Ice retreat in Wilkes Basin of East Antarctica during a warm interglacial.

Efforts to improve sea level forecasting on a warming planet have focused on determining the temperature, sea level and extent of polar ice sheets during Earth's past interglacial warm periods1-3. About 400,000 years ago, during the interglacial period known as Marine Isotopic Stage 11 (MIS11), the global temperature was 1 to 2 degrees Celsius greater2 and sea level was 6 to 13 metres higher1,3. Sea level estimates in excess of about 10 metres, however, have been discounted because these require a contribution from the East Antarctic Ice Sheet3, which has been argued to have remained stable for millions of years before and includes MIS114,5. Here we show how the evolution of 234U enrichment within the subglacial waters of East Antarctica recorded the ice sheet's response to MIS11 warming. Within the Wilkes Basin, subglacial chemical precipitates of opal and calcite record accumulation of 234U (the product of rock-water contact within an isolated subglacial reservoir) up to 20 times higher than that found in marine waters. The timescales of 234U enrichment place the inception of this reservoir at MIS11. Informed by the 234U cycling observed in the Laurentide Ice Sheet, where 234U accumulated during periods of ice stability6 and was flushed to global oceans in response to deglaciation7, we interpret our East Antarctic dataset to represent ice loss within the Wilkes Basin at MIS11. The 234U accumulation within the Wilkes Basin is also observed in the McMurdo Dry Valleys brines8-10, indicating11 that the brine originated beneath the adjacent East Antarctic Ice Sheet. The marine origin of brine salts10 and bacteria12 implies that MIS11 ice loss was coupled with marine flooding. Collectively, these data indicate that during one of the warmest Pleistocene interglacials, the ice sheet margin at the Wilkes Basin retreated to near the precipitate location, about 700 kilometres inland from the current position of the ice margin, which-assuming current ice volumes-would have contributed about 3 to 4 metres13 to global sea levels.

Rumen function and grazing behavior of early-lactation dairy cows supplemented with fodder beet.

Fodder beet (FB) is a source of readily fermentable carbohydrate that can mitigate early spring herbage deficits and correct the negative energy balance experienced during early lactation in pastoral dairy systems of New Zealand. However, the low-fiber and high-soluble carbohydrate content of both FB bulb and spring herbage are factors that promote subacute ruminal acidosis, impairing rumen function and limiting the marginal milk production response to supplement. In a crossover experiment, 8 Holstein Friesian × Jersey early-lactation dairy cows were used to test the effect of supplementing 16 kg of dry matter (DM) of a grazed perennial ryegrass herbage with 6 kg of DM/d of FB bulb (FBH) versus herbage only (HO) on changes in rumen function and grazing behavior. Following 20 d of adaptation to diets, DM disappearance (%) of FB bulb (FBH cows only) and herbage were measured in sacco, separately. Cows were fasted overnight, and the ruminal contents were bailed the following morning (~0930 h) again to determine the pool size of volatile fatty acids, ammonia, and particle size of digesta, as well as to estimate the rate of ruminal outflow and degradation of neutral detergent fiber. The FBH diet did not alter DM intake, milk yield, or milk solid (fat + protein) production compared with HO. Supplementation of herbage with FB reduced ruminal pH compared with HO between ~0800 h and 1300 h each day. During each period, 1 cow experienced severe subacute ruminal acidosis (pH <5.6 for >180 min/d) during final adaptation to the target FB allocation. The FBH diet reduced the ruminal pool of acetate and ammonia, but increased the ruminal pool of butyrate and lactate compared with HO. When fed FB, rumination and grazing time increased and grazing intensity declined compared with cows fed HO. Despite increased rumination, the comminution of large particles declined 28% between the first and second rumen bailing when cows were fed FB, and in sacco DM disappearance of perennial ryegrass declined 18% compared with cows fed HO. These results indicate that grazing dairy cows supplemented with FB (40% of daily intake) increase rumination and mastication intensity to counteract reduced ruminal degradation of ryegrass herbage due to low ruminal fluid pH.

Repetitive Diffuse Mild Traumatic Brain Injury Causes an Atypical Astrocyte Response and Spontaneous Recurrent Seizures.

Focal traumatic brain injury (TBI) induces astrogliosis, a process essential to protecting uninjured brain areas from secondary damage. However, astrogliosis can cause loss of astrocyte homeostatic functions and possibly contributes to comorbidities such as posttraumatic epilepsy (PTE). Scar-forming astrocytes seal focal injuries off from healthy brain tissue. It is these glial scars that are associated with epilepsy originating in the cerebral cortex and hippocampus. However, the vast majority of human TBIs also present with diffuse brain injury caused by acceleration-deceleration forces leading to tissue shearing. The resulting diffuse tissue damage may be intrinsically different from focal lesions that would trigger glial scar formation. Here, we used mice of both sexes in a model of repetitive mild/concussive closed-head TBI, which only induced diffuse injury, to test the hypothesis that astrocytes respond uniquely to diffuse TBI and that diffuse TBI is sufficient to cause PTE. Astrocytes did not form scars and classic astrogliosis characterized by upregulation of glial fibrillary acidic protein was limited. Surprisingly, an unrelated population of atypical reactive astrocytes was characterized by the lack of glial fibrillary acidic protein expression, rapid and sustained downregulation of homeostatic proteins and impaired astrocyte coupling. After a latency period, a subset of mice developed spontaneous recurrent seizures reminiscent of PTE in human TBI patients. Seizing mice had larger areas of atypical astrocytes compared with nonseizing mice, suggesting that these atypical astrocytes might contribute to epileptogenesis after diffuse TBI.SIGNIFICANCE STATEMENT Traumatic brain injury (TBI) is a leading cause of acquired epilepsies. Reactive astrocytes have long been associated with seizures and epilepsy in patients, particularly after focal/lesional brain injury. However, most TBIs also include nonfocal, diffuse injuries. Here, we showed that repetitive diffuse TBI is sufficient for the development of spontaneous recurrent seizures in a subset of mice. We identified an atypical response of astrocytes induced by diffuse TBI characterized by the rapid loss of homeostatic proteins and lack of astrocyte coupling while reactive astrocyte markers or glial scar formation was absent. Areas with atypical astrocytes were larger in animals that later developed seizures suggesting that this response may be one root cause of epileptogenesis after diffuse TBI.

Body weight of dairy heifers is positively associated with reproduction and stayability.

This study investigated the relationships between body weight (BW) and stayability, and BW and calving pattern, of 189,936 New Zealand dairy heifers. Heifers were classified into 5 breed groups: Holstein-Friesian (F), Holstein-Friesian crossbred (FX), Jersey (J), Jersey crossbred (JX), and Holstein-Friesian × Jersey crossbred (FJ). Body weight was predicted using Legendre polynomials at 6, 12, and 15 mo of age, and we analyzed their relationships with stayability, calving rate, and re-calving rate over the first 3 calvings. Approximately 92% of heifers calved for the first time at age 2 yr, 76% a second time at 3 yr, and 61% a third time at 4 yr. Heifers that were heavier were more likely to remain in the herd for first, second, and third calving compared with heifers that were lighter. Furthermore, we found positive curvilinear relationships between pre-breeding BW and reproductive performance of dairy heifers. Heifers that were heavier at 6, 12, and 15 mo were more likely to calve early for first calving compared with heifers that were lighter, regardless of breed group. In addition, we found a large range in BW where the probability of calving or re-calving early was high. For example, FJ heifers that were between 255 and 396 kg at 15 mo of age had 21-d calving and re-calving rates above 75 and 70%, respectively. For second and third lactations, however, heifer pre-breeding BW showed only small effects on the 21-d calving and re-calving rates. For heifers that were at the heaviest end of the BW range in the current study, slight declines in stayability and reproductive performance occurred, compared with heifers in the mid-range of BW. Consequently, for heifers that were above average in BW, the benefit of increasing BW before first breeding would be small and might even result in slight declines in stayability and reproductive performance. For heifers that were below average in BW, considerable beneficial effects on stayability and reproductive performance are predicted as a result of improving rearing practices to produce heavier heifers throughout the pre-breeding rearing phase.

Increased yearling weight as a proportion of 21-month weight was associated with increased milk production in dairy heifers.

Aims: To examine the relationship between liveweight (LWT) at 12 months as a proportion of LWT at 21 months of age (LWT(12/21)%) and first lactation and cumulative 3-year milk production in dairy heifers in New Zealand. Methods: Liveweight and milk production records were obtained for dairy heifers born from June to December (spring-calving season) between 2006-2007 and 2013-2014 dairy seasons; production records included first lactation (n = 140,113) and cumulative 3-year (n = 67,833) milksolids and energy-corrected milk (ECM) yields. Heifers were classified into five breed groups; Holstein-Friesian, Holstein-Friesian crossbred, Jersey, Jersey crossbred and Holstein-Friesian-Jersey crossbred. Within each breed group heifers were categorised into quintiles based on 21-month LWT. The LWT(12/21)% was calculated for each animal. Relationships between LWT(12/21)% and milk production within each breed group and LWT category were estimated using linear mixed effects models including the linear and quadratic effects of LWT(12/21)%. Results: The relationship between LWT(12/21)% and milk production was predominantly curvilinear, with lower milk production at lesser LWT(12/21)% compared with greater LWT(12/21)%. For all breed groups and most LWT categories, heifers that were 55 or 65% LWT(12/21)% produced greater ECM and milksolids yields compared with heifers that were 45% LWT(12/21)%. Holstein-Friesian, Holstein-Friesian crossbred and Holstein-Friesian-Jersey crossbred heifers that were 65% LWT(12/21)% produced greater cumulative 3-year ECM and milksolids yields compared with heifers of the same breed group that were 45% LWT(12/21)% Conclusions and clinical relevance: Heifers that were a greater proportion of their 21-month LWT at 12 months of age produced more first lactation and cumulative 3-year milk yields than heifers that were a lesser proportion of their 21-month LWT at 12 months of age. These results indicate that increased growth in early life of New Zealand dairy heifers is beneficial to future milk production.

Positive relationships between body weight of dairy heifers and their first-lactation and accumulated three-parity lactation production.

This study investigated the relationships between body weight (BW) and milk production of 140,113 New Zealand dairy heifers. Heifers were classified into 5 breed groups: Holstein-Friesian, Holstein-Friesian crossbred, Jersey, Jersey crossbred, and Holstein-Friesian-Jersey crossbred. Body weights were assessed at intervals of 3 mo from 3 to 21 mo of age and their relationships with first-lactation and accumulated milk production over the first 3 lactations (3-parity) were analyzed. We found positive curvilinear relationships between BW and milk production. The response to an increase in BW was greater for lighter heifers compared with heavier heifers, indicating possible benefits of preferentially feeding lighter heifers to attain heavier BW. Within the age range and BW range studied, an increase in BW was always associated with an increase in first-lactation energy-corrected milk (ECM) and milk solids (milk fat plus milk protein) yield for breed groups other than Holstein-Friesian. For Holstein-Friesian heifers, there was a positive relationship between BW and ECM and milk solids yields for all ages except for 3 mo of age, when no relationship existed. These results show the potential to increase first-lactation milk production of New Zealand dairy heifers by increasing heifer BW. Likewise, for 3-parity accumulated yields, the BW at which maximum ECM and milk solids yields occurred were at the heavier end of the BW range studied. The costs of rearing a heifer are incurred regardless of how long she remains in the herd. Potential bias exists from considering only cows that survived to lactate each year if particular cows had better survival than others. Therefore, the data in the current study for 3-parity production includes all heifers that were old enough to have completed 3 lactations, regardless of whether they did or not. Including the heifers that did not complete all 3 lactations describes the effect that BW of replacement heifers has on accumulated milk yields without discriminating whether the increased milk yield came from greater survival or from greater production per surviving cow. Further research on the relationships between BW and survival of heifers is required to confirm whether the heavier heifers survived longer than the lighter heifers, but could explain why the relationship between BW and 3-parity milk yields was more curvilinear than the relationship between BW and first-lactation milk production. Holstein-Friesian heifers that were 450 kg in BW at 21 mo of age were estimated to produce 168 and 509 kg more ECM than 425-kg Holstein-Friesian heifers in first-lactation and 3-parity accumulated yields, respectively. A further increase in BW at 21 mo of age, from 450 to 475 kg, was estimated to result in 157 and 409 kg more ECM in first-lactation and 3-parity accumulated yields, respectively. Consequently, for heifers that were average and below average in BW, considerable milk production benefits would occur over the first 3 lactations by improving rearing practices to result in heavier heifers throughout the precalving phase.

Dry matter intake, body condition score, and grazing behavior of nonlactating, pregnant dairy cows fed kale or grass once versus twice daily during winter.

The objective of this study was to examine the effect of wintering pregnant, nonlactating dairy cows outdoors on either kale or grass, fed in 1 [11 kg dry matter (DM) of kale or grass + 3 kg DM of baled barley straw offered in the morning] or 2 allocations (5.5 kg DM of kale or grass grazed + 1.5 kg DM of barley straw offered morning and afternoon) per day. The body condition score (BCS) gain over the 47-d winter feeding period was higher for grass-fed (0.5 BCS units) than kale-fed cows (0.3 BCS units), but was unaffected by feeding frequency. Forage DM utilization was higher for kale-fed (97%) than grass-fed cows (76%), leading to higher estimated dry matter intake (DMI) in kale-fed (10.7 kg of DM/cow per day) than grass-fed cows (7.7 kg of DM/cow per day). Forage DM utilization and estimated DMI were not affected by feeding frequency. Prehension bite rate was greater for grass-fed (37.3 bites/min) than kale-fed cows (7.6 bites/min), but more mastication bites were required for kale-fed cows. Cumulative DMI after 2, 3, and 6 h was greater in cows allocated forage once than twice a day and for kale than grass after 3 and 6 h. Mean eating time was greater for cows offered forage once (477 min) than twice (414 min) per day. In conclusion, increasing feeding frequency from once to twice per day decreased the intake rate within the first 6 h after allocation, but did not affect total daily DMI, DM utilization or BCS gain. Thus, moving cows more frequently would not have any significant advantage. It may increase labor requirements, thereby creating a more challenging wintering management than feeding once per day.

Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats.

This corrects the article DOI: 10.1038/ijo.2016.62.

Loss of anti-contractile effect of perivascular adipose tissue in offspring of obese rats.

RATIONALE: Maternal obesity pre-programmes offspring to develop obesity and associated cardiovascular disease. Perivascular adipose tissue (PVAT) exerts an anti-contractile effect on the vasculature, which is reduced in hypertension and obesity. OBJECTIVE: The objective of this study was to determine whether maternal obesity pre-programmes offspring to develop PVAT dysfunction in later life. METHODS: Female Sprague-Dawley rats were fed a diet containing 10% (control) or 45% fat (high fat diet, HFD) for 12 weeks prior to mating and during pregnancy and lactation. Male offspring were killed at 12 or 24 weeks of age and tension in PVAT-intact or -denuded mesenteric artery segments was measured isometrically. Concentration-response curves were constructed to U46619 and norepinephrine. RESULTS: Only 24-week-old HFD offspring were hypertensive (P<0.0001), although the anti-contractile effect of PVAT was lost in vessels from HFD offspring of each age. Inhibition of nitric oxide (NO) synthase with 100 µM l-NMMA attenuated the anti-contractile effect of PVAT and increased contractility of PVAT-denuded arteries (P<0.05, P<0.0001). The increase in contraction was smaller in PVAT-intact than PVAT-denuded vessels from 12-week-old HFD offspring, suggesting decreased PVAT-derived NO and release of a contractile factor (P<0.07). An additional, NO-independent effect of PVAT was evident only in norepinephrine-contracted vessels. Activation of AMP-activated kinase (with 10 µM A769662) was anti-contractile in PVAT-denuded (P<0.0001) and -intact (P<0.01) vessels and was due solely to NO in controls; the AMPK effect was similar in HFD offspring vessels (P<0.001 and P<0.01, respectively) but was partially NO-independent. CONCLUSIONS: The diminished anti-contractile effects of PVAT in offspring of HFD dams are primarily due to release of a PVAT-derived contractile factor and reduced NO bioavailability.

Assessing the impact of a nurse-delivered home dried blood spot service on uptake of testing for household contacts of hepatitis B-infected pregnant women across two London trusts.

Despite national guidance recommending testing and vaccination of household contacts of hepatitis B-infected pregnant women, provision and uptake of this is sub-optimal. The aim of this study was to evaluate the use of in-home dried blood spot (DBS) testing to increase testing and vaccination of household contacts of hepatitis B-infected pregnant women as an alternative approach to conventional primary-care follow-up. The study was conducted across two London maternity trusts (North Middlesex and Newham). All hepatitis B surface antigen-positive pregnant women identified through these trusts were eligible for inclusion. The intervention of in-home DBS testing for household contacts was introduced at North Middlesex Trust from November 2010 to December 2011. Data on testing and vaccination uptake from GP records across the two trusts were compared between baseline (2009) and intervention (2010-2011) periods. In-home DBS service increased testing uptake for all ages (P < 0·001) with the biggest impact seen in partners, where testing increased from 30·3% during the baseline period to 96·6% during the intervention period in North Middlesex Trust. Although impact on vaccine uptake was less marked, improvements were observed for adults. The provision of nurse-led home-based DBS may be useful in areas of high prevalence.

Effect of time of maize silage supplementation on herbage intake, milk production, and nitrogen excretion of grazing dairy cows.

The objective of this study was to evaluate the effect of feeding maize silage at different times before a short grazing bout on dry matter (DM) intake, milk production, and N excretion of dairy cows. Thirty-six Friesian × Jersey crossbred lactating dairy cows were blocked in 9groups of 4 cows by milk solids (sum of protein and fat) production (1.26±0.25kg/d), body weight (466±65kg), body condition score (4±0.48), and days in milk (197±15). Groups were then randomly assigned to 1 of 3 replicates of 3 treatments: control; herbage only, supplemented with 3kg of DM/cow of maize silage after morning milking approximately 9h before pasture allocation (9BH); and supplemented with 3kg of DM/cow of maize silage before afternoon milking approximately 2h before pasture allocation (2BH). Herbage allowance (above the ground level) was 22kg of DM/cow per day for all groups of cows. Cows were allocated to pasture from 1530 to 2030 h. Maize silage DM intake did not differ between treatments, averaging 3kg of DM/cow per day. Herbage DM intake was greater for control than 2BH and 9BH, and greater for 9BH than 2BH (11.1, 10.1, and 10.9kg of DM/cow per day for control, 2BH, and 9BH, respectively). The substitution rate (kilograms of herbage DM per kilograms of maize silage DM) was greater for 2BH (0.47) than 9BH (0.19). Milk solids production was similar between treatments (overall mean 1.2kg/cow per day). Body weight loss tended to be less for supplemented than control cows (-0.95, -0.44, and -0.58kg/cow per day for control, 2BH, and 9BH, respectively). Nitrogen concentration in urine was not affected by supplementation or time of supplementation, but estimated urinary N excretion tended to be greater for control than supplemented cows when urinary N excretion estimated using plasma or milk urea N. At the time of herbage meal, nonesterified fatty acid concentration was greater for control than supplemented cows and greater for 9BH than 2BH (0.58, 0.14, and 0.26mmol/L for control, 2BH, and 9BH, respectively). Timing of maize silage supplementation relative to a short and intensive herbage meal can reduce the substitution rate and increase herbage DM intake of grazing dairy cows.

Efficient national surveillance for health-care-associated infections.

BACKGROUND: Detecting novel healthcare-associated infections (HCAI) as early as possible is an important public health priority. However, there is currently no evidence base to guide the design of efficient and reliable surveillance systems. Here we address this issue in the context of a novel pathogen spreading primarily between hospitals through the movement of patients. METHODS: Using a mathematical modelling approach we compare the current surveillance system for a HCAI that spreads primarily between hospitals due to patient movements as it is implemented in Scotland with a gold standard to determine if the current system is maximally efficient or whether it would be beneficial to alter the number and choice of hospitals in which to concentrate surveillance effort. RESULTS: We validated our model by demonstrating that it accurately predicts the risk of meticillin-resistant Staphylococcus aureus bacteraemia cases in Scotland. Using the 29 (out of 182) sentinel hospitals that currently contribute most of the national surveillance effort results in an average detection time of 117 days. A reduction in detection time to 87 days is possible by optimal selection of 29 hospitals. Alternatively, the same detection time (117 days) can be achieved using just 22 optimally selected hospitals. Increasing the number of sentinel hospitals to 38 (teaching and general hospitals) reduces detection time by 43 days; however decreasing the number to seven sentinel hospitals (teaching hospitals) increases detection time substantially to 268 days. CONCLUSIONS: Our results show that the current surveillance system as it is used in Scotland is not optimal in detecting novel pathogens when compared to a gold standard. However, efficiency gains are possible by better choice of sentinel hospitals, or by increasing the number of hospitals involved in surveillance. Similar studies could be used elsewhere to inform the design and implementation of efficient national, hospital-based surveillance systems that achieve rapid detection of novel HCAIs for minimal effort.

The experiences of participating in winter among youths with a physical disability compared with their typically developing peers.

BACKGROUND: Having a physical disability and using a wheelchair can create difficulties in navigating the physical and built environment, especially during winter when snow and ice become problematic. Little is known about the experiences of winter among youth who use an assistive mobility device. This study aimed to understand how youth with a physical disability experience winter, compared with typically developing peers. METHODS: A purposive sample of 25 youths (13 with a physical disability; 12 typically developing) completed a 2-week weather journal and photographs in two Canadian cities during winter. These data were used to guide semi-structured interviews with participants. RESULTS: Youths with disabilities experienced many similar challenges in winter, such as health and safety concerns and accessibility issues, compared with typically developing youth - but to a greater extent. Youths with disabilities reported more challenges going outdoors during winter and negative psychosocial impacts, including loneliness and increased dependence, compared with peers without a disability. They also, however, described developing several adaptive strategies to cope with these challenges. CONCLUSIONS: There is a strong need to remove physical and environmental barriers to facilitate the participation and inclusion of youth with disabilities in winter.

Time-Scaled Evolutionary Analysis of the Transmission and Antibiotic Resistance Dynamics of Staphylococcus aureus Clonal Complex 398.

Staphylococcus aureus clonal complex 398 (CC398) is associated with disease in humans and livestock, and its origins and transmission have generated considerable interest. We performed a time-scaled phylogenetic analysis of CC398, including sequenced isolates from the United Kingdom (Scotland), along with publicly available genomes. Using state-of-the-art methods for mapping traits onto phylogenies, we quantified transitions between host species to identify sink and source populations for CC398 and employed a novel approach to investigate the gain and loss of antibiotic resistance in CC398 over time. We identified distinct human- and livestock-associated CC398 clades and observed multiple transmissions of CC398 from livestock to humans and between countries, lending quantitative support to previous reports. Of note, we identified a subclade within the livestock-associated clade comprised of isolates from hospital environments and newborn babies, suggesting that livestock-associated CC398 is capable of onward transmission in hospitals. In addition, our analysis revealed significant differences in the dynamics of resistance to methicillin and tetracycline related to contrasting historical patterns of antibiotic usage between the livestock industry and human medicine. We also identified significant differences in patterns of gain and loss of different tetracycline resistance determinants, which we ascribe to epistatic interactions between the resistance genes and/or differences in the modes of inheritance of the resistance determinants.

Plasma nitrogen isotopic fractionation and feed efficiency in growing beef heifers.

Fractionation of N isotopes occurs in many metabolic reactions which causes tissue proteins to become enriched in ¹5N while urea (urine) is depleted in ¹5N relative to the diet. We investigated ¹5N enrichment of whole plasma and its relationship with feed conversion efficiency (FCE) in growing beef heifers (n 84) offered 2 kg/d of concentrates with grass silage ad libitum. Heifers were on average 299 (SD 48·3) d old and weighed 311 (SD 48·8) kg. Plasma was obtained on day 79 (n 84) of the experiment and from a subset of animals (n 20) on four occasions between days 16 and 79. Silage DM intake (DMI) averaged 4·1 (SD 0·74) kg/d and concentrate DMI was 1·72 kg/d. Mean mid-test live weight was 333 (SD 47·6) kg, daily gain was 0·53 (SD 0·183) kg, FCE (g live-weight gain/g DMI) was 0·09 (SD 0·028) and residual feed intake (RFI) was 0 (SD 0·428). N isotopic fractionation (Δ¹5N; plasma δ¹5N - diet δ¹5N) averaged 3·58 ‰ on day 79 (n 84) and 3·90 ‰ for the subset of heifers. There was no relationship between Δ¹5N and RFI. Plasma δ¹5N and Δ¹5N were related to both FCE (negative) and animal weight (positive) for the whole population, and repeatable for the subset of animals over four time points. These relationships of Δ¹5N with FCE and animal weight are consistent with the anticipated negative relationship with N-use efficiency. There is potential to use Δ¹5N to provide rapid, low-cost estimates of FCE in cattle.

Efficiency of use of metabolizable energy for body weight gain in pasture-based, nonlactating dairy cows.

Four cohorts of nonlactating, pregnant dairy cows (n=50, 47, 45, and 42) were individually fed indoors to determine the amount of feed required for body weight (BW) gain from autumn pasture and commonly used supplementary feeds. These results were used to estimate the apparent efficiency with which metabolizable energy (ME) is used for BW gain (app_kg). Control cows were offered autumn pasture to estimated maintenance requirements (~0.55 MJ of ME/kg of BW(0.75)), with an additional 20 MJ of ME/d allocated for pregnancy and activity. All other cows received the same allowance of autumn pasture and an additional allowance (2.5 or 5.0 kg of dry matter/d) of autumn pasture (Past), spring pasture silage (Psil), maize silage (Msil), cracked maize grain (Mgr), or palm kernel expeller (PKE), resulting in a total of 11 treatments. Individual cow dry matter intake was determined daily; BW was recorded once per week for cohorts 1 and 2, and 3 times per week for cohorts 3 and 4. The ME contents of feeds were estimated from feed quality assays. Regression analyses were used on each feed to determine the ME requirement for 1 kg of BW gain. The app_kg of Past and Msil was 0.34 and 0.47, respectively; these estimates are in line with published literature. The app_kg of Psil (0.50) was consistent with the published kg for spring pasture, from which the silage was made. Palm kernel expeller had the greatest app_kg (0.61). The reasons for this cannot be deduced from the current study but may reflect the relatively high fat content of the feed and the high kg of fat. The app_kg for Mgr was low (0.38) in comparison with the other supplementary feeds and, in particular, relative to its feed ME and published kg estimates. Although the reason for the low app_kg cannot be deduced from the current data, the most plausible reason is the preferential use of propionate-derived glucose for conceptus metabolism rather than BW gain, a factor not accounted for in previous experimental models that did not use late-gestation cows. In summary, the app_kg for autumn pasture was low but consistent with historical growth rate trials in other ruminant species. In comparison, Msil, Psil, and PKE were used with a greater apparent efficiency (app_kg=0.47 to 0.61), but Mgr resulted in a relatively low rate of gain per MJ of ME (app_kg=0.38). These differences have implications for accurate feed budgeting on farm.

Developing medical simulations for opioid overdose response training: A qualitative analysis of narratives from responders to overdoses.

Medical simulation offers a controlled environment for studying challenging clinical care situations that are difficult to observe directly. Overdose education and naloxone distribution (OEND) programs aim to train potential rescuers in responding to opioid overdoses, but assessing rescuer performance in real-life situations before emergency medical services arrive is exceedingly complex. There is an opportunity to incorporate individuals with firsthand experience in treating out-of-hospital overdoses into the development of simulation scenarios. Realistic overdose simulations could provide OEND programs with valuable tools to effectively teach hands-on skills and support context-sensitive training regimens. In this research, semi-structured interviews were conducted with 17 individuals experienced in responding to opioid overdoses including emergency department physicians, first responders, OEND program instructors, and peer recovery specialists. Two coders conducted qualitative content analysis using open and axial thematic coding to identify nuances associated with illicit and prescription opioid overdoses. The results are presented as narrative findings complemented by summaries of the frequency of themes across the interviews. Over 20 hours of audio recording were transcribed verbatim and then coded. During the open and axial thematic coding process several primary themes, along with subthemes, were identified, highlighting the distinctions between illicit and prescription opioid overdoses. Distinct contextual details, such as locations, clinical presentations, the environment surrounding the patient, and bystanders' behavior, were used to create four example simulations of out-of-hospital overdoses. The narrative findings in this qualitative study offer context-sensitive information for developing out-of-hospital overdose scenarios applicable to simulation training. These insights can serve as a valuable resource, aiding instructors and researchers in systematically creating evidence-based scenarios for both training and research purposes.

Eribulin mesylate pharmacokinetics in patients with solid tumors receiving repeated oral ketoconazole.

Purpose To study the influence of repeated oral administration of ketoconazole, a potent CYP3A4 inhibitor, on the plasma pharmacokinetics of eribulin mesylate administered by single-dose intravenous infusion. Eribulin mesylate is a non-taxane microtubule dynamics inhibitor that is currently under development in phase I-III trials for the treatment of solid tumors. Experimental design A randomized, open-label, two treatments, two sequences, crossover phase I study was performed in patients with advanced solid tumors. Treatments were given on day 1 and day 15 and consisted of 1.4 mg/m(2) eribulin mesylate alone or 0.7 mg/m(2) eribulin mesylate plus 200 mg ketoconazole on the day of eribulin mesylate administration and the following day. Pharmacokinetic sampling for determination of eribulin plasma concentration was performed up to 144 h following administration of eribulin mesylate. Also safety and anti-tumor activity were determined. Results Pharmacokinetic sampling and analysis was completed in ten patients. Statistical analysis of dose-normalized log-transformed AUC0-∞ and Cmax indicated that single-dose exposure of eribulin was not statistically different when co-administered with ketoconazole (ratio of geometric least square means: 0.95 (90%CI: 0.80-1.12) and 0.97 (90%CI: 0.83-1.12), respectively) in patients with solid tumors. Ketoconazole had no effect on eribulin clearance and elimination half-life. The most frequently reported treatment related adverse events were fatigue and nausea, each reported in 8/12 patients. Seven patients (58.3 %) achieved stable disease as best overall response. Conclusions The results indicate that eribulin mesylate can be safely co-administered with ketoconazole. Drug-drug interactions are not expected with other CYP3A4 inhibitors.

Nitrogen partitioning and milk production of dairy cows grazing simple and diverse pastures.

Research was conducted to examine the effects of a diverse pasture mix on dry matter intake, milk yield, and N partitioning of lactating dairy cows. A pasture containing only ryegrass and white clover (RG), or high-sugar ryegrass and white clover (HS), was compared with a diverse pasture mix (HSD) including chicory, plantain, lotus, high-sugar ryegrass, and white clover. The experiment was conducted over a 10-d period using 3 groups of 12 cows in late lactation. No difference was observed in dry matter (14.3 kg of dry matter/cow per day) or N (583 g of N/cow per day) intake between treatments. The cows grazing the HSD pasture had an increased milk yield (16.9 kg/d) compared with those grazing the simple RG and HS pastures (15.2 and 14.7 kg/d, respectively). However, no differences were observed in milk solids yield for the 3 treatments. A tendency toward greater milk protein yields in the HSD group resulted in improved N use efficiency for milk of 20.4% from the cows fed HSD, compared with 17.8 and 16.7% from cows in the RG and HS treatments, respectively. Urinary N excretion was lower from the cows fed HSD, at 353.8 g/d, compared with 438.3 and 426.6 g/d for cows fed RG and HS, respectively. These results suggest that the use of pastures containing chicory, lotus, and plantain can contribute to the goal of reducing N losses from cows in late lactation.