Healthy environments for athleTes (HEAT): environmental conditions along a 90 km ultra-marathon event, South Africa.

This paper provides an overview of the HEAT (Healthy Environments for AthleTes) project, which aims to understand the impact of environmental conditions on athlete health and performance during major sporting events such as long-distance running, cycling, and triathlons. In collaboration with the SAFER (Strategies to reduce Adverse medical events For the ExerciseR) initiative, the HEAT project carried out a field campaign at the 2022 Comrades Marathon in the KwaZulu-Natal province of South Africa. The measurement campaign deployed seven weather stations, seven PM2.5 monitors and one spore trap along the 90 km route to capture spatially representative measurements of complex micro-climates, allergenic aerospora, and particulate matter exposure. The results indicate that runners were exposed to moderate risk heat stress conditions. Novel findings from this initial campaign shows elevated and potentially harmful PM2.5 levels at spectator areas, possibly coinciding with small fire events around the race day festivities. Our findings show values PM2.5 levels over the WHO 24-h guidelines at all stations, while 2000 µg/m3 at two stations. However, the lack of an acute exposure standard means direct health impacts cannot be quantified in the context of a sport event. The HEAT project highlights important aspects of race day monitoring; regional scale climatology has an impact on the race day conditions, the microclimatic conditions (pollution and meteorology) are not necessarily captured by proximity instruments and direct environmental measurements are required to accurately capture conditions along the route.

Tenecteplase Versus Alteplase for Acute Stroke: Mortality and Bleeding Complications.

STUDY OBJECTIVE: Intravenous thrombolysis with alteplase has been the foundation of initial treatment of acute ischemic stroke for several decades. Tenecteplase is a thrombolytic agent that offers logistical advantages in cost and administration relative to alteplase. There is evidence that tenecteplase has at least similar efficacy and safety outcomes compared with alteplase for stroke. In this study, we compared tenecteplase versus alteplase for acute stroke in a large retrospective US database (TriNetX) regarding the following 3 outcomes: (1) mortality, (2) intracranial hemorrhage, and (3) the need for acute blood transfusions. METHODS: In this retrospective study using the US cohort of 54 academic medical centers/health care organizations in the TriNetX database, we identified 3,432 patients treated with tenecteplase and 55,894 patients treated with alteplase for stroke after January 1, 2012. Propensity score matching was performed on basic demographic information and 7 previous clinical diagnostic groups, resulting in a total of 6,864 patients with acute stroke evenly matched between groups. Mortality rates, the frequency of intracranial hemorrhage, and blood transfusions (as a marker of significant blood loss) were recorded for each group over the ensuing 7- and 30-day periods. Secondary subgroup analyses were conducted on a cohort treated from 2021 to 2022 in an attempt to determine whether temporal differences in acute ischemic stroke treatment would alter the results. RESULTS: Patients treated with tenecteplase had a significantly lower mortality rate (8.2% versus 9.8%; risk ratio [RR], 0.832) and lower risk of major bleeding as measured by the frequency of blood transfusions (0.3% versus 1.4%; RR, 0.207) than alteplase at 30 days after thrombolysis for stroke. In the larger 10-year data set of patients with stroke treated after January 1, 2012, patients receiving tenecteplase were not found to have a statistically different incidence of intracranial hemorrhage (3.5% versus 3.0%; RR, 1.185) at 30 days after the administration of the thrombolytic agents in patients. However, a subgroup analysis of 2,216 evenly matched patients with stroke treated from 2021 to 2022 demonstrated notably better survival and statistically lower rates of intracranial hemorrhage than the alteplase group. CONCLUSION: In our large retrospective multicenter study using real-world evidence from large health care organizations, tenecteplase for the treatment of acute stroke demonstrated a lower mortality rate, decreased intracranial hemorrhage, and less significant blood loss. The favorable mortality and safety profiles observed in this large study, taken together with previous randomized controlled trial data and operational advantages in rapid dosing and cost-effectiveness, all support the preferential use of tenecteplase in patients with ischemic stroke.

CARE: Protocol of a randomised trial evaluating the feasibility of preoperative intentional weight loss to support postoperative recovery in patients with excess weight and colorectal cancer.

AIM: Excess weight increases the risk of morbidity following colorectal cancer surgery. Weight loss may improve morbidity, but it is uncertain whether patients can follow an intensive weight loss intervention while waiting for surgery and there are concerns about muscle mass loss. The aim of this trial is to assess the feasibility of intentional weight loss in this setting and determine progression to a definitive trial. METHODS: CARE is a prospectively registered, multicentre, feasibility, parallel, randomised controlled trial with embedded evaluation and optimisation of the recruitment process. Participants with excess weight awaiting curative colorectal resection for cancer are randomised 1:1 to care as usual or a low-energy nutritionally-replete total diet replacement programme with weekly remote behavioural support by a dietitian. Progression criteria will be based on the recruitment, engagement, adherence, and retention rates. Data will be collected on the 30-day postoperative morbidity, the typical primary outcome of prehabilitation trials. Secondary outcomes will include, among others, length of hospital stay, health-related quality of life, and body composition. Qualitative interviews will be used to understand patients' experiences of and attitudes towards trial participation and intervention engagement and adherence. CONCLUSION: CARE will evaluate the feasibility of intensive intentional weight loss as prehabilitation before colorectal cancer surgery. The results will determine the planning of a definitive trial.

Calcaneal offset index to measure hindfoot alignment in pes planus.

INTRODUCTION: Pes planus is a common three-dimensional (3D) deformity characterised by forefoot abduction, the collapse of the medial longitudinal arch, and hindfoot valgus. Several radiological measurements such as anteroposterior talocalcaneal angle (Kite's) and 'Calcaneal pitch angle' (CPA) exist to calculate the degree of hindfoot alignment in these patients with variable intra- and interobserver reliability. OBJECTIVE: To describe a new radiological ancillary method of measuring hindfoot alignment, the calcaneal offset index (COI). MATERIAL AND METHODS: Anteroposterior (mortise) and lateral view weight-bearing (WB) ankle radiographs of 200 consecutive patients referred for foot and ankle pain were reviewed. Demographic details, clinical indication, and COI calculation were undertaken on the mortise view along with the measurement of CPA for each patient. A one-way analysis of variance (ANOVA) was performed. Intraclass correlation coefficient (ICC) analysis was evaluated to assess the intraclass reliability between observers. RESULTS: There was a female preponderance of 2:1 in the study population with a mean age of 51.21 years (13-86 years). The calcaneal offset was increased in pes planus (hindfoot valgus). The p-value was 0.00023 on ANOVA. The COI gave an excellent interobserver correlation with ICC of 0.9 and moderate intraobserver reliability on the ICC analysis of 0.55. CONCLUSION: The COI can be an additional index of measuring hindfoot alignment in patients with pes planus. Contrary to the traditional angular measurements, this linear transverse plane measure is easier to calculate and reproducible. COI measurement has shown moderate intraobserver reliability but excellent interobserver reliability.

Effects of milk replacer allowances and levels of starch in pelleted starter on nutrient digestibility, whole gastrointestinal tract fermentation, and pH around weaning.

The objectives of this study were to examine the effects of pelleted starter diets differing in starch and neutral detergent fiber (NDF) content when fed differing levels of milk replacer (MR) on nutrient digestibility, whole gastrointestinal tract fermentation, pH, and inflammatory markers in dairy calves around weaning. Calves were randomly assigned to 1 of 4 dietary treatments (n = 12 per treatment) in a 2 × 2 factorial design based on daily MR allowance and amount of starch in pelleted starter (SPS): 0.691 kg of MR per day [dry matter (DM) basis] with starter containing low or high starch (12.0% and 35.6% starch on DM basis, respectively), and 1.382 kg of MR per day (DM) with starter containing low or high starch. All calves were housed in individual pens with straw bedding until wk 5 when bedding was covered. Calves were fed MR twice daily (0700 and 1700 h) containing 24.5% crude protein (DM) and 19.8% fat (DM), and had access to pelleted starter (increased by 50 g/d if there were no refusals before weaning and then 200 g/d during and after weaning) and water starting on d 1. Calves arrived between 1 and 3 d of age and were enrolled into an 8-wk study, with calves undergoing step-down weaning during wk 7. Starting on d 35, an indwelling pH logger was inserted orally to monitor rumen pH until calves were dissected at the end of the study in wk 8. Higher SPS calves showed an increase in rumen pH magnitude (1.46 ± 0.07) compared with low SPS calves (1.16 ± 0.07), a decrease in rumen pH in wk 8 (high SPS: 5.37 ± 0.12; low SPS: 5.57 ± 0.12), and a decrease in haptoglobin in wk 8 (high SPS: 0.24 ± 0.06 g/L; low SPS: 0.49 ± 0.06 g/L). The majority of differences came from increased starter intake in general, which suggests that with completely pelleted starters the differences in starch and NDF do not elicit drastic changes in fermentation, subsequent end products, and any resulting inflammation in calves around weaning.

Performance and visceral tissue growth and development of Holstein calves fed differing milk replacer allowances and starch concentrations in pelleted starter.

The objectives of this study were to investigate how milk replacer (MR) allowance and differing concentrations of starch and neutral detergent fiber in starter alters visceral tissue and overall growth of the calf. Calves were randomly assigned to 1 of 4 dietary treatments (n = 12 per treatment) arranged in a 2 × 2 factorial based on daily MR allowance (MRA) and amount of starch in pelleted starter (SPS) as follows: 0.691 kg of MR/d [dry matter (DM) basis] with starter containing low or high starch (12.0% and 35.6% starch, respectively) and 1.382 kg of MR/day (DM) with starter containing low or high starch. All calves were housed in individual pens with straw bedding until wk 5 when bedding was covered to minimize intake. Calves were fed MR twice daily (0700 and 1700 h) containing 24.5% crude protein (DM) and 19.8% fat (DM), and had access to pelleted starter (increased by 50 g/d if there were no refusals before weaning, and then 200 g/d during and after weaning) and water starting on d 1. Calves arrived between 1 and 3 d of age and were enrolled into an 8-wk study, with calves undergoing step-down weaning during wk 7. Intakes were measured daily, and body weight (BW) and blood samples were recorded and collected weekly. Calves were dissected in wk 8 for visceral tissue measurements. Overall, there was increased MR DM intake for the high- (0.90 ± 0.01 kg/d; ± SE) compared with the low-MRA (0.54 ± 0.01 kg/d) calves, whereas starter DM intake increased in low- (0.47 ± 0.05 kg/d) compared with high-MRA (0.20 ± 0.05 kg/d) calves, which was driven by increases in wk 6, 7, and 8. High-MRA calves had increased BW during wk 2, 3, 4, 5, 6, and 7. The difference in BW disappeared by wk 8, with overall average daily gain having a tendency to be increased in high (0.57 ± 0.04 kg/d) compared with low-MRA (0.50 ± 0.04 kg/d) calves, whereas average daily gain was increased in high-MRA calves during wk 2 and 3 and increased in low-MRA calves during wk 7 and 8. There were several differences throughout visceral tissue measurements, but most notably, an increase in rumen mass (i.e., full, empty, and digesta weights) in low- compared with high-MRA calves, as well as in low- compared with high-SPS calves was observed. The length, width, and 2-dimensional area of rumen papillae were also increased in low- (area: 0.88 ± 0.03 mm2) compared with high-MRA (0.46 ± 0.03 mm2) calves. The majority of differences were attributed to increased MR allowance, which contributed to reduced pelleted starter intake by more than 50% and reduced rumen development, whereas differences in starch intake from the completely pelleted starter had minimal effects on overall growth and tissue measurements.

Hard to Kill: Inactivation of Plasmodiophora brassicae Resting Spores Using Chemical Disinfectants.

Biosafety practices, such as bioexclusion via sanitization, can prevent the spread of infectious soilborne threats such as the clubroot pathogen Plasmodiophora brassicae. Twenty-three chemical disinfectants were evaluated for efficacy against P. brassicae resting spores. Evans blue staining was used to directly measure the viability of P. brassicae resting spores after 20-min exposures to 10 concentrations of each of the 23 chemical disinfectants. Only nine disinfectants were capable of >95% inactivation, and only five were capable of inactivating >99% of resting spores. Bleach (sodium hypochlorite) and Spray Nine were the most effective disinfectants for inactivation of clubroot resting spores. AES 2500, SaniDate, and ethanol also inactivated >99% of resting spores but only at very high concentrations. A time course experiment showed that 10- to 12-min contact time was sufficient for ≥95% resting spore inactivation with Spray Nine and sodium hypochlorite, but ≥30-min contact was required for other disinfectants evaluated. These results will assist in guiding management recommendations for sanitization aimed at bioexclusion and biocontainment of P. brassicae.

Mortality and AIDS-defining events among young people following transition from paediatric to adult HIV care in the UK.

OBJECTIVES: To investigate risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV. METHODS: Records of people aged ≥ 13 years on 31 December 2015 in the UK paediatric HIV cohort (Collaborative HIV Paediatric Study) were linked to those of adults in the UK Collaborative HIV Cohort (CHIC) cohort. We calculated time from transition to a new AIDS event/death, with follow-up censored at the last visit or 31 December 2015, whichever was the earliest. Cumulative incidence of and risk factors for AIDS/mortality were assessed using Kaplan-Meier and Cox regression. RESULTS: At the final paediatric visit, the 474 participants [51% female, 80% black, 60% born outside the UK, median (interquartile range) age at antiretroviral therapy (ART) initiation = 9 (5-13) years] had a median age of 18 (17-19) years and CD4 count of 471 (280-663) cell/µL; 89% were prescribed ART and 60% overall had a viral load ≤ 400 copies/mL. Over median follow-up in adult care of 3 (2-6) years, 35 (8%) experienced a new AIDS event (n = 25) or death (n = 14) (incidence = 1.8/100 person-years). In multivariable analyses, lower CD4 count at the last paediatric visit [adjusted hazard ratio = 0.8 (95% confidence interval: 0.7-1.0)/100 cells/µL increment] and AIDS diagnosis in paediatric care [2.7 (1.4-5.5)] were associated with a new AIDS event/mortality in adult care. CONCLUSIONS: Young people with perinatally acquired HIV transitioning to adult care with markers of disease progression in paediatric care experienced poorer outcomes in adult care. Increased investment in multidisciplinary specialized services is required to support this population at high risk of morbidity and mortality.

Effects of mixed tocopherols added to milk replacer and calf starter on intake, growth, and indices of stress.

Vitamin E comprises 8 fat-soluble isoforms: α-, ß-, γ-, and δ-tocopherol and α-, ß-, γ-, and δ-tocotrienol. Yet the body preferentially uses α-tocopherol, and only α-tocopherol supplementation can reverse vitamin E deficiency symptoms. However, other isoforms influence many biological functions in the body, including inflammation and stress. Therefore, the study objective was to determine metabolic and performance responses in young calves fed diets containing a constant amount of α-tocopherol and increasing amounts of soybean oil-derived mixed γ- and δ-tocopherols. Holstein calves [n = 48; 2-3 d of age; 40.2 kg of initial body weight (BW), standard error = 0.54] were assigned to receive approximately 0, 5, 10, or 15 mg/kg of BW daily (treatments T0, T1, T2, and T3, respectively) of mixed tocopherols (TMIX) provided in milk replacer (MR) and calf starter. The TMIX liquid contained 86% γδ-tocopherols and 9% α-tocopherol. Milk replacers were formulated to contain approximately 0, 400, 800, or 1,200 mg of TMIX/kg for treatments T0, T1, T2, and T3, respectively. Calf starters were formulated to contain approximately 0, 250, 500, or 750 mg of TMIX/kg for treatments T0, T1, T2, and T3, respectively. Mean consumption of γδ-tocopherols was 0.0, 6.5, 14.3, and 20.5 mg/kg of BW, respectively. Milk replacer contained 24% crude protein (CP) and 20% fat on a dry matter (DM) basis. Calf starters were pelleted and offered for ad libitum consumption from 0 to 56 d. Starters contained 18 to 20% CP and 9 to 12% starch in the DM. On d 28, 4 calves per treatment were randomly selected for slaughter, and necropsy was performed. Samples of liver, duodenum, ileum, and trapezius muscle were collected and stored before analysis for α-, ß-, γ-, and δ-tocopherols and δ-tocotrienol. Data were analyzed using a completely randomized design using mixed model ANOVA with orthogonal polynomials to determine linear and quadratic effects of TMIX. Repeated-measures analyses were performed for data collected over time. Increasing dietary TMIX increased or tended to increase change in hip width at 28 and 56 d, respectively, and improved average daily BW gain and gain-to-feed ratio at 56 d. Increasing TMIX reduced plasma xanthine oxidase at 0 h and tended to reduce concentrations at 24 h following vaccination with 2 commercial vaccines on d 28; however, we detected no effect of TMIX following vaccination on d 56. Concentration of α-tocopherol in skeletal muscle declined quadratically with increasing TMIX, whereas ileal and liver γ-tocopherol increased linearly with increasing TMIX. The number of mucin-2 cells in the ileum increased more than 2-fold in calves fed T3. Addition of mixed tocopherols to diets of young dairy calves improved animal growth and altered indices of antioxidant metabolism.

Effects of milk replacer feeding rate and fat content on Jersey calf nutrient digestion and performance to 4 months of age.

This study evaluated effects of milk replacer (MR) feeding rate and fat concentration in MR on total-tract digestion (TTD) and growth performance in Jersey calves. Jersey heifer calves (n = 100, 2 blocks of 50; initially 30 ± 3.0 kg of body weight; 4-11 d of age) were randomly assigned to 1 of 4 treatments in a 2 × 2 factorial arrangement of MR feeding rate [454 g for 42 d, and 227 g for 7 d (MOD); or 454 g for 7 d, 681 g for 35 d, and 341 g for 7 d (HI), as-fed basis] and MR fat content (17 or 24% fat as-fed basis). Milk replacers (24% crude protein as-fed basis) were reconstituted to 14% solids and fed in 2 equal feedings for 42 d, and then mornings only for 7 d. Textured calf starter (21% crude protein, 40% starch, dry matter basis) and water were offered for ad libitum consumption. From d 57 to 112, calf starter was mixed with 5% chopped grass hay. Calves were housed individually to d 56 and housed in groups (4-5 calves/pen) from d 57 to 112. Estimates of TTD were measured in 5 calves/treatment (block 1) at wk 3 of the study using acid-insoluble ash as an indigestible marker. From 0 to 56 d, calf starter intake (CSI) was greater for MOD vs. HI and 17 versus 24% fat; average daily gain was greater for HI versus MOD; and hip width change was greater for 17 versus 24% fat. Estimates of organic matter TTD were greater for HI versus MOD, but neutral detergent fiber TTD was greater for MOD versus HI and for 17 versus 24% fat. From 57 to 112 d, hip height change was greater for MOD versus HI, and hip width change was greater for 17 versus 24% fat. In this study, feeding Jersey calves more MR improved preweaning average daily gain, but had a negative effect on CSI and likely rumen development, as neutral detergent fiber TTD was reduced at 3 wk and frame growth was reduced from d 57 to 112. This resulted in similar final calf body weights between MR feeding rates at the end of the study. No benefits were observed for feeding more fat in MR as CSI or for NDF digestibility, and frame growth was reduced.

Starch-protein interaction in the rumen of weaned dairy calves.

The objectives of this study were to investigate the effect of starch and protein interaction on rumen environment, in situ digestion, and total-tract digestibility of nutrients in weaned dairy calves between 8 and 16 wk of age. Sixteen rumen-cannulated calves were randomly divided into 4 dietary treatment groups with 4 calves fed in each treatment. The treatment diets had 2 levels of starch [18%, low starch (LS), or 38%, high starch (HS)] and 2 levels of protein [16%, low protein (LP), or 22%, high protein (HP)] on a dry matter (DM) basis in calf grower: (1) LPLS, (2) LPHS, (3) HPLS, and (4) HPHS. Calves were fed for ad libitum intake (95% assigned grower and 5% grass hay), and refusals were collected weekly. Total-tract digestibility collection and in situ digestibility procedures were performed for each calf at 11 and 15 wk. Samples for in situ digestibility, grass hay (GH), soybean hulls (SBH), wheat middlings (WM), ground corn (GrC), and soybean meal (SBM) were incubated for 9 and 24 h. There was no starch and protein interaction on total-tract digestibility of calves. Total-tract DM, neutral detergent fiber (NDF) and acid detergent fiber (ADF) digestibility, and feed efficiency were affected by both protein and starch inclusion level in calf diet. Total-tract starch digestibility was lower for LS diets. Dry matter digestibility and feed efficiency were greater in calves fed HP and HS diets compared with calves fed LP and LS diets, respectively. Fiber digestibility (NDF and ADF) was less in calves fed HS diets compared with calves fed LS diets but was greater in calves fed HP diets compared with calves fed LP diets. Level of protein did not affect in situ DM and NDF disappearance of GH, but HP increased in situ DM and NDF disappearance of SBH. High-starch diets decreased DM and NDF disappearance of both GH and SBH. At 20 h after feeding, ruminal pH was 0.51 unit higher in calves fed HPHS compared with calves fed LPHS. Total ruminal VFA and proportion of propionate was greater with HS versus LS, whereas proportion of acetate was greater with LS versus HS. The DM disappearance of SBM and WM and NDF disappearance of WM was greater for calves fed HPHS compared with calves fed LPHS at 11 wk of age. In our study, when HP was fed with HS, rumen pH, in situ digestion of WM and SBM, and total-tract digestion of DM, NDF, and ADF increased. This provides evidence for starch-protein interaction in the rumen of recently weaned dairy calves. Improvements in total-tract and in situ digestibility suggest that both protein and starch levels are important for 8- to 16-wk-old calves.

Models to predict dry feed intake in Holstein calves to 4 months of age.

Voluntary daily dry feed intake (DFI) in Holstein calves was predicted using 60,761 individual daily observations collected from 1,235 Holstein calves in 30 experiments from 4 research stations in the United States and Europe. Consumption of dry feed (calf starter and hay, kg/d or percent of body weight) was measured from 3 to 114 d of age. Linear models and 2- and 3-parameter nonlinear models were evaluated to predict DFI using age of calf, intake of milk replacer, ambient temperature, percent forage, and neutral detergent fiber concentration in ration dry matter (DM) as independent variables. The initial data set was randomly divided within study location into development (80% of all observations) and validation data sets, and initial screening was conducted using the development data set. Five nonlinear models and 3 linear models (candidate models) were identified and used in further model evaluation. Cross-validation studies (n = 20) with the validation data set were conducted by linear regression of DFI with predicted DFI as independent variable. Candidate models were subsequently evaluated with data from 12 published studies in 2 analyses. The exponential model that best predicted daily DFI in Holstein calves in original and external data sets was DFI (kg/d) = 1.3207 × e[(-5.3892 + 0.6376 × MEgap) × EXP(-0.0392 × Age)] - 0.0013 × Temp + 0.0032 × NDFDM + 0.0026 × Age × MEgap - 0.3646 × PctForage [coefficient of determination (R2) = 0.92, concordance correlation coefficient (CCC) = 0.96, and mean square error of prediction (MSEP) = 0.10 kg]; where MEgap (Mcal/d) = difference of daily metabolizable energy (ME) requirement and ME intake from milk replacer; Age = age of calf (d) from 3 to 114, Temp = mean daily ambient temperature (°C), NDFDM = ration neutral detergent fiber (% DM); PctForage = percent forage in ration DM. The linear model that best predicted DFI was DFI (kg/d = -0.1349 + 0.0106 × Age + 0.1808 × MEgap + 0.0013 × Age × MEgap + 0.0001 × Temp + 0.00002 × Age × Temp (R2 = 0.93, CCC = 0.96, and MSEP = 0.10 kg). When Temp and ration characteristics were not included, optimal models were 1.4362 × e[(-4.6646 + 0.5234 × MEgap) × EXP(-0.0361 × Age)] + 0.0025 × Age × MEgap (R2 = 0.92, CCC = 0.96, and MSEP = 0.11 kg) and -0.1344 + 0.0102 × Age + 0.1810 × MEgap + 0.0013 × Age × MEgap [R2 = 0.93, CCC = 0.96, and MSEP = 0.10 kg]. Models of daily DFI may improve prediction of nutrient supply to young Holstein calves to approximately 4 mo of age, thereby increasing prediction of growth performance.

Effects of feeding milk replacer at a moderate rate, ad libitum, or with a step-up program on Holstein calf growth performance to 4 months of age.

The objective of this study was to evaluate 3 milk replacer (MR) feeding programs on calf performance to 4 mo of age. Male Holstein calves (n = 48; 2-3 d old) were randomly assigned to either a moderate rate of MR (MOD; 0.66 kg/d for 39 d, then 0.33 kg/d for 3 d), an ad libitum rate of MR (ADLIB; offered twice daily between 0630 and 0830 h and between 1430 and 1630 h for 35 d, 0.66 kg/d for 4 d, and 0.33 kg/d for 3 d), or a step-up rate of MR (STEPUP; increased from 0.32 to 0.62 kg/d in first 12 d, 0.66 kg/d for 27 d, and 0.33 kg/d for 3 d). The MR (25% CP, 18% fat) was fed twice daily to d 39 and once daily thereafter. During the nursery phase (0-56 d), calves were housed in individual pens and offered textured starter (40% starch, 21% CP on a DM basis) and water ad libitum. Calf body weight (BW) was measured initially and weekly thereafter. Hip widths (HW) were measured initially and every 2 wk thereafter. In the grower phase, (57-112 d), calves were grouped by previous treatment and moved to group pens (4 calves/pen). The same starter used in the nursery phase was blended with 5% chopped grass hay and offered ad libitum. Calf BW and HW were measured on d 56, 84, and 112. Total MR intake per calf averaged 27, 51, and 25 kg for MOD, ADLIB, and STEPUP programs, respectively, with a range of 42 to 63 kg for ADLIB. In the nursery phase, starter intake and feed efficiency were less for ADLIB versus MOD, whereas fecal scores and abnormal fecal score days were greater for calves fed ADLIB versus MOD. Calves fed STEPUP had lesser average daily gain than calves fed MOD. During the grower phase, initial BW was greater for ADLIB versus MOD, though final BW was not different between MOD and ADLIB or STEPUP. Calves previously fed MOD had greater average daily gain, feed efficiency, and HW change than calves fed ADLIB. In this study, feed efficiency was lower when MR was fed ad libitum, and growth advantages observed at 2 mo were lost by 4 mo of age.

Effect of increasing the amount of hay fed on Holstein calf performance and digestibility from 2 to 4 months of age.

A good transition from a mainly liquid diet to a solid diet of concentrates and forages is important considering the small size and development of the calf's rumen. However, the optimal amount of hay or other high-fiber ingredients in the diet of recently weaned calves is not well defined. The objective of this trial was to determine the effects of feeding 0, 5, or 10% chopped grass hay (6.5% crude protein, 64.6% neutral detergent fiber) with a textured, high-starch starter (20.5% crude protein, 38.4% starch, 14.1% neutral detergent fiber; protein pellet, whole corn, and oats) on performance and digestion in Holstein steer calves between 2 and 4 mo of age. Forty-eight calves (initial body weight = 90.7 ± 2.15 kg) were housed in group pens (4 per pen) and fed diets and water for ad libitum intake. Feed offered and refused was measured daily. Calf body weight, hip width, and body condition score (1-5 scale) were measured initially and at 28 and 56 d. Fecal samples were collected from the pen floor with care not to sample bedding material and composited by pen during d 5-9, 26-30, and 47-51 to estimate apparent total-tract digestibility using acid-insoluble ash. Data were analyzed as a completely randomized design with repeated measures and pen as the experimental unit. As grass hay increased, dry matter intake (kg/d) decreased linearly but tended to change quadratically. Dry matter intake as a % of body weight changed quadratically with increasing hay, increasing from 0 to 5%, and decreasing from 5 to 10% hay. Average daily gain (1.15, 1.12, and 0.95 kg/d), feed efficiency (0.336, 0.319, and 0.309 kg of average daily gain/kg of dry matter intake), and hip width change (4.6, 4.7, and 4.1) decreased linearly with 0, 5, and 10% hay, respectively. Overall estimates of dry matter, organic matter, neutral detergent fiber, acid detergent fiber, and crude protein digestibility changed quadratically with hay, increasing from 0 to 5%, and decreasing from 5 to 10% hay, whereas digestibility of starch, sugar, and fat decreased linearly with increasing hay. Digestibility of dry matter, organic matter, neutral detergent fiber, and acid detergent fiber increased from 2 to 3 mo of age, and decreased from 3 to 4 mo of age. Digestibility of starch decreased linearly and digestibility of fat and crude protein increased linearly with age. Digestive capacity did not appear mature by 4 mo of age. Feeding 5% chopped hay supported optimal digestion and growth in calves 2 to 4 mo of age, which agrees with previously published research.

Continuation of emtricitabine/lamivudine within combination antiretroviral therapy following detection of the M184V/I HIV-1 resistance mutation.

OBJECTIVES: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. METHODS: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV-1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. RESULTS: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71-0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73-1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80-1.19) amongst those on tenofovir-containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54-0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64-1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34-1.11). CONCLUSIONS: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir.

Postweaning response on growth and nutrient digestion to using different weaning strategies when feeding moderate and high amounts of milk replacer to Holstein calves.

Many changes occur in the rumen as calves transition from consuming a liquid diet to a completely solid diet. These changes can influence growth and calf health, being greatly affected by preweaning diet as well as the transitional steps used to wean calves. A 2 × 2 factorial design of moderate [MOD; 0.66 kg of dry matter (DM)] or high (HI; up to 1.1 kg of DM) feeding rates of milk replacer (MR) and abrupt (AB; 7-d step-down) or gradual weaning (GR; 21-d step-down) was used to study how preweaning program affects calf performance from 2 to 4 mo of age. Calves (n = 50) were randomly assigned to 1 of the 4 preweaning treatments. For the following 56-d grower portion of the experiment, calves were grouped into 12 pens based on MR program, with 4 to 5 calves per pen. Data were analyzed as a completely randomized design, with repeated measures when applicable, by PROC MIXED in SAS (version 9.4; SAS Institute Inc., Cary, NC). All calves received ad libitum access to water and a textured starter [42% starch and 20% crude protein (CP)] blended with 5% chopped grass hay. Overall, apparent digestibility coefficients (dC) of DM, neutral detergent fiber, and acid detergent fiber were greater for MOD compared with HI, and apparent dC of DM and ADF were greater for GR than for AB. No significant differences were detected between organic matter, CP, fat, starch, or sugar dC based on treatment, and no interactions were observed. However, by d 56 only starch dC differed by treatment. Weaning body weight (BW), hip width (HW), and hip height (HH) were greater for HI compared with MOD calves. Weaning HH was greater for AB than for GR calves. However, final BW, HW, HH, and body condition score, as well as average daily gain, did not differ among treatments. An interaction occurred where feed efficiency (gain/feed) was reduced with GR weaning in MOD, whereas the opposite occurred in the HI group. When feeding calves a moderate level of MR, a several-step gradual weaning is not necessary to ensure growth and development; however, calves should be gradually weaned when offered a high level of MR.

Effects of milk replacer feeding rates on growth performance of Holstein dairy calves to 4 months of age, evaluated via a meta-analytical approach.

Our objective was to evaluate effects of feeding milk replacer (MR) at 2 feeding rates on digestion, intake, and growth of young dairy calves, via a meta-analytical approach using individual data. A database was developed from 10 published studies from the Nurture Research Center (Provimi; Brookville, OH), in which 26 dietary treatments and 491 calves from 0 to 8 wk of age in 13 nursery trials, and 22 dietary treatments and 485 calves from 8 to 16 wk of age in 13 grower trials occurred. Male Holstein calves (n = 491; initial body weight 42.8 ± 4.9 kg) were randomly assigned to 1 of 2 treatments: (1) moderate (MOD), 0.64 to 0.66 kg of dry matter (DM)/d for the first 35 to 39 d, followed by half the allotment per d for 3 to 7 d, fed at the a.m. feeding only; (2) high (HI), 0.92 to 1.07 kg of DM/d for the first 35 to 44 d, followed by half the allotment per d for 5 to 7 d, fed at the a.m. feeding only. Calves were weaned at 6 to 7 wk of age. Milk replacer ranged from 24.8 to 28.6% crude protein (CP) and 17.6 to 20.2% fat; starter ranged from 17.3 to 22.2% CP and 3.0 to 4.3% fat on a DM basis. On d 56 calves (n = 485) moved into pens (4 calves/pen) by treatments and were fed starter (19.4 to 22.3% CP and 3.4 to 4.6% fat, DM basis) blended with 5% hay until d 112. In all nursery trials (d 0 to 56), calves fed MOD had lower average daily gain (ADG; 0.634 vs. 0.545 kg/d), gain/DMI (0.488 vs. 0.466 kg/kg), and hip width change (0.069 vs. 0.064 cm/d), but greater starter intake (0.473 vs. 0.696 kg/d) compared with calves fed HI. Apparent total-tract digestibility of DM (73.3 vs. 78.4%), organic matter (OM; 74.1 vs. 79.0%), CP (74.8 vs. 78.9%), and neutral detergent fiber (NDF; 40.8 vs. 53.9%) were greater for calves fed MOD vs. HI when estimated during wk 8. In all grower trials (d 56 to 112), ADG (1.015 vs. 0.976 kg/d), gain/DMI (0.375 vs. 0.349 kg/kg), and hip width change (0.089 vs. 0.081 cm/d) were greater, but dry feed intake per kg of BW0.75 did not differ (87.8 vs. 88.2 g/d) for calves previously fed MOD vs. HI. Apparent digestibility of DM (78.7 vs. 76.0%), OM (79.8 vs. 77.0%), CP (80.5 vs. 78.4%), and NDF (54.8 vs. 45.8%) were greater for calves fed MOD vs. HI when estimated between wk 11 to 13. Over the entire 112-d period, calves fed MOD had lower ADG (0.805 vs. 0.784 kg/d) but tended to have greater hip width change (8.415 vs. 8.589 cm) compared with calves fed HI. Under the conditions of this study, feeding higher MR rates caused calves to partially lose growth advantage during the weaning transition and further decreased BW gain and structural growth in the grower period (d 56 to 112), which could be due to reductions in nutrient digestibility as a result of feeding more MR.

Effect of starter form, starch concentration, and amount of forage fed on Holstein calf growth from 2 to 4 months of age.

Young, weaned calves are commonly offered ad libitum forage with limited amounts of starter, in contrast to the suggested amount of approximately 5% forage in the diet due to the limited capacity of the rumen, as well as limited ability to digest high fiber feeds. The objective of this research was to compare 2 types of starters (low starch, pelleted vs. high starch, textured), both fed either ad libitum with 5% chopped hay, or fed at restricted rates with ad libitum long grass hay to calves between 2 and 4 mo of age. In trial 1, 48 calves were housed in group pens (68.4 ± 3.37 kg of initial body weight ± standard deviation; 3 pens of 4 calves/pen) and randomly assigned to 1 of 4 diets: (1) low starch pelleted starter (8% starch) blended with 5% chopped hay fed free choice; (2) high starch textured starter (45% starch) blended with 5% chopped hay fed free choice; (3) low starch pelleted starter (8% starch) fed at a rate up to 2.3 kg of dry matter (DM)/d, with free-choice long grass hay; or (4) high starch textured starter (45% starch) fed at a rate up to 2.3 kg of DM/d, with free-choice long grass hay. Trial 1 was analyzed as a completely randomized design using a 2 × 2 arrangement of treatments. Repeated measures were used as appropriate. Pen was the experimental unit. In trial 2, 48 calves (76.4 ± 1.55 kg of initial body weight; 6 pens of 4 calves/pen) were randomly assigned to 1 of 2 diets: (1) ad libitum access to a blend of 95% high starch textured starter (42% starch) and 5% chopped grass hay; or (2) high starch textured starter fed up to 2.7 kg of DM/d with free-choice long grass hay. Trial 2 was analyzed as for trial 1, without factorial arrangement. Trials were 56 d long. In trial 1, feed efficiency, average daily gain (ADG), and change in hip width were greater for calves fed high versus low starch diet. Final hip width, ADG, DM intake, and change in hip width were greater for calves fed limited chopped versus free-choice long hay diets. In trial 2, intake, feed efficiency, and all growth measurements were greater in calves fed the ad libitum mixed diet compared with those limit-fed starter up to 2.7 kg as fed with ad libitum hay. Ad libitum hay intake was highly variable among pens and differed up to 2.5-fold by the last week of the trials. In both trials, restricted feeding of starter with ad libitum long grass hay reduced total DM intake by 13 to 17%, ADG by 20%, and hip width change by 10 to 23% compared with a blend of 95% starter and 5% chopped grass hay fed ad libitum.

Effect of amount of milk replacer fed and the processing of corn in starter on growth performance, nutrient digestibility, and rumen and fecal fibrolytic bacteria of dairy calves.

The aim of this study was to evaluate effects of milk replacer (MR) feeding rate and processing of corn in calf starter (CS) on growth performance, nutrient digestibility, and rumen and fecal fibrolytic bacteria in dairy calves. Holstein male calves (n = 48, 2-3 d of age) were randomly assigned to 1 of 4 treatments with a 2 × 2 factorial arrangement of MR level of 0.749 kg of MR/d (LO) or up to 1.498 kg of MR/d (HI); and whole corn or flaked corn in textured CS. Calves were weaned by reducing MR offered by 50% during wk 6. Intakes of MR and CS were recorded daily, whereas body weight (BW) was measured weekly. Rumen fluid and fecal matter were collected at wk 5 and 8 to quantify fibrolytic bacteria and nutrient digestibility. Data were analyzed as a completely randomized design using mixed model ANOVA. Repeated measures were used as appropriate. Calves fed HI had greater average daily gain than calves fed LO at wk 2, 3, 4, and 5, yet at wk 7 calves fed HI had lower average daily gain compared with calves fed LO. Starter intake was greater for calves fed LO compared with HI at wk 4, 5, 6, and 7. During wk 5 and 8, calves fed LO had increased ADF and NDF digestibility compared with calves fed HI. During wk 5, dry matter and organic matter digestibility were lower for LO-fed calves compared with HI-fed calves, but during wk 8 the opposite was observed, with HI-fed calves having lower dry matter and organic matter digestibility than LO-fed calves. At wk 5, Clostridium cluster IV and Butyrivibrio fibrisolvens proportions in rumen fluid tended to be higher and Clostridium cluster IV, Fecalibacterium sp., and Prevotella sp. proportions in fecal matter were higher in calves fed LO compared with HI. From wk 8 to 16, dry matter intake was unaffected by treatment; however, energy efficiency was greater in calves fed LO, causing LO calves to have higher BW gain during this period. Greater starter digestibility was observed for calves fed LO versus HI in concert with increased fibrolytic bacteria proportions (wk 5) in fecal and rumen samples, which resulted in greater postweaning BW gain and similar BW and frame measurements by 16 wk of age. Overall the results show that rate of MR feeding has a larger effect than the processing of corn in CS on performance, fiber digestibility, and rumen and fecal fibrolytic bacterial communities.

Effects of colostrum and milk replacer feeding rates on intake, growth, and digestibility in calves.

Newborn Holstein male calves (n = 50) born on a single dairy farm were assigned randomly at birth to receive 3 feedings of 1.8 L of pooled maternal colostrum (MC) at 1, 6, and 12 h of age or 1 feeding of 500 g of a colostrum replacer reconstituted to 1.8 L at 1 h of age, followed by 2 feedings of 227 g of a commercial milk replacer (MR) reconstituted to 1.8 L at 6 and 12 h of age (CR). All feedings were administered by esophageal feeder. At 2 to 3 d of age, calves were transported to the experimental facility and assigned within colostrum group to receive 0.66 kg/d dry matter (DM) of MR to 39 d, and then 0.33 kg/d to 42 d (MRM) or 0.77 kg/d of MR DM to d 13, 1.03 kg/d for 22 d, and 0.51 kg/d for 7 d (MRH). The MR contained 25.8% crude protein and 17.6% crude fat (DM basis) and was based on whey proteins and lard as the primary fat source. Calf starter (21.7% crude protein, 15.7% neutral detergent fiber, 37.4% starch, DM basis) and water were available for ad libitum consumption throughout the 56-d study. Serum IgG and total protein were measured at 2 to 3 d of age. Intakes of MR and calf starter were monitored daily. Calf health and fecal scores were also monitored daily. Body weight was measured weekly, and hip width and body condition score were monitored every 2 wk. Digestion of DM, organic matter, crude protein, and ether extract were determined at 1 and 3 wk from 5 calves randomly selected within treatment and using chromic oxide as a digestibility marker added to the MR. Calves fed CR had lower serum IgG and total protein than calves fed MC. Also, calves fed CR grew more slowly, consumed less calf starter, and were less efficient to 56 d than calves fed MC. The number of days calves were treated with veterinary medications was higher when calves were fed CR. Calves fed MC-MRH gained more BW than other calves from 3 to 8 wk of age. Calves fed CR-MRH consumed less calf starter than other calves during wk 7 and 8. Digestion of nutrients at 1 and 3 wk of the study was unaffected by type of colostrum or level of MR fed and did not change from 1 to 3 wk. Over the first 2 mo of life, the calves fed MRH consumed less calf starter than calves fed MRM, but average daily gain or hip width change did not differ. One feeding of CR followed by 2 feedings of MR in the first 24 h likely reduced absorption of IgG from CR and contributed to differences in health and growth. Differences in animal performance observed in this study were unrelated to MR digestibility.