Short communication: Temporal profiles of colostrum and milk haptoglobin and substance P in early lactation multiparous Holstein cows.

Milk markers have the potential to aid in the detection of cow disease in early lactation if the automation of milk analysis becomes commonplace. Characterising temporal profiles of milk markers in dairy cows will improve the understanding of basal concentrations in clinically healthy cows. The objective of this observational study was to characterise the variation and temporal profiles of colostrum and milk haptoglobin (Hp) and substance P concentrations within 21 days postcalving in clinically healthy multiparous Holstein dairy cows. Ninety Holstein dairy cows from a commercial dairy herd were included. Milk samples were collected on the day of calving (day 0), and on days 1 to 4, 7, 14, and 21 postcalving and concentrations of Hp and substance P in colostrum (days 0 to 3) and milk (days 4, 7, 14, and 21) were determined using Enzyme Linked Immunosorbent assay. Haptoglobin and substance P concentrations were, on average (raw means ± SD), 0.40 ± 0.26 µg/ml and 56.2 ± 38.7 pg/ml in colostrum, respectively, and 0.23 ± 0.23 µg/ml and 37.1 ± 27.8 pg/ml in milk, respectively. Haptoglobin and substance P were elevated and greatest 1 day postcalving (least squares mean ± SE of the mean; 0.53 ± 0.05 µg/ml and 46.5 ± 3.64 pg/ml, respectively) and substance P varied widely within 21 days postcalving. The presence of substance P in dairy cow colostrum was not documented previously. Elevated concentrations of Hp and substance P immediately postcalving may be due to physiological roles these inflammatory markers have in the dairy cow or neonate or may simply represent an accumulation in colostrum before the first milk is removed.

Animal- and herd-level factors associated with onset of puberty in grazing dairy heifers.

AIMS: To explore animal- and herd-level risk factors influencing age at puberty in predominantly Holstein-Friesian dairy heifers managed in seasonal, pasture-based systems. METHODS: Heifers born in spring 2018 (n = 5,010) from 54 commercial dairy herds in New Zealand were visited on three occasions when the mean heifer age, within herd, was 10 (visit 1; V1), 11 (V2) and 12 (V3) months old. Blood samples were collected on each visit and liveweight, stature and anogenital distance (AGD) were measured at V2. Heifers were defined as having reached puberty at the first visit where blood progesterone was elevated (≥ 1 ng/mL). Animal-level response variables included pubertal status by V1, V2 and V3, and age at puberty (or age at V3 plus 31 days for those that had not attained puberty by V3). To explore herd-level management factors, farmers answered a questionnaire relating to animal location, land type, health, feeding, and management between weaning and mating. A partial least squares regression was undertaken to identify herd-level factors associated with the greatest influence on puberty rate within herd. RESULTS: The mean age at puberty was 352 (SD 34.9) days. Heavier animals at a greater proportion of expected mature liveweight based on their breeding value for liveweight, or animals with a higher breed proportion of Jersey and lower breed proportion of Holstein, were associated with earlier puberty. Herd puberty rates varied widely among enrolled herds, and averaged 20%, 39% and 56% by V1, V2 and V3, respectively. Liveweight, followed by breed and land type, had the greatest influence on the herd puberty rate. Heifer herds with a greater mean liveweight (absolute and proportion of expected mature weight) or greater Jersey proportion had more animals that reached puberty at any visit, whereas herds located on steep land or with greater Holstein breed proportions had lower puberty rates. Management-related factors such as vaccinations, provision of feed supplements, and weighing frequency were also herd-level risk factors of puberty but had less influence. CONCLUSIONS AND CLINICAL RELEVANCE: This study highlights the importance of having well-grown heifers for increasing the chances of earlier puberty onset and the effect of breed and youngstock management to achieve growth targets. These outcomes have important implications for the optimal management of heifers to achieve puberty before their maiden breeding and for the timing of measurements to potentially incorporate a puberty trait in genetic evaluations.

[The history of lithium]. / De geschiedenis van lithium.

Background Lithium is the first choice for maintenance treatment of bipolar disorder. How was discovered that lithium is such an effective treatment for mood episodes? Aim To gain understanding in how lithium obtained its value in the pharmacotherapeutic treatment of bipolar disorder. Method Literature research into the use of lithium in the history of psychiatry. Results In 1949 John Cade discovered the usability of lithium in the treatment of mania. Subsequently, it was discovered that lithium prevents mood episodes in bipolar disorder, can be used in the treatment of unipolar depression as an addition to an antidepressant, and lowers the risk of suicidality. Conclusion Since the nineteenth century lithium is used in psychiatry. Mid twentieth century the therapeutic value of lithium was discovered in the treatment of bipolar disorder and many international guidelines consider lithium as ‘a golden standard’. However, with the arrival of other psychopharmaca lithium is prescribed less in the last decades. It is important to teach psychiatrists and nurse specialists how to use lithium because of its important value in the treatment of bipolar disorder.

Dynamic prediction of mortality in COVID-19 patients in the intensive care unit: A retrospective multi-center cohort study.

Background: The COVID-19 pandemic continues to overwhelm intensive care units (ICUs) worldwide, and improved prediction of mortality among COVID-19 patients could assist decision making in the ICU setting. In this work, we report on the development and validation of a dynamic mortality model specifically for critically ill COVID-19 patients and discuss its potential utility in the ICU. Methods: We collected electronic medical record (EMR) data from 3222 ICU admissions with a COVID-19 infection from 25 different ICUs in the Netherlands. We extracted daily observations of each patient and fitted both a linear (logistic regression) and non-linear (random forest) model to predict mortality within 24 h from the moment of prediction. Isotonic regression was used to re-calibrate the predictions of the fitted models. We evaluated the models in a leave-one-ICU-out (LOIO) cross-validation procedure. Results: The logistic regression and random forest model yielded an area under the receiver operating characteristic curve of 0.87 [0.85; 0.88] and 0.86 [0.84; 0.88], respectively. The recalibrated model predictions showed a calibration intercept of -0.04 [-0.12; 0.04] and slope of 0.90 [0.85; 0.95] for logistic regression model and a calibration intercept of -0.19 [-0.27; -0.10] and slope of 0.89 [0.84; 0.94] for the random forest model. Discussion: We presented a model for dynamic mortality prediction, specifically for critically ill COVID-19 patients, which predicts near-term mortality rather than in-ICU mortality. The potential clinical utility of dynamic mortality models such as benchmarking, improving resource allocation and informing family members, as well as the development of models with more causal structure, should be topics for future research.

Incidence and impact of anticoagulation-associated abnormal menstrual bleeding in women after venous thromboembolism.

Preliminary data and clinical experience have suggested an increased risk of abnormal uterine bleeding (AUB) in women of reproductive age treated with anticoagulants, but solid data are lacking. The TEAM-VTE study was an international multicenter prospective cohort study in women aged 18 to 50 years diagnosed with acute venous thromboembolism (VTE). Menstrual blood loss was measured by pictorial blood loss assessment charts at baseline for the last menstrual cycle before VTE diagnosis and prospectively for each cycle during 3 to 6 months of follow-up. AUB was defined as an increased score on the pictorial blood loss assessment chart (>100 or >150) or self-reported AUB. AUB-related quality of life (QoL) was assessed at baseline and the end of follow-up using the Menstrual Bleeding Questionnaire. The study was terminated early because of slow recruitment attributable to the COVID-19 pandemic. Of the 98 women, 65 (66%) met at least one of the 3 definitions of AUB during follow-up (95% confidence interval [CI], 57%-75%). AUB occurred in 60% of women (36 of 60) without AUB before VTE diagnosis (new-onset AUB; 95% CI, 47%-71%). Overall, QoL decreased over time, with a mean Menstrual Bleeding Questionnaire score increase of 5.1 points (95% CI, 2.2-7.9), but this decrease in QoL was observed only among women with new-onset AUB. To conclude, 2 of every 3 women who start anticoagulation for acute VTE experience AUB, with a considerable negative impact on QoL. These findings should be a call to action to increase awareness and provide evidence-based strategies to prevent and treat AUB in this setting. This was an academic study registered at www.clinicaltrials.gov as #NCT04748393; no funding was received.

Associations between peripartum lying and activity behaviour and blood non-esterified fatty acids and ß-hydroxybutyrate in grazing dairy cows.

During early lactation, most dairy cows experience negative energy balance (NEB). Failure to cope with this NEB, however, can place cows at greater risk of developing metabolic disease. Our objective was to characterise, retrospectively, lying behaviour and activity of grazing dairy cows grouped according to blood non-esterified fatty acids (NEFAs) and ß-hydroxybutyrate (BHB) as indicators of postpartum metabolic state. Blood was sampled weekly for up to 4 weeks precalving, on the day of calving (day 0), daily between 1 and 4 days postcalving, and then at least weekly between week 1 and week 5 postcalving for analysis of plasma NEFAs and BHB concentrations. Two hundred and forty-four multiparous Holstein-Friesian and Holstein-Friesian × Jersey cows were classified into one of three metabolic status groups based on maximum blood NEFAs and BHB concentrations during week 1 and 2 postcalving. A cow was classified as having either: (1) low NEFAs and low BHB (Lo-Lo; n = 78), when all blood samples were <1.0 mmol/L for NEFAs and ≤1.0 mmol/L for BHB during the first 2 weeks postcalving; (2) high NEFAs and low BHB (Hi-Lo; n = 134), when blood NEFAs were ≥1.0 mmol/L and blood BHB was ≤1.0 mmol/L at the same sampling time point during the first 2 weeks postcalving; or (3) high NEFAs and high BHB (Hi-Hi; n = 32), when blood NEFAs were ≥1.0 mmol/L and blood BHB was ≥1.2 mmol/L at the same sampling time point during the first 2 weeks postcalving. Accelerometers (IceTag or IceQube devices; IceRobotics Ltd.) were used to monitor lying and activity behaviours peripartum (-21 to +35 days relative to calving). Changes in lying behaviour and activity occurred before the mean day that cows were classified Hi-Hi and Hi-Lo (2.2 and 3.5 d postcalving, respectively). Up to 3 weeks preceding calving, Hi-Hi cows were more active, had fewer daily lying bouts (LBs), and spent less time lying than Lo-Lo cows. In addition, Hi-Hi cows had fewer daily LBs and were less active up to 4 weeks postcalving than Lo-Lo cows, but these differences were biologically small. Groups of grazing cows classified as experiencing a more severe metabolic challenge behave differently up to 3 weeks precalving than their herdmates with lower blood NEFAs and BHB postcalving. These altered behaviours may allow identification of individual cows at risk of a metabolic challenge, but further research is required.

Distribution of care expenditures for men and women with type 2 diabetes treated in primary care in the Netherlands: a case-control study (ZODIAC-59).

OBJECTIVE: This study aims to provide insight into the distribution of care expenditures for patients with type 2 diabetes mellitus (T2DM)- across multiple healthcare service categories and medical specialties-who receive diabetes care in the primary care setting. DESIGN: Observational, matched case-control study. SETTING: In the Netherlands, T2DM-specific care is mainly provided in the primary care setting. However, many patients with T2DM also use secondary care for complications and comorbidities, either related or unrelated to their diabetes. PARTICIPANTS: Patients with T2DM receiving diabetes care in primary care and participating in the Dutch Zwolle Outpatient Diabetes project Integrating Available Care cohort in the year 2011 were matched to persons without T2DM. Matching (1:2 ratio) was performed based on age, gender and socioeconomic status. Clinical data were combined with an all-payer claims database from 2011. RESULTS: In total, 43 775 patients with T2DM were identified of whom 37 240 could be matched with 74 480 controls. Total secondary care expenditures were €94 705 814, with a total annual median expenditure per patient of €2133 (1161 to 3340) for men and €2,535 (1374 to 5105) for women. The largest share of expenditures was on medication (26%), followed by secondary care (23%) and primary care services related (23%) to T2DM. The five most expensive specialties were: cardiology, surgery, internal medicine, orthopaedics and ophthalmology. Care expenditures for T2DM patients were twofold higher than those for persons without T2DM. Healthcare expenditures showed a skewed distribution, indicating that a small part of the studied population is responsible for a considerable part of the costs. CONCLUSIONS: Expenditures among primary care treated T2DM patients are higher than non-diabetic matched controls. Medication is the largest share of T2DM care expenditures. The present study provides insights into healthcare expenditures for T2DM; this may enable more efficient healthcare planning and reimbursement.

[Reverse abdominoplasty in the presence of bi-subcostal scar: Technical note]. / Abdominoplastie inversée en présence d'une cicatrice bi-sous-costale : note technique.

INTRODUCTION: The presence of horizontal supraumbilical scars increases the risk of vascular complications after a large abdominoplasty. We present here a technique of abdominal dermolipectomy with umbilical transposition called « reverse ¼, in the presence of a bi-subcostal scar. TECHNICAL NOTE: The reverse abdominoplasty technique consists in uninserting the umbilicus, detaching the supra-umbilical and sub-umbilical soft tissues by assessing the existing bi-subcostal scar in order to pull the skin upwards, and to remove the supra-umbilical excess skin, before bringing the umbilicus back to its proper position. DISCUSSION: This technique is a good alternative to perform an abdominal dermolipectomy in a patient with a history of bi-subcostal scarring without increasing the risk of abdominal skin necrosis, and without complicating or lengthening the conventional surgical procedure, provided that the upper redraping is achievable with sufficient upper excess skin and laxity.

Should germline genome editing be allowed? The effect of treatment characteristics on public acceptability.

STUDY QUESTION: To what extent do characteristics of germline genome editing (GGE) determine whether the general public supports permitting the clinical use of GGE? SUMMARY ANSWER: The risk that GGE would cause congenital abnormalities had the largest effect on support for allowing GGE, followed by effectiveness of GGE, while costs, the type of application (disease or enhancement) and the effect on child well-being had moderate effects. WHAT IS KNOWN ALREADY: Scientific progress on GGE has increased the urgency of resolving whether and when clinical application of GGE may be ethically acceptable. Various expert bodies have suggested that the treatment characteristics will be key in determining whether GGE is acceptable. For example, GGE with substantial risks (e.g. 15% chance of a major congenital abnormality) may be acceptable to prevent a severe disease but not to enhance non-medical characteristics or traits of an otherwise healthy embryo (e.g. eye colour or perhaps in the future more complex traits, such as intelligence). While experts have called for public engagement, it is unclear whether and how much the public acceptability of GGE is affected by the treatment characteristics proposed by experts. STUDY DESIGN, SIZE, DURATION: The vignette-based survey was disseminated in 2018 among 1857 members of the Dutch general public. An online research panel was used to recruit a sample representing the adult Dutch general public. PARTICIPANTS/MATERIALS, SETTING, METHODS: A literature review identified the key treatment characteristics of GGE: the effect on the well-being of the future child, use for disease or enhancement, risks for the future child, effectiveness (here defined as the chance of a live birth, assuming that if the GGE was not successful, the embryo would not be transferred), cost and availability of alternative treatments/procedures to prevent the genetic disease or provide enhancement (i.e. preimplantation genetic testing (PGT)), respectively. For each treatment characteristic, 2-3 levels were defined to realistically represent GGE and its current alternatives, donor gametes and ICSI with PGT. Twelve vignettes were created by fractional factorial design. A multinominal logit model assessed how much each treatment characteristic affected participants' choices. MAIN RESULTS AND THE ROLE OF CHANCE: The 1136 respondents (response rate 61%) were representative of the Dutch adult population in several demographics. Respondents were between 18 and 89 years of age. When no alternative treatment/procedure is available, the risk that GGE would cause (other) congenital abnormalities had the largest effect on whether the Dutch public supported allowing GGE (coefficient = -3.07), followed by effectiveness (coefficient = 2.03). Costs (covered by national insurance, coefficient = -1.14), the type of application (disease or enhancement; coefficient = -1.07), and the effect on child well-being (coefficient = 0.97) had similar effects on whether GGE should be allowed. If an alternative treatment/procedure (e.g. PGT) was available, participants were not categorically opposed to GGE, however, they were strongly opposed to using GGE for enhancement (coefficient = -3.37). The general acceptability of GGE was higher than participants' willingness to personally use it (P < 0.001). When participants considered whether they would personally use GGE, the type of application (disease or enhancement) was more important, whereas effectiveness and costs (covered by national insurance) were less important than when they considered whether GGE should be allowed. Participants who were male, younger and had lower incomes were more likely to allow GGE when no alternative treatment/procedure is available. LIMITATIONS, REASONS FOR CAUTION: Some (e.g. ethnic, religious) minorities were not well represented. To limit complexity, not all characteristics of GGE could be included (e.g. out-of-pocket costs), therefore, the views gathered from the vignettes reflect only the choices presented to the respondents. The non-included characteristics could be connected to and alter the importance of the studied characteristics. This would affect how closely the reported coefficients reflect 'real-life' importance. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first to quantify the substantial impact of GGE's effectiveness, costs (covered by national insurance), and effect on child well-being on whether the public considered GGE acceptable. In general, the participants were strikingly risk-averse, in that they weighed the risks of GGE more heavily than its benefits. Furthermore, although only a single study in one country, the results suggests that-if sufficiently safe and effective-the public may approve of using GGE (presumably combined with PGT) instead of solely PGT to prevent passing on a disease. The reported public views can serve as input for future consideration of the ethics and governance of GGE. STUDY FUNDING/COMPETING INTEREST(S): Young Academy of the Royal Dutch Academy of Sciences (UPS/RB/745), Alliance Grant of the Amsterdam Reproduction and Development Research Institute (2017-170116) and National Institutes of Health Intramural Research Programme. No competing interests. TRIAL REGISTRATION NUMBER: N/A.

Clinically relevant potential drug-drug interactions in intensive care patients: A large retrospective observational multicenter study.

PURPOSE: Potential drug-drug interactions (pDDIs) may harm patients admitted to the Intensive Care Unit (ICU). Due to the patient's critical condition and continuous monitoring on the ICU, not all pDDIs are clinically relevant. Clinical decision support systems (CDSSs) warning for irrelevant pDDIs could result in alert fatigue and overlooking important signals. Therefore, our aim was to describe the frequency of clinically relevant pDDIs (crpDDIs) to enable tailoring of CDSSs to the ICU setting. MATERIALS & METHODS: In this multicenter retrospective observational study, we used medication administration data to identify pDDIs in ICU admissions from 13 ICUs. Clinical relevance was based on a Delphi study in which intensivists and hospital pharmacists assessed the clinical relevance of pDDIs for the ICU setting. RESULTS: The mean number of pDDIs per 1000 medication administrations was 70.1, dropping to 31.0 when considering only crpDDIs. Of 103,871 ICU patients, 38% was exposed to a crpDDI. The most frequently occurring crpDDIs involve QT-prolonging agents, digoxin, or NSAIDs. CONCLUSIONS: Considering clinical relevance of pDDIs in the ICU setting is important, as only half of the detected pDDIs were crpDDIs. Therefore, tailoring CDSSs to the ICU may reduce alert fatigue and improve medication safety in ICU patients.

Supplementation of urea to a basal pasture diet fed to dairy cows to model N-partitioning relationships.

The main objective of this study was to investigate whether altering dietary crude protein (CP) through the supplementation of urea to a basal pasture diet fed to dairy cows accurately modeled N-partitioning relationships. To test this, we first needed to establish safe tolerance levels for urea in this setting. Fifteen multiparous, rumen-fistulated, mid-lactation Holstein-Friesian dairy cows were offered spring pasture (~20 kg of dry matter/cow per day) and allocated to 1 of 3 urea supplementation treatments: low N [0 g/d urea; 21% total dietary CP of dry matter (DM)], medium N (350 g/d urea; 26% total dietary CP of DM), or high N (690 g/d urea; 31% total dietary CP of DM), in a completely randomized design. The amount of urea provided daily increased gradually for all cows over a 21-d period, with target urea supplementation reached by d 21. Milk yield decreased linearly at a rate of 2.35 kg/100 g of urea intake when urea supplementation exceeded 350 g/d for 4 d (~2% of DM intake). Cows from the low- and medium-N treatments subsequently entered metabolism stalls from d 25 to 31 to collect urine, feces, and milk for total N collection. Estimated urinary N output (g/d) increased linearly with N intake (g/d), and the slope of the relationship (slope = 0.86; R2 = 0.82) was consistent with international published results. Because of the consistency of our results with previously documented relationships, our findings indicate that supplementation of urea to a basal pasture diet is a suitable technique for modeling different N intakes from pasture diets to evaluate urinary N mitigation strategies. Urea supplementation, however, should not exceed ~2% of DM intake.

Graduate Student Literature Review: Evaluating the appropriate use of wearable accelerometers in research to monitor lying behaviors of dairy cows.

Until recently, animal behavior has been studied through close and extensive observation of individual animals and has relied on subjective assessments. Wearable technologies that allow the automation of dairy cow behavior recording currently dominate the precision dairy technology market. Wearable accelerometers provide new opportunities in animal ethology using quantitative measures of dairy cow behavior. Recent research developments indicate that quantitative measures of behavior may provide new objective on-farm measures to assist producers in predicting, diagnosing, and managing disease or injury on farms and allowing producers to monitor cow comfort and estrus behavior. These recent research developments and a large increase in the availability of wearable accelerometers have led to growing interest of both researchers and producers in this technology. This review aimed to summarize the studies that have validated lying behavior derived from accelerometers and to describe the factors that should be considered when using leg-attached accelerometers and neck-worn collars to describe lying behavior (e.g., lying time and lying bouts) in dairy cows for research purposes. Specifically, we describe accelerometer technology, including the instrument properties and methods for recording motion; the raw data output from accelerometers; and methods developed for the transformation of raw data into meaningful and interpretable information. We highlight differences in validation study outcomes for researchers to consider when developing their own experimental methodology for the use of accelerometers to record lying behaviors in dairy cows. Finally, we discuss several factors that may influence the data recorded by accelerometers and highlight gaps in the literature. We conclude that researchers using accelerometers to record lying behaviors in dairy cattle should (1) select an accelerometer device that, based on device attachment and sampling rate, is appropriate to record the behavior of interest; (2) account for cow-, farm-, and management-related factors that could affect the lying behaviors recorded; (3) determine the appropriate editing criteria for the accurate interpretation of their data; (4) support their chosen method of recording, editing, and interpreting the data by referencing an appropriately designed and accurate validation study published in the literature; and (5) report, in detail, their methodology to ensure others can decipher how the data were captured and understand potential limitations of their methodology. We recommend that standardized protocols be developed for collecting, analyzing, and reporting lying behavior data recorded using wearable accelerometers for dairy cattle.

Considerations for the design of nutrition-sensitive production programmes in rural South Africa.

BACKGROUND: Very little has been researched about the efficacy, effectiveness, feasibility, sustainability and impact of food-based approaches on the diets and nutritional status of populations at risk of hunger and food insecurity. This study contributes knowledge about the impact of food-based approaches on the diets of populations at risk of hunger and food insecurity in four of the poorest rural communities in South Africa. The study investigated the consumption and production patterns of rural households (278 in summer and 280 in winter) in four sites in the poorest municipalities in South Africa. METHODS: A multistage stratified random sampling technique was applied to identify the communities and sample households for the quantitative survey and qualitative assessments. Qualitative and quantitative data were collected between 2013 and 2015 through focus group discussions (FGDs), key informant interviews and the two-round panel survey to cover both the summer and winter seasons at each site. RESULTS: Home gardening led to a significant positive increase in the consumption of white roots and tubers, dark green leafy vegetables, orange-coloured fruit and other fruit in the 24 h prior to the survey. Participation in a community garden led to significant increases in the consumption of dark green leafy vegetables and other vegetables. School gardening did not demonstrate any statistical relationships with the consumption of foods from the crop-related food groups. Crop production improved dietary diversity. Selling produce and irrigation showed a stronger improvement in dietary diversity. Seasonality affected the availability of fresh fruit and vegetables for home consumption in winter. CONCLUSIONS: Producing beyond that solely for home consumption has greater benefits for dietary diversity and a consumption-smoothing effect during the post-harvest period. Politicians and the scientific community should recognise the role that household and small-scale crop production plays in supporting household consumption and the provision of essential micronutrients despite constraints and disincentives. Production and education programmes should focus on strengthening existing good consumption patterns and promoting the consumption of foods that can improve dietary diversity.

Associations between lying behavior and activity and hypocalcemia in grazing dairy cows during the transition period.

Hypocalcemia is a common metabolic disorder of transition dairy cows that is considered a gateway disease, increasing the risk of other health disorders and reducing cow performance. Clinical milk fever is associated with long periods of recumbency, and it is plausible that cows experiencing non-paretic hypocalcemia may spend more time lying; hence, lying behavior and activity measures may be useful in identifying at-risk cows. The objective of this study was to describe associations among blood calcium (Ca) status at calving and lying behavior and activity measures during the transition period in grazing dairy cows. Blood was sampled on the day of calving (d 0), and d 1, 2, 3, and 4 postcalving, and analyzed for total plasma Ca concentration. Twenty-four multiparous Holstein-Friesian and Holstein-Friesian × Jersey grazing dairy cows were classified, retrospectively, as clinically hypocalcemic (CLIN; blood Ca ≤ 1.4 mmol/L at 1 or more consecutive samplings within 48 h postcalving, but without parturient paresis). These cows were pair-matched (using milk production potential from their estimated breeding value for milk protein, mean body weight at wk -5 and -6 precalving, and, where possible, parity) with 24 cows classified as subclinically hypocalcemic (SUB; blood Ca > 1.4 and < 2.0 mmol/L at 2 consecutive samplings within 48 h postcalving), and 24 cows classified as normocalcemic (NORM; blood Ca ≥ 2.0 mmol/L at 3 consecutive samplings within 72 h postcalving). Lying behavior and activity were monitored using triaxial accelerometers from -21 to +35 d relative to calving. Data were summarized to calculate daily lying time (h/d), daily number of lying bouts (LB; no./d), mean LB duration (min/bout), and the number of steps taken (steps/d). On d 0, the CLIN group were less active and spent approximately 2.6 h longer lying than the SUB and NORM groups, particularly between 0200 and 1400 h. On d 0, the NORM group had fewer LB (16.3/d) than the SUB and CLIN groups (18.2 and 19.2/d, respectively). These differences in behavior were no longer detected 2 d postcalving, and no further differences were observed. The day before calving, the CLIN group spent 1.4 h longer lying down than did the SUB and NORM groups. Further, the relative change in steps from a precalving baseline period (d -14 to -7) until d 0 was positively, linearly associated with blood Ca concentration within 24 h postcalving. Future work should consider daily and temporal changes in behavior in individual cows to determine the potential for these measures to allow early detection of hypocalcemia.

Lack of diagnostic utility of the ECG-derived ventricular gradient in patients with suspected acute pulmonary embolism.

INTRODUCTION: The YEARS algorithm was successfully developed to reduce the number of computed tomography pulmonary angiography (CTPA) investigations in the diagnostic management of patients with suspected pulmonary embolism (PE), although half of patients still needed to be referred for CTPA. We hypothesized that ECG derived ventricular gradient optimized for right ventricular pressure overload (VG-RVPO), an easy to use tool for detecting PE-induced pulmonary hypertension (PH), may further improve the efficiency of the YEARS algorithm. METHODS: In this post-hoc analysis of the Years study, ECGs of 479 patients with suspected PE managed according to the YEARS algorithm were available for analysis. The diagnostic performance of VG-RVPO was assessed and likelihood ratios were calculated. RESULTS: PE was diagnosed in 88 patients (18%). In patients with confirmed PE, 34% had an abnormal VG-RVPO versus 24% of those without PE (odds ratio 1.6; 95%CI 0.94-2.6). The mean VG-RVPO was -22 ± 13 and did not differ between the two patient groups (-22 versus -20; mean difference - 2, 95% CI -4.8 to 1.3). The sensitivity of VG-RVPO for PE was 24% (95%CI 34-45), the specificity 76% (95%CI 71-80) and the c-statistic 0.45 (95% CI 0.38-0.51). When combined with the YEARS algorithm, the likelihood ratios of VG-RVPO remained close to 1.0. Ruling out PE in patients with an indication for CTPA based on a normal VG-RVPO would have resulted in 58 missed cases. CONCLUSIONS: The VG-RVPO has no diagnostic value for suspected acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. CONDENSED ABSTRACT: This post-hoc analysis of the YEARS study failed to demonstrate incremental diagnostic value of VG-RVPO for acute PE, either as stand-alone diagnostic test or combined with the YEARS algorithm. Nevertheless, the role of VG-RVPO recorded on admission could potentially be valuable in the risk stratification of PE during hospitalization, although this remains to be studied.

The palatal mucosal graft: The adequate posterior lamellar reconstruction in extensive full-thickness eyelid reconstruction.

INTRODUCTION: Full-thickness eyelid defects exceeding 25% of the eyelid width should benefit from a skillful, immediate and simultaneous reconstruction of two layers; anterior and posterior lamella. In this article, we recall, through an original series of cases, the possibility of using a palatal fibromucosal graft during the reconstruction of the posterior lamella as well as the modalities of its optimal use. PATIENTS AND METHODS: Retrospective study, including 8 patients with an extensive full-thickness eyelid defect affecting more than half of the upper and/or lower eyelid, after tumor excisions. 4 cases were involved in lower eyelid reconstruction, 2 in upper one and 2 in both. Posterior lamella was reconstructed using a palatal mucosal graft. Anterior lamella was reconstructed using different flaps: Esser-Mustardé flap, medially and laterally based orbicularis oculi myocutaneous flap, Tripier and orbitonasolabial flaps. Mean follow-up was 12.75 months. RESULTS: The survival rate of grafts and flaps was excellent with only one flap border necrosis. The donor site healed in an average time of 3 weeks. Functional recovery, complete eye closure and opening, was obtained in all cases. Lining, texture and color was considered satisfactory in all cases. CONCLUSION: The palatal mucosal graft provides a good and lasting structural support to the eyelid, which is essential for the inferior eyelid, especially when combined with a flap. Slight overcorrection is recommended.

Selenium requirements in grazing dairy cows: a review.

In New Zealand, the recommended intake of Se for dairy cattle (0.03 mg/kg dry matter (DM)) is lower than in the United Kingdom and Australia (0.1 and 0.04 mg/kg DM, respectively), and much lower than in the United States of America (0.3 mg/kg DM). Advisors in New Zealand often suggest that New Zealand intake recommendations are far too low and that recommendations from the United States of America should be used. This has created confusion as farmers are given very different advice depending on which recommendations their advisor uses. In this review, we assess whether the published evidence supports the existing dietary requirements and associated Se status thresholds, or if change is required. We focus particularly on the evidence-base in cattle fed a primarily pasture-based diet, as it is critical that dietary recommendations are derived from data created using cows fed similar diets. Accordingly, we also consider whether the increased use of fodder crops, especially during the dry period, is likely to have altered the Se requirements of dairy cows in New Zealand. We report that the science behind the dietary requirements for Se is robust, being supported by factorial models validated using New Zealand data, and on-farm experimental studies. Published nutritional data suggest that the increased use of fodder crops is unlikely to have altered the dietary balance of pro- and antioxidant factors in New Zealand dairy cows in a way that would meaningfully affect Se requirements. However, the lack of specific data on the vitamin E and fatty acid content of the crops being fed in New Zealand means that more information is needed to confirm this conclusion. In general, the existing New Zealand recommendations for Se-status thresholds are supported, although studies are still lacking to properly characterise the upper threshold of the marginal range. Nevertheless many studies in New Zealand, of herds with marginal or low adequate Se status (using New Zealand recommendations), have failed to show an effect of Se supplementation on milk production, intramammary infection or reproductive performance, so it is highly unlikely that the upper threshold of the range is much higher than the current recommendation. Proponents of the hypothesis that Se intakes in New Zealand dairy cattle should be increased by at least 10 times the current recommendations are therefore not using the evidence base correctly.

Lying behavior and activity during the transition period of clinically healthy grazing dairy cows.

Lying behavior and activity may provide useful information for the prediction of an imminent calving and the health of transition dairy cows; however, it is important first to understand what constitutes typical lying behavior and activity because this has not been defined for grazing dairy cows during the transition period. Our objective was to describe changes in lying behavior and activity in grazing dairy cows during the transition period using varying phenotypes typical of commercial dairy herds under grazing systems. Behavior data from IceTag or IceQube (IceRobotics, Edinburgh, Scotland) triaxial accelerometers were collected for 310 cow parities from multiparous, mixed-age (mean ± standard deviation; 4.5 ± 1.65 yr), and mixed-breed [Holstein-Friesian (HF), n = 216; and HF × Jersey, n = 94] grazing dairy cows from 4 parent experiments. The IceTags or IceQubes captured lying and activity data during the transition period (-21 to 34 d relative to calving) to allow the calculation of daily lying time (h/d), daily lying bouts (LB; no./d), mean LB duration (min/bout), and the number of steps taken (steps/d). Lying behavior and activity were analyzed using a repeated measures ANOVA during 3 periods: PRE (-21 to -3 d), POST (3 to 21 d), and the day of calving (d 0). Lying time was lower on d 0 (7.25 h/d) compared with PRE and POST lying times (10.3 and 8.58 h/d, respectively), with more frequent LB on d 0 (12.9 no./d) compared with the PRE and POST daily LB (8.15 vs. 7.74 no./d). Cows took more steps POST (4,424 steps/d) compared with d 0 and PRE (4,105 and 2,289 steps/d, respectively). Regression analysis determined that daily lying time decreased substantially from -3 to 0 d (slope = -1.03 ± 0.07 h/d) and from -2 and -1 d for daily LB (slope = 5.09 ± 0.54 no./d), which may be due to the calving event itself but also reflect restlessness. Daily lying time, daily LB, LB duration, and number of steps taken were substantially altered at the time of the calving event in grazing dairy cows. Cows were more active, spent less time lying, and took more steps postcalving compared with precalving, and it appears that this behavior may largely be due to activity associated with twice daily milking. Mean lying behavior and activity measures were more highly variable across individuals than across groups. Information available via activity monitors may contribute to the improvement of individual management of transition dairy cows, and this research provides a benchmark for typical changes in behavior during the transition period in grazing systems.

[Breast reconstruction by latissimus dorsi myocutaneous flap and implant: The dorsal bra technique]. / Reconstruction mammaire par lambeau musculo-cutané de grand dorsal avec prothèse : la technique du soutien-gorge dorsal.

Despite the development of microsurgical techniques, latissimus dorsi myocutaneous pedicle flap remains mainly used in breast reconstruction surgery. It is reliable and could be performed on almost all the patients, even if they smoke. It is also a good indication in case of irradiation. The technical alternative, which combines latissimus dorsi myocutaneous flap and an implant, allows the reconstruction of the expected volume and enables controlateral implant augmentation if the patient desires. The dorsal skin paddle increases the cutaneous pocket. The muscle in-depth enhances the irradiated skin and protects the implant. Positioning the skin paddle on the breast area is essential: it should be based on the mastectomy scar or on an added contraincision barring it. Thus it allows the muscle to embrace the implant as a bra. The precise reference points helping the placement of the flap could be reproduced and ensure pleasant and stable results over time.

Reasons for being in favour of or against genome modification: a survey of the Dutch general public.

STUDY QUESTION: What are the general public's reasons for being in favour of or against the use of genome modification for five potential applications? SUMMARY ANSWER: Overall, 43 reasons for being in favour, 45 reasons for being against as well as 26 conditional reasons for the use of genome modification were identified. WHAT IS KNOWN ALREADY: Various applications of somatic genome modification are progressing towards clinical introduction and several recent studies have reported on germline genome modification. This has incited a debate on ethical and legal implications and acceptability. There is a growing plea to involve the general public earlier on in the developmental process of science and (bio)technology including genome modification. STUDY DESIGN SIZE DURATION: In April 2016, a cross-sectional survey was launched online among the Dutch general public. A documentary on genome modification on public television and calls in social media invited viewers and non-viewers, respectively, to participate. PARTICIPANTS/MATERIALS SETTING METHODS: The questionnaire introduced five potential future applications of genome modification: modified wheat for individuals with gluten intolerance; somatic modification for individuals with neuromuscular diseases; germline modification to prevent passing on a neuromuscular disease; germline modification to introduce resistance to HIV; and germline modification to increase intelligence. Participants were asked to indicate whether and why they would make use of genome modification in these scenarios. The reasons mentioned were analysed through content analysis by two researchers independently. The proportion of respondents that was willing to modify was described per scenario and associations with respondent characteristics were analysed. MAIN RESULTS AND THE ROLE OF CHANCE: The survey was completed by 1013 participants. Forty-three reasons for being in favour, 45 reasons for being against as well as 26 conditional reasons for the use of genome modification were identified. These could be categorized into 14 domains: safety of the individuals concerned; effectiveness; quality of life of the individuals concerned; existence of a clinical need or an alternative; biodiversity and ecosystems; animal homo sapiens (i.e. relating to effects on humans as a species); human life and dignity; trust in regulation; justice; costs; slippery slope; argument of nature; parental rights and duties; and (reproductive) autonomy. Participants' willingness to use genome modification was dependent on the application: most participants would eat modified wheat if gluten intolerant (74%), would use genome modification to cure his/her own neuromuscular disease (85%) and would apply germline modification to prevent passing on this neuromuscular disease (66%). A minority would apply germline modification to introduce resistance to HIV (30%) or increase intelligence (16%). Being young (odds ratio (OR) = 0.98 per year increase), being male (OR = 2.38), and having watched the documentary (OR = 1.82) were associated with being willing to apply genome modification in more scenarios. LIMITATIONS REASONS FOR CAUTION: Inquiring for reasons through open questions in a survey allowed for a larger sample size and intuitive responses but resulted in less depth than traditional face-to-face interviews. As the survey was disseminated through social media, the sample is not representative of the overall Dutch population, and hence the quantitative results should not be interpreted as such. WIDER IMPLICATIONS OF THE FINDINGS: Further public consultation and a more in-depth ethical and societal debate on principles and conditions for responsible use of (germline) genome modification is required prior to future clinical introduction. STUDY FUNDING/COMPETING INTERESTS: Funded by the University of Amsterdam and University Medical Centre Utrecht. No conflict of interest. TRIAL REGISTRATION NUMBER: Not applicable.