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Rationale: Chronic obstructive pulmonary disease (COPD) is a condition punctuated by acute exacerbations commonly triggered by viral and/or bacterial infection. Early identification of exacerbation triggers is important to guide appropriate therapy, but currently available tests are slow and imprecise. Volatile organic compounds (VOCs) can be detected in exhaled breath and have the potential to be rapid tissue-specific biomarkers of infection etiology. Objectives: To determine whether volatile organic compound measurement could distinguish viral from bacterial infection in COPD. Methods: We used serial sampling within in vitro and in vivo studies to elucidate the dynamic changes that occur in VOC production during acute respiratory viral infection. Highly sensitive gas chromatography–mass spectrometry techniques were used to measure VOC production from infected airway epithelial-cell cultures and in exhaled breath samples from healthy subjects experimentally challenged with rhinovirus (RV)-A16 and from subjects with COPD with naturally occurring exacerbations. Measurements and Main Results: We identified a novel VOC signature comprising decane and other long-chain alkane compounds that is induced during RV infection of cultured airway epithelial cells and is also increased in the exhaled breath from healthy subjects experimentally challenged with RV and from patients with COPD during naturally occurring viral exacerbations. These compounds correlated with the magnitude of antiviral immune responses, viral burden, and exacerbation severity but were not induced by bacterial infection, suggesting that they represent a specific virus-inducible signature. Conclusions: Our study highlights the potential for measurement of exhaled breath VOCs as rapid, noninvasive biomarkers of viral infection. Further studies are needed to determine whether measurement of these signatures could be used to guide more targeted therapy with antibiotic/antiviral agents for COPD exacerbations.

Objective Our objective was to compare metaphylaxis with tulathromycin (META) and vaccination with a pentavalent modified-live virus respiratory vaccine (MLV) in high-risk feedlot calves and their influence on health and growth performance during a 56-d receiving period. Materials and Methods Beef bulls (n = 372) and steers (n = 106) were stratified by initial BW (234 ± 1.32 kg), health status, and sex and randomly assigned to treatments arranged in a 2 × 2 factorial: (1) no META or MLV (CON), (2) META administration on d 0 (META), (3) MLV administration on d 0 with revaccination on d 14 (MLV), and (4) META and MLV administration (META+MLV). Interactions and main effects were analyzed within a generalized complete block design using a mixed statistical model with 10 pen replicates per treatment. Body weight and feed refusals were recorded periodically to determine interim and overall (d 0 to 56) performance and feed efficiency. A subset (n = 256) was affixed with a 3-axis accelerometer ear-tag to quantify activity and rumination time. A 7-d postmetaphylactic interval was implemented for META, and bovine respiratory disease cases were determined by treatment-blinded, trained investigators. Results and Discussion The META groups had greater ADG from d 0 to 14, from d 14 to 28, and overall (P ≤ 0.01) and BW on d 56 was increased (P Implications and Applications Health and performance of high-risk feedlot cattle was improved by META but not MLV.

The study objectives were to determine the effect of oral hydration therapy and bovine respiratory disease (BRD) on rumination behavior, rumen pH, and rumen temperature. A random subset of high-risk, auction-sourced bulls from 3 truckload blocks (initial BW = 188.9 ± 19.1 kg) were fitted with a collar containing a 3-axis accelerometer to quantify rumination time and activity (n = 58) and administered a rumen pH and temperature data logging bolus (n = 33). At arrival, subset calves (n = 2 per pen) were balanced across treatment pens (n = 15 per treatment; n = 10 animals per pen) and randomized to receive 0.57 L water/45.4 kg BW from a modified oral drenching apparatus (H2O) or no water administration (CON). Standard arrival processing procedures were implemented including surgical castration. Modified-live virus respiratory vaccination was delayed until day 28. Technicians assigned a clinical illness score (CIS) daily; calves with CIS ≥ 2 and rectal temperature ≥ 40 °C were considered a BRD case (RCASE) and treated with an antimicrobial. The fixed effect of BRD cases vs. nontreated cohorts (RCON) was determined retrospectively using data from the accelerometer collar (n = 19 and 29) and rumen bolus (n = 12 and 21, for RCASE and RCON, respectively). Daily means and hourly means across days throughout the 56-d observation period were generated. Fixed effects were analyzed using the mixed model procedure with repeated measures. Daily rumen temperature was altered (P = 0.04) such that peak rumen temperature occurred earlier for H2O, whereas CON had increased (P ≤ 0.01) rumen temperature following delayed vaccination on day 28. Calves diagnosed with BRD had a transiently decreased (P = 0.04) active minutes between days 9 and 32, decreased (P < 0.01) active minutes between 0800 and 2000 h, decreased (P < 0.01) rumination time between 2000 and 0400 h, greater (P < 0.01) rumen temperature until delayed vaccination on day 28, and greater (P < 0.01) hourly rumen temperature between 0900 and 0300, and altered (P < 0.01) rumen pH. Earlier peak rumen temperature observed in H2O may indicate physiological modification enabling a more pronounced inflammatory response. Differences in rumination behavior and activity may be useful for early BRD detection.

Our objective was to evaluate the effect of oral hydration therapy with water during initial processing of high-risk crossbred beef calves on health and performance during a 56-d feedlot receiving period. In Exp. 1, 6 arrival blocks of heifers (n = 664, initial BW = 197.1 ± 5.8 kg) were randomized to treatment pens (n = 6 per treatment). In Exp. 2, 3 arrival blocks (initial BW = 188.9 ± 19.1 kg) of bulls (n = 242) and steers (n = 55) were stratified by sex and purchase BW and randomly assigned to treatment pens (n = 15 per treatment) before initial processing. In both experiments, calves received either 0.57 L of water/45.4 kg of BW from a modified oral drenching apparatus (H2O) or no water administration (CON) at initial processing. Treatment-blinded technicians evaluated calves daily and assigned a clinical illness score for bovine respiratory disease (BRD). Cattle qualifying for BRD treatment were administered an antimicrobial. In Exp. 1, BW, ADG, and G:F did not differ (P ≥ 0.63); however, H2O numerically increased DMI (5.29 vs. 5.09 kg/d; P = 0.12) and tended to increase BRD morbidity (29.0 vs. 21.5%; P = 0.07). There was no difference (P ≥ 0.39) in second or third BRD morbidity rate or mortality rate. In Exp. 2, final BW (256.8 vs. 248.7 kg) and overall ADG (1.19 vs. 1.07 kg/d) tended to increase (P = 0.08) and DMI from d 42 to 56 (7.54 vs. 6.85 kg/d) was greater (P

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus, was first identified after a cluster of cases in Wuhan, China in December 2019. Whether vertical transmission or placental pathology might occur following maternal infection during pregnancy remains unknown. This review aimed to summarise all studies that examined the placenta or neonates following infection with SARS-CoV-2, or closely related highly pathogenic coronavirus (SARS-CoV-1, or the Middle East respiratory syndrome coronavirus (MERS-CoV)). Structured literature searches found 50 studies that met the inclusion criteria. Twenty studies reported placental histopathology findings in third trimester placentas following maternal SARS-CoV-2 infection. Using the Amsterdam Consensus criteria to categorise the histopathology results, evidence of both fetal vascular malperfusion (35.3% of cases; 95% Confidence Interval (CI) 27.7–43.0%) and maternal vascular malperfusion (46% of cases; 95% CI 38.0–54.0%) were reported, along with evidence of inflammation in the placentas (villitis 8.7% cases, intervillositis 5.3% of cases, chorioamnionitis 6% of cases). The placental pathologies observed in SARS-CoV-2 were consistent with findings following maternal SARS-CoV-1 infection. Of those tested, a minority of neonates (2%) and placental samples tested positive for SARS-CoV-2 infection (21%). Limited conclusions can be drawn about the effect of maternal SARS-CoV-2 infection on placental pathology as most lack control groups and the majority of reports followed third trimester infection. Collaboration to maximise the number of samples examined will increase the reliability and generalisability of findings. A better understanding of the association between maternal SARS-CoV-2 infection and placental pathology will inform maternity care during the coronavirus pandemic., Highlights • Placental findings following maternal COVID-19, SARS or MERS were reviewed. • Minority of infants (2%) and placentas (21%) tested were positive for COVID-19. • Fetal and maternal vascular malperfusion were most frequently noted following COVID-19. • Minority of placentas demonstrated inflammatory lesions. • The association between maternal COVID infection and placental pathology is unclear.

BackgroundAntepartum fetal monitoring aims to assess fetal development and wellbeing throughout pregnancy. Current methods utilised in clinical practice are intermittent and only provide a ‘snapshot’ of fetal wellbeing, thus key signs of fetal demise could be missed. Continuous fetal monitoring (CFM) offers the potential to alleviate these issues by providing an objective and longitudinal overview of fetal status. Various CFM devices exist within literature; this review planned to provide a systematic overview of these devices, and specifically aimed to map the devices’ design, performance and factors which affect this, whilst determining any gaps in development.MethodsA systematic search was conducted using MEDLINE, EMBASE, CINAHL, EMCARE, BNI, Cochrane Library, Web of Science and Pubmed databases. Following the deletion of duplicates, the articles’ titles and abstracts were screened and suitable papers underwent a full-text assessment prior to inclusion in the review by two independent assessors.ResultsThe literature searches generated 4,885 hits from which 43 studies were included in the review. Twenty-four different devices were identified utilising four suitable CFM technologies: fetal electrocardiography, fetal phonocardiography, accelerometry and fetal vectorcardiography. The devices adopted various designs and signal processing methods. There was no common means of device performance assessment between different devices, which limited comparison. The device performance of fetal electrocardiography was reduced between 28 to 36 weeks’ gestation and during high levels of maternal movement, and increased during night-time rest. Other factors, including maternal body mass index, fetal position, recording location, uterine activity, amniotic fluid index, number of fetuses and smoking status, as well as factors which affected alternative technologies had equivocal effects and require further investigation.ConclusionsA variety of CFM devices have been developed, however no specific approach or design appears to be advantageous due to high levels of inter-device and intra-device variability.

ObjectiveCurrent data on the role of the umbilical cord in pregnancy complications are conflicting; estimates of the proportion of stillbirths due to cord problems range from 3.4 to 26.7%. A systematic review and meta-analysis were undertaken to determine which umbilical cord abnormalities are associated with stillbirth and related adverse pregnancy outcomes.MethodsMEDLINE, EMBASE, CINAHL and Google Scholar were searched from 1960 to present day. Reference lists of included studies and grey literature were also searched. Cohort, cross-sectional, or case-control studies of singleton pregnancies after 20 weeks' gestation that reported the frequency of umbilical cord characteristics or cord abnormalities and their relationship to stillbirth or other adverse outcomes were included. Quality of included studies was assessed using NIH quality assessment tools. Analyses were performed in STATA.ResultsThis review included 145 studies. Nuchal cords were present in 22% of births (95% CI 19, 25); multiple loops of cord were present in 4% (95% CI 3, 5) and true knots of the cord in 1% (95% CI 0, 1) of births. There was no evidence for an association between stillbirth and any nuchal cord (OR 1.11, 95% CI 0.62, 1.98). Comparing multiple loops of nuchal cord to single loops or no loop gave an OR of 2.36 (95% CI 0.99, 5.62). We were not able to look at the effect of tight or loose nuchal loops. The likelihood of stillbirth was significantly higher with a true cord knot (OR 4.65, 95% CI 2.09, 10.37).ConclusionsTrue umbilical cord knots are associated with increased risk of stillbirth; the incidence of stillbirth is higher with multiple nuchal loops compared to single nuchal cords. No studies reported the combined effects of multiple umbilical cord abnormalities. Our analyses suggest specific avenues for future research.

RATIONALE: COPD exacerbations are prone to non-recovery but there are no data about the effectiveness of retreatment on these prolonged events. We examined whether further therapy with ciprofloxacin for incompletely resolved COPD exacerbations prolonged the time until the next event. METHODS: This multi-centre randomised double-blind placebo-controlled trial studied retreatment with oral ciprofloxacin 500mg or matched placebo twice daily for 7 days in patients with GOLD stage II - IV COPD with persistent symptoms and/or serum C-reactive protein (CRP) ≥8mg/L initiated 14 (+/- 3) days after an index COPD exacerbation. The primary outcome was the time to the next exacerbation within a 90-day period. RESULTS: Of 826 patients screened at 4 centres, 144 eligible participants with incomplete recovery were randomised to receive ciprofloxacin (n=72) or placebo (n=72). 57% of patients in the ciprofloxacin group had experienced 1 or more exacerbations, compared to 53% in the placebo group. The median time to the next exacerbation was 32.5 days (IQR 13-50) in the placebo arm and 34 days (IQR 17-62) in the ciprofloxacin arm, which was not significantly different (adjusted hazard ratio = 1.07, 95% CI 0.68-1.68; p=0.76). No significant differences were seen in quality of life scores or lung function between treatment groups. CONCLUSION: In patients with persistent symptoms and/or raised CRP 14 days following a COPD exacerbation, an additional course of ciprofloxacin resulted in no additional benefit compared to placebo. This suggests that non-recovered exacerbations are not driven by ongoing bacterial infection and may potentially be targeted with anti-inflammatory therapy.

BackgroundRespiratory syncytial virus (RSV) is the most common cause of bronchiolitis in young infants. However, it is also a significant pathogen in older adults. Validated biomarkers of RSV disease severity would benefit diagnostics, treatment decisions, and prophylactic interventions. This review summarizes knowledge of biomarkers for RSV disease in adults.MethodsA literature review was performed using Ovid Medline, Embase, Global health, Scopus, and Web of Science for articles published 1946–October 2016. Nine articles were identified plus 9 from other sources.ResultsFrom observational studies of natural infection and challenge studies in volunteers, biomarkers of RSV susceptibility or disease severity in adults were: (1) lower anti-RSV neutralizing antibodies, where neutralizing antibody (and local IgA) may be a correlate of susceptibility/severity; (2) RSV-specific CD8+ T cells in bronchoalveolar lavage fluid preinfection (subjects with higher levels had less severe illness); and (3) elevated interleukin-6 (IL-6), IL-8, and myeloperoxidase levels in the airway are indicative of severe infection.ConclusionsFactors determining susceptibility to and severity of RSV disease in adults have not been well defined. Respiratory mucosal antibodies and CD8+ T cells appear to contribute to preventing infection and modulation of disease severity. Studies of RSV pathogenesis in at-risk populations are needed.

Micronutrient deficiencies are common in pregnant women due to low dietary intake and increased requirements for fetal development. Low maternal micronutrient status is associated with a range of pregnancy pathologies involving placental dysfunction, including fetal growth restriction (FGR), small-for-gestational age (SGA), pre-eclampsia and preterm birth. However, clinical trials commonly fail to convincingly demonstrate beneficial effects of supplementation of individual micronutrients, attributed to heterogeneity and insufficient power, potential interactions and lack of mechanistic knowledge of effects on the placenta. We aimed to provide current evidence of relationships between selected micronutrients (vitamin D, vitamin A, iron, folate, vitamin B12) and adverse pregnancy outcomes, combined with understanding of actions on the placenta. Following a systematic literature search, we reviewed data from clinical,in vitroandin vivostudies of micronutrient deficiency and supplementation. Key findings are potential effects of micronutrient deficiencies on placental development and function, leading to impaired fetal growth. Studies in human trophoblast cells and rodent models provide insights into underpinning mechanisms. Interestingly, there is emerging evidence that deficiencies in all micronutrients examined induce a pro-inflammatory state in the placenta, drawing parallels with the inflammation detected in FGR, pre-eclampsia, stillbirth and preterm birth. Beneficial effects of supplementation are apparentin vitroand in animal models and for combined micronutrients in clinical studies. However, greater understanding of the roles of these micronutrients, and insight into their involvement in placental dysfunction, combined with more robust clinical studies, is needed to fully ascertain the potential benefits of supplementation in pregnancy.

Introduction: Antepartum stillbirth is often preceded by detectable signs of fetal compromise, including changes in fetal heart rate and movement. It is hypothesised that continuous fetal monitoring could detect these signs more accurately and objectively than current forms of fetal monitoring and allow for timely intervention. This systematic review aimed to explore available evidence on women’s experiences of continuous fetal monitoring to investigate its acceptability prior to clinical implementation and to inform clinical studies. Material and methods: Systematic searching of four electronic databases (Embase, PsycINFO, MEDLINE and CINAHL), using key terms defined by initial scoping searches, identified a total of 35 studies. Following title and abstract screening by two independent researchers five studies met the inclusion criteria. Studies were not excluded based on language, methodology or quality assessment. An integrative methodology was used to synthesise qualitative and quantitative data together. Results: Forms of continuous fetal monitoring used included Monica AN24 monitors (n=4) and phonocardiography (n=1). Four main themes were identified: practical limitations of the device, negative emotions, positive perceptions and device implementation. Continuous fetal monitoring was reported to have high levels of participant satisfaction and was preferred by women to intermittent cardiotocography. Conclusion: This review suggests that continuous fetal monitoring is acceptedby women. However, it has also highlighted both the paucity and heterogeneity of current studies and suggests further research should be conducted into women’s experiences of continuous fetal monitoring before such devices can be used clinically.

The study objective was to explore the feasibility of an alternative injection site, ischiorectal fossa (IRF), for modified-live virus (MLV) vaccination in Jersey steers. We hypothesized administration of MLV in the IRF would not cause injection site lesions and result in similar antibody response against bovine viral diarrhea virus (BVDV) compared to the neck. Jersey steers (n = 28; BW=517 ± 116 kg) were stratified by a previously assigned growth implant treatment and day-35 BVDV antibody titer and randomly assigned to 1 of 2 treatments with injection treatment equivalently represented in each of 2 pens. Treatments consisted of: 1) 2 mL MLV vaccine administered s.c. in the neck (NECK); or 2) 2 mL MLV vaccine administered s.c. in the IRF. Blood was collected on days -35, 0, 35, 70, and 105 to determine BVDV-specific antibody titers using the virus neutralization assay and BW was recorded on the same days to determine gain performance. Steers were harvested on day 106 and examined for lesions respective to injection site. Antibody titers and performance variables were statistically analyzed via a mixed model with animal as the experimental unit. Concentration of BVDV antibody increased (P = 0.05) with time, but there was no treatment difference (P = 0.94) or treatment × day interaction (P = 0.70). There was no treatment difference for BW on any day (P ≥ 0.78). There was also no treatment difference in ADG (P ≥ 0.45). However, there was a period effect, where ADG was reduced markedly (P < 0.0001) for the day 0 to 35 interim period immediately following MLV vaccination compared to day -35 to 0 (0.79 vs. 0.18 kg/d). No injection site lesions were observed during harvest and results from BVDV antibody titers and performance indicate IRF as a potential alternative route of administration for MLV vaccines.

Hydroxychloroquine (HCQ), a toll like receptor (TLR) 7 and 9 antagonist, is used during pregnancy for inflammatory conditions with limited understanding of its placental toxicology. We hypothesized that HCQ does not have toxic effects on the placenta and can modulate cytokine release in response to TLR7/9 activation. A systematic review was conducted and no studies of HCQ on multicellular human placental tissue were identified. Accordingly, placental villous explants were cultured for 7 days with HCQ +/- TLR7/9 agonists. HCQ did not affect cell turnover, nutrient transport or cytokine release but increased IL-10 (anti-inflammatory) secretion and promoted syncytiotrophoblast regeneration. Cytokine release stimulated by TLR7/9 agonists was unaffected by HCQ. In conclusion, HCQ did not adversely affect placental tissue and may have a protective anti-inflammatory function. Further research is needed to determine the mechanisms of HCQ actions on human placenta and whether they could be utilized to improve pregnancy outcomes.

Background Absent or reduced fetal movements (ARFM) are linked to adverse perinatal outcome in high income countries but the significance of this symptom in low and lower middle income countries (LMICs) is less established. The objective of this study was to report the current state of knowledge and practice regarding the association between ARFM and adverse pregnancy outcomes in LMICs. # Methods Systematic literature searches were undertaken in MEDLINE, Web of Science, Google Scholar, LILACS, and AJOL. Studies were included if they reported adverse perinatal outcome(s) following ARFM, clinical management strategies employed following ARFM, or women's knowledge regarding perception of ARFM. Qualitative data were tabulated, where possible meta-analysis was performed on quantitative data. # Results Nineteen full-text papers were included; five studies reported the association between ARFM and stillbirth in LMICs (1466 pregnancies including 296 stillbirths). The likelihood of stillbirth was higher in ARFM (odds ratio 14.13, 95% CI 3.46-57.77). Women's awareness of ARFM as a danger sign varied greatly from 3.1-62.3%. # Conclusions There is a lack of published literature regarding the significance of ARFM in LMICs, but available data suggest a significant association between ARFM and adverse outcomes. Strategies to increase women's awareness require evaluation in LMICs.

BACKGROUND: Stillbirth affects 2.6 million pregnancies worldwide each year. Whilst the majority of cases occur in low‐ and middle‐income countries, stillbirth remains an important clinical issue for high‐income countries (HICs) ‐ with both the UK and the USA reporting rates above the mean for HICs. In HICs, the most frequently reported association with stillbirth is placental dysfunction. Placental dysfunction may be evident clinically as fetal growth restriction (FGR) and small‐for‐dates infants. It can be caused by placental abruption or hypertensive disorders of pregnancy and many other disorders and factors Placental abnormalities are noted in 11% to 65% of stillbirths. Identification of FGR is difficult in utero. Small‐for‐gestational age (SGA), as assessed after birth, is the most commonly used surrogate measure for this outcome. The degree of SGA is associated with the likelihood of FGR; 30% of infants with a birthweight < 10th centile are thought to be FGR, while 70% of infants with a birthweight < 3rd centile are thought to be FGR. Critically, SGA is the most significant antenatal risk factor for a stillborn infant. Correct identification of SGA infants is associated with a reduction in the perinatal mortality rate. However, currently used tests, such as measurement of symphysis‐fundal height, have a low reported sensitivity and specificity for the identification of SGA infants. OBJECTIVES: The primary objective was to assess and compare the diagnostic accuracy of ultrasound assessment of fetal growth by estimated fetal weight (EFW) and placental biomarkers alone and in any combination used after 24 weeks of pregnancy in the identification of placental dysfunction as evidenced by either stillbirth, or birth of a SGA infant. Secondary objectives were to investigate the effect of clinical and methodological factors on test performance. SEARCH METHODS: We developed full search strategies with no language or date restrictions. The following sources were searched: MEDLINE, MEDLINE In Process and Embase via Ovid, Cochrane (Wiley) CENTRAL, Science Citation Index (Web of Science), CINAHL (EBSCO) with search strategies adapted for each database as required; ISRCTN Registry, UK Clinical Trials Gateway, WHO International Clinical Trials Portal and ClinicalTrials.gov for ongoing studies; specialist abstract and conference proceeding resources (British Library’s ZETOC and Web of Science Conference Proceedings Citation Index). Search last conducted in Ocober 2016. SELECTION CRITERIA: We included studies of pregnant women of any age with a gestation of at least 24 weeks if relevant outcomes of pregnancy (live birth/stillbirth; SGA infant) were assessed. Studies were included irrespective of whether pregnant women were deemed to be low or high risk for complications or were of mixed populations (low and high risk). Pregnancies complicated by fetal abnormalities and multi‐fetal pregnancies were excluded as they have a higher risk of stillbirth from non‐placental causes. With regard to biochemical tests, we included assays performed using any technique and at any threshold used to determine test positivity. DATA COLLECTION AND ANALYSIS: We extracted the numbers of true positive, false positive, false negative, and true negative test results from each study. We assessed risk of bias and applicability using the QUADAS‐2 tool. Meta‐analyses were performed using the hierarchical summary ROC model to estimate and compare test accuracy. MAIN RESULTS: We included 91 studies that evaluated seven tests — blood tests for human placental lactogen (hPL), oestriol, placental growth factor (PlGF) and uric acid, ultrasound EFW and placental grading and urinary oestriol — in a total of 175,426 pregnant women, in which 15,471 pregnancies ended in the birth of a small baby and 740 pregnancies which ended in stillbirth. The quality of included studies was variable with most domains at low risk of bias although 59% of studies were deemed to be of unclear risk of bias for the reference standard domain. Fifty‐three per cent of studies were of high concern for applicability due to inclusion of only high‐ or low‐risk women. Using all available data for SGA (86 studies; 159,490 pregnancies involving 15,471 SGA infants), there was evidence of a difference in accuracy (P < 0.0001) between the seven tests for detecting pregnancies that are SGA at birth. Ultrasound EFW was the most accurate test for detecting SGA at birth with a diagnostic odds ratio (DOR) of 21.3 (95% CI 13.1 to 34.6); hPL was the most accurate biochemical test with a DOR of 4.78 (95% CI 3.21 to 7.13). In a hypothetical cohort of 1000 pregnant women, at the median specificity of 0.88 and median prevalence of 19%, EFW, hPL, oestriol, urinary oestriol, uric acid, PlGF and placental grading will miss 50 (95% CI 32 to 68), 116 (97 to 133), 124 (108 to 137), 127 (95 to 152), 139 (118 to 154), 144 (118 to 161), and 144 (122 to 161) SGA infants, respectively. For the detection of pregnancies ending in stillbirth (21 studies; 100,687 pregnancies involving 740 stillbirths), in an indirect comparison of the four biochemical tests, PlGF was the most accurate test with a DOR of 49.2 (95% CI 12.7 to 191). In a hypothetical cohort of 1000 pregnant women, at the median specificity of 0.78 and median prevalence of 1.7%, PlGF, hPL, urinary oestriol and uric acid will miss 2 (95% CI 0 to 4), 4 (2 to 8), 6 (6 to 7) and 8 (3 to 13) stillbirths, respectively. No studies assessed the accuracy of ultrasound EFW for detection of pregnancy ending in stillbirth. AUTHORS' CONCLUSIONS: Biochemical markers of placental dysfunction used alone have insufficient accuracy to identify pregnancies ending in SGA or stillbirth. Studies combining U and placental biomarkers are needed to determine whether this approach improves diagnostic accuracy over the use of ultrasound estimation of fetal size or biochemical markers of placental dysfunction used alone. Many of the studies included in this review were carried out between 1974 and 2016. Studies of placental substances were mostly carried out before 1991 and after 2013; earlier studies may not reflect developments in test technology.

The study objectives were to determine the effect of oral hydration therapy and bovine respiratory disease (BRD) on rumination behavior, rumen pH, and rumen temperature. A random subset of high risk, auction-sourced bulls from 3 truckload blocks (initial BW=188.9 ± 19.1 kg) were fitted with a collar containing a 3-axis accelerometer to quantify rumination time and activity index (n=58), and administered a rumen pH and temperature data logging bolus (n=33). At arrival, subset calves (n = 2/pen) were balanced across treatment pens (n=15/treatment; n=10 animals/pen) and randomized to receive 0.57 L water/45.4 kg BW from a modified oral drenching apparatus (H2O) or no water administration (CON). Standard arrival processing procedures were implemented and bulls were surgically castrated. Modified-live virus respiratory vaccination was delayed until day 28. Daily rumen temperature was altered (P=0.04) such that peak rumen temperature occurred earlier for H2O; whereas, CON had increased (P≤0.01) rumen temperature following delayed vaccination on day 28. Technicians assigned a clinical illness score (CIS) daily; calves with CIS ≥2 and rectal temperature ≥40°C were considered a bovine respiratory disease case (BRD) and treated with an antimicrobial. The fixed effect of BRD cases vs. non-treated cohorts (RCON) was determined retrospectively using data from the accelerometer collar (n= 19 vs. 29) and rumen bolus (n= 12 vs. 21). Calves diagnosed with BRD had decreased (P

The study objective was to evaluate the health and performance impacts of oral hydration therapy during initial processing of high-risk calves during a 56-day receiving period. In experiment 1 (EXP1), 6 truckload blocks of crossbred heifers (n=664, initial BW = 197.1 ± 5.8 kg) were randomized to 1 of 2 treatment pens (n=6/treatment; 55 ± 3 animals/pen) by truck exit order before initial processing. In experiment 2 (EXP2), 3 truckload blocks of crossbred bull (n=242) and steer (n=55) calves (initial BW=188.9 ± 19.1 kg) were stratified by sex and purchase BW and randomly assigned to 1 of 2 treatment pens (n=15/treatment; 10 animals/pen) upon initial processing. At arrival, calves received 0.57 L water/45.4 kg BW from a modified oral drenching apparatus (H2O) or no water administration (CON) according to treatment pen assignment. Standard arrival processing procedures were implemented and bulls were surgically castrated and administered meloxicam in EXP2. Treatment-blinded technicians evaluated calves daily and assigned a clinical illness score (CIS) for bovine respiratory disease (BRD). Cattle qualifying for BRD treatment (EXP1: CIS ≥2; EXP2: CIS ≥2 and rectal temperature ≥40°C) were administered an antimicrobial. In EXP1, BW, ADG and G:F did not differ (P≥0.63); however, H2O numerically increased DMI (5.29 vs. 5.09 kg/day; P=0.12) and tended to increase BRD morbidity (29.0 vs. 21.5%; P=0.07). There was no difference (P≥0.39) in second or third BRD morbidity rate or mortality rate. In EXP2, final BW (256.8 vs. 248.7 kg) and overall ADG (1.19 vs. 1.07 kg/day) tended to increase (P=0.08) and DMI for day 42 to 56 (7.54 vs. 6.85 kg/day) was greater (P

Traceability for vector network analyzer (VNA) measurements in coaxial lines smaller than 2.4 mm is problematic. The common method for traceability is to use precision coaxial air lines as primary standards. Since slotless lines are not commercially available in lines of this size, the air lines used are difficult to connect, extremely delicate, and expensive to replace. This paper describes a method of characterizing artefacts to use as standards, including specially designed and manufactured air-dielectric shielded open-circuits of various offset lengths as well as offset short-circuits and well-matched loads available in commercial VNA calibration kits. This will provide traceability using more robust and easier to use standards for calibration of the VNA. The proposed method is illustrated by measurement results obtained in 1.85 mm coaxial line (to 65 GHz.)

International audience; BACKGROUND: A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism. METHODS: In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding. RESULTS: Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups. CONCLUSIONS: A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.).

Synchrotron light emitted from a bend magnet is being used to diagnose the electron beam stored in the main accelerator of the Advanced Light Source (ALS) at Berkeley Lab. The radiation has maximum intensity in the soft x-ray region and is imaged by a Kirkpatrick-Baez mirror pair from the source point inside the ring onto a Bismuth/Germanium-Oxide (BGO) crystal, converted into visible light, and magnified by an attached microscope. The final image is captured by a TV camera-tube and digitized by a frame-grabber device to obtain records of parameters such as beam size, center location, and profile. Data obtained from this diagnostic beamline have been very useful in day-to-day operation of the ALS storage ring to assess the quality and repeatability of the stored beam. The line has further been utilized in several dedicated research activities to measure bunch lengths under various conditions and observe transverse beam instabilities. A summary of obtained results is given in this paper, together with a de...

In an effort to delineate a better understanding of the principles of management of retrohepatic vein injuries and to determine our results with these injuries, we reviewed our experience for the past 5 years with particular attention to the anatomy of the injury and the operative technique employed

In every communications medium, today, including newspapers and magazines, television and radio, and even in personal conversations, we are constantly alerted to the problems of pollution. More often than not, we are asked to do something about these problems. Most of us are learning of little things we can do individually, in our personal lives, to help reduce pollution.