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CORD-19:a32993b4b78f5f8416251c365f8705364bebee58 JSONTXT 8 Projects

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Id Subject Object Predicate Lexical cue
T1 0-59 Sentence denotes in the Guide for rats weighing <100 g (17 in 2 per rat) 1 .
T2 60-243 Sentence denotes At Charles River Laboratories, rats younger than 5 weeks are commonly housed at higher densities without high frequency of wounds, failure to thrive or other visible stress reactions.
T3 244-375 Sentence denotes At 5 weeks of age, rats are either shipped to research facilities or housed according to the Guide's current space recommendations.
T4 376-475 Sentence denotes When they arrived at our facility, the F344 rats were 35-42 d old and the LE rats were 30-36 d old.
T5 476-839 Sentence denotes Rats were free of Sendai virus, pneumonia virus of mice, coronavirus, Kilham's rat virus, Toolan's H-1 virus, rat parvovirus, rat minute virus, reovirus, Mycoplasma pulmonis, lymphocytic choriomeningitis virus, hantavirus, ciliaassociated respiratory bacillus, Salmonella spp., Shigella spp., Leptospira spp., Spirillum minus, Helicobacter spp. and ectoparasites.
T6 840-925 Sentence denotes We continued to monitor rats with sentinel testing throughout all stages of research.
T7 926-1013 Sentence denotes First stage: housing density study Rats arrived at our facility weighing 75-110 g each.
T8 1014-1257 Sentence denotes Rats were ear-tagged for identification and then used in a separate study in which they were housed for 8 weeks at either a high density (5-7 rats per cage; 20.5-28 in 2 floor space per rat) or a low density (2 rats per cage; 72 in 2 per rat).
T9 1258-1299 Sentence denotes Rats were separated by gender and strain.
T10 1300-1458 Sentence denotes For high-density housing, LE and F344 rats were housed, respectively, at 2-3 times and 1.1-1.4 times less space per rat than what is recommended in the Guide.
T11 1459-1598 Sentence denotes For low-density housing, the amounts of floor space per rat for both strains were equal to or greater than the Guide's standard allowances.
T12 1599-1711 Sentence denotes During this stage of the study, all rats were subjected to similar manipulations and data collection procedures.
T13 1712-1829 Sentence denotes None of the rats showed evidence of dominant or submissive behavior such as biting or barbering (excessive grooming).
T14 1830-1911 Sentence denotes Each rat was within the expected weight range for its age, strain and gender 28 .
T15 1912-2047 Sentence denotes No other signs of excessive stress or aggression, including inappetence, hunched posture or lethargy, were observed in any of the rats.
T16 2048-2127 Sentence denotes Chromodacryorrhea was noted in some of the rats during this stage of the study.
T17 2128-2197 Sentence denotes We began the second stage of research when rats were 12-13 weeks old.
T18 2198-2299 Sentence denotes The average age of puberty for rats is blood cell (WBC) count and serum corticosterone concentration.
T19 2300-2443 Sentence denotes Changes to these parameters might indicate distress that is not evident by observation and that could affect research data collected from rats.
T20 2444-2716 Sentence denotes Previous studies have evaluated the effects of housing density on young mice or rats but have not continued to investigate whether these animals would be useful for research purposes if regrouped with unfamiliar animals at an older age 2, 4, 8, 9, 11, 12, [17] [18] [19] .
T21 2717-2882 Sentence denotes One group of researchers reported that housing post-pubertal Sprague Dawley rats at high densities resulted in decreased muscle mass in males but not in females 20 .
T22 2883-3178 Sentence denotes In another study, 56-d-old Sprague Dawley rats that were arbitrarily grouped at high densities (3 rats per cage) showed no significant differences in fighting frequency or weight gain compared with rats that were housed singly; in addition, grouphoused rats had lower blood pressure at night 3 .
T23 3179-3400 Sentence denotes In several studies of adult rats that were housed at high densities with unfamiliar rats, researchers observed behavioral changes associated with fighting and dominance in males, though not in females 17, [21] [22] [23] .
T24 3401-3680 Sentence denotes Studies that evaluated social behaviors related to fighting, dominance and territorial aggression reported that male rats older than 100 d showed territorial aggression and social dominance, whereas juvenile rats only showed play-fighting behavior [21] [22] [23] [24] [25] [26] .
T25 3681-3856 Sentence denotes Another researcher showed that in male Wistar rats, the behavioral and physiological effects of high-density housing were dependent on the developmental stage of the rats 27 .
T26 3857-3989 Sentence denotes These reports indicate that both gender and age may affect behavioral and physiological parameters in rats housed at high densities.
T27 3990-4167 Sentence denotes In this study, we examined male and female rats from two strains that are commonly used in research, the outbred Long Evans (LE) strain and the inbred Fischer 344 (F344) strain.
T28 4168-4266 Sentence denotes The results of this study might be helpful in defining space recommendations for LE and F344 rats.
T29 4267-4423 Sentence denotes The protocol in this experiment was reviewed and approved by the IACUC of Walter Reed Army Institute of Research/Naval Medical Research Center (WRAIR/NMRC).
T30 4424-4506 Sentence denotes All procedures were carried out in a facility accredited by AAALAC, International.
T31 4507-4653 Sentence denotes We obtained LE (n = 28; 14 males and 14 females) and F344 rats (n = 32; 16 males and 16 females) from Charles River Laboratories (Wilmington, MA).
T32 4654-4785 Sentence denotes At the breeding facility, LE rats were housed in groups of 40 in cages with total floor space of 24 in × 24 in (14.4 in 2 per rat).
T33 4786-4900 Sentence denotes F344 rats were housed in groups of 30 in cages with total floor space of 13.88 in × 22.63 in (10.47 in 2 per rat).
T34 4901-5079 Sentence denotes Rats were housed in these conditions from weaning until they were 5 weeks old (Technical Services Department, Charles River Laboratories, Wilmington, MA; personal communication).
T35 5080-5208 Sentence denotes These floor space allocations are slightly smaller than those recommended We maintained rats under these conditions for 4 weeks.
T36 5209-5329 Sentence denotes We changed cages two times a week for the LDH groups and an average of three times a week for the HDH groups, as needed.
T37 5330-5403 Sentence denotes We carried out cage changes after completing data collection for the day.
T38 5404-5467 Sentence denotes We handled and examined all rats for at least 20 s twice daily.
T39 5468-5641 Sentence denotes We examined rats for clinical and behavioral signs of stress, including chromodacryorrhea, hair loss, wounds, inappetence, lethargy, ruffled haircoat and hunched appearance.
T40 5642-5804 Sentence denotes We scored each rat's condition once daily, using a subjective system in which 0 indicated no signs of stress, and 1 indicated that at least one sign was observed.
T41 5805-5881 Sentence denotes At the end of the study period (29 d), we totaled these scores for each rat.
T42 5882-5986 Sentence denotes We also noted whether any rats required medical treatment, which would result in removal from the study.
T43 5987-6064 Sentence denotes We weighed each rat once per week (SK-LOK scale, A&D Co., Ltd, Seoul, Korea).
T44 6065-6350 Sentence denotes We collected blood once every 2 weeks at the same time of day (three samplings total; the first sampling was on the last day of the first stage of the study (day 0), before rats were regrouped, to evaluate WBC count, blood glucose concentration and serum corticosterone concentration).
T45 6351-6472 Sentence denotes For blood sampling, we anesthetized rats with 2% isoflurane using an IMPAC6 anesthesia system (VetEquip, Pleasanton, CA).
T46 6473-6579 Sentence denotes We collected blood samples (0.5-1.0 ml) from the orbital venous plexus using heparinized hematocrit tubes.
T47 6580-6753 Sentence denotes For WBC counts and measurement of glucose concentration, we collected blood samples (0.25-0.5 ml) from all rats and stored them in anticoagulant (K 2 -EDTA) microcontainers.
T48 6754-6902 Sentence denotes We measured glucose concentration immediately after blood collection using a commercial glucometer (ACCU-Check Advantage, Roche, Mannheim, Germany).
T49 6903-7040 Sentence denotes We obtained the WBC count within 2 h of blood sampling using a Beckman Coulter AcT Diff hematology analyzer (Beckman Coulter, Miami, FL).
T50 7041-7238 Sentence denotes For serum corticosterone analysis, we collected additional blood (0.25-0.5 ml) from at least one rat in each cage (n = 10 for each strain) and stored the samples in serum separator microcontainers.
T51 7239-7411 Sentence denotes We selected this subgroup of rats arbitrarily at the beginning of the study, and we collected blood for corticosterone analysis from the same rats at each sampling session.
T52 7412-7556 Sentence denotes We froze serum at -29 o C and sent it to the Michigan State College of Veterinary Medicine Endocrinology Laboratory for corticosterone analysis.
T53 7557-7632 Sentence denotes We considered the measurements recorded on day 0 to be baseline parameters.
T54 7633-7740 Sentence denotes We analyzed data separately for each strain, comparing cage groups according to gender and housing density.
T55 7741-7819 Sentence denotes We analyzed clinical and behavioral signs of stress 50 ± 10 d (7-9 weeks; ref.
T56 7820-7825 Sentence denotes 29) .
T57 7826-7911 Sentence denotes At this stage of the study, no rats were actively showing any unusual clinical signs.
T58 7912-8052 Sentence denotes We redistributed the groups of rats and rehoused them such that no rats that were previously housed together were assigned to the same cage.
T59 8053-8431 Sentence denotes Rats that had been housed at a high density during the first stage of the study continued to be housed at a higher density than recommended (these rats are hereafter referred to as 'HDH'), and rats that had been housed at a low density continued to be housed in an amount of space that was equal to or greater than that recommended in the Guide (hereafter referred to as 'LDH').
T60 8432-8521 Sentence denotes We separated rats by gender and strain; otherwise, the selection of groups was arbitrary.
T61 8522-8603 Sentence denotes All rats were subjected to the same manipulations and data collection procedures.
T62 8604-8736 Sentence denotes We housed LE rats in groups of six for HDH (24 in 2 floor space per rat) and in groups of two for LDH (72 in 2 floor space per rat).
T63 8737-8929 Sentence denotes At the beginning of this stage of the study, LE males and females weighed 360-440 g and 230-300 g, respectively, and at the end of the study they weighed 395-495 g and 255-330 g, respectively.
T64 8930-9049 Sentence denotes The HDH groups of LE rats were housed in 1.2-2.5 times less than the recommended floor space for rats of these weights.
T65 9050-9186 Sentence denotes We housed F344 rats in groups of seven for HDH (21 in 2 floor space per rat) and in groups of two for LDH (72 in 2 floor space per rat).
T66 9187-9381 Sentence denotes At the beginning of this stage of the study, F344 males and females weighed 245-280 g and 155-180 g, respectively, and at the end of the study they weighed 260-315 g and 165-195 g, respectively.
T67 9382-9503 Sentence denotes The HDH groups of F344 rats were housed in 1.1-1.9 times less than the recommended floor space for rats of these weights.
T68 9504-9632 Sentence denotes For each strain, there were two cages of HDH males, two cages of HDH females, one cage of LDH males and one cage of LDH females.
T69 9633-9802 Sentence denotes Most experiments at WRAIR/NMRC use rats housed at low densities as described above; therefore, we considered LDH rats to be a control group for comparison with HDH rats.
T70 9803-10016 Sentence denotes We housed rats in standard filter-top covered polycarbonate cages (144 in 2 of floor space, 8 in high; Lab Products, Inc., Seaford, DE) on woodchip bedding (Beta Chip, Northeastern Products Corp, Warrensburg, NY).
T71 10017-10228 Sentence denotes All rats received rodent chow ad libitum (LabDiet RMH3000, PMI Nutrition International, LLC, Brentwood, MO) and drank municipal water, which was filtered by reverse osmosis, through an automatic watering system.
T72 10229-10369 Sentence denotes For environmental enrichment, we put two plastic pipes (6 in long, 3 in in diameter) in each HDH cage and one plastic pipe in each LDH cage.
T73 10370-10627 Sentence denotes We maintained cages in a climate-controlled room with temperature set at 18-26 °C and humidity at 30-70%, with a light:dark cycle of 12 h:12 h. signs in LDH males was slightly higher than that in HDH males, though results were not statistically significant.
T74 10628-10735 Sentence denotes HDH females showed a significantly higher incidence of stress signs compared with LDH females (P < 0.0001).
T75 10736-10918 Sentence denotes Over the course of the 29-d study, we noted signs of stress in HDH females about 1.3 times on average for each rat, whereas in LDH females, we observed no signs of stress (Fig. 1b) .
T76 10919-11056 Sentence denotes On the first day of the second stage of the study, the weights of all subjects were within the expected range for rats aged 80-90 d (ref.
T77 11057-11062 Sentence denotes 28) .
T78 11063-11226 Sentence denotes In LE rats, initial weight was significantly influenced by gender (P < 0.0001; males were significantly heavier than females) but not by cage density (P = 0.3354).
T79 11227-11322 Sentence denotes At the end of the study, all rats gained weight, but males gained more weight than females did.
T80 11323-11474 Sentence denotes Weight gain (expressed as a percentage of rats' initial weight) was significantly influenced by both gender (P < 0.0165) and cage density (P = 0.0245).
T81 11475-11679 Sentence denotes By the end of the study, LDH males were heavier than HDH males, whereas HDH females were heavier than LDH females (Fig. 2a) ; this interaction effect was not statistically significant, however (P = 0.87).
T82 11680-11705 Sentence denotes using Poisson regression.
T83 11706-11783 Sentence denotes We used ANOVAs to analyze weight change and data obtained from blood samples.
T84 11784-11893 Sentence denotes As noted above, we analyzed blood glucose concentration and WBC count using three blood samples for each rat.
T85 11894-12024 Sentence denotes For serum corticosterone concentration, we examined samples taken from 10 rats (at least one rat per cage; three samples per rat).
T86 12025-12149 Sentence denotes For each parameter measured, we analyzed the difference between data obtained from the first blood sample and from the last.
T87 12150-12228 Sentence denotes The random term for statistical analyses was the assignment of rats to groups.
T88 12229-12341 Sentence denotes In LE rats, housing density did not affect the occurrence of clinical and behavioral signs of stress (P = 0.86).
T89 12342-12509 Sentence denotes Gender had a moderate effect on stress (P = 0.057); incidence of clinical and behavioral signs was more than two times higher in males than that in females (Fig. 1a) .
T90 12510-12650 Sentence denotes In F344 rats, the occurrence of clinical and behavioral signs of stress was not affected by cage density (P = 0.29) or by gender (P = 0.27).
T91 12651-12745 Sentence denotes The interaction effect between gender and housing density was highly significant (P < 0.0001).
T92 12746-12917 Sentence denotes The incidence of stress glucose concentration in the third blood sample, though in the first two samples glucose concentration was similar in HDH and LDH groups (Fig. 3) .
T93 12918-13082 Sentence denotes This effect can be attributed to a single LDH rat, in which glucose concentration in the third blood sample was 204 mg/dl, 50 mg/dl more than that in any other rat.
T94 13083-13144 Sentence denotes The rat's previous two readings were 100 mg/dl and 132 mg/dl.
T95 13145-13286 Sentence denotes If this data point is considered an outlier, the difference between the two cage densities is no longer statistically significant (P = 0.25).
T96 13287-13389 Sentence denotes In F344 rats, gender had some significant effects on all WBC readings and on the last glucose reading.
T97 13390-13506 Sentence denotes On average, measurements in males were higher than those in females for all physiologic parameters (Tables 4 and 5).
T98 13507-13684 Sentence denotes Gender had a slight effect on the difference between data from the first and last samples; in females, all measurements decreased, whereas in males, they increased (P = 0.0964).
T99 13685-13751 Sentence denotes Cage density only affected corticosterone concentration (Fig. 4) .
T100 13752-13946 Sentence denotes LDH rats had lower corticosterone concentrations at the second and third readings (65 μg/dl and 69 μg/dl on average, respectively) compared with HDH rats (259 μg/dl and 222 μg/dl, respectively).
T101 13947-14339 Sentence denotes This was a pilot study to determine whether housing rats at high densities from age 5 weeks through puberty, regrouping them with unfamiliar rats and then continuing to house them at high densities for 4 weeks would alter In F344 rats, initial weight was also significantly influenced by gender (P < 0.0001; males were significantly heavier than females) but not by cage density (P = 0.3189).
T102 14340-14467 Sentence denotes Weight gain was significantly influenced by gender (P < 0.0011), with males weighing more than females at the end of the study.
T103 14468-14663 Sentence denotes We observed a significant interaction effect between cage density and gender for weight gain in this strain, suggesting that LDH males gained slightly more weight than did HDH males (P = 0.0043).
T104 14664-14803 Sentence denotes Despite this observation, housing density had no significant effect on rats' overall weight at the end of the study (P = 0.1683; Fig. 2b ).
T105 14804-14963 Sentence denotes We analyzed WBC count, blood glucose concentration and serum corticosterone concentration from blood samples taken at 2-week intervals (three samples per rat).
T106 14964-15081 Sentence denotes We also compared data from the third blood sample (taken on day 28) with data from the first sample (taken on day 0).
T107 15082-15181 Sentence denotes In LE rats, at least one parameter for each sampling period was significantly influenced by gender.
T108 15182-15296 Sentence denotes Gender did not significantly affect the difference between data obtained from the first blood sample and the last.
T109 15297-15469 Sentence denotes Average blood glucose concentration and WBC were higher in males than in females, whereas corticosterone concentration was lower in males than in females (Tables 2 and 3) .
T110 15470-15605 Sentence denotes Cage density significantly affected all body weight, though it did affect weight gain; LDH males gained more weight than did HDH males.
T111 15606-15727 Sentence denotes All rats in both strains gained weight during the study, and their weights were in the accepted range for their ages 28 .
T112 15728-15798 Sentence denotes We did not submit rats for necropsy and did not measure organ weights.
T113 15799-15939 Sentence denotes There may have been alterations in the weights of some of the organs, similar to the alterations observed in another group-housing study 2 .
T114 15940-16008 Sentence denotes We obtained mixed results when we measured physiological parameters.
T115 16009-16129 Sentence denotes In LE rats, cage density did not affect WBC or corticosterone concentration, though it did affect glucose concentration.
T116 16130-16208 Sentence denotes Glucose concentration in LDH males seemed to be higher than that in HDH males.
T117 16209-16458 Sentence denotes We note, however, that this observation was based on one reading for a single rat, and this reading behavioral or physiologic parameters, compared with rats that were housed at low densities and were also rehoused with unfamiliar rats after puberty.
T118 16459-16578 Sentence denotes The Guide currently recommends housing rats of the weights of those used in this study in 23-60 in 2 of floor space 1 .
T119 16579-16702 Sentence denotes This recommendation is aimed at preventing stress and aggression, which may occur when rats are housed at higher densities.
T120 16703-16926 Sentence denotes To determine whether rats showed signs of stress, aggression or unthriftiness when housed at higher densities, we used a subjective scoring system to evaluate the incidence of common clinical and behavioral signs of stress.
T121 16927-17128 Sentence denotes Although we observed some signs of stress, neither strain showed a frequency or severity of abnormalities that would indicate that a decreased amount of floor space caused high stress in either gender.
T122 17129-17285 Sentence denotes We evaluated all clinical signs equally on a 'present or absent' basis but noted that chromodacryorrhea was the most prevalent abnormality (data not shown).
T123 17286-17405 Sentence denotes LE males in both housing densities showed more clinical and behavioral signs of stress than did females of this strain.
T124 17406-17503 Sentence denotes This may indicate that male LE rats are not as compatible as females in group housing situations.
T125 17504-17617 Sentence denotes Cage density did not have statistically significant effects on the incidence of signs of stress in either gender.
T126 17618-17689 Sentence denotes In F344 rats, LDH males showed more signs of stress than did HDH males.
T127 17690-17762 Sentence denotes LDH and HDH males all showed fewer signs of stress than did HDH females.
T128 17763-17818 Sentence denotes We did not observe signs of stress in F344 LDH females.
T129 17819-17946 Sentence denotes This may indicate that the females of this strain would not be as compatible as males in high-density group housing situations.
T130 17947-18056 Sentence denotes None of the observed abnormalities were severe enough to require medical attention or removal from the study.
T131 18057-18118 Sentence denotes We observed no overt signs of inappetence in any of the rats.
T132 18119-18194 Sentence denotes In LE rats, gender and cage density each had significant effects on weight.
T133 18195-18315 Sentence denotes As noted above, LDH males weighed more on average than did HDH males, whereas HDH females weighed more than LDH females.
T134 18316-18416 Sentence denotes In F344 rats, cage density did not affect over-FIGURE 3 | Average glucose concentrations in LE rats.
T135 18417-18458 Sentence denotes Data from males and females are combined.
T136 18459-18755 Sentence denotes One male rat in the LDH group had a single reading (on day 28) that was 50 mg/dl higher than those of any other rat and was markedly higher than other readings for the same rat. collected a representative serum sample from each cage in order to determine whether any trends could be extrapolated.
T137 18756-18872 Sentence denotes The differences noted suggest that corticosterone levels should be measured for all rats in future expanded studies.
T138 18873-19039 Sentence denotes Because normal husbandry activities can be stressful for animals, the different frequency of cage changes for LDH and HDH rats might have been a confounding variable.
T139 19040-19125 Sentence denotes To minimize this potential effect, we changed all cages after the collection of data.
T140 19126-19260 Sentence denotes Another variable that might confound comparison between strains is the difference in group size between the HDH groups of each strain.
T141 19261-19403 Sentence denotes The difference in the number of rats per cage in each strain was based on the differences in the average body weight of rats in these strains.
T142 19404-19533 Sentence denotes To make comparisons between the strains, it would be beneficial to standardize the group sizes and available floor space per rat.
T143 19534-19634 Sentence denotes Furthermore, group size may affect rats' behavior regardless of the amount of floor space available.
T144 19635-19799 Sentence denotes In larger groups of rats, the social hierarchy is more complex than that in smaller groups, which may lead to increased incidence of aggression or stress responses.
T145 19800-19930 Sentence denotes This variable should be considered when evaluating some of the differences seen between the HDH and LDH groups within each strain.
T146 19931-20241 Sentence denotes Our findings suggest that LE and F344 rats that have been housed at high densities from weaning through puberty may be arbitrarily regrouped and housed for at least 4 weeks at densities that are higher than the Guide's current recommendations, without adverse effects on behavioral or physiological parameters.
T147 20242-20396 Sentence denotes Housing density had little effect on the common indicators of stress that we evaluated (clinical and behavioral signs, weight and physiologic parameters).
T148 20397-20588 Sentence denotes We did note that in F344 rats, corticosterone concentration was higher in HDH rats compared with LDH rats, which may indicate that high-density housing is not optimal for rats of this strain.
T149 20589-20669 Sentence denotes In addition, gender affected stress in LE rats, whereas in F344 rats it did not.
T150 20670-20820 Sentence denotes All rats showed normal growth with no clinical signs of severe stress or serious behavioral abnormalities that would result in exclusion from a study.
T151 20821-21002 Sentence denotes More studies are needed to further investigate potential consequences of transferring post-pubertal group-housed rats into new was much higher than the rat's other two measurements.
T152 21003-21129 Sentence denotes Therefore, this data point is probably an outlier caused by a lab error or an unrecorded stress event at the time of sampling.
T153 21130-21255 Sentence denotes If this one value is discounted, none of the parameters indicate a difference in stress level between the two cage densities.
T154 21256-21327 Sentence denotes In F344 rats, cage density did not affect glucose concentration or WBC.
T155 21328-21413 Sentence denotes The average corticosterone concentration in LDH rats was lower than that in HDH rats.
T156 21414-21527 Sentence denotes According to these results, increasing cage density did not seem to cause adverse physiologic effects in LE rats.
T157 21528-21640 Sentence denotes F344 rats housed at high densities may have higher short-term stress compared with rats housed at low densities.
T158 21641-21866 Sentence denotes Although we did not find strain-specific published reference values for all of the physiological parameters we measured, most of the glucose and WBC measurements we obtained were within the accepted normal range for rats 29 .
T159 21867-22105 Sentence denotes Corticosterone concentrations were also mostly within the published normal ranges, so the increase we observed in HDH F344 rats, which was outside of the normal range, seems to be a true elevation indicating a physiologic stress response.
T160 22106-22308 Sentence denotes Handling and restraint are known to cause an increase of corticosterone concentration in rats, but as all rats were handled in the same manner, this effect should have been normalized for all groups 5 .
T161 22309-22390 Sentence denotes Baseline values of physiological parameters may differ for males and females 29 .
T162 22391-22496 Sentence denotes We did not collect corticosterone samples from all rats because of processing and logistical constraints.
T163 22497-22551 Sentence denotes Because this work was carried out as a pilot study, we