To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure firstname.lastname@example.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Four experiments examine how lack of awareness of inequality affect behaviour towards the rich and poor. In Experiment 1, participants who became aware that wealthy individuals donated a smaller percentage of their income switched from rewarding the wealthy to rewarding the poor. In Experiments 2 and 3, participants who played a public goods game – and were assigned incomes reflective of the US income distribution either at random or on merit – punished the poor (for small absolute contributions) and rewarded the rich (for large absolute contributions) when incomes were unknown; when incomes were revealed, participants punished the rich (for their low percentage of income contributed) and rewarded the poor (for their high percentage of income contributed). In Experiment 4, participants provided with public education contributions for five New York school districts levied additional taxes on mostly poorer school districts when incomes were unknown, but targeted wealthier districts when incomes were revealed. These results shed light on how income transparency shapes preferences for equity and redistribution. We discuss implications for policy-makers.
Inefficiencies in the national clinical research infrastructure have been apparent for decades. The National Center for Advancing Translational Science—sponsored Clinical and Translational Science Award (CTSA) program is able to address such inefficiencies. The Trial Innovation Network (TIN) is a collaborative initiative with the CTSA program and other National Institutes of Health (NIH) Institutes and Centers that addresses critical roadblocks to accelerate the translation of novel interventions to clinical practice. The TIN’s mission is to execute high-quality trials in a quick, cost-efficient manner. The TIN awardees are composed of 3 Trial Innovation Centers, the Recruitment Innovation Center, and the individual CTSA institutions that have identified TIN Liaison units. The TIN has launched a national scale single (central) Institutional Review Board system, master contracting agreements, quality-by-design approaches, novel recruitment support methods, and applies evidence-based strategies to recruitment and patient engagement. The TIN has received 113 submissions from 39 different CTSA institutions and 8 non-CTSA Institutions, with projects associated with 12 different NIH Institutes and Centers across a wide range of clinical/disease areas. Already more than 150 unique health systems/organizations are involved as sites in TIN-related multisite studies. The TIN will begin to capture data and metrics that quantify increased efficiency and quality improvement during operations.
Concentrate inclusion levels in dairy cow diets are often adjusted so that the milk yield responses remain economic. While changes in concentrate level on performance is well known, their impact on other biological parameters, including immune function, is less well understood. The objective of this study was to evaluate the effect of concentrate inclusion level in a grass silage-based mixed ration on immune function. Following calving 63 (45 multiparous and 18 primiparous) Holstein Friesian dairy cows were allocated to one of three isonitrogenous diets for the first 70 days of lactation. Diets comprised of a mixture of concentrates and grass silage, with concentrates comprising either a low (30%, LC), medium (50%, MC) or high (70%, HC) proportion of the diet on a dry matter (DM) basis. Daily DM intakes, milk yields and BW were recorded, along with weekly body condition score, milk composition and vaginal mucus scores. Blood biochemistry was measured using a chemistry analyzer, neutrophil phagocytic and oxidative burst assessed using commercial kits and flow cytometry, and interferon-γ production evaluated by ELISA after whole blood stimulation. Over the study period cows on HC had a higher total DM intake, milk yield, fat yield, protein yield, fat+protein yield, protein content, mean BW and mean daily energy balance, and a lower BW loss than cows on MC, whose respective values were higher than cows on LC. Cows on HC and MC had a lower serum non-esterified fatty acid concentration than cows on LC (0.37, 0.37 and 0.50 mmol/l, respectively, P=0.005, SED=0.032), while cows on HC had a lower serum β-hydroxybutyrate concentration than cows on MC and LC (0.42, 0.55 and 0.55 mmol/l, respectively, P=0.002, SED=0.03). Concentrate inclusion level had no effect on vaginal mucus scores. At week 3 postpartum, cows on HC tended to have a higher percentage of oxidative burst positive neutrophils than cows on LC (43.2% and 35.3%, respectively, P=0.078, SED=3.11), although at all other times concentrate inclusion level in the total mixed ration had no effect on neutrophil phagocytic or oxidative burst characteristics, or on interferon-γ production by pokeweed mitogen stimulated whole blood culture. This study demonstrates that for high yielding Holstein Friesian cows managed on a grass silage-based diet, concentrate inclusion levels in early lactation affects performance but has no effect on neutrophil or lymphocyte immune parameters.
This study compared the effect of feeding AmyPlus, a moist feed, as opposed to rolled wheat on the yield and composition of milk from dairy cows consuming grass silage based total mixed ration (TMR). Seventy-two Holstein-Friesian cows were distributed into AmyPlus (Treatment) and Wheat (Control) groups and loose housed on straw in an open shed. Each kg Wheat based concentrate contained 345g rolled wheat, 230g rapeseed meal, 115g sugarbeet pulp, 115g Molaferm 20, 115g soybean meal, 56g barley straw and 24g vitamin-minerals. In contrast, each kg AmyPlus based concentrate contained 501g AmyPlus (480g DM /kg), 105g rapeseed meal, 126g sugarbeet pulp, 126g Molaferm 20, 84g soybean meal, 41g barley straw and 17g vitamin-minerals. Here, AmyPlus was loaded directly into the mixer wagon to prepare fresh AmyPlus based TMR with a silage to concentrate ratio of 68:32. Each TMR was fed once daily to the corresponding group of cows also receiving 2kg of Distillers’ grains per cow in the parlour during milking. Daily milk yield and composition was recorded from November 1999 to February 2000. The overall daily Dry matter intake (DMI) of each TMR per cow remained uniform (20.19 vs 20.15 kg for Treatment and Control group respectively) across both groups. Daily milk yield and total cell counts per cow did not vary significantly (P>0.05) between groups during various months. While, milk fat and protein contents were greater in Treatment than Control group during each month, the differences were significant (P<0.05) only during November and December for fat and in January for protein. On average, the Treatment group tended to show a non-significant increase (P>0.05) in daily milk yield per cow by 0.144 kg than the Control group. The fat (46.2 vs 43.7) and protein (34.5 vs 33.5) contents in g /kg milk were also increased significantly (P<0.001) in Treatment compared with Control group. Total cell counts did not vary significantly (P>0.05) and remained within the acceptable limits. The cows consuming AmyPlus maintained their health as indicated by their intake, production, cell counts and general appearance. It would appear that AmyPlus can replace rolled wheat in TMR. However, it may be necessary to evaluate the storage, economic and environmental implications of using such moist co-products in silage based dairy rations.
Reliable and affordable technology for collecting and managing livestock production process information is being developed. The advances in data measurement, collection and transfer technology enable us to retrieve information from one or more remote sites to be processed and managed centrally. This opens up the opportunity to advance from open loop, prescriptive production to closed loop systems where factors influencing the actual performance of animals are used to modify and improve their production parameters (feed, environment, medication). We strive from producing animals by predicting what is needed using outdated data, to measuring what is actually happening as they grow, processing this information and acting to optimise animal performance by modifying production parameters in real time.
This paper describes commercially available systems that make possible the retrieval, collection, processing and distribution of near real time production information. Various aspects of production management using this technology are discussed, and examples of how it can be applied to monitor water usage, how it relates to pig performance and how energy usage can be influenced, are considered.
Nutritional management of pigs to optimise growth demands pig-specific, time-specific and place-specific determination and provision of nutritional requirement. These elements need to be incorporated into response prediction models that operate in a real-time (not retrospective) closed-loop control environment. This implies appropriate means for the on-line measurement of response to change in nutrient provision, and the simultaneous means for manipulation of feeding level and feed quality. The paper describes how response prediction modelling and response measurement may now be achieved. Optimisation may be pursued with mixed objectives, including those of production efficiency and environmental protection.
Anxiety is debilitating and associated with numerous mental and physical comorbidities. There is a need to identify and investigate low-risk prevention and treatment strategies. Therefore, the purpose of this study was to investigate cross-sectional and longitudinal associations between different volumes of moderate-to-vigorous physical activity (PA) and anxiety symptoms and status among older adults in Ireland.
Participants (n = 4175; 56.8% female) aged ⩾50 years completed the International PA Questionnaire (IPAQ) at baseline, and the anxiety subscale of the Hospital Anxiety and Depression Scale at baseline and follow-up (2009–2013). Participants were classified according to meeting World Health Organisation PA guidelines, and divided into IPAQ categories. Respondents without anxiety at baseline (n = 3165) were included in prospective analyses. Data were analysed in 2017.
Anxiety symptoms were significantly higher among females than males (p < 0.001). Models were adjusted for age, sex, waist circumference, social class, smoking status and pain. In cross-sectional analyses, meeting PA guidelines was associated with 9.3% (OR = 0.91, 95% confidence interval 0.78–1.06) lower odds of anxiety. Compared with the inactive group, the minimally- and very-active groups were associated with 8.4% (OR = 0.92, 0.76–1.10) and 18.8% (OR = 0.81, 0.67–0.98) lower odds of anxiety, respectively. In prospective analyses, meeting guidelines was associated with 6.3% (OR = 0.94, 0.63–1.40) reduced odds of anxiety. Compared with the inactive group, the minimally and very-active groups were associated with 43.5% (OR = 1.44, 0.89–2.32) increased, and 4.3% (OR = 0.96, 0.56–1.63) reduced odds of anxiety. The presence of pain, included in models as a covariate, was associated with a 108.7% (OR = 2.09, 1.80–2.42) increase in odds of prevalent anxiety, and a 109.7% (OR = 2.10, 1.41–3.11) increase in odds of incident anxiety.
High volumes of PA are cross-sectionally associated with lower anxiety symptoms and status, with a potential dose–response apparent. However, significant associations were not observed in prospective analyses. The low absolute number of incident anxiety cases (n = 109) potentially influenced these findings. Further, as older adults may tend to experience and/or report more somatic anxiety symptoms, and the HADS focuses primarily on cognitive symptoms, it is plausible that the HADS was not an optimal measure of anxiety symptoms in the current population.
In this paper, first results comparing modified Longin and ninhydrin collagen extraction methodologies are presented. The goal of this study is to investigate the bones of several species with different ages, preservation conditions, and collagen contents to determine the most suitable preparation method. Different types of samples are used such as VIRI samples, previously dated bones, and background samples. Each bone has undergone elemental analysis, infrared analysis, and 14C measurement. The results are presented and the advantages and disadvantages of each preparation method are discussed. In general, results obtained by the two methods are in accordance with the consensus value for 2σ uncertainty. For VIRI I and a mammoth bone, the ninhydrin preparation gives, respectively, 8450±70 BP and 14,870±60 BP whereas the modified Longin process gives 8365±45 BP and 14,750±100 BP in agreement with the expected values. From the experimental point of view, the modified Longin process is easier to implement than the ninhydrin protocol. From this approach, we can conclude that the modified Longin process could be preferred in most cases and particularly when the amount of bone is small and the sample is not too contaminated.
We obtained radiocarbon (14C) dates with accelerator mass spectrometry (AMS) of vascular plant samples and a charcoal sample collected from peat deposits near the prehistoric village site informally designated CR-03 on Carlisle Island in the Islands of Four Mountains group, Alaska, to determine the eruption age of the CR-02 tephra. A fine vitric ash erupted from Okmok caldera, Umnak Island (ca. 2 ka BP) was also discovered in the bog. The ages of the CR-02 tephra and Okmok II ash are estimated to be 1050 and 2000 cal BP, respectively. Because both tephras are distinctive and widespread, these are important chronostratigraphic markers for archaeological sites in this island group. The 14C dates obtained from this bog are 800 years younger than the dates of the charcoal fragments from cultural layers in the Unit 3 of prehistoric village site CR-02 (AMK-0003).
There is little information available in the literature on the validation of the currently adopted energy feeding systems developed from calorimetric data, using data obtained in production studies. The objective of the present study was to use production data from feeding studies to validate some metabolisable energy (ME) systems (AFRC, 1990 and 1993; SCA, 1990) and net energy (NE) systems (Van Es, 1978, INRA, 1989; NRC, 2001).
AFRC (1993) recommends a reduction of proportionately 0.018 in dietary metabolisble energy (ME) concentration with each unit increase in feeding level above maintenance in dairy cows (feeding level is calculated as total ME intake divided by ME requirement for maintenance). A similar value (0.016) was reported recently by Yan et al. (2001) using a number of linear and multiple regression techniques with lactating dairy cows offered grass silage-based diets. The objectives of the present study were to validate these two values and also to evaluate the effects of feeding level on nutrient digestibility and ME concentration in the mixed diets.
The energy feeding systems currently adopted for dairy cows in Western Europe and North America were developed from calorimetric data published 30 years ago. However, the calorimetric measurements were usually undertaken with a small number of trained animals, housed for a short period in respiration chambers. The objective of the present study was to use production data to develop the metabolisable energy (ME) requirement for maintenance (MEm) and the efficiency of ME use for lactation (kl) for dairy cows.
Sugarcane is an important forage resource in sub-tropical and tropical areas as it is used during the winter or dry season when the growth rate of pastures is significantly reduced. The current research study assessed the effect of four vertical sections of sugarcane in a pen trial and the level of sugarcane utilization in a grazing trial on the ingestive behaviour and forage intake of two age groups of steers (1 and 2 years old). The pen trial was comprised of two simultaneous 4 × 4 balanced Latin square designs (one for each age group of animals) of four periods, four animals and four feeding treatments, which consisted of four equal vertical sections of sugarcane. Dry matter (DM) and digestible DM (DDM) intake per kilogram of metabolic weight declined gradually from top to bottom of the sugarcane, with no significant differences between the age groups of steers. This difference in intake was associated with a decline in intake of neutral detergent fibre (NDF) as a proportion of the liveweight of the animal and an increase of total chewing time per kilogram of DM or NDF from top to bottom of the sugarcane. It was concluded that the toughness of plant material played a significant role regulating intake, which was higher for the top sections of sugarcane. In the grazing trial, steers of both age groups grazed down sugarcane in three plots over 9 days. Steers grazed up to four distinctive grazing strata. Digestible DM intake (DDM intake) was high at low levels of horizontal utilization of the top grazing stratum but DDM intake started to decline sharply when this stratum was removed in 0·92 of paddock area (i.e. equivalent to 0·08 of the pasture area remaining un-grazed). It was concluded that the proportion of un-grazed area of the pasture can be used as a grazing management strategy to control forage intake for sugarcane.
The semi-arid Hindu-Kush-Karakoram-Himalayan region of Pakistan covers 72,000 sq km with a rainfall of 100-400 mm per year5. Limited arable land and water scarcity have made subsistence farming the dominant agro-pastoral farming system. Each household keeps a range of ruminant livestock species such as goats, cattle, sheep, donkeys and yaks their proportion in the herd are 0.53, 0.23, 0.19, 0.03 and 0.02 respectively. In winter, livestock are confined and stall-fed on stored roughages or grazed on marginal lands and fallow agricultural fields close to the villages. The aim of this study was to quantify nutritional inputs in terms of metabolisable energy resources, and to compare these with ME requirements of the animals for maintenance over winter.
Wilting of grass prior to ensiling generally produces positive responses in dry matter (DM) intake of cattle, but the responses in animal performance are often small, or even negative. The primary objective of the present study was to compare energy utilization from heavily wilted and unwilted silages by growing cattle when given at equal metabolisable energy (ME) intakes. A secondary objective was to evaluate effects of silage additive type (inoculant v. formic acid) on energy utilization.
Four silages were produced from unwilted and wilted grasses (DM 193 and 450 g/kg) obtained from a perennial ryegrass sward. The wilted grass was dried in the field for 26 hours using rapid wilting techniques involving crop conditioning and spreading. At ensiling both the unwilted and wilted grasses were each treated with two additives, a bacterial inoculant (Ecosyl, Zeneca Bioproducts Limited) and a formic acid additive (ADD-F, BP Chemicals Ltd.).
Determination of the proportion of bovine tuberculosis (bTB) breakdowns attributed to a herd purchasing infected animals has not been previously quantified using data from the Animal and Public Health Information System (APHIS) database in Northern Ireland. We used a case–control study design to account for the infection process occurring in the disclosing bTB breakdown herds. Cases (N = 6926) were cattle moving to a future confirmed bTB breakdown where they would disclose as a confirmed bTB reactor or a Lesion at Routine Slaughter (LRS). Controls (N = 303 499) were cattle moving to a future confirmed bTB breakdown where they did not become a bTB reactor or LRS. Our study showed that the cattle leaving herds which disclosed bTB within 450 days had an increased odds of becoming a confirmed bTB reactor or LRS compared with the cattle which left herds that remained free for 450 days (odds ratio (OR) = 2·09: 95% CI 1·96–2·22). Of the 12 060 confirmed bTB breakdowns included in our study (2007–2015 inclusive), 31% (95% CI 29·8–31·5) contained a confirmed bTB reactor(s) or LRS(s) at the disclosing test which entered the herd within the previous 450 days. After controlling for the infection process occurring in the disclosing bTB breakdown herd, our study showed that 6·4% (95% CI 5·9–6·8) of bTB breakdowns in Northern Ireland were directly attributable to the movement of infected animals.
The Taipan galaxy survey (hereafter simply ‘Taipan’) is a multi-object spectroscopic survey starting in 2017 that will cover 2π steradians over the southern sky (δ ≲ 10°, |b| ≳ 10°), and obtain optical spectra for about two million galaxies out to z < 0.4. Taipan will use the newly refurbished 1.2-m UK Schmidt Telescope at Siding Spring Observatory with the new TAIPAN instrument, which includes an innovative ‘Starbugs’ positioning system capable of rapidly and simultaneously deploying up to 150 spectroscopic fibres (and up to 300 with a proposed upgrade) over the 6° diameter focal plane, and a purpose-built spectrograph operating in the range from 370 to 870 nm with resolving power R ≳ 2000. The main scientific goals of Taipan are (i) to measure the distance scale of the Universe (primarily governed by the local expansion rate, H0) to 1% precision, and the growth rate of structure to 5%; (ii) to make the most extensive map yet constructed of the total mass distribution and motions in the local Universe, using peculiar velocities based on improved Fundamental Plane distances, which will enable sensitive tests of gravitational physics; and (iii) to deliver a legacy sample of low-redshift galaxies as a unique laboratory for studying galaxy evolution as a function of dark matter halo and stellar mass and environment. The final survey, which will be completed within 5 yrs, will consist of a complete magnitude-limited sample (i ⩽ 17) of about 1.2 × 106 galaxies supplemented by an extension to higher redshifts and fainter magnitudes (i ⩽ 18.1) of a luminous red galaxy sample of about 0.8 × 106 galaxies. Observations and data processing will be carried out remotely and in a fully automated way, using a purpose-built automated ‘virtual observer’ software and an automated data reduction pipeline. The Taipan survey is deliberately designed to maximise its legacy value by complementing and enhancing current and planned surveys of the southern sky at wavelengths from the optical to the radio; it will become the primary redshift and optical spectroscopic reference catalogue for the local extragalactic Universe in the southern sky for the coming decade.
Archaeological fieldwork preceding housing development revealed a Mesolithic site in a primary context. A central hearth was evident from a cluster of calcined flint and bone, the latter producing a modelled date for the start of occupation at 8220–7840 cal bc and ending at 7960–7530 cal bc (95% probability). The principal activity was the knapping of bladelets, the blanks for microlith production. Impact-damaged microliths indicated the re-tooling of hunting weaponry, while microwear analysis of other tools demonstrated hide working and butchery activity at the site. The lithics can be classified as a Honey Hill assemblage type on the basis of distinctive leaf-shaped microlithic points with inverse basal retouch.
Such assemblages have a known concentration in central England and are thought to be temporally intermediate between the conventional British Early and Late Mesolithic periods. The lithic assemblage is compared to other Honey Hill type and related Horsham type assemblages from south-eastern England. Both assemblage types are termed Middle Mesolithic and may be seen as part of wider developments in the late Preboreal and Boreal periods of north-west Europe. Rapid climatic warming at this time saw the northward expansion of deciduous woodland into north-west Europe. Emerging new ecosystems presented changes in resource patterns and the Middle Mesolithic lithic typo-technological developments reflect novel foraging strategies as adaptations to the new opportunities of Boreal forest conditions. While Honey Hill-type assemblages are seen as part of such wider processes their distinctive typological signature attests to autochthonous, regional developments of human groups infilling the landscape. Such cultural insularity may reflect changing social boundaries with reduction in mobility range and physical isolation caused by rising sea level and the creation of the British archipelago.