Journal articles on the topic 'Nino Ferrer'

Centaurea Linnaeus (1753: 909) (Asteraceae) comprises a large number of taxa mainly occurring in the Mediterranean region and southwest Asia (Susanna & Garcia-Jacas 2007). The former wide concept of Centaurea resulted in a polyphyletic assemblage, and it has been recently split into several putatively monophyletic genera Centaurea, Psephellus Cass. and Rhaponticoides Vaill. (Wagenitz & Hellwig 2000; Greuter 2003; Hellwig 2004; Susanna & Garcia-Jacas 2007, 2009). Centaurea sibirica Linnaeus (1753: 913) is spreading from S Russia to W Siberia and Central Asia (Wagenitz & Hellwig 2000), it is one of the species of sixty-nine names in Centaurea described by Linnaeus and is currently accepted as Psephellus sibiricus (L.) Wagenitz (Wagenitz & Hellwig 2000: 37). However, from a nomenclatural standpoint, Centaurea sibirica has not been typified (Jarvis 2007, Ferrer-Gallego et al. 2014a, 2014b, 2014c, Altınordu & Ferrer-Gallego 2015, Ferrer-Gallego & Altınordu 2016, Iamonico & Peruzzi 2016). This paper designates a lectotype for C. sibirica based on the protologue and consultation of Linnaeus’s original material.

The Charipinae from Colombia has been recently studied. Nine Charipinae species are known to be present in this country: Alloxysta arcuata (Kieffer, 1902), Alloxysta castanea (Hartig, 1841), Alloxysta consobrina (Zetterstedt, 1838), Alloxysta hansoni Pujade-Villar, 2011, Alloxysta obscurata (Hartig, 1840), Alloxysta medinae Ferrer-Suay & Pujade-Villar, 2012, Alloxysta pilipennis (Hartig, 1840), Alloxysta torresi Ferrer-Suay & Pujade-Villar, 2012 and Phaenoglyphis villosa (Hartig, 1841). Here more Charipinae material has been studied from collections made with Malaise traps by the Humboldt Institute in several places of Colombia. In this study, two species are recorded for the first time from Colombia: Alloxysta mullensis (Cameron, 1883) and Alloxysta xanthopa (Thomson, 1862). Data of the capture of the specimens are given.

Nine juvenile ferrets ( Mustela putorius furo) with a history of diarrhea were severely dehydrated and had distended abdomens and thin-walled small intestines that contained gas and fluid. Histologically, small intestines exhibited acute superficial atrophic enteritis. Transmission electron microscopy of the small intestine showed rotavirus-like particles within apical vacuoles. Reverse transcription polymerase chain reaction (RT-PCR) was negative for group A rotavirus. A group C rotavirus-specific RT-PCR assay was developed using consensus primers designed from the alignment of VP6 gene sequences of porcine, bovine, and human strains. A 182-bp product of the VP6 gene was sequenced and showed significant similarity to group C rotavirus VP6 sequences. This strain was designated “Ferret Rota C-MSU.” The entire coding sequence of VP6 was determined and compared with other rotaviruses. Ferret Rota C-MSU virus was found to be most closely related to Shintoku group C rotavirus. This is the first definitive identification of a group C rotavirus in ferrets, based upon RT-PCR, sequencing, and genetic analysis.

ZusammenfassungViren können bei Reptilien bedeutende Krankheitserreger sein. In den letzten Jahren wurden auch zunehmend neue Viren bei Reptilien beschrieben. Zudem gibt es immer mehr Möglichkeiten, Virusinfektionen bei Reptilien nachzuweisen. Dieser Übersichtsartikel bietet einen Überblick über häufige und bedeutende Virusinfektionen bei Reptilien, die damit assoziierten Krankheiten sowie deren Diagnose. Besprochen werden v. a. Infektionen bei Reptilien, die häufig als Haustiere gehalten werden: Schlangen und Echsen (Squamaten) sowie Land- und Wasserschildkröten. Themen bei den Squamaten sind die insbesondere bei Bartagamen (Pogona vitticeps) extrem häufig vorkommenden Adenoviren, ferner Paramyxo- und Tobaniviren (auch als Nido- oder Serpentoviren bekannt), die insbesondere bei verschiedenen Schlangenspezies schwere Atemwegserkrankungen verursachen können. Weitere Abschnitte beschäftigen sich mit Reptarenaviren, die die Einschlusskörperchenkrankheit („inclusion body disease“, IBD) der Boas und Pythons auslösen, sowie mit den v. a. bei verschiedenen Echsenspezies beschriebenen Iridoviren (inklusive der Rana-, Invertebraten-Irido- und Hemocytiviren). Bei den Schildkröten werden die Herpesviren der Land- und Wasserschildkröten separat diskutiert, ferner die vorkommenden Rana- und Picornaviren. Vertreter aller 3 dieser Virusfamilien können neben Erkrankungen des oberen Respirations- und Verdauungstrakts andere klinische Veränderungen hervorrufen (z. B. schwere Panzererweichung bei juvenilen Landschildkröten durch Picornaviren).

Genetic studies of the ferret badgers Melogale conducted in Vietnam have shown that this area is inhabited by three species, M. moschata, M. personata, and M. cucphuongensis, which can be attributed to sibling species (cryptic species). M. personata was found to be widespread not only in southern and central Vietnam, but also in the northern provinces (Lang Son, Ha Giang, Ninh Binh), while M. cucphuongensis was found in the provinces Lang Son, Ha Giang, Cao Bang, and Dak Lak, apart from Ninh Binh, from where it was described. The data obtained suggest a sympatric distribution of all three species over the Vietnam area and confirm sympatry of M. personata and M. moschata in southern Vietnam, which has been earlier established on the basis of morphological data.

An experiment was conducted to evaluate the germination, survival, growth performance and biomass yield of nine indigenous multipurpose tree species of Eastern Himalayan region. On average, highest germination (> 80 %) was recorded in Artocarpus heterophyllus, Duabanga grandiflora and Michelia champaca. Germination in the species like Murraya koenghii and Terminalia myriocarpa ranged between 60.0-75.0%. Lowest germination, however, was recorded in Mesua ferrea (35.80%). After one year of growth, the survival percentage was recorded highest in Aquilaria malaccensis (87.80%), followed by M. champaca (85.23%). Among various species, lowest survival was recorded in Phoebe goalparensis (52.70%). So far in height growth was concerned, T. myriocarpa exhibited the highest (61.77cm), followed by D. grandiflora (60.07cm). Aquilaria malaccensis, however, exhibited lowest height growth (44.26cm). Likewise, collar diameter growth was also recorded highest in the seedlings of T. myriocarpa (0.83 cm), followed by D. grandiflora (0.78 cm). Lowest collar diameter growth was recorded in M. ferrea (0.49cm). Significant (P= 0.05) variations were recorded in germination, survival and growth performance of different tree species. Strong positive correlation (P= 0.01) was recorded between height and collar diameter growth of the seedlings. Significant variations (P = 0.05) were also observed in total biomass of the seedlings. Among various species, T. myriocarpa had the highest biomass (19.07g/seedlings) after one year of growth, followed by M. champaca (18.57g/seedling). Lowest biomass (7.11g/seedling) was recorded in A. malaccensis. Data on root-shoot ratio exhibited that A. heterophyllus, M. koenghii and M. ferrea had the comparatively heavier root systems than the other species. Height (P= 0.01) and collar diameter (P= 0.05) growth of the seedlings also exhibited significant positive correlation with biomass accumulation in the seedlings.

Differences between nine spring barley cultivars on structural and functional parameters of PSII operation are shown. Variability of the parameters used changed from 2.2…2.5 (oxidized quinones pool and maximum photochemical efficiency) to 24.6% (performance index PIABS_total). Parameters characterizing the values of excitation energy fluxes (ABS/RC; TRo/RC; ETo/RC) varied to a small extent - 3.1...6.5%, while the lost energy (DIo/RC) much stronger - 14.6%. The efficiency of electron transport from quinine QB and the entire PSII until the PSI’s primary acceptors varied even more - 18.1 and 17.4%, respectively. The PIABS integral performance index combined cultivars into two groups only; PIABS_total index showed more clear differences in cultivars. Cv. Novichok and Fermer were significantly inferior to cv. Forward, Belgorodsky 100, Boyarin and Bionic in most of the studied parameters. However, according to the results of a cluster analysis, cv. Novichok and Forward turned out to be similar to each other, as well as cv. Fermer, Boyarin and Bionic, which separated into the same cluster. Probably, the action of PSII in cultivars of the same cluster differs only quantitative but not qualitative. Therefore, for breeding work on pyramidizing the genes controlling operation of this photosystem, it is advisable to crossing cultivars belonging to different clusters.

Coronaviruses are enveloped RNA viruses capable of causing respiratory, enteric, or systemic diseases in a variety of mammalian hosts that vary in clinical severity from subclinical to fatal. The host range and tissue tropism are largely determined by the coronaviral spike protein, which initiates cellular infection by promoting fusion of the viral and host cell membranes. Companion animal coronaviruses responsible for causing enteric infection include feline enteric coronavirus, ferret enteric coronavirus, canine enteric coronavirus, equine coronavirus, and alpaca enteric coronavirus, while canine respiratory coronavirus and alpaca respiratory coronavirus result in respiratory infection. Ferret systemic coronavirus and feline infectious peritonitis virus, a mutated feline enteric coronavirus, can lead to lethal immuno-inflammatory systemic disease. Recent human viral pandemics, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and most recently, COVID-19, all thought to originate from bat coronaviruses, demonstrate the zoonotic potential of coronaviruses and their potential to have devastating impacts. A better understanding of the coronaviruses of companion animals, their capacity for cross-species transmission, and the sharing of genetic information may facilitate improved prevention and control strategies for future emerging zoonotic coronaviruses. This article reviews the clinical, epidemiologic, virologic, and pathologic characteristics of nine important coronaviruses of companion animals.

Abstract Recent outbreaks of swine-origin influenza A(H3N2) variant virus (H3N2v) in the U.S., mainly among young children with swine exposure, have raised concerns. Previous studies demonstrated older children and young adults had the highest hemagglutination-inhibition (HI) antibodies (Ab) to 2011 H3N2v viruses. In 2013, newly emerging antigenic variants of H3N2v viruses, responsible for 18 human infections, acquired N145K/R mutations in hemagglutinin (HA). Here, human and postinfection ferret sera were tested in HI assays against 2012-13 H3N2v viruses possessing 145N, K or R HA mutations, together with nine historical seasonal H3N2 (sH3N2) viruses circulating since 1968. We found the H3N2v viruses were antigenically distinct but retained a low degree of serologic cross-reactivity (CR) (with ferret antisera) to sH3N2 viruses that circulated in 1990s. Across all age groups (6-80+ years), approximately half were seropositive (HI titer≥40) to the H3N2v viruses. The age related seroprevalence among children were likely associated with primary exposure to sH3N2 viruses in 1990s. We observed a single substitution at 145 in HA was sufficient to change an individual’s seropositivity to the virus and significantly influenced the seroprevalence in certain age groups. The susceptibility to 2012-13 H3N2v viruses remains high in young children, and low in older children and young adults. Improved knowledge of age-related CR Ab is critical for influenza risk assessment and pandemic preparedness.

SUMMARYFourteen influenza A(H3N2) field isolates, mainly obtained during the first weeks of the 1982/83 influenza epidemic in The Netherlands, and nine influenza A(H3N2) reference strains were examined by means of haemagglutination inhibition (HI) tests with 23 potyclonal ferret sera. The resulting HI patterns were subjected to various methods of numerical taxonomy using, among others, taxonomic distance and correlation between strains for resemblance coefficients. Marked differences between distance and correlation coefficients were found in strains which differed in avidity only. The field isolates could be divided into four groups in respect of their taxonomic resemblance to the reference strains. The same grouping was found for five of the field isolates by testing these against 200 human sera.

Malaria is an infectious and parasitic disease caused by protozoa of the genus Plasmodium, which affects millions of people in tropical and subtropical areas. Recently, there have been multiple reports of drug resistance in Plasmodium populations, leading to the search for potential new active compounds against the parasite. Thus, we aimed to evaluate the in vitro antiplasmodial activity and cytotoxicity of the hydroalcoholic extract of Jucá (Libidibia ferrea) in serial concentrations. Jucá was used in the form of a freeze-dried hydroalcoholic extract. For the cytotoxicity assay, the(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method with the WI-26VA4 human cell line was used. For the antiplasmodial activity, Plasmodium falciparum synchronized cultures were treated with serial concentrations (0.2 to 50 μg/mL) of the Jucá extract. In terms of the chemical composition of the Jucá extract, gas chromatography coupled to mass spectrometry measurements revealed the main compounds as ellagic acid, valoneic acid dilactone, gallotannin, and gallic acid. The Jucá hydroalcoholic extract did not show cytotoxic activity per MTT, with an IC50 value greater than 100 µg/mL. Regarding the antiplasmodial activity, the Jucá extract presented an IC50 of 11.10 µg/mL with a selective index of nine. Because of its antiplasmodial activity at the tested concentrations and low toxicity, the Jucá extract is presented as a candidate for herbal medicine in the treatment of malaria. To the best of our knowledge, this is the first report of antiplasmodial activity in Jucá.

Raccoon dogs (Nyctereutes procynoides) are canids indigenous to Eastern Asia being one of the most invasive non-native animals in Europe and potential vectors for several hazardous parasitic and viral diseases. To present, there is a lack of studies regarding objective techniques used to appreciate the integrity and functionality of the nervous system in this species. Brainstem auditory evoked potentials (BAER) is a cost-effective, quick and noninvasive technique to assess the functionality of nervous system. The aim of the study is to provide reference values and evaluates the reliability of BAER recording with needle electrodes in clinically healthy raccoon dogs. Nine individuals were investigated for BAER under xylazine and ketamine general anesthesia. Four waves (I, II, III and V) were identified and evaluated for latencies, morphologically similarity to those previously reported for other species (dogs, horses, cats, and ferret). Our data can be used in further studies to asses objectively the auditory system function in raccoon dogs.

Este documento es una reseña acerca del libro Reduciendo desigualdades. Otros derechos y otros desarrollos, bajo el liderazgo editorial de Nina Ferrer Araujo, decana de la Facultad de Derecho de la Universidad de San Buenaventura, en Cartagena de Indias (Colombia). La publicación emerge en un panorama intelectual caracterizado por la urgencia que tiene nuestra época de reformular vocabularios, conceptos, metáforas y paradigmas científicos en un momento de la historia colombiana, latinoamericana y mundial en el que la Academia crítica –por consenso explícito o implícito– parece querer decir que, ante el imperio del Capital, este mundo no da para más. Como tal, la reseña se ocupa de responder a las siguientes tres preguntas: 1. ¿Cuál es la transición científica de la que se ocupa este libro? 2. ¿Cuál es el orden de exposición que nos proponen sus páginas? y 3. ¿Cuál es la visión de fondo que nutre a la obra en general y que por ende se refleja en cada capítulo? El documento concluye que esta publicación es altamente recomendable, necesaria, deseable y que, vista con ojos de esperanza, podría estar abriendo camino hacia una nueva concepción del derecho, más próxima a las realidades del Caribe colombiano y, por tanto, a las geografías físicas y simbólicas de nuestros sures. Palabras clave: desigualdad económica; desigualdad racial; derecho al desarrollo; derechos socioeconómicos; violencia económica; justicia.

Methemoglobin (MHb) formation is effective in treating cyanide (CN) poisoning. Endogenous activity of the enzyme MHb reductase (MR) reflects the capacity to reduce MHb and thus represents a key factor for evaluating anti-CN efficacy of MHb formers. MR activity was measured in whole blood of nine animal species and was compared with human MR activity. The animals in this comparative study included seven nonhuman primate (NHP) species, the beagle dog, and the ferret. Although exhibiting higher MR activity than in humans, the rhesus and aotus NHPs' average MR activity was the closest to humans', with raw data from each NHP showing overlap with human raw data. The beagle dog, used extensively to study anti-CN characteristics of MHb formers, was the sole species that displayed MR activity lower than in humans, with no data overlap. Based on MR activity, the rhesus and aotus NHPs may each represent a more accurate model for predicting human responses to MHb formers. The data from this study provides a unique interspecies enzyme comparison, which should facilitate future rational development of anti-CN MHb formers.

This paper is aimed at performing a group of experiments to evaluate the sensitivity to cumulus and microphysics schemes, as represented in numerical simulations of the Weather Research and Forecasting (WRF) model. The convective schemes of Kain-Fritsch (KF), Betts-Miller-Janjic (BMJ), Grell-Devenyi (GD), Grell-Freita (GF), Grell 3D (G3D), Tiedtke and New Tiedtke (NT) were tested in association with the microphysics schemes of Kessler, Purdue Lin, WSM3, WSM5, WSM6, ETA (Ferrier) and Goddard (totaling forty-nine experiments) in order to identify the combination which best represents the cumulative rainfall distribution in the Paraíba do Sul watershed. In order to evaluate the best performance experiments, they were submitted to statistical tests of bias (BIAS), root mean square error (RMSE), absolute mean error (MAE) and Coefficient of Determination (R2). Results show that combinations WSM5 and GD; Goddard and G3D; Perdue Lin and G3D; WSM5 and G3D form a group of four physical configurations statistically similar and able to predict well the mean rainfall in the Paraiba do Sul watershed. It was noticed also that the cumulus scheme has a greater weight than microphysics in rainfall simulations being GD3 the best performing.

Fine needle biopsy (FNB) is an effective, minimally invasive and inexpensive diagnostic technique. Under computed tomography (CT)-guidance, lesions that have a difficult approach can be sampled to reach a diagnosis. The aim of this study is to describe the use of CT-guidance to obtain FNB from vertebral and paravertebral lesions in small animals. Ten dogs and one ferret that had undergone CT-guided FNB of vertebral and paravertebral lesions and had a cytological or a histological diagnosis were included in this retrospective study. The FNB samples were taken in four cases from the vertebra, in two cases from the intervertebral disc and in five cases from the intervertebral foramen. Two infectious and nine neoplastic lesions were diagnosed. The percentage of successful FNB was 91%. The percentage of samples with a cytological diagnosis was 80%. The percentage of complications was 9%. Limitations were the small number of animals in the study, the lacking complementary percutaneous biopsies for comparison, the lacking final histological diagnoses in some cases and the intervention of multiple operators. Computed tomography-guided FNB is a useful and safe technique for the diagnosis of vertebral and paravertebral lesions in small animals. However, a degree of expertise is important.

The objectives of this work were to evaluate the floristic composition and dry biomass of weeds under the canopy of seven perennial species adapted to the Semi-Arid region of Brazil, and correlate these characteristics with growth traits of the perennial species. The following perennial species were evaluated in two experiments (E1 and E2): mesquite (Prosopis juliflora), jucá (Caesalpinia ferrea), white popinac (Leucaena leucocephala), mofumbo (Combretum leprosum), neem (Azadirachata indica), sabiá (Mimosa caesalpiniaefolia) and tamarind (Tamarindus indica). In E1, the seven species were evaluated in a random block design with four replicates and nine plants per plot. In E2, evaluation comprised four species (mesquite, jucá, white popinac, and tamarind) in a random block design with eight replicates and nine plants per plot. A circle with an area of 1.77 m² was established around the trunk of each plant, two years after they were transplanted to the permanent location. The weeds collected within this circle were cut even with the ground, classified and weighed. At this time, plant height, and crown and stem diameters were evaluated in all trees of each plot. In E1 there were no differences between tree species as to weed frequency under their canopies; however, weed growth was smaller under the canopy of sabiá trees. Mesquite and sabiá had the greatest plant height and crown diameter means, but only sabiá had the greatest stem diameter. In E2, the perennial species were not different with regard to weed frequency and growth under their canopies, but mesquite had the greatest growth, as measured by plant height (with significant results for jucá as well) and crown and stem diameter.

1. Corneas of mouse, rat, guinea pig, rabbit, sheep, cat, dog, pig and cow were quantitatively analysed for water, hydroxyproline, nucleic acid, total sulphated polyanion, chondroitin sulphate/dermatan sulphate and keratan sulphate, several samples or pools of tissue from each species being used. Ferret cornea was similarly analysed for water and hydroxyproline on one pool of eight corneas. Pooled frog (38) and ferret (eight) corneas and a single sample of human cornea were qualitatively examined for keratan sulphate and chondroitin sulphate/dermatan sulphate by electrophoresis on cellulose acetate membranes. Nine species (mouse, frog, rat, guinea pig, rabbit, sheep, cat, pig and cow) were examined by light microscopy and six (mouse, frog, rat, guinea pig, rabbit and cow) by electron microscopy, with the use of Alcian Blue or Cupromeronic Blue in critical-electrolyte-concentration (CEC) methods to stain proteoglycans. 2. Water (% of wet weight), hydroxyproline (mg/g dry wt.) and chondroitin sulphate (mg/g of hydroxyproline) contents were approximately constant across the species, except for mouse. 3. Keratan sulphate contents (mg/g of hydroxyproline) increased with corneal thickness, whereas dermatan sulphate contents decreased. The oversulphated domain of keratan sulphate was absent from mouse and frog corneas, increasing as percentage of total keratan sulphate with increasing corneal thickness. Sulphation of dermatan sulphate was essentially complete (i.e. one sulphate group per disaccharide unit). 4. Chondroitin sulphate/dermatan sulphate proteoglycans were present at the d bands of the collagen fibrils of all species examined, orthogonally arrayed, with high frequency, and occasionally at the e bands. Keratan sulphate proteoglycans were present at the a and c bands of all species examined, but with far higher frequency in the thicker corneas, where keratan sulphate contents were high. 5. Alcian Blue CEC staining showed much higher sulphation of keratan sulphate in thick corneas, e.g. that of cow, than in thin corneas, e.g. that of mouse, in keeping with biochemical analyses. 6. It is suggested that the constancy of interfibrillar volumes is regulated via the swelling and osmotic pressure of the interfibrillar polyanions, by adjustment of the extent of sulphation in two independent proteoglycan populations, to achieve an ‘average sulphation’ of the total polyanion similar to that of fully sulphated chondroitin sulphate/dermatan sulphate. 7. The balance of synthesis of the two kinds of proteoglycans may be determined by the O2 supply to the avascular cornea. O2 supply may also determine the conversion of chondroitin sulphate into dermatan sulphate.

Abstract Objective To determine the phenotype of naturally developing lymphomas in young ferrets. Animals 10 ferrets with lymphoma. Procedure Neoplastic tissues were graded histologically according to the National Cancer Institute's Working Formulation for non-Hodgkin’s lymphoma and phenotype was determined by means of immunohistochemical staining. A polyclonal anti-human CD3 and a monoclonal anti-human CD79 antibody were used to classify the lymphomas in situ as T-cell or B-cell origin. Specificity of antibodies was determined by evaluating lymphoid tissue from normal ferrets in situ, which was confirmed by western blot analyses. Results All 10 ferrets had clinically aggressive tumors, irrespective of the phenotype. Nine ferrets had T-cell lymphoma that extensively involved the mediastinum. Remnants of thymic tissue, indicative of thymic origin, were identified in lymphoma of these 9 ferrets. One ferret had a B-cell multicentric lymphoma without involvement of the mediastinum. Conclusions The majority of lymphomas in these young ferrets involved the mediastinum and were of T-cell phenotype. Impact for Human Medicine There are many similarities between the lymphoma syndrome of ferrets and the condition documented for cats and children with lymphoma of the mediastinal area. Clinical Relevance Differential diagnoses for young ferrets with clinical signs of lethargy or respiratory distress should include T-cell lymphoma of the mediastinum. ((Am J Vet Res 1998;59:1281-1286)

<p>Parasitoid <em>Anagyrus lopezi</em> (De Santis) (Hymenoptera: Encyrtidae) was introduced from Thailand into Indonesia in early 2014 to control the invasive cassava mealybug, <em>Phenacoccus manihoti</em> Matile-Ferrero (Hemiptera: Pseudococcidae). Research was conducted in laboratory with the objectives to determine effect of honey on adult longevity, to study fecundity, progeny production, and sex ratio, and to evaluate effect of increased host density to parasitization. Studies were carried out by exposing 3^rd instar nymphs of mealybug to parasitoids. Effect of honey on adult longevity was done in the absence of hosts. Fecundity was measured by the number of mummies formed. Results showed that adult females lived for 3.7 days, while males lived for 3.2 days when only provided water. Adult longevity increased significantly when honey was provided. Parasitoids with access to 50% honey lived almost six to nine fold longer than those provided water. Over its adult life, <em>A. lopezi</em> parasitized 96–287 mealybugs with an average of 203.7 or 34.6% of hosts were parasitized, and 24.86% were killed through host feeding. Development from egg to adult emergence required 17.97 and 17.67 days for males and females respectively. The average number of offspring produced per female was 88.8 individuals, of which 56.9% were females. The number of hosts parasitized at densities varying from 2–100 cassava mealybugs corresponded to a type III functional response.</p>

ABSTRACT The neuraminidase inhibitors zanamivir and oseltamivir are marketed for the treatment and prophylaxis of influenza and have been stockpiled by many countries for use in a pandemic. Although recent surveillance has identified a striking increase in the frequency of oseltamivir-resistant seasonal influenza A (H1N1) viruses in Europe, the United States, Oceania, and South Africa, to date there have been no reports of significant zanamivir resistance among influenza A (H1N1) viruses or any other human influenza viruses. We investigated the frequency of oseltamivir and zanamivir resistance in circulating seasonal influenza A (H1N1) viruses in Australasia and Southeast Asia. Analysis of 391 influenza A (H1N1) viruses isolated between 2006 and early 2008 from Australasia and Southeast Asia revealed nine viruses (2.3%) that demonstrated markedly reduced zanamivir susceptibility and contained a previously undescribed Gln136Lys (Q136K) neuraminidase mutation. The mutation had no effect on oseltamivir susceptibility but caused approximately a 300-fold and a 70-fold reduction in zanamivir and peramivir susceptibility, respectively. The role of the Q136K mutation in conferring zanamivir resistance was confirmed using reverse genetics. Interestingly, the mutation was not detected in the primary clinical specimens from which these mutant isolates were grown, suggesting that the resistant viruses either occurred in very low proportions in the primary clinical specimens or arose during MDCK cell culture passage. Compared to susceptible influenza A (H1N1) viruses, the Q136K mutant strains displayed greater viral fitness than the wild-type virus in MDCK cells but equivalent infectivity and transmissibility in a ferret model.

Abstract We report our experience treating 16 patients with newly diagnosed primary diffuse B-cell lymphoma of the central nervous system with the MATRix regimen as reported by Ferreri, et al in 2016. The median age was 66 years (y); 8 patients were men and 8 were women. Fourteen had cerebral mass lesions, 1 had a paraspinal mass, and 1 leptomeningeal disease. Treatment consisted of 4 cycles of rituximab 375 mg/sq m (Days 1, 6); methotrexate 3.5 g/sq m (Day 2); cytarabine 2 g/sq m every 12 h (Days 3, 4); and thiotepa 30 mg/sq m (Day 5). Patients without disease progression received carmustine 400 mg/sq m and thiotepa 4 X 5 mg/kg followed by autologous bone marrow transplantation. Four patients were switched to MATRix after 6 cycles of methotrexate and rituximab and received only 2 initial cycles including cytarabine and thiotepa. Overall, 12 patients completed initial chemotherapy. Eleven of these 12 went on to transplantation; one patient had early disease progression and did not proceed to transplantation. All 4 patients over 70 y died early after 1–2 cycles; the median age of these was 80 y, and the causes of early death were neutropenic fever, septic thrombophlebitis, and cardiac arrest. One patient who completed the entire regimen including transplantation died of fungal pneumonia; the other 11 experienced no serious acute toxicity. One patient had late disease progression; one developed symptomatic leukoencephalopathy. Nine of the 16 patients remain alive. At a median follow-up of 23 months, median time to progression was 421 days and overall survival 564 days. These preliminary data suggest that the MATRix regimen in safe and highly effective in the newly diagnosed setting. However, the high incidence of early death in patients over 70 y suggests that the regimen may be too toxic for elderly individuals.

AbstractThe impact of Phenacoccus manihoti Matile-Ferrero on growth and tuber yield of cassava, and the results of its biological control by the exotic parasitoid Epidinocarsis lopezi (De Santis) were investigated in a survey of 60 farmers' fields in Ghana and Ivory Coast over an area of 180 000 km2 of the savana and forest ecosystems. Twenty-nine variables associated with plant growth, agronomic and environmental factors, and insect populations were recorded. Densities of P. manihoti were closely correlated with stunting of the cassava shoot tips and, less so, with the rate of stunting early in the growing season. With increasing mealybug infestations, average harvest indices declined and populations of E. lopezi and of indigenous coccinellids increased, but parasitoids were found at lower host levels than were predators. The length of time E. lopezi had been present in an area was the most important factor influencing mealybug densities. Thus, P. manihoti populations were significantly lower where E. lopezi had been present for more than half the planting season than in areas where E. lopezi was lacking or had been only recently introduced. A significant proportion of the farmers in the savanna zone, where P. manihoti populations were much higher than in the forest zone, had observed this decline due to E. lopezi. Tuber yield losses due to P. manihoti in the absence of E. lopezi were tentatively estimated at 463 g/plant in the savanna zone. No significant effect was found in the forest region. When E. lopezi was present, average P. manihoti damage scores were reduced significantly, both in the savanna and forest regions. The increase in yields was 228g/plant or about 2.48 t/ha in the savanna region.

<p>Apresentamos o primeiro número do Brazilian Journal of Veterinary Research and Animal Science - BJVRAS do ano de 2015. Neste ano importantes decisões foram tomadas: 1) visando propiciar a internacionalização da revista, a partir de março de 2015 só serão aceitos trabalhos apresentados na língua inglesa; 2) a composição dos membros externos à Universidade de São Paulo, que ocupam a posição de Editores Associados da revista foi alterada, os novos participantes, Prof. Dr. Júlio Lopes Sequeira da Universidade Estadual Paulista, campus de Botucatu, Prof. Dr. Sidnei Miyoshi Sakamoto da Universidade Federal do Semi-Árido, campus de Mossoró, Prof. Dr. Milton Ricardo Azedo da Universidade Metropolitana de Santos e Prof. Dr. José Luiz Laus da Universidade Estadual Paulista, campus de Jaboticabal passaram a fazer parte, respectivamente, das áreas de patologia, medicina veterinária preventiva, clínica veterinária e cirurgia veterinária. Agradecendo a colaboração dos Editores Associados anteriores que muito contribuíram para o fortalecimento do BJVRAS, estamos seguros que os ingressantes irão adotar a mesma dedicação e esforço necessários à manutenção da qualidade científica da revista; 3) as normas da revista foram revisadas e foi introduzida a possibilidade da publicação de relatos de casos. No presente número são publicados dois trabalhos da área de ciências básicas: um tratando da vascularização renal de equinos Puro Sangue Inglês e outro analisando aspectos da relação entre pontos anatômicos do sistema nervoso central e os sintomas mentais considerados na homeopatia veterinária. Na área de cirurgia são apresentados quatro trabalhos, três experimentais investigando possibilidades da evolução pós-cirúrgica com o emprego de pericárdio homólogo, de plaquetas ou do extrato de frutos da planta Jucá (Lidibia ferrea) e um de casuísmo compilando os atendimentos efetuados pelo setor de cirurgia do Hospital da Faculdade de Medicina Veterinária e Zootecnia da USP no período de 1988 a 2007. Na área de patologia, constam dois trabalhos relacionados à aquicultura, um experimental avaliando o efeito da temperatura na infecção de tilápias do Nilo pelo Streptococcus agalactiae e outro relatando um surto de mortalidade por Edwardsiella tarda em tambacús. A área de reprodução conta com dois trabalhos: um que analisa o efeito do sombreamento na eficiência reprodutora de touros Brangus e um que compara os métodos empregados para a incorporação de DNA exógeno pelos espermatozoides de bovinos. Desejamos a todos uma boa leitura.</p>

Abstract Background: Chlamydia psittaci (Ch.ps.) DNA has been detected in tumor tissue of 80% of patients with ocular adnexal lymphoma (OAL) and in peripheral blood mononuclear cells (PBMCs) of 40% of them [Ferreri AJM, et al. J Natl Cancer Inst 96:586, 2004]. Chronic antigenic stimulation provided by Ch.ps. persistent infection may favor the development and sustaining of OAL. Removal of this stimulation with antibiotic therapy could result in lymphoma regression. Aim: To assess the rate of Ch.ps. eradication and anti-lymphoma activity of antibiotic therapy in OAL patients. Methods: Twelve patients with Ch.ps.-positive marginal zone B-cell lymphoma of the ocular adnexa, at diagnosis (n=5) or relapse, were treated with doxycycline 100 mg, bid orally, for three weeks. The presence of Ch.ps. DNA in lymphoma samples was assessed by multiplex touchdown PCR. Specificity of the amplified PCR fragments was confirmed by direct sequencing of both sense and anti-sense strands. The presence of Ch.ps. DNA in PBMCs collected before and one and 12 months after antibiotic therapy was evaluated in 11 cases. Six of these patients had Ch.ps.-positive PBMCs and were assessable for bacterial eradication rate. Nine patients had measurable disease at the time of therapy and were evaluable for objective response; a lymphomatous lesion of ocular adnexa was detected in all 9 evaluable patients: unilateral in three, bilateral in three, associated with regional lymphadenopathies in two, and with multiple subcutaneous nodules in one. Objective response was assessed one, three and six months after therapy conclusion and every six months during follow-up. Observation period after doxycycline ranged from 1 to 29 months (median 25). Results: All patients but one completed antibiotic therapy, with excellent tolerability. At one month from doxycycline assumption, Ch.ps. DNA was no longer detectable in PBMC of the six positive patients; these results were confirmed at one year of fw-up in all the three assessable cases. Objective response was complete in two patients (26+ and 9+ months), partial in two (29+ and 6+ m.) and lower than 50% in two (3+ and 5+ m.), whereas one patient had stable disease at one month of fw-up. Two patients experienced progression and received salvage treatment. Importantly, two patients showed lymphoma regression in previously irradiated orbit, and the two patients with regional lymphadenopathies achieved complete response; doxycycline was the 4th-line treatment in one of them. Time to the best response ranged from 3 to 24 months. All patients are alive and well (median fw-up: 54 m.). Conclusions: Ch.ps.-eradicating antibiotic therapy is followed by tumor regression in OAL patients, even after multiple relapses. Estimation of response rate requires a longer follow-up. A large phase II trial is warranted to confirm whether this fast, cheap and well-tolerated therapy may be a valid alternative to conventional, more aggressive strategies against OAL.

Abstract. Alba is a town of over 30 000 inhabitants located along the Tanaro River (Piedmont, northwestern Italy) and is famous for its wine and white truffles. Many important industries and companies are based in Alba, including the famous confectionery group Ferrero. The town suffered considerably from a flood that occurred on 5–6 November 1994. Forty-eight percent of the urban area was inundated, causing severe damage and killing nine people. After the flood, the Alba area was analysed in detail to determine the reasons for its vulnerability. Information on serious floods in this area since 1800 was gathered from official records, state technical office reports, unpublished documents in the municipal archives, and articles published in local and national newspapers. Maps, plans and aerial photographs (since 1954) were examined to reconstruct Alba's urban development over the last two centuries and the planform changes of the Tanaro River. The results were compared with the effects of the November 1994 flood, which was mapped from aerial photographs taken immediately after the flood, field surveys and eyewitness reports. The territory of Alba was subdivided into six categories: residential; public service; industrial, commercial and hotels; sports areas, utilities and standards (public gardens, parks, athletics grounds, private and public sport clubs); aggregate plants and dumps; and agriculture and riverine strip. The six categories were then grouped into three classes with different flooding-vulnerability levels according to various parameters. Using GIS, the three river corridors along the Tanaro identified by the Autorità di Bacino del Fiume Po were overlaid on the three classes to produce a final map of the risk areas. This study shows that the historic floods and their dynamics have not been duly considered in the land-use planning of Alba. The zones that were most heavily damaged in the 1994 flood were those that were frequently affected in the past and sites of more recent urbanisation. Despite recurrent severe flooding of the Tanaro River and its tributaries, areas along the riverbed and its paleochannels have been increasingly used for infrastructure and building (e.g., roads, a municipal dump, a prison, natural aggregate plants, a nomad camp), which has often interfered with the natural spread of the floodwaters. Since the 1994 flood, many remedial projects have been completed along the Tanaro and its tributaries, including levees, bank protection, concrete walls and floodway channels. In spite of these costly projects, some areas remain at high risk for flooding. The method used, which considered historical data, river corridors identified by hydraulic calculations, geomorphological aspects and land-use planning, can indicate with good accuracy flood-prone areas and in consequence to be an useful tool for the coherent planning of urban expansion and the mitigation of flood risk.

Abstract Abstract 4968 In our previous paper (Ferrero et al, BJH 2009) we reported the treatment of 63 MDS patients (median age 75, 16 RAEB1, 47 non RAEB) with a combination of human recombinant erythropoietin (alfa or beta epoetin, 30–80000 U/ week, median 65000U/week), 13-cis-retinoic acid (20 mg day) and dihydroxylated vitamin D3 (1 ug day). Eleven of the 16 RAEB1 patients also received intermittent, low dose of 6-thioguanine. In spite of adverse prognostic factors for response to erythropoietin (all patients with Hb <9.5 g/dl, 70% transfusion dependent, 51% IPSS intermediate 1 or 2) 64% of non RAEB and 50% of RAEB1 displayed an erythroid response according to Cheson et al (Blood 2006). At previous evaluation (41 months of follow-up) a survival advantage was evident for non RAEB patients with erythroid response. Now we updated the casistic after 3 years from the previous evaluation. Median follow up for alive patients is now 64 months (5 months - 12 years). Median duration of erythroid response is now increased to 25 (2-88+) months for non RAEB and 6 (2.5-34.5+) months for RAEB1, 32.5% of responses in non RAEB patients have lasted more than 3 years. Twenty-nine/46 non RAEB and 14/16 RAEB1 patients died, with a median survival respectively of 57 and 15 months. Acute myeloid leukemia evolution occurred to 10 patients (5 RAEB1 and 5 non RAEB patients). Although the erythroid response did not correlate with known risk factors such as IPSS score, caryotype and transfusion requirement, it confirmed its positive prognostic role for survival in non RAEB patients (p 0.04, HR 2.06): median survival 71.5 months (range 12–150+) for responders, 30.6 months (range 5–149) for non responders. A trend towards a better survival for responder was also observed among RAEB1 patients (median survival 17 months for responders, 10 months for non responders), however, due to the low numbers of patients in this group, the difference was not statistically significant, even if border line (p 0.052, HR 2.52). In conclusion our long term follow-up confirmed the positive role of our combined treatment for response duration and survival in a group of non RAEB patients, most of them with unfavorable prognostic features.Figure 1.Overall survival of myelodisplastyc patients according to erythroid response: A. Non-RAEB patients:“___” responsive patients, “—” not responsive patients (p 0.04, HR 2.06) B. RAEB patients: “___” responsive patients, “—” not responsive patients (p 0.05, HR 2.52)Figure 1. Overall survival of myelodisplastyc patients according to erythroid response: A. Non-RAEB patients:“___” responsive patients, “—” not responsive patients (p 0.04, HR 2.06) B. RAEB patients: “___” responsive patients, “—” not responsive patients (p 0.05, HR 2.52) Disclosures: Off Label Use: The use of 13-cis retinoic acid and 1; 25(OH)2 vitamin D3 in myelodisplastyc syndrome is off-label. In our study we used that drugs in combination with erythropoietin as differentiative agents.

Abstract Compounds in the diazo/hydrazino acid class require expression of Tpo receptor (TpoR) for activity. These compounds have demonstrated a remarkable species specificity in their Tpo receptor agonist activity, i.e., the activation of signalling pathways by this class of compounds has only been demonstrated in human and chimpanzee platelets. Platelets of other species demonstrate signalling in response to rhTpo, however, no signalling in response to SB-497115 is detectable by electrophoretic mobility shift assays using platelets of cynomolgus macaques, cat, mouse, mouse, rag, pig, ferret or tree shrew. Additionally, HepG2 cells transiently transfected with human TpoR, but not murine or cynomolgus monkey receptor results in STAT activated-reporter gene activity. To elucidate the mechanism by which this occurs, HepG2 cells were transiently transfected with a STAT-activated reporter gene and various chimeric and mutated receptors and treated with SKF-57626, a tool compound in this diazo class. A series of cyno and human TpoR chimeric receptors were constructed in which the complement receptor homology region 1 (CRH1), CRH2 and the transmembrane (TM) and cytoplasmic domains were interchanged. The functionality of all the chimeric receptors was confirmed by response to rhTpo. The minimal human composition of the chimeric TpoR activated by SKF-57626 was composed of human sequence within the membrane proximal region of the CRH2 domain and the TM domain. Two amino acids in this region are different between cyno and human, a Thr to Ala change in the extracellular CRH2 domain and a Leu at residue 499 in cynomolgus monkeys rather than His in humans in the TM domain. Sequencing of TpoR transmembrane domains of mice, dogs and ferrets, species in which these compounds are inactive, confirmed that the receptor contains Leu499, similar to cynomolgus macaques, while chimpanzee TpoR is similar to human with His at residue 499. To verify the requirement for His499 in the TM domain, a point mutation replacing only Leu499 with His in the cyno TpoR conferred activity when treated with compound. Replacement of His499 with Leu in the human TM domain resulted in an inactive human TpoR in response to compound, but not rhTpo. Further experiments involved mutations in the murine G-CSF receptor (mGCSFR). Human TpoR and mGCSFR have little homology in their TM domains and there is no detectable signalling, proliferation or differentiation responses following treatment of GCSFR expressing cells with either compound or rhTpo. A mGSFR point mutation was tested that contained a His residue nine amino acids into the hydrophobic TM domain of GCSFR, corresponding to His499 in the human and chimpanzee TpoR. HepG2 cells transiently transfected with this receptor and the reporter gene construct responded to compound. A double mutation in which an additional residue three amino acids N-terminal to the His was replaced with Thr, as in the hTpoR exhibited an increase in activity over the single mutation. These results suggest a model in which these TpoR agonist compounds interact with His499, in addition to Thr496, to either change conformation of TpoR or induce dimerization, resulting in activation of the signal transduction pathways of TpoR and imparting biologically relevant function.

Abstract Background Residual disease (RD) following neoadjuvant chemotherapy (NAC) in early HER2 negative breast cancer (BC) remains an unmet medical need. We hypothesized that combining T-VEC with Atezolizumab may offer clinical benefit in terms of residual cancer burden (RCB) rate in the pre-operative setting for patients with early BC with intermediate to high risk of recurrence who present RD after standard NAC. Methods SOLTI-1503 PROMETEO is an open-label, multicenter trial of T-VEC + Atezolizumab in patients with RD after completing standard NAC. Overall, 30 women with triple-negative BC (TNBC) or Luminal B-like/HER2-negative BC are planned to be included in the trial. RD must be confirmed by core-biopsy and tumor should have a diameter ≥ 10 mm measured by magnetic resonance imaging (MRI). Adequate organ function and ECOG PS 0-1 are required. T-VEC is administered intratumorally on week 1 (106 plaque-forming units/mL [pfu/mL]), then in week 4 and every 2 weeks thereafter (108 pfu/mL) for 4 injections. Atezolizumab (840 mg) is administered intravenously every 2 weeks for 4 infusions, starting at week 4. BC surgery is performed 1 to 3 weeks after completing the treatment. The primary objective is to evaluate the efficacy of the combination, measured by the rate of RCB class 0/1 at surgery. Secondary endpoints include rate of pCR, objective response rate (ORR; rate of complete response + partial response) assessed by MRI, safety, and the increase of mean expression of a gene signature tracking activated CD8+ T-cells. Here we present the safety and efficacy results of the interim analysis including the first 10 enrolled patients. Results: As of April 2021, 10 patients received the study treatment and were evaluable for primary endpoint and safety. Main patient characteristics were: median age 48 (37-71), ECOG PS 0 (70%) and post-menopausal (60%). Four patients had TNBC and 6 Luminal B-like BC; 5 patients had stage II BC and 4 stage III; 7 tumors were grade II and 3 were grade III; median Ki-67 was 44% (20-75). Mean tumor size by MRI after NAC was 30.5 mm (11-75). At surgery, one patient achieved RCB0. Two patients achieved an objective response, five patients a stable disease and disease progression was observed in three patients (2 TNBC and 1 Luminal-like tumor). Nine patients reported AEs. Only grade 1-2 adverse events were reported, being the most common Fever (n=6) Arthralgia ((n=4) AST increased (n=3) and ALT increased (n=3). Conclusion: The treatment of T-VEC and atezolizumab was feasible at the approved doses and the safety profile was consistent with that previously reported. One patient achieved RCB0. After the efficacy and safety analysis of the first 10 patients, it was decided to continue with the inclusion of up to 30 patients. Correlative analysis including gene expression analysis and centralized Tumor-infiltrating lymphocytes (TILs), PD-L1 (SP142) IHC will be presented. Citation Format: Tomás Pascual, Maria Vidal, Mafalda Oliveira, Juan M Cejalvo, Estela Vega, Esther Sanfeliu, Sergi Ganau, Ana Julve, Esther Zamora, Ignacio Miranda, Ana Delgado, Begoña Bermejo, Luis de la Cruz, Claudette Falato, Manel Juan, Juan M Ferrero-Cafiero, Xavier González-Farré, Patricia Villagrasa, Aleix Prat. Talimogene laherparepvec (T-VEC) + atezolizumab combination in early breast cancer (SOLTI-1503 PROMETEO): Safety and efficacy interim analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-13.

Abstract Abstract 1780 Background: The combination of high doses (HD) of methotrexate (MTX) and cytarabine (ara-C) (experimental arm of the IELSG #20 trial) is the standard upfront chemotherapy for patients ≤75 years old with primary CNS lymphomas (PCNSL) [Ferreri AJM, et al. Lancet 2009; 374:1512–20]. The addition of an alkylating agent could improve MTX-ara-C efficacy since these drugs are active against quiescent G0 cells and increase antimetabolites cytotoxicity. Thus, patients with PCNSL diagnosed in 2008 at five Italian and one Swiss centers were treated with a combination of HD-MTX, HD-ara-C and thiotepa (MAT regimen). With respect to the conventional MTX-ara-C combination, ara-C dose was reduced from 2 g/m2 to 1 g/m2 to minimize the risk of toxicity. Herein, we report tolerability, activity and efficacy of MAT regimen. Methods: HIV-negative patients with PCNSL diagnosed during 2008 and selected by using the same eligibility criteria of the IELSG #20 trial (age 18–75, ECOG-PS ≤3, measurable disease) were considered. Patients received four courses (interval 3 weeks) of MTX 3.5 g/m2 d1 + ara-C 1 g/m2 × 2/d, d2-3 + thiotepa 30 mg/m2 d4, followed by whole-brain irradiation (WBRT). Thirty-nine patients treated with MTX/ara-C combination and WBRT in the IELSG #20 trial were used as controls. Results: Twenty patients (median age 57 ys; range 42–74) were treated with MAT regimen. No significant differences in patient characteristics between MAT and MTX-ara-C groups were observed (Table). The comparison between MAT and MTX/ara-C regimens did not show any significant difference in terms of actually delivered courses (69% vs. 76%), chemotherapy interruption (65% vs. 44%), dose reductions (60% vs. 44%), G4 neutropenia (85% vs. 74%), G4 thrombocytopenia (85% vs. 64%), infections (45% vs. 30%), G4 non-hematological toxicity (15% vs. 8%), and toxic deaths (5% vs. 8%). Median relative dose intensity of MTX (75% vs. 77%) and ara-C (67% vs. 68%) were identical in MAT and MTX+ara-C combinations, but median dose intensity of ara-C was 898 mg/m2/week and 1.808 mg/m2/week, respectively. Response after MAT chemotherapy was complete in four patients (CRR: 20%; 95%CI: 3%-37%) and partial in three (ORR: 35%; 95%CI: 15%-55%), which were significantly lower with respect to those reported with MTX/ara-C combination (Table). The seven patients who responded to MAT received consolidation WBRT, with early progressive disease (PD) in three cases and systemic dissemination in one; only four of the 12 patients with PD after MAT received WBRT, without any benefit in three of them. At a median follow-up of 23 months, 17 (85%) MAT patients experienced failure (PD, relapse, death), with a 2-yr PFS of 20±9%, which is significantly worse with respect to those reported with MTX/ara-C (Table). Five patients treated with MAT and 18 treated with MTX/ara-C are alive, with a 2-yr OS of 23±9% and 56±8%, respectively. Conclusions: Tolerability of MAT regimen was similar to those reported with MTX-ara-C combination. Conversely, ara-C dose reduction was associated with a remarkably lower activity and efficacy, hiding a potential benefit of the addition of thiotepa. Four doses of ara-C 2 g/m2 per course are recommended in the upfront treatment of PCNSL. Disclosures: No relevant conflicts of interest to declare.

Abstract Cervical cancer is one of the most common cancers in women. Despite progress in prevention through Human Papilloma Virus (HPV) vaccination and success in early detection of cervical cancer through cytologic screening and HPV detection, there remains an unequal cervical cancer burden in low-resource settings, both in developed and developing countries. We have previously shown that the CervicalMethDx test can provide a Cervical Intraepithelial Neoplasia (CIN) grade 2-3 risk score, by assessing DNA methylation in a panel of three human genes (ZNF516, FKBP6 and INTS1) in samples from the United States (US), Puerto Rico, and Chile. We now tested the performance of the CervicalMethDx test on HPV-positive CIN2 and CIN3 cases (n=113) from Honduras collected from participants in the ESTAMPA clinical trial (NCT01881659). ESTAMPA (EStudio multicéntrico de TAMizaje y triaje de cáncer de cuello uterino con pruebas del virus del PApiloma humano; Spanish acronym) is a multicentric study of cervical cancer screening with HPV testing and assessment of triage methods in Latin America, which has accrued close to 50,000 participants from twelve recruitment centers in nine Latin American countries since 2013. We hypothesized that the CervicalMethDx test can identify HPV positive women most likely to be diagnosed with CIN grades 2 and 3 by anatomic pathologists, before they are referred to colposcopy-driven biopsies. We assessed DNA methylation by quantitative Real Time Methylation Specific PCR (qMSP) analysis of sodium bisulfite-modified genomic DNA. Primers and probes were previously designed to specifically amplify the promoters of the 3 genes of interest and the promoter of a reference gene, β-actin, to assess DNA input. We performed blinded retrospective studies on well-characterized clinical samples in PreservCyt sample transport media (ThinPrep, Hologic), comparing DNA methylation levels in samples from Honduras and 88 HPV-positive previously tested US samples with No Intraepithelial Lesions or Malignancy (NILM), as controls. Our results showed that the CervicalMethDx test can correctly classify 96% of CIN2 (n=62) samples with 92% Sensitivity, 98% Specificity, and an AUC of 0.96 as well as 97% of CIN3 (n=51) samples with 96% Sensitivity, 98% Specificity, and an AUC of 0.97. Moreover, the assay correctly classified 96% of CIN2-CIN3 samples combined (n=113) with 95% Sensitivity, 98% Specificity, and AUC of 0.97, when compared to samples with NILM (n=88). Our results suggest that the CervicalMethDx test is a new and valuable tool to stratify HPV positive women prior to colposcopy-driven biopsies in developed countries and ablative treatment in developing countries, most of which are unnecessary. These results warrant further evaluation of the CervicalMethDX test in prospective, population-based studies, assessing the use of precision DNA methylation algorithms to triage HPV positive women before referral to colposcopy-driven biopsies or ablative treatments in cervical cancer screening clinics world-wide. Citation Format: Laura Palmieri, Fernando Zamuner, Yessy Cabrera, Jafet Ortiz-Quintero, Dieila Giomo De Lima, Ana Purcell-Wiltz, Amanda García-Negrón, Ashley Ramos-López, Mariana Brait, David Sidransky, Annabelle Ferrera, Rafael E. Guerrero-Preston. A precision DNA methylation test to triage HPV positive women before referral to colposcopy-driven biopsies or ablative treatment in cervical cancer screening clinics worldwide [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB107.

Abstract Introduction: Over half of patients with chronic myeloid leukemia (CML) in sustained deep molecular remission do not lose the major molecular response (MMR) after stopping treatment with tyrosine kinase inhibitors (TKI). This strategy is safe in controlled clinical trials, but there is scarce information on its applicability in the real-life setting. We aimed to assess if treatment cessation was feasible in clinical practice in a large nationwide series of CML patients from Spain. Methods: This retrospective study comprised a series of 236 patients in chronic-phase CML who discontinued TKI treatment outside of clinical trials between April 2009 and February 2018 in 33 Spanish institutions. Inclusion criteria were: a) TKI treatment duration >3 years; b) sustained MR4.5 in >4 consecutive determinations (one single point in MR4 was acceptable) during >2 years; c) molecular monitoring in a reference laboratory expressing the results on the International Scale (IS). Patients who had undergone allogeneic hematopoietic stem-cell transplantation were excluded. Molecular relapse was defined as consecutively detectable BCR-ABL1 transcripts showing a ≥1 log increase or loss of MMR in any single sample. Treatment-free remission (TFR) was estimated by the method of Kaplan-Meier and defined as the time from TKI discontinuation to the date of restarting therapy for any reason or, if treatment was not restarted, the date of last contact. Incidence of molecular relapse was calculated using the cumulative incidence function with resumption of TKI treatment in the absence of molecular relapse and death in MMR as competing events. Analysis of factors predicting molecular relapse was done by the method of Fine and Gray. Results: Table 1 shows the main characteristics of the series. Median follow-up from treatment discontinuation was 21.5 months, and 5 patients died in MMR due to CML unrelated causes. TKI therapy was reinitiated due to molecular relapse (MMR loss: n=52, increase >1 log in BCR-ABL transcript level at two consecutive assessments without losing MMR: n=12), patient preference (n=2), and severe withdrawal syndrome (n=1). One additional patient lost MMR after 20 months from treatment cessation but decided not to be retreated, with spontaneous recovery of MMR. The probability of TFR at 4 years was 64% (95% Confidence Interval [CI]: 55%-72%)(Figure 1). The cumulative incidence of molecular recurrence was 33% (95% CI: 26%-38%) at 3 years (Figure 2). Forty-nine relapses (75% of total) occurred in the first 6 months. The latest MMR loss was detected 30 months after treatment stop. One patient restarted treatment 44 months after TKI discontinuation due to ≥1 log increase in BCR-ABL1 transcripts in two consecutive samples without losing MMR. In univariate analysis, duration of TKI treatment of less than 5 years (P=0.005) and time in RM4.5 shorter than 4 years before TKI discontinuation (P=0.003) were both significantly associated with a higher incidence of molecular recurrence. No patient progressed to the advanced phases of CML. At the time of restarting treatment, the median BCR-ABL1 IS was 0.3%, with this value being >5% in only 7 instances. Most patients (81%) received the same TKI that they were taking before the trial of treatment cessation. Median follow-up after treatment resumption was 20 months. Among the 64 patients who restarted treatment due to molecular relapse, 46 of 52 cases regained MMR after a median time of 3 months, and 47 of 64 regained MR4.5 after a median time of 5 months. Response status at last control was: MR4.5 (n=196), MR4 (n=15), MMR (n=14), complete cytogenetic response (n=10), and other (n=1). Fifty-one patients (22%) developed musculoskeletal or joint pain after treatment cessation. In patients stopping imatinib, a significant increase in Hb levels, leukocyte counts, total lymphocyte counts, platelet counts, and cholesterol levels was observed. At 6 months, an increase in Hb level >2 g/dL was observed in 47% of patients with anemia. By contrast, nilotinib discontinuation was not followed by any relevant change in laboratory values. Conclusions: Our results confirm that treatment discontinuation is feasible and safe in clinical practice in Spain. Duration of TKI treatment of less than 5 years and a time in RM4.5 shorter than 4 years before TKI discontinuation were significantly associated with a higher incidence of molecular recurrence. Disclosures Hernandez Boluda: Incyte: Consultancy; Novartis: Consultancy. García Gutiérrez:Incyte: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding. Ferrer Marin:Incyte: Consultancy; Novartis: Consultancy, Research Funding. Cervantes:Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hospital Clinic Barcelona: Employment.

Abstract In hematological disorders ALK expression is present in >50% of Anaplastic Large Cell Lymphomas (ALCL) as a result of a t(2;5)(p23;q35) translocation that causes the ALK gene on chromosome 2 to fuse with the NPM gene on chromosome 5. ALK + ALCL respond to cytotoxic drugs, but relapses occur and bear a poor prognosis(Stein, Foss et al. Blood 96 3681-95 2000; Ferreri, Govi et al. Crit Rev Oncol Hematol 83 293-302 2012). ALK-positive large B-cell lymphoma (ALK+ LBCL) is a rare lymphoma with a most frequent t(2;17)(p23;q23) translocation responsible for Clathrin-ALK fusion protein(Swerdlow, Campo et al. 2 2008). Crizotinib is the first ALK inhibitor which entered clinical practice: it is an orally bioavailable small-molecule inhibitor active on the ALK and MET receptor tyrosine kinases. While the activity of crizotinib in ALK+ lung cancer is documented (Kwak, Bang et al. N Engl J Med 363 1693-703 2010)no report on long term effects of crizotinib in ALK+ lymphomas exists; impressive short-term therapeutic activity was reported in two patients (Gambacorti-Passerini, Messa et al. N Engl J Med 364 775-6 2011), but no long-term data are available. In the present study, crizotinib was administered (250 mg BID) as monotherapy to 11 ALK+ lymphoma patients, diagnosed with ALK+ Non-Hodgkin lymphoma (NHL) by immunohistochemistry and FISH. Nine patients had a ALCL histology while the remaining 2 were DLBCL Patients had a refractory or relapsed disease after at least one prior chemotherapy regimen and measurable disease. All had involvement at multiple sites (nodal and extranodal) as well as B symptoms and an ECOG performance score of 1-4. Response to therapy was assessed according to RECIST criteria (Therasse, Arbuck et al. J Natl Cancer Inst 92 205-16 2000) The Overall Response Rate (ORR) was 10/11 (91%, 95% CI: 60-99%) and included 9 CR (82%, 95% CI: 51-96%) and 1 PR. Evidence of response by PET/CAT scan was present as early as 12 days. B symptoms disappeared promptly and LDH levels normalized within 30 days after the start of crizotinib. Disease status at the latest follow-up (June 2013) is as follows: 4 patients are in CR under continuous crizotinib treatment; they also test negative by RT-PCR for NPM/ALK (Mussolin, Damm-Welk et al. Leukemia 27 416-22 2012). Three patients (2 with LBCL and 1 with ALCL) died due to disease progression; 1 patient obtained CR, relapsed after 2 months of treatment and is now in CR on continued brentuximab treatment (month 29); 1 patient obtained CR on crizotinib and after 2 months stopped treatment, received an alloBMT and is still in CR; 2 patients treated for relapses post alloBMT obtained CR and are still in CR but they stopped crizotinib after 8-10 months. The two patients with ALK+ LBCL died within 3 months; in those with ALCL the CR rate was 9/9 (100%, 95% CI, 74-100%) with a median duration of 10 months (range 2-37). The 3 years PFS and OS rates are 62% (95% CI, 35-85%) and 73% (95% CI, 40-93%) respectively, with a plateau in the curve after the initial 6 months. In two relapsed patients the kinase domain of NPM-ALK could be amplified from peripheral blood samples obtained at the time of relapse (month 5 and 2). Deep sequencing of these products revealed the presence of different mutations: Q1064R at high prevalence (95%,) in patient (pt) #2 and I1171N (33%) plus M1328I (14%) in pt #6. All these mutations were not present in samples obtained before crizotinib treatment. I1171N was already discovered in an in-vitro screening (Ceccon, Mologni et al. Mol Cancer Res 11 122-32 2012): it commands an intermediate level of resistance to crizotinib (RI: 5.8) which however is cross resistant with other anti-ALK TKI such as AP26113 and NVP-TAE684. The other two mutations were not previously described: they present a RI to crizotinib of 2.4 (M1328I) and 8.5 (Q1064R). Since these residues do not form direct contacts with crizotinib, they probably interact with different structures within the catalytic domain such as the hydrophobic R-spine (I1171N) (Ceccon, Mologni et al. Mol Cancer Res 11 122-32 2012), the activation loop (M1328I), or yet unidentified regions (Q1064R). In conclusion, these positive results extend our initial observation on two patients (Gambacorti-Passerini, Messa et al. N Engl J Med 364 775-6 2011) and provide long-term follow up data. Crizotinib exerted a potent antitumor activity in advanced ALK+ lymphoma and produced durable responses in this population of heavily pre-treated patients, with a benign safety profile. Disclosures: Gambacorti-Passerini: Pfizer: Consultancy, Research Funding; BMS: Consultancy.

Purpose: Hodgkin's lymphoma (HL) is a highly curable disease even in advanced-stage, with &gt;90% of long-term survivors. Currently, the standard of care is ABVD (doxorubicin, etoposide, vinblastine and dacarbazine), as it is less toxic and as effective as other more intensive chemotherapy regimens. Alternatively, BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) has been proposed as front-line intensified regimen with a better initial disease control and prolonged time to relapse when compared to ABVD. However, this advantage is associated with higher rates of severe hematologic toxicity, treatment-related deaths, secondary neoplasms and infertility. To date, the debate regarding which regimen should be preferred as first line for advanced-stage HL is still ongoing. To shed some light on this open question we compared efficacy and safety of both regimens in clinical practice. Patients and Methods: From October 2009 to October 2018, patients with HL stage III-IV treated with either ABVD or BEACOPP escalated (BEACOPPesc) were retrospectively assessed in 7 European cancer centers. Results: A total of 372 consecutive patients were included in the study. One-hundred and ten patients were treated with BEACOPPesc and 262 with ABVD. The baseline characteristics of the two groups did not differ significantly, except for a higher rate of high-risk patients in the BEACOPPesc group in contrast to the ABVD one (47% vs 18%; p= 0.003). Complete response rate (CR) assessed by PET imaging at the end of the second cycle was 67% and 78% for the ABVD and BEACOPPesc group (p= 0.003), respectively. Thirteen patients of the ABVD group achieved stable disease (SD) and 6 had a progression disease (PD). On the other hand, 4 of the patients in the BEACOPPesc group progressed, another 2 interrupted therapy because life-threatening toxicity. At the end of the therapy, CR was 76% in the ABVD group and 85% in the BEACOPPesc group (p= 0.01). A total of 20% patients in the ABVD group and 14% patients in the BEACOPPesc group received consolidation radiotherapy on the mediastinal mass at the dose of 30Gy. After radiotherapy, the number of patients with CR increased to 79% and 87% in the two groups (p= 0.041), respectively. Thirty-nine patients (35%) in the BEACOPPesc group required dose reduction of chemotherapy due to toxicity compared to 12 patients (5%; p= &lt;0.001) in the ABVD group. Overall, the rate of severe toxicities was higher in the BEACOPPesc group in comparison with the ABVD cohort. In particular, there was a significant increased frequency of acute grade 3-4 hematologic adverse events (neutropenia 61% vs 24%; anemia 29% vs 4%; thrombocytopenia 29% vs 3%), febrile neutropenia (29% vs 3%), severe infections (18% vs 3%). Myeloid growth factors were administered to 85% and 59% of patients in the BEACOPPesc group compared to the ABVD group. Blood transfusions were required in 51% and 6% of patients in the BEACOPPesc group compared to the ABVD cohort. Progression during or shortly after treatment occurred in 5 patients in the BEACOPPesc group (4%) and in 16 patients in the ABVD group (6%; p= 0.62). Among the 96 patients who achieved a CR after BEACOPPesc and radiotherapy, 8 relapsed (8%), compared to 29 of 208 patients in the ABVD group (14%; p= 0.04). At a median follow-up period of 5 years, no statistical difference in progression free survival (PFS; p=0.11) and event-free survival (EFS; p=0.22) was observed between the BEACOPPesc and ABVD cohorts. Similarly, overall survival (OS) did not differ between the two groups (p=0.14). The baseline international prognostic score (IPS &lt;3 vs ≥ 3) significantly influenced the EFS with an advantage for the high-risk group treated with BEACOPPesc (Figure 1A; p=0.03), but not the PFS (Figure 1B; p=0.06) and OS (Figure 1C; p=0.14). During the follow-up period, in the BEACOPPesc group one patient developed myelodysplasia and one acute leukemia. Second solid tumors developed in one patient in the ABVD group (lung cancer) and one in BEACOPPesc group (breast cancer). Conclusion: We confirm that the ABVD regimen is an effective and less toxic therapeutic option for advanced-stage HL. Although BEACOPP results in better initial tumor control especially in high-risk patients, the long-term outcome remains similar between the two regimens. Disclosures Ferrero: EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Servier: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Speakers Bureau. Martinelli:BMS: Consultancy; Pfizer: Consultancy; ARIAD: Consultancy; Roche: Consultancy; Novartis: Consultancy. Willenbacher:European Commission: Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Myelom- und Lymphomselbsthilfe Österreich: Consultancy, Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Science: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; IQVIA: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees; oncotyrol: Employment, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Fujimoto: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Tirol Program: Research Funding; Abbvie: Consultancy, Honoraria; Sandoz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

The military parachutists are responsible of special air operations who require certain capabilities in their physical condition, due to their intense professional career. The analysis of oxygen con-sumption (VO2) and heart rate (HR) allows the determination of aerobic (VT1) and anaerobic (VT2) thresholds and used to study the adequacy of the organism to exercise and in the analysis of sporting performance. The aim of this study was to determine the effect of tactical equipment on the stress test performance of elite parachutists. 10 parachutists parti-cipated in the study, between 22 and 36 years old with an average of 27.75 years (±4.20). Anthropometric values were determined of: weight 75.69 kg (±8.79), height 173.34 cm (±5.72) and body mass index (BMI) 25.23 (±2.98). Each one, performed 2 maximal treadmill exercise testing: one a conventional stress test (A) and another with the tactical equipment (weight 20 kg) (B). We obtained maximum oxygen consumption (Metalyzer 3B) and monitored the electrocardiogram continuously. The test started at a speed of 6km/h and a slope of 1%. The results of the two test were compared. The average value and standard deviation (SD) of different variables with equipment (B) and without it (A) and p-value were obtained: velocity (A: 14.80±3.29; B: 11.50±1.42 Km/h; p=0.073), HR (A: 182.7±58.62; B: 177.75±9.71 b/m; p=0.038), VO2 (A: 51.75±13.60; B: 54.00±30.82 ml/Kg/min; p=0.891). Al-so, the values of ventilatory thresholds: VT1 and VT2 of both tests were obtained, with sig-nificant differences. Tactical equipment causes a decrease in stress test performance with changes in VT1 and VT2.

Abstract. Salinity plays an important role for phenomenon identification of upwelling and downwelling. Upwelling that occurs in the Indian Ocean south of Java to South of Bali is influenced by monsoons, ENSO (El Nino Southern Oscillation) and IOD (Indian Dipole Oscillation Mode). Upwelling and downwelling patterns based on vertical structure of salinity and its seasonal variability within seven years (2004 to 2010) is studied here. Argo Float dataset is used in this study, processed by Ferret software for a vertical schematic model, and Pearson correlated with IOD and SOI indexes. The aim of this study is to obtain the pattern of upwelling and downwelling based on profile of seasonal salinity during the period 2004-2010 in Indian Ocean south of Java – Bali and correlated with ENSO and IOD. Further discussion on upwellling is provided since it is more important to the fisheries activity. Result shows an intensive upwelling phenomenon occurs at 110°E correlated with fishing ground area. ENSO and IOD phenomena has been founded also affect upwelling. Upwelling increasing in intensity during the La Nina - IOD (+). The upwelling is negative linear correlated with SOI(-0,89643), but its positive linear correlated with IOD (+0,798168).Keywords : vVrtical structure salinity; Seasonal upwelling; Indian Ocean; South Java-Bali Seas. Abstrak. Salinitas berperan penting untuk mengidentifikasi fenomena upwelling dan downwelling. Upwelling yang terjadi di samudera Hindia Selatan Jawa hingga Selatan Bali dipengaruhi oleh angin musim, ENSO (El Nino Southern Oscillation) dan IOD (Indian Oscillation Dipole Mode). Dalam peneletian ini dikaji pola upwelling dan downwelling berdasarkan distribusi salinitas secara vertikal dan vaeriabilitas musiman dikaji dalam waktu tujuh tahun (2004 – 2010). Data hasil akuisisi argo float digunakan dalam penelitian ini, diolah menggunakan software Ferret selanjutnya dilakukan pembuatan model skematik dan analisa korelasi pearson terhadap Indeks IOD dan SOI. Tujuan dari penelitian ini untuk memperoleh pola upwelling dan downwelling terhadap musim berdasarkan profil salinitas selama periode 2004 – 2010 di Samudera Hindia Selatan Jawa hingga Bali dan hubungannya dengan fenomena ENSO dan IOD.Penelitian lebih lanjut tentang upwelling penting untuk industri perikanan. Hasil penelitian menunjukkan Fenomena upwelling secara intensif terjadi pada koordinat bujur 110°BT, menunujukkan adanya kesesuaian dengan lokasi daerah penangkapan ikan. Fenomena ENSO dan IOD juga mempengaruhi upwelling, intensitasnya meningkat saat periode La Nina-IOD (+). Upwelling berkorelasi negatif terhadap SOI (-0,89643), sedangkan upwelling berkorelasi posetif dengan IOD (+0,798168).Kata Kunci: Struktur vertikal salinitas; Upwelling musiman; Samudera Hindia; Laut Selatan Jawa-Bali

Abstract An algorithm to re-create virtual aggregates with realistic shapes is presented in this paper. The algorithm has been implemented in the Unity 3D platform. The idea is to re-create realistically the virtual coarse and crushed aggregates that are normally used as a material for the construction of roads. This method consists of two major procedures: (i) to combine a spherical density function with a noise matrix based on the Perlin noise to obtain shapes of appropriate angularity and, (ii) deform the shapes until their minor ferret, aspect ratio and, thickness are equivalent to those wanted. The efficiency of the algorithm has been tested by reproducing nine types of aggregates from different sources. The results obtained indicate that the method proposed can be used to realistically re-create in 3D coarse aggregates. Graphic abstract

In contrast to dog-associated human rabies cases decline year by year due to the rabies vaccination coverage rates increase in China, ferret badger (FB, Melogale moschata)-associated human rabies cases emerged in the 1990s, and are now an increasingly recognized problem in southeast China. To investigate epidemiology, temporal evolution dynamics, transmission characterization, and pathogenicity of FB-associated rabies viruses (RABVs), from 2008 to 2018, we collected 3,622 FB brain samples in Jiangxi and Zhejiang Province, and detected 112 RABV isolates. Four FB-related lineages were identified by phylogenetic analysis (lineages A–D), the estimated Times to Most Recent Common Ancestor were 1941, 1990, 1937, and 1997 for lineages A–D, respectively. Furthermore, although no FB-associated human rabies case has been reported there apart from Wuyuan area, FB-RABV isolates are mainly distributed in Jiangxi Province. Pathogenicity of FB-RABVs was assessed using peripheral inoculation in mice and in beagles with masseter muscles, mortality-rates ranging from 20 to 100% in mice and 0 to 20% in beagles in the groups infected with the various isolates. Screening of sera from humans with FB bites and no post-exposure prophylaxis to rabies revealed that five of nine were positive for neutralizing antibodies of RABV. All the results above indicated that FB-RABV variants caused a lesser pathogenicity in mice, beagles, and even humans. Vaccination in mice suggests that inactivated vaccine or recombinant subunit vaccine products can be used to control FB-associated rabies, however, oral vaccines for stray dogs and wildlife need to be developed and licensed in China urgently.

RationaleThe purpose of this study was to investigate whether the proximity in anatomical locations of the Achilles (AT) and plantaris (PT) tendons promotes histopathological changes common to both tendons and their shared paratenon. The Achilles and plantaris tendons (ATs and PTs, respectively) share close anatomical locations in the foreleg, which has led to a proposed association between pathological findings in these tendons. Previous studies have identified such an association in specimens with known tendinopathy. This study aimed to determine whether similar correlation could be found in a group of cadavers without any record of tendon pathology.Materials and methodsThe subjects in this study were 20 donor cadavers (11 females and nine males) fixated in formalin, provided by the Department of Anatomy at Midwestern University. The mean age was 81 (±12). Twenty left, and 19 right legs were dissected. The ATs and PTs were assessed based on their gross anatomical characteristics, then samples of the tendons were harvested from two sites, one where the ATs and PTs ran closely together and a second where the PT was unassociated with the AT. The collected specimens were fixed, processed for paraffin embedding, sectioned, and stained with hematoxylin and eosin for histological analysis. Tissues were examined for the presence of inflammatory cells and for the evidence of stress‐induced conversion of the tendons’ dense connective tissue into fibrocartilage.ResultsIn four specimens (10.2%) the ATs and PTs ran separately, in eight (20.5%) specimens they were fused, and in three specimens the plantaris muscle was absent (7.7%). In the rest of the specimens the ATs and PTs were closely associated, but not fused. Histologically, no distinct evidence of inflammation was found at either the related or unrelated AT and PT sites. A presence of fibrocartilage with chondrocytes within the AT was noted in six (15.4%) specimens.ConclusionThe results of this study did not demonstrate any significant histopathologic changes in the areas of close contact between the ATs and PTs. The presence of fibrocartilage in the Achilles but not in the plantaris tendons suggests that the AT may be more affected by compression‐induced stress than the PT. These findings suggest that within the control group, close contact between AT and PT does not result in interrelated histopathologic changes. However, it is possible that histopathology may be observed in patients with mid‐portion Achilles tendinopathy.Support or Funding InformationZachary Belford and Benjamin Ferrel were supported by the Midwestern University Research Fellowship Program. Eric Leland and Andrew Cheung were supported by the Midwestern University work‐study program.

RationaleThe purpose of this study was to examine the frequency of mechanical wear, chronic inflammation and tendinosis of the flexor hallucis longus (FHL) tendon at areas of structural vulnerability. FHL tendonitis is strongly associated with ballet dancers and athletes, thus clinicians typically do not expect to find such a condition in the non‐athletic patient with foot pain. This commonly leads to misdiagnoses or delayed diagnosis, incurring expensive testing and raising the risk of complications. We hypothesized that signs of chronic mechanical wear and inflammation of the FHL tendon are commonly present in the general population, thus providing evidence that clinicians should entertain a higher level of suspicion for this condition in the non‐athletic population.Materials and methodsThe subjects in this study were 20 donor cadavers (11 females and nine males) fixated in formalin, provided by the Department of Anatomy at Midwestern University. The mean age was 81 (±12). Twenty left, and 19 right legs were dissected. First, tendon samples were assessed based on their gross anatomical characteristics. Next, samples of the FHL tendon were harvested from four sites of suspected mechanical wear (medial talar tubercle, sustentaculum tali, knot of Henry, sesamoid bones) and from a control site, where FHL tendon was not in contact with any bony structures. The collected specimens were fixed, processed for paraffin embedding, sectioned, and stained with hematoxylin and eosin for histological analysis. Tissues were examined for the presence of inflammatory cells and for the evidence of the local compressive force‐induced conversion of the tendons’ dense connective tissue into fibrocartilage.ResultsHistologically, no evidence of inflammatory cells was found at any of the tendon sites. However, cartilage‐specific transformation of tendons with a significant presence of chondrocytes was observed in the FHL tendons harvested from the areas associated with sesamoid bones (94.7% of specimens), the medial talar tubercle (79.5% of specimens), and the sustentaculum tali (20% of specimens). Only a few chondrocytes were present in the area of the knot of Henry and in the control tendons. There appeared to be no correlation between the gross anatomical characteristics of individual tendons and the presence of chondrocytes.ConclusionFHL tendons examined in this study did not show any signs of inflammation. However, the significant evidence of chondrocytes at specific sites may indicate the presence of consistent mechanical wear resulting in stress‐related changes in tendons. Fibrocartilage may be a sign of pathology that could lead to degeneration and rupture of the tendon. Thus, the areas of FHL tendon associated with sesamoid bones and the talar tubercule appear most vulnerable to injury.Support or Funding InformationBenjamin Ferrel and Zachary Belford were supported by the Midwestern University Research Fellowship Program. Andrew Cheung and Eric Leland were supported by the Midwestern University work‐study program.

Globalisation is often identified as the pre-eminent push towards a global social order. Some see globalisation as an all encompassing and inevitable process towards an emerging “hyperglobal” world order (Held et al.); an “inexorable integration of markets, nation states and technologies to a degree never witnessed before” (Friedman); a world that has become a “single place” (Robertson). Some contend that this emergent global order signals the end of the nation state (Ohmae), while others argue it is a deliberate project of capitalism, imposing intense market forces on states and individuals (McMichael, Hirst and Thompson). Some, like Wallerstein, question the ‘newness’ of this global order, pointing to continuities with earlier capitalist and imperialist movements. Across these diverse views, there is a central shared notion that globalisation moves us towards a global social order (past, present, or future), an order that is in need of interrogation and critique. In an era of global power monopolies, intense social upheaval and inequality, how can order be anything but suspect? Order is at the crux of power; we associate it with domination and control, a system imposed. Social and cultural critics, influenced by liberation movements of the past 50 years, are vigilant in questioning the existing order, and work to expose the inequalities inscribed within it. Order serves the interests of the powerful, at the expense of the weak. We see it as a social construct, negotiated as much through our very ways of knowing (‘the order of things’) and systems of representation and belief as it is through institutions of regulation and enforcement. Social inquiry is the critique of order, seeing order as an effect of power and domination. Yet our own inquiry is fraught with order. Order, more than progress, is the end point of Modernity, the promise of knowledge and technology; a new order of global economic and social prosperity. Implicit in critique is a call for reform, for a different social order. The idea of a new order underpins social critique. The drive to understand is a drive towards order. Or is such ordered sense-making just a particular kind of inquiry, the totalising project of modernity, resisted by poststructuralist, postmodernist, and postcolonial social critics? Following this tradition of resistance, many contemporary social debates are characterised by a scepticism towards order, whether of the past, present, or identified as emerging, to be struggled towards or resisted. In a ‘post’ mode of inquiry, cultural critics such as those included in this issue of M/C Journal deconstruct order, reluctant to impose or propose another order. Some identify alternative formations that emerge, tentatively, in spite of order, or out of disorder. These diverse social and cultural formations can be thought of as examples of ‘spontaneous order’, following mathematician Steven Strogatz’s work (revising chaos and complexity theory) on synchrony in complex natural phenomena. Many critics look to the spaces of new media to explore questions of social order, imposed or spontaneous, hegemonic or liberatory. Just as the city is emblematic of modernity’s order, the Internet and converged media are emblematic of the ‘hyperglobal’ order, and the various dispersed formations of ‘spontaneous order’. The articles in this issue of M/C Journal engage with this topic of ‘order’ from a variety of perspectives. Our feature article by Mark Nunes deals with what is perhaps the most important struggle for ‘order’ of the present time – the Bush administration’s ‘war on terror’ and its implications for the networked environment. Far from the quagmire of the Iraqi conflict, Nunes finds a new kind of order being imposed through new policies in the ‘homeland’ itself. Another, far less life-threatening but nonetheless important, ideological conflict is currently playing out closer to M/C’s home in Australia, following the recent changes to the tertiary education system imposed by the Federal government. Tara Brabazon’s article “Freedom from Choice” questions the implications of the new policies, and asks how they will re-order the educational value system in this country. Derek Wallace adds a wider perspective to this line of thought, examining the implications of continuing moves towards a knowledge society or knowledge economy in many leading nations of the Western hemisphere: whose order is being pursued here, and is it a beneficial one? In turn, Teodor Mitew examines sites of resistance to these and other attempted re-orderings. In his view, autonomous activist movements such as the Critical Art Ensemble desire a ‘beta-utopian order’, an unfinished order existing in ‘eternal pre-release form’ and constantly requiring debugging. The computer metaphor is carried through to Jussi Parikka’s article, describing the continuing virus threat as a form of digital disorder. He suggests that viruses uncover ideological and political aspects of digital order which would otherwise remain unseen. We remain in the digital realm with our subsequent articles. In his contribution to this issue, Mark McGuire analyses Habbo Hotel, a highly ordered community space for teenagers which appears not unlike an online version of some of the privatised townships now run by Disney and other corporations. Providing further insight into how such ordering of commercial online spaces is performed, Kylie Jarrett offers an examination of the correlations between the rhetorical, hypertext, and database structures of ninemsn, Microsoft’s Australian partnership with the Nine TV network. The rhetoric of social and communal order is also the topic of Rob Garbutt’s article “Local Order”, which investigates the power of that simple term ‘local’ as it is applied to or withheld from residents in the town of Lismore, New South Wales. Being a local is an honour not awarded lightly, as Garbutt shows. And such local order exists even in anarchist communities, as Jeff Shantz shows: while resisting dominant paradigms, ‘DIY’ anarchists “occupy their own ground” in autonomous zones (‘A-zones’), and offer alternative orderings of their environment. The last three articles in this issue all deal with the ordering power of the media. Stephen Stockwell discusses the response of Hollywood to the 11 September attacks and subsequent wars, showing the mainstream film industry’s support for the Bush administration’s campaign at home and abroad while painting a different picture for television drama. Ben Isakhan offers a crucial counterpoint to the all-too-common myths and omissions dominating news coverage from the Iraqi conflict, and Solrun Hoass finally turns our gaze towards another member of the infamous ‘axis of evil’, pleading for a more considered engagement with North Korea which could be informed by a look at the movies and television series produced there. Order is multifaceted and omnipresent. The articles in this issue offer glimpses of some of the flashpoints of the many struggles between order and disorder, and between various ordering paradigms. In doing so, they provide a snapshot of current world conflicts. References Albrow, M. The Global Age. Stanford: Stanford University Press, 1997. Friedman, T. The Lexus and the Olive Tree. London: Harper Collins, 2000. Globalization. 3 Feb. 2005 http://www.sociology.emory.edu/globalization/>. Held, D., et al. Global Transformations. Oxford: Polity, 1999. Hirst, P., and G. Thompson. Globalization in Question: The International Economy and the Possibilities of Governance. Cambridge, UK.: Polity Press, 1999. McMichael, P. Development and Social Change: A Global Perspective. Thousand Oaks, Calif.: Pine Forge Press, 2000. Ohmae, K. The End of the Nation-State. New York: Free Press, 1995. Robertson, R. Globalization: Social Theory and Global Culture. London: Sage, 1992. Strogatz, Steven. Synch: The Emerging Science of Spontaneous Order. New York: Theia, 2003. Wallerstein, I., and T. Hopkins. The Age of Transition: The World System 1945-2025. Atlantic Highlands, NJ.: Zed Books, 1996. Citation reference for this article MLA Style Ferrier, Liz, and Axel Bruns. "Editorial: Fraught with Order." M/C Journal 7.6 (2005). echo date('d M. Y'); ?> <http://journal.media-culture.org.au/0501/00-editorial.php>. APA Style Ferrier, L., and A. Bruns. (Jan. 2005) "Editorial: Fraught with Order," M/C Journal, 7(6). Retrieved echo date('d M. Y'); ?> from <http://journal.media-culture.org.au/0501/00-editorial.php>.

Although the sodium hypochlorite (NaOCl) solution has been part of the endodontic arsenal for more than one century, current investigations have been unable to determine which NaOCl volume and concentration or which time of application are able to dissolve organic matter without weakening the dental structure during the phase of biomechanical preparation of the root canal. Thus, the objective of the present study was to conduct a systematic literature review with no restriction of publication year or language in order to resolve these questions. The search strategy included the following databases: PubMed, LILACS, Web of Science and ClinicalTrials.gov, and only in vivo human clinical trials were included in the final review. After the removal of duplicates, the systematic literature review yielded 3,717 articles. Of these, 3,685 were excluded after applying the exclusion criteria (ex vivo studies, animal studies, cell-culture studies, narrative review, and studies with no available full texts). A total of 32 full-text articles were assessed for eligibility. After evaluating the full text, all articles were excluded for different reasons. No studies fulfilled our inclusion criteria. This review was unable to answer what time of irrigation, concentration or volume of NaOCl solution can be of maximum effectiveness in endodontic treatment without producing significant changes in the mechanical properties of dentin. Thus, future human clinical studies are needed in order to resolve these questions.Descriptors: Endodontics; Sodium Hypochlorite; Review.ReferênciasSiqueira JF Jr, Guimarães-Pinto T, Rôças IN. Effects of chemomechanical preparation with 2.5% sodium hypochlorite and intracanal medication with calcium hydroxide on cultivable bacteria in infected root canals. 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J Endod. 2015;41(9):1515-19.Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006-12.Hand RE, Smith ML, Harrison JW. Analysis of the effect of dilution on the necrotic tissue dissolution property of sodium hypochlorite. J Endod. 1978;4(2):60-4.Thé SD. The solvent action of sodium hypochlorite on fixed and unfixed necrotic tissue. Oral Surg Oral Med Oral Pathol. 1979;47(6):558-61.Ringel AM, Patterson SS, Newton CW, Miller CH, Mulhern JM. In vivo evaluation of chlorhexidine gluconate solution and sodium hypochlorite solution as root canal irrigants. J Endod.1982;8(5):200-4.Ercan E, Ozekinci T, Atakul F, Gül K. Antibacterial activity of 2% chlorhexidine gluconate and 5.25% sodium hypochlorite in infected root canal: in vivo study. J Endod.2004;30(2):84-7.Siqueira JF Jr, Rôças IN, Paiva SS, Guimarães-Pinto T, Magalhães KM, Lima KC. Bacteriologic investigation of the effects of sodium hypochlorite and chlorhexidine during the endodontic treatment of teeth with apical periodontitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;104(1),122–30.Estrela C, Silva JA, de Alencar AH, Leles CR, Decurcio DA. Efficacy of sodium hypochlorite and chlorhexidine against Enterococcus faecalis--a systematic review. J Appl Oral Sci.2008;16(6):364-68.Fedorowicz Z, Sequeira P. Efficacy of sodium hypochlorite and chlorhexidine against Enterococcus faecalis--a systematic review. J Appl Oral Sci.2008;16(6):364-68.Gomes BP, Martinho FC, Vianna ME. Comparison of 2.5% sodium hypochlorite and 2% chlorhexidine gel on oral bacterial lipopolysaccharide reduction from primarily infected root canals. J Endod; 2009;35(10):1350-53.Abbaszadegan A, Khayat A, Motamedifar M. Comparison of antimicrobial efficacy of IKI and NaOCl irrigants in infected root canals: an in vivo study. Iran Endod J.2010;5(3):101-6.Bashetty K, Hegde J. Comparison of 2% chlorhexidine and 5.25% sodium hypochlorite irrigating solutions on postoperative pain: a randomized clinical trial. Indian J Dent Res.2010;21(4):523-27.Haapasalo M, Shen Y, Qian W, Gao Y. Irrigation in endodontics. Dent Clin North Am. 2010;54(2):291-312.Huffaker SK, Safavi K, Spangberg LS, Kaufman B. Influence of a passive sonic irrigation system on the elimination of bacteria from root canal systems: a clinical study. J Endod. 2010;36(8):1315-18.Kandaswamy D, Venkateshbabu N. Root canal irrigants. J cons dent.2010;13(4),256-64.Kaya S, Yiğit-Özer S, Adigüzel O. Evaluation of radicular dentin erosion and smear layer removal capacity of self-adjusting file using different concentrations of sodium hypochlorite as an initial irrigant. Oral Surg Oral Med Oral Pathol Oral Radiol and Endod.2011;112(4):524-30.Paudel KR, Jaiswal A, Parajuli U, Bajracharya M. Different pharmacological solutions in intracanal irrigation. Nepal Med Coll J. 2011;13(2):111-14.Rôças IN, Siqueira JF Jr. Comparison of the in vivo antimicrobial effectiveness of sodium hypochlorite and chlorhexidine used as root canal irrigants: a molecular microbiology study. J Endod.2011;37(2):143-50.van der Vyver PJ, Botha FS, de Wet FA. Antimicrobial efficacy of nine different root canal irrigation solutions. SADJ. 2014;69(4):158-60,162-65.Beus C, Safavi K, Stratton J, Kaufman B (2012) Comparison of the effect of two endodontic irrigation protocols on the elimination of bacteria from root canal system: a prospective, randomized clinical trial. J Endod. 2012; 38(11):1479-83.Keenan AV. No evidence favouring one irrigant versus another in root canal treatments. Evid Based Dent.2012;13(4):107.Pawar R, Alqaied A, Safavi K, Boyko J, Kaufman B. Influence of an apical negative pressure irrigation system on bacterial elimination during endodontic therapy: a prospective randomized clinical study. 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The effects of sodium hypochlorite and chlorhexidine irrigants on the antibacterial activities of alkaline media against Enterococcus faecalis. Arch Oral Biol.2015;60(7):1075-81.Podar R, Kulkarni GP, Dadu SS, Singh S, Singh SH. In vivo antimicrobial efficacy of 6% Morinda citrifolia, Azadirachta indica, and 3% sodium hypochlorite as root canal irrigants. Eur J Dent.2015;9(4):529-34.Arias-Moliz MT, Morago A, Ordinola-Zapata R, Ferrer-Luque CM, Ruiz-Linares M, Baca P. Effects of dentin debris on the antimicrobial properties of sodium hypochlorite and etidronic acid. J Endod. 2016;42(2):771-75.Rôças IN, Provenzano JC, Neves MA, Siqueira JF Jr. Disinfecting effects of rotary instrumentation with either 2.5% sodium hypochlorite or 2% chlorhexidine as the main irrigant: a randomized clinical study. J Endod. 2016;42(6):943–47.Kist S, Kollmuss M, Jung J, Schubert S, Hickel R, Huth KC. Comparison of ozone gas and sodium hypochlorite/chlorhexidine two-visit disinfection protocols in treating apical periodontitis: a randomized controlled clinical trial. Clin Oral Investig. 2017;21(4):995-1005.Nourzadeh M, Amini A, Fakoor F, Raoof M, Sharififar F. Comparative antimicrobial efficacy of Eucalyptus Galbie and Myrtus Communis L. extracts, chlorhexidine and sodium hypochlorite against Enterococcus Faecalis. Iran Endod J.2017.12(2):205-10.Dakin HD. On the use of certain antiseptic substances in the treatment of infected wounds. Br Med J. 1915; 2(2852):318-20.Walker A. A definite and dependable therapy for pulpless teeth. J Am Dent Assoc. 1922;23(8):1418-25.Grossman LI. Irrigation of root canals. J Am Dent Assoc. 1943;30:1915-17.Bajaj D, Sundaram N, Nazari A, Arola D. Age, dehydration and fatigue crack growth in dentin. Biomaterials. 2006;27(11):2507-17.Kruzic JJ, Nalla RK, Kinney JH, Ritchie RO. 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Refereed publications (also known as peer-reviewed) are the currency of academia, yet many PhD theses in Australia result in only one or two such papers. Typically, a doctoral thesis requires the candidate to present (and pass) a public Confirmation Seminar, around nine to twelve months into candidacy, in which a panel of the candidate’s supervisors and invited experts adjudicate upon whether the work is likely to continue and ultimately succeed in the goal of a coherent and original contribution to knowledge. A Final Seminar, also public and sometimes involving the traditional viva voce or oral defence of the thesis, is presented two or three months before approval is given to send the 80,000 to 100,000 word tome off for external examination. And that soul-destroying or elation-releasing examiner’s verdict can be many months in the delivery: a limbo-like period during which the candidate’s status as a student is ended and her or his receipt of any scholarship or funding guerdon is terminated with perfunctory speed. This is the only time most students spend seriously writing up their research for publication although, naturally, many are more involved in job hunting as they pin their hopes on passing the thesis examination.There is, however, a slightly more palatable alternative to this nail-biting process of the traditional PhD, and that is the PhD by Published Papers (also known as PhD by Publications or PhD by Published Works). The form of my own soon-to-be-submitted thesis, it permits the submission for examination of a collection of papers that have been refereed and accepted (or are in the process of being refereed) for publication in academic journals or books. Apart from the obvious benefits in getting published early in one’s (hopefully) burgeoning academic career, it also takes away a lot of the stress come final submission time. After all, I try to assure myself, the thesis examiners can’t really discredit the process of double-blind, peer-review the bulk of the thesis has already undergone: their job is to examine how well I’ve unified the papers into a cohesive thesis … right? But perhaps they should at least be wary, because, unfortunately, the requirements for this kind of PhD vary considerably from institution to institution and there have been some cases where the submitted work is of questionable quality compared to that produced by graduates from more demanding universities. Hence, this paper argues that in my subject area of interest—film and television studies—there is a huge range in the set requirements for doctorates, from universities that award the degree to film artists for prior published work that has undergone little or no academic scrutiny and has involved little or no on-campus participation to at least three Australian universities that require candidates be enrolled for a minimum period of full-time study and only submit scholarly work generated and published (or submitted for publication) during candidature. I would also suggest that uncertainty about where a graduate’s work rests on this continuum risks confusing a hard-won PhD by Published Papers with the sometimes risible honorary doctorate. Let’s begin by dredging the depths of those murky, quasi-academic waters to examine the occasionally less-than-salubrious honorary doctorate. The conferring of this degree is generally a recognition of an individual’s body of (usually published) work but is often conferred for contributions to knowledge or society in general that are not even remotely academic. The honorary doctorate does not usually carry with it the right to use the title “Dr” (although many self-aggrandising recipients in the non-academic world flout this unwritten code of conduct, and, indeed, Monash University’s Monash Magazine had no hesitation in describing its 2008 recipient, musician, screenwriter, and art-school-dropout Nick Cave, as “Dr Cave” (O’Loughlin)). Some shady universities even offer such degrees for sale or ‘donation’ and thus do great damage to that institution’s credibility as well as to the credibility of the degree itself. Such overseas “diploma mills”—including Ashwood University, Belford University, Glendale University and Suffield University—are identified by their advertising of “Life Experience Degrees,” for which a curriculum vitae outlining the prospective graduand’s oeuvre is accepted on face value as long as their credit cards are not rejected. An aspiring screen auteur simply specifies film and television as their major and before you can shout “Cut!” there’s a degree in the mail. Most of these pseudo-universities are not based in Australia but are perfectly happy to confer their ‘titles’ to any well-heeled, vanity-driven Australians capable of completing the online form. Nevertheless, many academics fear a similarly disreputable marketplace might develop here, and Norfolk Island-based Greenwich University presents a particularly illuminating example. Previously empowered by an Act of Parliament consented to by Senator Ian Macdonald, the then Minister for Territories, this “university” had the legal right to confer honorary degrees from 1998. The Act was eventually overridden by legislation passed in 2002, after a concerted effort by the Australian Universities Quality Agency Ltd. and the Australian Vice-Chancellors’ Committee to force the accreditation requirements of the Australian Qualifications Framework upon the institution in question, thus preventing it from making degrees available for purchase over the Internet. Greenwich University did not seek re-approval and soon relocated to its original home of Hawaii (Brown). But even real universities flounder in similarly muddy waters when, unsolicited, they make dubious decisions to grant degrees to individuals they hold in high esteem. Although meaning well by not courting pecuniary gain, they nevertheless invite criticism over their choice of recipient for their honoris causa, despite the decision usually only being reached after a process of debate and discussion by university committees. Often people are rewarded, it seems, as much for their fame as for their achievements or publications. One such example of a celebrity who has had his onscreen renown recognised by an honorary doctorate is film and television actor/comedian Billy Connolly who was awarded an Honorary Doctor of Letters by The University of Glasgow in 2006, prompting Stuart Jeffries to complain that “something has gone terribly wrong in British academia” (Jeffries). Eileen McNamara also bemoans the levels to which some institutions will sink to in search of media attention and exposure, when she writes of St Andrews University in Scotland conferring an honorary doctorate to film actor and producer, Michael Douglas: “What was designed to acknowledge intellectual achievement has devolved into a publicity grab with universities competing for celebrity honorees” (McNamara). Fame as an actor (and the list gets even weirder when the scope of enquiry is widened beyond the field of film and television), seems to be an achievement worth recognising with an honorary doctorate, according to some universities, and this kind of discredit is best avoided by Australian institutions of higher learning if they are to maintain credibility. Certainly, universities down under would do well to follow elsewhere than in the footprints of Long Island University’s Southampton College. Perhaps the height of academic prostitution of parchments for the attention of mass media occurred when in 1996 this US school bestowed an Honorary Doctorate of Amphibious Letters upon that mop-like puppet of film and television fame known as the “muppet,” Kermit the Frog. Indeed, this polystyrene and cloth creation with an anonymous hand operating its mouth had its acceptance speech duly published (see “Kermit’s Acceptance Speech”) and the Long Island University’s Southampton College received much valuable press. After all, any publicity is good publicity. Or perhaps this furry frog’s honorary degree was a cynical stunt meant to highlight the ridiculousness of the practice? In 1986 a similar example, much closer to my own home, occurred when in anticipation and condemnation of the conferral of an honorary doctorate upon Prince Philip by Monash University in Melbourne, the “Members of the Monash Association of Students had earlier given a 21-month-old Chihuahua an honorary science degree” (Jeffries), effectively suggesting that the honorary doctorate is, in fact, a dog of a degree. On a more serious note, there have been honorary doctorates conferred upon far more worthy recipients in the field of film and television by some Australian universities. Indigenous film-maker Tracey Moffatt was awarded an honorary doctorate by Griffith University in November of 2004. Moffatt was a graduate of the Griffith University’s film school and had an excellent body of work including the films Night Cries: A Rural Tragedy (1990) and beDevil (1993). Acclaimed playwright and screenwriter David Williamson was presented with an Honorary Doctorate of Letters by The University of Queensland in December of 2004. His work had previously picked up four Australian Film Institute awards for best screenplay. An Honorary Doctorate of Visual and Performing Arts was given to film director Fred Schepisi AO by The University of Melbourne in May of 2006. His films had also been earlier recognised with Australian Film Institute awards as well as the Golden Globe Best Miniseries or Television Movie award for Empire Falls in 2006. Director George Miller was crowned with an Honorary Doctorate in Film from the Australian Film, Television, and Radio School in April 2007, although he already had a medical doctor’s testamur on his wall. In May of this year, filmmaker George Gittoes, a fine arts dropout from The University of Sydney, received an honorary doctorate by The University of New South Wales. His documentaries, Soundtrack to War (2005) and Rampage (2006), screened at the Sydney and Berlin film festivals, and he has been employed by the Australian Government as an official war artist. Interestingly, the high quality screen work recognised by these Australian universities may have earned the recipients ‘real’ PhDs had they sought the qualification. Many of these film artists could have just as easily submitted their work for the degree of PhD by Published Papers at several universities that accept prior work in lieu of an original exegesis, and where a film is equated with a book or journal article. But such universities still invite comparisons of their PhDs by Published Papers with honorary doctorates due to rather too-easy-to-meet criteria. The privately funded Bond University, for example, recommends a minimum full-time enrolment of just three months and certainly seems more lax in its regulations than other Antipodean institution: a healthy curriculum vitae and payment of the prescribed fee (currently AUD$24,500 per annum) are the only requirements. Restricting my enquiries once again to the field of my own research, film and television, I note that Dr. Ingo Petzke achieved his 2004 PhD by Published Works based upon films produced in Germany well before enrolling at Bond, contextualized within a discussion of the history of avant-garde film-making in that country. Might not a cynic enquire as to how this PhD significantly differs from an honorary doctorate? Although Petzke undoubtedly paid his fees and met all of Bond’s requirements for his thesis entitled Slow Motion: Thirty Years in Film, one cannot criticise that cynic for wondering if Petzke’s films are indeed equivalent to a collection of refereed papers. It should be noted that Bond is not alone when it comes to awarding candidates the PhD by Published Papers for work published or screened in the distant past. Although yet to grant it in the area of film or television, Swinburne University of Technology (SUT) is an institution that distinctly specifies its PhD by Publications is to be awarded for “research which has been carried out prior to admission to candidature” (8). Similarly, the Griffith Law School states: “The PhD (by publications) is awarded to established researchers who have an international reputation based on already published works” (1). It appears that Bond is no solitary voice in the academic wilderness, for SUT and the Griffith Law School also apparently consider the usual milestones of Confirmation and Final Seminars to be unnecessary if the so-called candidate is already well published. Like Bond, Griffith University (GU) is prepared to consider a collection of films to be equivalent to a number of refereed papers. Dr Ian Lang’s 2002 PhD (by Publication) thesis entitled Conditional Truths: Remapping Paths To Documentary ‘Independence’ contains not refereed, scholarly articles but the following videos: Wheels Across the Himalaya (1981); Yallambee, People of Hope (1986); This Is What I Call Living (1988); The Art of Place: Hanoi Brisbane Art Exchange (1995); and Millennium Shift: The Search for New World Art (1997). While this is a most impressive body of work, and is well unified by appropriate discussion within the thesis, the cynic who raised eyebrows at Petzke’s thesis might also be questioning this thesis: Dr Lang’s videos all preceded enrolment at GU and none have been refereed or acknowledged with major prizes. Certainly, the act of releasing a film for distribution has much in common with book publishing, but should these videos be considered to be on a par with academic papers published in, say, the prestigious and demanding journal Screen? While recognition at awards ceremonies might arguably correlate with peer review there is still the question as to how scholarly a film actually is. Of course, documentary films such as those in Lang’s thesis can be shown to be addressing gaps in the literature, as is the expectation of any research paper, but the onus remains on the author/film-maker to demonstrate this via a detailed contextual review and a well-written, erudite argument that unifies the works into a cohesive thesis. This Lang has done, to the extent that suspicious cynic might wonder why he chose not to present his work for a standard PhD award. Another issue unaddressed by most institutions is the possibility that the publications have been self-refereed or refereed by the candidate’s editorial colleagues in a case wherein the papers appear in a book the candidate has edited or co-edited. Dr Gillian Swanson’s 2004 GU thesis Towards a Cultural History of Private Life: Sexual Character, Consuming Practices and Cultural Knowledge, which addresses amongst many other cultural artefacts the film Lawrence of Arabia (David Lean 1962), has nine publications: five of which come from two books she co-edited, Nationalising Femininity: Culture, Sexuality and Cinema in Britain in World War Two, (Gledhill and Swanson 1996) and Deciphering Culture: Ordinary Curiosities and Subjective Narratives (Crisp et al 2000). While few would dispute the quality of Swanson’s work, the persistent cynic might wonder if these five papers really qualify as refereed publications. The tacit understanding of a refereed publication is that it is blind reviewed i.e. the contributor’s name is removed from the document. Such a system is used to prevent bias and favouritism but this level of anonymity might be absent when the contributor to a book is also one of the book’s editors. Of course, Dr Swanson probably took great care to distance herself from the refereeing process undertaken by her co-editors, but without an inbuilt check, allegations of cronyism from unfriendly cynics may well result. A related factor in making comparisons of different university’s PhDs by Published Papers is the requirements different universities have about the standard of the journal the paper is published in. It used to be a simple matter in Australia: the government’s Department of Education, Science and Training (DEST) held a Register of Refereed Journals. If your benefactor in disseminating your work was on the list, your publications were of near-unquestionable quality. Not any more: DEST will no longer accept nominations for listing on the Register and will not undertake to rule on whether a particular journal article meets the HERDC [Higher Education Research Data Collection] requirements for inclusion in publication counts. HEPs [Higher Education Providers] have always had the discretion to determine if a publication produced in a journal meets the requirements for inclusion in the HERDC regardless of whether or not the journal was included on the Register of Refereed Journals. As stated in the HERDC specifications, the Register is not an exhaustive list of all journals which satisfy the peer-review requirements (DEST). The last listing for the DEST Register of Refereed Journals was the 3rd of February 2006, making way for a new tiered list of academic journals, which is currently under review in the Australian tertiary education sector (see discussion of this development in the Redden and Mitchell articles in this issue). In the interim, some university faculties created their own rankings of journals, but not the Faculty of Creative Industries at the Queensland University of Technology (QUT) where I am studying for my PhD by Published Papers. Although QUT does not have a list of ranked journals for a candidate to submit papers to, it is otherwise quite strict in its requirements. The QUT University Regulations state, “Papers submitted as a PhD thesis must be closely related in terms of subject matter and form a cohesive research narrative” (QUT PhD regulation 14.1.2). Thus there is the requirement at QUT that apart from the usual introduction, methodology and literature review, an argument must be made as to how the papers present a sustained research project via “an overarching discussion of the main features linking the publications” (14.2.12). It is also therein stated that it should be an “account of research progress linking the research papers” (4.2.6). In other words, a unifying essay must make an argument for consideration of the sometimes diversely published papers as a cohesive body of work, undertaken in a deliberate journey of research. In my own case, an aural auteur analysis of sound in the films of Rolf de Heer, I argue that my published papers (eight in total) represent a journey from genre analysis (one paper) to standard auteur analysis (three papers) to an argument that sound should be considered in auteur analysis (one paper) to the major innovation of the thesis, aural auteur analysis (three papers). It should also be noted that unlike Bond, GU or SUT, the QUT regulations for the standard PhD still apply: a Confirmation Seminar, Final Seminar and a minimum two years of full-time enrolment (with a minimum of three months residency in Brisbane) are all compulsory. Such milestones and sine qua non ensure the candidate’s academic progress and intellectual development such that she or he is able to confidently engage in meaningful quodlibets regarding the thesis’s topic. Another interesting and significant feature of the QUT guidelines for this type of degree is the edict that papers submitted must be “published, accepted or submitted during the period of candidature” (14.1.1). Similarly, the University of Canberra (UC) states “The articles or other published material must be prepared during the period of candidature” (10). Likewise, Edith Cowan University (ECU) will confer its PhD by Publications to those candidates whose thesis consists of “only papers published in refereed scholarly media during the period of enrolment” (2). In other words, one cannot simply front up to ECU, QUT, or UC with a résumé of articles or films published over a lifetime of writing or film-making and ask for a PhD by Published Papers. Publications of the candidate prepared prior to commencement of candidature are simply not acceptable at these institutions and such PhDs by Published Papers from QUT, UC and ECU are entirely different to those offered by Bond, GU and SUT. Furthermore, without a requirement for a substantial period of enrolment and residency, recipients of PhDs by Published Papers from Bond, GU, or SUT are unlikely to have participated significantly in the research environment of their relevant faculty and peers. Such newly minted doctors may be as unfamiliar with the campus and its research activities as the recipient of an honorary doctorate usually is, as he or she poses for the media’s cameras en route to the glamorous awards ceremony. Much of my argument in this paper is built upon the assumption that the process of refereeing a paper (or for that matter, a film) guarantees a high level of academic rigour, but I confess that this premise is patently naïve, if not actually flawed. Refereeing can result in the rejection of new ideas that conflict with the established opinions of the referees. Interdisciplinary collaboration can be impeded and the lack of referee’s accountability is a potential problem, too. It can also be no less nail-biting a process than the examination of a finished thesis, given that some journals take over a year to complete the refereeing process, and some journal’s editorial committees have recognised this shortcoming. Despite being a mainstay of its editorial approach since 1869, the prestigious science journal, Nature, which only publishes about 7% of its submissions, has led the way with regard to varying the procedure of refereeing, implementing in 2006 a four-month trial period of ‘Open Peer Review’. Their website states, Authors could choose to have their submissions posted on a preprint server for open comments, in parallel with the conventional peer review process. Anyone in the field could then post comments, provided they were prepared to identify themselves. Once the usual confidential peer review process is complete, the public ‘open peer review’ process was closed and the editors made their decision about publication with the help of all reports and comments (Campbell). Unfortunately, the experiment was unpopular with both authors and online peer reviewers. What the Nature experiment does demonstrate, however, is that the traditional process of blind refereeing is not yet perfected and can possibly evolve into something less problematic in the future. Until then, refereeing continues to be the best system there is for applying structured academic scrutiny to submitted papers. With the reforms of the higher education sector, including forced mergers of universities and colleges of advanced education and the re-introduction of university fees (carried out under the aegis of John Dawkins, Minister for Employment, Education and Training from 1987 to 1991), and the subsequent rationing of monies according to research dividends (calculated according to numbers of research degree conferrals and publications), there has been a veritable explosion in the number of institutions offering PhDs in Australia. But the general public may not always be capable of differentiating between legitimately accredited programs and diploma mills, given that the requirements for the first differ substantially. From relatively easily obtainable PhDs by Published Papers at Bond, GU and SUT to more rigorous requirements at ECU, QUT and UC, there is undoubtedly a huge range in the demands of degrees that recognise a candidate’s published body of work. The cynical reader may assume that with this paper I am simply trying to shore up my own forthcoming graduation with a PhD by Published papers from potential criticisms that it is on par with a ‘purchased’ doctorate. Perhaps they are right, for this is a new degree in QUT’s Creative Industries faculty and has only been awarded to one other candidate (Dr Marcus Foth for his 2006 thesis entitled Towards a Design Methodology to Support Social Networks of Residents in Inner-City Apartment Buildings). But I believe QUT is setting a benchmark, along with ECU and UC, to which other universities should aspire. In conclusion, I believe further efforts should be undertaken to heighten the differences in status between PhDs by Published Papers generated during enrolment, PhDs by Published Papers generated before enrolment and honorary doctorates awarded for non-academic published work. Failure to do so courts cynical comparison of all PhD by Published Papers with unearnt doctorates bought from Internet shysters. References Brown, George. “Protecting Australia’s Higher Education System: A Proactive Versus Reactive Approach in Review (1999–2004).” Proceedings of the Australian Universities Quality Forum 2004. Australian Universities Quality Agency, 2004. 11 June 2008 ‹http://www.auqa.edu.au/auqf/2004/program/papers/Brown.pdf>. Campbell, Philip. “Nature Peer Review Trial and Debate.” Nature: International Weekly Journal of Science. December 2006. 11 June 2008 ‹http://www.nature.com/nature/peerreview/> Crisp, Jane, Kay Ferres, and Gillian Swanson, eds. Deciphering Culture: Ordinary Curiosities and Subjective Narratives. London: Routledge, 2000. 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Kermit the Frog. “Kermit’s Commencement Address at Southampton Graduate Campus.” Long Island University News 19 May 1996. 11 June 2008 ‹http://www.southampton.liu.edu/news/commence/1996/kermit.htm>. McNamara, Eileen. “Honorary senselessness.” The Boston Globe 7 May 2006. ‹http://www. boston.com/news/local/articles/2006/05/07/honorary_senselessness/>. O’Loughlin, Shaunnagh. “Doctor Cave.” Monash Magazine 21 (May 2008). 13 Aug. 2008 ‹http://www.monash.edu.au/pubs/monmag/issue21-2008/alumni/cave.html>. Queensland University of Technology. “Presentation of PhD Theses by Published Papers.” Queensland University of Technology Doctor of Philosophy Regulations (IF49). 12 Oct. 2007. 11 June 2008 ‹http://www.mopp.qut.edu.au/Appendix/appendix09.jsp#14%20Presentation %20of%20PhD%20Theses>. Swinburne University of Technology. Research Higher Degrees and Policies. 14 Nov. 2007. 11 June 2008 ‹http://www.swinburne.edu.au/corporate/registrar/ppd/docs/RHDpolicy& procedure.pdf>. University of Canberra. 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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus , is causing a serious worldwide COVID-19 pandemic. The emergence of strains with rapid spread and unpredictable changes is the cause of the increase in morbidity and mortality rates. A number of drugs as well as vaccines are currently being used to relieve symptoms, prevent and treat the disease caused by this virus. However, the number of approved drugs is still very limited due to their effectiveness and side effects. In such a situation, medicinal plants and bioactive compounds are considered a highly valuable source in the development of new antiviral drugs against SARS-CoV-2. This review summarizes medicinal plants and bioactive compounds that have been shown to act on molecular targets involved in the infection and replication of SARS-CoV-2. Keywords: Medicinal plants, bioactive compounds, antivirus, SARS-CoV-2, COVID-19 References [1] R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. 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