Impurity Quantum Phase Transitions

We review recent work on continuous quantum phase transitions in impurity models, both with fermionic and bosonic baths - these transitions are interesting realizations of boundary critical phenomena at zero temperature. The models with fermion bath are generalizations of the standard Kondo model, with the common feature that Kondo screening of the localized spin can be suppressed due to competing processes. The models with boson bath are related to the spin-boson model of dissipative two-level systems, where the interplay between tunneling and friction results in multiple phases. The competition inherent to all models can generate unstable fixed points associated with quantum phase transitions, where the impurity properties undergo qualitative changes. Interestingly, certain impurity transitions feature both lower-critical and upper-critical "dimensions" and allow for epsilon-type expansions. We present results for a number of observables, obtained by both analytical and numerical renormalization group techniques, and make connections to experiments.Comment: 22 pages, 11 figs, review article to be published in Phil. Ma

A pattern of care analysis: Prosthetic rehabilitation of head and neck cancer patients after radiotherapy

Background While some medical associations provide guidelines for the implant‐prosthetic rehabilitation of head and neck cancer patients, the circulation and implementation in the everyday routine of practicing dentists remain unknown. Purpose To analyze patterns of care for the prosthetic rehabilitation of head and neck cancer patients after radiotherapy in German speaking countries. Materials and methods An online survey consisting of 34 questions separated into three sections, (a) general inquiries, (b) treatment concepts, and (c) patient cases, was forwarded to university hospital departments for Prosthetic Dentistry and Oral and Maxillofacial Surgery, and members of different medical associations. Statistical differences between groups were analyzed using chi‐squared test (P < .05). Results From May to October 2019, 118 participants completed the survey. The majority practiced in university hospitals, had more than 5 years of work experience, and reported to be involved in <10 post radiation prosthetic rehabilitation cases per year. Rehabilitation protocols involving dental implants were implemented by oral/oral‐ and maxillofacial surgeons and prosthetic dentists, while general dentists favored implant‐free solutions. Xerostomia was recognized as a common problem for a successful prosthetic rehabilitation. The subsequent treatment choice with either fixed dental prostheses or removable dentures was divided among participants. Conclusions As treatment planning differed with regard to the participants' field of expertise and work environment, and most practitioners only handle a low number of cases, patients might benefit from centralization in larger institutes with a multidisciplinary structure. A high agreement between the practitioners' treatment concepts and the current state of research was observed. While the choice between a mucosa‐ or tooth‐supported, and an implant‐supported restoration depends on numerous individual factors, guidelines derived from longitudinal studies would enhance evidence‐based treatment in this field

Electroweak Gauge-Boson Production at Small q_T: Infrared Safety from the Collinear Anomaly

Using methods from effective field theory, we develop a novel, systematic framework for the calculation of the cross sections for electroweak gauge-boson production at small and very small transverse momentum q_T, in which large logarithms of the scale ratio M_V/q_T are resummed to all orders. These cross sections receive logarithmically enhanced corrections from two sources: the running of the hard matching coefficient and the collinear factorization anomaly. The anomaly leads to the dynamical generation of a non-perturbative scale q_* ~ M_V e^{-const/\alpha_s(M_V)}, which protects the processes from receiving large long-distance hadronic contributions. Expanding the cross sections in either \alpha_s or q_T generates strongly divergent series, which must be resummed. As a by-product, we obtain an explicit non-perturbative expression for the intercept of the cross sections at q_T=0, including the normalization and first-order \alpha_s(q_*) correction. We perform a detailed numerical comparison of our predictions with the available data on the transverse-momentum distribution in Z-boson production at the Tevatron and LHC.Comment: 34 pages, 9 figure

Fitness Ranking of Individual Mutants Drives Patterns of Epistatic Interactions in HIV-1

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Microfluidic characterisation reveals broad range of SARS-CoV-2 antibody affinity in human plasma.

Funder: Herchel Smith FundFunder: St John’s College CambridgeFunder: Centre for Misfolding Diseases, CambridgeFunder: Swiss FCS and the Forschungskredit of the University of ZurichFunder: Frances and Augustus Newman FoundationFunder: BBRSCFunder: NOMIS FoundationThe clinical outcome of SARS-CoV-2 infections, which can range from asymptomatic to lethal, is crucially shaped by the concentration of antiviral antibodies and by their affinity to their targets. However, the affinity of polyclonal antibody responses in plasma is difficult to measure. Here we used microfluidic antibody affinity profiling (MAAP) to determine the aggregate affinities and concentrations of anti-SARS-CoV-2 antibodies in plasma samples of 42 seropositive individuals, 19 of which were healthy donors, 20 displayed mild symptoms, and 3 were critically ill. We found that dissociation constants, K d, of anti-receptor-binding domain antibodies spanned 2.5 orders of magnitude from sub-nanomolar to 43 nM. Using MAAP we found that antibodies of seropositive individuals induced the dissociation of pre-formed spike-ACE2 receptor complexes, which indicates that MAAP can be adapted as a complementary receptor competition assay. By comparison with cytopathic effect-based neutralisation assays, we show that MAAP can reliably predict the cellular neutralisation ability of sera, which may be an important consideration when selecting the most effective samples for therapeutic plasmapheresis and tracking the success of vaccinations

Hermansky-Pudlak syndrome type 1 causes impaired anti-microbial immunity and inflammation due to dysregulated immunometabolism

Hermansky-Pudlak syndrome (HPS) types 1 and 4 are caused by defective vesicle trafficking. The mechanism for Crohn's disease-like inflammation, lung fibrosis, and macrophage lipid accumulation in these patients remains enigmatic. The aim of this study is to understand the cellular basis of inflammation in HPS-1. We performed mass cytometry, proteomic and transcriptomic analyses to investigate peripheral blood cells and serum of HPS-1 patients. Using spatial transcriptomics, granuloma-associated signatures in the tissue of an HPS-1 patient with granulomatous colitis were dissected. In vitro studies were conducted to investigate anti-microbial responses of HPS-1 patient macrophages and cell lines. Monocytes of HPS-1 patients exhibit an inflammatory phenotype associated with dysregulated TNF, IL-1α, OSM in serum, and monocyte-derived macrophages. Inflammatory macrophages accumulate in the intestine and granuloma-associated macrophages in HPS-1 show transcriptional signatures suggestive of a lipid storage and metabolic defect. We show that HPS1 deficiency leads to an altered metabolic program and Rab32-dependent amplified mTOR signaling, facilitated by the accumulation of mTOR on lysosomes. This pathogenic mechanism translates into aberrant bacterial clearance, which can be rescued with mTORC1 inhibition. Rab32-mediated mTOR signaling acts as an immuno-metabolic checkpoint, adding to the evidence that defective bioenergetics can drive hampered anti-microbial activity and contribute to inflammation

Hepatitis E Virus Seroprevalence among Blood Donors in Southwest Switzerland

Aim: The aim of this study was to determine the seroprevalence of Hepatitis E virus (HEV) among blood donors in southwest Switzerland.Background: HEV is recognized as a food-borne disease in industrialized countries, transmitted mainly through pork meat. Cases of transmission through blood transfusion have also been reported. Recent studies have revealed seroprevalence rates of 13.5%, 16.6% and 20.6% among blood donors in England, France and Denmark, respectively.Methods: We analyzed 550 consecutive blood donor samples collected in the region of Lausanne, canton of Vaud, Switzerland, for the presence of anti-HEV IgG, using the MP Diagnostics HEV ELISA kit. For each donor, we documented age, sex and alanine aminotransferase (ALT) value.Results: The study panel was composed of 332 men (60.4%) and 218 women (39.6%). Overall, anti-HEV IgG was found in 27 of 550 samples (4.9%). The seroprevalence was 5.4% (18/332) in men and 4.1% (9/218) in women. The presence of anti-HEV IgG was not correlated with age, gender or ALT values. However, we observed a peak in seroprevalence of 5.3% in individuals aged 51 to 70 years old.Conclusions: Compared with other European countries, HEV seroprevalence among blood donors in southwest Switzerland is low. The low seroprevalence may be explained by the sensitivity of commercial tests used and/or the strict regulation of animal and meat imports. Data regarding HEV prevalence in Swiss livestock are lacking and merit exploration

CCC meets ICU: Redefining the role of critical care of cancer patients

<p>Abstract</p> <p>Background</p> <p>Currently the majority of cancer patients are considered ineligible for intensive care treatment and oncologists are struggling to get their patients admitted to intensive care units. Critical care and oncology are frequently two separate worlds that communicate rarely and thus do not share novel developments in their fields. However, cancer medicine is rapidly improving and cancer is eventually becoming a chronic disease. Oncology is therefore characterized by a growing number of older and medically unfit patients that receive numerous novel drug classes with unexpected side effects.</p> <p>Discussion</p> <p>All of these changes will generate more medically challenging patients in acute distress that need to be considered for intensive care. An intense exchange between intensivists, oncologists, psychologists and palliative care specialists is warranted to communicate the developments in each field in order to improve triage and patient treatment. Here, we argue that "critical care of cancer patients" needs to be recognized as a medical subspecialty and that there is an urgent need to develop it systematically.</p> <p>Conclusion</p> <p>As prognosis of cancer improves, novel therapeutic concepts are being introduced and more and more older cancer patients receive full treatment the number of acutely ill patients is growing significantly. This development a major challenge to current concepts of intensive care and it needs to be redefined who of these patients should be treated, for how long and how intensively.</p

Use of platelet glycoprotein IIb/IIIa inhibitors in diabetics undergoing PCI for non-ST-segment elevation acute coronary syndromes: impact of clinical status and procedural characteristics

Background: The most recent ESC guidelines for percutaneous coronary intervention (PCI) recommend the use of glycoprotein IIb/IIIa inhibitors (GPI) in high risk patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), particularly in diabetics. Little is known about the adherence to these guidelines within Europe. Methods and results: Between May 2005 and April 2008 a total of 47,407 consecutive patients undergoing PCI were prospectively enrolled into the PCI-Registry of the Euro Heart Survey Programme. In the present analysis we examined the use of GPI in 2,922 diabetics who underwent PCI for NSTE-ACS. In this high risk population only 22.2% received a GPI; 8.9% upstream and 13.4% during PCI. The strategy of the individual institution had a major impact on the usage of GPI. In the multiple regression analysis clinical instability and complex lesion characteristics were strong independent determinants for the use of GPI, whereas renal insufficiency was negatively associated with its use. After adjustment for confounding variables no significant differences in hospital mortality could be observed between the cohorts, but a significantly higher rate of non-fatal postprocedural myocardial infarction was observed among patients receiving GPI upstream. Conclusions: Despite the recommendation for its use in the current ESC guidelines, only a minority of the diabetics in Europe undergoing PCI for NSTE-ACS received a GPI. The use of GPI was mainly triggered by high-risk interventional scenarios

β-Microseminoprotein Endows Post Coital Seminal Plasma with Potent Candidacidal Activity by a Calcium- and pH-Dependent Mechanism

The innate immune factors controlling Candida albicans are mostly unknown. Vulvovaginal candidiasis is common in women and affects approximately 70–75% of all women at least once. Despite the propensity of Candida to colonize the vagina, transmission of Candida albicans following sexual intercourse is very rare. This prompted us to investigate whether the post coital vaginal milieu contained factors active against C. albicans. By CFU assays, we found prominent candidacidal activity of post coital seminal plasma at both neutral and the acid vaginal pH. In contrast, normal seminal plasma did not display candidacidal activity prior to acidification. By antifungal gel overlay assay, one clearing zone corresponding to a protein band was found in both post coital and normal seminal plasma, which was subsequently identified as β-microseminoprotein. At neutral pH, the fungicidal activity of β-microseminoprotein and seminal plasma was inhibited by calcium. By NMR spectroscopy, amino acid residue E71 was shown to be critical for the calcium coordination. The acidic vaginal milieu unleashed the fungicidal activity by decreasing the inhibitory effect of calcium. The candidacidal activity of β-microseminoprotein was mapped to a fragment of the C-terminal domain with no structural similarity to other known proteins. A homologous fragment from porcine β-microseminoprotein demonstrated calcium-dependent fungicidal activity in a CFU assay, suggesting this may be a common feature for members of the β-microseminoprotein family. By electron microscopy, β-microseminoprotein was found to cause lysis of Candida. Liposome experiments demonstrated that β-microseminoprotein was active towards ergosterol-containing liposomes that mimic fungal membranes, offering an explanation for the selectivity against fungi. These data identify β-microseminoprotein as an important innate immune factor active against C. albicans and may help explain the low sexual transmission rate of Candida