Flavor Phenomenology in General 5D Warped Spaces

We have considered a general 5D warped model with SM fields propagating in the bulk and computed explicit expressions for oblique and non-oblique electroweak observables as well as for flavor and CP violating effective four-fermion operators. We have compared the resulting lower bounds on the Kaluza-Klein (KK) scale in the RS model and a recently proposed model with a metric modified towards the IR brane, which is consistent with oblique parameters without the need for a custodial symmetry. We have randomly generated 40,000 sets of O(1) 5D Yukawa couplings and made a fit of the quark masses and CKM matrix elements in both models. This method allows to identify the percentage of points consistent with a given KK mass, which in turn provides us with a measure for the required fine-tuning. Comparison with current experimental data on Rb, FCNC and CP violating operators exhibits an improved behavior of our model with respect to the RS model. In particular, allowing 10% fine-tuning the combined results point towards upper bounds on the KK gauge boson masses around 3.3 TeV in our model as compared with 13 TeV in the RS model. One reason for this improvement is that fermions in our model are shifted, with respect to fermions in the RS model, towards the UV brane thus decreasing the strength of the modifications of electroweak observables.Comment: 28 pages, 7 figures, 4 table

Absolutely stable proton and lowering the gauge unification scale

A unified model is constructed, based on flipped SU(5) in which the proton is absolutely stable. The model requires the existence of new leptons with masses of order the weak scale. The possibility that the unification scale could be extremely low is discussed

Flavour Physics in the Soft Wall Model

We extend the description of flavour that exists in the Randall-Sundrum (RS) model to the soft wall (SW) model in which the IR brane is removed and the Higgs is free to propagate in the bulk. It is demonstrated that, like the RS model, one can generate the hierarchy of fermion masses by localising the fermions at different locations throughout the space. However, there are two significant differences. Firstly the possible fermion masses scale down, from the electroweak scale, less steeply than in the RS model and secondly there now exists a minimum fermion mass for fermions sitting towards the UV brane. With a quadratic Higgs VEV, this minimum mass is about fifteen orders of magnitude lower than the electroweak scale. We derive the gauge propagator and despite the KK masses scaling as $m_n^2\sim n$, it is demonstrated that the coefficients of four fermion operators are not divergent at tree level. FCNC's amongst kaons and leptons are considered and compared to calculations in the RS model, with a brane localised Higgs and equivalent levels of tuning. It is found that since the gauge fermion couplings are slightly more universal and the SM fermions typically sit slightly further towards the UV brane, the contributions to observables such as $\epsilon_K$ and $\Delta m_K$, from the exchange of KK gauge fields, are significantly reduced.Comment: 33 pages, 15 figures, 5 tables; v2: references added; v3: modifications to figures 4,5 and 6. version to appear in JHE

Improving the normalization of complex interventions: measure development based on normalization process theory (NoMAD): study protocol

<b>Background</b> Understanding implementation processes is key to ensuring that complex interventions in healthcare are taken up in practice and thus maximize intended benefits for service provision and (ultimately) care to patients. Normalization Process Theory (NPT) provides a framework for understanding how a new intervention becomes part of normal practice. This study aims to develop and validate simple generic tools derived from NPT, to be used to improve the implementation of complex healthcare interventions.<p></p> <b>Objectives</b> The objectives of this study are to: develop a set of NPT-based measures and formatively evaluate their use for identifying implementation problems and monitoring progress; conduct preliminary evaluation of these measures across a range of interventions and contexts, and identify factors that affect this process; explore the utility of these measures for predicting outcomes; and develop an online users’ manual for the measures.<p></p> <b>Methods</b> A combination of qualitative (workshops, item development, user feedback, cognitive interviews) and quantitative (survey) methods will be used to develop NPT measures, and test the utility of the measures in six healthcare intervention settings.<p></p> <b>Discussion</b> The measures developed in the study will be available for use by those involved in planning, implementing, and evaluating complex interventions in healthcare and have the potential to enhance the chances of their implementation, leading to sustained changes in working practices

Refined clothespin relocation test and assessment of motion

Background: Advancements in upper limb prosthesis design have focused on providing increased degrees of freedom for the end effector through multiple articulations of a prosthetic hand, wrist and elbow. Measuring improvement in patient function with these devices requires development of appropriate assessment tools. Objectives: This study presents a refined clothespin relocation test for measuring performance and assessing compensatory motion between able-bodied subjects and subjects with upper limb impairments. Study Design: Comparative analysis Methods: Trunk and head motions of 13 able-bodied subjects who performed the refined clothespin relocation test were compared to the motion of a transradial prosthesis user with a single degree of freedom hand. Results: There were observable differences between the prosthesis user and the able-bodied group. The assessment used provided a clear indication of the differences in motion through analysis of compensatory motion. Conclusion: The refined clothespin relocation test provides additional benefits over the standard clothespin assessment and makes identification of compensatory motions easily identifiable to the researcher. While this paper establishes the method for the new assessment, further validation will need to be performed with more users

Effects of luteectomy in early pregnancy on the maintenance of gestation and plasma progesterone concentrations in the viviparous temperate lizard Barisia imbricata imbricata

<p>Abstract</p> <p>Background</p> <p>Several studies have shown that the corpus luteum is the principal source of progesterone during the gravidity period in reptiles; however, its participation in the maintenance of gestation in the viviparous squamata is in dispute. The effects of ovariectomy or luteectomy vary according to the species and the time at which the procedure is performed. In this paper, we describe the effects of luteectomy during early pregnancy on the maintenance of gestation and progesterone concentrations in the temperate Mexican viviparous lizard <it>Barisia imbricata imbricata.</it></p> <p>Methods</p> <p>Twenty-four lizards were subjected to three different treatments: luteectomy, sham luteectomy or non-surgical treatment, and blood samples were obtained before and after surgical treatment at different stages of gestation to determine the effects of luteectomy on the maintenance of gestation and progesterone concentrations.</p> <p>Results</p> <p>Spontaneous abortion was not observed in any of the females. However, luteectomy provoked abnormal parturition and a significant reduction in the number of young born alive. Parturition was normal in untreated females as well as those submitted to sham luteectomy. The surgical treatment also caused a significant reduction in progesterone concentrations in luteectomised females during early and middle gestation. However, no significant differences in hormone concentrations were observed among the three groups during late gestation or immediately post-parturition.</p> <p>Conclusions</p> <p>Our observations indicate that the presence of the corpus luteum is not necesary for the maintenance of gestation, but that it does participate in parturition control. Moreover, the corpus luteum of the viviparous lizard <it>B. i. imbricata</it> produces progesterone, at least during the first half of pregnancy, and that an extra-ovarian source of progesterone must maintain gestation in the absence of luteal tissue.</p

2019 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations : summary from the basic life support; advanced life support; pediatric life support; neonatal life support; education, implementation, and teams; and first aid task forces

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

Polymorphisms in the CD28/CTLA4/ICOS genes: Role in malignant melanoma susceptibility and prognosis?

The appearance of vitiligo and spontaneous regression of the primary lesion in melanoma patients illustrate a relationship between tumor immunity and autoimmunity. T lymphocytes play a major role both in tumor immunity and autoimmunity. CD28, Cytotoxic T lymphocyte antigen 4 (CTLA4) and inducible costimulator (ICOS) molecules are important secondary signal molecules in the T lymphocyte activation. Single nucleotide polymorphisms (SNPs) in the CD28/CTLA4/ICOS gene region were reported to be associated with several autoimmune diseases including, type-1 diabetes, SLE, autoimmune thyroid diseases and celiac disease. In this study, we investigated the association of SNPs in the CD28, CTLA4 and ICOS genes with the risk of melanoma. We also assessed the prognostic effect of the different polymorphisms in melanoma patients. Twenty-four tagging SNPs across the three genes and four additional SNPs were genotyped in a cohort of 763 German melanoma patients and 734 healthy German controls. Influence on prognosis was determined in 587 melanoma cases belonging to stage I or II of the disease. In general, no differences in genotype or allele frequencies were detected between melanoma patients and controls. However, the variant alleles for two polymorphisms in the CD28 gene were differentially distributed in cases and controls. Similarly no association of any polymorphism with prognosis, except for the rs3181098 polymorphism in the CD28 gene, was observed. In addition, individuals with AA genotype for rs11571323 polymorphism in the ICOS gene showed reduced overall survival. However, keeping in view the correction for multiple hypothesis testing our results suggest that the polymorphisms in the CD28, CTLA4 and ICOS genes at least do not modulate risk of melanoma and nor do those influence the disease prognosis in the investigated population

Genetic diversity at the Dhn3 locus in Turkish Hordeum spontaneum populations with comparative structural analyses

We analysed Hordeum spontaneum accessions from 21 different locations to understand the genetic diversity of HsDhn3 alleles and effects of single base mutations on the intrinsically disordered structure of the resulting polypeptide (HsDHN3). HsDHN3 was found to be YSK2-type with a low-frequency 6-aa deletion in the beginning of Exon 1. There is relatively high diversity in the intron region of HsDhn3 compared to the two exon regions. We have found subtle differences in K segments led to changes in amino acids chemical properties. Predictions for protein interaction profiles suggest the presence of a protein-binding site in HsDHN3 that coincides with the K1 segment. Comparison of DHN3 to closely related cereals showed that all of them contain a nuclear localization signal sequence flanking to the K1 segment and a novel conserved region located between the S and K1 segments [E(D/T)DGMGGR]. We found that H. vulgare, H. spontaneum, and Triticum urartu DHN3s have a greater number of phosphorylation sites for protein kinase C than other cereal species, which may be related to stress adaptation. Our results show that the nature and extent of mutations in the conserved segments of K1 and K2 are likely to be key factors in protection of cells

Phase II study of continuous daily sunitinib dosing in patients with previously treated advanced non-small cell lung cancer

Background:Sunitinib malate (SUTENT) has promising single-agent activity given on Schedule 4/2 (4 weeks on treatment followed by 2 weeks off treatment) in advanced non-small cell lung cancer (NSCLC).Methods:We examined the activity of sunitinib on a continuous daily dosing (CDD) schedule in an open-label, multicentre phase II study in patients with previously treated, advanced NSCLC. Patients ⩾18 years with stage IIIB/IV NSCLC after failure with platinum-based chemotherapy, received sunitinib 37.5 mg per day. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), overall survival (OS), 1-year survival rate, and safety.Results:Of 47 patients receiving sunitinib, one patient achieved a confirmed partial response (ORR 2.1% (95% confidence interval (CI) 0.1, 11.3)) and 11 (23.4%) had stable disease (SD) ⩾8 weeks. Five patients had SD>6 months. Median PFS was 11.9 weeks (95% CI 8.6, 14.1) and median OS was 37.1 weeks (95% CI 31.1, 69.7). The 1-year survival probability was 38.4% (95% CI 24.2, 52.5). Treatment was generally well tolerated.Conclusions:The safety profile and time-to-event analyses, albeit relatively low response rate of 2%, suggest single-agent sunitinib on a CDD schedule may be a potential therapeutic agent for patients with advanced, refractory NSCLC