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Neonatal dairy and beef calves are required to ingest adequate volumes of high-quality colostrum during their first hours of life to acquire transfer of passive immunity (TPI). As such, immunoglobulin G (IgG) has largely been the focus of colostrum research over recent decades. Yet, little is known about the additional bioactive compounds in colostrum that potentially influence newborn calf development and metabolism. The purpose of this narrative review is to synthesize research regarding the effects of colostrum management practices on TPI, as well as to address the potential role of additional colostral bioactive molecules, including oligosaccharides, fatty acids, insulin, and insulin-like growth factor-I, in promoting calf development and metabolism. Due to the importance of IgG in ensuring calf immunity and health, we review past research describing the process of colostrogenesis and dam factors influencing the concentrations of IgG in an effort to maximize TPI. We also address the transfer of additional bioactive compounds in colostrum and prepartum management and dam factors that influence their concentrations. Finally, we highlight key areas of future research for the scientific community to pursue to ultimately improve the health and welfare of neonatal dairy calves.

Dairy calf nutrition is traditionally one of the most overlooked aspects of dairy management, despite its large effect on the efficiency and profitability of dairy operations. Unfortunately, among all animals on the dairy farm, calves suffer from the highest rates of morbidity and mortality. These challenges have catalyzed calf nutrition research over the past decade to mitigate high incidences of disease and death, and improve animal health, growth, welfare, and industry sustainability. However, major knowledge gaps remain in several crucial stages of development. The purpose of this review is to summarize the key concepts of nutritional physiology and programming from conception to puberty and their subsequent effects on development of the calf, and ultimately, future performance. During fetal development, developmental plasticity is highest. At this time, maternal energy and protein consumption can influence fetal development, likely playing a critical role in calf and heifer development and, importantly, future production. After birth, the calf's first meal of colostrum is crucial for the transfer of immunoglobulin to support calf health and survival. However, colostrum also contains numerous bioactive proteins, lipids, and carbohydrates that may play key roles in calf growth and health. Extending the delivery of these bioactive compounds to the calf through a gradual transition from colostrum to milk (i.e., extended colostrum or transition milk feeding) may confer benefits in the first days and weeks of life to prepare the calf for the preweaning period. Similarly, optimal nutrition during the preweaning period is vital. Preweaning calves are highly susceptible to health challenges, and improved calf growth and health can positively influence future milk production. Throughout the world, the majority of dairy calves rely on milk replacer to supply adequate nutrition. Recent research has started to re-evaluate traditional formulations of milk replacers, which can differ significantly in composition compared with whole milk. Transitioning from a milk-based diet to solid feed is critical in the development of mature ruminants. Delaying weaning age and providing long and gradual step-down protocols have become common to avoid production and health challenges. Yet, determining how to appropriately balance the amount of energy and protein supplied in both liquid and solid feeds based on preweaning milk allowances, and further acknowledging their interactions, shows great promise in improving growth and health during weaning. After weaning and during the onset of puberty, heifers are traditionally offered high-forage diets. However, recent work suggests that an early switch to a high-forage diet will depress intake and development during the time when solid feed efficiency is greatest. It has become increasingly clear that there are great opportunities to advance our knowledge of calf nutrition; yet, a more concentrated and rigorous approach to research that encompasses the long-term consequences of nutritional regimens at each stage of life is required to ensure the sustainability and efficiency of the global dairy industry.

Serum total protein (STP) refractometry is a widely used indicator of failed transfer of passive immunity (FTPI), defined as serum IgG concentrations of

Serum IgG concentrations in dairy calves change throughout their first weeks of life, peaking at 24 h and then steadily decreasing until calves begin to produce endogenous IgG. The objective of this study was to observe serum IgG dynamics from birth until 16 wk of life in calves fed either maternal colostrum (MC) or colostrum replacer (CR). A total of 44 Holstein calves were randomly assigned to 1 of the 4 colostrum treatments and followed throughout the study. Treatments consisted of feeding high-quality MC, low-quality MC supplemented with CR, or 1 of 2 distinct levels of IgG concentration from CR. Overall, the interaction between type of colostrum fed and sampling time was significant. Individual differences for this effect were found at d 1, 7, 14, 21, 28, and 98, while the other time points were not different.

Calves might experience an upper limit of IgG absorption from colostrum ingestion at birth, but it is not clear whether the total IgG mass fed in the first meal or feeding frequencies can saturate the IgG transport mechanism and therefore limit IgG absorption. The objective of this study was to determine whether different colostrum replacer (CR) feeding frequencies affect serum IgG levels or apparent efficiency of absorption (AEA) in neonatal calves. Male Holstein calves (n = 40) were separated from their dams immediately after parturition and randomly assigned to receive CR [12% of birth body weight (BW)], following either (1) a low-frequency (LF; n = 20) or (2) a high-frequency (HF; n = 20) feeding protocol. Low-frequency calves received 2 CR meals (8% and 4% birth BW within 1 h after birth and 12 h after first CR feeding, respectively), whereas HF calves received 3 CR meals (4% of BW for each meal; within 1 h after birth, 6, and 12 h after first CR feeding). The CR powder fed had a dry matter IgG concentration of 30% and an IgG concentration of 70.5 g/L when reconstituted. All CR was fed via esophageal tube within 1 h after birth. Calves were bottle-fed pasteurized milk (5% birth BW) at 24, 36, and 48 h after the first CR feeding. Blood was collected before first CR feeding and at the following intervals post-CR feeding: every 2 h until 18 h; every 3 h from 18 to 30 h; and every 6 h from 30 to 48 h after the first CR feeding. Serum IgG values at 24 h did not differ between LF and HF (25.79 ± 0.93 and 25.66 ± 0.88 g/L, respectively). In the first meal, calves fed LF ingested a higher total IgG mass than HF (257.98 ± 4.16 g and 126.72 ± 4.05 g, respectively); however, AEA at 24 h did not differ for calves fed HF or LF (27.68 ± 1.16% and 27.63 ± 1.26%, respectively). The IgG area under the curve (AUC) at 24 h was greater for calves fed LF than HF (443.13 ± 15.17 and 379.59 ± 13.99 g of IgG/L × h, respectively). Additionally, AUC at 6 h, 12 h, and 48 h were greater for calves fed LF than HF. These results indicate that, although LF calves had a greater AUC, HF calves were still able to absorb IgG in the second and third meal, allowing HF calves to achieve serum IgG levels similar to those of LF calves at 24 h. In addition, the provision of 3 meals at 70.5 g/L of IgG within the first 12 h of life did not result in added benefits to serum IgG or AEA levels.

Successful passive transfer of antibodies in neonatal calves can be achieved by feeding an adequate quantity and quality of maternal colostrum (MC) or colostrum replacer (CR). An alternative could be feeding low-quality maternal colostrum (LMC) with added IgG from a CR. The objective of this study was to determine if a commercial whey-based CR product containing low levels of casein (Premolac PLUS Bovine IgG; Zinpro Corporation, Eden Prairie, MN) fed to replace MC or supplement LMC could lead to adequate serum IgG levels and apparent efficiency of absorption (AEA) in neonatal dairy calves. Holstein calves (n = 20 per treatment) were separated from their dam after birth and randomly assigned to be fed 3.79 L of MC (106 g/L of IgG; 401 g of IgG fed), LMC (30 g/L IgG) supplemented with CR (41 g/L IgG; 154 g of IgG total fed; LMC-CR), or 1.3 L of 1 of 2 levels of CR (110 or 150 g of IgG fed; CR-110 or CR-150) within 1.5 h of birth. Colostrum was obtained from the first (MC) or second and third milkings (LMC) of cows from Pennsylvania State University dairy and pooled by source into large batches. Blood samples were taken from calves before colostrum feeding and 24 h after birth and were analyzed for serum total protein, total IgG, hematocrit, and Brix percentage. Calves fed MC had higher 24-h IgG values (means ± SEM) than calves fed LMC-CR (27.04 ± 1.07 vs. 22.33 ± 1.08 mg/mL, respectively). Feeding 150 g of IgG from CR led to higher 24-h serum IgG values than feeding 110 g of IgG (16.90 ± 1.09 vs. 12.79 ± 1.08 mg/mL). Serum IgG levels were different between the CR-fed calves and the calves fed LMC-CR and MC, but all had average values >10 mg/mL IgG. Calves fed LMC-CR had greater AEA than calves fed MC (54.58 ± 2.39 vs. 24.38 ± 2.36%, respectively). Among calves fed CR-110 or CR-150, AEA did not differ. Serum total protein and Brix percentage had strong correlations with actual IgG values across the entire study. We found no differences in average daily gain or health variables measured, and no differences in final hip width, withers height, or body weight for calves fed MC, LMC-CR, CR-150, or CR-110. These results indicate that CR can be fed successfully as an alternative to MC or as a supplement to colostrum with low IgG.

Purpose To perform an evaluation on safety and efficacy of uterine artery embolization (UAE) in the patients with symptomatic cervical leiomyomata. Methods Patients with symptomatic cervical leiomyomata who underwent UAE in one specialized hospital were retrospectively analyzed, both clinically and with MR imaging. The 3-month outcomes were assessed with MR imaging and a validated questionnaire. Long-term follow-up was assessed by direct contact or file review. To determine the efficacy of UAE for cervical leiomyomata, the primary objective was to assess the clinical outcome with the UFS-QOL questionnaire, containing the health-related quality of life (HRQOL) and symptom severity score (SSS). To assess safety, the secondary objective included leiomyomata volume reduction, the infarction/complication rate and secondary interventions were needed. Results Between 2006 and 2017, eight of 1180 patients underwent UAE and were eligible for inclusion. All embolizations were technically successful (n = 8). At 3 months, all patients showed cervical leiomyomata volume reduction with a median reduction of 41.5% (38.8 cm3) compared to baseline (p = 0.012). No complications occurred. At a median follow-up of 3 months (range 1–7, n = 7), the HRQOL and SSS improved with a median difference of 13 points (range − 5 to 60, p = 0.063) and − 13 points (range − 79 to 3, p = 0.046), respectively. Long-term follow-up showed two secondary interventions (median of 43.5 months). Six patients reported no symptom recurrence. Conclusion UAE in women with symptomatic cervical leiomyomata is effective and safe with significant improvement in symptoms and quality of life. UAE is a valuable option for women seeking a non-surgical solution. Electronic supplementary material The online version of this article (10.1007/s00270-018-2081-2) contains supplementary material, which is available to authorized users.

Objectives Previous research into pelvic venous reflux has suggested that the size of the ovarian veins indicates the presence or absence of reflux. It is already known that vessel diameter is not an indicator of reflux in the great saphenous vein. However, to this day, physicians still use vein size to plan treatment of refluxing ovarian veins. The authors aimed to investigate whether or not vessel diameter can be used as an indicator of reflux in the ovarian veins. Methods Nineteen female patients (mean 40.2 years, range 29–60) presenting to a specialist vein unit with leg varicose veins underwent duplex ultrasonography (DUS). All were found to have a significant pelvic contribution to their leg reflux on transvaginal duplex ultrasonography (TVS) and were referred to an interventional radiologist for treatment by transjugular coil embolization. During the procedure, the diameter of the ovarian veins was measured using digital subtraction venography. Results Thirty-four ovarian veins were measured (17 right, 17 left) and of these 18 were found to be non-refluxing while 16 displayed reflux. The mean diameter of the non-refluxing veins was 7.2 mm (range 3–13 mm) and that of the refluxing veins was 8.5 mm (range 4–13 mm). This difference was found to be insignificant at a 95% confidence level (Student t test, p = .204). Conclusions There is no significant difference between the diameters of competent and refluxing ovarian veins and, as such, techniques that measure vein diameter may not be suitable for the diagnosis of venous reflux in the ovarian veins.

Background: Triple negative breast cancers (TNBCs) are the most aggressive and profoundly heterogeneous form of breast cancer (BC), treatment of which is a prevalent challenge faced in clinics. CEP55, discovered first by our laboratory, is a key regulator of cytokinesis, error in which roots to multi-nucleation. Function of CEP55 is critically delimited by ERK2/PLK1 dependent phosphorylation, for accurate cytokinesis. Research has demonstrated connotation of CEP55 with numerous cancers including BC as higher CEP55 mRNA expression is allied to worse prognosis and poor survival. We hypothesised that, CEP55 controls fate of aneuploid cell population among aggressive BC that are heavily reliant on mitotic genes for tumour progression, thus can be targeted for therapy development. Methods: Using in vitro studies we demonstrated that depletion of CEP55 sensitizes TNBC cells to anti-mitotic drugs like PLK1 inhibitor to induce CDK1-Caspase 3-dependent mitotic catastrophe due to unscheduled CDK1/Cyclin B activation. Also we showed ERK1/2 transcriptionally controls CEP55 hence inhibition of MEK1/2 using the small molecule inhibitor Selumetinib, can mimic depletion of CEP55 in vivo. Results: We rationalised the usage of a MEK1/2 inhibitor in combination with a PLK1 inhibitor across a series of BC cell lines. We observed synthetic lethality among the aggressive hormone receptor negative lines with higher CEP55 expression compared to normal like and receptor positive lines with lower CEP55 level. The combination synergistically amplified apoptosis of aneuploid population via premature entry of these cells into mitosis in the presence of antimitotic drugs due to exhaustion of CEP55. We have also validated this synergistic effect of MEK1/2 and PLK1 inhibition using xenograft models, results of which imitated the in vitro findings. Conclusions: We propose a novel treatment tactic of MEK1/2 -PLK1 dual combination for selectively targeting CEP55 over-expressing BC in the clinics.

Until recently, the main indication for pelvic vein embolization (PVE) in women was to treat pelvic venous congestion syndrome (PVC) but increasingly, patients with refluxing pelvic veins associated with leg varicosities are also being treated. A more unusual reason for PVE is to treat pelvic venous malformations, although such lesions may be treated with sclerotherapy alone. Embolotherapy for treating PVC has been performed for many years with several published studies included in this review, whilst an emerging indication for PVE is to treat lower limb varicosities associated with pelvic vein reflux. Neither group, however, has been subjected to an adequate randomized, controlled trial. Consequently, some of the information presented in this review should be considered anecdotal (level III evidence) at this stage, and a satisfactory ‘proof’ of clinical efficacy remains deficient until higher-level evidence is presented. Furthermore, a wide range of techniques not accepted by all are used, and some standardization will be required based on future mandatory prospective studies. Large studies have also clearly shown an unacceptably high recurrence rate of leg varicose veins following venous surgery. Furthermore, minimally or non-invasive imaging is now revealing that there is a refluxing pelvic venous source in a significant percentage of women with de novo leg varicose veins, and many more with recurrent varicosities. Considering that just over half the world’s population is female and a significant number of women not only have pelvic venous reflux, but also have associated leg varicosities, minimally invasive treatment of pelvic venous incompetence will become a common procedure.

The HiPER reactor design is exploring different reaction chambers. In this study, we tackle the neutronics and activation studies of a preliminary reaction chamber based in the following technologies: unprotected dry wall for the First Wall, self-cooled lead lithium blanket, and independent low activation steel Vacuum Vessel. The most critical free parameter in this stage is the blanket thickness, as a function of the 6 Li enrichment. After a parametric study, we select for study both a “thin” and “thick” blanket, with “high” and “low” 6 Li enrichment respectively, to reach a TBR = 1.1. To help to make a choice, we compute, for both blanket options, in addition to the TBR, the energy amplification factor, the tritium partial pressure, the 203 Hg and 210 Po total activity in the LiPb loop, and the Vacuum Vessel thickness required to guarantee the reweldability during its lifetime. The thin blanket shows a superior performance in the safety related issues and structural viability, but it operates at higher 6 Li enrichment. It is selected for further improvements. The Vacuum Vessel shows to be unviable in both cases, with the thickness varying between 39 and 52 cm. Further chamber modifications, such as the introduction of a neutron reflector, are required to exploit the benefits of the thin blanket with a reasonable Vacuum Vessel.

The Tokamak Complex will accommodate the ITER tokamak and some of the plant systems needed for the machine operation. In order to obtain radiation maps in the Tokamak Complex, a new MCNP model was released on September 2016. This model, based on a conservative representation of the latest baseline design, represents a version controlled, computationally stable, user-friendly and easy-to-update and maintain MCNP input of the Tokamak Complex. Every modification of the initial CAD models was reviewed, recorded and version controlled. The MCNP model of the Tokamak Complex uses the most stable MCNP geometry implementations, avoiding the use of universes and macrobodies. The input exhibits a low particle loss rate (

In this work, the total heating of the ITER superconducting Poloidal Field Coil #2 (PFC #2) has been calculated due to 16N decay photon radiation emitted from the activated water in the Blanket Manifolds, the Chimney pipes and the Tokamak Cooling Water System (TCWS) manifolds. In order to reduce the total nuclear heating of the PFC #2, shielding measures have been proposed; a set of conceptual stainless-steel shields has been designed and inserted into the computational model of the ITER machine covering the Upper Port Stub (UPS) Chimney and the UPS Chimneybox. The results have shown a 42% reduction of the PFC #2 heating, i.e. from 275 W down to 160 W, when 10 cm thick plates have been placed on the mentioned UP structures. At the same time, the maximum specific heating of the PFC #2 has been decreased by 63%, from 40 W/m3 down to 15 W/m3. A recommendation has been given for further reduction of the PFC #2 heating by improving the on-going design of the TCWS duct.