Key determinants of adaptive strategies of goats to a 2-day nutritional challenge during early lactation.

Little is known about the key determinants of the physiological adaptations to environmental challenges and how these determinants interact. We evaluated how the response/recovery profiles to a short-term nutritional challenge during early lactation are affected by early-life nutritional strategies in dairy goats divergently selected for functional longevity. We used 72 females, split into two cohorts, daughters of Alpine bucks divergently selected for functional longevity. The females from the two lines were fed with two divergent diets, normal vs low-energy, from weaning until the middle of first gestation, and then fed with the same standard diet. Individual BW, body condition score, morphology, and plasma samples were collected from birth to first kidding. The adaptative physiological strategy to a nutritional challenge was assessed via a 2-day feed restriction challenge, during early lactation, which consisted of a five-day control period on a standard lactation diet followed by a 2-day challenge with straw-only feeding and then a 10-day recovery period on a standard lactation diet. During the challenge, DM intake, BW, milk yield (MY), and plasma and milk metabolite composition were recorded daily. Linear mixed-effects models were used to analyze all traits, considering the individual nested in the cohort as a random effect and the 2 × 2 treatments (i.e., line and rearing diet) and litter size as fixed effects. Linear mixed-effects models using a piecewise arrangement were used to analyze the response/recovery profiles to nutritional challenge. Random parameters estimated for each individual, using the mixed-effects models without the fixed effects of rearing diet and genetic line, were used in a stepwise model selection based on R2 to identify key determinants of an individual's physiological adaptations to environmental challenges. Differences in stature and body reserves created by the two rearing diets diminished during late gestation and the 5-day control period. Genetic line did not affect body reserves during the rearing phase. Rearing diet and genetic line slightly affected the recovery profiles of evaluated traits and had no effects on prechallenge and response to challenge profiles. The prekidding energy status measures and MY before challenge were selected as strong predictors of variability in response-recovery profiles of milk metabolites that have strong links with body energy dynamics (i.e., isoCitrate, ß-hydroxybutyrate, choline, cholesterol, and triacylglycerols; R2 = 35%). Our results suggested that prekidding energy status and MY are key determinants of adult resilience and that rearing diet and genetic line may affect adult resilience insofar as they affect the animals' energy status.

Radiation dose to multidisciplinary staff members during complex interventional procedures.

INTRODUCTION: Complex interventional radiology procedures involve extensive fluoroscopy and image acquisition while staff are in-room. Monitoring occupational radiation dose is crucial in optimization. The purpose was to determine radiation doses received by staff involved in complex interventional procedures performed in a dedicated vascular or neuro intervention room. METHODS: Individual real-time radiation dose for all staff involved in vascular and neuro-interventional procedures in adult patients was recorded over a one-year period using wireless electronic dosimeters attached to the apron thyroid shield. A reference dosimeter was attached to the C-arm near the tube housing to measure scattered, unshielded radiation. Radiology staff carried shoulder thermo-luminescent dosimeters with monthly read-out to monitor dose over time. RESULTS: Occupational radiation dose was measured in 99 interventional procedures. In many cases prostate artery embolization procedures exposed radiologists to high radiation doses with a median of 15.0 µSv and a very large spread, i.e. 0.2-152.5 µSv. In all procedures except uterine fibroid embolization radiographers were exposed to lower doses than those of radiologists, with endovascular aortic repair being the procedure with highest median exposure to assisting radiographers, i.e. 2.2 µSv ranging from 0.1 to 36.1 µSv. Median radiation dose for the reference dosimeter was 670 µGy while median staff dose for all procedures combined was 3.2 µGy. CONCLUSION: Radiation doses for multiple staff were determined and the ratio between staff dose and reference dosimeter indicated proper use of shielding in general. Some high-dose procedures may need further optimization for certain staff members, especially those not primarily employed in radiology. IMPLICATIONS FOR PRACTICE: The study provides benchmark doses that may be used widely in audits and in the ongoing effort to optimize radiation protection for staff in interventional radiology.

Prediction of key milk biomarkers in dairy cows through milk mid-infrared spectra and international collaborations.

At the individual cow level, suboptimum fertility, mastitis, negative energy balance, and ketosis are major issues in dairy farming. These problems are widespread on dairy farms and have an important economic impact. The objectives of this study were (1) to assess the potential of milk mid-infrared (MIR) spectra to predict key biomarkers of energy deficit (citrate, isocitrate, glucose-6 phosphate [glucose-6P], free glucose), ketosis (ß-hydroxybutyrate [BHB] and acetone), mastitis (N-acetyl-ß-d-glucosaminidase activity [NAGase] and lactate dehydrogenase), and fertility (progesterone); (2) to test alternative methodologies to partial least squares (PLS) regression to better account for the specific asymmetric distribution of the biomarkers; and (3) to create robust models by merging large datasets from 5 international or national projects. Benefiting from this international collaboration, the dataset comprised a total of 9,143 milk samples from 3,758 cows located in 589 herds across 10 countries and represented 7 breeds. The samples were analyzed by reference chemistry for biomarker contents, whereas the MIR analyses were performed on 30 instruments from different models and brands, with spectra harmonized into a common format. Four quantitative methodologies were evaluated to address the strongly skewed distribution of some biomarkers. Partial least squares regression was used as the reference basis, and compared with a random modification of distribution associated with PLS (random-downsampling-PLS), an optimized modification of distribution associated with PLS (KennardStone-downsampling-PLS), and support vector machine (SVM). When the ability of MIR to predict biomarkers was too low for quantification, different qualitative methodologies were tested to discriminate low versus high values of biomarkers. For each biomarker, 20% of the herds were randomly removed within all countries to be used as the validation dataset. The remaining 80% of herds were used as the calibration dataset. In calibration, the 3 alternative methodologies outperform the PLS performances for the majority of biomarkers. However, in the external herd validation, PLS provided the best results for isocitrate, glucose-6P, free glucose, and lactate dehydrogenase (coefficient of determination in external herd validation [R2v] = 0.48, 0.58, 0.28, and 0.24, respectively). For other molecules, PLS-random-downsampling and PLS-KennardStone-downsampling outperformed PLS in the majority of cases, but the best results were provided by SVM for citrate, BHB, acetone, NAGase, and progesterone (R2v = 0.94, 0.58, 0.76, 0.68, and 0.15, respectively). Hence, PLS and SVM based on the entire dataset provided the best results for normal and skewed distributions, respectively. Complementary to the quantitative methods, the qualitative discriminant models enabled the discrimination of high and low values for BHB, acetone, and NAGase with a global accuracy around 90%, and glucose-6P with an accuracy of 83%. In conclusion, MIR spectra of milk can enable quantitative screening of citrate as a biomarker of energy deficit and discrimination of low and high values of BHB, acetone, and NAGase, as biomarkers of ketosis and mastitis. Finally, progesterone could not be predicted with sufficient accuracy from milk MIR spectra to be further considered. Consequently, MIR spectrometry can bring valuable information regarding the occurrence of energy deficit, ketosis, and mastitis in dairy cows, which in turn have major influences on their fertility and survival.

Biomolecular characterization of 3500-year-old ancient Egyptian mummification balms from the Valley of the Kings.

Ancient Egyptian mummification was practiced for nearly 4000 years as a key feature of some of the most complex mortuary practices documented in the archaeological record. Embalming, the preservation of the body and organs of the deceased for the afterlife, was a central component of the Egyptian mummification process. Here, we combine GC-MS, HT-GC-MS, and LC-MS/MS analyses to examine mummification balms excavated more than a century ago by Howard Carter from Tomb KV42 in the Valley of the Kings. Balm residues were scraped from now empty canopic jars that once contained the mummified organs of the noble lady Senetnay, dating to the 18th dynasty, ca. 1450 BCE. Our analysis revealed balms consisting of beeswax, plant oil, fats, bitumen, Pinaceae resins, a balsamic substance, and dammar or Pistacia tree resin. These are the richest, most complex balms yet identified for this early time period and they shed light on balm ingredients for which there is limited information in Egyptian textual sources. They highlight both the exceptional status of Senetnay and the myriad trade connections of the Egyptians in the 2nd millennium BCE. They further illustrate the excellent preservation possible even for organic remains long removed from their original archaeological context.

Towards optimal use of antithrombotic therapy of people with cancer at the end of life: A research protocol for the development and implementation of the SERENITY shared decision support tool.

BACKGROUND: Even though antithrombotic therapy has probably little or even negative effects on the well-being of people with cancer during their last year of life, deprescribing antithrombotic therapy at the end of life is rare in practice. It is often continued until death, possibly resulting in excess bleeding, an increased disease burden and higher healthcare costs. METHODS: The SERENITY consortium comprises researchers and clinicians from eight European countries with specialties in different clinical fields, epidemiology and psychology. SERENITY will use a comprehensive approach combining a realist review, flash mob research, epidemiological studies, and qualitative interviews. The results of these studies will be used in a Delphi process to reach a consensus on the optimal design of the shared decision support tool. Next, the shared decision support tool will be tested in a randomised controlled trial. A targeted implementation and dissemination plan will be developed to enable the use of the SERENITY tool across Europe, as well as its incorporation in clinical guidelines and policies. The entire project is funded by Horizon Europe. RESULTS: SERENITY will develop an information-driven shared decision support tool that will facilitate treatment decisions regarding the appropriate use of antithrombotic therapy in people with cancer at the end of life. CONCLUSIONS: We aim to develop an intervention that guides the appropriate use of antithrombotic therapy, prevents bleeding complications, and saves healthcare costs. Hopefully, usage of the tool leads to enhanced empowerment and improved quality of life and treatment satisfaction of people with advanced cancer and their care givers.

Multivariate analysis of milk metabolite measures shows potential for deriving new resilience phenotypes.

In a context of growing interest in breeding more resilient animals, a noninvasive indicator of resilience would be very valuable. We hypothesized that the time-course of concentrations of several milk metabolites through a short-term underfeeding challenge could reflect the variation of resilience mechanisms to such a challenge. We submitted 138 one-year-old primiparous goats, selected for extreme functional longevity (i.e., productive longevity corrected for milk yield [60 low longevity line goats and 78 high longevity line goats]), to a 2-d underfeeding challenge during early lactation. We measured the concentration of 13 milk metabolites and the activity of 1 enzyme during prechallenge, challenge, and recovery periods. Functional principal component analysis summarized the trends of milk metabolite concentration over time efficiently without preliminary assumptions concerning the shapes of the curves. We first ran a supervised prediction of the longevity line of the goats based on the milk metabolite curves. The partial least square analysis could not predict the longevity line accurately. We thus decided to explore the large overall variability of milk metabolite curves with an unsupervised clustering. The large year × facility effect on the metabolite concentrations was precorrected for. This resulted in 3 clusters of goats defined by different metabolic responses to underfeeding. The cluster that showed higher ß-hydroxybutyrate, cholesterol, and triacylglycerols increase during the underfeeding challenge was associated with poorer survival compared with the other 2 clusters. These results suggest that multivariate analysis of noninvasive milk measures show potential for deriving new resilience phenotypes.

Reproductive performance of rabbit females from three paternal lines with a different potential for growth rate and resilience.

A total of 197 nulliparous rabbits (from three paternal lines) were used to test potential strategies to overcome the consequences on reproduction associated with the selection for high growth rate. The R line was selected for growth rate during the growing period for 37 generations, the RF line was founded through a high selection intensity of elite animals of the R line, and the RFLP line, which was obtained by backcrossing RF animals with the LP line (a long-lived productive maternal line, characterised by high resilience). BW, perirenal fat thickness, fertility, daily feed intake, milk yield and blood metabolites of females were controlled from 1st artificial insemination to 3rd parturition. Litter size, litter weight, individual weight and feed ingestion of kits were controlled from birth to weaning. Our results show that RF females were significantly lighter than R and RFLP females throughout the trial (-5.0%; P < 0.05). Furthermore, RF animals had a higher fertility rate than RFLP females, at first cycle (+10.5 percentage points; P < 0.05). However, RFLP had a higher fertility rate than RF females at second cycle (+21.5 percentage points; P < 0.01). On average, RFLP females had higher perirenal fat thickness than R females at parturition (+3.0%; P < 0.05) and higher daily feed intake than of R and RF females during gestation and late lactation (+9.7 and +8.7%, respectively; P < 0.05). RFLP females produced more milk than R and RF females in the two first lactations (+18.5%; P < 0.001). In the first three parturitions, R females delivered fewer kits born alive (-1.7 kits than RF and RFLP; P < 0.05). In addition, R females' blood had a higher concentration of glutamine and glutamate than RFLP (+24 and +22.7%, respectively; P < 0.05). RFLP litters were heavier than both R and RF litters throughout lactation. However, R kits were heavier at birth than RF and RFLP (+7.9%). Results suggest that the foundation of a paternal line using elite animals could generate females with better early reproductive performance. In addition, backcrossing the RF line with a maternal LP line resulted in a genetic line whose females had a different resource allocation strategy to foster reproduction during the studied period.

Milk metabolites can characterise individual differences in animal resilience to a nutritional challenge in lactating dairy goats.

The aim of this study is built in two phases: to quantify the ability of novel milk metabolites to measure between-animal variability in response and recovery profiles to a short-term nutritional challenge, then to derive a resilience index from the relationship between these individual variations. At two different stages of lactation, sixteen lactating dairy goats were exposed to a 2-d underfeeding challenge. The first challenge was in late lactation, and the second was carried out on the same goats early in the following lactation. During the entire experiment period, samples were taken at each milking for milk metabolite measures. For each metabolite, the response profile of each goat was characterised using a piecewise model for describing the dynamic pattern of response and recovery profiles after the challenge relative to the start of the nutritional challenge. Cluster Analysis identified three types of response/recovery profiles per metabolite. Using cluster membership, multiple correspondence analyses (MCAs) were performed to further characterise response profile types across animals and metabolites. This MCA analysis identified three groups of animals. Further, discriminant path analysis was able to separate these groups of multivariate response/recovery profile type based on threshold levels of three milk metabolites: ß-hydroxybutyrate, free glucose and uric acid. Further analyses were done to explore the possibility of developing an index of resilience from milk metabolite measures. Different types of performance response to short-term nutritional challenge can be distinguished using multivariate analyses of a panel of milk metabolites.

eHealth technology use and eHealth literacy after percutaneous coronary intervention.

AIMS: Electronic health (eHealth) sources have great potential to improve patients' access to health information for self-management of secondary prevention after percutaneous coronary intervention (PCI). It remains unclear, however, whether patients are health-related digitally active and whether they have sufficient eHealth literacy. This study aimed to determine the extent to which patients after PCI are health-related digitally active at baseline, 2 and 6 months after PCI, and to determine the association between patients' eHealth literacy and their health-related digital activity. METHODS AND RESULTS: This multicentre cohort study included patients at three large referral PCI centres in Norway (n = 1970). Data were collected from medical records, national registries, and patients' self-reports. The eHealth Literacy Scale (eHEALS) assessed patients' eHealth literacy. At baseline, 67% had used the internet to find health information. The mean eHEALS score was 25.71 (standard deviation 6.22), illustrating a lower level of eHealth literacy. There were substantial associations between eHealth literacy and use of the internet to find health information [coefficient 10.90, 95% confidence interval (CI) 8.05-14.57]. At the 2-month follow-up, there were substantial associations between baseline eHealth literacy and use of the internet to find information about health, prevention, illness, or treatment [odds ratio (OR) 1.19, 95% CI 1.14-1.24] and use of health applications (OR 1.15, 95% CI 1.08-1.22). CONCLUSION: This study provides evidence that patients' level of eHealth literacy after PCI is associated to how patients use, and can make use of, eHealth technology for health information. REGISTRATION: ClinicalTrials.gov (NCT03810612).

Can advanced edge enhancement software improve image quality to visualise tubes, catheters and wires in digital chest radiographs?

INTRODUCTION: This study aimed to test whether Advanced Edge Enhancement (AEE) software could improve the localisation of tubes, catheters or wires, while also affecting the overall image quality in chest x-rays (CXR). METHODS: In total, 50 retrospective CXRs were included. All images were obtained utilising the Canon X-ray system (CANON/Arcoma Precision T3 DR System, Canon Europe, Amsterdam, NL) with a CXDI-810C wireless detector. A clinical image, plus three additional AEE algorithms were applied using post processing (two intensity variations 1 and 4) on all CXRs totalling 350 different images. Three radiologists evaluated the images using a subjective Absolute Visual Grading Analysis (VGA). The clinical images used in post processing were not applied as reference in the analysis. Each radiologist graded the images separately in a randomized order, with a score of three indicating suitability for diagnostic assessment. RESULTS: The three AEE algorithms contributed to an overall improvement (average 16-49%) in visualisation of tube, catheter or wire on CXR images. The Mann-Whitney U tests showed a statistically significant (p < 0.05) improvement in contrast resolution and sharpness, indicating an increased ability to differentiate tubes, wires or catheters tips from surrounding tissues. For the noise criterion, not applying any AEE algorithm showed a significantly higher homogeneity in soft tissue (p < 0.001), reducing the ability to visualise soft tissue. The high-intensity catheter algorithm was the only algorithm to achieve a statistically significant (p = 0.017) increase in the ability to differentiate pulmonary tissues of similar density. CONCLUSION: An overall improvement in the visualisation of tube, catheter and wire placement was obtained using the three AEE-algorithms. The bone and catheter algorithms showed the highest consistency, with the small structure algorithm underperforming in resolution and low contrast resolution. In general, image noise increased regardless of algorithm type or applied intensity. The AEE-algorithms should therefore be seen as a supplementary tool to the clinical image protocol, while having the potential to improve image quality to specific clinical situations. IMPLICATIONS FOR PRACTICE: AEE filtered images appear to be a supplement to the current practice of using CXRs in the diagnosis in placement of catheters, tubes and wires in the chest region. The use of AEE-algorithms has the potential to improve the daily work in clinical practice, which serves the basis for further investigation of its effect on radiographic practices.

Elements in Mental Health Interventions Associated with Effects on Emotion Regulation in Adolescents: A Meta-Analysis.

PURPOSE: Adolescence is a sensitive period for developing mental health problems. Interventions targeting emotion regulation have shown promising transdiagnostic effects for this group, but optimization efforts are called for. In the current study, we used an element-based approach to identify potentially active ingredients in interventions measuring emotion regulation, to guide further optimization. METHODS: We coded practice elements in 30 studies based on a systematic review of mental health interventions measuring emotion regulation in adolescents (N = 2,389 participants, mean age 13-17 years). Using a three-level modeling approach, we then investigated the difference in effect on emotion regulation between studies of interventions with and without these practice elements. RESULTS: We identified 75 practice elements and 15 element categories used in the included interventions. Results showed significantly stronger effects on emotion regulation when interventions included the practice elements Setting goals for treatment (difference in d = 0.40, 95% CI [0.09, 0.70], p = .012) and Psychoeducation about acceptance (difference in d = 0.58, 95% CI [0.09, 1.07], p = .021). Furthermore, a total of 11 elements and four overall categories were identified as potentially active ingredients, based on an effect size difference of > 0.20 between interventions with and without the elements. CONCLUSION: The results can direct experimental research into the selection of practices that are most likely key to mechanisms of change in interventions addressing emotion regulation for adolescents. The challenge of measuring emotion regulation is discussed.

Fluorometric determination of isocitrate dehydrogenase (EC 1.1.1.42; 1; NADP+ dependent) in ruminant milk.

The enzyme isocitrate dehydrogenase (EC 1.1.1.42; 1; NADP+ dependent) located in the mammary cell cytosol mediates the synthesis of the majority of reducing equivalents for the energetically demanding milk fat and cholesterol synthesis in mammary cell cytosol. The present article presents a novel fluorometric method for quantification of the activity of this enzyme (IDH) in ruminant milk without pretreatment of the sample. Further, 493 goat milk samples - harvested before, during and after a nutritional restriction - were analysed for IDH activity i) with addition of extra substrate (isocitrate), and ii) with the intrinsic isocitrate solely. The IDH activity ranged from 0.22 to 15.4 units [nano moles product/(ml * min)] (un-supplemented) and from 0.22 to 45.6 units (isocitrate supplemented). The IDH activity increased considerably in milk during the nutritional restriction period concomitant with the increase in the metabolite isocitrate concentration and somatic cell count and returned to the initial level shortly after restriction period. The present 'high through-put' analytical method may be beneficial in future studies to phenotype modifications in mammary energy metabolism and milk fat synthesis, for which IDH activity may be a biomarker.

Impact of childhood trauma on antipsychotic effectiveness in schizophrenia spectrum disorders: A prospective, pragmatic, semi-randomized trial.

Antipsychotic medications are generally effective in ameliorating psychotic symptoms in schizophrenia spectrum disorders (SSDs). Identifying predictors associated with poor treatment response is important for a personalized treatment approach. Childhood trauma (CT) may have a general and differential effect on the effectiveness of different types of antipsychotics in SSDs. The Bergen-Stavanger-Trondheim-Innsbruck (BeSt InTro) study is a pragmatic, researcher-initiated, semi-randomized trial. The present study aimed to investigate symptom change (the Positive and Negative Syndrome Scale) from baseline to 1, 3, 6, 12, 26, 39 and 52 weeks of antipsychotic treatment (amisulpride, aripiprazole and olanzapine) by group (CT/no CT). Participants (n = 98) with diagnoses within the schizophrenia spectrum (F20-29 in the International Classification of Diseases - 10th Revision) were randomized to receive amisulpride, aripiprazole or olanzapine, and for this study categorized into groups of none and low CT, and moderate to severe CT according to thresholds defined by the Childhood Trauma Questionnaire Short-Form manual. CT in SSDs predicted an overall slower treatment response and less antipsychotic effectiveness after 26 weeks of treatment, which was statistically nonsignificant at 52 weeks. Secondary analyses showed a differential effect of CT related to type of antipsychotic medication: patients with SSDs and CT who received olanzapine showed less antipsychotic effectiveness throughout 52 weeks of treatment. The intention-to-treat and per-protocol analyses were convergent. Our findings indicate that in patients with SSD and CT, delayed response to antipsychotics could be expected, and a longer evaluation period before considering change of medication may be recommended.

Exploring radiographers' experience with mobile X-ray of patients in their homes.

INTRODUCTION: To offer citizens with frailty or dementia living in nursing homes or other institutions a less stressful and anxious X-ray examination, a Danish hospital offers to perform the examination in the citizen's residence. This has changed the working procedure for the radiographers performing the examination. The aim of this study was to explore if the radiographers self-perceived competencies have changed whilst working in the mobile X-ray unit and if so, how these competencies are utilised within the department-based medical imaging team. METHOD: This study had a qualitative design following a hermeneutic approach. Individual semi structured interviews included nine radiographers, four radiographers working in the mobile X-ray unit and five radiographers working exclusively in the medical imaging team. RESULTS: Radiographers who worked in the mobile X-ray unit did acquire new competencies such as better communication and creative positioning skills. All nine participants recognised the advantage of sharing experiences and competencies with colleagues, and recommended a formal forum to do so. They sought opportunities for the use of the mobile X-ray unit to be more widespread within their own region, and within the profession. CONCLUSION: This study indicates that radiographers working with mobile X-ray unit gained new competencies in communication and positioning, but without spread of new knowledge to colleagues in the medical imaging team. IMPLICATION FOR PRACTICE: The use of home-based mobile X-ray is a new way to provide health care services and gain new competencies for the radiographers to focus on patient centred care.

Milk metabolites and fatty acids as noninvasive biomarkers of metabolic status and energy balance in early-lactation cows.

The objective was to study the effects of week of lactation (WOL) and experimental nutrient restriction on concentrations of selected milk metabolites and fatty acids (FA), and assess their potential as biomarkers of energy status in early-lactation cows. To study WOL effects, 17 multiparous Holstein cows were phenotyped from calving until 7 WOL while allowed ad libitum intake of a lactation diet. Further, to study the effects of nutrient restriction, 8 of these cows received a diet containing 48% straw (high-straw) for 4 d starting at 24 ± 3 days in milk (mean ± SD), and 8 cows maintained on the lactation diet were sampled to serve as controls. Blood and milk samples were collected weekly for the WOL data set, and daily from d -1 to 3 of nutrient restriction (or control) for the nutritional challenge data set. Milk ß-hydroxybutyrate (BHB), isocitrate, glucose, glucose-6-phosphate (glucose-6P), galactose, glutamate, creatinine, uric acid, and N-acetyl-ß-d-glucosaminidase activity (NAGase) were analyzed in p.m. and a.m. samples, and milk FA were analyzed in pooled p.m. and a.m. samples. Average energy balance (EB) per day ranged from -27 MJ/d to neutral when cows received the lactation total mixed ration, and from -109 to -87 ± 7 MJ/d for high-straw (least squares means ± standard error of the mean). Plasma nonesterified FA concentration was 1.67 ± 0.13 mM and BHB was 2.96 ± 0.39 mM on the d 3 of high-straw (least squares means ± standard error of the mean). Milk concentrations of BHB, glucose, glucose-6P, glutamate, and uric acid differed significantly between p.m. and a.m. milkings. Milk isocitrate, glucose-6P, creatinine, and NAGase decreased, whereas milk glucose and galactose increased with WOL. Changes in milk BHB, isocitrate, glucose, glucose-6P, and creatinine were concordant during early lactation and in response to nutrient restriction. Milk galactose and NAGase were modulated by WOL only, whereas glutamate and uric acid concentrations responded to nutrient restriction only. The high-straw increased milk concentrations of FA potentially mobilized from adipose tissue (e.g., C18:0 and cis-9 C18:1 and sum of odd- and branched-chain FA (OBCFA) with carbon chain greater than 16; ∑ OBCFA >C16), and decreased concentrations of FA synthesized de novo by the mammary gland (e.g., sum of FA with 6 to 15 carbons; ∑ C6:0 to C15:0). Similar observations were made during early lactation. Plasma nonesterified FA concentrations had the best single linear regression with EB (R2 = 0.62). Milk isocitrate, Σ C6:0 to C15:0. and cis-9 C18:1 had the best single linear regressions with EB (R2 ≥ 0.44). Milk BHB, isocitrate, galactose, glutamate, and creatinine explained up to 64% of the EB variation observed in the current study using multiple linear regression. Milk concentrations of ∑ C6:0 to C15:0, C18:0, cis-9 C18:1, and ∑ OBCFA >C16 presented some of the best correlations and regressions with other indicators of metabolic status, lipomobilization, and EB, and their responses were concordant during early lactation and during experimental nutrient restriction. Metabolites and FA secreted in milk may serve as noninvasive indicators of metabolic status and EB of early-lactation cows.

Fungal quinones: diversity, producers, and applications of quinones from Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium.

Quinones represent an important group of highly structurally diverse, mainly polyketide-derived secondary metabolites widely distributed among filamentous fungi. Many quinones have been reported to have important biological functions such as inhibition of bacteria or repression of the immune response in insects. Other quinones, such as ubiquinones are known to be essential molecules in cellular respiration, and many quinones are known to protect their producing organisms from exposure to sunlight. Most recently, quinones have also attracted a lot of industrial interest since their electron-donating and -accepting properties make them good candidates as electrolytes in redox flow batteries, like their often highly conjugated double bond systems make them attractive as pigments. On an industrial level, quinones are mainly synthesized from raw components in coal tar. However, the possibility of producing quinones by fungal cultivation has great prospects since fungi can often be grown in industrially scaled bioreactors, producing valuable metabolites on cheap substrates. In order to give a better overview of the secondary metabolite quinones produced by and shared between various fungi, mainly belonging to the genera Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium, this review categorizes quinones into families such as emodins, fumigatins, sorbicillinoids, yanuthones, and xanthomegnins, depending on structural similarities and information about the biosynthetic pathway from which they are derived, whenever applicable. The production of these quinone families is compared between the different genera, based on recently revised taxonomy. KEY POINTS: • Quinones represent an important group of secondary metabolites widely distributed in important fungal genera such as Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium. • Quinones are of industrial interest and can be used in pharmacology, as colorants and pigments, and as electrolytes in redox flow batteries. • Quinones are grouped into families and compared between genera according to the revised taxonomy.

Fava beans can substitute soybean meal and rapeseed meal as protein source in diets for lactating dairy cows.

The effect of replacing mixtures of wheat and soybean meal and wheat and rapeseed meal by toasted fava beans, and the effect of toasting fava beans on feed intake, milk yield, and composition of milk and feces were investigated using 40 Holstein cows in each of two 4 × 4 Latin square design trials conducted simultaneously. In trial 1, the 4 treatment concentrates were untreated fava beans, toasted fava beans, 42% soybean meal + 58% rolled wheat, and a 21, 29, and 50% mix of soybean meal, rolled wheat, and toasted fava beans, respectively [on dry matter (DM) basis]. In trial 2, the 4 experimental treatments were untreated fava beans, toasted fava beans, 64% rapeseed meal + 36% rolled wheat, and a 32, 18, and 50% mix of rapeseed meal, rolled wheat, and toasted fava beans, respectively (on DM basis). In each trial, 16 primiparous and 24 multiparous cows were fed the treatment concentrates as part of a partial mixed ration, of which the forage consisted of 50% corn silage and 50% grass-clover silage. Substitution of soybean meal and wheat or rapeseed meal and wheat with toasted fava beans did not affect total DM intake, and no linear effects were observed on milk yield or energy-corrected milk (ECM) yield. However, in trial 2, a quadratic effect was observed on milk yield when substituting rapeseed meal and wheat with toasted fava beans. In both trials, substitution of soybean meal and wheat or rapeseed meal and wheat with toasted fava beans increased milk lactose concentration and decreased milk protein yield and concentration of protein in milk. In both trials, fecal concentration of starch increased linearly when substituting soybean meal and wheat or rapeseed meal and wheat with toasted fava beans. In trial 2, fecal concentration of P decreased when substituting rapeseed meal and wheat with toasted fava beans. In situ investigations showed increased rumen undegradable protein concentration and thereby increased estimated metabolizable protein supply when toasting fava beans. However, in both trials, milk protein yield and concentration decreased when cows were fed toasted compared with untreated fava beans. Furthermore, when cows were fed toasted compared with untreated fava beans in trial 1, milk yield, ECM yield, and nitrogen efficiency decreased. We conclude that toasted fava beans could substitute soybean meal and wheat or rapeseed meal and wheat with regard to ECM yield. However, milk protein yield decreased when substituting soybean meal and wheat or rapeseed meal and wheat with toasted fava beans. Compared with untreated fava beans, toasting had no positive effect on milk production and nitrogen efficiency.

Andreev Modes from Phase Winding in a Full-Shell Nanowire-Based Transmon.

We investigate transmon qubits made from semiconductor nanowires with a fully surrounding superconducting shell. In the regime of reentrant superconductivity associated with the destructive Little-Parks effect, numerous coherent transitions are observed in the first reentrant lobe, where the shell carries 2π winding of superconducting phase, and are absent in the zeroth lobe. As junction density was increased by gate voltage, qubit coherence was suppressed then lost in the first lobe. These observations and numerical simulations highlight the role of winding-induced Andreev states in the junction.

Developmental stage and morphology of the competent blastocyst are associated with sex of the child but not with other obstetric outcomes: a multicenter cohort study.

STUDY QUESTION: Are transfer day, developmental stage and morphology of the competent blastocyst in pregnancies leading to live birth associated with preterm birth, birthweight, length at birth and sex of the child? SUMMARY ANSWER: A high score in blastocyst developmental stage and in trophectoderm (TE) showed a significant association with the sex of the child, while no other associations with obstetric outcomes were observed. WHAT IS KNOWN ALREADY: The association between blastocyst assessment scores and obstetric outcomes have been reported in small single-center studies and the results are conflicting. STUDY DESIGN, SIZE, DURATION: Multicenter historical cohort study based on exposure data (transfer day (blastocyst developmental stage reached by Day 5 or Day 6)) blastocyst developmental stage (1-6) and morphology (TE and inner cell mass (ICM): A, B, C)) and outcome data (preterm birth, birthweight, length at birth, and sex of the child) from women undergoing single blastocyst transfer resulting in a singleton pregnancy and live birth. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data from 16 private and university-based facilities for clinical services and research were used. A total of 7246 women, who in 2014-2018 underwent fresh-embryo transfer with a single blastocyst or frozen-thawed embryo transfer (FET) with a single blastocyst resulting in a singleton pregnancy were identified. Linking to the Danish Medical Birth Registry resulted in a total of 4842 women with a live birth being included. Cycles with pre-implantation genetic testing and donated gametes were excluded. The analyses were adjusted for female age (n = 4842), female BMI (n = 4302), female smoking (n = 4290), parity (n = 4365), infertility diagnosis (n = 4765), type of treatment (n = 4842) and center (n = 4842); some analyses additionally included gestational age (n = 4368) and sex of the child (n = 4833). MAIN RESULTS AND THE ROLE OF CHANCE: No statistically significant associations between blastocyst assessment scores (transfer day, developmental stage, TE, ICM) and preterm birth (8.3%) or birthweight (mean 3461.7 g) were found. The adjusted association between blastocysts with a TE score of C and a TE score of A and length at birth (mean 51.6 cm) were statistically significant (adjusted mean difference 0.4 cm (95% CI: 0.02; 0.77)). Blastocysts transferred with developmental stage score 5 compared to blastocysts transferred with score 3 had a 34% increased probability of being a boy (odds ratio (OR) 1.34 (95% CI: 1.09; 1.64). Further, TE score B blastocysts compared to TE score A blastocysts had a 31% reduced probability of being a boy (OR 0.69 (95% CI: 0.60; 0.80)). LIMITATIONS, REASONS FOR CAUTION: It is possible that some residual confounding remains. WIDER IMPLICATIONS OF THE FINDINGS: Blastocyst selection during ART does not appear to introduce any negative effects on obstetric outcome. Therefore, clinicians and patients can be reassured that the assessment scores of the selected blastocyst will not in themselves pose a risk of preterm birth or affect birthweight and the length at birth. STUDY FUNDING/COMPETING INTEREST(S): Unrestricted grant from Gedeon Richter Nordics AB, Sweden. None of the authors have any competing interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Parity-Protected Superconductor-Semiconductor Qubit.

Coherence of superconducting qubits can be improved by implementing designs that protect the parity of Cooper pairs on superconducting islands. Here, we introduce a parity-protected qubit based on voltage-controlled semiconductor nanowire Josephson junctions, taking advantage of the higher harmonic content in the energy-phase relation of few-channel junctions. A symmetric interferometer formed by two such junctions, gate-tuned into balance and frustrated by a half-quantum of applied flux, yields a cos(2φ) Josephson element, reflecting coherent transport of pairs of Cooper pairs. We demonstrate that relaxation of the qubit can be suppressed tenfold by tuning into the protected regime.