A carbon footprint study of the Canadian medical residency interview tour.

BACKGROUND: Each spring, thousands of Canadian medical students travel across the country to interview for residency positions, a process known as the CaRMS tour. Despite the large scale of travel, the CaRMS tour has received little environmental scrutiny. PURPOSE: To estimate the national carbon footprint of flights associated with the CaRMS tour, as well as reductions in emissions achievable by transitioning to alternative models. METHODS: We developed a three-question online commuter survey to collect the unique travel itineraries of applicants in the 2020 CaRMS tour. We calculated the emissions associated with all flights and modelled expected emissions for two alternative in-person interview models, and two virtual interview models. RESULTS: We collected 960 responses out of 2943 applicants across all 17 Canadian medical schools. We calculated the carbon footprint of flights for the 2020 CaRMS as 4239 tCO2e (tonnes of carbon dioxide equivalents), averaging 1.44 tCO2e per applicant. The average applicant's tour emissions represent 35.1% of the average Canadian's annual household carbon footprint, and the emissions of 26.7% of respondents exceeded their entire annual '2050 carbon budget.' Centralized in-person interviews could reduce emissions by 13.7% to 74.7%, and virtual interviews by at least 98.4% to 99.9%. CONCLUSIONS: Mandatory in-person residency interviews in Canada contribute significant emissions and reflect a culture of emissions-intensive practices. Considerable decarbonization of the CaRMS tour is possible, and transitioning to virtual interviews could eliminate the footprint almost entirely.

Impact of Covid-19 on farming systems in Europe through the lens of resilience thinking.

Context: Resilience is the ability to deal with shocks and stresses, including the unknown and previously unimaginable, such as the Covid-19 crisis. Objective: This paper assesses (i) how different farming systems were exposed to the crisis, (ii) which resilience capacities were revealed and (iii) how resilience was enabled or constrained by the farming systems' social and institutional environment. Methods: The 11 farming systems included have been analysed since 2017. This allows a comparison of pre-Covid-19 findings and the Covid-19 crisis. Pre-Covid findings are from the SURE-Farm systematic sustainability and resilience assessment. For Covid-19 a special data collection was carried out during the early stage of lockdowns. Results and conclusions: Our case studies found limited impact of Covid-19 on the production and delivery of food and other agricultural products. This was due to either little exposure or the agile activation of robustness capacities of the farming systems in combination with an enabling institutional environment. Revealed capacities were mainly based on already existing connectedness among farmers and more broadly in value chains. Across cases, the experience of the crisis triggered reflexivity about the operation of the farming systems. Recurring topics were the need for shorter chains, more fairness towards farmers, and less dependence on migrant workers. However, actors in the farming systems and the enabling environment generally focused on the immediate issues and gave little real consideration to long-term implications and challenges. Hence, adaptive or transformative capacities were much less on display than coping capacities. The comparison with pre-Covid findings mostly showed similarities. If challenges, such as shortage of labour, already loomed before, they persisted during the crisis. Furthermore, the eminent role of resilience attributes was confirmed. In cases with high connectedness and diversity we found that these system characteristics contributed significantly to dealing with the crisis. Also the focus on coping capacities was already visible before the crisis. We are not sure yet whether the focus on short-term robustness just reflects the higher visibility and urgency of shocks compared to slow processes that undermine or threaten important system functions, or whether they betray an imbalance in resilience capacities at the expense of adaptability and transformability. Significance: Our analysis indicates that if transformations are required, e.g. to respond to concerns about transnational value chains and future pandemics from zoonosis, the transformative capacity of many farming systems needs to be actively enhanced through an enabling environment.

Improving the Voltammetric Determination of Hg(II): A Comparison Between Ligand-Modified Glassy Carbon and Electrochemically Reduced Graphene Oxide Electrodes.

A new thiosemicarbazone ligand was immobilized through a Cu(I)-catalyzed click reaction on the surface of glassy carbon (GC) and electrochemically reduced graphene oxide (GC-ERGO) electrodes grafted with phenylethynyl groups. Using the accumulation at open circuit followed by anodic stripping voltammetry, the modified electrodes showed a significant selectivity and sensibility for Hg(II) ions. A detection limit of 7 nM was achieved with the GC modified electrodes. Remarkably, GC-ERGO modified electrodes showed a significantly improved detection limit (0.8 nM), sensitivity, and linear range, which we attribute to an increased number of surface binding sites and better electron transfer properties. Both GC and GC-ERGO modified electrodes proved their applicability for the analysis of real water samples.

Linear and nonlinear parameters of heart rate variability in ischemic stroke patients.

INTRODUCTION: Cardiovascular system presents cortical modulation. Post-stroke outcome can be highly influenced by autonomic nervous system disruption. Heart rate variability (HRV) analysis is a simple non-invasive method to assess sympatho-vagal balance. OBJECTIVES: The purpose of this study was to investigate cardiac autonomic activity in ischemic stroke patients and to asses HRV nonlinear parameters beside linear ones. METHODS: We analyzed HRV parameters in 15 right and 15 left middle cerebral artery ischemic stroke patients, in rest condition and during challenge (standing and deep breathing). Data were compared with 15 age- and sex-matched healthy controls. RESULTS: There was an asymmetric response after autonomic stimulation tests depending on the cortical lateralization in ischemic stroke patients. In resting state, left hemisphere stroke patients presented enhanced parasympathetic control of the heart rate (higher values for RMSSD, pNN50 and HF in normalized units). Right hemisphere ischemic stroke patients displayed a reduced cardiac parasympathetic modulation during deep breathing test. Beside time and frequency domain, using short-term ECG monitoring, cardiac parasympathetic modulation can also be assessed by nonlinear parameter SD1, that presented strong positive correlation with time and frequency domain parameters RMSSD, pNN50, HFnu, while DFA α1 index presented negative correlation with the same indices and positive correlation with the LFnu and LF/HF ratio, indicating a positive association with the sympatho-vagal balance. CONCLUSIONS: Cardiac monitoring in clinical routine using HRV analysis in order to identify autonomic imbalance may highlight cardiac dysfunctions, thus helping preventing potential cardiovascular complications, especially in right hemisphere ischemic stroke patients with sympathetic hyperactivation.

Ultrastable Silicon Cavity in a Continuously Operating Closed-Cycle Cryostat at 4 K.

We report on a laser locked to a silicon cavity operating continuously at 4 K with 1×10^{-16} instability and a median linewidth of 17 mHz at 1542 nm. This is a tenfold improvement in short-term instability, and a 10^{4} improvement in linewidth, over previous sub-10-K systems. Operating at low temperatures reduces the thermal noise floor and, thus, is advantageous toward reaching an instability of 10^{-18}, a long-sought goal of the optical clock community. The performance of this system demonstrates the technical readiness for the development of the next generation of ultrastable lasers that operate with an ultranarrow linewidth and long-term stability without user intervention.

1.5 µm Lasers with Sub-10 mHz Linewidth.

We report on two ultrastable lasers each stabilized to independent silicon Fabry-Pérot cavities operated at 124 K. The fractional frequency instability of each laser is completely determined by the fundamental thermal Brownian noise of the mirror coatings with a flicker noise floor of 4×10^{-17} for integration times between 0.8 s and a few tens of seconds. We rigorously treat the notorious divergences encountered with the associated flicker frequency noise and derive methods to relate this noise to observable and practically relevant linewidths and coherence times. The individual laser linewidth obtained from the phase noise spectrum or the direct beat note between the two lasers can be as small as 5 mHz at 194 THz. From the measured phase evolution between the two laser fields we derive usable phase coherence times for different applications of 11 to 55 s.

Ridaforolimus as a single agent in advanced endometrial cancer: results of a single-arm, phase 2 trial.

BACKGROUND: This open-label, multicentre, phase 2 trial evaluated the efficacy and tolerability of the mammalian target of rapamycin inhibitor ridaforolimus in women with advanced endometrial cancer. METHODS: Women with measurable recurrent or persistent endometrial cancer and documented disease progression were treated with ridaforolimus 12.5 mg intravenously once daily for 5 consecutive days every 2 weeks in a 4-week cycle. The primary end point was clinical benefit response, defined as an objective response or prolonged stable disease of 16 weeks or more. RESULTS: In all, 45 patients were treated with single-agent ridaforolimus. Clinical benefit was achieved by 13 patients (29%), including 5 (11%) with confirmed partial responses and 8 (18%) with prolonged stable disease. All patients with clinical benefit response received ridaforolimus for more than 4 months. In this heavily pretreated population, the 6-month progression-free survival was 18%. Ridaforolimus was generally well tolerated: adverse events were predictable and manageable, consistent with prior studies in other malignancies. Overall, the most common adverse events were diarrhoea (58%) and mouth sores (56%); most common grade 3 or higher adverse events were anaemia (27%) and hyperglycaemia (11%). CONCLUSION: Single-agent ridaforolimus has antitumor activity and acceptable tolerability in advanced endometrial cancer patients. Further clinical evaluation of ridaforolimus is warranted.

Mortality and need of surgical treatment in acute upper gastrointestinal bleeding: a one year study in a tertiary center with a 24 hours / day-7 days / week endoscopy call. Has anything changed?

BACKGROUND: Acute upper gastrointestinal bleeding, previously often a surgical problem, is now the most common gastroenterological emergency. AIM: To evaluate the current situation in terms of mortality and need of surgery. SUBJECTS AND METHODS: Retrospective non-randomised clinical study performed between 1st January-31st December 2011, at "Professor Dr. Octavian Fodor" Regional Institute of Gastroenterology and Hepatology in Cluj Napoca. 757 patients with upper gastrointestinal bleeding were endoscopically examined within 24 hours from presentation in the emergency unit. Data were collected from admission charts and Hospital Manager programme. Statistical analysis was performed with GraphPad 2004, using the following tests: chi square, Spearman, Kruskall-Wallis, Mann-Whitney, area under receiver operating curve. RESULTS: Non-variceal etiology was predominant, the main cause was bleeding being peptic ulcer. In hospital global mortality was of 10.43%, global rebleeding rate was 12.02%, surgery was performed in 7.66% of patients. Urgent haemostatic surgery was needed in 3.68% of patients with nonvariceal bleeding. The need for surgery correlated with the postendoscopic Rockall score (p=0.0425). In peptic ulcer, the need for surgery was not influenced by time to endoscopy or type of treatment (p=0.1452). Weekend (p=0.996) or night (p=0.5414) admission were not correlated with a higher need for surgery. CONCLUSIONS: Over the last decade, the need for urgent surgery in upper gastrointestinal bleeding has decreased by half, but mortality has remained unchanged.

Synthesis and evaluation of poly(propylene fumarate)-grafted graphene oxide as nanofiller for porous scaffolds.

In an effort to obtain porous scaffolds with improved mechanical properties and biocompatibility, the current study discusses nanocomposite materials based on poly(propylene fumarate)/N-vinyl pyrrolidone(PPF/NVP) networks reinforced with polymer-modified graphene oxide (GO@PPF). The GO@PPF nanofiller was synthesized through a facile and convenient surface esterification reaction, and the successful functionalization was demonstrated by complementary techniques such as FT-IR, XPS, TGA and TEM. The PPF/NVP/GO@PPF porous scaffolds obtained using NaCl as a porogen were further characterized in terms of morphology, mechanical properties, sol fraction, and in vitro degradability. SEM and nanoCT examinations of NaCl-leached samples revealed networks of interconnected pores, fairly uniform in size and shape. We show that the incorporation of GO@PPF in the polymer matrix leads to a significant enhancement in the mechanical properties, which we attribute to the formation of denser and more homogenous networks, as suggested by a decreased sol fraction for the scaffolds containing a higher amount of GO@PPF. Moreover, the surface of mineralized PPF/NVP/GO@PPG scaffolds is uniformly covered in hydroxyapatite-like crystals having a morphology and Ca/P ratio similar to bone tissue. Furthermore, the preliminary biocompatibility assessment revealed a good interaction between PPF/PVP/GO@PPF scaffolds and murine pre-osteoblasts in terms of cell viability and proliferation.

One-dimensional to three-dimensional ripple-to-dome transition for SiGe on vicinal Si (1 1 10).

SiGe heteroepitaxy on vicinal Si (1 1 10) is studied as a model system for one-dimensional (1D) to three-dimensional growth mode transitions. By in situ scanning tunneling microscopy it is shown that the 1D-3D transition proceeds smoothly from perfectly facetted 1D nanoripples to coarsened superripples, tadpoles, asymmetric domes, and barns without involving coalescence or agglomeration. By extension of the studies to a wide range of SiGe compositions, a 1D-3D growth phase diagram is obtained. Total energy calculations reveal that the observed critical transition volumes are fully consistent with thermodynamic driven strain relaxation.

Formation of Ge nanoripples on vicinal Si (1110): from Stranski-Krastanow seeds to a perfectly faceted wetting layer.

Ge growth on high-indexed Si (1110) is shown to result in the spontaneous formation of a perfectly {105} faceted one-dimensional nanoripple structure. This evolution differs from the usual Stranski-Krastanow growth mode because from initial ripple seeds a faceted Ge layer is formed that extends down to the heterointerface. Ab initio calculations reveal that ripple formation is mainly driven by lowering of surface energy rather than by elastic strain relief and the onset is governed by the edge energy of the ripple facets. Wavelike ripple replication is identified as an effective kinetic pathway for the transformation process.

Structural investigation of 1,1'-biphenyl-4-thiol self-assembled monolayers on Au(111) by scanning tunneling microscopy and low-energy electron diffraction.

Self-assembled monolayers (SAMs) of 1,1'-biphenyl-4-thiol (H-(C(6)H(4))(2)-SH) on Au(111) were prepared from solution or via vapor deposition in ultrahigh vacuum and characterized by scanning tunneling microscopy (STM), low-energy electron diffraction (LEED), and X-ray photoelectron spectroscopy (XPS). In contrast to the typically observed for densely packed alkane-thiol SAMs on Au(111) (√3 × âˆš3)R30° structure, the densely packed aromatic biphenylthiol SAMs prepared by both methods exhibit an unusual hexagonal (2 × 2) structure. Upon annealing at 100 °C, this structure evolves into the (2 × 7√3) structure resulting in the formation of highly ordered pinstripes oriented along the [1 -1 0] directions. Lower density SAMs, prepared by vapor deposition in vacuum, show mixed structures comprising the hexagonal (2 × 2) structure and two rectangular arrangements with the unit cells of (3√3 × 9) and (2√3 × 8). An extinction of the (3√3 × 9) structure in the favor of the (2√3 × 8) structure is observed upon annealing at temperatures of ~100 °C.

Critical Design Factors for Electrochemical Aptasensors Based on Target-Induced Conformational Changes: The Case of Small-Molecule Targets.

Nucleic-acid aptamers consisting in single-stranded DNA oligonucleotides emerged as very promising biorecognition elements for electrochemical biosensors applied in various fields such as medicine, environmental, and food safety. Despite their outstanding features, such as high-binding affinity for a broad range of targets, high stability, low cost and ease of modification, numerous challenges had to be overcome from the aptamer selection process on the design of functioning biosensing devices. Moreover, in the case of small molecules such as metabolites, toxins, drugs, etc., obtaining efficient binding aptamer sequences proved a challenging task given their small molecular surface and limited interactions between their functional groups and aptamer sequences. Thus, establishing consistent evaluation standards for aptamer affinity is crucial for the success of these aptamers in biosensing applications. In this context, this article will give an overview on the thermodynamic and structural aspects of the aptamer-target interaction, its specificity and selectivity, and will also highlight the current methods employed for determining the aptamer-binding affinity and the structural characterization of the aptamer-target complex. The critical aspects regarding the generation of aptamer-modified electrodes suitable for electrochemical sensing, such as appropriate bioreceptor immobilization strategy and experimental conditions which facilitate a convenient anchoring and stability of the aptamer, are also discussed. The review also summarizes some effective small molecule aptasensing platforms from the recent literature.

Robust but weak winter atmospheric circulation response to future Arctic sea ice loss.

The possibility that Arctic sea ice loss weakens mid-latitude westerlies, promoting more severe cold winters, has sparked more than a decade of scientific debate, with apparent support from observations but inconclusive modelling evidence. Here we show that sixteen models contributing to the Polar Amplification Model Intercomparison Project simulate a weakening of mid-latitude westerlies in response to projected Arctic sea ice loss. We develop an emergent constraint based on eddy feedback, which is 1.2 to 3 times too weak in the models, suggesting that the real-world weakening lies towards the higher end of the model simulations. Still, the modelled response to Arctic sea ice loss is weak: the North Atlantic Oscillation response is similar in magnitude and offsets the projected response to increased greenhouse gases, but would only account for around 10% of variations in individual years. We further find that relationships between Arctic sea ice and atmospheric circulation have weakened recently in observations and are no longer inconsistent with those in models.

Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group.

OBJECTIVE: This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). METHODS: Primary endpoints were maximum tolerated dose of sorafenib with weekly topotecan (phase I) and response rate (phase II). Secondary endpoints were progression free survival (PFS), overall survival (OS), toxicity, and rate of clinical benefit. Eligibility included recurrent platinum-resistant OC or PPC, <3 prior regimens, normal end-organ function. 3+3 dose escalation was used for phase I, sorafenib being tested at 400mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m(2) to 3.5mg/m(2) IV weekly. The phase II regimen was sorafenib 400mg daily and topotecan 3.5mg/m(2) weekly on days 1, 8, 15 of a 28 days cycle. RESULTS: 16 patients were enrolled in phase I and 14 patients in phase II. Median age was 52.5 years (range 35-79), 27 patients had OC, and 3 PPC. Median number of cycles administered was 2.5 (0-15). There were 5 partial responses (PR) (16.7%), and 14 patients (46.7%) with stable disease (SD). Four PRs were recorded during phase I and 1 during phase II. One of those PRs occurred in a patient with platinum-sensitive disease. Grade 3/4 toxicities included leukopenia/neutropenia (23%), thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One case of grade 3 hand-foot syndrome was recorded. CONCLUSIONS: The combination of sorafenib and topotecan causes significant toxicity, precluding administration of full doses and resulting in modest clinical efficacy in platinum resistant OC or PPC.

A novel nomogram predicting lymph node invasion among patients with prostate cancer: The importance of extracapsular extension at multiparametric magnetic resonance imaging.

PURPOSE: To develop a novel risk tool that allows the prediction of lymph node invasion (LNI) among patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND). METHODS: We retrospectively identified 742 patients treated with RARP + ePLND at a single center between 2012 and 2018. All patients underwent multiparametric magnetic resonance imaging (mpMRI) and were diagnosed with targeted biopsies. First, the nomogram published by Briganti et al. was validated in our cohort. Second, three novel multivariable logistic regression models predicting LNI were developed: (1) a complete model fitted with PSA, ISUP grade groups, percentage of positive cores (PCP), extracapsular extension (ECE), and Prostate Imaging Reporting and Data System (PI-RADS) score; (2) a simplified model where ECE score was not included (model 1); and (3) a simplified model where PI-RADS score was not included (model 2). The predictive accuracy of the models was assessed with the receiver operating characteristic-derived area under the curve (AUC). Calibration plots and decision curve analyses were used. RESULTS: Overall, 149 patients (20%) had LNI. In multivariable logistic regression models, PSA (OR: 1.03; P= 0.001), ISUP grade groups (OR: 1.33; P= 0.001), PCP (OR: 1.01; P= 0.01), and ECE score (ECE 4 vs. 3 OR: 2.99; ECE 5 vs. 3 OR: 6.97; P< 0.001) were associated with higher rates of LNI. The AUC of the Briganti et al. model was 74%. Conversely, the AUC of model 1 vs. model 2 vs. complete model was, respectively, 78% vs. 81% vs. 81%. Simplified model 1 (ECE score only) was then chosen as the best performing model. A nomogram to calculate the individual probability of LNI, based on model 1 was created. Setting our cut-off at 5% we missed only 2.6% of LNI patients. CONCLUSIONS: We developed a novel nomogram that combines PSA, ISUP grade groups, PCP, and mpMRI-derived ECE score to predict the probability of LNI at final pathology in RARP candidates. The application of a nomogram derived cut-off of 5% allows to avoid a consistent number of ePLND procedures, missing only 2.6% of LNI patients. External validation of our model is needed.

How often we diagnose allergy to ranitidine?

H2 receptors' antagonists (H2RA) are widely used drugs and they are generally well-tolerated. Ranitidine hypersensitivity reactions (HR) are rarely reported. The article emphasizes the importance of recognizing ranitidine as a cause of anaphylaxis and the advantages and limits of allergological evaluation to establish a positive diagnose. We reviewed a series of published cases of ranitidine-induced hypersensitivity reactions, starting from a clinical case presentation. Moreover, we analyzed the ranitidine related adverse events in the Eudravigilance European database of adverse reactions. Most of the allergic reactions induced by ranitidine are type I HR with immediate onset after exposure, with variable clinical presentation. But in a few cases, there were also described delayed reactions, some after occupational exposure. The article underlines the importance of allergy evaluation to avoid future contact with the drug to reduce the risk of more severe reactions. The suspected reactions should be reported, allowing pharmacovigilance systems to analyse them and to establish further recommendations for clinicians.

Celiac disease: a multi-faceted medical condition.

Celiac disease (CD) is a systemic condition of autoimmune origin, affecting genetically predisposed individuals who at some point lose tolerance towards dietary gluten. Prevalence in the general population is 0.5 - 1%, with a higher frequency in women. The most important environmental factor for CD is ingestion of specific gluten peptides. It triggers a sequence of molecular events, involving the intestinal permeability and the immune system, which ends in damage of the intestinal mucosa. A number of studies have demonstrated the correlation between the intestinal microbiota and celiac disease. MicroRNAs through their regulatory role on gene expression have been implicated in the pathogenesis of CD and suggested as potential biomarkers. In the pediatric and adult population, CD displays different clusters of clinical symptoms. Persistent diarrhea, abdominal pain and involuntary weight loss are the classic symptoms of CD. In the majority of cases diagnosis relies on the combination of serum autoantibodies (anti-transglutaminase and anti-endomisium IgA) and duodenal biopsy showing villous atrophy, crypt hyperplasia and intraepithelial lymphocytes. Observance of a lifelong gluten-free diet, which interrupts the immune response to gluten peptides, is the only effective treatment of CD.

Phase II trial of estramustine phosphate and oral etoposide in patients with hormone-refractory prostate cancer.

BACKGROUND: There is a need for active agents with a better safety profile than docetaxel, yet good activity, for patients with hormone-refractory prostate cancer (HRPC). We carried out a phase II trial to determine the activity and safety of estramustine plus oral etoposide in HRPC. PATIENTS AND METHODS: Patients were given estramustine (280 mg twice daily) and etoposide (100 mg/day, days 1-21) in 28-day cycles until disease progression or unacceptable toxicity. Primary end points were overall response rate and safety, as determined by prostate-specific antigen (PSA) levels and lesion assessment. RESULTS: From November 2001 to February 2007, 75 patients were enrolled. All patients were assessable for safety; 17 (22.6%) had grade 3/4 toxicity. PSA response was assessable in 69, 14 of whom had a >50% reduction in PSA. Of 10 patients with one or more measurable lesions, two (20%) had partial response and two (20%) disease stabilization. Overall, median time to progression was 4.4 months (range 1 week-43 months); median survival was 23 months (range 3 weeks-64+ months). CONCLUSIONS: Estramustine plus etoposide is active and has a manageable safety profile in patients with HRPC. In asymptomatic patients with nonaggressive disease this combination could be useful to delay the start of more demanding treatments.

Rutile RuxTi1-xO2 nanobelts to enhance visible light photocatalytic activity.

We herein report on the synthesis by a facile sol-gel method without templates for preparing rutile RuxTi1-xO2 (x = 0.16; 0.07; 0.01) nanobelts with exposed (001) facets. The rutile nanobelts with exposure (001) facets, favor the separation photogenerated electron-hole pairs and inhibit the recombination of the electron-hole pairs resulting in the increase of the number of main superoxide and hydroxyl radicals. The photocatalytic properties of the rutile RuxTi1-xO2 nanobelts were evaluated by discoloring of MB (methylene blue) dye under sunlight irradiation at an intensity of 40000 lx. It was also done a thorough interface analysis to determine the band energy.