Integrating testing for chronic strongyloidiasis within the Indigenous adult preventive health assessment system in endemic communities in the Northern Territory, Australia: An intervention study

Background The life-threatening clinical manifestations of strongyloidiasis are preventable with early detection and effective treatment. The aim of this study was to assess if there was an increase to the number and proportion of persons tested for chronic strongyloidiasis, as a result of integrating Strongyloides stercoralis serology into the existing preventive health assessment system in four Aboriginal health services in endemic communities. Methodology A prospective, longitudinal, before-and-after intervention study was conducted in four Aboriginal health services in remote endemically infected communities in the Northern Territory, Australia, from July 2012 to December 2016. The electronic patient information and recall systems enabled the integration of Strongyloides stercoralis serology into the adult preventive health assessment. Strongyloides reports for each health service were extracted half-yearly to examine the number and proportion of persons tested for chronic strongyloidiasis during the study and to measure the effect of the intervention. Principal findings The number and proportion of persons tested increased significantly during the study. From a total resident population of 3650 Indigenous adults over 15 years of age, 1686 persons (47.4%) were tested. The percentage of adults who had at least one serology test increased in all four health services to between 41% (446/1086) and 81.9% (172/210). Of the 1686 persons tested, 680 positive cases of chronic strongyloidiasis (40.3%) were identified. Conclusions/Significance This population health systems intervention increased the number and proportion of persons tested for chronic strongyloidiasis in four health services in endemically infected communities. This intervention is relevant to other health services with high-risk populations

Mutations in the 3'-untranslated region of GATA4 as molecular hotspots for congenital heart disease (CHD)

<p>Abstract</p> <p>Background</p> <p>The 3'-untranslated region (3'-UTR) of mRNA contains regulatory elements that are essential for the appropriate expression of many genes. These regulatory elements are involved in the control of nuclear transport, polyadenylation status, subcellular targetting as well as rates of translation and degradation of mRNA. Indeed, 3'-UTR mutations have been associated with disease, but frequently this region is not analyzed. To gain insights into congenital heart disease (CHD), we have been analyzing cardiac-specific transcription factor genes, including <it>GATA4</it>, which encodes a zinc finger transcription factor. Germline mutations in the coding region of <it>GATA4 </it>have been associated with septation defects of the human heart, but mutations are rather rare. Previously, we identified 19 somatically-derived zinc finger mutations in diseased tissues of malformed hearts. We now continued our search in the 609 bp 3'-UTR region of <it>GATA4 </it>to explore further molecular avenues leading to CHD.</p> <p>Methods</p> <p>By direct sequencing, we analyzed the 3'-UTR of <it>GATA4 </it>in DNA isolated from 68 formalin-fixed explanted hearts with complex cardiac malformations encompassing ventricular, atrial, and atrioventricular septal defects. We also analyzed blood samples of 12 patients with CHD and 100 unrelated healthy individuals.</p> <p>Results</p> <p>We identified germline and somatic mutations in the 3'-UTR of <it>GATA4</it>. In the malformed hearts, we found nine frequently occurring sequence alterations and six dbSNPs in the 3'-UTR region of <it>GATA4</it>. Seven of these mutations are predicted to affect RNA folding. We also found further five nonsynonymous mutations in exons 6 and 7 of <it>GATA4</it>. Except for the dbSNPs, analysis of tissue distal to the septation defect failed to detect sequence variations in the same donor, thus suggesting somatic origin and mosaicism of mutations. In a family, we observed c.+119A > T in the 3'-UTR associated with ASD type II.</p> <p>Conclusion</p> <p>Our results suggest that somatic <it>GATA4 </it>mutations in the 3'-UTR may provide an additional molecular rationale for CHD.</p

Exponential Distribution of Locomotion Activity in Cell Cultures

In vitro velocities of several cell types have been measured using computer controlled video microscopy, which allowed to record the cells' trajectories over several days. On the basis of our large data sets we show that the locomotion activity displays a universal exponential distribution. Thus, motion resulting from complex cellular processes can be well described by an unexpected, but very simple distribution function. A simple phenomenological model based on the interaction of various cellular processes and finite ATP production rate is proposed to explain these experimental results.Comment: 4 pages, 3 figure

Measurement of the Luminosity in the ZEUS Experiment at HERA II

The luminosity in the ZEUS detector was measured using photons from electron bremsstrahlung. In 2001 the HERA collider was upgraded for operation at higher luminosity. At the same time the luminosity-measuring system of the ZEUS experiment was modified to tackle the expected higher photon rate and synchrotron radiation. The existing lead-scintillator calorimeter was equipped with radiation hard scintillator tiles and shielded against synchrotron radiation. In addition, a magnetic spectrometer was installed to measure the luminosity independently using photons converted in the beam-pipe exit window. The redundancy provided a reliable and robust luminosity determination with a systematic uncertainty of 1.7%. The experimental setup, the techniques used for luminosity determination and the estimate of the systematic uncertainty are reported.Comment: 25 pages, 11 figure

Older Adults Walking the Camino de Santiago Pilgrimage: motivations, transformations, and spiritual perspectives

© The Author(s) 2020. This mixed-method study describes reasons that older people chose to complete the Camino de Santiago pilgrimage route in Spain and their assessment of how they were changed by the experience. The study is framed in Maslow’s (1988) self-actualization and Tornstam’s (2005) concept of gerotranscendence. We analyzed a subset of 121 participants age 65 and over who completed an online survey. Motivation included five themes: gratitude and transitions, cultural or historical curiosity. relationships, challenge and adventure, and spirituality. Transformations since their return involved greater strength, self-understanding, peace, desire to live lightly and to integrate their experience. Older individuals who walked the Camino have done so for a variety of reasons. Spiritual reasons may be more difficult to disclose. Half responded in the open-ended question, but a later spirituality question added many more respondents. Older people envision many forms of benefit to walking the pilgrimage and find growth in the experience

A New 76Ge Double Beta Decay Experiment at LNGS

This Letter of Intent has been submitted to the Scientific Committee of the INFN Laboratori Nazionali del Gran Sasso (LNGS) in March 2004. It describes a novel facility at the LNGS to study the double beta decay of 76Ge using an (optionally active) cryogenic fluid shield. The setup will allow to scrutinize with high significance on a short time scale the current evidence for neutrinoless double beta decay of 76Ge using the existing 76Ge diodes from the previous Heidelberg-Moscow and IGEX experiments. An increase in the lifetime limit can be achieved by adding more enriched detectors, remaining thereby background-free up to a few 100 kg-years of exposure.Comment: 67 pages, 19 eps figures, 17 tables, gzipped tar fil

Arene oxidation with malonoyl peroxides

Malonoyl peroxide 7, prepared in a single step from the commercially available diacid, is an effective reagent for the oxidation of aromatics. Reaction of an arene with peroxide 7 at room temperature leads to the corresponding protected phenol which can be unmasked by aminolysis. An ionic mechanism consistent with the experimental findings and supported by isotopic labeling, Hammett analysis, EPR investigations and reactivity profile studies is proposed

Dasatinib inhibits CXCR4 signaling in chronic lymphocytic leukaemia cells and impairs migration towards CXCL12

Chemokines and their ligands play a critical role in enabling chronic lymphocytic leukaemia (CLL) cells access to protective microenvironmental niches within tissues, ultimately resulting in chemoresistance and relapse: disruption of these signaling pathways has become a novel therapeutic approach in CLL. The tyrosine kinase inhibitor dasatinib inhibits migration of several cell lines from solid-organ tumours, but effects on CLL cells have not been reported. We studied the effect of clinically achievable concentrations of dasatinib on signaling induced by the chemokine CXCL12 through its' receptor CXCR4, which is highly expressed on CLL cells. Dasatinib pre-treatment inhibited Akt and ERK phosphorylation in CLL cells upon stimulation with CXCL12. Dasatinib also significantly diminished the rapid increase in actin polymerisation observed in CLL cells following CXCL12 stimulation. Moreover, the drug significantly inhibited chemotaxis in a transwell assay, and reduced the percentage of cells able to migrate beneath a CXCL12-expressing murine stromal cell line. Dasatinib also abrogated the anti-apoptotic effect of prolonged CXCL12 stimulation on cultured CLL cells. These data suggest that dasatinib, akin to other small molecule kinase inhibitors targeting the B-cell receptor signaling pathway, may redistribute CLL cells from protective tissue niches to the peripheral blood, and support the investigation of dasatinib in combination strategies