Modifiable Risk Factors for Accelerated Decline in Processing Speed: Results from Three Dutch Population Cohorts.

BACKGROUND: Several lifestyle, cardiovascular and psychosocial factors are associated with risk of cognitive decline and dementia. We studied the independent associations of a broad set of modifiable risk factors with decline in processing speed in three large population-based cohorts with up to 23 years of follow-up. METHODS: We used data of 9,666 participants from the Doetinchem Cohort Study, the Longitudinal Aging Study Amsterdam, and the Maastricht Aging Study. Decline in processing speed was measured with the letter digit substitution task or the alphabet coding task and modeled using quadratic latent growth curves. Associations of modifiable risk factors with level and rate of decline in processing speed were investigated by estimating associations with level of processing speed at different centering ages. RESULTS: Latent growth curves showed that decline in processing speed accelerated with age. Smoking, not drinking alcohol and depressive symptoms were associated with a lower level of processing speed in all cohorts. In two of the cohorts, more physical activity, drinking more than two glasses of alcohol per day, higher BMI and diabetes were associated with a lower level of processing speed. Depressive symptoms and diabetes were also associated with faster decline in processing speed. CONCLUSION: Several modifiable risk factors are associated with the level of processing speed in older age, while few are also related to the rate of decline.

Effect of prepartum dietary energy sources on productive and reproductive performance in Nili Ravi buffaloes.

Feeding of dietary energy sources has been extensively studied in dairy cows but not well described in dairy buffaloes. The objective of this study was to evaluate the effect of prepartum dietary energy sources on productive and reproductive performance in Nili Ravi buffaloes (n = 21). The buffaloes were offered isocaloric (1.55 Mcal/kg DM NEL (net energy for lactation)) glucogenic (GD), lipogenic (LD), and mixed diet (MD) during 63 days prepartum and maintained (1.27 Mcal/kg DM NEL) at lactation diet (LCD) during 14 weeks postpartum. Effects of dietary energy sources and week on animals were analyzed with the mixed model. The DMI, BCS, and body weights remained similar during the pre- and postpartum periods. The prepartum diets did not affect birth weight, blood metabolites, milk yield, and composition. The GD tended to early uterine involution, more follicle numbers, and early follicle formation. The prepartum feeding of dietary energy source had a similar effect on first estrus expression, days open, conception rate, pregnancy rate, and calving interval. So, it could be concluded that prepartum feeding of an isocaloric dietary energy source had a similar effect on the performance of buffaloes.

Feeding behavior in relation to ovarian cyclicity in cows with no or a short dry period.

The objective of this study was to investigate relations between feeding behavior (FB) variables focusing on intake of the basal ration during 3 wk prepartum until 3 wk postpartum, and postpartum onset of luteal activity (OLA) in dairy cows subjected to no (0-d) or a short (30-d) dry period (DP). Feeding behavior of the basal ration intake (concentrate intake excluded) was continuously recorded by computerized feeders for 123 dairy cows and analyzed from 3 wk prepartum to 3 wk postpartum. Cows were subjected to a DP length: 0-d DP (n = 81), or 30-d DP (n = 42). Milk progesterone concentration was determined 3 times per week until 100 DIM to determine OLA, which was classified as early OLA (<21 DIM) and late OLA (≥21 DIM). Relations between FB and OLA class were analyzed using mixed models. During 3 wk prepartum, FB differed between parity class (parity 2 or ≥3 after calving). Cows with a 30-d DP prepartum, regardless of their OLA class, had more visits per meal, higher meal duration, total meal time, total daily feeding time, and lower feed intake and feeding rate compared with cows with 0-d DP. During the first 2 d postpartum, cows with OLA <21 had more visits per day and visits per meal compared with cows with OLA ≥21. During the first 3 wk postpartum, cows within the 30-d DP group with OLA <21 had greater meal size, feed intake, and feeding rate compared with cows with OLA ≥21 of this group. Cows within the 0-d DP group with OLA <21 had higher meal duration, total daily meal time, total daily feeding time, and meal size, but a lower feeding rate compared with cows with OLA ≥21 of this group. Concluding from the current study, cows with OLA <21 had a postpartum FB that reflected a cow with faster recovery from parturition and better adaptation to onset of lactation compared with OLA ≥21. No or a short DP affected prepartum FB, suggesting that prepartum management affects FB. This study provides evidence of different FB between cows with different timing of resumption of ovarian cyclicity.

[Socio-economic position: more than a background characteristic in psychiatry]. / Sociaal-economische positie: méér dan een achtergrondkenmerk in de psychiatrie.

Background Mental illness is more common and has a less favorable course in people with a low socioeconomic position (SEP). Aim To clarify the concept of SEP and what mechanisms underlie socioeconomic differences in mental illness. Method Review of theoretical and empirical scientific research. Results For determining socioeconomic differences in mental illness, it matters whether one looks at educational level, occupational level, or income. Mechanisms of social causation and social selection play a role. Among other mechanisms, SEP contributes to mental illness through exposure to stressors, unfavorable living conditions, unhealthy behaviors, and social exclusion. Conversely, mental health problems can negatively influence SEP. Conclusion Researchers and practitioners should be aware that SEP is more than a background characteristic of a patient or a statistical control variable; over the life course there is a complex interaction between SEP and both the etiology and course of mental illness.

Revenues and costs of dairy cows with different voluntary waiting periods based on data of a randomized control trial.

Based on modeling studies, a 1-yr calving interval for dairy cows is generally considered optimal from an economic point of view. Recently some dairy farmers are deliberately extending the voluntary waiting period for insemination (VWP) to extend the calving interval. Reasons to extend the VWP are to reduce the frequency of transitions such as dry-off and calving to improve health, to reduce labor associated with these transitions, and to reduce the number of surplus calves. This study aimed to evaluate yearly revenues, yearly costs, and yearly net partial cash flow (NPCF) for individual cows with a VWP of 50, 125, or 200 d based on data from a randomized control trial. The NPCF included revenues and costs for milk yield, calves born, inseminations, concentrate supply, partial mixed ration (PMR) supply, veterinary treatments, discarded milk due to veterinary treatments, culling, and labor (for milking, calving cows, inseminations, and veterinary treatments). Holstein-Friesian dairy cows (n = 153) within one herd were blocked for parity, calving season, and expected (primiparous cows) or previous (multiparous cows) 305-d milk yield. Cows were randomly assigned within the blocks to 1 of 3 VWP (VWP50, VWP125, or VWP200) in wk 6 after calving, and monitored from wk 6 after calving until wk 6 after the next calving or until culling. Revenues and costs were calculated per individual cow and expressed per cow per year. Revenues from milk and costs for PMR and concentrate contributed most to the yearly NPCF. Total yearly revenues were greater in VWP50 compared with VWP200 (€3,169 vs. €2,832), mainly because of €334 greater milk revenues. Total yearly costs were also greater in VWP50 compared with VWP200 (€1,964 vs. €1,729), mainly because of €102 greater concentrate costs. The VWP was not significantly associated with the NPCF per cow per year. A change in milk, feed, or calf price, or a change in labor costs for calving cows or for inseminations had a greater effect on the yearly NPCF of cows in VWP50 compared with cows in VWP200. To investigate variation in NPCF, cows were grouped for yearly NPCF and categorized into 3 economic classes (EC): EC1 (<€1,100/yr), EC2 (€1,100-€1,400/yr), and EC3 (>€1,400/yr). Cows in EC3 had greatest lactation production per day in the experiment (i.e., kg of milk, protein, fat, lactose), and lowest number of veterinary treatments during the experiment.

The impact of the COVID-19 pandemic and behavioral restrictions on electricity consumption and the daily demand curve in Turkey.

The rapid spread of COVID-19 has severely impacted many sectors, including the electricity sector. The reliability of the electricity sector is critical to the economy, health, and welfare of society; therefore, supply and demand need to be balanced in real-time, and the impact of unexpected factors should be analyzed. During the pandemic, behavioral restrictions such as lockdowns, closure of factories, schools, and shopping malls, and changing habits, such as shifted work and leisure hours at home, significantly affected the demand structure. In this research, the restrictions and their corresponding timing are classified and mapped with the Turkish electricity demand data to analyze the estimated impact of the restrictions on total demand and daily demand profile. A modulated Fourier Series Expansion evaluates deviations from normal conditions in the aggregate demand and the daily consumption profile. The aggregate demand shows a significant decrease in the early phase of the pandemic, during the period March-June 2020. The shape of the daily demand curve is analyzed to estimate how much demand shifted from daytime to night-time. A population-based restriction index is proposed to analyze the relationship between the strength and coverage of the restrictions and the total demand. The persistency of the changes in the daily demand curve in the post-contingency period is analyzed. These findings imply that new scheduling approaches for daily and weekly loads are required to avoid supply-demand mismatches in the future. The long-term policy implications for the energy transition and lessons learned from the COVID-19 pandemic experience are also presented.

Short communication: Variance and autocorrelation of deviations in daily milk yield are related with clinical mastitis in dairy cows.

Daily milk production, and fluctuations therein, can provide information on health and resilience of dairy cows. We studied variance and autocorrelation of deviations in daily milk yield in relation to the occurrence of clinical mastitis (no, early or later in lactation). Individual lactation curves were fitted to 305-d lactations of 414 dairy cows using quantile regression. Log-transformed variance (lnVar) and autocorrelation of the quantile residuals of daily milk yield (predicted - observed) were evaluated for intervals until 30 and until 305 days in milk (DIM). Cows were classified as having no mastitis (n = 249), early mastitis that first occurred before 30 DIM (n = 29); or later mastitis (n = 136). Subsequently, linear models were used to assess effects of mastitis and parity class (primiparous or multiparous) on lnVar and autocorrelations; and logistic regression analyses were performed to predict mastitis from lnVar or autocorrelation and parity. From 10 to 30 DIM, lnVar was greater for cows with early mastitis than for cows with no or late mastitis, and autocorrelation tended to be lower for cows with early mastitis than for cows with no mastitis. The lnVar and autocorrelation from 10 to 30 DIM were not predictive of late mastitis. From 10 to 305 DIM, lnVar was greater and autocorrelation was lower for both cows with early and late mastitis than for cows with no mastitis; and both were predictive of having mastitis in the 305-d lactation. Primiparous cows had lower lnVar than multiparous cows. In cows without mastitis, autocorrelation values were positively correlated with lnVar. Results confirm that increased lnVar is associated with clinical mastitis.

Effects of extended voluntary waiting period from calving until first insemination on body condition, milk yield, and lactation persistency.

A 1-yr calving interval (CInt) is usually associated with maximized milk output, due to the calving-related peak in milk yield. Extending CInt could benefit cow health and production efficiency due to fewer transition periods per unit of time. Extending CInt can affect lactation performance by fewer days dry per year, delayed pregnancy effect on milk yield, and greater milk solid yield in late lactation. This study first investigated the effects of 3 different voluntary waiting periods (VWP) from calving until first insemination on body weight, body condition, milk yield, and lactation persistency. Second, individual cow characteristics in early lactation were identified that contributed to milk yield and persistency of cows with different VWP. Holstein-Friesian dairy cows (n = 154) within 1 herd were blocked for parity, calving season, and expected milk yield. Cows were randomly assigned within the blocks to 1 of 3 VWP (50, 125, or 200 d: VWP50, VWP125, or VWP200, respectively) and monitored through 1 complete lactation and the first 6 wk of the subsequent lactation, or until culling. Minimum and mean CInt (384 vs. 452 vs. 501 d for VWP50 vs. VWP125 vs. VWP200) increased with increasing VWP, but maximum CInt was equal for the 3 VWP. Fat- and protein-corrected milk yield (FPCM) was analyzed weekly. Milk yield and FPCM were also expressed per day of CInt, to compare yields of cows with different VWP. Persistency was determined between d 100 and d 200 of the lactation, as well as between d 100 and dry-off. Values are presented as least squares means ± standard error of the mean. During the first 44 wk of lactation, VWP did not affect FPCM yield in both primiparous and multiparous cows. The VWP did not affect milk yield per day of CInt. The VWP did not affect FPCM yield per day of calving interval for primiparous cows. Multiparous cows in VWP125 had FPCM yield per day of CInt similar to that of VWP50. Multiparous cows in VWP200 had lower FPCM yield per day of CInt compared with VWP50 (27.2 vs. 30.4 kg/d). During the last 6 wk before dry-off, cows in VWP125 had lower yield compared with cows in VWP50, which could benefit their udder health in the dry period and after calving. Persistency was better for cows in VWP200 compared with cows in VWP50 (-0.05 vs. -0.07 kg/d). Body weight was not different among VWP groups. Multiparous cows in VWP200 had a higher body condition score in the last 3 mo before dry-off and the first 6 wk of the next lactation, compared with multiparous cows in VWP125 and VWP50. The VWP could be extended from 50 d to 125 d without an effect on daily yield per day of calving interval. Extending VWP until 200 d for primiparous cows did not affect their daily milk yield, but multiparous cows with a 200-d VWP had a reduced milk yield per day of calving interval and an increased body condition in late lactation and the subsequent lactation, compared with multiparous cows with a 50-d VWP.

Fertility and milk production on commercial dairy farms with customized lactation lengths.

Drying-off, calving, and start of lactation are critical transition events for a dairy cow. As a consequence, most animal health issues occur during these periods. By extending the voluntary waiting period for first insemination after calving, calving interval (CInt) can be extended, with possible positive effects for fertility and health. Some cows might be better suited for an extended CInt than others, due to differences in milk yield level, lactation persistency, or health status, which would justify a customized CInt based on individual cow characteristics. This study aims to investigate 13 farms with customized CInt, with respect to calving to first service interval (CFSI), accomplished CInt, services per conception (SC), conception rate at first artificial insemination (CR1AI), peak yield, lactation persistency, 305-d yield, and effective lactation yield. In total, 4,858 complete lactations of Holstein Friesian cows between 2014 and 2019 from the 13 farms were grouped by parity (1 or 2+) and CFSI (CFSI class; CFSI-1 < 84; 84 ≤ CFSI-2 < 140; 140 ≤ CFSI-3 < 196; 196 ≤ CFSI-4 < 252, CFSI-5 ≥ 252 d) or CInt (CInt class; CInt-1 < 364; 364 ≤ CInt-2 < 420; 420 ≤ CInt-3 < 476; 476 ≤ CInt-4 < 532, CInt-5 ≥ 532 d). Cow inseminations, available for 11 out of 13 farms (3,597 complete lactations), were grouped by parity (1 and 2+) and CFSI class or CInt class. The fertility and milk production characteristics were analyzed with generalized and general linear mixed models. The CFSI class was not associated with SC, but extended CInt class was associated with increased SC (CInt-1-5; 1.11-3.70 SC). More than 50% of cows in the CFSI class <84 d ended up in longer than expected CInt (>364 d), showing that these cows were not able to conceive for the desired CInt. More than 50% of cows in CInt classes 3 and higher (CInt ≥ 420 d) had an earlier first insemination before successful insemination (CFSI class 1; <196 d), showing that these extended CInt classes consisted of both cows with an extended waiting period for first insemination and cows that failed to conceive at earlier insemination(s). On most farms, lactation persistency was greatest in CInt class 1 (<364 d), probably related to the low peak yield in this class. When this shortest CInt class was excluded, persistency increased with extended CInt classes on most farms. Although at the majority of farms 305-d yield was greater in CInt ≥ 532 d, effective lactation yield at most farms was greatest in CInt from 364 to 531 d, especially for multiparous cows. Based on the results of this study, a CInt between 364 and 531 days seems most optimal for milk production, when high-yielding cows were selected.

Evaluation of customized dry-period strategies in dairy cows.

Shortening or omitting the dry period to improve the energy balance in early lactation have the trade-offs of reduction in milk production and loss of opportunity for dry-cow therapy (DCT; i.e., intramammary antibiotic use at dry-off). Customized dry-period strategies (i.e., deciding upon DCT and dry-period length per cow) could mitigate negative effects of short or no dry periods on milk production and udder health and simultaneously retain benefits from improved energy balance and fertility. In this study, we evaluated 3 decision trees to customize dry-period strategies for individual cows. In the control tree (CT), all cows had a 60-d dry period, with DCT if somatic cell count (SCC) was >150,000 cells/mL before dry-off. In decision tree 1 (T1), parity 1 and parity >1 cows were assigned DCT if SCC was ≥150,000 cells/mL and SCC ≥50,000 cells/mL, respectively; whereas in decision tree 2 (T2), the threshold for DCT was SCC ≥200,000 cells/mL for all animals. In T1 and T2, cows with DCT were assigned a 60-d dry period, whereas cows without DCT were assigned a 30-d or 0-d dry period if their milk production remained >12 kg/d at 67 and 37 d before calving, respectively. Cows were monitored from 8 wk before to 14 wk after calving. Milk production and composition, SCC, body condition score, body weight, and occurrence of treatment for disease (related to calving and start of lactation) were compared between CT (n = 61 cows), T1 (n = 59 cows), and T2 (n = 63 cows). Effects of decision trees (CT, T1, T2) and of dry-period strategies (60-d dry with or without antibiotics, 30-d dry, or 0-d dry) on measured variables were analyzed separately with mixed models, effects on udder-health status with a logistic regression, and occurrence of treatment for diseases with a Pearson chi-squared test. In T1, 36% of cows qualified for 30-d and 2% for 0-d dry periods, whereas in T2 this was 51% and 30% for 30-d and 0-d dry periods, respectively. Compared with CT, cows in T1 and T2 on average produced more milk in the 8 wk before calving (0.2 vs. 3.9 vs. 7.1 kg/d in CT vs. T1 vs. T2), and less in the 14 wk after calving (40.0 vs. 37.0 vs. 35.2 kg/d in CT vs. T1 vs. T2). There was no difference in udder-health status in the transition period among decision trees. In the first 14 wk after calving, recovery of body weight was greater for T2 than CT and T1. Overall, 30-d and 0-d dry periods reduced milk revenues, but this might be financially compensated by improved cow health with customized dry-period strategies.

COVID-19 during pregnancy: non-reassuring fetal heart rate, placental pathology and coagulopathy.

We report a case of a pregnant woman with COVID-19 who developed coagulopathy in the absence of severe clinical symptoms. A polymerase chain reaction test of a vaginal swab was positive for SARS-CoV-2 RNA, suggesting a possibility of perinatal transmission. Cesarean delivery was performed because of a non-reassuring fetal heart rate; the placenta showed increased perivillous fibrin deposition and intervillositis. Moreover, placental infection with SARS-CoV-2 was demonstrated by placental immunostaining. The findings suggest a possible relationship between placental fibrin deposition and chronic and acute intervillositis, non-reassuring fetal heart rate and coagulopathy in pregnant women with COVID-19. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Validation of Geant4 for silicon microdosimetry in heavy ion therapy.

Microdosimetry is a particularly powerful method to estimate the relative biological effectiveness (RBE) of any mixed radiation field. This is particularly convenient for therapeutic heavy ion therapy (HIT) beams, referring to ions larger than protons, where the RBE of the beam can vary significantly along the Bragg curve. Additionally, due to the sharp dose gradients at the end of the Bragg peak (BP), or spread out BP, to make accurate measurements and estimations of the biological properties of a beam a high spatial resolution is required, less than a millimetre. This requirement makes silicon microdosimetry particularly attractive due to the thicknesses of the sensitive volumes commonly being ∼10 [Formula: see text]m or less. Monte Carlo (MC) codes are widely used to study the complex mixed HIT radiation field as well as to model the response of novel microdosimeter detectors when irradiated with HIT beams. Therefore it is essential to validate MC codes against experimental measurements. This work compares measurements performed with a silicon microdosimeter in mono-energetic [Formula: see text], [Formula: see text] and [Formula: see text] ion beams of therapeutic energies, against simulation results calculated with the Geant4 toolkit. Experimental and simulation results were compared in terms of microdosimetric spectra (dose lineal energy, [Formula: see text]), the dose mean lineal energy, y  D and the RBE10, as estimated by the microdosimetric kinetic model (MKM). Overall Geant4 showed reasonable agreement with experimental measurements. Before the distal edge of the BP, simulation and experiment agreed within ∼10% for y  D and ∼2% for RBE10. Downstream of the BP less agreement was observed between simulation and experiment, particularly for the [Formula: see text] and [Formula: see text] beams. Simulation results downstream of the BP had lower values of y  D and RBE10 compared to the experiment due to a higher contribution from lighter fragments compared to heavier fragments.

Review: Dry period length in dairy cows and consequences for metabolism and welfare and customised management strategies.

Shortening or omitting the dry period improves the energy balance and metabolic status of dairy cows in early lactation. Metabolic, behaviour and welfare effects throughout lactation, however, are unclear. The current paper reviews long-term metabolic and welfare consequences of short and no dry period, as well as feeding strategies and individual cow characteristics that could support in optimising management of cows with a short or no dry period. The paper will conclude with impacts of short and no dry periods at herd level and in practice. Energy balance after no or a short dry period is more positive during the complete subsequent lactation. After the initial improvement in early lactation, cows after no dry period tend to fatten and may have a too low lactation persistency to be continuously milked until the onset of the subsequent lactation. Reducing dietary energy level for cows with no dry period reduced fattening during the complete lactation but did not improve lactation persistency. Feeding a more lipogenic diet for cows with a short or no dry period did not affect the energy balance or lactation persistency during the complete lactation, although a lipogenic diet resulted in lower plasma insulin and IGF-1 concentration and greater plasma growth hormone concentration, compared with a glucogenic diet. Effects of dry period length on udder health are ambiguous, whereas short and no dry periods improved fertility in most studies. Omission of the dry period changed behaviour of cows both before and after calving, with a longer lying time and greater feed intake after calving, suggesting a better adaptation to a new lactation. Individual cow characteristics like parity, genotype, prepartum body condition score, and milk yield level determined the metabolic response of cows to a short or no dry period. In conclusion, short or no dry periods increase the energy balance in the complete lactation. Feeding strategies can be used to limit fattening of cows with no or short dry period, but the studied feeding strategies did not increase lactation persistency. Improved fertility and behavioural changes around calving suggest a better adaptation to a new lactation in case of no dry period. Customised dry period lengths for individual cows could improve metabolic status of cows at risk of a severe negative energy balance while minimising milk losses.

Relationship between metabolic status and behavior in dairy cows in week 4 of lactation.

Blood metabolite and hormone concentrations are indicative of metabolic status, but blood sampling and analysis is invasive and time-consuming. Monitoring behavior can be done automatically, and behaviors may also be used as indicators of metabolic status. The aim of this study was to analyze the relationships between metabolic status and feeding behavior, lying behavior, motion index and steps of dairy cows in week 4 postpartum. Behavioral data from 81 Holstein-Friesian cows were collected using computerized feeders and accelerometers, and blood samples were collected for analysis of free-fatty acid (FFA), ß-hydroxybutyrate (BHB), glucose, insulin, IGF-1 and growth hormone (GH) concentrations. First, cluster analysis was performed to categorize cows as having poor, average, good or very good metabolic status based on their plasma FFA, BHB, glucose, insulin, IGF-1 and GH concentration. Subsequently, the performance and behavior of cows in clusters with poor, average and good metabolic status were compared using GLM. Cows with a poor or average metabolic status tended to have greater fat-and-protein-corrected milk yield than cows with good metabolic status. Furthermore, cows with a poor metabolic status had a lower energy balance and dry matter intake (DMI) than cows with an average or good metabolic status and had a lower number of meals than cows with good metabolic status. Daily number of visits to the feeder and lying time tended to be positively related with metabolic status. Feeding rate (kg/min), daily meal time (min/day), number of lying bouts per day, steps and motion index were not related with metabolic status. In conclusion, better metabolic status in dairy cows in early lactation was associated with a greater DMI, increased feeding activity and a tendency to more time spent lying, compared with poor metabolic status. These results suggest that compromised metabolic status is reflected in altered cow's behavior in week 4 of lactation.

Production, partial cash flows and greenhouse gas emissions of simulated dairy herds with extended lactations.

The transition period is the most critical period in the lactation cycle of dairy cows. Extended lactations reduce the frequency of transition periods, the number of calves and the related labour for farmers. This study aimed to assess the impact of 2 and 4 months extended lactations on milk yield and net partial cash flow (NPCF) at herd level, and on greenhouse gas (GHG) emissions per unit of fat- and protein-corrected milk (FPCM), using a stochastic simulation model. The model simulated individual lactations for 100 herds of 100 cows with a baseline lactation length (BL), and for 100 herds with lactations extended by 2 or 4 months for all cows (All+2 and All+4), or for heifers only (H+2 and H+4). Baseline lactation length herds produced 887 t (SD: 13) milk/year. The NPCF, based on revenues for milk, surplus calves and culled cows, and costs for feed, artificial insemination, calving management and rearing of youngstock, was k€174 (SD: 4)/BL herd per year. Extended lactations reduced milk yield of the herd by 4.1% for All+2, 6.9% for All+4, 1.1% for H+2 and 2.2% for H+4, and reduced the NPCF per herd per year by k€7 for All+2, k€12 for All+4, k€2 for H+2 and k€4 for H+4 compared with BL herds. Extended lactations increased GHG emissions in CO2-equivalents per t FPCM by 1.0% for All+2, by 1.7% for All+4, by 0.2% for H+2 and by 0.4% for H+4, but this could be compensated by an increase in lifespan of dairy cows. Subsequently, production level and lactation persistency were increased to assess the importance of these aspects for the impact of extended lactations. The increase in production level and lactation persistency increased milk production of BL herds by 30%. Moreover, reductions in milk yield for All+2 and All+4 compared with BL herds were only 0.7% and 1.1% per year, and milk yield in H+2 and H+4 herds was similar to BL herds. The resulting NPCF was equal to BL for All+2 and All+4 and increased by k€1 for H+2 and H+4 due to lower costs for insemination and calving management. Moreover, GHG emissions per t FPCM were equal to BL herds or reduced (0% to -0.3%) when lactations were extended. We concluded that, depending on lactation persistency, extending lactations of dairy cows can have a positive or negative impact on the NPCF and GHG emissions of milk production.

Identification of Single Nucleotide Non-coding Driver Mutations in Cancer.

Recent whole-genome sequencing studies have identified millions of somatic variants present in tumor samples. Most of these variants reside in non-coding regions of the genome potentially affecting transcriptional and post-transcriptional gene regulation. Although a few hallmark examples of driver mutations in non-coding regions have been reported, the functional role of the vast majority of somatic non-coding variants remains to be determined. This is because the few driver variants in each sample must be distinguished from the thousands of passenger variants and because the logic of regulatory element function has not yet been fully elucidated. Thus, variants prioritized based on mutational burden and location within regulatory elements need to be validated experimentally. This is generally achieved by combining assays that measure physical binding, such as chromatin immunoprecipitation, with those that determine regulatory activity, such as luciferase reporter assays. Here, we present an overview of in silico approaches used to prioritize somatic non-coding variants and the experimental methods used for functional validation and characterization.

Effect of dry period length on milk yield over multiple lactations.

Shortening or omitting the dry period (DP) can improve the energy balance of dairy cows in early lactation through a decrease in milk yield after calving. Little is known about the effect of a short or no DP on milk yield over multiple lactations. Our objectives were (1) to assess the effect of DP length over multiple lactations on milk yield, and (2) to assess if the prediction of milk yield in response to DP length could be improved by including individual cow characteristics before calving. Lactation data (2007 to 2015) of 16 Dutch dairy farms that apply no or short DP were used to compute cumulative milk yield in the 60 d before calving (additional yield) and in the 305 d after calving (305-d yield), and the mean daily yield over the interval from 60 d before calving to 60 d before next calving (effective lactation yield). The DP categories were no (0 to 2 wk), short (3 to 5wk), standard (6 to 8 wk), and long (9 to 12 wk). The effect of current DP and previous DP on yields was analyzed with mixed models (n=1,420 lactations). The highest effective lactation yield of fat- and protein-corrected milk (FPCM) was observed for cows with a standard current DP (27.6kg per day); a daily decrease was observed of 0.6kg for a long DP, 1.0kg for a short DP, and 2.0kg for no DP. Previous DP did not significantly affect the effective lactation yield. Thus, cows can be managed with short or no DP over consecutive lactations without a change in quantity of milk losses. Cows that received no DP for consecutive lactations had a lower additional yield before calving (-172kg of FPCM), but a higher 305-d yield (+560kg of FPCM), compared with cows that received no DP for the first time. This could lessen the improvement of the energy balance in early lactation when no DP is applied a second time compared with the first time. For the second objective, a basic model was explored to predict effective lactation yield based on parity, DP length, and first-parity 305-d yield (n=2,866 lactations). The basic model was subsequently extended with data about recent yield, days open, and somatic cell count. Extending the model reduced the error of individual predictions by only 6%. Therefore, the basic model seems sufficient to predict the effect of DP length on effective lactation yield. Other individual cow characteristics can still be relevant, however, to make a practical and tailored decision about DP length.

Multi-strip silicon sensors for beam array monitoring in micro-beam radiation therapy.

We present here the latest results from tests performed at the ESRF ID17 and ID21 beamlines for the characterization of novel beam monitors for Microbeam Radiation Therapy (MRT), which is currently being implemented at ID17. MRT aims at treating solid tumors by exploiting an array of evenly spaced microbeams, having an energy spectrum distributed between 27 and 600keV and peaking at 100keV. Given the high instantaneous dose delivered (up to 20kGy/s), the position and the intensity of the microbeams has to be precisely and instantly monitored. For this purpose, we developed dedicated silicon microstrip beam monitors. We have successfully characterized them, both with a microbeam array at ID17, and a submicron scanning beam at ID21. We present here the latest results obtained in recent tests along with an outlook on future developments.

Effects of dry period length and dietary energy source on lactation curve characteristics over 2 subsequent lactations.

This study evaluated the effects of dry period (DP) length and dietary energy source on lactation curve characteristics over 2 subsequent lactations. It also evaluated the relationships of energy balance or metabolic status in early lactation with lactation curve characteristics in dairy cows. Holstein-Friesian dairy cows (n=167) were assigned randomly to 1 of 3 DP lengths (0-, 30-, or 60-d) and 1 of 2 early-lactation diets (glucogenic or lipogenic) for 2 subsequent lactations. In the second lactation following DP length treatments, 19 cows in the 0-d DP group were assigned to a 0→67-d DP group (actual days dry: 67±8d). Cows were allocated to this new group when they had a milk yield of <4kg/d at least 30d before their expected calving date. Fat- and protein-corrected milk (FPCM) was calculated weekly per cow in both lactations. Blood samples were taken weekly from calving to wk 4 after calving. A Wilmink lactation curve for each lactation was modeled based on FPCM yield records from calving through 305 DIM. During the first lactation following DP length treatments, cows with a 0- or 30-d DP had lower peak yield, later time of peak yield, and lower FPCM305 than cows with a 60-d DP. In the second lactation following DP length treatments, cows with a 0- or 30-d DP had lower peak yield than cows with a 60-d DP. In both lactations, lactation persistency was not affected by DP length and none of the lactation curve characteristics were affected by diet. In parity >2 cows, total FPCM yield and average daily FPCM yield throughout 2 lactations did not differ among DP lengths. In addition, average energy balance in the first 4wk after calving had a negative relationship with peak yield and FPCM305, and a positive relationship with lactation persistency. Average plasma concentrations of free fatty acids and ß-hydroxybutyrate had a positive relationship with peak yield and FPCM305, and a negative relationship with lactation persistency. Shortening or omitting the DP affected lactation curve characteristics in both lactations after implementation of DP length treatments but did not compromise FPCM yield compared with a conventional DP of 60d in parity >2 cows. Severe negative energy balance and poor metabolic status were related to greater peak yield, FPCM305, and lower lactation persistency.

Effective lactation yield: A measure to compare milk yield between cows with different dry period lengths.

To compare milk yields between cows or management strategies, lactations are traditionally standardized to 305-d yields. The 305-d yield, however, gives no insight into the combined effect of additional milk yield before calving, decreased milk yield after calving, and a possible shorter calving interval in the case of a shortened dry period. We aimed to develop a measure that would enable the comparison of milk yield between cows with different dry period (DP) lengths. We assessed the importance of accounting for additional milk yield before calving and for differences in calving interval. The 305-d yield was compared with a 365-d yield, which included additional milk yield in the 60 d before calving. Next, an effective lactation yield was computed, defined as the daily yield from 60d before calving to 60 d before the next calving, to account for additional milk yield before calving and for differences in calving interval. Test-day records and drying-off dates of 15 commercial farms were used to compute the 305-d, 365-d, and effective lactation yields for individual cows. We analyzed 817 second-parity lactations preceded by no DP, a short DP (20 to 40 d), or a conventional DP (49 to 90 d). Compared with cows with a conventional DP, the 305-d yield of cows with no DP was 7.0 kg of fat- and protein-corrected milk (FPCM) per day lower, and the 305-d yield of cows with a short DP was 2.3 kg of FPCM per day lower. Including additional milk yield before calving in the 365-d yield reduced this difference to 3.4 kg of FPCM per cow per day for cows with no DP and to 0.9 kg of FPCM per cow per day for cows with a short DP. Compared with cows with a conventional DP, median days open were reduced by 25d for cows with no DP and by 18d for cows with a short DP. Accounting for these differences in calving interval in the effective lactation yield further decreased yield reductions for cows with no DP or a short DP by 0.3 kg of FPCM per cow per day. At the herd level, estimated 365-d yield losses for cows with no DP or a short DP differed from effective lactation yield losses by 0.4 to -0.8 kg FPCM per cow per day. Accounting for additional milk yield before calving had a major and consistent effect on yield comparisons of cows with different DP lengths. The effect of correcting for calving interval was more variable between farms and will especially be important when calving interval is affected by DP length.