The impact of endoxifen-guided tamoxifen dose reductions on endocrine side-effects in patients with primary breast cancer.

BACKGROUND: Tamoxifen is important in the adjuvant treatment of hormone-sensitive breast cancer and substantially reduces recurrence; however, almost 50% of patients are non-compliant mainly due to side-effects. The aim of this study was to investigate whether endoxifen-guided tamoxifen dose reduction could lead to fewer side-effects. MATERIALS AND METHODS: Effects of tamoxifen dose reduction were investigated in patients with bothersome side-effects and endoxifen levels ≥32 nM and compared to patients with side-effects who remained on tamoxifen 20 mg. Endocrine symptoms and health-related quality of life (HR-QOL) were assessed after 3 months with the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) questionnaire. RESULTS: Tamoxifen dose was reduced in 20 patients, 17 of whom were assessable for side-effect analyses. A clinically relevant improvement of >6 points was observed in endocrine symptoms and HR-QOL in 41% and 65% of the patients, respectively. In total, there was a significant and clinically relevant improvement in endocrine symptoms [5.7, 95% confidence interval (CI) -0.5-11.5] and HR-QOL (8.2, 95% CI 0.9-15.4) after dose reduction. This was not seen in patients whose doses were not reduced (n = 60). In 21% of patients, endoxifen dropped slightly below the 16-nM threshold (12.8, 15.5, 15.8, 15.9 nM). CONCLUSIONS: Endoxifen-guided dose reduction of tamoxifen significantly improved tamoxifen-related side-effects and HR-QOL. Nearly 80% of patients remained above the most conservative endoxifen threshold.

Single nucleotide polymorphism (SNP) rs3751143 in P2RX7 is associated with therapy failure in chronic Q fever while rs7125062 in MMP1 is associated with fewer complications.

OBJECTIVES: Chronic Q fever is a persistent infection with the intracellular bacterium Coxiella burnetii. Development of chronic Q fever is associated with single nucleotide polymorphisms (SNPs) in genes encoding for pattern recognition receptors, for phagolysosomal pathway components and for matrix metalloproteinases (MMPs). We evaluated the association of SNPs in these innate-immunity and MMP genes with clinical outcomes. METHODS: SNPs were selected from previous association studies and analysed in a cohort of patients with chronic Q fever. The primary outcome was all-cause mortality; secondary outcomes were therapy failure and chronic Q fever-related complications. Subdistribution hazard ratios (SHR) were calculated. RESULTS: Nineteen SNPs were analysed in 134 patients with proven and 29 with probable chronic Q fever. In multivariable analysis, none of the selected SNPs was associated with all-cause mortality. However, SNP rs3751143 located in P2RX7 appeared to be associated with therapy failure (SHR 2.42; 95% confidence interval, 1.16-5.05; p 0.02), which is in line with other reports, showing that a loss of function of the P2X7 receptor leads to inefficient killing of intracellular organisms. In addition, SNP rs7125062 located in MMP1, involved in the cleavage of extracellular matrix, was associated with fewer chronic Q fever-related complications such as acute aneurysms (SHR 0.49; 95% confidence interval, 0.29-0.83; p 0.008). CONCLUSIONS: A polymorphism in P2RX7, known to lead to loss of function of the receptor and inefficient killing of intracellular organisms, and a polymorphism in MMP1 were respectively associated with more therapy failures and fewer complications such as acute aneurysms in patients with chronic Q fever.

Light-based monitoring devices to assess range use by laying hens.

Access to an outdoor range has many potential benefits for laying hens but range use can be poor due to factors only partly understood. Techniques to monitor individual range use within commercial flocks are crucial to increase our understanding of these factors. Direct observation of individual range use is difficult and time-consuming, and automatic monitoring currently relies on equipment that is difficult to use in an on-farm setting without itself influencing range use. We evaluated the performance of a novel small, light and readily portable light-based monitoring system by validating its output against direct observations. Six commercial houses (2000 hens/house) and their adjacent ranges were used, three of which were equipped with more structures on the range than the others (to determine whether cover would influence monitoring accuracy). In each house, 14 hens were equipped with light monitoring devices for 5 discrete monitoring cycles of 7 to 8 consecutive days (at 20, 26, 32, 36 and 41 weeks of age). Light levels were determined each minute: if the reading on the hen-mounted device exceeded indoor light levels, the hen was classified as outside. Focal hens were observed directly for 5 min/hen per week. Accuracy (% of samples where monitoring and direct observations were in agreement) was high both for ranges with more and with fewer structures, although slightly better for the latter (92% v. 96% ± 1 SEM, F1,19 = 5.2, P = 0.034). Furthermore, accuracy increased over time (89%, 94%, 95%, 98% ± 1 SEM for observations at 26, 32, 36 and 41 weeks, respectively, F3,19 = 3.2, P = 0.047), probably due to progressively reduced indoor light levels resulting from partial closing of ventilation openings to sustain indoor temperature. Light-based monitoring was sufficiently accurate to indicate a tendency for a greater percentage of monitored time spent outside when more range structures were provided (more: 67%, fewer: 56%, SEM: 4, $\chi_1^2 = 2.9$, P = 0.089). Furthermore, clear and relatively consistent individual differences were detected. Individuals that were caught outside at the start of the experiment ranged more throughout its duration (caught outside: 72%, caught inside 51%, SEM: 4, $\chi_1^2 = 10.0$, P = 0.002), and individual range use was correlated between monitoring cycles (for adjacent monitoring cycles: $r_s^2 = 0.5-0.7$, P < 0.0001). This emphasizes the importance of studying range use on an individual level. In conclusion, our light-based monitoring system can assess individual range use accurately (although accuracy was affected by house characteristics to some extent) and was used to show that both cover availability and individual characteristics affected range use.

Assessing keel bone damage in laying hens by palpation: effects of assessor experience on accuracy, inter-rater agreement and intra-rater consistency.

Accurate assessment is essential when evaluating keel bone damage. Palpation is commonly used to assess keel bone damage in living hens. However, there is little information on the accuracy of assessment of deviations and fractures on different parts of the keel, and on the consistency within, and agreement between, assessors. Crucially, although the importance of experience is commonly emphasized, knowledge on its effect is scarce. Ten assessors with or without prior experience palpated the same 50 75-wk-old hens for deviations, medial fractures, and caudal fractures (scored as present/absent). Accuracy, sensitivity, specificity, precision, and negative predictive value were determined by comparing palpation scores to post-dissection assessment, and then compared between experienced and inexperienced assessors. To determine the effect of the experience gained during the experiment, hens were subsequently re-assessed. Consistency within, and agreement between, assessors were also determined. Assessors with prior experience were more accurate (proportion of accurately assessed deviations: experienced 0.83 vs. inexperienced 0.79±0.01, P = 0.04; medial fractures: 0.82 vs. 0.68±0.03 in session 1 only, P = 0.04; caudal fractures: 0.41 vs. 0.29±0.03, P = 0.03), and inexperienced assessors classified medial fractures more accurately in session 2 (session 1: 0.68 vs. session 2: 0.77±0.04, P = 0.04). However, effect sizes were small for deviations and even experienced assessors lacked accuracy when assessing caudal fractures. Unexpectedly, deviations tended to be assessed more accurately in session 1 than in session 2, regardless of assessor status (1: 0.83 vs. 2: 0.79±0.01, P = 0.06), suggesting that prolonged assessment contributes to errors. Prior experience decreased specificity and precision of fracture assessment (more unfractured keels were classified as fractured) even though overall accuracy was greater. Intra-rater consistency was fair to good (0.55 to 0.67) for deviations and medial fractures, but poor to fair (0.36 to 0.44) for caudal fractures, and unaffected by prior experience (P = 0.49 to 0.89). In conclusion, experience improves accuracy to a limited extent but does not guarantee high accuracy for all types of damage. Future research should determine if other training methods (e.g., comparison to post-dissection scores or to radiographs) improve accuracy.

Systematic review of the safety and efficacy of contrast injection via venous catheters for contrast-enhanced computed tomography.

OBJECTIVE: To examine the safety and efficacy of contrast injection through a central venous catheter (CVC) for contrast-enhanced computed tomography (CECT). METHODS: A systematic literature search was performed using PubMed. Studies were deemed eligible if they reported on the use of CVCs for contrast administration. Selected articles were assessed for their relevance and risk of bias. Articles with low relevance and high risk of bias or both were excluded. Data from included articles was extracted. RESULTS: Seven studies reported on the use of CVCs for contrast administration. Catheter rupture did not occur in any study. The incidence of dislocation ranged from 2.2-15.4%. Quality of scans was described in three studies, with less contrast enhancement of pulmonary arteries and the thoracic aorta in two studies, and average or above average quality in one study. Four other studies used higher flowrates, but did not report quality of scans. CONCLUSION: Contrast injection via CVCs can be performed safely for CECT when using a strict protocol. Quality of scans depended on multiple factors like flow rate, indication of the scan, and cardiac output of the patient. In each patient, an individual evaluation whether to use the CVC as access for contrast media should be made, while bolus tracking may be mandatory in most cases.

Sensitivity of the Welfare Quality® broiler chicken protocol to differences between intensively reared indoor flocks: which factors explain overall classification?

There is a large demand for holistic welfare assessment systems that result in a singular balanced summary of welfare. The Welfare Quality® (WQ) broiler protocol summarizes 18 welfare measures into four principles ('good feeding', 'good housing', 'good health' and 'appropriate behaviour'), which are then integrated into one overall category ('excellent', 'enhanced', 'acceptable' or 'not classified'). But the protocol is time consuming which hampers implementation. Furthermore, WQ's aim to assess animal welfare in a wide range of husbandry systems may decrease its ability to discriminate between flocks from the same system. We applied the protocol in the context of intensive indoor rearing to assess whether it discriminated sufficiently between flocks, could be shortened without losing essential information, and provided a balanced summary of welfare. The vast majority of the flocks (88%) received the same overall classification (acceptable) whilst all other flocks received an adjacent classification (enhanced), suggesting poor discriminative capacity. For 95% of the flocks overall classification was explained by two measures only ('drinker space' and 'stocking density'). A system based on these two measures would reduce assessment time from 3.5 h to a few minutes. However, both measures' validity can be questioned as they are risk factors for poor welfare rather than animal-based outcome measures and they suffer from methodological weaknesses. Furthermore, the possibility for such an extreme simplification raises doubts on whether the overall classification reflects a balanced summary of different welfare aspects. In line with this, overall classification was not affected by replacing single measures within the 'good health' and 'appropriate behaviour' principles with realistically attainable minima or maxima for intensively reared flocks. Even replacing either of these two principles entirely with their realistically obtainable minimum or maximum did not affect classification. Such insensitivity to change may discourage attempts to improve the welfare of intensively reared flocks when assessments are made based on the overall classification. This calls for an adjustment of the classification system, which is currently being developed by the Welfare Quality Network.

Effect of locomotion score on sows' performances in a feed reward collection test.

Sows housed in groups have to move through their pen to fulfil their behavioural and physiological needs such as feeding and resting. In addition to causing pain and discomfort, lameness may restrict the ability of sows to fulfil such needs. The aim of our study was to investigate the extent to which the mobility of sows is affected by different degrees of lameness. Mobility was measured as the sow's willingness or capability to cover distances. Feed-restricted hybrid sows with different gait scores were subjected to a feed reward collection test in which they had to walk distances to obtain subsequent rewards. In all, 29 group-housed sows at similar gestation stage (day 96.6 ± 7 s.d.) were visually recorded for gait and classified as non-lame, mildly lame, moderately lame or severely lame. All sows received 2.6 kg of standard commercial gestation feed per day. The test arena consisted of two feeding locations separated from each other by a Y-shaped middle barrier. Feed rewards were presented at the two feeders in turn, using both light and sound cues to signal the availability of a new feed reward. Sows were individually trained during 5 non-consecutive days for 10 min/day with increasing barrier length (range: 0 to 3.5 m) each day. After training, sows were individually tested once per day on 3 non-consecutive days with the maximum barrier length such that they had to cover 9.3 m to walk from one feeder to the other. The outcome variable was the number of rewards collected in a 15-min time span. Non-lame and mildly lame sows obtained more rewards than moderately lame and severely lame sows (P<0.01). However, no significant difference was found between non-lame and mildly lame sows (P=0.69), nor between moderately lame and severely lame sows (P=1.00). This feed reward collection test indicates that both moderately lame and severely lame sows are limited in their combined ability and willingness to walk, but did not reveal an effect of mild lameness on mobility. These findings suggest that moderately and more severely lame sows, but not mildly lame sows, might suffer from reduced access to valuable resources in group housing systems.

Effects of semi-group housing and floor type on pododermatitis, spinal deformation and bone quality in rabbit does.

The most common housing system for reproduction rabbits, individual cage housing on a wire floor, is increasingly scrutinized because of its potential detrimental impact on animal welfare. We compared three types of housing: (1) individual cage housing on a wire floor (3952 cm2/doe, maximum roof height 63 cm, one 1000 cm2 plastic footrest/doe), (2) semi-group housing on a wire floor (5000 cm2/doe, roofless, one 1000 cm2 plastic footrest/doe) and (3) the same semi-group housing, but with a fully plastic slatted floor. In all housing systems, does had free access to an elevated platform. In the semi-group housing pens, four does were housed communally during 21 days of the reproduction cycle (to allow more space for locomotion and to increase opportunities for social contact), and individually during the other 21 days of the cycle (to minimize doe-doe and doe-kit aggression that peaks around kindling). In all, 24 Hycole does were included per system. The does entered the experiment at 203 days of age (after their first parity). The experiment consisted of four reproductive cycles, ending at 369 days of age. Pododermatitis was scored in cycles 1, 2 and 4. At the end of the 4th cycle the does were euthanized and X-rays were taken to assess spinal deformation. Tibia and femur length, width and cortical thickness were determined and bone strength was assessed using a shear test, as a measure of bone quality. Although severe pododermatitis was absent, the prevalence of plantar hyperkeratosis (hair loss and callus formation) at the end of the 4th cycle was much greater on the wire floor (65% and 68% for semi-group housing and individual cages, respectively) than on the plastic floor (5%, P<0.0001), even though the wire floors were equipped with a plastic footrest known to decrease hyperkeratosis. In contrast to our expectations, semi-group housing did not affect the prevalence of spinal deformations (P>0.10), but in line with our expectations bone quality was affected favourably by semi-group housing. The tibial cortex (and to a lesser extent the femoral cortex) was thicker in semi-group housing than in individual cages (1.45, 1.46 and 1.38 mm for semi-group housing on wire, semi-group housing on plastic and individual housing on wire, respectively, P=0.045). What this increase in cortical thickness means in terms of doe welfare requires further study, as it may reflect an increase in activity resulting either from increased space for locomotion, or from fleeing aggressive pen mates.

Performance of an animal-based test of thirst in commercial broiler chicken farms.

Animal-based measures of thirst are currently absent from animal welfare monitoring schemes due to the lack of a well-validated indicator applicable for on-farm use. In the present study, an on-farm test based on voluntary water consumption from an unfamiliar open drinker was validated in a (semi-)commercial setting. To investigate the effect of thirst on water consumption, we subjected 4 flocks of 1,500 broilers to either 0 or 12 h of water deprivation and subsequently measured the amount of water that small subgroups consumed after the deprivation period (first experiment). Broilers that were water deprived before the test drank more than control broilers (P < 0.001). In a second experiment, a similar test was performed using 20 commercial broiler flocks in Belgium and Brazil. After a pretreatment water consumption test, the birds were subjected to 0 or 6 h of water deprivation, and a posttreatment water consumption test was conducted. Only in Brazil, deprived birds drank significantly more than controls in the posttreatment water consumption test (P < 0.001). A tendency for a difference was found in Belgium (P = 0.083). Pre- and posttreatment water consumption was higher in Brazil than in Belgium (P < 0.001). Stocking density and temperature influenced, respectively, the pretreatment and the control's posttreatment water consumption in Brazil, but not in Belgium. These results indicate that the water consumption test is sufficiently sensitive to discriminate between control and 12 h deprived flocks, and in Brazil even between control and 6 h deprived birds. The location of the test within the house did not affect the amount of water consumed in either experiment, suggesting that this variable does not have to be standardized. However, the amount of water consumed by broilers able to drink freely for a long period depended on indoor climatic variables (in Brazil only) and possibly genotype. This suggests that these variables need to be considered when interpreting the test outcome in terms of the thirst level experienced by the broilers.

Dehydration indicators for broiler chickens at slaughter.

Freedom of (prolonged) thirst is considered to be of paramount importance for animal welfare. This emotion normally results from dehydration, which can be measured using physiological indicators. Because no reliable physiological indicator for thirst was available for broilers, we aimed to identify such a measure in this study. This indicator would ideally be integrated into quality control systems in commercial slaughter plants. In the first experiment, water deprivation was manipulated systematically by withdrawing water for different durations (total water withdrawal for 0 (control), 24, 36, or 48 h, or a 10-d period with restricted access to water for 2 times 10 min per day). A significant decrease in drained blood content and BW occurred from 36 h of total water deprivation onward (both P = 0.03), whereas long-term restricted access tended to decrease drained blood content (P = 0.05). No effect of water deprivation or restriction on skin turgor was found. In the second experiment, water was withdrawn for 0 (control), 6, 12, 24, or 48 h. Plasma chloride concentration was increased after 6 h of water withdrawal, but did not rise further with longer withdrawal. If assessed at slaughter, chloride will thus mainly reflect the catching-to-slaughter interval. In contrast, plasma creatinine and hematocrit levels showed a numerical decrease after 6 h of water withdrawal, but rose again after prolonged withdrawal. Plasma creatinine values were significantly higher in 24-h-deprived birds than in 6-h-deprived birds (P < 0.01), allowing for discernment between water withdrawal during catching and transport from dehydration that had occurred on the farm. Blood sodium concentrations and plasma osmolality showed a steady increment between 0 and 24 h of water deprivation (P < 0.001 and P < 0.001 for both), and may thus be used to assess the combined effects of water deprivation on farm and during the catching-to-slaughter interval. These findings may form the basis of an on-farm or at-slaughter test that could be included in integrated animal welfare assessment schemes.

The influence of stocking density on broiler chicken bone quality and fluctuating asymmetry.

Because broiler chickens are juvenile animals undergoing physical development, stocking density during rearing may influence this development. Some of these physical changes may cause welfare problems, for example, decreased bone quality, which may lead to fracture during catching and transport. Others do not influence welfare directly but can be used as indicators of the animal's ability to cope with its environment (e.g., fluctuating asymmetry). The present study evaluates the effect of stocking density on bone quality and fluctuating asymmetry. Birds were stocked at densities of 2.4, 5.8, 8.8, 12.1, 13.6, 15.5, 18.5, and 21.8 birds/m(2) from 1 until 39 d of age. Increased stocking density had a negative effect on some aspects of bone quality (tibia curvature and shear strength). Tibias were shorter at high density, possibly due to increased curvature. Several other bone quality aspects (tibia weight, torsion, and dyschondroplasia, and femur curvature and epiphysis shape) remained unaffected. Middle-toe length was the only character that showed a significant increase with increasing density when each character was analyzed separately. Nevertheless, a composite index of fluctuating asymmetry, which combined data on all 11 measured characters, tended to increase with stocking density. Such increased fluctuating asymmetry may indicate decreased welfare. However, one of the assumptions of fluctuating asymmetry is that the animal is subjected to the same environmental influences on both sides. This assumption may not be fulfilled when leg deformations occur, as these may lead to asymmetric changes in bone growth by altering the division of force over the 2 legs. In addition, leg deformations decrease the accuracy of bone length measurements made in a straight line. This raises some concerns on the applicability of fluctuating asymmetry measurements on broiler chicken legs, especially because stocking density did not effect the asymmetry of the head.

Cage size and enrichment effects on the bone quality and fluctuating asymmetry of fattening rabbits.

We studied the effect of increased cage size on different aspects of bone quality (bone strength, diameter, weight, and length) and fluctuating asymmetry (FA). Such characteristics may indicate improved animal welfare, as greater bone quality may decrease fracture incidence during handling, whereas decreased FA has been suggested to signal decreased stress. As stress is likely not only influenced by the quantity of space, but also by its quality, we also studied the effect of environmental enrichment. Groups of 8 rabbits were housed in wire open-top cages of 0.40, 0.46, 0.53, 0.64, 0.80, 1.07, and 1.60 m(2) from weaning until slaughter. All cages of 0.40 and 0.46 m(2) (12 cages/size) were left barren to allow sufficient mobility. One-half of the larger cages were enriched with a wooden-enrichment structure that could be used to gnaw on, hide in, or lie in (6 cages per size × enrichment treatment). Increased cage size led to an increase in tibiofibula diameter (P = 0.008), a tendency for increased tibiofibula weight (P = 0.051), and decreased FA (P = 0.010), suggesting improved welfare. Bone length and strength were not affected by cage size (P > 0.1). Enrichment did not affect FA (P > 0.1), in contrast with our expectations based on previous glucocorticoid analysis. This discrepancy between indicators may be due to sensitivity to other types of stressors or different sensitive periods. In summary, rabbits housed in larger cages had wider, heavier bones, but the absence of changes in bone strength indicate that this is unlikely to result in decreased fracture incidence. In larger cages, FA was lower, suggesting a favorable effect on welfare, whereas no effect of enrichment was shown.

Adherence and profile of non-persistence in patients treated for osteoporosis--a large-scale, long-term retrospective study in The Netherlands.

SUMMARY: We analyzed 12-month compliance for all ten oral osteoporosis drugs in the Netherlands by medication possession ratio (MPR ≥ 80%) in 105,506 patients, and persistence in 8,626 starters indicated high MPR (91%), low persistence (43%), and no restart in 78% of the stoppers after 18 months. INTRODUCTION: We studied compliance and persistence for all available oral osteoporosis medications on a national scale in the Netherlands. METHODS: We analyzed the IMS Health's longitudinal prescription database, which represents 73% of all pharmacies in the Netherlands. Twelve-month compliance was measured by medication possession ratio (MPR) in a cross-sectional cohort of 105,506 patients who received at least three prescriptions. Twelve-month persistence (no gap in refills for >6 months) was measured in all 8,626 consecutive patients starting therapy, with a further follow-up in non-persistent patients during an additional 18 months for evaluation of switching, restart, or definitive stopping oral medication. Multivariate logistic regression analysis was used to analyze the odds ratios (ORs) with 95% confidence intervals (CI) of characteristics of non-persistence. RESULTS: MPR of ≥80% was found in 91% of patients. Persistence was 43% (range, 29-52%). Persistence was related to age >60 years (ORs, 1.41 to 1.64), pharmacy outside very dense urban area (ORs, 1.39 to 1.44), additional use of calcium and/or vitamin D supplementation (OR, 1.26 and CI, 1.13, 1.39) and use of glucocorticoids (OR, 0.65 and CI, 0.59, 0.72) or cardiovascular medication (OR, 0.88 and CI, 0.79, 0.97). Of non-persistent patients, 22% restarted within 18 months with oral osteoporosis drugs. CONCLUSIONS: One-year compliance for all available oral osteoporosis medications was high, but 1-year persistence was low. Most stoppers did not restart or switch during an additional 18-month follow-up. These data indicate a major failure to adequately treat patients at high risk for fractures in daily practice.

Stocking density effects on broiler welfare: identifying sensitive ranges for different indicators.

Although stocking density is perceived as a topic of major importance, no consensus has been reached on what density would allow for good welfare. In the present study, the welfare of 4 replicates of birds stocked at 8, 19, 29, 40, 45, 51, 61, and 72 broilers per pen (or 6, 15, 23, 33, 35, 41, 47, and 56 kg actually achieved BW/m(2)) was studied using 6 welfare indicators. Density did not affect bursa weight, mortality, or concentrations of corticosterone metabolites in droppings but did influence leg health (P = 0.015) and footpad and hock dermatitis (P < 0.001) and tended to influence fearfulness (P = 0.078). However, not every increase in density or group size, or both, led to poorer welfare for the affected indicators: leg health and fearfulness showed unexpected peaks at intermediate densities. Furthermore, the indicators were influenced at different densities: leg strength showed a steep decrease from 6 to 23 kg/m(2), hock dermatitis rose from 35 to 56 kg/m(2), and footpad dermatitis and fearfulness were only significantly higher at the highest density of 56 kg/m(2). No threshold stocking density above which all aspects of welfare were suddenly altered was found in this study. Instead, different aspects of welfare were influenced at different densities or group sizes, or both. Thus, evaluating the effects of stocking density on welfare as a whole would require either identification of acceptable levels for each separate indicator or a weighting of the indicators in an integrated welfare score. A tentative attempt to such an integration, made using equal weights for all parameters, showed a decrease in welfare as density increased (P < 0.001). The lowest 2 densities (6 and 15 kg/m(2)) scored better than most middle densities (23, 33, 35, and 47 kg/m(2)), whereas all densities scored better than the highest density (56 kg/m(2)).