Intestinal parasites from public and private latrines and the harbour canal in Roman Period Ephesus, Turkey (1st c. BCE to 6th c. CE)

To improve our knowledge of the parasite species affecting the inhabitants of Roman period Asia Minor, we analysed faecal material from Ephesus, Turkey. Mineralised material from the drain from a private house latrine (3rd c. CE), sediment samples from the sewer drain of a public communal latrine (6th c. CE), and sediment from the harbour canal (ca. 1st c. BCE to ca. 6th c. CE) were studied for the presence of intestinal parasites. Samples were viewed by light microscopy for helminth eggs, and commercial enzyme-linked immunosorbent assay (ELISA) kits were used to test for protozoal parasites that cause dysentery. Eggs of roundworm were found in the public latrine, whipworm in the house latrine, and both whipworm and roundworm in the harbour canal. Sequential sampling of the harbour core suggests that whipworm was by far the most common parasite throughout the Roman period, and there was no clear evidence for change in parasite species over the centuries. Whipworm and roundworm are both spread by the contamination of food and drink by human faeces. Despite the large number of travellers to Ephesus, as the capital of its province and a major port city in the Roman Empire, there was a surprising lack of diversity in parasite species found. This is especially apparent when we consider that ten species of intestinal parasite have been found across the Roman Empire. This is the first Roman site to be directly assessed for differences between infection in individuals using private latrines, public latrines, and mixed town effluent (in the harbour) at the same site.This research was supported by a doctoral award from the Social Sciences and Humanities Research Council of Canada [752-2016-2085] and a Tidmarsh Cambridge Scholarship from the Cambridge Commonwealth, European and International Trust and Trinity Hall Colleg

Closed incision management with negative pressure wound therapy after forelimb amputation in a dog

A four-year-old male castrated German shepherd dog was presented with severe left front leg lameness due to a fibrosarcoma lateral to the elbow. The ill-defined mass was not amendable to wide local excision and a curative-intent limb amputation was performed. Immediately postoperatively, closed incision management with negative pressure wound therapy (NPWT) was applied to minimize the risk of postoperative complications. The incision line was covered with a Prevena (TM) dressing attached to a NPWT pump set at a continuous negative pressure of -125 mmHg. The dressing was removed 72 hours later. No wound complications were evident and further healing was unremarkable

Acidic Extracellular pH Promotes Activation of Integrin αvβ3

Acidic extracellular pH is characteristic of the cell microenvironment in several important physiological and pathological contexts. Although it is well established that acidic extracellular pH can have profound effects on processes such as cell adhesion and migration, the underlying molecular mechanisms are largely unknown. Integrin receptors physically connect cells to the extracellular matrix, and are thus likely to modulate cell responses to extracellular conditions. Here, we examine the role of acidic extracellular pH in regulating activation of integrin [alpha]v[beta]3. Through computational molecular dynamics simulations, we find that acidic extracellular pH promotes opening of the [alpha]v[beta]3 headpiece, indicating that acidic pH can thereby facilitate integrin activation. This prediction is consistent with our flow cytometry and atomic force microscope-mediated force spectroscopy assays of integrin [alpha]v[beta]3 on live cells, which both demonstrate that acidic pH promotes activation at the intact cell surface. Finally, quantification of cell morphology and migration measurements shows that acidic extracellular pH affects cell behavior in a manner that is consistent with increased integrin activation. Taken together, these computational and experimental results suggest a new and complementary mechanism of integrin activation regulation, with associated implications for cell adhesion and migration in regions of altered pH that are relevant to wound healing and cancer.National Institute of Biomedical Imaging and Bioengineering (U.S.) (Award Number T32EB006348)Massachusetts Institute of Technology (Collamore-Rogers Fellowship)National Institutes of Health (U.S.) (NIH Cell Migration Consortium Grant U54-GM069668)National Science Foundation (U.S.) (CAREER Award)Singapore-MIT Alliance for Research and Technology (BioSystem and Micromechanics (BioSyM) Interdisciplinary Research Group

Meta-analysis of Genome Wide Association Studies Identifies Genetic Markers of Late Toxicity Following Radiotherapy for Prostate Cancer.

Nearly 50% of cancer patients undergo radiotherapy. Late radiotherapy toxicity affects quality-of-life in long-term cancer survivors and risk of side-effects in a minority limits doses prescribed to the majority of patients. Development of a test predicting risk of toxicity could benefit many cancer patients. We aimed to meta-analyze individual level data from four genome-wide association studies from prostate cancer radiotherapy cohorts including 1564 men to identify genetic markers of toxicity. Prospectively assessed two-year toxicity endpoints (urinary frequency, decreased urine stream, rectal bleeding, overall toxicity) and single nucleotide polymorphism (SNP) associations were tested using multivariable regression, adjusting for clinical and patient-related risk factors. A fixed-effects meta-analysis identified two SNPs: rs17599026 on 5q31.2 with urinary frequency (odds ratio [OR] 3.12, 95% confidence interval [CI] 2.08-4.69, p-value 4.16×10(-8)) and rs7720298 on 5p15.2 with decreased urine stream (OR 2.71, 95% CI 1.90-3.86, p-value=3.21×10(-8)). These SNPs lie within genes that are expressed in tissues adversely affected by pelvic radiotherapy including bladder, kidney, rectum and small intestine. The results show that heterogeneous radiotherapy cohorts can be combined to identify new moderate-penetrance genetic variants associated with radiotherapy toxicity. The work provides a basis for larger collaborative efforts to identify enough variants for a future test involving polygenic risk profiling.This work was supported by Cancer Research UK (C1094/A11728 to CMLW and NGB for the RAPPER study, C26900/A8740 to GCB, and C8197/A10865 to AMD), the Royal College of Radiologists (C26900/ A8740 to GCB), the National Institute for Health Research (GCB; no grant number), Addenbrooke's Charitable Trust (GCB; no grant number), Institute of Cancer Research (National Institute for Health Research) Biomedical Research Centre (C46/A2131 to DPD and SG), the National Institute for Health Research Cambridge Biomedical Research Centre (NGB; no grant number), UK Medical Research Council (RG70550 to LD), the Joseph Mitchell Trust (AMD; no grant number), the Experimental Cancer Medicine Centre (CMLW; no grant number), Cancer Research UK Program grant Section of Radiotherapy (C33589/ A19727 to SLG), the United States National Institutes of Health (1R01CA134444 to BSR and HO, 2P30CA014520-34 to SB, and 1K07CA187546-01A1 to SLK), the American Cancer Society (RSGT-05- 200-01-CCE to BSR), the U.S. Department of Defense (PC074201 to BSR and HO), Mount Sinai Tisch Cancer Institute Developmental Fund Award (BSR; no grant number), the Instituto de Salud Carlos III (FIS PI10/00164 and PI13/02030 to AV and PI13/01136 to AC), Fondo Europeo de Desarrollo Regional (FEDER 2007–2013 to AV and AC; no grant number), Instituto de Salud Carlos III (FIS PI10/00164 and PI13/ 02030 to AV and PI13/01136 to AC), Xunta de Galicia and the European Social Fund (POS-A/2013/034 to LF), and the Alberta Cancer Board Research Initiative Program (103.0393.71760001404 to MP). AMD receives support from the REQUITE study, which is funded by the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 601826. Laboratory infrastructure for the RAPPER study was funded by Cancer Research UK [C8197/A10123] and the Manchester Experimental Cancer Medicine Centre. The RAPPER cohort comprises individuals and data recruited into the RT01 and CHHiP UK radiotherapy trials. The RT01 trial was supported by the UK Medical Research Council. The CHHiP trial (CRUK/06/016) was supported by the Department of Health and Cancer Research UK (C8262/A7253); trial recruitment was facilitated within centers by the National Institute for Health Research Cancer Research Network. DPD and SLG acknowledge NHS funding to the NIHR Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and Institute of Cancer Research.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.ebiom.2016.07.02

Age and sex-associated variation in the multi-site microbiome of an entire social group of free-ranging rhesus macaques

Background: An individual’s microbiome changes over the course of its lifetime, especially during infancy, and again in old age. Confounding factors such as diet and healthcare make it difficult to disentangle the interactions between age, health, and microbial changes in humans. Animal models present an excellent opportunity to study age- and sex-linked variation in the microbiome, but captivity is known to influence animal microbial abundance and composition, while studies of free-ranging animals are typically limited to studies of the fecal microbiome using samples collected non-invasively. Here, we analyze a large dataset of oral, rectal, and genital swabs collected from 105 free-ranging rhesus macaques (Macaca mulatta, aged 1 month-26 years), comprising one entire social group, from the island of Cayo Santiago, Puerto Rico. We sequenced 16S V4 rRNA amplicons for all samples. Results: Infant gut microbial communities had significantly higher relative abundances of Bifidobacterium and Bacteroides and lower abundances of Ruminococcus, Fibrobacter, and Treponema compared to older age groups, consistent with a diet high in milk rather than solid foods. The genital microbiome varied widely between males and females in beta-diversity, taxonomic composition, and predicted functional profiles. Interestingly, only penile, but not vaginal, microbiomes exhibited distinct age-related changes in microbial beta-diversity, taxonomic composition, and predicted functions. Oral microbiome composition was associated with age, and was most distinctive between infants and other age classes. Conclusions: Across all three body regions, with notable exceptions in the penile microbiome, while infants were distinctly different from other age groups, microbiomes of adults were relatively invariant, even in advanced age. While vaginal microbiomes were exceptionally stable, penile microbiomes were quite variable, especially at the onset of reproductive age. Relative invariance among adults, including elderly individuals, is contrary to findings in humans and mice. We discuss potential explanations for this observation, including that age-related microbiome variation seen in humans may be related to changes in diet and lifestyle. 4_dARqKdohA9mAZyu7q9YNVideo abstrac

Azimuthal anisotropy and correlations at large transverse momenta in p+pp+p and Au+Au collisions at sNN\sqrt{s_{_{NN}}}= 200 GeV

Results on high transverse momentum charged particle emission with respect to the reaction plane are presented for Au+Au collisions at $\sqrt{s_{_{NN}}}$= 200 GeV. Two- and four-particle correlations results are presented as well as a comparison of azimuthal correlations in Au+Au collisions to those in $p+p$ at the same energy. Elliptic anisotropy, $v_2$, is found to reach its maximum at $p_t \sim 3$ GeV/c, then decrease slowly and remain significant up to $p_t\approx 7$ -- 10 GeV/c. Stronger suppression is found in the back-to-back high-$p_t$ particle correlations for particles emitted out-of-plane compared to those emitted in-plane. The centrality dependence of $v_2$ at intermediate $p_t$ is compared to simple models based on jet quenching.Comment: 4 figures. Published version as PRL 93, 252301 (2004

Azimuthal anisotropy in Au+Au collisions at sqrtsNN = 200 GeV

The results from the STAR Collaboration on directed flow (v_1), elliptic flow (v_2), and the fourth harmonic (v_4) in the anisotropic azimuthal distribution of particles from Au+Au collisions at sqrtsNN = 200 GeV are summarized and compared with results from other experiments and theoretical models. Results for identified particles are presented and fit with a Blast Wave model. Different anisotropic flow analysis methods are compared and nonflow effects are extracted from the data. For v_2, scaling with the number of constituent quarks and parton coalescence is discussed. For v_4, scaling with v_2^2 and quark coalescence is discussed.Comment: 26 pages. As accepted by Phys. Rev. C. Text rearranged, figures modified, but data the same. However, in Fig. 35 the hydro calculations are corrected in this version. The data tables are available at http://www.star.bnl.gov/central/publications/ by searching for "flow" and then this pape