise lithography. To address this issue, we have developed an on-chip STM based on Microelectromechanical-Systems (MEMS) technology. The device reported here has one degree of freedom, replacing the Z axis in a conventional STM. The small footprint of the on-chip STM provides a great opportunity to increase STM throughput by incorporating a number of on-chip STMs in an array to realize parallel STM. The tip methodology adopted for the on-chip STM presented here, which is a batch-fabricated Si tip, makes our design conducive to this goal. In this work, we investigate the capability of this on-chip STM with an integrated Si tip for STM imaging. We integrate the on-chip STM into a commercial ultrahigh-vacuum STM system and perform imaging with atomic resolution on par with conventional STMs but at higher scan speeds due to the higher sensitivity of the MEMS actuator relative to a piezotube. The results attest that it is possible to achieve a parallel and high-throughput STM platform, which is a fully batch-fabricated MEMS STM nanopositioner capable of performing atomic-resolution STM imaging.

Investigating the Benefits of Tectonite Dust as an Amendment for Bark Substrates and Dryland Crops.

This study investigates the potential benefits of using tectonite dust as a soil amendment in central Oregon. Tectonite, a rare mineral byproduct of the Warm Springs Composite Products Company, has unique properties that can enhance soil fertility and water-holding capacity. The study includes analyses of tectonite's physical and chemical properties, small-scale growth trials, and farm-scale experiments to measure grain yield. Physical property analysis demonstrated that tectonite increased water-holding capacity and improved soil structure when added to bark substrates. Responses varied in mineral soils, affecting air space, and water-holding capacity. Small-scale trials showed positive growth responses in wheat height and biomass, indicating improved early growth and establishment. Farm-scale experiments confirmed increased grain yields with tectonite application. These findings suggest that tectonite enhances soil health and crop yields by improving structure, nutrient availability, and water retention. Careful sourcing and testing are necessary to address potential heavy metal contamination risks. Using tectonite as a soil amendment aligns with sustainability goals, reducing waste, and greenhouse gas emissions. It may also offer cost savings compared to synthetic fertilizers and stimulate the local economy. Further research is needed to understand the long-term effects of tectonite on edible crops and heavy metal content. Nevertheless, tectonite shows promise as a sustainable soil amendment for promoting agriculture in central Oregon. By exploring its potential benefits, farmers can enhance soil fertility, improve water-use efficiency, and contribute to a more sustainable agricultural system. This study highlights the importance of utilizing waste byproducts in agriculture to achieve environmental and economic sustainability. Tectonite has the potential to play a significant role in addressing water scarcity and enhancing crop productivity in arid regions like central Oregon.

Clinical applications of gene therapy for rare diseases: A review.

Rare diseases collectively exact a high toll on society due to their sheer number and overall prevalence. Their heterogeneity, diversity, and nature pose daunting clinical challenges for both management and treatment. In this review, we discuss recent advances in clinical applications of gene therapy for rare diseases, focusing on a variety of viral and non-viral strategies. The use of adeno-associated virus (AAV) vectors is discussed in the context of Luxturna, licenced for the treatment of RPE65 deficiency in the retinal epithelium. Imlygic, a herpes virus vector licenced for the treatment of refractory metastatic melanoma, will be an example of oncolytic vectors developed against rare cancers. Yescarta and Kymriah will showcase the use of retrovirus and lentivirus vectors in the autologous ex vivo production of chimeric antigen receptor T cells (CAR-T), licenced for the treatment of refractory leukaemias and lymphomas. Similar retroviral and lentiviral technology can be applied to autologous haematopoietic stem cells, exemplified by Strimvelis and Zynteglo, licenced treatments for adenosine deaminase-severe combined immunodeficiency (ADA-SCID) and ß-thalassaemia respectively. Antisense oligonucleotide technologies will be highlighted through Onpattro and Tegsedi, RNA interference drugs licenced for familial transthyretin (TTR) amyloidosis, and Spinraza, a splice-switching treatment for spinal muscular atrophy (SMA). An initial comparison of the effectiveness of AAV and oligonucleotide therapies in SMA is possible with Zolgensma, an AAV serotype 9 vector, and Spinraza. Through these examples of marketed gene therapies and gene cell therapies, we will discuss the expanding applications of such novel technologies to previously intractable rare diseases.

Methods to Reduce Energy and Polymer Consumption for Fused Filament Fabrication 3D Printing.

Fused Filament Fabrication (FFF) 3D printing is an additive technology used to manufacture parts. Used in the engineering industry for prototyping polymetric parts, this disruptive technology has been adopted commercially and there are affordable printers on the market that allow for at-home printing. This paper examines six methods of reducing the energy and material consumption of 3D printing. Using different commercial printers, each approach was investigated experimentally, and the potential savings were quantified. The modification most effective at reducing energy consumption was the hot-end insulation, with savings of 33.8-30.63%, followed by the sealed enclosure, yielding an average power reduction of 18%. For material, the most influential change was noted using 'lightning infill', reducing material consumption by 51%. The methodology includes a combined energy- and material-saving approach in the production of a referenceable 'Utah Teapot' sample object. Using combined techniques on the Utah Teapot print, the material consumption was reduced by values between 55.8% and 56.4%, and power consumption was reduced by 29% to 38%. The implementation of a data-logging system allowed us to identify significant thermal management and material usage opportunities to minimise power consumption, providing solutions for a more positive impact on the sustainable manufacturing of 3D printed parts.

Urinary concentrations and determinants of glyphosate and glufosinate in pregnant Canadian participants in the MIREC study.

BACKGROUND: Glyphosate is the most widely applied herbicide in agriculture. Glufosinate is a broad spectrum herbicide used to manage glyphosate-resistant weeds. Despite the widespread use of these herbicides, biomonitoring data - which inform risk assessment and management - are sparse. OBJECTIVES: To identify determinants of urinary concentrations of these herbicides and their metabolites in pregnancy. METHODS: We measured urinary concentrations of glyphosate, glufosinate, and their primary metabolites aminomethylphosphonic acid (AMPA) and 3-methylphosphinicopropionic acid (3-MPPA) in a single spot urine specimen collected during the first trimester of pregnancy from the Maternal-Infant Research on Environmental Chemicals (MIREC) study. MIREC recruited about 2000 pregnant women from 10 Canadian cities between 2008 and 2011. We used UItra-Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) with sensitive limits of detection to quantify analyte concentrations. We examined urinary concentrations according to maternal sociodemographics, sample collection characteristics, reported pesticide use, and consumption of fruits, vegetables, legumes, and grain products. We used ANOVA models with specific gravity-standardized chemical concentrations as the dependent variable to determine associations with maternal and sample determinants. RESULTS: Among women with biobanked urine samples (n = 1829-1854), 74% and 72% had detectable concentrations of glyphosate and AMPA, respectively. In contrast, one and six percent of women had detectable concentrations of glufosinate and 3-MPPA, respectively. The specific gravity-standardized geometric mean (95% CI) concentrations of glyphosate and AMPA were 0.112 (0.099-0.127) µg/L and 0.159 (0.147-0.172) µg/L, respectively. We observed a dose-response relationship between consumption of whole grain bread and higher urinary glyphosate concentrations. Season of urine collection and self-reported pesticide use were not associated with increased concentrations of any analyte. CONCLUSIONS: We detected glyphosate and AMPA in the majority of pregnant women from this predominantly urban Canadian cohort. Diet was a probable route of exposure.

Circulatory health risks from additive multi-pollutant models: short-term exposure to three common air pollutants in Canada.

Numerous studies have reported adverse health effects of ambient air pollution on circulatory health outcomes mainly based on single-pollutant models. However, limited studies have focused on adjusted effect of multi-pollutant exposures on public health. This study aimed to examine short-term effects of three common air pollutants-ground-level ozone (ozone), nitrogen dioxide (NO2), and fine particulate matter (PM2.5)-through multi-pollutant models for mixed effect of adjustment. Daily data (circulatory hospitalization and mortality) and hourly data (air pollutants and temperature) were collected for 24 Canadian cities for 2001-2012. We applied generalized additive over-dispersion Poisson regression models with 1, 2, or 3 pollutants for city-specific risks, and Bayesian hierarchical models for national risks. This study found little mixed effect of adjustment through multi-pollutant models (ozone and/or NO2 and/or PM2.5) for circulatory hospitalization or mortality in Canada for 2001-2012, indicating that the 1-pollutant model did not result in considerable under- or over-estimates. It seemed weak-to-moderate correlations among air pollutants did not change the significant effect of one air pollutant after accounting for others. Inconsistent findings between other previous studies and this study indicate the need of comparable study design for multi-pollutant effect analysis.

Type and duration of water stress influence host selection and colonization by exotic ambrosia beetles (Coleoptera: Curculionidae).

Fungus-farming ambrosia beetles in the tribe Xyleborini tunnel into plants and trees to establish chambers for cultivating their nutritional fungal mutualists and rearing offspring. Some xyleborine ambrosia beetles preferentially infest and perform better in living but weakened trees. Flood stress predisposes horticultural tree crops to infestation, but the impact of drought stress has not been well studied. Our objectives were to compare the effects of flood stress vs. drought stress on host selection and colonization by xyleborine ambrosia beetles and to assess the duration of flooding. Container-grown Cornus florida L. trees were flood stressed using a pot-in-pot system to submerge the roots in water while drought-stressed conditions were imposed by withholding irrigation and precipitation. When experimental trees were held under field conditions for 14 days, 7.5 × more ambrosia beetles landed on stems of the flood-stressed than on the drought-stressed trees. During two additional experiments over 14 and 22 days, ambrosia beetles tunneled into the flood-stressed trees but not the drought-stressed or standard irrigation trees. By simultaneously deploying trees that were flood stressed for varying lengths of time, it was found that more tunnel entrances, and xyleborine adults and offspring were recovered from trees that were flooded for 1-16 days and 7-22 days than from trees that were flooded for 14-29 days and 28-43 days. These results indicate that acute and severe drought stress does not predispose C. florida to infestation, but flood stress and the duration of flooding influence ambrosia beetle host selection and colonization. Understanding the role of host quality on ambrosia beetle preference behavior will assist with predicting the risk of infestation of these opportunistic insects in horticultural tree crops.

Decompensated cirrhosis: targeted training of acute medical teams to improve quality of care in first 24 hours.

BACKGROUND: A quality improvement project in a secondary care centre was initiated to investigate and evaluate the impact of staff education and the use of the British Society of Gastroenterology/British Association for the Study of the Liver cirrhosis care bundle in improving care of patients admitted to hospital with decompensated liver cirrhosis. METHOD: A staff training programme was implemented, involving around 30 health professionals consisting of consultants, junior doctors, physician associates and nurses from the acute medical unit. A review of electronic documentation and analysis of key clinical parameters, pre- and post-intervention, was carried out. RESULTS: The data show that the intervention has led to an improvement in patient management and clinical outcomes. CONCLUSION: This project illustrates that collaboration between hepatology and medical teams, with emphasis on education and training, benefits patients who present to hospital with decompensated liver cirrhosis.

Fluid biomarkers and risk of neurodegenerative disease in retired athletes with multiple concussions: results from the International Concussion and Head Injury Research Foundation Brain health in Retired athletes Study of Ageing and Impact-Related Neurodegenerative Disease (ICHIRF-BRAIN study).

Objectives: To investigate the association and utility of blood plasma markers of neurodegeneration in a population of retired athletes self-reporting multiple concussions throughout a sporting career. It is hypothesised that this type of athletic history would cause an increased prevalence of neurodegenerative disease, as detected by biomarkers for neurodegenerative disease processes. Methods: One hundred and fifty-nine participants were recruited (90 males, 69 females, mean age 61.3±9.13 years), including 121 participants who had retired from playing professional or semiprofessional sports and self-reported ≥1 concussion during their careers (range 1-74; mean concussions=10.7). The control group included 38 age-matched and sex-matched controls, with no history of concussion. We measured neurofilament light (NfL) and tau (neurodegeneration markers), glial fibrillar acidic protein (GFAP) (astrocytic activation marker) and 40 and 42 amino acid-long amyloid beta (Aß40 and Aß42) (Alzheimer-associated amyloid pathology markers) concentrations using ultrasensitive single molecule array technology. Results: We found retired athletes reporting one or more concussions throughout an athletic career showed no significant changes in NfL, tau, GFAP and Aß40 and Aß42 concentrations in comparison to a control group. No correlations were found between biomarkers and number of concussions (mean=10.7). A moderate correlation was found between NfL concentration and age. Conclusion: No difference in blood concentrations of neurodegeneration markers NfL, tau, GFAP and Aß40 and Aß42 was found in retired athletes with a history of concussion compared with controls. An increased prevalence of neurodegenerative diseases is not detected by biomarkers in a population self-reporting multiple concussions. Trial registration number: ISRCTN 11312093.

Individual and mixture associations of perfluoroalkyl substances on liver function biomarkers in the Canadian Health Measures Survey.

BACKGROUND: Perfluoroalkyl substances can disrupt hepatic metabolism and may be associated with liver function biomarkers. We examined individual and mixture associations of PFAS on liver function biomarkers in a representative sample of Canadian adults. We explored the potential for effect modification by sex and body mass index, as well as by physical activity level which may attenuate the deleterious effect of PFAS on metabolic disorders. METHODS: We analyzed data from participants aged 20-74 from the Canadian Health Measures Survey. We used linear regression to examine associations between plasma concentrations of PFOA, PFOS, PFHxS, PFNA, PFDA, and PFUDA on serum concentrations of aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), alanine aminotransferase (ALT) and total bilirubin. We used quantile g-computation to estimate associations with a PFAS mixture for each simultaneous, one-quartile change in PFAS concentrations. RESULTS: Each doubling of PFOA, PFOS, PFHxS, or PFNA concentrations was associated with higher AST, GGT, and ALP concentrations. Each doubling of PFOA concentrations was associated with 16.5% (95%CI: 10.4, 23.0) higher GGT concentrations among adults not meeting Canada's physical activity guidelines vs. 6.6% (95%CI: -1.6, 15.5) among those meeting these guidelines. Sex and BMI also modified some associations, though to a lesser extent. We did not observe associations between ALT and PFOA (1.2% change; 95%CI: -2.5, 4.9), PFOS (2.2% change; 95%CI: -0.8, 5.3), or PFHxS (1.5% change; 95%CI: -0.4, 3.4). We also did not observe consistent associations for PFDA and PFUDA or with total bilirubin. In quantile g-computation models, each simultaneous one-quartile increase in the PFAS mixture was positively associated with AST (7.5% higher; 95%CI: 4.0, 10.4), GGT (9.7% higher; 95%CI: 1.7, 17.0), and ALP (2.8% higher; 95%CI: 0.5, 5.4). CONCLUSION: Higher plasma concentrations of PFOA, PFOS, PFHxS, and PFNA - both individually and as a mixture - were associated with higher serum concentrations of liver function biomarkers. These results contribute to emerging evidence suggesting that higher levels of physical activity appear to be protective against the hepatotoxic effects of PFOA. This work contributes to a growing body of evidence supporting the hepatotoxic effects of PFAS.

What are the relevant sources and factors affecting event mean concentrations (EMCs) of nutrients and sediment in stormwater?

Urbanization increases runoff, sediment, and nutrient loadings downstream, causing flooding, eutrophication, and harmful algal blooms. Stormwater control measures (SCMs) are used to address these concerns and are designed based on inflow loads. Thus, estimating nutrient and sediment loads is important for meeting restoration objectives. Pollutants accumulate on surfaces during dry periods, making Event Mean Concentration (EMC) a function of antecedent dry period (ADP). An EMC results from wash-off of accumulated pollutants from catchment surface during runoff events. However, several studies found little to no correlation between constituent concentrations in stormwater and ADP. The objective of this study is to verify this finding and discover which climatological or catchment characteristics most significantly affect stormwater quality. Stormwater quality data were obtained from the National Stormwater Quality Database (NSQD), which is the largest data repository of stormwater quality data in the U.S. Bayesian Network Structure Learner (BNSL) was used to assess the relationships between catchment characteristics, climatological information, and stormwater quality for selected land uses. Given the optimal BN structure, it was determined which parameters most affect stormwater quality EMCs. The results demonstrate that both catchment and rain characteristics affected stormwater quality EMCs. Among catchment characteristics, land use (LU) was the most important factor and catchment size was the least. Precipitation depth (P) and duration (D) affected Total Phosphorus (TP), Total Nitrogen (TN), and Total Suspended Solids (TSS). This indicated that it is likely that P and D had a greater influence on stormwater quality more than ADP. P, D, and ADP affected the dissolved constituents of TN (i.e. NO2-N/NO3-N) and TP (i.e. Ortho-P). Compared to other factors (i.e. P and D), the effect of ADP on TSS was negligible. Stormwater quality EMCs related to nitrogen were not affected by catchment slope (S). However, TSS and Ortho-P were influenced by S.

Efficacy of the Systane iLux Thermal Pulsation System for the Treatment of Meibomian Gland Dysfunction After 1 Week and 1 Month: A Prospective Study.

OBJECTIVES: To assess 1-week and 1-month efficacy of Systane iLux thermal pulsation treatment for meibomian gland dysfunction (MGD). METHODS: This prospective, nonrandomized, open-label, multicenter study enrolled 30 adult patients (60 eyes) who had a Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire score greater than 6 and total meibomian gland secretion (MGS) score equal to or less than 12 in each eye. All participants received thermal pulsation treatment bilaterally. Primary efficacy measures included MGS score (sum of grades for 15 glands graded on a scale of 0-3; 0 [no secretion], 1 [inspissated], 2 [cloudy], and 3 [clear liquid]) and tear breakup time (TBUT). Secondary efficacy measures were SPEED and Ocular Surface Disease Index (OSDI) scores. RESULTS: The mean age of patients was 52.9±11.9 years. After 1 week, the mean MGS score improved significantly from 4.1±3.1 to 15.8±7.1 (right eye, OD) and 3.7±3.1 to 16.7±7.6 (left eye, OS); mean TBUT improved significantly from 4.9±4.1 to 8.4±3.6 (OD) and 5.2±4.2 to 8.9±3.9 (OS); and mean SPEED and OSDI scores improved significantly from 16.1±5.3 to 7.2±6.1 and 45.2±21.3 to 19.0±16.8, respectively (all P<0.001). After 1 month, the mean MGS score improved to 18.3±8.2 (OD) and 18.6±7.3 (OS); mean TBUT improved to 9.7±3.8 (OD) and 9.6±3.5 (OS); and mean SPEED and OSDI scores improved to 7.0±5.6 and 16.7±14.5, respectively (all P<0.001). No adverse events were reported. CONCLUSIONS: Systane iLux thermal pulsation treatment for MGD resulted in a statistically significant increase in meibomian gland secretion, improvement in tear film stability, and reduction in dry eye symptoms as early as both 1 week and 1 month.

Application of Molecular Vapour Deposited Al2O3 for Graphene-Based Biosensor Passivation and Improvements in Graphene Device Homogeneity.

Graphene-based point-of-care (PoC) and chemical sensors can be fabricated using photolithographic processes at wafer-scale. However, these approaches are known to leave polymer residues on the graphene surface, which are difficult to remove completely. In addition, graphene growth and transfer processes can introduce defects into the graphene layer. Both defects and resist contamination can affect the homogeneity of graphene-based PoC sensors, leading to inconsistent device performance and unreliable sensing. Sensor reliability is also affected by the harsh chemical environments used for chemical functionalisation of graphene PoC sensors, which can degrade parts of the sensor device. Therefore, a reliable, wafer-scale method of passivation, which isolates the graphene from the rest of the device, protecting the less robust device features from any aggressive chemicals, must be devised. This work covers the application of molecular vapour deposition technology to create a dielectric passivation film that protects graphene-based biosensing devices from harsh chemicals. We utilise a previously reported "healing effect" of Al2O3 on graphene to reduce photoresist residue from the graphene surface and reduce the prevalence of graphene defects to improve graphene device homogeneity. The improvement in device consistency allows for more reliable, homogeneous graphene devices, that can be fabricated at wafer-scale for sensing and biosensing applications.

Active elimination of intestinal cells drives oncogenic growth in organoids.

Competitive cell interactions play a crucial role in quality control during development and homeostasis. Here, we show that cancer cells use such interactions to actively eliminate wild-type intestine cells in enteroid monolayers and organoids. This apoptosis-dependent process boosts proliferation of intestinal cancer cells. The remaining wild-type population activates markers of primitive epithelia and transits to a fetal-like state. Prevention of this cell-state transition avoids elimination of wild-type cells and, importantly, limits the proliferation of cancer cells. Jun N-terminal kinase (JNK) signaling is activated in competing cells and is required for cell-state change and elimination of wild-type cells. Thus, cell competition drives growth of cancer cells by active out-competition of wild-type cells through forced cell death and cell-state change in a JNK-dependent manner.

Advanced Scanning Probe Nanolithography Using GaN Nanowires.

A fundamental understanding and advancement of nanopatterning and nanometrology are essential in the future development of nanotechnology, atomic scale manipulation, and quantum technology industries. Scanning probe-based patterning/imaging techniques have been attractive for many research groups to conduct their research in nanoscale device fabrication and nanotechnology mainly due to its cost-effective process; however, the current tip materials in these techniques suffer from poor durability, limited resolution, and relatively high fabrication costs. Here, we report on employing GaN nanowires as a robust semiconductor material in scanning probe lithography (SPL) and microscopy (SPM) with a relatively low-cost fabrication process and the capability to provide sub-10 nm lithography and atomic scale (<1 nm) patterning resolution in field-emission scanning probe lithography (FE-SPL) and scanning tunneling microscopy (STM), respectively. We demonstrate that GaN NWs are great candidates for advanced SPL and imaging that can provide atomic resolution imaging and sub-10 nm nanopatterning on different materials in both vacuum and ambient operations.

Assessing undergraduate medical education through a generalist lens.

PROBLEM BEING ADDRESSED: Medical schools aim to integrate the values of generalism into their undergraduate programs. However, currently no program has been described to measure the degree to which formal curricular materials represent generalist principles. OBJECTIVE OF PROGRAM: To quantify the generalism principles present in undergraduate medical education learning materials and to provide recommendations to enhance generalism content. PROGRAM DESCRIPTION: A review of the literature and accreditation documents was conducted to identify key elements of medical generalism. An evidence-informed tool, the Toronto Generalism Assessment Tool, was developed and applied to the new preclerkship undergraduate cases at the University of Toronto in Ontario. The findings regarding the presence of generalism principles and recommendations to enhance generalism content were provided to case developers. The recommendations were valued and were incorporated into subsequent iterations of the cases. CONCLUSION: This is the first report of a successful evidence-informed program to assess the degree of generalism reflected in undergraduate medical education curricular documents. This program can be used by other institutions wishing to review their curricula through a generalist lens.

MIL-101(Cr), an Efficient Heterogeneous Catalyst for One Pot Synthesis of 2,4,5-tri Substituted Imidazoles under Solvent Free Conditions.

A chromium-containing metal-organic framework (MOF), MIL-101 (Chromium(III) benzene-1,4-dicarboxylate), was used to catalyze the one pot, three component synthesis of some 2,4,5-trisubstituted imidazoles under solvent-free conditions. The advantages of using this heterogeneous catalyst include short reaction time, high yields, easy and quick isolation of catalyst and products, low amount of catalyst needed, and that the addition of solvent, salt, and additives are not needed. This catalyst is highly efficient and can be recovered at least 5 times with a slight loss of efficiency. The structure of the metal-organic frameworks (MOF) was confirmed by X-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM). Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (HNMR) were performed to confirm some of the synthesized products. Experimental data indicated that the optimum amount of catalyst was 5 mg for benzil (1 mmol), 4-chlorobenzaldehyde (1 mmol), and ammonium acetate (2.5 mmol), and the synthetic route to the various imidazoles is performed in 10 min by 95% yield, an acceptable result rivalling those of other catalysts.

Apolipoprotein E polymorphism influences orthotopic liver transplantation outcomes in patients with hepatitis C virus-induced liver cirrhosis.

BACKGROUND: Hepatitis C virus (HCV) infection is responsible for a chronic liver inflammation, which may cause end-stage liver disease and hepatocellular carcinoma. Apolipoprotein E (protein: ApoE, gene: APOE), a key player in cholesterol metabolism, is mainly synthesized in the liver and APOE polymorphisms may influence HCV-induced liver damage. AIM: To determine whether APOE alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation (OLT). METHODS: This was a cohort study in which 179 patients, both genders and aged 34-70 years, were included before or after (up to 10 years follow-up) OLT. Liver injury severity was assessed using different criteria, including METAVIR and models for end-stage liver disease. APOE polymorphisms were analyzed by quantitative real-time polymerase chain reaction. RESULTS: The APOE3 allele was the most common (67.3%). In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant, the degree of severe inflammation (A3F4, 0.0%) was significantly less frequent than in patients with minimal and moderate degree of inflammation (≤ A2F4, 16.2%) P = 0.048, in patients carrying the APOE4 allele when compared to non-APOE4. In addition, a significant difference was also found (≤ A2F4, 64.4% vs A3F4, 0.0%; P = 0.043) and (A1F4, 57.4% vs A3F4, 0.0%; P = 0.024) in APOE4 patients when compared to APOE3 carriers. The fibrosis degree of the liver graft in 8 of 91 patients and the lack of the E4 allele was associated with more moderate fibrosis (F2) (P = 0.006). CONCLUSION: Our results suggest that the E4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.

The Nature and Origins of Sub-Neptune Size Planets.

Planets intermediate in size between the Earth and Neptune, and orbiting closer to their host stars than Mercury does the Sun, are the most common type of planet revealed by exoplanet surveys over the last quarter century. Results from NASA's Kepler mission have revealed a bimodality in the radius distribution of these objects, with a relative underabundance of planets between 1.5 and 2.0 R ⊕ . This bimodality suggests that sub-Neptunes are mostly rocky planets that were born with primary atmospheres a few percent by mass accreted from the protoplanetary nebula. Planets above the radius gap were able to retain their atmospheres ("gas-rich super-Earths"), while planets below the radius gap lost their atmospheres and are stripped cores ("true super-Earths"). The mechanism that drives atmospheric loss for these planets remains an outstanding question, with photoevaporation and core-powered mass loss being the prime candidates. As with the mass-loss mechanism, there are two contenders for the origins of the solids in sub-Neptune planets: the migration model involves the growth and migration of embryos from beyond the ice line, while the drift model involves inward-drifting pebbles that coagulate to form planets close-in. Atmospheric studies have the potential to break degeneracies in interior structure models and place additional constraints on the origins of these planets. However, most atmospheric characterization efforts have been confounded by aerosols. Observations with upcoming facilities are expected to finally reveal the atmospheric compositions of these worlds, which are arguably the first fundamentally new type of planetary object identified from the study of exoplanets.