Vaccinations, infections and antibacterials in the first grass pollen season of life and risk of later hayfever

Published source: Bremner, S. A., Carey, I. M., DeWilde, S., Richards, N., Maier, W. C., Hilton, S. R., Strachan, D. P. and Cook, D. G. (2007), Vaccinations, infections and antibacterials in the first grass pollen season of life and risk of later hayfever. Clinical & Experimental Allergy, 37: 512–517. doi: 10.1111/j.1365-2222.2007.02697.

A Seamless Convergence of the Digital and Physical Factory Aiming in Personalized Product Emergence Process (PPEP) for Smart Products within ESB Logistics Learning Factory at Reutlingen University

AbstractA seamless convergence of the digital and physical factory aiming in personalized Product Emergence Process (PPEP) for smart products within ESB Logistics Learning Factory at Reutlingen University.A completely new business model with reference to Industrie4.0 and facilitated by 3D Experience Software in today's networked society in which customers expect immediate responses, delightful experience and simple solutions is one of the mission scenarios in the ESB Logistics Learning Factory at ESB Business School (Reutlingen University).The business experience platform provides software solutions for every organization in the company respectively in the factory. An interface with dashboards, project management apps, 3D - design and construction apps with high end visualization, manufacturing and simulation apps as well as intelligence and social network apps in a collaborative interactive environment help the user to learn the creation of a value end to end process for a personalized virtual and later real produced product.Instead of traditional ways of working and a conventional operating factory real workers and robots work semi-intuitive together. Centerpiece in the self-planned interim factory is the smart personalized product, uniquely identifiable and locatable at all times during the production process – a scooter with an individual colored mobile phone – holder for any smart phone produced with a 3D printer in lot size one. Smart products have in the future solutions incorporated internet based services – designed and manufactured - at the costs of mass products. Additionally the scooter is equipped with a retrievable declarative product memory. Monitoring and control is handled by sensor tags and a raspberry positioned on the product. The engineering design and implementation of a changeable production system is guided by a self-execution system that independently find amongst others esplanade workplaces.The imparted competences to students and professionals are project management method SCRUM, customization of workflows by Industrie4.0 principles, the enhancements of products with new personalized intelligent parts, electrical and electronic self-programmed components and the control of access of the product memory information, to plan in a digital engineering environment and set up of the physical factory to produce customer orders. The gained action-orientated experience refers to the chances and requirements for holistic digital and physical systems

The Burden Patients with Myasthenia Gravis Experience in Terms of Breathing, Fatigue, Sleep, Mental Health, Discomfort and Usual Activities in Comparison to the General Population

Introduction: Myasthenia gravis (MG) is a rare neuromuscular disorder marked by a variable combination of weakness of eye, bulbar, respiratory, axial, and limb muscles. This study compared the experience of people with MG regarding breathing, fatigue, sleep, pain/discomfort, mental health, and usual activities with the general population. Methods: The MyRealWorld-MG digital, multinational study enrolled patients with MG and collected demographics, PROMIS-Dyspnea, PROMIS-Sleep Disturbance, FACIT-Fatigue, EQ-5D-5L, Health Utilities Index (HUI-3), Hospital Anxiety and Depression Scale (HADS), MG-Activities of Daily Living (MG-ADL), and MG-Quality-of-Life (MG-QoL-15r). Comparisons with the general population were based on PROMIS population norms, published literature, or on data from a digital, multinational, observational study which enrolled a representative sample of the general population (POPUP). Results: In MyRealWorld-MG (N = 2074), patients experienced higher intensity, frequency, and duration of PROMIS shortness of breath than a US population (p &lt; 0.0001). Patients with MG had higher PROMIS-Sleep Disturbance scores than POPUP (53.7 vs 50.0, p &lt; 0.0001), and 54.9% of patients had clinically severe FACIT-Fatigue scores vs 6.8% in POPUP (p &lt; 0.0001). Among patients with MG, 69.6% and 18.5% had moderate-to-severe HADS-Anxiety and HADS-Depression compared to 20.3% and 6.9% in POPUP (p &lt; 0.001). Statistically significant and strong associations were found between fatigue, sleep, dyspnea, usual activities, and emotions. All outcomes worsened with more severe disease. Conclusion: A considerable burden was observed in this comparison of breathing, sleep, fatigue, mental health, and usual activities between patients with MG and the general population, using data from two international studies and published population norms. Even mildly affected patients had significantly worse outcomes than the general population.</p

People Diagnosed with Myasthenia Gravis have Lower health-related quality of life and Need More Medical and Caregiver Help in Comparison to the General Population:Analysis of Two Observational Studies

Introduction: Myasthenia gravis (MG) is a neuromuscular disease causing extreme muscular fatigue, triggering problems with vision, swallowing, speech, mobility, dexterity, and breathing. This analysis intended to estimate the health-related quality-of-life impact, the medical burden, and the need for caregiver help of people diagnosed with MG. Methods: MyRealWorld-MG (MRW) is an observational study among adults diagnosed with MG in 9 countries. The General Population Norms (POPUP) observational study enrolled representative members of the general population in 8 countries. In both digital studies, respondents entered personal characteristics and provided data on medical conditions, EQ-5D-5L, HUI3, MG-Activities of Daily Living (MG-ADL), sick leave, caregiver help, and medical care utilization. Results: In MRW (n = 1859), 58.4% of respondents had moderate-to-severe MG. Average utility values were lower in MRW versus POPUP (0.739 vs. 0.843 for EQ-5D-5L; 0.493 vs. 0.746 for HUI3), and declined with more severe disease (0.872, 0.707, 0.511 EQ-5D-5L utilities and 0.695, 0.443, 0.168 HUI3 utilities for mild, moderate, and severe MG, respectively). Taking sick leave in the past month was 2.6 times more frequent among people diagnosed with MG compared to the general population (34.4% vs. 13.2%) and four times more people diagnosed with MG reported needing help from a caregiver (34.8% vs. 8.3%). Use of medical care was twice as likely in MRW in comparison with POPUP (51.9% vs. 24.6%). Conclusion: This direct comparison of people diagnosed with MG and the general population using two large international studies revealed significant negative impact of MG. Results were consistent across all outcomes, in all countries.</p

Do good health and material circumstances protect older people from the increased risk of death after bereavement?

This is an open access Article. Copyright @ 2012 The AuthorsAn increased risk of death in persons who have suffered spousal bereavement has been described in many populations. The impact of modifying factors, such as chronic disease and material circumstances, is less well understood. The authors followed 171,120 couples 60 years of age or older in a United Kingdom primary care database between 2005 and 2010 for an average of 4 years. A total of 26,646 (15.5%) couples experienced bereavement, with mean follow up after bereavement of 2 years. In a model adjusted for age, sex, comorbid conditions at baseline, material deprivation based on area of residence, season, and smoking status, the hazard ratio for mortality in the first year after bereavement was 1.25 (95% confidence interval: 1.18, 1.33). Further adjustment for changes in comorbid conditions throughout follow up did not alter the hazard ratio for bereavement (hazard ratio = 1.27, 95% confidence interval: 1.19, 1.35). The association was strongest in individuals with no significant chronic comorbid conditions throughout follow up (hazard ratio = 1.50, 95% confidence interval: 1.28, 1.77) and in more affluent couples (P = 0.035). In the first year after bereavement, the association between bereavement and death is not primarily mediated through worsening or new onset of chronic disease. Good health and material circumstances do not protect individuals from increased mortality rates after bereavement.This study was funded by a grant from the Dunhill Medical Trust

Phase Space Reduction for Star-Products: An Explicit Construction for CP^n

We derive a closed formula for a star-product on complex projective space and on the domain $SU(n+1)/S(U(1)\times U(n))$ using a completely elementary construction: Starting from the standard star-product of Wick type on $C^{n+1} \setminus \{ 0 \}$ and performing a quantum analogue of Marsden-Weinstein reduction, we can give an easy algebraic description of this star-product. Moreover, going over to a modified star-product on $C^{n+1} \setminus \{ 0 \}$, obtained by an equivalence transformation, this description can be even further simplified, allowing the explicit computation of a closed formula for the star-product on \CP^n which can easily transferred to the domain $SU(n+1)/S(U(1)\times U(n))$.Comment: LaTeX, 17 page

High resolution crystal structures of the <i>Cerebratulus lacteus</i> mini-Hb in the unligated and carbomonoxy states

The nerve tissue mini-hemoglobin from Cerebratulus lacteus (CerHb) displays an essential globin fold hosting a protein matrix tunnel held to allow traffic of small ligands to and from the heme. CerHb heme pocket hosts the distal TyrB10/GlnE7 pair, normally linked to low rates of O2 dissociation and ultra-high O2 affinity. However, CerHb affinity for O2 is similar to that of mammalian myoglobins, due to a dynamic equilibrium between high and low affinity states driven by the ability of ThrE11 to orient the TyrB10 OH group relative to the heme ligand. We present here the high resolution crystal structures of CerHb in the unligated and carbomonoxy states. Although CO binds to the heme with an orientation different from the O2 ligand, the overall binding schemes for CO and O2 are essentially the same, both ligands being stabilized through a network of hydrogen bonds based on TyrB10, GlnE7, and ThrE11. No dramatic protein structural changes are needed to support binding of the ligands, which can freely reach the heme distal site through the apolar tunnel. A lack of main conformational changes between the heme-unligated and -ligated states grants stability to the folded mini-Hb and is a prerequisite for fast ligand diffusion to/from the heme

Novel Human/Non-Human Primate Cross-Reactive Anti-Transferrin Receptor Nanobodies for Brain Delivery of Biologics

The blood-brain barrier (BBB), while being the gatekeeper of the central nervous system (CNS), is a bottleneck for the treatment of neurological diseases. Unfortunately, most of the biologicals do not reach their brain targets in sufficient quantities. The antibody targeting of receptor-mediated transcytosis (RMT) receptors is an exploited mechanism that increases brain permeability. We previously discovered an anti-human transferrin receptor (TfR) nanobody that could efficiently deliver a therapeutic moiety across the BBB. Despite the high homology between human and cynomolgus TfR, the nanobody was unable to bind the non-human primate receptor. Here we report the discovery of two nanobodies that were able to bind human and cynomolgus TfR, making these nanobodies more clinically relevant. Whereas nanobody BBB00515 bound cynomolgus TfR with 18 times more affinity than it did human TfR, nanobody BBB00533 bound human and cynomolgus TfR with similar affinities. When fused with an anti-beta-site amyloid precursor protein cleaving enzyme (BACE1) antibody (1A11AM), each of the nanobodies was able to increase its brain permeability after peripheral injection. A 40% reduction of brain Aβ1–40 levels could be observed in mice injected with anti-TfR/BACE1 bispecific antibodies when compared to vehicle-injected mice. In summary, we found two nanobodies that could bind both human and cynomolgus TfR with the potential to be used clinically to increase the brain permeability of therapeutic biologicals