Sub group analysis and long-term interim analysis are planned in the next few years. The completed and ongoing trials studying cetuximab in the adjuvant treatment of colon cancer are summarized

in Table 1. Pathophysiology of macrometastasis versus micrometastasis So why the failure of two classes of biologic agents- anti-VEGF and anti-EGFR- in the adjuvant setting despite success in metastatic disease? One explanation may be the differing pathophysiology of macrometastatic Inhibitors,research,lifescience,medical versus micrometastatic disease. Different genes, pathways and molecules may be required for a cell to establish itself as a metastatic foci (micrometastatic disease) rather than flourish as a metastatic mass. Micrometastasis may simply have different molecular features than macrometastasis and thus respond Inhibitors,research,lifescience,medical differently to biologic agents (36,37). Some have proposed that micrometastasis may actually grow faster than macrometastasis (Gompertz’s principle) (38), making them

more responsive to cytotoxic chemotherapy than to biologic therapies widely thought to be cytostatic (17). The evolution of a tumor with malignant potential to a tumor that actualizes that potential by establishing metastatic foci is complicated. Certainly the ability to create a new blood supply for tumor growth – angiogenesis- is required. Also required is the ability to make the epithelial-mesenchymal transition (39). Cell-cell adherence must initially be reduced Inhibitors,research,lifescience,medical allowing migration and spread Inhibitors,research,lifescience,medical (40) but later cells must have an analogous mesenchymal to epithelial transition to re-gain cell-cell adherence to make a stable metastasis (41). EGFR is thought to have a significant role in the epithelial-mesenchymal transition of metastatic cells (42). The failure of biologic agents in the adjuvant setting supports the theory that micrometastasis behave differently than clinically apparent Inhibitors,research,lifescience,medical foci of metastatic disease. One theory is that micrometastatic disease may develop

early resistance mechanisms to anti-angiogenic therapy such as increased invasiveness (43) or upregulation of pro-angiogenic mechanisms (44). Others hypothesize that tumor cell dormancy develops in the presence of adjuvant therapy, with tumor re-growth occurring once the biologic and chemotherapeutic Thalidomide agents are no longer present (45). Thus the early benefit of anti-VEGF agents seen in some of the adjuvant trials is lost once bevacizumab is discontinued when cells that were quiescent start to proliferate again (46). Some preclinical and animal model data raise concerns that anti-VEGF therapies may actual select for a more aggressive tumor type with enhanced angiogenic capabilities (43,44,46,47). For example, in a mouse lung cancer model, cells treated with anti-VEGF agents exhibited 50-60% buy Talazoparib regression of tumor vasculature, however returned to pre-treatment vascularization levels with 7 days of removal of the anti-VEGF receptor drug (48). Similarly, Paez-Ribes et al.

Lastly, results of TIV-controlled studies by influenza type and subtype were not explored by Rhorer et al. The objective of this analysis was to evaluate the efficacy of LAIV in children 2–17 years of age overall and by type/subtype, including the effects LBH589 supplier of various subject characteristics, using data from all available randomized controlled trials. This is the first meta-analysis conducted for children 2–17 years of age, the age group for whom LAIV is approved for use. Of the 9 randomized, controlled trials evaluating the efficacy of LAIV against culture-confirmed influenza in children, one was conducted exclusively in children younger than 24 months and was excluded

from analysis. Of the remaining 8 trials that enrolled children 2–17 years of age, 5 compared LAIV with placebo, of which 4 evaluated children vaccinated for 2 consecutive influenza seasons (Table 1) [9], [11], [12], [13], [14] and [15]. Placebo-controlled trials enrolled children in year 1 who had not been previously vaccinated against influenza. Three trials compared LAIV with TIV (Table 1) [16], [17] and [18] over a single influenza

season. These trials enrolled children regardless of previous influenza vaccination. In the Ashkenazi et al. study, all subjects received 2 doses of vaccine, while in the Fleming et al. study, all subjects received a single dose of vaccine [16] and [18]. In the study by Belshe et al., previously unvaccinated children received 2 doses of vaccine, while previously vaccinated children were administered a single dose of vaccine [17]. All previous analyses of the studies in question have shown that efficacy results Rutecarpine were similar

AP24534 for the per-protocol and intent-to-treat populations. Accordingly, the current analysis was limited to the per-protocol population of children ≥24 months of age at vaccination. Efficacy in year 1 was measured for children ≥24 months of age at enrollment; efficacy in year 2 was measured for children ≥24 months of age at year 2 vaccination. The prespecified endpoints of interest were efficacy relative to placebo and TIV against culture-confirmed influenza illness caused by antigenically similar strains and all strains regardless of antigenic match. Dosing regimens inconsistent with the recommended use of LAIV (e.g. low titer formulations or use of a single dose in previously unvaccinated children) were not examined. Predefined subgroup analyses included efficacy by influenza type/subtype (A/H3N2, AH1N1, B), by gender, and by region. Classification of drifted, antigenic variant influenza B Libraries viruses varied across trials, with some classifying them as antigenically similar and others classifying them as antigenically dissimilar [20]. In the current analysis, illnesses caused by drifted influenza B viruses were analyzed as originally classified by the trials and secondarily by classifying all antigenic variants of B viruses as dissimilar.

9 It could merely be that depressed patients were more likely to smoke, and that smoking caused heart disease. Anda, a cardiovascular epidemiologist with the Communicable Disease Center in the US Public Health Service, was the first to control for smoking, as well as multiple other cardiac risk factors that might Influence the relationship with depression.10 Using a hopelessness scale rather than a diagnosis

of MDD, the relationship again persisted. The more depressed the Individual, the more likely that Individual was to suffer a MI and to die from cardiac Inhibitors,research,lifescience,medical causes. In 2002, less than 10 years after Anda’s original study, Wulsin at the National Heart, Lung, and Blood Institute published a meta-analysis that found ten large studies that now controlled for cardiovascular risk factors, including smoking.2 All ten found coronary heart disease to be more common in depressed patients, and the increase was statistically significant in seven of the ten studies. The risk existed not only In major depression, but also Inhibitors,research,lifescience,medical In minor depression, and It existed In both males and females (Figure 1). Figure 1. Relative Inhibitors,research,lifescience,medical risk of coronary artery disease (CAD) in depressed

patients; a meta-analysis of 10 studies. Adapted from ref 2: Wulsin LR, Singal BM. Do depressive symptoms increase the risk for the onset of coronary disease? A systematic quantitative review. … The evidence that has been presented up until now Is primarily

from epidemiological studies that started with essentially medically healthy, depressed young adults and followed them for long periods of time. Beginning with medically healthy Individuals avoided the potential Inhibitors,research,lifescience,medical criticism that the association of depression with heart disease was merely the result of the patient’s depressive reaction to the symptoms of heart disease. However, such studies required either very large samples or decades of follow-up. In the late 1980s, Carney suggested that depression might have an adverse impact on the course of coronary artery disease In depressed patients who already have heart disease.11 Inhibitors,research,lifescience,medical Using this approach, Nancy Frasure-Smlth and Resminostat Françoise Lesperance were able to show that post-MI patients with a diagnosis of MDD were more than three and a half times more likely to die than post-MI patients without MDD.12 In their 1993 study, they performed a structured psychiatric examination in 222 consecutive post-MI cases at the Montreal Heart Hospital and followed them for 6 months. Using similar approaches, multiple Investigators have now looked at this effect of depression on the course of coronary artery disease following an ML In 2005, Evidence Reports/Technology Assessment of the Agency for Health Care Research and Quality (AHRQ), a branch of the US OTX015 department of Health and Human Services, found 17 post-MI studies that assessed the relationship between depression and subsequent mortality.

Occasionally, however, they are so intense and persistent that they need special attention. In such instances the content of the fear or accompanying nightmares might be revealing. Once more, behavioral treatment is reported to be very effective. Needless to say, the child’s reluctance to go to bed because he or she is genuinely afraid must be distinguished from pretending to be afraid as a delaying tactic. Worry and anxiety about daytime matters may cause difficulty in getting to sleep or staying asleep. However, the original source of concern may no longer exist but the difficulty falling asleep may persist because the child has

Inhibitors,research,lifescience,medical developed the habit of lying awake in bed in an agitated state (“conditioned insomnia”). Restless legs syndrome, which (as mentioned before) is now described in children, consists of disagreeable leg Inhibitors,research,lifescience,medical sensations with an irresistible urge to move the legs causing difficulty getting to sleep. It is often accompanied by periodic limb movements. “Growing pains,” said to be a cause of sleep difficulties in otherwise healthy children, is an ill-defined condition. Where they occur around bedtime, the restless legs syndrome is a possibility.9 Inhibitors,research,lifescience,medical In older children and later, early-morning wakening may be part of an anxiety or depressive disorder. Otherwise, the child may have been woken too early by noise or other environmental factors which intrude into his or her sleep. Adolescence The generally ver}’ efficient sleep of prepubertal

children changes to less satisfactory sleep in adolescence for both physiological Inhibitors,research,lifescience,medical and psychosocial reasons. Worries, anxiety, and depression are commonly quoted easons for not being able to sleep at this age. Nicotine, alcohol, and caffeine-containing

drinks, as well as illicit drug use, arc additional possible influences. However, inability to get off to sleep and to wake up in the morning is often part of DSPS, to which reference was made earlier. This condition, which is reported to be particularly common in Inhibitors,research,lifescience,medical adolescence, is potentially very disruptive educationally and socially. As such, it deserves further discussion. DSPS is commonly misconstrued as something other than a sleep disorder. The problem usually arises from the sleep phase delay Parvulin at puberty and habitually staying up late for social or other reasons, especially at weekends or during holidays. The BGB324 price result is that it becomes impossible to go to sleep earlier by choice. The features of DSPS are persistently severe difficulty getting to sleep (possibly until well into the night), uninterrupted sound sleep for just a few hours, but then great difficulty getting up for school, college, or work because of not having nearly enough sleep. This causes sleepiness and underfunctioning, especially during the first part of the day. The abnormal sleep pattern is maintained by sleeping in very late when able to do so at weekends and during holidays. “Chronotherapy” includes gradually changing the sleep phase to an appropriate time.

6 Cataplexy refers to partial or generalized loss of skeletal muscle tone in response to emotion, especially joy or

anger. Sleep paralysis refers to the inability to move at the beginning or the end of sleep. Finally, patients can present hypnagogic hallucinations, vivid dream-like experiences at the start of sleep, which can Lapatinib manufacturer accompany sleep paralysis. People with narcolepsy enter rapid eye movement (REM) sleep more quickly than usual (sometimes immediately) when they fall asleep. Cataplexy, sleep paralysis, and hallucinations represent intrusion of REM sleep into wakefulness. The impact of narcolepsy Inhibitors,research,lifescience,medical on psychosocial functioning has been long recognized. A detailed survey comparing life effects of narcolepsy in 180 subjects matched with local controls and drawn from centers in Canada, Japan, and Europe Inhibitors,research,lifescience,medical is a classic study in this area.7 Occupational problems were

prevalent in this study (over 75%) and included deleterious effects upon performance, promotion, earning capacity, fear of or actual job loss, and increased disability Inhibitors,research,lifescience,medical insurance. Work or home accidents attributed to sleepiness or sleep (49%) or related to smoking (49%) were much more common in these patients. There were also deleterious effects on education, recreation, and personality related to disease. A similar pattern of impairment of health status has been shown using the Short Form 36 Health Survey (SF-36) by Beusterien et al8 in 481 narcoleptics who were not taking

any stimulant medication. Inhibitors,research,lifescience,medical Compared with the general population, subjects with narcolepsy are most profoundly affected in vitality, social functioning, and difficulty when performing usual activities due to physical and emotional problems. Patients suffering from narcolepsy experience Inhibitors,research,lifescience,medical health-related quality of life effects as bad as or worse than patients with Parkinson’s disease, epilepsy, or migraine. These extensive emotional and psychosocial correlates of narcolepsy have also been confirmed in other studies.9,10 Broughton et al7 also outlined the difficulties in driving encountered by narcoleptics. Patients fell asleep at the wheel more frequently (66%) and had near or actual road accidents due to drowsiness or falling asleep (67%). The proportion of narcoleptics reporting sleep-related motor vehicle accidents is four times more most than in controls.11 These findings are confirmed by studies using a computer driving simulation task,12-14 in which performance improves with methamphetamine treatment.15 Finally, approximately half of patients with narcolepsy suffer from subjective memory problems, mainly involving recent events.7 In various studies, subjective memory complaints were not related to objective findings,16-20 although patients had more difficulties maintaining attention, suggesting that their deficits are not cognitive in nature, but represent an inability to maintain wakefulness and produce a sustained performance.

The protein that converts pri-miRNA into pre-miRNA is an RNase III enzyme,

Drosha. Generally, Drosha requires the DiGeorge syndrome critical region 8 (DGCR8) protein as a cefaclor for activation. Together with DGCR8, Drosha forms a large complex known as the “microprocessor complex.” Drosha removes the flanking segments and ≈ 11 base pair (bp) stem region of the pri-miRNA. The pre-miRNAs are then transported out of the Inhibitors,research,lifescience,medical nucleus via the exportin transfer system, which consists of Exportin 5 and guanosine triphosphate -bound Ran (RanGTP). Pre-miRNA is released into the cytoplasm upon hydrolysis of GTP to GDP. The premiRNAs are further processed in the cytoplasm by the RNase III enzyme Dicer, which coverts pre-miRNA into double-stranded mature small RNA (miRNA/miRNA* duplexes) of approximately 22 nucleotides (nt) long.40 Dicer requires cofactors such as HIV-1 transactivating response (TAR) RNA-binding protein (TRBP) or Inhibitors,research,lifescience,medical protein kinase R (PKR)-activating protein (PACT). One of the miRNA/miRNA* duplexes is loaded onto an Argonaute (Ago) homologue protein (isoform of the CAL-101 solubility dmso eukaryotic

translation initiation factor [eIF] 2C) to generate the effector complex, known as RNA-induced silencing complex (RISC). The other miRNA* strand is degraded. miRNA-mediated regulation of target mRNAs and expression Inhibitors,research,lifescience,medical RISC binds to specific “short-seed” sequences located predominantly within the 3′ untranslated region (3′ UTR) of target mRNAs, and can interfere with the translation of mRNA and/or reduce mRNA levels. miRNA-mediated translational inhibition also depends upon the 5′ cap region of the target mRNA. Ago proteins can stimulate miRNA-dependent translation inhibition by competing with efF4E for the 5′ cap binding site, thus preventing circularization of mRNA and lowering initiation efficiency.41 Although miRNAs Inhibitors,research,lifescience,medical target transcripts through imperfect base-pairing to multiple sites in 3′ UTRs,

Watson-Crick base-pairing to the 5′ end of miRNAs, especially to the so-called “seed” that Inhibitors,research,lifescience,medical comprises nucleotides 2 to 7, is also crucial for targeting.42 This provides a mechanism by which one miRNA can target several mRNAs. RISC can also associate with both the 60S ribosome and eIF6.43 eIF6 regulates the formation of the translationally active CYTH4 SOS subunit. By regulating eIF6, miRNAs can modify polysome formation and expose target mRNAs for degradation.43 In addition to the direct sequence-specific interaction of RISC with mRNAs, other proteins that bind nearby sites within the 3′ UTR (eg, fragile X mental retardation protein [FMRP] homologues, Hu protein B [HuB] family members, and other adenylate-uridylate-rich element [ARE]-binding proteins) may control the magnitude and even the direction of miRNA effects. In certain circumstances (eg, depending on the phase of the cell cycle in dividing cells, which possibly reflects reversible phosphorylation or methylation of FMRP homologues), miRNAs may actually enhance, rather than inhibit, translation.

In patients with primary infection, the median (min–max) of the number (/106 PBMC) of ASC (IgA + IgG + IgM) was 241 (175–613) for those specific to Salmonella Typhi, 85 (32–225) to Paratyphi A, 30 (24–133) to Paratyphi B and 8 (6–10) to Paratyphi C ( Fig. 3A). In the patient with the relapse, the numbers of ASC were 28, 14, 28 and 4/106 PBMC, respectively ( Fig. 3 B). In the patient with a Salmonella Paratyphi A infection, the respective numbers were 13, 23, 19 and 0/106 PBMC, with no response to Salmonella Egusi ( Fig. 3C). The

expressions of HR (mean ± SD) on Salmonella Typhi – and Salmonella Tariquidar mw Paratyphi B-specific ASC in the vaccinees are shown in Fig. 4. Almost all of the ASC expressed the intestinal HR, α4β7-integrin (95 ± 5% to Salmonella Typhi and 97 ± 6% to Salmonella Paratyphi B), while the peripheral lymph node HR, l-selectin, and the Modulators cutaneous HR, CLA, were found on smaller proportions of them (27 ± 17% and 0.4 ± 1% to Salmonella Typhi and 49 ± 18% and 7 ± 8% to Salmonella Paratyphi B, respectively). The expressions of HR on pathogen-specific ASC in patients with enteric fever are shown in Fig. 4. Almost all ASC expressed α4β7-integrin (92 ± 7%), while l-selectin and CLA were expressed less frequently (50 ± 25% and 8 ± 10%), SKI-606 clinical trial thus resembling the HR-profile of the Salmonella Typhi- and Paratyphi B-specific responses in vaccinees in this and previous studies [18] and [31]. There are no vaccines

against paratyphoid fever in clinical use. This study presents immunological evidence supporting studies that have previously reported the potential of Ty21a vaccine to protect against paratyphoid fever. There

are four studies evaluating the protective efficacy of either Ty21a or the old parenteral whole cell vaccine (no longer in use) against Salmonella Paratyphi A. Two of these report protection [3] and [18] and two of them do not [19] and [41]. In a study in travelers to Nepal, the majority of those immunized with a whole-cell parenteral vaccine and some Methisazone with Ty21a, Schwartz et al. estimated an overall efficacy of 95% against Salmonella Typhi and 72–75% against Salmonella Paratyphi A [18]. Meltzer et al. evaluated imported cases of enteric fever in Israeli travelers to India in an observational study. Travellers were immunized with Ty21a until 2001 and after that with parenteral Vi-polysaccharide vaccine. The general attack rate by Salmonella Paratyphi A was 0.26 in 10,000 during Ty21a and 0.79 during Vi-vaccination. Thus, Ty21a was suggested to confer some protection against Salmonella Paratyphi A [3]. In contrast to these studies, in a large field trial in Plaju, Indonesia, Ty21a was not found to protect against paratyphoid A [19]. However, in that study three doses of Ty21a were administered at an interval of seven instead of two days between doses, leading also to a poor protective efficacy of only 42% against typhoid fever.

He was reviewed on day 7 by psychiatry and was relaxed, coherent and appropriate. There was no evidence of any ongoing psychotic symptoms or abnormal movements. He scored 27/30 on the Mini-Mental State Exam (MMSE). When reviewed on day 11 he remained well. Mood was euthymic and he scored 30/30 on the MMSE.

There were no psychotic symptoms. The likely diagnosis of NMS was explained to the patient and both venlafaxine and quetiapine discontinued completely, only to be recommenced in future with marked caution and under strict supervision. Discussion We believe that the above case adds to the literature base describing NMS in association with both Inhibitors,research,lifescience,medical quetiapine and venlafaxine. It is acknowledged that there exists no universally accepted set of diagnostic criteria for NMS and that there is considerable overlap of features between NMS and serotonin syndrome, allowing Inhibitors,research,lifescience,medical for significant diagnostic blurring [Sachdev, 2005]. We believe that in this case the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for NMS were satisfied given the presence of muscle rigidity and elevated temperature accompanied by diaphoresis, altered consciousness,

tachycardia, labile blood pressure, leukocytosis Inhibitors,research,lifescience,medical and markedly elevated CK [American Psychiatric Association, 2000]. The slow duration of onset and recovery are felt to be more suggestive of a diagnosis of NMS than serotonin syndrome [Susman, 2001]. The recent stability in the patient’s medication regime, the history of opioid dependence and hepatitis C status and the prescription of the second-generation antipsychotic quetiapine are Inhibitors,research,lifescience,medical at odds with Sternbach’s criteria for a diagnosis of serotonin syndrome which include a recent change in a potent serotonergic agent, the absence of a history of substance misuse or infectious (or metabolic) disease and the absence of an antipsychotic agent [Sternbach, 1991]. Prominent autonomic instability and the presence of a leukocytosis Inhibitors,research,lifescience,medical lend further support

to the diagnosis of NMS [Marlowe and Schirgel, 2006]. NMS has been described with all second-generation antipsychotics such as quetiapine, including however even the recently licensed preparation asenapine [Singh and Wise, 2010]. It has also been described in several cases of antipsychotics being prescribed in combination with both selective serotonin reuptake selleck chemical inhibitor (SSRI) and serotonin–norepinephrine reuptake inhibitor (SNRI) antidepressants, the latter class of which includes venlafaxine [Stevens, 2008]. In their recent comparison of NMS induced by first- and second-generation antipsychotics, Trollor and colleagues noted a high rate of concurrent prescription of serotonergic antidepressants in their sample [Trollor et al. 2012].

biomedcentral.com/1471-227X/11/9/prepub Acknowledgements This study could not have been carried out without help from the three participating EMCCs. We also want to thank Tone Morken for help in statistical challenges, and all the doctors on call and personnel at casualty clinics and air ambulance crews who sent us copies of medical records.
PREDICT is a prospective, population-based cohort study of four patient care strategies provided by RAD001 concentration regional EMS services Inhibitors,research,lifescience,medical to patients with chest pain and suspected ischemia. 1. 3-lead PHECG and transported to the nearest receiving ED who were not eligible for bypass based on transport time. 2. 3-lead PHECG and transported to Inhibitors,research,lifescience,medical the nearest receiving ED

who were eligible for bypass based on transport time, if 12 lead PHECG was possible. 3. 12-lead PHECG and prehospital notification transported to the nearest receiving ED who were not eligible for bypass to a PCI center based

on transport time. 4. 12-lead PHECG with prehospital notification and eligible for Inhibitors,research,lifescience,medical bypassing the nearest receiving ED with transport to a PCI center. Bypass eligibility was based on transport distance of patients from their pick-up location to PCI center and the cut-off point was 60 kilometres. Inclusion and Exclusion Criteria Inclusion criteria ○ Patients who call 911, and are: ○ Suspected by the paramedics to have ischemic chest pain for greater than 30 minutes but less than 6 hours, and ○ 18 years of age or older ○ Experiencing chest pain that fails to resolve with nitrates given as per protocol Exclusion Criteria ○ Age < 18 years of age Setting This study Inhibitors,research,lifescience,medical is set in regions of Ontario with a population of 3,043,853 served by 14 EMS services, under the medical control of 4 regional Base Hospital programs (Table ​(Table11)[27]. These regions represent 25% of

the population of Ontario and 9.6% of the population of Canada. This geographic region covers 206,727 km2 with variable population densities from 0.6 to Inhibitors,research,lifescience,medical 574 persons per km2 representing rural, suburban, urban, and metropolis areas[27]. Table 1 List of regional base hospital programs and emergency medical services participating in PREDICT study Sample Size Calculation The recruitment goal is to enrol 100 STEMI Rebamipide prospective subjects per group (e.g. as in the WEST trial)[28], for a total of 400 STEMI subjects. The primary estimate is based on a difference in the proportion of patients who received reperfusion (fibrinolysis or PCI) within target door-to-intervention times. We based our calculation using estimates from Canto et al., 2002[29]. In that study there was an increase in the percentage of the patients who received lytic therapy within 30 minutes, from 31% to 50% (an absolute difference of 19%). The percentage of patients who received PCI within 90 minutes increased from 29% to 48% (an absolute difference of 19%).

However, if 100% prevention of Modulators infection is not possible to achieve,

then some consideration needs to be given to a vaccine that mainly prevents ascending infections that lead to disease pathology. In fact, one argument might be to focus on the disease pathology, as this is the major consequence of infection. A vaccine that could do both would clearly be ideal. The reality though is that any vaccine needs to be evaluated GPCR Compound Library in clinical trials and the measurement of reduction of infection is more readily quantifiable than immune-mediated damage, such as PID or infertility. Until recently, the majority of efforts have focused on evaluating prototype vaccines by measuring the reduction in infectious burden following live challenge of vaccinated animals, almost totally in the mouse model. As already mentioned, these vaccines are much easier to evaluate through the regulatory process. Recently though, there have been increasing and encouraging reports of vaccine strategies that can protect against the downstream adverse pathology [95]. The other aspect of a C. trachomatis vaccine is the target group. All efforts to date have been directed at developing prophylactic vaccines, with the assumption that the vaccine would be administered to young girls prior to sexual activity. In reality though, a therapeutic vaccine that could be safely administered

to women who either had a past or even current infection, would be very useful. There are very few published studies in this area, although the report of Carey et al. [86] in the C. muridarum – mouse model also buy CH5424802 suggest that vaccinating either presently infected or previously infected individuals may not result in a strong immune response. There are no absolute criteria for the properties that a vaccine should have before it can be recommended for wide use in programmes to improve the health of populations. The World Health Organization recommends vaccines which have long-term protection and high efficacy [89] and [96], however, vaccines which offer lower levels

of protection are suggested for use in certain circumstances or populations [97], [98], [99], [100] and [101]. When it is anticipated that only partially effective vaccines may become available, mathematical models have been used to investigate the potential epidemiological impact for the infectious disease in question, associated with different vaccine properties and implementation strategies [102]. Most theoretical vaccine modelling studies for sexually transmissible infections have been for HIV (e.g. [103], [104], [105], [106], [107], [108], [109] and [110]), but numerous vaccine modelling studies have emerged for HPV in recent years due to the availability and implementation of the cervical cancer vaccine in many countries [111], [112], [113] and [114].