Use of cellular telephones has been widely increasing and has become part of everyday life. Concerns about adverse health effects of radiofrequency signals have been raised in the last 10 years. Lately, many research papers argued about the adverse effects of radiofrequency signals emitted from the cellular phones on the salivary glands and brain tissues as they are the mostly localized exposure target regions to the radiation. Studies that approached reasonable exposure latencies found significantly high risks to the development of neoplastic diseases. On the other hand, most of the studies showed no evidence of the potentiality of mobile phones to cause tumors. Yet, most of the studies had some methodological deficiencies as the short duration of mobile phone use, recall bias and the inadequate number of cases. The results of the present studies are questionable and causal association between cellular mobile use and adverse health effect can't be ruled out. Therefore, further scientific research is needed to find whether mobile phones can really affect parotid gland, brain and the health in general.
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During the most recent decades, there has been rapid development of the use of wireless telephone communication. The wireless technology was introduced early in the 1980's and large expansion in its use has occurred science late 1990's.Nonetheless,the introduction of wireless communication has been technically driven without proper laboratory testing or epidemiological studies regarding its effects on health .
A concern of mobile health effects has been raised in respect to the radiofrequency radiation emitted by the mobile phones which is assumed to have certain biological effects like tumor promotion, genes mutation and functional abnormalities1. Furthermore, the scientific studies suggested that mobile radiation might increase the risk of developing cancer of the radiosensitive organs, located in the ipsilateral side of the head, such as the parotid salivary glands and the brain2. However, these concerns are not well documented by scientific studies. A number of studies regarding the adverse health effect of mobile phone use were conducted and others are still investigating this association. Nevertheless, the results of these studies are inconclusive concerning the hazardous effect of mobile phones3 (reference hessa al2assasy).
This review illuminates the results of studies done to asses the relation between mobile phones and adverse health effect, in order to clarify whether mobile phones can alter the function and contribute to tumor formation and promotion in the parotid gland, brain and other structures in the head in the side of mobile use.
Physics and biology of mobile phones
Worldwide, more than 500 million mobile phones are in use and the number is expected to increase in the subsequent years4 .The rapidly evolving mobile phone technology raised public concern about the possible adverse health impacts from exposure to the radiation emitted by the mobile phone.
Mobile phones emit non ionizing microwave radiation which is transmitted between the base station and the transportable handset over a certain distance. These radiations can produce some thermal and non thermal impacts on biological tissues as a result of radiation absorption by the human tissues. Unfortunately, the radiation emitted may cause other biological effects on the tissues unrelated to temperature raise and heating effects5 (ask hessa.
Mobile telephone is based on two-way radio communication between a portable handset and the nearest base station. Every base-station serves a cell, varying from hundreds of meters in extent in densely populated areas to kilometers in rural areas, and is both connected to the conventional land-line telephone network. As the user of a mobile phone moves from cell to cell, the call is transferred between the base-stations without interruption3.
The radio communication uses microwaves at 450 and 1800 MHz to carry voice information via small modulations of the wave's frequency. The dosimetric quantity of microwaves is given by the Specific Absorption Rate (SAR) which is defined as the absorbed power per unit mass (W/kg)6. The antenna of the handset radiates equally in all directions but a base station produces a beam that is more directional. Although the transmitted power of the base stations is much higher than that of the handheld mobile phone, the exposure of the user by the base stations is much less due to the larger distance as compared to the handheld mobile phone.
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The use of mobile phones can produce thermal and non thermal effects on the biological tissues
Heating of biological tissue is a consequence of microwave energy absorption by the tissue's water content. The amount of heating produced in a living organism depends primarily on the intensity (or power density) of the radiation once it has penetrated the system, besides the efficiency of the body's thermoregulation mechanism. Above a certain intensity of the microwaves, temperature homoeostasis is not maintained, and effects on health result once the temperature rise exceeds about 1 o C3.
Exposure of the whole body with an average SAR of 4 W/kg will lead to a temperature rise of 1 o C, which means that tissue heating may only occur at high SAR values. The temperature rise in the brain due to a mobile phone was found to be less than 0. 1 o C, lasting effects due to heating are not expected. The most thermally vulnerable areas of the body are the eyes and the testes because of their low blood supply, therefore cataract formation and reduced sperm hazards are possible results6.
Non thermal impacts
The microwave radiation has certain well defined frequencies, which facilitate its discernment by a living organism, and via which the organism can, in turn, be affected. The human body is an electrochemical instrument of exquisite sensitivity whose function and control are underpinned by oscillatory electrical processes of various kinds. Some endogenous biological electrical activities can be interfered via oscillatory aspects of the incoming radiation. The biological electrical activities that are vulnerable to interference from the mobile radiation include highly organized electrical activities at a cellular level. A good example of human vulnerability to a non-thermal electromagnetic influence is the ability of a light flashing at about 15 Hz to induce seizures in people with photosensitivity epilepsy7.
There are other biological effects resulted from the use of mobile phones:
Tumor promotion and progression
Most of the studies, which have been performed to investigate an association between long term low level microwave exposure and tumor promotion or progression, did not find a significant difference between the exposed and the control groups. Recently, an experiment done indicated that long term microwave radiation does not increase lymphoma incidence 8. Two recently published studies with similar experimental design also showed no significant effect 9, 10.
Permeability of blood-brain-barrier
In animal experiments, a study found an increased permeability of the blood-brain-barrier for continuous as well as for pulsed microwave radiation11. Studies of other authors, however, could not confirm these findings12.Another study showed a significant increased permeability only for the highest SAR values of 7.5 W/kg, but not for lower values 13. Such high SAR values, however, do not occur when using mobile phones and it was suspected that the positive findings may have been produced by thermal effects.
Subjective symptoms such as headache, feelings of discomfort and warmth on the ear were reported by users of mobile phones. In comparison between analogue and digital mobile phone systems, the prevalence for the symptoms for the analogue was found to be higher than for the digital system14.
Ca efflux in nervous tissue
Calcium ions play an important role in the signal chain of neurons and other cells. There is some evidence that microwave exposure of brain tissue may increase the calcium efflux from cells15. Experiments demonstrated increased calcium efflux for an extremely low frequency modulated 147 MHz microwave carrier frequency. Increased calcium efflux may stabilize neurons and reduce their excitability. As long there is no significant temperature rise, the exposure does not produce obvious effects. Effects on neurotransmitters have also been observed16.
Influence on blood pressure
The impact of microwaves from mobile phones on resting blood pressure was investigated by a study which found that systolic and diastolic blood pressure was significantly higher in the exposed compared to the placebo group17. A more recent study published by the same author also found a significant increase in blood pressure independent from the exposure pattern by the mobile phone radiation. 18. It was therefore concluded that mobile radiation does not affect blood pressure in humans.
Mobile phones and parotid gland
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The parotid gland is the largest of the three paired salivary glands. The anatomic location of the parotid gland (at the anterior border of the external ear and between the mandibular ramus and the sternocleidomastoid muscle, 4-10 mm deep in the skin surface) makes tumors plausible candidates for being influenced by exposure to cellular phones, on the side of the head where the cellular phone is held.
A number of case-control studies were performed by Hardell19 regarding the tumor risk due to exposure to microwaves emitted by cellular phones. These studies took place in Sweden as it's one of the first countries that introduced the use of wireless technology.
The first study 20 showed no increased risk for salivary tumors due to the use of analogue cellular phones, digital or cordless phones for using periods ranging from 1 year to up to ten years (three categorizes >1 year,> 5 years and > 10years). The results were limited due to few cases with long-term use of the phone types. Only 6 cases had used an analogue phone for more than ten years and no one had used a digital or cordless phone using that latency period. No significant increased odd ratio was found ipsilateral exposure.
Another study that evaluated the relation between cellular phone use and cancer is a nationwide retrospective cohort study in the Denmark 21, this study involved a number of 420,095 cellular telephone users who subscribed between 1982 -which was the year in which the service was put in operation- and 1995 .The cancer incidences were determined by linkage with the Danish cancer registry that was initiated in 1942.
The result showed no evidence for an association between parotid gland risk and cellular telephone use among either short-term or long-term users.
Another case-control study 22was done in Sweden, in which the cases were assessed from the six regional cancer registries in Sweden. A total of 293 living cases and 1172 controls were included. The study covered all information about the phone types, different anatomical localization of tumors and histopathology types of the different salivary tumors.For all studied phone types no association was found with tumors in the parotid gland, with no effect of latency period or cumulative use of hours. On the other hand, an increased risk was found for all studied phone types and for tumors in the submaxillary gland; however, this result is based on low numbers of cases. In addition to that an increased risk was found for squamous cell carcinoma for both cellular and cordless telephones, but their finding was based on few cases, so the result does not permit any conclusion according to this type of cancer.
Generally, the result of this study did not show any association between use of cellular or cordless telephones and salivary gland tumors
A study was done in both Denmark and Sweden23 to test the hypothesis that exposure to radiofrequency electromagnetic field from mobile phones increases the risk for malignant parotid gland tumor and benign pleomorphic adenomas, even though the parotid gland tumors are very rare and the etiology is largely unknown. Two population-based case-controls were done, one in Denmark and one in Sweden following the same core study protocol. All the cases with malignant and benign were identified continuously during the study period (2000-2002) and aged 20-69years. Detailed information about phone use was collected (by personal interview, telephone interview, mailed questionnaire or if the case had died, the closet family member was asked to participate) from 60 cases of malignant parotid gland tumors, 112 benign pleomorphic adenomas and 681 controls who were randomly selected from the study population base.The study included all information about the mobile phone use ( regular or not regular use), number of years of regular mobile use( which categorized as less than 5 years, 5-9 years, 10 or more), numbers of hours of mobile phone use and number of mobile phone calls, type of mobile as the usages of analog phone and digital mobile phone were analyzed separately ( because it is believed that the old analogy phones emits on average higher than the digital one) and separate analyses were also done for persons reporting mobile phone use mainly in urban areas, in rural areas, and in both urban and rural areas, because higher exposure levels have been reported for phone use in rural areas.
Also the possible association between laterality of phone use and laterality of tumors was analyzed. Exposure was defined as ipsilateral phone use or use of the phone on both sides, whereas contralateral use was considered unexposed, on other hand they made similar analyses where contralateral phone use or use on both sides was considered exposed, and ipsilateral use was consider unexposed.
For regular mobile phone use, the estimated odd ratio was 0.7(95 % confidence interval: 0.4 - 1.3) for malignant parotid tumors and 0.9(95% confidence interval: 0.5 - 1.5) for benign plemorphic adenomas. The risk estimated did not increase with the amount of use or duration (similar results were found for more than 10 years of mobile phone use). Separate analyses of digital and analog phone use did not show any increased risk and similar result of no increased odd ratios for use of mobile phones mainly in rural or urban.
The results for benign tumors displayed higher odds ratios for ipsilateral use compared with those for malignant tumors, although the confidence intervals were relatively wide and no estimates were significantly different from (1.0). The risk estimates for contralateral exposure showed decreased odds ratio for both malignant and tumors.
The results of this study do not indicate any association between mobile use in hours or number of calls and the risk of malignant or benign parotid gland tumors. so their findings agrees with the previous results in studies of the association between use of mobile phones and risk of malignant parotid gland tumors, while this study was the first report that looked for any association between benign parotid gland tumors and mobile phone use.
The Nationwide Danish cohort study was followed up and the update was published in 2006 five years from the first study 24. The same number of subscribers who subscribed between 1992 and 1995 was followed but the follow up period increased to 8.5 years as an average and 21 years as maximum. They also found no increased risk of salivary gland tumors , and no association between salivary gland tumors and cellular telephone use among either short-term or long-terms users.
A nationwide case-control study conducted in Israel 25 evaluated the risk of benign and malignant parotid tumor and cellular phone use. The study included 402 benign and 58 malignant cases in 2001-2003 and 1,266 population individuals as controls. The results suggested a positive relation between the long term use (five years and more) and the parotid gland tumors.
Likewise, a dose response relation was established as the tumor risk was found to be elevated in the ipsilateral side and both sides use for a regular use of five and more years, while no significant result was found for the contralateral use.
In addition, a positive association was seen for cellular phone use in the rural areas, which was not seen in the urban areas .This can be explained by the higher output power (power in watts of radio frequency energy) in the rural areas as the base stations are located far apart in comparison to the urban areas.
Generally, the study concluded that the increased risk for parotid gland tumors and mobile use is positively related to the long term use.
Another case-cohort study which was done in Israel26 assessed if there are any physiological changes associated with handheld mobile phone (MPH) in terms of secretion rates and protein levels in the secreted saliva between dominant and less dominant sides of subjects from healthy population who use MPH.
The study included 50 healthy volunteers (25 men, 25 women; mean age 27 Â± 3.2 years) with a mean of 7 years of MPH use. More than half reported using MPH at least five times a day, with only 2% using MPH twice a day and 80% used the right ear more frequently. Exclusion criteria included systemic chronic diseases, past head or neck injury, trauma, drug abuse, chronic alcohol or smoking abuse, pregnancy, no preferable custom to side holding the MPH, and history of xerostomia. All subjects used MPH that do not exceed the permitted SAR (specific absorption rate) limits.
Stimulated salivary secretion rate of both parotid glands of the volunteers was assessed by asking the cases not to eat, drink, or brush their teeth an hour before collection of saliva. Salivary flow was stimulated with 2% critic acid.
The study found that a 2.54-fold increase in salivary secretion rate between the dominant and non-dominant sides. In addition to that middling correlation strength was found between the dominant and non-dominant sides and the number of years of MPH use, while no correlation was found between daily MPH time use and the saliva secretion rate.
According to protein concentration, the mean of protein concentration showed significantly higher concentration in saliva secreted in the left gland in subjects whose dominant side was right, while in subjects whose dominant side was left; the study showed no significant differences between the two parotid glands. Overall the total protein per ml concentration was slightly higher in dominant side by 1-2-folds with no significant difference.
No correlation was found between protein concentration and the number of years of MPH use and also no correlation was found between daily MPH time use and the protein concentration.
The study explained that the increase in the salivary flow may be related to the microwave energy eliminated by MPH which elevates the skin temperature and induces an increase in the perfusion of the tissue to cool it down, so enriched capillary bed adjacent to the parotid glands may result in an increase in the perfusion because of the blood vessels propagation over an extensive time of exposure to heat, leading to an increase in the salivary rate flow.
Another explanation for the results of the study was also related to thermal effect of MPH which may be attributed to secretory parenchymal tissue expansion.
According to this study, there were changes in the salivary secretion and protein concentration associated with MPH use and they expect a decrease in the ratio of saliva secretion between the dominant and non-dominant sides when the number of years of MPH use increased (>7 years) and a possible explanation of this is the compensatory mechanism (a process known to occur in salivary glands) resulting from continuous insult to the dominant MPH side.
Mobile phones and the brain
Brain cancer is considered as a leading cause of cancer-related death, and it cannot be presently attributed to known risk factors. Recently a great attention was focused in the possible link between cellular phone use and brain cancer as the brain is directly exposed to radio waves emitted by the cellular phone. A wide number of studies investigated this link and illustrations of some of the most recent studies follow.
Braune et al. 27have reported acute effects on blood pressure in human volunteers exposed
to a conventional GSM (Global System for Mobile Communications) digital mobile phone positioned close to the right side of the head. After 35 minutes of exposure, heart rate, blood pressure and capillary perfusion were measured with the subject either supine or standing for 60 seconds. They found that the heart rate during these tests was slightly lower after exposure to RF radiation than following unexposed control sessions, and both systolic and diastolic blood pressure were elevated by 5-10 mm of mercury.
A study carried out to see if mobile phone radiation disturbs sleep patterns at the
University of Zurich in year 200028. Electromagnetic fields from mobile phone use in bed
significantly increases brain activity during early, non-rapid-eye-movement sleep. 16 people were subjected to electromagnetic radiation similar to mobile phone use for 30 minutes
before they went to sleep. Increased brain activity lasted up to 50 minutes. This effectively
means that people will soon have to accept that mobile phone do have a biological effect.
Blood-brain barrier, which prevents large molecules from crossing into the cerebrospinal
fluid from the blood, might be susceptible to low level pulsed RF fields. Frey et al 29
reported increased penetration of the blood-brain barrier of anaesthetized rats after acute low level exposure to pulsed or continuous-wave 1.2 GHz fields.
Two recently published large case-control studies have compared cell phone use among brain cancer patients and individuals free of brain cancer. The first study compared 469 brain cancer patients diagnosed between 1994 and 1998 in New York, Providence, and Boston, with 422 controls 30.The second that is larger compared 782 brain cancer patients diagnosed in Phoenix, Boston, and Pittsburgh between1994 and 1998 with 799 controls 31.
The two case-control studies had similar results including that the brain cancer patients did not report more cellular phone use overall than the controls. In fact, most of the studies showed a tendency toward lower risk of brain cancer among cellular phone users, for unclear reasons. When individual types of brain cancer were considered, none was consistently associated with cell phone use .Furthermore, when specific locations of tumors within the brain were considered separately, no associations with cell phone use were observed and none of the studies showed a "dose response relationship" between cell phone use and brain tumor risk. Finally none of the studies showed a clear link between the side of the head on which the brain cancer occurred and the side on which the cellular phone was used.
The case-control studies performed by Hardell19 regarding the tumor risk due to exposure to microwaves emitted by cellular phones investigated brain tumor risk as well .
The first study 20 showed no increased risk for brain tumors due to the use of analogue cellular phones, digital or cordless phones for using periods ranging from 1 year to up to ten years (three categorizes >1 year,> 5 years and > 10years).only 16 cases had used analogue cellular phones for more than ten years, while the digital phones had been used by 4 cases for a latency period over the five years and no case for over ten years. This study is limited by low numbers of exposed cases & short latency periods; therefore, no firm conclusion could be drawn. However, elevated odds ratios (2.6- 95%CI 1.02-6.7) were recognized for tumors in the ipsilateral use of mobile phones (predominant mobile phone use at the site of tumor).
The following two case-control studies32, 33 on brain tumors were larger and encompassed a larger number of participants (1254 case with benign tumors, 905 with malignant brain tumor and 2162 controls).These two studied involved a number of brain tumor types. On type is meningioma which is a benign brain tumor of adult attached to the durra and arising from the arachnoid. The results showed that the risk of meningioma increased with latency period and no significant trend was found in regard to phone types studied (analogue, cordless or digital phone). Another type of brain tumor evaluated was astrocytoma which is tumor of the astrocytes and it is classified into four classes according to its aggressiveness (from grade I to grade IV).for the astrocytoma grade I-II no significance results were found and no trend of increasing odd ratios with increasing latency period was found. On the contrary, for astrocytoma grade III-IV increased odd ratios were observed with increasing latency period, and it was highest with a latency period over the ten years. The two case-control studies also evaluated the risk of acoustic neuroma which is a benign intracranial tumor of the myelin-forming cells of the vestibulocochlear nerve. All phone types showed increased risk, and in fact the highest odd ratio in the brain tumors was found to be in acoustic neuroma. This tumor might be the "signal" tumor type that shows increased risk from microwave exposure, since it is located in an anatomical area with high exposure during calls with cellular or cordless phones.
Another study that evaluated the relation between cellular phone use and cancer is the nationwide retrospective cohort study in the Denmark21. Regarding the brain tumors, the study found that the number of the brain and nervous system tumors is remarkably close to the expected on the basis of the incidence rates in general population. The Standard Incidence Rate (SIR: the number of observed cancer cases to the expected number of cases) for brain tumors was 0.95 with 95%CI(0.81-1.12) which indicated no increased risk .the SIRs of brain tumors were not related to the latency period, the age at the first subscription and the type of cellular telephone system used . Moreover, analysis by anatomic location of the brain tumor within the head revealed no unusual clustering that could be related to increased exposure to the radiofrequency radiation from cellular telephones including the occipital lobe which would be closest to the antenna of cellular phone when in use. The absence of increased risk was also seen in the acoustic neuroma.
Although this study included more than 420000 cellular phone users, a number of limitations had possibly influenced the result. On limitation is that the latency period (average of 3.1 years) was believed to be too short to detect an early stage effect or an effect on the slowly growing brain tumors. Furthermore, the duration of phone usage seemed to be overestimated as the subscribers are not necessarily the sole users of the phone.
Similarly, in the follow up of the nationwide cohort Danish study 24 no increased risk of brain tumors was found even in the long term users of ten years and more.
The findings with respect to acoustic neuroma are of interest in view of the results of a recent pooled analysis from five countries (Denmark, Sweden, Norway, Finland, United Kingdom; part of the Interphone study)34. Although there was no increased risk in acoustic neuroma overall (odds ratio = 0.9) or among those using cellular phones for more than 10 years (odds ratio =1.0), a risk among long-term users could not be completely ruled out because a statistically significant increased risk (odds ratio =1.8) was found for tumors that developed on ipsilateral head side. The risk for contralateral tumors was decreased (OR=0.9), and, after considering multiple sources of potential bias, the authors concluded that no firm conclusions could be drawn. Overall risk for acoustic neuroma (SIC = 0.73) was consistent with that form the interphone study (overall OR=0.9). The study has several strengths including the large number of the cohort and the long follow up period as they were able to address potential risks many years after first telephone use that has not been possible in most studies. On the other hand, the study has a number of limitations .one limitation is the exclusion of the users whose subscription was in the name of their company which resulted in reduction in the proportion of users besides elimination of some of the most active subscribers. A further limitation is that the study included none of the subscribers after the 1995, which means that they were included in the reference population. In other words, the majority of the reference population consisted of recent cellular phone users providing a potential source of underestimation of risk. The study concluded that no evidence for an association between brain tumor risk and cellular telephone use among either short-term or long -term users was found.
Another case control study carried out in the United States also stated negative results 35. In this case-control study, 90 acoustic neuroma cases were compared with hospital controls. The odd ratio was estimated to be 0.9, and no risk was found to be linked with the frequency, duration, or lifetime hours of use.The intratemporal facial nerve (IFN) is exposed to higher levels of cellular telephone radiation than intracranial tissues. Cellular telephones are held in close proximity to the temporal bone. Hence, the IFN, particularly the tympanic segment, is exposed to relatively high doses of microwave radiation.
A case-control study 36 conducted to determine whether cellular telephone use is associated with an increased risk of IFN tumors. In this study a structured telephone survey was completed by patients with IFN tumors and patients treated for acoustic neuroma and control subjects. Risk of facial nerve tumorigenesis was compared by extent of cellular telephone use and other risk factors.There was no association with regular use of handheld cellular telephones in patients (cases) with IFN tumor (OR _ 0.4; 95% CI, 0.1-2.1) or in subjects with acoustic neuroma (OR _ 1.0; 95% CI, 0.4-2.2). There are numbers of possible reasons why no link between cellular telephone use and development of IFN tumors and acoustic neuroma was observed in the present study.
The first reason is the study was based on self reporting of cellular telephone use so people may not respond truthfully, either because they cannot remember or because they wish to present themselves in a socially acceptable manner. Another possible reason is the recall bias is thought to act in the opposite direction with patients (cases) being more likely to recall past exposures than control subjects because they have a serious illness and have been thinking about possible causes.
Finally a well accepted reason is the insufficient period of exposure to cellular telephone radiation as cellular telephones have only been at the consumer market in the past 5 to 10 years which is inadequate to assess a relative risk between cellular telephone use and the incidence of IFN tumors.
As regard to the acoustic neuroma a case-control study conducted in Japan37 to find out whether the cellular telephone use is associated with an increased risk of acoustic neuroma. The study included 101 acoustic neuroma cases, which were 30-69 years of age and resided in the Tokyo. The results showed no significant increased risk of acoustic neuroma in association with mobile phone use in Japan as no risk was observed using a cumulative call time (300-900 hours), cumulative length of use (4-8years) and no significant risk was seen in those who used digital and analog phones and who used digital mobile phones only. Besides, laterality of mobile phone use wasn't associated with the tumors.
As cellular telephones are a relatively new technology, a clear conclusion can not be drawn about the association between the use of mobile phones and both parotid salivary gland and brain cancer. Because mobile phones were invented only since early 1980s, long-term follow-up on their possible biological effects can not be accomplished. It is impossible to prove that any product or exposure is absolutely safe, especially in the absence of very long-term follow-up. The lack of ionizing radiation and the low energy level emitted from cell phones and absorbed by human tissues make it doubtful that these devices can cause cancer.
Several epidemiological studies done did not show reliable results due to some methodological deficiencies such as small number of cases and short term follow up. Furthermore, numerous well designed studies did not support the hypothesis of an association between the use of handheld mobile phones and both parotid salivary gland and brain tumors. Further explorations are necessary to confirm the findings of the previous conducted studies and to eliminate the methodological problems encountered.