de Sitter spacetime: effects of metric perturbations on geodesic motion

Gravitational perturbations of the de Sitter spacetime are investigated using the Regge--Wheeler formalism. The set of perturbation equations is reduced to a single second order differential equation of the Heun-type for both electric and magnetic multipoles. The solution so obtained is used to study the deviation from an initially radial geodesic due to the perturbation. The spectral properties of the perturbed metric are also analyzed. Finally, gauge- and tetrad-invariant first-order massless perturbations of any spin are explored following the approach of Teukolsky. The existence of closed-form, i.e. Liouvillian, solutions to the radial part of the Teukolsky master equation is discussed.Comment: IOP macros, 10 figure

Carotid Artery Stenting Using a Novel Self-Expanding Braided Nickel–Titanium Stent: Feasibility and Safety Porcine Trial

We studied the deliverability and safety of a braided, self-expanding, closed-cell nickel–titanium (NiTi) stent (E-volution, Jotec GmbH, Hechingen, Germany) especially designed for the endovascular treatment of carotid artery bifurcation stenosis with special regard to in-stent stenosis and thrombosis compared with a laser-cut reference nitinol stent in a porcine model of percutaneous vascular interventions. We aimed to assess histopathologic response in minipig carotid and subclavian arteries. Eight minipigs received a total of 42 stents: 14 reference stents and 28 E-volution stents. Eleven of the E-volution stents were additionally coated with heparin. Control angiography was obtained immediately before and after vascular intervention as well as 4 weeks after the procedure. Primary endpoints were 28 days of angiographic analyses as well as histomorphometric analysis, including injury score, inflammation score, luminal diameter, vessel diameter, maximal neointimal thickness, and area of in-stent stenosis. Secondary end points were procedural success, 28-day mortality, and stent thrombosis. All stents could be delivered successfully without procedural complications, morbidity, or mortality during our observation time. As confirmed by histology, no in-stent thrombosis was observed. Compared with common carotid arteries, subclavian arteries are significantly more vulnerable to developing in-stent stenosis caused by neointima proliferation (p < 0.05). Compared with the use of 1 single stent/artery, serial application of two stents leads to a more excessive but not significantly different neointimal proliferation (p > 0.05). The E-volution stent, especially when heparin coated, is in line with the comparison to the laser-cut reference stent displaying similar results of angiographic, histologic, and histomorphometric analyses (p > 0.05). Compared with the reference laser-cut stent, the self-expanding nitinol stent (E-volution) with its advanced braiding technology is feasible and safe. In our opinion, the high radial resistive force and the advanced braided design with tight stent-strut interstices may be beneficial in terms of plaque stabilization. Further studies are necessary and warranted

Current status and future opportunities for serial crystallography at MAX IV Laboratory

Over the last decade, serial crystallography, a method to collect complete diffraction datasets from a large number of microcrystals delivered and exposed to an X-ray beam in random orientations at room temperature, has been successfully implemented at X-ray free-electron lasers and synchrotron radiation facility beamlines. This development relies on a growing variety of sample presentation methods, including different fixed target supports, injection methods using gas-dynamic virtual-nozzle injectors and high-viscosity extrusion injectors, and acoustic levitation of droplets, each with unique requirements. In comparison with X-ray free-electron lasers, increased beam time availability makes synchrotron facilities very attractive to perform serial synchrotron X-ray crystallography (SSX) experiments. Within this work, the possibilities to perform SSX at BioMAX, the first macromolecular crystallography beamline at MAX IV Laboratory in Lund, Sweden, are described, together with case studies from the SSX user program: an implementation of a high-viscosity extrusion injector to perform room temperature serial crystallography at BioMAX using two solid supports - silicon nitride membranes (Silson, UK) and XtalTool (Jena Bioscience, Germany). Future perspectives for the dedicated serial crystallography beamline MicroMAX at MAX IV Laboratory, which will provide parallel and intense micrometre-sized X-ray beams, are discussed

Integrating innovations:a qualitative analysis of referral non-completion among rapid diagnostic test-positive patients in Uganda's human African trypanosomiasis elimination programme

BACKGROUND: The recent development of rapid diagnostic tests (RDTs) for human African trypanosomiasis (HAT) enables elimination programmes to decentralise serological screening services to frontline health facilities. However, patients must still undertake multiple onwards referral steps to either be confirmed or discounted as cases. Accurate surveillance thus relies not only on the performance of diagnostic technologies but also on referral support structures and patient decisions. This study explored why some RDT-positive suspects failed to complete the diagnostic referral process in West Nile, Uganda. METHODS: Between August 2013 and June 2015, 85% (295/346) people who screened RDT-positive were examined by microscopy at least once; 10 cases were detected. We interviewed 20 RDT-positive suspects who had not completed referral (16 who had not presented for their first microscopy examination, and 4 who had not returned for a second to dismiss them as cases after receiving discordant [RDT-positive, but microscopy-negative results]). Interviews were analysed thematically to examine experiences of each step of the referral process. RESULTS: Poor provider communication about HAT RDT results helped explain non-completion of referrals in our sample. Most patients were unaware they were tested for HAT until receiving results, and some did not know they had screened positive. While HAT testing and treatment is free, anticipated costs for transportation and ancillary health services fees deterred many. Most expected a positive RDT result would lead to HAT treatment. RDT results that failed to provide a definitive diagnosis without further testing led some to question the expertise of health workers. For the four individuals who missed their second examination, complying with repeat referral requests was less attractive when no alternative diagnostic advice or treatment was given. CONCLUSIONS: An RDT-based surveillance strategy that relies on referral through all levels of the health system is inevitably subject to its limitations. In Uganda, a key structural weakness was poor provider communication about the possibility of discordant HAT test results, which is the most common outcome for serological RDT suspects in a HAT elimination programme. Patient misunderstanding of referral rationale risks harming trust in the whole system and should be addressed in elimination programmes

HPV vaccine decision making in pediatric primary care: a semi-structured interview study

<p>Abstract</p> <p>Background</p> <p>Despite national recommendations, as of 2009 human papillomavirus (HPV) vaccination rates were low with < 30% of adolescent girls fully vaccinated. Research on barriers to vaccination has focused separately on parents, adolescents, or clinicians and not on the decision making process among all participants at the point of care. By incorporating three distinct perspectives, we sought to generate hypotheses to inform interventions to increase vaccine receipt.</p> <p>Methods</p> <p>Between March and June, 2010, we conducted qualitative interviews with 20 adolescent-mother-clinician triads (60 individual interviews) directly after a preventive visit with the initial HPV vaccine due. Interviews followed a guide based on published HPV literature, involved 9 practices, and continued until saturation of the primary themes was achieved. Purposive sampling balanced adolescent ages and practice type (urban resident teaching versus non-teaching). Using a modified grounded theory approach, we analyzed data with NVivo8 software both within and across triads to generate primary themes.</p> <p>Results</p> <p>The study population was comprised of 20 mothers (12 Black, 9 < high school diploma), 20 adolescents (ten 11-12 years old), and 20 clinicians (16 female). Nine adolescents received the HPV vaccine at the visit, eight of whom were African American. Among the 11 not vaccinated, all either concurrently received or were already up-to-date on Tdap and MCV4. We did not observe systematic patterns of vaccine acceptance or refusal based on adolescent age or years of clinician experience. We identified 3 themes: (1) Parents delayed, rather than refused vaccination, and when they expressed reluctance, clinicians were hesitant to engage them in discussion. (2) Clinicians used one of two strategies to present the HPV vaccine, either presenting it as a routine vaccine with no additional information or presenting it as optional and highlighting risks and benefits. (3) Teens considered themselves passive participants in decision making, even when parents and clinicians reported including them in the process.</p> <p>Conclusions</p> <p>Programs to improve HPV vaccine delivery in primary care should focus on promoting effective parent-clinician communication. Research is needed to evaluate strategies to help clinicians engage reluctant parents and passive teens in discussion and measure the impact of distinct clinician decision making approaches on HPV vaccine delivery.</p

Stat1 Phosphorylation Determines Ras Oncogenicity by Regulating p27Kip1

Inactivation of p27Kip1 is implicated in tumorigenesis and has both prognostic and treatment-predictive values for many types of human cancer. The transcription factor Stat1 is essential for innate immunity and tumor immunosurveillance through its ability to act downstream of interferons. Herein, we demonstrate that Stat1 functions as a suppressor of Ras transformation independently of an interferon response. Inhibition of Ras transformation and tumorigenesis requires the phosphorylation of Stat1 at tyrosine 701 but is independent of Stat1 phosphorylation at serine 727. Stat1 induces p27Kip1 expression in Ras transformed cells at the transcriptional level through mechanisms that depend on Stat1 phosphorylation at tyrosine 701 and activation of Stat3. The tumor suppressor properties of Stat1 in Ras transformation are reversed by the inactivation of p27Kip1. Our work reveals a novel functional link between Stat1 and p27Kip1, which act in coordination to suppress the oncogenic properties of activated Ras. It also supports the notion that evaluation of Stat1 phosphorylation in human tumors may prove a reliable prognostic factor for patient outcome and a predictor of treatment response to anticancer therapies aimed at activating Stat1 and its downstream effectors

Conditional Stat1 Ablation Reveals the Importance of Interferon Signaling for Immunity to Listeria monocytogenes Infection

Signal transducer and activator of transcription 1 (Stat1) is a key player in responses to interferons (IFN). Mutations of Stat1 cause severe immune deficiencies in humans and mice. Here we investigate the importance of Stat1 signaling for the innate and secondary immune response to the intracellular bacterial pathogen Listeria monocytogenes (Lm). Cell type-restricted ablation of the Stat1 gene in naïve animals revealed unique roles in three cell types: macrophage Stat1 signaling protected against lethal Lm infection, whereas Stat1 ablation in dendritic cells (DC) did not affect survival. T lymphocyte Stat1 reduced survival. Type I IFN (IFN-I) signaling in T lymphocytes reportedly weakens innate resistance to Lm. Surprisingly, the effect of Stat1 signaling was much more pronounced, indicating a contribution of Stat1 to pathways other than the IFN-I pathway. In stark contrast, Stat1 activity in both DC and T cells contributed positively to secondary immune responses against Lm in immunized animals, while macrophage Stat1 was dispensable. Our findings provide the first genetic evidence that Stat1 signaling in different cell types produces antagonistic effects on innate protection against Lm that are obscured in mice with complete Stat1 deficiency. They further demonstrate a drastic change in the cell type-dependent Stat1 requirement for memory responses to Lm infection