Effects of heat stress on feed intake, milk yield, milk composition, and feed efficiency in dairy cows: A meta-analysis.

Heat stress compromises dairy production by decreasing feed intake and milk yield, and it may also alter milk composition and feed efficiency. However, little information is available for evaluating such effects across different levels of heat stress and cows enrolled in heat stress studies. The objectives of this study were to evaluate the effects of heat stress on dry matter intake (DMI), energy-corrected milk (ECM), milk composition, and feed efficiency (kg ECM/kg DMI) and to investigate the relationship between such effects and heat stress intervention and animal characteristics by using meta-analytical approaches. Data from 31 studies (34 trials) fulfilled the inclusion criteria and were used for analysis. Results showed that heat stress decreased DMI, ECM, and milk protein concentration, but did not alter milk fat concentration or feed efficiency. Meta-regression confirmed that such reductions in DMI and ECM were significantly associated with increasing temperature-humidity index (THI). Over the period of heat stress, for each unit increase in THI, DMI and ECM decreased by 4.13% and 3.25%, respectively, in mid-lactation cows. Regression models further revealed the existence of a strong interaction between THI and lactation stage, which partially explained the large heterogeneity in effect sizes of DMI and ECM. The results indicated a need for more research on the relationship between the effect of heat stress and animal characteristics. This study calls for the implementation of mitigation strategies in heat-stressed herds due to the substantial decrease in productivity.

Retrospective cohort study of management procedures associated with dairy herd-level eradication of Streptococcus agalactiae in the Danish surveillance program.

The aim of this observational retrospective cohort study was to identify management procedures that are associated with herd-level eradication of Streptococcus agalactiae in dairy herds. The objective was to compare herds that recovered from Strep. agalactiae with herds that remained infected with Strep. agalactiae on the basis of specific management procedures. Data from the Danish surveillance program for Strep. agalactiae, where all milk delivering dairy herds are tested yearly, were used to identify study herds. One hundred ninety-six herds that were classified in the program as infected with Strep. agalactiae, in both January 2013 and January 2014, were identified as study herds. These were followed until January 2017. One hundred forty-four herds remained infected every year until January 2017. Forty-six herds recovered from Strep. agalactiae after January 2014 (were tested negative continuously after January 2015, January 2016, or January 2017 and remained noninfected in the program from recovery until January 2017). Herd characteristics and management procedures were obtained through the Danish Cattle Database. Herd characteristics included herd size, yield, milking system, and bulk milk somatic cell count (SCC). Management procedures included the proportion of cows culled within 100 d after calving due to mastitis, the extent of diagnoses relative to the extent of mastitis treatments, the proportion of cows treated for mastitis during lactation, the proportion of cows treated for mastitis early in lactation, the proportion of cows treated at dry-off, and the median length of the dry period for cows receiving dry cow treatment. All variables were calculated on herd level. Multivariable logistic regression was used to analyze the association between herd infection status and management procedures. A higher proportion of culling due to mastitis within 100 d from calving was associated with a higher probability of herd-level recovery from Strep. agalactiae in herds with conventional milking system. For example, herds with conventional milking, a bulk milk SCC of 260,000 cells/mL, and 10% early culling due to mastitis had a recovery probability of 0.13, whereas similar herds with 20% early culling due to mastitis had a recovery probability of 0.15. A higher proportion of mastitis treatments within 250 d postcalving was associated with a higher probability of herd-level recovery for herds with a relatively high bulk milk SCC. For example, herds with conventional milking, a bulk milk SCC of 260,000 cells/mL, and 10% lactational mastitis treatments had a recovery probability of 0.12, whereas similar herds with 20% lactational mastitis treatments had a recovery probability of 0.15. Herds with a low bulk milk SCC (<220,000 cells/mL) combined with a low proportion of lactational treatments (<0.2) had a relatively high probability of herd-level recovery (>0.2). Additional variables, including the proportion of dry cow treatments, were not associated with herd-level recovery from Strep. agalactiae.

Effect of enhanced hygiene on transmission of Staphylococcus aureus, Streptococcus agalactiae, and Streptococcus dysgalactiae in dairy herds with automatic milking systems.

The objective of the study was to evaluate the effect of hygiene measures in automatic milking units on the transmission of 3 mastitis pathogens considered to be mainly or partly transmitted from cow to cow during milking events. Two studies were conducted as within-herd experimental trials in 2 Danish commercial dairy herds (A and B) with automatic milking systems. Interventions to enhance hygiene were implemented on the automatic milking units. The 2 studies evaluated separate interventions. In herd A, the hygiene interventions were manual wash with the Lely foam unit and adjustments on the brush-mediated teat cleaning procedure. In herd B, the hygiene intervention included automatic disinfection spray on the upper surface of the brush motor and daily change of brushes. Composite milk samples were collected longitudinally at 3- or 4-wk intervals from all lactating cows. Additional milk samples were taken from cows entering or leaving the study groups. Milk samples were analyzed with quantitative PCR. A hidden Markov model implemented within a Bayesian framework was used to estimate the transmission probability. For analysis, 701 samples from 156 cows were used for herd A, and 1,349 samples from 390 cows were used for herd B. In the intervention group in herd B, transmission of Streptococcus agalactiae was reduced to 19% (95% posterior credibility interval: 0.00-64%) of the transmission in the control group, whereas transmission of Streptococcus dysgalactiae was reduced to 17% (95% posterior credibility interval: 0.00-85%) of transmission in the control group. This suggests that automatic spray on the upper surface of the brush motor with disinfectant along with daily change of brushes collectively reduced transmission of Strep. agalactiae and Strep. dysgalactiae. Results on Staphylococcus aureus in herd B and results on manual foam cleaning and brush-mediated teat cleaning adjustments in herd A were inconclusive.

Genetic consequences of terminal crossbreeding, genomic test, sexed semen, and beef semen in dairy herds.

The development of breeding tools, such as genomic selection and sexed semen, has progressed rapidly in dairy cattle breeding during the past decades. In combination with beef semen, these tools are adopted increasingly at herd level. Dairy crossbreeding is emerging, but the economic and genetic consequences of combining it with the other breeding tools are relatively unknown. We investigated 5 different sexed semen schemes where 0, 50, and 90% of the heifers; 50% of the heifers + 25% of the first-parity cows; and 90% of the heifers + 45% of the first-parity cows were bred to sexed semen. The 5 schemes were combined in scenarios managing pure-breeding or terminal crossbreeding, including genomic testing of all newborn heifers or no testing, and keeping Swedish Red or Swedish Holstein as an initial breed. Thus, 40 scenarios were simulated, combining 2 stochastic simulation models: SimHerd Crossbred (operational returns) and ADAM (genetic returns). The sum of operational and genetic returns equaled the total economic return. Beef semen was used in all scenarios to limit the surplus of replacement heifers. Terminal crossbreeding implied having a nucleus of purebred females, where some were inseminated with semen of the opposite breed. The F1 crossbred females were inseminated with beef semen. The reproductive performance played a role in improving the benefit of any of the tools. The most considerable total economic returns were achieved when all 4 breeding tools were combined. For Swedish Holstein, the highest total economic return compared with a pure-breeding scenario, without sexed semen and genomic test, was achieved when 90% sexed semen was used in heifers and 45% sexed semen was used for first-parity cows combined with genomic test and crossbreeding (+€58, 33% crossbreds in the herd). The highest total economic return for Swedish Red compared with a pure-breeding scenario, without sexed semen and genomic test, was achieved when 90% sexed semen was used in heifers combined with genomic test and crossbreeding (+€94, 46% crossbreds in the herd). Terminal crossbreeding resulted in lower genetic returns across the herd compared with the corresponding pure-breeding scenarios but was compensated by a higher operational return.

Thyroid hormone treatment in the management of treatment-resistant unipolar depression: a systematic review and meta-analysis.

BACKGROUND: Treatment with thyroid hormones is occasionally used in the management of treatment-resistant depression. However, the evidence supporting this treatment is not fully established. The aim of this study was to systematically review the literature on the effect of adjunctive thyroid hormone in the management of treatment-resistant unipolar depression and to provide a pooled estimate of its efficacy. METHODS: The study is registered with PROSPERO (reg. no. CRD42018108088) and followed the PRISMA guidelines. Searches were carried out on June 24, 2019, in PubMed, EMBASE, and PsycINFO. Each record was screened independently by at least two reviewers. In instances of discrepancies, consensus was reached upon discussion. Pooled efficacy estimates were calculated based on response rates (decrease of ≥50% on the primary outcome measure) using random effect statistics. RESULTS: The search yielded 1355 records. Based on the screening of these records, we identified 10 studies that met the inclusion criteria (total number of patients = 663). The comparison of response to thyroid hormones vs. placebo resulted in an odds ratio of 1.56 (95% CI: 0.50-4.84). Similarly, the comparison of response to thyroid hormones vs. lithium resulted in an odds ratio of 1.91 (95% CI: 0.85-4.26). Thus, adjunctive therapy with thyroid hormones was not superior to placebo or lithium in the management of treatment-resistant unipolar depression. CONCLUSION: According to this review and meta-analysis, there is not sufficient evidence to support the use of adjunctive thyroid hormones for treatment-resistant unipolar depression.

Economic consequences of dairy crossbreeding in conventional and organic herds in Sweden.

This study simulated the consequences of crossbreeding between Swedish Holstein and Swedish Red on herd dynamics and herd profitability under Swedish conditions. Two base herds were simulated using a stochastic herd simulation model, SimHerd Crossbred. The herds reflected average Swedish conventional and organic herds having purebred Swedish Holstein. For each base herd, 3 breeding strategies were simulated: pure-breeding, 2-breed terminal crossbreeding, and 2-breed rotational crossbreeding. The terminal crossbreeding strategy implied having a nucleus of Swedish Holstein and a proportion of F1 Swedish Red × Swedish Holstein crossbred cows within the same herd. The crossbreds in this herd did not produce replacement heifers but exclusively beef × dairy cross calves. Beef semen was also used in the pure-breeding (10-20% in cows) and the rotational crossbreeding (40% in cows) strategies to retain a limited surplus of replacement heifers. To ensure an adequate number of crossbreds in the terminal crossbreeding strategy, X-sorted sexed semen was used for insemination in all the purebred heifers. The outcome was 67% purebred and 31% F1 crossbreds in the herd. In addition, 31% heterosis was expressed compared with 67% heterosis expressed using a 2-breed rotational crossbreeding strategy. Compared with the pure-breeding strategy, crossbreeding increased the annual contribution margin per cow by €20 to €59, with the rotational crossbreeding strategy creating the largest profitability. The increased profitability was mainly due to improved functional traits, especially fertility. For the conventional production system, the replacement rate was 39.3% in the pure-breeding strategy and decreased to 35.8 and 30.1% in the terminal and rotational crossbreeding strategy, respectively. Similar changes happened in the organic production system. Additionally, the crossbreeding strategies earned €22 to €42 more annually per cow from selling live calves for slaughter due to the extended use of beef semen. Milk production was similar between pure-breeding and terminal crossbreeding, and only decreased 1 to 2% in rotational crossbreeding. These results show that crossbreeding between Swedish Holstein and Swedish Red can be profitable in both conventional and organic Swedish herds using the strategies we have simulated. However, some aspects remain to be investigated, such as the economically optimal breeding strategy, genetic improvement, and transition strategies.

Only few benefits from propylene glycol drench in early lactation for cows identified as physiologically imbalanced based on milk spectra analyses.

The main objective of this study was to test the efficiency of a management system combining metabolic clustering of cows based on Fourier-transform mid-infrared (FT-MIR) spectra of milk and targeted treatment of metabolically imbalanced cows with propylene glycol drench. We hypothesized that cows identified in a metabolically imbalanced status during early lactation were associated with subsequent impaired health, reproduction, and production, and that treatment with propylene glycol treatment would improve health, reproduction, and production relatively more in these cows than in control cows. We completed a prospective, randomized controlled trial with 356 early-lactation cows in 2 private dairy herds in Denmark from December 2017 to April 2018. Milk samples of cows were collected before treatment, from 4 to 9 d in milk, and after treatment, from 22 to 27 d in milk. Milk samples were analyzed using FT-MIR spectroscopy. We also measured 4 milk metabolites (ß-hydroxybutyrate, isocitrate, malate, and glutamate) and fat and protein contents. Based on FT-MIR spectra and cluster analyses, cows were clustered into groups of metabolically imbalanced and healthy cows. Within each group, cows were allocated randomly to treatment with propylene glycol (500 mL for 5 d) or no treatment. We analyzed the effect of the treatment on cow-level variables: metabolic cluster, milk metabolites, fat and protein contents, and fat-to-protein ratio at a milk sampling after the treatment. Furthermore, we analyzed daily milk yield, calving to first service interval, and disease occurrence. Results showed only a few effects of propylene glycol treatment and few interactions between treatment and metabolic clusters. We found no significant main effects of propylene glycol treatment in any of these analyses. A negative effect of the imbalanced metabolic cluster was found for the outcome of calving to first service interval for multiparous cows. In conclusion, we found a longer calving to first service interval in metabolically imbalanced cows, but we were not able to demonstrate overall benefits from the applied detection of cows in imbalanced metabolic status in early lactation and follow-up by treatment with propylene glycol.

Face and predictive validity of the ClockΔ19 mouse as an animal model for bipolar disorder: a systematic review.

Mice carrying the circadian locomotor output cycles Kaput delta 19 N-ethyl-N-nitrosoure (ENU) mutation (ClockΔ19) are used as an animal model for bipolar disorder (BD). We aimed to systematically review the face validity (phenotypical and pathophysiological resemblance with BD) and predictive validity (responsiveness to treatments used in BD) of this model in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. We carried out a systematic search of the databases PubMed and Embase, combining search terms covering BD and ClockΔ19. The 22 studies included in the review (from a total of 1281 identified records) show that the behavioral phenotype of the ClockΔ19 mouse is characterized by hyperactivity, decreased anxiety-like behavior, decreased depression-like behavior and increased preference for rewarding stimuli. This is highly consistent with mania in humans. Moreover, the ClockΔ19 mouse exhibits rapid mood cycling (a manic-like phenotype during the day followed by euthymia at night), which is consistent with BD. Chronic administration of lithium, a drug with well established mood-stabilizing effect in humans with BD, reverses the majority of the bipolar-like traits and most of the neurobiological abnormalities observed in the ClockΔ19 mouse. In conclusion, the ClockΔ19 mouse has substantial face validity as an animal model for BD. The predictive validity of the ClockΔ19 mouse has primarily been investigated via studies using lithium challenge. Therefore, further studies are needed to determine how the ClockΔ19 mouse responds to other mood-stabilizing treatments of BD such as valproate, lamotrigine, carbamazepine, oxcarbazepine, antipsychotics, electroconvulsive therapy and various light interventions.

In utero exposure to selective serotonin reuptake inhibitors and development of mental disorders: a systematic review and meta-analysis.

OBJECTIVE: Several studies have investigated whether in utero exposure to selective serotonin reuptake inhibitors (SSRIs) is associated with increased risk of developing mental or behavioural disorders. The aim of this study was to perform a systematic review and meta-analysis based on this literature. METHODS: A systematic search of eligible literature in PubMed, EMBASE, and PsycINFO and subsequent meta-analysis was conducted in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. RESULTS: A total of 20 studies were included in the review, and results from 18 of these were meta-analyzed. We found a statistically significant positive association between in utero exposure to SSRIs and mental or behavioural disorders such as autism spectrum disorder (hazard ratio (HR) = 1.27; 95% confidence interval (CI) = 1.10-1.47), attention-deficit/hyperactivity disorder (HR = 1.33; 95% CI = 1.06-1.66) and mental retardation (HR = 1.41; 95% CI = 1.03-1.91). Confounding by indication was identified in five of seven studies investigating this aspect. CONCLUSION: Exposure to SSRIs in utero is associated with increased risk of developing mental or behavioural disorders. However, these associations do not necessarily reflect a causal relationship since the results included in this meta-analysis are likely affected by residual confounding by indication, which is likely to account for some (or all) of the positive association.

Predicting mechanical restraint of psychiatric inpatients by applying machine learning on electronic health data.

OBJECTIVE: Mechanical restraint (MR) is used to prevent patients from harming themselves or others during inpatient treatment. The objective of this study was to investigate whether incident MR occurring in the first 3 days following admission could be predicted based on analysis of electronic health data available after the first hour of admission. METHODS: The dataset consisted of clinical notes from electronic health records from the Central Denmark Region and data from the Danish Health Registers from patients admitted to a psychiatric department in the period from 2011 to 2015. Supervised machine learning algorithms were trained on a randomly selected subset of the data and validated using an independent test dataset. RESULTS: A total of 5050 patients with 8869 admissions were included in the study. One hundred patients were mechanically restrained in the period between one hour and 3 days after the admission. A Random Forest algorithm predicted MR with an area under the curve of 0.87 (95% CI 0.79-0.93). At 94% specificity, the sensitivity was 56%. Among the ten strongest predictors, nine were derived from the clinical notes. CONCLUSIONS: These findings open for the development of an early warning system that may guide interventions to reduce the use of MR.

Patterns and predictors of conversion to bipolar disorder in 91 587 individuals diagnosed with unipolar depression.

OBJECTIVE: Conversion from unipolar depression (UD) to bipolar disorder (BD) is a clinically important event that should lead to treatment modifications. Unfortunately, recognition of this transition is often delayed. Therefore, the objective of this study was to identify predictors of diagnostic conversion from UD to BD. METHOD: Historical prospective cohort study based on 91 587 individuals diagnosed with UD in Danish hospital psychiatry between 1995 and 2016. The association between a series of potential predictors and the conversion from UD to BD during follow-up (702 710 person-years) was estimated by means of Cox regression with death as competing risk. RESULTS: During follow-up, 3910 individuals with UD developed BD. The cumulative incidence of conversion was slightly higher in females (8.7%, 95% CI: 8.2-9.3) compared to males (7.7%, 95% CI: 7.0-8.4). The strongest predictor of conversion from UD to BD was parental history of BD (adjusted hazard ratio (aHR) = 2.60, 95% CI: 2.20-3.07)). Other predictors included psychotic depression at the index UD episode (aHR = 1.73, 95% CI: 1.48-2.02), a prior/concomitant non-affective psychosis (aHR = 1.73, 95% CI: 1.51-1.99), and in-patient treatment at the index episode (aHR = 1.76, 95% CI: 1.63-1.91). CONCLUSION: Diagnostic conversion from UD to BD is predicted by severe depression requiring in-patient treatment, psychotic symptomatology, and parental history of BD.

The validity and sensitivity of PANSS-6 in treatment-resistant schizophrenia.

OBJECTIVE: To test the validity and sensitivity of the six-item version (PANSS-6) of the 30-item Positive and Negative Syndrome Scale (PANSS-30) in treatment-resistant schizophrenia (TRS). METHOD: Using data from the clozapine phase (2E) of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, we investigated the following: (i) The scalability of PANSS-6 and PANSS-30; (ii) The correlation between PANSS-6 and PANSS-30 total scores; (iii) Whether PANSS-6 could identify cross-sectional symptom remission; and (iv) The efficacy of clozapine, olanzapine, risperidone and quetiapine in TRS using the 'speed of change' on PANSS-6 and PANSS-30 (change in total score per week) as outcome measures. RESULTS: We found that (i) only PANSS-6 and not PANSS-30 was scalable; (ii) The correlation between PANSS-6 and PANSS-30 total scores was high (Spearman coefficient: 0.85), (iii) PANSS-6 accurately identified cross-sectional symptom remission as defined by the Andreasen et al. criteria; and (iv) The only antipsychotic that caused improvement (speed of change significantly lower than 0 during the first three months of treatment) was clozapine, both when using PANSS-6 (speed of change: -0.50 points/week; 95%CI: -0.84, -0.17) and PANSS-30 (speed of change: -1.41 points/week; 95%CI: -2.80, -0.02) as outcome measures. CONCLUSION: PANSS-6 validly measures severity, remission and antipsychotic efficacy in TRS.

A Systematic Review of the Clinimetric Properties of the 6-Item Version of the Hamilton Depression Rating Scale (HAM-D6).

BACKGROUND: In a study aimed at identifying the items carrying information regarding the global severity of depression, the 6-item Hamilton Depression Rating Scale (HAM-D6) was derived from the original 17-item version of the scale (HAM-D17). Since then, the HAM-D6 has been used in a wide range of clinical studies. We now provide a systematic review of the clinimetric properties of HAM-D6 in comparison with those of HAM-D17 and the Montgomery Asberg Depression Rating Scale (MADRS). METHODS: We conducted a systematic search of the literature in PubMed, PsycInfo, and EMBASE databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Studies reporting data on the clinimetric validity of the HAM-D6 and either the HAM-D17 or MADRS in non-psychotic unipolar or bipolar depression were included in the synthesis. RESULTS: The search identified 681 unique records, of which 51 articles met the inclusion criteria. According to the published literature, HAM-D6 has proven to be superior to both HAM-D17 and MADRS in terms of scalability (each item contains unique information regarding syndrome severity), transferability (scalability is constant over time and irrespective of sex, age, and depressive subtypes), and responsiveness (sensitivity to change in severity during treatment). CONCLUSIONS: According to the published literature, the clinimetric properties of HAM-D6 are superior to those of both the HAM-D17 and MADRS. Since the validity of HAM-D6 has been demonstrated in both research and clinical practice, using the scale more consistently would facilitate translation of results from one setting to the other.

The mortality rate of electroconvulsive therapy: a systematic review and pooled analysis.

OBJECTIVE: Electroconvulsive therapy (ECT) remains underutilized because of fears of cognitive and medical risks, including the risk of death. In this study, we aimed to assess the mortality rate of ECT by means of a systematic review and pooled analysis. METHOD: The study was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The ECT-related mortality rate was calculated as the total number of ECT-related deaths reported in the included studies divided by the total number of ECT treatments. RESULTS: Fifteen studies with data from 32 countries reporting on a total of 766 180 ECT treatments met the inclusion criteria. Sixteen cases of ECT-related death were reported in the included studies yielding an ECT-related mortality rate of 2.1 per 100 000 treatments (95% CI: 1.2-3.4). In the nine studies that were published after 2001 (covering 414 747 treatments), there was only one reported ECT-related death. CONCLUSION: The ECT-related mortality rate was estimated at 2.1 per 100 000 treatments. In comparison, a recent analysis of the mortality of general anesthesia in relation to surgical procedures reported a mortality rate of 3.4 per 100 000. Our findings document that death caused by ECT is an extremely rare event.

Economic opportunities for using sexed semen and semen of beef bulls in dairy herds.

Dairy farmers can increase the number of dairy heifer calves born in their herd by using sexed semen. They can reduce the number of both dairy bull and heifer calves by using beef semen. Long before sexed semen became commercially available, it was believed that it would provide opportunities for increasing genetic level in both herds and populations. In this study, we studied the potential for increasing the genetic level of a herd by using beef semen in combination with sexed semen. We tested the hypothesis that the potential of increasing the genetic level and the overall net return would depend on herd management. To test this hypothesis, we simulated 7 scenarios using beef semen and sexed semen in 5 herds at different management levels. We combined the results of 2 stochastic simulation models, SimHerd and ADAM. SimHerd simulated the effects of the scenarios and management levels on economic outcomes (i.e., operational return) and on technical outcomes such as the parity distribution of the dams of heifer calves, but it disregarded genetic progress. The ADAM model quantified genetic level by using the dams' parity distributions and the frequency of sexed and beef semen to estimate genetic return per year. We calculated the annual net return per slot as the sum of the operational return and the genetic return, divided by the total number of slots. Net return increased up to €18 per slot when using sexed semen in 75% genetically superior heifers and beef semen in 70% genetically inferior, multiparous cows. The assumed reliability of selection was 0.84. These findings were for a herd with overall high management for reproductive performance, longevity, and calf survival. The same breeding strategy reduced net return by €55 per slot when management levels were average. The main reason for the large reduction in net return was the heifer shortage that arose in this scenario. Our hypothesis that the potential for beef semen to increase genetic level would be herd-specific was supported. None of the scenarios were profitable under Danish circumstances when the value of the increased genetic level was not included. A comparable improvement in genetic level could be realized by selectively selling dairy heifer calves rather than using beef semen.

Revisiting the immunocytochemical detection of Neurogenin 3 expression in mouse and man.

During embryonic development, endocrine cells of the pancreas are specified from multipotent progenitors. The transcription factor Neurogenin 3 (NEUROG3) is critical for this development and it has been shown that all endocrine cells of the pancreas arise from endocrine progenitors expressing NEUROG3. A thorough understanding of the role of NEUROG3 during development, directed differentiation of pluripotent stem cells and in models of cellular reprogramming, will guide future efforts directed at finding novel sources of ß-cells for cell replacement therapies. In this article, we review the expression and function of NEUROG3 in both mouse and human and present the further characterization of a monoclonal antibody directed against NEUROG3. This antibody has been previously been used for detection of both mouse and human NEUROG3. However, our results suggest that the epitope recognized by this antibody is specific to mouse NEUROG3. Thus, we have also generated a monoclonal antibody specifically recognizing human NEUROG3 and present the characterization of this antibody here. Together, these antibodies will provide useful tools for future studies of NEUROG3 expression, and the data presented in this article suggest that recently described expression patterns of NEUROG3 in human foetal and adult pancreas should be re-examined.

PANSS-6: a brief rating scale for the measurement of severity in schizophrenia.

OBJECTIVE: The 30-item Positive and Negative Syndrome Scale (PANSS-30) is the most widely used rating scale in schizophrenia, but too long for clinical use. Shorter PANSS versions have been proposed, including the PANSS-14 and PANSS-8. However, none of these PANSS versions has been validated using the parametric Rasch rating scale model, which evaluates 'scalability'. Scalability means that each item in a rating scale provides unique information regarding syndrome severity and is a statistical prerequisite for using the total score as a measure of overall severity. METHOD: Based on data from two randomized placebo-controlled trials in schizophrenia, we tested the scalability of PANSS-30, PANSS-14 and PANSS-8 by means of the parametric Rasch rating scale model. Furthermore, we tested whether a scalable PANSS version could separate efficacy of haloperidol and sertindole from placebo. RESULTS: Neither PANSS-30, PANSS-14 nor PANSS-8 was scalable. However, PANSS-6, consisting of the items: P1-Delusions, P2-Conceptual disorganization, P3-Hallucinations, N1-Blunted Affect, N4-Social withdrawal, N6-Lack of spontaneity and flow of conversation, was scalable. Furthermore, PANSS-6 captured superior symptom reduction and higher remission rates during treatment with haloperidol and sertindole vs. placebo. CONCLUSION: PANSS-6 is a short schizophrenia severity rating scale that adequately separates antipsychotic efficacy from that of placebo.

Invited review: Carryover effects of early lactation feeding on total lactation performance in dairy cows.

In comparison with the intensive research on the direct effects of energy supply on dairy cow lactation performance, little attention has been paid to the effect of early lactation feeding on subsequent production. The present paper reviews 9 studies carried out with the aim of quantifying the immediate and subsequent responses in milk production and body weight to early lactation feeding. Most results showed that a more generous feeding in early lactation caused a positive carryover effect on subsequent production, whereas an inadequate level of feed in early lactation has been shown to reduce subsequent milk yield. The carryover periods ranged from 3 to 12 wk and the difference in milk yield between cows in the carryover periods ranged between 1.5 and 4.5kg of milk/cow per day. When calculated as a percentage of the immediate effect, the carryover effect ranged from 22 to 63%. In 2 of the 9 papers reviewed, the authors found no carryover effect, probably due to the long post-treatment periods in these studies. This is supported by the other studies in which the carryover effect was only significant in a limited period after end of treatment. The magnitude of the carryover effect seems to be determined by several factors including duration of the treatment and post-treatment feeding level. The most important factor though appears to be the magnitude of over- or underfeeding (i.e., a strong relationship between the treatment period feeding level and the subsequent response in production).

Use of inline measures of l-lactate dehydrogenase for classification of posttreatment mammary Staphylococcus aureus infection status in dairy cows.

An automated method for determining whether dairy cows with subclinical mammary infections recover after antibiotic treatment would be a useful tool in dairy production. For that purpose, inline l-lactate dehydrogenase (LDH) measurements was modeled using a dynamic linear model; the variance parameters were estimated using the expectation-maximization algorithm. The method used to classify cows as infected or uninfected was based on a multiprocess Kalman filter. Two learning data sets were created: infected and uninfected. The infected data set consisted of records from 48 cows with subclinical Staphylococcus aureus infection from 4 herds collected in 2010. The uninfected data set came from 35 uninfected cows collected during 2013 from 2 herds. Bacteriological culturing was used as gold standard. To test the model, we collected data from the 48 infected cows 50 d after antibiotic treatment. As a result of the treatment, this test data set consisted of 25 cows that still had a subclinical infection and 23 cows that were recovered. Model sensitivity was 36.0% and specificity was 82.6%. To a large extent, l-lactate dehydrogenase reflected the cow's immune response to the presence of pathogens in the udder. However, cows that were classified correctly before treatment had a better chance of correct classification after treatment. This indicated a variation between cows in immune response to subclinical mammary infection that may complicate the detection of subclinically infected cows and determination of recovery.

Brains striving for coherence: Long-term cumulative plot formation in the default mode network.

Many everyday activities, such as engaging in conversation or listening to a story, require us to sustain attention over a prolonged period of time while integrating and synthesizing complex episodic content into a coherent mental model. Humans are remarkably capable of navigating and keeping track of all the parallel social activities of everyday life even when confronted with interruptions or changes in the environment. However, the underlying cognitive and neurocognitive mechanisms of such long-term integration and profiling of information remain a challenge to neuroscience. While brain activity is generally traceable within the short time frame of working memory (milliseconds to seconds), these integrative processes last for minutes, hours or even days. Here we report two experiments on story comprehension. Experiment I establishes a cognitive dissociation between our comprehension of plot and incidental facts in narratives: when episodic material allows for long-term integration in a coherent plot, we recall fewer factual details. However, when plot formation is challenged, we pay more attention to incidental facts. Experiment II investigates the neural underpinnings of plot formation. Results suggest a central role for the brain's default mode network related to comprehension of coherent narratives while incoherent episodes rather activate the frontoparietal control network. Moreover, an analysis of cortical activity as a function of the cumulative integration of narrative material into a coherent story reveals to linear modulations of right hemisphere posterior temporal and parietal regions. Together these findings point to key neural mechanisms involved in the fundamental human capacity for cumulative plot formation.