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Humans have been shown to have biases when reading medical images, raising questions about whether humans are uniform in their disease gradings. Artificial intelligence (AI) tools trained on human-labeled data may have inherent human non-uniformity. In this study, we used a radiographic knee osteoarthritis external validation dataset of 50 patients and a six-year retrospective consecutive clinical cohort of 8,273 patients. An FDA-approved and CE-marked AI tool was tested for potential non-uniformity in Kellgren-Lawrence grades between the right and left sides of the images. We flipped the images horizontally so that a left knee looked like a right knee and vice versa. According to human review, the AI tool showed non-uniformity with 20–22% disagreements on the external validation dataset and 13.6% on the cohort. However, we found no evidence of a significant difference in the accuracy compared to senior radiologists on the external validation dataset, or age bias or sex bias on the cohort. AI non-uniformity can boost the evaluated performance against humans, but image areas with inferior performance should be investigated. [ABSTRACT FROM AUTHOR]

Most people don't want their teachers, scientists, or journalists to be too ideological. Calling someone an "ideologue" isn't a compliment. But what is ideology and why exactly is it a threat? I propose that ideology is fruitfully understood in terms of three ingredients: a basic moral claim, a worldview built on top of that claim, and the attempt to politicize this worldview by injecting it into social institutions. I further argue that the central danger of ideology is that activating these three ingredients tends to undermine liberal social institutions. And yet a certain amount of ideology is both unavoidable and desirable, as I show, since it supplies us with important goods like social cohesion and mobilization. This means the best we can do is to try and set boundaries on ideology. [ABSTRACT FROM AUTHOR]

Introduction: Surgical procedures in contemporary practice frequently employ energy-based devices, yet comprehensive education surrounding their safety and effectiveness remains deficient. We propose an innovative course for residents that aims to provide basic electrosurgery knowledge and promote the safe use of these devices. Methods: We developed a simulated training course for first-year general surgery and orthopedic residents. First, a survey was conducted regarding their knowledge perception about energy devices. The course consisted of two online theoretical sessions, followed by three in-person practical sessions. First-year residents performed three video-recorded attempts using a cadaveric model and were assessed through a digital platform using the Objective Structured Assessment of Technical Skill (OSATS), a Specific Rating Scale (SRS), and a surgical energy-based devices scale (SEBS). Third-year residents were recruited as a control group. Results: The study included 20 first-year residents and 5 third-year residents. First-year residents perceived a knowledge gap regarding energy devices. Regarding practical performance, both OSATS and checklist scores were statistically different between novices at their first attempt and the control group. When we analyzed the novice's performance, we found a significant increase in OSATS (13 vs 21), SRS (13 vs 17.5), and SEBS (5 vs 7) pre- and post-training scores. The amount of feedback referred to skin burns with the electro-scalpel reduced from 18 feedbacks in the first attempt to 2 in the third attempt (p-value = 0.0002). When comparing the final session of novices with the control group, no differences were found in the SRS (p = 0.22) or SEBS (p = 0.97), but differences remained in OSATS (p = 0.017). Conclusion: This study supports the implementation of structured education in electrosurgery among surgical trainees. By teaching first-year residents about electrosurgery, they can acquire a skill set equivalent to that of third-year residents. The integration of such courses can mitigate complications associated with energy device misuse, ultimately enhancing patient safety. [ABSTRACT FROM AUTHOR]

In order to improve the ability of clinical diagnosis to differentiate articular cartilage (AC) injury of different origins, this study explores the sensitivity of mid-infrared (MIR) spectroscopy for detecting structural, compositional, and functional changes in AC resulting from two injury types. Three grooves (two in parallel in the palmar-dorsal direction and one in the mediolateral direction) were made via arthrotomy in the AC of the radial facet of the third carpal bone (middle carpal joint) and of the intermediate carpal bone (the radiocarpal joint) of nine healthy adult female Shetland ponies (age = 6.8 ± 2.6 years; range 4–13 years) using blunt and sharp tools. The defects were randomly assigned to each of the two joints. Ponies underwent a 3-week box rest followed by 8 weeks of treadmill training and 26 weeks of free pasture exercise before being euthanized for osteochondral sample collection. The osteochondral samples underwent biomechanical indentation testing, followed by MIR spectroscopic assessment. Digital densitometry was conducted afterward to estimate the tissue's proteoglycan (PG) content. Subsequently, machine learning models were developed to classify the samples to estimate their biomechanical properties and PG content based on the MIR spectra according to injury type. Results show that MIR is able to discriminate healthy from injured AC (91%) and between injury types (88%). The method can also estimate AC properties with relatively low error (thickness = 12.7% mm, equilibrium modulus = 10.7% MPa, instantaneous modulus = 11.8% MPa). These findings demonstrate the potential of MIR spectroscopy as a tool for assessment of AC integrity changes that result from injury. [ABSTRACT FROM AUTHOR]

Gut bacterial communities have a profound influence on the health of humans and animals. Early-life gut microbial community structure influences the development of immunological competence and susceptibility to disease. For the Thoroughbred racehorse, the significance of early-life microbial colonisation events on subsequent health and athletic performance is unknown. Here we present data from a three-year cohort study of horses bred for racing designed to explore interactions between early-life gut bacterial community structure, health events in later life and athletic performance on the racetrack. Our data show that gut bacterial community structure in the first months of life predicts the risk of specific diseases and athletic performance up to three years old. Foals with lower faecal bacterial diversity at one month old had a significantly increased risk of respiratory disease in later life which was also associated with higher relative abundance of faecal Pseudomonadaceae. Surprisingly, athletic performance up to three years old, measured by three different metrics, was positively associated with higher faecal bacterial diversity at one month old and with the relative abundance of specific bacterial families. We also present data on the impact of antibiotic exposure of foals during the first month of life. This resulted in significantly lower faecal bacterial diversity at 28 days old, a significantly increased risk of respiratory disease in later life and a significant reduction in average prize money earnings, a proxy for athletic performance. Our study reveals associations between early-life bacterial community profiles and health events in later life and it provides evidence of the detrimental impact of antimicrobial treatment in the first month of life on health and performance outcomes in later life. For the first time, this study demonstrates a relationship between early-life gut bacterial communities and subsequent athletic performance that has implications for athletes of all species including humans. [ABSTRACT FROM AUTHOR]

In some fish lineages, evolution has led to unique sensory adaptations that provide information which is not available to terrestrial animals. These sensory systems include, among others, electroreception, which together with the ability of fish to generate electric discharges plays a role in social communication and object location. Most studies on electric phenomena in aquatic animals are dedicated to selected groups of electric fishes that regularly generate electric signals (Mormyriformes, Gymnotiformes). There exist, however, several species (hitherto described as non-electric) which, though able to perceive electric signals, have now been found to also generate them. In this article, we introduce a tool that we have designed to investigate such electric activity. This required significant adaptations of the equipment used in fish with regular discharge generation. The necessary improvements were realized by using a multielectrode registration setup allowing simultaneous visualization and quantification of behavior and associated electric activity of fish, alone or in groups, with combined electro-video clips. Precise synchronization of locomotor and electric behaviors made it possible to determine the electrically active fish in a group, and also the location of the electrogenic structure inside the fish's body. Our simple registration procedure, together with data presentation, should attract a broad audience of scientists taking up the challenge of uncovering electric phenomena in aquatic animals currently treated as electrically inactive. [ABSTRACT FROM AUTHOR]

Improving child behavior and promoting family well-being is a key objective of evidence-based parenting programs, such as the Triple P–Positive Parenting Program. To achieve this goal, parenting programs are delivered using a multidisciplinary workforce. Previous researchers have collectively examined the entire workforce of parenting practitioners to determine the factors that influence program delivery, primarily using self-report measures. However, these findings did not highlight the unique factors relevant to specific practitioner disciplines. Educators are one practitioner discipline that play an integral role in delivering parenting programs through schools and early childhood learning settings. This study aimed at exploring the facilitators and barriers that impact frequency of program use for educator practitioners using both qualitative and quantitative analyses. Data from 404 Triple P educator practitioners were extracted from a larger dataset of 1202 practitioners from English-speaking countries who completed self-report questionnaires and responded to three open-ended questions. Hierarchical multiple regressions were conducted using eight independent variables (with participant characteristics as control variables), revealing seven positive and one negative predictor for frequency of use. A thematic analysis was then conducted on the qualitative responses, producing 11 themes and 28 subthemes. The quantitative analysis revealed organisational support, perceived usefulness, and practitioner self-regulation were the most important positive predictors. The qualitative analysis supported these findings and revealed novel barriers including Covid-19/work from home, online delivery, parent factors, and specific organisational factors. These findings highlight the need for online resources, reliable virtual delivery methods, improved ways to reach and engage families, and additional trained education practitioners to distribute high workloads. [ABSTRACT FROM AUTHOR]

Background: Risk-reducing mastectomy (RRM) is offered to women with a BRCA1 or BRCA2 pathogenic variant, however, there are limited data on the impact on breast cancer mortality. Methods: Participants were identified from a registry of women with BRCA1/2 pathogenic variants. We used a pseudo-randomised trial design and matched one woman with a RRM to one woman without a RRM on year of birth, gene, and country. We estimated the hazard ratio (HR) and 95% confidence intervals (CI) for dying of breast cancer in the follow-up period. Results: There were 1654 women included; 827 assigned to the RRM arm and 827 assigned to the control arm. After a mean follow-up of 6.3 years, there were 20 incident breast cancers (including 15 occult cancers) and two breast cancer deaths in the RRM arm, and 100 incident breast cancers and 7 breast cancer deaths in the control arm (HR = 0.26; 95% CI 0.05–1.35; p = 0.11). The probability of dying of breast cancer within 15 years after RRM was 0.95%. Conclusions: In women with a BRCA1 or BRCA2 pathogenic variant, RRM reduces the risk of breast cancer, and the probability of dying of breast cancer is low. [ABSTRACT FROM AUTHOR]

This article defines the term valorization of biodiversity and ecosystem services (BES) measures, as distinguished from their valuation, and underpins it with an assessment of private valorization examples along the agri-food value chain. Valorization incentivizes measures for promoting BES, while valuation refers to its quantification. Valuation can be a step of valorization but is not indispensable. In scientific literature, the terms valorization and valuation are often used interchangeably. In addition, there is a lack of research on private options versus conventional, public policy options. Therefore, we searched for private valorization options primarily in public sources (gray literature and websites). This led to the identification of four clusters (markets for voluntary services, labeling, and certification, environmental management/CSR, and tradable permits and quotas). Based on these clusters the options were assessed from a legal and systems dynamics perspective. In addition, the viability of selected valorization options in different future scenarios was examined. The analysis revealed a wide range of private valorization options, which in contrast to public policy options that focus almost entirely on the production stage, are spread across the agri-food value chain. Their suitability differs under different future scenarios, legal and systems conditions. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma is an immunogenic tumour with a prominent dysfunctional immune cell infiltrate, unable to control tumour growth. Although tyrosine kinase inhibitors and immunotherapy have improved the outlook for some patients, many individuals are non-responders or relapse despite treatment. The hostile metabolic environment in RCC affects the ability of T-cells to maintain their own metabolic programme constraining T-cell immunity in RCC. We investigated the phenotype, function and metabolic capability of RCC TILs correlating this with clinicopathological features of the tumour and metabolic environment at the different disease stages. Flow cytometric analysis of freshly isolated TILs showed the emergence of exhausted T-cells in advanced disease based on their PD-1high and CD39 expression and reduced production of inflammatory cytokines upon in vitro stimulation. Exhausted T-cells from advanced stage disease also displayed an overall phenotype of metabolic insufficiency, characterized by mitochondrial alterations and defects in glucose uptake. Nanostring nCounter cancer metabolism assay on RNA obtained from 30 ccRCC cases revealed significant over-expression of metabolic genes even at early stage disease (pT1-2), while at pT3-4 and the locally advanced thrombi stages, there was an overall decrease in differentially expressed metabolic genes. Notably, the gene PPARGC1A was the most significantly down-regulated gene from pT1-2 to pT3-4 RCC which correlated with loss of mitochondrial function in tumour-infiltrating T-cells evident at this tumour stage. Down-regulation of PPARGC1A into stage pT3-4 may be the 'tipping-point' in RCC disease progression, modulating immune activity in ccRCC and potentially reducing the efficacy of immunotherapies in RCC and poorer patient outcomes. [ABSTRACT FROM AUTHOR]

The document discusses an analysis of the NEUROPROTECT study, comparing hemodynamic therapy in comatose survivors of cardiac arrest. The authors used hemodynamic data to calculate measures related to venous return physiology, highlighting the ambiguity of certain derived measures due to assumptions about resistance to venous return. The study emphasizes the importance of interpreting measures related to venous return alongside cardiac output and resistance, revealing novel insights into interventions like IV fluids. The authors stress the need to consider multiple factors when analyzing measures dependent on the pressure gradient for venous return. [Extracted from the article]

Irrigation water is an expensive and limited resource and optimal scheduling can boost water efficiency. Scheduling decisions often need to be made several days prior to an irrigation event, so a key aspect of irrigation scheduling is the accurate prediction of crop water use and soil water status ahead of time. This prediction relies on several key inputs including initial soil water status, crop conditions and weather. Since each input is subject to uncertainty, it is important to understand how these uncertainties impact soil water prediction and subsequent irrigation scheduling decisions. This study aims to develop an uncertainty-based analysis framework for evaluating irrigation scheduling decisions under uncertainty, with a focus on the uncertainty arising from short-term rainfall forecasts. To achieve this, a biophysical process-based crop model, APSIM (The Agricultural Production Systems sIMulator), was used to simulate root-zone soil water content for a study field in south-eastern Australia. Through the simulation, we evaluated different irrigation scheduling decisions using ensemble short-term rainfall forecasts. This modelling produced an ensemble of simulations of soil water content, as well as ensemble simulations of irrigation runoff and drainage. This enabled quantification of risks of over- and under-irrigation. These ensemble estimates were interpreted to inform the timing of the next irrigation event to minimize both the risks of stressing the crop and/or wasting water under uncertain future weather. With extension to include other sources of uncertainty (e.g., evapotranspiration forecasts, crop coefficient), we plan to build a comprehensive uncertainty framework to support on-farm irrigation decision-making. [ABSTRACT FROM AUTHOR]

In this study, we mapped and quantified changes of proteoglycan (PG) content and biomechanical properties in articular cartilage in which either blunt or sharp grooves had been made, both close to the groove and more remote of it, and at the opposing joint surface (kissing site) in equine carpal joints. In nine adult Shetland ponies, standardized blunt and sharp grooves were surgically made in the radiocarpal and middle carpal joints of a randomly chosen front limb. The contralateral control limb was sham-operated. At 39 weeks after surgery, ponies were euthanized. In 10 regions of interest (ROIs) (six remote from the grooves and four directly around the grooves), PG content as a function of tissue-depth and distance-to-groove was estimated using digital densitometry. Biomechanical properties of the cartilage were evaluated in the six ROIs remote from the grooves. Compared to control joints, whole tissue depth PG loss was found in sites adjacent to sharp and, to a larger extent, blunt grooves. Also, superficial PG loss of the surgically untouched kissing cartilage layers was observed. Significant PG loss was observed up to 300 µm (sharp) and at 500 µm (blunt) from the groove into the surrounding tissue. Equilibrium modulus was lower in grooved cartilage than in controls. Grooves, in particular blunt grooves, gave rise to severe PG loss close to the grooved sites and to mild degeneration more remote from the grooves in both sharply and bluntly grooved cartilage and at the kissing sites, resulting in loss of mechanical strength over the 9-month period. [ABSTRACT FROM AUTHOR]

Humanized liver rodent models, in which the host liver parenchyma is repopulated by human hepatocytes, have been increasingly used for drug development and disease research. Unlike the leading humanized liver mouse model in which Fumarylacetoacetate Hydrolase (Fah), Recombination Activating Gene (Rag)-2 and Interleukin-2 Receptor Gamma (Il2rg) genes were inactivated simultaneously, generation of similar recipient rats has been challenging. Here, using Velocigene and 1-cell-embryo-targeting technologies, we generated a rat model deficient in Fah, Rag1/2 and Il2rg genes, similar to humanized liver mice. These rats were efficiently engrafted with Fah-expressing hepatocytes from rat, mouse and human. Humanized liver rats expressed human albumin and complement proteins in serum and showed a normal liver zonation pattern. Further, approaches were developed for gene delivery through viral transduction of human hepatocytes either in vivo, or in vitro prior to engraftment, providing a novel platform to study liver disease and hepatocyte-targeted therapies. [ABSTRACT FROM AUTHOR]

Background: One potential benefit of neoadjuvant therapy (NAT) in node-positive, estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2−) patients is axillary downstaging to avoid axillary dissection. Objective: The aim of this study was to evaluate axillary response to NAT with chemotherapy (NCT) or endocrine therapy (NET) and identify potential predictors of response. Methods: A prospectively collected database was queried for node-positive, ER+, HER2− breast cancer patients treated with NAT and surgery from January 2011 to September 2020. Axillary response was categorized into pathologic complete response (pCR) versus no pCR, and was correlated to demographic and clinicopathologic parameters in a logistic regression model. Results: A cohort of 176 eligible patients was identified and 178 breast cancers were included in the study. The overall axillary pCR rate was 12.3% (22/178). NCT and NET achieved response rates of 13.9% (19/137) and 7.3% (3/41), respectively (p = 0.232). A significantly higher axillary pCR rate was identified in patients with clinical stage II at diagnosis (12/60, 20%) compared with stage III (10/118, 8.4%; p = 0.03). NET patients with ypN0 were younger and were treated for a longer period of time (>6 months). Completion axillary dissection was omitted in the majority (73.7%) of NCT patients achieving axillary pCR. Conclusions: For patients with node-positive, ER+, HER2− breast cancer, a lower burden of disease at the time of diagnosis (stage II) is associated with a significantly higher axillary pCR, enabling those patients to be spared axillary dissection. Further studies are necessary to define the role of genomic profiling in predicting axillary response. [ABSTRACT FROM AUTHOR]

By combining qualitative scenarios and life cycle assessment (LCA), we place the latter in a larger context. This study outlines the importance of the integration of future perspectives into LCA, and also the significance of taking changes in the environment of technology into account, rather than just technological development itself. Accordingly, we focused on adapting the background system of an attributional LCA in the agri-food sector. The proposed technology was assumed not have evolved in the considered time horizon. In this context, the objectives of this paper were twofold: (i) to methodologically prove the applicability of integrating qualitative scenarios into LCA and (ii) to focus on changes in the background system, which is sometimes overlooked in the context of future-oriented LCA. This allowed to evaluate the future potential of different technologies, assessing their environmental impact under uncertain future developments. Methodologically, the qualitative information from scenarios was transformed into quantitative data, which was successively fed into the life cycle inventory (LCI) of the LCA approach. This point of integration into the second phase of LCA translates into future changes in the entire environment in which a technology is used. This means that qualitatively described scenario narratives need to be converted into value estimates in order to be incorporated into the LCA model. A key conclusion is that changes in the background of an LCA—the changing framework expressed through the inventory database—can be very important for the environmental impact of emerging technologies. This approach was applied to a food processing technology to produce apple juice. The proposed methodology enables technology developers to make their products future-proof and robust against socioeconomic development. In addition, the market perspective, if spelled out in the scenarios, can be integrated, leading to a more holistic picture of LCA with its environmental focus, while simultaneously empowering actors to make the right strategic decisions today, especially when considering the long investment cycles in the agri-food sector. [ABSTRACT FROM AUTHOR]

Background: TIA and stroke, both ischemic and hemorrhagic, may complicate Fabry disease at young-adult age and be the first manifestation that comes to the clinician's attention. No definite indications have yet been elaborated to guide neurologists in Fabry disease diagnostics. In current practice, it is usually sought in case of cryptogenic strokes (while Fabry-related strokes can also occur by classical pathogenic mechanisms) or through screening programs in young cerebrovascular populations. Data on recurrence and secondary prevention of Fabry's stroke are scanty. Methods: The study had a prospective observational design involving 33 Italian neurological Stroke Units. Considering the incidence of TIA/stroke in the European population aged < 60 years and the frequency of Fabry disease in this category (as foreseen by a pilot study held at the Careggi University-Hospital, Florence), we planned to screen for Fabry disease a total of 1740 < 60-year-old individuals hospitalized for TIA, ischemic, or hemorrhagic stroke. We investigated TIA and stroke pathogenesis through internationally validated scales and we gathered information on possible early signs of Fabry disease among all cerebrovascular patients. Every patient was tested for Fabry disease through dried blood spot analysis. Patients who received Fabry disease diagnosis underwent a 12-month follow-up to monitor stroke recurrence and multi-system progression after the cerebrovascular event. Discussion: The potential implications of this study are as follows: (i) to add information about the yield of systematic screening for Fabry disease in a prospective large cohort of acute cerebrovascular patients; (ii) to deepen knowledge of clinical, pathophysiological, and prognostic characteristics of Fabry-related stroke. [ABSTRACT FROM AUTHOR]

Introduction: RELAY was a global, double-blind, placebo-controlled phase III study that demonstrated superior progression-free survival (PFS) for ramucirumab plus erlotinib (RAM + ERL) versus placebo plus erlotinib (PBO + ERL) in the first-line treatment of patients with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 (L858R) mutation-positive, metastatic non-small-cell lung cancer (NSCLC). Objective: This article provides an in-depth analysis of the safety profile of RAM + ERL versus PBO + ERL observed in RELAY. Methods: Eligible patients met these criteria: stage IV NSCLC; EGFR exon 19 deletion or exon 21 substitution (L858R) mutation; Eastern Cooperative Oncology Group performance status 0 or 1; and no central nervous system metastases. Patients were randomized (1:1) to receive erlotinib 150 mg/day orally plus either ramucirumab 10 mg/kg intravenously or matching placebo once every 2 weeks, until disease progression or unacceptable toxicity. The primary endpoint was PFS. Safety was evaluated based on reported treatment-emergent adverse events (AEs) and clinical laboratory assessments. Results: The safety population comprised 446 patients (221 in RAM+ERL arm; 225 in PBO + ERL arm) who received at least one dose of study drug between January 2016 and February 2018. The overall incidence of grade ≥ 3 AEs was higher with RAM + ERL than with PBO + ERL, primarily driven by grade 3 hypertension. Grade ≥ 3 dermatitis acneiform and diarrhea were also reported more frequently in the RAM + ERL arm. The increased incidence of AEs with RAM + ERL was easily detected through routine monitoring and managed through dose adjustments and appropriate supportive care. Conclusion: This in-depth safety analysis from RELAY supports that RAM + ERL, irrespective of the increased incidence of AEs, does not affect a patient's ability to benefit from treatment. Clinical Trial Registration Number: NCT02411448. [ABSTRACT FROM AUTHOR]

Dimensional accuracy in parts manufactured by wire EDM (WEDM) can be lost due to wire lag (where the wire electrode bends into an arc away from the machining direction). Wire lag effects are at issue when extremely narrow tolerances on curved or sharply angled geometries are desired. The feasibility of a program to modify machining G-code to compensate for wire lag at sharp corners is investigated here. Program development was informed by machining experiments. First, the effect of surface feed rate on profile accuracy was investigated. It was found that feed influences wire lag and profile accuracy. A wire lag model is demonstrated, and methods for developing modifications to incorporate both surface feed and eliminate the need for an ex situ measurement to minimize wire lag are presented. A method for relating pulse duration and voltage to each plasma discharge's area is demonstrated. Lastly, an outline for a program that compensates for wire lag at threshold angles is shown. It is found that the developed application can predict wire lag or corner error within ±10% of the experimental value. It is also found that profile accuracy can be significantly improved using a cutback method by calculating the amount of wire lag from the modified model and modifying CNC G-codes using the developed application to apply cutbacks at designated corners. [ABSTRACT FROM AUTHOR]

A finite-element mathematical model is developed to describe the transformation of the surface cracks of continuously cast slabs made of low-alloy pipe steels into sheet defects during hot rolling. The transformation of axial, edge, rib, and side cracks of a slab is investigated. It is found that, depending on the deformation conditions, surface cracks on rolling a slab into a thick sheet can close in the first passages under compressive stresses, come to the surface, form folds, twist toward the edge, or completely rolled out. [ABSTRACT FROM AUTHOR]

Purpose: It is not known whether the risk of breast cancer among BRCA1 and BRCA2 mutation carriers after age 60 is high enough to justify intensive screening or prophylactic surgery. Thus, we conducted a prospective analysis of breast cancer risk in BRCA1 and BRCA2 mutation carriers from age 60 until age 80. Methods: Subjects had no history of cancer and both breasts intact at age 60 (n = 699). Women were followed until a breast cancer diagnosis, prophylactic bilateral mastectomy or death. We calculated the annual cancer rate and cumulative incidence of breast cancer (invasive and in situ) from age 60 to age 80. We assessed the associations between hormone replacement therapy, family history of breast cancer and bilateral oophorectomy and breast cancer risk. Results: Over a mean follow-up of 7.9 years, 61 invasive and 20 in situ breast cancers were diagnosed in the cohort. The mean annual rate of invasive breast cancer was 1.8% for BRCA1 mutation carriers and 1.7% for BRCA2 mutation carriers. The cumulative risk of invasive breast cancer from age 60 to 80 was 20.1% for women with a BRCA1 mutation and was 17.3% for women with a BRCA2 mutation. Hormone replacement therapy, family history and oophorectomy were not associated with breast cancer risk. Conclusions: Findings from this large prospective study indicate that the risk of developing breast cancer remains high after age 60 in both BRCA1 and BRCA2 mutation carriers. These findings warrant further evaluation of the role of breast cancer screening in older mutation carriers. [ABSTRACT FROM AUTHOR]

Porcine circovirus 2 (PCV-2) is the causative agent of porcine circovirus diseases (PCVD). A study was undertaken to determine whether PCV-2 was present in samples collected from commercial pigs (n = 46) and warthogs (n = 42) in Namibia between 2019 and 2020. Twenty-three of the collected samples were positive by PCR (13 from pigs and 10 from warthogs), and a phylogenetic analysis of ORF2 identified three genotypes (PCV-2b and PCV-2d in pigs and PCV-2c in warthogs). This is the first time that PCV-2 has been identified in warthogs and in Namibia. It is also the first report of PCV-2c in Africa. [ABSTRACT FROM AUTHOR]

CRISPR-based transcriptional activation is a powerful tool for functional gene interrogation; however, delivery difficulties have limited its applications in vivo. Here, we created a mouse model expressing all components of the CRISPR-Cas9 guide RNA-directed Synergistic Activation Mediator (SAM) from a single transcript that is capable of activating target genes in a tissue-specific manner. We optimized Lipid Nanoparticles and Adeno-Associated Virus guide RNA delivery approaches to achieve expression modulation of one or more genes in vivo. We utilized the SAM mouse model to generate a hypercholesteremia disease state that we could bidirectionally modulate with various guide RNAs. Additionally, we applied SAM to optimize gene expression in a humanized Transthyretin mouse model to recapitulate human expression levels. These results demonstrate that the SAM gene activation platform can facilitate in vivo research and drug discovery. CRISPR-Cas9 is a gene editing tool that can be used to modulate gene expression. Here, the authors report the generation of a mouse model that express all components of the CRISPR-Cas9 guide directed Synergistic Activation Mediator (SAM), demonstrate that gene activation can be achieved with various delivery methods and include generation of a disease model of hypercholesterolemia [ABSTRACT FROM AUTHOR]

Large-scale mean patterns in Rayleigh–Bénard convection, also referred to as turbulent superstructures, have mainly been studied by means of numerical simulations so far, but experimental investigations are still rare. However, the analysis of turbulent superstructures, which are of great importance due to their effect on the local transport of heat and momentum, require both numerical and experimental data. Therefore, within the scope of this study measurements were performed in the horizontal mid plane and in a horizontal plane closer to the top of a Rayleigh–Bénard cell with an aspect ratio of Γ = l / h = 25 , thereby showing the initial formation of turbulent superstructures and their long-time rearrangement. The turbulent superstructures are investigated experimentally by noninvasive simultaneous measurements of temperature and velocity fields, using the color signal of thermochromic liquid crystals (TLCs) for the evaluation of the temperature and their temporal displacement for the determination of all three velocity components in the measurement planes via stereoscopic particle image velocimetry (stereo-PIV). Applying this measuring technique it is demonstrated that the time-averaging of instantaneous temperature and velocity fields uncovers the turbulent superstructures in both fields. Furthermore, the combination of the temperature and velocity data is used to characterize the local heat flux quantified by the local Nusselt number, which confirms that the turbulent superstructures strongly enhance the heat transfer in Rayleigh–Bénard convection. [ABSTRACT FROM AUTHOR]

Complete removal of cancerous tissue and preservation of breast cosmesis with a single breast conserving surgery (BCS) is essential for surgeons. New and better options would allow them to more consistently achieve this goal and expand the number of women that receive this preferred therapy, while minimizing the need for re-excision and revision procedures or more aggressive surgical approaches (i.e., mastectomy). We have developed and evaluated a regenerative tissue filler that is applied as a liquid to defects during BCS prior to transitioning to a fibrillar collagen scaffold with soft tissue consistency. Using a porcine simulated BCS model, the collagen filler was shown to induce a regenerative healing response, characterized by rapid cellularization, vascularization, and progressive breast tissue neogenesis, including adipose tissue and mammary glands and ducts. Unlike conventional biomaterials, no foreign body response or inflammatory-mediated "active" biodegradation was observed. The collagen filler also did not compromise simulated surgical re-excision, radiography, or ultrasonography procedures, features that are important for clinical translation. When post-BCS radiation was applied, the collagen filler and its associated tissue response were largely similar to non-irradiated conditions; however, as expected, healing was modestly slower. This in situ scaffold-forming collagen is easy to apply, conforms to patient-specific defects, and regenerates complex soft tissues in the absence of inflammation. It has significant translational potential as the first regenerative tissue filler for BCS as well as other soft tissue restoration and reconstruction needs. [ABSTRACT FROM AUTHOR]

Background: Postoperative nausea and vomiting (PONV) following sleeve gastrectomy (SG) is a common occurrence. The effect of specific interventions in PONV prevention within enhanced recovery pathways remains unclear. The aim of this study was to evaluate the impact of a comprehensive approach for the prevention of PONV on patient outcomes and hospital resource utilization. Methods: A prospective randomized trial was conducted for patients undergoing SG. The intervention group received aprepitant and transdermal scopolamine preoperatively followed by ondansetron and dexamethasone intraoperatively, with total intravenous anesthesia. The control group received inhalational anesthetic and two intraoperative antiemetics without preoperative prophylaxis. The primary endpoint was a PONV-related delay in hospital discharge. Results: Eighty-three patients completed the study (41 in the intervention and 42 in the control group). Eighty-nine percent of patients were discharged home on the first postoperative day. Four patients in the control group and none in the intervention group experienced a PONV-related delay in discharge (9.5% vs 0, p = 0.119). Intervention patients reported significantly lower PONV scores at all in-hospital time points examined (p = 0.0392 for verbal scores and p < 0.0001 for Rhodes Index) and significantly higher self-rated quality of recovery at 24 h (Quality of Recovery-15 instrument, p < 0.05). Conclusions: A multilevel approach to PONV leads to significantly lower severity of PONV and improved self-reported quality of recovery, compared with control. PONV-related readmissions, ED visits, and discharge delays were uncommon within the overall enhanced recovery cohort. [ABSTRACT FROM AUTHOR]

Introduction: To develop a simulation model assessing the efficiency of using cladribine tablets versus infusion-based disease-modifying drugs (DMDs) for the treatment of relapsing-remitting multiple sclerosis (RRMS) from a facility perspective in the UK. Methods: A scheduling algorithm was developed to simulate day-case admissions and calculate the mean changes to resource use and time burden for patients in a facility that transitions from infusion-based treatments to cladribine tablets over 1 year. Model inputs and assumptions were based on previous research and expert opinion. Model validation and quality checks were performed and additional scenario analyses were also conducted. Results: The model successfully scheduled all infusion treatments in the base case and no patients were left off the schedule as a result of lack of capacity. Modeled base-case outcomes increased in future scenarios owing to a 35% increase in demand. The introduction of cladribine tablets reduced these impacts. Specifically, the difference in mean daily utilization was reduced in the future scenario from 13% to 3% as 8% of patients moved to cladribine tablets; annual administration costs decreased by 96% and annual time burden decreased by 90%. Results from additional scenarios showed the largest benefits from switching current infusion patients to cladribine tablets were realized in facilities having moderate to high resource utilization. Conclusions: This model provides facility decision-makers the ability to assess the efficiency of using cladribine tablets rather than an infusion-based DMD. The simulation quantified the benefits gained from reducing the burden on facility resources by switching some patients with RRMS from infusion-based DMDs to cladribine tablets. Overall, modeled outcomes increased in future scenarios owing to an increase in demand, although the introduction of cladribine tablets reduced this impact. [ABSTRACT FROM AUTHOR]

We investigate the role of teachers' unions in state policymaking in the context of No Child Left Behind. Our analyses of panel data show that political party control and region moderate the influence of teachers' unions in the adoption of accountability policies by states. Our analyses of marginal effects show that teachers' unions are not always against the adoption of stronger accountability policies and neither do they always align with the Democratic Party. Our findings suggest that the current dominant prescription in the policy debate for curtailing the collective bargaining rights of teachers' unions is not fully substantiated. [ABSTRACT FROM AUTHOR]

Background: Occult breast cancer (OBC) is a rare clinical entity. Current surgical management includes axillary lymphadenectomy (ALND) with or without mastectomy. We sought to investigate the role of sentinel lymph node biopsy (SLNB) in patients with OBC treated with neoadjuvant chemotherapy (NAC). Methods: Patients with clinical T0N+ breast cancer were selected from the National Cancer Data Base (NCDB, 2004–2014) and compared according to axillary surgical approach, SLNB (≤ 4 LNs) or ALND (> 4 LNs). Primary outcome was overall survival (OS), calculated using Kaplan–Meier methods. Secondary outcome was complete pathological response (pCR). Results: A total of 684 patients with OBC were identified: 470 (68.7%) underwent surgery upfront and 214 (31.3%) received NAC. Of the NAC patients, 34 (15.9%) underwent SLNB and 180 (84.1%) ALND. One hundred and fifty-three (72%) patients received radiotherapy (RT). There was no difference in pCR rates between the ALND and SLNB (34.3% vs 24.5%, respectively p = 0.245). In patients undergoing surgery first, improved OS was observed with ALND compared to SLNB (106.9 vs 85.5 months, p = 0.013); however, no difference in OS was found in patients who received NAC (105.6 vs 111.3 months, p = 0.640). RT improved OS in patients who underwent NAC followed by SLNB (RT, 123 months vs no RT, 64 months, p = 0.034). Of NAC patients who did not undergo RT, ALND had superior survival compared to SLNB (113 vs 64 months, p = 0.013). Conclusion: This is the first comparative analysis assessing the surgical management of the axilla in patients with OBC who underwent NAC. In this population, there was a decrease in survival in patients who underwent SLNB alone; however, with the addition of RT, there was no difference in OS between SLNB and ALND. SLNB plus RT may be considered as an alternative to ALND in patients with OBC who have a good response to NAC. [ABSTRACT FROM AUTHOR]

This study presents an investigation regarding the applicability of neural networks for temperature measurements using thermochromic liquid crystals (TLCs) and discusses advantages as well as disadvantages of common calibration approaches. For the characterization of the measurement technique, the dependency of the color of the TLCs on the temperature as well as on the observation angle and, therefore, on the position within the field of view of a color camera is analyzed in detail. In order to consider the influence of the position within the field of view on the color, neural networks are applied for the calibration of the temperature measurements. In particular, the focus of this study is on analysis of the error of temperature measurement for different network configurations as well as training methods, yielding a mean absolute deviation and a mean standard deviation in the range of 0.1 K for instantaneous measurements. On the basis of a comparison of this standard deviation to that of two further calibration approaches, it is shown that neural networks are suited for temperature measurements via the color of TLCs. Finally, the applicability of this measurement technique is illustrated at an exemplary temperature measurement in a horizontal plane of a Rayleigh–Bénard cell with large aspect ratio, which clearly shows the emergence of convective flow patterns by means of the temperature field. [ABSTRACT FROM AUTHOR]

This paper documents the use of Geographic Information System (GIS) in the delivery of recent major sporting events with a specific focus on the Gold Coast 2018 Commonwealth Games (GC2018). It details the process that was undertaken by GC2018 Partner organisations in managing an integrated GIS solution. Governance structures, data sets, information custodianship and implementation timelines are explored to provide a holistic understanding of the GC2018 GIS journey. The paper then explores the challenges that were faced and conversely the recommendations for future Host Cities. Integrated GIS use was a critical element in the success of GC2018 and provided a City legacy in terms of information sharing, governance and broader use of GIS systems. It recognises that whilst GIS was an integral part of the planning and operations of GC2018 significant benefits could be derived by Host Cities by ensuring integration of GIS into Games governance and committing to roles and responsibilities three or 4 years in advance of the event. [ABSTRACT FROM AUTHOR]

The current study is a community-based research project identifying ways to better define and support sexual well-being of college students on campus. The data explore how students self-define their own sexual well-being, how it relates to access of the institution's health and counseling services, as well as how it relates to physiological, emotional, relational, and social factors. From in-depth individual interviews, the study compares individual students' varying perspectives of their own sexual well-being situated within the campus community. Results from thematic analysis show that definitions of sexual well-being are multifaceted—ranging from sex positive, behavioral, mental and emotional, social identity-related, relational, and related to campus resources. Our findings can be used to inform sexual health education and services offered to college students. [ABSTRACT FROM AUTHOR]

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The Asian broadhead walking catfish (Clarias macrocephalus) generates weak electric monopolar pulses during spawning. Males emit a single pulse when attracting a female, and while in amplexus, only females emit a single burst of similar pulses. This burst is a necessary component in the mating ritual of C. macrocephalus. Release of milt occurs about 5 s prior to the onset of a burst, which is immediately followed by the release of eggs. Following sperm release, the male remains in tight embrace with the female. Though both male and female could perceive each other's electric pulses via ampullary receptors (communication mode), we postulate that egg release can be facilitated by direct action of the female's burst on the male's neuromuscular system (contraction mode). Shedding light on the function of weak episodic electric emission, we propose that the modification of electrogenic structures evolved towards increasing the efficiency of direct bodily impact. As extant clariids exhibit intermediate features between non-electric and strongly electric catfishes, Clarias should be considered a "serviceable transition," which Charles Darwin deemed a possible intermediate form between these two groups. [ABSTRACT FROM AUTHOR]

In the last decade, extensive research has been carried out on the microstructural behavior of high-entropy alloys (HEA), for which the in-situ formation of nanoparticles has been reported. However, studies of the incorporation of nanoparticles in HEA have been rarely reported. In this work, the addition of zinc oxide nanoparticles (ZnO NP) as reinforcement in a CoCrFeMoNi high-entropy alloy matrix, as well as the morphological, structural, and microstructural evolution of composites synthesized via powder metallurgy, were studied. Scanning electron microscopy and X-ray diffraction analysis were performed in order to study the microstructural and phase characterization of the composites. After sintering, it was found that the ZnO NP addition (0.5wt%, 1wt% and 2wt%) had a significant influence on the micro-structure and hardness of the CoCrFeMoNi high-entropy alloy. Stronger bonding among metal particles was promoted with the additions of ZnO NP. A reduction in porosity as a function of ZnO NP content was also observed. The microhardness results showed that the composite reached its highest reinforcement in bulk samples with 1wt% ZnO NP (HV 870), which represented a 20% improvement over the unrein-forced HEA matrix. [ABSTRACT FROM AUTHOR]

Background: Women with a BRCA1 or BRCA2 mutation face high risks of breast and ovarian cancer. In the current study, we report on uptake of cancer screening and risk-reduction options in a cohort of BRCA mutation carriers from ten countries over two time periods (1995 to 2008 and 2009 to 2017).Methods: Eligible subjects were identified from an international database of female BRCA mutation carriers and included women from 59 centres from ten countries. Subjects completed a questionnaire at the time of genetic testing, which included past use of cancer prevention options and screening tests. Biennial follow-up questionnaires were administered.Results: Six-thousand two-hundred and twenty-three women were followed for a mean of 7.5 years. The mean age at last follow-up was 52.1 years (27-96 years) and 42.3% of the women had a prior diagnosis of breast cancer. In all, 27.8% had a prophylactic bilateral mastectomy and  64.7% had a BSO. Screening with breast MRI increased from 70% before 2009 to 81% at or after 2009. There were significant differences in uptake of all options by country.Conclusion: For women who received genetic testing more recently, uptake of prophylactic mastectomy and breast MRI is significantly higher than those who received genetic testing more than 10 years ago. However, uptake of both BSO and breast MRI is not optimal, and interventions to increase uptake are needed. [ABSTRACT FROM AUTHOR]

Purpose: Following a diagnosis of breast cancer, BRCA mutation carriers face an increased risk of developing a second (contralateral) cancer in the unaffected breast. It is important to identify predictors of contralateral cancer in order to make informed decisions about bilateral mastectomy. The impact of bilateral salpingo-oophorectomy (i.e., oophorectomy) on the risk of developing contralateral breast cancer is unclear. Thus, we conducted a prospective study of the relationship between oophorectomy and the risk of contralateral breast cancer in 1781 BRCA1 and 503 BRCA2 mutation carriers with breast cancer. Methods: Women were followed from the date of diagnosis of their first breast cancer until the date of diagnosis of a contralateral breast cancer, bilateral mastectomy, date of death, or date of last follow-up. Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of contralateral breast cancer associated with oophorectomy. Oophorectomy was included as a time-dependent covariate. We performed a left-censored analysis for those women who reported a primary breast cancer prior to study entry (i.e., from completion of baseline questionnaire). Results: After an average of 9.8 years of follow-up, there were 179 (7.8%) contralateral breast cancers diagnosed. Oophorectomy was not associated with the risk of developing a second breast cancer (HR 0.92; 95% CI 0.68–1.25). The relationship did not vary by BRCA mutation type or by age at diagnosis of the first breast cancer. There was some evidence for a decreased risk of contralateral breast cancer among women with an ER-positive primary breast cancer, but this was based on a small number of events (n = 240). Conclusion: Overall, our findings suggest that oophorectomy has little impact on the risk of contralateral breast cancer. [ABSTRACT FROM AUTHOR]