"˜Regression toward the mean" in replications of fundamental research studies on homeopathic high potencies?

Author(s):  
P Christian Endler ◽  
Corinne Kraus ◽  
Wilhelm Mosgöller ◽  
Harald Lothaller

Around 100 high-potency studies, each one replicating earlier studies, were located in a bibliometric study on fundamental research [1]. 70% of the replication studies yielded the same result as the original study, 10% the opposite result, and 20% found no difference between the test and control groups. This is to say, the final standing was 70 positive, 10 negative and 20 undecided results. Among the replication studies performed by the original laboratory, the outcomes were 83 positive and 5 negative (12 undecided); in the ones performed in laboratories of independent researchers invited to participate in a multicentric study the corresponding outcomes were 75 and 11 (14), and the ones of studies performed by external researchers 48 and 14 (38). Had the experiments been performed on purely random phenomena the most probable outcomes would have been 33 : 33 : 33. In a follow-up study we sought to establish whether the outcomes of the replication studies might be attributed to regression toward the means. As is known, this term describes the situation in which a random experiment yields an extreme result, while subsequent replications give average results quite independent from the initial one. By contrast, when the experiment is not entirely based entirely on chance, subsequent replications tend to yield results that deviate from the average in the same direction as the initial one. We thus grouped the studies into 3 clusters of at least 7 articles according to their date of publication. The relative frequencies of positive, undecided and negative results were graphically represented through by curves to allow for visual comparison of the initial result versus the results of the replication studies for each of the 3 clusters. Regression towards the mean was neither observed in the results of the replication studies taken together nor in the group of laboratory-internal replication studies. By contrast, the group of multicentric replication studies exhibited increase of the relative frequency of undecided results and decrease of the one of positive results. In the group of external replication studies the relative frequency of undecided results increased and the one of positive and of negative results decreased. The statistical probability of drawing a ‘positive result’ from a total of 3 equally probable options (positive, undecided, negative) is 33.3%. By contrast, within the entirety of replication studies the frequency of positive results was 77% on the first replication, 66.7% on the second and 66.7% on the third. Unlike the results from the group of laboratory-internal studies, the ones of multicentric and external replications are suggestive of regression towards the mean. However the magnitude of this effect is far weaker than would be expected from a purely random distribution of results. One question that remains is why there appears to have been practically no regression in the laboratory-internal replications. This should not be cheaply attributed to publication bias. Especially in experiments on homoeopathic high potencies, it could well be that numerous, in some part hidden factors of influence are involved, which internal laboratories – possibly unwittingly through unreflected working habits– are better at controlling than external laboratories, regardless of the effort invested to this end. Keywords: high dilution, replication experiments, regression to the mean References [1] Endler PC, Bellavite P, Bonamin L, Jäger T. Mazon S. Replications of fundamental research models in ultra high dilutions, 1994 and 2015: an update on a bibliometric study. Homeopathy 2015;104:235-245

1933 ◽  
Vol 5 (1) ◽  
pp. 15-28 ◽  
Author(s):  
J. F. Malcolm

1. Of 21,569 samples of mixed cow's milk taken under fair conditions of cleanliness and examined by means of the coliform test, 48·3 per cent, gave negative results with 1/10, 1/100 and 1/1000 c.c. amounts; 21–4 per cent, gave positive results with only 1/10 c.c.; 14·0 per cent, gave positive results with only 1/10 and 1/100 c.c.; and 16·3 per cent, gave positive results with 1/10, 1/100 and 1/1000 c.c. It is probable that these results are better than those generally obtained.2. The proportion of coliform-positive samples was much higher in summer and early autumn than during the winter and spring. This seasonal variation was largely due to atmospheric temperature, there being a well-marked direct correlation between the proportion of coliform-positive samples and the mean of the minimum and maximum atmospheric temperatures.3. Of 21,857 samples examined, 10,458 were coliform negative and had an average bacterial content of 25,294 per c.c; 11,399 were coliform positive and had an average bacterial content of 160,577 per c.c. The coliform-positive samples contained on an average 6·3 times as many bacteria as the coliform negative.


2020 ◽  
Vol 35 (1) ◽  
pp. 98-106
Author(s):  
Sasiwimon Traiyan ◽  
Wiparat Manuyakorn ◽  
Watcharoot Kanchongkittiphon ◽  
Cherapat Sasisakulporn ◽  
Wanlapa Jotikasthira ◽  
...  

Background Skin prick test (SPT) or Phadiatop, a multi-allergen IgE screening test, was used as a tool for detecting aeroallergen sensitization. Objective To compare SPT and Phadiatop as a tool for diagnosis allergic rhinitis (AR) using the nasal provocation test (NPT) as a comparative standard. Methods Children aged 5-18 years with rhinitis symptoms more than 6 times in the past year were enrolled. SPT to 13 common aeroallergens, serum for Phadiatop, and NPT to Dermatophagoides pteronyssinus (Der p) were performed. NPT to mixed cockroach (CR) were performed in children who had CR sensitization and negative NPT to Der p. Children who had a disagreement between the result of SPT and Phadiatop or having negative results were evaluated for specific IgE (sIgE) to common aeroallergens. Results One hundred-forty children were enrolled with the mean age of 9.8 ± 3 years, 56% were male. Of 92 children (65.7%) with positive SPT to any aeroallergens, 88 children (95.6%) were sensitized to house dust mite (HDM). NPT showed positive results in 97 children (69.3%). Of 48 children who showed negative SPT, 4 children (8.3%) had sIgE to aeroallergens but NPT was positive in 1 child. Eighty-eight children (62.9%) had positive tests for Phadiatop and 4 (4.5%) of them had negative results for NPT to Der p. Among 52 children who had negative results for Phadiatop, 4 children (7.6%) had sIgE to aeroallergens but NPT was positive in 2 children (3.8%). SPT and Phadiatop showed 94.2% agreement: with Kappa 0.876, p < 0.001. Using NPT as a comparative standard for diagnosis for AR, SPT showed a sensitivity of 89.6% and specificity of 88.3% and Phadiatop provided the sensitivity of 88.6% and specificity of 95.3%. Conclusions SPT to aeroallergen and Phadiatop have good and comparable sensitivity and specificity for the diagnosis of AR in children.


2020 ◽  
Vol 3 (2) ◽  
pp. 37-40
Author(s):  
Ehsan Arjmandzadeh ◽  
◽  
Fariba Binesh ◽  
◽  

Introduction: Breast cancer is known as the most common type of cancer among women in the world. Several methods have been proposed to predict the behavior of breast carcinoma. Recently calretinin has been found to be a reliable factor in predicting tumor survival rate in breast cancer. The aim of this study was to evaluate the relative frequency of calretinin expression in patients with breast cancer in Yazd,Iran. Material and methods: In this cross-sectional retrospective study, the clinicopathologic features and the outcome of patients with breast cancer from 2017 to 2018 were reviewed at Shahid Sadoughi Hospital, Yazd, Iran. The influence of potential prognostic parameters in the overall survival was investigated by log-rank test and Cox regression analysis. Results: Among 100 cases with breast carcinoma, 14.5% were positive for calretinin. The distribution of the rate of positivity of IHC markers including ER, PR, P53, Ki67 and Her2 was 62.9%, 57.1%, 46.2%, 80.5% and 22.1%, respectively. The most common grade and stage were grade2 and stage3 respectively. There was no significant difference in the status of IHC markers (including ER, PR, Her2 and Ki67) in terms of calretinin. 66.7% of the patients with calretinin positive results were P53 positive. The results of the mean tumor size distribution in the two groups of positive and negative calretinin showed a significant difference (P-value = 0.05). A lower age at the time of diagnosis was found in patients with calretinin positive results (P-value = 0.119). The mean survival rate in calretinin positive group was 6.71 years and 6.62 years in calretinin negative patients which was not statistically significant. Conclusion: The results of this study indicated an association between calretinin expression and other IHC markers (although not statistically significant) in predicting poor prognosis in breast cancer patients. In addition, we found a statistically significant association among calretinin with smaller tumor size and lower age at the time of diagnosis in patients with breast cancer.


PEDIATRICS ◽  
1984 ◽  
Vol 74 (6) ◽  
pp. 1065-1068 ◽  
Author(s):  
K. L. Tan ◽  
A. Loganath ◽  
A. C. Roy ◽  
H. H. Goh ◽  
S. M. Karim ◽  
...  

Umbilical cord plasma α-fetoprotein (AFP) values were determined in 127 infants with hyperbilirubinemia (56 glucose-6-phosphate dehydrogenase (G-6-PD) deficient and 71 G-6-PD normal) and 136 control subjects (73 G-6-PD deficient and 63 G-6-PD normal). The mean α-fetoprotein value of 173 ± 35.2 (SD) mg/L for the group of infants with hyperbilirubinemia was significantly greater than that (122 ± 21.7 mg/L) for the control infants (P &lt; .001). G-6-PD status and sex did not significantly affect the α-fetoprotein values. Using an α-fetoprotein level of 130 mg/L as a "cut-off" value, the incidence of false-positive results was 25.5% and the incidence of false-negative results was 11.8%. This test can be used as a screening procedure to detect infants at high risk for hyperbilirubinemia.


Author(s):  
Corinne Kraus ◽  
Wilhelm Mosgöller ◽  
Harald Lothaller ◽  
P Christian Endler

In a bibliometric study [1] we located around 100 high-potency studies, each of which scrutinized an earlier study. An expert round was set to discuss whether it was justified to use the null hypothesis that no difference would be found between the respective test and control groups. The following two viewpoints were juxtaposed: 1) The classical null hypothesis states that the results from a test group and its respective control will not differ. If difference is found, the null hypothesis must be rejected. In this case, whether the values found in the test group were higher or lower than the ones of the control group is irrelevant. However, in some instances lack of difference between the test and the control groups is not helpful to make an informed decision. In the case of the analyzed bibliometric study, the research question is as follows: is the number of replication studies which produced a result of the same kind as the original study greater than the number of replication studies which produced a result of the opposite kind? 2) Often there is a pragmatic interest in a one-sided difference or in a deviation in one specific direction. A null hypothesis to this end will state, for example, that the result of the test group will not be better than that of the control group. If difference in favor of the test group is found, the null hypothesis must then be rejected. If, conversely, no difference is found or the result of the control group is better, the null hypothesis can be maintained. For the analyzed bibliometric study the question is: is the number of replication studies which yielded a result of the same kind as the original study greater than the number of all other replication studies? From viewpoint (1) the outcome was that 70% of replication studies yielded the same result as the original study, 10% per cent the opposite result, and in 20% no difference was found between test and control. From this view point the standing is 70 positive, 10 negative and 20 undecided results. Broken down further, the outcome for laboratory-internal replication was 83 and 5 (12 undecided results) while the outcome for multicenter replication was 75 and 11 (14) and that for external replication was 48 and 14 (38). From viewpoint (2) the outcome was that 70% of replication studies yielded the same result as the original study, and that 30% (= 10% + 20%) either resulted in no difference between the test and the control group or a result opposite to the one of the original study. From this viewpoint the standing is 70 ‘for reproducibility’ versus 30 ‘not for reproducibility.’ Broken down further, the outcome for laboratory-internal replication was 83 and 17 (= 5 + 12), while that for multicenter replication 75 and 25 (= 11 + 14) and the one for external replication 48 and 52 (= 14 + 38). We conclude that the 2 two viewpoints should be treated as equally valid when discussing the outcome of the analyzed bibliometric study Keywords: high dilution, experiment repetition, null hypothesis References [1] Endler PC, Bellavite P, Bonamin L, Jäger T. Mazon S. Replications of fundamental research models in ultra high dilutions, 1994 and 2015: an update on a bibliometric study. Homeopathy 2015;104:235-245


1924 ◽  
Vol 14 (2) ◽  
pp. 240-267 ◽  
Author(s):  
V. H. Blackman

Four years' additional experimental work on the application of a high tension discharge to the growth of field crops is described. Ten experiments with spring-sown oats and barley, two with winter-sown wheat, one with spring-sown wheat, and four with clover-hay have now been described.The discharge was usually given at the rate of 0·5 to 1·0 milliamp. per acre from thin insulated wires stretched above the crop at a height of about 7 ft. and charged to a voltage of 40,000 to 80,000 (crest value). The discharge was usually given for 6 hours a day in two periods, 3 hours in the morning and 3 hours in the afternoon.If the two experiments with spring-sown oats described in previous papers are included and the experiment of 1919 with spring-sown wheat (which yielded only 8 bushels to the acre) is excluded a series of 18 results is available spread over a period of 6 years. Of these 18 field experiments with various crops, 14 gave positive results in favour of the electrified plots, while 4 showed negative results, i.e. decreased yields compared with the controls. Of the 14 positive results only 3 show increases of less than 10 per cent, while 9 show increases of 30 per cent, and over, some reaching 50 per cent, and over. Of the 4 negative none shows a decrease of as much as 10 per cent.Of the 12 experiments with spring-sown cereals 10 were positive and 2 negative. Of the positive results only 2 show increases of less than 10 per cent, while 6 show increases of 30 per cent, to 57 per cent.; on the other hand both the negative results are quite small, being 6 per cent. and 9 per cent. respectively.The effect of electrification in increasing the yield of spring-grown oats and barley has thus been demonstrated. The mean increase in yield for such crops was 22 per cent.A beneficial effect of the discharge on clover-hay is probable while the effect on winter-sown wheat is still uncertain.Our knowledge of the proper conditions under which the discharge should be given is still so meagre that there is no reason to believe that the increased yields here described are the maximum obtainable as a result of electrification.The mode of action of the current in producing increased growth and yield is still obscure. In several cases the electrified field crops showed a deeper green tint than that of the controls, and work already published has shown that in the case of the coleoptile (plumule sheath) of barley minute electric currents are able to bring about an increase in the rate of growth.The effect of the discharge is of the nature of a stimulus. The additional energy available from the current is too small to have any direct effect since it is only about 1/1000th, or less, of the energy which the plant obtains from sunlight.There is no evidence that gaseous products of the discharge play any part in the stimulation of growth. The additional supply of nitrogen brought to the soil from oxides of nitrogen produced as a result of electrification must be exceedingly small.


Author(s):  
J.A. Eades ◽  
E. Grünbaum

In the last decade and a half, thin film research, particularly research into problems associated with epitaxy, has developed from a simple empirical process of determining the conditions for epitaxy into a complex analytical and experimental study of the nucleation and growth process on the one hand and a technology of very great importance on the other. During this period the thin films group of the University of Chile has studied the epitaxy of metals on metal and insulating substrates. The development of the group, one of the first research groups in physics to be established in the country, has parallelled the increasing complexity of the field.The elaborate techniques and equipment now needed for research into thin films may be illustrated by considering the plant and facilities of this group as characteristic of a good system for the controlled deposition and study of thin films.


1974 ◽  
Vol 31 (02) ◽  
pp. 273-278
Author(s):  
Kenneth K Wu ◽  
John C Hoak ◽  
Robert W Barnes ◽  
Stuart L Frankel

SummaryIn order to evaluate its daily variability and reliability, impedance phlebography was performed daily or on alternate days on 61 patients with deep vein thrombosis, of whom 47 also had 125I-fibrinogen uptake tests and 22 had radiographic venography. The results showed that impedance phlebography was highly variable and poorly reliable. False positive results were noted in 8 limbs (18%) and false negative results in 3 limbs (7%). Despite its being simple, rapid and noninvasive, its clinical usefulness is doubtful when performed according to the original method.


2018 ◽  
Vol 1 (March 2018) ◽  
Author(s):  
S.A Okanlawon ◽  
O.O Odunjo ◽  
S.A Olaniyan

This study examined Residents’ evaluation of turning transport infrastructure (road) to spaces for holding social ceremonies in the indigenous residential zone of Ogbomoso, Oyo State, Nigeria. Upon stratifying the city into the three identifiable zones, the core, otherwise known as the indigenous residential zone was isolated for study. Of the twenty (20) political wards in the two local government areas of the town, fifteen (15) wards that were located in the indigenous zone constituted the study area. Respondents were selected along one out of every three (33.3%) of the Trunk — C (local) roads being the one mostly used for the purpose in the study area. The respondents were the residents, commercial motorists, commercial motorcyclists, and celebrants. Six hundred and forty-two (642) copies of questionnaire were administered and harvested on the spot. The Mean Analysis generated from the respondents’ rating of twelve perceived hazards listed in the questionnaire were then used to determine respondents’ most highly rated perceived consequences of the practice. These were noisy environment, Blockage of drainage by waste, and Endangering the life of the sick on the way to hospital; the most highly rated reasons why the practice came into being; and level of acceptability of the practice which was found to be very unacceptable in the study area. Policy makers should therefore focus their attention on strict enforcement of the law prohibiting the practice in order to ensure more cordial relationship among the citizenry, seeing citizens’ unacceptability of the practice in the study area.


2018 ◽  
Vol 64 (6) ◽  
pp. 799-804
Author(s):  
Darya Ryzhkova ◽  
M. Poyda

Purpose: To study the diagnostic value of PET-CT with 68Ga-PSMA-11 in the diagnosis of a primary prostate cancer, preoperative staging, and the detection of recurrence of prostate cancer (PCa). Methods: 28 patients aged 64.7 ± 8.74 years were included. 10 patients primary prostate cancer, and 18 patients with biochemical recurrence of the disease after radical treatment were examined. All patients underwent PET-CT with 68Ga-PSMA-11 according the whole body protocol. Interpretation of images was performed visually and quantitatively by calculation of SUL max. Results: High focal or diffuse 68Ga-PSMA-11 uptake was found in prostate parenchyma in patients with primary prostate cancer. Additionally metastases in regional lymph nodes were diagnosed in 4 patients and bone metastases were found in one patient. The correlation between 68Ga-PSMA-11 uptake level and Gleason index in the primary tumor (R Spearmen = 0.25, p = 0.57) was not observed. PET-positive results were obtained in 14 patients and PET-negative results in 4 patients with biochemical recurrence of PCa. The relationship between the frequency of PET-positive results and Gleason index was not revealed (R Spearmen = 0.2, p = 0.39). We found a weak but significant correlation between the frequency of PET-positive results and the prostate tumor stage according to the T category (R Spearmen = 0.49, p = 0.049). In patients with low values of PSA (less than 1.0 ng/ml) in 4 out of 9 cases, PET-negative results were obtained. In patients with PSA level more than 1.0 ng/ml PET-positive results were obtained in all cases. Conclusions: PET/CT with 68Ga-PSMA-11 allows to diagnose the primary prostate cancer, to establish the stage of the disease in categories N and M, and also to determine the localization and dissemination of the tumor in patients with biochemical recurrence of prostate cancer. The relationship between 68Ga-PSMA-11 uptake in primary tumor and Gleason index was not found. The probability of obtaining PET-positive results in cases of biochemical recurrence is affected by a PSA level above 1 ng/ml and a high stage of the disease according to the T category (T3-T4).


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