During the first two days after challenge little effect of the vi

During the first two days after challenge little effect of the virus infection was seen. By day three animals started to loose

weight. This weight loss was higher in the mice which had been immunized with adjuvanted vaccines than in non-immunized mice and BLU9931 mw in mice which received unadjuvanted vaccines. Weight loss correlated with the strength of the induced immune responses but not with GPI-0100 dose. Three days after virus challenge, the animals were sacrificed and virus titers were determined in lung homogenates to evaluate protection elicited by the vaccines. The HNE buffer group showed an average lung virus titer of 6.45 10log (Fig. 4). The average titer in lungs of mice receiving a low dose of unadjuvated HA (0.04 and 0.2 μg) was not statistically different from that of the buffer group. Only mice receiving 1 μg unadjuvanted HA showed a statistically significant reduction in lung virus titers (p < 0.05). Immunization with GPI-0100-adjuvanted vaccine resulted in significantly decreased lung virus titer at all tested antigen doses (p values between buffer and the adjuvanted vaccines were ≤0.01 for all antigen doses tested, p values between unadjuvanted and adjuvanted vaccines were ≤0.05 or ≤0.01, at HA doses of 1 μg or 0.04 and 0.2 μg, SNS 032 respectively). The result shows that GPI-0100 improves vaccine-elicited protection against influenza virus infection even at an extremely low antigen dose of 0.04 μg HA. GPI-0100 is a stable semi-synthetic

saponin derivative, which has been demonstrated to stimulate both the humoral and the cellular arm of the immune system [10], [11], [12], [17] and [22]. In the present study we evaluated the immunogenicity and protective efficacy of GPI-0100-adjuvanted A/PR8 influenza subunit vaccine in mice. The results show that GPI-0100 boosts influenza-specific antibody

responses of the IgG1 and especially Phosphatidylinositol diacylglycerol-lyase the IgG2a subtype in a dose-dependent manner. There was also a trend towards higher numbers of influenza-specific cytokine-producing T cells in mice immunized with GPI-0100 adjuvanted vaccine though differences were not significant for all antigen doses studied. Furthermore, GPI-0100-enhanced immune responses provided better protection against influenza virus infection as demonstrated by reduced lung virus titers after challenge. Remarkably, an adjuvanted 0.04 μg HA dose presented a better formulation than an unadjuvanted 1 μg HA dose for all immune parameters studied. In line with earlier studies using OVA, HagB antigen of P. gingivalis and gD antigen of HSV-1, here we confirm that GPI-0100 boosts antigen-specific antibody responses with a Th1 IgG isotype profile in a dose-dependent manner [11], [12], [14] and [16]. High levels of antigen-specific IgG2a titers were induced in addition to IgG1 titers, resulting in a more balanced Th1/Th2 antibody response. In addition, we observed that GPI-0100 stimulates antigen-specific IFN-γ responses, which has also been reported previously in OVA studies [11].

Many survey items related to education had a positive influence o

Many survey items related to education had a positive influence on knowledge, attitudes and, to a lesser buy GSK1120212 extent, professional use. The professional use of cancer predictive genetic tests in Italy might be not completely appropriate, and physicians reported a high level of interest in receiving additional

specific training in the field. Overall, this study clearly indicates that priority must be given to targeted educational programs (Mazzucco et al., 2012). However, lessons drawn from many other areas of medicine indicate that education alone may not translate into the effective and appropriate adoption of innovative practices (Greco and Eisenberg, 1993 and Grol and Grimshaw, 2003). A specific policy regarding public health genomics needs to be developed at the national level, which is currently being undertaken in Italy by the Ministry of Health (Simone et al., 2013). Additional research is needed to characterize Trichostatin A in vitro further the contextual factors that influence the incorporation of cancer predictive genetic testing into clinical practice, and the organizational changes needed within the health care system to provide these services both effectively and efficiently. The authors declare that there are no conflicts of interest. This work was supported by the Agenzia Sanitaria Regionale Abruzzo, Italy, 2009

within the project: ‘I test di suscettibilità genetica al carcinoma mammario e colorettale: valutazione dell’appropriatezza dello screening in soggetti ad alto rischio in alcune regioni italiane’ (Genetic susceptibility tests for colorectal and breast cancer: assessment of appropriateness of screening in high-risk individuals in four Italian Regions). The work of Stefania Boccia was partly supported by the Associazione

Italiana per la Ricerca sul Cancro (AIRC, Contract No. IG 10491 to S. B.). “
“In the past two decades, promoting walking and cycling has gained increased policy attention in multiple sectors including health, transport and climate change (Chief Medical Officers of England, Scotland, Wales, Carnitine dehydrogenase and Northern Ireland, 2011, Department of Health and Department for Transport, 2010, THE PEP, 2009 and WHO, 2002). It is increasingly recognised that creating a supportive built environment may play a crucial role in enabling the success of individual-level interventions (Giles-Corti, 2006) and in promoting enduring population behaviour change (Butland et al., 2007, Institute of Medicine and National Research Council of the National Academies, 2009 and NICE, 2008). Nevertheless, several reviews have highlighted the paucity of controlled, longitudinal studies evaluating new infrastructure for walking or cycling (e.g. Krizek et al., 2009, McCormack and Shiell, 2011, NICE, 2008 and Pucher et al., 2009) and many of the studies that do exist have used repeat cross-sectional rather than cohort designs (Ogilvie et al.

Furthermore, the radiolabel showed stability as predicted from th

Furthermore, the radiolabel showed stability as predicted from the previous radiolabel stability experiment (Fig. 3), and the pertechnetate remained at the injection site bound to the NFC hydrogel. 123I-NaI was mostly distributed into the thyroid glands and stomach, in addition to being excreted to urine. 5 h post injection, no trace of 123I-NaI was found at the injection site. To explore the use of the NFC hydrogel as a drug release matrix, we selected a small drug (123I-β-CIT) and a large protein drug (99mTc-HSA) to evaluate the effect of molecule size on the rate of release from the NFC hydrogel. The in vivo release and

distribution of 123I-β-CIT and 99mTc-HSA were investigated after injecting the NFC hydrogels imbedded with the study compounds. The study compound and saline solution mixtures were used as controls (injections without the NFC hydrogel). The differences between the HSA–NFC hydrogel “implants” and saline injections

find more were observed as 99mTc-HSA expressed a delayed release from the NFC hydrogel and 41% of the injected dose remained within the hydrogel 5 h post injection (Fig. 5a). Linear release was observed in the beginning of the study, and release selleck compound rates calculated from the early time points (from first to 5 h) resulted in −0.0233 μg/h and −0.0139 μg/h for saline solution and hydrogel injections, respectively. Release of 99mTc-HSA was steady during the whole study. In addition, a large distribution of 99mTc-HSA was shown in the subcutaneous tissue surrounding the injection site indicating a very poor absorption of 99mTc-HSA into the circulatory system (Fig. 5b). Slight activity was detected within the bloodstream, as indicated by the radioactivity in heart and left kidney (Fig. 6). However, the distinctions between the compound itself and its metabolites cannot be made, as it is well known that 99mTc-HSA does not pass the glomerular filtration under normal renal activity. Slow absorption is probably due to the large protein size and low enzymatic activity within the subcutaneous tissue. It was shown that injections given with NFC hydrogel retained

99mTc-HSA in a smaller area within or around the hydrogel than saline solution injections (Fig. 5b), therefore 99mTc-HSA did not freely distribute into the subcutaneous tissue. This might indicate that rate of release from the hydrogel Liothyronine Sodium is limiting 99mTc-HSA absorption. Heart and the left kidney were selected to estimate the 99mTc-HSA absorption into the cardiovascular system. No apparent accumulation of 99mTc-HSA to any other organ was detected. No differences between the saline and hydrogel injections were observed in blood pool activity, i.e. heart (Fig. 6a). However, slight differences were detected in the left kidney of the study animals (Fig. 6b). The amount accumulated in the left kidney during the study period was low in addition to some of the activity might be due to metabolized 99mTc-HSA.

Les données ont été recueillies sur des cahiers de recueil électr

Les données ont été recueillies sur des cahiers de recueil électroniques, permettant un contrôle de qualité des données instantané, Dorsomorphin price par des techniciens d’études cliniques envoyés sur les différents sites pendant la période de l’étude. De très nombreuses données ont ainsi été collectées, permettant de caractériser au mieux la typologie des patients et leur mode de prise en charge. Un suivi au long cours centralisé est organisé au sein de la Société française de cardiologie avec le concours de l’unité de recherche clinique URCEST de l’hôpital Saint-Antoine (Paris). FAST-MI 2010 s’inscrit dans la continuité des précédents

registres nationaux d’infarctus, USIK 1995, USIC 2000 et FAST-MI 2005, tous construits sur le même principe d’un recueil ponctuel de données pendant une période d’un mois chez les patients hospitalisés selleck chemicals pour un infarctus récent, quel que soit le type d’établissement hospitalier [2], [3] and [4]. Le registre FAST-MI 2010 a été soutenu par le Collège national des cardiologues des hôpitaux, le Collège national des cardiologues français, la Société française de médecine d’urgence et Samu de France. Le financement de l’étude a été assuré par les laboratoires Merck, l’Alliance Eli-Lilly-Daiichi-Sankyo, AstraZeneca, GSK, sanofi-aventis

et Novartis. Le protocole de l’étude a été approuvé par le comité de protection des personnes de l’hôpital Saint-Louis et par la Commission nationale de l’informatique et des libertés. La moyenne d’âge des patients hospitalisés

pour infarctus avec sus-décalage (STEMI) est très sensiblement inférieure à celle des patients hospitalisés pour infarctus sans sus-décalage (NSTEMI) (63 ± 15 ans versus 69 ± 14 ans) ; parmi les patients de 75 ans et plus, 45,5 % ont un STEMI, alors que la proportion est de 60 % chez les moins de 75 ans (figure 1). De même, l’âge de survenue d’un infarctus est nettement plus élevé chez les femmes que chez les hommes (72 ± 14 ans versus 63 ± 14 ans), et 52 % des femmes hospitalisées pour un infarctus ont plus de 75 ans, contre 23,5 % chez les hommes (figure 2). Dans l’infarctus STEMI, les symptômes initiaux Rolziracetam varient largement avec l’âge (tableau I). Si la douleur reste le symptôme majeur (plus de 80 %, quel que soit l’âge), l’insuffisance cardiaque et la syncope sont des symptômes dont la fréquence augmente nettement avec l’âge ; à l’inverse, l’arrêt cardiaque initial est moins souvent retrouvé. L’intensité de la douleur tend à diminuer avec l’âge ; sur une échelle de douleur de 10, la moyenne est de 6,2 pour les moins de 65 ans, tandis qu’elle n’est plus que de 5,1 chez les patients de 85 ans et plus ; la proportion de patients ayant une douleur de 7 ou plus est de 21 % en dessous de 65 ans, de 15 % entre 65 et 74 ans, de 11 % entre 75 et 84 ans et de 4,5 % à partir de 85 ans.

A possible role for longitudinal data would be to validate some o

A possible role for longitudinal data would be to validate some of the underlying assumptions about the steady state and ‘no efficacy for duration’. In particular, if there is need to disentangle the effects on acquisition and duration, longitudinal data are needed. Optimal study designs for the estimation of acquisition and clearance rates from repeated measurement of colonisation have been considered by Mehtälä et al. [18]. Finally,

a baseline study is useful in establishing see more the baseline prevalence and serotype distribution of pneumococcal colonisation, even when frequent longitudinal sampling is not feasible. The information about the frequency of colonisation by serotypes included in the current PCV can be used to interpret results from head-to-head trials. This study was supported as a part of the research of the PneumoCarr Consortium funded by a grant (37875) from the Bill and Melinda Gates Foundation through the Grand Challenges in Global Health Initiative. “
“Between 1998 and 2001 the World Health Organization (WHO1) convened the Pneumococcal Carriage Working Group. This group was charged with formulating a set of core methods for conducting studies of pneumococcal nasopharyngeal (NP) colonization primarily in the context of pneumococcal conjugate vaccine (PCV) efficacy

trials [1]. The PCV efficacy trials led to PCV licensure and now widespread inclusion of PCV in routine immunization programs around the world. Numerous MYO10 studies of PCV effect on NP colonization were published in the pre-licensure period and were available for consideration by regulators, although no indication was sought for this outcome. Selleckchem Protease Inhibitor Library PCV impact studies have also included carriage components, thereby providing important lessons about the performance and impact of PCV on a population level [2], [3] and [4]. Carriage studies have provided the key biological link to the indirect effect of

PCV on pneumococcal disease [2], shown that there is no change in the invasiveness of pneumococcal strains since PCV implementation [2] and [3], anticipated the impact of PCV on cross-reacting serotypes [2], [5] and [6], contributed to the identification of new pneumococcal serotypes [7] and [8], and have been central to our understanding of antimicrobial resistance evolution and impact [9] and [10]. The variability in results from pneumococcal carriage studies across diverse epidemiologic settings can be understood to derive from biologic effects rather than methodological differences, in large part because many of the standard pneumococcal carriage methods have been widely adopted. In the decade since last convening the working group there have been many key accomplishments including sequencing of 90 pneumococcal capsular loci [11], the advent of molecular detection and quantification of pneumococci in NP specimens and serotype-specific detection including improved detection of multiple serotype colonization.

Control volunteers (n = 6) were recruited to undergo malaria chal

Control volunteers (n = 6) were recruited to undergo malaria challenge without vaccination to confirm the infective efficacy of the sporozoite challenge. Vaccine follow-up visits for groups 1–7 were on days 2, 7 and 28 following each vaccination with additional visits on day 90 (groups 1–5) and day 150 after first vaccination (groups 6 and 7). In addition, all challengees were seen regularly

during the three weeks following challenge (see sporozoite challenge below) and then 35 and 150 days CHIR-99021 solubility dmso following challenge. Blood was collected regularly for safety assessments and immunogenicity. FP9-PP and MVA-PP were manufactured according to Good Manufacturing Practice (GMP) regulations by Impfstoffwerk Dessau-Tornau (IDT, Roßlau, Germany). The polyprotein vaccine insert (‘L3SEPTL’) has been fully described

before [4]. It contains six pre-erythrocytic malaria antigens linked together in a single protein (from N to C terminus): liver stage antigen 3 (LSA3) [12], sporozoite threonine and asparagine www.selleckchem.com/screening/anti-diabetic-compound-library.html rich protein (STARP) [13], exported protein-1 (Exp1) [14], Pfs16 [15], thrombospondin-related adhesion protein (TRAP) [16] and liver stage antigen-1 (LSA1) [17]. All except possibly Pfs16 are pre-erythrocytic antigens; LSA3, Exp1 and STARP are also expressed by blood-stage parasites and Pfs16 is also a sexual-stage antigen [4]. Vaccines were stored at the trial site at −80 °C and thawed shortly before administration. Each dose was given intradermally into the skin overlying the deltoid muscle of the upper arm. Doses

were divided equally between both arms. Vaccine sites were temporarily covered with an absorbent dressing which was removed when the vaccine sites were reassessed approximately 30 min later. Volunteers were asked to complete study diary cards for the first seven days after vaccination, beginning with the evening of the vaccination day. These recorded local reactions (pain, redness, swelling, itching, warmth and scaling) and systemic symptoms (oral temperature, feverishness, myalgia, arthralgia, nausea or vomiting, lethargy, headache and malaise). Temperature was measured with an oral digital thermometer (Servoprax GmbH) supplied by the investigators and redness and swelling were recorded as maximal diameters (ensuring also the measurement passed through the puncture site). On each clinic attendance the investigators independently collected the same measurements. Adverse events (AEs) were recorded at each clinic visit in response to direct questioning, self-reporting on volunteer diary cards and examination of the vaccine site at each attendance by the investigators. Severity scales used for grading are shown in Online Table A. AEs were judged as either unrelated or possibly, probably or definitely related to vaccination by the investigator, taking into account the symptoms and time since vaccination. All AEs were followed until resolution where possible.

Three longitudfinal studies have reported that the development of

Three longitudfinal studies have reported that the development of elbow and wrist contractures could be predicted by baseline measures of weakness, spasticity and upper limb function (Ada et al 2006, Malhotra et al 2011, Pandyan et al 2003). However these studies were small (n ≤ 30 in all three studies), did not examine multivariate predictors (Malhotra et al 2011, Pandyan et 2003), and considered few potential predictors (Ada et al 2006, Malhotra et al 2011, Pandyan et al 2003). The research questions

for this study were: 1. What is the incidence of contractures six months after stroke? What is already known on this topic: Contractures are common after stroke. They can Crizotinib ic50 limit functional performance and cause

complications such as pain, pressure ulcers, and falls. What this study adds: Within six months after stroke, about half of all patients develop NLG919 a contracture. Muscle strength is a significant predictor of elbow, wrist, and ankle contractures but cannot be used to accurately predict contractures in these joints. Simple clinical measures do not accurately predict who will develop a contracture. A prospective inception cohort study was conducted. Consecutive patients admitted to the accident and emergency department of St George Hospital (from January 2009 to January 2010) with a diagnosis of stroke or transient ischemic attack were screened. St George Hospital is a large teaching hospital that serves residents of southern Sydney, Australia, and admits more than 500 patients a year with stroke and transient ischaemic attacks (SESIAHS 2010). Participants were folflowed up six months after stroke. Patients

were eligible for inclusion Thiamine-diphosphate kinase if they were over 18 years old, had a medically documented stroke (WHO 1988), were able to respond to basic commands, and understood English. Patients who received recombinant tissue plasminogen activator were included if they had persisting neurological symptoms 24 hours after receiving treatment. Patients with subarachnoid haemorrhages were included only if they had neurological symptoms consistent with the WHO definition of stroke (WHO 1988). Consent was sought from patients or, where patients were unable to consent, from guardians. All patients received standard medical and allied health care. Although no attempt at standardisation was made, care was generally administered in a way that was broadly consistent with the recommendation of the National Stroke Foundation guidelines (National Stroke Foundation, 2010a and National Stroke Foundation, 2010b). Three physiotherapists collected the data. Joint range of motion was measured as soon as possible (within four weeks) and six months folflowing stroke. All measurements were performed with the participants either in supine or sitting. The folflowing procedures were used.

This has important implications for the interpretation of immunog

This has important implications for the interpretation of immunogenicity measurements made after the 4th month post-vaccination. In particular, the change point would imply that immunogenicity measurements made during the second slower period of antibody decay, for example at 6 months, are indicative of longer-term seroprotection levels. Our estimation of the duration of this initial period

of rapid decline should be interpreted with some caution as it is dependent on the number of observation points during the first year post-vaccination. We were able to rely in our analysis on BMS-387032 concentration measurements made at days 28, 56 and at 6 months but more observation points between 6 months and 1 year after vaccination would have helped refine this analysis. Apart from the number of available antibody measurements, our study had three main limitations. Firstly we used data collected in study conducted in adults in an area where JE does not circulate. Our estimates would therefore likely to be conservative if applied to populations living in areas where the virus is endemic. The study population for our analyses were mostly

flavivirus-negative at baseline (10% positive to flaviviruses and 5% positive to JE and dengue specifically) with limited natural exposure. In settings where exposure to JE is more common, natural boosting is likely to lead to higher antibody titres and longer-lasting seroprotection. Dolutegravir datasheet Another source of potential bias is the loss to follow-up by year 5 if the distribution of early antibody titres was different among those still present at year 5 versus those who were not. However, we

compared antibody titres observed at 6 months between these two sub-groups and found no difference (p = 0.51; Kruskal–Wallis test of centrality). Another limitation of our study is that the findings were restricted to adults. Our conclusions may not extend to a paediatric population; antibody persistence data in children and toddlers would help confirm our findings for younger age groups. Our analyses were based on data from a study described in a previous paper [11]. While Farnesyltransferase the overall conclusions on the long-term seroprotection concord, some of our findings differ from those reported in this paper. This can in fact be explained by differences in the methodological approach. They notably chose the Kaplan–Meier method as their primary statistical analysis and found that 87% of 90 subjects who did not receive a second dose of JE-CV and who were seroprotected at 6 months were still protected at 5 years. Unlike the Kaplan–Meier method, our analyses keeps under observation those subjects who miss one antibody test but return for a test in a later year. Our estimate of protection at year 5 was more optimistic at 93.5% amongst those seroprotected at 28 days. This is also reflected in our model-based estimate of 94.7% seroprotection at 5 years.

Statistical analysis was performed using SAS version 9 1 (SAS Ins

Statistical analysis was performed using SAS version 9.1 (SAS Institute Inc, Cary, NC). Normally distributed continuous variables are presented as mean ± SD. Those variables not normally distributed are shown as median ± interquartile range. Categorical variables are expressed as frequencies and percentages. Baseline characteristics were compared using Student’s t test for parametric variables or the Mann–Whitney U test when not normally distributed.

Categorical variables were compared using chi-square test or Fisher’s exact test as appropriate. From 03/2011 to 03/2012, there were a total of 470 STEMI system activations; CHap was used in 83 cases (17.7%). (Fig. 3) In the overall population of STEMI cases, the mean age was 61 years. The majority was male (69.6%) and Caucasian (52%), with 43.8% being African-American. Baseline demographic and clinical characteristics of EPZ-6438 supplier STEMI patients who underwent PCI in which CHap was used were GSK2118436 comparable to those treated via standard channels of activation. (Table 1) Likewise, baseline and angiographic procedural characteristics between groups were very similar. (Table 2) Of note, non-significant trends toward higher incidences of diabetes mellitus

and a higher number of lesions treated were present in patients managed via standard channels of activation. In-hospital outcomes are presented in Table 3. None of the evaluated end points differed significantly between groups. An unfavorable trend toward higher in-hospital MACE was present for patients

managed via standard channels of activation, contributed by cardiac death, urgent TLR, and the need for coronary artery bypass surgery (Table 3). Quality measures evaluating the STEMI system of care are presented in Table 4. When the CHap was utilized to activate the management flow of a possible STEMI case, a significantly shorter DTB time was achieved (CHap 103 minutes, 95% CI [87.0–118.3] vs. standard 149 minutes, 95% CI [134.0–164.8], either p < 0.0001). Similarly, call-to-lab and call-to-balloon were significantly shortened (CHap 33 minutes, 95% CI [26.2–40.1] vs. standard 56 minutes, 95% CI [49.9–61.3], p < 0.0001) and (CHap 70 minutes, 95% CI [60.8–79.5] vs. standard 92 minutes, 95% CI [85.8–98.9], p = 0.0002), respectively. Notably, all parameters evaluating management before the initial call (door-to-EKG, door-to-call and EKG-to-call) were similar between the two cohorts. Likewise, all parameters evaluating management after arrival at the receiving hospital (lab-to-balloon, lab-to-case start, and case start-to-balloon) did not differ between the two routes used to activate the system of STEMI care. Table 5 describes the rate of ‘true positive’ activations in each study arm as a comparative measure of triage effectiveness. From the 470 STEMI system activations, CHap was used in 83 cases (17.7%), compared to standard channels used in 387 cases (82.3%). (Fig.

(1) is a special case of Eq (12) when there are no DNA inactivat

(1) is a special case of Eq. (12) when there are no DNA inactivation steps. After enzyme digestion, any DNA segment takes the form: equation(14) Br+1cBr+2c…cBr+XBr+1cBr+2c…cBr+Xwhere r is an integer and X, representing the length of the DNA segment, is a random variable. Let p denote the probability for enzyme to cleave bond c, as defined in Section 2.1. Note that the length of the

above DNA segment is the same as the number selleck kinase inhibitor of failed attempts made by the enzyme at cutting through the bonds c’s before it successfully disrupts the bond c right after nucleotide Br + X. The length X, in essence, can be described by a geometric distribution with parameter p [11]. In other words: equation(15) Pr[X=k]=(1−p)k−1p,k=1,2, …, M−1.Pr[X=k]=(1−p)k−1p,k=1,2, …, M−1. The theoretical median of X is given by equation(16) median=−log 2log(1−p). If the residual DNA size distribution can be quantified, the median can be empirically estimated. Using Eq. (16), we could estimate the enzyme cutting

Adriamycin in vitro efficiency p, which in turn can be used to estimate the safety factor in Eq. (12). In clinical research laboratories, various analytical methods such as agarose, polyacrylamide and capillary electrophoresis are used to measure the size distribution of residual DNA in biological products. These methodologies resolve purified DNA in a suitable matrix where the DNA length can be estimated relative to known DNA size markers. After the distribution of residual DNA is quantified, parameters of the distribution such as mean and median can readily be obtained. Org 27569 Let Med0 denote the median size of residual DNA, determined by one of the aforesaid methods. Equating Med0 to the theoretical median in Eq. (16) gives rise to an estimate of enzyme efficiency p: equation(17) pˆ=1−2−1/Med0 The relationship between

enzyme efficiency and median size of residual DNA is depicted in Fig. 1. It is evident that the more efficient the enzyme is, the smaller the median size of residual DNA is. Combining Eq. (12) and (17), we establish the following relationship between the safety factor and other characteristics of the manufacture process: equation(18) SF=Om∑i=1I02−(mi−1)/Med0miME[U]. Since the safety factor is a decreasing factor of the median size Med0 of residual DNA, the smaller the size of residual DNA is, the larger the safety factor is. A similar formula can be derived for safety factor concerning infectivity. It is given as follows: equation(19) SF1=Qm∑i=1J02−(ni−1)/Med0niNE[U]where Qm, J0 and ni are viral genome amount required to induce an infection, total number of proviruses contained in MDCK cell genome and their sizes ni, respectively, and N is the diploid size of the host cell genome. The safety factor for oncogenicity is calculated based on Eq. (18). As discussed in Section 2, the observational and experimental data suggest: (a) Om = 9.