A Shift in Systems: (Co-)conceptualising Pedagogy in an Era of Continuous Complexity

As a result of complex co-constructive entanglements of contemporary lived-ex-perience, this paper develops ideas from posthumanist and material perspectives on education, that recognise, unpack and analyse the particular dynamic, co-con-structive nature of the postdigital entanglements of technology with the epistemic and ontological development of students (Bozalek, Braidotti, Shefer and Zemby-las, 2018). Drawing from Haraway’s idea of symbiogenesis, (2016), this paper suggests that a critical facet of contemporary pedagogy requires an understanding of the key skill of poiesis, to render visible the entangled ontology of the contem-porary postdigital adolescent to better inform appropriate pedagogic developments

Generating a high-resolution global magnetic model for oil and mineral exploration

This is the final contribution to the trilogy of articles on global potential-field data compilations. Getech's continental and national magnetic data compilations commenced in 1989 and were designed specifically for use in petroleum and mineral exploration. These studies complemented the continental-scale gravity-compilation studies that were the subject of the TLE “Meter Reader” contributions in March and May of this year. The success of these projects resulted from strategic partnerships, especially with Paterson, Grant and Watson Ltd. (PGW), and links to a wide range of national organizations. Early compilations covering the whole of Africa, South America, and China were followed by large-scale, small-scale, and national compilations and continue to this day with compilations of U. S. surveys. The projects spawned a range of technical developments, including approaches to remove survey-line noise, the integration of survey grids and disparate ship-track data, and the preservation of the longest-wavelength anomalies associated with the crustal magnetic field. The resulting global gravity and magnetic grids now form an invaluable resource for resource exploration

Elevated Liver Enzymes in Patients with COVID-19: Look, but Not Too Hard

Coronavirus Disease 2019 (COVID-19), due to infection with the virus termed SARS-CoV-2, has complicated the evaluation of elevated liver enzymes. Elevated liver enzymes occur in a median of 15% [1] and up to 58% [2] of patients with COVID-19. Though the most common patterns of liver enzyme abnormalities in patients with SARS-CoV-2 include elevated aminotransferases, with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) typically 1–2 times the upper limit of normal [2], the prognostic significance of abnormal liver biochemistries remains uncertain. There are many potential contributing etiologies to elevated liver enzymes in patients with SARS-CoV-2 including direct liver injury, associated inflammatory responses, congestive hepatopathy, hepatic ischemia, drug-induced liver injury (DILI), and muscle breakdown [3, 4]. In one meta-analysis, an estimated 3% of patients had recognized chronic liver disease at the time of COVID-19 infection [5]. As a result, consultations for abnormal liver biochemistries in patients with COVID-19 are likely common and difficult to resolve. Clarifying a diagnosis is further complicated by the desire to limit exposure of staff assisting with or performing diagnostic testing (e.g., abdominal ultrasound or liver biopsy). In this context, there is need for more information on how best to evaluate these patients

Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA

The manifestation of mitochondrial DNA (mtDNA) diseases depends on the frequency of heteroplasmy (the presence of several alleles in an individual), yet its transmission across generations cannot be readily predicted owing to a lack of data on the size of the mtDNA bottleneck during oogenesis. For deleterious heteroplasmies, a severe bottleneck may abruptly transform a benign (low) frequency in a mother into a disease-causing (high) frequency in her child. Here we present a high-resolution study of heteroplasmy transmission conducted on blood and buccal mtDNA of 39 healthy mother–child pairs of European ancestry (a total of 156 samples, each sequenced at ∼20,000× per site). On average, each individual carried one heteroplasmy, and one in eight individuals carried a disease-associated heteroplasmy, with minor allele frequency ≥1%. We observed frequent drastic heteroplasmy frequency shifts between generations and estimated the effective size of the germ-line mtDNA bottleneck at only ∼30–35 (interquartile range from 9 to 141). Accounting for heteroplasmies, we estimated the mtDNA germ-line mutation rate at 1.3 × 10−8 (interquartile range from 4.2 × 10−9 to 4.1 × 10−8) mutations per site per year, an order of magnitude higher than for nuclear DNA. Notably, we found a positive association between the number of heteroplasmies in a child and maternal age at fertilization, likely attributable to oocyte aging. This study also took advantage of droplet digital PCR (ddPCR) to validate heteroplasmies and confirm a de novo mutation. Our results can be used to predict the transmission of disease-causing mtDNA variants and illuminate evolutionary dynamics of the mitochondrial genome

A Role of Cholesterol in Modulating the Binding of α-Synuclein to Synaptic-Like Vesicles.

α-Synuclein (αS) is a presynaptic protein whose aggregation is associated with Parkinson's disease (PD). Although the physiological function of αS is still unclear, several lines of evidence indicate that this protein may play a role in the trafficking of synaptic vesicles (SVs) during neurotransmitter release, a task associated with its ability to bind SVs and promote their clustering. It is therefore crucial to identify the cellular factors that modulate this process. To address this question, using nuclear magnetic resonance (NMR) spectroscopy we have characterized the role of cholesterol, a major component of the membrane of SVs, in the binding of αS with synaptic-like vesicles. Our results indicate that cholesterol can act as a modulator of the overall affinity of αS for SVs by reducing the local affinity of the region spanning residues 65-97 in the non-amyloid-β component (NAC) of the protein. The increased population of bound states that expose the region 65-97 to the solvent was found to induce stronger vesicle-vesicle interactions by αS. These results provide evidence that cholesterol modulates the clustering of synaptic vesicles induced by (α)S, and supports the role of the disorder-to-order equilibrium of the NAC region in the modulation of the biological properties of the membrane-bound state of αS

Letter: are opioid prescriptions associated with hepatic encephalopathy in patients with compensated cirrhosis? Authors’ reply

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154393/1/apt15669.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154393/2/apt15669_am.pd

Opioid prescriptions are associated with hepatic encephalopathy in a national cohort of patients with compensated cirrhosis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154367/1/apt15639_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154367/2/apt15639.pd

Uncertainty prior to pulmonary rehabilitation in primary care

Pulmonary rehabilitation (PR) is recommended for patients functionally restricted by chronic obstructive pulmonary disease (COPD). However, attendance and adherence to PR remains suboptimal. No previous research has explored COPD patient experiences during the key period from referral to initiation of PR in the United Kingdom. This research aimed to explore the lived experience of COPD patients referred to PR programmes prior to participation. COPD participants were recruited from referrals to two community PR programmes. Semi-structured interviews withCOPDparticipants occurred followingPRreferral, but prior to programme initiation. Data were analyzed using applied interpretive phenomenology. Twenty-five COPD participants aged 42–90 were interviewed. ‘Uncertainty’ affected participants throughout their lived experience of COPD that negatively impacted illness perceptions, PR perceptions and increased participant’s panic and anger. Participants who perceivedCOPDless as a chronic condition andmore as a cyclical process experienced fewer feelings of panic or anger. The experience of uncertainty was disabling for these COPD participants. Recognition of the role that uncertainty plays in patients withCOPDis the first step towards developing interventions focused on reducing this uncertainty, thereby reducing the burden of the disease for the individual patient and facilitating PR attendance.NHS Education South Centra

Declining liver graft quality threatens the future of liver transplantation in the United States

National liver transplantation (LT) volume has declined since 2006, in part because of worsening donor organ quality. Trends that degrade organ quality are expected to continue over the next 2 decades. We used the United Network for Organ Sharing (UNOS) database to inform a 20-year discrete event simulation estimating LT volume from 2010 to 2030. Data to inform the model were obtained from deceased organ donors between 2000 and 2009. If donor liver utilization practices remain constant, utilization will fall from 78% to 44% by 2030, resulting in 2230 fewer LTs. If transplant centers increase their risk tolerance for marginal grafts, utilization would decrease to 48%. The institution of "opt-out" organ donation policies to increase the donor pool would still result in 1380 to 1866 fewer transplants. Ex vivo perfusion techniques that increase the use of marginal donor livers may stabilize LT volume. Otherwise, the number of LTs in the United States will decrease substantially over the next 15 years. In conclusion, the transplant community will need to accept inferior grafts and potentially worse posttransplant outcomes and/or develop new strategies for increasing organ donation and utilization in order to maintain the number of LTs at the current level

Time to Rethink Antiviral Treatment for Hepatitis C in Patients with Coexisting Mental Health/Substance Abuse Issues

A new era has dawned in the treatment of chronic hepatitis C (HCV) virus with the use of direct-acting antiviral medications augmenting combination therapy. Unfortunately, the significant impact of improvements may not be realized if antiviral treatment is not expanded to include a larger proportion of patients, many of whom have coexisting mental health and/or substance abuse issues and have been historically deferred from treatment