Help seeking for mental health problems in an adolescent population: the effect of gender.

Background: While the onset of many mental health problems occurs in adolescence, these problems are severely undertreated in this age group. To inform early intervention for adolescents, we investigated the effect of gender and education type on perception of barriers to help seeking, mental health literacy, and the awareness and use of mental health services. Method: A web-based survey using vignettes, open-ended and multiple choice items was administered to upper secondary school students in two counties in Norway. Results: The survey was completed by 1249 students (88% response rate) with an average age of 17.6 years and 56% were female. Compared to males, the females were better in identifying psychological problems of anxiety and trauma, awareness of mental health services (p < 0.001) and perceived more barriers for seeking help (cost and waiting time; p < 0.001). For use of all mental health services, the effect of education type was greater than the effect of gender. Conclusion: For adolescents, gender appears to play a significant, but not exclusive, role in the inclination to seek professional help for mental health problems. We hypothesise that the observed gender difference in use of services is related to the gender difference in awareness of referral pathway services and the influence of parents in help-seeking process.

Prion Type-Dependent Deposition of PRNP Allelic Products in Heterozygous Sheep.

UNLABELLED: Susceptibility or resistance to prion infection in humans and animals depends on single prion protein (PrP) amino acid substitutions in the host, but the agent's modulating role has not been well investigated. Compared to disease incubation times in wild-type homozygous ARQ/ARQ (where each triplet represents the amino acids at codons 136, 154, and 171, respectively) sheep, scrapie susceptibility is reduced to near resistance in ARR/ARR animals while it is strongly enhanced in VRQ/VRQ carriers. Heterozygous ARR/VRQ animals exhibit delayed incubation periods. In bovine spongiform encephalopathy (BSE) infection, the polymorphism effect is quite different although the ARR allotype remains the least susceptible. In this study, PrP allotype composition in protease-resistant prion protein (PrP(res)) from brain of heterozygous ARR/VRQ scrapie-infected sheep was compared with that of BSE-infected sheep with a similar genotype. A triplex Western blotting technique was used to estimate the two allotype PrP fractions in PrP(res) material from BSE-infected ARR/VRQ sheep. PrP(res) in BSE contained equimolar amounts of VRQ- and ARR-PrP, which contrasts with the excess (>95%) VRQ-PrP fraction found in PrP in scrapie. This is evidence that transmissible spongiform encephalopathy (TSE) agent properties alone, perhaps structural aspects of prions (such as PrP amino acid sequence variants and PrP conformational state), determine the polymorphic dependence of the PrP(res) accumulation process in prion formation as well as the disease-associated phenotypic expressions in the host. IMPORTANCE: Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative and transmissible diseases caused by prions. Amino acid sequence variants of the prion protein (PrP) determine transmissibility in the hosts, as has been shown for classical scrapie in sheep. Each individual produces a separate PrP molecule from its two PrP gene copies. Heterozygous scrapie-infected sheep that produce two PrP variants associated with opposite scrapie susceptibilities (136V-PrP variant, high; 171R-PrP variant, very low) contain in their prion material over 95% of the 136V PrP variant. However, when these sheep are infected with prions from cattle (bovine spongiform encephalopathy [BSE]), both PrP variants occur in equal ratios. This shows that the infecting prion type determines the accumulating PrP variant ratio in the heterozygous host. While the host's PrP is considered a determining factor, these results emphasize that prion structure plays a role during host infection and that PrP variant involvement in prions of heterozygous carriers is a critical field for understanding prion formation.

Protecting effect of PrP codons M142 and K222 in goats orally challenged with bovine spongiform encephalopathy prions.

Breeding towards genetic resistance to prion disease is effective in eliminating scrapie. In sheep, classical forms of scrapie have been eradicated almost completely in several countries by breeding programs using a prion protein (PrP) gene (PRNP) amino acid polymorphism. For goats, field and experimental studies have provided evidence for several amino acid polymorphisms that are associated with resistance to scrapie, but only limited data are available concerning the susceptibility of caprine PRNP genotypes to BSE. In this study, goat kids representing five PRNP genotypes based on three polymorphisms (M142, Q211 and K222 and the wild type I142, R211 and Q222) were orally challenged with bovine or goat BSE. Wild type goats were killed with clinical signs between 24-28 months post inoculation (mpi) to both challenges, and goats with genotype R/Q211 succumbed between 29-36 mpi. I/M142 goats developed clinical signs at 44-45 mpi and M/M142 goats remained healthy until euthanasia at 48 mpi. None of the Q/K222 goats showed definite clinical signs. Taken together the highest attack ratios were seen in wild type and R/Q211 goats, and the lowest in I/M142, M/M142 and Q/K222. In all genotype groups, one or more goats remained healthy within the incubation period in both challenges and without detectable PrP deposition in the tissues. Our data show that both the K222 and M142 polymorphisms lengthen the incubation period significantly compared to wild type animals, but only K222 was associated with a significant increase in resistance to BSE infection after oral exposure to both BSE sources.

Variation in the prion protein sequence in Dutch goat breeds.

Scrapie is a neurodegenerative disease occurring in goats and sheep. Several haplotypes of the prion protein increase resistance to scrapie infection and may be used in selective breeding to help eradicate scrapie. In this study, frequencies of the allelic variants of the PrP gene are determined for six goat breeds in the Netherlands. Overall frequencies in Dutch goats were determined from 768 brain tissue samples in 2005, 766 in 2008 and 300 in 2012, derived from random sampling for the national scrapie surveillance without knowledge of the breed. Breed specific frequencies were determined in the winter 2013/2014 by sampling 300 breeding animals from the main breeders of the different breeds. Detailed analysis of the scrapie-resistant K222 haplotype was carried out in 2014 for 220 Dutch Toggenburger goats and in 2015 for 942 goats from the Saanen derived White Goat breed. Nine haplotypes were identified in the Dutch breeds. Frequencies for non-wild type haplotypes were generally low. Exception was the K222 haplotype in the Dutch Toggenburger (29%) and the S146 haplotype in the Nubian and Boer breeds (respectively 7 and 31%). The frequency of the K222 haplotype in the Toggenburger was higher than for any other breed reported in literature, while for the White Goat breed it was with 3.1% similar to frequencies of other Saanen or Saanen derived breeds. Further evidence was found for the existence of two M142 haplotypes, M142 /S240 and M142 /P240 . Breeds vary in haplotype frequencies but frequencies of resistant genotypes are generally low and consequently selective breeding for scrapie resistance can only be slow but will benefit from animals identified in this study. The unexpectedly high frequency of the K222 haplotype in the Dutch Toggenburger underlines the need for conservation of rare breeds in order to conserve genetic diversity rare or absent in other breeds.

An agent-based modeling approach for determining corn stover removal rate and transboundary effects.

Bioenergy production involves different agents with potentially different objectives, and an agent's decision often has transboundary impacts on other agents along the bioenergy value chain. Understanding and estimating the transboundary impacts is essential to portraying the interactions among the different agents and in the search for the optimal configuration of the bioenergy value chain. We develop an agent-based model to mimic the decision making by feedstock producers and feedstock-to-biofuel conversion plant operators and propose multipliers (i.e., ratios of economic values accruing to different segments and associated agents in the value chain) for assessing the transboundary impacts. Our approach is generic and thus applicable to a variety of bioenergy production systems at different sites and geographic scales. We apply it to the case of producing ethanol using corn stover in Iowa, USA. The results from the case study indicate that stover removal rate is site specific and varies considerably with soil type, as well as other factors, such as stover price and harvesting cost. In addition, ethanol production using corn stover in the study region would have strong positive ripple effects, with the values of multipliers varying with greenhouse gas price and national energy security premium. The relatively high multiplier values suggest that a large portion of the value associated with corn stover ethanol production would accrue to the downstream end of the value chain instead of stover producers.

Selection of monitoring locations for storm water quality assessment.

Storm water runoff is a major contributor to the pollution of receiving waters. Storm water characteristics may vary significantly between locations and events. Hence, for each given location, this necessitates a well-designed monitoring campaign prior to selection of an appropriate storm water management strategy. The challenge for the design of a monitoring campaign with a given budget is to balance detailed monitoring at a limited number of locations versus less detailed monitoring at a large number of locations. This paper proposes a methodology for the selection of monitoring locations for storm water quality monitoring, based on (pre-)screening, a quick scan monitoring campaign, and final selection of locations and design of the monitoring setup. The main advantage of the method is the ability to prevent the selection of monitoring locations that turn out to be inappropriate. In addition, in this study, the quick scan resulted in a first useful dataset on storm water quality and a strong indication of illicit connections at one of the monitoring locations.

Comparison of core sampling and visual inspection for assessment of concrete sewer pipe condition.

Sewer systems are costly to construct and even more costly to replace, requiring proper asset management. Sewer asset management relies to a large extent on available information. In sewer systems where pipe corrosion is the dominant failure mechanism, visual inspection by closed circuit television (CCTV) and core sampling are among the methods mostly applied to assess sewer pipe condition. This paper compares visual inspection and drill core analysis in order to enhance further understanding of the limitations and potentials of both methods. Both methods have been applied on a selected sewer reach in the city of The Hague, which was reportedly subject to pipe corrosion. Results show that both methods, visual inspection and core sampling, are associated with large uncertainties and that there is no obvious correlation between results of visual inspection and results of drill core analysis.

Proteinase K-resistant material in ARR/VRQ sheep brain affected with classical scrapie is composed mainly of VRQ prion protein.

Classical scrapie is a prion disease in sheep and goats. In sheep, susceptibility to disease is genetically influenced by single amino acid substitutions. Genetic breeding programs aimed at enrichment of arginine-171 (171R) prion protein (PrP), the so-called ARR allele, in the sheep population have been demonstrated to be effective in reducing the occurrence of classical scrapie in the field. Understanding the molecular basis for this reduced prevalence would serve the assessment of ARR adaptation. The prion formation mechanism and conversion of PrP from the normal form (PrP(C)) to the scrapie-associated form (PrP(Sc)) could play a key role in this process. Therefore, we investigated whether the ARR allele substantially contributes to scrapie prion formation in naturally infected heterozygous 171Q/R animals. Two methods were applied to brain tissue of 171Q/R heterozygous sheep with natural scrapie to determine the relative amount of the 171R PrP fraction in PrP(res), the proteinase K-resistant PrP(Sc) core. An antibody test differentiating between 171Q and 171R PrP fragments showed that PrP(res) was mostly composed of the 171Q allelotype. Furthermore, using a novel tool for prion research, endoproteinase Lys-C-digested PrP(res) yielded substantial amounts of a nonglycosylated and a monoglycosylated PrP fragment comprising codons 114 to 188. Following two-dimensional gel electrophoresis, only marginal amounts (<9%) of 171R PrP(res) were detected. Enhanced 171R(res) proteolytic susceptibility could be excluded. Thus, these data support a nearly zero contribution of 171R PrP in PrP(res) of 171R/Q field scrapie-infected animals. This is suggestive of a poor adaptation of classical scrapie to this resistance allele under these natural conditions.

Effects of considering greenhouse gas consequences on fertilizer use in loblolly pine plantations.

Fertilizer use, widely practiced in forest plantation management to stimulate tree growth, contributes to greenhouse gas (GHG) emissions. We explore how accounting for GHG consequences affects optimal fertilizer application rates of commercial forest plantations. A generic model that maximizes the equivalent annual net benefit of timber production and GHG balance is developed and applied to loblolly pine (Pinus taeda L.) plantations in the southern United States. We find that fertilizer use still is a viable practice for managing loblolly pine plantations in the region although fertilizer application rate should be reduced when GHG consequences are valued. A greater reduction in fertilizer application rate is recommended where wood is used for paper production because life cycle GHG emissions of paper products are much higher than those of solid wood or bioenergy products. A higher fertilizer rate should be applied when forest residues are used for the production of bioenergy that offsets GHG emissions from consuming fossil fuels.

Settlement as a driver for sewer rehabilitation.

This paper assesses the influence of (differential) settlement on sewer system functioning. Based on historical data of the vertical position of sewer invert levels, tilt measurements and in-sewer inspection videos, settlement and settlement related influences are analyzed for a case study area in Amsterdam. The average settlement rate of this system was 4 mm/year. Given this settlement rate, it is shown that settlement significantly influences sewer system functioning within the lifetime of a sewer (system).

Monitoring the performance of a storm water separating manifold with distributed temperature sensing.

Storm water separating manifolds in house connections have been introduced as a cost effective solution to disconnect impervious areas from combined sewers. Such manifolds have been applied by the municipality of Breda, the Netherlands. In order to investigate the performance of the manifolds, a monitoring technique (distributed temperature sensing or DTS) using fiber optic cables has been applied in the sewer system of Breda. This paper describes the application of DTS as a research tool in sewer systems. DTS proves to be a powerful tool to monitor the performance of (parts of) a sewer system in time and space. The research project showed that DTS is capable of monitoring the performance of house connections and identifying locations of inflow of both sewage and storm runoff. The research results show that the performance of storm water separating manifolds varies over time, thus making them unreliable.

Assessing characteristic time and space scales of in-sewer processes by analysis of one year of continuous in-sewer monitoring data.

Long-term and high-frequency in-sewer monitoring opens up a broad range of possibilities to study (influences on) water quantity and quality variations. Using data from the Eindhoven wastewater system in The Netherlands both dry weather flow and wet weather flow situations have been studied. For approximately 160 dry weather days mean diurnal variations of flow and pollutant concentrations have been derived. For wet weather situations (≈ 40 storm events) peak load factors have been studied. Generally, peak load factors for all considered pollutant parameters are larger than one. Peak load factors for particulate matter are larger than for dissolved constituents. Also, the smallest catchment area consistently shows the largest mean peak factors and vice versa.

Differentiation of ruminant transmissible spongiform encephalopathy isolate types, including bovine spongiform encephalopathy and CH1641 scrapie.

With increased awareness of the diversity of transmissible spongiform encephalopathy (TSE) strains in the ruminant population, comes an appreciation of the need for improved methods of differential diagnosis. Exposure to bovine spongiform encephalopathy (BSE) has been associated with the human TSE, variant Creutzfeldt-Jakob disease, emphasizing the necessity in distinguishing low-risk TSE types from BSE. TSE type discrimination in ruminants such as cattle, sheep, goats and deer, requires the application of several prion protein (PrP)-specific antibodies in parallel immunochemical tests on brain homogenates or tissue sections from infected animals. This study uses in a single incubation step, three PrP-specific antibodies and fluorescent Alexa dye-labelled anti-mouse Fabs on a Western blot. The usual amount of brain tissue needed is 0.5 mg. This multiplex application of antibodies directed towards three different PrP epitopes enabled differential diagnosis of all established main features of classical scrapie, BSE and Nor98-like scrapie in sheep and goats, as well as the currently known BSE types C, H and L in cattle. Moreover, due to an antibody-dependent dual PrP-banding pattern, for the first time CH1641 scrapie of sheep can be reliably discriminated from the other TSE isolate types in sheep.

An integrated approach for urban water quality assessment.

This paper introduces an integrated approach for the assessment of receiving water quality and the relative contribution of the urban drainage system to perceived receiving water quality problems. The approach combines mass balances with relatively simple receiving water impact models. The research project has learned that the urban drainage system is only one of the determining factors with respect to receiving urban water quality problems. The morphology of the receiving waters and the non-sewer sources of pollution, such as waterbirds, dogs, or inflow of external surface water might be equally important. This conclusion underlines the necessity to changes today's emission based approach and adopt an integral and immission based approach. The integrated approach is illustrated on a case study in Arnhem, where the receiving water quality remained unsatisfactory even after retrofitting a combined sewer system into a separated sewer system.

Are multi family groups appropriate for patients with first episode psychosis? A 5-year naturalistic follow-up study.

OBJECTIVE: To compare outcome over 5 years for patients who participated in multi family groups (MFGs) to those who refused or were not offered participation. METHOD: Of 301 first episode psychotic patients aged 15-65 years, 147 participated in MFGs. Outcome was measured by drop-out rates, positive and negative syndrome scale (PANSS) symptom scores, and duration of psychotic episodes during the follow-up period. RESULTS: Multi family group participants had a significantly lower drop-out rates at 5-year follow-up than patients who did not participate. However, the MFG participants had significantly less improvement in PANSS positive and excitative symptoms and had significantly longer duration of psychotic symptoms during the follow-up period. CONCLUSION: Multi family groups appear to increase the chance of retaining patients in a follow-up study, but adjustment of the programme may be necessary with first episode psychosis patients to meet their needs better.

Baseline profiles of adolescent vs. adult-onset first-episode psychosis in an early detection program.

OBJECTIVE: Psychotic disorders often start in adolescence. We aim to investigate premorbid and baseline differences characterizing patients with an onset of psychosis in adolescence versus adulthood. METHOD: We compare first-episode, DSM-IV non-affective psychosis with onset before (n = 43) and after (n = 189) 18 years on duration of untreated psychosis (DUP), level of symptoms, suicidal behaviour, and other baseline clinical and demographic characteristics. RESULTS: Adolescent onset patients had poorer premorbid functioning, a longer DUP, higher suicidality, and more depressive symptoms. They also had better cognition, fewer psychotic symptoms, and were more likely to be treated on an out-patient basis. CONCLUSION: Adolescents with first-episode psychosis may have a slower and more silent, i.e. insidious onset, and are at risk of experiencing longer treatment delays than adults. They fit the description of what used to be labeled process (versus reactive) schizophrenia.

Plant-derived vaccine protects target animals against a viral disease.

The successful expression of animal or human virus epitopes on the surface of plant viruses has recently been demonstrated. These chimeric virus particles (CVPs) could represent a cost-effective and safe alternative to conventional animal cell-based vaccines. We report the insertion of oligonucleotides coding for a short linear epitope from the VP2 capsid protein of mink enteritis virus (MEV) into an infectious cDNA clone of cowpea mosaic virus and the successful expression of the epitope on the surface of CVPs when propagated in the black-eyed bean, Vigna unguiculata. The efficacy of the CVPs was established by the demonstration that one subcutaneous injection of 1 mg of the CVPs in mink conferred protection against clinical disease and virtually abolished shedding of virus after challenge with virulent MEV, demonstrating the potential utility of plant CVPs as the basis for vaccine development. The epitope used occurs in three different virus species-MEV, canine parvovirus, and feline panleukopenia virus- and thus the same vaccine could be used in three economically important viral hosts-mink, dogs, and cats, respectively.

Performance evaluation of a smart buffer control at a wastewater treatment plant.

Real time control (RTC) is increasingly seen as a viable method to optimise the functioning of wastewater systems. Model exercises and case studies reported in literature claim a positive impact of RTC based on results without uncertainty analysis and flawed evaluation periods. This paper describes two integrated RTC strategies at the wastewater treatment plant (WWTP) Eindhoven, the Netherlands, that aim to improve the use of the available tanks at the WWTP and storage in the contributing catchments to reduce the impact on the receiving water. For the first time it is demonstrated that a significant improvement can be achieved through the application of RTC in practice. The Storm Tank Control is evaluated based on measurements and reduces the number of storm water settling tank discharges by 44% and the discharged volume by an estimated 33%, decreasing dissolved oxygen depletion in the river. The Primary Clarifier Control is evaluated based on model simulations. The maximum event NH4 concentration in the effluent reduced on average 19% for large events, while the load reduced 20%. For all 31 events the reductions are 11 and 4% respectively. Reductions are significant taking uncertainties into account, while using representative evaluation periods.

Immunohistochemical features of PrP(d) accumulation in natural and experimental goat transmissible spongiform encephalopathies.

Scrapie is a transmissible spongiform encephalopathy (TSE) or prion disease, which naturally affects sheep and goats. Immunohistochemical epitope mapping of abnormal PrP accumulations (PrP(d)) in brain can help in characterizing sheep TSE sources or strains and in identifying potential bovine spongiform encephalopathy (BSE) infections of sheep. Natural and experimental TSE infections of goats were examined to determine whether the epitope mapping approach could also be applied to aid recognition of BSE infection in goats. Goats experimentally infected with the SSBP/1 or CH1641 sheep scrapie strains or with cattle BSE, together with four field cases of natural TSE in goats, were examined immunohistochemically with six different antibodies. CH1641 and SSBP/1 infections in goats, as in sheep, showed PrP(d) accumulations which were mainly intracellular. Some differences in targeting, particularly of Purkinje cells, was evident in inter-species comparisons of CH1641 and SSBP/1. PrP(d) labelling of goat BSE experimental cases showed extensive intracellular and extracellular accumulations, also similar to those in sheep BSE. Intra-neuronal PrP(d) in both goat and sheep BSE was labelled only by antibodies recognizing epitopes located C-terminally of residue His99, whereas in natural sheep TSE sources, and in sheep and goat SSBP/1, PrP(d) was also detected by antibodies to epitopes located between residues Trp93 and His99. Testing of four natural goat TSE samples showed one case in which epitope mapping characteristics and the overall patterns of PrP(d) accumulation was identical with those of experimental goat BSE. The four natural goat scrapie cases examined showed some degree of immunohistochemical phenotype variability, suggesting that multiple strains exist within the relatively small UK goat population.

Establishment and characterization of a melanoma cell line from a xeroderma pigmentosum patient: activation of N-ras at a potential pyrimidine dimer site.

Patients suffering from the genetic disorder xeroderma pigmentosum (XP) display an extreme sensitivity of their skin to sun (UV) exposure and predisposition to skin cancer due to deficiencies in the excision DNA repair pathway. Here we describe the establishment and characterization of the first tumor cell line derived from an XP patient (belonging to complementation group C). The melanoma cell line designated XP44RO(Mel) has retained its tumorigenic and XP phenotype (UV sensitivity, reduced unscheduled DNA synthesis) and showed karyotypic abnormalities characteristic of melanomas. Transfection of XP44RO(Mel) DNA to NIH3T3 cells and oligonucleotide hybridization revealed that the N-ras oncogene was activated by an A.T to T.A or C.G transversion at the third position of codon 61. This mutation occurs at a dipyrimidine site. It is likely initiated by a UV-induced pyrimidine dimer and is of a type rarely observed in mammalian shuttle vector systems and endogenous genes after UV irradiation.