9 EFFECTS OF MECLOFENAMIC ACID ON LUTEAL FUNCTION OF BEEF CATTLE

2012 ◽  
Vol 24 (1) ◽  
pp. 115
Author(s):  
C. A. Messerschmidt ◽  
F. M. Abreu ◽  
L. H. Cruppe ◽  
M. V. Biehl ◽  
M. L. Day ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Corpus Luteum ◽  
Standard Error ◽  
Animal Health ◽  
Progesterone Concentration ◽  
Luteal Function ◽  
Meclofenamic Acid ◽  
Pfizer Animal Health ◽  
The Mean ◽  
Acid Administration

The objective of this study was to determine the effects of meclofenamic acid, a nonsteroidal anti-inflammatory, on luteal function of beef cattle. A total of 18 Angus cows, aged between 2 and 3 years old, were enrolled in the experiment. All cows were synchronized using a 5-day CIDR protocol. Briefly, cows received 100 μg of gonadorelin diacetate tetrahydrate (GnRH; Cystorelin®, Merial, Athens, GA, USA) and a controlled internal drug release insert (CIDR; Eazi-BreedTM CIDR®, Pfizer Animal Health, New York, NY, USA). Five days later, the CIDR was removed and 50 mg of dinoprost (Lutalyse®, Pfizer Animal Health) was administered intramuscularly. Oestrus was determined by twice daily observations of mounting behaviour and tail painting scores (day of oestrus = Day 0). At 72 h after dinoprost, a second dose of gonadorelin (100 μg, IM) was administered. On Day 14, cows were randomly assigned to the following treatment groups: 1) control: 10 mL of saline solution administered IM; 2) systemic: 2 g of meclofenamic acid administered IM; and 3) oral: 2 g of meclofenamic acid administered orally. Cows were treated once daily for 11 days (i.e. until Day 24) and no adverse reactions were observed. Blood sampling and ovarian ultrasonography were performed every 72 h from Day 0 until Day 12 and then every 48 h until the end of the study. Serum progesterone concentrations were determined by radioimmunoassay and were used to determine functional luteolysis (i.e. progesterone <1 ng mL–1). Ovaries were evaluated for the presence of a corpus luteum and to evaluate follicular growth and subsequent ovulation. One-way ANOVA was used to compare the day of peak progesterone concentration, lifespan of the corpus luteum and the length of the oestrous cycle between groups. Significance was set at P < 0.05 and data are presented as means ± standard error of the mean (Table 1). There were no effects of meclofenamic acid administration on any of the parameters evaluated (P > 0.05). In conclusion, meclofenamic acid administration did not affect luteal function in our study. Potentially, higher doses of meclofenamic acid may be necessary to inhibit prostaglandin synthesis and prevent luteolysis. Table 1.Effects of meclofenamic acid administration on the day of peak progesterone concentration, lifespan of the corpus luteum (CL) and the length of oestrous cycle in beef cows (mean ± standard error of the mean) Funding was provided by The Ohio State University, College of Veterinary Medicine, USDA-Animal Health Formula Funds. The authors are also grateful to the staff at the OSU Beef Center Facility for helping with animal handling and care.

PROGESTERONE IN THE HUMAN PERIPHERAL BLOOD IN THE PREOVULATORY PERIOD OF THE MENSTRUAL CYCLE

1967 ◽  
Vol 55 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Benno Runnebaum ◽  
Josef Zander
Keyword(s):  
Menstrual Cycle ◽  
Corpus Luteum ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Progesterone Concentration ◽  
Plasma Progesterone ◽  
Progesterone Secretion ◽  
Graafian Follicle ◽  
The Mean ◽  
Mean Concentration

ABSTRACT Progesterone was determined and identified in human peripheral blood during the preovulatory period of the menstrual cycle, by combined isotope derivative and recrystallization analysis. The mean concentration of progesterone in 1.095 ml of plasma obtained 9 days before ovulation was 0.084 μg/100 ml. However, the mean concentration of progesterone in 1.122 ml of plasma obtained 4 days before ovulation was 0.279 μg/100 ml. These data demonstrate a source of progesterone secretion other than the corpus luteum. The higher plasma-progesterone concentration 4 days before ovulation may indicate progesterone secretion of the ripening Graafian follicle of the ovary.

162 FERTILITY OF BEEF RECIPIENTS FOLLOWING A FIXED-TIME EMBRYO TRANSFER PROTOCOL WHICH INCLUDED FOLLICLE STIMULATING HORMONE DILUTED IN HYALURONAN

2013 ◽  
Vol 25 (1) ◽  
pp. 229
Author(s):  
J. W. Thorne ◽  
C. R. Looney ◽  
J. F. Hasler ◽  
D. K. Hockley ◽  
D. W. Forrest
Keyword(s):  
Corpus Luteum ◽  
Pregnancy Rate ◽  
Embryo Transfer ◽  
Transfer Rate ◽  
Animal Health ◽  
Fixed Time ◽  
Control Groups ◽  
Pfizer Animal Health ◽  
And Control ◽  
Estradiol 17Β

This study was performed to test the viability of administering Folltropin-V® (FSH, Bioniche Animal Health) diluted in hyaluronan (MAP-5 50 mg, sodium hyaluronate, Bioniche Animal Health) to beef cows enrolled in a recipient synchronization protocol to evaluate its effect on recipient fertility. All recipients were administered an estradiol 17β (2.5 mg, IM) and progesterone (50 mg, IM) combination injection on Day 0, a CIDR® (progesterone 1.34 g, Pfizer Animal Health, Groton, CT, USA) was inserted for 7 days. Lutalyse® (dinoprost tromethamine, Pfizer Animal Health, 25 mg, IM) was administered at the time of CIDR removal on Day 7, and estradiol 17β (1 mg, IM) was administered on Day 8. On Day 16, the presence of at least one corpus luteum, detected via ultrasound, resulted in the recipient receiving an embryo (both fresh and frozen–thawed embryos were used). Embryos were not transferred into cows that did not show ultrasonic evidence of a CL. Dependent variables for which data were collected included circulating progesterone levels at the time of transfer and CL diameter, area, and circumference; measured in millimeters. The total study (n = 274) consisted of both wet (n = 85) and dry (n = 189) cows and included both Bos indicus (Brahman-influenced) crossbred (n = 93) and Bos taurus (Angus-based) cows (n = 181). The experiment consisted of cows being placed in either the treated or control groups, with treated cows receiving a single 40 mg (1 mL) IM injection of Folltropin-V in hyaluronan on Day 5 and control cows receiving no additional injections. Results are shown in Table 1. Transfer rate, conception rate, and pregnancy rate were tested for significance with chi-square analysis and remaining statistics were analyzed with a t-test: two-sample assuming equal variances. There were no significant differences found between the treated and control groups for transfer rate, conception rate, or pregnancy rate. Corpus luteum diameter was shown to be larger in control cows (P < 0.05); however, CL area and circumference did not differ significantly. Folltropin-V given with hyaluronan at a 40-mg dose on Day 5 did not improve fertility, induce a larger CL, or increase circulating progesterone levels in synchronized beef recipients as hypothesized. Further work is needed with Folltropin-V in hyaluronan to determine if an alternative dose or timing of administration would be more appropriate for improving fertility in recipients. Table 1.Fertility data in beef recipients following synchronization for fixed-time embryo transfer with a protocol that included (Treated) or did not include (Control) FSH in hyaluronan

98 INFLUENCE OF INJECTION ALTRENOGEST IN UTERINE TONE AND EMBRYONIC VESICLE GROWTH IN RECIPIENT MARES

2017 ◽  
Vol 29 (1) ◽  
pp. 157
Author(s):  
V. H. Vallejo Aristizabal ◽  
H. D. Mogollón Garcia ◽  
J. A. Dell'aqua Junior
Keyword(s):  
Statistical Analysis ◽  
Corpus Luteum ◽  
Standard Error ◽  
Winter Season ◽  
Conception Rate ◽  
Chi Square ◽  
Recipient Group ◽  
The Mean ◽  
Made In

The objective of this study was to compare the influence of injectable altrenogest on uterine tone (UT) and embryonic vesicle growth (EVG) in non-cyclic recipient mares in anestrus and transition with cyclic mares. This study was conducted in Brazil in the winter season (June to September) between 2011 and 2014. One-hundred fifty-five embryo transfers (ET) were made in crossbreed mares from 4 to 10 years of age, between 350 and 450 kg of weight. The recipient mares were distributed into 3 groups: G1: anestrus (n = 67), mares with follicles less than 15 mm and absence of corpus luteum; G2: transition (n = 14), mares with follicles between 15 and 20 mm and absence of corpus luteum; and G3: cyclic (n = 74), mares with follicles larger than 20 mm and presence of corpus luteum. On Day 0 (day of donor mare ovulation), recipient mares in G1 and G2 received a single IM dose of 17β-oestradiol (10 mg). Recipients were examined by ultrasound on Days 1 and 2 to evaluate the presence of uterine oedema. On Day 2, once oedema was confirmed, recipients were given 180 mg of altrenogest IM, and altrenogest treatment was repeated every 8 days until Day 90 of gestation. The G3 recipient mares were not treated with 17β-oestradiol and altrenogest. For mares in G1 and G2, ET was performed 6 days after the initiation of altrenogest treatment. For recipients in G3, ET was performed between Days 6 and 8. Uterine tone was evaluated before ET on a scale of 0 to 3 (tonus absent 0, and tonus intense 3). Conception rate was determined by ultrasound at Day 15. The diameter of the EVG was calculated by measuring the length and width of the embryonic vesicle on Days 15, 20, 25, 30, 35, 40, and 45 using ultrasonography. Analysis of the variables UT and EVG was performed with Proc Mixed. Results are represented as ± standard error of the mean. Statistical analysis for conception rate was made by chi-square distribution adjusted with the Fisher’s test when it was required. All data were analysed with the SAS statistical package. There was no difference (P > 0.05) in UT between recipient groups (G1: 2.6 ± 0.04; G2: 2.6 ± 0.09; G3: 2.5 ± 0.04). In addition, there was no effect of recipient group nor an interaction between recipient group and day of gestation for EVG (P > 0.05). However, conception rate was greater (P < 0.05) in G2 (11/14 = 78%) and G3 (44/74 = 59%) compared with G1 (26/67 = 39%). Results of the present study demonstrate the effectiveness of injectable altrenogest for use in managing anestrus and transition mares for ET.

11 EFFECTS OF CIDR-BASED PRESYNCHRONIZATION AND eCG ON FERTILITY FOR A GnRH-BASED TIMED-AI PROTOCOL IN BEEF CATTLE

2006 ◽  
Vol 18 (2) ◽  
pp. 114 ◽  
Author(s):  
M. Colazo ◽  
J. Small ◽  
J. Kastelic ◽  
H. Davis ◽  
D. Ward ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Factorial Design ◽  
Pregnancy Rate ◽  
Animal Health ◽  
Beef Cows ◽  
Beef Heifers ◽  
Treatment Control ◽  
Pfizer Animal Health ◽  
Exogenous Progesterone ◽  
To Receive

The objectives were to determine the effects of presynchronization and eCG on fertility for a GnRH-based timed-AI (TAI) protocol in beef cattle. Previously autoclaved once-used CIDR inserts (Colazo et al. 2004 Anim. Reprod. Sci. 81, 25-34) were used for experimental purposes so that all cattle had equivalent exogenous progesterone after Day 7 in Experiment 1, and to induce GnRH-responsive follicles in Experiment 2. In Experiment 1, 12-15 month old beef heifers (n = 447) were used (three locations, A, B, and C). On Day 0, half received a new CIDR insert (Pfizer Animal Health, Montreal, Quebec, Canada) and 500 �g of cloprostenol i.m. (PGF: Estrumate; Schering-Plough Animal Health, Pointe-Claire, Quebec, Canada). On Day 7, the remainder received an autoclaved once-used CIDR and all received 100 �g of GnRH i.m. (Cystorelin; Merial Canada, Inc., Victoriaville, Quebec, Canada). On Day 14, CIDR inserts were removed, PGF was given to all heifers, and heifers were given either 300 IU eCG i.m. (Pregnacol; Bioniche Animal Health, Belleville, Ontario, Canada) or no treatment (2 � 2 factorial design). On Day 16 (54-56 h after CIDR removal and PGF administration), heifers were given 100 �g of GnRH i.m., concurrent with TAI. Transrectal ultrasonography was done on Day 0 to assess ovarian structures, and on approximately Day 50 (range, 44-69) to confirm pregnancy. Overall, 72.7% of heifers were puberal on Day 0 (150/150, 5/37, and 170/260 for locations A, B, and C, respectively; P < 0.001). Pregnancy rate was affected (P < 0.001) by location (27.3, 62.2, and 51.1% for the three locations, respectively) but was not affected (P = 0.3) by puberal status at locations B and C. Pregnancy rate was not affected (P = 0.5) by presynchronization, but tended (P = 0.1) to be reduced by eCG treatment (40.4 vs. 47.7%, respectively). In Experiment 2, lactating crossbred beef cows (n = 411), 2-12 years of age were randomly allocated to receive either a previously used, autoclaved CIDR for 7 days and 25 mg of dinoprost i.m. (PGF: Lutalyse; Pfizer Animal Health) or no treatment (control; Day 0). At CIDR removal (Day 7), all cows received 100 �g of GnRH. On Day 14, all cows received PGF and were allocated to receive either 400 IU of eCG i.m. or no treatment (2 � 2 factorial design). On Day 16 (54-56 h after PGF), cows were given 100 �g of GnRH concurrent with TAI. Transrectal ultrasonographic examinations were done on approximately 65 cows in each group on Days 0, 7, and 14 to assess ovarian structures and on all cows on Day 42 to confirm pregnancy. Overall, 88.8% of cows had a corpus luteum (CL) on Day 0. Presynchronization increased both the proportion of cows that ovulated to GnRH treatment on Day 7 (76.7 vs. 55.0%; P < 0.001) and pregnancy rate (58.2 vs. 45.4%; P = 0.03) for cows that had received a CIDR vs. control cows. However, eCG treatment did not affect pregnancy rate (P = 0.3) in either group. In summary, presynchronization with a used CIDR and PGF prior to a Cosynch protocol increased ovulation rate to the first GnRH treatment and pregnancy rate in cows but not in heifers. In a GnRH-based TAI protocol, treatment with eCG had no significant effect on fertility in cows, but tended to decrease fertility in heifers.

16 PROGESTERONE RELEASE PATTERNS FROM CUE-MATE IN COMPARISON TO OTHER INTRAVAGINAL PROGESTERONE-RELEASING DEVICES IN LACTATING DAIRY COWS

2007 ◽  
Vol 19 (1) ◽  
pp. 126 ◽  
Author(s):  
D. Rogan ◽  
M. F. Martinez ◽  
G. A. Bo ◽  
P. Chesta ◽  
F. Feresin ◽  
...  
Keyword(s):  
Los Angeles ◽  
Repeated Measures ◽  
Buenos Aires ◽  
Animal Health ◽  
Plasma Progesterone ◽  
Pfizer Animal Health ◽  
The Mean ◽  
Main Effects ◽  
To Receive ◽  
Mean Concentration

Various intravaginal progesterone-releasing devices are commercially available and each is impregnated with different amounts of progesterone. An experiment was designed to characterize plasma progesterone release profiles from Cue-Mate in comparison with other commercially available progesterone-releasing devices. Cycling, lactating Holstein cows (n = 60; BCS between 2.0 and 3.0 out of 5) from commercial dairy farms in Argentina were used in 2 replicates. All cows received 2 injections of D+ cloprostenol (PGF, Bioprost-D�; Biotay, Buenos Aires, Argentina) 14 days apart and were randomly assigned to one of four groups to receive intravaginal devices as follows: Cue-Mate (1.56 g progesterone; Bioniche Animal Health, A/Asia Pty, Armidale, Australia; n = 10), DIB (1 g progesterone; Syntex SA, Argentina; n = 10), CIDR with 1.9 g progesterone (Pfizer Salud Animal S.A., Buenos Aires, Argentina; n = 10), or CIDR with 1.38 g progesterone (Pfizer Animal Health, Groton, CT, USA; n = 10). All devices were inserted 24 hours after the second PGF and were left in place for 31 days. Blood samples were taken for progesterone analysis at 6-hour intervals for the first 24 hours, then daily for a week, and every 2 days for an additional 25 days. Plasma progesterone concentrations were measured with a modified human double-antibody RIA kit (DPC Coat-A-Count�; Diagnostic Products Corporation, Los Angeles, CA, USA). Cows were observed twice daily to confirm that vaginal inserts were still in place. Time-series hormone data were analyzed using the MIXED procedure for repeated measures (SAS Institute, Inc., Cary, NC, USA). Main effects of device and time, the highest mean concentration of progesterone, and the mean day on which this occurred were compared by a protected LSD test. There was no evidence of cow discomfort with any of the vaginal devices, and loss rates did not differ. There was an effect of group (P &lt; 0.001) and day (P &lt; 0.001) for progesterone concentrations, but there was no interaction (P = 0.89). Peak concentrations of progesterone (ng mL-1) did not differ among groups (Cue-Mate: 5.0 � 1.1; DIB: 3.9 � 0.6; 1.9-g CIDR: 4.6 � 0.6; 1.38-g CIDR: 3.7 � 0.4; P = 0.51). Mean (� SEM) concentrations of progesterone over the 31-day insertion period differed between 1.9-g CIDR (1.8 � 0.2 ng mL-1) and DIB (1.5 � 0.1 ng mL-1, P &lt; 0.006), with Cue-Mate (1.5 � 0.2 ng mL-1) and 1.38-g CIDR (1.6 � 0.1 ng mL-1) intermediate and not different from either. When data were evaluated from insertion until Day 7, mean plasma progesterone concentrations did not differ among groups (Cue-Mate: 2.2 � 0.2 ng mL-1; DIB: 2.2 � 0.1 ng mL-1; 1.9-g CIDR: 2.6 � 0.2 ng mL-1; 1.38-g CIDR: 2.1 � 0.1 ng mL-1). However, progesterone concentrations from insertion until Day 21 were higher (P &lt; 0.03) in cows with a 1.9-g CIDR (2.1 � 0.1 ng mL-1) than in those with a DIB (1.6 � 0.1 ng mL-1) or a 1.38-g CIDR (1.6 � 0.1 ng mL-1), with Cue-Mate (1.7 � 0.1 ng mL-1) intermediate and not different. Based on progesterone release patterns, it was concluded that Cue-Mate intravaginal devices can be used in protocols for synchronization of estrus and ovulation as with other progesterone-releasing devices.

LUTEAL FUNCTION IN THE MERINO EWE AND THE EFFECT OF EXOGENOUS PROGESTAGEN

1969 ◽  
Vol 44 (1) ◽  
pp. 79-89 ◽  
Author(s):  
J. F. SMITH ◽  
T. J. ROBINSON
Keyword(s):  
Corpus Luteum ◽  
Jugular Vein ◽  
Ovarian Vein ◽  
Progesterone Concentration ◽  
Plasma Progesterone ◽  
Luteal Function ◽  
Positive Correlations ◽  
Cyclic Changes

SUMMARY Progesterone levels were determined in the ovarian and jugular vein plasma and the corpus luteum of 68 cyclic Merino ewes (controls) and of 32 ewes which had been treated with intravaginal sponges containing a synthetic progestagen (Cronolone, Searle). The weight and diameter of the corpus luteum and the rate of flow of the ovarian vein blood were also recorded. No corrections for procedural losses were made. The control ewes showed highly significant (P < 0·001) cyclic changes in the progesterone contents of the ovarian vein plasma and the corpus luteum, and in the mass of the corpus luteum. There were positive correlations (P < 0·001) between ovarian vein plasma progesterone concentration and the weight (r = 0·651), diameter (r = 0·692), total progesterone content (r = 0·775) and progesterone concentration (r = 0·574) of the corpus luteum. Cyclic changes in the progesterone content of the jugular vein failed to attain significance (0·1 < P < 0·2) but the levels were positively correlated with those in the ovarian vein (r = 0·465, P < 0·001) and with weight (r = 0·432, P < 0·001) and diameter (r = 0·303, P < 0·05) of the corpus luteum. The Cronolone-treated ewes showed cyclic changes in luteal function similar to those in controls, with the exception of animals treated on the day of oestrus. In ewes in which ovulation was not suppressed, the duration of activity of the corpus luteum, as measured by progesterone concentration in ovarian vein plasma, and concentration and content in the corpus luteum was significantly reduced. By the 12th day of the cycle the corpus luteum had almost completely regressed both morphologically and functionally.

Multi-Center Calibration of the Second Reference Material for Thromboplastin, Rabbit, Plain, Coded CRM 149R

1991 ◽  
Vol 65 (03) ◽  
pp. 263-267 ◽  
Author(s):  
A M H P van den Besselaar ◽  
R M Bertina
Keyword(s):  
Reference Material ◽  
Standard Error ◽  
Standard Errors ◽  
Sensitivity Index ◽  
Long Term Stability ◽  
Significant Bias ◽  
The Mean ◽  
The Relationship ◽  
International Sensitivity Index

SummaryIn a collaborative trial of eleven laboratories which was performed mainly within the framework of the European Community Bureau of Reference (BCR), a second reference material for thromboplastin, rabbit, plain, was calibrated against its predecessor RBT/79. This second reference material (coded CRM 149R) has a mean International Sensitivity Index (ISI) of 1.343 with a standard error of the mean of 0.035. The standard error of the ISI was determined by combination of the standard errors of the ISI of RBT/79 and the slope of the calibration line in this trial.The BCR reference material for thromboplastin, human, plain (coded BCT/099) was also included in this trial for assessment of the long-term stability of the relationship with RBT/79. The results indicated that this relationship has not changed over a period of 8 years. The interlaboratory variation of the slope of the relationship between CRM 149R and RBT/79 was significantly lower than the variation of the slope of the relationship between BCT/099 and RBT/79. In addition to the manual technique, a semi-automatic coagulometer according to Schnitger & Gross was used to determine prothrombin times with CRM 149R. The mean ISI of CRM 149R was not affected by replacement of the manual technique by this particular coagulometer.Two lyophilized plasmas were included in this trial. The mean slope of relationship between RBT/79 and CRM 149R based on the two lyophilized plasmas was the same as the corresponding slope based on fresh plasmas. Tlowever, the mean slope of relationship between RBT/79 and BCT/099 based on the two lyophilized plasmas was 4.9% higher than the mean slope based on fresh plasmas. Thus, the use of these lyophilized plasmas induced a small but significant bias in the slope of relationship between these thromboplastins of different species.

Effect of purity and dose of inhibin gene vaccine on corpus luteum development of beef cattle

2013 ◽  
Vol 38 (3) ◽  
pp. 300-304
Author(s):  
Wei-xin JIANG ◽  
You-sheng LIU ◽  
Li-qun XUE ◽  
Xiao-jun CHEN ◽  
Li-guo YANG ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Corpus Luteum ◽  
Gene Vaccine

scholarly journals An alternative to the rejection of observations

1932 ◽  
Vol 137 (831) ◽  
pp. 78-87 ◽  
Keyword(s):  
Standard Deviation ◽  
Continuous Function ◽  
Large Deviations ◽  
Opposite Direction ◽  
Standard Error ◽  
The Other ◽  
Cause Of Error ◽  
The Mean ◽  
Normal Law ◽  
Usual Rule

1. It is widely felt that any method of rejecting observations with large deviations from the mean is open to some suspicion. Suppose that by some criterion, such as Peirce’s and Chauvenet’s, we decide to reject observations with deviations greater than 4 σ, where σ is the standard error, computed from the standard deviation by the usual rule; then we reject an observation deviating by 4·5 σ, and thereby alter the mean by about 4·5 σ/ n , where n is the number of observations, and at the same time we reduce the computed standard error. This may lead to the rejection of another observation deviating from the original mean by less than 4 σ, and if the process is repeated the mean may be shifted so much as to lead to doubt as to whether it is really sufficiently representative of the observations. In many cases, where we suspect that some abnormal cause has affected a fraction of the observations, there is a legitimate doubt as to whether it has affected a particular observation. Suppose that we have 50 observations. Then there is an even chance, according to the normal law, of a deviation exceeding 2·33 σ. But a deviation of 3 σ or more is not impossible, and if we make a mistake in rejecting it the mean of the remainder is not the most probable value. On the other hand, an observation deviating by only 2 σ may be affected by an abnormal cause of error, and then we should err in retaining it, even though no existing rule will instruct us to reject such an observation. It seems clear that the probability that a given observation has been affected by an abnormal cause of error is a continuous function of the deviation; it is never certain or impossible that it has been so affected, and a process that completely rejects certain observations, while retaining with full weight others with comparable deviations, possibly in the opposite direction, is unsatisfactory in principle.

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