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Professor Arno Penzias, you discovered, with Robert Wilson, the ‘cosmic microwave background radiation’,19which helped establish the Big Bang theory of cosmology. For this, you won the Nobel Prize in Physics in 1978. Briefly, you were using an antenna to capture signals. A strange background noise remained after all the interferences had been eliminated. After checking the equipment, removing pigeons nesting in the antenna and cleaning out their droppings, the noise remained: the cosmic microwave background radiation.
Human DNA is packed into forty-six chromosomes inside the cells of our body. At each end of the chromosome are the so-called telomeres: if the chromosome is a shoelace, the telomeres would be the protective plastic ends at the end of the shoelace. Cell divisions are essential to life, and they continuously take place in our body. However, the more the cell divides, the more telomeres are shortened, and the more the cell ages. In return, an enzyme called telomerase ‘rebuilds’ the telomeres, thus restoring the protection of the chromosome and delaying cellular senescence. The relationship between telomeres and telomerase is a delicate equilibrium. You won the Nobel Prize in 2009 for the discovery of ‘how chromosomes are protected by telomeres and the enzyme telomerase’.
To determine metrics and provider characteristics associated with inappropriate antibiotic prescribing for respiratory tract diagnoses (RTDs).
Retrospective cohort study.
Primary care practices in a university health system.
Patients seen by an attending physician or advanced practice provider (APP) at their primary care office visit with International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM)–coded RTDs.
Medical records were reviewed for 1,200 randomly selected office visits in which an antibiotic was prescribed to determine appropriateness. Based on this gold standard, metrics and provider characteristics associated with inappropriate antibiotic prescribing were determined.
Overall, 69% of antibiotics were inappropriate. Metrics utilizing prespecified RTDs most strongly associated with inappropriate prescribing were (1) proportion prescribing for RTDs for which antibiotics are almost never required (eg, bronchitis) and (2) proportion prescribing for any RTD. Provider characteristics associated with inappropriate antibiotic prescribing were APP versus physician (72% vs 58%; P = .02), family medicine versus internal medicine (76% vs 63%; P = .01), board certification 1997 or later versus board certification before 1997 (75% vs 63%; P = .02), nonteaching versus teaching practice (73% vs 51%; P < .01), and nonurban vs urban practice (77% vs 57%; P < .01).
Metrics utilizing proportion prescribing for RTDs for which antibiotics are almost never required and proportion prescribing for any RTD were most strongly associated with inappropriate prescribing. APPs and clinicians with family medicine training, with board certification 1997 or later, and who worked in nonteaching or nonurban practices had higher proportions of inappropriate prescribing. These findings could inform design of interventions to improve prescribing and could represent an efficient way to track inappropriate prescribing.
This review assesses regenerative medicine of the upper aerodigestive tract during the first two decades of the twenty-first century, focusing on end-stage fibrosis and tissue loss in the upper airways, salivary system, oropharynx and tongue.
PubMed, Embase, Google Scholar, Cochrane Library, Medline and clinicaltrials.org were searched from 2000 to 2019. The keywords used were: bioengineering, regenerative medicine, tissue engineering, cell therapy, regenerative surgery, upper aerodigestive tract, pharynx, oropharynx, larynx, trachea, vocal cord, tongue and salivary glands. Original studies were subcategorised by anatomical region. Original human reports were further analysed. Articles on periodontology, ear, nose and maxillofacial disorders, and cancer immunotherapy were excluded.
Of 716 relevant publications, 471 were original studies. There were 18 human studies included, within which 8 reported airway replacements, 5 concerned vocal fold regeneration and 3 concerned salivary gland regeneration. Techniques included cell transplantation, injection of biofactors, bioscaffolding and bioengineered laryngeal structures.
Moderate experimental success was identified in the restoration of upper airway, vocal fold and salivary gland function. This review suggests that a shift in regenerative medicine research focus is required toward pathology with a higher disease burden.
Over the last decade, the Iraq War (2003-2011) has become a common subject in mainstream literary fiction. In this chapter, I analyze three key examples of veteran-authored novels: Nico Walker’s Cherry (2018), Michael Pitre’s Fives and Twenty-Fives (2014), and Kevin Powers’ The Yellow Birds (2012). I argue that it is important to read these novels not only as war literature but also as significant cultural representations of contemporary white masculinity. I show how, through their representations of the soldier as both a laboring white body and (as veteran) the traumatized bearer of witness to combat violence, these novels place their white, male protagonists in an exceptional space in which they are insulated from accountability. As such, they illustrate how trauma is used to shore up a particular version of white masculinity that is vulnerable in many ways but still claims a particular kind of authority and narrative control.
Although bovine embryo in vitro production (IVP) is a common assisted reproductive technology, critical points warrant further study, including sperm traits and oxidative status of sperm for in vitro fertilization (IVF). Our aim was to evaluate whether the lipid peroxidation index of commercial bull semen is influenced by sperm traits and oxidative status of sperm populations selected using Percoll® gradient. Semen straws from 48 batches from 14 Nelore bulls were thawed individually, analyzed for motility and subjected to Percoll selection. After Percoll, the lipid peroxidation index of the extender was evaluated, whereas selected sperm were analyzed for motility, acrosome and membrane integrity, mitochondrial membrane potential, chromatin resistance and oxidative potential under IVF conditions. Batches were divided retrospectively in four groups according to lipid peroxidation index. Sperm from Group 4 with the lowest index of lipid peroxidation had, after Percoll selection, greater plasma membrane integrity (81.3%; P = 0.004), higher mitochondrial potential (81.1%; P = 0.009) and lower oxidative potential (135.3 ng thiobarbituric acid reactive substances (TBARS)/ml; P = 0.026) compared with Group 1 with highest lipid peroxidation index (74.3%, 73% and 213.1 ng TBARS/ml, respectively). Furthermore, we observed negative correlations for the lipid peroxidation index with motility, membrane integrity and mitochondrial potential, and positive correlations with oxidative potential. In conclusion, oxidative stress in semen straws, as determined using lipid peroxidation in the extender, is associated with sperm traits and their oxidative potential under IVF conditions. These results provided further insights regarding the importance of preventing oxidative stress during semen handling and cryopreservation, as this could affect sperm selected for IVF. Finally, Percoll selection did not completely remove sperm with oxidative markers.
The changes to the Irish exclusionary rule introduced by the judgment in People (DPP) v JC mark an important watershed in the Irish law of evidence and Irish legal culture more generally. The case relaxed the exclusionary rule established in People (DPP) v Kenny, one of the strictest in the common law world, by creating an exception based on ‘inadvertence’. This paper examines the decision through the lens of legal culture, drawing in particular on Lawrence Friedman's distinction between ‘internal’ and ‘external’ legal culture to help understand the factors contributing to the decision. The paper argues that Friedman's concept and, in particular, the dialectic between internal and external legal culture, holds much utility at a micro as well as macro level, in interrogating the cultural logics at work in judicial decision-making.
The complexity of human roles and responsibilities in the health and continuance of Earth and all its life has been explored by Indigenous writers and activists from a wide variety of perspectives. Of particular importance is the profound relationship between humans and water, the fundamental compact on which all others rely. Through an analysis of literary representations of water, this chapter examines Indigenous stories that center relationships and responsibilities, recognizing the interlocking systems on which all life relies. Authors Linda Hogan (Chickasaw), Leslie Marmon Silko (Laguna), and Tommy Pico (Kumeyaay) engage these concerns by connecting characters and their current conflicts of drought and/or environmental degradation to story traditions about the perils of imbalance and the repercussions of human greed. The life of water represented by seasonal rains, drought, and dynamic waterways reminds readers of the vital roles humans and the more-than-human world play in the climate cycles that support environmental wellbeing.
ABSTRACT IMPACT: Knowledge of which aspects of social connectedness most strongly associate with caregiver health and health behaviors can inform intervention targets to improve caregiver health OBJECTIVES/GOALS: Stressed dementia caregivers are at risk of poor health. Social connectedness may reduce adverse health effects, yet it is unknown about which aspects relate most strongly to health. This is a barrier to intervention development. Our study identifies aspects of social connectedness most strongly associate with caregivers’ daily health behaviors. METHODS/STUDY POPULATION: Data. Enrolled spousal caregivers completed 14 consecutive days of online surveys. Measures. We examined multiple health behaviors each day, which included: 1) number of occurrences of 3 potential binge-eating behaviors (range 0 to 30), 2) whether participants engaged in at least 30 minutes of physical activity, and 3) perceived sleep quality, rated 1 (very bad) to 5 (very good). We also examined a count of health symptoms caregivers experienced (e.g., backache; range: 0 to 7). Measures of social connectedness included: spousal emotional support, perceived spousal appreciation, emotional support from any source, and loneliness. Analysis. We applied bivariate multi-level mixed effects models to examine the association between each aspect of social connectedness and health behaviors day-to-day. RESULTS/ANTICIPATED RESULTS: Since November 2020, 5 of N=40 participants were enrolled, of whom 3 had completed all diary surveys. Participants were women ages 59 to 73, and included 4 non-Hispanic white and 1 Hispanic caregivers. Data included 51 days of surveys (93% adherence). No differences in eating behaviors nor physical activity according to social connectedness were found. Emotional support from any source was positively associated with sleep quality (B= 0.20; SE=0.08; p-value 0.015). On days when caregivers indicated their spouse appreciated them ‘A lot’ versus ‘Not at all,’ sleep quality was marginally better (B=0.73, SE=0.42; p-value-0.08). Finally, days when caregivers felt lonely at least ‘Some of the time’ versus ‘Not at all’ were associated with experiencing more adverse health symptoms (B=1.54; SE=0.58; p-value<0.001). DISCUSSION/SIGNIFICANCE OF FINDINGS: Improved emotional support from any source may support better sleep quality among caregiving spouses, while loneliness appears to contribute to more adverse health symptoms. Findings, if confirmed, can be translated to develop intervention programs that target loneliness and perceived emotional support among caregivers.
Left ventricular non-compaction has been associated with heart failure, arrhythmia, thromboembolism and sudden death. The prevalence of non-compaction in patients with coarctation of the aorta and its clinical significance remains unknown, although obstructive left heart disease is common in patients with non-compaction. We sought to evaluate the prevalence of left ventricular non-compaction in patients with repaired aortic coarctation as well as its effect on left ventricular size and systolic function.
Methods and results:
In total, 268 patients (Mean age 26 (inter-quartile range 21–37) years, 63% male) undergoing cardiac magnetic resonance imaging for clinical follow-up were included from three tertiary centres for adult congenital heart disease. Clinical data was obtained from medical records and correlated with ventricular volumes and function. Left ventricular non-compaction was defined as a diastolic non-compacted:compacted dimension ratio >2.3 in the worst affected segment on a long-axis view. Left ventricular non-compaction was present in 8.2% of patients with repaired coarctation. Left ventricular end-diastolic volumes and stroke volumes were significantly higher in patients with non-compaction compared to those without. There were no significant differences in ventricular mass or ejection fraction in these two groups.
Left ventricular non-compaction is relatively common in patients with repaired coarctation of the aorta and correlates with increased left ventricular end-diastolic volumes.
This chapter seeks to give an overview of the place of Quality Management (QM) in contemporary fertility practice. It provides the reader with an understanding of the terminology used in QM and explores the definition of quality and success in fertility care. An examination of process modelling in the organisation of services is outlined and an analysis in practical terms as to how QM is applied in practice is provided, covering key issues such as document control, organisational structure and the role of the quality manager. Audit as a tool for improving quality is a fundamental tool and its use within a clinical governance framework including risk management/assessment, and other key responsibilities is detailed. Measuring what we do, analysing performance and setting targets to improve should be fundamental to how we approach our work in contemporary clinical practice.
This chapter discusses the epidemiology of infertility and the importance of the initial assessment of the infertile individual. Profound changes in society over the last two decades challenge previously agreed on norms in our understanding of the nature of parenthood and family. Defining infertility in a contemporary context has thus also changed as the profile of those seeking advice has evolved. Nevertheless it remains essential that efficient mechanisms for referral and investigation are established for those involved in the planning of fertility services. These must involve good liaison between primary care providers and medical, nursing and diagnostic laboratory staff in specialist centres. Adherence to agreed on protocols will facilitate appropriate and timely investigation along standardised paths, thereby minimising risk of delay and repetition of tests which those seeking assistance find particularly demoralising. Once a diagnosis is reached it should be possible to offer people with infertility an accurate prognosis and the opportunity to consider the issues relevant to treatment choices for their particular situation.
An authoritative account of the causes of infertility that fully explores the clinical assessment of patients and covers the decision-making behind treatment options. The content follows the MRCOG syllabus as well as delving deeper into subjects covered by the RCOG Advanced Training Skills Modules (ATSMs), leaving readers well prepared for their examinations. Written by nationally recognised leaders in the field, this volume concisely reviews contemporary clinical practice. Using an aetiology-based approach, chapters discuss ovulatory dysfunction, endometriosis, male infertility, uterine/tubal factors and unexplained infertility. The increasing use of third-party reproduction and surrogacy is explored, along with the psychosocial aspects of this type of treatment. Ethical dilemmas surrounding reproductive medicine and their management are covered in depth. With an emphasis on practical approaches to the delivery and organisation of clinical and laboratory services, readers learn how to ensure the support and care they offer is of the highest quality.
Finely laminated (cm–μm scale) metalliferous precipitates are widespread in the surficial environment, especially around mineral deposits and reflect biogeochemical processes that can pervade near-surface environments on a larger scale. Examples in this paper involve precipitates of the transition metals Fe, Cu and Mn with minor Co, Ni, V and Zn; the metalloids As and Sb; and authigenic Au. Mobility and re-precipitation are driven primarily by geochemical disequilibrium, especially with respect to pH and redox states, that arises from complex interactions between biological processes, geological processes, and variations in the surrounding environment. Different degrees of chemical disequilibrium arise on small spatial scales on time scales of days to millennia. Interactions between biota, waters and rocks in these small near-surface settings affect the biogeochemical environments. Sulfur- and iron-oxidising bacteria are common biogeochemical agents associated with sulfide-bearing lithologies, but localised reductive environments can also develop, leading to gradients in pH and redox state and differential metal mobility. In general, there is commonly a spatial separation of Fe-rich precipitates from those with Cu and Mn, and other transition metals also follow Cu and Mn rather than Fe. Metalloids As and Sb have a strong affinity for Fe under oxidising conditions, but not under more reducing conditions. However, complex biogeochemical parageneses of laminated metalliferous deposits preclude prediction of finer formation details. The textures, mineral species, and metal associations within these deposits are likely to be encountered in all facets of mineral deposit development: initial exploration activity of near-surface locations, mining of shallow portions of orebodies, especially supergene zones, and downstream environmental management with respect to discharging metalliferous waters.