The 25th Anniversary of the Baby Doe Rules: Perspectives from the Fields of Law, Health Care, Ethics, and Disability Policy

A highly publicized and controversial case involving the withholding of medical treatment from a “Baby Doe” with Down syndrome gave rise in 1984 to the federal law known as the Baby Doe Rules, which went into effect the following year. The law conditions the grant of federal funds for any state’s child protective services program on the state’s assurance that it can respond to reports of medical neglect, which may include the withholding of medical treatment from disabled infants with life-threatening conditions. Leading scholars and practitioners from the fields of health care, law, ethics, and disability policy who are experts in the field of neonatal medicine and decision-making involving very premature and other medically at-risk infants gathered to provide thoughtful commentary and debate on the occasion of the 25th Anniversary of the Baby Doe Rules. The Georgia State University Law Review will publish a symposium volume on the topic in Fall 2009

The KLEVER Survey: spatially resolved metallicity maps and gradients in a sample of 1.2 < z < 2.5 lensed galaxies

We present near-infrared observations of 42 gravitationally lensed galaxies obtained in the framework of the KMOS Lensed Emission Lines and VElocity Review (KLEVER) Survey, a programme aimed at investigating the spatially resolved properties of the ionized gas in 1.2 3σ) ‘inverted’ gradients are also found, showing an anticorrelation between metallicity and star formation rate density on local scales, possibly suggesting recent episodes of pristine gas accretion or strong radial flows in place. Nevertheless, the individual metallicity maps are characterized by a variety of different morphologies, with flat radial gradients sometimes hiding non-axisymmetric variations on kpc scales, which are washed out by azimuthal averages, especially in interacting systems or in those undergoing local episodes of recent star formation

NEMO oligomerization and its ubiquitin-binding properties

The IKK [IκB (inhibitory κB) kinase] complex is a key regulatory component of NF-κB (nuclear factor κB) activation and is responsible for mediating the degradation of IκB, thereby allowing nuclear translocation of NF-κB and transcription of target genes. NEMO (NF-κB essential modulator), the regulatory subunit of the IKK complex, plays a pivotal role in this process by integrating upstream signals, in particular the recognition of polyubiquitin chains, and relaying these to the activation of IKKα and IKKβ, the catalytic subunits of the IKK complex. The oligomeric state of NEMO is controversial and the mechanism by which it regulates activation of the IKK complex is poorly understood. Using a combination of hydrodynamic techniques we now show that apo-NEMO is a highly elongated, dimeric protein that is in weak equilibrium with a tetrameric assembly. Interaction with peptides derived from IKKβ disrupts formation of the tetrameric NEMO complex, indicating that interaction with IKKα and IKKβ and tetramerization are mutually exclusive. Furthermore, we show that NEMO binds to linear di-ubiquitin with a stoichiometry of one molecule of di-ubiquitin per NEMO dimer. This stoichiometry is preserved in a construct comprising the second coiled-coil region and the leucine zipper and in one that essentially spans the full-length protein. However, our data show that at high di-ubiquitin concentrations a second weaker binding site becomes apparent, implying that two different NEMO–di-ubiquitin complexes are formed during the IKK activation process. We propose that the role of these two complexes is to provide a threshold for activation, thereby ensuring sufficient specificity during NF-κB signalling

Attenuation of Colon Inflammation through Activators of the Retinoid X Receptor (Rxr)/Peroxisome Proliferator–Activated Receptor γ (Pparγ) Heterodimer: A Basis for New Therapeutic Strategies

The peroxisome proliferator–activated receptor γ (PPARγ) is highly expressed in the colon mucosa and its activation has been reported to protect against colitis. We studied the involvement of PPARγ and its heterodimeric partner, the retinoid X receptor (RXR) in intestinal inflammatory responses. PPARγ1/− and RXRα1/− mice both displayed a significantly enhanced susceptibility to 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis compared with their wild-type littermates. A role for the RXR/PPARγ heterodimer in the protection against colon inflammation was explored by the use of selective RXR and PPARγ agonists. TNBS-induced colitis was significantly reduced by the administration of both PPARγ and RXR agonists. This beneficial effect was reflected by increased survival rates, an improvement of macroscopic and histologic scores, a decrease in tumor necrosis factor α and interleukin 1β mRNA levels, a diminished myeloperoxidase concentration, and reduction of nuclear factor κB DNA binding activity, c-Jun NH2-terminal kinase, and p38 activities in the colon. When coadministered, a significant synergistic effect of PPARγ and RXR ligands was observed. In combination, these data demonstrate that activation of the RXR/PPARγ heterodimer protects against colon inflammation and suggest that combination therapy with both RXR and PPARγ ligands might hold promise in the clinic due to their synergistic effects

Ethical Criteria for the Admission and Management of Patients in the ICU Under Conditions of Limited Medical Resources: A Shared International Proposal in View of the COVID-19 Pandemic

Introduction The present pandemic has exposed us to unprecedented challenges that need to be addressed not just for the current state, but also for possible future similar occurrences. It is worth pointing out that discussions on the allocation of medical resources may not necessarily refer to an exception, but, unfortunately, to a regular condition for a large part of humanity (1). The criteria for admission to an Intensive Care Unit (ICU) setting generally take into account multiple factors. There must be a diagnostic and prognostic basis for the decisions made, considering both biological factors and patient values and wishes. Furthermore, the decision-making process should, whenever possible, respect the patient's advance directives as well as the relationship with the patient's family or attorney. Therapeutic neglect should be avoided. Having applied standard clinical evaluation criteria for the appropriate treatment of patients with COVID-19, including consideration of prognosis, if a hospital then finds itself unable to provide optimal treatment (e.g., due to a disproportion between the number of patients and the availability of beds, healthcare providers, ventilators, and drugs in the ICU), it becomes necessary to evaluate, case by case, how to achieve justice and the best possible good for the greatest number of patients. It is therefore mandatory to explore alternative solutions; these include increasing available beds and healthcare providers, implementing alternative, though suboptimal, approaches (where appropriate), transferring patients to other clinical units, etc. Making these decisions properly also involves the recovery of the political role of medicine and science (2). If the imbalance between needs and resources reaches a critical level, an emergency triage protocol, following the operational and ethical indications of “disaster medicine,” should be activated. These have been deployed in major and serious natural (earthquakes or tsunamis for example) and technological (factory explosions, public transport accidents for example) disasters, as well as following terrorist attacks (3, 4). The question of the feasibility of developing a clinical evaluation algorithm to support the decision-making of the triage team remains open, though many such protocols have been written. According to the above, we propose the following five ethical criteria for the triage of patients in conditions of limited resources, such as the COVID pandemic. They are the result of an interdisciplinary and intercultural dialogue between specialists from different disciplines. Several of the authors are working in the main epicenters of the crisis and currently are playing a central role in the bioethical, clinical, social and legal aspects of the management of the COVID-19 pandemic

Morphometry of subaerial shield volcanoes and glaciovolcanoes from Reykjanes Peninsula, Iceland: Effects of eruption environment

We present a morphometric study of 33 basaltic volcanic edifices from the Reykjanes Peninsula, Iceland, using a 20 m resolution digital elevation model (DEM). Slope values distinguish subaerial from intraglacial eruption environments, with glaciovolcanic edifices having average slope values that are > 5° higher than subaerial shields. The 26 analyzed glaciovolcanic edifices are separated into 3 groups based on size, and are also categorized following the new classification scheme of tuyas by Russell et al. (2014), into 15 tindars, 1 conical tuya, 3 flat-topped tuyas and 7 complex tuyas. The glaciovolcanic edifices show a continuum of landforms ranging from small elongated tindars to large equidimensional flat-topped tuyas. The smaller edifices ( 0.1 km3) are flat-topped tuyas. The mid-sized edifices (0.01–0.1 km3) show a wide variety of shapes and classify either as tindars or as complex tuyas, with only one edifice classifying as a conical tuya. Edifice elongation tends to decrease with volume, suggesting that small edifices are primarily fissure controlled, whereas larger edifices are mainly controlled by a central vent. The mid-sized complex tuyas are transitional edifices, suggesting that some intraglacial eruptions start as fissure eruptions that subsequently concentrate into one or more central vents, whereas the mid-sized tindars suggest a sustained fissure eruption. There is a tectonic control on the orientation of the edifices evidenced by a strong correlation between edifice elongation azimuth and mapped faults and fractures. Most edifice elongations cluster between 020° and 080°, coinciding with the strike of normal faults within and at the boundary of regional volcanic systems, but some edifices have elongations that correlate with N–S striking book-shelf faults. This implies that intraglacial eruptions are controlled by pre-existing pathways in the crust, as has been previously observed for subaerial fissure eruptions. In terms of classification, quantification of the limits between the four tuya types proposed by Russell et al. (2014) is difficult because of the transitional nature shown by several edifices. A threshold of 1.8 in ellipticity index (E.I.) values can be used to distinguish tindars from the other three types. Flat-topped tuyas are distinguished by their greater overall size, their large and relatively flat summit regions, reflected in bimodal slope distributions, and their low E.I. and low to intermediate irregularity index (I.I.) values. The only analyzed conical tuya has very low E.I. and I.I. values, very small summit regions and very steep flank slopes. The complex tuyas have variable morphometries, but are in general characterized by high I.I. values and very irregular slope distributions. No correlation is observed between edifice-scale morphology and lithology (e.g. pillow dominated or hyaloclastite dominated).Fil: Pedersen, G. B. M.. University of Iceland. Institute of Earth Sciences. Nordic Volcanological Center; IslandiaFil: Grosse, Pablo. Fundación Miguel Lillo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán; Argentin