Human herpesvirus-6 infection in liver transplantation

Rejection and infections are the two most common complications after liver transplantation. Human herpesvirus-6 (HHV-6) belongs to the betaherpesviruses, together with its close relatives cytomegalovirus (CMV) and human herpesvirus-7 (HHV-7). The impact of CMV in liver transplantation is well characterized, but the roles of the other two betaherpesviruses have been acknowledged only recently. Although, HHV-6 reactivation after transplantation is usually asymptomatic, the virus may infect the liver transplant, cause an intragraft lymphocyte dominated inflammatory reaction and graft dysfunction. HHV-6 is also suggested to be associated with liver allograft rejection but the mechanisms are unclear. The aim of this study was to investigate the intragraft immunological processes associated with HHV-6, the involvement of HHV-6 in acute liver failure (ALF) and the hepatic HHV-6 infection of the same patients after transplantation. In addition, the occurrence of HHV-6 and HHV-7 was investigated in liver transplant patients with symptomatic CMV infection. HHV-6 infection of the liver graft was associated with portal lymphocyte infiltration and with a significant increase of adhesion molecules (ICAM-1 and VCAM-1) and the number of cells expressing their ligand molecules (LFA-1, VLA-4) and class II antigens. HHV-6 infection was associated with significant immunological changes, but the immune response was limited to lymphocyte infiltration and the adhesion molecule level. However, one third of these patients developed chronic rejection during the follow-up. Of the patients with ALF of unknown origin, most patients demonstrated HHV-6 antigens in the liver, whereas the opposite was seen in ALF patients with a known disease. After transplantation, HHV-6 recurrence was found in the liver transplant in half of these patients with pre-transplant HHV-6 infection of the liver, whereas no post-transplant HHV-6 infection of the liver was seen in patients without pre-transplant HHV-6. Our studies further demonstrated that both HHV-6 and HHV-7 antigenemia often appeared in association with CMV disease in liver transplant patients. The time-related occurrence of the viruses differed, as HHV-6 appeared early after transplantation and regularly preceded CMV whereas HHV-7 often appeared concurrently with CMV. In conclusion, these results indicate that all three betaherpesviruses are common after liver transplantation, often associated with each other. The immunological events caused by HHV-6 in the liver transplant may be involved in, or trigger mechanisms of allograft rejection. In addition, HHV-6 could be one of the causes of ALF, and pre-transplant HHV-6 infection in ALF patients is a risk factor for post-transplant HHV-6 infection of the graft. These results strongly support the clinical significance of HHV-6 in liver transplantation. Even though the reactivation is usually asymptomatic, in some individuals HHV-6 infection may lead to severe manifestations, such as liver failure or in transplant patients, graft dysfunction and rejection.

Fatigue fractures in military conscripts : A study on risk factors, diagnostics and long-term consequences

Fatigue fracture is an overuse injury commonly encountered in military and sports medicine, and known to relate to intensive or recently intensified physical activity. Bone responds to increased stress by enhanced remodeling. If physical stress exceeds bone s capability to remodel, accumulation of microfractures can lead to bone fatigue and stress fracture. Clinical diagnosis of stress fractures is complex and based on patient s anamnesis and radiological imaging. Bone stress fractures are mostly low-risk injuries, healing well after non-operative management, yet, occurring in high-risk areas, stress fractures can progress to displacement, often necessitating surgical treatment and resulting in prolonged morbidity. In the current study, the role of vitamin D as a predisposing factor for fatigue fractures was assessed using serum 25OHD level as the index. The average serum 25OHD concentration was significantly lower in conscripts with fatigue fracture than in controls. Evaluating TRACP-5b bone resorption marker as indicator of fatigue fractures, patients with elevated serum TRACP-5b levels had eight times higher probability of sustaining a stress fracture than controls. Among the 154 patients with exercise induced anterior lower leg pain and no previous findings on plain radiography, MRI revealed a total of 143 bone stress injuries in 86 patients. In 99% of the cases, injuries were in the tibia, 57% in the distal third of the tibial shaft. In patients with injury, forty-nine (57%) patients exhibited bilateral stress injuries. In a 20-year follow-up, the incidence of femoral neck fatigue fractures prior to the Finnish Defence Forces new regimen in 1986 addressing prevention of these fractures was 20.8/100,000, but rose to 53.2/100,000 afterwards, a significant 2.6-fold increase. In nineteen subjects with displaced femoral neck fatigue fractures, ten early local complications (in first postoperative year) were evident, and after the first postoperative year, osteonecrosis of the femoral head in six and osteoarthritis of the hip in thirteen patients were found. It seems likely that low vitamin D levels are related to fatigue fractures, and that an increasing trend exists between TRACP-5b bone resorption marker elevation and fatigue fracture incidence. Though seldom detected by plain radiography, fatigue fractures often underlie unclear lower leg stress-related pain occurring in the distal parts of the tibia. Femoral neck fatigue fractures, when displaced, lead to long-term morbidity in a high percentage of patients, whereas, when non-displaced, they do not predispose patients to subsequent adverse complications. Importantly, an educational intervention can diminish the incidence of fracture displacement by enhancing awareness and providing instructions for earlier diagnosis of fatigue fractures.

Evaluating China’s aspirations for cultural soft power in a post-globalisation era

‘Soft power’ has been a concept that has generated great political and scholarly interest in China, as it raises the question of how to achieve cultural standing commensurate with the nation’s growing economic significance. But from the perspectives of communication and cultural studies, we can identify limits with both ‘soft power’ as a concept and how it understands culture and communication, and the assumptions made about the capacities of state cultural promotion through media to appeal to global audiences. Drawing upon case studies of the United States, the United Kingdom, Russia, India, Japan and South Korea, this article identified challenges and opportunities for China in growing its international cultural soft power in a ‘post-globalisation’ era.

Long-term results of operative treatment for Hirschsprung's disease and internal anal sphincter achalasia

The aim of the study was to evaluate long-term results of operative treatment for Hirschsprung's disease(HD) and internal anal sphincter achalasia. Fecal continence and quality of life were evaluated by a questionnaire in 100 adult patients who had undergone surgery for HD, during 1950-75. Fecal continence was evaluated using a numerical scoring described by Holschneider. Fifty-four of the 100 patients underwent clinical examination, rigid sigmoidoscopy and manometric evaluation. In anorectal manometry basal resting pressure(BRP)and maximal squeeze pressure(MSP) were measured and voluntary sphincter force(VSF) was calculated by subtracting the BRP from MSP. The results of operative treatment for adult HD were compared with the results of the patients operated in childhood. In adult HD the symptoms are such mild that the patients attain adolescence or even adulthood. The patients with HD and cartilage-hair-hypoplasia were specifically evaluated. The outcome of the patients with internal anal sphincter achalasia operated on by myectomy was evaluated by a questionnaire and continence was evaluated using a numerical scoring described by Holschneider. Of the 100 patients operated on for HD 38 patients had completely normal bowel habits. A normal or good continence score was found in 91 our of 100 patients. Nine patients had fair continence. One of the patients with fair continence had Down's syndrome and two were mentally retarded for other reasons. Only one patient suffered from constipation. In anorectal manometry the difference in BRP between patients with normal and good continence was statistically significant, whereas the difference between good and fair continence groups was not statistically significant. The differences on MSP and VSF between patient groups with different continence outcome were not statistically significant. The differences between patient groups and normal controls were statistically significant in BRP and MSP. In VSF there was not statistically significant difference between the patients and the normal controls. The VSF reflects the working power of the muscles including external sphincter, levator ani and gluteal muscles. The patients operated at adult age had as good continence as patients operated in childhood. The patients with HD and cartilage-hair-hypoplasia had much more morbidity and mortality than non-cartilage-hair-hypoplasia HD patients. The mortality was as high as 38%. In patients with internal anal sphincter achalasia the constipation was cured or alleviated by myectomy whereas a significant number suffered from soiling-related social problems.

Cancer incidence, mortality, and pregnancy outcome among women treated for cervical intraepithelial neoplasia

Cervical cancer develops through precursor lesions, i.e. cervical intraepithelialneoplasms (CIN). These can be detected and treated before progression to invasive cancer. The major risk factor for developing cervical cancer or CIN is persistent or recurrent infection with high-risk human papilloma virus (hrHPV). Other associated risk factors include low socioeconomic status, smoking, sexually transmitted infections, and high number of sexual partners, and these risk factors can predispose to some other cancers, excess mortality, and reproductive health complications as well. The aim was to study long-term cancer incidence, mortality, and reproductive health outcomes among women treated for CIN. Based on the results, we could evaluate the efficacy and safety of CIN treatment practices and estimate the role of the risk factors of CIN patients for cancer incidence, mortality, and reproductive health. We collected a cohort of 7 599 women treated for CIN at Helsinki University Central Hospital from 1974 to 2001. Information about their cancer incidence, cause of death, birth of children and other reproductive endpoints, and socio-economic status were gathered through registerlinkages to the Finnish Cancer Registry, Finnish Population Registry, and Statistics Finland. Depending on the endpoints in question, the women treated were compared to the general population, to themselves, or to an age- and municipality-matched reference cohort. Cervical cancer incidence was increased after treatment of CIN for at least 20 years, regardless of the grade of histology at treatment. Compared to all of the colposcopically guided methods, cold knife conization (CKC) was the least effective method of treatment in terms of later CIN 3 or cervical cancer incidence. In addition to cervical cancer, incidence of other HPV-related anogenital cancers was increased among those treated, as was the incidence of lung cancer and other smoking-related cancers. Mortality from cervical cancer among the women treated was not statistically significantly elevated, and after adjustment for socio-economic status, the hazard ratio (HR) was 1.0. In fact, the excess mortality among those treated was mainly due to increased mortality from other cancers, especially from lung cancer. In terms of post-treatment fertility, the CIN treatments seem to be safe: The women had more deliveries, and their incidence of pregnancy was similar before and after treatment. Incidence of extra-uterine pregnancies and induced abortions was elevated among the treated both before and after treatment. Thus this elevation did not occur because they were treated rather to a great extent was due to the other known risk factors these women had in excess, i.e. sexually transmitted infections. The purpose of any cancer preventive activity is to reduce cancer incidence and mortality. In Finland, cervical cancer is a rare disease and death from it even rarer, mostly due to the effective screening program. Despite this, the women treated are at increased risk for cancer; not just for cervical cancer. They must be followed up carefully and for a long period of time; general health education, especially cessation of smoking, is crucial in the management process, as well as interventions towards proper use of birth control such as condoms.

Exploring the post-genomic world: Differing explanatory and manipulatory functions of post-genomic sciences

Richard Lewontin proposed that the ability of a scientific field to create a narrative for public understanding garners it social relevance. This article applies Lewontin's conceptual framework of the functions of science (manipulatory and explanatory) to compare and explain the current differences in perceived societal relevance of genetics/genomics and proteomics. We provide three examples to illustrate the social relevance and strong cultural narrative of genetics/genomics for which no counterpart exists for proteomics. We argue that the major difference between genetics/genomics and proteomics is that genomics has a strong explanatory function, due to the strong cultural narrative of heredity. Based on qualitative interviews and observations of proteomics conferences, we suggest that the nature of proteins, lack of public understanding, and theoretical complexity exacerbates this difference for proteomics. Lewontin's framework suggests that social scientists may find that omics sciences affect social relations in different ways than past analyses of genetics.

Primary polyestradiol phosphate versus orchiectomy for advanced prostate cancer : Studies on the efficacy, cardiovascular complications and prognostic factors

Paikallisesti levinnyttä (T3-4 M0) ja luustoon levinnyttä (T1-4 M1) eturauhassyöpää sairastaneet potilaat satunnaistettiin kirurgiseen kastraatioon (orkiektomia) tai lääkkeelliseen kastraatioon lihaksensisäisellä polyestradiolifosfaatilla (PEP) annoksella 240 mg/kk. Verrattiin hoitojen kliinistä tehoa sekä sydän- ja verisuonikomplikaatioita (SV-komplikaatioita). Verrattiin myös hoitoa edeltäviä plasman testosteroni (T) ja estradioli (E2) pitoisuuksia T3-4 M0 ja T1-4 M1 potilaiden välillä sekä selvitettiin potilaiden yleistilan vaikutusta näihin hormonitasoihin. Lopuksi luotiin T1-4 M1 potilaille eturauhassyövän aiheuttaman kuoleman ennusteellinen riskiluokittelu kolmeen riskiryhmään käyttämällä hoitoa edeltäviä ennustetekijöitä. Kliinisessä tehossa ei orkiektomian ja PEP-hoidon välillä todettu tilastollisesti merkitsevää eroa. Odotetusti T1-4 M1 potilaiden ennuste oli huonompi kuin T3-4 M0 potilaiden. T1-4 M1 potilailla ei ollut SV-kuolemissa hoitoryhmien välillä tilastollista eroa, mutta ei-tappavia SV-komplikaatioita oli PEP ryhmässä (5.9%) enemmän kuin orkiektomia ryhmässä (2.0%). T3-4 M0 potilailla PEP-hoitoon liittyi tilastollisesti merkitsevä SV-kuolleisuus riski orkiektomiaan verrattuna (p = 0.001). PEP ryhmässä 67% kuolemista oli akuutteja sydäninfarkteja. Tämä PEP hoitoon liittyvä sydäninfarktiriski (mukaan lukien myös ei-tappavat sydäninfarktit) oli merkitsevästi pienempi potilailla, joiden hoitoa edeltävä E2 taso oli vähintään 93 pmol/l (p = 0.022). E2 taso oli merkitsevästi matalampi T1-4 M1 potilailla (74.7 pmol/l) kuin T3-4 M0 potilailla (87.9 pmol/l), mutta vastaavaa eroa ei ollut T tasoissa. Sekä T3-4 M0 että T1-4 M1 potilailla yleistilan lasku osittain selitti yksilöllisen T ja E2 tasojen laskun. Eturauhassyövän aiheuttaman kuoleman riskiryhmäluokittelu (Rg) kolmeen ryhmään luotiin käyttämällä alkalista fosfataasia (AFOS), prostata spesifistä antigeenia (PSA), laskoa (La) ja potilaan ikää. Yksi riskipiste annettiin, jos AFOS > 180 U/l (tällä hetkellä käytössä olevalla menetelmällä AFOS > 83 U/l), PSA > 35 µg/l, La > 80 mm/h ja ikä < 60 vuotta. Lopuksi pisteet laskettiin yhteen. Muodostettiin seuraavat ryhmät: Rg-a (0 -1 riskipistettä), Rg-b (2 riskipistettä) ja Rg-c (3 – 4 riskipistettä). Eturauhassyövän aiheuttama kuoleman riski lisääntyi merkitsevästi siirryttäessä riskiryhmästä seuraavaan (p < 0.001). Rg-luokittelu oli kliinisesti käytännöllinen ja hyvä havaitsemaan huonon ennusteen potilaat.

The AOL Huffington Post merger

This article examines the merger between AOL and the Huffington Post. The broader issues around the merger will be investigated, especially the implication for rights, in particular free expression, and their conditions for exercise and actual exercise online. One major issue is that of the status of user-generated content and how the existing legal regime reflects the ethical concerns of users over how their content, data and information is used and commodified by the for-profit Internet intermediaries and platforms, especially when they start to merge and form concentrations. The extent to which the current legal regimes, especially human rights, deal with these problems in an adequate fashion will be assessed, along with the presentation of some suggestions of alternative approaches which may be more effective in practice.

The third post-Newtonian gravitational wave polarizations and associated spherical harmonic modes for inspiralling compact binaries in quasi-circular orbits

The gravitational waveform (GWF) generated by inspiralling compact binaries moving in quasi-circular orbits is computed at the third post-Newtonian (3PN) approximation to general relativity. Our motivation is two-fold: (i) to provide accurate templates for the data analysis of gravitational wave inspiral signals in laser interferometric detectors; (ii) to provide the associated spin-weighted spherical harmonic decomposition to facilitate comparison and match of the high post-Newtonian prediction for the inspiral waveform to the numerically-generated waveforms for the merger and ringdown. This extension of the GWF by half a PN order (with respect to previous work at 2.5PN order) is based on the algorithm of the multipolar post-Minkowskian formalism, and mandates the computation of the relations between the radiative, canonical and source multipole moments for general sources at 3PN order. We also obtain the 3PN extension of the source multipole moments in the case of compact binaries, and compute the contributions of hereditary terms (tails, tails-of-tails and memory integrals) up to 3PN order. The end results are given for both the complete plus and cross polarizations and the separate spin-weighted spherical harmonic modes.