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EU to throw patents in with the bath water
The EU software patent directive will be passed by the EU Council next week, at the same time as a law on bathing water quality
By Ingrid Marson | December 17, 2004 -- 17:15 GMT (09:15 PST) | Topic: Government : UK
The controversial EU directive that opponents fear will allow software patenting within Europe will be passed without vote or debate on Monday.
According to a Council agenda, the Computer Implemented Inventions Directive will be adopted during an Environment meeting, which is also due to deal with the issues of bathing water quality and batteries.
Scottish National Party MEP Ian Hudghton said he is unhappy that the EU Council is hastily pushing this directive through, given the concerns that have been raised.
"The apparent rush on this issue is unacceptable," said Hudghton. "The proposed software patents directive caused a great deal of controversy both in the European Parliament and the Council. Issues of this nature should not be fast-tracked onto the statute book."
Once the Council has adopted the directive, it will go back to the EU Parliament for a second reading. Parliament will then have three months in which to make its views known. Hudghton said it is likely that the proposal will evoke discussion in Parliament as a large number of MEPs are against the proposal.
"The Council should think again if they believe that they are going to get an easy ride through the Parliament during this directive's second reading," said Hudghton. "There is a sizeable proportion of MEPs who believe that the whole proposal is misconceived. The Council must recognise this and understand that the democratically elected representatives will not allow their views to be ignored."
Politicans from Holland, Germany, Poland and Austria have publicly spoken out against the directive.
If the directive is passed by the EU Parliament there is disagreement about what will happen next. Some have expressed concerns about "patent war" breaking out, where patents are used by large corporations to crush smaller competitors or open source projects. Linux creator Linus Torvalds has said that software patents constitute the single biggest threat to the future success of the open source operating system.
But these concerns are rejected by pro-patent organisation EICTA, which is supported by various large multinationals including IBM and HP. Peter Hayward, a director at the UK Patent Office (UKPO), also rejected this fear at a meeting at the Department of Trade and Industry (DTI) earlier this week. "We, the UK, have written some protection [into the directive] to make sure it can't open the floodgates," Hayward said.
Steve Probert, a deputy director at the UKPO, claimed that it will be easier to contest software patents that shouldn't have been granted as the law will be clarified.
"We have conceded that patents have been granted that shouldn't have been," Probert told the DTI. "It's a heck of a lot easier to challenge patents if you have a law. If any have slipped through it should be easier to invalidate them using [the directive]."
Update: The EU directive will now be passed on Tuesday -- for more details please click here.
United Kingdom EU Security Innovation CXO
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Better than the original water softener as this unit has a multi-step valve for use, recharge, discharge, etc. Although you may have soft water in your area, it is still a good idea to install a water softener for even the slightest of calcium/lime deposits that can accumulate in your commercial espresso machine.
This water softener is the best in the industry because it is rechargeable with salt and the unit does not need a filter cartridge replacement, and recharging with salt, which can be picked up at a local hardware or plumbing supply house for a few dollars, is cheaper than replacing other filter-type water softeners which create more landfill waste.


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Fransje Willemien van der Waals (Heemstede (Noord-Holland), 25 februari 1950) is een (voormalig) Nederlands huisarts, SCEN-arts (SCEN staat voor Steun en Consultatie bij Euthanasie in Nederland) en hoogleraar.

Ze was dochter van Jacob Cornelis van der Waals en Christine Luise Elisabeth Helene Johanna Adelheid (Tine) Koenigs. De levenspartner van Van der Waals is viroloog Jaap Goudsmit. Het koppel heeft drie dochters.

Haar middelbare school doorliep ze in Haarlem (Coornhert Lyceum|College, 1963-1969). Daarna ging ze geneeskunde studeren aan de Universiteit van Amsterdam (UvA, 1970-1978). Aanvullend startte ze in 1978 een onderzoek aan het National Institutes of Health in Bethesda (Maryland). Ze vestigde zich in 1981 als huisarts in Amsterdam met een praktijk aan de Reguliersgracht. Ze zou die tot 2021 voeren. Dit combineerde ze tussen 1987 en 1999 met de functie Hoofd Vrouwenstudies Geneeskunde bij de UvA en van 1991 tot 1995 met een promotieonderzoek naar het verschil van gebruik en werking van benzodiazepine bij mannen en vrouwen. Ook is ze vanaf 2001 SCEN-arts. Ze richtte in 2003 bovendien Hearthefoundation op, waarvan ze tussen 2203 en 2021 directeur was. Die stichting zet zich in voor educatieve programma's voor aanstaande medici in bijvoorbeeld ontwikkelingslanden Als basis gold de bestrijding van het Hivvirus, maar in later jaren breidde het palet van de stichting zich uit. Tot slot was ze tussen 2014 en 2020 hoogleraar Global Health Education aan de UvA.

Van der Waals schreef artikelen omtrent de behandeling van gezondheidsproblemen bij vrouwen in een tijd dat de behandeling van ziektes nog altijd gebaseerd was op bij de behandeling van dezelfde ziekte bij mannen. Dat resulteerde in een aantal boeken daarover bijvoorbeeld Het lieve lijf uit 1983.  Van haar verschenen medische artikelen over het probleem in tijdschriften Elle, Marie Claire en Santé.

Gedurende de tijd dat ze als huisarts functioneerde was ze SCEN-arts, waarbij ze ook regelmatig betrokken was in overlegcircuits om hoe om te gaan tussen de theorie en praktijk binnen de euthanasieregelgeving, als ook het verschil in beleid tussen Nederland en de rest van de wereld. Ze kreeg in de 21e eeuw te maken met de tegenstelling wilsbekwaamheid en dementie binnen de behandeling naar euthanasie.

In 2021 ging ze met pensioen, maar omdat ze niet stil kan zetten, zette ze zich in als vrijwilliger binnen de gezondheidswereld (huisartsenposten, vaccinatie etc.)

Nederlands medicus
Nederlands hoogleraar

redpajama_set_name: RedPajamaWikipedia


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Q: Bus error with little remaining disk space and a Python program Several times I was getting "bus error" when trying to run Python with CPython (2.7, x64, RHEL) in a peculiar situation of very little disk space remaining.
This resulted in some of the .pyc files being damaged (I checked their MD5 checksum against MD5 of .pyc files when the program is working as usual) and trying to run the Python program resulted in "bus error" over and over again.
Freeing a good deal of diskspace and deleting all the .pyc files reliably solved the problem (i.e. the same program was running correctly).
My question is why that "bus error" happened in such conditions?

redpajama_set_name: RedPajamaStackExchange


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Q: How to remain the delegate method being called in native instead of react native firebase? PROBLEM
I'm setting up Firebase cloud messaging on my app run on Native(ios & android) which hybrid with React Native on a module. I'm facing problem in receiving message delegate method in iOS native is not call if I use React-Native-Firebase library in react native.
DESCRIPTION
This is happened when I have react-native-firebase on my react-native module. It seems like the delegate methods in native being hijacked by the listener in react-native.
I have tried turned off the react-native module and run the app, the native delegate method would be called once I sent the test notification from Firebase.
EXPECTATION
I expect both delegate method in iOS native and react-native will be called.
The main ideal is I would like both iOS native and react-native can received the notification and proceed the different action accordingly.
Thanks!


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Champions Cup 2019 team presentations - women
This is the first time that the IFF Champions Cup will be played in its new format. The champions from the top four floorball countries: Czech Republic, Finland, Sweden and Switzerland will participate. On Thursday (3rd of January) the teams will play semi-finals and the medal matches will be played on Friday.
SB-Pro Nurmijärvi, 1. SC Tempish Vitkovice, IKSU and Piranha Chur are playing for the Women's Champions Cup title.
SB-Pro Nurmijärvi (FIN)
SB-Pro Nurmijärvi has been a successful team in the Finnish women's floorball league during the last ten years. They play hard, their counterattacks are fast, defence is precise and their goalkeeper is their final lock.
Players to watch:
#35 Tiltu Siltanen
Finnish national team goalkeeper who was nominated as the best goalkeeper in the WFC 2017 All Star team.
#5 Silja Eskelinen
Eskelinen plays in the Finnish national team and has gained international experience from women's WFC in 2015 and 2017 and through playing in Piranha Chur.
#8 Jaana Lirkki
Jaana Lirkki is a national team forward, who has been to women's WFC in 2015 and has played for Women's Word University Championships.
1. SC Tempish Vitkovice (CZE)
A young team with full of desire and enthusiasm to become famous. After winning the Czech league, many experienced players have gone abroad, so they are bringing some new blood into their team. Their goal is to gain experience from every minute of the game, enjoy it and catch every chance.
#16 Zuzana Šponiarová
Suffered from a knee injury last season and became Vitkovice's key player after being ready to play. Young but very experienced two-way forward with exceptional talent.
#69 Justyna Krzywak
Justyna started playing for Vitkovice in 2017 and after her rookie season, she has been a key part of their young team. Why? Because just like she always does, when she sees an opportunity to go for something, she goes for it.
#19 Veronika Enenkelová
Czech national team forward and the most experienced player of Vitkovice right now. Having experiences from the SSL, Veronika is the right one to follow, if you want to learn some good floorball.
IKSU (SWE)
Fast and hard working team with an ambition to keep the opponent team under high pressure as often as possible.
#17 Cornelia Fjellstedt
Exceptional control of the ball and razor sharp split vision. Her creativity makes floorball more fun to watch.
#28 Veera Kauppi
Perhaps the best shooting ability in the world of women´s floorball. Hard work and talent made her the best player in the world last year.
#26 Emelie Wibron
Team captain and the heart and soul of IKSU innebandy. Can do it all, strong on the ball and equipped with world class shooting and passing abilities.
Piranha Chur (SUI)
Piranha Chur is a team with a mix of experienced national team players and young talents from their own offspring and they want to compete with the best teams in Europe. The strength of the team results from the variety of player types with special abilities. Tireless fighting spirit, commitment and a strong team spirit are the keys to success.
#21 Corin Rütimann
Has a very good stick handling and brings in the experience of 100 international matches with the Swiss national team.
#24 Flurina Marti
A good game overview and her hard shot are among her strengths.
#6 Sanni Nieminen
A fast player with tireless effort on the field.
Men's CC 2019 team presentations will be published tomorrow.
More information about Champions Cup 2019:
CC Website: www.floorballchampionscup.eu
CC Facebook: www.facebook.com/FloorballChampionsCup
CC Twitter: twitter.com/floorballcc
CC Instagram: www.instagram.com/floorballcc
CC live-stream, highlights & other clips: www.youtube.com/iffchannel
News Champions Cup Champions Cup 2019
Remember to vote for Czech Men's U19 WFC 2019 gold team
iff-graphics
Ali Karimi from Protocol Sports Marketing about floorball and partnership with the IFF
Top transfer of the week - Klara Fjorder
The international transfer period ends today
Floorball in the media

redpajama_set_name: RedPajamaCommonCrawl


I will not whine a lot starting today.
For the past three days that I was on leave, I spent each day in UP Diliman processing my readmission and cleaning up my self-made stupid cloud as regards enrollment. As of today, I managed to enlist in… four, repeat, four classes, the confirmation of which I'm unable to see because that darn UP Information System site said that my log in name and password were invalid, when those were the same things I used to enlist myself a few hours ago. I tried logging in again and I was successful! However, only three of my four desired classes were confirmed. Yay!
In addition, I so don't understand the concept of enlisting now then viewing if you did get the slots the next day or at 7 p.m. the same day. Who gets to decide in the course of a few hours if you will get it or not? Why can't we get a slot, subtract one from the available slots for the benefit of the next enlistee, then print your choice subjects right then and there? Post-advising, as the term implies, will occur after that, after which you can go ahead and finalize your enrollment OR go back to the computer lab to cancel/replace subjects as your adviser deems fit. Life is easier that way.
I am actually pissed now because yes, I can access CRS, IUS, or whatever you call it, but it won't recognize my log in details. I just need to see if the magical CRS banshee enlisted me in those four classes. It seems it doesn't like me or I might have done something wrong with my log in details, though I am bound to believe the former. The banshee threw in some limited love my way. Gracias.
My next free schedule is on Monday, Veteran's Day, and only by then will I be able to fix my webmail problem (if it doesn't fix itself overnight – I'm giving it a chance because my classmate-friend was unable to check hers last night but was able to this morning, so tomorrow, we'll see), confirm my enlistment, undergo post-advising, pay my tuition fee and settle everything related to it. Take note, November 9 is the official start of classes… I am skipping it because of a plan I have had weeks before this. Yes, a date is more important than a class. Ha-ha. Well, this class was the one that didn't get confirmed. The banshee might have read this entry and decided that since I'm off to a bad start anyway, might as well not give it to me. Sayang, it's going to be Sir Velasco pa naman. Mataas magbigay ng grade, hahaha!!!
Edit: I am going to try the Faculty Prerogative option next week, just to see if I can get in to one more class. I so want to take 12 units this semester, and if they will allow 15 units I'll even go for it. There's an Area III class (every Thursday, 5:30 – 8:30 p.m.) that still has 4 slots available. Either that or any of the Anthropology 225 classes which were both closed as of today. Ang tigas ng ulo ni Octavo, God is already telling me to take 3 subjects only pero mapilit pa rin! Hopeless case!
Another thing I have to settle on Monday is my ID. Have you ever gotten interested on something trivial, something that you don't normally pay attention to, then realize later on that the reason why you took notice of that was because something related to it will happen to you? It's quite like thinking of someone randomly then you will bump into the very same person a little later.
While at the enlistment queue, I noticed a board beside Room 115 which said that this so-and-so place is the best place to go if you lost your valuables. A good 10 minutes after that, while fixing my things at the Faculty Center restroom, I noticed that my ID's missing. Nah, I wasn't bothered. Who would want it anyway? Besides, I'm thinking I could drop by that board again on Monday, go to the room mentioned, with the hope that someone took it there. If it's not there, I will just apply for a new one. I don't like my picture in that ID anyway. When I applied for it, I was wearing a sloppy shirt with a fishbone on it. It was too late when I realized that the photo guy may have found it cute so he included it in the shot. I didn't like the outcome because it's too distracting to see a graduate school ID whose photo has a blue fishbone contrasting heavily with the maroon background.
My Monday will be jampacked. I should be there as early as 8 a.m. It's the start of my happy doom.


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by Loshini Naidoo
The narratives of the migrant women in this paper reveal the challenges of 'uprooting and resettling' faced by many migrant women in Australia who leave their home country to settle in a host nation. It is evident that in the cultural identity development of the women in this paper, the importance of self-selected cultural identity labels as well as the role of the homeland in the development of cultural identity is prominent. Symbols of ethnicity, religion and language identity also illustrate the complexity of cultural identity development among these women who differ in many ways yet share common struggles of developing bicultural or multiple cultural identities in Australia.
This paper attempts to provide an understanding of the challenges that migrant woman, particularly women from the Indian sub-continent face in cultural identity construction. Many experience difficulty in reconciling a previous cultural identity with the 'Australianization' of home, work and family. Some resist the native culture being challenged. West argues that "we all have multiple positions in terms of constructing our identities; there's no such thing as having one identity or of there being one essential identity that fundamentally defines who we actually are."1 Similarly, the poststructural conception of identity considers individuals to be dynamic and contradictory, and identity therefore to be multiple rather than unitary. The resulting multiple identities may be viewed as "a powerful instrument that facilitates adaptation to new sociocultural environments, new roles, and different circumstances."2 For immigrants, assuming different identities "come[s] naturally and permit[s] them to function in multiethnic and multicultural environments."3


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text in Spanish
English (pdf) | Spanish (pdf)
Revista colombiana de Gastroenterología
Rev Col Gastroenterol vol.33 no.2 Bogotá Apr./June 2018
https://doi.org/10.22516/25007440.168
Genotyping of cagA and the intermediate region of vacA in strains of Helicobacter pylori isolated from Colombian adult patients and associations with gastric diseases
M. Camila Melo-Narváez1 *
Diana F. Rojas-Rengifo1
Luisa F. Jiménez-Soto2
María del Pilar Delgado1
Belén Mendoza de Molano3
José Fernando Vera-Chamorro3
Carlos Jaramillo1
1Laboratorio de Diagnóstico Molecular y Bioinformática (LDMB). Universidad de los Andes. Bogotá D.C., Colombia.
2Max von Pettenkoffer Institute for Hygiene and Clinical Microbiology. LMU München. Department of Bacteriology. Múnich, Alemania.
3División de Gastroenterología y Endoscopía Digestiva. Fundación de Santa Fe de Bogotá. Bogotá D. C., Colombia
This study characterizes the diversity of cagA and vacA virulence genes in Colombian patients to determine possible associations between them and the severity of endoscopic findings. It considers all four genotypes reported for the vacA gene (s, m and i).
Materials and methods:
Helicobacter pylori was detected in biopsies of 62 patients through culturing and by molecular methods. Genotypes of cagA and vacA (m/i/s) were determined by PCR and sequencing.
One hundred twenty four strains from 62 patients were isolated. Of these, 48.5% (n = 48) were vacA s2/m2/i2 - cagA (-) which were mostly found in patients with follicular gastritis; 32.3% (n = 32) were vacA s1/m1/i1-cagA (+) which were mostly found in patients with follicular gastritis, chronic gastritis and possible metaplasia. Significant associations were found between the presence of cagA and the vacA s1/m1/i1 genotype and the absence of cagA and the vacA s2/m2/i2 genotype (p <0.001). No significant association was found between the severity of endoscopic findings and the cagA-vacA status of the strains.
We found a low prevalence of cagA (+) strains, the cagA-vacA status is not a predictor of risk in this population. Moreover, the presence of heterogenous infections without tropism suggests a need for biopsies from both the corpus and the antrum of the stomach in routine clinical practice.
Keywords: vacA subtypes; cagA; Helicobacter pylori; Colombia
este estudio caracteriza la diversidad de los genes de virulencia cagA (gen asociado con la citotoxina A) y vacA (citotoxina vacuolizante) en pacientes colombianos para determinar posibles asociaciones entre estos 2 genes y la severidad de los hallazgos endoscópicos teniendo en cuenta todos los genotipos reportados para el gen vacA (s, m e i).
Materiales y métodos:
Helicobacter pylori fue detectado por cultivo y por métodos moleculares en biopsias de 62 pacientes. Los genotipos de cagA y vacA (m/i/s) se determinaron por reacción en cadena de la polimerasa (PCR) y secuenciación.
se aislaron 124 cepas de 62 pacientes; de estas, el 48,5% (n = 48) fueron vacA s2/m2/i2-cagA (-) presente en su mayoría en pacientes con gastritis folicular; mientras el 32,3% (n = 32) fueron vacA s1/m1/i1-cagA (+) presentes mayormente en pacientes con gastritis folicular, gastritis crónica y posible metaplasia. Se encontró una asociación significativa entre la presencia de cagA y el genotipo vacA s1/m1/i1 y la ausencia de cagA y el genotipo vacA s2/m2/i2 (p <0,001). No se encontró una asociación significativa entre la severidad de los hallazgos endoscópicos y el estatus cagA-vacA de las cepas.
se encontró una baja prevalencia de cepas cagA (+), el estatus cagA-vacA no es un predictor de riesgo en la población estudiada y la presencia de infecciones heterogéneas sin tropismo sugieren la necesidad de tomar biopsias tanto del cuerpo como del antro del estómago en la práctica clínica rutinaria.
Palabras clave: Subtipos de vaca; cagA; Helicobacter pylori; Colombia
Helicobacter pylori are spiral-shaped, microaerophilic gram-negative bacteria that infect more than 50% of the world's population. 1 The infection has been associated with diseases such as gastritis, peptic ulcers, MALT (mucosa-associated lymphoid tissue) lymphoma and gastric adenocarcinoma. 2 H. pylori's most important virulence factors are the cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA). 3 Depending on whether the cagA gene is present, strains are classified as positive (type I) which is more virulent due to the visible gastric damage induced, and negative (type II) which is less virulent and acts more like commensal bacteria than pathogens. 4
The VacA protein causes a series of alterations in human gastric cells that include formation of cytoplasmic vacuoles, 5,6 permeabilization of the plasma membrane, 6 mitochondrial secretion of cytochrome c, 7 mitochondrial fragmentation, 8 activation of mitogen-activated kinases. 9 and induction of autophagy. 6 It has been classified as an immunomodulatory protein. 6,10 The vacA gene has 3 polymorphic regions that are involved in the development of the disease: the signal region (s), the intermediate region (i), and the middle region (m). 2,3,6,11,12,13
The s region is involved in the efficiency of channel formation, and the m region affects tropism towards host cells. 3. Although the i region has only recently been described, it has been observed that the vacuolating activity of variant VacA i1 is stronger than that of subtype VacA i2. 3,6 Some analyses of the nucleotide and amino acid sequence of this gene have revealed polymorphisms grouped in clusters A, B and C. Of these, the amino acids in clusters B and C are responsible for the vacuolating activity of the protein. 11
To classify a strain as i1, i2 or i3, the amino acid sequence is compared with sequences of reference strains (60190 for i1 and Tx30a for i2). The i3 variant of vacA includes strains whose B cluster is similar to that of i1 and whose C cluster is similar to that of i2. 11 Different combinations of the 3 regions have been described: vacA s1/m1 strains have vacuolating activity and pose greater risk of gastric atrophy and adenocarcinoma than do the less virulent vacA s2/m2 strains. 11,12 vacA i1 strains have also been associated with gastric adenocarcinoma. 2,11,12
Recently, epidemiological studies have suggested that the interaction between cagA and vacA virulence factors, 6 factors of host susceptibility such as differences between men and women, 14,15,16 and environmental factors modulate development of the disease. 4,12
Several genotyping studies of H. pylori isolates from different Colombian populations have been published. Taking into account that the intermediate region can change the behavior of the toxin, this study complements data on genotyping of these two toxins including characterization of this region of vacA in isolates from a Colombian Andean population with gastric diseases of varying severity and evaluates correlations between genotype and the development of gastric disease.
Patients and Study Population
We included 62 patients from Bogotá, Colombia who were over the age of 18 years, who were infected with H. pylori, and who had gastric symptoms and indications for endoscopy. Patients who had ingested proton pump inhibitors (PPI) within the 15 days prior to the procedure, antacids within the 12 hours prior to the procedure, or antibiotics in month prior to the procedure were excluded. Also excluded were patients suffering from cardiovascular and respiratory diseases, cancer patients who had undergone radiation therapy or chemotherapy in the six months prior to the procedure, and patients with coagulopathies or amyloidosis.
Strains and DNA Purification
Biopsies were macerated and a 10-1 dilution was seeded on GC agar (Oxoid, Germany) supplemented with cholesterol (1X, Gibco) and DENT (Oxoid, Germany). 17 They were incubated at 37° C in a controlled atmosphere with 10% carbon dioxide (CO2) for four to ten days. The Quick-gDNA Miniprep kit (Zymo Research, California, United States) was used to extract DNA in accordance with the manufacturer's instructions. The strains were selected by culture and confirmed as H. pylori by polymerase chain reaction (PCR) of the 23S gene with the HPY-S and HPY-A primers previously reported. 18
Detection of cagA
PCR was performed with the primers designed in this study and the previously reported protocol as modified and described in Table 1. 19 The PCR had a final volume of 25 μL with GoTaq Green Master Mix 1X (Promega, Wisconsin, United States) and 0.25 mM of each primer. Visualization was performed on 1.5% agarose gels.
Table 1 Primers and protocol used for amplification of cagA and vacA
bp: base pairs
vacA Genotyping
The 3 polymorphic regions of the vacA gene were characterized by means of PCR with a final volume of 25 μL containing GoTaq Green Master Mix 1X (Promega, Wisconsin, United States) and 0.25 mM of the corresponding primers for each region according to the previously reported protocols as modified in this study (Table 1).
For the visualization of the products, 2% agarose gels were used for the m and i regions and 10% polyacrylamide was used for the s region. (29: 1) Polyacrylamide gels were stained with a 3X GelRed solution (15 μL of Gelred 10,000X and 5 mL of sodium chloride [NaCl] 1M) for 1 hour under constant stirring at room temperature.
Samples that tested positive for both subtypes (vacA i1 and i2) were sequenced (Macrogen, Seoul, Korea). Sequence analysis was performed with CLC Genomics Workbench 10, and amino acid sequences were compared with reference sequences 60190 (GenBank No. U05676) and Tx30a (GenBank No. U29401). Strains were defined as i3 when the B cluster was similar to that of reference strain i1 and the C cluster was similar to reference strain i2.11
Fisher's exact test was used to determine possible associations between the cagA status and the vacA genotype of the strains, and a generalized linear model was used to determine which variables had significant associations. The same statistical analysis was performed for polymorphic regions of the vacA gene and cagA status and between and among cagA status, vacA gene subtypes and severity of endoscopic findings. A chi squared (χ2) test was used to determine associations between the patient's sex and cagA status, and the patient's sex and severity of endoscopic findings. Endoscopic findings were classified as either mild gastric disease and severe gastric disease (Table 2). R software 20 was used for analysis and a p value <0.05 was considered significant.
Table 2 Classification of endoscopic findings*
* Prevalence of endoscopic findings is shown with classification as either mild or severe according to medical criteria.
Patients and Isolation of H. pylori
We analyzed 124 H. pylori strains from 62 patients who had a variety of symptoms (Table 3). Their average age was 50.2 ± 16.2 years, and the male-female ratio was 1.48/1.
Table 3 Distribution of gastric symptoms reported by patients*
* Patients reported various gastric symptoms before digestive endoscopy.
Genotyping of cagA and vacA
PCR with corresponding primers established that 52 (48.1%) of the 124 strains analyzed were positive for cagA. No significant associations were found between the severity of endoscopic findings and the presence of cagA (χ2, p> 0.05) (Table 4). There were also no significant associations between the sex of the patients and the presence of cagA (χ2, p> 0.05), between the severity of the endoscopic findings and sex (Fisher's exact test, p> 0.05), or between the severity of the endoscopic findings and the presence of cagA (χ2, p> 0.05) (Table 4).
Table 4 Association between severity of endoscopic findings, cagA status and polymorphic regions of the vacA gene*
* No significant relationships were found between the severity of endoscopic findings and cagA or vacA status. Patients who had different genotypes in the gastric antrum and corpus were excluded. Fisher's exact test and a generalized linear binomial model (p> 0.05) were used.
In the case of vacA, 16 strains were discarded (n = 8 patients) because it was not possible to determine the genotype for the s region in three cases (37.5%), the m region in three cases (37.5%), the s region in one case (12.5%) and for all three regions in one other case (12.5%). Of the remaining 108 strains, fifty strains were s1, fifty-eight were s2, forty-one were m1, and sixty-seven were m2. Thirty-four strains were i1 and 55 i2. Nineteen of the samples sequenced (17.6%) showed amplification for both vacA i1 and vacA i2 subtypes (GenBank No. MF457450 to MF457477). Of these, four were classified as i1, three as i2, three as i3 and nine as i1i2. The last group was eliminated in subsequent analyses. No significant associations were found the severity of the endoscopic findings and either vacA subtypes or the full vacA genotype (χ2, p> 0.05) (Table 4).
Twenty-eight strains (22.6%) were discarded from the evaluation of the relationship between the two genes because they had different genotypes of cagA and vacA between antrum and corpus. No significant tropism or correlation was found between the genotype and location within the stomach of these strains. However, a significant association was found between cagA status and the vacA gene subtypes looked at separately (Fisher's exact test, p <0.05) (Figure 1) and combined as follows: s1/m1/i1-cagA positive (32.3%), s1/m2/i1-cagA positive (2.02%) and s1/m2/i2 (7.07%). Of these 71.4% were cagA positive, 2.02% were s1/m1/i3-cagA positive, 1.01% were s1/m2/i3-cagA positive, 2.02% were s2/m1/i1-cagA positive, and 48.5% were s2/m2/i2-cagA negative (Fisher's exact test, p <0.001, generalized linear model binomial p <0.05). In addition, all vacA i3 strains were cagA positive.
Figure 1 Association between cagA status and vacA subtypes. There is a significant association between cagA status and vacA subtypes. Patients with cagA status or vacA genotypes that differed between the antrum and corpus were excluded. Fisher's exact test and a generalized linear binomial model (p <0.001) were used.
This study characterizes the diversity of virulence genes cagA and vacA in Colombian patients to determine possible associations between these two genes and the severity of the endoscopic findings. It considers all three genotypes reported for the vacA gene: s, m and i. The combination of genetic variability, host factors and environmental factors plays a fundamental role in the development of pathologies during H. pylori infections. 3,4,6,12,21,22,23. It has been reported that patients infected with vacA s1/m1/i1-cagA (+) strains are at greater risk of developing gastric carcinomas than are patients infected with the less virulent vacA s2/m2/i2-cagA (-). 2,4,11,23,13,19,24
In the Colombian population studied, a prevalence of 48.1% was found for infections with cagA positive strains. This is lower than previously reported in studies conducted in Bogotá, Colombia which found a prevalence of 73%, 24 but it is similar to that reported in patients from Tolima, Colombia for whom prevalence of cagA positive strains was 43%. 25 The prevalence reported here also differs from those found in other regions of the world such as Senegal (73.3%), 26 the Middle East (100%), the United States (80%), and Western Europe and Latin America (60% to 70%). 11 This is probably due to the fact that the selected population was of medium and high socioeconomic class since it has been seen that the prevalence of the infection is higher in lower socioeconomic levels with poor sanitary conditions. 27,28
This study also shows that 22.6% of the patients were infected with two different strains of either or both cagA and vacA in the gastric antrum and corpus but without any tropism. It is possible that these patients have been infected on more than one occasion by different strains of H. pylori because the prevalence of multiple infections seems to be higher in places like Colombia where the risk of H. pylori infection is high. 29,30 The presence of these types of infections reaffirms the need to routinely take biopsies from both the corpus and antrum.
The relationship between the presence of cagA and the vacA s1 genotype has been described by several authors. 31,32 In this study, 68.1% of positive cagA strains were vacA s1/m1/i1 and only 6.4% were vacA s2/m2/i2. Thus, the vacA s1/m1/i1 genotype has a significant association with the presence of the cagA gene. In the case of vacA s1/m2 strains, it has been observed that whether the prevalence of type i1 is greater that the prevalence of i2 strains and vice versa depends on the geographical region. 2,26 A low prevalence of the vacA s2/m1 combination was found in this study. This agrees with previous findings which suggests that the low prevalence of this genotype may be explained by negative selection of this subtype because it is unfavorable for microorganisms. 26
In addition, this study describes intermediate region of the vacA gene strains in strains circulating in this Colombian population. Almost all of the vacA s1/m1 strains (94.4%) were i1 and almost all the vacA s2/m2 strains were i2. This agrees with what was reported in the first description of the intermediate region. 2 The majority of strains analyzed were vacA i2, and only three patients were found to be infected by vacA i3 strains defined as those with cluster B similar to i1 and cluster C similar to type i2. (11) The i3 variant could reflect a recombination process between type i1 and i2 strains. 6,11 The clinical or pathological importance of this variant remains unknown, and our study found no significant associations with endoscopic findings. However, all vacA i3 strains were cagA positive. A larger sample of patients infected with i3 strains is needed to gain a better understanding of the nature of this genotype and the development of the disease in these patients.
In contrast to the significant associations between the vacA s1/m1/i1-cagA (+) genotype and some severe digestive diseases such as atrophic gastritis, ulcers and gastric adenocarcinoma observed in other studies, 33 no significant associations were found between the cagA-vacA status of the strains and the severity of the endoscopic findings in this study despite the fact that most of the strains isolated were vacA s2/m2/i2-cagA (-) from patients who mostly presented follicular gastritis (Figure 2). This could be the result of the small sample sizes of each of the categories of severity of endoscopic findings (mild or severe) and the high prevalence of type II strains in the patients. For this reason, the vacA genotype cannot be used to identify high-risk patients in the study population.
Figure 2 Relative prevalence of endoscopic findings according to the genotype of H. pylori strains isolated in these patients. 52.5% of patients were infected with H. pylori vacA s2/m2/i2-cagA negative strains which were mostly related to follicular gastritis. Patients who had different cagA or vacA genotypes in the antrum and corpus were excluded. Suspicion of metaplasia (SM), gastric ulcer (UG), atrophic gastritis (GA), petechial gastritis (GP), erosive gastritis (GE), chronic gastritis (GC) and follicular gastritis (GF).
In conclusion, this study provides new information on the prevalence of cagA and vacA virulence factors, and their association with endoscopic findings. Studies conducted on the west coast and in the southern Colombian Andes differ from the findings of this investigation highlighting the need to increase the number of studies that compare different regions and Colombian populations. 34,35 This is especially true since the data published in Colombia show great variations in the presence of genetic markers of pathogenicity and their correlations with the severity of gastric pathologies.
On the other hand, recent studies have indicated that H. pylori strains in the Colombian population originating in the European line (HpEurope) have evolved independently. 36 It is likely that molecular mechanisms typically associated with severe gastric diseases associated H. pylori behave differently in the Colombian population thanks to the different ancestries present. 37 If the bacterium-host relationship is considered, it is possible that the lack of correlations between cagA and vacA and the pathology of the infection relative to the findings of other studies could be thoroughly investigated only if the ancestral distributions in the various regions of Colombia.
The authors would like to thank Sebastián Posada MD, Laura Camila Zuluaga MD, Daniela Campaz, MD and Manuel Arrieta MD for their help in the collection of samples and management of the database. We would also like to thank Verónica Arévalo Jaimes for her help with molecular processing and identification of strains by means of PCR of the 23S region. We thank Professor Adolfo Amézquita and Cindy Ulloa for their support in statistical analysis.
1. Peleteiro B, Bastos A, Ferro A, et al. Prevalence of Helicobacter pylori infection worldwide: a systematic review of studies with national coverage. Dig Dis Sci. 2014;59(8):1698-709. doi: 10.1007/s10620-014-3063-0. [ Links ]
2. Rhead JL, Letley DP, Mohammadi M, et al. A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterology. 2007;133(3):926-36. doi: 10.1053/j.gastro.2007.06.056. [ Links ]
3. Jones KR, Jang S, Chang JY, et al. Polymorphisms in the intermediate region of VacA impact Helicobacter pylori-induced disease development. J Clin Microbiol. 2011;49(1):101-10. doi: 10.1128/JCM.01782-10. [ Links ]
4. García CA, Barra TR, Delgado SC, et al. Genotipificación de aislados clínicos de Helicobacter pylori en base a genes asociados a virulencia cagA, vacA y babA2: primer aislamiento de una cepa babA2 positiva en pacientes chilenos. Rev Médica Chile. 2006;134(8):981-8. doi: 10.4067/S0034-98872006000800006. [ Links ]
5. Cover TL, Blaser MJ. Purification and characterization of the vacuolating toxin from Helicobacter pylori. J Biol Chem. 1992;267(15):10570-5. [ Links ]
6. Kim I-J, Blanke SR. Remodeling the host environment: modulation of the gastric epithelium by the Helicobacter pylori vacuolating toxin (VacA). Front Cell Infect Microbiol. 2012;2:37. doi: 10.3389/fcimb.2012.00037. [ Links ]
7. Foo JH, Culvenor JG, Ferrero RL, et al. Both the p33 and p55 Subunits of the Helicobacter pylori VacA Toxin Are Targeted to Mammalian Mitochondria. J Mol Biol. 2010;401(5):792-8. doi: 10.1016/j.jmb.2010.06.065. [ Links ]
8. Jain P, Luo Z-Q, Blanke SR. Helicobacter pylori vacuolating cytotoxin A (VacA) engages the mitochondrial fission machinery to induce host cell death. Proc Natl Acad Sci U S A. 2011;108(38):16032-7. doi: 10.1073/pnas.1105175108. [ Links ]
9. Nakayama M, Kimura M, Wada A, et al. Helicobacter pylori VacA Activates the p38/Activating Transcription Factor 2-mediated Signal Pathway in AZ-521 Cells. J Biol Chem. 2004;279(8):7024-8. doi: 10.1074/jbc.M308898200. [ Links ]
10. Boncristiano M, Paccani SR, Barone S, et al. The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms. J Exp Med. 2003;198(12):1887-97. doi: 10.1084/jem.20030621. [ Links ]
11. Chung C, Olivares A, Torres E, et al. Diversity of vacA intermediate region among Helicobacter pylori strains from several regions of the world. J Clin Microbiol . 2010;48(3):690-6. doi: 10.1128/JCM.01815-09. [ Links ]
12. Ferreira RM, Machado JC, Letley D, et al. A novel method for genotyping the Helicobacter pylori vacA Intermediate region directly in gastric biopsy specimens. J Clin Microbiol . 2012;50(12):3983-9. doi: 10.1128/JCM.02087-12. [ Links ]
13. González-Rivera C, Algood HMS, Radin JN, et al. The intermediate region of Helicobacter pylori vacA is a determinant of toxin potency in a jurkat t cell assay. Infect Immun. 2012;80(8):2578-88. doi: 10.1128/IAI.00052-12. [ Links ]
14. Agah S, Khedmat H, Ghamar-Chehred ME, et al. Female gender and Helicobacter pylori infection, the most important predisposition factors in a cohort of gastric cancer: a longitudinal study. Casp J Intern Med. 2016;7(2):136-41. [ Links ]
15. Naja F, Kreiger N, Sullivan T. Helicobacter pylori infection in Ontario: Prevalence and risk factors. Can J Gastroenterol. 2007;21(8):501-6. doi: 10.1155/2007/462804. [ Links ]
16. Zhu Y, Zhou X, Wu J, et al. Risk factors and prevalence of Helicobacter pylori infection in persistent high incidence area of gastric carcinoma in Yangzhong City. Gastroenterol Res Pract. 2014;2014:e481365. [ Links ]
17. Jiménez-Soto LF, Rohrer S, Jain U, et al. Effects of cholesterol on Helicobacter pylori growth and virulence properties in vitro. Helicobacter. 2012;17(2):133-9. doi: 10.1111/j.1523-5378.2011.00926.x. [ Links ]
18. Ménard A, Santos A, Mégraud F, et al. PCR-restriction fragment length polymorphism can also detect point mutation A2142C in the 23S rRNA gene, associated with Helicobacter pylori resistance to clarithromycin. Antimicrob Agents Chemother. 2002;46(4):1156-7. doi: 10.1128/AAC.46.4.1156-1157.2002. [ Links ]
19. Secka O, Antonio M, Berg DE, et al. Mixed infection with cagA positive and cagA negative strains of Helicobacter pylori lowers disease burden in The Gambia. PLoS ONE. 2011;6(11):e27954. doi: 10.1371/journal.pone.0027954. [ Links ]
20. R Development Core Team. R: A language and environment for statistical computing. R Foundation for Statistical Computing ENT#091;internetENT#093; 2008 ENT#091;acceso el 24 de noviembre de 2016ENT#093;. Disponible en: Disponible en: http://www.R-project.org . [ Links ]
21. Argent RH, Thomas RJ, Letley DP, et al. Functional association between the Helicobacter pylori virulence factors vacA and cagA. J Med Microbiol. 2008;57(2):145-50. doi: 10.1099/jmm.0.47465-0. [ Links ]
22. Jang S, Jones KR, Olsen CH, et al. Epidemiological link between gastric disease and polymorphisms in vacA and cagA. J Clin Microbiol . 2010;48(2):559-67. doi: 10.1128/JCM.01501-09. [ Links ]
23. Yamazaki S, Yamakawa A, Okuda T, et al. Distinct Diversity of vacA, cagA, and cagE Genes of Helicobacter pylori Associated with Peptic Ulcer in Japan. J Clin Microbiol . 2005;43(8):3906-16. doi: 10.1128/JCM.43.8.3906-3916.2005. [ Links ]
24. Quiroga AJ, Cittely DM, Bravo MM. Frecuencia de los genotipos babA2, oipA y cagE de Helicobacter pylori en pacientes colombianos con enfermedades gastroduodenales. Biomédica. 2005;25:325-34. doi: 10.7705/biomedica.v25i3.1357. [ Links ]
25. Molina Delgado A, Jaramillo Henao C, Delgado Perafán M, et al. Detección y genotipificación de Helicobacter pylori sobre la base de los genes ADNr 16S y el gen asociado a citotoxina (cagA) y posible asociación con enfermedades gastrointestinales. Revista Cubana de Medicina Tropical. 2008;60:105-10. [ Links ]
26. Basso D, Zambon C-F, Letley DP, et al. Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology. 2008;135(1):91-9. doi: 10.1053/j.gastro.2008.03.041. [ Links ]
27. Parente JML, da Silva BB, Palha-Dias MPS, et al. Helicobacter pylori infection in children of low and high socioeconomic status in northeastern Brazil. Am J Trop Med Hyg. 2006;75(3):509-12. [ Links ]
28. Ramírez Ramos A, Chinga Alayo E, Mendoza Requena D, et al. Variación de la prevalencia del H. pylori en el Perú período (1985-2002), en una población de nivel socioeconómico medio y alto. Rev Gastroenterol Perú. 2003;23(2):92-8. [ Links ]
29. Mendoza-Elizalde S, Cortés-Márquez AC, Giono-Cerezo S, et al. Analysis of the genotypic diversity of strains of Helicobacter pylori isolated from pediatric patients in Mexico. Infect Genet Evol. 2015;29:68-74. doi: 10.1016/j.meegid.2014.11.002. [ Links ]
30. Pinto-Ribeiro I, Ferreira RM, Batalha S, et al. Helicobacter pylori vacA genotypes in chronic gastritis and gastric carcinoma patients from Macau, China. Toxins (Basel). 2016;8(5). pii: E142. doi: 10.3390/toxins8050142. [ Links ]
31. Atherton JC, Cao P, Peek RM Jr, et al. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem. 1995;270(30):1-7. doi: 10.1074/jbc.270.30.17771. [ Links ]
32. Nagiyev T, Yula E, Abayli B, et al. Prevalence and genotypes of Helicobacter pylori in gastric biopsy specimens from patients with gastroduodenal pathologies in the Cukurova Region of Turkey. J Clin Microbiol . 2009;47(12):4150-3. doi: 10.1128/JCM.00605-09. [ Links ]
33. Breurec S, Michel R, Seck A, et al. Clinical relevance of cagA and vacA gene polymorphisms in Helicobacter pylori isolates from Senegalese patients. Clin Microbiol Infect. 2011;18(2):153-9. doi: 10.1111/j.1469-0691.2011.03524.x. [ Links ]
34. Bravo MM, Trujillo E, Quiroga A, et al. Genotipificación de Helicobacter pylori en individuos de dos regiones de Colombia con riesgo de cáncer gástrico opuesto. Rev Colomb Cancerol. 2013;17(4):178-9. [ Links ]
35. Nogueira C, Figueiredo C, Carneiro F, et al. Helicobacter pylori genotypes may determine gastric histopathology. Am J Pathol. 2001;158(2):647-54. doi: 10.1016/S0002-9440(10)64006-0. [ Links ]
36. Muñoz-Ramírez ZY, Mendez-Tenorio A, Kato I, et al. Whole genome sequence and phylogenetic analysis show Helicobacter pylori strains from Latin America have followed a unique evolution pathway. Front Cell Infect Microbiol. 2017;7:50. doi: 10.3389/fcimb.2017.00050. [ Links ]
37. Ossa H, Aquino J, Pereira R, et al. Outlining the ancestry landscape of Colombian admixed populations. PLoS One. 2016;11(10):e0164414. doi: 10.1371/journal.pone.0164414. [ Links ]
Financing This study was supported by the Faculty of Sciences of the Universidad de los Andes through the project entitled "Factors of virulence cagA and vacA of strains of H. pylori and its relationship with pathology in symptomatic Colombian adult patients" code P16.160322.001/01-BIO01 (according to a decision of the Research Projects Committee on 12/11/2015) and by DFG research grant (JI 221/1-1) for LFJ-S.
Received: September 28, 2017; Accepted: April 13, 2018
Carrera 19C No. 86-14 Oficina 203, Bogotá, D.C. Colombia
Teléfono: 6169950 - 6168315
revistagastro@gastrocol.com


text:
Tre passi nel delirio (Histoires extraordinaires) – film franco-italiano del 1968
I racconti di Edgar Allan Poe (Histoires extraordinaires) – serie televisiva francese trasmessa nel 1981


text:
PWD         := $(shell pwd)
VENDOR_PATH := $(PWD)/vendor
BIN_PATH    := $(PWD)/bin
BUILD_PATH  := $(PWD)/build
NOW         := $(shell date +%Y-%m-%d--%H-%M-%S)
REPO        := "https://github.com/ronanguilloux/php-gpio"
BRANCH      := 'master'
# Colors
YELLOW      := $(shell tput bold ; tput setaf 3)
GREEN       := $(shell tput bold ; tput setaf 2)
RESETC      := $(shell tput sgr0)

############################################################################
# Mandatory tasks:

all: build .git/hook/pre-commit vendor/autoload.php help done

build:
	@mkdir -p build/cov
	@mkdir -p build/logs

vendor/autoload.php:
	@composer self-update
	@composer install --optimize-autoloader

install:
	@composer self-update
	@composer install --optimize-autoloader

update:
	@composer install --optimize-autoloader

.git/hook/pre-commit:
	@curl -s -o .git/hooks/pre-commit https://raw.githubusercontent.com/polypodes/Build-and-Deploy/master/hooks/pre-commit
	@chmod +x .git/hooks/pre-commit

############################################################################
# Generic sf2 tasks:

help:
	@echo "\n${GREEN}Usual tasks:${RESETC}\n"
	@echo "\tTo initialize:\t\tmake"
	@echo "\tTo check code quality:\tmake quality"
	@echo "\tTo run tests suite:\tmake tests"
	@echo "\tTo fix code style:\tmake cs-fix"

	@echo "\n${GREEN}Other specific tasks:${RESETC}\n"
	@echo "\tTo evaluate code coverage:\t\t\tmake codecoverage"
	@echo "\tTo run a simple continuous tests server:\tmake continuous"
	@echo "\tTo dry-fix code style issues:\t\t\tmake dry-fix"
	@echo "\tTo evaluate code quality stats:\t\t\tmake stats"
	@echo "\tTo update vendors using Composer:\t\tmake update\n"

unit: vendor/autoload.php
	@echo "Run unit tests..."
	@php bin/phpunit -v

continuous: vendor/autoload.php
	@echo "Starting continuous tests..."
	@while true; do bin/phpunit -c build/phpunit.xml -v; done

sniff: vendor/autoload.php
	@bin/phpcs --standard=PSR2 src -n
	@bin/phpcs --standard=PSR2 tests -n

dry-fix:
	@bin/php-cs-fixer fix . --config=sf23 --dry-run -vv

cs-fix:
	@bin/phpcbf --standard=PSR2 src
	@bin/phpcbf --standard=PSR2 tests
	@bin/php-cs-fixer fix . --config=sf23 -vv

#quality must remain quiet, as far as it's used in a pre-commit hook validation
quality: sniff dry-fix

# packagist-based dev tools to add to your composer.json. See http://phpqatools.org
stats: quality done
	@echo "Some stats about code quality"
	@bin/phploc src
	@bin/phploc tests
	@bin/phpcpd src
	@bin/phpcpd tests
	@bin/pdepend --summary-xml=./build/summary.xml --jdepend-chart=./build/jdepend.svg --overview-pyramid=./build/pyramid.svg src
	@bin/phpmd src text codesize,unusedcode

done:
	@echo
	@echo "${GREEN}Done.${RESETC}"

tests: vendor/autoload.php
	@echo "Run tests & build code coverage report..."
	@bin/phpunit -v --coverage-html ./build/codecoverage
	@echo "\n${GREEN}Check code coverage:${RESETC}\n"
	@echo "\t(OS X)\t\topen build/codecoverage/index.html"
	@echo "\t(Linux)\t\txdg-open build/codecoverage/index.html\n"

############################################################################
# .PHONY tasks list

.PHONY: all install update help unit codecoverage continuous
.PHONY: sniff dry-fix cs-fix quality stats done tests
# vim:ft=make

redpajama_set_name: RedPajamaGithub


text:
Sefton Preparing for Adulthood Workshop15thJanuary 2020
Sefton Preparing for Adulthood Workshop 15th January 2020
for parents and carers of young people with SEND who want to know more about what to doand what is availablewhen their young person turns 14 years of age. For parents and carers of young people with SEND who want to know more about what to doand what is availablewhen their young person turns 14 years of age. For more info, please click on the link below.
Sefton Preparing for Adulthood Workshop Flyer
Slideshow Administration
Discover Litherland High School
Welcome to Litherland High School
Welcome to Litherland High School's website. It is a pleasure and a privilege to introduce you to our school. This website gives you an insight of what the school is about; it celebrates our student's achievements and allows you to see some of the opportunities available to students. Litherland High School is a mixed 11-16 school where every student is valued and treated as an individual. Our core purpose is "Success for All" and we aim to create a positive climate for learning where expectations and standards are high and our students are supported to do their best and achieve their full potential.
Click on the links below to explore our Photo Galleries.
The Heath Family (NW) Multi-Academy Trust
On Sunday 1st March 2015, Litherland High School officially changed its status to become an academy, part of The Heath Family (NW) Multi-Academy Trust.
School leaders fromacross the trust are working very closely to bring about rapid and sustained improvements throughout the school, involving students, teachers, parents and the local community in order to bring a bright future for all students at Litherland High School. This was underlined by the recent Ofsted report which stated 'The partnership with the Heath Family Multi-Academy Trust has been highly beneficial.' The report went on to say that the students feel safe in school and they make a key contribution to a well-ordered and harmonious school. The HMI noted that the school continues its improvement journey at an ever increasing pace.
The Heath Family is centred on raising standards of achievement and aspirations for all students to the highest standard by developing and nurturing both primary and secondary academies. For more information click on the link in the About Us section above.
What's going on at LHS?!
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text:
Home Lifestyle Global partners commit $12 billion to UN-backed fund to fight AIDS, Tuberculosis,...
Global partners commit $12 billion to UN-backed fund to fight AIDS, Tuberculosis, Malaria
UN News Service
UNAIDS Executive Director Michel Sidibé. Photo: B.Hamilton/UN
The Joint United Nations Programme on HIV/AIDS (UNAIDS) welcomed today a $12 billion commitment by international partners to the Global Fund to Fight AIDS, Tuberculosis and Malaria at its fourth replenishment meeting in Washington, DC.
"Support for the Global Fund comes at a crucial point – in many parts of the world we are entering into a 'make or break' point in progressing towards our goals," said Michel Sidibé, Executive Director of UNAIDS, applauding the commitments made at the meeting, which comes on the heels of Sunday's commemoration of World AIDS Day.
"These pledges are a demonstration of global solidarity and trust to move towards ending the three diseases," he said.
Echoing that sentiment was Mark Dybul, Executive Director of the Global Fund, who said in closing remarks: "The 21st century ideals that led to the founding of the Global Fund are now stronger than ever: partnership, shared responsibility, and mutual accountability. In many ways, this is a replenishment of hope. It is a lifting up of the human spirit."
"We've had a terrific beginning," said Dr. Nafsiah Mboi, Chair of the Board of the Global Fund, who led the pledging session, which aimed to generate funds for the next three years. "I offer heartfelt thanks for the generosity of all partners in this effort. Now let's go to work."
Delivering remarks on behalf of UN Secretary-General Ban Ki-moon, Mr. Sidibé said that while ongoing support has led to many advances in the response, AIDS, TB and malaria financing from the international community remains a lifeline for millions of people.
"We must act with resolve to preserve these gains, which remain fragile. If bed nets and anti-malarials are not delivered and used in time, malaria will continue to spread. Drug-resistant tuberculosis is on the increase, he said, adding that an AIDS-free world is in sight, but success depends on our unwavering resolve to bring treatment to the nearly three in 10 children and adults who still do not have access to it.
"We need to work smarter and better to truly end these infectious diseases."
Opened by United States President Barack Obama, the meeting was also an opportunity for world leaders and partners to review progress and look to the future. According to UNAIDS, the new commitments represent a sharp increase compared to pledges made at the previous replenishment conference of $9.2 billion.
Shared responsibility by countries has also grown. Domestic spending on HIV has increased, accounting for approximately of 53 per cent of global HIV resources in 2012. The total global resources available for HIV in 2012 were estimated at $18.9 billion.
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1100 Tulip Avenue, Victoria, BC V8Z 7Z2, Canada. Built in 2007, it has 28, single storey townhouses. Crossroad are Wilkinson Road and West Burnside Road. Close to Marigold Park, Hyacinth Park, Victoria Saanich Women's Softball Association, Ecole Marigold School, Spectrum Community School, Impulse Foods and Burnside Food Market.
Maintenance fees includes building insurance, management, water and yard maintenance.


text:
The Royal Forums > Reigning Houses > Dutch Royals > Princess Mabel and Children
Princess Mabel and 'The Elders' and 'Girls Not Brides'
Marika86
Heir Apparant
Picture of the Week Team Member
Location: Villa San Giovanni, Italy
Mabel van Oranje at TEDWomen:
"It's very special, as Kate is very special. It's my way of making sure my mother didn't miss out on today and the excitement." Prince William, November 16 2010
Royal Blogger, TRF Author
Location: Brussels, Belgium
Princess Mabel has been to Cyprus, with several members of the elders (among them Desmond Tutu) to attend the talks between the leaders of Greek Cyprus and Turkish Cyprus.
Since 2008 the Elders are trying to solve the split of the islands, but with little result thus far.
Source: royalblog.
TRF Rules and FAQ
On January 25, Princess Mabel spoke at "4th Global Competitiveness Forum"
Global Competitiveness Forum: The Event
http://www.youtube.com/watch?v=Q4I_fxqHKSg
Tsarevitch
Location: Maastricht, Netherlands
I admire Princess Mabel for her lifelong zest in democratization, justice and equal opportunities. She did it before her marriage with the Soros Foundation, the Open Society Institute, War Child and she continues it now with The Elders.
Location: Spring Hill, United States
She is a person to admire.
Location: Amsterdam, Netherlands
HRH Princess Mabel,CEO of " The Elders" travels to North-Korea today on a mission that includes former US President Jimmy Carter,former President of Finland Martti Ahtisaari,former President of Ireland Mary Robinson and former PM of Norway Gro Brundlandt in a bid to ease tensions between the two Korea's.The Princess is the first member of the Dutch Royal Family to visit North-Korea.HRH was in Beijing over the Easter weekend as part of a six day mission to Beijing,Pyongyang and Seoul with The Elders.The group will return to Seoul on the 27th till the 29th of April after which the Princess will leave for The Netherlands to celebrate Koninginnedag with the rest of the Family.Admirable woman indeed.
Mission statement | The Elders
After a full schedule the past week,and Queensday celebrations here in The Netherlands,the Princess,CEO of The Elders,just arrived in Cote d ' Ivoire,Africa on yet another Peace mission
with The Elders.Admirable Lady!
Princess Mabel was yesterday present for the meeting of The Elders, an independent group of global leaders who work together for peace and human rights. The meeting took place at the Royal Palace in Oslo, Norway on May 7, 2012. Members of the Norwegian Royal Family - King Harald, Queen Sonja, and Crown Prince Haakon - were also present, as was Jimmy Carter (former US President).
- The Picture
I am really glad to see Mabel again. This must be a horrible time for her, but life goes on and she should focus on that.
Artemisia's Royal Jewels *** Artemisia's Royal Den
I am, always, amazed, at someone as knowledgeable as Mabel, allowing this situation to continue, but then, again, it is her situation, and who am I to judge.
The Princess Mabel has resigned as CEO of The Elders as of now due to her "personal situation" .
The Elders accepted the resignation with great and deep regret.
princess gertrude
Location: Columbia, United States
So sad to hear about her resignation. What a wonderful opportunity she's had being their CEO. Hopefully she will cherish the memories and find something as meaningful and fulfilling that will allow her to spend time with her husband without traveling so much.
I am sure that she feels torn between her attention due her job and her attention to her children. I can't imagine she can spend much time the the prince.
Originally Posted by princess gertrude
She has something very meaningfull and fullfilling,being with her daughters as much as possible and being at her husbands bedside,every day.Something she already did.Much of her work could be done from home,and that's where she was almost all the time these past 2 months.The travelling as a CEO would become too much of a strain at present as we all understand I think.Adjusting to situations asks time and courage.I admire her for her courage and have the greatest respect for her choices.
Apparently she will work part-time until they found a replacement.
Sad, but quite understandable, esp. as she has to take care of her two daughters without the support of her husband now.
Absoluetly, she is much to be admired. A terrible position.
rominet09
Location: LIEGE, Belgium
I think she is right her daughters need her. What an awful situation with children too young to understand and who ask for their father !
Originally Posted by lucien
I do think that you might have mistaken what I was saying. I was not implying that her husband and children weren't meaningful or fulfilling. As most of us know families are the most precious thing that we have. I was only thinking that she could be involved with some type of organization in London that would benefit greatly from her expertise, which in turn would give her an outlet. No more, no less. And it was a great lose for the Elders.
No no no,I understood.Another job,the very thought of it,is not opportune not to say out of the question at this point.HRH still is a part-time adviser to The Elders,like Marengo explained untill they found a replacement.Will be a tough job to fill.You?...
Oh, I don't think she needs to run out and find something right now. Just in the future (6 months, a year, whenever). I think that Mabel is a very intellegent woman with a load of potential to do good.
Location: San Francisco, United States
Press release from The Elders:
Mabel van Oranje resigns as CEO of The Elders | The Elders
Sii forte.
princess mabel
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Lady Davina Lewis & Lady Rose Gilman and Families, News 1: September 2007 - Genia British Royals 162 05-25-2019 08:29 AM
Little girls and Princesses Alastair_r General Royal Discussion Archive 7 07-30-2009 05:57 PM


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by Jazz Monroe
Associate Staff Writer
Bonnaroo 2019 Attendee Dies After "Medical Situation" on Campgrounds
The man, 27, had an underlying condition, organizers say
Bonnaroo 2019, photo by FilmMagic/FilmMagic for Bonnaroo Arts And Music Festival
A Bonnaroo attendee died after suffering a "medical situation" on the festival campgrounds yesterday (June 15), festival organizers say (via The Tennessean). The 27-year-old Tennessee man, who was at the 80,000-capacity festival with his father, received CPR from medics minutes after being found unresponsive. He was pronounced dead after being moved to the hospital. Organizers said the victim appears to have had an underlying medical condition.
Further details have not yet been released. Read the festival's full statement below.
The well-being of our patrons, staff, volunteers and artists is our primary concern, and we work diligently to ensure the safest festival possible. Yesterday, our medical team in Plaza 11 was asked to respond to a medical situation in a nearby campsite. The Bonnaroo Medical team and Coffee County Emergency Services were on the scene within minutes. A 27-year-old male patron camping with his father was unresponsive. The medical team administered CPR, and he was transported to the hospital where he died. We understand that he had an underlying medical condition, but we have no further information at this time. Our thoughts and prayers go out to his family and friends.


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Barry Brook may refer to:

Barry Brook (scientist) (born 1974), Australian earth scientist
Barry S. Brook (1918–1997), American musicologist

See also
Barry Brooks (disambiguation)


(Reuters) - Waymo, the autonomous vehicle arm of Alphabet Inc (GOOGL.O), said on Friday it would launch a self-driving trucks pilot in Atlanta to carry cargo for Google's data centers.
The announcement comes two days after rival Uber Technologies [UBER.UL] said its self-driving trucks will haul cargo on Arizona highways.
Waymo had been road testing its self-driving trucks in California and Arizona over the last year, since making it public in July 2017.
Autonomous vehicles offer a multi-billion-dollar opportunity to remake urban transportation systems, and companies ranging from Tesla Inc (TSLA.O) and Apple Inc (AAPL.O) to traditional car makers such as Ford (F.N) and General Motors (GM.N) are vying to dominate the market.
Waymo, which is among the leaders for this technology, expects autonomous vehicles to be able to take over longer distance trucking in the coming years, while allowing human drivers to handle local pickup and delivery routes.
"If you are in the Atlanta area, look for a bright blue Waymo truck making a run," Waymo said.


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Quality of Life Comparison
If you lived in China instead of Mongolia, you would:
live 5.3 years longer
In Mongolia, the average life expectancy is 71 years (67 years for men, 75 years for women) as of 2020. In China, that number is 76 years (74 years for men, 78 years for women) as of 2020.
be 69.9% less likely to be obese
In Mongolia, 20.6% of adults are obese as of 2016. In China, that number is 6.2% of people as of 2016.
make 32.8% more money
Mongolia has a GDP per capita of $13,700 as of 2018, while in China, the GDP per capita is $18,200 as of 2018.
be 51.2% less likely to be unemployed
In Mongolia, 8.0% of adults are unemployed as of 2017. In China, that number is 3.9% as of 2017.
be 88.9% less likely to be live below the poverty line
In Mongolia, 29.6% live below the poverty line as of 2016. In China, however, that number is 3.3% as of 2016.
pay a 4.5 times higher top tax rate
Mongolia has a top tax rate of 10.0% as of 2016. In China, the top tax rate is 45.0% as of 2016.
be 35.6% less likely to die during childbirth
In Mongolia, approximately 45.0 women per 100,000 births die during labor as of 2017. In China, 29.0 women do as of 2017.
be 40.6% less likely to die during infancy
In Mongolia, approximately 19.2 children die before they reach the age of one as of 2020. In China, on the other hand, 11.4 children do as of 2020.
have 30.1% fewer children
In Mongolia, there are approximately 16.6 babies per 1,000 people as of 2020. In China, there are 11.6 babies per 1,000 people as of 2020.
be 22.2% more likely to have access to electricity
In Mongolia, approximately 82% of the population has electricity access as of 2016. In China, 100% of the population do as of 2016.
be 2.3 times more likely to have internet access
In Mongolia, approximately 23.7% of the population has internet access as of 2018. In China, about 54.3% do as of 2018.
China: At a glance
China (sometimes abbreviated PRC) is a sovereign country in East/Southeast Asia, with a total land area of approximately 9,326,410 sq km. For centuries China stood as a leading civilization, outpacing the rest of the world in the arts and sciences, but in the 19th and early 20th centuries, the country was beset by civil unrest, major famines, military defeats, and foreign occupation. After World War II, the communists under MAO Zedong established an autocratic socialist system that, while ensuring China's sovereignty, imposed strict controls over everyday life and cost the lives of tens of millions of people. After 1978, MAO's successor DENG Xiaoping and other leaders focused on market-oriented economic development and by 2000 output had quadrupled. For much of the population, living standards have improved dramatically and the room for personal choice has expanded, yet political controls remain tight. Since the early 1990s, China has increased its global outreach and participation in international organizations.
How big is China compared to Mongolia? See an in-depth size comparison.
More quality of life comparisons
Mongolia vs. India
Mongolia vs. Ireland
Mongolia vs. Turkey
Mongolia vs. Italy
Mongolia vs. Russia
Mongolia vs. Hong Kong
The statistics on this page were calculated using the following data sources: The World Factbook, General Department of National Taxation, State Administration of Taxation.
Join the Elsewhere community and ask a question about China. It's a free, question-and-answer based forum to discuss what life is like in countries and cities around the world.
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PERC H840 RAID Adapter for External MD14XX Only, 8GB NV Cache, Full Height, Customer InstallThe PERC H840 RAID Controller from Dell offers reliability and performance in addition to providing management with the tolerant disk subsystem failures. This RAID controller offers expandable 4GB storage capacity to improve the performance of your server systems. The double module channel provides high-speed connectivity. This product has been tested and validated on Dell systems to ensure compatibility with your computer. It is supported by Dell Technical Support when used with a Dell system.
The PERC H840 RAID Controller from Dell offers reliability and performance in addition to providing management with the tolerant disk subsystem failures. This RAID controller offers expandable 4GB storage capacity to improve the performance of your server systems. The double module channel provides high-speed connectivity. This product has been tested and validated on Dell systems to ensure compatibility with your computer. It is supported by Dell Technical Support when used with a Dell system.


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SCIENCE SOURCE
NGC 7331, Caldwell 30, The Milky Way's Twin, Spiral Galaxy
Sunflower Galaxy, M63, NGC 5055
M101, NGC 5457, Pinwheel Galaxy, Spiral Galaxy
Milky Way, Barred Spiral Galaxy
NGC 2207 and IC 2163, Merging Galaxies
NGC 5128, Centaurus A, Lenticular Galaxy
Messier 33, M33, NGC 598, Triangulum Spiral Galaxy
Orion Nebula, M42, NGC 1976
IC 342, Caldwell 5, Intermediate Spiral Galaxy
Maffei 2, Intermediate Spiral Galaxy
NGC 2841, Unbarred Spiral Galaxy in the Constellation Ursa Major
Open Star Cluster, NGC 346, SMC
NGC 7000, Caldwell 20, North America Nebula
DR22, Space Cloud
Large Magellanic Cloud, LMC, Irregular Galaxy
M17 and M17 SWex, The Invisible Dragon
Messier 81, M81, NGC 3031, Bode's Galaxy, Spiral Galaxy
Messier 58, M58, NGC 4579, Barred Spiral Galaxy
NGC 300, Caldwell 70, Spiral Galaxy
NGC 1097, Caldwell 67, Barred Spiral Galaxy
Description: NGC 1097, is located 50 million light-years away. It is spiral-shaped like our Milky Way, with long, spindly arms of stars. The "eye" at the center of the galaxy is actually a monstrous black hole surrounded by a ring of stars. In this color-coded infrared view from Spitzer, the area around the invisible black hole is blue and the ring of stars, white. The black hole is huge, about 100 million times the mass of our sun, and is feeding off gas and dust along with the occasional unlucky star. The ring around the black hole is bursting with new star formation. An inflow of material toward the central bar of the galaxy is causing the ring to light up with new stars. The galaxy's red spiral arms and the swirling spokes seen between the arms show dust heated by newborn stars. Older populations of stars scattered through the galaxy are blue. The fuzzy blue dot to the left, which appears to fit snuggly between the arms, is a companion galaxy. Other dots in the picture are either nearby stars in our galaxy, or distant galaxies. This image was taken during Spitzer's cold mission, before it ran out of liquid coolant. The observatory's warm mission is ongoing, with two infrared channels operating at about 30 Kelvin (minus 406 degrees Fahrenheit). Infrared light with a wavelength of 3.6 microns is blue; 4.5-micron light is green and 8.0-micron light is red. The contribution from starlight measured at 3.6 microns has been subtracted from the 8.0-micron image to enhance the visibility of the dust features.
NASA/JPL-Caltech/Science Source
Legacy Identifier: BV0059
barred spiral galaxy
celestial body
epromo11282018
infrared array camera
infrared image
irac
spitzer space telescope mission
spritzer cold mission
sst mission


Here is the lovely Rose Byrne (in Valentino) at the season 4 premiere of her shoe Damages. I love, love, love her purple lipstick.
This entry was posted in Red Carpet, Rose Byrne and tagged Red Carpet, Rose Byrne by SM. Bookmark the permalink.


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Новые Раскаецы () — село в Штефан-Водском районе Молдавии. Наряду с селом Раскаецы входит в состав коммуны Раскаецы.

География
Село расположено на высоте 148 метров над уровнем моря.

Население
По данным переписи населения 2004 года, в селе Рэскэеций Ной проживает 669 человек (338 мужчин, 331 женщина).

Этнический состав села:

Примечания

Населённые пункты Штефан-Водского района


Taylor, Nadia C.Happiness in transition: socioeconomic change and concepts of well-being in Vietnam. 2009.
Luciak-Donsberger C, Piribauer F, Taylor NC. Enabling general physicians to perform periodontal screening during nationwide periodic health examinations. J Evid Based Dent Pract. 2008 Sep; 8(3):186-94. PMID: 18783766.
Prinzmetal W, Taylor N. Color singleton pop-out does not always poop out: an alternative to visual search. Psychon Bull Rev. 2006 Aug; 13(4):576-80. PMID: 17201354.
Bauer H, Pripfl J, Lamm C, Prainsack C, Taylor N. Functional neuroanatomy of learned helplessness. Neuroimage. 2003 Oct; 20(2):927-39. PMID: 14568463.