Conceptualizing autonomy in the context of chronic physical illness: relating philosophical theories to social scientific perspectives

The aim of this article is to conceptualize autonomy in the context of chronic physical illness. To this end, we compare and contrast a selection of contemporary philosophical theories of autonomy with social scientific perspectives on chronic illness, particularly models of disability and symbolic interactionism. The philosophical theories mainly depart from a positive conceptualization of autonomy, which involves actively shaping one's life and identifying with fundamental values. This conceptualization is preferred over a negative conceptualization, which defines autonomy as non-interference, for its compatibility with social models of disability and with the assumption that people are interdependent. Interference may disable, but also enable people with a chronic illness to shape their lives. What matters is that people can realize what they want to realize. We suggest that, in the context of chronic physical illness, autonomy might be conceptualized as correspondence between what people want their lives to be like and what their lives are actually like. Disturbed autonomy might be restored either by expanding opportunities to arrange life or by adjusting how one wants life to be arranged. The grounds for the latter approach might be questioned, first, if people have not adjusted what they want carefully, and second, if reorganization of the material and social environment would have made it unnecessary to adjust one's arrangement of life

Heavy Quark Thermalization in Classical Lattice Gauge Theory: Lessons for Strongly-Coupled QCD

Thermalization of a heavy quark near rest is controlled by the correlator of two electric fields along a temporal Wilson line. We address this correlator within real-time, classical lattice Yang-Mills theory, and elaborate on the analogies that exist with the dynamics of hot QCD. In the weak-coupling limit, it can be shown analytically that the dynamics on the two sides are closely related to each other. For intermediate couplings, we carry out non-perturbative simulations within the classical theory, showing that the leading term in the weak-coupling expansion significantly underestimates the heavy quark thermalization rate. Our analytic and numerical results also yield a general understanding concerning the overall shape of the spectral function corresponding to the electric field correlator, which may be helpful in subsequent efforts to reconstruct it from Euclidean lattice Monte Carlo simulations.Comment: 22 pages. v2: a reference and clarifications added; published versio

Heavy quark diffusion in QCD and N=4 SYM at next-to-leading order

We present the full details of a calculation at next-to-leading order of the momentum diffusion coefficient of a heavy quark in a hot, weakly coupled, QCD plasma. Corrections arise at O(g_s); physically they represent interference between overlapping scatterings, as well as soft, electric scale (p ~ gT) gauge field physics, which we treat using the hard thermal loop (HTL) effective theory. In 3-color, 3-flavor QCD, the momentum diffusion constant of a fundamental representation heavy quark at NLO is kappa = (16\pi/3) alpha_s^2 T^3 (log(1/g) + 0.07428 + 1.9026 g). We extend the computation to a heavy fundamental representation ``probe'' quark in large N_c, N=4 Super Yang-Mills theory, where the result is kappa^{SYM}= (lambda^2 T^3)(6\pi) (log(1/\sqrt{\lambda}) + 0.4304 + 0.8010 \sqrt{lambda}) (where lambda=g_s^2 N_c is the t'Hooft coupling). In the absence of some resummation technique, the convergence of perturbation theory is poor.Comment: 40 pages, 14 figure

Loop-Generated Bounds on Changes to the Graviton Dispersion Relation

We identify the effective theory appropriate to the propagation of massless bulk fields in brane-world scenarios, to show that the dominant low-energy effect of asymmetric warping in the bulk is to modify the dispersion relation of the effective 4-dimensional modes. We show how such changes to the graviton dispersion relation may be bounded through the effects they imply, through loops, for the propagation of standard model particles. We compute these bounds and show that they provide, in some cases, the strongest constraints on nonstandard gravitational dispersions. The bounds obtained in this way are the strongest for the fewest extra dimensions and when the extra-dimensional Planck mass is the smallest. Although the best bounds come for warped 5-D scenarios, for which the 5D Planck Mass is O(TeV), even in 4 dimensions the graviton loop can lead to a bound on the graviton speed which is comparable with other constraints.Comment: 18 pages, LaTeX, 4 figures, uses revte

Observations of fog‐aerosol interactions over central Greenland

Supercooled fogs can have an important radiative impact at the surface of the Greenland Ice Sheet, but they are difficult to detect and our understanding of the factors that control their lifetime and radiative properties is limited by a lack of observations. This study demonstrates that spectrally resolved measurements of downwelling longwave radiation can be used to generate retrievals of fog microphysical properties (phase and particle effective radius) when the fog visible optical depth is greater than ∼0.25. For 12 cases of fog under otherwise clear skies between June and September 2019 at Summit Station in central Greenland, nine cases were mixed-phase. The mean ice particle (optically-equivalent sphere) effective radius was 24.0 ± 7.8 µm, and the mean liquid droplet effective radius was 14.0 ± 2.7 µm. These results, combined with measurements of aerosol particle number concentrations, provide evidence supporting the hypotheses that (a) low surface aerosol particle number concentrations can limit fog liquid water path, (b) fog can act to increase near-surface aerosol particle number concentrations through enhanced mixing, and (c) multiple fog events in quiescent periods gradually deplete near-surface aerosol particle number concentrations

Long-term acquired everolimus resistance in pancreatic neuroendocrine tumours can be overcome with novel PI3K-AKT-mTOR inhibitors

Background:The mTOR-inhibitor everolimus improves progression-free survival in advanced pancreatic neuroendocrine tumours (PNETs). However, adaptive resistance to mTOR inhibition is described.Methods:QGP-1 and BON-1, two human PNET cell lines, were cultured with increasing concentrations of everolimus up to 22 weeks to reach a dose of 1 μM everolimus, respectively, 1000-fold and 250-fold initial IC 50. Using total DNA content as a measure of cell number, growth inhibitory dose-response curves of everolimus were determined at the end of resistance induction and over time after everolimus withdrawal. Response to ATP-competitive mTOR inhibitors OSI-027 and AZD2014, and PI3K-mTOR inhibitor NVP-BEZ235 was studied. Gene expression of 10 PI3K-Akt-mTOR pathway-related genes was evaluated using quantitative real-time PCR (RT-qPCR).Results:Long-term everolimus-treated BON-1/R and QGP-1/R showed a significant reduction in everolimus sensitivity. During a drug holiday, gradual return of everolimus sensitivity in BON-1/R and QGP-1/R led to complete reversal of resistance after 10-12 weeks. Treatment with AZD2014, OSI-027 and NVP-BEZ235 had an inhibitory effect on cell proliferation in both sensitive and resistant cell lines. Gene expression in BON-1/R revealed downregulation of MTOR, RICTOR, RAPTOR, AKT and HIF1A, whereas 4EBP1 was upregulated. In QGP-1/R, a downregulation of HIF1A and an upregulation of ERK2 were observed.Conclusions:Long-term everolimus resistance was induced in two human PNET cell lines. Novel PI3K-AKT-mTOR pathway-targeting drugs can overcome everolimus resistance. Differential gene expression profiles suggest different mechanisms of everolimus resistance in BON-1 and QGP-1

New Alien Mediterranean Biodiversity Records (August 2022)

In this Collective Article on alien and cryptogenic diversity in the Mediterranean Sea we report a total of 19 species belonging to nine Phyla and coming from nine countries. Several of these records concern fish species, and of particular interest are the first records of: Terapon puta for Italian waters; Pteragopus trispilus from Malta; Plotosus lineatus from Cyprus; and the northernmost Mediterranean record of Lagocephalus sceleratus. The northernmost Mediterranean record was also reported for the sea urchin Diadema setosum. The portunid crab Thalamita poissonii was recorded for the first time in Libya. The copepod Pseudodiaptomus marinus was recorded for the first time in the Marmara Sea. The polychaete Branchiomma luctuosum was recorded for the first time from the Mediterranean coast of France. The alien anemone Diadumene lineata was recorded for the first time from Slovenia. The macroalgae Sargassum furcatum was recorded for the first time from Italy. The new Mediterranean records here reported help tracing abundance and distribution of alien and cryptic species in the Mediterranean Sea

No additional prognostic value of genetic information in the prediction of vascular events after cerebral ischemia of arterial origin

Background: Patients who have suffered from cerebral ischemia have a high risk of recurrent vascular events. Predictive models based on classical risk factors typically have limited prognostic value. Given that cerebral ischemia has a heritable component, genetic information might improve performance of these risk models. Our aim was to develop and compare two models: one containing traditional vascular risk factors, the other also including genetic information. Methods and Results: We studied 1020 patients with cerebral ischemia and genotyped them with the Illumina Immunochip. Median follow-up time was 6.5 years; the annual incidence of new ischemic events (primary outcome, n=198) was 3.0%. The prognostic model based on classical vascular risk factors had an area under the receiver operating characteristics curve (AUC-ROC) of 0.65 (95% confidence interval 0.61-0.69). When we added a genetic risk score based on prioritized SNPs from a genome-wide association study of ischemic stroke (using summary statistics from the METASTROKE study which included 12389 cases and 62004 controls), the AUC-ROC remained the same. Similar results were found for the secondary outcome ischemic stroke. Conclusions: We found no additional value of genetic information in a prognostic model for the risk of ischemic events in patients with cerebral ischemia of arterial origin. This is consistent with a complex, polygenic architecture, where many genes of weak effect likely act in concert to influence the heritable risk of an individual to develop (recurrent) vascular events. At present, genetic information cannot help clinicians to distinguish patients at high risk for recurrent vascular events

Candidate CSPG4 mutations and induced pluripotent stem cell modeling implicate oligodendrocyte progenitor cell dysfunction in familial schizophrenia

Schizophrenia is highly heritable, yet its underlying pathophysiology remains largely unknown. Among the most well-replicated findings in neurobiological studies of schizophrenia are deficits in myelination and white matter integrity; however, direct etiological genetic and cellular evidence has thus far been lacking. Here, we implement a family-based approach for genetic discovery in schizophrenia combined with functional analysis using induced pluripotent stem cells (iPSCs). We observed familial segregation of two rare missense mutations in Chondroitin Sulfate Proteoglycan 4 (CSPG4) (c.391G > A [p.A131T], MAF 7.79 × 10−5 and c.2702T > G [p.V901G], MAF 2.51 × 10−3). The CSPG4A131T mutation was absent from the Swedish Schizophrenia Exome Sequencing Study (2536 cases, 2543 controls), while the CSPG4V901G mutation was nominally enriched in cases (11 cases vs. 3 controls, P = 0.026, OR 3.77, 95% CI 1.05–13.52). CSPG4/NG2 is a hallmark protein of oligodendrocyte progenitor cells (OPCs). iPSC-derived OPCs from CSPG4A131T mutation carriers exhibited abnormal post-translational processing (P = 0.029), subcellular localization of mutant NG2 (P = 0.007), as well as aberrant cellular morphology (P = 3.0 × 10−8), viability (P = 8.9 × 10−7), and myelination potential (P = 0.038). Moreover, transfection of healthy non-carrier sibling OPCs confirmed a pathogenic effect on cell survival of both the CSPG4A131T (P = 0.006) and CSPG4V901G (P = 3.4 × 10−4) mutations. Finally, in vivo diffusion tensor imaging of CSPG4A131T mutation carriers demonstrated a reduction of brain white matter integrity compared to unaffected sibling and matched general population controls (P = 2.2 × 10−5). Together, our findings provide a convergence of genetic and functional evidence to implicate OPC dysfunction as a candidate pathophysiological mechanism of familial schizophrenia