Combined optimization of spot positions and weights for better FLASH proton therapy.

Objective.In Intensity Modulated Proton Therapy (IMPT), the weights of individual pencil-beams or spots are optimized to fulfil dosimetric constraints. Theses spots are usually located on a regular lattice and their positions are fixed during optimization. In many cases, the range of spot weights may however be limited, leading sometimes to sub-optimal plan quality. An emblematic use case is the delivery of a plan at ultra-high dose rate (FLASH-RT), for which the spot weights are typically constrained to high values.Approach. To improve further the quality of IMPT FLASH plans, we propose here a novel algorithm to optimize both the spot weights and positions directly based on the objectives defined by the treatment planner.Main results. For all cases considered, optimizing the spot positions lead to an enhanced dosimetric score, while maintaining a high dose rate.Significance. Overall, this approach resulted in a substantial plan quality improvement compared to optimizing only the spot weights, and in a similar execution time.

Parasitism of the deer ked, Lipoptena cervi, on the moose, Alces alces, in eastern Finland.

The deer ked, Lipoptena cervi L. (Diptera: Hippoboscidae), is an ectoparasitic fly that spread to Finland in the early 1960s from the southeast across the Soviet border. It is currently a common parasite of the moose, Alces alces (Artiodactyla: Cervidae), in the southern part of the country and its area of distribution is gradually spreading to Finnish Lapland, where it will come into contact with another potential cervid host, the semi-domesticated reindeer, Rangifer tarandus tarandus. The aim of this study was to determine the intensity of deer ked parasitism on the moose in eastern Finland. Whole skins of 23 moose were examined for the presence of deer keds, which were extracted and their total numbers estimated. The intensity of deer ked parasitism was correlated to the age, sex, skin area and anatomical region of the host. Bulls had the highest total number of keds (10616 ± 1375) and the highest deer ked density (35.7 ± 4.4 keds/dm(2) of skin). Cows had a higher total number of keds than calves (3549 ± 587 vs. 1730 ± 191), but ked densities on cows and calves were roughly equal (11.8 ± 1.7 vs. 9.4 ± 1.1 keds/dm(2) of skin). The density of keds was highest on the anterior back, followed by the posterior back, front limbs, abdomen, head and hind limbs. The sex ratio of deer keds was close to equal (male : female, 1.0 : 1.1). After they had consumed blood, male keds were heavier than females. As the total numbers and densities of deer keds were higher than reported previously on moose or for any other louse fly species, the effects of parasitism on the health of the host species should be determined.

Ophiostoma spp. associated with pine- and spruce-infesting bark beetles in Finland and Russia.

The timber and pulp industries of Finland rely heavily on importations from Russia as source of raw timber. These imports raise the risk of accidentally importing forest pests and pathogens, especially bark beetles and their associated fungi, into Finland. Although ophiostomatoid fungi have previously been reported from Finland and Russia, the risks of accidentally moving these fungi has prompted a first survey to compare the diversity of conifer-infesting bark beetles and associated fungi from boreal forests on both sides of the Finnish-Russian border. The aim of the present study was to identify and characterise Ophiostoma species isolated in association with 11 bark beetle species infesting Pinus sylvestris and Picea abies during this survey in the eastern parts of Finland and neighbouring Russia. Fungal isolates were grouped based on morphology and representatives of each morphological group were subjected to DNA sequence comparisons of the internal transcribed spaced region (ITS1, 5.8S, ITS2) and ß-tubulin gene region. A total of 15 species of Ophiostoma were identified, including seven known species, five new species, and three species for which the identity remains uncertain. In the O. piceae-complex we identified O. canum, O. floccosum, O. karelicum and O. rachisporum sp. nov., and related to these, some isolates belonging to the European clade of O. minus in the O. minus-complex. Ophiostoma bicolor and O. fuscum sp. nov. were identified in the O. ips-complex, while O. ainoae, O. brunneo-ciliatum, O. tapionis sp. nov. and O. pallidulum sp. nov. were shown to group close to, but not in a strict monophyletic lineage with species of the O. ips-complex. Together with a single O. abietinum-like isolate, the only species that grouped close to the Sporothrix schenckii- O. stenoceras complex, was O. saponiodorum sp. nov.

A dual-step fluorescence resonance energy transfer-based quenching assay for screening of caspase-3 inhibitors.

The control of cell death is an intricate process involving a multitude of intracellular modulators. Among these molecules, the caspases have a central role and have become an interesting group of enzymes in the current pharmaceutical industry. We have developed a novel dual-step fluorescence energy transfer-based separation-free assay method for the primary screening of caspase-3 inhibitors in vitro. This method relies on fluorescent europium(III)-chelate-doped nanoparticle donors coated with streptavidin in conjunction with a dual-labeled (N-terminal Alexa Fluor 680 fluorescent acceptor and C-terminal BlackBerry Quencher 650) caspase-3-specific peptide substrate modified with a biotinyl moiety. In the assay, the nanoparticle donor excites the fluorescent acceptor, whose emission is monitored with time-resolved measurements. The intensity of the acceptor reflects the activity of the enzyme because the intensity is controlled by the proximity of the quencher. Owing to the dual-step fluorescence resonance energy transfer, this method enables a sensitized fluorescence signal directly proportional to the extent of enzymatic activity with relatively background fluorescence-free measurements in the event of complete enzyme inhibition. The generic nanoparticle donors further promote versatility and cost-efficiency of the method. The performance evaluated as the inhibitor (Z-DEVD-FMK) dose-response curve (IC(50) value of approximately 12 nM) was in good agreement with that of the recent methods found in literature. This assay serves as a model application proving the feasibility of the europium-chelate-doped nanoparticle labels in a homogeneous assay for proteolytic activity.

Do elevated temperature and CO2 generally have counteracting effects on phenolic phytochemistry of boreal trees?

Global climate change includes concomitant changes in many components of the abiotic flux necessary for plant life. In this paper, we investigate the combined effects of elevated CO2 (720 ppm) and temperature (+2 K) on the phytochemistry of three deciduous tree species. The analysis revealed that elevated CO(2) generally stimulated increased carbon partitioning to various classes of phenolic compounds, whereas an increase in temperature had the opposite effect. The combined effects of both elevated CO2 and temperature were additive, i.e., canceling one another's individual effects. Obviously, the effects of global climate change on leaf chemistry must simultaneously consider both temperature and CO2. If these results are generally applicable, then the counteracting effect of the temperature is likely to play a major role in alpine, boreal, and arctic zones in determining the balance between populations of plants and herbivores.

Effects of space allowance and earthen floor on welfare-related physiological and behavioural responses in male blue foxes.

Welfare-related physiological and behavioural responses were studied in farm-bred male blue foxes (Alopex lagopus). Three different-sized cages (80-cm long [CL80], 120-cm long [CL120], and 240-cm long [CL240]; each 105-cm wide x 70-cm high) with wire-mesh floors and one enlarged cage (CL240E) with both wire-mesh floor (240-cm long x 105-cm wide x 70-cm high) and earthen floor (80-cm long x 105-cm wide x 70-cm high) were compared. N = 30 males for each group. The experiments lasted from weaning in July to pelting in December. Statistical analyses were based on the models accounting for litter as a block effect. Breaking strength of tibia was highest for foxes having access to both wire-mesh and ground floors (CL240E). Stress-induced hyperthermia was evident during capture and immobilisation. The highest rectal temperature (mean +/- SEM) was found in CL240E (capture: 39.6 +/- 0.09 degrees C, restraint:40.0 +/- 0.09 degrees C) and the lowest in CL80 (capture: 39.1 +/- 0.09 degrees C, restraint: 39.7 +/- 0.09 degrees C). Likewise, capture time (median; interquartile range) in the home cage was highest in CL240E (29; 18 to 44) and lowest in CL80 (12; 9 to 14). During capture, foxes tended to withdraw to the farthest site within the cage. CL240E foxes typically showed the most fear towards human. The most confident animals were found in CL80. The cortisol:creatinine ratio (median; interquartile range) obtained from circadian urine did not reveal statistically significant differences among CL80 (3. 5; 2.6 to 4.1), CL120 (2.3; 1.5 to 3.8) and CL240 (2.3, 1.5 to 3.7). The earthen flooring complicated the urine sampling and conclusions for CL240E (1.7; 1.2 to 2.2). CL240E foxes were the most active and explorative on both wire-mesh- and ground-floored open-field arenas. Altogether, 53% of furs from CL240E were classified as very dirty. Dirtiness of furs in other test groups was slight. In conclusion, the present results did not reveal an unambiguous superiority of any of the studied cage options for well-being of farmed blue foxes.

Growth and development of a generalist insect herbivore, Operophtera brumata, on original and alternative host plants.

A generalist feeding strategy is common among eruptive insect herbivores but the ultimate reasons for a generalist strategy are not clear. Although generalist insect herbivores are able to complete their life cycle on several species of host plants, there is wide variation in the performance of individuals grown on different hosts. We examined whether different populations of Operophtera brumata are adapted to use the host species which is locally most abundant, and how the host plant affects growth and development of the insect. We reared two allopatric populations (eastern Finland, Prunus padus; south-west Finland, Quercus robur) on four species of host plants (Pr. padus, Populus tremula, Q. robur, Salix phylicifolia) from neonate larvae to the adult stage and measured the growth and development of individuals and the timing of adult hatching. The performance of both populations was best on Pr. padus, and the south-western population, originally on Q. robur, was well adapted to this host. The host affected the growth of females more than that of males. The host plant had an unexpected effect on hatching times of the adults. Individuals grown on the original host hatched in normal synchrony, i.e. males 6-7 days before females; but on alternative hosts this synchrony was disturbed. As is common in eruptive, capital-breeding generalist moths where female fecundity is linked to weight, host quality is critical for the flightless females of O. brumata. We suggest that in a heterogeneous environment the disturbing effect of alternative host plants on adult emergence may decrease the population density and growth rate compared to the potential maximum in a homogeneous environment.

Attitudes towards genetic testing: analysis of contradictions.

A survey study was conducted among 1169 people to evaluate attitudes towards genetic testing in Finland. Here we present an analysis of the contradictions detected in people's attitudes towards genetic testing. This analysis focuses on the approval of genetic testing as an individual choice and on the confidence in control of the process of genetic testing and its implications. Our analysis indicated that some of the respondents have contradictory attitudes towards genetic testing. It is proposed that contradictory attitudes towards genetic testing should be given greater significance both in scientific studies on attitudes towards genetic testing as well as in the health care context, e.g. in genetic counselling.

Acceptance of genetic testing in a general population: age, education and gender differences.

The aim of the study was to analyze effects of age, education and gender on acceptance of genetic testing. Subjects, n = 1967 aged 15-69, were a stratified random sample of the Finnish population. One thousand, one hundred and sixty nine subjects, 530 men and 639 women, returned the questionnaire. The majority of the respondents approved of the availability of genetic testing. Young, aged 15-24, were more favourable towards testing and more willing to undergo suggested tests, but they were also more worried than others about the misuse of test results. Men aged 45-69 with only basic education were more in favour of mandatory genetic testing than other respondents. Respondents with university education were more critical towards genetic testing and expressed their worry about eugenics more often than other education groups. In conclusion, there are age, education and gender related differences in acceptance of genetic testing which need to be taken into account when considering screening programmes and informing the public.

Attitudes toward genetic testing among the general population and relatives of patients with a severe genetic disease: a survey from Finland.

In the present study we explore the attitudes of the Finnish population toward genetic testing by conducting a questionnaire study of a stratified sample of the population as well as of family members of patients with a severe hereditary disease, aspartylglucosaminuria (AGU). The questionnaire evaluated attitudes toward gene tests in general and also respondents' preparedness to undergo gene tests for predictive testing, carrier detection, prenatal diagnosis, and selective abortion, in theoretical situations. The results of the study indicate that both the Finnish population in general and family members of AGU patients have a favorable attitude toward genetic testing. However, a commonly expressed reason against testing was that test results might lead to discrimination in employment or insurance policies. Based on the responses, we predict that future genetic testing programs will most probably be met with a high acceptance rate by the Finnish population.

Polyphagy and adult body size in geometrid moths.

We compared the average body size (wing span) of Finnish geometrid moth species in relation to their degree of polyphagy and quality of food. The first hypothesis, originally constructed for mammals and birds, states that smaller species should more often be specialists than large species, because of the different relationships between body size and home range size, and body size and daily energy requirements. According to the second hypothesis, smaller species should feed more often on herbs than do larger species, because of the different defence mechanisms of herbs and woody plants. The results support both of these hypotheses. Specialist species are smaller than oligophagous or polyphagous species, and small species concentrate on herbs. We conclude that quality and quantity of food resources may explain the pattern.

Evaluation of the relationship between social status and reproductive performance in farmed blue foxes.

An experimental cage system was designed for evaluating the association of social status and reproductive performance in blue foxes under fur-farm conditions. The present test cage apparatus consisted of 6 small cages and 1 large cage that were connected. The small cages were utilized for males of different social status and the large cage for females coming on heat. The results showed that this type of testing apparatus can be used for evaluating a female's acceptance of males of different social rank. The locomotor activity of males significantly depended on their social status; thus the most active individuals in the test were the most dominant, and vice versa. Females most often accepted higher-ranking males. Juvenile males were the least dominant and also the least accepted by females. Urination activity was not necessarily related to dominance.

The first abortion - and the last? A study of the personality factors underlying repeated failure of contraception.

The causes leading to a second abortion were outlined in a psychological study comparing 30 women expecting a second abortion with 29 women who had successfully prevented conception after a first abortion. It was found that both groups improved their contraceptive practices after the first abortion. However, while the latter group continued with their improved practices, the former group went back to the earlier inefficient or non-existent contraceptive behavior. The inability to improve contraception in the long run was not related to differences in educational level or knowledge about contraceptive techniques but to the developmental level of personality structures. The women expecting their second abortion rated lower in control of impulsivity, emotional balance, realism, self-esteem and stability of life as well as capacity for more integrated personal relationships. The differences in personality development and consequently in the capacity for long-term contraception were found to be due to growth conditions in childhood.

Cost-benefit analysis of posterior fusion of the lumbosacral spine.

In this study the cost-benefit ratio of posterior fusion of the lumbosacral spine was assessed. The calculations were based on 118 operated patients, followed up for an average of 4.8 years. Costs were calculated using the average costs of treatment at central hospitals, visits to the outpatient department and travelling. The costs for one patient exceeded on average 5,569 US dollars. The economic benefits derived from the operations were estimated by the work output of those 36 patients who postoperatively returned to their previous or a corresponding occupation. The postoperative work output was estimated using the coefficients for known causes of retirement (emigration, mortality, disability). The benefits of one lumbosacral fusion amounted on average to 16,075 US dollars. Fusion of the lumbosacral spine prove to be profitable at a cost-benefit ratio of 1 : 2.9. If the selection of patients for operation could be made so as to guarantee that working capacity is restored by operative treatment, the cost-benefit ratio might be improved to 1 : 9.5. It is emphasized that cost-benefit analyses of surgical procedures are important from the standpoint of principles of treatment and priority of operations. This study deals with economic aspects only. The medical aspects of the present material have been presented in two previous papers.