Search

Following a period of slow progress, the completion of genome sequencing and the paradigm shift relative to the cell of origin for high grade serous ovarian cancer (HGSOC) led to a new perspective on the biology and therapeutic solutions for this deadly cancer. Experimental models were revisited to address old questions, and improved tools were generated. Additional pathways emerging as drivers of ovarian tumorigenesis and key dependencies for therapeutic targeting, in particular, VEGF-driven angiogenesis and homologous recombination deficiency, were discovered. Molecular profiling of histological subtypes of ovarian cancer defined distinct genetic events for each entity, enabling the first attempts toward personalized treatment. Armed with this knowledge, HGSOC treatment was revised to include new agents. Among them, PARP inhibitors (PARPis) were shown to induce unprecedented improvement in clinical benefit for selected subsets of patients. Research on mechanisms of resistance to PARPis is beginning to discover vulnerabilities and point to new treatment possibilities. This Review highlights these advances, the remaining challenges, and unsolved problems in the field. [ABSTRACT FROM AUTHOR]

"The Real World of College: What Higher Education Is and What It Can Be" by Wendy Fischman and Howard Gardner is a book that examines the state of higher education in the United States. The authors conducted 2,000 interviews over five years at ten colleges to gain insight into current expectations and experiences of higher education. The book explores different justifications for engaging in higher education, such as inertia, transaction, exploration, and transformation. While the book defends traditional humanist scholarship, it could have made a stronger case for the liberal arts. However, it lacks awareness of sociological problems associated with the university and does not consider the broader issues affecting higher education. Overall, the book provides a harmless addition to the library of defenses of liberal education. [Extracted from the article]

As a legal aid union president in New Haven, laboring within shouting distance of a different large research university, I recall how our membership rolled our eyes when Professors Greiner, Pattanayak, and Hennesy of Harvard published their study providing evidence, through a randomized control trial, that law clinic housing work made no difference for clients.1 Representing, as I was, "lawyers, secretaries, and paralegals who have dedicated their careers to serving poor clients in crisis,"2 the authors' conclusion generated first shock, then denial, and then an anxious realization that somebody's job was to research and disseminate such conclusions. In a 2013 United States where there was one legal aid lawyer for every 8,893 people who qualified,3 where federal Legal Services Corporation funding had dropped 40% over ten years in real dollars,4 and in an America that spends as much on Halloween costumes for its pets as it does legal aid for the poor,5 the inquiry felt like a pile-on. It made no more sense to us than asking if a teacher is "good for students," a nurse "good for the sick," or a chef "good for the hungry."6 [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic laid bare systemic inequities shaped by social determinants of health (SDoH). Public health agencies, legislators, health systems, and community organizations took notice, and there is currently unprecedented interest in identifying and implementing programs to address SDoH. This special issue focuses on the role of medical-legal partnerships (MLPs) in addressing SDoH and racial and social inequities, as well as the need to support these efforts with evidence-based research, data, and meaningful partnerships and funding. [ABSTRACT FROM AUTHOR]

The book "Art, Science, and the Politics of Knowledge" by Hannah Star Rogers explores the intersection of art, science, and technology studies (ASTS). The author examines specific episodes in the history of science where science has generated aesthetic objects and instances where artists have attempted to insert themselves into scientific endeavors. However, the reviewer criticizes the book for its narrow focus and lack of historical depth, suggesting that it offers a frivolous perspective on the distinction between art and science. The reviewer finds the book's use of lofty language and references to be wearisome and lacking in substance. [Extracted from the article]

Background: Tumour characteristics such as thickness and ulceration, along with sentinel lymph node (SLN) status, have been essential in predicting survival in patients with locally invasive melanomas at the time of diagnosis. It is unclear if these prognostic factors are relevant 1, 2 or 5 years after diagnosis. Objectives: The key aim of this project was to analyse conditional survival in a cohort of Queensland patients with stage IB to IIIA melanomas (American Joint Committee on Cancer's staging system, 8th version) and to test the relevance of clinicopathological prognostic factors for melanoma outcome after varying intervals of survival time. Methods: Patients with primary invasive cutaneous melanoma who were referred to a tertiary melanoma clinic and underwent SLN biopsy between 1994 and 2011 were ascertained. The effect of patient and tumour characteristics on melanoma survival were calculated using multivariate Cox proportional hazard models at diagnosis and at variable times after diagnosis. Results: The final analysis included 651 patients (average age 49 years, 55.5% male) with stage IB to IIIA melanoma. At diagnosis, and after 1 and 2 years survived, SLN positivity, thickness and ulceration were predictive of 10‐year survival since diagnosis. However, once patients survived 5 years, only SLN status was predictive. Overall conditional melanoma survival improved with increasing time survived. Five years after diagnosis, 10‐year conditional melanoma survival (MSS) was 91% (95% CI 86%–95%) compared with 85% (82%–88%) predicted at diagnosis. The improvement in MSS was observed mainly for Stage II melanoma patients and not for those with a positive SLN biopsy. Conclusions: This study confirms the improvement of prognosis according to time survived since diagnosis suggesting that after 5 years survival the classic prognostic indicators may not have the same influence. [ABSTRACT FROM AUTHOR]

This study constructs machine learning algorithms that are trained to classify samples using sound symbolism, and then it reports on an experiment designed to measure their understanding against human participants. Random forests are trained using the names of Pokémon, which are fictional video game characters, and their evolutionary status. Pokémon undergo evolution when certain in-game conditions are met. Evolution changes the appearance, abilities, and names of Pokémon. In the first experiment, we train three random forests using the sounds that make up the names of Japanese, Chinese, and Korean Pokémon to classify Pokémon into pre-evolution and post-evolution categories. We then train a fourth random forest using the results of an elicitation experiment whereby Japanese participants named previously unseen Pokémon. In Experiment 2, we reproduce those random forests with name length as a feature and compare the performance of the random forests against humans in a classification experiment whereby Japanese participants classified the names elicited in Experiment 1 into pre-and post-evolution categories. Experiment 2 reveals an issue pertaining to overfitting in Experiment 1 which we resolve using a novel cross-validation method. The results show that the random forests are efficient learners of systematic sound-meaning correspondence patterns and can classify samples with greater accuracy than the human participants. [ABSTRACT FROM AUTHOR]

Background: Educational interventions promoting the role of physical activity (PA) aim to address knowledge, poor exercise self-efficacy, and low outcome expectations, which are well-researched barriers to PA participation in healthy and in people with chronic conditions. However, little is known about the effectiveness of educational interventions in addressing these barriers in people with Parkinson's (PwP). Objective: To examine the content of education interventions that promote PA behavior in PwP, and to assess their effectiveness on physical and psychosocial outcomes. Methods: An electronic search (12/2021) of MEDLINE, EMBASE, CINAHL, PubMed PsycINFO, the Web of Science and the Cochrane Library was conducted from 1990 to 2021. Education interventions, alone or combined with other strategies, promoting PA in PwP were included. Quality was assessed using the Johanna Briggs Institute and National Institute of Health quality assessment tools. A narrative synthesis was performed. Results: Six studies were identified. Five interventions were comprised of education and exercise sessions. Improvement in physical and psychosocial outcomes were suggested but delineating the exact impact of education was impeded due to lack of assessment. Conclusion: Few interventions exist that provide knowledge, and skills promoting PA participation, and fewer are addressed towards newly diagnosed PwP. There is lack of assessment over the effectiveness of education as a tool to facilitate PA participation in PwP. Lack of assessment poses the risk of potentially disregarding effective interventions or adopting ineffective approaches without the evidence. Education interventions can boost PA engagement by increasing factors such as exercise self-efficacy, but further interventions are required to assess this model of relationship. [ABSTRACT FROM AUTHOR]

Schistosomiasis, also known as bilharzia or snail fever, is a debilitating neglected tropical disease (NTD), caused by parasitic trematode flatworms of the genus Schistosoma, that has an annual mortality rate of 280,000 people in sub-Saharan Africa alone. Schistosomiasis is transmitted via contact with water bodies that are home to the intermediate host snail which shed the infective cercariae into the water. Schistosome lifecycles are complex, and while not all schistosome species cause human disease, endemic regions also typically feature animal-infecting schistosomes that can have broader economic and/or food security implications. Therefore, the development of species-specific Schistosoma detection technologies may help to inform evidence-based local environmental, food security and health systems policy making. Crucially, schistosomiasis disproportionally affects low- and middle-income (LMIC) countries and for that reason, environmental screening of water bodies for schistosomes may aid with the targeting of water, sanitation, and hygiene (WASH) interventions and preventive chemotherapy to regions at highest risk of schistosomiasis transmission, and to monitor the effectiveness of such interventions at reducing the risk over time. To this end, we developed a DNA-based biosensor termed Specific Nucleic AcId Ligation for the detection of Schistosomes or 'SNAILS'. Here we show that 'SNAILS' enables species-specific detection from genomic DNA (gDNA) samples that were collected from the field in endemic areas. Author summary: Schistosomiasis is a neglected tropical disease, caused by the parasitic trematodes of the genus Schistosoma. Schistosomiasis is endemic to regions within Africa, Asia and South America with at least 250 million people infected and a further 779 million at risk of infection. The lifecycle of schistosomes are complex and involve specific freshwater intermediate snail hosts which shed infective cercariae into the waterbodies they inhabit. Schistosomiasis is subsequently transmitted to humans or animals that contact cercariae contaminated water. In Africa, human disease is largely caused by Schistosoma mansoni and Schistosoma haematobium. However, endemic regions also typically feature animal-infecting schistosomes that can have broader economic and/or food security implications. Therefore, the development of species-specific Schistosoma detection technologies may help to inform local environmental, food security and health programmes. To this end, we re-purposed a nucleic acid detection technology to enable the detection of different schistosome species. Our DNA-biosensor, abbreviated as 'SNAILS', employs carefully designed probes that recognise species-specific DNA sequences, coupled with enzymatic amplification steps, and a fluorescent signal-dye to indicate a positive detection. 'SNAILS' successfully differentiates between S. mansoni and S. haematobium samples and could conceivably be employed within future global health programmes. [ABSTRACT FROM AUTHOR]

The present article analyses parts of Sobre héroes y tumbas from the perspective of the essayistic work of Ernesto Sabato. The principal purpose of this analysis is to understand the metaphysical preoccupations and worries of the author and situate them within a philosophical context. I suggest that paranoia is the logical result of the collapse of the classical system of metaphysics in the wake of Kant, and that this rupture in the history of metaphysics is the central problem of the work of Sabato. I also pay additional attention to the evolution of Sabato's thought from its origins in the philosophy of science through to Heidegger, by way of Husserl. This rupture causes an epistemological crisis that makes metaphysical knowledge impossible, while at the very same time presupposing that metaphysical knowledge is necessary in order not to fall into paranoia. [ABSTRACT FROM AUTHOR]

In this article, we aim to describe our modern‐day approach to total thyroidectomy, detailing the subtle refinements of our technique, as it has evolved over three decades and 21 000 cases. Since Delbridge's seminal paper in 2003, the major changes to our approach include a retrograde approach to the recurrent laryngeal nerve that allows dissection of the distal RLN from fascial bands within the ligament of Berry before medialisation of the thyroid lobe. Routine use of intraoperative nerve monitoring systems has increased our awareness of temporary neuropraxia, facilitated a reduction in the risk of bilateral RLN palsy and improved our identification and preservation of the external branch of the superior laryngeal nerve. The increasing use of advanced energy devices has been associated with a reduction in post‐operative haematoma rates. We adopt a low threshold to parathyroid auto‐transplantation, unless all glands are assessed to be clearly not at risk, and routinely supplement patients with Caltrate in the immediate post‐operative period to minimize the risk of symptomatic hypocalcaemia. Ultimately, when we reflect on the subtle refinements that have contributed to improved outcomes, the fundamental principles of exposure and dissection that have evolved over decades remain the basis of our surgical approach and must continue to do so. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: We aimed to determine whether vaginal laxity (VL) may be an early symptom of pelvic organ prolapse (POP). Methods: This was a retrospective observational study including patients referred to a urogynecological clinic owing to symptoms of pelvic floor dysfunction. The interview included inquiry about VL and POP symptoms. Clinical examination and translabial ultrasound (TLUS) were performed to assess for POP and levator hiatal ballooning. Analysis of ultrasound datasets was performed with the reviewer blinded against all other data. Linear regression models were used to evaluate associations between age categories and symptoms. Results: The analysis included 531 patients. Mean age was 59.7 years (range 17.6–92.0), mean body mass index (BMI) was 29.5 kg/m2 (14.7–53.5) and 458 (86%) were vaginally parous. Overall, POP symptoms were reported by 258 patients (49%) and VL by 118 (22%). Significant clinical POP was diagnosed in 384 patients (72%). Levator hiatal ballooning on TLUS was noticed in 56%. VL and POP symptoms showed a divergent association with age (p = 0.02). This trend remained significant after controlling for clinically significant POP (p = 0.01) and levator hiatal ballooning (p = 0.002). Of 384 women with significant objective POP, 231 (60%) reported symptoms of POP. Of 153 women with asymptomatic POP, 7 (5%) reported symptoms of VL. Conclusions: With increasing age the prevalence of VL decreases, whereas symptoms of POP increase. However, only very few women with objective POP perceive VL as their only symptom, independent of age at presentation. Therefore, vaginal laxity does not seem to be an early symptom of prolapse. [ABSTRACT FROM AUTHOR]

A binary preference relation on a real vector space satisfying four (natural) axioms is shown to induce a utility function composed of a linear function to the reals and a weakly monotonic function. The key axiom is decomposition, and the utility function can be taken to be linear if and only if this axiom’s converse is also satisfied. Important consequences follow for risk-sensitive discounted Markov decision processes, decision trees, and the discounted utility model in economics. Since the four axioms imply that preferences correspond to discounting, the four axioms without the converse imply that preferences are consistent with discounting without risk neutrality. [ABSTRACT FROM AUTHOR]

• Analyzing the impacts of FDA Breakthrough Therapy Designation. • This study unveils intriguing economic and developmental outcomes for biotechnology and small pharmaceutical companies. • There is the potential for significant short-term share price jumps and improved approval rates. • Cautionary insights into long-term market performance are discussed. Biotechnology and small pharma companies must recognize the opportunity presented by FDA Breakthrough Therapy Designation (BTD) to expedite drug development for serious conditions. This paper evaluates BTD economic and developmental impacts on such companies. Analysis of 29 BTD events from 2017 to 2022 revealed immediate share price boosts and improved drug approval rates, alongside faster development times. Yet, long-term share prices underperformed relative to the broader market, underscoring the persistent risks in pharma investments. Although offering new insights, the limited sample size calls for further investigation. [ABSTRACT FROM AUTHOR]

Summary: Background: The gut microbiota has been implicated in the pathogenesis of inflammatory bowel disease (IBD), with Faecalibacterium prausnitizii associated with protection, and certain genera (including Shigella and Escherichia) associated with adverse features. The variability of patient response to medical therapies in IBD is incompletely understood. Given the recognised contribution of the microbiota to treatment efficacy in other conditions, there may be interplay between the gut microbiota, IBD medical therapy and IBD phenotype. Aims: To evaluate the bidirectional relationship between IBD medical therapies and the gut microbiota. Methods: We conducted a systematic search of MEDLINE and EMBASE. All original studies analysing interactions between the gut microbiota and established IBD medical therapies were included. Results: We screened 1296 records; 19 studies were eligible. There was heterogeneity in terms of sample analysis, treatment protocols, and outcome reporting. Increased baseline α‐diversity was observed in responders versus non‐responders treated with exclusive enteral nutrition (EEN), infliximab, ustekinumab or vedolizumab. Higher baseline Faecalibacterium predicted response to infliximab and ustekinumab. A post‐treatment increase in Faecalibacterium prausnitzii was noted in responders to aminosalicylates, anti‐TNF medications and ustekinumab; conversely, this species decreased in responders to EEN. Escherichia was a consistent marker of unfavourable drug response, and its presence in the gut mucosa correlated with inflammation in aminosalicylate‐treated patients. Conclusions: Both gut microbiota diversity and specific taxonomic features (including high abundance of Faecalibacterium) are associated with the efficacy of a range of IBD therapies. These findings hold promise for a potential role for the gut microbiota in explaining the heterogeneity of patient response to IBD treatments. [ABSTRACT FROM AUTHOR]

A correction to the article "Introduction: Medical-Legal Partnerships: Equity, Evolution, and Evaluation" that was published in the March 13, 2024 issue is presented.

The increasing use of geographic information systems (GIS) in everyday life is profoundly shaping how humans navigate and interact with their surroundings. Behavioural and ethnographic experimental research indicates that increased usage of GPS devices is having a significant impact on human neurocognitive systems, especially memory and perception (Gramann et al. 2017). Despite this, there has only been a limited investigation of the implications of the spread of GIS technologies. In this paper, we explore how habitual reliance on GPS technology undermines autonomous decision-making through "nudging" (Sunstein and Thaler 2008)—that is, the alteration of psychological behaviour without the explicit forbidding of choice. In particular, we make a novel distinction between what we refer to as "suggestive nudging"—the suggesting of certain routes to take to get to a destination—and "disclosure nudging"—the normalisation of constant tracking and disclosing of our locations to government and corporate actors. We shall argue that although suggestive and disclosure nudging are in principle separate, that in practice they are intertwined in the design of modern GPS devices. Additionally, since human spatial cognition is highly plastic and susceptible to being sculpted by cultural practices (Hutchins 1995; Levinson 2003), this exacerbates the negative implications of the 'in practice' link of suggestive and disclosure nudging by making the latter harder to avoid and opt-out of. We argue that this state of affairs necessitates re-designing GPS devices. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic surfaced and deepened entrenched preexisting health injustice in the United States. Racialized, marginalized, poor, and hyper-exploited populations suffered disproportionately negative outcomes due to the pandemic. The structures that generate and sustain health inequity in the United States-including in access to justice, housing, health care, employment, and education-have produced predictably disparate results. The authors, law school clinicians and professors involved with medical-legal partnerships, discuss the lessons learned by employing a health justice framework in teaching students to address issues of health inequity during the pandemic. The goal of health justice is to eliminate health disparities that are linked to structural causes like subordination, discrimination, and poverty. This Article suggests six maxims for law school clinics to advance health justice, centering on themes of transdisciplinary collaboration, upstream interventions, adaptability, racial justice, systemic advocacy, and community-based strategies. The discussion draws on analyses of the scholarly literature on medical-legal partnerships and examples from the authors' clinics. These maxims for health justice are particularly relevant during a global public health emergency, but they also transcend the current moment by contributing to the long-running cross-clinic dialogue about teaching and designing clinics for social justice. [ABSTRACT FROM AUTHOR]

Objectives: Autism Spectrum Disorder (ASD) is a complex range of neurodegenerative conditions that impact individuals' social behaviour and communication skills. However, ASD data often contains far more controls than cases. This poses a serious challenge when creating classification models due to deriving models that favour controls during the classification of individuals. This problem is known as class imbalance, and it may reduce the performance in classification models derived by machine learning (ML) techniques due to individuals may remain undetected.Methods: ML appears to help in the distressing disorder by improving outcome quality besides speeding up the access to early diagnosis and consequential treatment. A screening dataset that consists of over 1100 instances was used to perform extensive quantitative analysis using different data resampling techniques and according to specific evaluation metrics. We measure the effect of class imbalance on autism screening performance using different data resampling techniques with a ML classifier and with respect to sensitivity, specificity, and F1-measure. We would like to know which resampling methods work well in balancing autism screening data.Results: The results reveal that data resampling, and especially oversampling, improve results derived by the considered ML classifier. More importantly, there was superiority in terms of sensitivity and specificity for models derived by Naive Bayes classifier when oversampling methods have been used for data pre-processing on the autism data considered.Conclusion: The results reported encourages further improvement of the design and implementation of ASD screening systems using intelligent technology. [ABSTRACT FROM AUTHOR]

Sepsis is common and represents a major public health burden with significant associated morbidity and mortality. However, despite substantial advances in sepsis recognition and management in well-resourced health systems, there remains a distinct lack of research into sepsis in Africa. The lack of evidence affects all levels of healthcare delivery from individual patient management to strategic planning at health-system level. This is particular pertinent as African countries experience some of the highest global burden of sepsis. The 2017 World Health Assembly resolution on sepsis and the creation of the Africa Sepsis Alliance provided an opportunity for change. However, progress so far has been frustratingly slow. The recurrent Ebola virus disease outbreaks and the COVID-19 pandemic on the African continent further reinforce the need for urgent healthcare system strengthening. We recommend that African countries develop national action plans for sepsis which should address the needs of all critically ill patients. [ABSTRACT FROM AUTHOR]

This article states a claim about the fundamental nature of monarchy as something which in antiquity and medievality straddled the immanent and transcendent worlds but which is only half understood in a modernity where the world which is wholly immanent and so has a politics which must be theorised in wholly consistent terms. It draws on theories of antique monarchy, medieval monarchy, constitutional monarchy and popular sovereignty, and asserts three distinctive arguments: that politics is always fundamentally torn between law and power, that the philosophy of political history requires us to see that our resources for attempting to resolve the two have been narrowed in the last two hundred years, and that monarchy, theoretically considered, is best understood as something which has a transconsistent political logic. [ABSTRACT FROM AUTHOR]

Perovskite solar cells have emerged as a promising and highly efficient solar technology. Despite efficiencies continuing to climb, the prospect of industrial manufacture is in part hampered by concerns regarding the safety and sustainability of the solvents used in lab scale manufacture. In this paper, we aim to present a methodology for green solvent selection informed by EHS considerations from the CHEM-21 solvent guide for successful methylammonium lead triiodide (MAPbI3) precursor dissolution. Through the use of this methodology we present a N,N-dimethylformamide (DMF)-free alternative solvent system for deposition of MAPbI3 precursors (MAI and PbI2) consisting of dimethyl sulfoxide (DMSO), dimethylpropyleneurea (DMPU), 2-methyltetrahydrofuran (2-MeTHF) and ethanol (EtOH). We have investigated 3 candidate solutions with slightly different compositions of these four solvents, all of which produce dense, uniform and pinhole-free perovskite films via spin coating. All three candidate solutions (A–C) match the average device efficiencies of the DMF/DMSO control devices (12.4%) with candidate A, which consists of 40% DMSO, 30% DMPU, 20% 2-MeTHF and 10% EtOH (vol%), producing a champion PCE of 16.1% compared to 16.2% for DMF/DMSO (80/20 vol%). Perovskite films cast from the three candidate solutions show improved crystallinity, higher fluorescence emission, and improved crystal size uniformity than those cast from DMF/DMSO. This work aims to: highlight the key solvent parameters which determine effective MAPbI3 precursor dissolution; provide a set of criteria for appropriate alternative solvent selection; and demonstrate the application of green chemistry principles to solvent selection for perovskite photovoltaic manufacturing. [ABSTRACT FROM AUTHOR]

• Unveiling the impact of the FDA's orphan drug designation (ODD) on small pharma: a tale of significant short-term gains and complex long-term performance. • This study provides insight in-to how regulatory milestones can affect the financial landscapes of the small pharmaceutical companies. This analysis explores the impact of the FDA's orphan drug designation (ODD) on biotechnology companies' share prices in the short and long term. Our analysis reveals that there is a significant immediate increase in share prices following an ODD announcement, which underscores its potential as a robust indicator of short-term investor returns. However, the long-term findings present a more complex picture, with a sustained impact within the biotech industry but a significant depreciation against the broader market over time. These findings elucidate the nuanced effects of regulatory milestones on the financial performance of pharmaceutical companies and highlight the need for more comprehensive studies to further unravel these complex dynamics. [ABSTRACT FROM AUTHOR]

• This study delves into the financial implications of the FDA's Fast Track Designation (FTD) on biotechnology companies. • This study provides a compelling analysis of significant share price boosts following FTD announcements, offering crucial insights for investors and industry practitioners alike. This study examines the effect of the FDA's Fast Track Designation (FTD) on biotech company share prices. Using an event-study approach on 25 FTD announcements between June 2019 and June 2020, notable short- and long-term share price hikes were observed, with a 5-day cumulative average abnormal returns of 21.59%, 30-day at 38.34%, 1-year at 76.64% and 3-year at 111.37% against the XBI benchmark. These surges surpass prior research findings, indicating stronger investor reactions. The role of the COVID-19 pandemic as a confounder is discussed. Although the sample size is limited, the results offer valuable insights for investors and small pharma firms. Further research is recommended to delve into the driving market factors. [ABSTRACT FROM AUTHOR]

Although it is well-established that particular bacteria may cause gastroenteritis and other infections when present in the gut, it is only recently that scientists have made significant inroads into understanding the huge number of other bacteria and additional microbes that live within the gastrointestinal tract, referred to as the gut microbiome. In particular, it is now recognised that bacteria within the gut microbiome have a wide variety of roles in maintaining different aspects of human health, and that disturbances of these bacteria may potentially cause or contribute to a number of different medical conditions, including particular infections, certain cancers, and chronic conditions, including inflammatory bowel disease. Moreover, there is increasing awareness that these bacteria help determine how the body responds to medication, including antibiotics and chemotherapy. There has been growing interest in different approaches to alter the gut microbiome as a novel approach to medical therapy. This article provides an overview of the importance of the gut microbiome, with a particular focus on critical care. [ABSTRACT FROM AUTHOR]

Special attention goes to the Swabian League (1488-1534), in which Close finds antecedents of the successes and failures of leagues and alliances through to the eighteenth century. Negotiation has always been at the heart of Christopher Close's work, and in his latest book, he aims to put it at the heart of European history too. By putting the structure of these leagues at the centre of his analysis, Close is able to distinguish more finely between them than previous scholars, giving considerable novelty and power to his account of why some alliances were successful whilst others failed. [Extracted from the article]

Introduction: The EQ-5D-3L (3L) and EQ-5D-5L (5L) are both frequently used measures of health status. Previous studies have found the EQ-5D-5L to have superior measurement properties but no study has compared the two measures in a large general population survey using matched respondents.Methods: Using data from the GP Patient Survey, coarsened exact matching was used to match individuals completing the 3L in 2011 with those completing the 5L in 2012. Measurement properties were assessed for a general population and multimorbid population (chronic conditions ≥ 2), with ceiling effects, informativity and distribution of response compared. Changes in the direction of response, as well as the impact on utility distributions, were quantified.Results: Matching resulted in a cohort of 1,023,218 respondents (2011: 511,609; 2012: 511,609) for analysis. Ceiling effects for the 5L were lower than the 3L (43.8% vs. 54.4%). The 5L had improved informativity and broader spread of responses than the 3L (5L top 50 profiles: 77.4% vs. 3L: 98.8%). Overall, there was an upwards shift in utility values for the 5L versus the 3L as respondents using the 5L reported ill health more frequently but with less severity. Measurement improvements and effects on utility values were more pronounced for the multimorbid population.Conclusion: The 5L had superior measurement properties than the 3L and should be preferred in general population surveys and for use in individuals with multimorbidity. At increasing levels of morbidity, the 5L is currently associated with higher utility values than the 3L. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Evidence regarding how women feel about episiotomies is not recorded in the literature. As the most common surgical procedure, there is a need to understand how women feel about episiotomy. Methods: The primary outcome was to identify the percentage of women who would accept an episiotomy if required. A literature review was compiled to provide nulliparous women in their third trimester with evidence-based information about episiotomies and perineal tears. Questions eliciting demographics, pre-information level of anxiety and acceptance of episiotomy were asked. After reading the information sheets, anxiety and knowledge were assessed again. Changes in anxiety levels from pre- to post-information were investigated using paired samples t tests. Because anxiety was measured on a scale, we assessed potential departures from normality by using the Wilcoxon signed-rank test. Questions also assessed the value women placed on this form of education. Results: There were 105 responses, with 88% accepting episiotomy, 2% declining and 10% seeking more information to decide. Eighty-one percent of women agreed that the information provided helped them to understand more about childbirth and 62% agreed that they felt more comfortable with the birthing process after reading the material. There was a reduction in anxiety levels regarding episiotomies after reading information (p = 0.002) and perineal tears (p = 0.02). Conclusions: Most women will accept an episiotomy if required. Antenatal education about episiotomies is important to women and helps them feel more comfortable with the birthing process. Written information increases acceptance and reduces anxiety levels regarding episiotomies. [ABSTRACT FROM AUTHOR]

The built environment is a significant determinant of human health. Globally, the growing prevalence of preventable cancers suggests a need to understand how features of the built environment shape exposure to cancer development and distribution within a population. This scoping review examines how researchers across disparate fields understand and discuss the built environment in primary and secondary cancer prevention. It is focused exclusively on peer-reviewed sources published from research conducted in Australia, Canada, Ireland, New Zealand, the United Kingdom, and the United States from 1990 to 2017. The review captured 9958 potential results in the academic literature, and this body of results was scoped to 268 relevant peer-reviewed journal articles indexed across 13 subject databases. Spatial proximity, transportation, land use, and housing are well-understood features of the built environment that shape cancer risk. Built-environment features predominantly influence air quality, substance use, diet, physical activity, and screening adherence, with impacts on breast cancer, lung cancer, colorectal cancer, and overall cancer risk. The majority of the evidence fails to provide direct recommendations for advancing cancer prevention policy and program objectives for municipalities. The expansion of interdisciplinary work in this area would serve to create a significant population health impact. [ABSTRACT FROM AUTHOR]

Using Foucault's theory of governmentality, we trace the development of activist consultancy firms (ACFs), providing an in-depth description of two ACFs: Boutique Activist Consultancy and the Solutions Institute. We explore how these ACFs enact neoliberal governmentality. The ACFs' ambivalent engagement with professionalization is the most notable finding of our research. [ABSTRACT FROM AUTHOR]

What is a university? In the nineteenth century John Henry Newman famously spoke of "the idea of a university." This phrase has dominated all discussions of the nature of the university since. Most contemporary writers are against any attempt to theorise the university in terms of a single idea. But against the now standard view that universities should only be characterised empirically as institutions that perform many different activities, I attempt to defend the idea of the university, not by reviving a single idea of the university but by suggesting that there are, at root, three ideas of the university. These are rival ideas, and strictly incommensurable, though they often exist together in a state of tension in actual universities. I call them the eternal, the immortal, and the immediate ideas of the university. [ABSTRACT FROM AUTHOR]

In this paper, we analyse how GPS-based navigation systems are transforming some of our intellectual virtues and then suggest two strategies to improve our practices regarding the use of such epistemic tools. We start by outlining the two main approaches in virtue epistemology, namely virtue reliabilism and virtue responsibilism. We then discuss how navigation systems can undermine five epistemic virtues, namely memory, perception, attention, intellectual autonomy, and intellectual carefulness. We end by considering two possible interlinked ways of trying to remedy this situation: [i] redesigning the epistemic tool to improve the epistemic virtues of memory, perception, and attention; and [ii] the cultivation of cognitive diligence for wayfinding tasks scaffolding intellectual autonomy and carefulness. [ABSTRACT FROM AUTHOR]

In order to consider the question of whether empire is a subject for philosophy, I do three things. I sketch an original typology of three types of state, which I call polis , imperium and cosmopolis , in order to show that the second is an important philosophical conception which lies behind the terminology of empire and imperialism. I also consider modern theories of empire and imperialism in order to indicate some of their limitations as theories. And finally I indicate that it is important even for philosophers to recognise that all imperial terminology emerges out of a very complicated history in which the concept of imperium has been extended and distorted in meaning, so that, at best, any good theory of empire or imperialism can only be some sort of recapitulation of that history. Neither the second nor the third of these claims undermines the claim of imperium to be a concept of the state which is of great political and philosophical significance. [ABSTRACT FROM AUTHOR]

Sporadic colorectal cancer (CRC) remains a major cause of worldwide mortality. Epidemiological evidence of markedly increased risk in populations that migrate to Western countries, or adopt their lifestyle, suggests that CRC is a disease whose aetiology is defined primarily by interactions between the host and his environment. The gut microbiome sits directly at this interface and is now increasingly recognised as a modulator of colorectal carcinogenesis. Bacteria such as Fusobacterium nucleatum and Escherichia coli (E. Coli) are found in abundance in patients with CRC and have been shown in experimental studies to promote neoplasia. A whole armamentarium of bacteria-derived oncogenic mechanisms has been defined, including the subversion of apoptosis and the production of genotoxins and pro-inflammatory factors. But the microbiota may also be protective: for example, they are implicated in the metabolism of dietary fibre to produce butyrate, a short chain fatty acid, which is anti-inflammatory and anti-carcinogenic. Indeed, although our understanding of this immensely complex, highly individualised and multi-faceted relationship is expanding rapidly, many questions remain: Can we define friends and foes, and drivers and passengers? What are the critical functions of the microbiota in the context of colorectal neoplasia. [ABSTRACT FROM AUTHOR]

As global temperatures rise, streams and rivers are predicted to be more severely impacted than other ecosystems, due in part to the limited mobility of aquatic invertebrates. Compared to many terrestrial animals, freshwater snails have particularly low potential for migration and thus are not expected to be able to compensate for climate warming with active dispersal. In freshwater animals, several behaviors are affected by elevated temperatures, including burrowing and escape responses, among others. This laboratory study aimed to assess the impacts of elevated temperatures on righting behavior and survival in two species of freshwater caenogastropod snails: fine-ridged elimia (Elimia semicarinata) and Shawnee rocksnails (Lithasia obovata). Righting time (the time to turn the body right-side-up when placed on the dorsal side of the shell) was assessed before beginning the experiment and again after chronic (10 day) exposure to an elevated temperature. There was no significant change in righting time at any temperature for either species, but there was significantly more failure to right within the time limit at elevated temperatures. For fine-ridged elimia, 30% of the snails failed to right in 30°C, compared to 2.5% in the control temperature (20°C). Similarly, 47.8% of Shawnee rocksnails failed to right at 27°C, while 19.4% failed to right in the 20°C group. Mortality was significantly higher at 35°C for fine-ridged elimia and 30°C for Shawnee rocksnails compared to the mortality of each species’ control group. Predicted rates of climate warming and current average temperatures suggest that fine-ridged elimia face more imminent risk of large-scale failure to right within natural populations, but the lower lethal temperature for Shawnee rocksnails suggests relatively high risk as well. These results contribute to the growing body of evidence that freshwater snails will be negatively impacted by climate warming, and may face large losses in the years to come. [ABSTRACT FROM AUTHOR]

Simple Summary: Sampling stools from animals is a useful way of diagnosing diseases. Faeces contain large numbers of micro-organisms, including bacteria, and, to preserve these, farmers and owners are advised to store the stool samples in a fridge at 4 °C. However, in a farm setting, access to working onsite refrigeration is not guaranteed. This means that samples can often sit at ambient temperature for several days until they are sent to the laboratory for analysis, and these may be located at significant distances from the farms. Leaving faeces at room temperature can lead to a change in bacterial composition, which can result in bacterial overgrowth and difficulty in detecting certain species for diagnosis, such as Salmonella (S.) species. In this study, a commercially available animal stool storage kit was tested for its ability to chemically preserve bacterial DNA, without relying on cold storage. The kit successfully preserved Salmonella spp. in cow stool at room temperature. The success of kits such as this could enable the accurate diagnoses of bacterial disease where cold storage is not available. Stool sampling is a useful tool for diagnosing gastrointestinal disease in veterinary medicine. The sub-clinical disease burden of Salmonella spp. in cattle can become significant for farmers. However, current methods of faecal sampling in a rural setting for diagnosis are not consistently sufficient for the preservation of Salmonella spp. in faeces. This study evaluated the use of a commercial stool storage kit for bacterial preservation in cow faecal samples compared to unpreserved stools placed into refrigeration at different time-points. A stool sample was collected per-rectum from one apparently healthy Holstein–Freisen cow. The sample was weighed and aliquoted into two sterile Falcon tubes and into two commercial kit tubes. The aliquots were then placed into refrigeration at 4 °C at 0, 24, and 96 h after processing. One commercial kit tube was not aliquoted and remained at ambient temperature. After 2 weeks, DNA was extracted from the samples and analysed using endpoint PCR, revealing a sub-clinical infection with Salmonella spp. The bacterium was best preserved when the stool was stored in the commercial kit at ambient temperature and re-homogenised immediately prior to DNA extraction. The unpreserved stool did not maintain obvious levels of Salmonella spp. after 24 h at ambient temperature. This commercial kit should be considered for use in the diagnosis of salmonellosis in cattle. [ABSTRACT FROM AUTHOR]

The purpose of this report is to describe the case and management of an unexplained vitreous haemorrhage that occurred after repeated roller-coaster riding. The authors inadvertently demonstrate the value of observation over immediate surgery in certain situations and review the literature on vitreoretinal and other ocular complications after roller-coaster riding. A 26-year-old male presented 12 h after riding high-velocity roller-coasters with a left vitreous haemorrhage. A hazy view of the retina and B-scan revealed a bullous area of superior-temporal retinal lifting. A diagnosis of a presumed macula-on retinal detachment was made and the patient was listed for a pars plana vitrectomy retinal detachment repair. An abnormal clotting result, which was subsequently found out to be erroneous, ultimately delayed the procedure. During this delay the vision and retinal view improved to an extent whereby the diagnosis of a retinoschisis with an intraretinal cyst was made and surgery was avoided. The patient regained 6/6 vision, without the need to undergo surgery. Historically the management of an unexplained vitreous haemorrhage was observation with serial B-scans. The current evidence and practice for treating unexplained vitreous haemorrhage have since moved towards early surgical intervention. The authors highlight that despite the current trend, a place remains for conservative management for selected cases. [ABSTRACT FROM AUTHOR]

Regeneration of the zebrafish caudal fin following amputation occurs through wound healing, followed by formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. We show that ptpn11a-/- ptpn11b-/- zebrafish embryos, lacking functional Shp2, fail to regenerate their caudal fin folds. Rescue experiments indicated that Shp2a has a functional signaling role, requiring its catalytic activity and SH2 domains but not the two C-terminal tyrosine phosphorylation sites. Surprisingly, expression of Shp2a variants with increased and reduced catalytic activity, respectively, rescued caudal fin fold regeneration to similar extents. Expression of mmp9 and junbb, indicative of formation of the wound epidermis and distal blastema, respectively, suggested that these processes occurred in ptpn11a-/- ptpn11b-/- zebrafish embryos. However, cell proliferation and MAPK phosphorylation were reduced. Pharmacological inhibition of MEK1 in wild-type zebrafish embryos phenocopied loss of Shp2. Our results suggest an essential role for Shp2a-mitogen-activated protein kinase (MAPK) signaling in promoting cell proliferation during zebrafish embryo caudal fin fold regeneration. [ABSTRACT FROM AUTHOR]

Zebrafish are able to completely regrow their caudal fin-folds after amputation. Following injury, wound healing occurs, followed by the formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. Here we show that, surprisingly, the phosphatase and tumor suppressor Pten, an antagonist of phosphoinositide-3-kinase (PI3K) signaling, is required for zebrafish caudal fin-fold regeneration. We found that homozygous knock-out mutant ( ptena−/−ptenb−/−) zebrafish embryos, lacking functional Pten, did not regenerate their caudal fin-folds. AKT phosphorylation was enhanced, which is consistent with the function of Pten. Reexpression of Pten, but not catalytically inactive mutant Pten-C124S, rescued regeneration, as did pharmacological inhibition of PI3K. Blastema formation, determined by in situ hybridization for the blastema marker junbb, appeared normal upon caudal fin-fold amputation of ptena−/−ptenb−/− zebrafish embryos. Whole-mount immunohistochemistry using specific markers indicated that proliferation was arrested in embryos lacking functional Pten, and that apoptosis was enhanced. Together, these results suggest a critical role for Pten by limiting PI3K signaling during the regenerative outgrowth phase of zebrafish caudal fin-fold regeneration. [ABSTRACT FROM AUTHOR]

We prove that the group algebra KG of a group G over a field K is primitive, provided that G has a non-abelian free subgroup with the same cardinality as G , and that G satisfies the following condition ( ⁎ ) : for each subset M of G consisting of a finite number of elements not equal to 1, and for any positive integer m , there exist distinct a , b , and c in G so that if ( x 1 − 1 g 1 x 1 ) ⋯ ( x m − 1 g m x m ) = 1 , where g i is in M and x i is equal to a , b , or c for all i between 1 and m , then x i = x i + 1 for some i . This generalizes results of [1,9,17] , and [18] , and proves that, for every countably infinite group G satisfying ( ⁎ ) , KG is primitive for any field K . We use this result to determine the primitivity of group algebras of one relator groups with torsion. [ABSTRACT FROM AUTHOR]

Background: This pilot study assessed the diagnostic accuracy of rapid evaporative ionization mass spectrometry (REIMS) in colorectal cancer (CRC) and colonic adenomas.Methods: Patients undergoing elective surgical resection for CRC were recruited at St. Mary's Hospital London and The Royal Marsden Hospital, UK. Ex vivo analysis was performed using a standard electrosurgery handpiece with aspiration of the electrosurgical aerosol to a Xevo G2-S iKnife QTof mass spectrometer (Waters Corporation). Histological examination was performed for validation purposes. Multivariate analysis was performed using principal component analysis and linear discriminant analysis in Matlab 2015a (Mathworks, Natick, MA). A modified REIMS endoscopic snare was developed (Medwork) and used prospectively in five patients to assess its feasibility during hot snare polypectomy.Results: Twenty-eight patients were recruited (12 males, median age 71, range 35-89). REIMS was able to reliably distinguish between cancer and normal adjacent mucosa (NAM) (AUC 0.96) and between NAM and adenoma (AUC 0.99). It had an overall accuracy of 94.4 % for the detection of cancer versus adenoma and an adenoma sensitivity of 78.6 % and specificity of 97.3 % (AUC 0.99) versus cancer. Long-chain phosphatidylserines (e.g., PS 22:0) and bacterial phosphatidylglycerols were over-expressed on cancer samples, while NAM was defined by raised plasmalogens and triacylglycerols expression and adenomas demonstrated an over-expression of ceramides. REIMS was able to classify samples according to tumor differentiation, tumor budding, lymphovascular invasion, extramural vascular invasion and lymph node micrometastases (AUC's 0.88, 0.87, 0.83, 0.81 and 0.81, respectively). During endoscopic deployment, colonoscopic REIMS was able to detect target lipid species such as ceramides during hot snare polypectomy.Conclusion: REIMS demonstrates high diagnostic accuracy for tumor type and for established histological features of poor prognostic outcome in CRC based on a multivariate analysis of the mucosal lipidome. REIMS could augment endoscopic and imaging technologies for precision phenotyping of colorectal cancer. [ABSTRACT FROM AUTHOR]

Two-dimensional magnetic recording (TDMR) offers the opportunity to provide areal density (AD) gain, but questions were unanswered as to how the gain is achieved and what can be done to maximize the gain from this new technology. In this paper, we offer some reasons why different investigators might report different AD gain opportunities. We present data collected on a spin stand with two reader heads and processed with a commercially available field programmable gate array TDMR channel. The implications of this paper should provide guidelines on reader geometries, placement, and performance. [ABSTRACT FROM AUTHOR]

This article summarizes the evolution of functional family therapy ( FFT) based upon four decades of clinical practice and scientific scrutiny through research evidence. FFT research has evolved from an initial focus upon clinical process research, which examined sequential exchanges between therapists and family members. A key element of this research has been an examination of the way in which clinicians acquire, consolidate, and maintain the skills needed to implement FFT effectively with youth and families. Many randomized efficacy and effectiveness studies have evaluated the impact of FFT across diverse clinical populations. Subsequent research investigated factors that influence the effectiveness of implementation across more than 300 clinical settings in which more than 2,500 trained clinicians have provided service to nearly 400,000 families. Another important set of investigations concerned the cost-effectiveness of the interventions . [ABSTRACT FROM AUTHOR]