Electrochemical simulation of phase I metabolism for 21 drugs using four different working electrodes in an automated screening setup with MS detection.

BACKGROUND Electrochemical conversion of xenobiotics has been shown to mimic human phase I metabolism for a few compounds. MATERIALS & METHODS Twenty-one compounds were analyzed with a semiautomated electrochemical setup and mass spectrometry detection. RESULTS The system was able to mimic some metabolic pathways, such as oxygen gain, dealkylation and deiodination, but many of the expected and known metabolites were not produced. CONCLUSION Electrochemical conversion is a useful approach for the preparative synthesis of some types of metabolites, but as a screening method for unknown phase I metabolites, the method is, in our opinion, inferior to incubation with human liver microsomes and in vivo experiments with laboratory animals, for example.

Proteome-wide screening of the European porcine reproductive and respiratory syndrome virus reveals a broad range of T cell antigen reactivity.

The porcine reproductive and respiratory syndrome virus (PRRSV) is a rapidly evolving and diversifying pathogen necessitating the development of improved vaccines. Immunity to PRRSV is not well understood although there are data suggesting that virus-specific T cell IFN-γ responses play an important role. We therefore aimed to better characterise the T cell response to genotype 1 (European) PRRSV by utilising a synthetic peptide library spanning the entire proteome and a small cohort of pigs rendered immune to PRRSV-1 Olot/91 by repeated experimental infection. Using an IFN-γ ELISpot assay as a read-out, we were able to identify 9 antigenic regions on 5 of the viral proteins and determine the corresponding responder T cell phenotype. The diversity of the IFN-γ response to PRRSV proteins suggests that antigenic regions are scattered throughout the proteome and no one single antigen dominates the T cell response. To address the identification of well-conserved T cell antigens, we subsequently screened groups of pigs infected with a closely related avirulent PRRSV-1 strain (Lelystad) and a divergent virulent subtype 3 strain (SU1-Bel). Whilst T cell responses from both groups were observed against many of the antigens identified in the first study, animals infected with the SU1-Bel strain showed the greatest response against peptides representing the non-structural protein 5. The proteome-wide peptide library screening method used here, as well as the antigens identified, warrant further evaluation in the context of next generation vaccine development.

Training primary care physicians to offer their patients faecal occult blood testing and colonoscopy for colorectal cancer screening on an equal basis: a pilot intervention with before-after and parallel group surveys.

OBJECTIVES Primary care physicians (PCPs) should prescribe faecal immunochemical testing (FIT) or colonoscopy for colorectal cancer screening based on their patient's values and preferences. However, there are wide variations between PCPs in the screening method prescribed. The objective was to assess the impact of an educational intervention on PCPs' intent to offer FIT or colonoscopy on an equal basis. DESIGN Survey before and after training seminars, with a parallel comparison through a mailed survey to PCPs not attending the training seminars. SETTING All PCPs in the canton of Vaud, Switzerland. PARTICIPANTS Of 592 eligible PCPs, 133 (22%) attended a seminar and 106 (80%) filled both surveys. 109 (24%) PCPs who did not attend the seminars returned the mailed survey. INTERVENTION A 2 h-long interactive seminar targeting PCP knowledge, skills and attitudes regarding offering a choice of colorectal cancer (CRC) screening options. OUTCOME MEASURES The primary outcome was PCP intention of having their patients screened with FIT and colonoscopy in equal proportions (between 40% and 60% each). Secondary outcomes were the perceived role of PCPs in screening decisions (from paternalistic to informed decision-making) and correct answer to a clinical vignette. RESULTS Before the seminars, 8% of PCPs reported that they had equal proportions of their patients screened for CRC by FIT and colonoscopy; after the seminar, 33% foresaw having their patients screened in equal proportions (p<0.001). Among those not attending, there was no change (13% vs 14%, p=0.8). Of those attending, there was no change in their perceived role in screening decisions, while the proportion responding correctly to a clinical vignette increased (88-99%, p<0.001). CONCLUSIONS An interactive training seminar increased the proportion of physicians with the intention to prescribe FIT and colonoscopy in equal proportions.

Screening for anemia in Red Cross blood donor clinics

Accurate screening for anemia at Red Cross blood donor clinics is essential to maintain a safe national blood supply. Despite the importance of identifying anemia correctly by measurement of hemoglobin or hematocrit (hemoglobin/hematocrit) there is no consensus regarding the efficacy of the current two stage screening method which uses the Readacrit$\sp{\rm tm}$ microhematocrit in conjunction with copper sulfate.^ A cross-sectional study was implemented in which hemoglobin/hematocrit was measured, with the present method and four new devices, on 504 prospective blood donors at a Canadian Red Cross permanent blood donor clinic in London, Canada. Concurrently gathered, venous and capillary blood samples were tested by each device and compared to Coulter S IV$\sp{\rm tm}$ determined venous standard readings. Instrument hemoglobin/hematocrit means were statistically calibrated to the standard ones in order to appraise systematic deviations from the standard. Classification analysis was employed to assess concordance between each instrument and the standard when classifying prospective donors as anemic or non-anemic. This was done both when each instrument was used alone (single stage) and when copper sulfate was used as a preliminary screen (two stage) and simulated over a range of anemia prevalences. The Hemoximeter$\sp{\rm tm}$ and Compur M1000$\sp{\rm tm}$ devices had the highest correlations of hemoglobin measurements with the standard ones for both capillary (n.s.) and venous blood (p $<$.05). Analysis of variance (anova) also showed them to be the most accurate (p $<$.05), as did both single and two stage classification analysis, therefore, they are both recommended. There was a smaller difference between instruments for two stage than for single stage screening; therefore instrument choice is less crucial for the former. The present method was adequate for two stage screening as tested but simulations showed that it would discriminate poorly in populations with a higher prevalence of anemia. The Stat-crit and Readacrit, which measure hematocrit, became less accurate at crucial low hematocrit levels. In light of this finding and the introduction of new, effective and easy to use hemoglobin measuring instruments, the continued use of hematocrit as a surrogate for hemoglobin, is not recommended. ^

Yield response of rice (Oryza sativa L.) genotypes to drought under rainfed lowlands 4. Vegetative stage screening in the dry season

Screening for drought resistance of rainfed lowland rice using drought score (leaf death) as a selection index has a long history of use in breeding programs. Genotypic variation for drought score during the vegetative stage in two dry season screens was examined among 128 recombinant inbred lines from four biparental crosses. The genotypic variation detected for drought score in the dry season was used to examine the reliability of the dry season screening method to estimate relative grain yield of genotypes under different types of drought stress in the wet season. Large genotypic variation for drought score existed in two experiments (A and B). However, there was no relationship between the drought scores of genotypes determined in these two experiments. Different patterns of development and severity of drought stress in these two experiments, i.e. slow development and mild plant water deficit in experiment A and fast development and severe plant water deficit in experiment B, were identified as the major factors contributing to the genotypes responding differently. Larger drought score in the dry season experiments was associated with lower grain yield under specific drought stress conditions in the wet season, but the association was weak to moderate and significant only in particular drought conditions. In most cases, a significant phenotypic and moderate genetic correlation between drought score in the dry season and grain yield in the wet season existed only when both drought score and grain yield of genotypes were affected by similar patterns and severity of drought stress in their respective experimental environments. The dry season environments used to measure genotypic variation for drought score should be managed to correspond to relevant types of drought environment that are frequent in the wet season. The efficiency of using the drought score as an indirect selection criterion for improving grain yield for drought conditions was lower than the direct selection for grain yield, and hence wet season screening with grain yield as a selection criterion would be more efficient. However, using drought score as a selection index, a larger number of genotypes can be evaluated than for wet season grain yield. Therefore, it is possible to apply higher selection intensities using the drought score system, and the selected lines can be further tested for grain yield in the wet season. (C) 2004 Elsevier B.V. All rights reserved.

Screening of obstructive and central apnoea/hypopnoea in children using variability: A preliminary study

Aim: Polysomnography (PSG) is the current standard protocol for sleep disordered breathing (SDB) investigation in children. Presently, there are limited reliable screening tests for both central (CE) and obstructive (OE) respiratory events. This study compared three indices, derived from pulse oximetry and electrocardiogram ( ECG), with the PSG gold standard. These indices were heart rate (HR) variability, arterial blood oxygen de-saturation (SaO(2)) and pulse transit time (PTT). Methods: 15 children (12 male) from routine PSG studies were recruited (aged 3 - 14 years). The characteristics of the three indices were based on known criteria for respiratory events (RPE). Their estimation singly and in combination was evaluated with simultaneous scored PSG recordings. Results: 215 RPE and 215 tidal breathing events were analysed. For OE, the obtained sensitivity was HR (0.703), SaO(2) (0.047), PTT (0.750), considering all three indices (0) and either of the indices (0.828) while specificity was (0.891), (0.938), (0.922), (0.953) and (0.859) respectively. For CE, the sensitivity was HR (0.715), SaO(2) (0.278), PTT (0.662), considering all indices (0.040) and either of the indices (0.868) while specificity was (0.815), (0.954), (0.901), (0.960) and (0.762) accordingly. Conclusions: Preliminary findings herein suggest that the later combination of these non-invasive indices to be a promising screening method of SDB in children.

Home-based urinary HPV DNA testing in women who do not attend cervical cancer screening clinics

International audience

Efficacy of ACL injury risk screening methods in identifying high-risk landing patterns during a sport-specific task

Screening methods sensitive to movement strategies that increase anterior cruciate ligament (ACL) loads are likely to be effective in identifying athletes at-risk of ACL injury. Current ACL injury risk screening methods are yet to be evaluated for their ability to identify athletes' who exhibit high-risk lower limb mechanics during sport-specific maneuvers associated with ACL injury occurrences. The purpose of this study was to examine the efficacy of two ACL injury risk screening methods in identifying high-risk lower limb mechanics during a sport-specific landing task. Thirty-two female athletes were screened using the Landing Error Scoring System (LESS) and Tuck Jump Assessment. Participants' also completed a sport-specific landing task, during which three-dimensional kinematic and kinetic data were collected. One-dimensional statistical parametric mapping was used to examine the relationships between screening method scores, and the three-dimensional hip and knee joint rotation and moment data from the sport-specific landing. Higher LESS scores were associated with reduced knee flexion from 30 to 57 ms after initial contact (P = 0.003) during the sport-specific landing; however, no additional relationships were found. These findings suggest the LESS and Tuck Jump Assessment may have minimal applicability in identifying athletes' who exhibit high-risk landing postures in the sport-specific task examined.

Optimal planning of electric-vehicle charging stations in distribution systems

With the progressive exhaustion of fossil energy and the enhanced awareness of environmental protection, more attention is being paid to electric vehicles (EVs). Inappropriate siting and sizing of EV charging stations could have negative effects on the development of EVs, the layout of the city traffic network, and the convenience of EVs' drivers, and lead to an increase in network losses and a degradation in voltage profiles at some nodes. Given this background, the optimal sites of EV charging stations are first identified by a two-step screening method with environmental factors and service radius of EV charging stations considered. Then, a mathematical model for the optimal sizing of EV charging stations is developed with the minimization of total cost associated with EV charging stations to be planned as the objective function and solved by a modified primal-dual interior point algorithm (MPDIPA). Finally, simulation results of the IEEE 123-node test feeder have demonstrated that the developed model and method cannot only attain the reasonable planning scheme of EV charging stations, but also reduce the network loss and improve the voltage profile.

Feasibility of using technology to disseminate evidence to rural nurses and improve patient outcomes

Background: Rural African American women receive less frequent mammography screening and die of breast cancer at a higher rate than is seen in the general population. To overcome this disparity, it is necessary to assist rural providers in their efforts to influence women to obtain screening. Method: This study examined the feasibility of using distance education to disseminate knowledge about timely and appropriate mammography screening to rural nurses, using patient outcome data to evaluate the effectiveness of this intervention. Results: Overall, there was a decline in referrals and mammography screening, but the intervention group centers showed a smaller decline after the educational intervention than did the control group. Conclusion: The findings show the effect of dissemination of information and the feasibility of using patient outcome data for educational evaluation. Neighboring academic health centers and nursing schools should include in their mission the provision of educational programs for relatively isolated rural nurses.

A staining protocol for identifying secondary compounds in Myrtaceae

• Premise of the study: Here we propose a staining protocol using TBO and Ruthenium red in order to reliably identify secondary compounds in the leaves of some species of Myrtaceae. • Methods and results: Leaves of 10 species representing 10 different genera of Myrtaceae were processed and stained using five different combinations of Ruthenium red and TBO. Optimal staining conditions were determined as 1 min of Ruthenium red (0.05% aqueous) and 45 sec of TBO (0.1% aqueous). Secondary compounds clearly identified under this treatment include mucilage in mesophyll, polyphenols in cuticle, lignin in fibers and xylem, tannins and carboxylated polysaccharides in epidermis and pectic substances in primary cell walls. • Conclusions: Potential applications of this protocol include systematic, phytochemical and ecological investigations in Myrtaceae. It might be applicable to other plant families rich in secondary compounds and could be used as preliminary screening method for extraction of these elements.

Comparison of visual status of Iranian military and commercial drivers

Background There is no legal requirement for Iranian military truck drivers to undergo regular visual checkups as compared to commercial truck drivers. Objectives This study aimed to evaluate the impact of drivers’ visual checkups by comparing the visual function of Iranian military and commercial truck drivers. Patients and Methods In this comparative cross-sectional study, two hundred military and 200 commercial truck drivers were recruited and their Visual Acuity (VA), Visual Field (VF), color vision and Contrast Sensitivity (CS) were assessed and compared using the Snellen chart, confrontation screening method, D15 test and Pelli-Robson letter chart, respectively. A questionnaire regarding driving exposure and history of motor-vehicle crashes (MVCs) was also filled by drivers. Results were analyzed using an independent samples t-test, one-way ANOVA (assessing difference in number of MVCs across different age groups), chi-square test and Pearson correlation at statistical significance level of P < 0.05. Results Mean age was 41.6 ± 9.2 for the military truck drivers and 43.4 ± 10.9 for commercial truck drivers (P > 0.05). No significant difference between military and commercial drivers was found in terms of driving experience, number of MVCs, binocular VA, frequency of color vision defects and CS scores. In contrast, the last ocular examination was significantly earlier in military drivers than commercial drivers (P < 0.001). In addition, 4% of military drivers did not meet the national standards to drive as opposed to 2% of commercial drivers. There was a significant but weak correlation between binocular VA and age (r = 0.175, P < 0.001). However, CS showed a significantly moderate correlation with age (r = -0.488, P < 0.001). Conclusions The absence of legal requirement for regular eye examination in military drivers caused the incompetent drivers to be missed in contrast to commercial drivers. The need for scientific revision of VA standard for Iranian drivers is also discussed. The CS measurement in visual checkups of older drivers deserves to be investigated more thoroughly.

Rapid typing of P multocida

Fowl cholera, caused by P. multocida, is a serious disease of poultry with sudden surges in mortality and an emerging disease of the free ranged poultry industries. This project will develop a more rapid and cost effective screening method for P. multocida. The impacts of this new method are manifold: It will lead to an improved understanding of the epidemiology of fowl cholera and the possible sources of entry onto the farm leading to improved biosecurity measures and control programs. Another impact is improved serotyping, which will ensure more effective and targeted vaccination programs. Improving prevention and control programs and decreasing the reliance on antibiotics will enhance the sustainability and profitability of the industry.

Terveyteen liittyvä elämänlaatu laitoskuntoutuksen vaikuttavuuden arvioinnissa : RAND-36-mittarin soveltuvuus työikäisten laitoskuntoutuksen ongelmaprofiilin määrittämiseen ja kuntoutuksen vaikutusten arvioimiseen

The aim of the present research was to examine the validity of the RAND-36 measure of health-related quality of life among the working age rehabilitation clients. The research included two cross-sectional studies and one follow-up study. The subjects of the first study (n = 794) participated in the first period of the five following types of rehabilitation: occupationally oriented medical rehabilitation, musculoskeletal rehabilitation, medical rehabilitation for job burnout, rehabilitation for supporting the work ability and capacity of disabled subjects (vocational rehabilitation) and individualized rehabilitation between October 2000 and October 2001. The subjects of the second study (n = 990) participated in the same rehabilitation during their first rehabilitation period between May 2007 and May 2008. The first subjects participated in a follow-up period no later than May 2003 with the exception of the individual rehabilitation clients (n = 588). Based on the ICF classification, the RAND-36 provides a diverse measure of the health-related quality of life and of the capacity for subjective, perceived physical and psycho-social functioning. The construct properties of the RAND-36 measure proved to be very consistent on the basis of both the cluster and confirmatory factor analyses. At the group level, the RAND-36 measure was shown to be illustrative and sensitive in differentiating the clients’ rehabilitation needs. The results of cluster analyses with the two cross-sectional data indicated a consistent five-cluster solution of rehabilitation groups on the basis of the eight subscales of health-related quality of life. Each of these clusters represented a clear difference in their need for rehabilitation. The RAND-36 measure proved to be sensitive to change. The changes observed in the pre- and post-conditions in relation to all the subscales of quality of life were statistically significant. Depending on the rehabilitation type, different changes in the subscales of the measure were observed, and these changes corresponded to the different emphasis and goals of the specific type of rehabilitation intervention. Similarly, changes in the subscales of the measure were observed in relation to the RAND groups formed by cluster analysis, which were logical and corresponded to the problem profiles of these groups. The confirmatory factor analysis indicated a two-factor solution: an index of the capacity for physical functioning (self-rated general health, bodily pain, physical functioning, physical role functioning) and an index of the capacity for psycho-social functioning (psychological well-being, social functioning, psychological role functioning and energy). These two indices describing functional capacity proved also to be sensitive to change. This two-factor solution seems to be usable for group level analyses when assessing the effects of rehabilitation. The moderately strong correlation between the RAND-36 and work ability index suggests that they partly measure the same phenomenon: perceived health-related quality of life, subjective capacity for activity and perceived work ability have strong links. As expected, the capacity for physical functioning had a stronger correlation with work ability index than with the capacity for psycho-social functioning. According to the present research, the RAND-36 measure can be considered as a screening method for rehabilitation orientation in relation to rehabilitation needs and as a follow-up measure for the health-related quality of life among the working age clients. The RAND-36 measure is also shown to be a useful instrument in estimating the benefits of rehabilitation as well as in effectiveness research.

Genotyping for genetic association studies: Methods and applications

In this thesis, two separate single nucleotide polymorphism (SNP) genotyping techniques were set up at the Finnish Genome Center, pooled genotyping was evaluated as a screening method for large-scale association studies, and finally, the former approaches were used to identify genetic factors predisposing to two distinct complex diseases by utilizing large epidemiological cohorts and also taking environmental factors into account. The first genotyping platform was based on traditional but improved restriction-fragment-length-polymorphism (RFLP) utilizing 384-microtiter well plates, multiplexing, small reaction volumes (5 µl), and automated genotype calling. We participated in the development of the second genotyping method, based on single nucleotide primer extension (SNuPeTM by Amersham Biosciences), by carrying out the alpha- and beta tests for the chemistry and the allele-calling software. Both techniques proved to be accurate, reliable, and suitable for projects with thousands of samples and tens of markers. Pooled genotyping (genotyping of pooled instead of individual DNA samples) was evaluated with Sequenom s MassArray MALDI-TOF, in addition to SNuPeTM and PCR-RFLP techniques. We used MassArray mainly as a point of comparison, because it is known to be well suited for pooled genotyping. All three methods were shown to be accurate, the standard deviations between measurements being 0.017 for the MassArray, 0.022 for the PCR-RFLP, and 0.026 for the SNuPeTM. The largest source of error in the process of pooled genotyping was shown to be the volumetric error, i.e., the preparation of pools. We also demonstrated that it would have been possible to narrow down the genetic locus underlying congenital chloride diarrhea (CLD), an autosomal recessive disorder, by using the pooling technique instead of genotyping individual samples. Although the approach seems to be well suited for traditional case-control studies, it is difficult to apply if any kind of stratification based on environmental factors is needed. Therefore we chose to continue with individual genotyping in the following association studies. Samples in the two separate large epidemiological cohorts were genotyped with the PCR-RFLP and SNuPeTM techniques. The first of these association studies concerned various pregnancy complications among 100,000 consecutive pregnancies in Finland, of which we genotyped 2292 patients and controls, in addition to a population sample of 644 blood donors, with 7 polymorphisms in the potentially thrombotic genes. In this thesis, the analysis of a sub-study of pregnancy-related venous thromboses was included. We showed that the impact of factor V Leiden polymorphism on pregnancy-related venous thrombosis, but not the other tested polymorphisms, was fairly large (odds ratio 11.6; 95% CI 3.6-33.6), and increased multiplicatively when combined with other risk factors such as obesity or advanced age. Owing to our study design, we were also able to estimate the risks at the population level. The second epidemiological cohort was the Helsinki Birth Cohort of men and women who were born during 1924-1933 in Helsinki. The aim was to identify genetic factors that might modify the well known link between small birth size and adult metabolic diseases, such as type 2 diabetes and impaired glucose tolerance. Among ~500 individuals with detailed birth measurements and current metabolic profile, we found that an insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene was associated with the duration of gestation, and weight and length at birth. Interestingly, the ACE insertion allele was also associated with higher indices of insulin secretion (p=0.0004) in adult life, but only among individuals who were born small (those among the lowest third of birth weight). Likewise, low birth weight was associated with higher indices of insulin secretion (p=0.003), but only among carriers of the ACE insertion allele. The association with birth measurements was also found with a common haplotype of the glucocorticoid receptor (GR) gene. Furthermore, the association between short length at birth and adult impaired glucose tolerance was confined to carriers of this haplotype (p=0.007). These associations exemplify the interaction between environmental factors and genotype, which, possibly due to altered gene expression, predisposes to complex metabolic diseases. Indeed, we showed that the common GR gene haplotype associated with reduced mRNA expression in thymus of three individuals (p=0.0002).