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Postgraduate Training Course in Reproductive Health/Chronic Disease
Carcinoma of the cervix
The role of Human Papilloma Virus and prospects for primary prevention
Review prepared for the 12th Postgraduate Course in Reproductive Medicine and Biology, Geneva, Switzerland
Dr. R.A. Kwame-Aryee
University of Ghana Medical School
Tutor: Dr. Pierre Vassilakos
University of Geneva
See also presentation
Cancer of the cervix is the most common female genital cancer in developing countries. Every year about 500,000 women acquire the disease and about 75% are from developing countries. About 300,000 women also die from the disease annually and of these 75% are from developing countries.
The objectives of this paper are to review the aetiology of carcinoma of the cervix and the possible preventive procedures that are available.
The literature was reviewed using databases from the PUBMED, MEDLINE, OB/GYN.NET / MEDCARE and the WHO and its collaborative institutions such as Path.
The aetiology of cervical carcinoma is basically from HPV infection which occurs usually as a sexually transmitted disease. The mode of infection and the host factors that enhance the acquisition and persistence of the virus in host cells have been described. The literature has revealed the mode of inhibition of the cervical cellular p53 and Rb anti-ongenes by the production of proteins from the viral genome E6 and E7 regions, the integration of viral DNA into the host cell and mutation of the host cell nucleus resulting in uninhibited proliferation of cervical cells with subsequent carcinoma formation. Other host factors favouring the persistence of HPV in the female genital tract have also been clearly outlined. Factors such as early coitarche, frequent change of sexual partners, cigarette smoking and prolonged use of combined oral contraceptives and immune suppression have been shown to be associated with carcinoma of the cervix.
The different cervical screening procedures with their attendant problems are discussed. Screening with the traditional Pap smear technique shows sensitivity and specificity of 51% and 98% respectively. Other screening procedures such as VIA have been shown to be effective in screening for the cervical cancer with a sensitivity and specificity of 76% and 64%, respectively (1). VIA may hold the key to effective screening in low resource areas of the world. DNA testing has also been developed and this is likely to enhance the detection of the HPV in the female genital tract.
It is also worth noting that different vaccines are in the process of development and this may well prove cost effective for the primary prevention of carcinoma of the cervix. Until the vaccine is fully certified for use for the prevention of cancer of the cervix it is advised that safe sex should be practised by all.
Cancer of the cervix uteri is the most common female cancer in developing countries. Worldwide about 500 000 women acquire the disease annually and about 75% are from developing countries (1). About 300 000 women die of the disease annually.
Until recently the aetiology of cancer of the cervix has not been clear. Many suggestions were made to link cancer of the cervix with certain viral infections. In the seventies and early eighties Cytomegalovirus and Herpes Simplex II were implicated as their proteins were found in a large number of invasive cervical cancer lesions (2). Until recently the Human Papilloma Virus (HPV) had not been linked with the pathogenesis of cervical cancer. The Human Papilloma Virus has been known since antiquity to be associated with warty growths of the hands, vulva and vagina and other parts of the skin (3) but the link with cancer of the cervix has now been elucidated.
HPV is now considered a sexually transmitted disease with particular types being highly oncogenic. The WHO’s International Agency for Research on Cancer (IARC) has classified the HPV into three groups: “carcinogenic (HPV types 16 and 18); probably carcinogenic (HPV types 31 and 33) and possibly carcinogenic (other HPV types except 6 and 11) (4). Today over 120 types of the HPV have been described. The diagnosis of genital HPV infection has been done by indirect means (cytology). Recently highly specific HPV DNA tests (e.g. Polymerase Chain Reaction tests and the Hybrid II Capture tests) have been developed for the detection of HPV in cervical / vaginal preparations. These tests are very sensitive and could contribute significantly to the early detection of the virus in the genital tract in the very near future.
Screening for precursor lesions of the cervix have been in use for a long time in the industrially advanced countries. The screening test has led to a marked reduction in cervical cancer death rate by about 70% (1). The main screening test, the Pap smear, developed by George Papanicolaou in 1943 has been the gold standard of for the detection of pre-malignant and indeed early malignant lesions of the cervix.
In developing countries or low resource countries, the development of the naked eye visual inspection of the cervix (VIA) is likely to help reduce the high morbidity and mortality associated with cancer of the cervix. The VIA has been shown to be sensitive and specific enough to take the role of a good screening method. It has also been shown to be easy to teach nurses and midwives to perform the test and to go one step ahead to treat premalignant changes in the cervix by cryotherapy.
With the advances in technology vaccines are being developed against the HPV with the hope of achieving primary prevention of the disease. It is my fervent hope that it will not take too long for the vaccines to be approved for use. Until the vaccine becomes available for mass population use it will still be prudent to practise safe sex.
The objectives of this study are:
- To conduct a review of literatures on the available evidence on the aetiology of carcinoma of the cervix.
- To study the different types of screening methods available and their efficacy as well as to find which of them may be more useful in low resource settings.
- To identify possible preventive measures to reduce the risk of carcinoma of the cervix.
This literature review is undertaken through electronic search using the databases such as PUBMED, MEDLINE, Cochrane library, etc. to find most up to date studies on the subject. Recent publications from the WHO and collaborative institutions such as PATH were also reviewed.
For the electronic search the following key words were used:
- Cervical carcinoma / cancer.
- Human Papilloma Virus.
- Screening for cervical cancer.
- Cervical cytology.
Manual searches were also conducted at the WHO and the Geneva Medical School libraries. An extensive body of knowledge is available on this topic; therefore, the search was limited to recent literature published between 1995-2003. A few references were sought from earlier years.
References related to the following topics were reviewed:
- The Human Papilloma Virus as an aetiological factor for cancer of the cervix.
- The characteristics of the Human Papilloma Virus.
- Cervical screening procedures and the methods of reporting.
- New cervical screening procedures.
- Use of cervical DNA test in the detection of HPV in the female genital tract.
- The use of vaccines to prevent HPV infection in women.
The findings are discussed under the different headings below.
Aetiology of cervical carcinoma
A number of papers reviewed the aetiology of cervical carcinoma. In the 1960s and 1970s and early eighties the cause of cervical carcinoma was attributed to the Cytomegalovirus and later the Herpes Simplex Type II infections (2) as viral antibodies were found in cervical cancer patients. After many years of research it has now become evident, beyond all reasonable doubt, that the cancer is closely related to certain highly oncogenic strains of the HPV, notably types 16 and 18 (1,5). A press release in 1996 by the WHO (1), summarising the conclusions of an informed Technical Consultation involving, 55 experts from 17 countries, declared HPV as a major cause of the cancer of the cervix.
From the literature review it would appear that there are other strains of the HPV which are also oncogenic but by far the commonest type causing cervical cancer is the type 16 which can be retrieved in over 80% of cervical cancer specimens. Type 18 which may be seen in a few cancer specimens may be associated with a rapid onset of disease and it usually affects the endocervical glands. To date over 99.7% of cases of cervical cancer and severe CIN II/III are associated with previous oncogenic HPV infection (6,7). The other types involved in cervical changes include but are not limited to the following: types 31, 33, 51, 53, 35 etc.
Recently, anecdotal reports from a few investigators have indicated that not be all cases of cervical carcinoma can be traced to HPV infection. Morrison et al (8) provide evidence for 5 cases of unusual variants of large invasive squamous cell carcinoma of the cervix diagnosed during hysterectomy for benign uterine disease (prolapse – 2, fibroids 1 and VVF – 2). Four of the patients had normal Pap smears and the fifth had ASCUS. HPV PCR test could not detect HPV DNA in the specimens. (Could the lesions have been due to yet unidentified types of HPV)?
It must be emphasised that HPV is the most prevalent sexually transmitted infection in the world occurring in up to 75% of sexually active women (9,10). Men and women get infected soon after becoming sexually active but it may take up to 20 years for the cervical cancer changes to appear on the cervix. Only about 10% of infected women would go on to develop cervical dysplasia and of these and only a few would develop overt cancer of the cervix. From the mechanisms of malignant change (discussed below) it becomes fairly obvious that other risk factors may be involved in the carcinomatous change. It seems that even though the infection is sexually transmitted there seem to be a number of behavioural, social, cultural and economic factors playing roles as risk factors for the carcinomatous change.
The following risk factors which have been known for a long time to be associated with carcinoma of the cervix may play key roles in the cancer formation. Early onset of intercourse and the change of multiple partners increase exposure to HPV and other sexually transmitted diseases. The sexual behaviour of the woman’s male partner may also increase the risk of exposure (10) for it has been known that partners of men that develop penile carcinoma are at high risk of developing carcinoma of the cervix.
History of cervical carcinoma in close relatives may also be an important (12) factor. Cigarette smoking has also been implicated as a co-factor. The nicotine and other by-products of smoke are concentrated in the cervical mucous with a resultant reduction in the immunity of the Langerhan's (dendritic) cells. Ylitalo et al 1999 (13), in a case control study in a population based cohort consisting of women participating in a cytological screening test in a Swedish county between 1965 and 1999 confirm the association between smoking and cervical cancer.
Conditions that reduce the immunity are also associated with cancer formation (14,15) as they enhance viral persistence in host cervical cells. The Human Immune Deficiency Syndrome is therefore a contributor to carcinomatous change. The chronic use of corticosteroids such as for unrelenting asthmatic attacks may also play a role in cervical cancer formation.
Recently the role of the combined oral contraceptive pill as a risk factor for cervical carcinoma has also been clarified (16).
The Human Papilloma Virus
Much research has been done to characterise the Human Papilloma Virus. In 1995 the WHO (2) published in its monograph the Summary of Data Reported and Evaluation of the the Human Papilloma Virus. In this monograph much of the information on HPV has been summarised. The HPV, a Papovavirus, is a small double-stranded DNA virus with a diameter of 55 nm. It is encased in a protein capsid with the viral genome existing in a circular or epitomal configuration. The viral genome can be divided into 3 regions: the Upstream Regulatory Region (URR), the Early Region (E) and the Late Region (L). The URR is involved in viral replication and the control of transcription in some sequences in the Early region. The Early Region encodes for proteins that are responsible for viral replication which occurs early in the viral life cycle. The late region encodes for viral structural proteins necessary for capsid production late in the viral life cycle. The Early Region is responsible for maintaining high numbers of HPV and the oncogenic types also encode for proteins that promote the transformation of the host cell to cancer (immortalisation). There are some areas in the Early Region that can encode for proteins and are designated as E1, E2, E3, E4, E5, E6 and E7. The E6 and E7 regions are responsible for the oncogenic properties of the HPV.
Thomas Cox et al (3) indicate that nearly 120 types of HPV have been described with about 20-30% unclassified. The types are numbered according to their discovery and a new type is identified if it has at least 10% of the gene sequence at E6, E7 and L1 different from any previously known type. Types 16, 18, 31, 35, 45, 51, 52 and 56 are considered high risk types because of the association lower genital tract cancers and pre-cancers.
It is well established that HPV is transmitted sexually and may persist in the genital tract for a very long time with resultant cervical changes. Genital-to-genital transmission is easy as micro-trauma at the fourchette, labia minora or vagina may enhance the entry of the viruses into the host cells. The viruses may take up to 3 months after exposure to show any clinical lesion (1,3) and may take up to 20 years to show carcinomatous change. Some of the infections may be sub-clinical without any visible expression.
As the virus invades the genital cell the HPV loses its protein capsule but to be infective the capsule is required. The HPV DNA therefore exists in the host cell without its shell. Infective HPV may be found only in the upper layers of the epithelium where infective genomes of HPV are released as dying koilocytes. The 2 late regions of the HPV are responsible for proteins involved in the construction of the capsid of the infective HPV genome. The infection is usually found at the basal cell layer and it does not go through the basement membrane of the epithelium. The infection of the female genital tract may take 2 main courses – transient infection and persistent infection. Up to 65% of infected individuals may show disease expression but most of the infections quickly resolve due to a complex interplay of host, viral and environmental factors with resultant increased dominance over the viral intruder (2,3). When the virus escapes the host's immune reaction the infection becomes persistent. Persistence of the viral genome in the host's cells may ultimately result in the cervical changes leading to carcinoma (2,3).
The host cell genes p53 and Rb (the retinoblastoma gene) are responsible for repairing damages (mistakes, or mutations) during cell replication. If the damage is irreparable the cell is destroyed by a process called apoptosis. In persistent HPV infection the anti-oncogenic activity of p53 and Rb is blocked by the production of proteins by E6 and E7 from the HPV resulting in un-inhibited host cellular growth and lack of repair of damaged cells. Abnormal cell proliferation then results with the integration of the viral DNA into the host cellular DNA with resultant immortalisation of the host cell which then becomes capable of invasion (17). Some of the wildly growing cells may develop irreparable, permanent changes in the genetic structure (mutation). This eventually results in the production of cancerous cells.
As the HPV cells occupy the host cells various cellular changes occur in the epithelial squamous cells detectable by cytology. The first to occur is the koilocytic atypia in which the host cellular nucleus is displaced to the side with a 'hollow' appearance of the cytoplasm (perinuclear cavitation) (18). The squamous cells, as the disease advances, then begin to show signs of change in size and shape with sometimes nuclear changes. The cellular atypia resulting is termed Atypical Squamous Cells of Undetermined Significance (ASCUS). The equivalent in the cervical glandular cells is Atypical Glandular Cells of Undetermined Significance (AGUS). About 60% of such cases may regress spontaneously; 20-35% would persist unchanged and the remaining 10% are likely to develop High Grade Intra-epithelial Lesion (HGIL) with increased cellular changes, reduced nuclear/cytoplasmic ratio and mitotic elements. As the whole epithelium is replaced with mutant cells cervical intra-epithelial neoplasia (CIN) III or carcinoma in situ develops. Tongues of growing squamous cells first break through the basement membrane (micro-invasion) and as more tongues grow and coalesce frank invasion may occur. Detection of CIN III peaks between 25 – 29 years about 4 to 7 after the peak incidence of CIN I. In Caucasian women it takes approximately 15 years after the peak incidence of CIN III to develop invasive cancer which may therefore be seen between the ages of 40 and 45 years (2).
Screening for premalignant lesions of the cervix
Screening for pre-malignant lesions of the cervix using exfoliated cells (cervical cytology) has been going on for well over 50 years. In the 1940's George Papanicolaou (19) first described five classes of cellular changes in exfoliated cells of the cervix. His classification was as follows:
- Class 1: Absence Of Atypical Or Abnormal Cells
- Class 2: Atypical Cytology But No Evidence Of Malignancy.
- Class 3: Cytology Suggestive But Not Conclusive.
- Class 4: Cytology Strongly Suggestive Of Malignancy
- Class 5: Cytology Conclusive For Malignancy.
This original classification was adopted worldwide and it has been the cornerstone of the screening programs in the Nordic countries since the 1960's (20,21). These Nordic authors have indicated the usefulness of the Papanicolaou classification in acquiring a highly successful screening programme in Finland. They do not see the need for change of the classification.
In order to correlate the histological findings with the appropriate cytological abnormality the British Society for Clinical Cytology (BSCC) introduced a new system of classification of the cytological specimens in the 1980's. This system employed the term dyskariosis which was further subdivided into mild, moderate and severe. These subdivisions are supposed to correlate very well with the histological grades of CIN I, II, and III (22).
In 1988 the National Cancer Institute of the USA came out with a new system, the Bethesda System (TBS) for reporting cervical and vaginal cytological diagnosis (23) . Still not satisfied with the new classification the National Cancer Institute reconvened another workshop in 1991. After the workshop the report was published in the Journal of the American Medical Association in 1992 (24) and in a monograph (25) in 1994. This new system simplified the three system of mild, moderate and severe dyskariosis, to Low Grade Squamous Intra-epithelial Lesion (LSIL) High Grade Squamous Intra-epithelial Lesion (HSIL). Cytological reports are then given as follows:
within normal limits
atypical squamous cells of undetermined significance
Cellular changes suggestive of :
With the better understanding of the disease process and the development of more sophisticated techniques of detecting HPV and cervical pre-cancer it was found necessary to review the 1991 Bethesda System of cytology reporting. In 2001 the third Bethesda System was published in the JAMA by Solomon et al (26). In the same edition of JAMA Wright et al (27) published the 2001 Consensus Guidelines For The Management Of Women With Cervical Cytological Abnormalities. The 2001 system sees a lot of improvement in the previous system. It is however too complex to repeat here.
It is not intended to go into the details of the classification systems but whichever system is used the literature reveals adequate guidelines for the management of the patients.
Traditionally the cervical specimens have been taken by wooden or plastic spatulae or brushes. The specimen is then smeared on a glass slide and fixed immediately with alcohol.
Even though the cytological screening methods have been used for years and has been definitely associated with 70% reduction in cervical cancer deaths (1,28) in areas with well developed screening it is still associated with many false negative reports which may need re-examination with repeat pap smears / cytology and / or colposcopy.
In order to improve on the specimen collection with the hope of improving the sensitivity of the cytology the liquid based preparations of sample collection were developed. The spatula or brush is broken and the part used for collecting the specimen is inserted into a tube with preservative solution and sent to the laboratory with the necessary precautions. The advantage offered here is that all the cells harvested are sent to the laboratory. The specimen is centrifuged with removal of blood and mucus. The cellular pellet is removed and suspended in diluent and a nice smear is then made on the slide. The smear when dry is ready to be read by the cyto-technician or pathologist. This method improves on the sensitivity of the test with a higher SIL detection rate. Vassilakos (29) et al, working in 3 different laboratories in Europe demonstrated an increased detection of LSIL by 59% and HSIL by 78.9%. The rate of detection of ASCUS was also reduced by 43.38%. In a meta-analysis of 12 published papers using the liquid based thin prep 2000, Martha Hutchinson (30) indicates that the thin prep improves screening quality and increases the SIL detection rate. On average these studies demonstrate a 66% increase in the detection of LSIL and a 57% increase in the detection of HGIL with an attendant reduction in the diagnosis of ASCUS.
This system has been improved further with automation. In the automated computerised system the computer screens all the normal slides and refers those complicated slides to be read by the cyto- technician or the pathologist. This system can handle many cases daily and it has the good prospect for telemedicine use. Dr. P. Vassilakos (31) has been involved in the telemedicine practice for some time now. This may also pave the way for difficult slides taken in less endowed areas of the world to get assistance with the interpretation.
These systems that have been described so far are very expensive and are not within easy reach of most developing countries. There is therefore the need to develop screening systems with fairly high sensitivity and specificity but at the same time easily available, affordable and easily accessible and user friendly. These attributes can be given to the visual inspection (naked eye) of the cervix with acetic acid (VIA).
Visual Inspection of the cervix with Acetic Acid (VIA)
In low resource settings naked eye visualisation of the cervix was tried with the hope of diagnosing some of the pre-malignant lesions of the cervix. This technique was found to be woefully inadequate with very low sensitivity.
With the addition of acetic acid to the examination the results have markedly improved. In this approach the cervix is swabbed with 4-5% acetic acid or vinegar prior to visualisation. Abnormal cells temporarily turn white (aceto-white) as seen during colposcopy. This technique is simple, easy to perform and quite cheap. Nurses and midwives can be taught to do it. The other advantage is that diagnosis is made immediately and treatment may be given by cryotherapy or patient can be referred to hospital according to the stage of cervical disease.
Many comparative studies have been done which suggest that the efficacy of VIA is comparable to that of cytology. In 1999 the University of Zimbabwe and the JHPIEGO (32) published the results of their project involving 10 934 patients and found that VIA was more sensitive but less specific than cytology. The sensitivity for VIA was 76.7% (95% CI. 70.3-82.3) and that for cytology was 44.3% (95% CI, 37.3-51.4). The specificity for VIA was however less than that for cytology (64.1% versus 90.6%). Denny L (33) et al in South Africa also reported favourable findings after the examination of 2944 people aged between 35 and 65 years. The same authors (34) published in 2002 after studying 2754 patients their confirmation of the VIA test as a primary screening test for low resource areas. In the last test they indicated the sensitivity for VIA (without magnification) for HSIL as 70% with a specificity of 79%. (Magnification did not significantly improve the sensitivity). In rural China, after examining 1997 patients, Belinson et al in 2001 (35) showed a sensitivity of 71% for HSIL with a specificity of 74%. They concluded that the sensitivity of VIA equalled or exceeded reported rates for conventional cytology.
In his article ‘Costs and Benefits of Different Strategies To Screen For Cervical Cancer In Less-Developed Countries’ Mandelblatt explains the cost-effectiveness of VIA (36). From the foregoing VIA has everything to recommend it for routine use for low resource settings even though patients with false positive results still have to bear extra costs of hospital treatment or stand the risk of cryotherapy of their otherwise normal cervices.
Visual Inspection with Magnification (VIAM)
Studies are ongoing to find out if the addition of a hand-held magnifying glass would improve the sensitivity and specificity of the VIA. The Avi Scope, a low-power (x4), hand-held visual inspection device with an in-built light system is expected to improve the results of VIA. Even though the manufacturers have indicated a better sensitivity for the instrument (37) the South African study (34) did not show any improvement. Further randomised control trials of its use are awaited before its use can be disproved or encouraged. Its cost effectiveness is also yet to ascertain.
This involves the use of a camera. The cervix is photographed after the application of acetic acid. The photograph (cervigram) obtained are examined by a colposcopist as projected slides. Its sensitivity is said to approach those of cytology (38). The equipment is however expensive.
HPV DNA Testing
Two tests have been developed to identify the HPV DNA – the PCR test and the Hybrid Capture II test (HC II). The HC II test has been approved for use by the FDA of USA. It is being incorporated into some screening programmes because of its high sensitivity (80-90%) and a specificity of 57-89% (39). Large studies in Costa Rica and Zimbabwe reveal high sensitivity and specificity for HSIL (39,40). Other studies by Liaw et al show similar results (41).
Feitcher et al (18) have suggested that in industrialised countries application of HPV testing, as part of cervical cancer screening, is expected to reduce the cost of cervical cancer screening because of the increased precision of screening that would further justify longer screening intervals. They have also suggested that HPV testing is usually carried out to improve the quality of conventional cytological screening; improve the diagnosis of questionable cases such as ASCUS and identify asymptomatic patients at high risk of developing cervical cancer.
The detailed review of the various treatment modalities of the various types of cervical changes from ASCUS / AGUS, through LSIL, HSIL, and overt cancer is beyond the scope of this paper. It may suffice to indicate that for overt carcinoma of the cervix the following modalities of treatment have been effective according to the stage of the disease and the patient’s condition: radical surgery, radiotherapy (or a combination of the 2). The use of Cis-Platin based chemotherapy is being investigated.
The problem with management really lies with the precancerous lesions of ASCUS/AGUS, LSILand HSIL. LSIL can be managed with local cervical ablative surgery such as cryotherapy, laser photo-vaporisation, or electro-cautery of the cervix. Repeat cytology may be indicated. With HSIL colposcopic evaluation with directed biopsies are advised. Treatment may then involve conisation of the cervix using the cold knife or LLETZ.
Primary prevention of cervical carcinoma through vaccination
With the strong association found between the high-risk types of HPV and cervical carcinoma (compare hepatitis B infection with hepatocellular carcinoma) the stage is now set to develop an effective vaccine for primary prevention (prophylactic) and if possible for treatment (therapeutic) of the cancer.
Much work is being done in this field. As indicated by Steller MA (42) and Murakami M (43), prophylactic vaccine under investigation focuses on the induction of effective humoral and cellular- immune responses that are potentially protective against subsequent HPV infection. HPV-like particles have been synthesised to induce neutralising antibody responses and impressive prophylactic effects have been demonstrated. For therapeutic vaccine techniques to improve cellular immunity by enhancing viral antigen recognition are being studied. It is hoped that with successful prophylactic and therapeutic vaccines available the need for extensive cytological screening would be obviated (44) and probably the treatment for the disease would also be modified.
In this review the strong association between the high risk HPV infection and carcinoma of the cervix has been demonstrated. Notably high risk types such as types 16, 18, 31, 33 etc have been elucidated by DNA testing to be the main causes of cervical cancer.
VIA has also been found, from several randomised trials, to be effective as a screening tool for developing countries. The addition of immediate treatment by cryotherapy and the easy application that can be learnt by nurses and midwives make it a very remarkable test and I hope that Governments of poor nations would help institute the screening programs in their countries with the hope of eliminating or reducing the impact of the disease on the population.
Effective DNA tests have also been provided (PCR and Hybrid Capture II) for the detection of the cervical HPV infection. With the elucidation of the immortalisation process of the cervical cells by the HPV DNA effective prophylactic and therapeutic vaccines are currently being tried with the hope of conquering the disease once and for all. From the literature it would seem both feasible and cost effective and cost effective approach to the eradication of the virus and the prevention of cancer of the cervix.
If an effective vaccine comes into use it would still be advisable to practice safe behaviour in the form of ‘safe sex’ with the hope of reducing the incidence of sexually transmitted infections in general and HIV infection as well.
I am very grateful for the course organsiers of the Geneva Foundation for Medical Education and Research, Professor Aldo Campana and his team. Mrs Eva Marthur and Dr. Regina Kulier and Miss Silvie Ngo Ntama deserve my gratitude.
I am also grateful to all the teachers who has given me new dimensions in life.
My sincere gratitude go to my sponsors of IAMANEH through whose efforts I was able to join this wonderful programme. Finally I wish to thank Dr. A. H. K. Collison of the University of Ghana Medical School and Chairman of IAMANEH (Africa) for proposing me to join the course.
I also wish to thank Dr. Vassilakos, my tutor, for giving me a lot of reading material and supervising this work very closely.
Finally my special gratitude goes to Margaret Usher Patel and Archana Shah for helping me with the final corrections.
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- Solomon D, Davey D, Kurman R, Moriarty A, O'Connor D, Prey M, Raab S, Sherman M, Wilbur D, Wright T Jr, Young N. The 2001 Bethesda System: terminology for reporting results of cervical cytology. JAMA. 2002 Apr 24;287(16):2114-9. [PubMed]
- Wright TC Jr, Cox JT, Massad LS, Twiggs LB, Wilkinson EJ. 2001 Consensus Guidelines for the management of women with cervical cytological abnormalities. JAMA. 2002 Apr 24;287(16):2120-9. [PubMed]
- Monsonego J. Chapter Editors Introduction: Global challenge of cervical cancer screening and prevention. CME Journal of Gynecologic Oncology. 2000 5(1):5-7.
- Vassilakos P, Saurel J, Rondez R. Direct-to-vial use of the AutoCyte PREP liquid-based preparation for cervical-vaginal specimens in three European laboratories. Acta Cytol. 1999 Jan-Feb;43(1):65-8. [PubMed]
- Hutchinson ML. Liquid based ThinPrep 2000 cytology improves screening accuracy and specimen adequacy. CME Journal of Gynecologic Oncology. March 2000 5(1): 21-25.
- Vassilakos P. 2003. Personal Communication.
- Visual inspection with acetic acid for cervical-cancer screening: test qualities in a primary-care setting. University of Zimbabwe/JHPIEGO Cervical Cancer Project. Lancet. 1999 Mar 13;353(9156):869-73. [PubMed]
- Denny L, Kuhn L, Pollack A, Wright TC Jr. Direct visual inspection for cervical cancer screening: an analysis of factors influencing test performance. Cancer. 2002 Mar 15;94(6):1699-707. [PubMed]
- Denny L, Kuhn L, Pollack A, Wainwright H, Wright TC Jr. Evaluation of alternative methods of cervical cancer screening for resource-poor settings. Cancer. 2000 Aug 15;89(4):826-33. [PubMed]
- Belinson JL, Pretorius RG, Zhang WH, Wu LY, Qiao YL, Elson P. Cervical cancer screening by simple visual inspection after acetic acid. Obstet Gynecol. 2001 Sep;98(3):441-4. [PubMed]
- Mandelblatt JS, Lawrence WF, Gaffikin L, Limpahayom KK, Lumbiganon P, Warakamin S, King J, Yi B, Ringers P, Blumenthal PD. Costs and benefits of different strategies to screen for cervical cancer in less-developed countries. J Natl Cancer Inst. 2002 Oct 2;94(19):1469-83. [PubMed]
- Planning Appropriate Cervical Cancer Prevention Programs. Program for Appropriate Technology in Health (PATH). March 1997. [Free Full Text]
- Cuzick J. Human papillomavirus testing for primary cervical cancer screening. JAMA. 2000 Jan 5;283(1):108-9. [PubMed]
- Schiffman M, Herrero R, Hildesheim A, Sherman ME, Bratti M, Wacholder S, Alfaro M, Hutchinson M, Morales J, Greenberg MD, Lorincz AT. HPV DNA testing in cervical cancer screening: results from women in a high-risk province of Costa Rica. JAMA. 2000 Jan 5;283(1):87-93. [PubMed]
- Womack SD, Chirenje ZM, Gaffikin L, Blumenthal PD, McGrath JA, Chipato T, Ngwalle S, Munjoma M, Shah KV. HPV-based cervical cancer screening in a population at high risk for HIV infection. Int J Cancer. 2000 Jan 15;85(2):206-10. [PubMed]
- Kai-Li Liaw, Schiffman MH, Cope JU, Glass AG, Manos M, Sherman ME, Burk RD, Hildesheim A, Lörincz AT. Update on recent clinical studies using HPV testing for screening and diagnosis of cervical neoplasia. CME Journal of Gynecologic Oncology . March 2000 5(1):41-44.
- Steller MA. Cervical cancer vaccines: progress and prospects. J Soc Gynecol Investig. 2002 Sep-Oct;9(5):254-64. [PubMed]
- Murakami M, Gurski KJ, Steller MA. Human papillomavirus vaccines for cervical cancer. J Immunother. 1999 May;22(3):212-8. [PubMed]
- Davidson EJ, Kitchener HC, Stern PL. The use of vaccines in the prevention and treatment of cervical cancer. Clin Oncol (R Coll Radiol). 2002 Jun;14(3):193-200. [PubMed]

domain: medical


text:
at 7:30 PM
Boogie and The Yo-Yoz
Fox Cities Performing Arts Center - Dec 14, 2018 at 7:30PM - Appleton, WI
400 West College Ave, Appleton, WI 54911
- We are a resale marketplace
- Prices may be above face value
- We are not owned by any venue
Independent resale marketplace, prices may exceed face value.

domain: artistic


text:
Altres edicions - Mostra-ho tot
Amanda Anti-jacobin Review Apostles appear Arminian attention baptism Bishop blessing called Calvin Calvinistic cause character Christian Observer Church of England clergy conduct considered Consul death divine divine grace doctrine duty Editor effect endeavour established Eusebia evil express faith father favour fear feel France French friends give Gospel grace hath heart holy honour hope irreligion ject Jesus Christ labour late letter ligion liturgy Lord means ment mercy mind minister moral nature neral ness object opinion passage peace persons piety prayer preached present principles professed prove racter readers religion religious remarks respect Reverend Review salvation Scrip scripture sense sentiments sermon shew sins sion soul specting spirit suppose Theodosia ther things thou tion tism Treaty of Amiens true truth ture unto word
Pàgina 290 - I venerate the man whose heart is warm, Whose hands are pure, whose doctrine and whose life, Coincident, exhibit lucid proof That he is honest in the sacred cause.
Pàgina 390 - Then answered one of the servants and said, Behold, I have seen a son of Jesse the Beth-lehemite, that is cunning in playing, and a mighty valiant man, and a man of war, and prudent in matters, and a comely person, and the LORD is with him.
Pàgina 219 - But when they deliver you up, take no thought how or what ye shall speak ; for it shall be given you in that same hour what ye shall speak. For it is not ye that speak, but the Spirit of your Father which speaketh in you.
Pàgina 463 - Albeit that Good Works, which are the fruits of Faith, and follow after Justification, cannot put away our sins, and endure the severity of God's judgment; yet are they pleasing and acceptable to God in Christ, and do spring out necessarily of a true and lively Faith; insomuch that by them a lively Faith may be as evidently known as a tree discerned by the fruit.
Pàgina 168 - And will you maintain and preserve inviolably the settlement of the Church of England, and the doctrine, worship, discipline, and government thereof, as by law established, within the kingdoms of England and Ireland, the dominion of Wales, and town of Berwick upon Tweed, and the territories thereunto belonging...
Pàgina 290 - Himself, as conscious of his awful charge, And anxious mainly that the flock he feeds May feel it too; affectionate in look, And tender in address, as well becomes A messenger of grace to guilty men.
Pàgina 452 - Then said they unto him, What shall we do, that we may work the works of God ? Jesus answered and said unto them, This is the work of God, that ye believe on him whom he hath sent.
Pàgina 162 - THIS is atheism : for every indication of contrivance, every manifestation of design, which existed in the watch, exists in the works of nature ; with the difference, on the side of nature, of being greater and more, and that in a degree which exceeds all computation.

domain: literature


In the current landscape of pop hip-hop, there are ideas you can depend on. Much like the speed of light, they are constants. Theres Drake, the smooth, sweater-wearing rapper who will always be at basketballs largest events and whose popularity knows no bounds.
Kanye West is another constant. One can depend on his actions and statements often about his musical abilities to overshadow his musical product.
Then theres Tyler, The Creator. The musician, producer and graphic designer is a polarizing figure. Along with Odd Future, a hip-hop collective comprised by the likes of Frank Ocean, Hodgy Beats and others, Tyler, The Creator brings a sense of millennial weirdness to a genre that rarely steps beyond the bounds of being outlandish.
Tyler, The Creator and Odd Future DJ Taco are performing 8 p.m. May 31 at Diamond Ballroom, 8001 S. Eastern Ave.
Tyler, The Creator, whose real name is Tyler Okonma, was born in Ladera Heights and grew up in Hawthorne, both communities in southwest Los Angeles County. His first musical release was The Odd Future Tape, Odd Futures 2008 debut mixtape. His debut solo album, Bastard, followed in 2009. It landed at No. 32 on Pitchforks list of The Top 50 Albums of 2010.
Bastard was followed in 2011 by Goblin, which reached No. 5 on the U.S. Billboard 200 with singles Sandwitches, Yonkers and She. Okonma was named Best New Artist at the 2011 MTV Video Music Awards.
The video for Yonkers also introduced the mainstream music audience to the intense and uncomfortable world Okonma can create. Perched on a stool, Okonma, alone on screen, plays with a cockroach, then appears to eat it and vomit seconds later. Later, Okonma hangs himself in a noose.
Since then, Okonma has released two records 2013s Wolf and 2015s Cherry Bomb to positive reviews. However, his lyrical content has been criticized and described as homophobic. In an Arsenio Hall interview, Okonma spoke about the subject and his friendship with Odd Future musician Frank Ocean.
Franks gay, and I use that word all the time, he said. He doesnt care. He knows me. He knows when I say that word, Im not thinking of someones sexual orientation. Its just another word that has no meaning.
His lyrics got him banned from the United Kingdom. In August 2015, the Home Office, the United Kingdoms ministerial department responsible for security, immigration and law and order, informed The Quietus, a British rock music and pop culture website, of its reasoning: Coming to the UK is a privilege, and we expect those who come here to respect our shared values.
Okonma also is a graphic designer and creates the artwork for Odd Futures releases, including his own. His work often features bright colors and is best described as bizarre. He also designs a clothing line that dips into the same artistic well.
His work is now mobile; its published along with animation and music through the app Golf Media. The description in Apples App Store reads Golf Media is basically my brain in one place.
The one thing that we know for sure about Okonma is there is no place in rap like his brain.
Print headline: Clever originator, Multitalented artist Tyler, The Creator brings his tour to Diamond Ballroom.


text:
I believe it is an artist's responsibility to effectively communicate their ideas which is why right now, I'm confused and a little embarrassed about the artist statement I wrote and distributed last week:
"She is (I AM) Light" is about healing, self-love, and having blind faith in the creation process that can take you there.
"She is (I AM) Light" speaks to body image and of self-awareness, of being able to see within yourself what others see in you. ("At your core, you are perfect.") The large blue body (armor) is starting to crack but can't do so without acceptance (arms spread) of fear, resistance and imperfection. (Depicted here through repetition of energetic prayers in the form of mantra and affirmation.) The Six Guardian mandala pieces speak to our never having to do the work alone. Angels, Ancestors, and Spirit Guides watch over us and gently guide us to becoming our whole, true selves - "Who I am but only that others can see" is the me that will be revealed to all.
I apologize. It seemed clear in the moment.
This is my new statement:
"She is (I AM) Light" is about the acknowledgment and acceptance of our full radiant selves. It is about healing, self-love, and having faith that we can become whole again. During this process, our armor begins to crack and will eventually fall away as we begin to embrace that which we have resisted most: Our Greatness.
The Six Guardian Mandalas are representative of our never having to do the work alone - angels, ancestors, and spirit guides are always around us, gently nudging and guiding us along our path to becoming our whole, true selves.
After Friday's opening of this exhibit, I will finish the "in progress" series of posts. I think I'm finished with all 7 pieces... I just need to sign them.
You can also view all my photos from this project on Flickr.


text:
Monte Veronese is an Italian cheese made from cow’s milk which is produced in the northern part of the Province of Verona. It is regarded as the great cheese of the Lessini mountains or the Veronese prealps and was awarded Italian Denominazione di Origine status in 1993 and EU PDO (Italian: DOP) status in 1996. Like Asiago, the cheese comes in two versions, one fresh and one matured.
The fresh cheese, made from whole milk, has a brief aging period and has a sweet, intense flavor. The hard paste Monte Veronese, made from skimmed milk, is aged longer and is slightly piquant.

domain: geography


text:
Chicago invented conventions, and now our metropolis and state is a first-class vacation spot for guests from world wide.
Earlier than the pandemic, there have been round 550,000 jobs between eating places, lodges, conventions and museums. This business is the second largest employer in Illinois, with almost 63 % of these individuals being individuals of coloration. It’s estimated that we misplaced 120,000 of those jobs in 2020.
Now for the large numbers: In 2019, tourism generated $ 43 billion in financial exercise in Illinois. This financial engine drives $ 3.5 billion in income annually to state and native financial institution accounts.
Enter COVID-19. Every part modified in a single day.
Governor JB Pritzker deserves excessive marks for his dealing with of the pandemic, given the dire lack of management and inadequate assist from Washington.
However now we’re on the helm for a yr. Vaccinations for all adults are promised by Might. Both method, the sunshine on the finish of the tunnel is seen, making it crucial to unveil a plan to carry again the conventions now.
Conventions and different occasions like weddings require at the very least a six month planning ramp. Select Chicago has estimated that Chicago has misplaced greater than 60 conventions, with solely 29 left on the books for 2021. Radio silence on a plan by choice makers resulted in three conventions settling in final month.
Comparable states like Michigan, Colorado, Nevada, and Ohio have unveiled forward-thinking plans for conference facilities to extend customer numbers, albeit progressively. These mitigation plans act like a thermostat dial, moderately than an on / off swap.
Illinois should unexpectedly undertake an analogous technique or different occasions shall be in jeopardy and even perhaps misplaced ceaselessly to different states.
Sara feigenholtz is an Illinois State Senator and Chairman of the Illinois Senate Tourism and Hospitality Committee.

domain: news


text:
A superb old world style desk globe made in Italy.
Made from brass and wood with paper details, this small desk globe has a wonderful antique feel. I believe it dates to the 1950’s.
All the writing is in Italian. The stand, which is separate to the globe, has the astrological signs around the edge and four feet. The globe itself has a frame with brass north and south fixtures and has measurements around the edge. The globe has lovely old world design with diagrams of ships and sea monsters.
The globe lifts out of the stand for closer inspection. A paper note marked ‘Made in Italy’ is stuck to the base.
The piece stands approx. 22cm tall and approx. 20cm wide. The globe measures approx. 11cm in diameter.
It is in good condition with a few chips off the wood and a couple of nicks to the globe which gives it a nice vintage look.


text:
By Dalga Khatinoglu
Iran has exported averagely 504,000 barrels of gas condensate per day, since achieving an interim nuclear accord with Sextet powers in November 2013.
Iran Custom Administration released a 229-page detailed statistics about the country's trade turnover during last Iranian calendar year, which ended on March 20.
The report indicates that the country increased condensate export volume from 195,000 barrels per day during first eight months (March 20, 2013 to November 20, 2013) to 504,000 barrels per day during the last four months of Iran's calendar year, which covers November 21, 2013 to March 19, 2014).
Iran's average condensate exports after nuclear deal is 258 percent more than before that.
The U.S. and EU imposed tough sanctions over Iran's banking system as well as whose which targeted oil and petrochemical products exports in mid-2012, but some of sanctions, including petrochemical-related ones and insurance services for oil tankers have been eased due to nuclear deal obtained in November 24 and took effect on January 20.
Iran exported about 12.873 million tons of condensate during last Iranian calendar year, indicating a 32.74 percent increase compared to the previous year and even is more than pre-sanctions level. Iran's condensate exports before the West's sanctions were about 269,000 barrels per day, which increased to above 294,000 during last year on average.
Gas condensate is a type of light crude oil, which is extracted mostly from gas fields.
Iran's revenues from condensate exports reached $10.295 billion during last Iranian calendar year, indicates 15.93 percent increase, based on Custom reports.
It is not clear why Iran's condensate export volume increased by 32.74 percent, but its value grew only 15.93 percent.
The Custom statistics indicates that Iran sold a ton of condensate at $922,222 two years ago, while during the first eight months of last year this figure was $885,704, but during the latest four month of last year, Iran sold each ton of condensate at $805,366.
With regard to the OPEC crude basket price, it has decreased below 5 percent since 2012, so it seems Iran is selling gas condensate significantly below international prices to encourage customers. Iran's crude oil and gas exports decreased from 2.5 mbpd in 2011 to 1.07 mbpd in 2013.
According to the International Energy Agency's latest released report, Iran's oil and condensate exports reached to 1.41 million barrels daily in February 2014, indicates significant recovery.
Iran includes gas condensate in non-oil exports basket. It shares about 25 percent of total non-oil exports.
Iran's non-oil exports during last year reached to $41.628 billion, indicates a 0.43 percent increase compared to the previous year. The country also imported $50.818 billion, indicates a 4.92 percent decrease during the mentioned period.
Dalga Khatinoglu is Trend Iran News Service head

domain: finance


text:
Objective We performed a systematic review and meta-analysis to determine the association of fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) on brain MRI and prognosis after acute ischaemic stroke (AIS).
Methods We searched Medline, Embase and Cochrane Central Register of Controlled Trials for studies reporting clinical or imaging outcomes with presence of FLAIR-HAs after AIS. Two researchers independently assessed eligibility of retrieved studies and extracted data, including from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Outcomes were unfavourable functional outcome (primary, modified Rankin scale scores 3–6 or 2–6), death, intermediate clinical and imaging outcomes. We performed subgroup analyses by treatment or types of FLAIR-HAs defined by location (at proximal/distal middle cerebral artery (MCA), within/beyond diffusion-weighted imaging (DWI) lesion) or extent.
Results We included 36 cohort studies (33 prospectively collected) involving 3577 patients. FLAIR-HAs were not associated with functional outcome overall (pooled risk ratio 0.87, 95% CI 0.71 to 1.06), but were significantly associated with better outcome in those receiving endovascular therapy (0.56, 95% CI 0.41 to 0.75). Contrary to FLAIR-HAs at proximal MCA or within DWI lesions, FLAIR-HAs beyond DWI lesions were associated with better outcome (0.67, 95% CI 0.57 to 0.79). FLAIR-HAs favoured recanalisation (1.21, 95% CI 1.06 to 1.38) with increased risk of intracerebral haemorrhage (2.07, 95% CI 1.37 to 3.13) and early neurological deterioration (1.93, 95% CI 1.30 to 2.85).
Conclusions FLAIR-HAs were not associated with functional outcome overall but were associated with outcome after endovascular therapy for AIS. FLAIR-HAs were also associated with early recanalisation or haemorrhagic complications, and early neurologic deterioration.
PROSPERO registration number CRD42019131168.
Statistics from Altmetric.com
Fluid-attenuated inversion recovery (FLAIR) hyperintense arteries (FLAIR-HAs) are a common sign (>45%) on brain MRI in patients with acute ischaemic stroke (AIS).1 2 Although recognised for nearly two decades,3 4 the prognostic significance of FLAIR-HAs has not been well defined despite reflecting the presence of a large ischaemic penumbra and good collateral circulation from slow retrograde flow distal to the occluded vessel (‘clot’) or ischaemic lesion.5–7 Potential reasons for this uncertainty in the literature include the limitations of retrospective design, small sample size, varying assessment of FLAIR-HAs, different treatments administered to patients and heterogeneity of endpoints across studies.8–14
Our previous analyses of thrombolysis-treated AIS patients (n=293) from the alteplase-dose arm of the international Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED)15 showed that presence of FLAIR-HAs was independently associated with a favourable 90-day functional outcome, defined on the modified Rankin scale (mRS) (scores 0–1 (n=144), adjusted OR 4.14, 95% CI 1.63 to 10.50) despite an increased risk of haemorrhagic infarct (adjusted OR 4.77, 95% CI 1.12 to 20.26) after adjusting for baseline covariables (unpublished). Herein, we extended this work through a systematic review and meta-analysis of the association of FLAIR-HAs with early vascular recanalisation or reperfusion, intracerebral haemorrhage (ICH), cerebral infarct growth and clinical outcomes in AIS.
The protocol followed the Preferred Reporting Items for Systemic Reviews and Meta-Analyses statement,16 and was registered with PROSPERO international prospective register of systematic reviews. Our search strategy was based on a combination of the following medical subject headings terms or keywords: [‘arterial hyperintensity’ OR ‘hyperintense vessels’ OR ‘vascular hyperintensities’] AND [‘FLAIR’ OR ‘MRI’] AND [‘cerebrovascular disease’ OR ‘stroke’ OR ‘cerebral infarction’] (Methods S1 in the online supplemental material). Medline, Embase and the Cochrane Central Register of Controlled Trials were searched from inception to the end of October 2019. The clinicaltrials.gov website was searched for randomised controlled trials (RCTs) registered as completed but not yet published. There was no language restriction. Reference lists of all retrieved studies and related review articles were cross-checked for further relevant studies until no further publications were found.
We included the ENCHANTED trial and other RCTs or cohort studies that recruited AIS patients (age ≥18 years) where baseline brain MRI was performed after admission and before intravenous thrombolysis or endovascular therapy. We aimed to extract data on vascular recanalisation or reperfusion, infarct growth, ICH, short/long-term clinical outcomes (measured by National Institutes of Health Stroke Scale (NIHSS) or mRS score) from reports. We excluded: (i) studies where outcomes were not reported separately for participants who did and did not have FLAIR-HAs; (ii) where the primary aim was to assess the effect of FLAIR-HAs change before and after thrombolysis on clinical prognosis, or to explore the association of FLAIR-HAs with other imaging features such as collateral flow, perfusion status or perfusion-diffusion mismatch; and (iii) reviews, editorials, letters, case or case series reports, guidelines, technical notes and book chapters. Conference abstracts were not excluded if the data could be extracted.
In this report, we also included 220 ENCHANTED15 17–19 participants (198 from alteplase-dose arm and 22 from blood pressure lowering arm) who had middle cerebral artery (MCA) infarct identified on MRI obtained within 4.5 hours of symptom onset with both FLAIR and diffusion-weighted imaging (DWI).
Study selection and data extraction
The screen of potentially eligible studies identified by searches was conducted by two authors (ZZ and AM) to select reports for review in full text. Each full text article was reviewed for eligibility by these authors and, for each included study, data were extracted independently using a standardised electronic form; any disagreement was settled by discussion or in consultation with two other authors (SY and CD). Extracted data included: (i) first author, year of publication, publication type, country or region, study design, sample size, inclusion criteria, clinical and imaging characteristics of recruited participants at baseline (age, sex, hypertension, diabetes mellitus, dyslipidaemia, atrial fibrillation (AF), coronary artery disease, history of stroke, current smoking status, NIHSS score, time from stroke onset to MRI, infarct volume, hypoperfusion volume, proximal arterial or large vessel occlusion and collateral grade); (ii) treatment administered to the study patients (intravenous thrombolysis, endovascular therapy, conservative treatment or mixed treatments); (iii) FLAIR-HAs definition or assessment method by location or extent: at proximal (M1 or M1-2 segment) or distal (M3-6 segment) MCA, within or beyond DWI lesion, FLAIR-HAs score (0–10, calculated by using 10 consecutive axial slices from the first slice with an appearance of the M1 segment of MCA, absence of FLAIR-HAs on one slice rated 0 and ≥1 present rated 1 point),9 modified Alberta Stroke Program Early CT Score (ASPECTS) grade for FLAIR-HAs (0–7, calculated according to the spatial distribution in seven cortical areas of ASPECTS (insula, M1-M6), absence of FLAIR-HAs in one area rated 0 and present rated 1 point)7; and (iv) primary and other outcomes in patients who did and did not have FLAIR-HAs on baseline MRI. In cases of missing data, the authors were contacted using details given in articles or identified by internet search. Two authors (ZZ and AM) also judged the quality of each included studies according to the Cochrane Collaboration’s tool for RCT20 or the Newcastle-Ottawa Scale (NOS) for cohort studies.21
The primary outcome of interest was unfavourable functional outcome, defined by mRS scores 2–6 or 3–6. Other outcomes were: 90-day unfavourable functional outcome, any death, intermediate clinical outcomes (early neurological improvement (ENI), early neurological deterioration (END), NIHSS score change before and after treatment), and intermediate imaging outcomes (early vascular recanalisation or reperfusion, ICH, infarct growth).
The number of dichotomous outcomes was summarised. Mean values with SD or median values with ranges or IQRs were collated for continuous outcomes. Pooled risk ratios (RR) with 95% CI were estimated for dichotomous outcomes using the DerSimonian and Laird random-effects model.22 For changes in NIHSS scores and infarct growth, the extracted data were only tabulated, given their non-normal distribution and it was not common to estimate pooled median differences through meta-analysis. In every case, a two-sided p value≤0.05 was deemed significant. The percentage of variability across the pooled estimates attributable to heterogeneity beyond chance was estimated using the I2 statistic, and by calculating the p value for heterogeneity. I2 values of 25%, 50% and 75% were regarded as low, moderate and high heterogeneity, respectively. Where there was a high likelihood of heterogeneity in pooled primary outcome, sensitivity analyses were performed by excluding individual studies: those without prospective data collection or studies where participants had late brain MRI (>24 hours after onset). As planned, subgroup analyses were performed for the primary outcome by treatment administered to patients, or types of FLAIR-HAs defined by location or extent. In addition, a random-effects meta-analysis was undertaken to show the association of clinical and imaging factors with the presence of FLAIR-HAs on baseline MRI. Evidence of publication bias was assessed using Egger’s regression test for funnel asymmetry in addition to visual inspection of the funnel plots. All statistical analyses were performed using Stata V.12.0.
Study selection and characteristics
The literature search in April 2019 yielded 219 potentially eligible articles or conference abstracts, of which 44 articles were reviewed in full (figure 1). After search updating by the end of October 2019 and including data from the ENCHANTED trial, a total of 36 cohort studies (33 with prospective data collection, 6 from conference abstracts) involving 3577 AIS patients met the inclusion criteria.5–7 9–13 23–49 Excluded studies included: not original research, no eligible research objectives or outcomes of interest, duplicate cohorts or outcome data not separately obtainable in patients with and without FLAIR-HAs.
Included studies were published between 2007 and 2019, and the sample sizes ranged from 3011 to 325,40 with MCA infarct being the predominant lesion type (online supplementary table 1). Twenty-six studies involving 2681 patients7 9 11 12 23 25–27 29–33 35 36 38–44 46 48 49 were pooled for an assessment of functional outcome, in which 23 studies involving 2500 patients had this reported at 90 days.7 9 12 23 25–27 29 30 32 33 35 36 38–44 46 48 The number of eligible studies (patients) for meta-analysis of recanalisation or reperfusion at 24–48 hours was 17 (n=1487),5 7 9 12 13 23 25 26 30 31 33–36 46 47 ICH 7 (n=1114),9 13 28 31 40 45 ENI 5 (n=644),7 24 30 36 END 4 (n=738)29 40 48 and any death 3 (n=635).12 40 Seventeen studies (n=1677)5–7 12 13 23 25 29 31 34–37 40 42 46 reported infarct volume on admission or within 5 days after admission, in which six studies (n=705)6 7 12 25 37 40 reported infarct growth. Data from 21 studies6 7 9 10 12 13 23 25 29 31 33–38 40 42 43 48 were pooled for predictors with the presence of FLAIR-HAs. Only one study13 had low quality, with more than half of the total items (6/9) being assessed as having a high risk of bias (online supplementary table 2).
Association of FLAIR-HAs with functional outcome
Prior AF (pooled RR 1.17, 95% CI 1.01 to 1.36; p=0.04) and proximal arterial occlusion (pooled RR 1.88, 95% CI 1.28 to 2.77; p=0.001) were significantly associated with the presence of FLAIR-HAs (table 1). Overall, compared with no FLAIR-HAs, the presence of FLAIR-HAs was not associated with poor functional outcome (pooled RR 0.87, 95% CI 0.71 to 1.06; p=0.17). However, there was a significant association with better functional outcome in patients who had endovascular therapy (pooled RR 0.56, 95% CI 0.41 to 0.75; p<0.001) (figure 2). Comparable results were observed in sensitivity analyses for 90-day functional outcome (online supplementary figure 1) and after excluding studies without prospective data collection and early brain MRI (online supplementary figure 2). There was high heterogeneity in results pooled for functional outcome (I2=86.4%), which persisted in sensitivity analyses. There were diverging associations in subgroup analyses by different types of FLAIR-HAs and functional outcome: being associated with unfavourable outcome for FLAIR-HAs in relation to proximal MCA (pooled RR 2.01, 95% CI 1.39 to 2.89; p<0.001) and within DWI lesions (pooled RR 1.74, 95% CI 1.05 to 2.88; p=0.03), and associated with better outcome for FLAIR-HAs beyond a DWI lesion (pooled RR 0.67, 95% CI 0.57 to 0.79; p<0.001) (figure 3). There was no association with functional outcome for FLAIR-HAs related to distal MCA and with greater extent (FLAIR-HAs scores>4 or FLAIR-HAs ASPECTS grade>4). Heterogeneity for associations was generally high across studies, except in the assessment of FLAIR-HAs in relation to proximal MCA (I2=0.0%) or beyond DWI lesion (I2=52.7%).
Association of FLAIR-HAs with other outcomes
Presence of FLAIR-HAs was associated with recanalisation or reperfusion at 24 to 48 hours (pooled RR 1.21, 95% CI 1.06 to 1.38; p=0.005), increased risk of ICH (pooled RR 2.07, 95% CI 1.37 to 3.13; p=0.001) and END (pooled RR 1.93, 95% CI 1.30 to 2.85; p=0.001), all with low to moderate heterogeneity (I2 from 21.1% to 51.8%) (figure 4). There was no significant association with ENI (pooled RR 1.44, 95% CI 0.83 to 2.49; p=0.19) or death (pooled RR 3.60, 95% CI 0.65 to 19.81; p=0.14). Funnel plots and Egger’s regression tests identified no strong evidence of publication bias for all dichotomous outcomes except recanalisation or reperfusion (p=0.01) (online supplementary figure 3). Data from the ENCHANTED trial as well as several other studies had shown that patients with FLAIR-HAs had greater NIHSS scores at baseline and early follow-up than those without, but there was no apparent imbalance in the level of NIHSS scores according to FLAIR-HAs beyond a DWI lesion (online supplementary table 3). Moreover, compared with those without FLAIR-HAs, those with FLAIR-HAs had greater reduction in NIHSS scores between baseline and early follow-up and were more likely to have larger initial and subsequent growth in infarct volumes (online supplementary table 4).
In this systematic review and meta-analysis, we have identified the key determinants of FLAIR-HAs on MRI after AIS as prior AF and proximal arterial occlusion. While overall, FLAIR-HAs were not associated with functional outcome, it is associated with favourable recovery when endovascular therapy is performed. FLAIR-HAs were also associated with early recanalisation or haemorrhagic complications, and early neurologic deterioration.
We did not identify a significant association of FLAIR-HAs with functional outcome, but there was an apparent benefit in those with MCA AIS who received endovascular therapy, where the FLAIR-HAs was located beyond a DWI lesion, and when there was no proximal FLAIR-HAs or FLAIR-HAs within the DWI lesion. FLAIR-HAs were more likely to be seen with proximal arterial occlusion, suggesting they indicate retrograde filling in the ischaemic territory by leptomeningeal collateral flow. This explanation also provides a plausible mechanism for improved outcome in such patients treated with thrombectomy. Data from ENCHANTED showed a possibility that proximal arterial occlusion status mediated the association of FLAIR-HAs with 90-day functional outcome. FLAIR-HAs, if present, are also more likely to be assessed as within rather than beyond the DWI lesions in cases where proximal arterial occlusion tends to cause a large ischaemic lesion on DWI. This may explain the variable associations of FLAIR-HAs within versus beyond the DWI lesion with the functional outcome.
We also found the presence of FLAIR-HAs favoured early recanalisation or reperfusion after reperfusion treatment, which is consistent with prior studies reporting good leptomeningeal collateral flow being associated with recanalisation or reperfusion after either intravenous thrombolysis or endovascular therapy.50–53 Good leptomeningeal collaterals have been shown to be associated with permeable thrombus,54 which is easier to lyse based on larger contact surface area between the thrombus and alteplase for use of intravenous thrombolysis or ease of thrombectomy with stent retrievers due to reduced wall tension.55–57 Association between FLAIR-HAs and ICH could be supported by the concept that reperfusion can lead to haemorrhagic infarct (HI): Miller Fisher found petechial HI around infarcts (mainly occipital lobe) in a small post-mortem study in the 1950s;58 or that HI is more common with proximal arterial occlusion: another small contemporaneous post-mortem study reported worse HI with proximal arterial occlusion and peripheral collaterals replicated in primates.59 Our prior analysis of ENCHANTED participants showed that a significant increase in the risk of ICH after intravenous thrombolysis was driven by HI (adjusted OR 4.77, 95% CI 1.12 to 20.26; p=0.03) rather than parenchymal haemorrhage (adjusted OR 0.78, 95% CI 0.21 to 2.91; p=0.71) after adjustment of baseline covariables, which may explain why the clinical prognosis is not influenced even after haemorrhagic complications occur in those with FLAIR-HAs.
It is interesting that the pooled results for ENI and END were contradictory. The small number of studies included in our meta-analysis, and the different definitions of ENI or END across studies (online supplementary table 5), limits the robustness of these results and raises the potential influence of the play of chance. The consistent results from the ENCHANTED data were that FLAIR-HAs were associated with an increased risk of END, and a decrease in ENI, which may be related to a greater likelihood of ICH after reperfusion in those with FLAIR-HAs versus without, but this needs further confirmation in the future.
A key limitation of the study is the low number of studies and participants to allow examination of associations in subgroups and for some intermediate outcomes, raising the potential for chance finding. While caution is warranted over the interpretation of the findings in relation to FLAIR-HAs in patients who received endovascular therapy, early recanalisation or reperfusion remains the most plausible explanatory mechanism for the positive association of FLAIR-HAs and good functional outcome. Evidence on the use of MRI in wake-up stroke patients has been provided recently.60 Whether FLAIR-HAs may serve as an additional imaging marker to select these and other types of stroke patients with DWI-FLAIR mismatch for endovascular therapy warrants future investigation. Another issue is that we were not able to provide a strong estimate of the relation with NIHSS score change or infarct growth, which were undertaken in the ENCHANTED trial and varied according to types of FLAIR-HAs defined by location or extent. A future collaboration towards producing an individual participant data meta-analysis could provide more insights.
In summary, FLAIR-HAs were not associated with functional outcome overall but were associated with outcome after endovascular therapy for AIS. FLAIR-HAs were also associated with early recanalisation or haemorrhagic complications, and early neurologic deterioration.
We thank Professor Mark Woodward for his statistical advice during analysis of these data. We thank all investigators, study teams and patients participating in the Enhanced Control of Hypertension and Thrombolysis Stroke Study trial. ZZ received overseas visiting funding from Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University (2016–2018) and a Scientia PhD scholarship from the University of New South Wales, Sydney (2018–2022) during the conduct of the study.
Contributors Conception and design: ZZ, GM, RASS, JMW, RIL, CSA; literature search and data extraction: ZZ, AM, SY, CD; analysis and interpretation of data: all authors; initial drafting of manuscript: ZZ, AM, CD, CSA; critical revision of the manuscript for intellectual content: all authors; final approval of the manuscript: all authors.
Funding The Enhanced Control of Hypertension and Thrombolysis Stroke Study trial is supported by grants from the National Health and Medical Research Council of Australia (project grant numbers 1020462 and 1101113), the Stroke Association of the UK (TSA 2012/01 and 2015/01), the Ministry of Health and the National Council for Scientific and Technological Development of Brazil (CNPQ: 467322/2014-7, 402388/2013-5), the Ministry for Health, Welfare and Family Affairs of the Republic of Korea (HI14C1985) (for the alteplase-dose arm) and a research grant from Takeda for conduct of the study in China. The work was done by the authors with no involvement of the funder in the design or conduct of the study; collection, management, analysis or interpretation of the data; preparation, review or approval of the manuscript; or decision to submit the manuscript for publication.
Competing interests GM reports grants from The Stroke Association. AMD reports personal fees from Medtronic and Daiichi Sankyo (outside the work). JMW reports grants from The Stroke Association and UK Medical Research Council. CSA reports honorarium from Takeda, Boehringer Ingelheim and Amgen.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information except the data in Table 1 and individual participant data from ENCHANTED which are available upon reasonable request.
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West Virginia, often referred to as the “Mountain State,” boasts a rich agricultural heritage.
Its diverse topography, from rolling hills to fertile valleys, makes it an ideal location for various farming activities.
Here are some of the prime farmland regions in West Virginia.
Ridgeley is one of the regions in West Virginia known for its fertile lands.
The area offers a mix of agricultural activities, making it a sought-after location for farming enthusiasts.
2. Scott Depot
Scott Depot is another region in West Virginia that is recognized for its agricultural potential.
The land here is suitable for various crops and livestock farming.
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The region is home to several farms that contribute significantly to the state's agricultural output.
Hedgesville is a region that combines the beauty of nature with the productivity of fertile lands.
The farms here are known for their sustainable farming practices and high-quality produce.
5. Seneca Rocks
Located near the confluence of Seneca, Seneca Rocks is one of the best rural places to live in West Virginia.
The community is surrounded by fertile lands, making it an ideal location for farming.
West Virginia's farming heritage is deeply rooted in its history.
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Joint City/County Commission Town Hall Addresses Bridge Question
February 9, 2018
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By: Stephen Kent
Monday morning, February, 5, found the majority of the Bay City Commission AND the Bay County Commission sitting at a long table in the Doubletree Hotel and Conference Center. Arrayed before them was a room full of stakeholders, citizens, business people, politicians and representatives of organizations such as the Chamber of Commerce, Bay Future, and the Great Lakes Bay Regional Alliance.
Everyone was there to hear these diverse players gather, in the same room, to discuss the controversial Liberty and Independence Bridge
As most Bay City residents and those in neighboring counties and communities know, the fate of the bridges has become a hot issue. Everyone agrees that something is going to have to be done. The bridges are at the end of their lifespans and have significant structural issues that must be addressed.
Everyone also knows that the millions of dollars to complete such work on these City-owned structures is far outside the ability of the city to cover.
The two hottest issues are 1) the prospect of selling the bridges to an outside firm, which would repair Liberty and rebuild Independence, and 2) for that company to charge a toll to cross the bridges. There would be no cost to the City because the firm would collect a toll to cross the bridge and make their money back that way. Many speakers said that any toll was too expensive and they would choose a different bridge.
A side issue is that the proposed replacement for the Independence Bridge would be a very tall, fixed span over the river. By all accounts, this would be similar to the Zilwaukee Bridge in Saginaw. Many speakers were vocally opposed to that plan. No one seemed ready to defend the idea. A consensus seemed to be that such a large bridge would be out of place in the city and that the approaches would be far too long.
Other concerns dealt with the potential for a millage, closing some of the bridges, asking that boaters pay a toll rather than the vehicle traffic, getting the state and/or federal government to contribute, getting surrounding counties and towns to pay a share.
The majority of the commissioners speaking to the millage made it clear that getting a millage passed would be a heavy lift. The city might pass it, but outlying communities probably would not. Some commissioners even said they would not support such a proposal.
Once the commissioners, and many people from other organizations, had spoken, the floor was opened to public comment. Sixteen people rose to speak.
The option to close the bridges came up several times. "Just open them and leave them open. We'd see who really gets concerned." Currently, the Independence Bridge is closed for needed repair. By the time it's open again people will have a pretty good idea what it would be like to not have that bridge.
The Independence Bridge was first opened to traffic in 1973 and sees some 23,780 crossings a day. The Liberty Bridge was opened in 1983 to replace the Third Street Bridge, which had fallen several years before. Liberty sees 16,849 crossings a day.
The toll option and the private owner were soundly rejected by most people. One businessman did say that his trucks would pay the toll, but he didn't seem to like it. He also said that closing a bridge would be a tragedy.
Just opening a bridge and leaving it open was an attractive idea, but not practical. Laws require that if a bridge is left open the owner must present a proposal for maintenance within a short time, or would have to remove the bridge. Removal has been estimated at 10 million dollars.
As to tolls for boats, that doesn't seem an option. Boats cannot be charged a toll to use a navigable waterway, just as such a waterway can't be blocked.
The one point everyone could agree on was that the bridges must be supported by the state and, hopefully, by the federal government. People who had explored that option indicated that it was by no means a given, but that it might be accepted.
As the meeting wrapped up, Commission President Andrew Niedzinski called for volunteers to work on three committees:
- Lansing lobby committee - to lobby in Lansing.
- Community Infrastructure committee - to focus on problems in townships and surrounding areas with similar problems.
- Information Group - to give bridge presentations etc. to the public to keep the community informed.
Although no specific proposals were made, everyone seemed pleased that all of the interested parties had sat down in the same room to discuss the issue. We hope this initiative continues.
City and County Commissioners participate in joint public meeting to discuss bridges.
Steve Kent and his family have lived in Bay City for 40 years. He is VP of Technical Services at MMCC which produces MyBayCity.Com. Kent is active in many Bay City civic organizations.
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Constructing new houses nowadays come with different decision-making complications. Especially with the improvement of innovation nowadays even eco-friendly painting has also become a concept. Like so people are more concerned about making homes a place of health and calmness more than just a place to live.
One main thing many people overlook when constructing or renting houses is to have more open spaces. Even if open spaces may not be your thing, they come as an important concept of a healthy home-style. Here are few reasons why you should have more open spaces in your house if you’re constructing or renting one.
Kids don’t care about how expensive or stylish the furniture of the house is. And when there isn’t enough space for kids to play around or do their thing, there are even possibilities the kids can ruin your interiors playing inside the house.
Moreover, if you’re in a busy or insecure neighbourhood you’ll always feel reluctant to send your kids out to play. But at the same time, it would be very unfair to steal your child’s childhood from them. So, try to incorporate more open spaces like an outside playroom or playhouse, depending on your budget. This will keep them exposed to fresh air, nature, and give them a beautiful playtime.
A home is indeed a place where we connect and create relationships with our loved ones. It’s a place where we share our emotions, be it good or bad. An open space dedicated to better conversations, or even just to sit by and talk while sipping a cup of tea promotes healthier relationships.
It’s also ideal to create such a space facing the entrance of your house where you can get a better and pleasant view. Try to incorporate a good outdoor seating, a small coffee table with magazines or newspapers to read or even a swing depending on the space.
If you don’t have such a space or are confused about how to create such a spacious layout in your house, the best would be to hire verandah builders. They can construct just the right open space in your house that will encourage this purpose depending on your house space and layout.
Encourages a fitness lifestyle
A house filled with chairs and a sofa every inch of the house will only encourage lazy slumbering. In contrast, if you have an open space where you can simply walk or even engage in meditation, work out, or even do Zumba around fresh air can encourage you into a fitness regime.
If you don’t have a large outdoor space, you can even form an open space in your house with fewer partitions and minimal furnishing. All it takes is a good contractor who can bring your idea into the available layout or space around your house.
As it clear, open spaces enhances the healthy concept of a house in and out. Despite the age categories that may live in your house, having more open spaces benefits everybody health-wise. So even if you may have only a small space to utilize for an open space in your new house, try to let your contractors know what you need. They will come up with a creative layout to make you open space.


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Development of the Doctrine on Certain Personal Incorporeal Rights in European Countries
The article considers the main aspects of the development of doctrines on personal incorporeal rights in European countries. The conceptual approaches of researchers to such rights have been analyzed. A comparative legal analysis of the legal regulation of personal incorporeal rights in European countries has been conducted as well. The trends and approaches to the ways of consolidating such countries in the system of private law have been studied.
 Gribanov V.P. 2001. Implementation and protection of civil rights. M., S. 222.
 Kant, I. 1965. Works. In 6 vol. T. 4, part 2. M., S. 205–206.
 Kapuściński, R. 2007. Lapidarium VI, Warszawa, p. 92.
 Kostruba, Anatoliy V. 2019. The Notion and Attributes of Right – Terminating Legal Facts. Journal of Advanced Research in Law and Economics, vol. 10, 1: 254-262. Available at: https://journals.aserspublishing.eu/jarle/article/view/4354. Date accessed: 21 may 2020. Doi: https://doi.org/10.14505//jarle.v10.1(39).26.
 Le code de la propriete intellectuelle of acquisitions by law vid 1 lipnya 1992 p. No. 92-597 (loi no 92-597 du 1er juillet 1992), publications in the official journal 3 Lipnya 1992 p. (publie au Journal du 3 juillet 1992). [Electronic resource] – Access to resource mode: https://www.legifrance.gouv.fr.
 Lucas A., Lucas H.-J., Lucas-Schloetter A. 2012. Traité de la propriété littéraire et artistique. Paris, 2012. P. 438.
 Mazurkiewicz J. O uprzedmiotowieniu autorów, wszechwładzy wydawców i nędzy prawa autorskiego. Prawo autorskie w czasach restauracji kapitalizmu w Polsce, RPEiS 2015b/2, c. 251–262.
 Mazurkiewicz J., ‘Cześć, prywatność I zgon pilnie sprzedam!’ Wokół dopuszczalności rozporządzania prawami osobistymi [in:] Współczesne ystema prawa zobowiązań, rev. A. Olejniczak, J. Haberko, A. Pyrzyńska, D. Sokołowska, Warszawa 2015a, p. 432–456.
 Owen L. 2000. Acquisition and sale of copyright in literary works. [Electronic resource] / L. Owen // Aspect Press. Access mode to the resource: http://bibliotekar.kz/priobretenie-i-prodazha-avtorskih-prav-n/1-koncepcija-avtorskogo-prava-zapadnaja-.html.
 Posikalyuk, O. O. 2011. Special rights of non-mainstream rights in Roman, German, English-American private law systems: monograph / ed. : A. M. Shadrina; Nat Acad. Right Sciences of Ukraine, NDI privat. Rights and rights. Kiev, 204 c. S. 53.
 Protsenko, Iryna; Savchuk, Кostiantyn. 2020. Sovereign Rights of the State and the Scope of their Implementation in the Context of Development of the International Human Rights Law. Journal of Advanced Research in Law and Economics, v. 11, 1: 164 – 168, mar. 2020. ISSN 2068-696X. Available at: https://journals.aserspublishing.eu/jarle/article/view/4768. Date accessed: 21 may. Doi: https://doi.org/10.14505//jarle.v11.1(47).20.
 Sandel, M. J. 2013. Czego nie można kupić za pieniądze: moralne granice rynku, translation A. Chromik, T. Sikora, Warszawa 2013, passim, and P. Ondřejek, Inspection book M.J. Sandela with the title What Can’t Buy. The Moral Limits of Markets, Bulletin Advokacie 2012/11, c. 56-57.
 Sirinelli P. 1997. European and international systems for the protection of copyright and related rights // Copyright and related rights in the European Union and the Russian Federation: coll. Reports and discussions on the materials of international seminars on the protection of intellectual property in the field of culture and art. M., S. 33–41.
 Soros G. 1997. Globalne społeczeństwo otwarte, Rzeczpospolita 299, p. 8.
 Sundara Rajan M. T. 2011. Moral Rights: Principles, Practice and New Technology. P. 60–64.
 Tafforeau Patrick. 2015. Les exceptions à la propriété littéraire et artistique aux ﬁns de recherche et d’enseignement , Cahiers Droit, Sciences et Technologies [En ligne], 3 | 2010, mis en ligne le 01 novembre 2015, consulté le 08 juillet 2020. URL : http://journals.openedition.org/cdst/229; DOI: https://doi.org/10.4000/cdst.229
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The Beautiful Truth
I realize most women hate the Proverbs 31 Woman. However, I love her. She embodies everything I want to be. She is organized, giving, wise, well-dressed, happy, secure, selfless, and beautiful.
If you take time to read through the many things that endears this woman to members of her home and those in the community, you will not hear mention of her height, weight, coloring. You will not hear the length of her hair or fingernails. What you will read is the power of her contributions to the lives of those around her.
Do another exercise.
Go to Bible Gateway, look up Proverbs 31, copy it to a Word document, and print it out.
Now, highlight all the places and ways this woman contributes to those around her.
Go ahead. Do it right now. It’ll take less than 5 minutes. You’ll spend longer reading forwarded jokes in your email today, and they won’t bless you nearly as much. I’ll meet you back here (hopefully) tomorrow.
Copyright Jerri Phillips 2008


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Organizations team up to feed, shelter linemen working in Louisiana
BATON ROUGE, La. (WAFB) - Organizations across south Louisiana are teaming up to feed and shelter out-of-state linemen working to turn the lights back on in areas affected by Hurricane Ida.
- Shelter set up in Hammond
WEST BATON ROUGE PARISH:
- Addis Community Center (7520 LA 1 in Addis) is set up as a fully stocked shelter to house and feed more than 100 linemen.
Click here to report a typo.
Copyright 2021 WAFB. All rights reserved.


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Yourself dating a single dad, you may have some reservations if you find. It is ok to feel stressed about dating somebody with young ones. Luckily for us, by setting several easy boundaries set up, you are able to supply the relationship the chance that is best at succeeding.
Steer clear of the Stress of Fulfilling Their Children Too Rapidly
Probably one of the most key elements of this relationship to think about is, needless to say, the kids. DonвЂ™t feel stress to quickly meet them more than you’re feeling prepared for. You ought to become familiar with anyone youвЂ™re relationship before you meet their young ones.
If things donвЂ™t work down if they meet someone who is gone a week later between you two, it will be confusing for the kids. You and your partner should discuss when the best time to meet the children would be if you feel the relationship is going well. „Just how to Set Boundaries Whenever Dating a Single Dad“ weiterlesen

domain: sociology


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The project empowers more people to switch to sustainable waste management
As part of the Green Business Network Initiative, The Environment Agency Abu Dhabi has launched a new campaign. This is in collaboration with AD Ports Group.
The project aims to empowering industrial entities to switch to more sustainable waste management practices and minimize single-use plastics.
The ‘Clean your perimeter campaign’ has set parameters until December 2022. The aim is to educate people at large about the industrial facilities and increase awareness regarding the importance of keeping the capital clean.
It also engages employees in corporate social responsibility ( CSR ) activities such as Citizen Science clean-ups of near by areas.
This is in addition to supporting citizen science research on the volume of single-use plastics and other types of waste
entering the environment.
For great results to this campaign, facilities are requested to conduct internal awareness sessions for all employees. These include supervisors, contractors, security teams and broader support staff such as truck drivers. They emphasize on how to reduce the impact of littering and help protect the shared environment.
Circulation of internal awareness collaterals such as facts, infographic videos and more will support the outreach.
As part of the campaign, facilities will get the chance to be recognised for their efforts through the social media channels of Environment Agency Abu Dhabi
At the end of this year, a ceremony will be organized to express appreciation for the success of the ‘Clean your Perimeter’ campaign.


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NBA suspends Mayo 1-game for punchMILWAUKEE, WI - MARCH 5: O.J. Mayo #00 of the Milwaukee Bucks shoots against Ray McCallum #3 of the Sacramento Kings on March 5, 2014 at the BMO Harris Bradley Center in Milwaukee, Wisconsin. (Photo by Gary Dineen/NBAE via Getty Images)
The incident occurred with 1:52 remaining in the first quarter of Milwaukee's 112-104 loss to the Pelicans on Friday. Mayo got tied up with Stiemsma as he tried to get around a screen set by the big man.
Mayo was assessed a flagrant four 2 and ejected. He will serve the suspension Saturday night when the Bucks host the Washington Wizards.