All statements were scored on a five-point ordinal scale (‘totally disagree’ to ‘totally agree’) and average domain scores were used for analyses.26 More information about the psychometric validity of the outcome measures, as well as detailed assessment procedures have been described elsewhere.13 and 18 The assessment procedure was as follows: at home, the parents and children completed the AQuAA, the Multidimensional Fatigue Scale, and the attitude questionnaires. At the hospital body height and weight were measured, and several family characteristics were determined (siblings, parental

marital status, parental educational level and sports frequency of the immediate family). Selective motor control was assessed with the MK-2206 supplier modified Trost test, during which the ability of children to dorsiflex the ankle and extend the knee in an isolated movement was scored in four categories: N/A = not able to make the movement, 0 = completely synergistic, 1 = partly synergistic, 2 = no synergy.27 Scores for each joint and leg were added to obtain a total score for

selective motor control. Parents also indicated the sports frequency of immediate family members in five categories (from 1 = never to 5 = daily), from which a mean score was Selleckchem GSK-3 inhibitor calculated. Children then completed mobility capacity assessments and fitness tests, after which the ca-librated accelerometer was provided to register walking activity for one week. Additionally, children and parents received a diary to record their daily activities and accelerometer registration time. Information on data processing and controlling data quality of the accelerometer has been described elsewhere.18 A priori sample size calculation indicated that 22 children were needed in each group to detect a clinically relevant difference of 1000 strides per day between groups.28 Power was set at 80%, significance level at 5% and the standard deviation of the difference was set at 1175 strides (unpublished pilot data of CYTH4 Dutch children with cerebral palsy). To allow for 10% loss

to follow-up, 25 children were included in each group. To determine the intervention effect, intention-to-treat analyses were performed using linear regression, or logistic regression for dichotomous outcomes (p < 0.05). Outcomes at 4 months, 6 months, and 12 months were the dependent variables, and group allocation and the measured outcome at baseline were the independent variables in the analyses. To correct for performing statistical tests over multiple time points, the critical p-value was divided by the number of tests performed, resulting in an alpha < 0.025 for outcomes measured three times, and an alpha < 0.017 for outcomes measured four times. Variables with non-normally distributed residuals were logarithmically transformed prior to performing linear regression analyses, after which the results were transformed back, providing a between-group change ratio.

5). To investigate the effects of infant Selleckchem Epigenetics Compound Library PCV7 immunization on CD4+T cell subsets production during AAD, CD4+T cell subsets in MLN

were analyzed. As expected, OVA sensitized and challenged mice exhibited dramatically decreased Foxp3+Treg, Th1 cells production (8.66 ± 0.37% vs 10.49 ± 0.57%, P < 0.05, 2.08 ± 0.37% vs 4.87 ± 0.14%, respectively, P < 0.001) and significantly increased Th2, Th17 cells production (0.75 ± 0.07% vs 0.35 ± 0.04%, P < 0.001, 2.17 ± 0.23% vs 0.93 ± 0.10%, P < 0.001) compared with the control group mice. However, the production of Foxp3+Treg and Th1 cells in the infant PCV7 immunized group mice was significantly higher than that in the OVA group mice (12.53 ± 0.28% vs 8.66 ± 0.37%, P < 0.001, 3.64 ± 0.20% vs 2.08 ± 0.37%, P < 0.001), Th2 and Th17 cells were significantly lower in the infant PCV7 immunized

group mice than that in the OVA group mice (0.44 ± 0.04% vs 0.75 ± 0.10%, P < 0.01, 1.63 ± 0.10% vs 2.17 ± 0.23%, P < 0.05) ( Fig. 6A–H). These data indicated that infant PCV7 immunization promoted Foxp3+Treg, Th1 while suppressed Th2, Th17 cells production in young adulthood mice during AAD. Epidemiological studies in humans and experimental work in animals suggest that PCV7 can suppress allergic airway inflammation [7] and [8]. Previous studies suggested PCV7 immunization check details in adult mice inhibited hallmark features of AAD through the induction of Tregs and suppression of Th2 cells [8]. In this investigation we have demonstrated infant PCV7 immunization suppress young adulthood hallmark features of AAD in mouse models. Our study indicated that infant PCV7 immunization

not only promote Foxp3+Treg and Th1 cells, but also inhibit Th2 and Th17 cells production, which resulted in the increased secretion of IL-10, IFN-γ and decreased Rolziracetam production of IL-13, IL-17A during AAD mouse model. Infant PCV7 immunization can alter adaptive immune response in young adulthood life and suppress the development of young adulthood mice allergic asthma, which suggested its potential role as an immunoregulatory treatment to prevent young adulthood asthma. Sensitization and challenge with OVA induces strong polarized Th2 immune response. Th2 cells have important role in the pathogenesis of asthma [14] and [15]. Th2 cells recruited into the airway cause mucus hypersecretion, airway remodeling, and AHR. Th2 cells associated cytokines can initiate and accelerate allergic inflammation [14] and [16]. IL-13 may play a vital role in asthma pathogenesis. IL-13 can induce airway inflammation, AHR, mucus secretion, and tissue remodeling [16], [17] and [18]. IL-13 can facilitate the production of antigen specific antibodies [19] and mucous cells in the bronchial epithelium [20].

However, it is important to point out that the pD1 SNA GMT levels were considerably higher in these populations than those in developed countries. Therefore, achievement of a seroresponse, which by definition, requires a ≥3-fold increase from pD1 to PD3, might Nintedanib cost have been more difficult in these populations because of the higher pD1 GMT levels, which is likely a reflection of SNA acquired transplacentally or via breastmilk. The lower immunogenicity and efficacy of PRV in poor developing countries could be explained, in part, by higher titers of SNA in breast milk at the time of immunization

[30]. For serotype G3, the ≥3-fold SNA response rates in Vietnamese subjects were approximately 10 percentage points higher than those exhibited by subjects in the developed world settings. Coincidentally, rotavirus strains belonging to the G3 genotype were the most prevalent during the duration of the study [15], also suggesting the possibility that natural exposure might have contributed to the appearance of a relatively enhanced G3 specific SNA response in Vietnam. Looking at the baseline SNA responses (Fig. 3), the pD1 SNA titers to serotype G3 were high not only in Vietnam but also PLX4032 manufacturer in Bangladesh: 24.2 and 18.4 dilution units/mL of pD1 GMT in Bangladesh

and Vietnam, respectively. This may indicate common circulation of G3 strains in both countries before and/or during the clinical trial. Nevertheless, G3 rotavirus strains were not identified in Bangladesh among the rotavirus cases detected and enrolled during the clinical trial. In terms of the GMT levels at PD3, there was TCL a decrease of about 2.5-fold in the GMTs corresponding to the G1 and P1A[8] serotypes

in the Bangladeshi subjects who received PRV in this study when compared to the GMT levels shown in studies conducted in the US, EU, Taiwan, Korea, and Latin America [12], [13], [18], [21], [22], [23] and [24]. The GMTs for serotypes G2, G3, and G4 among Bangladeshi subjects who received PRV were generally similar when they were compared to GMTs for the corresponding rotavirus serotypes among subjects who received PRV in the other studies. There was little (1.5-fold) to no decrease in the GMTs to serotypes G1, G2, G3, G4, and P1A[8] in the Vietnamese subjects who received PRV in this study when compared to the GMTs to the same rotavirus serotypes in subjects who received PRV in studies conducted in these US, EU, Taiwan, Korea, and Latin America [12], [13], [18], [21], [22], [23] and [24]. Interestingly, approximately 18% (∼17% in Bangladesh and ∼19% in Vietnam) of the subjects who received placebo had an IgA seroresponse.

On retrouve fréquemment des paresthésies (fourmillements, see more engourdissements) et/ou des dysesthésies (fourmillements, engourdissements ou picotements perçus comme désagréables). La douleur a une topographie neurologique systématisée, fonction de la lésion anatomique causale. L’examen clinique objective un trouble de la sensibilité superficielle dans la région douloureuse (hypoesthésie cutanée au tact ou à la piqûre, voire anesthésie complète localisée), éventuellement associé à une allodynie, une hyperalgésie, une hyperpathie (encadré 1). Le diagnostic est principalement clinique. Le questionnaire DN4 (disponible en complément électronique) est un outil

diagnostique essentiel et simple d’utilisation : selleck products validé en 2005 [7], il est basé sur des caractéristiques douloureuses recueillies à l’interrogatoire et sur des données d’examen clinique. Un score supérieur ou égal à 4/10 établit une forte probabilité de douleur neuropathique. Allodynie Douleur causée par un stimulus qui normalement ne produit pas de douleur ; elle peut être de différents types : • tactile ou mécanique : – à l’effleurement

cutanée : allodynie dite dynamique Hyperalgésie Réponse exagérée à un stimulus qui normalement est douloureux Hyperpathie Syndrome douloureux caractérisé par une réaction anormalement douloureuse Parvulin à un stimulus (en particulier un stimulus répétitif), avec extension du champ récepteur Hyperesthésie Sensibilité exagérée à une stimulation (terme moins utilisé, à abandonner) On citera les douleurs aiguës nociceptives consécutives à un geste invasif diagnostique ou thérapeutique (biopsies, myélogrammes, ponctions veineuses, ponctions lombaires, injections intraveineuses, sous-cutanées …), les douleurs induites itératives (pansements, sondage urinaire, soins, toilette …), les douleurs postopératoires d’exérèse tumorale et les séquelles chirurgicales douloureuses après mastectomie, thoracotomie, curage ganglionnaire ou après prostatectomie radicale, amputation

du rectum etc. À ces douleurs s’ajoutent les douleurs post-chimiothérapie liées aux médicaments cytotoxiques, responsables de mucites (avec surinfections fréquentes), de neuropathies périphériques sensitivomotrices (où la toxicité et la douleur sont dose-dépendantes et de réversibilité variable). Parmi les douleurs post-radiothérapie, on retrouve des mucites, des radiodermites douloureuses (moins fréquentes qu’auparavant), des ostéoradionécroses (notamment en cancérologie ORL), des plexites radiques (brachiale ou lombo-sacrée) après irradiation cervicale ou axillaire ou bien lombopelvienne, des myélites radiques, des atteintes viscérales radiques pouvant toucher différents organes comme l’œsophage, la vessie, le grêle, le rectum.

Thus, “intrinsic” permeability refers to the passive lipoidal or carrier-mediated permeability of the test compound in its uncharged form. The mathematical treatment of such “normalization” and use of the pCEL-X software is described in detail in Appendix A. The objective of our study was to convert the measured apparent permeability, Papp, from two different model systems

to a common (intrinsic) standard state. The hydrodynamic environments of the two permeability assays (in vitro cell monolayer and in situ brain perfusion) are very different. In the meta-analysis of several in vitro endothelial cell models of blood–brain see more barrier permeability (benchmarked by in situ brain perfusion measurements), Avdeef (2011) found that log Papp poorly correlated to log PCin situ. The r2 factors for the porcine, bovine, rodent, and human in vitro models were 0.33, 0.09, 0.04, and 0.14, respectively. However, when the log of the intrinsic permeability coefficients were compared, the corresponding r2 values rose to 0.57–0.58. Published Papp measured in other in vitro porcine BBB monoculture models ( Franke et al., 1999, Franke et al., 2000, Lohmann et al., 2002 and Zhang et al., 2006) and rodent in situ brain perfusion data ( Dagenais et al., 2009 and Avdeef, 2012) were collected from the literature and NVP-BGJ398 solubility dmso analyzed in pCEL-X to correct for ABL

and ionization (for in vitro and in vivo data), paracellular permeability and filter restriction (for in vitro data only) to derive the intrinsic transcellular permeability those P0. The in vitro P0 were plotted against the P0in situ to obtain the in vitro–in vivo correlation (IVIVC; Avdeef, 2011). In the present study, the P0 values of the compounds analyzed were incorporated into the previous IVIVC data. The linear regression coefficient was obtained for the pooled in vitro and in vivo (in situ) data. Table 1 lists the molecules analyzed in the study along with their measured and predicted physicochemical properties. Table 2 summarizes the in vitro PBEC measured

data, together with the characteristics of the permeability experiments. Table 3 lists the permeability model refinement results. Table 4 summarizes the averaged log P0in situ values compiled from published rodent in situ brain perfusion studies from multiple sources ( Avdeef, 2012). These log P0in situ values were compared to log P0 based on PBEC measurements in the IVIVC. To determine the intrinsic transcellular permeability (P0) of propranolol, the permeability assay was first carried out at multiple pH using cell monolayers grown on Corning Transwell® polyester membrane (Transwell®-Clear) filter inserts. The polyester membrane was preferred because of cell visibility under the microscope. pH-dependent permeability was expected for propranolol.

108 of 255 cases (42%) did not fulfill any of the BC case definitions for ASM, ENC, MYE, or ADEM. Among these 108 cases, 35 were negative control cases carrying either a discharge diagnosis of “bacterial

meningitis” (n = 28), or the text indicated that meningitis had been “ruled out” (n = 7). Entinostat purchase In additional 10 cases, the clinician considered two possibilities, “bacterial or aseptic meningitis”, but the cases failed to meet BC ASM criteria. 39 of 108 cases carried a diagnostic label of “aseptic meningitis” but failed to fulfill the BC criteria for ASM: 34 due to unavailable gram stain results, 1 due to unavailable CSF counts, 1 with normal CSF results. Three cases were discharged with a diagnosis of “aseptic meningitis”, but positive bacterial culture results received after discharge from the hospital excluded from the BC criteria. Twenty-four cases carried a clinical diagnosis of “encephalitis” (n = 12) or “meningoencephalitis” (n = 5),

“encephalomyelitis” (n = 1), “myelitis” (n = 5), or “ADEM” (n = 1) but simultaneous evidence of alternative diagnoses excluded from the respective BC definitions. The reported study illustrates the added value of using the Brighton Collaboration case definitions for aseptic meningitis, encephalitis, myelitis, and ADEM in retrospective chart reviews. In the absence of universally applicable gold standard methods for the diagnosis of aseptic meningitis, encephalitis, myelitis,

or ADEM, we are first restricted selleck chemicals to comparing the BC algorithm as a new diagnostic test or “confirmatory tool” to an imperfect reference standard: the clinical diagnosis [28], [29], [30], [31] and [32]. Clinical diagnoses as reported in hospital discharge summaries, are observer-dependent, diagnostic procedures may or may not be available, and overlap between competing CNS diagnoses is common. Clinical guidelines may diminish some of this variability, but analyses have shown that very few of the currently practiced decision rules to discriminate between bacterial and aseptic meningitis for example, have ever been validated [52]. While the clinician may be well advised to “err on the side of caution”, for example to suspect bacterial meningitis rather than withholding antibiotic treatment, the case ascertainment process in the context of epidemiological investigations requires a different degree of conceptual clarity. Prospective clinical trials and paired studies of diagnostic accuracy will be required to determine the sensitivity and specificity of BC algorithms as well as the sensitivity and specificity of routine clinical diagnoses [53] and [54]. To this end, a gold standard procedure would be required to discriminate true positives from false positives. In the instance of CNS disease, a gold standard method would likely entail invasive procedures, limiting its feasibility in large-scale prospective settings.

RF captured all CLSM images and prepared them for publication. DX, BM, RP and JGC conceived, co-ordinated, designed and procured the funding for the study. All authors have read and approved the final article. This work was supported by the Medical

Research Council (grant no. G0801955). The authors would like to thank Dr. Katrina Davidson, Dr. Clair Lyle and Dr. Johann Partridge of XstalBio Ltd. for their invaluable technical advice and support throughout this study. We would also like to thank Dr. Fatme Mawas and David Eastwood (NIBSC) for advice on flow cytometry and Mrs. Margaret Mullin (University of Glasgow) for her support with SEM. Conflicts of interest: BM is a shareholder in XstalBio Ltd. which is a private company commercially developing CaP-PCMCs. “
“Bluetongue virus is the type species of MAPK inhibitor genus Orbivirus, family Reoviridae [1] and [2]. Bluetongue viruses (BTV) are transmitted by adult Culicoides midges, causing ‘bluetongue’ (BT), a non-contagious but economically important disease of ruminants (sheep, cattle and some species of deer) [3] and [4]. Currently 26 BTV serotypes have been identified, 10 of which (BTV-1, 2, 4, 6, 8,

9, 11, 14, 16 and 25) have been detected in Europe since 1998 [5], [6] and [7]. It is estimated that over one million sheep have died during repeated BT incursions into the Mediterranean selleck chemicals basin between 1998 and 2005 [5]. An outbreak caused by BTV-8 that started in the Netherlands during 2006, subsequently spread across most of Europe, causing high levels aminophylline of mortality in sheep (15–32%, reaching ∼50% is some areas), as well as significant clinical signs but low mortality (<1%) in cattle [8], [9], [10], [11], [12] and [13]. However, inactivated-virus vaccines were used successfully, leading to the rapid eradication of BTV-8 from the region.

These inactivated vaccines, which were made available for serotypes 1, 2, 4 and 8 of BTV are thought to work primarily through generation of a protective serotype-specific neutralising-antibody response targeting the VP2 antigen [2], [14], [15], [16], [17], [18], [19], [20] and [21]. The BTV particle is made of seven structural proteins (VP1–VP7) [2], [22] and [23]. VP2 represents a primary target for neutralising antibodies [1], [2], [16] and [17] and determines virus serotype [24]. VP2 shows 22.4–73% aa sequence variation between BTV serotypes [24]. VP5 of BTV, the second most variable BTV protein (aa identity of 41–79% between BTV serotypes [25] and [26]) enhances neutralising antibody response to VP2 [1], [2], [14] and [27]. Selected structural-proteins of BTV-4, including two domains of VP2 (aa 63–471 and 555–956), VP5 (from which a coiled-coil sequence [amino acids 1–100] was deleted to improve solubility) and full-length VP7, were expressed in bacteria as soluble fusion-proteins with glutathione S-transferase (GST).

One four-arm trial (Itoh et al 2007) compared traditional Chinese acupuncture with acupuncture directed at ‘trigger points’, acupuncture directed to regions adjacent to ‘trigger points’, and sham acupuncture. The three acupuncture groups in this trial were combined to create a single pair-wise comparison. Pooled outcomes

from five trials (Itoh et al 2007, Nabeta and Kawakita 2002, Petrie and Hazleman 1986, Vas et al 2006, White et al 2004) showed no significant difference in pain outcomes between acupuncture and control at the conclusion of a course of treatment (WMD –12, 95% CI –23 to 0.1). Pooled results from the three trials (Petrie and Hazleman 1986, Vas et al 2006, White et al 2004) that reported

medium-term pain outcomes showed acupuncture to be no more Epigenetics Compound Library price effective Carfilzomib datasheet than control (WMD –4, 95% CI –15 to 7), consistent with the single trial (White et al 2004) that reported long-term pain outcomes (MD –4, 95% CI –13 to 7). Pooled outcomes from five trials (Itoh et al 2007, Petrie and Hazleman 1986, Vas et al 2006, White et al 2004, Witt et al 2006) showed a significant but small difference in disability outcomes in favour of acupuncture at the conclusion of treatment (WMD –8, 95% CI –13 to –2). Pooled outcomes from the three trials (Petrie and Hazleman 1986, White et al 2004, Witt et al 2006) that reported medium-term disability outcomes Bay 11-7085 demonstrated that acupuncture was not more effective than control (WMD –1, 95% CI –2 to 0.3), consistent with the single trial (White et al 2004) that reported long-term disability outcomes (MD –4, 95% CI –10 to 2). Exercise: Five trials investigated exercise for non-specific neck pain. One three-arm trial ( Kjellman and Oberg 2002)

compared McKenzie exercise with general exercise and with sham ultrasound. Four trials compared various exercise approaches with minimal intervention. The exercise approaches included ‘proprioceptive’ exercises ( Revel et al 1994), a combined program of neck stabilisation, relaxation, eye fixation, behavioural support, and posture training ( Taimela et al 2000), group gymnastic exercises ( Takala et al 1994), and muscle strengthening ( Viljanen et al 2003). Pooled outcomes from three trials (Kjellman and Oberg 2002, Revel et al 1994, Taimela et al 2000) showed significant reduction in pain at the conclusion of a course of specific exercises (WMD –12, 95% CI –22 to –2). The single trial that reported medium- (MD –6, 95% CI –17 to 5) and long-term (MD 1, 95% CI –12 to 14) pain outcomes for specific exercise programs did not demonstrate similar benefit (Kjellman and Oberg 2002). One trial (Kjellman and Oberg 2002) showed no significant difference in disability at the conclusion of a course of specific exercises (MD –3, 95% CI –10 to 4) and medium- (MD –3, 95% CI –11 to 5) and long-term (MD 2, 95% CI –6 to 10) follow-up.

Lesser influence of bevacizumab treatment on systemic levels of VEGF also has been found in patients in the discontinuous treatment

arm of the Inhibit VEGF in Age-related choroidal Neovascularization (IVAN) trial.35 The biopsy technique applied was performed specifically to collect vitreous samples as close as possible to the macula, under microscope visualization, to obtain a representative vitreal sample in close proximity to neovascular membranes.31 This accurate sampling by vitreous biopsy directly adjacent to the macula also may explain in part the higher levels of VEGF-A detected in our patients with wet AMD when compared with previous reports.36 and 37 Despite high levels of LCPUFA metabolites in retinal tissue,29 lipidomic analysis of the undiluted vitreous in wet AMD did not yield consistent results, and we were not able to detect consistent levels of omega-3 and GW-572016 concentration omega-6 metabolites (data not shown). Epidemiologic studies consistently have shown protective relationships of increased omega-3 LCPUFA-rich food intake with advanced AMD.19, 20, 21, 22 and 23 The Age-Related Eye Disease Study 2 did not report a protective effect

of 350 mg/day of DHA plus 650 mg/day of EPA supplementation for progression to wet AMD in their phase 3 clinical trial.24 The lack of positive results in this trial could be because it was performed on a very well-nourished study population, in which 11% of the placebo group were taking omega-3 LCPUFAs outside the study regimen,

or that a higher supplemental dose or higher composition DNA Damage inhibitor of DHA plus EPA was needed for efficacy.24 The Nutritional AMD Treatment 2 study research team randomly assigned high-risk AMD patients to 840 mg/day DHA plus 270 mg/day EPA or a placebo for 3 years. Time to occurrence PAK6 of CNV did not differ between omega-3 vs placebo groups; however, patients in the group receiving omega-3 LCPUFAs were in the higher tertile of the area under the receiver operating characteristic curve for serum and red blood cell membrane levels of DHA plus EPA and had nearly a 70% lower risk of developing CNV when compared with the lower tertile.38 The limitations of the current pilot study include its small sample size, the inability to detect vitreal lipid profiles, lack of DHA serum levels measurements, and perhaps low doses of omega-3 LCPUFAs in supplements. In summary, we demonstrated that daily omega-3 fatty acid supplementation as part of a formulation also containing antioxidants, zinc, lutein, and zeaxanthin in patients with wet AMD and being treated with anti-VEGF injections (group 1) was associated with significantly lower vitreous levels of VEGF-A than those observed in patients treated with bevacizumab plus daily omega-3-free supplements (group 2).

Most vaccines aim to increase the T-cell immune response using viral vectors, recombinant DNA or other. Nine unsuccessful studies are summarized by Stern et al. [68]. Limited success was recently shown using synthetic or recombinant HPV16E6 related peptides. Clinicaltrial.gov lists 3 active, on-going trials on therapeutic HPV vaccines. Safety issues and issues of administration of the vaccine limit the potential use of 4 non-clinicaltrial.gov-listed compounds currently selleck compound in phase I or II (personal communication, Genticel, France). Recently a phase

I trial using recombinant HPV16E7 and HPV18E7 concluded that the product was safe to use and a phase II trial has been planned (personal communication, Genticel, France). The currently available vaccines, Cervarix™

and Gardasil™, are recommended for prophylactic use. They will not clear an existing infection or disease. http://www.selleckchem.com/screening/pi3k-signaling-inhibitor-library.html To obtain optimal benefit of the vaccine, it must be given before exposure to HPV, which is before sexual debut [22] and [69]. The vaccines can be administered to persons 9 years old and above. Although specific target age groups may differ among countries, many countries start the vaccination for girls at age 11–12 years [70]. In the United Kingdom, catch-up vaccination is considered cost-effective for females aged 13–18 years [71]. Currently, vaccination for males is not recommended [22], though some countries, like Australia and USA, do vaccinate males as well [37] and [41]. Adding males in a HPV vaccination programme might have direct benefits in protecting

against HPV-related cancers in men and anogenital warts [72]. However, mathematical models revealed that increasing vaccine uptake among adolescent girls is more effective in reducing HPV infection rather than including boys in existing vaccination programmes [72] and [73]. Vaccinating the sex with the highest prevalence will reduce the population prevalence most effectively [73]. The cost-effectiveness of including males depend on the predicted herd immunity in heterosexual males derived from vaccinating females, and the proportion of all male HPV-related disease in homosexual men [72]. However, the HPV-related burden of disease is lower in males than in females through [72], and the incremental benefits of adding boys are dependent on the coverage in girls [74]. If coverage in girls is higher than 50%, including boys in the vaccination programme is likely not cost-effective [72]. The introduction of HPV vaccine in industrialised countries (e.g. United Kingdom, Australia, Belgium) is achieving good coverage through school-based vaccination programmes. These countries aim to vaccinate all girls around the age of 12 years, and also include catch-up vaccination of slightly older adolescents during the first years of introduction. Vaccination coverage of above 70% has been observed in both Australia and the United Kingdom [75] and [76]. In Belgium, 83.