Arithmetic fluency and number processing skills in identifying students with mathematical learning disabilities.

BACKGROUND: Students with mathematical learning disabilities (MLD) struggle with number processing skills (e.g., enumeration and number comparison) and arithmetic fluency. Traditionally, MLD is identified based on arithmetic fluency. However, number processing skills are suggested to differentiate low achievement (LA) from MLD. AIMS: This study investigated the accuracy of number processing skills in identifying students with MLD and LA, based on arithmetic fluency, and whether the classification ability of number processing skills varied as a function of grade level. METHODS AND PROCEDURES: The participants were 18,405 students (girls = 9080) from Grades 3-9 (ages 9-15). Students' basic numerical skills were assessed with an online dyscalculia screener (Functional Numeracy Assessment -Dyscalculia Battery, FUNA-DB), which included number processing and arithmetic fluency as two factors. OUTCOMES AND RESULTS: Confirmatory factor analyses supported a two-factor structure of FUNA-DB. The two-factor structure was invariant across language groups, gender, and grade levels. Receiver operating characteristics curve analyses indicated that number processing skills are a fair classifier of MLD and LA status across grade levels. The classification accuracy of number processing skills was better when predicting MLD (cut-off < 5 %) compared to LA (cut-off < 25 %). CONCLUSIONS AND IMPLICATIONS: Results highlight the need to measure both number processing and arithmetic fluency when identifying students with MLD.

Maintenance of permanent sexual activity throughout the year in seasonal bucks using short photoperiodic cycles in open barns.

Seasonality of reproductive activity in rams and bucks is the major constraint in temperate and subtropical zones. Rapid alternation between 1 month of short days and 1 month of long days (LD) over three years in lightproof buildings eliminates this seasonality. We examined if this would also work in open barns, using only supplementary light. Over two years, one group of bucks (n = 7) was subjected to alternate 1 month of LD and 1 month of permanent light (LD-LL) and another group (n = 7) to alternate 1 month of LD and 1 month of natural light (LD-NL). A simultaneous control group, used for both experiments (CG1, n = 6; CG2, n = 6), remained under natural photoperiod. BW, testis weight (TW), plasma testosterone (T) and cortisol (C) were evaluated in all bucks. CG1 and CG2 bucks showed identical dramatic seasonal variations in BW (stable or decreasing in summer), TW (from 85 ± 12 g in February to 127 ± 7 g in July) and T (from 2.7 ± 1.2 ng/mL in January-April to 24.3 ± 3.2 ng/mL in June-October). By contrast, BW of LD-LL and LD-NL bucks increased regularly during the experiment. From 5 and 9 months after the experiment onset, LD-LL and LD-NL bucks, respectively, maintained constant TW of 115 ± 5 g until the experiment end. After the first 3 months <5 ng/mL, T of LD-LL bucks remained constant (5-10 ng/mL) until the experiment end. By contrast, T of LD-NL bucks showed four periods of low (<5 ng/mL) and two periods of high concentrations (18.1 ± 2.6 and 11.9 ± 3.4 ng/mL). Plasma C remained low (5-8 ng/mL) and did not change with group or light treatment. These results show for the first time in any seasonal photoperiodic species that it is possible to maintain the sexual activity of males all year round in open buildings using alternating periods of LD and LL. By contrast, return to NL instead of LL every other month does not prevent seasonality in T concentration. These results raise interesting questions about the photoperiodic control of neuroendocrine regulation of seasonal sexual activity and suggest that these treatments can be used to manage males in open barns in farms and in artificial insemination centres. (Spanish and French versions of the full text are available as Supplementary Materials S1 and S2).

Patterns of Athlete Medication Use at the 2018 PyeongChang Paralympic Games: A Descriptive Cohort Study.

OBJECTIVE: Medication use among elite athletes has received growing attention over the past decades. However, only limited studies have focused on para athletes, and trends in medication use among this cohort remain unclear. The aims of this study were (1) to describe the pattern of medication use in elite Paralympic athletes, with a particular focus on analgesics, (2) to analyze whether medications declared by athletes were included in the 2018 World Anti-Doping Agency's prohibited list and monitoring program, (3) to report on a variety of novel supplements, and (4) to review whether athlete analgesic needs will be met by the new Olympic & Paralympic Model Formulary. DESIGN: This is a retrospective, descriptive cohort study. RESULTS: Of all athletes who underwent doping control, 21% declared the use of an analgesic medication. Athletes with limb deficiency and para snowboarders declared the most analgesic medications in their respective categories. It was determined that 84% of the athletes' analgesic medication needs were provided from the new Olympic & Paralympic Model Formulary. CONCLUSIONS: Analgesic use among athletes who participated at the 2018 PyeongChang Winter Paralympics was high. Para snowboarders and athletes with limb deficiency declared the most analgesics. The new Olympic & Paralympic Model Formulary adequately addressed the medication needs of the athletes attending the 2018 games.

Study of Haloperidol for Abdominal Pain in the Emergency Department (SHAPE).

INTRODUCTION: Intravenous haloperidol has been shown to decrease milligram morphine equivalents (MME) of analgesia and reduce hospital admissions for diabetic gastroparesis. The objective of this study was to evaluate whether haloperidol decreases MME for the treatment of non-specific abdominal pain diagnoses in the emergency department (ED), including gastroparesis, cyclic vomiting, cannabinoid hyperemesis syndrome, and unspecified abdominal pain. The primary outcome compared the difference in MME between encounters. Secondary outcomes included admission rate, pain scores, length of stay, rescue therapy administration, and adverse effects. METHODS: This retrospective chart review included patients ≥ 18 years old who presented to the ED. Patients must have had ≥ 2 ED encounters for abdominal pain, one in which they received conventional therapy with opioids (C-encounter), and the other in which they received haloperidol (H-encounter). Agitated patients were excluded. Seventy-five patients were needed to detect a 3 MME difference with 80% power and two-sided alpha of 0.05. RESULTS: We analyzed 107 patients with self-matched encounters. The median dose of haloperidol administered was 5.0 milligrams (mg) (interquartile range [IQR] 2.0 - 5.0). C-encounters had significantly more MME administered than H-encounters (median 5.7 mg [IQR 4.0 - 8.0] vs 0.0 mg [IQR 0.0 - 2.5], P < 0.001). These results remained significant despite route of haloperidol administration. C-encounters had higher rates of rescue therapy administration than H-encounters, (56% vs 33.6%, P < 0.001). There were higher rates of ketorolac administration in the H-encounter (P = 0.02). CONCLUSION: Encounters in which patients received haloperidol and ketorolac for abdominal pain had a statistically significant reduction in MME administered and lower rates of rescue therapy administration than encounters in which patients were treated with opioids.

Genome-wide association study for age at puberty and resumption of cyclicity in a crossbred dairy cattle population.

Fertility is of primary economic importance in dairy cattle and the most common reason for involuntary culling. However, standard fertility traits have very low heritability that renders genetic selection slow and difficult. In this study, we explored fertility from an endocrine standpoint. A total of 1,163 crossbred Holstein-Normande females in a 3-generation familial design were studied for progesterone level measured every 10 d to determine age at puberty (PUB) and commencement of postpartum luteal activity (CPLA). Genetic parameters were estimated using REML with WOMBAT software. The heritability estimates were 0.38 ± 0.10 and 0.16 ± 0.07 for PUB and CPLA, respectively. Moreover, the 2 traits were genetically correlated (0.45 ± 0.23), suggesting a partially common determinism. Because of the family structure, a linkage disequilibrium and linkage analysis approach was preferred over standard genome-wide association study to map genomic regions associated with these traits. Ten quantitative trait loci (QTL) were detected for PUB on chromosomes 1, 3, 11, 13, 14, 21, and 29, whereas 3 QTL were associated with CPLA on chromosomes 21 and 26. Only the QTL on chromosome 21 was common to both traits. Four functional candidate genes (NCOA2, GAS2, OVOL1, and FOSL1) were identified in the detected regions. These findings will contribute to a clearer understanding of fertility determinism and enhance the value of introducing endocrinological data in fertility studies.

Combined robotic approach and enhanced recovery after surgery pathway for optimization of costs in patients undergoing proctectomy.

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways are beneficial in proctocolectomy, but their impact on robotic low rectal proctectomy is not fully investigated. This study assessed the impact of an ERAS pathway on the outcomes and cost of robotic (RTME) versus laparoscopic (LTME) total mesorectal excision. METHODS: A retrospective review was performed of patients with rectal cancer in a single French tertiary centre for three yearly periods: 2011, LTME; 2015, RTME; and 2018, RTME with ERAS. Patient characteristics, operative and postoperative data, and costs were compared among the groups. RESULTS: A total of 220 consecutive proctectomies were analysed (71 LTME, 58 RTME and 91 RTME with ERAS). A prevalence of lower and locally advanced tumours was observed with RTME. The median duration of surgery increased with the introduction of RTME, but became shorter than that for LTME with greater robotic experience (226, 233 and 180 min for 2011, 2015 and 2018 respectively; P < 0·001). The median duration of hospital stay decreased significantly for RTME with ERAS (11, 10 and 8 days respectively; P = 0·011), as did the overall morbidity rate (39, 38 and 16 per cent; P = 0·002). Pathology results, conversion and defunctioning stoma rates remained stable. RTME alone increased the total cost by €2348 compared with LTME. The introduction of ERAS and improved robotic experience decreased costs by €1960, compared with RTME performed in 2015 without ERAS implementation. In patients with no co-morbidity, costs decreased by €596 for RTME with ERAS versus LTME alone. CONCLUSION: ERAS is associated with cost reductions in patients undergoing robotic proctectomy.

ANTECEDENTES: Las vías clínicas ERAS son beneficiosas en la proctocolectomía, pero su impacto en la proctectomía rectal baja robótica no se ha investigado exhaustivamente. El objetivo de este estudio fue evaluar el impacto de la vía clínica ERAS sobre los resultados y el coste de la proctectomía robótica (resección total del mesorrecto robótica, robotic total mesorectal excision, RTME) versus procedimientos laparoscópicos de resección total del mesorrecto (laparoscopic total mesorectal excision, LTME). MÉTODOS: Revisión retrospectiva de pacientes con cáncer de recto tratados en un único centro terciario francés durante un periodo de tres años: 1) 2011: resección total del mesorrecto laparoscópica (LTME); 2) 2015: TME robótica y 3) 2018: TME robótica plus ERAS. Se compararon las características de los pacientes, los datos operatorios y postoperatorios, y los costes entre subgrupos utilizando análisis estadísticos. RESULTADOS: Se analizaron 220 proctectomías consecutivas que incluían 71 LTME, 58 RTME y 91 RTME plus ERAS. Se observó un predominio de tumores inferiores y localmente avanzados en la RTME. La mediana del tiempo operatorio aumentó con la introducción de RTME, pero llegó a ser inferior que en la LTME con una mayor experiencia robótica (226, 233 y 180 minutos para los periodos 1, 2 y 3, respectivamente; P = 0,0001). La mediana de la estancia hospitalaria disminuyó significativamente con la RTME plus ERAS (11, 10 y 8 días; P = 0,01), así como la morbilidad global (40%, 38% y 16%; P = 0,002). Los resultados de la anatomía patológica, las tasas de conversión y de estomas de protección permanecieron estables. La RTME sola aumentó el coste total en €2.348 comparado con la LTME. La introducción de ERAS y una mejora en la experiencia robótica disminuyeron los costes en €1.960 versus RTME realizada en 2015 sin la implementación de ERAS. En pacientes sin comorbilidades, los costes disminuyeron en €1.196 con RTME plus ERAS versus LTME sola. CONCLUSIÓN: ERAS se asocia con reducciones de coste en la proctectomía robótica.

Impacts of drainage, restoration and warming on boreal wetland greenhouse gas fluxes.

Northern wetlands with organic soil i.e., mires are significant carbon storages. This key ecosystem service may be threatened by anthropogenic activities and climate change, yet we still lack a consensus on how these major changes affects their carbon sink capacities. We studied how forestry drainage and restoration combined with experimental warming, impacts greenhouse gas fluxes of wetlands with peat. We measured CO2 and CH4 during two and N2O fluxes during one growing season using the chamber method. Gas fluxes were primarily controlled by water table, leaf area and temperature. Land use had a clear impact of on CO2 exchange. Forestry drainage increased respiration rates and decreased field layer net ecosystem CO2 uptake (NEE) and leaf area index (LAI), while at restoration sites the flux rates and LAI had recovered to the level of undrained sites. CH4 emissions were exceptionally low at all sites during our study years due to natural drought, but still somewhat lower at drained compared to undrained sites. Moderate warming triggered an increase in LAI across all land use types. This was accompanied by an increase in cumulative seasonal NEE. Restoration appeared to be an effective tool to return the ecosystem functions of these wetlands as we found no differences in LAI or any gas flux components (PMAX, Reco, NEE, CH4 or N2O) between restored and undrained sites. We did not find any signs that moderate warming would compromise the return of the ecosystem functions related to C sequestration.

A bovine-specific FSH enzyme immunoassay and its application to study the role of FSH in ovarian follicle development during the postnatal period.

The primary aim of this study was to develop a FSH enzyme immunoassay (EIA) for the bovine species. The newly developed EIA was validated for FSH determination in bovine plasma by comparison with an existing bovine FSH radioimmunoassay. The EIA detected bovine FSH with a high sensitivity (0.1 ng/ml). Cross-reactivity of the EIA was 0.01% with bovine LH, 51% with ovine FSH, <0.1% with porcine FSH and <0.01% with equine FSH. Using this EIA on different time series of plasma in cows, we have confirmed the presence of a FSH pre-ovulatory peak at estrus, of periodic FSH fluctuations accompanying the waves of terminal follicular development, and of FSH pulses, mainly asynchronous with LH ones, in the peri-ovulatory phase of the cycle. In a second objective, the EIA was used to assess the role of FSH in regulating the development of ovarian follicles up to the small antral stage in young calves. To answer this question, six calves were submitted to weekly blood sampling during their first 3 months of life, and FSH changes were studied concomitantly to those of anti-Müllerian hormone (AMH), a well-established endocrine marker of the ovarian population of small antral follicles in cows. In the ovaries of 3-month calves, the population of 3 to 5 mm follicles contained the highest intra-follicular AMH amounts, and the number of 3 to 5 mm follicles on ovaries was closely correlated with AMH concentrations in the plasma of calves at this age (rs = 0.94). Before 3 months of age, only two out of six calves showed a clear postnatal FSH peak in plasma, and no correlation was found between plasma FSH and AMH concentrations. These results indicate that female calves undergo different patterns of FSH secretion and that postnatal activation of follicular growth up to the small antral stage appears independent and not directly related to circulating FSH levels.

Successional change of testate amoeba assemblages along a space-for-time sequence of peatland development.

It is well established that in ombrotrophic bogs, water-table depth (WTD) is the primary environmental control on testate amoeba distribution. However, the environmental controls on testate amoebae in minerotrophic fens are less well known and successional change in their assemblages associated with fen-bog peatland development has been scarcely investigated. Here we investigate a peatland space-for-time sequence resulting from postglacial rebound on the west coast of Finland, to assess successional patterns in testate amoeba communities and their relationships with environmental variables during peatland development. Sample sites along a 10-km transect from coast to inland ranged from a recently emerged wet meadow to a mature bog. Environmental variables (e.g., peat thickness, carbon and nitrogen content, pH, WTD and vegetation) were measured alongside testate amoeba samples. Results showed that even though the distribution of testate amoebae was to some extent determined by the succession stage, many taxa had wide WTD and pH ranges. The primary environmental control for many taxa changed along the succession. In conclusion, the ecological constraints on testate amoebae in minerotrophic systems are more complex than in bogs. The detected patterns also complicate the use of testate amoebae as a primary proxy in palaeoecological reconstructions where fen-to-bog shifts occur.

MicroMegascope.

Atomic force microscopy (AFM) allows us to reconstruct the topography of surfaces with resolution in the nanometer range. The exceptional resolution attainable with the AFM makes this instrument a key tool in nanoscience and technology. The core of a standard AFM set-up relies on the detection of the change of the mechanical motion of a micro-oscillator when approaching the sample to image. This is despite the fact that AFM is nowadays a very common instrument for both fundamental and applied research. The fabrication of the micrometric scale mechanical oscillator is still a very complicated and expensive task requiring dedicated platforms. Being able to perform AFM with a macroscopic oscillator would make the instrument more versatile and accessible for an even larger spectrum of applications and audience. Here, we present atomic force imaging with a centimetric oscillator, an aluminum tuning fork of centimeter size as a sensor on which an accelerometer is glued on one prong to measure the oscillations. We show that it is possible to perform topographic images of nanometric resolution with a gram tuning fork. In addition to the stunning sensitivity, we show the high versatility of such an oscillator by imaging both in air and liquid. The set-up proposed here can be extended to numerous experiments where the probe has to be heavy and/or very complex, and so too the environment.

Incrementing the Frequency of Dynamic Strain on SMC-Cellularised Collagen-Based Scaffolds Affects Extracellular Matrix Remodeling and Mechanical Properties.

Notwithstanding the efforts injected in vascular tissue engineering in the past 30 years, the clinical translation of engineered artery constructs is far from being successful. One common approach to improve artery regeneration is the use of cyclic mechanical stimuli to guide cellular remodeling. However, there is a lack of information on the effect of cyclic strain on cells within a 3D environment. To this end, this work explored the effect of gradual increase in stimulation frequency on the response of human umbilical artery smooth muscle cells (HUASMCs) embedded in a 3D collagen matrix. The results demonstrate that, with an applied strain of 5%, the gradual increase of frequency from 0.1 to 1 Hz improved collagen remodeling by HUASMCs compared to samples constantly stimulated at 1 Hz. The expression of collagen, elastin and matrix metalloproteinase-2 (MMP-2) genes was similar at 7 days for gradual and 1 Hz samples which showed lower amounts than static counterparts. Interestingly the mechanical properties of the constructs, specifically the amplitude of the time constants and the elastic equilibrium modulus, were enhanced by gradual increase of frequency. Taken together, these results show an increase in collagen remodeling by the HUASMCs overtime under incremental cyclic mechanical strain. This work suggests that only the in-depth investigation of the effects of stimulation parameters on the behavior of vSMC under cyclic strain in a 3D environment could lead to the design of optimized control strategies for enhanced vascular tissue generation and maturation in bioreactors.

High Plasma Lipid Levels Reduce Efficacy of Adenovirus-Mediated Gene Therapy.

Adenoviruses are very efficient vectors for delivering therapeutic genes in preclinical and clinical trials. However, randomized controlled human trials have often been lacking clear clinically relevant results. We hypothesized that high lipid levels and specific lipoproteins could significantly decrease adenoviral transduction efficiency in vivo. Here we demonstrate that mice on a high fat diet have lower transgene expression compared to mice on a regular chow. In addition, on a high fat diet, ApoE-/- mice have much higher plasma transgene levels compared to LDLR-deficient mice. We also found that specific lipoprotein receptors play an important role in adenoviral transduction. These findings suggest that high plasma lipid levels, especially apoE-containing lipoproteins, reduce efficacy of adenoviral transduction in mice, which implies that high cholesterol levels in humans could be protective against viral infections and also lead to insufficient transgene expression in clinical trials using adenoviral vectors.

The association of the HLA-A*24:02, B*39:01 and B*39:06 alleles with type 1 diabetes is restricted to specific HLA-DR/DQ haplotypes in Finns.

BACKGROUND: We analysed the previously reported association of the HLA-A*24:02, B*18 and B*39 alleles with type 1 diabetes and diabetes associated autoimmunity in the Finnish population applying HLA-DR/DQ stratification. MATERIALS & METHODS: Haplotype transmission was analysed in 2424 nuclear families from the Finnish Paediatric Diabetes Register. Survival analysis was applied to study the development of islet autoantibodies and further progression to clinical diabetes in the prospective follow-up cohort from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study. The subjects were genotyped for specific HLA class I alleles by sequence-specific hybridization using lanthanide labelled nucleotide probes. RESULTS: The HLA-B*39:06 allele was found almost exclusively on the (DR8)-DQB1*04 haplotype in which its presence changed the disease risk status of the whole haplotype from neutral to predisposing. The HLA-A*24:02 and the B*39:01 alleles increased the diabetes-associated risk of the DRB1*04:04-DQA1*03-DQB1*03:02 haplotype but the alleles were in linkage disequilibrium and no independent effect could be detected. Within the DIPP cohort, neither the A*24:02 nor the B*39:01 allele were associated with seroconversion but were in contrast associated with increased progression from seroconversion to clinical disease. DISCUSSION & CONCLUSIONS: The independent predisposing effect of the HLA-B*39:06 allele with type 1 diabetes was confirmed in the Finnish population but the association of the A*24:02 and B*39:01 alleles remained inconclusive whilst both A*24:02 and B*39:01 affected the progression rate from seroconversion to autoantibody positivity to overt type 1 diabetes.

Assessing the effect of pregnancy stage on milk composition of dairy cows using mid-infrared spectra.

Changes in milk production traits (i.e., milk yield, fat, and protein contents) with the pregnancy stage are well documented. To our knowledge, the effect of pregnancy on the detailed milk composition has not been studied so far. The mid-infrared (MIR) spectrum reflects the detailed composition of a milk sample and is obtained by a nonexhaustive and widely used method for milk analysis. Therefore, this study aimed to investigate the effect of pregnancy on milk MIR spectrum in addition to milk production traits (milk yield, fat, and protein contents). A model including regression on the number of days pregnant was applied on milk production traits (milk yield, fat, and protein contents) and on 212 spectral points from the MIR spectra of 9,757 primiparous Holstein cows from Walloon herds. Effects of pregnancy stage were expressed on a relative scale (effect divided by the squared root of the phenotypic variance); this allowed comparisons between effects on milk traits and on 212 spectral points. Effect of pregnancy stage on production traits were in line with previous studies indicating that the model accounted well for the pregnancy effect. Trends of the relative effect of the pregnancy stage on the 212 spectral points were consistent with known and observed effect on milk traits. The highest effect of the pregnancy was observed in the MIR spectral region from 968 to 1,577 cm-1. For some specific wavenumbers, the effect was higher than for fat and protein contents in the beginning of the pregnancy (from 30 to 90 or 120 d pregnant). In conclusion, the effect of early pregnancy can be observed in the detailed milk composition through the analysis of the MIR spectrum of bovine milk. Further analyses are warranted to explore deeply the use of MIR spectra of bovine milk for breeding and management of dairy cow pregnancy.

Enhanced oral delivery of celecoxib via the development of a supersaturable amorphous formulation utilising mesoporous silica and co-loaded HPMCAS.

Stabilization of amorphous formulations via mesoporous silica has gained considerable attention for oral delivery of poorly soluble drugs. The release of the drug from the silica is expected to generate supersaturation which is often associated with subsequent precipitation. The aim of the study was hence to develop a novel supersaturable amorphous formulation through the co-loading of a BCS class II drug Celecoxib (CXB) with a precipitation inhibitor hydroxypropyl methylcellulose acetate succinate (HPMCAS) onto the silica. The addition of HPMCAS did not hamper the adsorption but on the contrary promoted the complete solid state conversion of the drug as proved by DSC analysis. In an in vitro pH shift assay, the CXB-HPMCAS co-loaded silica achieved a 5-fold solubility increase over the crystalline CXB and over the CXB-loaded silica blended with HPMCAS which did not show any enhancement. The drug co-loaded silica was then suspended in an aqueous vehicle facilitating the dosing to animals. The CXB-HPMCAS co-loaded silica suspension achieved 15-fold solubility increase in vitro over the crystalline counterpart which translated in 1.35-fold Cmax increase in vivo after oral dosing in rats. This approach represents a novel formulation strategy to maximize in vivo exposure of poorly soluble drugs critical for discovery studies.

Comparison of electric field strength and spatial distribution of electroconvulsive therapy and magnetic seizure therapy in a realistic human head model.

BACKGROUND: This study examines the strength and spatial distribution of the electric field induced in the brain by electroconvulsive therapy (ECT) and magnetic seizure therapy (MST). METHODS: The electric field induced by standard (bilateral, right unilateral, and bifrontal) and experimental (focal electrically administered seizure therapy and frontomedial) ECT electrode configurations as well as a circular MST coil configuration was simulated in an anatomically realistic finite element model of the human head. Maps of the electric field strength relative to an estimated neural activation threshold were used to evaluate the stimulation strength and focality in specific brain regions of interest for these ECT and MST paradigms and various stimulus current amplitudes. RESULTS: The standard ECT configurations and current amplitude of 800-900mA produced the strongest overall stimulation with median of 1.8-2.9 times neural activation threshold and more than 94% of the brain volume stimulated at suprathreshold level. All standard ECT electrode placements exposed the hippocampi to suprathreshold electric field, although there were differences across modalities with bilateral and right unilateral producing respectively the strongest and weakest hippocampal stimulation. MST stimulation is up to 9 times weaker compared to conventional ECT, resulting in direct activation of only 21% of the brain. Reducing the stimulus current amplitude can make ECT as focal as MST. CONCLUSIONS: The relative differences in electric field strength may be a contributing factor for the cognitive sparing observed with right unilateral compared to bilateral ECT, and MST compared to right unilateral ECT. These simulations could help understand the mechanisms of seizure therapies and develop interventions with superior risk/benefit ratio.

On the role of mid-infrared predicted phenotypes in fertility and health dairy breeding programs.

Fertility and health traits are of prime importance in dairy breeding programs. However, these traits are generally complex, difficult to record, and lowly heritable (<0.10), thereby hampering genetic improvement in disease resistance and fertility. Hence, indicators are useful in the prediction of genetic merit for fertility and health traits as long as they are easier to measure than direct fitness traits, heritable, and genetically correlated. Considering that changes in (fine) milk composition over a lactation reflect the physiological status of the cow, mid-infrared (MIR) analysis of milk opens the door to a wide range of potential indicator traits of fertility and health. Previous studies investigated the phenotypic and genetic relationships between fertility and MIR-predicted phenotypes, most being related to negative postpartum energy balance and body fat mobilization (e.g., fat:protein ratio, urea, fatty acids profile). Results showed that a combination of various fatty acid traits (e.g., C18:1 cis-9 and C10:0) could be used to improve fertility. Furthermore, occurrence of (sub)clinical ketosis has been related to milk-based phenotypes such as fat:protein ratio, fatty acids, and ketone bodies. Hence, MIR-predicted acetone and ß-hydroxybutyrate contents in milk could be useful for breeding cows less susceptible to ketosis. Although studies investigating the genetic association among mastitis and MIR-predicted phenotypes are scarce, a wide range of traits, potentially predicted by MIR spectrometry, are worthy of consideration. These include traits related to the disease response of the cow (e.g., lactoferrin), reduced secretory activity (e.g., casein), and the alteration of the blood-milk barrier (e.g., minerals). Moreover, direct MIR prediction of fertility and health traits should be further considered. To conclude, MIR-predicted phenotypes have a role to play in the improvement of dairy cow fertility and health. However, further studies are warranted to (1) grasp underlying associations among MIR-predicted indicator and fitness traits, (2) estimate the genetic parameters, and (3) include these traits in broader breeding strategies.

Capitalizing on fine milk composition for breeding and management of dairy cows.

The challenge of managing and breeding dairy cows is permanently adapting to changing production circumstances under socio-economic constraints. If managing and breeding address different timeframes of action, both need relevant phenotypes that allow for precise monitoring of the status of the cows, and their health, behavior, and well-being as well as their environmental impact and the quality of their products (i.e., milk and subsequently dairy products). Milk composition has been identified as an important source of information because it could reflect, at least partially, all these elements. Major conventional milk components such as fat, protein, urea, and lactose contents are routinely predicted by mid-infrared (MIR) spectrometry and have been widely used for these purposes. But, milk composition is much more complex and other nonconventional milk components, potentially predicted by MIR, might be informative. Such new milk-based phenotypes should be considered given that they are cheap, rapidly obtained, usable on a large scale, robust, and reliable. In a first approach, new phenotypes can be predicted from MIR spectra using techniques based on classical prediction equations. This method was used successfully for many novel traits (e.g., fatty acids, lactoferrin, minerals, milk technological properties, citrate) that can be then useful for management and breeding purposes. An innovation was to consider the longitudinal nature of the relationship between the trait of interest and the MIR spectra (e.g., to predict methane from MIR). By avoiding intermediate steps, prediction errors can be minimized when traits of interest (e.g., methane, energy balance, ketosis) are predicted directly from MIR spectra. In a second approach, research is ongoing to detect and exploit patterns in an innovative manner, by comparing observed with expected MIR spectra directly (e.g., pregnancy). All of these traits can then be used to define best practices, adjust feeding and health management, improve animal welfare, improve milk quality, and mitigate environmental impact. Under the condition that MIR data are available on a large scale, phenotypes for these traits will allow genetic and genomic evaluations. Introduction of novel traits into the breeding objectives will need additional research to clarify socio-economic weights and genetic correlations with other traits of interest.

[The impact of screening sickle-cell carriers in the general population. A retrospective study in the Paris screening center]. / L'impact du dépistage du trait drépanocytaire en population. Une étude rétrospective au Centre d'information et de dépistage de la drépanocytose (Paris).

BACKGROUND: Since 2006 the CIDD, the Paris information and screening center for sickle-cell disease, provides free assistance for adults who may be at risk of having children with sickle-cell disease. Recently, an increasing number of parents of a silent-carrier newborn detected by systematic neonatal screening are attending the center. We present a retrospective study of the impact of such information and screening on people. METHODS: The study involved 81 silent-carrier men and women aged 18 to 45 years, interviewed using a telephone questionnaire (n=70) or during consultation (n=11) one to three years after screening. RESULTS: The study group represented 12% of individuals attending the center with the same characteristics. In general, the information delivered concerning sickle-cell disease and silent-carriers was well understood although concerns about personal and family history and the correctness of prior knowledge revealed a lack of information input from the environment (media, schools, health professionals). Poorly assimilated information involved three subjects: the difference between trait and disease; the difference between type of hemoglobin and blood group; and Mendelian transmission. The screening result was not a cause of separation among couples and was often passed on to family or friends. Disparities in adherence to prenatal diagnosis and termination of pregnancy were mainly related to different representations of disease severity. CONCLUSION: Joint screening of newborns and their parents is a good measure for adults, who are satisfied with being informed despite the psychological difficulties involved. However the implication for children detected remains a relevant issue because of the persistent perception of the trait as a pseudo-disease and the risk of reification of a biological difference between relatives.

A hyperparasite affects the population dynamics of a wild plant pathogen.

Assessing the impact of natural enemies of plant and animal pathogens on their host's population dynamics is needed to determine the role of hyperparasites in affecting disease dynamics, and their potential for use in efficient control strategies of pathogens. Here, we focus on the long-term study describing metapopulation dynamics of an obligate pathogen, the powdery mildew (Podosphaera plantaginis) naturally infecting its wild host plant (Plantago lanceolata) in the fragmented landscape of the Åland archipelago (southwest Finland). Regionally, the pathogen persists through a balance of extinctions and colonizations, yet factors affecting extinction rates remain poorly understood. Mycoparasites of the genus Ampelomyces appear as good candidates for testing the role of a hyperparasite, i.e. a parasite of other parasites, in the regulation of their fungal hosts' population dynamics. For this purpose, we first designed a quantitative PCR assay for detection of Ampelomyces spp. in field-collected samples. This newly developed molecular test was then applied to a large-scale sampling within the Åland archipelago, revealing that Ampelomyces is a widespread hyperparasite in this system, with high variability in prevalence among populations. We found that the hyperparasite was more common on leaves where multiple powdery mildew strains coexist, a pattern that may be attributed to differential exposure. Moreover, the prevalence of Ampelomyces at the plant level negatively affected the overwinter survival of its fungal host. We conclude that this hyperparasite may likely impact on its host population dynamics and argue for increased focus on the role of hyperparasites in disease dynamics.