A survey in the West Midlands of the United Kingdom of current practice in managing hypotension in lower segment caesarean section under spinal anaesthesia.

BACKGROUND: Spinal anaesthesia, the most common form of anaesthesia for caesarean section, leads to sympathetic blockade and profound maternal hypotension resulting in adverse maternal and neonatal outcomes. Hypotension, nausea and vomiting remain common but until the publication of the National Institute of Health and Care Excellence (NICE) 2021 guidance, no national guideline existed on how best to manage maternal hypotension following spinal anaesthesia for caesarean section. A 2017 international consensus statement recommended prophylactic vasopressor administration to maintain a systolic blood pressure of >90% of an accurate pre-spinal value, and to avoid a drop to <80% of this value. This survey aimed to assess regional adherence to these recommendations, the presence of local guidelines for management of hypotension during caesarean section under spinal anaesthesia, and the individual clinician's treatment thresholds for maternal hypotension and tachycardia. METHODS: The West Midlands Trainee-led Research in Anaesthesia and Intensive Care Network co-ordinated surveys of obstetric anaesthetic departments and consultant obstetric anaesthetists across 11 National Health Service Trusts in the Midlands, England. RESULTS: One-hundred-and-two consultant obstetric anaesthetists returned the survey and 73% of sites had a policy for vasopressor use; 91% used phenylephrine as the first-line drug but a wide range of recommended delivery methods was noted and target blood pressure was only listed in 50% of policies. Significant variation existed in both vasopressor delivery methods and target blood pressures. CONCLUSIONS: Although NICE has since recommended prophylactic phenylephrine infusion and a target blood pressure, the previous international consensus statement was not adhered to routinely.

The relationship between myocardial microstructure and strain in chronic infarction using cardiovascular magnetic resonance diffusion tensor imaging and feature tracking.

BACKGROUND: Cardiac diffusion tensor imaging (cDTI) using cardiovascular magnetic resonance (CMR) is a novel technique for the non-invasive assessment of myocardial microstructure. Previous studies have shown myocardial infarction to result in loss of sheetlet angularity, derived by reduced secondary eigenvector (E2A) and reduction in subendocardial cardiomyocytes, evidenced by loss of myocytes with right-handed orientation (RHM) on helix angle (HA) maps. Myocardial strain assessed using feature tracking-CMR (FT-CMR) is a sensitive marker of sub-clinical myocardial dysfunction. We sought to explore the relationship between these two techniques (strain and cDTI) in patients at 3 months following ST-elevation MI (STEMI). METHODS: 32 patients (F = 28, 60 ± 10 years) underwent 3T CMR three months after STEMI (mean interval 105 ± 17 days) with second order motion compensated (M2), free-breathing spin echo cDTI, cine gradient echo and late gadolinium enhancement (LGE) imaging. HA maps divided into left-handed HA (LHM, - 90 < HA < - 30), circumferential HA (CM, - 30° < HA < 30°), and right-handed HA (RHM, 30° < HA < 90°) were reported as relative proportions. Global and segmental analysis was undertaken. RESULTS: Mean left ventricular ejection fraction (LVEF) was 44 ± 10% with a mean infarct size of 18 ± 12 g and a mean infarct segment LGE enhancement of 66 ± 21%. Mean global radial strain was 19 ± 6, mean global circumferential strain was - 13 ± - 3 and mean global longitudinal strain was - 10 ± - 3. Global and segmental radial strain correlated significantly with E2A in infarcted segments (p = 0.002, p = 0.011). Both global and segmental longitudinal strain correlated with RHM of infarcted segments on HA maps (p < 0.001, p = 0.003). Mean Diffusivity (MD) correlated significantly with the global infarct size (p < 0.008). When patients were categorised according to LVEF (reduced, mid-range and preserved), all cDTI parameters differed significantly between the three groups. CONCLUSION: Change in sheetlet orientation assessed using E2A from cDTI correlates with impaired radial strain. Segments with fewer subendocardial cardiomyocytes, evidenced by a lower proportion of myocytes with right-handed orientation on HA maps, show impaired longitudinal strain. Infarct segment enhancement correlates significantly with E2A and RHM. Our data has demonstrated a link between myocardial microstructure and contractility following myocardial infarction, suggesting a potential role for CMR cDTI to clinically relevant functional impact.

First Leptophobic Dark Matter Search from the Coherent-CAPTAIN-Mills Liquid Argon Detector.

We report the first results of a search for leptophobic dark matter (DM) from the Coherent-CAPTAIN-Mills (CCM) liquid argon (LAr) detector. An engineering run with 120 photomultiplier tubes (PMTs) and 17.9×10^{20} protons on target (POT) was performed in fall 2019 to study the characteristics of the CCM detector. The operation of this 10-ton detector was strictly light based with a threshold of 50 keV and used coherent elastic scattering off argon nuclei to detect DM. Despite only 1.5 months of accumulated luminosity, contaminated LAr, and nonoptimized shielding, CCM's first engineering run has already achieved sensitivity to previously unexplored parameter space of light dark matter models with a baryonic vector portal. With an expected background of 115 005 events, we observe 115 005+16.5 events which is compatible with background expectations. For a benchmark mediator-to-DM mass ratio of m_{V_{B}}/m_{χ}=2.1, DM masses within the range 9 MeV≲m_{χ}≲50 MeV are excluded at 90% C. L. in the leptophobic model after applying the Feldman-Cousins test statistic. CCM's upgraded run with 200 PMTs, filtered LAr, improved shielding, and 10 times more POT will be able to exclude the remaining thermal relic density parameter space of this model, as well as probe new parameter space of other leptophobic DM models.

Divergent Genital Morphologies and Female-Male Covariation in Watersnakes.

Genital evolution can be driven by diverse selective pressures. Across taxa we see evidence of covariation between males and females, as well as divergent genital morphologies between closely related species. Quantitative analyses of morphological changes in coevolving male and female genitalia have not yet been shown in vertebrates. This study uses 2D and 3D geometric morphometrics to quantitatively compare the complex shapes of vaginal pouches and hemipenes across three species of watersnakes (the sister taxa Nerodia fasciata, N. sipedon, and a close relative N. rhombifer) to address the relationship between genital morphology and divergence time in a system where sexual conflict may have driven sexually antagonistic coevolution of genital traits. Our pairwise comparisons of shape differences across species show that the sister species have male and female genitalia that are significantly different from each other, but more similar to each other than to N. rhombifer. We also determine that the main axes of shape variation are the same for males and females, with changes that relate to deeper bilobation of the vaginal pouch and hemipenes. In males, the protrusion of the region of spines at the base of the hemipene trades off with the degree of bilobation, suggesting amelioration of sexual conflict, perhaps driven by changes in the relative size of the entrance of the vaginal pouch that could have made spines less effective.

A de novo paradigm for male infertility.

De novo mutations are known to play a prominent role in sporadic disorders with reduced fitness. We hypothesize that de novo mutations play an important role in severe male infertility and explain a portion of the genetic causes of this understudied disorder. To test this hypothesis, we utilize trio-based exome sequencing in a cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare (MAF < 0.1%) protein-altering de novo mutations are classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of loss-of-function de novo mutations in loss-of-function-intolerant genes (p-value = 1.00 × 10-5) in infertile men compared to controls. Additionally, we detected a significant increase in predicted pathogenic de novo missense mutations affecting missense-intolerant genes (p-value = 5.01 × 10-4) in contrast to predicted benign de novo mutations. One gene we identify, RBM5, is an essential regulator of male germ cell pre-mRNA splicing and has been previously implicated in male infertility in mice. In a follow-up study, 6 rare pathogenic missense mutations affecting this gene are observed in a cohort of 2,506 infertile patients, whilst we find no such mutations in a cohort of 5,784 fertile men (p-value = 0.03). Our results provide evidence for the role of de novo mutations in severe male infertility and point to new candidate genes affecting fertility.

Prevalence, predictors and outcomes of thyroid dysfunction in patients with acute myocardial infarction: the ThyrAMI-1 study.

PURPOSE: Thyroid dysfunction in patients with cardiac disease is associated with worse outcomes. This study aimed to evaluate the prevalence and analyse predictors and outcomes of thyroid dysfunction in patients presenting with an acute myocardial infarction (AMI). METHODS: A prospective multicentre observational study of patients recruited from six acute hospitals within the North of England. Consecutive patients without previous thyroid disease presenting with both ST-elevation AMI (STEMI) and non-ST-elevation AMI (NSTEMI) were recruited to the Thyroxine in Acute Myocardial Infarction 1 (ThyrAMI-1) cohort study between December 2014 and 2016. Thyroid profile, standard biochemistry measurements and demographic information were obtained within 12 h of admission to hospital. Multivariable logistic regression analyses were performed to assess the predictors of thyroid dysfunction and Cox proportional hazards analyses were utilised to compare all-cause mortality by categories of thyroid dysfunction up to June 2019. RESULTS: Of the 1802 participants analysed, 1440 (79.9%) were euthyroid, 312 (17.3%) had subclinical hypothyroidism (SCH), 22 (1.2%) had subclinical hyperthyroidism (SHyper) and 25 (1.3%) had low T3 syndrome (LT3S). Predictors for SCH were increasing age, female sex, higher thyroid peroxidase antibody (TPOAb) levels, higher serum creatinine levels and early morning sampling time (between 00:01-06:00 h). The predictors of SHyper were lower body mass index and afternoon sampling time (between 12:01 and 18:00 h). Predictors of LT3S were increasing age, higher creatinine levels and presence of previous ischaemic heart disease. Compared to the euthyroid group, patients with LT3S had higher all-cause mortality; adjusted hazard ratio (95% CI) of 2.02 (1.03-3.95), p = 0.04, whereas those with SCH and SHyper did not exhibit significantly increased mortality; adjusted hazard ratios (95% CI) of 1.05 (0.74-1.49), p = 0.79 and 0.27 (0.04-1.95), p = 0.19, respectively. CONCLUSIONS: Thyroid dysfunction is common in AMI patients on admission to hospital and our data provide an understanding regarding which factors might influence thyroid dysfunction in these patients. Furthermore, the negative association between LT3S and increased mortality post-AMI has once again been highlighted by this study. More research is required to assess if treatment of thyroid dysfunction improves clinical outcomes.

The ORNATE India Project: United Kingdom-India Research Collaboration to tackle visual impairment due to diabetic retinopathy.

INTRODUCTION: The ORNATE India project is funded by the UK Research and Innovation (UKRI) through the Global Challenges Research Fund. The aim is to build research capacity and capability in India and the UK to tackle global burden of diabetes-related visual impairment. As there are over 77 million people with diabetes in India, it is challenging to screen every person with diabetes annually for sight-threatening diabetic retinopathy (DR). Therefore, alternate safe approaches need to be developed so that those at-risk of visual impairment due to DR is identified promptly and treated. METHODS: The project team utilised diverse global health strategies and research methods to co-design work packages to build research capacity and capability to ensure effective, affordable and efficient DR services are made available for the population. The strategies and methods employed included health system strengthening; implementation science; establishing care pathways; co-designing collaborative studies on affordable technologies, developing quality standards and guidelines to decrease variations in care; economic analysis; risk modelling and stratification. Five integrated work packages have been developed to deal with all aspects of DR care. These included implementation of a DR screening programme in the public health system in a district in Kerala, evaluating regional prevalence of diabetes and DR and assessing ideal tests for holistic screening for diabetes and its complications in 20 areas in India, utilising artificial intelligence on retinal images to facilitate DR screening, exploring biomarker and biosensor research to detect people at risk of diabetes complications, estimating cost of blindness in India and risk modelling to develop risk-based screening models for diabetes and its complications. A large collaborative network will be formed to propagate research, promote shared learning and bilateral exchanges between high- and middle-income countries to tackle diabetes-related blindness.

Cardiovascular MRI evidence of reduced systolic function and reduced LV mass in rheumatoid arthritis: impact of disease phenotype.

The accelerated risk of cardiovascular disease (CVD) in Rheumatoid Arthritis (RA) requires further study of the underlying pathophysiology and determination of the at-risk RA phenotype. Our objectives were to describe the cardiac structure and function and arterial stiffness, and association with disease phenotype in patients with established) RA, in comparison to healthy controls, as measured by cardiovascular magnetic resonance imaging (CMR). 76 patients with established RA and no history of CVD/diabetes mellitus were assessed for RA and cardiovascular profile and underwent a non-contrast 3T-CMR, and compared to 26 healthy controls. A univariable analysis and multivariable linear regression model determined associations between baseline variables and CMR-measures. Ten-year cardiovascular risk scores were increased in RA compared with controls. Adjusting for age, sex and traditional cardiovascular risk factors, patients with RA had reduced left ventricular ejection fraction (mean difference - 2.86% (- 5.17, - 0.55) p = 0.016), reduced absolute values of mid systolic strain rate (p < 0.001) and lower late/active diastolic strain rate (p < 0.001) compared to controls. There was evidence of reduced LV mass index (LVMI) (- 4.56 g/m2 (- 8.92, - 0.20), p = 0.041). CMR-measures predominantly associated with traditional cardiovascular risk factors; male sex and systolic blood pressure independently with increasing LVMI. Patients with established RA and no history of CVD have evidence of reduced LV systolic function and LVMI after adjustment for traditional cardiovascular risk factors; the latter suggesting cardiac pathology other than atherosclerosis in RA. Traditional cardiovascular risk factors, rather than RA disease phenotype, appear to be key determinants of subclinical CVD in RA potentially warranting more effective cardiovascular risk reduction programs.

Highly integrated workflows for exploring cardiovascular conditions: Exemplars of precision medicine in Alzheimer's disease and aortic dissection.

For precision medicine to be implemented through the lens of in silico technology, it is imperative that biophysical research workflows offer insight into treatments that are specific to a particular illness and to a particular subject. The boundaries of precision medicine can be extended using multiscale, biophysics-centred workflows that consider the fundamental underpinnings of the constituents of cells and tissues and their dynamic environments. Utilising numerical techniques that can capture the broad spectrum of biological flows within complex, deformable and permeable organs and tissues is of paramount importance when considering the core prerequisites of any state-of-the-art precision medicine pipeline. In this work, a succinct breakdown of two precision medicine pipelines developed within two Virtual Physiological Human (VPH) projects are given. The first workflow is targeted on the trajectory of Alzheimer's Disease, and caters for novel hypothesis testing through a multicompartmental poroelastic model which is integrated with a high throughput imaging workflow and subject-specific blood flow variability model. The second workflow gives rise to the patient specific exploration of Aortic Dissections via a multi-scale and compliant model, harnessing imaging, computational fluid-dynamics (CFD) and dynamic boundary conditions. Results relating to the first workflow include some core outputs of the multiporoelastic modelling framework, and the representation of peri-arterial swelling and peri-venous drainage solution fields. The latter solution fields were statistically analysed for a cohort of thirty-five subjects (stratified with respect to disease status, gender and activity level). The second workflow allowed for a better understanding of complex aortic dissection cases utilising both a rigid-wall model informed by minimal and clinically common datasets as well as a moving-wall model informed by rich datasets.

Charge migration in photo-ionized aromatic amino acids.

Attosecond pump-probe spectroscopy is a unique tool for the direct observation of the light-activated electronic motion in molecules and it offers the possibility to capture the first instants of a chemical reaction. Recently, advances in attosecond technology allowed the charge migration processes to be revealed in biochemically relevant molecules. Although this purely electronic process might be key for a future chemistry at the electron time scale, the influence of this ultrafast charge flow on the reactivity of a molecule is still debated. In this work, we exploit extreme ultraviolet attosecond pulses to activate charge migration in two aromatic amino acids, namely phenylalanine and tryptophan. Advanced numerical calculations are performed to interpret the experimental data and to discuss the effects of the nuclear dynamics on the activated quantum coherences. By comparing the experimental results obtained in the two molecules, we show that the presence of different functional groups strongly affects the fragmentation pathways, as well as the charge rearrangement. The observed charge dynamics indeed present peculiar aspects, including characteristic periodicities and decoherence times. Numerical results indicate that, even for a very large molecule such as tryptophan, the quantum coherences can survive the nuclear dynamics for several femtoseconds. These results open new and important perspectives for a deeper understanding of the photo-induced charge dynamics, as a promising tool to control the reactivity of bio-relevant molecules via photo-excitation. This article is part of the theme issue 'Measurement of ultrafast electronic and structural dynamics with X-rays'.

Real-time determination of enantiomeric and isomeric content using photoelectron elliptical dichroism.

The fast and accurate analysis of chiral chemical mixtures is crucial for many applications but remains challenging. Here we use elliptically-polarized femtosecond laser pulses at high repetition rates to photoionize chiral molecules. The 3D photoelectron angular distribution produced provides molecular fingerprints, showing a strong forward-backward asymmetry which depends sensitively on the molecular structure and degree of ellipticity. Continuously scanning the laser ellipticity and analyzing the evolution of the rich, multi-dimensional molecular signatures allows us to observe real-time changes in the chemical and chiral content present with unprecedented speed and accuracy. We measure the enantiomeric excess of a compound with an accuracy of 0.4% in 10 min acquisition time, and follow the evolution of a mixture with an accuracy of 5% with a temporal resolution of 3 s. This method is even able to distinguish isomers, which cannot be easily distinguished by mass-spectrometry.

Blood clotting and traumatic injury with shock mediates complement-dependent neutrophil priming for extracellular ROS, ROS-dependent organ injury and coagulopathy.

Polymorphonuclear (PMN) leucocytes participate in acute inflammatory pathologies such as acute respiratory distress syndrome (ARDS) following traumatic injury and shock, which also activates the coagulation system systemically. Trauma can prime the PMN nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex for an enhanced respiratory burst, but the relative role of various priming agents in this process remains incompletely understood. We therefore set out to identify mediators of PMN priming during coagulation and trauma-shock and determine whether PMN reactive oxygen species (ROS) generated in this manner could influence organ injury and coagulation. Initial experiments demonstrated that PMN are primed for predominantly extracellular ROS production by products of coagulation, which was abrogated by CD88/C5a receptor(C5aR) inhibition. The importance of this was highlighted further by demonstrating that known PMN priming agents result in fractionally different amounts of extracellular versus intracellular ROS release depending on the agent used. Plasma from trauma patients in haemodynamic shock (n = 10) also primed PMN for extracellular ROS in a C5a-dependent manner, which correlated with both complement alternative pathway activation and thrombin generation. Furthermore, PMN primed by preincubation with products of blood coagulation directly caused loss of endothelial barrier function in vitro that was abrogated by C5aR blockade or NADPH oxidase inhibition. Finally, we show in a murine model of trauma-shock that p47phox knock-out (KO) mice with PMN incapable of generating ROS were protected from inflammatory end-organ injury and activated protein C-mediated coagulopathy. In summary, we demonstrate that trauma-shock and coagulation primes PMN for predominantly extracellular ROS production in a C5a-dependent manner that contributes to endothelial barrier loss and organ injury, and potentially enhances traumatic coagulopathy.

Effects of hyperaemia on left ventricular longitudinal strain in patients with suspected coronary artery disease : A first-pass stress perfusion cardiovascular magnetic resonance imaging study.

AIMS: Myocardial perfusion imaging during hyperaemic stress is commonly used to detect coronary artery disease. The aim of this study was to investigate the relationship between left ventricular global longitudinal strain (GLS), strain rate (GLSR), myocardial early (E') and late diastolic velocities (A') with adenosine stress first-pass perfusion cardiovascular magnetic resonance (CMR) imaging. METHODS AND RESULTS: 44 patients met the inclusion criteria and underwent CMR imaging. The CMR imaging protocol included: rest/stress horizontal long-axis (HLA) cine, rest/stress first-pass adenosine perfusion and late gadolinium enhancement imaging. Rest and stress HLA cine CMR images were analysed using feature-tracking software for the assessment of myocardial deformation. The presence of perfusion defects was scored on a binomial scale. In patients with hyperaemia-induced perfusion defects, rest global longitudinal strain GLS (-16.9 ± 3.7 vs. -19.6 ± 3.4; p-value = 0.02), E' (-86 ± 22 vs. -109 ± 38; p-value = 0.02), GLSR (69 ± 31 vs. 93 ± 38; p-value = 0.01) and stress GLS (-16.5 ± 4 vs. -21 ± 3.1; p < 0.001) were significantly reduced when compared with patients with no perfusion defects. Stress GLS was the strongest independent predictor of perfusion defects (odds ratio 1.43 95% confidence interval 1.14-1.78, p-value <0.001). A threshold of -19.8% for stress GLS demonstrated 78% sensitivity and 73% specificity for the presence of hyperaemia-induced perfusion defects. CONCLUSIONS: At peak myocardial hyperaemic stress, GLS is reduced in the presence of a perfusion defect in patients with suspected coronary artery disease. This reduction is most likely caused by reduced endocardial blood flow at maximal hyperaemia because of transmural redistribution of blood flow in the presence of significant coronary stenosis.

In situ regeneration of retinal pigment epithelium by gene transfer of E2F2: a potential strategy for treatment of macular degenerations.

The retinal pigment epithelium (RPE) interacts closely with photoreceptors to maintain visual function. In degenerative diseases such as Stargardt disease and age-related macular degeneration, the leading cause of blindness in the developed world, RPE cell loss is followed by photoreceptor cell death. RPE cells can proliferate under certain conditions, suggesting an intrinsic regenerative potential, but so far this has not been utilised therapeutically. Here, we used E2F2 to induce RPE cell replication and thereby regeneration. In both young and old (2 and 18 month) wildtype mice, subretinal injection of non-integrating lentiviral vector expressing E2F2 resulted in 47% of examined RPE cells becoming BrdU positive. E2F2 induced an increase in RPE cell density of 17% compared with control vector-treated and 14% compared with untreated eyes. We also tested this approach in an inducible transgenic mouse model of RPE loss, generated through activation of diphtheria toxin-A gene. E2F2 expression resulted in a 10-fold increase in BrdU uptake and a 34% increase in central RPE cell density. Although in mice this localised rescue is insufficiently large to be demonstrable by electroretinography, a measure of massed retinal function, these results provide proof-of-concept for a strategy to induce in situ regeneration of RPE for the treatment of RPE degeneration.

A new technique for probing chirality via photoelectron circular dichroism.

We present a proof-of-principle approach for discriminating chiral enantiomers based on the phenomenon of multiphoton photoelectron circular dichroism. A novel stereo detection setup was used to measure the number of photoelectrons emitted from chiral molecules in directions parallel or anti-parallel to the propagation of the ionising femtosecond laser pulses. In this study, we show how these asymmetries in the ketones camphor and fenchone depend upon the ellipticity of the laser pulses and the enantiomeric excess of the sample. By using a high repetition rate femtosecond laser, enantiomer excesses with uncertainties at the few-percent level could be measured in close to real-time. As the instrument is compact, and commercial turnkey femtosecond lasers are readily available, the development of a stand-alone chiral analysis instrument for a range of applications is now possible.

The evolution of acute burn care - retiring the split skin graft.

The skin graft was born in 1869 and since then, surgeons have been using split skin grafts for wound repair. Nevertheless, this asset fails the big burn patient, who deserves an elastic, mobile and robust outcome but who receives the poorest possible outcome based on donor site paucity. Negating the need for the skin graft requires an autologous composite cultured skin and a material capable of temporising the burn wound for four weeks until the composite is produced. A novel, biodegradable polyurethane chemistry has been used to create two such products. This paper describes the design, production, optimisation and evaluation of several iterations of these products. The evaluation has occurred in a variety of models, both in vitro and in vivo, employing Hunterian scientific principles, and embracing Hunter's love and appreciation of comparative anatomy. The process has culminated in significant human experience in complex wounds and extensive burn injury. Used serially, the products offer robust and elastic healing in deep burns of any size within 6 weeks of injury.

Ultrafast dynamics in the DNA building blocks thymidine and thymine initiated by ionizing radiation.

Understanding how energetic charged particles damage DNA is crucial for improving radiotherapy techniques such as hadron therapy and for the development of new radiosensitizer drugs. In the present study, the damage caused by energetic particles was simulated by measuring the action of extreme ultraviolet (XUV) attosecond pulses on the DNA building blocks thymine and thymidine. This allowed the ultrafast processes triggered by direct ionization to be probed with an optical pulse with a time resolution of a few femtoseconds. By measuring the yields of fragment ions as a function of the delay between the XUV pulse and the probe pulse, a number of transient processes typically lasting 100 femtoseconds or less were observed. These were particularly strong in thymidine which consists of the thymine base attached to a deoxyribose sugar. This dynamics was interpreted as excited states of the cation, formed by the XUV pulse, rapidly decaying via non-adiabatic coupling between electronic states. This provides the first experimental insight into the mechanisms which immediately proceed from the action of ionizing radiation on DNA and provides a basis on which further theoretical and experimental studies can be conducted.

Incorporating mixed rations and formulated grain mixes into the diet of grazing cows: Effects on milk composition and coagulation properties, and the yield and quality of Cheddar cheese.

Effects of different strategies for feeding supplements to grazing dairy cows on the composition and coagulation properties of milk and the subsequent yield and quality of Cheddar cheese were measured. The experiment used milk from 72 Holstein-Friesian cows, averaging 45d in milk, fed according to 1 of 3 feeding strategies: (1) cows grazed a restricted allowance of perennial ryegrass pasture [approximately 14kg of dry matter (DM)/cow per day, to ground level] supplemented with milled wheat grain fed in the milking parlor and alfalfa hay offered in the paddock (control); (2) same pasture and allowance as control, supplemented with a formulated grain mix containing wheat grain, corn grain, and canola meal fed in the parlor and alfalfa hay fed in the paddock (FGM); or (3) same pasture and allowance as control, supplemented with a partial mixed ration comprising the same formulated grain mix but mixed with alfalfa hay and presented on a feed pad after each milking (PMR). For all strategies, supplements provided the same metabolizable energy and grain:forage ratio (78:22, DM basis). Within each feeding strategy, milk was sampled from cows receiving either 8 or 16kg (DM) of supplement/cow per day. There were 2 replicated groups of 6 cows per supplement amount per dietary strategy; approximately 250L of milk was sampled from each for analyses of composition and coagulation properties and the manufacture of Cheddar cheese. The experiment had a 14-d adaptation period and a 14-d measurement period. For cows fed according to the control strategy, those fed 16kg/cow per day produced milk with lower concentrations of milk fat than cows fed 8kg/cow per day. This effect was not observed for cows fed according to the FGM and PMR strategies. Milk from cows fed 16kg of DM/cow per day according to the control strategy yielded less Cheddar cheese than milk from cows fed according to the PMR strategy, with cheese yields from FGM cows being intermediate. Amount of supplement offered had minor effects on percentages of some fatty acids. We observed few other effects of feeding strategy on milk composition, types of milk protein, milk coagulation properties, or the composition and quality of the resultant Cheddar cheese. These data show that, compared with the traditional control strategy, feeding PMR or FGM may increase milk fat concentration and the subsequent yield of Cheddar cheese without compromising cheese composition or quality.