Macro- and micro-genetic environmental sensitivity of yearling weight in Angus beef cattle.

Australian beef cattle experience variable conditions, which may give rise to genotype-by-environment interactions depending on the genotypes' macro- and/or micro-genetic environmental sensitivity (GES). Macro-GES gives rise to genotype-by-environment interactions across definable and shared environments, while micro-GES causes heritable variation of phenotypes, e.g., the performance of progeny from one sire may be more variable than other sires. Yearling weight (YW) is a key trait in Australian Angus cattle that may be impacted by both macro- and micro-GES. Current models for genetic evaluation of YW attempt to account for macro-GES by fitting sire-by-herd interactions (S × H). Variation in micro-GES had not yet been estimated for YW in Australian Angus. The aim of this study was to estimate genetic variation due to macro- and micro-GES in YW of Australian Angus cattle. A reaction norm with contemporary group effects as the environmental covariate was fitted either as an alternative to or in combination with a random S × H effect to account for macro-GES. Double hierarchical generalised linear models (DHGLM), fitted as sire models, were used to estimate the genetic variance of the dispersion as a measure of micro-GES. Variation due to both macro- and micro-GES were found in YW. The variance of the slope of the reaction norm was 0.02-0.03 (SEs 0.00), while the S × H variance accounted for 7% of the phenotypic variance in all models. Results showed that both a random S × H effect and a reaction norm should be included to account for both macro-GES and the additional variation captured by an S × H effect. The heritability of the dispersion on the measurement scale ranged from 0.06 to 0.10 (SEs 0.00) depending on which model was used. It should therefore be possible to alter both macro- and micro-GES of YW in Australian Angus through selection. However, care should be taken to ensure an appropriate data structure when including sire-by-herd interactions in the mean part of a DHGLM; otherwise, it can cause biased estimates of micro-GES.

The effect of circulating iron on barrier integrity of primary human endothelial cells.

Iron is hypothesized to be one of the contributors to cardiovascular disease and its levels in the circulation may correlate with cardiovascular risk. The aim of this study is to investigate the mechanisms that underlie the effects of iron on the barrier function of primary human endothelium. We used Human Umbilical Vein Endothelial Cells (HUVEC) to investigate the effects of Fe3+ using electric cell-substrate impedance sensing, microscopy, western blot and immunofluorescence microscopy. Exposure to Fe3+ caused EC elongation and upregulation of stress-induced proteins. Analysis of barrier function showed a dose-dependent drop in endothelial integrity, which was accompanied by Reactive Oxygen Species (ROS) production and could partly be prevented by ROS scavengers. Inhibition of contractility by the ROCK inhibitor Y27632, showed even more effective rescue of barrier integrity. Using western blot, we detected an increase in expression of the small GTPase RhoB, an inducer of EC contraction, and a small decrease in VE-cadherin, suggestive for an iron-induced stress response. Co-stimulation by TNFα and iron, used to investigate the role of low-grade inflammation, revealed an additive, negative effect on barrier integrity, concomitant with an upregulation of pro-inflammatory markers ICAM-1 and RhoB. Iron induces a response in HUVEC that leads to endothelial activation and a pro-inflammatory state measured by loss of barrier integrity which can be reversed by ROS scavengers, combined with inhibition of contractility. These data suggest that ROS-mediated damage of the vascular endothelium could contribute to the increased cardiovascular risk which is associated with elevated levels of circulating iron.

Trombosis del stent 10 años después de la intervención coronaria percutánea con stents nuevos frente a stents de la primera generación. Observaciones del metanálisis DECADE / Ten-year patterns of stent thrombosis after percutaneous coronary intervention with new- versus early-generation drug-eluting stents: insights from the DECADE cooperation

Introducción y objetivos El metanálisis DECADE es un análisis de datos de pacientes individuales de ensayos de stents liberadores de fármacos (SLF) con un seguimiento de 10 años. El objetivo del estudio es analizar el riesgo de trombosis definitiva del stent (TS) hasta 10 años después de la intervención coronaria percutánea (ICP) en pacientes tratados con DES de primera y de nueva generación. Métodos Se agruparon los datos de pacientes individuales de cinco ensayos de SLF con un seguimiento de 10 años. El objetivo primario fue la TS hasta 10 años después de la ICP. Los pacientes se dividieron en 2 grupos según la generación de stent implantada (primera y nueva). El análisis de los datos de los participantes individuales se realizó mediante el enfoque de una etapa. Resultados Se incluyeron 9.700 pacientes, 6.866 en el grupo de SLF nuevos y 2.834 en el grupo de SLF de primera generación. A los 10 años, la TS se produjo en 69 de los 6.866 pacientes tratados con SLF de nueva generación y en 91 de los 2.834 pacientes tratados con la SLF de primera generación (1,0% frente a 3,5%, razón de tasas 0,32; IC95%, 0,23-0,45). La tasa de TS fue menor en el grupo de SLF de nueva generación en comparación con el grupo de SLF de primera, de 1-5 años (razón de tasas 0,14; IC95%, 0,08-0,26) y de 5-10 años (razón de tasas 0,23; IC95%, 0,08-0,61) después de la ICP. Conclusiones La incidencia de TS hasta 10 años después de la ICP con los SLF de nueva generación es del 1%. Los SLF de nueva generación se asocian a una menor incidencia de TS a 10 años comparados con los SLF de primera generación, especialmente después de 1 año de la ICP (AU)

Introduction and objectives The DECADE cooperation is a pooled analysis of individual patient data from drug-eluting stent (DES) trials with a 10-year follow-up. This analysis reports the risk of definite stent thrombosis (ST) through to 10 years after percutaneous coronary intervention (PCI) in patients treated with early- and new-generation DES. Methods Individual patient data from 5 DES trials with a 10-year follow-up were pooled. The primary endpoint was definite ST up to 10 years after PCI. Patients were divided into 2 groups as per the generation of DES implanted (early and new DES). Individual participant data were analyzed using a 1-stage approach. Results We included 9700 patients, 6866 in the new DES group and 2834 in the early DES group. Through to 10 years, definite ST occurred in 69 of 6866 patients treated with new DES and in 91 of 2834 patients treated with early DES (1.0% vs 3.5%, adjusted hazard ratio, 0.32; 95%CI, 0.23-0.45). The rate of definite ST was lower in the new DES group than in the early DES group from 1 to 5 years (rate ratio, 0.14; 95%CI, 0.08-0.26) and from 5 to 10 years (rate ratio, 0.23; 95%CI, 0.08-0.61) after PCI. Conclusions The incidence of definite ST through to 10 years after PCI with new-generation DES was 1%. New-generation DES are associated with a lower 10-year incidence of definite ST than early-generation DES, particularly beyond 1 year after PC (AU)

Homogeneity assessment of the SuperCam calibration targets onboard rover perseverance.

The SuperCam instrument, onboard the Perseverance rover (Mars 2020 mission) is designed to perform remote analysis on the Martian surface employing several spectroscopic techniques such as Laser Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman (TRR), Time-Resolved Fluorescence (TRF) and Visible and Infrared (VISIR) reflectance. In addition, SuperCam also acquires high-resolution images using a color remote micro-imager (RMI) as well as sounds with its microphone. SuperCam has three main subsystems, the Mast Unit (MU) where the laser for chemical analysis and collection optics are housed, the Body Unit (BU) where the different spectrometers are located inside the rover, and the SuperCam Calibration Target (SCCT) located on the rover's deck to facilitate calibration tests at similar ambient conditions as the analyzed samples. To perform adequate calibrations on Mars, the 22 mineral samples included in the complex SCCT assembly must have a very homogeneous distribution of major and minor elements. The analysis and verification of such homogeneity for the 5-6 replicates of the samples included in the SCCT has been the aim of this work. To verify the physic-chemical homogeneity of the calibration targets, micro Energy Dispersive X-ray Fluorescence (EDXRF) imaging was first used on the whole surface of the targets, then the relative abundances of the detected elements were computed on 20 randomly distributed areas of 100 × 100 µm. For those targets showing a positive Raman response, micro-Raman spectroscopy imaging was performed on the whole surface of the targets at a resolution of 100 × 100 µm. The %RSD values (percent of relative standard deviation of mean values) for the major elements measured with EDXRF were compared with similar values obtained by two independent LIBS set-ups at spot sizes of 300 µm in diameter. The statistical analysis showed which elements were homogeneously distributed in the 22 mineral targets of the SCCT, providing their uncertainty values for further calibration. Moreover, nine of the 22 targets showed a good Raman response and their mineral distributions were also studied. Those targets can be also used for calibration purposes of the Raman part of SuperCam using the wavenumbers of their main Raman bands proposed in this work.

Estimation of macro- and micro-genetic environmental sensitivity in unbalanced datasets.

Genotype-by-environment interaction is caused by variation in genetic environmental sensitivity (GES), which can be subdivided into macro- and micro-GES. Macro-GES is genetic sensitivity to macro-environments (definable environments often shared by groups of animals), while micro-GES is genetic sensitivity to micro-environments (individual environments). A combined reaction norm and double hierarchical generalised linear model (RN-DHGLM) allows for simultaneous estimation of base genetic, macro- and micro-GES effects. The accuracy of variance components estimated using a RN-DHGLM has been explicitly studied for balanced data and recommendation of a data size with a minimum of 100 sires with at least 100 offspring each have been made. In the current study, the data size (numbers of sires and progeny) and structure requirements of the RN-DHGLM were investigated for two types of unbalanced datasets. Both datasets had a variable number of offspring per sire, but one dataset also had a variable number of offspring within macro-environments. The accuracy and bias of the estimated macro- and micro-GES effects and the estimated breeding values (EBVs) obtained using the RN-DHGLM depended on the data size. Reasonably accurate and unbiased estimates were obtained with data containing 500 sires with 20 offspring or 100 sires with 50 offspring, regardless of the data structure. Variable progeny group sizes, alone or in combination with an unequal number of offspring within macro-environments, had little impact on the dispersion of the EBVs or the bias and accuracy of variance component estimation, but resulted in lower accuracies of the EBVs. Compared to genetic correlations of zero, a genetic correlation of 0.5 between base genetic, macro- and micro-GES components resulted in a slight decrease in the percentage of replicates that converged out of 100 replicates, but had no effect on the dispersion and accuracy of variance component estimation or the dispersion of the EBVs. The results show that it is possible to apply the RN-DHGLM to unbalanced datasets to obtain estimates of variance due to macro- and micro-GES. Furthermore, the levels of accuracy and bias of variance estimates when analysing macro- and micro-GES simultaneously are determined by average family size, with limited impact from variability in family size and/or cohort size. This creates opportunities for the use of field data from populations with unbalanced data structures when estimating macro- and micro-GES.

A novel case of neonatal severe hyperparathyroidism successfully treated with a type II calcimimetic drug.

We report a boy with hypercalcemia due to neonatal severe hyperparathyroidism (NSHPT) caused by a compound heterozygous mutation in the calcium sensing receptor (CaSR) managed successfully on a type II calcimimetic drug. The hypercalcemia was temporarily treated by hyperhydration, bisphosphonate and calcium depleted milk. At 29 days of age cinacalcet was introduced. The starting dose was 0.5 mg/kg/day and was subsequently titrated to the point of efficacy (5.2 mg/kg/day) when a persuasive reduction in parathyroid hormone and calcium concentrations was observed. We propose a trial of type II calcimimetics in newborns with NSHPT irrespective of the genetic mutation and advocate that residual functionality of the CaSR predict the drug efficacy.

The Mars 2020 Perseverance Rover Mast Camera Zoom (Mastcam-Z) Multispectral, Stereoscopic Imaging Investigation.

Mastcam-Z is a multispectral, stereoscopic imaging investigation on the Mars 2020 mission's Perseverance rover. Mastcam-Z consists of a pair of focusable, 4:1 zoomable cameras that provide broadband red/green/blue and narrowband 400-1000 nm color imaging with fields of view from 25.6° × 19.2° (26 mm focal length at 283 µrad/pixel) to 6.2° × 4.6° (110 mm focal length at 67.4 µrad/pixel). The cameras can resolve (≥ 5 pixels) ∼0.7 mm features at 2 m and ∼3.3 cm features at 100 m distance. Mastcam-Z shares significant heritage with the Mastcam instruments on the Mars Science Laboratory Curiosity rover. Each Mastcam-Z camera consists of zoom, focus, and filter wheel mechanisms and a 1648 × 1214 pixel charge-coupled device detector and electronics. The two Mastcam-Z cameras are mounted with a 24.4 cm stereo baseline and 2.3° total toe-in on a camera plate ∼2 m above the surface on the rover's Remote Sensing Mast, which provides azimuth and elevation actuation. A separate digital electronics assembly inside the rover provides power, data processing and storage, and the interface to the rover computer. Primary and secondary Mastcam-Z calibration targets mounted on the rover top deck enable tactical reflectance calibration. Mastcam-Z multispectral, stereo, and panoramic images will be used to provide detailed morphology, topography, and geologic context along the rover's traverse; constrain mineralogic, photometric, and physical properties of surface materials; monitor and characterize atmospheric and astronomical phenomena; and document the rover's sample extraction and caching locations. Mastcam-Z images will also provide key engineering information to support sample selection and other rover driving and tool/instrument operations decisions.

Evening aspirin intake results in higher levels of platelet inhibition and a reduction in reticulated platelets - a window of opportunity for patients with cardiovascular disease?

Cardiovascular events occur most frequently in the early morning. Similarly, the release of reticulated platelets (RP) by megakaryocytes has a peak in the late night and early morning. Which aspirin regimen most effectively inhibits platelets during these critical hours is unknown. Hence, the primary objective of this trial was to assess platelet function and RP levels at 8.00 AM, in stable cardiovascular (CVD) patients, during three different aspirin regimens. In this open-label randomized cross-over study subjects were allocated to three sequential aspirin regimens: once-daily (OD) 80 mg morning; OD-evening, and twice-daily (BID) 40 mg. Platelet function was measured at 8.00 AM & 8.00 PM by serum Thromboxane B2 (sTxB2) levels, the Platelet Function Analyzer (PFA)-200® Closure Time (CT), Aspirin Reaction Units (ARU, VerifyNow®), and RP levels. In total, 22 patients were included. At 8.00 AM, sTxB2 levels were the lowest after OD-evening in comparison with OD-morning (p = <0.01), but not in comparison with BID. Furthermore, RP levels were similar at 8.00 AM, but statistically significantly reduced at 8.00 PM after OD-evening (p = .01) and BID (p = .02) in comparison with OD-morning. OD-evening aspirin intake results in higher levels of platelet inhibition during early morning hours and results in a reduction of RP levels in the evening. These findings may, if confirmed by larger studies, be relevant to large groups of patients taking aspirin to reduce cardiovascular risk.

Association between glycaemic outcome and BMI in Danish children with type 1 diabetes in 2000-2018: a nationwide population-based study.

AIM: To describe the development of HbA1c and BMI over time in Danish children with type 1 diabetes; and to investigate the association between HbA1c and BMI including influence of age, gender, diabetes duration, severe hypoglycaemia and treatment method. METHODS: We used the nationwide Danish Registry of Childhood and Adolescent Diabetes, DanDiabKids, including annual registrations of all children with diabetes treated at Danish hospitals. With linear mixed-effects models and splines we analyzed the HbA1c and BMI development over time as well as the association between HbA1c and BMI including effects of gender, age, disease duration, hypoglycaemia and treatment method. BMI z-scores were calculated for these analyses. RESULTS: For the period from 2000 to 2018, 6097 children with type 1 diabetes were identified from the DanDiabKids database. The median (interquartile range) HbA1c level was 65 (57-74) mmol/mol (8.1%) and the median BMI z-score was 0.85 in girls and 0.67 in boys. A non-linear association was found between HbA1c and BMI z-score, with the highest BMI z-score observed for HbA1c values in the range of approximately 60-70 mmol/mol (7.6-6.8%). The association was modified by gender, age and diabetes duration. Severe hypoglycaemia and insulin pump treatment had a small positive impact on BMI z-score. CONCLUSION: The association between HbA1c and BMI z-score was non-linear, with the highest BMI z-score being observed for intermediate HbA1c levels; however, specific patterns depended on gender, age and diabetes duration.

SuperCam Calibration Targets: Design and Development.

SuperCam is a highly integrated remote-sensing instrumental suite for NASA's Mars 2020 mission. It consists of a co-aligned combination of Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), Visible and Infrared Spectroscopy (VISIR), together with sound recording (MIC) and high-magnification imaging techniques (RMI). They provide information on the mineralogy, geochemistry and mineral context around the Perseverance Rover. The calibration of this complex suite is a major challenge. Not only does each technique require its own standards or references, their combination also introduces new requirements to obtain optimal scientific output. Elemental composition, molecular vibrational features, fluorescence, morphology and texture provide a full picture of the sample with spectral information that needs to be co-aligned, correlated, and individually calibrated. The resulting hardware includes different kinds of targets, each one covering different needs of the instrument. Standards for imaging calibration, geological samples for mineral identification and chemometric calculations or spectral references to calibrate and evaluate the health of the instrument, are all included in the SuperCam Calibration Target (SCCT). The system also includes a specifically designed assembly in which the samples are mounted. This hardware allows the targets to survive the harsh environmental conditions of the launch, cruise, landing and operation on Mars during the whole mission. Here we summarize the design, development, integration, verification and functional testing of the SCCT. This work includes some key results obtained to verify the scientific outcome of the SuperCam system.

Impact of oral preoperative and perioperative immunonutrition on postoperative infection and mortality in patients undergoing cancer surgery: systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Infectious complications occur in 4-22 per cent of patients undergoing surgical resection of malignant solid tumours. Improving the patient's immune system in relation to oncological surgery with immunonutrition may play an important role in reducing postoperative infections. A meta-analysis was undertaken to evaluate the potential clinical benefits of immunonutrition on postoperative infections and 30-day mortality in patients undergoing oncological surgery. METHODS: PubMed, Embase and Cochrane Library databases were searched to identify eligible studies. Eligible studies had to include patients undergoing elective curative surgery for a solid malignant tumour and receiving immunonutrition orally before surgery, including patients who continued immunonutrition into the postoperative period. The main outcome was overall infectious complications; secondary outcomes were surgical-site infection (SSI) and 30-day mortality, described by relative risk (RR) with trial sequential analysis (TSA). Risk of bias was assessed according to Cochrane methodology. RESULTS: Some 22 RCTs with 2159 participants were eligible for meta-analysis. Compared with the control group, immunonutrition reduced overall infectious complications (RR 0·58, 95 per cent c.i. 0·48 to 0·70; I2 = 7 per cent; TSA-adjusted 95 per cent c.i. 0·28 to 1·21) and SSI (RR 0·65, 95 per cent c.i. 0·50 to 0·85; I2 = 0 per cent; TSA-adjusted 95 per cent c.i. 0·21 to 2·04). Thirty-day mortality was not altered by immunonutrition (RR 0·69, 0·33 to 1·40; I2 = 0 per cent). CONCLUSION: Immunonutrition reduced overall infectious complications, even after controlling for random error, and also reduced SSI. The quality of evidence was moderate, and mortality was not affected by immunonutrition (low quality). Oral immunonutrition merits consideration as a means of reducing overall infectious complications after cancer surgery.

ANTECEDENTES: Entre un 4-22% de los pacientes a los que se realiza una resección quirúrgica de tumores sólidos malignos presentan complicaciones infecciosas. Mejorar el sistema inmunitario del paciente quirúrgico oncológico mediante inmunonutrición puede tener un papel relevante en la reducción de las infecciones postoperatorias. Se realizó un metaanálisis para evaluar los posibles beneficios clínicos de la inmunonutrición en las infecciones postoperatorias y la mortalidad a los 30 días en pacientes sometidos a cirugía oncológica. MÉTODOS: Se realizó una búsqueda en las bases de datos de Pubmed, Embase y Cochrane para identificar los estudios clave. Se consideraron aquellos estudios que incluyeron pacientes con cirugía curativa electiva de un tumor maligno sólido que recibieron inmunonutrición por vía oral antes de la cirugía, así como también los que siguieron con inmunonutrición en el postoperatorio. La variable principal fueron las complicaciones infecciosas generales y las secundarias fueron la infección de la herida quirúrgica y la mortalidad a los 30 días, presentadas como el riesgo relativo (RR) obtenido a partir en un análisis secuencial de experimentos (trial sequential analysis, TSA). El riesgo de sesgo se evaluó según la metodología Cochrane. RESULTADOS: Para el metaanálisis se identificaron 22 ensayos clínicos con 2.075 participantes. En comparación con el grupo de control, la inmunonutrición redujo las complicaciones infecciosas generales (RR 0,58, i.c. del 95% 0,48-0,70, I2 = 7%, TSA ajustado i.c. del 95% 0,28-1,21) y las infecciones de la herida quirúrgica (RR 0,65, i.c. del 95% 0,50-0,85, I2 = 0%, TSA ajustado, i.c. del 95% 0,21-2,04). No hubo diferencias en la mortalidad a los 30 días (RR 0,69, i.c. del 95% 0,32-1,4, I2 = 0%). CONCLUSIÓN: la inmunonutrición redujo las complicaciones infecciosas generales, incluso después de controlar el error aleatorio. La inmunonutrición también redujo la infección de la herida quirúrgica. La calidad de la evidencia fue moderada y la mortalidad no se vio afectada por la inmunonutrición (baja calidad). La inmunonutrición oral debería ser tenida en cuenta como una forma de reducir las complicaciones infecciosas generales después de la cirugía del cáncer.

Combined analysis of group recorded feed intake and individually recorded body weight and litter size in mink.

In the mink industry, feed costs are the largest variable expense and breeding for feed efficient animals is warranted. Implementation of selection for feed efficiency must consider the relationships between feed efficiency and the current selection traits BW and litter size. Often, feed intake (FI) is recorded on a cage with a male and a female and there is sexual dimorphism that needs to be accounted for. Study aims were to (1) model group recorded FI accounting for sexual dimorphism, (2) derive genetic residual feed intake (RFI) as a measure of feed efficiency, (3) examine the relationship between feed efficiency and BW in males (BWM) and females (BWF) and litter size at day 21 after whelping (LS21) in Danish brown mink and (4) investigate direct and correlated response to selection on each trait of interest. Feed intake records from 9574 cages, BW records on 16 782 males and 16 875 females and LS21 records on 6446 yearling females were used for analysis. Genetic parameters for FI, BWM, BWF and LS21 were obtained using a multivariate animal model, yielding sex-specific additive genetic variances for FI and BW to account for sexual dimorphism. The analysis was performed in a Bayesian setting using Gibbs sampling, and genetic RFI was obtained from the conditional distribution of FI given BW using genetic regression coefficients. Responses to single trait selection were defined as the posterior distribution of genetic superiority of the top 10% of animals after conditioning on the genetic trends. The heritabilities ranged from 0.13 for RFI in females and LS21 to 0.59 for BWF. Genetic correlations between BW in both sexes and LS21 and FI in both sexes were unfavorable, and single trait selection on BW in either sex showed increased FI in both sexes and reduced litter size. Due to the definition of RFI and high genetic correlation between BWM and BWF, selection on RFI did not significantly alter BW. In addition, selection on RFI in either sex did not affect LS21. Genetic correlation between sexes for FI and BW was high but significantly lower than unity. The high correlations across sex allowed for selection on standardized averages of animals' breeding values (BVs) for RFI, FI and BW, which yielded selection responses approximately equal to the responses obtained using the sex-specific BVs. The results illustrate the possibility of selecting against RFI in mink with no negative effects on BW and litter size.

Thyroid hormone treatment in the management of treatment-resistant unipolar depression: a systematic review and meta-analysis.

BACKGROUND: Treatment with thyroid hormones is occasionally used in the management of treatment-resistant depression. However, the evidence supporting this treatment is not fully established. The aim of this study was to systematically review the literature on the effect of adjunctive thyroid hormone in the management of treatment-resistant unipolar depression and to provide a pooled estimate of its efficacy. METHODS: The study is registered with PROSPERO (reg. no. CRD42018108088) and followed the PRISMA guidelines. Searches were carried out on June 24, 2019, in PubMed, EMBASE, and PsycINFO. Each record was screened independently by at least two reviewers. In instances of discrepancies, consensus was reached upon discussion. Pooled efficacy estimates were calculated based on response rates (decrease of ≥50% on the primary outcome measure) using random effect statistics. RESULTS: The search yielded 1355 records. Based on the screening of these records, we identified 10 studies that met the inclusion criteria (total number of patients = 663). The comparison of response to thyroid hormones vs. placebo resulted in an odds ratio of 1.56 (95% CI: 0.50-4.84). Similarly, the comparison of response to thyroid hormones vs. lithium resulted in an odds ratio of 1.91 (95% CI: 0.85-4.26). Thus, adjunctive therapy with thyroid hormones was not superior to placebo or lithium in the management of treatment-resistant unipolar depression. CONCLUSION: According to this review and meta-analysis, there is not sufficient evidence to support the use of adjunctive thyroid hormones for treatment-resistant unipolar depression.

Evidence of Isotopic Fractionation During Vapor Exchange Between the Atmosphere and the Snow Surface in Greenland.

Several recent studies from both Greenland and Antarctica have reported significant changes in the water isotopic composition of near-surface snow between precipitation events. These changes have been linked to isotopic exchange with atmospheric water vapor and sublimation-induced fractionation, but the processes are poorly constrained by observations. Understanding and quantifying these processes are crucial to both the interpretation of ice core climate proxies and the formulation of isotope-enabled general circulation models. Here, we present continuous measurements of the water isotopic composition in surface snow and atmospheric vapor together with near-surface atmospheric turbulence and snow-air latent and sensible heat fluxes, obtained at the East Greenland Ice-Core Project drilling site in summer 2016. For two 4-day-long time periods, significant diurnal variations in atmospheric water isotopologues are observed. A model is developed to explore the impact of this variability on the surface snow isotopic composition. Our model suggests that the snow isotopic composition in the upper subcentimeter of the snow exhibits a diurnal variation with amplitudes in δ18O and δD of ~2.5‰ and ~13‰, respectively. As comparison, such changes correspond to 10-20% of the magnitude of seasonal changes in interior Greenland snow pack isotopes and of the change across a glacial-interglacial transition. Importantly, our observation and model results suggest, that sublimation-induced fractionation needs to be included in simulations of exchanges between the vapor and the snow surface on diurnal timescales during summer cloud-free conditions in northeast Greenland.

Seed germination and dormancy traits of forbs and shrubs important for restoration of North American dryland ecosystems.

In degraded dryland systems, native plant community re-establishment following disturbance is almost exclusively carried out using seeds, but these efforts commonly fail. Much of this failure can be attributed to the limited understanding of seed dormancy and germination traits. We undertook a systematic classification of seed dormancy of 26 species of annual and perennial forbs and shrubs that represent key, dominant genera used in restoration of the Great Basin ecosystem in the western United States. We examined germination across a wide thermal profile to depict species-specific characteristics and assessed the potential of gibberellic acid (GA3 ) and karrikinolide (KAR1 ) to expand the thermal germination envelope of fresh seeds. Of the tested species, 81% produce seeds that are dormant at maturity. The largest proportion (62%) exhibited physiological (PD), followed by physical (PY, 8%), combinational (PY + PD, 8%) and morphophysiological (MPD, 4%) dormancy classes. The effects of chemical stimulants were temperature- and species-mediated. In general, mean germination across the thermal profile was improved by GA3 and KAR1 for 11 and five species, respectively. We detected a strong germination response to temperature in freshly collected seeds of 20 species. Temperatures below 10 °C limited the germination of all except Agoseris heterophylla, suggesting that in their dormant state, the majority of these species are thermally restricted. Our findings demonstrate the utility of dormancy classification as a foundation for understanding the critical regenerative traits in these ecologically important species and highlight its importance in restoration planning.

Renal tumor biopsies are associated with a low complication rate.

BACKGROUND: Due to the high incidence of benign lesions in renal masses, numerous studies have been performed to clarify the value of core needle biopsies. The aim of the present study was to describe the complication rate after renal tumor biopsies (RTB), in order to make recommendations on observation after the procedure. MATERIALS AND METHODS: Data from all patients who underwent percutaneous ultrasound-guided RTB between February 2013 and October 2016 due to CT verified solid renal masses were prospectively collected and kept in a well-maintained database. Complications were collected retrospectively and classified according to the Clavien-Dindo (CD) classification system. RESULTS: Data from 224 consecutive patients were retrieved. Thirteen patients underwent unilateral repeat biopsies and three patients underwent bilateral biopsies; thus, a total of 240 procedures were analyzed. A total of 124 patients (51.7%) were discharged within 4 hours after the RTB procedures and 110 patients (45.8%) were discharged within 24 hours. The remaining six patients (2.5%) were hospitalized for more than 1 day, all due to co-morbidities which were unrelated to the procedure. In total, five patients (2.1%) experienced post-biopsy complications: one case of iatrogenic pneumothorax, one case of spontaneously resolving hematuria and three cases of fever. All complications were CD ≤2 and all patients with complications were discharged within 24 hours, except for one patient who was hospitalized for 3 days due to management of bone pain. No correlation was found between the number of biopsies and complication rate. CONCLUSION: The overall complication rate following ultrasound-guided biopsies of renal tumors was low and all complications were mild. Given the current evidence, it is believed that ultrasound-guided RTB can be done as an outpatient procedure without the need for hospitalization.

The effect of time from diagnosis to surgery on oncological outcomes in patients undergoing surgery for colon cancer: A systematic review.

Many countries have implemented cancer pathways with strict time limits dictating the pace of diagnostic testing and treatment. There are concerns that prehabilitation may worsen long-term oncological outcomes if surgery is delayed. We aimed to systematically review the literature investigating the association between increased time between diagnosis of colon cancer and surgical treatment, with special focus on survival outcomes. METHODS: Through a systematic search and analysis of the databases PubMed (1966-2017), EMBASE (1974-2017), CINHAL (1981-2017), and The Cochrane Library performed on June 7th, 2017, the effect of treatment delays on overall survival in colon cancer patients was reviewed. Treatment delay was defined as time from diagnosis to initiation of surgical treatment. All patients included were diagnosed with colon cancer and treated with elective curative surgery without neoadjuvant chemotherapy. This review was prospectively registered on the PROSPERO database of systematic review protocols with registration number CRD42017059774. RESULTS: Five observational studies including 13,514 patients were included. The treatment delay intervals ranged from 1 to ≥56 days. Four of the five studies found no association between time elapsed from diagnosis to surgery and reduced overall survival. One study found a clinically insignificant association between longer treatment delays and overall survival. Three studies investigated the effect on disease specific survival and found no negative associations. CONCLUSION: The available data showed no association between treatment delay and reduced overall survival in colon cancer patients.

Volume of ropivacaine 0.2% and common peroneal nerve block duration: a randomised, double-blind cohort trial in healthy volunteers.

The volume-duration relationship using low concentrations of ropivacaine for peripheral nerve blocks is unknown, even though low concentrations of ropivacaine are increasingly used clinically. We investigated the effect of ropivacaine 0.2% on common peroneal nerve block duration. With ethical committee approval, 60 consenting, healthy volunteers were randomly allocated to receive one of five volumes of ropivacaine 0.2% (2.5, 5.0, 10, 15 or 20 ml) administered by ultrasound-guided, catheter-based injection (at 10 ml.min-1 ) near the common peroneal nerve. Our primary outcome was duration of sensory block, defined by insensitivity to a cold stimulus. Our secondary outcome was duration of motor block. Outcomes were assessed every hour from onset of block to complete remission. Intergroup differences were tested using one-way ANOVA followed by regression analyses using the 20 ml intervention group as reference. Block durations varied significantly (p < 0.0001) between groups. Mean (SD) sensory block durations were 9.2 (3.3), 12.5 (3.0), 15.5 (4.4), 17.3 (3.5) and 17.3 (4.6) h. Mean (SD) motor block durations were 3.3 (2.1), 7.2 (2.5), 9.2 (2.2), 12.7 (2.5) and 12.5 (2.5) h. Regression analysis showed that the effect of volume on block duration was progressively smaller with increasing volume, reaching a threshold volume above which there was no effect on nerve block duration (10 ml for sensory block and 15 ml for motor block). We conclude that there is a ceiling effect of increasing volume of ropivacaine 0.2% on both sensory and motor block duration of the common peroneal nerve.