“
“Les relais anticoagulants sont une situation à risque embolique et hémorragique. Une évaluation des attitudes thérapeutiques des médecins généralistes pour la gestion des périodes encadrant un geste invasif ou opératoire. “
“Depuis quelques années ont été développées dans la fibrillation atriale de nouvelles molécules, alternatives aux anti-vitamines K dans la prévention des accidents thromboemboliques artériels chez les sujets à risque. Les nouveaux anticoagulants oraux (NACO), aussi Ruxolitinib in vivo appelés anti-thrombotiques directs, ont pour avantage de dispenser de surveiller l’INR, du fait d’une moindre variabilité interindividuelle par rapport aux anti-vitamines K (AVK). Cependant, l’erreur de prescription, en termes

d’indication ou de posologie, l’interaction médicamenteuse

ou le défaut d’éducation thérapeutique n’a pas disparu pour autant. Le risque hémorragique ou thrombotique est toujours présent chez les patients sous NACO. Les effets indésirables des anticoagulants ont été et seront toujours redoutés par les patients et les praticiens, d’autant plus dans le contexte actuel de méfiance des patients vis-à-vis des nouvelles molécules commercialisées par les firmes pharmaceutiques. Ainsi, il est de notre devoir Selleck Pfizer Licensed Compound Library de savoir prescrire ces nouvelles molécules, de connaître leurs avantages comme leurs inconvénients, et surtout leurs limites. La dispense de surveillance d’INR ne doit pas se transformer en une absence de surveillance du patient. Cette mise au point passe en revue les situations à risque d’accident,

aux deux extrémités du spectre de la fenêtre thérapeutique afin d’éviter les hémorragies graves et les accidents thromboemboliques sous traitement. Les trois nouvelles molécules actuellement disponibles en France et en Europe – dabigatran, rivaroxaban et apixaban – seront étudiées en profondeur, avec un complément d’information pour l’edoxaban, qui n’a pas encore obtenu l’autorisation de mise sur le marché à ce jour dans cette indication. La fibrillation atriale est une cause majeure de mortalité et de morbidité. Elle est responsable de la formation de thrombus dans l’auricule gauche, dont to l’embolisation peut entraîner des accidents vasculaires cérébraux, de conséquence gravissime, en termes de mortalité ou de handicap. C’est une affection fréquente, qui croît en même temps que le vieillissement de la population, atteignant 1 à 2 % de la population générale, et 5 à 15 % de la population de plus de 80 ans. La fibrillation atriale multiplie le taux d’incidence d’accident vasculaire cérébral (AVC) par 5, par rapport à la population générale [1]. Les AVK sont le traitement de référence pour la prévention des complications thromboemboliques de la fibrillation atriale. Ils ont montré une réduction relative du risque d’AVC de 64 % par rapport au placebo, ce qui équivaut à une réduction absolue annuelle du risque d’AVC de 2,7 % [2].

Their model included a calculation of the opportunity cost of equity, based on the health improvements that would be forgone in order to select the most equitable PI3K inhibitor solutions. Jehu-Appiah et al. demonstrated the usefulness

of a similar modeling approach to quantify the trade-offs between efficiency and equity in health investment priorities in Ghana [16]. One of the simplest approaches to assessing distributional effects is to explicitly estimate costs and impacts for distinct sub-populations. This may include stratifying by age, sex, socio-economic status and/or geographic regions. Coyle et al. provide a general framework for population stratified cost-effectiveness analysis [17] and Sculpher describes the application of the approach in contexts such as the UK’s NICE evaluation process [18]. We used an existing country-level rotavirus impact and cost-effectiveness model [1] that has been updated with newly available data [5]. Estimates here are for vaccinating a single birth cohort, including outcomes

during their first five years of life. National rotavirus mortality estimates were based on recently published figures [19]. Estimates of inpatient and outpatient visits are also from previously published studies [20]. Vaccine efficacy estimates Selleckchem KU 55933 were based on region and mortality strata [21], [22] and [23]. Estimates for high mortality countries were based on pooled estimates from recent trials [21] and are described in full detail in Atherly et al. [5]. Efficacy was adjusted for

the expected age at which first and second dose would be received in each country, based on DPT1 and DPT2 coverage from DHS surveys [3] and [24]. This was done by modeling coverage of 1 and 2 doses of vaccine at 0–2, 3–5, 6–8 and 9–11 months. Reported DPT1 and DPT2 coverage among 12–23 month old children was used to estimate the fraction of those that would receive each vaccine at the different age ranges [5]. Vaccination effectiveness was based on the fraction of children at each age with 0, 1, or 2 doses and the expected protection of each, assuming 50% lower efficacy for a single dose in the 2-dose regime. For each age band, the effectiveness was isothipendyl applied to the proportion of rotavirus deaths that would occur during that period. Current SAGE recommendations suggest that children over 8 months or 32 weeks not receive a vaccine in order to avoid potential adverse effects. The model used in this study assumes that children receiving their second DPT dose between 8 and 12 months of age would still receive it [25]. Medical treatment costs were estimated for inpatient and outpatient visits, using cost-estimates from WHO-CHOICE for facility charges and extrapolations of medication and diagnostic costs from published studies, as described elsewhere [1] and [3]. Medical costs were in 2010 US Dollars and presented in more detail elsewhere [5]. All costs and DALY estimates were discounted at 3%.

Specifically, inappropriately timed type-1 cytokine expression and polarisation of Th1 immunity in some circumstances can be counterproductive to both cell mediated and humoral responses. Examination of the anti-HIV p55-gag response following control i.n. FPV-HIV/i.m. VV-HIV

prime-boost immunisation demonstrated significant levels of both IgG1 and IgG2a in the sera of mice. More surprisingly, following immunisation of mice with the IL-4C118 adjuvant HIV vaccine, which induced enhanced high avidity HIV specific CD8+ T cells with IL-2 and IFN-γ expression also induced elevated HIV p55-gag IgG2a check details antibody responses six weeks post booster vaccination and was sustained over time. The recent RV144 trial included both a canarypox virus (very similar to rFPV) expressing gag/pol/env antigens followed by a protein booster to enhance the anti-env humoral response. Selleckchem DAPT In that study the 31% protective efficacy observed was linked to antibody-mediated immunity, no cytotoxic CD8 T cell responses were observed, which may explain the partial protective efficacy. Interestingly, isotype switching and high levels of IgG2 antibodies directed towards the gag protein have been linked to protection, specifically in HIV controllers not carrying the ‘protective’ human leucocyte antigen HLA B alleles [58]. Although, the mechanism by which gag-specific antibodies provided delayed progressions remains unknown, in some

HIV controllers, antibodies have shown to play a role in ADCC [59] and [60]. It has been thought that production of IFN-γ and gag-specific antibodies particularly IgG2 may provide stimulation of plasmacytoide DC’s, which are typically reduced in HIV infected patients but not in controllers [61] and [62]. These observations suggest that induction of gag-specific antibodies could play a pivotal role in providing the best protection possible against HIV-1. Our out IL-4R antagonist vaccine has shown to induce excellent long lasting IgG2a antibody immunity. The induction of both high quality T and robust B cell

immunity make our IL-4R antagonist HIV vaccine a good candidate for the future. Considering the similarity of the T cell responses between the IL-4C118 adjuvant HIV vaccine and our previous IL-13Rα2 adjuvanted vaccine study [23] the majority of the observed effects on the induced quality of HIV specific CD8+ T cell responses are likely due to the inhibition of IL-13 cell-signalling via the type-II IL-4R (IL-4Rα/IL-13Rα1). Sequestration of IL-13 using a decoy IL-13R will reduce IL-13 binding to both type II IL-4R and plasma membrane IL-13Rα2, however IL-4 will still available to engage with type-I/II IL-4R for signalling. In contrast, expression of the IL-4C118 antagonist will block both type-I/II IL-4R to IL-4 and IL-13 mediated signalling, however plasma membrane IL-13Rα2 could still bind free IL-13 (see Suppl. Diagram 1).

Both researchers (CS, SM) kept a journal of critical reflections and discussed findings with other team members. They also undertook a process of critical reflection of the literature, which provided

researcher triangulation and confirmation of broader generalisability of key issues identified (Mudge et al 2013, Neergaard et al 2009). Five pairs of physiotherapists and patients were recruited. Of the five patients there was a range of ages (20–80 yr), two men and three women, and diagnoses encompassed stroke (n = 2), spinal cord injury (n = 2), and cerebral palsy. Two of the patients self-identified as MÐori (the indigenous population of New Zealand). The physiotherapists were all female, aged between 25 and 45 years, New Zealand European,

and had between 5 and 16 years of experience working in neurological rehabilitation. This lack of ethnic diversity in the physiotherapists reflects the demographic make-up of the physiotherapy profession FG-4592 solubility dmso in New Zealand. Three of the five physiotherapists had completed postgraduate qualifications in rehabilitation. The types of behaviour change techniques used in the activity coaching sessions are described in Box 3. The techniques were focused on practical steps such as goal setting and negotiation, goal pursuit, feedback and encouragement. Technique type Technique description Example of usage Goal setting and negotiation Goal setting (behaviour): The person is encouraged to make a behavioural resolution or intention. I will walk more next week. Action planning: The person is supported to develop learn more detailed planning of what they will do including, as a minimum, when, in which situation and/or where Histone demethylase to act. ‘When’ may describe frequency (such as how many times a day/week or duration (eg, for how long). I will walk outside around the block on Monday, Wednesday and Fridays for half an hour at 7:00 am before breakfast. Barrier identification/problem solving: The person is prompted to think about

potential barriers and identify the ways of overcoming them. Things that might get in the way of carrying out my plan may be if I sleep in because I have a bad night, or I don’t feel very motivated. I could overcome this if I had another time to walk or could tell myself something encouraging. Goal pursuit Provide feedback on performance: The person is provided with data about their own recorded behaviour. The physiotherapist records walking endurance using the 6-min walk test and says ‘Your test shows a 10% improvement in how far you can walk compared to last week.’ Prompt review of behavioural goals: The physiotherapist provides a review or analysis of the extent to which previously set behavioural goals (eg, walk more outside) were achieved. Last week you said you wanted to walk for half an hour 3 times a week. How often are you managing to walk outside? Provide general encouragement: The physiotherapist provides praise or rewards for steps toward achieving behaviour or achieving behaviour.

The samples were considered positive if the OD values were ≥X2 above the day 0 sera. To assess the likely disruptive effect of the A− G-H loop deletion, the predicted amino

acid sequences of the VP1 polypeptides BIBW2992 cell line of either A+ or A− were substituted for that of O1/BFS 1860/UK/67 (accession 1FOD; [18]) using the structural prediction software ESyPred3D [19]. The subsequent structures were plotted using RasMol 2.7.3.1 [20]. Sequence comparison of the capsid coding regions of A+ and A− confirmed the absence of the VP1 G-H loop in A− (13 deletions located at residues 142–154) and only 2 other amino acid substitutions, both in VP1; residues 141 (A to V) and 155 (A to K). A comparison of the A+ and A− VP1 polypeptides CB-839 molecular weight using ESyPred3D, and based on the co-ordinates of O1/BFS 1860/UK/67 [18], demonstrated that the residual G-H loop amino acids of the A− virus were sufficient to form a smaller loop leaving the core tertiary structure of the protein unchanged (Fig. 1). To confirm the loss of

the antigenic site in the shortened VP1 G-H loop of A−, the characteristics of A+ and A− were examined by a panel of MAbs generated against A22/IRQ/24/64 (Fig. 2) whose epitopes are located on the VP1 G-H loop coding region and were similar to that of A+, differing at only six amino acid residues. These positions, namely 133, 136, 139, 140, 142 and 160, were not predicted as antigenically significant by Bolwell et al. [16]. All six of the anti VP1 G-H loop MAbs reacted well with A+ and homologous A22/IRQ/24/64 but did not react with A− or trypsin crotamiton treated A+ (Fig. 2). Sera collected on days 0, 7, 14 and 21 were tested by virus neutralisation test (VNT) to assess the virus neutralising antibody response to vaccination. Fig. 3 shows that vaccines prepared from A− or A+ produced a similar response and induced

detectable levels of anti-FMDV neutralising antibody as early as 7 days post vaccination with an identical response at day 21. In order to determine whether a vaccine prepared from A− is likely to protect cattle from challenge against the homologous and A+ viruses, serum antibody titres were used to calculate the degree of predicted protection by cross referencing serum neutralising titres obtained in this study against protection titres defined by Brehm et al. [21]. Brehm et al. [21] demonstrated that serum neutralising titres of 0.5, 1.0, 1.5, 2.0 and 2.5 can provide protection in 44%, 79%, 85%, 94% and 100%, respectively, of animals vaccinated with a high potency serotype A vaccine and then challenged with different serotype A viruses of variable antigenic relatedness to the vaccine strain [21]. Taking into account that this is a new approach for predicting protection which encompassed different sera and viruses and did not include control sera from the original Brehm study, relationship values (r1) were also determined from the serum neutralising antibody titres.

Standardized case information was abstracted from the hospital record. Sequelae were defined as complications attributable to IMD still present at discharge. The surveillance methodology has been detailed elsewhere [19] and [20]. Ethics approval was obtained at all participating hospitals. All IMPACT MenB cases with a viable isolate that occurred from 2006 to 2009 and were identified

as of August 2010 were included. NML determined serogroup, serotype, sub-serotype and PorA sequencing of case isolates. The clonal identity of isolates (defined by Multilocus Sequence Typing (MLST) [21]) and PorA variants were determined following the guidelines buy CP-673451 included in the Neisseria pubMLST website [22].

The classification of fHbp followed the scheme available in the public fHbp database which divides peptide subvariants among three major variants, 1, 2 and 3 [22]. This peptide ID is similar to the Novartis classification, although in the Novartis classification it is preceded by the major variant number. NHBA and NadA classification followed Lucidarme et al. [23] and Bambini et al. [24]. HPA studied the levels of expression and cross-reactivity of NadA, fHbp, and NHBA in the MenB isolates using the MATS ELISA relative potency (RP) [15]. The MATS method established a minimum level of RP, named the positive bactericidal click here threshold (PBT) that predicts whether a given MenB isolate would be susceptible to killing in the human serum bactericidal antibody assay by antibodies induced by 4CMenB. Strain coverage was defined as the proportion of strains with RP above the PBT for at least one vaccine antigen in the MATS ELISA or matched to the PorA subtype P1.4 [15]. PD184352 (CI-1040) To account for inter-laboratory differences

in the MATS, the 95% confidence intervals (CI) for vaccine strain coverage were calculated according to an inter-laboratory standardization study [25]. Chi-square and Fisher’s exact tests were used to test for significant difference between groups. SAS version 9.3 (SAS Institute, Cary NC) was used for all analyses. A total of 157/200 (78.5%) MenB cases were tested. A viable isolate was not available for 2 cases and 41 cases were confirmed solely by PCR. No significant differences in PCR confirmation rates were found by age or center (data not shown). The most frequent ccs among the 68 different STs identified were cc41/44 (n = 51), cc269 (n = 51), cc35 (n = 11), cc32 (n = 8) and cc60 (n = 6) cc213 (n = 2). Of the remaining 28 isolates, 21 were unassigned and 7 were singularly occurring ccs. Although cc41/44 and cc269 occurred with the same frequency, 25 different sequence types (ST) were identified among isolates in cc41/44 and only three of these contained multiple isolates (ST-154 (n = 15) and ST-571 (n = 11) and ST-340 (n = 3). In contrast, only 9 STs were found in cc269 and 90.

Specifically, approximately 10 h after Buparlisib receipt of a 60-μg dose of rLP2086 vaccine, Prevenar®, Infanrix hexa®, Meningitec®, and Rotarix®, the subject developed

a fever (39.0 °C). A lumbar puncture was performed, and initial results showed 500 cells (95% PMNs), protein 0.5 mg/dl (normal), glucose 60 mg/dl (normal), and red blood cell count of 10 mm3. The subject was treated with cefotaxime and vancomycin after the lumbar puncture; the fever cleared by the next evening and the child remained afebrile and well. The workup did not identify a causative organism; blood and cerebrospinal fluid (CSF) bacterial and viral cultures were negative; polymerase chain reaction tests of the ATM Kinase Inhibitor mw CSF were also negative. Although the aseptic meningitis was ultimately considered not vaccine related by the treating physician, review of safety data by a project-independent safety committee revealed 80% of vaccine recipients at the 60-μg dose experienced

mild to moderate fever (90% including the case of aseptic meningitis). The sponsor decided to terminate the trial after the vaccine was deemed not acceptable in this population. Forty-six subjects were randomized: 22 received 20 μg rLP2086, 10 received 60 μg rLP2086, and 14 received routine childhood vaccines only. Mean age was 65.5 days; 48% were girls; all were white. All subjects received 1 vaccine dose; no postvaccination blood samples were drawn. At least

1 local reaction was reported for 11 (50%) subjects in the 20-μg group, 7 (70%) subjects in the 60-μg group, and 5 (36%) subjects in the control group. The rates of all reactions, except erythema, were lowest in the control group and highest in the 60-μg group (Table 1). The most common local reaction was tenderness, with a mean duration of 1.3 days, 2.7 days, and 1.0 day in the 20-μg, 60-μg, and control groups, respectively. Five subjects receiving rLP2086 experienced tenderness that interfered with limb movement. Most subjects experienced ≥1 systemic event. The most common event was irritability, reported for 17 (77%), 9 (90%), and 9 (64%) subjects in the 20-μg, 60-μg, and control groups. Rates of the other systemic reactions Chlormezanone and anti-pyretic medication use were lowest in the control group and highest in the 60-μg group, with the exception of decreased sleep (Table 1). Duration of events was 1.0–3.3 days. Fever ≥38 °C was reported in the majority of rLP2086 vaccine recipients: 14 (64%) in the 20-μg group and 8 (80%) in the 60-μg group compared with 4 (29%) in the control group (Fig. 2). In most cases, the temperature was 38.0–39.0 °C; 2 subjects in the 20-μg group and 1 subject in the 60-μg group had fever of >39.0–40.0 °C. No fevers were >40.0 °C. The mean duration of fever was 1.0–2.1 days. The subject with aseptic meningitis also reported a fever between >39.0 and 40.

In the laboratory, he loved data. Pleasantries of the day were easily skipped if an assay were in the offing that might yield new data. He exhibited the excitement and glee of a child when exciting new data emerged. The generation of scientists whose career spanned till the last half of the 20th century witnessed the disappearance of many common childhood diseases and advances that were equal to the discoveries

of Pasteur and Koch near the end of the 19th century. From the development of cell culture to molecular biology to new possibilities introduced by modern Perifosine price sequencing technologies this group of investigators enabled practical applications of science through vaccine development that have had an unparalleled impact on public health. As we enter the 21st century with technologies and investigative tools that were unimaginable 50 years ago, we are still left with a host of microbial pathogens that are persistent or emerging [6]. We now work toward and hope for a new era of ON-01910 datasheet translational science that will have the same type of impact accomplished by the investigators represented by Karzon and Chanock. “
“In our article, there were two detected errors. The ICTV approved name for all fish alphaviruses is

SPDV (salmon pancreas disease virus) and the numerous isolates are now considered to belong to this one virus specie. Also Pharmaq A.S. was erroneously included as having a PD vaccine in Table 5 when there is none commercialized by this company. “
“The Authors would like to amend an error in Table 1 of the above article, where the statistical significance value was incorrectly given as ‘P < 0.005’, and should have been ‘P < 0.05’. The Publisher apologises for this error and reproduces the corrected table in full here. "
“Vaccination is one of the most cost-effective health interventions. It is estimated that over 2.5 million deaths are averted through vaccination every year [1] and [2]. However, vaccine coverage either rates are different

according to health services accessibility and socio-economic and cultural characteristics [3]. Although immunization services have been strengthened worldwide, there is continuing concern at the failure to achieve high immunization coverage [3], [4] and [5]. Brazil has performed very well with the Programa Nacional de Imunizações as an integrated programme of the global immunization strategies of the World Health Organization (WHO), putting into practice routines, campaigns and mass vaccination with free vaccines [6]. Despite of its success, there are still ongoing challenges [7]. One would expect vaccine coverage rates among children attending nurseries of day-care centres (DCCs) in Brazil to be high, because adequate vaccination is a criterion for enrollment and nurseries employ a health professional responsible for the health care of the children. In order to gain insight into these issues we conducted a study to estimate the proportion of children with incomplete vaccination and to identify risk factors.

The HBV-positive group was divided into tree subgroups: anti-HBc-positives, HBsAg positive and chronic carriers (HBsAg positives for whom this antigen remained positive during the second sampling). The study area was divided into three

areas according to their endemicity level: hyperendemic with more than 8% of the population being HBsAg positive; meso-endemic with 2–7% of the population being HBsAg positive and hypo-endemic area with less than 2% of the population being HBsAg positive. Demographic, socio-economic information and HBV markers test results were merged in the same database using Oracle release 6 software. All the entered data was cleaned by comparing electronic information against source documents. SPSS version 13.0 was used to perform the statistical analysis of data. Prevalence Paclitaxel solubility dmso of HBV infection was estimated via sample proportions, and exact binomial computation was used in estimating 95% confidence intervals

[CIs]. see more All prevalences were standardized by age to allow comparisons between districts. Mean values (±SD) for age were compared between the HBV groups using the ANOVA test. The Chi-square test was used to evaluate gender distribution differences. After adjustment for age, an analysis of the relationship between HBV groups, demographic characteristics, and identified risk factors was conducted. A multivariate logistic regression model was also developed. All variables were initially included in the model. Possible interactions between age, gender and other variables were also explored. Only statistically significant demographic and exposure no characteristics were retained in the final multivariate logistic model. Significance values below the 0.05 level were considered significant. The force of infection (FOI), defined as the instantaneous per capita rate at which susceptible individuals acquire infection [5], was estimated by fitting a polynomial

function to observed data using the loglikelihood method by Matlab 7.7 software [6]. The basic reproductive number R0 was estimated as proposed by Anderson and May by the reverse of the proportion of susceptible (1/x*) [7]. In total 9486 subjects were enrolled in the study of which 2223 were from Beja, and 7235 from Tataouine. The mean age of HBV tested subjects was 26.3 ± 20.7 years (min 0.02 max 95.8), while 57.6% were female, 32.4% were illiterate, and only 12.5% had sanitation in their houses. 80 of the 246 HBsAg positive patients during the first measurement were not evaluated 3 years later (32.5%). The mean age of anti-HBc, HBsAg subjects and chronic carriers was 36.2 ± 22.6 years, 26.9 ± 19.1 years, and 23.9 ± 16.4 years, respectively. The male to female ratio was 0.79 for anti-HBc subjects, 1.06 for HBsAg subjects and 1.09 for chronic carriers. The overall prevalence of anti-HBc, HBsAg and chronic carriage was 28.5% CI95% [27.6–29.4%], 5.3% CI95% [4.8–5.8%] and 2.9% CI95% [2.6–3.2%], respectively.

, 2012 and Frieden, 2010). Together, the articles in this issue provide a glimpse into strategies that communities used to prevent chronic diseases and associated health disparities in the United States. This issue complements an ever-increasing body of literature that describes Bcl-2 inhibitor implementation and evaluations of CPPW strategies (Baronberg et al., 2013, Barragan et al., 2014, Beets et al., 2012, Brokenleg et al., 2014, Cavanaugh et al., 2013, Cavanaugh et al., 2014, Cole et al., 2013, Drach et al., 2012, Dunn et al., 2012, Huberty et al., 2013, Jaskiewicz et al., 2013, Jilcott Pitts et

al., 2012, Johns et al., 2012, Jordan et al., 2012, Kern et al., 2014, Lafleur et al., 2013, Larson et al., 2013, Leung et al., 2013, Mandel-Ricci et al., 2013, Pitts et al., 2013a, Pitts et al., 2013b, Robles et al., 2013, Wilson et al., 2012 and Young et al., 2013). In addition, the core principles for strengthening the science of community health described in the commentary by Goodman and colleagues (in this issue) highlight the demonstrated successes of the CPPW program.

Sustaining PSE changes will lay the groundwork for future successes and emerging approaches to achieve the collective goal of improving our nation’s health. Although CPPW was funded KRX-0401 datasheet for only 2 years, community-based prevention strategies were designed to have a continuous effect in lowering chronic disease rates. CPPW had the potential to reach more than 55 million people in 381 locations (Bunnell et al., 2012). The extensive reach of this large-scale effort to improve environmental influences on obesity and tobacco use should result ultimately in a substantial reduction in chronic diseases throughout the United States. The authors declare that there are no conflicts of interests. The Centers for Disease Control and Prevention (CDC) supported awardees in the Communities Putting Prevention to Work initiative through cooperative agreements; this

supplement is supported in PAK6 part by CDC contract no. 200-2007-22643-0003 to ICF International, Inc. However, the findings and conclusions in this article are those of the authors and do not necessarily represent the views of the US Department of Health and Human Services or CDC. Users of this document should be aware that every funding source has different requirements governing the appropriate use of those funds. Under US law, no federal funds are permitted to be used for lobbying or to influence, directly or indirectly, specific pieces of pending or proposed legislation at the federal, state, or local levels. Organizations should consult appropriate legal counsel to ensure compliance with all rules, regulations, and restriction of any funding sources.