Heterogeneity in vaccination coverage explains the size and occurrence of measles epidemics in German surveillance data

The objective of this study was to characterize empirically the association between vaccination coverage and the size and occurrence of measles epidemics in Germany. In order to achieve this we analysed data routinely collected by the Robert Koch Institute, which comprise the weekly number of reported measles cases at all ages as well as estimates of vaccination coverage at the average age of entry into the school system. Coverage levels within each federal state of Germany are incorporated into a multivariate time-series model for infectious disease counts, which captures occasional outbreaks by means of an autoregressive component. The observed incidence pattern of measles for all ages is best described by using the log proportion of unvaccinated school starters in the autoregressive component of the mode

Dynamics, correlations and phases of the micromaser

The micromaser possesses a variety of dynamical phase transitions parametrized by the flux of atoms and the time-of-flight of the atom within the cavity. We discuss how these phases may be revealed to an observer outside the cavity using the long-time correlation length in the atomic beam. Some of the phase transitions are not reflected in the average excitation level of the outgoing atom, which is the commonly used observable. The correlation length is directly related to the leading eigenvalue of the time evolution operator, which we study in order to elucidate the phase structure. We find that as a function of the time-of-flight the transition from the thermal to the maser phase is characterized by a sharp peak in the correlation length. For longer times-of-flight there is a transition to a phase where the correlation length grows exponentially with the flux. We present a detailed numerical and analytical treatment of the different phases and discuss the physics behind them.Comment: 60 pages, 18 figure files, Latex + \special{} for the figures, (some redundant figures are eliminated and others are changed

Platelets mediate lymphovenous hemostasis to maintain blood-lymphatic separation throughout life

Mammals transport blood through a high-pressure, closed vascular network and lymph through a low-pressure, open vascular network. These vascular networks connect at the lymphovenous (LV) junction, where lymph drains into blood and an LV valve (LVV) prevents backflow of blood into lymphatic vessels. Here we describe an essential role for platelets in preventing blood from entering the lymphatic system at the LV junction. Loss of CLEC2, a receptor that activates platelets in response to lymphatic endothelial cells, resulted in backfilling of the lymphatic network with blood from the thoracic duct (TD) in both neonatal and mature mice. Fibrin-containing platelet thrombi were observed at the LVV and in the terminal TD in wild-type mice, but not Clec2-deficient mice. Analysis of mice lacking LVVs or lymphatic valves revealed that platelet-mediated thrombus formation limits LV backflow under conditions of impaired valve function. Examination of mice lacking integrin-mediated platelet aggregation indicated that platelet aggregation stabilizes thrombi that form in the lymphatic vascular environment to prevent retrograde blood flow. Collectively, these studies unveil a newly recognized form of hemostasis that functions with the LVV to safeguard the lymphatic vascular network throughout life

Quantitative wave-particle duality and non-erasing quantum erasure

The notion of wave-particle duality may be quantified by the inequality V^2+K^2 <=1, relating interference fringe visibility V and path knowledge K. With a single-photon interferometer in which polarization is used to label the paths, we have investigated the relation for various situations, including pure, mixed, and partially-mixed input states. A quantum eraser scheme has been realized that recovers interference fringes even when no which-way information is available to erase.Comment: 6 pages, 4 figures. To appear in Phys. Rev.

On Taylor series of functions regular in Gaier regions

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41617/1/13_2005_Article_BF01899316.pd

The Symptom Monitoring with Feedback Trial (SWIFT):protocol for a registry‑based cluster randomised controlled trial in haemodialysis

BACKGROUND: Kidney failure prevalence is increasing worldwide. Haemodialysis, peritoneal dialysis or kidney transplantation are undertaken to extend life with kidney failure. People receiving haemodialysis commonly experience fatigue, pain, nausea, cramping, itching, sleeping difficulties, anxiety and depression. This symptom burden contributes to poor health-related quality of life (QOL) and is a major reason for treatment withdrawal and death. The Symptom monitoring WIth Feedback Trial (SWIFT) will test the hypothesis that regular symptom monitoring with feedback to people receiving haemodialysis and their treating clinical team can improve QOL. METHODS: We are conducting an Australia and New Zealand Dialysis and Transplant (ANZDATA) registry-based cluster randomised controlled trial to determine the clinical- and cost-effectiveness at 12 months, of 3-monthly symptom monitoring using the Integrated Palliative Outcome Scale-Renal (IPOS-Renal) survey with clinician feedback, compared with usual care among adults treated with haemodialysis. Participants complete symptom scoring using a tablet, which are provided to participants and to clinicians. The trial aims to recruit 143 satellite haemodialysis centres, (up to 2400 participants). The primary outcome is change in health-related QOL, as measured by EuroQol 5-Dimension, 5-Level (EQ-5D-5L) instrument. Secondary outcomes include overall survival, symptom severity (including haemodialysis-associated fatigue), healthcare utilisation and cost-effectiveness. DISCUSSION: SWIFT is the first registry-based trial in the Australian haemodialysis population to investigate whether regular symptom monitoring with feedback to participants and clinicians improves QOL. SWIFT is embedded in the ANZDATA Registry facilitating pragmatic recruitment from public and private dialysis clinics, throughout Australia. SWIFT will inform future collection, storage and reporting of patient-reported outcome measures (PROMs) within a clinical quality registry. As the first trial to rigorously estimate the efficacy and cost-effectiveness of routine PROMs collection and reporting in haemodialysis units, SWIFT will provide invaluable information to health services, clinicians and researchers working to improve the lives of those with kidney failure. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12620001061921. Registered on 16 October 2020 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06355-0

Small Molecule Inhibitors of the Neuropilin-1 Vascular Endothelial Growth Factor A (VEGF-A) Interaction†

We report the molecular design and synthesis of EG00229, 2, the first small molecule ligand for the VEGF-A receptor neuropilin 1 (NRP1) and the structural characterization of NRP1-ligand complexes by NMR spectroscopy and X-ray crystallography. Mutagenesis studies localized VEGF-A binding in the NRP1 b1 domain and a peptide fragment of VEGF-A was shown to bind at the same site by NMR, providing the basis for small molecule design. Compound 2 demonstrated inhibition of VEGF-A binding to NRP1 and attenuated VEGFR2 phosphorylation in endothelial cells. Inhibition of migration of endothelial cells was also observed. The viability of A549 lung carcinoma cells was reduced by 2, and it increased the potency of the cytotoxic agents paclitaxel and 5-fluorouracil when given in combination. These studies provide the basis for design of specific small molecule inhibitors of ligand binding to NRP1

Whole system valuation of arable, agroforestry and tree-only systems at three case study sites in Europe

There is an increasing demand to study the long-term effects of land use from both local farm and wider societal and environmental perspectives. This study applied an approach to evaluate both the financial profitability of arable, agroforestry, and tree-only systems and the wider societal benefits over a period of 30-60 years. The biophysical inputs and yields from the three systems were modelled for three case study sites in the United Kingdom, Spain, and Switzerland, using a tree and crop simulation model called Yield-SAFE. A bio-economic model called Farm-SAFE was then used to compare the financial (EAVF) and economic (or societal) equivalent annual values (EAVE) by including monetary values for five environmental externalities: carbon dioxide emissions, carbon sequestration, soil erosion by water, and nitrogen and phosphorus balances. Across the three case studies, arable farming generated higher farm incomes than the agroforestry or tree-only systems, but the arable systems also created the greatest environmental costs. By comparison the agroforestry and tree-only systems generated lower CO2 emissions and sequestered more carbon. Applying monetary values to the environmental externalities meant that the EAVE of the agroforestry and tree-only systems were greater or similar to that for the arable system in the UK case study. In Spain, the slow predicted growth of the trees meant that, even after including the environmental externalities, the arable system created greater societal benefit than the agroforestry and tree-only systems. In Switzerland, including the environmental externalities increased the attraction of the tree-only system, but the high subsidies for arable and agroforestry systems meant that the EAVE for the agroforestry and arable systems were the most attractive from a farmer’s perspective. A breakeven analysis was used to determine the environmental externality values at which the agroforestry and tree-only systems produced the same societal return as the arable system in each case study. In the UK, a carbon price of ₠16 (t CO2)-1 allowed the EAVE of the agroforestry system to attain parity with the arable EAVE. In both the UK and Spain, an environmental nitrogen cost of ₠3-6 (kg N)-1 was sufficient for the EAVE of the agroforestry and tree-only systems to match those of arable farming. Because trees on farms provide ‘‘economies of multifunction’’ for environmental benefits, the breakeven values will be less if environmental benefits are considered together as packages. The described approach provides a method for governments and others to examine the cost effectiveness of new agri-environment measure

Mimicry of a constitutively active pre–B cell receptor in acute lymphoblastic leukemia cells

Pre–B cells undergo apoptosis unless they are rescued by pre–B cell receptor–dependent survival signals. We previously showed that the BCR-ABL1 kinase that is expressed in pre–B lymphoblastic leukemia bypasses selection for pre–B cell receptor–dependent survival signals. Investigating possible interference of BCR-ABL1 with pre–B cell receptor signaling, we found that neither SYK nor SLP65 can be phosphorylated in response to pre–B cell receptor engagement. Instead, Bruton's tyrosine kinase (BTK) is constitutively phosphorylated by BCR-ABL1. Activated BTK is essential for survival signals that otherwise would arise from the pre–B cell receptor, including activation of PLCγ1, autonomous Ca(2+) signaling, STAT5-phosphorylation, and up-regulation of BCLX (L). Inhibition of BTK activity specifically induces apoptosis in BCR-ABL1 (+) leukemia cells to a similar extent as inhibition of BCR-ABL1 kinase activity itself. However, BCR-ABL1 cannot directly bind to full-length BTK. Instead, BCR-ABL1 induces the expression of a truncated splice variant of BTK that acts as a linker between the two kinases. As opposed to full-length BTK, truncated BTK lacks kinase activity yet can bind to BCR-ABL1 through its SRC-homology domain 3. Acting as a linker, truncated BTK enables BCR-ABL1–dependent activation of full-length BTK, which initiates downstream survival signals and mimics a constitutively active pre–B cell receptor