(2005). In these physical experiments of Hammack et al., as well as in the numerical simulation

of Fuhrman and Madsen (2006), a linear wavemaker method was used to generate the (nonlinear) short-crested waves. The nonlinear model, and the physical experiment, responded by releasing spurious free harmonics due to the fact that third-order components in the wave generation are neglected. This resulted in modulations in the computational domain and in the physical experiment. Fuhrman and Madsen showed that inclusion of the third-order wave components in the wave generation reduces significantly the first-harmonic spurious modulations. Dasatinib ic50 This shows that wavemaker theory should take higher order harmonic steering into account when dealing with highly

nonlinear waves. The appearance of spurious free waves can also be expected in embedded wave generation methods if the force function is derived for a linear(ized) wave model. Wei and Kirby (1998) used a this website numerical filtering method proposed by Shapiro (1970) in order to reduce the effects of the spurious free waves. They conclude that the method is cumbersome to write and inconvenient to code in the program. Instead of using higher order steering or numerical filtering, we propose to use an adjustment for nonlinear wave generation that is motivated by Dommermuth (2000). Dommermuth remarked that nonlinear dispersive Phospholipase D1 wave models can be initialized with linear wave fields if the flow field is given sufficient time to adjust. For the initial value problem which he investigated, he introduced an adjustment scheme

in time that allows the natural development of nonlinear self-wave (locked modes) and wave-wave (free modes) interactions. To implement this idea in nonlinear wave models, the higher-order terms, denoted by F  , are multiplied by a slowly increasing function from 0 to 1 in a time interval T  a, leading to the adjustment F˜ given by F˜=[1−exp(−(t/Ta)n)]Ffor some positive power n. In his examples, the optimal length of the time interval Ta should be larger than two times the period of the longest waves in the simulation. For embedded wave generation, which takes place in time during the whole simulation, we modify the adjustment accordingly: the influxed waves are propagated away from the influx position by a spatially dependent increase of the nonlinear terms of the equation. Specifically, consider embedded influxing in a nonlinear Hamiltonian model with force functions (14) and with additional nonlinear (higher order) terms N  1 and N  2, given by ∂tη=Dgϕ+G1+N1∂tϕ=−gη+G2+N2The adjustment scheme in space uses a characteristic function χ(x,La)χ(x,La) that gradually grows from 0 to 1 in a transition zone with length L  a; multiplying the nonlinear terms to N  1 and N  2 with this function results in equation(22) ∂tη−Dgϕ−G1=χN1 equation(23) ∂tϕ+gη−G2=χN2∂tϕ+gη−G2=χN2Fig.

Total serum creatine

kinase (CK) and its isoenzyme MB (CK–MB) are well established and widely accepted markers for the diagnosis and follow-up of heart injury or myocardial infarction (Bachmaier et al., 1995). Biochemical analyses showed an increase in CK and CK-MB levels (Fig. 3A and B, respectively). Increased CK concentrations were observed see more in envenomed animals (4850 UI/mL) compared to the control group (injection of PBS) (1293 UI/mL). Levels of CK–MB were also higher in the envenomed group (1980 UI/mL) than in the control group (413 UI/mL). We have demonstrated previously, in dogs envenomed with Tityus fasciolatus scorpion venom ( Pinto et al., 2010), that the occurrence of myocardium damage is correlated with high serum levels of CK and CK–MB. As we

also observed higher levels of these two markers of heart injury of the envenomed rats, we suggest in this study that H. lunatus venom has cardiotoxic effects, possibly through the action of neurotoxins acting on voltage gated ion channels present in the heart ( Chen and Heinemann, 2001; Korolkova et al., 2004). The soluble venom of H. lunatus was fractionated by HPLC and showed more than 20 components ( Fig. 4A). As with other chromatographic profiles of scorpion venoms ( Batista et al., 2004), the separation in C18 reverse column is completed at approximately 60 min of the Natural Product Library cell line gradient, at a flow rate of 1 mL/min. According to the authors mentioned above, the fractionated components during

the first 20–40 min of the gradient would be the minor peptides corresponding to K+- and Na+- channel neurotoxins. It is known that most scorpion Phloretin toxic peptides have molecular masses lower than 10 kDa. These basic peptides are neurotoxins of low molecular mass that bind to ion channels with high affinity, exerting their noxious effect ( Catterall et al., 2007). These small proteins may be responsible for the typical symptoms of neurotoxic envenoming observed in inoculated mice. Several components purified after RT (retention time) 30 min showed PLA2 activities (peaks 10 to 19, except the fraction 13). Fraction 15 (from 35 to 40 min RT), which showed highest PLA2 activity, was further analyzed by MALDI–TOF and the individual components clearly identified. The molar masses ( Fig. 4B) found were 11,914.5 Da and 13,650.6 Da. In the final part of our study and as a preliminary step in the production of an anti-H. lunatus anti-venom with therapeutic properties, we have attempted to study by ELISA and immunoblotting the antigenic/immunogenic potential and cross-reactivity of rabbit anti-H. lunatus serum. Immune sera anti-H. lunatus and anti-T. serrulatus (for comparative purposes), were raised in rabbits and their reactivities against H. lunatus, T. serrulatus, C. sculpturatus and Androctonus australis hector venoms evaluated. Fig. 5 shows the ELISA (absorbance at 490 nm) at different serum dilutions (1:100 to 1:12,800).

It is our institution’s practice to remove all appendixes even if there were no macroscopic features of acute appendicitis intraoperatively. EPZ-6438 solubility dmso This is guided by existing data, which revealed that up to 33% of macroscopically normal appendixes have features of inflammation on histology.12 The range of AS for which patients were least likely to benefit from CT evaluation was determined by identifying AS ranges that had positive likelihood ratios not significantly different from those of CT scans. Likelihood ratios were

selected as the parameter for comparison because they were independent of disease prevalence and depended only on the intrinsic ability of the diagnostic test to distinguish between diseased and nondiseased individuals. The pairwise comparisons of predictive values and likelihood ratios are based on the methods described by Moskowitz and Pepe (2006)13 and Nofuentes and Castillon (2007),14 respectively. The above statistics were sub-analyzed by sex because the performance of the AS has been shown to vary according to sex.15 Statistical analyses were performed using Statistical Package for the Social Sciences (SPSS) Version 17. Performance measures, including sensitivity, specificity, positive and negative CDK inhibitor predictive values, and diagnostic likelihood

ratios were calculated and compared using the BDT comparator program.16 A p value of less than 0.05 was considered to indicate statistical significance. The study was carried out under the approval of the Centralized Institutional Review Board of the Singapore Health Services. There were 450 patients admitted for suspected appendicitis from August 2013 to March 2014. One hundred patients were not evaluated with CT scans and were excluded from the study. Altogether, 350 patients underwent CT evaluation. There were no cases of missed diagnosis in these patients, who were all evaluated with CT scans. There were 134 males (38.3%) and 216 females (61.7%). The overall

Interleukin-2 receptor median age of the patients was 33 years (range 15 to 82 years): 32 years for males and 33 years for females. Among the 350 patients who presented with suspected appendicitis and were evaluated with CT scans, the overall prevalence of appendicitis was 44.3% in the total study population; 37.5% in females and 55.2% in males (Fig. 1). Nineteen (5.4%) of the CT scans were deemed equivocal, 11 in females and 8 in males. Surgery was performed for 168 patients (48%), of whom 40, 126, and 2 underwent open appendectomy, laparoscopic appendectomy, and laparotomy, respectively. The overall negative appendectomy rate was 7.7%. The number of patients within each AS cut off category is illustrated in Table 2. The sensitivity, specificity, positive and negative predictive values, and positive likelihood ratio of the various AS cut-off values compared with CT scan are illustrated in Table 3. Sub-analysis of the positive likelihood ratios of the various AS values stratified by sex and compared with CT scan are illustrated in Table 4.

Functionalized Au-NPs were stabilized by adding 20 μl of 10% bovine serum albumin (BSA), followed by gentle shaking for 30 min at room temperature. Unbound oligonucleotides were removed by three times centrifugation (9.300 ×g for 10 min) through a discontinuous glycerol gradient in 2 ml Eppendorf tubes. The gradient consisted of 800 μl PBS containing 30% glycerol (w/v) and

1% BSA (w/v), overlaid with 1 ml of functionalized Au-NPs. The small molecule library screening pellet was finally resuspended in 1 ml of PBS containing 1% BSA, 0.05% Tween 20, 20% glycerol and 0.02% NaN3. In some experiments Au-NPs were functionalized with BSA instead of antibody. Absorption spectra were recorded with a UV-1601 spectrophotometer (Shimadzu Corporation, Kyoto, Japan) equipped with software package UVProbe (Shimadzu) and quartz cells

(200 μl) with 10 mm path length. Nickel electron microscopy grids coated with pioloform were glow discharged and coated with poly-l-lysine. Au-NPs functionalized with antibodies or KU-60019 solubility dmso with BSA were allowed to settle on the coated grids. After 10 min, the grids were washed in PBS and free protein-binding sites were blocked for 15 min with 0.1% BSA in PBS. Grids with bound Au-NPs were then incubated with the secondary antibody (goat anti-rabbit IgG, conjugated with 5 nm Au-NPs), diluted 1:10 in PBS-0.1% BSA. After 30 min the grids were washed three times for 5 min each with PBS. The grids were fixed in 2.5% glutaraldehyde in PBS for 10 min. Finally, samples were washed twice with MilliQ water (Millipore, Billerica, MA, USA) for 1 min, air-dried and examined with a JEOL JEM-1200EX transmission electron microscope (JEOL, Tokyo, Japan) operating at 60 kV. For detection of cytokines by Nano-iPCR, two methods were used differing in the mode of anchoring the antibodies to plastic surface. In Nano-iPCR next I biotinylated antibody was attached to immobilized extravidin, whereas in Nano-iPCR II the antibody was directly bound to the plate. One hundred microliter aliquotes of extravidin

(1–2 μg/ml in 100 mM borate buffer, pH 9.5) were added into each well of real-time 96-well plate or real-time tube strip (Eppendorf, Hamburg, Germany) and incubated for 1 h at 37 °C. After adsorption of the protein, the wells were washed with PBS containing 0.05% Tween 20 (TPBS) and the remaining binding sites were blocked by 2 h incubation at 37 °C with TPBS supplemented with 2% BSA. The wells were then washed three times with 200 μl of TPBS, followed by addition of 100 μl biotinylated anti-SCF or anti-IL-3 antibody (1 μg/ml in TPBS-1% BSA). After incubation for 1 h at 37 °C, unbound antibody was rinsed out and 100 μl sample aliquotes were probed for the presence of SCF or IL-3.

There is a wide spectrum of presentations, varying from a clinically silent form to the classical

malabsorption syndrome.1 Although primarily affecting the small bowel, CD is a multisystem illness. The potential target organs include the liver, pancreas, heart, kidney, thyroid gland, bone, skin and nervous system, giving rise to a variety of extraintestinal manifestations.1 and 2 A number of hepatobiliary disorders have been documented in patients with CD. The most common pattern of liver damage is a gluten sensitive form of hepatitis (celiac hepatitis). The usual manifestation consists of PARP phosphorylation an isolated elevation of aminotransferases. In this context, liver biopsy check details is usually of limited value, since the histological findings are nonspecific and there is a complete response

to dietary treatment. 2 More rarely, CD is associated with a group of liver disorders sharing common genetic factors and immunopathogenesis, such as autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). If this is the case, gluten withdrawal is usually insufficient to normalize liver tests and to prevent progressive liver damage and a specific management is required. 3 and 4 A 21-year-old woman was referred to evaluation because of an unclear elevation of liver enzymes. The patient was asymptomatic and routine laboratory tests made six months earlier incidentally detected a 1.5 to 2-fold elevation of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT). She

denied any history of alcohol or illicit drugs use and she was not taking any medications, including nonprescription ones. There was no evidence of risk factors for viral hepatitis. Her past medical history was unremarkable and no family history of liver or gastrointestinal disorders could be identified. The physical examination was normal, with a body mass index (BMI) of 19 kg/m2 and no signs of liver disease. The initial laboratory study evidenced AST 40 U/L (upper limit of reference, 31 U/L) and ALT 64 U/L (upper limit of reference, 34 U/L), with normal alkaline fosfatase, γ-glutamyl transferase, bilirubin and normal hemogram. Abdominal ultrasound examination was normal. A complete screen selleck chemicals for the possible etiology of abnormal liver tests was performed. Serologic markers for viral hepatitis were negative. Transferrin saturation, ferritin, ceruloplasmin, α1-antitrypsin and thyroid function tests were normal. The serum protein electrophoresis and immunoglobulin study disclosed an elevation of serum immunoglobulin (Ig) G concentrations (19.7 g/L; normal 7–16 g/L) and low serum IgA (0.24 g/L; normal 0.7–4 g/L). The autoantibody profile was characterized by positive antinuclear (+++), anti-double-strand DNA (6.1 U/mL; normal < 4.

Previous cross-sectional comparisons and short-term training studies of the elderly generally support our viewpoint. Shinkai et al. (1998) saw little difference in CD3+, CD4+, CD8+, CD16+ or CD19+

counts between aerobically active and inactive elderly non-smokers; very fit individuals showed a superior T cell proliferative response to both PHA, and pokeweed mitogen, but the mixed lymphocyte reaction was not enhanced, making it unlikely that their T cell effector function was enhanced. Likewise, Arai et al. (2006) found that in elderly men the proliferative response to PHA was enhanced by aerobic training. Nieman et al. (1993) also made a cross-sectional GSK126 research buy comparison between fit and unfit women aged 67–85 years; the highly trained individuals had a 54% advantage of lytic activity and a 56% greater T cell proliferative response to PHA, but there were no inter-group differences in lymphocyte subset counts, and a 12-week training programme did not enhance either T cell function or resting NK cell activity in the sedentary group. Woods et al. (1999) also found no significant increase of NK activity with six months of aerobic training in elderly men. A dissident report from Crist et al. (1989) noted a 33% increase

in resting NK cell activity in seven elderly subjects following 16 weeks of aerobic training. There is even less evidence of a positive response of immune parameters to resistance training (Raso et al., 2007, Flynn et al., 1999 and Kapasi et al., 2003), although McFarlin et al. (2004) did observe some increase of NK cell activity. In reviewing available reports, HKI-272 molecular weight Bruunsgaard and Pedersen (2000) concluded that physical training programmes acceptable to an elderly population are unable to bring about any major restoration of the senescent immune system. Our observations have been based on fitness scores, rather than questionnaire estimates of habitual physical activity. Although fitness scores reflect both the genetic characteristics of an individual and his Fluorouracil manufacturer or her habitual physical activity, this approach to classifying the activity habits

of the elderly avoids the problems of recent memory often encountered when using questionnaires in such populations. Our subjects were typical of most elderly people, not athletic and relatively unfit compared with some previously reported groups; as might be predicted from previous reports on the general elderly population, there was little evidence that lymphocyte counts and sub-sets, the proportion of naive and memory cells, NK cell sub-sets, co-stimulatory molecules, apoptotic markers and activation markers differed between the upper and lower halves of the fitness spectrum, whether this was assessed in terms of aerobic power or muscle strength. Furthermore, three subjects who were immunologically “at risk” had similar levels of fitness to the remainder of our subjects.

According to these PK analysis, TDM results on day 2 can be evaluable as a steady state in patients with a normal renal function

and mild renal dysfunction. Tanigawara et al. reported that ABK clearance was related to Ccr, age, and body weight. check details The volume of distribution was different in healthy subjects and infected patients, and this difference was more pronounced among disease types [13]. Ikeda et al. [14] reported that duration time of infusion, Ccr, body mass index (BMI), serum albumin level, and presence of chronic heart failure were significant factors influencing Cpeak. Based on these findings, frequent follow-up TDM is recommended for patients with severe infection, impaired renal function, obesity or underweight, concomitant use of nephrotoxic agents (aminoglycosides, amphotericin B, cyclosporine, contrast media, etc.), and particular clinical conditions which cause fluctuating volumes of distribution. In a nationwide questionnaire survey (203 institutions) concerning TDM of ABK, Cmax was used in 88 institutions, and Cmin was used in 79 institutions as the target serum

concentrations that indicate clinical efficacy [15]. Although previous reports mainly analyzed based on Cmax, recent studies used Cpeak as an indicator of clinical efficacy [4], [9], [10], [11], [12], [16] and [17]. Regarding the optimum administration method of ABK based on the PK-PD theory, it has been reported that the trough concentration (OR = 2.00) and patient’s age (OR = 1.06) were indices of the development EPZ015666 purchase of renal dysfunction on multiple logistic regression analysis. The mean

trough concentrations were 2.6 μg/mL in patients with developing nephrotoxicity and 0.5 μg/mL in patients without nephropathy [9]. Sato et al. described that incidences of nephrotoxicity were 2.5%, 5.2%, and 13.1% in patients with a trough value of CYTH4 1 μg/mL, 2 μg/mL, and 5 μg/mL, respectively [4]. As for ototoxicity, Suzuki et al. demonstrated that there was no significant correlation between auditory brainstem response abnormality with either peak ABK concentration 20 μg/mL, trough concentration 4 μg/mL, or total dose100 mg/kg [18]. a. Clinical effect can be expected when the Cmax/MIC ratio was 8 or higher, and target Cpeak of 15–20 μg/mL is recommend (C1-III). In studies using Cmax as an indicator of clinical efficacy in patients with once daily administration at the approved dose of 150–200 mg, Kawano et al. [10] reported that the mean Cmax was 14.7 μg/mL, and the mean trough concentration was 0.74 μg/mL. Aikawa et al. [12] described that the mean Cmax and trough concentration were 16.2 and 1.1 μg/mL, respectively. Sato et al. [4] performed PK-PD analysis involving 174 patients with MRSA infection. On logistic regression analysis, the efficacy was high when Cmax was 7.9–12.5 μg/mL (OR = 6.7), and the incidences of nephrotoxicity were 2.5, 5.2, and 13.

We chose to use a percentile-type parameter to avoid the effects of negative HsHs. Regarding the extreme wave climate, we analyze the 50-year return value of HsHs, which was computed as in Casas-Prat and Sierra (2013) using a Generalized Pareto Distribution model. Fig. 16 and Fig. 17 show the median HsHs projected using Setting 5, with the predictors being derived before and after applying B-Raf inhibitor drug the adjustments to the model data, respectively. The upper panels show the present-day climatological values; whereas the

lower panels show the projected changes in future climates that are expressed as a portion of the present-day climatological value. Each column corresponds to one of the five sets of model simulations (see Section 3.2). As shown in Fig. 16, HIR_E model has a clear positive bias (overestimation of projected HsHs). The other models show more similar present-day wave climates, which have much smaller positive

biases. When forced by the same GCM ECHAM5, all four RCMs (HIR_E, RAC_E, REM_E, RCA_E) project future changes that share a common tendency for HsHs to increase in the NE part of the domain (up to 10%). An increase is projected for the area near the Gulf of Genoa, suggesting Navitoclax mw an increase in future cyclone activity in this important cyclogenesis area in the Mediterranean (see Section 2.1). This is consistent with the Urease projected increase in mean gust of gust event days in winter (October–March) reported by Schwierz et al. (2010), who analyzed CHRM (a RCM) simulations with the ECHAM5 and HadCM3/HadAM3 lateral boundary conditions. In the SW part of the domain, HsHs tends to decrease (up to 10%) but the extent of decrease varies between RCMs. HIR_E projects a more pronounced decrease; whereas the REM_E and RCA_E models project much more limited decreases. Similar patterns of projected mean wave climate were obtained by Casas-Prat and Sierra (2013) using dynamical downscaling. However, they simulated the area of increase (in the

NE part of the domain) closer to the Catalan coast. On the other hand, RCA_H (which is forced by the HadCM3Q3 global model) projects a general decrease of HsHs (up to 10%) over the entire domain (especially in the SE part). Close to the east-facing coasts, HsHs reduction is smaller and in some stretches it tends to remain the same or even to slightly increase. This spatial pattern of change is in agreement with what is projected by global models as presented in the study of Donat et al. (2010) and by the regional dynamical downscaling of Casas-Prat and Sierra (2013). Donat et al. (2010) found an increase of E flow for a model similar to HadCM3Q3 but a tendency of the increased W flow for those forced by the ECHAM5 global model.

Slice selective images demonstrating SQUARE MRI contrast (Fig. 3A–D) and the resulting T1 map (Fig. 3E) were acquired using a single animal. Images were processed and reconstructed in Prospa (v. 3.06, Magritek, Wellington, New Zealand)

by applying a sine-bell squared window function to the raw data before two-dimensional Fourier transformation. The two dimensional image data were exported for further analysis using IGOR Pro (v. 6.01; Wavemetrics, Lake Oswego, OR, USA). To construct the T1 map shown in Fig. 3E the image data were combined into a three dimensional matrix having two spatial dimensions (the slice selective images) and Everolimus one time dimension (the delay before acquisition). Linear regression analysis of the natural logarithm of the signal intensity as a function of delay time was used to obtain spatially resolved T1 values in Fig. 3E. Representative data from four selected volume elements in Fig. 3E are shown in Fig. 4. T1 values calculated outside the lung region were composed solely of background noise and were not displayed in Fig. 3E. The final T1 map was overlaid onto the lung image at delay time td = 0 s for clarity of presentation. Male Sprague–Dawley

rats (350–400 g, Charles River UK Ltd, Margate, UK) were euthanized by overdose of pentobarbital (Sigma-Aldrich Ltd, Gillingham, UK) in accordance with local animal welfare guidelines and the Animals (Scientific Procedures) Act (1986). Immediately after confirmation of death, a catheter was inserted into the caudal vena cava to allow flushing of the pulmonary circulation with VEGFR inhibitor 20–30 cm3 heparin 100 IU/cm3

(Wockhardt UK Ltd, Wrexham, UK) in 0.9% saline solution (Baxter Healthcare Ltd, Thetford, UK) followed with phosphate buffer solution (PBS, Sigma-Aldrich Ltd, Gillingham, UK) in order to remove residual blood from the pulmonary circulation. The heart and lungs were removed en masse. A polytetrafluorethylene (PTFE) adapter tube was inserted 5–10 mm above the carina and sutured into place. The heart and lungs were suspended in 5% glucose solution (weight/volume) with the trachea next pointing downwards in a custom-built acrylic ventilation chamber, as detailed in Fig. 1. The ex vivo lungs were repeatedly inflated with 8–10 cm3 of room air to check for leakage either from the suture around the trachea or the lungs themselves. For the presented work the lung harvesting procedure was completed with 100% success of removing the lungs intact. Normally with a skilled operator the ex vivo technique results in over 90% of lungs being suitable for imaging. The lungs were chilled to 278 K for transportation to the imaging facility. The pure gas phase relaxation time of 83Kr is sufficiently long with T1 times of several minutes at ambient pressure [16] to permit hp gas extraction and transfer.

Measurement of these factors is in keeping with previous research that has assessed CRC screening knowledge [52] and the UK General Medical Council guidelines GSK J4 mw for consent [15]. The phrasing and response options mirrored the gist-based style of the leaflet [53] and [54]. We calculated the total number of individuals who answered each statement correctly (statement totals) as well as the mean number of statements correctly answered per participant (individual

totals). Data from the semi-structured interviews were digitally recorded, transcribed verbatim, and analysed using thematic analysis, which is a qualitative technique for identifying patterns (themes) within data [55]. The purpose of the thematic analysis was to pin-point the particular areas of the gist-based leaflet that caused difficulties with comprehension. The majority of participants were female (75%), employed (54%), white (54%), had a GCSE level of education or below (57%), adequately literate (82%), without a partner (68%), ICG-001 spoke English as a first language (75%), and had either received a cancer diagnosis themselves (11%) or knew someone that had (82%). The majority had used written documents in their current of previous employment at least some of the time (75%) (see Table 1). As rounds progressed, more individuals had a lower level of education,

marginal or inadequate health literacy scores, spoke English as a second language, or were from a minority ethnic group. As demonstrated in Table 2, the majority of the Palmatine statements were answered correctly by at least 80% of participants. However, two statements (‘The FOB test is done at home’ [T] and ‘People with an abnormal result always have cancer’ [F]), were answered correctly by less than 80% of participants. At an individual level, participants were able to answer a mean of 7.2 out of

8 statements correctly (range = 5–8). In response to the threshold not being met for the statement that ‘the FOB test is done at home’, we changed the word ‘post’ to ‘home’ in the following sentence to clarify where the test was completed: ‘A FOB test kit with instructions is sent through to the home’. More than 20% of individuals did not correctly answer the statement that an abnormal test result does not necessarily mean cancer has been found. One participant commented that: ‘I do wonder about the fact that if you have an abnormal test that it doesn’t necessarily indicate that you’ve got cancer. That’s inferred but it doesn’t necessarily say that’ (AL, 55 years, female, degree level education). To improve comprehension of the meaning of an abnormal result, we added the following sentence: ‘An abnormal result does not always mean cancer has been found’.