Dairy goat doe-kid rearing systems: Farmers' motivations and a description of practices, benefits and drawbacks.

In French dairy goat systems, kids are generally separated from their mother does shortly after birth. The main drivers of this practice are related to health-especially the prevention of the Caprine Arthritis Encephalitis Virus (CAEV) transmission-and economics. However, the separation of young ruminants from their does is being increasingly questioned by society and has raised concerns about the satisfaction of their behavioral needs. Some farmers choose to leave their female kids with their does. The aims of this study were to understand their motivations for leaving kids with their does, to describe how kids are reared in this case and how farmers perceive different aspects of the impacts of this practice. Individual semi-structured interviews were carried out with 40 farmers who had implemented the kids-with-does practice for at least one year. Compared with the national database describing the French population of dairy goat farmers, the characteristics of the interviewed farmers differed from those of the general population. They were younger and had done longer studies. Their farms were smaller, mainly with rare breeds and milk was mainly processed on-farm under an organic certification system. They chose to implement this practice for different reasons: ethical considerations, improving integration of kids within the herd, saving time and increasing comfort at work or improving the kids' growth, welfare, and health. The doe-kid rearing contact practices varied greatly between farms, with some kids staying with their does from a period of 45 d to never being separated; furthermore, some kids remained with their does all day, while others remained together part of the day or for a limited time, and daily contact evolved over time. Overall, farmers were satisfied as the benefits quoted were coherent with their motivations to implement this rearing practice. Most have decided to continue the practice, though usually with changes. However, as 40% of them had only 3 years or less of experience of doe-kid rearing, some had not sufficient hindsight into long-term issues such as the transmission of CAEV. It is crucial to tackle challenges associated with this practice, i.e., potentially wild kids, health issues, and economic consequences stemming from a reduction in marketable milk.

Prognosis and molecular characteristics of IBD-associated colorectal cancer: Experience from a French tertiary-care center.

BACKGROUND: Little is known about the prognosis of colorectal cancer associated with inflammatory bowel disease (CRC-IBD) in a real-world cohort in France. METHODS: We conducted a retrospective observational study including all patients presenting CRC-IBD in a French tertiary center. RESULTS: Among 6510 patients, the rate of CRC was 0.8% with a median delay of 19.5 years after IBD diagnosis (median age 46 years, ulcerative colitis 59%, initially localized tumor 69%). There was a previous exposure to immunosuppressants (IS) in 57% and anti-TNF in 29% of the cases. A RAS mutation was observed in only 13% of metastatic patients. OS of the whole cohort was 45 months. OS and PFS of synchronous metastatic patients was 20.4 months and 8.5 months respectively. Among the patients with localized tumor those previously exposed to IS had a better PFS (39 months vs 23 months; p = 0.05) and OS (74 vs 44 months; p = 0.03). The IBD relapse rate was 4%. No unexpected chemotherapy side-effect was observed CONCLUSIONS: OS of CRC-IBD is poor in metastatic patients although IBD is not associated with under-exposure or increased toxicity to chemotherapy. Previous IS exposure may be associated with a better prognosis.

Prognosis associated with initial care of increased fasting glucose in early pregnancy: A retrospective study.

AIM: To evaluate whether the initial care of women with fasting plasma glucose (FPG) levels at 5.1-6.9mmol/L before 22 weeks of gestation (WG), termed 'early fasting hyperglycaemia', is associated with fewer adverse outcomes than no initial care. METHODS: A total of 523 women with early fasting hyperglycaemia were retrospectively selected in our department (2012-2016) and separated into two groups: (i) those who received immediate care (n=255); and (ii) those who did not (n=268), but had an oral glucose tolerance test (OGTT) at or after 22 WG, with subsequent standard care if hyperglycaemia (by WHO criteria) was present. The number of cases of large-for-gestational age (LGA) infants, shoulder dystocia and preeclampsia with initial care of early fasting hyperglycaemia were compared after propensity score modelling and accounting for covariates. RESULTS: Of the 268 women with no initial care, 134 had hyperglycaemia after 22 WG and then received care. Women who received initial care vs those who did not were more likely to be insulin-treated during pregnancy (58.0% vs 20.9%, respectively; P<0.00001), gained less gestational weight (8.6±5.4kg vs 10.8±6.1kg, respectively; P<0.00001), had a lower rate of preeclampsia [1.2% vs 2.6%, respectively; adjusted odds ratio (aOR): 0.247 (0.082-0.759), P=0.01], and similar rates of LGA infants (12.2% vs 11.9%, respectively) and shoulder dystocia (1.6% vs 1.5%, respectively). When initial FPG levels were ≥5.5mmol/L (prespecified group, n=137), there was a lower rate of LGA infants [6.7% vs 16.1%, respectively; aOR: 0.332 (0.122-0.898); P=0.03]. CONCLUSION: Treating women with early fasting hyperglycaemia, especially when FPG is ≥5.5mmol/L, may improve pregnancy outcomes, although this now needs to be confirmed by randomized clinical trials.

Impact of an Education Programme on IBD Patients' Skills: Results of a Randomised Controlled Multicentre Study [ECIPE].

BACKGROUND: Better patient knowledge on inflammatory bowel disease [IBD] could improve outcome and quality of life. The aim of this study was to assess if an education programme improves IBD patients' skills as regards their disease. METHODS: The GETAID group conducted a prospective multicentre randomised controlled study. IBD patients were included at diagnosis, or after a significant event in the disease course. Patients were randomised between 'educated' or control groups for 6 months. Education was performed by trained health care professionals. A psycho-pedagogic score [ECIPE] was evaluated by a 'blinded' physician at baseline and after 6 and 12 months [M6 and M12]. The primary endpoint was the increase of ECIPE score at M6 of more than 20%. RESULTS: A total of 263 patients were included in 19 centres (male:40%; median age:30.8; Crohn's disease [CD]:73%). Of these, 133 patients were randomised into the educated group and 130 into the control group. The median relative increase in ECIPE score at M6 was higher in the educated group as compared with the control group (16.7% [0-42.1%] vs 7% [0-18.8%], respectively, p = 0.0008). The primary endpoint was met in 46% vs 24% of the patients in the educated and control groups, respectively [p = 0.0003]. A total of 92 patients met the primary endpoint. In multivariate analysis, predictors of an increase of at least 20% of the ECIPE score were randomisation in the educated group (odds ratio [OR] = 2.59) and no previous surgery [OR = 1.92]. CONCLUSIONS: These findings support the set-up of education programmes in centres involved in the management of IBD patients.

Initially untreated fasting hyperglycaemia in early pregnancy: prognosis according to occurrence of gestational diabetes mellitus after 22 weeks' gestation: a case-control study.

AIMS: To evaluate the percentage of women with untreated fasting hyperglycaemia in early pregnancy who develop gestational diabetes mellitus after 22 weeks' gestation, the determinants of gestational diabetes development in such women and the prognosis of early fasting hyperglycaemia according to whether the women go on to develop gestational diabetes. METHODS: From a large cohort of women who delivered in our hospital between 2012 and 2016, we retrospectively selected all those who had untreated early fasting hyperglycaemia and separated them into a 'gestational diabetes' and a 'no-gestational diabetes' group according to oral glucose tolerance test results after 22 weeks' gestation. We compared the incidence of a predefined composite outcome (preeclampsia or large-for-gestational-age infant or shoulder dystocia or neonatal hypoglycaemia) in both groups. RESULTS: A total of 268 women (mean fasting plasma glucose 5.3 ± 0.3 mmol/l at a mean ± sd of 10.2 ± 4.2 weeks' gestation) were included. Gestational diabetes developed in 134 women and was independently associated with early fasting plasma glucose ≥ 5.5 mmol/l [odds ratio 3.16 (95% CI 1.57, 6.33)], age ≥ 30 years [odds ratio 2.78 (95% CI 1.46, 5.31)], preconception obesity [odds ratio 2.12 (95% CI 1.11, 4.02)], family history of diabetes [odds ratio 1.87 (95% CI 1.00, 3.50)] and current employment [odds ratio 0.46 (95% CI 0.26, 0.83)]. Despite treatment, gestational diabetes induced a significant increase in the composite outcome as compared to no gestational diabetes (odds ratio 2.16 [95% CI 1.08, 4.34]). The association disappeared after adjustment for risk factors. CONCLUSIONS: Only half of the women with early fasting hyperglycaemia and no specific care subsequently developed gestational diabetes, and these women had a poor prognosis despite gestational diabetes treatment. Poor prognosis was mostly attributable to risk factors. Our results suggest that only women with certain risk factors should be screened for early fasting hyperglycaemia.

Performance of a selective screening strategy for diagnosis of hyperglycaemia in pregnancy as defined by IADPSG/WHO criteria.

AIM: Our study evaluated the performance of a selective screening strategy for hyperglycaemia in pregnancy (HIP) based on the presence of risk factors (RFs; body mass index≥25kg/m2, age≥35years, family history of diabetes, personal history of HIP or macrosomic infant) to diagnose HIP and to predict HIP-related events. METHODS: Women with no known diabetes who had undergone complete universal screening (early, before 22weeks of gestation and, if normal, in the second part of pregnancy) at our department (2012-2016) were selected, resulting in four groups of women according to the presence of HIP and/or RFs, with a predefined composite endpoint (preeclampsia or large-for-gestational-age infant or shoulder dystocia). RESULTS: Included were 4518 women: 23.5% had HIP and 71.1% had at least one RF. The distribution among our four groups was: HIP-/RF- (n=1144); HIP-/RF+ (n=2313); HIP+/RF- (n=163); and HIP+/RF+ (n=898). HIP was more frequent when RFs were present rather than absent (33.1% vs 15.4%, respectively; P<0.001). Incidence of the composite endpoint differed significantly (P<0.0001) across groups [HIP-/RF- 6.3%; HIP-/RF+ 13.2%; HIP+/RF- 8.6%; and HIP+/RF+ 17.1% (HIP effect: P<0.05; RF effect: P<0.001; interaction HIP * RF: P=0.94)] and significantly increased with the number of RFs (no RF: 6.3%, 1 RF: 10.8%, 2 RFs: 14.7%, 3 RFs: 28.0%, 4-5 RFs: 25.0%; P<0.0001). CONCLUSION: RFs are predictive of HIP, although 15.4% of women with HIP have no RFs. Also, irrespective of HIP status, RFs are predictive of HIP-related events, suggesting that overweight/obesity, the only modifiable RFs, could be targets of interventions to improve pregnancy prognosis.

Enriched dairy fat matrix diet prevents early life lipopolysaccharide-induced spatial memory impairment at adulthood.

Polyunsaturated fatty acids (PUFAs) are essential fatty acids, which are critical for brain development and later life cognitive functions. The main brain PUFAs are docosahexaenoic acid (DHA) for the n-3 family and arachidonic acid (ARA) for the n-6 family, which are provided to the post-natal brain by breast milk or infant formula. Recently, the use of dairy lipids (DL) in replacement of vegetable lipids (VL) was revealed to potently promote the accretion of DHA in the developing brain. Brain DHA, in addition to be a key component of brain development, display potent anti-inflammatory activities, which protect the brain from adverse inflammatory events. In this work, we evaluated the protective effect of partial replacement of VL by DL, supplemented or not with DHA and ARA, on post-natal inflammation and its consequence on memory. Mice were fed with diets poor in vegetal n-3 PUFA (Def VL), balanced in vegetal n-3/n-6 PUFA (Bal VL), balanced in dairy lipids (Bal DL) or enriched in DHA and ARA (Supp VL; Supp DL) from the first day of gestation until adulthood. At post-natal day 14 (PND14), pups received a single administration of the endotoxin lipopolysaccharide (LPS) and brain cytokine expression, microglia phenotype and neurogenesis were measured. In a second set of experiments, memory and neurogenesis were measured at adulthood. Overall, our data showed that lipid quality of the diet modulates early life LPS effect on microglia phenotype, brain cytokine expression and neurogenesis at PND14 and memory at adulthood. In particular, Bal DL diet protects from the adverse effect of early life LPS exposure on PND14 neurogenesis and adult spatial memory.

The outcome of infliximab dose doubling in 157 patients with ulcerative colitis after loss of response to infliximab.

BACKGROUND: Optimising infliximab therapy is recommended in inflammatory bowel disease (IBD) patients who lose response to infliximab; however, there are no data on the outcome of ulcerative colitis (UC) patients after doubling the dose. AIM: To determine the efficacy and safety of infliximab dose doubling in UC patients with a loss of response to infliximab. METHODS: From January 2006 to May 2013, we retrospectively reviewed the outcome of the consecutive UC patients who were treated with infliximab dose doubling (10 mg/kg) for loss of response in four French academic centres. The clinical response and remission were assessed. A composite event-free survival analysis was performed using the log-rank test and the Cox model. RESULTS: One hundred and fifty-seven patients [84 males; median age 37. 6 (IQR 28.2-49.4) years] were included. The median follow-up after infliximab dose doubling was 1.8 (1.0-3.1) years. At weeks 8 and 24, 55% and 43% of the patients achieved a clinical response respectively. The probabilities of the event-free survival were 71%, 61% and 55% at 6 months, 1 year and 2 years respectively. In the multivariate analysis, the predictors of infliximab dose doubling failure were the absence of the introduction of an immunomodulator concomitantly to dose doubling, a partial Ulcerative Colitis Disease Activity Index >6, a C-reactive protein level >10 mg/L, a leucocyte count >8000/mm(3) and a haemoglobin level <12.5 g/dL. Adverse events were reported in 12 patients (8%). CONCLUSIONS: Infliximab dose doubling led to short- and long-term event-free survival in UC patients, who had a loss of response to infliximab, in greater than 50% of the cases. The benefits of such a strategy were significantly improved by adding a concomitant immunomodulator.

Serosurvey of Schmallenberg Virus Infection in the Highest Goat-Specialized Region of France.

The monitoring of both the spread and clinical impact of Schmallenberg virus (SBV) infection within its full host range is important for the control of the epidemic and potential new outbreaks. In France, a national surveillance plan based on voluntary notifications of congenital malformations in newborn ruminants revealed that goats were the less affected host species. However, seroprevalence studies only targeted sheep and cattle, preventing accurate estimations of the real impact of SBV infection in goats. Here, a serological survey was conducted in the highest goat-specialized region of France between June 2012 and January 2013. A total of 1490 goat sera from 50 herds were analysed by ELISA. The between-herd and within-herd prevalences were estimated at 62% and 13.1%, respectively. Seroprevalence was not uniformly distributed throughout the territory and markedly differed between intensive and extensive herds. The low within-herd seroprevalence demonstrates that a large fraction of the French goat population remains susceptible to SBV infection.

Low prevalence of colonoscopic surveillance of inflammatory bowel disease patients with longstanding extensive colitis: a clinical practice survey nested in the CESAME cohort.

BACKGROUND: Surveillance colonoscopy is recommended for inflammatory bowel disease (IBD) patients with longstanding extensive colitis (LEC). AIMS: To assess modalities and results of colonoscopic surveillance in a subset of CESAME cohort patients at high risk of colorectal cancer (CRC) and followed in university French hospitals. METHODS: Among 910 eligible patients with more than a 7-year history of extensive colitis at CESAME enrolment, 685 patients completed a questionnaire on surveillance colonoscopy and 102 were excluded because of prior proctocolectomy. Finally, 583 patients provided information spanning a median period of 41months (IQR 38-43) between cohort enrolment and the end of follow-up. Details of the colonoscopic procedures and histological findings were obtained for 440 colonoscopies in 270 patients. RESULTS: Only 54% (n=312) of the patients with LEC had at least one surveillance colonoscopy during the study period, with marked variations across the nine participating centres (27% to 70%, P≤0.0001). Surveillance rate was significantly lower in Crohn's colitis than in ulcerative colitis (UC) (48% vs. 69%, P≤0.0001). Independent predictors of colonoscopic surveillance were male gender, UC IBD subtype, longer disease duration, previous history of CRC and disease management in a centre with large IBD population. Random biopsies, targeted biopsies and chromoendoscopy were performed during respectively 71%, 27 and 30% of surveillance colonoscopies. Two cases of high-grade dysplasia were detected in patients undergoing colonoscopic surveillance. Two advanced-stage CRC were diagnosed in patients who did not have colonosocopic surveillance. CONCLUSIONS: Colonoscopic surveillance rate is low in IBD patients with longstanding extensive colitis.

[The safety of blood donors]. / La sécurité des donneurs.

For a long time, safety has been patient-centred and taken for granted. Indeed, it needed a dramatic accident and the study of post-donation information for the question to be looked into again. However, under various statutory, organizational aspects and the professionalization of the staffs, safety has always accompanied the donor throughout its course of donation. Self-sufficiency is, certainly, the first mission of the Établissement Français du Sang: while we have to supply patients with sufficient blood products complying with quality criteria, we must not however forget the essential respect for the safety of the donor.

Estimated prevalence of Mycobacterium avium subspecies paratuberculosis infection in herds of dairy goats in France.

A study of the prevalence of Mycobacterium avium subspecies paratuberculosis (MAP) infection in dairy goats was carried out in France, using a serological ELISA. One hundred and five herds were randomly selected in different regions, and all the goats aged six months or older (11,847 goats) were sampled. An estimation had previously been made of the accuracy of the ELISA, and the Rogan-Gladen estimator was used to convert apparent prevalence values into estimates of true prevalence values. Given that sensitivity and specificity at herd level are functions of sample size, and because the sizes of the herds varied considerably, the true prevalence of infection at herd level was estimated using a weighted average depending on the herd size stratum. At the level of the individual animal, the total true prevalence was estimated by applying a weighted average in accordance with the regional distribution of the animals in the target population. At herd level, apparent prevalence and estimated true prevalence were 55.2 and 62.9 per cent, respectively; at individual animal level they were 2.9 and 6.6 per cent, respectively. In herds that were seropositive for MAP, the average within-herd apparent prevalence was 5.9 per cent and the estimated average within-herd true prevalence was 11.1 per cent.

Attention and awareness in synchrony.

Interactions between functional areas are often considered to account for subtle aspects of cognitive functions, although direct experimental evidence is scarce. A recent study by Gross et al. relates the strength of synchrony between human parietal, frontal and occipital regions to the availability of attentional resources. These results support the current view that attention and awareness emerge from dynamic interactions in distributed networks.

Oscillatory synchrony between human extrastriate areas during visual short-term memory maintenance.

How do we keep an object in mind? Based on evidence from animal electrophysiology and human brain-imaging techniques, it is commonly held that short-term memory relies on sustained activity in a network distributed over sensory and prefrontal cortices. How does neural firing persist in such a distributed network in the absence of visual input? Hebb's influential but so far unproved proposal, developed more than 50 years ago, is that sustained activation in short-term memory networks is maintained by reverberating activity in neuronal loops. We hypothesized that synchronized oscillatory activity, proposed to provide a dynamic link between distributed areas, could not only coordinate activity in the network but also establish reentrant loops in the system to enable both sustained firing and temporal coincidence of inputs. We show in human intracranial recordings that limited regions of extrastriate visual areas, separated by several centimeters, become synchronized in an oscillatory mode during the rehearsal of an object in visual short-term memory. Synchrony occurs specifically in the beta range (15-25 Hz) and disappears in a control condition. These findings thus confirm experimentally the hypothesis of a functional role of synchronized oscillatory activity in the coordination of distributed neural activity in humans, and support Hebb's popular but unproved concept of short-term memory maintenance by reentrant activity within the activated network.

Cortical mapping of gamma oscillations in areas V1 and V4 of the macaque monkey.

To characterize the temporal and spatial parameters of gamma activity evoked by visual stimuli in areas V1 and V4 of the monkey cortex, we recorded the electrocorticogram (ECoG) with an implanted array of 28 and 31 subdural electrodes placed over the surface of the operculum in two anesthetized monkeys. This intermediate level of recordings should help to bridge the gap between multiunit and scalp recordings. Both averaged and single-trial responses to small flashed stimuli, for which we varied the retinotopic position, the luminance and the color, were analyzed in the time-frequency domain using a wavelet-based decomposition of the signal. Large gamma oscillations (40-55 Hz), not phase locked to stimulus onset, were observed during the whole stimulus presentation, whereas visual evoked potentials (VEPs) were present mainly at stimulus onset and offset. Cortical mapping showed that both activities were restricted in spatial extent and followed the retinotopic organization of area V1 on the operculum, thus strongly suggesting they were generated in the underlying cortex. Oscillatory burst detection in single trials showed that one to two bursts lasting from 100 ms to 500 ms occurred in the first 500 ms following stimulus onset, and that bursts occurring during the subsequent phases of the response had a smaller amplitude and duration. Finally, we showed that gamma activity was stronger with higher luminances and for red than for green, yellow, or white stimuli of same luminance. In one animal we recorded gamma activity over area V4. This was of lower magnitude than the activity recorded over V1 and was delayed by 40 ms with respect to the beginning of gamma activity in V1, in contrast with the VEPs that were delayed by 20 ms only. Both gamma oscillations and early VEP followed the retinotopic organization of V4 over the prelunate gyrus. The results show that gamma oscillations are dependent upon the same parameters as the VEPs (retinotopic position, luminance, and color). However, the differences in the time course of VEPs and gamma activity (transient vs. sustained) suggests that these two responses may reflect different cell populations, different networks, or different firing modes.

Oscillatory gamma activity in humans: a possible role for object representation.

The coherent representation of an object has been suggested to be established by the synchronization in the gamma range (20-100 Hz) of a distributed neural network. So-called '40-Hz' activity in humans could reflect such a mechanism. We have presented here experimental evidence supporting this hypothesis, both in the visual and auditory modalities. However, different types of gamma activity should be distinguished, mainly the evoked 40-Hz response and the induced gamma activities. Only induced gamma activities seem to be related to coherent object representations. In addition, their topography depends on sensory modality and task, which is in line with the idea that they reflect the oscillatory synchronization of task-dependent networks. They can also be functionally and topographically distinguished from the classical evoked potentials and from the alpha rhythm. It was also proposed that the functional role of gamma oscillations is not restricted to object representation established through bottom-up mechanisms of feature binding, but also extends to the cases of internally driven representations and to the maintenance of information in memory.

Variability and immunogenicity of caprine arthritis-encephalitis virus surface glycoprotein.

The complete surface glycoprotein (SU) nucleotide sequences of three French isolates of caprine arthritis-encephalitis virus (CAEV) were determined and compared with those of previously described isolates: three American isolates and one French isolate. Phylogenetic analyses revealed the existence of four distinct and roughly equidistant evolutionary CAEV subtypes. Four conserved and five variable domains were identified in the SU. The fine specificities of antibodies produced against these domains during natural infection were examined using a pepscan analysis. Nine immunogenic segments were delineated throughout the conserved and variable domains of SU, two of them corresponding to conserved immunodominant epitopes. Antigenic determinants which may be involved in the immunopathogenic process induced by CAEV were identified. These results also provide sensitive and specific antigen peptides for the serological detection and differentiation of CAEV and visna/maedi virus infections.