Unrestrained individuals were studied during 40-60 min while supine, sitting and upright/walking. Position was changed repeatedly every 510 min. Initial qualitative diagnostic calibration followed by volume scaling in absolute units during 20 breaths in different positions

by flow meter provided position-specific volume-motion coefficients for RIP. These were applied during subsequent monitoring in corresponding positions according to feedback from 4 accelerometers placed at the chest and thigh. Accuracy of RIP was evaluated by face mask pneumotachography. Results: Position sensor feedback allowed accurate adjustment of RIP calibration during repeated position changes in subjects and patients as reflected in a minor mean difference (bias) in breath-by-breath tidal selleck volumes estimated by RIP and flow meter of 0.02 liters (not significant) and limits of agreement (+/- 2 SD) of +/- 19% (2,917 comparisons). An average of 10 breaths improved precision of RIP (limits of agreement 8 14%). Conclusions:

RIP calibration incorporating position sensor feedback greatly enhances the application of RIP as a valuable, unobtrusive tool to investigate respiratory physiology and ventilatory limitation in unrestrained healthy subjects and patients with lung disease during everyday activities including position changes. Copyright (C) 2009 S. Karger AG, Basel”
“Purpose Ruboxistaurin of reviewTo review research on the use of circulating biomarkers to predict unfavorable tumor pathology in the setting of active surveillance, or in clinical contexts that are informative for active surveillance, such Selleck CCI-779 as men with low-risk prostate cancer evaluated for upgrading or upstaging at surgery.Recent

findingsBiomarkers have been evaluated in serum, plasma, urine, and expressed prostatic secretions. Only a small number of biomarkers have been evaluated in multiple studies: %free prostate-specific antigen (PSA), PSA velocity, PSA doubling time, proPSA, PCA3, TMPRSS2-ERG. Single studies with relevance to active surveillance have evaluated microRNAs, circulating tumor cells, and exosomes. The most consistent significant associations with unfavorable tumor pathology have been with %free PSA. Associations with [-2]proPSA and Prostate Health Index have also been consistent; however, three of four studies come from the same active surveillance patient cohort.SummaryCirculating biomarkers represent a promising approach to identify men with apparently low-risk biopsy pathology, but who harbor potentially aggressive tumors unsuitable for active surveillance. Research is still at an early stage; existing biomarkers need rigorous validation with consistent methodology, and additional biomarkers need to be evaluated. Successful clinical translation would reduce the frequency of surveillance biopsies, and may enhance acceptance of active surveillance.”
“Introduction: Alloimmunization is the main cause of fetal anemia.

The manufacturing process involves fermentation of the production organism, extraction and purification of the l-asparaginase to make drug substance (DS), and finally formulation and lyophilisation to generate drug product (DP). The extensive manufacturing experience with the product was used to establish ranges for all process parameters and product quality attributes. The product and in-process intermediates were rigorously characterised, and new assays, such as size-exclusion and reversed-phase UPLC, were developed, validated, and used to analyse several pre-validation batches.

Finally, three prospective process validation batches see more were manufactured and product quality data generated using both the existing and the new analytical methods. These data demonstrated the process to be robust, highly reproducible and consistent, and the validation was successful, contributing to the granting of an FDA product license in November, 2011.”
“The reaction of dihydroquinopimaric acid methyl ester with bromine was found to be chemo- and stereoselective. Regardless of the solvent (acetic acid, methanol, dioxane), bromination of the title compound with an equimolar amount of bromine occurs as electrophilic addition at the double C-19=C-20 bond with formation of

14 alpha-hydroxy- CA4P or 14 alpha-methoxy-19R-bromo derivatives. The reaction with excess bromine (3 equiv) leads to the formation of 16S-bromo derivatives. The bromination process is accompanied by formation of epoxy bridge between the C-14 and C-20 atoms. X-Ray analysis revealed two polymorphic modifications of (16S,19R)-16,19-dibromo-14 beta,20-epoxydihydroquinopimaric P5091 mw acid methyl ester.”
“Shikonin (beta-alkannin), a naphthazarin derivative, has shown a variety of abilities such as anti-inflammatory, antitumoral, cytotoxic, and antimicrobial activities. In the presence of Cu(II), shikonin caused breakage of supercoiled plasmid pBR322 DNA. Other

metal ions tested [Mg(II), Ca(II), and Ni(II)] were ineffective and only Fe(II) has the same ability in the DNA breakage reaction. The involvement of active oxygen in the reaction was established by the inhibition of DNA breakage by superoxide dismutase, catalase, thiourea, sodium azide, potassium iodide, and sodium benzoate. Cu(I) was shown to be an essential intermediate using the Cu(I)-specific sequestering reagent neocuproine. Shikonin induced HeLa cell apoptosis involved in the mechanism of increasing intracellular reactive oxygen species (ROS). It was suggested that shikonin generated ROS as a pro-oxidant in the presence of Cu(II), and ROS resulted in DNA damage and apoptotic cell death in cells.”
“Armillaria sp. F022 is a white-rot fungus isolated from a tropical rain forest in Indonesia that is capable of utilizing pyrene as a source of carbon and energy.

Integrated care changed the patient distribution, allowing the cardiologist to focus on serious pathologies while cardiovascular risk factors and stable patients were monitored in primary care. In ischemic heart disease,

improvement was observed in cholesterol management and blood pressure control; optimal medical treatment was more frequently prescribed and ventricular function evaluated more often. In heart failure, beta-blockers CBL0137 Apoptosis inhibitor treatment increased and functional class was assessed more often. In atrial fibrillation, an increase in anticoagulation prescription and echocardiography evaluation was observed. Satisfaction parameters improved with integrated care. The use of resources was not increased.

Conclusions: Using our integration model, follow-up and chronic treatment of patients with ischemic heart disease, heart failure, and atrial fibrillation were improved. Monitoring of chronic patients was redistributed between primary care

and cardiology, and family physicians’ satisfaction levels improved. There was no increase in use of resources. (C) 2011 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S. L. All rights reserved.”
“The aim of the present review is to provide an update of the epidemiological evidence of the effects of air pollution on buy JNK inhibitor neuropsychological development and impairment, as well as of the evidence on individual susceptibility to these effects. Animal studies have shown deposition of ultrafine particles containing

metals in olfactory bulb and frontal cortical and subcortical areas, and overexpression of inflammatory responses, white matter lesions and vascular pathology in these areas that could be the basis for functional and structural brain effects. Several observational studies in the general population have observed cognitive deficits and behavioural impairment in children and the elderly. These effects, however, are not conclusive given the limited number of studies, their small size and their methodological constraints.”
“We assessed knowledge and perceptions of epilepsy held by Korean adolescents in the general population, and PI3K inhibitor investigated factors important in adolescents’ perceptions of stigma with respect to epilepsy. Surveys were distributed to students at 22 schools. A total of 1377 students participated. Fewer than half of all students (45.1%) reported hearing or reading about epilepsy. Overall, students showed a general lack of familiarity with and knowledge of epilepsy. Stigma perception scores were significantly higher in boys than in girls (P<0.05) and in middle school than in high school (P<0.05) students. We also found that stigma perception scores were significantly correlated with both younger age (r=-0.074, P=0.006) and lower knowledge scores (r=-0.404, P=0.000). Linear regression analysis showed that stigma-related perception was associated with lower knowledge scores (P<0.001) and middle school (P<0.05).

18; P = .035), higher New York Heart Association functional class (rank sums: P = .022) and impaired renal function (eGFR: r = -0.53; P < .0001; cystatin C: r = 0.60; P < .0001). Plasma NGAL levels selleck chemicals llc were modestly associated with indices of diastolic dysfunction (mitral E/Ea: r = 0.27; P = .002; LAVi: r = 0.25; P = .011; tricuspid E/Ea: r = 0.20; P = .029), but not after adjustment for renal function (P > .10 for all). In Cox proportional hazards analysis, plasma NGAL predicted cardiac death or transplantation after adjustment for age, gender, left ventricular ejection fraction, and mitral E/Ea (hazard ratio 1.68, 95% confidence interval 1.08-2.57; P = .022), but not after adjustment for renal function (P = .83). In

the acute HF cohort, we did not observe any relationship between NGAL and hemodynamic indices, but NGAL strongly correlated with renal function.

Conclusions: Systemic NGAL levels are largely learn more determined by underlying impairment of renal rather than myocardial function. Our findings did not support any prognostic significance or relationship between systemic NGAL levels and indices of cardiac structure and function after adjustment for underlying renal function. (J Cardiac Fail 2011;17:472-478)”
“Radioprotective agents are synthetic compounds or natural products that are immediately administrated before irradiation to reduce injuries caused by ionizing radiation. Toxicity, short duration,

and the unfavorable routes of administration, have prevented the widespread use of most radioprotective agents in practice. This study aimed to evaluate the use of slowly release- long circulation biodegradable polymer Poly(lactide-co-glycolide) (PLGA) as carrier for

radioprotective agents. Penicillamine and KI were selected as models for water soluble radioprotectors that can be used to protect against both internal radionuclide (chronic radiation exposure) and external-beam irradiation (acute radiation exposure). Emulsion-solvent evaporation method (ESE) was used to prepare hydrophilic-drug loaded PLGA Nanoparticles (PLGA- NPs) in an efficient and reproducible manner. The radioprotective efficacy was assessed by 30 days-survival percentage, relative body weights, and (liver & spleen) total cell counts. Results revealed that just single oral administration of Penicillamine-NPs or KI-NPs Selleck Epigenetic inhibitor was as effective as free drug taken for 5 successive days which indicate that PLGA-NPs could be used to modulate radioprotective drug activity in biological system, and to improve drug efficacy in different body organs for longer duration than the equal dose of free drug.”
“The structural, magnetic, and magnetostrictive properties of 75 nm Fe(100-x)Ga(x) films (0 <= x <= 30) have been studied to determine how a forming field during growth affects these properties. Two film sets were grown using a cosputtering-evaporation technique with and without a forming field of 65 kA m(-1).

Operative notes for patients taking tamsulosin at the time of surgery were reviewed. Preoperative dilated pupil diameter; use of prophylactic intracameral lidocaine epinephrine; and presence of billowing iris, iris prolapse, and pupil constriction were recorded. Intraoperative floppy-iris syndrome was defined as the occurrence of any of the 3 phenomena constituting the syndrome.

RESULTS: DMH1 cost Review of 1163 charts identified 59 patients (81 eyes) taking tamsulosin at the time of surgery. The overall incidence of IFIS was 29.6%. Of those who received prophylactic intracameral lidocaine epinephrine, the incidence of IFIS was 38.5%. The incidence of IFIS was 44.8% in eyes with preoperative dilated pupil diameter

smaller than 6.5 mm and 21.7% in eyes with ZD1839 datasheet a preoperative dilated pupil diameter larger than 6.5 mm. A preoperative dilated pupil diameter smaller than 6.5 mm was significantly associated with IFIS (P = .032).

CONCLUSIONS: The incidence of IFIS was lower than previously reported. Use of prophylactic intracameral lidocaine epinephrine did not reduce the incidence of IFIS. A preoperative dilated pupil diameter smaller than 6.5 mm was significantly associated with

an increased incidence of IFIS.”
“BACKGROUND: Used frequently for right ventricular dysfunction (RVD), the clinical benefit of inhaled nitric oxide (iNO) is still unclear. We conducted a randomized, double-blind, controlled trial to determine the effect of iNO on post-operative outcomes in the setting of left ventricular assist device (LVAD) placement.

METHODS: Included were 150 patients undergoing LVAD placement with pulmonary vascular resistance >= 200 dyne/sec/cm(-5). Patients received iNO (40 ppm) or placebo (an equivalent concentration

of nitrogen) until 48 hours after separation from cardiopulmonary bypass, extubation, or upon meeting study-defined RVD. For ethical reasons, crossover to open-label iNO was allowed during the 48-hour treatment period if RVD criteria were met.

RESULTS: RVD criteria were met by 7 of 73 patients (9.6%; 95% confidence interval, 2.8-16.3) in the iNO group compared with 12 of 77 (15.6%; 95% confidence interval, 7.5-23.7) MAPK inhibitor who received placebo (p = 0.330). Time on mechanical ventilation decreased in the iNO group (median days, 2.0 vs 3.0; p = 0.077), and fewer patients in the iNO group required an RVAD (5.6% vs 10%; p = 0.468); however, these trends did not meet statistical boundaries of significance. Hospital stay, intensive care unit stay, and 28-day mortality rates were similar between groups, as were adverse events. Thirty-five patients crossed over to open-label iNO (iNO, n = 15; placebo, n = 20). Eighteen patients (iNO, n = 9; placebo, n = 9) crossed over before RVD criteria were met.

CONCLUSIONS: Use of iNO at 40 ppm in the perioperative phase of LVAD implantation did not achieve significance for the primary end point of reduction in RVD.

FYMC or estimated cost per life saved Ricolinostat ic50 for IS or TIA/unspecified was lower relative to SAH or ICH; however,

their estimated cost per life-year saved became higher because of reduced life expectancy. Copyright (C) 2013 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved.”
“Purpose: The proximal abdominal aortic aneurysm (AAA) neck expands significantly during the cardiac cycle, both before and after endovascular aneurysm repair (EVAR). Clinical consequences of this pulsatility were anticipated but have never been reported. This study investigated whether there is a relation between stent graft migration and preoperatively measured pulsatility of the proximal aneurysm neck.

Methods: EVAR patients with a preoperative this website dynamic computed tomography angiography (CTA), an immediate postoperative, and a CTA at 3 years after EVAR were included. The preoperative dynamic CTAs consisted of eight images per heartbeat. Aortic diameter and area changes per heartbeat were measured at two levels: (A) 3 cm above and (B) 1 cm below the most distal renal artery. Postoperatively,

the distance between the most distal renal artery and the most proximal stent graft ring was measured. Two patient groups were distinguished according to whether migration during follow-up occurred (group 1) or had not occurred (group 2). The aneurysm neck dynamics of the two groups were compared by using the t-test for unpaired data and multivariable logistic regression analyses

were performed. Mean values are presented with the standard deviation.

Results: Included were 26 patients (19 Talent, 6 Excluder and 1 Lifepath). Stent graft migration of >= 5 mm occurred in 11 patients (group 1). The pulsatility of the AAA neck in these patients was compared with the pulsatility in 15 patients with no graft migration (group 2). There were no significant differences in aortic neck characteristics (angulation, length and diameter) or degree of stent graft oversizing between the two groups. At level A in group 1 versus group 2, the diameter increase during the cardiac cycle was 2.0 +/- 0.3 versus 1.7 +/- 0.3 mm and the aortic area increase was 49 +/- 15 versus 33 +/- 12 mm(2). At level B in group 1 versus group 2, the diameter increase per heartbeat was 1.8 +/- 0.3 versus 1.6 +/- 0.4 mm, and the area increase was 37 +/- 10 Navitoclax versus 25 +/- 15 mm(2). The heartbeat-dependent diameter and area changes at both levels were significantly higher in group 1 compared with group 2. Multivariate regression analysis showed suprarenal aortic pulsatility was a significant predictor for stent graft migration after 3 years.

Conclusion: The preoperative heartbeat-dependent aneurysm neck distension is significantly associated with stent graft migration after 3 years. The aortic pulsatility in patients with stent graft migration is significantly higher than the pulsatility in patients without stent graft migration.

Subsequent damage to PSII might be the reason for the slow, or lack of recovery, for most of the parameters measured. (C) 2011 Elsevier Masson SAS. All rights reserved.”
“Write margin analysis of the bit patterned media (BPM) was experimentally carried out using a static tester. Sample BPM were fabricated from hard/soft-stacked (exchange-coupled composite; ECC) base media with a Pt/Co multilayer hard layer and a Co soft layer. Write

margins of 60-nm-dot (140 nm period) and 40-nm-dot (100 nm period) media were confirmed to be 80 nm and 50 nm, respectively. An analysis of the margin loss factor found a large residual margin loss. The loss factors of 60-nm-dot and 40-nm-dot media were 57 nm and 44 nm, respectively, and these values almost correspond to the dot diameter. The residual margin loss was identified Selleck GM6001 as due to the formation of a multi-domain structure within some dots under certain recording conditions. (C) 2011 American Institute of Physics. [doi:10.1063/1.3554201]“
“PURPOSE: To compare anterior chamber parameters in normal eyes and eyes with mild to moderate keratoconus corneas using rotating

Scheimpflug imaging and evaluate trends in corneal protrusion progression.

SETTING: Department of Ophthalmology, Semmelweis University, Budapest, Hungary.

METHODS: The anterior chamber depth (ACD) at the corneal center, thinnest point of the cornea, and 1.0 mm, 2.0 mm, and 3.0 mm paracentrally; central pachymetry; and posterior elevation were check details measured by Scheimpflug imaging (Pentacam) in eyes with keratoconus and eyes of refractive surgery candidates. A generalized estimating equation (GEE) was used to identify predictors

of keratoconus. Correlations between posterior elevation and ACD at minimum pachymetry were analyzed by linear and piecewise linear regression.

RESULTS: The keratoconus group comprised 41 eyes (24 patients) and the control group, 70 eyes (41 patients). The ACD was significantly deeper in the keratoconus group than in the control group (P<.05) Crenigacestat and was significantly correlated with posterior elevation. In the multivariable GEE model, posterior elevation (odds ratio [OR], 1.46; P<.001) and ACD at minimum pachymetry (OR, 7.54; 95% confidence interval, 1.35-42.05) were significant predictors of keratoconus. Segmented analysis of the correlation between posterior elevation and central ACD showed a better fit to data than linear regression and identified a 40 mu m threshold level for posterior elevation. The GEE determined 450 mu m as a similar threshold for central corneal thickness.

CONCLUSION: There was a threshold level of posterior corneal elevation and corneal thickness values beyond which the level of corneal protrusion in keratoconus accelerated.

This phenomenon, combined with chronic administration of L-DOPA, leads to persistent and intermittent hyper-activation of the cAMP signaling cascade. Activation of cAMP signaling results in increased activity of the cAMP-dependent protein kinase (PKA) and of the dopamine and cAMP-dependent phosphoprotein of 32 kDa (DARPP-32), which regulate several downstream effector targets implicated in the control of the excitability of striatal

MSNs. Dyskinesia is also accompanied by augmented activity of the extra cellular Dibutyryl-cAMP in vivo signal-regulated kinases (ERK) and the mammalian target of rapamycin complex 1 (mTORC1), which are involved in the control of transcriptional and translational efficiency. Pharmacological or genetic interventions aimed at reducing abnormal signal transduction at the level of these various intracellular cascades have been shown to attenuate LID in different animal models. For instance, LID is reduced in mice deficient for DARPP-32, or following inhibition of PKA. Blockade of ERK obtained genetically or using specific inhibitors is also able to attenuate dyskinetic behavior in rodents and non-human primates. Finally, administration buy SU5402 of rapamycin, a drug which blocks mTORC1, results in a strong reduction

of LID. This review focuses on the abnormalities in signaling affecting the D1R-expressing MSNs and on their potential relevance

for the design of novel anti-dyskinetic therapies.”
“Purpose Polycystic ovary syndrome (PCOS) is a most common endocrine disorder of reproductive age women. Interleukin-6 is involved in the pathophysiological characteristics associated with polycystic ovary syndrome (PCOS). The-174 G/C IL-6 gene promoter region single nucleotide polymorphism (SNP) may influence or modulate gene function and/or transcriptional efficiency. The current study was aimed to evaluate the association between IL-6 gene -174 G/C promoter polymorphism and Polycystic Ovary SB202190 solubility dmso Syndrome in South Indian women.

In the present study, we examined the genotypic and allele distribution among the PCOS patients (n = 104) and controls (n = 156). The genotypes of IL-6 -174 G/C SNP were analyzed by polymerase chain reaction (PCR) and sequencing analysis. The allele frequency and genotype distributions of cases and controls were analyzed using Fisher’s exact test.

The genotype frequencies observed among the 104 cases and 156 controls were G/G 66.3 % and 49.4 %, G/C 29.8 % and 46.8 %, and C/C 3.8 % and 3.8 % (OR: 1.6226, CI: 1.0574-2.4899). The G and C allele frequencies were 81.25 % and 72.8 %, and 18.75 % and 27.2 %, respectively. The genotype and allele distribution revealed significant differences between PCOS patients and controls (all P values < 0.05).

There were significant differences among the journals with regard to the use of the intention-to-treat principle. The relative number of trials in which the principle was used increased each year. The authors adhered to the strict definition of the intention-to-treat principle in forty-five of the ninety-six studies in which it was claimed that this principle had been used. In forty-four randomized trials, patients who had been lost to follow-up were excluded from the final analysis; LY333531 in vitro this practice was most notable in studies of

surgical interventions. The most popular method of adjusting for missing data was the “”last observation carried forward”" technique.

Conclusions: In most of the randomized clinical trials published in the orthopaedic literature, the investigators did not adhere to the stringent use of the intention-to-treat principle, with the most conspicuous problem being a lack of accounting for patients lost to follow-up. This omission

might introduce bias to orthopaedic randomized clinical trials and their analysis.”
“In this study, the composition of fatty oil from Semen Ziziphi Spinosae and its cardiotonic activity on the heart isolated from a toad were studied. Oil-in-water (O/W) emulsions of fatty oil were prepared ALK targets by the perfusion method. The fatty oil had a positive inotropic effect on isolated rat hearts at a concentration between 5 x 10(-3) and 2 x 10(-2) mL/10 mL, and the effect was in positive correlation with the concentration of calcium ions. In addition, this effect was inhibited by 2 mg/mL nifedipine, suggesting that the cardiotonic mechanism could be responsible for accelerating the inflow of calcium ions. Gas chromatography-mass spectrometry analysis showed that the main constituents of the fatty oil were 9-octadecenoic acid (43.32%), 9,12-octadecadienoic acid (42.57%), hexadecanoic acid (4.76%), 9-eicosenoic acid (2.95%), stearic acid (2.41%) and arachidic acid (0.81%). This preliminary study revealed that the fatty

oil of Semen Ziziphi Spinosae exhibited remarkable cardiotonic activity in the tested models, and it is necessary to further reveal the effective substances of the fatty oil.”
“The goal of this study is to evaluate the accuracy of patient-specific CT-based rapid prototype drill templates for C2 translaminar p38 MAPK inhibitor review screw insertion.

Volumetric CT scanning was performed in 32 cadaveric cervical spines. Using computer software, the authors constructed drill templates that fit onto the posterior surface of the C2 vertebrae with drill guides to match the slope of the patient’s lamina. Thirty-two physical templates were created from the computer models using a rapid prototyping machine. The drill templates were used to guide drilling of the lamina and post-operative CT images were obtained. The entry point and direction of the planned and inserted screws were measured and compared.

Sixty-four C2 translaminar screws were placed without violating the cortical bone of a single lamina.

5% and 37.3%.”
“Objective-To develop a syndromic surveillance system based on visual inspection from outside the livestock pens that could be used for detection of disease among livestock entering an auction market.

Design-Cross-sectional study.

Animals-All livestock (beef and dairy cattle, sheep, goats, horses, and pigs) entering a single auction market in Colorado during 30 business days.

Procedures-Livestock

were enumerated and visually inspected for clinical signs of disease by a veterinarian outside the pens, and clinical signs that were GS-1101 observed were categorized into 12 disease syndromes. Frequency of clinical signs and disease syndromes was then calculated.

Results-Data MK-2206 nmr were recorded for a total of 29,371 animal observation days. For all species combined, the most common disease syndrome was respiratory tract disease (218.9 observations/10, 000 animal observation days), followed by thin body condition and abnormal ambulation or posture (80.7 and 272 observations/10, 000 animal observation days, respectively). Together, these 3 disease syndromes accounted for 92.8% of all clinical signs of disease observed. The syndromes least commonly identified were non-injury-related hemorrhage, death, and injury-related hemorrhage (0.0, 0.3, and 0.7 observations/10,000

animal observation days, respectively).

Conclusions and Clinical Relevance-Results suggested that a syndromic surveillance system based on visual inspection alone could be developed to identify

possible disease conditions among livestock at an auction market. Further studies are needed to determine the sensitivity and specificity of visual observation in detecting disease. (J Am Vet Med Assoc 2009;234:658-664)”
“This paper reviews the state of knowledge on modelling air flow and concentration fields at road intersections. The first part covers the available literature from the past two decades on experimental (both field and wind tunnel) and modelling activities in order to provide insight into the physical basis of flow behaviour at a typical cross-street intersection. This check details is followed by a review of associated investigations of the impact of traffic-generated localised turbulence on the concentration fields due to emissions from vehicles. There is a discussion on the role of adequate characterisation of vehicle-induced turbulence in making predictions using hybrid models, combining the merits of conventional approaches with information obtained from more detailed modelling. This concludes that, despite advancements in computational techniques, there are crucial knowledge gaps affecting the parameterisations used in current models for individual exposure.