Resonant generation of propagating second-harmonic spin waves in nano-waveguides.

Generation of second-harmonic waves is one of the universal nonlinear phenomena that have found numerous technical applications in many modern technologies, in particular, in photonics. This phenomenon also has great potential in the field of magnonics, which considers the use of spin waves in magnetic nanostructures to implement wave-based signal processing and computing. However, due to the strong frequency dependence of the phase velocity of spin waves, resonant phase-matched generation of second-harmonic spin waves has not yet been achieved in practice. Here, we show experimentally that such a process can be realized using a combination of different modes of nano-sized spin-wave waveguides based on low-damping magnetic insulators. We demonstrate that our approach enables efficient spatially-extended energy transfer between interacting waves, which can be controlled by the intensity of the initial wave and the static magnetic field.

Effect of supplemental trace minerals on standard and novel measures of bull fertility.

Two studies were conducted to evaluate the effects of trace mineral supplementation on traditional and novel measures of bull fertility. In Experiment 1, 37 mature bulls received one of three dietary supplements daily for 71 d: 1) Supplement without Cu, Zn, and Mn (CON); 2) Supplement with Cu, Zn, and Mn sulfate (SULF); and 3) Supplement with basic Cu chloride, and Zn and Mn hydroxychloride (CHLR). In Experiment 2, 128 Angus or Angus-Hereford bull calves were maintained on a growing diet for 75 d (year 1) or 119 d (year 2) in Calan gate equipped pens without mineral supplementation. Bulls (n = 32 head/treatment) received one of four trace mineral supplements daily for 84 d: 1) Zn with no Cu (ZN), 2) Cu with no Zn (CU), 3) Cu and Zn (ZNCU), or 4) no Cu or Zn (CON). Bull fertility measures included a breeding soundness evaluation (BSE) and novel fertility measures conducted using flow cytometry. In mature bulls, final liver Zn concentration was positively correlated (P = 0.02) with sperm concentration (r = 0.31) and tended (P = 0.06) to be negatively correlated with acrosome damage (r = -0.39). Peripubertal bulls receiving ZNCU had greater ADG than bulls in the CU group (P = 0.05). Each BSE and novel fertility component improved from Day 0-84 in peripubertal bulls and were not affected (P > 0.10) by mineral supplementation. Bulls that received no supplement (CON) had greater (P < 0.01) percentage of sperm with distal midpiece reflex (6.9 vs 4.0% for CON and TM supplement, respectively) and Dag or Dag-like defect (2.6 vs 1.4% for CON and TM supplement, respectively) in their ejaculates. Sperm viability after 30 min of incubation were not affected by trace mineral supplementation, but after 3 h incubation, sperm viability tended to differ (P = 0.06) between treatments and tended to be less for CON bulls (48.5%) compared to ZNCU bulls (55.1%). Among contrast comparisons, trace mineral supplemented bulls had greater (P < 0.05) percentage of viable sperm at 3 h post collection and reactive oxygen resistant sperm than CON bulls. Addition of Zn to trace mineral containing Cu (ZNCU) improved (P < 0.05) percentage of sperm in the ejaculate with high mitochondrial energy potential and viable sperm with intact acrosome membrane. In summary, it appears the homeostasis mechanisms for bull trace mineral maintenance are extremely efficient and mineral supplementation of mature and peripubertal bulls did not have major improvements in any laboratory or chute-side measures of bull fertility, however bulls exposed to breeding or in environments with diet antagonists might respond differently.

Pre-synchronization of ovulation timing and delayed fixed-time artificial insemination increases pregnancy rates when sex-sorted semen is used for insemination of heifers.

This study was conducted to determine effects of pre-synchronization of ovulation timing among heifers and delayed fixed-time artificial insemination (TAI) with sex-sorted semen on proportion of heifers pregnant after TAI (PR/AI). Heifers were assigned to one of eight treatments: 1 and 2), 7-d CO-Synch + CIDR treatment regimen with administration of gonadotropin-releasing hormone and a CIDR insert on Day 0, prostaglandin F2α (PGF) at CIDR removal on Day 7, and TAI occurring 54 h later with conventionally processed (CTRL54-CNV) or sex-sorted semen (CTRL54-SEX); 3 and 4), same as CTRL54 but TAI delayed to 72 h with conventionally processed (CTRL72-CNV) or sex-sorted semen (CTRL72-SEX); 5 and 6), same as CTRL54 but additional administration of PGF on Day -7 and TAI with conventionally processed (PRE54-CNV) or sex-sorted semen (PRE54-SEX); 7 and 8), same as PRE54 treatments but TAI delayed to 72 h with conventionally processed (PRE72-CNV) or sex-sorted semen (PRE72-SEX). Proportion of heifers pregnant after TAI was greater (P ≤  0.02) with conventionally processed semen compared with sex-sorted semen, yet PR/AI did not differ (P =  0.14) between heifers in PRE72-CNV and PRE72-SEX groups. There were greater PR/AI in the PRE72-SEX (P =  0.03) than CTRL54-SEX group (46.1 % and 36.9 %) and there was no difference (P =  0.31) in PR/AI between CTRL54-CNV and PRE72-SEX groups (50.4 % and 46.1 %). In conclusion, pre-synchronization of ovulation timing among heifers combined with delayed TAI resulted in increased PR/AI with sex-sorted semen compared with the 7-d CO-Synch+CIDR treatment regimen.

Transparency and sustainability in global commodity supply chains.

Over the last few decades rapid advances in processes to collect, monitor, disclose, and disseminate information have contributed towards the development of entirely new modes of sustainability governance for global commodity supply chains. However, there has been very little critical appraisal of the contribution made by different transparency initiatives to sustainability and the ways in which they can (and cannot) influence new governance arrangements. Here we seek to strengthen the theoretical underpinning of research and action on supply chain transparency by addressing four questions: (1) What is meant by supply chain transparency? (2) What is the relevance of supply chain transparency to supply chain sustainability governance? (3) What is the current status of supply chain transparency, and what are the strengths and weaknesses of existing initiatives? and (4) What propositions can be advanced for how transparency can have a positive transformative effect on the governance interventions that seek to strengthen sustainability outcomes? We use examples from agricultural supply chains and the zero-deforestation agenda as a focus of our analysis but draw insights that are relevant to the transparency and sustainability of supply chains in general. We propose a typology to distinguish among types of supply chain information that are needed to support improvements in sustainability governance, and illustrate a number of major shortfalls and systematic biases in existing information systems. We also propose a set of ten propositions that, taken together, serve to expose some of the potential pitfalls and undesirable outcomes that may result from (inevitably) limited or poorly designed transparency systems, whilst offering guidance on some of the ways in which greater transparency can make a more effective, lasting and positive contribution to sustainability.

Haematobia irritans parasitism of F1 yak × beef cattle (Bos grunniens × Bos taurus) hybrids.

The horn fly Haematobia irritans (Diptera: Muscidae) is a blood obligate ectoparasite of bovids that causes annual losses to the U.S. beef cattle industry of over US$1.75 billion. Climate warming, the anthropogenic dispersion of bovids and the cross-breeding of beef cattle with other bovid species may facilitate novel horn fly-host interactions. In particular, hybridizing yaks [Bos grunniens (Artiodactyla: Bovidae)] with beef cows (Bos taurus) for heterosis and carcass improvements may increase the exposure of yak × beef hybrids to horn flies. The present paper reports on the collection of digital images of commingled beef heifers (n = 12) and F1 yak × beef hybrid bovids (heifers, n = 7; steers, n = 5) near Laramie, Wyoming (∼ 2200 m a.s.l.) in 2018. The total numbers of horn flies on beef heifers and F1 yak × beef heifers [mean ± standard error (SE): 88 ± 13 and 70 ± 17, respectively] did not differ significantly; however, F1 yak × beef steers had greater total horn fly abundance (mean ± SE: 159 ± 39) than female bovids. The present report of this experiment is the first such report in the literature and suggests that F1 yak × beef bovids are as susceptible as cattle to horn fly parasitism. Therefore, similar monitoring and treatment practices should be adopted by veterinarians, entomologists and producers.

Influence of post-insemination nutrition on embryonic development in beef heifers.

Previous studies have demonstrated that a decrease in nutrition immediately following AI reduces pregnancy success in beef heifers. The objective of this experiment was to determine if nutrient restriction following AI impacted early embryonic development among non-super ovulated heifers. Beef heifers in eight replications (Rep; Rep 1; n = 14, Rep 2; n = 15, Rep 3; n = 15, Rep 4; n = 14, Rep 5; n = 15, Rep 6; n = 15, Rep 7; n = 25, Rep 8; n = 25) across two locations (UMN, SDSU) were developed in a dry-lot and fed 125% NRC requirements from weaning to timed-AI (d 0). Heifers were timed-AI to a single sire in all replications. Immediately following AI, heifers were assigned, based on age, weight, and estrous response to one of two post-AI nutritional treatments. Half the heifers in each replication continued on the pre-insemination diet, serving as the control treatment (CON) and the remaining heifers were restricted to a sub-maintenance diet (RES). At UMN, heifers in the RES treatment were fed the same diet, but intake was limited to 80% NEm, while at SDSU, DMI remained the same, but diet composition was altered with the addition of straw to reduce NEm to 50% of requirements. On d 6, single embryos were collected nonsurgically and recovered embryos (CON; n = 46, RES; n = 42) were evaluated to determine quality (grade 1-9) and stage (1-4). Embryos were then stained and evaluated to determine the number of dead cells and total blastomeres. In Reps 1 through 6, concentrations of IGF-1 were assessed on d 0 and 6 and progesterone concentrations on d 4 and 6. Data were analyzed using the Mixed procedures of SAS. There were no treatment by Rep or treatment by location interactions for any embryo parameter evaluated, thus all data were pooled. Embryo stage and quality were improved (P < 0.01) in the CON (4.4 ± 0.16, 2.2 ± 0.19, respectively) compared to RES treatment (3.7 ± 0.16, 2.9 ± 0.19, respectively). Embryos in the CON treatment had greater total blastomeres (66.9 ± 5.05; P < 0.01) and tended to have a greater percentage of live cells (P < 0.10; 80.9 ± 4.19%) compared to RES (47.9 ± 5.41; 69.7 ± 4.39%, respectively). Progesterone and IGF-1 concentrations did not differ between treatments. In summary, nutrient restriction for 6 days immediately following AI resulted in poorer quality embryos that were delayed in stage of development, suggesting that immediate changes in nutritional status after insemination can alter early embryonic development.

Understanding the patient's lived experience of neovascular age-related macular degeneration: a qualitative study.

PURPOSE: In industrialised populations age-related macular degeneration (ARMD) is the leading cause of visual disability of the elderly. Successful new treatment with anti-endothelial growth factors for neovascular-classified ARMD has led to a divergence in treatment and experiences of people ARMD. This study aimed to understand the participant's experience of neovascular ARMD, including ongoing treatment with anti-vascular endothelial growth factor. METHODS: Twenty-five participants from one clinical site were qualitatively interviewed to elicit their experiences of treatment for neovascular ARMD. RESULTS: Two major themes were identified. A life negotiated by neovascular ARMD captures the participants' experience of living with the condition and treatment regime for neovascular ARMD. The second major theme: Uncertainty displayed their appraisal of life, treatment and their perceived future. CONCLUSIONS: Anxieties concerning the injections, new limitations to lifestyles, and an uncertain future all emerged from the data analysis. However, thankfulness for the treatment, the importance of familiar patterns in treatments and recovery and a guarded optimism also emerged. Knowledge of the experiences, anxieties and concerns of this patient population can be used to inform clinical practice and lead to patient-centred care.

The requirement of GnRH at the beginning of the five-day CO-Synch + controlled internal drug release protocol in beef heifers.

The objective of this study was to determine if the omission of GnRH at controlled internal drug release device (CIDR) insertion would impact pregnancy rates to timed AI (TAI) in beef heifers enrolled in a 5-d CO-Synch + CIDR protocol that used 1 PGF2α dose given at CIDR removal. Yearling beef heifers in Ohio in 2 consecutive breeding seasons (2011, n = 151, and 2012, n = 143; Angus × Simmental), Utah (2012, n = 265; Angus × Hereford), Idaho (2012, n = 127; Charolais), and Wyoming (2012, n = 137; Angus) were enrolled in the 5-d CO-Synch + CIDR protocol. At CIDR insertion (d -5), heifers were randomly assigned either to receive 100 µg GnRH (GnRH+; n = 408) or not to receive GnRH (GnRH-; n = 415). At CIDR removal (d 0 of the experiment), 25 mg PGF2α was administered to all heifers. All heifers were inseminated by TAI and given 100 µg GnRH 72 h after PGF2α (d 3). In heifers at the Ohio locations (n = 294), presence of a corpus luteum (CL) at CIDR insertion (d -5) was determined via assessment of progesterone concentrations (2011) and ovarian ultrasonography (2012). Subsequently, in both years, ovarian ultrasound was conducted on d 0 to determine the presence of a new CL. In this same subgroup of heifers, blood samples for progesterone analysis were collected on d 3 to assess luteal regression. Pregnancy diagnosis was performed between 32 and 38 d after TAI. At CIDR withdrawal, presence of a new CL was greater (P < 0.05) in the GnRH+ (55.8%, 82/147) than GnRH- (26.5%, 39/147) treatment. Incidence of failed luteal regression did not differ between the GnRH+ (3.4%) and GnRH- (0.7%) treatments. Pregnancy rate to TAI did not differ between the GnRH+ (50.5%) and GnRH- (54.9%) treatments. In conclusion, although the incidence of a new CL at CIDR removal was increased in the GnRH+ treatment, omission of the initial GnRH treatment in the 5-d CO-Synch + CIDR protocol did not influence TAI pregnancy rate in yearling beef heifers. In addition, a single dose of PGF2α at CIDR removal was effective at inducing luteolysis in yearling beef heifers enrolled in the 5-d CO-Synch + CIDR protocol, regardless of whether or not the initial GnRH treatment was given.

Comparison of three CIDR-based fixed-time AI protocols in beef heifers.

Several effective fixed-time AI (FTAI) protocols have been developed to facilitate AI in beef heifers that circumvent the need for estrus detection. Among these are the 5-d CO-Synch + controlled intravaginal progesterone insert (CIDR) protocol (5dCO), PGF2α (PG) 6-d CIDR protocol (PG-6dCIDR), and 14-d CIDR-PG protocol (14dCIDR-PG). Although each of these protocols varies in duration and approach to synchronizing estrus and ovulation, each has been reported as an effective method to facilitate FTAI in beef heifers. Therefore, the objective of this study was to compare FTAI pregnancy rates in beef heifers synchronized with these 3 CIDR-based protocols. Virgin beef heifers (n = 801) at 4 locations were synchronized with 1 of 3 protocols: 1) 5dCO, an injection of GnRH (100 µg) and insertion of a CIDR on d -5, PG (25 mg) and CIDR removal on d 0 with a second injection of PG (>4 h after CIDR removal) on d 0 and FTAI at 72 h after CIDR removal, 2) PG-6dCIDR, PG (25 mg) on d -9, GnRH (100 µg) and insertion of a CIDR on d -6, PG and CIDR removal on d 0, and FTAI at 66 h after CIDR removal, or 3) 14dCIDR-PG, a 14-d CIDR insert from d -30 to -16, PG (25 mg) on d 0, and FTAI at 66 h after PG. All heifers received an injection of GnRH (100 µg) concurrent with FTAI. Timing of treatment initiation was offset to allow all heifers to receive FTAI concomitantly and at random. Pregnancy success was determined between 35 and 40 d after FTAI by transrectal ultrasonography. Blood samples were collected before the beginning of each protocol and at the initiation of each protocol to determine estrous cycling status (77%). Data were analyzed using the GLIMMIX procedures of SAS. As expected, because of the duration of protocols, fewer heifers in the 14dCIDR-PG treatment were pubertal at initiation of synchronization than in the 5dCO (P < 0.05) and PG-6dCIDR (P = 0.10) treatments. Fixed-time AI pregnancy success did not differ between treatments (P = 0.14; 62.6%, 56.9%, and 53.3% for 5dCO, PG-6dCIDR, and 14dCIDR-PG, respectively). However, heifers that had reached puberty by initiation of synchronization had greater (P < 0.01) pregnancy success compared to heifers that were prepubertal (60.7% and 47.3%, respectively). In summary, all 3 protocols had similar FTAI pregnancy success, and puberty status had the greatest impact on pregnancy success.

Early metabolic imprinting events increase marbling scores in fed cattle.

Early weaning of calves to a high concentrate diet results in greater fat deposition and suggests early postnatal metabolic imprinting events may be exploited as a management tool to improve cattle value. Our objective was to implement a short, high energy dietary intervention before a typical grazing period to manipulate intramuscular fat deposition in finishing cattle. Fall-born, Angus-sired steer calves (n = 24) were stratified by sire and randomly assigned to normal weaned (NW) or metabolic-imprinted (MIP) treatments. At 105 ± 6d (135kg), MIP calves were transitioned to a diet containing 20% CP and 1.26 Mcal/kg NEg. Metabolic-imprinted calves were fed ad libitum as a group. Normal weaned calves remained on their dam until 253 ± 6 d of age. At this time, treatment groups were combined and grazed for 156 d on a mixed summer pasture. Following the grazing phase, steers were adapted to a corn silage-based feedlot diet and performance was monitored on 28-d intervals. Calves were staged for harvest based on backfat endpoint (target 1.0 to 1.2 cm). Metabolic-imprinted calves were heavier (P < 0.05) than NW calves (341 vs. 265 ± 4.2 kg) at normal weaning age. During the grazing phase, NW steers gained more weight than (P < 0.05) MIP steers (0.69 vs. 0.35 ± 0.03 kg/d). Feedlot performance and USDA yield grade were similar (P > 0.20) between treatments. However, MIP steers produced heavier (P < 0.05) carcasses (564 vs. 524 ± 5.6 kg) with higher (P < 0.001) marbling scores (645 vs. 517 ± 23). Therefore, calves consuming a high concentrate diet for 148 d after early weaning produced higher quality carcasses. This suggests early weaning and feeding a high concentrate before grazing is a viable strategy to increase marbling deposition compared with a traditional production system.

Cross-Linked Fiber Network Embedded in Elastic Matrix.

The mechanical behavior of a three-dimensional cross-linked fiber network embedded in matrix is studied in this work. The network is composed from linear elastic fibers which store energy only in the axial deformation mode, while the matrix is also isotropic and linear elastic. Such systems are encountered in a broad range of applications, from tissue to consumer products. As the matrix modulus increases, the network is constrained to deform more affinely. This leads to internal forces acting between the network and the matrix, which produce strong stress concentration at the network cross-links. This interaction increases the apparent modulus of the network and decreases the apparent modulus of the matrix. A model is developed to predict the effective modulus of the composite and its predictions are compared with numerical data for a variety of networks.

Effects of feeding corn modified wet distillers grain plus solubles co-ensiled with chopped whole plant corn on heifer growth performance and diet digestibility in beef cattle.

Two experiments were conducted to evaluate the effect of feeding corn modified wet distillers grain plus solubles (MWDGS; 48% DM) co-ensiled with chopped whole plant corn (WC) on growth performance, dietary intake, and nutrient digestibility of beef cattle. In Exp. 1, 96 Angus-crossed heifers (2 yr old; 522 ± 49.1 kg BW; 5.3 ± 0.1 BCS) were stratified and blocked according to BW and stratified by BCS in each block in a randomized complete block design (24 pens; 4 heifers/pen; 6 treatment replications). Groups were assigned to 1 of 4 dietary treatments for a 62 d trial. Treatments were 1) corn silage (CS) and soybean meal (CON), 2) MWDGS co-ensiled with chopped whole plant corn (WC; CO-EN), 3) CS mixed with MWDGS at feeding (CS+WDG), and 4) CS mixed with dry distillers grain plus solubles (DDGS) at feeding (CS+DDG). In Exp. 2, 4 crossbred beef steers (initial BW = 278 ± 18 kg) fitted with permanent ruminal cannulas were used in a balanced 4 × 4 Latin square to test the effects of feeding MWDGS co-ensiled with WC on DM intake, ruminal fermentation characteristics, and total tract digestibility. There were four 14-d periods, with 10 d for diet adaptation and 4 d for samples collection. Orthogonal contrasts were used and compared CON vs. diets containing distillers grains (DGD), CO-EN vs. diets where distillers grains were mixed at feeding (MIX), and CS+WDG vs. CS+DDG. In Exp. 1, the CON fed heifers resulted in greater G:F (P = 0.04) compared with those fed DGD. However, ADG (P = 0.03), final BW (P = 0.04), and BW gain (P = 0.03) were greatest for DGD diets compared with CON and greatest (P = 0.04) for CO-EN when compared with MIX. Apart from a slightly greater acetate concentration (P = 0.05), which resulted in a greater acetate to propionate ratio (P = 0.03) for the CON diet compared with DGD, no important differences were observed on intake, diet digestibility, or fermentation characteristics when comparing the CON treatment with DGD or when comparing CS+WDG with CS+DDG. However, the CO-EN diet resulted in decreased DMI (P = 0.05) and consequently decreased OM (P = 0.05), N (P = 0.04), and NDF (P = 0.02) intakes compared with MIX. Data from these studies suggest that MWDGS co-ensiled with WC can successfully replace traditional corn-based diets supplemented with soybean meal and corn silage diets supplemented with distillers grains without compromising digestibility and growth performance in pregnant heifers.

Mortality, morbidity and evidence-based management amongst patients in regional New Zealand with severe left ventricular systolic dysfunction (1997-2011).

BACKGROUND: Heart failure and its management represents a significant health burden, the extent of which is poorly understood in regional New Zealand. AIMS: To investigate mortality, quality of life, hospitalisation, and evidence-based medical and device management of severe left ventricular (LV) systolic dysfunction in a regional New Zealand setting. METHODS: A retrospective case series was undertaken of 1126 patients with a LV ejection fraction <36% on transthoracic echocardiograms performed between 1 October 1997 and 31 March 2011 in Nelson Marlborough District Health Board. All-cause mortality and hospitalisation data were analysed for all participants. Substudies were undertaken regarding pharmacotherapy, demographics, implantable cardioverter-defibrillator implantation rates and quality of life based on the EQ-5D questionnaire and New York Heart Association class. RESULTS: Five-year cumulative survival was 44.5%. The mean annual medical admission rate was 204/100 000; 54.84% of which were readmissions in the same year. Prescription rates for angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, beta-blockers and spironolactone were 68.3%, 74.2% and 24.9%, respectively, with only 17.6%, 19.0% and 16.4% on maximum recommended doses. implantable cardioverter-defibrillator devices were inserted in 11.5% of eligible patients. Quality of life was impaired in patients <70 years relative to the age-approximated New Zealand index population. Mean EQ-5D visual analogue score was 72.6 ± 0.032 and self-reported New York Heart Association class 2.09 ± 0.107 CONCLUSION: Patients with severe LV systolic dysfunction in this regional New Zealand community experience similar mortality and first hospitalisation rates to those seen elsewhere in patients with clinical heart failure, but a greater number of readmissions. Medical and device therapy utilisation was suboptimal, and quality of life impaired, together supporting the need for a dedicated heart failure service.

Molecular pathology of uveal melanoma.

Like other cancers, uveal melanomas (UM) are characterised by an uncontrolled, clonal, cellular proliferation, occurring as a result of numerous genetic, and epigenetic aberrations. Signalling pathways known to be disrupted in UM include: (1) the retinoblastoma pathway, probably as a result of cyclin D1 overexpression; p53 signalling, possibly as a consequence of MDM2 overexpression; and the P13K/AKT and mitogen-activated protein kinase/extracellular signal-related kinase pathway pathways that are disturbed as a result of PTEN and GNAQ/11 mutations, respectively. Characteristic chromosomal abnormalities are common and include 6p gain, associated with a good prognosis, as well as 1p loss, 3 loss, and 8q gain, which correlate with high mortality. These are identified by techniques such as fluorescence in situ hybridisation, comparative genomic hybridisation, microsatellite analysis, multiplex ligation-dependent probe amplification, and single-nucleotide polymorphisms. UM can also be categorised by their gene expression profiles as class 1 or class 2, the latter correlating with poor survival, as do BRCA1-associated protein-1 (BAP1) inactivating mutations. Genetic testing of UM has enhanced prognostication, especially when results are integrated with histological and clinical data. The identification of abnormal signalling pathways, genes and proteins in UM opens the way for target-based therapies, improving prospects for conserving vision and prolonging life.

Conjunctival melanoma and melanocytic intra-epithelial neoplasia.

The rarity of conjunctival melanoma has impeded progress in the management of patients with this cancer; however, much progress has occurred in recent years. Primary acquired melanosis is now differentiated histologically into hypermelanosis and conjunctival melanocytic intra-epithelial neoplasia, for which an objective reproducible scoring system has been developed. Mapping and clinical staging of conjunctival disease has improved. Adjunctive radiotherapy and topical chemotherapy have made tumour control more successful, with reduced morbidity. Genetic analyses have identified BRAF and other mutations, which may predict responsiveness to new chemotherapeutic agents, for example Vemurafenib, should metastatic disease develop. Multicentre studies are under way to enhance survival prediction by integrating clinical stage of disease with histological grade of malignancy and genetic abnormalities. Such improved prognostication would not only be more relevant to individual patients, but would also provide greater opportunities for basic science research.

Determination of the appropriate delivery of prostaglandin F2α in the five-day CO-Synch + controlled intravaginal drug release protocol in suckled beef cows.

The objective of this experiment was to determine if 2 doses of prostaglandin F(2α) (PGF) administered concurrently at controlled intravaginal drug release (CIDR) removal was an efficacious method for delivery of PGF in the 5-d CO-Synch + CIDR protocol. Postpartum beef cows (n = 2,465) from 13 herds in 8 states were enrolled in the 5-d CO-Synch + CIDR protocol and assigned to receive 2 doses of PGF (25 mg/dose) 8 h apart with the initial injection given at CIDR insert removal (8h-PGF), 2 doses (25 mg/dose) of PGF delivered in 2 injection sites, both administered at CIDR insert removal (Co-PGF), or a single 25-mg dose of PGF at CIDR insert removal (1x-PGF). Cows were fixed timed-artificially inseminated (FTAI) 72 h after CIDR removal concurrent with GnRH administration. Estrus-cycling status (54% cyclic) was determined by evaluation of progesterone in 2 blood samples collected before CIDR insertion. Determination of pregnancy was performed by transrectal ultrasonography 39 ± 0.1 d after FTAI and at least 35 d after the conclusion of the breeding season. Fixed timed-AI pregnancy rates were greater (P < 0.05) for the 8h-PGF (55%) than the 1x-PGF (48%) treatment, with the Co-PGF (51%) treatment intermediate and not different (P > 0.10) from the other treatments. Contrast analysis demonstrated that cows receiving 50 mg of PGF (8h-PGF and Co-PGF) had greater (P < 0.05) FTAI pregnancy rates than those receiving 25 mg (1x-PGF). Pregnancy rates to FTAI were greater (P < 0.05) in cyclic (55%) than noncyclic (47%) and greater (P < 0.05) in multiparous (≥3 yr of age; 54%; n = 1,940) than primiparous cows (40%; n = 525). Luteolysis after PGF treatment was assessed in a subset of cows (n = 277) and treatment tended (P = 0.09) to affect the proportion of cows having luteolysis. The percentage of cows that had luteolysis was least in the 1x-PGF treatment (89%) and greatest in the 8h-PGF treatment (97%), with the Co-PGF treatment (94%) being intermediate. Breeding season pregnancy rate (88%) did not differ (P > 0.10) among treatments but was greater (P < 0.01) in multiparous (90%) than primiparous (78%) cows. In summary, 50 mg of PGF was required in the 5-d CO-Synch + CIDR protocol to maximize pregnancy rates; however, pregnancy rate did not differ when 50 mg of PGF was administered simultaneously with CIDR removal or split with 25 mg administered at 0 and 8 h after CIDR removal.

Effects of feeding corn modified wet distillers grain plus solubles co-ensiled with direct-cut forage on feedlot performance, carcass characteristics, and diet digestibility of finishing steers.

Two experiments were conducted to evaluate the effects of feeding corn modified wet distillers grain plus solubles (MWDGS) co-ensiled with direct-cut forage (DC) to beef steers, on feedlot performance and total tract digestibility. In Exp. 1, sixty-four crossbred Angus steers (n = 64; 329 ± 43 kg) were blocked by BW and randomly assigned to 1 of 4 dietary treatments: 1) corn-silage and soybean meal (CON), 2) DC co-ensiled with MWDGS (CO-EN), 3) haylage mixed with MWDGS at feeding (H+WDG), and 4) haylage mixed with dry distillers grains plus solubles at feeding (H+DDG). Steers were harvested when they reached an endpoint of 1.1 cm of 12th-rib back fat. In Exp. 2, four ruminally cannulated beef steers (initial BW = 556 ± 31 kg) were used in a 4 × 4 Latin square to evaluate digestibility of diets used in Exp. 1. Experimental periods were 14 d in length with 10 d for diet adaptation and 4 d for sample collection. Three linear orthogonal contrasts were used to compare effects of 1) CON vs. diets containing distillers grains (DGD), 2) CO-EN vs. diets where distillers grains were mixed at feeding (MIX), and 3) H+WDG vs. H+DDG. In Exp. 1, DMI was less (P < 0.001) for steers fed CON compared with those fed DGD and greatest (P < 0.001) for steers fed CO-EN compared with MIX. Corn-silage- and soybean-meal-fed steers had more days on feed than those fed DGD (P = 0.001). Body weight gain (P = 0.02) was greater for CO-EN compared with MIX. Fat thickness at the 12th and 13th ribs was greater (P = 0.03) for DGD steers compared with CON steers. Hot carcass weight was greater (P = 0.03) for steers fed CO-EN compared with those fed MIX. Steers fed CON resulted in greater marbling scores (P = 0.01) compared DGD-fed steers. Longissimus muscle area was greater (P = 0.01) for CON-fed steers compared with all other treatments. In Exp. 2, no differences (P > 0.10) in DM, OM, or N intakes were observed. Apparent total tract DM (P = 0.01) and N (P = 0.02) digestibility were greatest in steers fed CON compared with all others. Steers fed DGD had less (P = 0.02) rumen NH(3) concentrations compared with CON. The CON diet resulted in greater molar concentrations of VFA (P = 0.03) and decreased acetate to propionate ratio (P = 0.03) compared with all DGD. These data suggest that feeding MWDGS co-ensiled with direct-cut forage results in reduced diet digestibility but equal or greater feedlot performance and similar carcass and characteristics when compared with a corn diet supplemented with soybean meal and diets where MWDGS and DDGS were added at the mixer.

Alemtuzumab more effective than interferon ß-1a at 5-year follow-up of CAMMS223 clinical trial.

OBJECTIVE: To report the long-term safety and efficacy results from CAMMS223 comparing alemtuzumab with interferon ß-1a in early, active relapsing-remitting multiple sclerosis (RRMS). What are the long-term effects of alemtuzumab treatment, received 36 to 48 months previously, on relapse and disability in early, active RRMS? This study provides evidence of the effectiveness of alemtuzumab in reducing the relapse rate and accumulation of disability compared with interferon ß-1a (IFNß-1a) through extended follow-up (up to 60 months from baseline). METHODS: Of 334 patients originally randomized, 198 participated in the extension phase (151 [68%] alemtuzumab and 47 [42%] IFNß-1a). Disability, relapses, and safety were assessed as in the original study period. Efficacy outcomes were analyzed from baseline of the original trial period to 60 months. Safety data extended beyond 60 months. RESULTS: Over 5 years, alemtuzumab lowered the risk of sustained accumulation of disability by 72% and the rate of relapse by 69% compared with IFNß-1a (both p < 0.0001). The annualized relapse rate from baseline to month 60 was 0.11 for alemtuzumab and 0.35 for IFNß-1a. Complete safety follow-up reflected 988 and 376 person-years for alemtuzumab and IFNß-1a patients, respectively. Serious infections were seen in 7% of alemtuzumab patients and 3% of IFNß-1a patients, and thyroid disorders were seen in 30% of alemtuzumab patients vs 4% of IFNß-1a patients. Immune thrombocytopenia occurred in 3% of alemtuzumab patients and 0.9% of IFNß-1a patients during the initial study period; no additional events were reported during the extension phase. One alemtuzumab patient developed Goodpasture disease 39 months after the second annual cycle of alemtuzumab. CONCLUSIONS: Through extended follow-up, alemtuzumab remained significantly more efficacious than IFNß-1a, with a safety profile consistent with previous reports. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that alemtuzumab is more effective than interferon ß-1a in reducing relapses and disability in patients with RRMS in a long-term follow-up of a rater-blinded, randomized clinical trial with 59.5% of patients participating in the extended follow-up period.

A single-arm, open-label study of alemtuzumab in treatment-refractory patients with multiple sclerosis.

BACKGROUND: Alemtuzumab (CD52-specific humanized monoclonal antibody) was found to be an effective therapy for treatment-naive patients with relapsing-remitting multiple sclerosis. OBJECTIVE: Evaluate alemtuzumab's effects in patients with treatment-refractory relapsing-remitting multiple sclerosis. METHODS: Forty-five relapsing-remitting multiple sclerosis patients who experienced ≥2 relapses during 2 years prior to the study entry whilst receiving interferon therapy were administered 24 mg i.v. alemtuzumab/day for 5 days at baseline and 3 days 12 months later. Patients received premedication with 1 g i.v. methylprednisolone on days 1-3 at both times. RESULTS: After 2-year follow-up, the annualized relapse rate was reduced by 94% compared to pre-treatment levels, from 1.6 (2 years prior to treatment) to 0.17 for the 2 years following (P<0.0001). Moreover, 86% of patients showed stable or improved scores on the Expanded Disability Status Scale, and only 1 experienced an increase in disability lasting ≥6 months. The majority (70-88%) showed stable or improved leg, arm and cognitive function as measured by the Multiple Sclerosis Functional Composite. Serious adverse events observed in single patients were transient neutropenia and pneumonia, pulmonary emboli and deep vein thrombosis. Five patients developed clinical thyroid disorders but no opportunistic infections or cases of immune thrombocytopenic purpura were observed. CONCLUSIONS: Alemtuzumab effectively reduced relapse rates and improved clinical scores in patients with active relapsing-remitting multiple sclerosis not controlled by interferon therapy.