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Purpose: Electronic (e) patient-reported outcomes (PROs) have been shown to improve the quality of life and survival in chemotherapy treated advanced cancer patients. We hypothesized that multidimensional ePRO centered approach could improve symptom management, streamline patient flow, and optimize the use of healthcare resources. Methods: In this multicenter trial (NCT04081558), colorectal cancer (CRC) patients receiving oxaliplatin-based chemotherapy as adjuvant or in the first- or second-line setting in advanced disease were included in the prospective ePRO cohort, while a comparative retrospective cohort was collected from the same institutes. The investigated tool consisted of a weekly e-symptom questionnaire integrated to an urgency algorithm and laboratory value interface, which generated semi-automated decision support for chemotherapy cycle prescription and individualized symptom management. Results: Recruitment to the ePRO cohort occurred 1/2019–1/2021 (n = 43). The comparator group (n = 194) consisted of patients treated in the same institutes 1–7/2017. The analysis was limited to adjuvant treated (n = 36 and n = 35). The feasibility of the ePRO follow-up was good with 98% reporting easy usage and 86% improved care, while health care personnel valued the easy use and logical workflow. In the ePRO cohort, 42% needed a phone call before planned chemotherapy cycles, while this was 100% in the retrospective cohort (p = 1.4e−8). Peripheral sensory neuropathy was detected significantly earlier with ePRO followed (p = 1e−5) but did not translate to earlier dose reduction, delays, or unplanned therapy termination compared to the retrospective cohort. Conclusion: The results suggest that the investigated approach is feasible and streamlines workflow. Earlier symptom detection may improve the quality in cancer care.

In many populations, the peak period of incidence of type 1 diabetes (T1D) has been observed to be around 10–14 years of age, coinciding with puberty, but direct evidence of the role of puberty in the development of T1D is limited. We therefore aimed to investigate whether puberty and the timing of its onset are associated with the development of islet autoimmunity (IA) and subsequent progression to T1D. A Finnish population-based cohort of children with HLA-DQB1-conferred susceptibility to T1D was followed from 7 years of age until 15 years of age or until a diagnosis of T1D (n = 6920). T1D-associated autoantibodies and growth were measured at 3- to 12-month intervals, and pubertal onset timing was assessed based on growth. The analyses used a three-state survival model. IA was defined as being either positive for islet cell antibodies plus at least one biochemical autoantibody (ICA + 1) or as being repeatedly positive for at least one biochemical autoantibody (BC1). Depending on the IA definition, either 303 (4.4%, ICA + 1) or 435 (6.3%, BC1) children tested positive for IA by the age of 7 years, and 211 (3.2%, ICA + 1)) or 198 (5.3%, BC1) developed IA during follow-up. A total of 172 (2.5%) individuals developed T1D during follow-up, of whom 169 were positive for IA prior to the clinical diagnosis. Puberty was associated with an increase in the risk of progression to T1D, but only from ICA + 1-defined IA (hazard ratio 1.57; 95% confidence interval 1.14, 2.16), and the timing of pubertal onset did not affect the association. No association between puberty and the risk of IA was detected. In conclusion, puberty may affect the risk of progression but is not a risk factor for IA.

ICIs are a standard of care in several malignancies; however, according to overall response rate (ORR), only a subset of eligible patients benefits from ICIs. Thus, an ability to predict ORR could enable more rational use. In this study a ML-based ORR prediction model was built, with patient-reported symptom data and other clinical data as inputs, using the extreme gradient boosting technique (XGBoost). Prediction performance for unseen samples was evaluated using leave-one-out cross-validation (LOOCV), and the performance was evaluated with accuracy, AUC (area under curve), F1 score, and MCC (Matthew’s correlation coefficient). The ORR prediction model had a promising LOOCV performance with all four metrics: accuracy (75%), AUC (0.71), F1 score (0.58), and MCC (0.4). A rather good sensitivity (0.58) and high specificity (0.82) of the model were seen in the confusion matrix for all 63 LOOCV ORR predictions. The two most important symptoms for predicting the ORR were itching and fatigue. The results show that it is possible to predict ORR for patients with multiple advanced cancers undergoing ICI therapies with a ML model combining clinical, routine laboratory, and patient-reported data even with a limited size cohort.

Background: Immune-checkpoint inhibitors (ICIs) have introduced novel immune-related adverse events (irAEs), arising from various organ systems without strong timely dependency on therapy dosing. Early detection of irAEs could result in improved toxicity profile and quality of life. Symptom data collected by electronic (e) patient-reported outcomes (PRO) could be used as an input for machine learning (ML) based prediction models for the early detection of irAEs. Methods: The utilized dataset consisted of two data sources. The first dataset consisted of 820 completed symptom questionnaires from 34 ICI treated advanced cancer patients, including 18 monitored symptoms collected using the Kaiku Health digital platform. The second dataset included prospectively collected irAE data, Common Terminology Criteria for Adverse Events (CTCAE) class, and the severity of 26 irAEs. The ML models were built using extreme gradient boosting algorithms. The first model was trained to detect the presence and the second the onset of irAEs. Results: The model trained to predict the presence of irAEs had an excellent performance based on four metrics: accuracy score 0.97, Area Under the Curve (AUC) value 0.99, F1-score 0.94 and Matthew’s correlation coefficient (MCC) 0.92. The prediction of the irAE onset was more difficult with accuracy score 0.96, AUC value 0.93, F1-score 0.66 and MCC 0.64 but the model performance was still at a good level. Conclusion: The current study suggests that ML based prediction models, using ePRO data as an input, can predict the presence and onset of irAEs with a high accuracy, indicating that ePRO follow-up with ML algorithms could facilitate the detection of irAEs in ICI-treated cancer patients. The results should be validated with a larger dataset. Trial registration: Clinical Trials Register (NCT3928938), registration date the 26th of April, 2019.

Purpose: To evaluate fitting quality and repeatability of four mathematical models for diffusion weighted imaging (DWI) during tumor progression in mouse xenograft model of prostate cancer. Methods: Human prostate cancer cells (PC-3) were implanted subcutaneously in right hind limbs of 11 immunodeficient mice. Tumor growth was followed by weekly DWI examinations using a 7T MR scanner. Additional DWI examination was performed after repositioning following the fourth DWI examination to evaluate short term repeatability. DWI was performed using 15 and 12 b-values in the ranges of 0–500 and 0–2000 s/mm², respectively. Corrected Akaike information criteria and F-ratio were used to evaluate fitting quality of each model (mono-exponential, stretched exponential, kurtosis, and bi-exponential). Results: Significant changes were observed in DWI data during the tumor growth, indicated by ADCm, ADCs, and ADCk. Similar results were obtained using low as well as high b-values. No marked changes in model preference were present between the weeks 1−4. The parameters of the mono-exponential, stretched exponential, and kurtosis models had smaller confidence interval and coefficient of repeatability values than the parameters of the bi-exponential model. Conclusion: Stretched exponential and kurtosis models showed better fit to DWI data than the mono-exponential model and presented with good repeatability.

BACKGROUND: Finnish men used to have higher semen quality than Danish men. However, recent studies showed that semen quality in Finland has declined, but it has been relatively stable in Denmark.OBJECTIVE: This study aimed to compare new data on semen quality of the young Finnish men to that of Danish men.MATERIALS AND METHODS: In this cross-sectional study, 18- to 19-year-old men residing in Turku, Finland and Copenhagen, Denmark, were invited to participate in 2008-2011. Each man filled in a questionnaire, provided one semen sample and underwent andrological examination. Semen samples were analyzed according to WHO. Multiway ANOVA was used to adjust semen variables for duration of sexual abstinence and age (and time from ejaculation to the start of semen analysis for sperm motility).RESULTS: Altogether 287 Finnish men and 873 Danish men participated in the study. The adjusted median sperm concentrations were 49 and 47 million/mL for Finnish and Danish men, respectively (p = 0.48). The adjusted median total sperm counts were 148 million in Finland and 146 million in Denmark (p = 0.87). The adjusted median percentages of morphologically normal spermatozoa were 6.9% in Finland and 6.5% in Denmark, p = 0.27. Finnish men had higher adjusted median percentages of motile spermatozoa (A+B+C) than Danish men (80% vs. 69%, p < 0.001). The proportion of men who had low semen quality (sperm concentration, percentage of morphologically normal spermatozoa or percentage of progressively motile spermatozoa below WHO reference limits) was lower in Finland (25.4%) than in Denmark (34.6%), p = 0.004.DISCUSSION: Considerable percentage of men in both countries had low semen quality. The deteriorating semen quality in Finland may result in decreasing fecundity, which is a cause of concern.CONCLUSION: The formerly high semen quality in Finland has converged to the lower Danish levels. Our findings demonstrate the importance of continuing surveil

Purpose: Patient-reported outcome (PRO) follow-up has been shown to improve quality of life (QoL) and survival of cancer patients receiving chemotherapy. Kaiku Health application is a web-based electronic PRO (ePRO) tool which is designed for follow-up of cancer patients receiving immune checkpoint inhibitors (ICI). Purpose of the current study is to investigate whether symptoms collected by Kaiku Health ePRO tool on cancer patients receiving immune checkpoint inhibitors (ICI) follows to symptoms reported in clinical trials and whether coupling of specific symptoms does occur. Methods: We retrospectively collected data on symptom timing and severity, and QoL of patients followed with Kaiku Health IO module in two Finnish cancer centers between 2017 and 2018. Kaiku Health IO module consists of 18 adaptive questions, which assess the presence and severity of symptoms. Patients were requested (via e-mail) to fill online symptom questionnaires with 3–7 day interval and QoL questionnaires (QLQ-C30) with 1–2 month interval. Results: The IO module was used to follow 37 patients who had filled in total 559 symptom questionnaires. There was good adherence to ePRO follow-up with a median of 11 questionnaires filled per patient. The reported symptoms and their severity follow closely what has been seen in clinical trials investigating ICIs. Correlation analysis of the symptoms showed the strongest positive correlations between itching and rash; nausea and vomiting, decreased appetite, or stomach pain; cough and shortness of breath. Conclusions: The results of the current study suggest that real-world symptom data collected through the ePRO application on cancer patients receiving ICI therapy aligns with the data from clinical trials. Correlations between different symptoms occur, which might reflect therapeutic efficiency, side effects, or tumor progression. These correlations should be further investigated with data coupled to clinical outcomes.

STUDY QUESTION Is the Leydig cell function of young European men associated with semen quality? SUMMARY ANSWER Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. WHAT IS ALREADY KNOWN Semen quality of young European men shows a heterogeneous pattern. Many have sperm counts below and in the lower WHO reference where there nevertheless is a significant risk of subfecundity. Little is known about differences in Leydig cell function between men with semen quality below and within the WHO reference range. STUDY DESIGN, SIZE AND DURATION A coordinated, cross-sectional population-based study of 8182 men undertaken in 1996–2010. PARTICIPANTS, SETTING AND METHOD Young men (median age 19.1 years) were investigated in centres in Denmark, Estonia, Finland, Germany Latvia, Lithuania, and Spain. The men originated from the general populations, all were young, almost all were unaware of their fecundity and each provided a semen and blood sample. Associations between semen parameters and serum levels of testosterone and luteinising hormone (LH), calculated free testosterone, and ratios between serum testosterone and LH were determined. MAIN RESULT AND ROLE OF CHANCE Serum testosterone levels were not associated with sperm concentrations, total sperm counts, or percentage of motile or morphologically normal spermatozoa. There was an inverse association between the semen parameters and serum LH levels, and accordingly a positive association to testosterone/LH ratio and calculated-free-testosterone/LH ratio. LIMITATIONS, REASON FOR CAUTION The size of the study mitigates the intra-individual variability concern. The distinction between different sub-categories of sperm motility and sperm morphology is subjective despite training. However, inter-observer variation would tend towards non-differential misclassificat, STUDY QUESTION: Is the Leydig cell function of young European men associated with semen quality? SUMMARY ANSWER: Compensated reduction in Leydig cell function, defined as increased LH concentration combined with adequate testosterone production is associated with lower semen quality. WHAT IS ALREADY KNOWN: Semen quality of young European men shows a heterogeneous pattern. Many have sperm counts below and in the lower WHO reference where there nevertheless is a significant risk of subfecundity. Little is known about differences in Leydig cell function between men with semen quality below and within the WHO reference range. STUDY DESIGN, SIZE AND DURATION: A coordinated, cross-sectional population-based study of 8182 men undertaken in 1996-2010. PARTICIPANTS, SETTING AND METHOD: Young men (median age 19.1 years) were investigated in centres in Denmark, Estonia, Finland, Germany Latvia, Lithuania, and Spain. The men originated from the general populations, all were young, almost all were unaware of their fecundity and each provided a semen and blood sample. Associations between semen parameters and serum levels of testosterone and luteinising hormone (LH), calculated free testosterone, and ratios between serum testosterone and LH were determined. MAIN RESULT AND ROLE OF CHANCE: Serum testosterone levels were not associated with sperm concentrations, total sperm counts, or percentage of motile or morphologically normal spermatozoa. There was an inverse association between the semen parameters and serum LH levels, and accordingly a positive association to testosterone/LH ratio and calculated-free-testosterone/LH ratio. LIMITATIONS, REASON FOR CAUTION: The size of the study mitigates the intra-individual variability concern. The distinction between different sub-categories of sperm motility and sperm morphology is subjective despite training. However, inter-observer variation would tend towards non-differential misclassification and would decrease

In animal studies, exposure to dioxins has been associated with disrupted development of the male reproductive system, including testicular maldescent. Some polychlorinated biphenyls (PCBs) have also dioxin-like effects. In addition, one previous case-control study has reported an association between congenital cryptorchidism and colostrum PCB levels. We performed a case-control study to evaluate whether congenital cryptorchidism in boys was associated with increased levels of dioxins or PCBs in placenta reflecting foetal exposure. In addition, associations between placenta levels of these chemicals and reproductive hormone levels in boys at 3 months were studied. Placentas were collected in a Danish-Finnish joint prospective cohort study on cryptorchidism (1997-2001). The boys were examined for cryptorchidism at birth and at 3 months. Altogether, 280 placentas [112 Finnish (56 cases, 56 controls) and 168 Danish (39 cases, 129 controls)] were analysed for 17 toxic polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and 37 PCBs (including 12 dioxin-like PCBs). Infant serum samples taken at 3 months were analysed for reproductive hormones. No significant differences between cases and controls were observed in either country in dioxin WHO-TEq levels (median 9.78 vs. 8.47 pg/g fat, respectively, in Finland, and 11.75 vs. 10.88 pg/g fat in Denmark) or PCB WHO-TEq levels (median 2.12 vs. 2.15 pg/g fat in Finland, 2.34 vs. 2.10 pg/g fat in Denmark) or total-TEq levels (median 11.66 vs. 10.58 pg/g fat in Finland, 13.94 vs. 13.00 pg/g fat in Denmark). Placenta WHO-TEq levels of dioxins were not associated with infant reproductive hormone levels at 3 months. In Finland, PCB WHO-TEq levels in placenta associated positively with infant LH levels. WHO-TEq levels of dioxins and PCBs and total-TEq levels were higher in Danish than Finnish samples. In conclusion, no association between placenta levels of dioxins or PCBs and congenital cryptorchidism was found. Significant

During the past four decades, there has been an increase in the incidence rate of male reproductive disorders in some, but not all, Western countries. The observed increase in the prevalence of male reproductive disorders is suspected to be ascribable to environmental factors as the increase has been too rapid to be explained by genetics alone. To study the association between complex chemical exposures of humans and congenital cryptorchidism, the most common malformation of the male genitalia, we measured 121 environmental chemicals with suspected or known endocrine disrupting properties in 130 breast milk samples from Danish and Finnish mothers. Half the newborns were healthy controls, whereas the other half was boys with congenital cryptorchidism. The measured chemicals included polychlorinated biphenyls (PCBs), polybrominated diphenyl-ethers, dioxins (OCDD/PCDFs), phthalates, polybrominated biphenyls and organochlorine pesticides. Computational analysis of the data was performed using logistic regression and three multivariate machine learning classifiers. Furthermore, we performed systems biology analysis to explore the chemical influence on a molecular level. After correction for multiple testing, exposure to nine chemicals was significantly different between the cases and controls in the Danish cohort, but not in the Finnish cohort. The multivariate analysis indicated that Danish samples exhibited a stronger correlation between chemical exposure patterns in breast milk and cryptorchidism than Finnish samples. Moreover, PCBs were indicated as having a protective effect within the Danish cohort, which was supported by molecular data recovered through systems biology. Our results lend further support to the hypothesis that the mixture of environmental chemicals may contribute to observed adverse trends in male reproductive health.

Investigations are described into the use of anode bag technology for sulphate-based Ni electrowinning. Anode bags are more efficient than cathode bags in relation to the suppression of acid mist and Ni emissions. Laboratory studies were first carried out to investigate electrolyte flow control through the diaphragm inside the anode bags. A high anolyte sulphuric acid concentration of up to 120 g/l was obtained at a current density of 200 A/m2. Tests were carried out using a commercial-scale pilot cell containing anodes with specially designed bags over a period of two years during which easily operated bag frames were developed. A small amount of sodium lauryl sulphate was added to obtain smooth cathode surfaces. Catholyte overflow from the cell was circulated and the pH controlled by neutralisation. The anolyte acid concentration and the difference in Ni concentration between the rich electrolyte and the anolyte, delta-Ni, were optimised by controlling the catholyte flow through the diaphragm, and an acid concentration of 80 g/l and a delta-Ni of 50 g/l were obtained. The current efficiency was very high, typically 98%. The oxygen content of the gas in the bags was about 98 vol% allowing it to be recovered and recycled to the leaching stage. An automatic cell monitoring system was used to detect changes in cell voltage and temperature which resulted in a higher current efficiency and a lower number of torn bags., Investigations are described into the use of anode bag technology for sulphate-based Ni electrowinning. Anode bags are more efficient than cathode bags in relation to the suppression of acid mist and Ni emissions. Laboratory studies were first carried out to investigate electrolyte flow control through the diaphragm inside the anode bags. A high anolyte sulphuric acid concentration of up to 120 g/l was obtained at a current density of 200 A/m2. Tests were carried out using a commercial-scale pilot cell containing anodes with specially designed bags over a period of two years during which easily operated bag frames were developed. A small amount of sodium lauryl sulphate was added to obtain smooth cathode surfaces. Catholyte overflow from the cell was circulated and the pH controlled by neutralisation. The anolyte acid concentration and the difference in Ni concentration between the rich electrolyte and the anolyte, delta-Ni, were optimised by controlling the catholyte flow through the diaphragm, and an acid concentration of 80 g/l and a delta-Ni of 50 g/l were obtained. The current efficiency was very high, typically 98%. The oxygen content of the gas in the bags was about 98 vol% allowing it to be recovered and recycled to the leaching stage. An automatic cell monitoring system was used to detect changes in cell voltage and temperature which resulted in a higher current efficiency and a lower number of torn bags.

Impaired semen quality and testicular cancer may be linked through a testicular dysgenesis syndrome of foetal origin. The incidence of testis cancer has been shown to increase among Finnish men, whereas there is no recent publication describing temporal trends in semen quality. Therefore, we carried out a prospective semen quality study and a registry study of testis cancer incidence among Finnish men to explore recent trends. A total of 858 men were investigated in the semen quality study during 1998-2006. Median sperm concentrations were 67 (95% CI 57-80) million/mL, 60 (51-71) and 48 (39-60) for birth cohorts 1979-81, 1982-83 and 1987; total sperm counts 227 (189-272) million, 202 (170-240) and 165 (132-207); total number of morphologically normal spermatozoa 18 (14-23) million, 15 (12-19) and 11 (8-15). Men aged 10-59 years at the time of diagnosis with testicular cancer during 1954-2008 were included in the registry study, which confirmed the increasing incidence of testicular cancer in recent cohorts. These simultaneous and rapidly occurring adverse trends suggest that the underlying causes are environmental and, as such, preventable. Our findings necessitate not only further surveillance of male reproductive health but also research to detect and remove the underlying factors.

High current densities are desirable in Cu electrowinning but the conditions must be modified to increase the limiting current density above a certain level to obtain a smooth deposit. One possibility is to decrease the Cu2+ boundary layer around the cathode by enhancing agitation using, for example, gas sparging, and a second is to modify the electrowinning parameters to increase the diffusion of Cu ions. The two methods were compared in bench-scale experiments carried out at a current density of 450 A/m2 using a 120 cm high cell to obtain a representative vertical profile for the deposited Cu cathodes. Under typical electrowinning conditions only nodular and dendritic Cu cathodes were deposited. A specially designed manifold was used to provide different sizes of bubbles and gas sparging produced good surface quality Cu cathodes. Optimum electrowinning parameters in relation to temperature and sulphuric acid and Cu concentrations without gas sparging were tested and good surface quality Cu cathodes were also obtained. Different electrowinning parameters also affected the Cu crystal growth. In practice the use of the optimum electrowinning parameters would require changes in the solvent extraction/electrowinning flowsheet. Theoretically, the rich electrolyte Cu concentration from solvent extraction could be increased to some extent without serious reduction in Cu recovery, but the solubility of Cu places some limits. Solvent extraction and electrowinning should be considered together in process optimisation. Utilising a high current density, either by optimising the electrowinning conditions or using air sparging, leads to a smaller number of cells and savings in the capital expenses of the tankhouse., High current densities are desirable in Cu electrowinning but the conditions must be modified to increase the limiting current density above a certain level to obtain a smooth deposit. One possibility is to decrease the Cu2+ boundary layer around the cathode by enhancing agitation using, for example, gas sparging, and a second is to modify the electrowinning parameters to increase the diffusion of Cu ions. The two methods were compared in bench-scale experiments carried out at a current density of 450 A/m2 using a 120 cm high cell to obtain a representative vertical profile for the deposited Cu cathodes. Under typical electrowinning conditions only nodular and dendritic Cu cathodes were deposited. A specially designed manifold was used to provide different sizes of bubbles and gas sparging produced good surface quality Cu cathodes. Optimum electrowinning parameters in relation to temperature and sulphuric acid and Cu concentrations without gas sparging were tested and good surface quality Cu cathodes were also obtained. Different electrowinning parameters also affected the Cu crystal growth. In practice the use of the optimum electrowinning parameters would require changes in the solvent extraction/electrowinning flowsheet. Theoretically, the rich electrolyte Cu concentration from solvent extraction could be increased to some extent without serious reduction in Cu recovery, but the solubility of Cu places some limits. Solvent extraction and electrowinning should be considered together in process optimisation. Utilising a high current density, either by optimising the electrowinning conditions or using air sparging, leads to a smaller number of cells and savings in the capital expenses of the tankhouse.

Udgivelsesdato: 2009-Sep-24, Summary Recent reports have confirmed a worldwide increasing trend of testicular cancer incidence, and a conspicuously high prevalence of this disease and other male reproductive disorders, including cryptorchidism and hypospadias, in Denmark. In contrast, Finland, a similarly industrialized Nordic country, exhibits much lower incidences of these disorders. The reasons behind the observed trends are unexplained, but environmental endocrine disrupting chemicals (EDCs) that affect foetal testis development are probably involved. Levels of persistent chemicals in breast milk can be considered a proxy for exposure of the foetus to such agents. Therefore, we undertook a comprehensive ecological study of 121 EDCs, including the persistent compounds dioxins, polychlorinated biphenyls (PCBs), pesticides and flame retardants, and non-persistent phthalates, in 68 breast milk samples from Denmark and Finland to compare exposure of mothers to this environmental mixture of EDCs. Using sophisticated, bioinformatic tools in our analysis, we reveal, for the first time, distinct country-specific chemical signatures of EDCs with Danes having generally higher exposure than Finns to persistent bioaccumulative chemicals, whereas there was no country-specific pattern with regard to the non-persistent phthalates. Importantly, EDC levels, including some dioxins, PCBs and some pesticides (hexachlorobenzene and dieldrin) were significantly higher in Denmark than in Finland. As these classes of EDCs have been implicated in testicular cancer or in adversely affecting development of the foetal testis in humans and animals, our findings reinforce the view that environmental exposure to EDCs may explain some of the temporal and between-country differences in incidence of male reproductive disorders.

Aim: To reach consensus among specialists from the Nordic countries on the present state-of-the-art in treatment of undescended testicles. Methods: A group of specialists in testicular physiology, paediatric surgery/urology, endocrinology, andrology, pathology and anaesthesiology from all the Nordic countries met for two days. Before the meeting, reviews of the literature had been prepared by the participants. Recommendations: The group came to the following unanimous conclusions: (1) In general, hormonal treatment is not recommended, considering the poor immediate results and the possible long term adverse effects on spermatogenesis. Thus, surgery is to be preferred. (2) Orchiopexy should be done between 6 and 12 months of age, or upon diagnosis, if that occurs later. (3) Orchiopexy before age one year should only be done at centres with both paediatric surgeons/urologists and paediatric anaesthesiologists. (4) If a testis is found to be undescended at any age after 6 months, the patient should be referred for surgery—to paediatric rather than general surgeons/urologists if the boy is less than one year old or if he has bilateral or non-palpable testes, or if he has got relapse of cryptorchidism.

New techniques are presented for real-time monitoring of tank house performance, supervisory control and control decision support. The information produced is analysed with statistical and other methods. The applications of these techniques are described for Outokumpu's Harjavalta Metals Refinery and a refining unit at Pori., New techniques are presented for real-time monitoring of tank house performance, supervisory control and control decision support. The information produced is analysed with statistical and other methods. The applications of these techniques are described for Outokumpu's Harjavalta Metals Refinery and a refining unit at Pori.

Fully automated cell systems have been developed incorporating advances in material handling, process control and monitoring. The equipment's versatility allows for either partial or full automation of the tankhouse unit operations. Improved production capacity, cathode quality and current efficiency can be achieved while minimising labour and maintenance requirements. Brief technical data from the Kokkola, Guixi and Minimill projects are listed., Fully automated cell systems have been developed incorporating advances in material handling, process control and monitoring. The equipment's versatility allows for either partial or full automation of the tankhouse unit operations. Improved production capacity, cathode quality and current efficiency can be achieved while minimising labour and maintenance requirements. Brief technical data from the Kokkola, Guixi and Minimill projects are listed.

The main steps in this new Outokumpu process, developed at Pori in Finland, are copper leaching at atmospheric pressure, roasting, silver leaching, precious metal leaching and treatment of impurities in the solution. It allows simple, fast refining of precious metals and takes into account existing circumstances in copper refineries. Its characteristics are compared with those of the Kennecott pressure-leach, Phelps Dodge pressure-leach/roast and old dore pressure-leach/smelt processes., The main steps in this new Outokumpu process, developed at Pori in Finland, are copper leaching at atmospheric pressure, roasting, silver leaching, precious metal leaching and treatment of impurities in the solution. It allows simple, fast refining of precious metals and takes into account existing circumstances in copper refineries. Its characteristics are compared with those of the Kennecott pressure-leach, Phelps Dodge pressure-leach/roast and old dore pressure-leach/smelt processes.

A project to develop new copper tankhouse technology was begun in 1997 by Outokumpu Harjavalta Metals, which operates a copper refinery in Pori, Finland, and Outokumpu Wenmec, which supplies equipment to copper refineries. The first phase, completed in 1998, involved the development and small-scale testing of many innovations and novel solutions, while the second phase was focused on full-scale use and operating practice. The advanced tankhouse concept that resulted has two parts: the electrolytic cell concept, which integrates a jumbo cell, cell-top insulators and bus bars, a permanent cathode and a copper anode with separate lifting lugs; and the materials handling system, which includes cranes and bales, short-circuit detection and removal, anode slime removal and automation of upper-level material handling. The elements of the two concepts are described in detail., A project to develop new copper tankhouse technology was begun in 1997 by Outokumpu Harjavalta Metals, which operates a copper refinery in Pori, Finland, and Outokumpu Wenmec, which supplies equipment to copper refineries. The first phase, completed in 1998, involved the development and small-scale testing of many innovations and novel solutions, while the second phase was focused on full-scale use and operating practice. The advanced tankhouse concept that resulted has two parts: the electrolytic cell concept, which integrates a jumbo cell, cell-top insulators and bus bars, a permanent cathode and a copper anode with separate lifting lugs; and the materials handling system, which includes cranes and bales, short-circuit detection and removal, anode slime removal and automation of upper-level material handling. The elements of the two concepts are described in detail.