Three persons, three genetic contributors, three parents: Mitochondrial donation, genetic parenting and the immutable grammar of the ‘three x x’

ESRC Future Research Leaders award (ref. ES/ K00901X/1

Debating CRISPR/cas9 and mitochondrial donation: Continuity and transition performances at scientific conferences

Conferences are important performative sites. Here we detail a UK science policy conference debating the novel biomedical techniques CRISPR/cas9 and mitochondrial donation. Both techniques have received significant attention from scientists and bioethicists about their clinical potential, social implications, and the prospects of genetic and germline modification. In many countries the policy debates on regulating both technologies is ongoing and operating in tandem. The UK, however, is operating in a distinct policy context in that mitochondrial donation was formally legalized under license in 2015, meaning the British CRISPR/cas9 debates occur in the light of a confirmed policy position on mitochondrial donation. Our analysis of the Progress Educational Trust 2015 annual conference ‘From Three-Person IVF to Genome Editing’ argues that this event conducted important staging work in articulating the relationship between these two technologies in the UK. These efforts constitute what we call a ‘transition performance’ that (i) enacted the successful resolution of the mitochondrial donation policy debate, (ii) performed the success of British biomedical politics, and (iii) opened the space for a public debate on CRISPR/cas9 in line with a specifically configured set of legitimacy practices. Subsequently the conference contrasts to many other conferences that fit what we term a ‘continuity performance’ that seek to assert consistency and progress through iteration. We close by articulating further applications and developments of these notions in Science and Technology Studies.The research reported in this article was funded by ESRC Future Research Leaders award (ref. ES/K00901X/1) held by Dr. Dimond

Doing laboratory ethnography: reflections on method in scientific workplaces

Laboratory ethnography extended the social scientist’s gaze into the day-to-day accomplishment of scientific practice. Here we reflect upon our own ethnographies of biomedical scientific workspaces to provoke methodological discussion on the doing of laboratory ethnography. What we provide is less a ‘how to’ guide and more a commentary on what to look for and what to look at. We draw upon our empirical research with stem cell laboratories and animal houses, teams producing robotic surgical tools, musicians sonifying data science, a psychiatric genetics laboratory, and scientists developing laboratory grown meat. We use these cases to example a set of potential ethnographic themes worthy of pursuit: science epistemics and the extended laboratory, the interaction order of scientific work, sensory realms and the rending of science as sensible, conferences as performative sites, and the spaces, places and temporalities of scientific work

In vitro meat: Zombies on the menu?

In April 2008 the In Vitro Meat Consortium held its first meeting at the Norwegian Food Research Institute. They are a group of scientists and advocates who seek to turn the techniques of tissue engineering to the production of food, producing meat in laboratories that has at no point been part of a living animal. This is a fascinating technology, and one that fits well with the topic of this SCRIPTed analysis section: the ‘zombification’ of meat products. I have been conducting interviews with scientists who are involved in In Vitro Meat research at the three main research sites to explore the emergent social, ethical and regulatory issues of the technology. In this discussion I first provide detail on the current level of scientific development in the field and then describe the social context and promise of In Vitro Meat, before finally returning to the central question of what exactly In Vitro Meat is: zombie or not

The intracellular loop between domains I and II of the B type calcium channel confers aspects of G protein sensitivity to the E type calcium channel

Neuronal voltage-dependent calcium channels undergo inhibitory modulation by G-protein activation, generally involving both kinetic slowing and steady-state inhibition. We have shown previously that the b-subunit of neuronal calcium channels plays an important role in this process, because when it is absent, greater receptor-mediated inhibition is observed (Campbell et al., 1995b). We therefore hypothesized that the calcium channel b-subunits normally may occlude G-proteinmediated inhibition. Calcium channel b-subunits bind to the cytoplasmic loop between transmembrane domains I and II of the a1-subunits (Pragnell et al., 1994). We have examined the hypothesis that this loop is involved in G-protein-mediated inhibition by making chimeras containing the I–II loop of a1B or a1A inserted into a1E (a1EBE and a1EAE, respectively). This strategy was adopted because a1B (the molecular counterpart of N-type channels) and, to a lesser extent, a1A (P/Q-type) are G-protein-modulated, whereas this has not been observed to any great extent for a1E. Although a1B, coexpressed with a2-d and b1b transiently expressed in COS-7 cells, showed both kinetic slowing and steady-state inhibition when recorded with GTPgS in the patch pipette, both of which were reversed with a depolarizing prepulse, the chimera a1EBE (and, to a smaller extent, a1EAE) showed only kinetic slowing in the presence of GTPgS, and this also was reversed by a depolarizing prepulse. These results indicate that the I–II loop may be the molecular substrate of kinetic slowing but that the steady-state inhibition shown by a1B may involve a separate site on this calcium channel

Survival and health economic outcomes in heart failure diagnosed at hospital admission versus community settings: a propensity-matched analysis

BACKGROUND AND AIMS: Most patients with heart failure (HF) are diagnosed following a hospital admission. The clinical and health economic impacts of index HF diagnosis made on admission to hospital versus community settings are not known. METHODS: We used the North West London Discover database to examine 34 208 patients receiving an index diagnosis of HF between January 2015 and December 2020. A propensity score-matched (PSM) cohort was identified to adjust for differences in socioeconomic status, cardiovascular risk and pre-diagnosis health resource utilisation cost. Outcomes were stratified by two pathways to index HF diagnosis: a 'hospital pathway' was defined by diagnosis following hospital admission; and a 'community pathway' by diagnosis via a general practitioner or outpatient services. The primary clinical and health economic endpoints were all-cause mortality and cost-consequence differential, respectively. RESULTS: The diagnosis of HF was via hospital pathway in 68% (23 273) of patients. The PSM cohort included 17 174 patients (8582 per group) and was matched across all selected confounders (p>0.05). The ratio of deaths per person-months at 24 months comparing community versus hospital diagnosis was 0.780 (95% CI 0.722 to 0.841, p<0.0001). By 72 months, the ratio of deaths was 0.960 (0.905 to 1.020, p=0.18). Diagnosis via hospital pathway incurred an overall extra longitudinal cost of £2485 per patient. CONCLUSIONS: Index diagnosis of HF through hospital admission continues to dominate and is associated with a significantly greater short-term risk of mortality and substantially increased long-term costs than if first diagnosed in the community. This study highlights the potential for community diagnosis-early, before symptoms necessitate hospitalisation-to improve both clinical and health economic outcomes

SCAMP:standardised, concentrated, additional macronutrients, parenteral nutrition in very preterm infants: a phase IV randomised, controlled exploratory study of macronutrient intake, growth and other aspects of neonatal care

<p>Abstract</p> <p>Background</p> <p>Infants born <29 weeks gestation are at high risk of neurocognitive disability. Early postnatal growth failure, particularly head growth, is an important and potentially reversible risk factor for impaired neurodevelopmental outcome. Inadequate nutrition is a major factor in this postnatal growth failure, optimal protein and calorie (macronutrient) intakes are rarely achieved, especially in the first week. Infants <29 weeks are dependent on parenteral nutrition for the bulk of their nutrient needs for the first 2-3 weeks of life to allow gut adaptation to milk digestion. The prescription, formulation and administration of neonatal parenteral nutrition is critical to achieving optimal protein and calorie intake but has received little scientific evaluation. Current neonatal parenteral nutrition regimens often rely on individualised prescription to manage the labile, unpredictable biochemical and metabolic control characteristic of the early neonatal period. Individualised prescription frequently fails to translate into optimal macronutrient delivery. We have previously shown that a standardised, concentrated neonatal parenteral nutrition regimen can optimise macronutrient intake.</p> <p>Methods</p> <p>We propose a single centre, randomised controlled exploratory trial of two standardised, concentrated neonatal parenteral nutrition regimens comparing a standard macronutrient content (maximum protein 2.8 g/kg/day; lipid 2.8 g/kg/day, dextrose 10%) with a higher macronutrient content (maximum protein 3.8 g/kg/day; lipid 3.8 g/kg/day, dextrose 12%) over the first 28 days of life. 150 infants 24-28 completed weeks gestation and birthweight <1200 g will be recruited. The primary outcome will be head growth velocity in the first 28 days of life. Secondary outcomes will include a) auxological data between birth and 36 weeks corrected gestational age b) actual macronutrient intake in first 28 days c) biomarkers of biochemical and metabolic tolerance d) infection biomarkers and other intravascular line complications e) incidence of major complications of prematurity including mortality f) neurodevelopmental outcome at 2 years corrected gestational age</p> <p>Trial registration</p> <p>Current controlled trials: <a href="http://www.controlled-trials.com/ISRCTN76597892">ISRCTN76597892</a>; EudraCT Number: 2008-008899-14</p

Dual-gated bilayer graphene hot electron bolometer

Detection of infrared light is central to diverse applications in security, medicine, astronomy, materials science, and biology. Often different materials and detection mechanisms are employed to optimize performance in different spectral ranges. Graphene is a unique material with strong, nearly frequency-independent light-matter interaction from far infrared to ultraviolet, with potential for broadband photonics applications. Moreover, graphene's small electron-phonon coupling suggests that hot-electron effects may be exploited at relatively high temperatures for fast and highly sensitive detectors in which light energy heats only the small-specific-heat electronic system. Here we demonstrate such a hot-electron bolometer using bilayer graphene that is dual-gated to create a tunable bandgap and electron-temperature-dependent conductivity. The measured large electron-phonon heat resistance is in good agreement with theoretical estimates in magnitude and temperature dependence, and enables our graphene bolometer operating at a temperature of 5 K to have a low noise equivalent power (33 fW/Hz1/2). We employ a pump-probe technique to directly measure the intrinsic speed of our device, >1 GHz at 10 K.Comment: 5 figure

Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design.

INTRODUCTION: The Alzheimer's biomarkers in daily practice (ABIDE) project is designed to translate knowledge on diagnostic tests (magnetic resonance imaging [MRI], cerebrospinal fluid [CSF], and amyloid positron emission tomography [PET]) to daily clinical practice with a focus on mild cognitive impairment (MCI). METHODS: ABIDE is a 3-year project with a multifaceted design and is structured into interconnected substudies using both quantitative and qualitative research methods. RESULTS: Based on retrospective data, we develop personalized risk estimates for MCI patients. Prospectively, we collect MRI and CSF data from 200 patients from local memory clinics and amyloid PET from 500 patients in a tertiary setting, to optimize application of these tests in daily practice. Furthermore, ABIDE will develop strategies for optimal patient-clinician conversations. DISCUSSION: Ultimately, this will result in a set of practical tools for clinicians to support the choice of diagnostic tests and facilitate the interpretation and communication of their results