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Objective: We evaluated the impressions and perceived workflow consequences following installation of a touch-free aseptic stethoscope barrier dispenser in the clinical environment. Methods: Beginning in 2020, we conducted a volunteer survey of aseptic stethoscope diaphragm barrier (AseptiScope, San Diego, CA) users in multiple departments at 7 US healthcare facilities. A 10-question survey was presented on an iPad near the aseptic barrier dispenser, which was usually located in the patient exam room, to be available immediately after the practitioner completed their examination, which included the use of the stethoscope barrier. This evaluation was considered a quality improvement project and was exempt from institutional review board approval. For this analysis, only 1 survey per practitioner was included. Results: Overall, 147 surveys were obtained from 7 institutions geographically distributed across the United States, immediately after placement of the DiskCover system in the patient care environment. Responses were generally positive and included ease of use (95.2% rated easy or very easy), comparison to a disposable stethoscope (97.9% as similar to, improved over, or significant improvement), workflow changes (53.7% improvement, 97.3% no impact, or improved), and perceived effect on patient safety (90.3% felt that patient safety was improved or significantly improved). Conclusions: The use of a touch-free aseptic stethoscope barrier system was reported to be easy to use, superior to a disposable stethoscope, and an improvement to practitioner workflow and perceived patient safety.
Hans-Georg Gadamer argues that consciousness not only historically constrains experience but also allows strangeness to intelligibly speak to it. This historically effected and effective consciousness features in Gadamer's idea that a common language is unearthed for the interpretive horizons of those involved in dialogue with each other through a logic of question and answer. I argue, however, that this reveals a conceptual uncertainty about evaluating progress in interpretive understanding. Gadamer's failure to escape from this uncertainty risks the possibility of a problematic relativism. Effectively, even if sufficient interpretation occurs when horizons are infinitely structured, this does not preclude incoherence between a horizon's elements.
This paper brings forward Justice Pal's dissenting opinion at the Tokyo Tribunal to add to Third World Approaches to International Law (TWAIL) literature on international criminal law and the rules of evidence and procedure. It is part of a TWAIL effort to scrutinize the everyday practices of international prosecutions through procedural and evidentiary rules. By locating and situating Justice Pal's reasoning within the broader academic literature on dissents in international criminal law, it is possible to illustrate how and why Justice Pal's views were obscured as a relevant dissent. From this vantage point, this paper pursues Justice Pal's legacy as it relates to the rules of evidence and procedure in the International Criminal Tribunal for the Former Yugoslavia and International Criminal Tribunal for Rwanda. It traces the evolution of the judicial power to draft and amend these rules, and examines the impact of these decisions on the everyday functions of the tribunals and how truth is determined.
Attempts to create a national opera in Spain repeatedly failed throughout the 19th century. Some authors have attributed this phenomenon to a deficit in the nationalization process. Others, to the contrary, have proved that there was a strong sense of Spanish national musicality from the middle of the 19th century onward. This article tries to explain this paradox underlining some essential elements that are not always attended by specialists: the importance of transnational, social, and economic dynamics that interfered in the process of the cultural construction of modern national identities. The projects of the Spanish nationalist intellectuals of the 19th century in relation to the definition of a national music were marked by the Romantic construction of Spanish musical exoticism, the new industry of entertainment, the existential situation of Spanish musicians, the formation of new artistic and musical fields, and the appearance of new forms of social distinction in the aftermath of the Spanish Liberal Revolution of the 1830s.
OBJECTIVES/GOALS: Inflammatory Breast Cancer (IBC) is the most aggressive form of breast cancer and does not have targeted therapy. GPR30, a 7-transmembrane estrogen receptor, may play a role in regulating cell growth and proliferation of cancerous cells. Here, we evaluated changes in gene expression while inhibiting GPR30 to determine putative targets to treat IBC. METHODS/STUDY POPULATION: IBC cell lines (SUM149PT) were cultured in medium with serum stripped from growth factor and hormones for 48 hours. Cells were then exposed to either G15 (GPR30 inhibitor) at a concentration of 1ÂµM or ETOH (vehicle negative control) 3 hours in triplicates. After exposure, total RNA was extracted using the Qiagen RNAeasy Mini kit and RNA was sequenced using the Illumina NextSeq (2 X 75bp). The higher-quality reads were aligned, annotated, and quantified to the human genome (HG38) using STAR and RSEM softwares. Gene expression analysis was performed in R statistical software (packages tximport and DESeq2). Functional and enrichment analyses were performed using Metascape and STRING database, respectively. RESULTS/ANTICIPATED RESULTS: There were 656 significantly expressed genes (p < 0.05) between groups (G15 vs. ETOH). The top 5 significant genes include: SMIM7, FANCG, ARID1A, MAML2, and ATF3. Significantly impacted biological processes and pathways include: electron transport chain, mitotic cell cycle process, microtubule cytoskeleton organization, cellular component morphogenesis and DNA-dependent DNA replication (adj p < 0.05). Additionally, physical and functional interaction networks showed 3 major clusters (â‰¥ 12 genes), which contained several gene hubs including BRCA1, BRCA2, FOS (proto-oncogene), PLK1 and PAK1 (both serine/threonine-protein kinases), among others. Interestingly, the network analysis showed the previously known interaction between FANCG and BRCA2, which were both dysregulated by GPR30 inhibition. DISCUSSION/SIGNIFICANCE: Through gene expression, functional and enrichment analyses we found several targets genes that could be associated with the pathogenesis of IBC. Validation of candidates genes (qRT-PCR and Western blot), and functional assays (cell proliferation, motility, and invasion) will be performed to understand the potential of these genes in treating IBC.
Large, conglomerate caves in north-eastern Iberia have been significant places since the Neolithic through to historical times; however, their significance during the Palaeolithic has barely been explored. This project is the first systematic study of the use of these iconic geological landmarks among Pleistocene hunter-gatherers.
Trematodes are the main macroparasites in coastal waters. The most abundant and widespread form of these parasites is metacercaria. Their impact on their host fitness is considered relatively low but metacercarial larvae of some species can have deleterious effects on individuals and/or populations. This review focused on the cockle Cerastoderma edule and four species of the genus Himasthla; a common host–parasite system in marine coastal environments. Our aims were (1) to review literature concerning Himasthla continua, Himasthla elongata, Himasthla interrupta and Himasthla quissetensis in cockles; (2) to provide molecular signatures of these parasites and (3) to analyse infection patterns using a 20-year monthly database of cockle monitoring from Banc d'Arguin (France). Due to identification uncertainties, the analysis of the database was restricted to H. interrupta and H. quissetensis, and it was revealed that these parasites infect cockles of the same size range. The intensity of parasites increased with cockle size/age. During the colder months, the mean parasite intensity of a cockle cohort decreased, while infection occurred in the warmest season. No inter-specific competition between trematode parasites was detected. Furthermore, even if the intensity of H. interrupta or H. quissetensis infection fluctuated in different years, this did not modify the trematode community structure in the cockles. The intensity of infection of both species was also positively correlated with trematode species richness and metacercarial abundance. This study highlighted the possible detrimental role of Himasthla spp. in cockle population dynamics. It also revealed the risks of misidentification, which should be resolved by further molecular approaches.
Cassowaries (Casuarius) are one of the largest indigenous animal species of New Guinea. Researchers have long been trying to understand their local socio-cultural significance. Here we present new results from interviews recorded in 2018 on ethnography associated with bone daggers, a material culture ornament and tool carved from the cassowary's tibiotarsus. We present a ‘storied notion’—a contemporary narrative from oral history of why cassowary is not simply a bird, and briefly describe cassowary bone ornamentation in Auwim, East Sepik Province of Papua New Guinea. By exploring the material history of Casuarius through a ‘storied notion’ approach, we reveal that cassowary bone daggers in rock art are narrative ideas of the species from its landscape to ornamentation and through to people's cosmological beliefs surrounding Casuarius. We argue that the cassowary bone dagger stencil can be seen as part of the life history of this animal.
Within-year variation in infection is a ubiquitous feature of natural populations, but is determined by a complex interplay of environmental, parasitological and host factors. At the same time, co-infection is the norm in the wild. Longitudinal dynamics of co-infecting parasites may therefore be further complicated by covariation across multiple parasites. Here, we used fecal parasite egg and oocyst counts collected repeatedly from individually marked wild Soay sheep to investigate seasonal dynamics of six gastrointestinal parasite groups. Prevalence and abundance tended to be higher in spring and summer, and abundance was higher in lambs compared to adults. We found that within-year variation in highly prevalent strongyle nematode counts was dependent on adult reproductive status, where reproductive ewes had distinct dynamics compared to males and barren ewes. For similarly prevalent coccidia we found an overall peak in oocyst counts in spring but no differences among males, barren and pregnant ewes. Using multivariate mixed-effects models, we further show that apparent positive correlation between strongyle and coccidia counts was driven by short-term within-individual changes in both counts rather than long-term among-individual covariation. Overall, these results demonstrate that seasonality varies across demographic and parasite groups and highlight the value of investigating co-infection dynamics over time.
We evaluated the relationship between plasma levels of anti-Müllerian hormone (AMH) and the number of antral follicles at the restart of the follicular wave in crossbred Holstein cows reared under extensive grazing systems over 2500 m above sea level. The study included 140 cows from 15 farms that were in average at the 75.3 ± 2.10 d post partum. Animals were synchronized according to the following regime: day 0 = intravaginal progesterone releasing device (IPD) + estradiol benzoate (EB); day 7: withdrawal of IPD + prostaglandin; and day 8: EB, for restart of the follicular wave on day 11. On this day 11, antral follicle counts (AFCs) were made by transrectal ultrasound, and a plasma sample was taken for the determination of AMH. The mean AMH plasma level was 0.06 ± 0.03 ng/ml and the mean AFC was 17.26 ± 0.38 follicles. A strong positive linear correlation was found between these two variables (r = 0.783, r = 0.613, P < 0.0001). Cows were categorized according to AMH concentration as high (>0.09 ng/ml), intermediate (0.09–0.05 ng/ml) or low (<0.05 ng/ml). Cows with high AMH presented a higher AFC (25.0 ± 2.21 follicles) than those with low AMH (14.08 ± 2.68 follicles; P < 0.001. Our results suggest that the cut-off value of AMH = 0.09 ng/ml may be useful for selecting donors in multiple ovulation embryo transfer programs involving cows with these characteristics. Our data further suggest that AMH plasma concentration correlates with AFC and can be used as an endocrine biomarker of the number of antral follicles present at a given moment of the estrous cycle in crossbred Holstein cows raised at altitudes above 2500 m.
This work aimed to investigate the effects of early progeny exposure to methylglyoxal (MG), programming for metabolic dysfunction and diabetes-like complications later in life. At delivery (PN1), the animals were separated into two groups: control group (CO), treated with saline, and MG group, treated with MG (20 mg/kg of BW; i.p.) during the first 2 weeks of the lactation period. In vivo experiments and tissue collection were done at PN90. Early MG exposure decreased body weight, adipose tissue, liver and kidney weight at adulthood. On the other hand, MG group showed increased relative food intake, blood fructosamine, blood insulin and HOMA-IR, which is correlated with insulin resistance. Besides, MG-treated animals presented dyslipidaemia, increased oxidative stress and inflammation. Likewise, MG group showed steatosis and perivascular fibrosis in the liver, pancreatic islet hypertrophy, increased glomerular area and pericapsular fibrosis, but reduced capsular space. This study shows that early postnatal exposure to MG induces oxidative stress, inflammation and fibrosis markers in pancreas, liver and kidney, which are related to metabolic dysfunction features. Thus, nutritional disruptors during lactation period may be an important risk factor for metabolic alterations at adulthood.
The reimbursement of medicines by the Spanish National Health System (NHS) is based on a set of criteria included in the Royal Legislative Decree 1/2015 (RDL 1/2015). The Interministerial Committee on Pricing of Medicines and Healthcare Products (CIPM) is responsible for the final price and reimbursement (P&R) decision, including on its resolutions the criteria listed in the law by which the reimbursement of a drug is approved or denied. Nevertheless, the information behind its reasoning is not provided. The present study aims to characterize the P&R criteria of the RDL 1/2015 through criteria definitions from other countries to improve the P&R evaluation in Spain.
A multidisciplinary experts panel with relevant experience in drug evaluation and decision making at national, regional, and local level in Spain was selected for this study. A literature review to characterize the criteria listed in the RDL 1/2015 was performed based on the most relevant and recognized Health Technology Assessment (HTA) agencies in Europe, UK, and Canada. Eventually, a feasibility study was performed to evaluate the novel drug cefiderocol using the characterized criteria, including a reflective discussion of the results.
Consensus was reached among the multidisciplinary experts on the characterization of the criteria set by the law. The feasibility of their application to a new drug was exploratory, notwithstanding it showed the potential to improve the transparency as well as to offer a more structured rationale for the CIPM to evaluate the inclusion of new drugs in the Spanish NHS.
The management of out-of-hospital traumatic cardiac arrest (TCA) for professional rescuers entails Advanced Life Support (ALS) with specific actions to treat the potential reversible causes of the arrest: hypovolemia, hypoxemia, tension pneumothorax (TPx), and tamponade. The aim of this study was to assess the impact of specific rescue measures on short-term outcomes in the context of resuscitating patients with a TCA.
This retrospective study concerns all TCA patients treated in two emergency medical units, which are part of the Northern French Alps Emergency Network (RENAU), from January 2004 through December 2017. Utstein variables and specific rescue measures in TCA were compiled: fluid expansion, pelvic stabilization, tourniquet application, bilateral thoracostomy, and thoracotomy procedures. The primary endpoint was survival rate at Day 30 with good neurological status (Cerebral Performance Category [CPC] score CPC 1 and CPC 2).
In total, 287 resuscitation attempts in TCA were included and 279 specific interventions were identified: 262 fluid expansions, 41 pelvic stabilizations, five tourniquets, and 175 bilateral thoracostomies (including 44 with TPx).
Among the standard resuscitation measures to treat the reversible causes of cardiac arrest, this study found that bilateral thoracostomy and tourniquet application on a limb hemorrhage improve survival in TCA. A larger sample for pelvic stabilization is needed.
Extrapolation methods are commonly used to model the cost-effectiveness of health technologies beyond observed data. Reassessing cost-effectiveness estimates using updated clinical trial data has the potential to reduce uncertainty and optimize decision-making. We present a case study based on percutaneous repair (PR) with the Mitraclip system, a technology to treat severe secondary mitral regurgitation (MR). For the study purpose, we considered the COAPT trial that evaluated the effectiveness of adding PR to medical treatment versus medical treatment alone.
We developed a time-varying Markov model to assess the cost-effectiveness of PR. Clinical inputs were based on reconstructed individual patient data from the COAPT trial results reported at 2 years, and at 3 years.
We developed parametric modeling for overall survival (OS) and heart failure hospitalizations (HFH) to obtain clinically plausible extrapolations beyond observed data. We adopted the French perspective and used a 30-year time horizon. We expressed incremental cost-effectiveness ratios (ICERs) as cost per quality-adjusted life year (QALY).
Based on 2 year-data, preferred parametric models for OS and HFH were exponential and log-logistic respectively, yielding an ICER of EUR21,918/QALY and >0.5 probability of PR being cost-effective (EUR50,000/QALY threshold).
Updated analyses at 3 years showed a change of OS trajectory for PR that justified the use of piecewise modelling, yielding an updated ICER that went up to EUR77,904/QALY (base-case), and to a minimum of EUR58,175/QALY (scenario analysis). Using data at 3 years, PR had <0.5 probability of being cost-effective.
In this case study, the availability of updated survival analyses of the main trial is likely to have some impact on decision-making and/or pricing discussion as part of health-technology assessment (HTA). We aim to provide further updated analyses as 4 years results of the COAPT study become available.
More broadly, original technology appraisals are frequently undertaken when mid/long-term follow-up trial data may be lacking. Our example suggests the need for continuous HTA review as new clinical data are released.
Electron microprobe-based quantitative compositional measurement of first-row transition metals using their L$\alpha$ X-ray lines is hampered by, among other effects, self-absorption. This effect, which occurs when a broad X-ray line is located close to a broad absorption edge, is not accounted for by matrix corrections. To assess the error due to neglecting self-absorption, we calculate the L$\alpha$ X-ray intensity emitted from metallic Fe, Ni, Cu, and Zn targets, assuming a Lorentzian profile for the X-ray line and taking into account the energy dependence of the mass absorption coefficient near the absorption edge. We find that calculated X-ray intensities depart increasingly, for increasing electron beam energy, from those obtained assuming a narrow X-ray line and a single fixed absorption coefficient (conventional approach), with a maximum deviation of $\sim$15% for Ni and of $\sim$10% for Fe. In contrast, X-ray intensities calculated for metallic Zn and Cu do not differ significantly from those obtained using the conventional approach. The implications of these results for the analysis of transition-metal compounds by electron probe microanalysis as well as strategies to account for self-absorption effects are discussed.
The ingestion of excess lipids often produces the accumulation of liver fat. The modulation of diet energy partition affects this process and other metabolic responses, and oestrogens and androgens are implied in this process. Ten-week-old male and female rats were fed with either standard rat chow (SD), SD enriched with coconut oil (high-fat diet, HF), SD enriched with protein (high-protein diet, HP) or a ‘cafeteria’ diet (CAF) for 1 month. HF and CAF diets provided the same lipid-derived percentage of energy (40 %), HP diet protein energy derived was twice (40 %) that of the SD. Animals were killed under anaesthesia and samples of blood and liver were obtained. Hepatic lipid content showed sex-related differences: TAG accumulation tended to increase in HF and CAF fed males. Cholesterol content was higher only in the CAF males. Plasma oestradiol in HF and HP males was higher than in CAF. Circulating cholesterol was inversely correlated with plasma oestradiol. These changes agreed with the differences in the expression of some enzymes related to lipid and energy metabolism, such as fatty acid synthetase or phosphoglycolate phosphatase. Oestrogen protective effects extend to males with ‘normal’ diets, that is, not unbalanced by either lipid or protein, but this protection was not enough against the CAF diet. Oestradiol seems to actively modulate the liver core of 2C-3C partition of energy substrates, regulating cholesterol deposition and lactate production.