Animal experiments were approved by the Ethical committee of Utre

Animal experiments were approved by the Ethical committee of Utrecht University, and performed according to its regulations. The following antigens were used for vaccination and determination of specificity of monoclonal antibodies (mAb):

recombinant MAP Hsp 65 kD (rMAP Hsp60) and Hsp 70 kD (rMAP Hsp70). These antigens were produced as described earlier [6] and [17]. A recombinant C-terminal deletion mutant protein of the Hsp70 molecule was constructed, comprising the receptor binding part. It consisted of N-terminal amino acids 1–359 of wildtype Hsp70, had a molecular weight of approximately 45 kD and was designated RBS70. RBS70 was constructed by restriction endonuclease digestion of the original Selleck A 1210477 recombinant MAP Hsp70 pTrcHis expression vector with AflII (NE Biolabs, USA) and HindIII (Gibco-Invitrogen, the Netherlands) using 5 units of each enzyme Protein Tyrosine Kinase inhibitor per μg DNA. The digested fragment was separated from the vector DNA by agarose gel (1%) electroforesis and isolated from the gel using a QIAEXII

kit (Promega, the Netherlands). The vector DNA was blunted by using T4 DNA polymerase (Fermentas, Germany) subsequently purified using a DNA cleaning kit (Zymo Research, USA), religated using T4 DNA ligase (Quick Ligation kit, NE Biolabs, USA) and purified using the DNA cleaning kit. Finally, chemically competent Top10 bacteria (Invitrogen, the Netherlands) were transformed with the vector DNA using a heat shock protocol provided by the manufacturer. Transformed bacteria were selected and protein expression and purification was performed similar to the procedure described for recombinant MAP Hsp70 [6]. In addition, the following antigens were used: recombinant M. tuberculosis Hsp70 (MTb), recombinant Escherichia coli (E. coli) Hsp70 and bovine Hsc70 purified from bovine brain (generous gifts from Stressgen, Canada). Purified

protein derivatives (PPDs) were produced at CVI (Lelystad, the Netherlands) as previously described [18], from MAP strain 3+5/C (PPDP), M. bovis (MB) strain AN5 (PPDB), and M. avium ssp. avium (MAA) strain D4 (PPDA). MAP strain nearly 316F was grown at the CVI (generous gifts from D. Bakker). To define peptides for the screening of monoclonal antibodies and sera from cattle and goats the following HSP70 Genbank-derived sequences were used: Q00488 (MAP Hsp70); A0QLZ6 (MAA Hsp70); P0A5C0 (MB Hsp70); P0A5B9 (MTb Hsp70); P04475 (E. coli Hsp70); NP776975 (Bos taurus Hsp70-1A). A first set of 124 synthetic 14-mer peptides, with an aminoterminal cysteine, a 5 amino acids (aa) shift and an overlap of 9 aa, covering the MAP Hsp70 molecule, was synthesized using the simultaneous multiple peptide synthesis (SMPS) technique described previously [19]. To enable di-sulphate binding of peptides to the solid phase ELISA plate, an amino-terminal cysteine residue was coupled to each peptide during synthesis. For primary screening peptides were pooled in 11 groups of sequential peptides.

The compound was prepared as per the general procedure mentioned

4, 139.7, 139.3, 138.6, 134.3, 132.5, 132.1, 131.4, 131.1, 128.3, 128.0, 125.1, 124.3, 123.1, 118.2, 115.3, 56.2; HRMS (EI)

m/z calcd for C22H14BrClN2OS: 467.9699; found: 467.9696. The compound was prepared as per the general procedure mentioned above purified and isolated as colorless solid; yield 76.10%; mp 186 °C; IR (KBr) vmax 2988, 1170, 750, 550 cm−1; 1H NMR (CDCl3) δ ppm; 7.28–8.10 (m, 10H, Ar–H), 2.01 (s, 3H, SCH3); 13C NMR (CDCl3) δ ppm; 158.2, 141.3, 139.2, 139.1, 138.2, 137.2, 35.2, 132.1, 131.2, 131.1, 129.1, 129.0, 128.1, 127.7, 127.4, 127.1, 126.1, 124.2, 118.2, 15.2; HRMS (EI) m/z calcd for C22H13BrCl2N2S2: 517.9081; found: 517.9077. This compound was prepared as per the above mentioned procedure Selinexor cost purified and isolated as pale yellow solid: yield 91.38% mp 209 °C; IR (KBr) vmax 2966, 1477, 1320, 765 cm−1; 1H NMR (CDCl3) δ ppm; 7.21–8.0 (m, 11H, Ar–H), 3.80 (s, 6H, OCH3); 13C NMR (CDCl3) δ ppm; 162.3, 157.2, 139.3, 138.3, 137.2, 132.3, 131.3, 129.3, 128.3, 125.2, 125.0, 123.5, 122.3, 115.2, 56.2; HRMS (EI) m/z calcd for C23H17ClN2O2S: 420.0699; found: 420.0694. The compound was prepared as per the general procedure mentioned above purified and isolated as colorless solid; yield 89.15%; mp 196 °C; IR (KBr) vmax 2978, 1320, 1170, 750, cm−1; 1H NMR (CDCl3) δ ppm; 7.10–7.68 (m,10H, Ar–H), 2.31 (s, 3H, SCH3); 13C NMR (CDCl3) δ ppm;

158.1, Abiraterone ic50 141.2, 139.2, 138.2, 137.2, 136.2, 135.2, 132.1, 130.2, 129.6, 129.0, 129.7, 128.7, 127.5, 127.1, 127.0, 125.2, 124.3, 122.4, 15.8; HRMS (EI) m/z calcd for C22H13Cl3N2S2: 473.9586; found: 473.9581. The compound was prepared as per the general procedure mentioned above purified and isolated as yellow solid; yield 76.00%; mp 214 °C; IR (KBr) vmax 2869,1496, 1290, 750 cm−1; 1H NMR (CDCl3) δ ppm; 7.28–8.16 (m, 10H, Ar–H),

2.43, 2.72 (s, 6H, CH3); 13C NMR (CDCl3) δ ppm; 158.2, 140.3, 137.2, 136.2, 135.2, 135.0, 134.2, 132.3, 130.9, 130.4, 130.0, 129.8, 129.2, 128.4, 128.0, 127.6, 126.4, 125.4, 125.0, 122.3, 22.4, 21.3, 18.6; HRMS (EI) m/z calcd for C23H16 Cl2 N2 S: 422.0411found: 422.0407. All authors have none to declare. The authors Dr. Jitender K Malik would like to thank to Dr. Malleshappa Noolvi and Director General, Department of Science and Technology, New Delhi for funding the project (Grant. No. SR/FT/LS-0024/2008). 17-DMAG (Alvespimycin) HCl
“The heterocyclic system containing benzotriazole moieties system is of wide interest because of their diverse biological activities1 and 2 including anticonvulsant and anti-inflammatory activities,3 diuretic,4 analgesic,5 pesticidal.6 Recent publications reported synthetic protocols in solvent-less conditions7, 8 and 9 and in presence of ultrasonic radiation.10, 11, 12 and 13 Anthelmintic infections are now being recognized as cause of much chronic ill health amongst the tropical people.

Patrick Dillon and Hamid Ghanbari In this article, a review of th

Patrick Dillon and Hamid Ghanbari In this article, a review of the diagnostic evaluation and outpatient follow-up of patients with atrial fibrillation is presented.

After exploring details of symptoms, past medical history, quality of life, and physical exam findings, diagnostic tools are then discussed. Furthermore, important considerations after the initial diagnosis and treatment of patients with atrial fibrillation are discussed. Colby Halsey and Aman Chugh Treatment of patients with symptomatic atrial fibrillation Gemcitabine mouse (AF) with antiarrhythmic drug therapy in general improves their symptom scores and exercise tolerance; however, large randomized trials have failed to show a mortality benefit with a rhythm-control compared with a rate-control strategy. Catheter ablation in patients Enzalutamide in vitro who have failed or not tolerated medical therapy has been shown to alleviate symptoms and improve quality of life. However, catheter ablation cannot undo the structural remodeling that contributed to the arrhythmia in the first place. Patients should be alerted to modifiable factors that may decrease the likelihood of unchecked structural remodeling

and AF recurrence. Muhammad Rizwan Sardar, Wajeeha Saeed, and Peter R. Kowey Atrial fibrillation (AF) is the most frequently encountered arrhythmia. Prevalence increases with advancing age and so as its associated comorbidities, like heart failure. Choice of pharmacologic therapy depends on whether the goal of treatment is maintaining sinus rhythm or tolerating AF with adequate control of ventricular rates. Antiarrhythmic therapy and conversion of AF into sinus rhythm comes with the side effect profile, and we should select best antiarrhythmic therapy, individualized to the patient. New antiarrhythmic drugs are

being tested in clinical trials. Drugs that Adenosine target remodeling and inflammation are being tested for their use as prevention of AF or as upstream therapy. Rakesh Latchamsetty and Fred Morady Strategies and technology related to catheter ablation for atrial fibrillation (AF) continue to advance since its inception nearly 20 years ago. Broader selections of patients are now offered ablation with a similar level of procedural outcome and safety standards. It is hoped that improved understanding of the pathophysiologic processes of the initiation and maintenance of AF will refine target selection during ablation and improve long-term procedural efficacy, particularly in patients with persistent and long-standing persistent AF. Christopher P. Lawrance, Matthew C. Henn, and Ralph J.

However, despite these limitations, a careful analysis of the ava

However, despite these limitations, a careful analysis of the available data can suggest a rational approach to vaccinating children with cancer in order to assure adequate protection against vaccine-preventable diseases without significantly increasing the occurrence of adverse events.

The main aim of this review is to analyse data regarding the immunogenicity, efficacy, safety and tolerability of the vaccines usually recommended in the first years of life in order to help pediatricians choose the best Selleck AT13387 immunisation programme for children with cancer receiving standard-dose chemotherapy. Most children with cancer still seem to have a perfectly functioning immune system at the time of disease presentation. The concentrations of total immunoglobulins and antibodies against specific vaccine antigens are usually in the normal range [8], [9], [10] and [11]. Peripheral blood T cell levels seem

to be reduced in only a marginal number of cases: significant lymphopenia has been Pomalidomide in vivo found in only a small number of patients with leukemia [12] and in a few subjects with previously untreated Hodgkin’s lymphoma [13], Burkitt’s lymphoma [14] or sarcoma [15]. This means that the protection offered by vaccines administered before the onset of cancer is maintained by humoral and cellular immunity in most children. Moreover, if a vaccine is administered between the onset of cancer and its diagnosis, a poor immune response and severe adverse reactions seem to be unlikely [12] and [15] except in the case of conditions such as Hodgkin’s or Burkitt’s disease in which the number and function

of T lymphocytes may be significantly impaired [13] and [14]. However, after the start of chemotherapy, the immune system is rapidly and significantly compromised. Most of the drugs used to treat malignancies have a negative effect on humoral and cellular immunity, and the damage to the immune system is related to both the dose and the duration of administration [1], [16] and [17]. Cyclophosphamide, TCL 6-mercaptopurine, fludarabine and steroids seem to induce the greatest damage [1]. The most important aspect of cytotoxic antineoplastic therapy-induced immunosuppression is lymphocyte depletion. This only marginally affects NK cells but has a profound impact on circulating CD3+ and CD4+ T cells [16], whose number dwindles immediately after the start of cancer therapy and remains significantly lower than normal throughout its continuation [1]. Furthermore, T cells may undergo major functional alterations, such as a heightened susceptibility to activation-induced programmed cell death [17], or their activity may be inhibited by the suppressor factors produced by the expanded monocyte population [1]. B cells are also subject to profound depletion and, although serum IgG levels are not always significantly reduced, serum IgM and IgA levels are considerably decreased [1].

K-level 1 to 4

participants received the standardised out

K-level 1 to 4

participants received the standardised outpatient prosthetic rehabilitation service, as detailed in Appendix 1 (see eAddenda). An independent research assistant contacted potential participants from the Amputee Physiotherapy Service database to obtain informed verbal consent for the interview. The interview process involved coordinating telephone interviews with country physiotherapists on remote community visits, Aboriginal Health workers, nurses, and the use of telehealth. Medical records were audited for potential predictor variables and this was undertaken blind to the interviews. Box 1 outlines the predictor variable domains investigated. All potential variables were dichotomised (eg, amputation cause: atraumatic or traumatic). Receiver Operator Characteristic (ROC) curves were used to generate a threshold for dichotomous classification click here of continuous variables (eg, age). This was performed with an equal weighting for sensitivity and specificity. Table 1 in the eAddenda details the dichotomous variable classifications. Intrinsic predictor variables Amputation predictor variables Functional predictor variables • gender • age • indigenous status • metropolitan versus country • accommodation at discharge: home versus residential care • medical comorbidities: diabetes type I or II, peripheral arterial disease,

cardiac condition, renal failure, stroke, transient ischaemic attack, lower limb pathology • number of medical comorbidities, including mental health issues and musculoskeletal pathology • amputation R428 solubility dmso cause • amputation level • bilateral lower limb amputation • time to second lower limb amputation • time from amputation to prosthetic milestones: casting, fitting and definitive

prosthesis • mobility level achieved without a prosthesis: wheelchair mobility, transfers, hopping • independence with donning and doffing prosthesis, and monitoring prosthetic fit at discharge • mobility for aid use at discharge • mobility level achieved using a prosthesis at discharge: walking indoors, outdoors, stairs, slopes, grass, gravel, uneven terrain, high-level balance activities and running Full-size table Table options View in workspace Download as CSV Medical comorbidities (including mental health issues and musculoskeletal pathology) were recorded and counted for each participant. Charlson Comorbidity Index and Combined Age Charlson Comorbidity Index were calculated from medical comorbidities data.31 In the present study, amputation level was classified as transtibial or above transtibial. Bilateral lower limb amputation was defined as having undergone two major lower limb amputations. Participants were classified as able to independently perform the locomotor skill or being dependent (ie, required assistance or unable to perform). Mobility aids were either used or not used, and the aid type was not statistically weighted for its level of support.

However even with a practice of routine NPA testing for respirato

However even with a practice of routine NPA testing for respiratory related illness, not

all children will have specimens collected for laboratory confirmation. In our analysis we have made estimates of possible increased disease burden had all children had specimens taken. The laboratory surveillance at PWH suggested that up to 1.6% of infants aged above 6 days and below 6 months of age and 5.2% of children Z-VAD-FMK solubility dmso aged above 6 days to below 18 years are admitted to hospital as a result of influenza infection. We adjusted the CMS flu diagnosis estimates using factors derived from linking our laboratory surveillance results at PWH to the CMS coded diagnoses and then extrapolated these adjustments to the whole of Hong Kong. These adjusted rates were generally higher than the unadjusted rates (Fig. 2 and Fig. 3). During the A(H1N1)pdm09 pandemic in 2009/10 the proportion of children aged above 6 days to below 18 years admitted to hospital who had a diagnosis of influenza almost doubled (9.8%). Reasons for this increase incidence during 2009/2010 IOX1 could reflect a genuine increase in disease burden or alternatively

it could reflect changes in admission policy e.g. all suspected A(H1N1)pdm09 infections, including mild cases, were recommended for admission. Measures for severity of illness in the current study were length of stay, intensive care unit admission and outcome. Severity of influenza as measured by mortality mafosfamide and

length of stay did not appear to be greater in the 6M group as compared to the 18Y group. The median length of stay for the A(H1N1)pdm09 admissions was similar to the that of the non-A(H1N1)pdm09 influenza admissions (Appendix 12) but when categorised into groups, a greater proportion of children with A(H1N1)pdm09 had a length of stay less than 2 days (Table 3), possibly reflecting less severe disease or a greater proportion of admissions with mild disease. However the number of intensive care unit admissions with any CMS diagnosis of influenza was highest during 2009/10. Incidence estimates based on adjustment factor 3 (PWH laboratory confirmed influenza rate) tended to be higher than the other incidence estimates except during 2009/10 (Fig. 2), possibly reflecting a sustained high level of routine NPA testing for influenza during the whole study period at PWH, but with other HA hospitals only increasing their NPA testing for influenza from 2009/10. Limitations to our incidence estimates include a number of assumptions related to admissions to public HA hospitals and the resident Hong Kong population. The proportion of admissions to public hospitals has fallen in recent years and there has been a marked increase in the number of mothers from mainland China delivering in Hong Kong.

Other common activities reported include recommendations related

Other common activities reported include recommendations related to high-risk buy GSK1349572 groups, vaccine formulation, research priorities, and implications of adverse events. Other less commonly reported topics for which committees issue recommendations include those for vaccine coverage, logistics, supply, and regulation; supplementary immunization activities (for example, activities associated with polio eradication); vaccine and immunization program financing; and

communicable or vaccine preventable disease surveillance, control, or outbreak response. Additional activities include responding to questions from key groups or the public and educational efforts related to vaccines and immunization. The process of committee member nomination is diverse. The broadest recruitment process is used by countries like the United States and United Kingdom, which advertise nationally and accept nominations from any source. In France, nominations come through the general medical community. In four countries, members are selected based on positions allocated to the central government or professional organizations. In the case of the former, members serve as long as they remain in their position and in the case of the latter they are nominated by the organization. For the selleck screening library remaining five countries for

whom this information is known, the MOH, the NITAG itself, or both put forward nominations. Regardless of the nomination process, MOH representatives play a central role on almost all the committees, either by Olopatadine virtue of holding the position of chairperson or secretary, holding various fixed positions, or acting as the committee secretariat. In some instances, numerous MOH agencies (including regulatory) have committee representation. Expertise represented on the committees is primarily medical or public health and includes paediatricians, family practitioners, infectious disease

experts, experts on vaccinology or immunization, public health experts, and in rare cases economists. Community representation was included on four committees: a consumer representative in South Korea and the United States, a consumer expert in Australia, and a “lay person” in the United Kingdom. Appointment to committees varies from 2 years to unlimited, for example, positions assigned to specific government positions. The most common duration is 4 years, and usually reappointment is allowed (either a limited or indefinite number of times). Korea, with the shortest period of appointment at 2 years, does not allow reappointment nor does the United States. The total number of official committee members that vote or participate in consensus decisions (depending on the decision-making process) varies from 5 in Honduras (all paediatricians) and 10 in Oman to 33 in India and 38 in Sri Lanka. The median number is 19.

As depicted in Fig 1, the 2007 outbreak strains formed a distinc

As depicted in Fig. 1, the 2007 outbreak strains formed a distinct cluster within G9 VP7 Lineage III, sub-lineage D. The strains in Lineage III exhibited 93.3-99.1% nucleotide identity

to the Alice Springs outbreak samples. The 2007 outbreak strains exhibited closest similarity to a G9P[8] strain isolated in Brazil in 2006, with 99.0–99.1% nucleotide similarity and 99.8–99.9% amino acid identity. DAPT ic50 Comparison of the deduced amino acid sequences of the VP7 genes from the 2007 outbreak strains with VP7 from G9P[8] strains previously identified in Australia also revealed a close relationship with the previous circulating Australian G9P[8] strains in Lineage III, with a 98.0–98.7% nucleotide and 94.0–96.3% amino acid sequence similarity observed. Three conserved amino acid substitutions were identified at positions 44 (Ala/Val-Thr), 263 (Val-Ile) and 279 (Ala-Thr) in the Ipatasertib research buy 2007 outbreak strains when compared to other G9 strains analysed. A 663 bp region of the VP8* subunit of the VP4 gene was sequenced for six G9P[8] samples, including three from vaccinated infants.

The sequences were highly conserved with 99.6–100% nucleotide identity and 98.7% amino acid homology observed. No conserved nucleotide or amino acid changes were observed between samples obtained from vaccinated and non-vaccinated patients. Phylogenetic analysis of the nucleotide sequence of the VP8* subunit of the G9P[8] 2007 outbreak strains and previously published P[8] human strains was performed. As depicted in Fig. 2, many the 2007 outbreak strains formed a distinct cluster within P[8] Lineage 3 (P[8]-3). The strains in P[8] Lineage 3 exhibited 97.3–99.7%

nucleotide identity to the Alice Springs outbreak samples. The 2007 outbreak strains revealed close similarity to G9P[8] strains isolated in the USA, Russia and Ireland, displaying 98.6–99.3% nucleotide and 97.0–99.1% amino acid identity. When compared to a 2001 Australian G9P[8] isolate, the outbreak strains exhibited 98.3–98.6% nucleotide and 97.8–98.7% amino acid identity. The 2007 outbreak strains contained two unique amino acid substitutions at positions 237 (Ser-Leu) and 242 (Thr-Ser) when compared to all other P[8] strains analysed. The 750 bp of the NSP4 gene was sequenced for 14 G9P[8] outbreak strains including three from vaccinated infants. The sequences were all highly conserved displaying 99.4–100% nucleotide and 99.9–100% amino acid identity. No conserved changes were observed between samples obtained from vaccinated and non-vaccinated patients. Phylogenetic analysis of the nucleotide sequence of the NSP4 gene of the G9P[8] 2007 outbreak strains and previously published NSP4 genes was performed. As depicted in Fig. 3, the NSP4 from the 2007 outbreak strains formed a distinct cluster within the E1 Genogroup. The strains in E1 Genogroup exhibited 90.6–99.

By the end of January 2010 [1], the coverage of adults ranged fro

By the end of January 2010 [1], the coverage of adults ranged from 8.7% to 34.4% (Fig. 2). States varied in their

approaches to Navitoclax research buy implementing their H1N1 vaccination programs in an unprecedented situation. While the literature addressed factors related to uptake of seasonal influenza vaccine at the individual level [12] and [13], states and regions used their best judgment and knowledge of their jurisdictions to guide their decisions on distribution and system design, given the lack of scientific evidence in that area. The purpose of this study was to determine supply chain and system factors associated with H1N1 coverage rates at the state-wide level for adults in order to inform Sorafenib future events of this nature. We hypothesized that characteristics of the vaccine supply chain in each state and decisions around targeting vaccine could predict uptake. One classic supply

chain study, for example, has demonstrated that a product stocked in a large number of locations increases the probability that a particular location will be stocked out, and may also reduce the distance traveled by the final consumer [14]. Some of these characteristics of the state vaccine supply included the number of locations where vaccine was available, prioritization of the ACIP-recommended target groups, the type of providers to whom vaccine was directed, and the lead-time between vaccine allocation and availability in a state, which largely reflects differences in states’ ordering processes. Because other factors affect uptake, as evidenced by state-to-state variation in seasonal influenza coverage and individual-level studies [15], [16], [17] and [18], underlying population differences such as demographic characteristics, utilization of preventive health services, and healthcare infrastructure were also examined. It is relevant to mention that individual-level studies differ from those with a regional or ecological view. Others have used this

Bay 11-7085 ecological approach in the analysis of other health-related problems such as water fluoridation and tooth decay [19] and [20]. Data from the centralized distribution system on vaccine shipments from October 5, 2009 through December 9, 2009 were made available for analysis, thus allowing us to focus the analysis on the period during which vaccine was in short supply. We examined the relationship between state vaccination rates in persons 18 and over with variables covering population and health-related state characteristics and state-specific vaccination campaign information. The outcome measure is state estimates of vaccination coverage, as calculated by the CDC [1]. Participants 18 and over on the Behavioral Risk Factor Surveillance System (BRFSS) and National H1N1 Flu Survey (NHFS) were asked if they had received an H1N1 vaccine during October 2009–January 2010.

The maximum number of dependent data points was 51 with a large n

The maximum number of dependent data points was 51 with a large number of variables to consider; however, the best models had less than ten variables each. We kept “outliers” in the analysis because we consider they speak to real extreme state cases and not to data deformities, and examined quantile–quantile (Q–Q) plots to determine whether additional transformations were needed. Models were evaluated on adjusted R-square values and the F-statistic, with an individual variable evaluated on its p-value (below 5%). The regressions were performed with R statistical software package version 2.11.1 [36]. Some descriptive

statistics were calculated in Microsoft Excel versions 11 and 12. Seven variables including lead-time from allocation

to ordering and shipment, the maximum number of ship-to sites per thousand population, past seasonal influenza coverage for non-high risk adults age 18–49, percentage selleck of doses categorized as sent to internists and specialists, percentage of women 18 and older with a Pap smear in the last three years, percentage of weeks with ILI above 2.3 after week 30, and the percentage of residents mTOR kinase assay of Hispanic or Latino origin were significant for predicting vaccination coverage in adults (Table 1). The best model found explained the variation in state-specific adult vaccination coverage with an adjusted R-squared of 0.76 and a p-value

close to 0 ( Table 2). For supply decisions, a long lead-time was associated with lower coverage, and the associated coefficient has a relatively large magnitude. Additional analysis of lead-time indicated that a state’s relative lag tended to be consistent throughout the months considered. We also found that lead-time is correlated with some variables related to shipment choice (e.g., positively with use of third parties for distribution, and negatively with shipments per ship-to site). The vaccine allocated to internists and specialists as a percentage of the total shipped was negatively associated with coverage, and having a large number of maximum ship-to sites was positively associated with coverage. Vaccination coverage was positively associated with past influenza vaccination coverage; while we found a strong mafosfamide association, there were several other effects that were also large in magnitude. Coverage was also positively associated with the percentage of women with a Pap smear, and the percent of the population that is Hispanic. A long duration of ILI severity peaks (defined by the percentage of weeks in the Fall with percent ILI more than 2.3) was negatively associated with coverage. To provide more information on our modeling, Supplementary Table 2 presents examples of other variables highly correlated with those factors in our final model.