Novel artificial intelligence approach for automatic differentiation of fetal occiput anterior and non-occiput anterior positions during labor.

OBJECTIVES: To describe a newly developed machine-learning (ML) algorithm for the automatic recognition of fetal head position using transperineal ultrasound (TPU) during the second stage of labor and to describe its performance in differentiating between occiput anterior (OA) and non-OA positions. METHODS: This was a prospective cohort study including singleton term (> 37 weeks of gestation) pregnancies in the second stage of labor, with a non-anomalous fetus in cephalic presentation. Transabdominal ultrasound was performed to determine whether the fetal head position was OA or non-OA. For each case, one sonographic image of the fetal head was then acquired in an axial plane using TPU and saved for later offline analysis. Using the transabdominal sonographic diagnosis as the gold standard, a ML algorithm based on a pattern-recognition feed-forward neural network was trained on the TPU images to discriminate between OA and non-OA positions. In the training phase, the model tuned its parameters to approximate the training data (i.e. the training dataset) such that it would identify correctly the fetal head position, by exploiting geometric, morphological and intensity-based features of the images. In the testing phase, the algorithm was blinded to the occiput position as determined by transabdominal ultrasound. Using the test dataset, the ability of the ML algorithm to differentiate OA from non-OA fetal positions was assessed in terms of diagnostic accuracy. The F1 -score and precision-recall area under the curve (PR-AUC) were calculated to assess the algorithm's performance. Cohen's kappa (κ) was calculated to evaluate the agreement between the algorithm and the gold standard. RESULTS: Over a period of 24 months (February 2018 to January 2020), at 15 maternity hospitals affiliated to the International Study group on Labor ANd Delivery Sonography (ISLANDS), we enrolled into the study 1219 women in the second stage of labor. On the basis of transabdominal ultrasound, they were classified as OA (n = 801 (65.7%)) or non-OA (n = 418 (34.3%)). From the entire cohort (OA and non-OA), approximately 70% (n = 824) of the patients were assigned randomly to the training dataset and the rest (n = 395) were used as the test dataset. The ML-based algorithm correctly classified the fetal occiput position in 90.4% (357/395) of the test dataset, including 224/246 with OA (91.1%) and 133/149 with non-OA (89.3%) fetal head position. Evaluation of the algorithm's performance gave an F1 -score of 88.7% and a PR-AUC of 85.4%. The algorithm showed a balanced performance in the recognition of both OA and non-OA positions. The robustness of the algorithm was confirmed by high agreement with the gold standard (κ = 0.81; P < 0.0001). CONCLUSIONS: This newly developed ML-based algorithm for the automatic assessment of fetal head position using TPU can differentiate accurately, in most cases, between OA and non-OA positions in the second stage of labor. This algorithm has the potential to support not only obstetricians but also midwives and accoucheurs in the clinical use of TPU to determine fetal occiput position in the labor ward. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Radiofrequency echographic multispectrometry compared with dual X-ray absorptiometry for osteoporosis diagnosis on lumbar spine and femoral neck.

An innovative, non-ionizing technique to diagnose osteoporosis on lumbar spine and femoral neck was evaluated through a multicenter study involving 1914 women. The proposed method showed significant agreement with reference gold standard method and, therefore, a potential for early osteoporosis diagnoses and possibly improved patient management. INTRODUCTION: To assess precision (i.e., short term intra-operator precision) and diagnostic accuracy of an innovative non-ionizing technique, REMS (Radiofrequency Echographic Multi Spectrometry), in comparison with the clinical gold standard reference DXA (dual X-ray absorptiometry), through an observational multicenter clinical study. METHODS: In a multicenter cross-sectional observational study, a total of 1914 postmenopausal women (51-70 years) underwent spinal (n = 1553) and/or femoral (n = 1637) DXA, according to their medical prescription, and echographic scan of the same anatomical sites performed with the REMS approach. All the medical reports (DXA and REMS) were carefully checked to identify possible errors that could have caused inaccurate measurements: erroneous REMS reports were excluded, whereas erroneous DXA reports were re-analyzed where possible and otherwise excluded before assessing REMS accuracy. REMS precision was independently assessed. RESULTS: In the spinal group, quality assessment on medical reports produced the exclusion of 280 patients because of REMS errors and 78 patients because of DXA errors, whereas 296 DXA reports were re-analyzed and corrected. Analogously, in the femoral group there were 205 exclusions for REMS errors, 59 exclusions for DXA errors, and 217 re-analyzed DXA reports. In the resulting dataset (n = 1195 for spine, n = 1373 for femur) REMS outcome showed a good agreement with DXA: the average difference in bone mineral density (BMD, bias ± 2SD) was -0.004 ± 0.088 g/cm2 for spine and - 0.006 ± 0.076 g/cm2 for femur. Linear regression showed also that the two methods were well correlated: standard error of the estimate (SEE) was 5.3% for spine and 5.8% for femur. REMS precision, expressed as RMS-CV, was 0.38% for spine and 0.32% for femur. CONCLUSIONS: The REMS approach can be used for non-ionizing osteoporosis diagnosis directly on lumbar spine and femoral neck with a good level of accuracy and precision. However, a more rigorous operator training is needed to limit the erroneous acquisitions and to ensure the full clinical practicability.

Emerging and re-emerging infectious disease in otorhinolaryngology.

SUMMARY: Emerging and re-emerging infectious disease in otorhinolaryngology (ENT) are an area of growing epidemiological and clinical interest. The aim of this section is to comprehensively report on the epidemiology of key infectious disease in otorhinolaryngology, reporting on their burden at the national and international level, expanding of the need of promoting and implementing preventive interventions, and the rationale of applying evidence-based, effective and cost- effective diagnostic, curative and preventive approaches. In particular, we focus on i) ENT viral infections (HIV, Epstein-Barr virus, Human Papilloma virus), retrieving the available evidence on their oncogenic potential; ii) typical and atypical mycobacteria infections; iii) non-specific granulomatous lymphadenopathy; iv) emerging paediatric ENT infectious diseases and the prevention of their complications; v) the growing burden of antimicrobial resistance in ENT and the strategies for its control in different clinical settings. We conclude by outlining knowledge gaps and action needed in ENT infectious diseases research and clinical practice and we make references to economic analysis in the field of ENT infectious diseases prevention and care.

Automatic ultrasound technique to measure angle of progression during labor.

OBJECTIVE: To evaluate the accuracy and reliability of an automatic ultrasound technique for assessment of the angle of progression (AoP) during labor. METHODS: Thirty-nine pregnant women in the second stage of labor, with fetus in cephalic presentation, underwent conventional labor management with additional translabial sonographic examination. AoP was measured in a total of 95 acquisition sessions, both automatically by an innovative algorithm and manually by an experienced sonographer, who was blinded to the algorithm outcome. The results obtained from the manual measurement were used as the reference against which the performance of the algorithm was assessed. In order to overcome the common difficulties encountered when visualizing by sonography the pubic symphysis, the AoP was measured by considering as the symphysis landmark its centroid rather than its distal point, thereby assuring high measurement reliability and reproducibility, while maintaining objectivity and accuracy in the evaluation of progression of labor. RESULTS: There was a strong and statistically significant correlation between AoP values measured by the algorithm and the reference values (r = 0.99, P < 0.001). The high accuracy provided by the automatic method was also highlighted by the corresponding high values of the coefficient of determination (r2 = 0.98) and the low residual errors (root mean square error = 2°27' (2.1%)). The global agreement between the two methods, assessed through Bland-Altman analysis, resulted in a negligible mean difference of 1°1' (limits of agreement, 4°29'). CONCLUSIONS: The proposed automatic algorithm is a reliable technique for measurement of the AoP. Its (relative) operator-independence has the potential to reduce human errors and speed up ultrasound acquisition time, which should facilitate management of women during labor. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Treatment of dynamic claw toe deformity flexor digitorum brevis tendon transfer to interosseous and lumbrical muscles: a literature survey.

The authors report the results of a literature survey of corrective surgical treatment based on FDL and FDB tendon transfer for dynamic claw toe deformities. The study revealed that FDL transfer was first described in 1967 by Malcolm A. Brahms in "Common Foot Problems", and FDB transfer was first mentioned in 1993 in the first edition of the treatise by G. Pisani "Trattato di Chirurgia del Piede". The paper also discusses the functional effect of FDB transfer, compared to FDL transfer.

Use of oxidized and regenerated cellulose in thyroid surgery: a prospective analysis as cause of postoperative hypocalcemia on 485 patients consecutively treated.

AIM: The intraoperative hemorrage determines an higher risk of parathyroid glands lesions, and laryngeal nerve injuries. We have examined if the use of oxidized and regenerated cellulose could be a cause of postoperative hypocalcemia because of the compression on the parathyroid glands or for tissue adhesions METHODS: From June 2009 to December 2010 we have examined 485 patients consecutively treated with total thyroidectomy. The cases examined were divided in two groups on the use of ionized cellulose (group A and B). 24 hours after surgical procedure, all patients were submitted to serum calcium evaluation. The data were analyzed with χ2 test and t-student test; P<0.05 was statistically significant. RESULTS: We have selected 372 cases out of 485 examined. We have registered after 10 hours from surgical procedure a case of hemorrhage with reintervention in group B (no use of cellulose). The cost of ionized cellulose is € 46; we have used this device in 212 cases on 372 patients undergone to total thyroidectomy, with a cost of € 9 752. The mean value of the serum calcium was statistically different between pre- and postoperative evaluation in all cases (P<0.0001) divided both on gender and on the use of hemostatic devices. CONCLUSION: In our experience, there isn't a statistically significant difference on incidence of postoperative hypocalcemia, related to use of ionized and regenerated cellulose on mean surgical time in all patients either treated with traditional surgery or with video-assisted procedure.

The molecular causes of low ATM protein expression in breast carcinoma; promoter methylation and levels of the catalytic subunit of DNA-dependent protein kinase.

AIMS: To investigate whether aberrant methylation of the ATM promoter or loss of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) may be the underlying causes of reduced ATM protein levels often seen in breast tumours. METHODS AND RESULTS: Methylation-specific polymerase chain reaction was used to determine the ATM promoter status and DNA-PKcs levels were measured by immunohistochemistry. None of the 74 invasive carcinomas (ICs) studied showed ATM promoter hypermethylation, whereas promoter methylation of CDKN2A/p16 (1.8%) and GSTP1 (15.8%) was detected. Of 92 ICs examined, 68 had reduced DNA-PKcs levels, supporting previous findings that alterations in double-strand break repair are associated with breast cancer pathogenesis. Although no association was found between the DNA-PKcs and ATM scores for the series of 92 tissues and 22/24 tissues with normal DNA-PKcs had reduced ATM, 29 tumours showed low expression of both DNA-PKcs and ATM compared with normal tissues. CONCLUSIONS: No evidence was found that the reduction in ATM protein levels seen in breast carcinoma is the result of epigenetic silencing. However, cross-regulation between DNA-PKcs and ATM may be a possible cause in a subset of tumours and warrants further investigation.

Human papillomavirus and cervical cancer from a prospective study in Khon Kaen, Northeast Thailand.

The risk of developing carcinoma of the cervix in women infected with human papillomavirus (HPV) was estimated in a nested case-control analysis of 33 cancers (invasive and in situ) and 113 controls, matched by age and sex, from an ongoing cohort study of lifestyle and cancer in a rural population of Northeast Thailand. Oncogenic HPV types were present in 10.8% of control women and in 31/33 of the carcinoma cases, corresponding to an odds ratio of 130.6 (95% CI 11.7-1457.0). There was no significant difference in risk between prevalent cancer cases (diagnosed less than 3 months after HPV testing) and incident cases (diagnosed an average of 2.1 years later). HPV 16 and 18 were the most prevalent oncogenic HPV types present. The results confirm that some two of three of cervical cancer cases in this population of Northeast Thailand are caused by HPV 16 and 18.

A prospective study of diet, lifestyle, and genetic factors and the risk of cancer in Khon Kaen Province, northeast Thailand: description of the cohort.

Cohort studies are the preferred design in observational epidemiology, but few involving the general population have been performed in Asia, and most concern affluent urban populations. The Khon Kaen study has recruited about 25,000 subjects, aged mainly 35-64, from villages in the relatively underdeveloped north-east of Thailand. All subjects underwent simple physical examination, completed an interviewer-administered questionnaire (including sections on lifestyle, habits, and diet) and donated specimens of blood, which were processed and stored in a biological bank at -20 degrees C. Female subjects (about 16,500) were offered screening by Pap smear, and specimens of cells from the cervix were stored at -20 degrees C. This paper describes the methodology of the study, and the characteristics of the participants. Almost all subjects are peasant farmers, with low annual income and body mass, although 14.6% of women had a BMI in the obese range (>30 kg/m(2)). Smoking was common among men (78% regular smokers, most of whom used home-produced cigarettes), but rare among women. Fertility levels were relatively high, with a more than half the women having four or more live births. 23.4% of subjects were infected with the liver fluke Opisthorchis viverrini, known to be highly endemic in this region. Follow-up of the cohort is by record-linkage to the provincial cancer registry. By 2003, 762 cancer cases had occurred, the most common being cancers of the liver (363 cases) and cervix uteri (44 cases). The antecedents of these cancers are being investigated using a nested case-control approach. The cohort will yield increasing numbers of cancers for study in the next decade, giving important information on the relative importance of dietary and lifestyle factors in a rural population, undergoing gradual transition to a more westernised lifestyle.

Prevalence of Opisthorchis viverrini infection and incidence of cholangiocarcinoma in Khon Kaen, Northeast Thailand.

Liver cancer is the most common cancer in Khon Kaen, Northeast Thailand, because of the high incidence of cholangiocarcinoma (CHCA). Opisthorchis viverrini (OV), a liver fluke, is endemic in the area, and has been evaluated as a cause of CHCA by International Agency for Research on Cancer. Residents of 20 districts in the province were invited to attend a mobile screening programme between 1990 and 2001. Of 24 723 participants, 18 393 aged 35-69 years were tested for OV infection, by examining stools for the presence of eggs. Prevalence of infection in each district was estimated from the sample of the population who had been tested. The incidence of liver cancer in 1990-2001 was obtained for each district from the cancer registry. The average crude prevalence of OV infection in the sample subjects was 24.5%, ranging from 2.1% to 70.8% in different districts. Truncated age-standardized incidence of CHCA at ages >35 years varied threefold between districts, from 93.8 to 317.6 per 100,000 person-years. After adjustment for age group, sex and period of sampling, there was a positive association between prevalence of OV infection and incidence of CHCA at the population level. Associations between CHCA and active OV infection in individuals have become hard to demonstrate, because of effective anti-OV treatment. The relationship may, however, be clear in comparisons between populations, which, for infectious diseases, take into account the contextual effects of group exposure in determining individual outcome. The cancer registry is an appropriate tool for disease monitoring in small areas.

Trends in postoperative radiotherapy delay and the effect on survival in breast cancer patients treated with conservation surgery.

The adequate timing of adjuvant radiotherapy (RT) in breast cancer has become a subject of increasing interest in recent years. A population-based study was undertaken to determine the influence of demographic and clinical factors on the postoperative RT delay in patients treated with breast-conserving surgery (BCS) and to assess the impact of delay on survival. In total, 7800 breast cancer patients treated with BCS and adjuvant RT between 1986 and 1998 in Yorkshire were included in the study. The median interval between surgery and the start of RT (S-RT interval) was 8 weeks (7 weeks for chemotherapy negative and 11 for chemotherapy positive patients). This interval increased substantially over time from 5 weeks during 1986-1988, irrespective of patients' chemotherapy status, to 10 and 17 weeks among chemotherapy negative and chemotherapy positive patients, respectively, in 1997-1998. The S-RT interval was also significantly influenced by travel time to RT centre, year and at which RT centre patient had the treatment (P<0.001). Overall, 5-year survival was 82%. Patients with S-RT intervals longer than 9 weeks had a trend towards an increased relative risk of death. This reached a statistical significance at 20-26 weeks (RR 1.49, 95% CI (1.16-1.92)). The findings of our study suggest that delaying the initiation of RT for 20-26 weeks after surgery is associated with decreased survival in patients treated with conservation surgery.

Declining mortality from breast cancer in Yorkshire, 1983-1998: extent and causes.

Incidence and mortality data, stage of disease and treatment information for female breast cancer were obtained for the years 1975-1999 for the former Yorkshire Regional Health Authority area, from the Northern and Yorkshire Cancer Registry and Information Service. Deaths by age group and 3-year calendar period were separated into those occurring among cases diagnosed 0-2 and 3-4 years preceding death (short- and medium-term survivors, respectively), and among longer-term survivors and age-adjusted rates were calculated separately by survival time. The 3-year survival of cases incident in 1991-1999 and in 1982-1990 were compared, adjusting for stage and treatment. Breast cancer mortality in Yorkshire stopped increasing around 1983 and has since consistently declined, primarily among short- and medium-term survivors. The 3-year survival was significantly improved in cases diagnosed in 1991-1999, compared with 1982-1990, in all age groups (hazard ratio (HR)=0.75, 95% c.l. 0.71-0.78). The improvement was least in the 65+ years age group (HR=0.83, 95% c.l. 0.79-0.88), intermediate in the youngest (<50 years) cases (HR=0.71, 95% c.l. 0.63-0.80) and greatest in the age group 50-64 years, offered routine screening after 1988 (HR=0.51, 95% c.l. 0.47-0.57). The benefit for cases diagnosed in the 1990s persisted, but was reduced after adjustment for stage in cases <65 years, while it disappeared in older cases (HR=1.01). Below age 65 years, the use of systemic therapy increased substantially, but did not explain the residual improvements in short-term prognosis. A greater decline in breast cancer mortality in Yorkshire from 1982 to 1984 was observed among short- and medium-term, than in longer-term, survivors. Much of the improvement in survival in cases <65 years could be attributed to a more favourable stage at diagnosis, whereas this accounted for nearly all the improvement in survival among older cases. Systemic therapy had little or no impact on 3-year survival. Continuing declines in mortality can be expected in the current decade, as a result of the long-term effects of both mammography screening and increased use of systemic therapy.

Visual inspection in oral cancer screening in Cuba: a case-control study.

A case-control study was conducted to evaluate the efficacy of an on-going oral cancer screening programme in Cuba in preventing advanced oral cancer in Cuba. The cases for the study consisted of 200 oral cancer patients with stage III and IV disease. Three apparently healthy subjects per case, matched for sex, age (plus or minus 5 years) and residing within a perimeter of 200 m of the house with the case, and willing to be interviewed, were recruited as the controls. Information on socio-economic indicators, smoking, drinking, diet and screening history in the form of visits to the dentist were collected by personal interview with the subjects. Odds ratio (OR), with 95% confidence intervals (CI), of being diagnosed with an advanced oral cancer, in relation to the screening experience at the date of diagnosis of case, 1, 2, 3, 6, and 12 months prior to the date of diagnosis of case were estimated by conditional logistic regression for matched data. The odds ratio of advanced oral cancer associated with screening in relation to screening experience 3 months prior to the diagnosis of the case was 0.67 (95% CI: 0.46-0.95). The odds ratio was 0.91 (95% CI: 0.60-1.37) for a single screening test and 0.41 (95% CI: 0.24-0.68) for two or more tests. The protection offered by screening persisted up to 3 years since the last test. The results of a descriptive evaluation of the programme also revealed limited evidence towards a shift from advanced to early stages after the introduction of the programme. Nonetheless, the results should be interpreted with caution in view of the several limitations in the study, particularly the fact that screening history was established indirectly by interviews and advanced oral cancers constituted the cases, rather than those who died from the disease.

Reduction of Death Certificate Only (DCO) Registrations by Active Follow Back.

Death certificates are an important source of information for cancer registries that help to improve completeness of case finding. In many countries where routine mortality data are considered of poor quality, this source is often regarded as being of little value. We evaluated the contribution of death certificates to the total number of registrations in the years 1993-1997, in the Manila Cancer Registry (MCR). We compared the "standard" practice of retrieving clinical information if the death certificate was completed in a hospital, with active search of additional information from the deceased's relatives when the death was certified at home.The standard procedure allowed us to reduce the proportion of cases registered from a death certificate by 5%. The improvement varied significantly among the most common sites with a reduction of 10% for lymphomas to less than 1% for cancers of the cervix.The proportion of liver cancers registered from a death certificate only (DCO), originally 47%, was reduced to 29% by contacting relatives of the deceased patients. In countries with limited investment in information systems, death certificates, even when recognised as being of poor quality, are an important source of information for cancer registries.

Overweight as an avoidable cause of cancer in Europe.

There is growing evidence that excess body weight increases the risk of cancer at several sites, including kidney, endometrium, colon, prostate, gallbladder and breast in post-menopausal women. The proportion of all cancers attributable to overweight has, however, never been systematically estimated. We reviewed the epidemiological literature and quantitatively summarised, by meta-analysis, the relationship between excess weight and the risk of developing cancer at the 6 sites listed above. Estimates were then combined with sex-specific estimates of the prevalence of overweight [body mass index (BMI) 25-29 kg/m(2)] and obesity (BMI > or = 30 kg/m(2)) in each country in the European Union to obtain the proportion of cancers attributable to excess weight. Overall, excess body mass accounts for 5% of all cancers in the European Union, 3% in men and 6% in women, corresponding to 27,000 male and 45,000 female cancer cases yearly. The attributable proportion varied, in men, between 2.1% for Greece and 4.9% for Germany and, in women, between 3.9% for Denmark and 8.8% for Spain. The highest attributable proportions were obtained for cancers of the endometrium (39%), kidney (25% in both sexes) and gallbladder (25% in men and 24% in women). The largest number of attributable cases was for colon cancer (21,500 annual cases), followed by endometrium (14,000 cases) and breast (12,800 cases). Some 36,000 cases could be avoided by halving the prevalence of overweight and obese people in Europe.

[Complications in thyroid surgery]. / Le complicanze della chirurgia tiroidea.

Today, when performed applying stringent technique, thyroid surgery can be considered a procedure with low risk of post-surgical complications. Post-surgical hypoparathyroidism is frequent (1.6-53.6% of the cases) although most of these cases are temporary, linked to functional stupor of the parathyroid glands and/or other reversible factors. Analysis of the literature has shown that preservation of 3 or more parathyroid glands is a highly positive (95%) predictive factor for normal post-operative calcemia. The incidence of recurrent definitive paralysis ranges around 0.3-2% of the nerves at risk of iatrogeneous lesions and is usually correlated with thyroid histology and with the extension and type of ablative treatment performed. The authors retrospectively consider a 10-year case study of 218 patients (222 surgical procedures, of which 17 undergoing surgery twice) analyzing endocrinological, hemorrhagic and neurological complications and paying particular attention to any vocal dysfunctions arising at a later date, even in the absence of an ascertained neurological deficit. Considering 116 total and subtotal thyroidectomies, the percentages of acute hypoparathyroidism (AH) and definitive hypoparathyroidism (DH) were, respectively, 43.9% and 6%. Four of the 7 cases of DH presented one of the factors known to increate the risk of complications: malignant thyroid histology, second surgery and/or lymph node dissection. As regards neurological sequele, the authors report an incidence of recurrent definitive paralysis of 1.8% (3 out of 35 nerves at risk examined using EMG of the cricothyroid muscle). Spectroacoustic analysis of samples from 42 subjects showed an alteration in the vocal parameters considered (jitter, shimmer, NHR and DSH) in 14-27% of the cases, even in the absence of any laryngeal nerve deficit. It may be that iatrogeneous lesions and/or scarring of prethyroid strap muscles, known to play a role in phonation mechanisms, are implicated in determining post-thyroidectomy vocal dysfunctions, seen even in patients with anatomfunctionally intact laryngeal nerves.

Environmental exposure to asbestos and risk of pleural mesothelioma: review and meta-analysis.

A number of epidemiological studies have addressed the risk of pleural mesothelioma from environmental (household and neighborhood) exposure to asbestos, but no overall risk estimate is available. We reviewed the epidemiological studies on risk of pleural mesothelioma and household or neighborhood exposure to asbestos. We identified eight relevant studies; most were conducted in populations with relatively high exposure levels. We combined the risk estimates in a meta-analysis based on the random-effects model. The relative risks (RRs) of pleural mesothelioma for household exposure ranged between 4.0 and 23.7, and the summary risk estimate was 8.1 (95% confidence interval [CI]: 5.3-12). For neighborhood exposure, RRs ranged between 5.1 and 9.3 (with a single RR of 0.2) and the summary estimate was 7.0 (95% CI: 4.7-11). This review suggests a substantial increase in risk of pleural mesothelioma following high environmental exposure to asbestos; however, the available data are insufficient to estimate the magnitude of the excess risk at the levels of environmental exposure commonly encountered by the general population in industrial countries.