Risk factors for thromboembolic complications in isolated severe head injury.

PURPOSE Patients with traumatic brain injury (TBI) are at high risk for venous thromboembolism (VTE). The aim of the present study is to identify factors independently associated with VTE events. Specifically, we hypothesized that the mechanism of penetrating head trauma might be an independent factor associated with increased VTE events when compared with blunt head trauma. METHODS The ACS-TQIP database (2013-2019) was queried for all patients with isolated severe head injuries (AIS 3-5) who received VTE prophylaxis with either unfractionated heparin or low-molecular-weight heparin. Transfers, patients who died within 72 h and those with a hospital length of stay < 48 h were excluded. Multivariable analysis was used as the primary analysis to identify independent risk factors for VTE in isolated severe TBI. RESULTS A total of 75,570 patients were included in the study, 71,593 (94.7%) with blunt and 3977 (5.3%) with penetrating isolated TBI. Penetrating trauma mechanism (OR 1.49, CI 95% 1.26-1.77), increasing age (age 16-45: reference; age > 45-65: OR 1.65, CI 95% 1.48-1.85; age > 65-75: OR 1.71, CI 95% 1.45-2.02; age > 75: OR 1.73, CI 95% 1.44-2.07), male gender (OR 1.53, CI 95% 1.36-1.72), obesity (OR 1.35, CI 95% 1.22-1.51), tachycardia (OR 1.31, CI 95% 1.13-1.51), increasing head AIS (AIS 3: reference; AIS 4: OR 1.52, CI 95% 1.35-1.72; AIS 5: OR 1.76, CI 95% 1.54-2.01), associated moderate injuries (AIS = 2) of the abdomen (OR 1.31, CI 95% 1.04-1.66), spine (OR 1.35, CI 95% 1.19-1.53), upper extremity (OR 1.16, CI 95% 1.02-1.31), lower extremity (OR 1.46, CI 95% 1.26-1.68), craniectomy/craniotomy or ICP monitoring (OR 2.96, CI 95% 2.65-3.31) and pre-existing hypertension (OR 1.18, CI 95% 1.05-1.32) were identified as independent risk factors for VTE complications in isolated severe head injury. Increasing GCS (OR 0.93, CI 95% 0.92-0.94), early VTE prophylaxis (OR 0.48, CI 95% 0.39-0.60) and LMWH compared to heparin (OR 0.74, CI 95% 0.68-0.82) were identified as protective factors for VTE complications. CONCLUSION The identified factors independently associated with VTE events in isolated severe TBI need to be considered in VTE prevention measures. In penetrating TBI, an even more aggressive VTE prophylaxis management may be justified as compared to that in blunt

On-chip generation and dynamic piezo-optomechanical rotation of single photons

Integrated photonic circuits are key components for photonic quantum technologies and for the implementation of chip-based quantum devices. Future applications demand flexible architectures to overcome common limitations of many current devices, for instance the lack of tuneabilty or built-in quantum light sources. Here, we report on a dynamically reconfigurable integrated photonic circuit comprising integrated quantum dots (QDs), a Mach-Zehnder interferometer (MZI) and surface acoustic wave (SAW) transducers directly fabricated on a monolithic semiconductor platform. We demonstrate on-chip single photon generation by the QD and its sub-nanosecond dynamic on-chip control. Two independently applied SAWs piezo-optomechanically rotate the single photon in the MZI or spectrally modulate the QD emission wavelength. In the MZI, SAWs imprint a time-dependent optical phase and modulate the qubit rotation to the output superposition state. This enables dynamic single photon routing with frequencies exceeding one gigahertz. Finally, the combination of the dynamic single photon control and spectral tuning of the QD realizes wavelength multiplexing of the input photon state and demultiplexing it at the output. Our approach is scalable to multi-component integrated quantum photonic circuits and is compatible with hybrid photonic architectures and other key components for instance photonic resonators or on-chip detectors

On-chip generation and dynamic piezo-optomechanical rotation of single photons

Integrated photonic circuits are key components for photonic quantum technologies and for the implementation of chip-based quantum devices. Future applications demand flexible architectures to overcome common limitations of many current devices, for instance the lack of tuneabilty or built-in quantum light sources. Here, we report on a dynamically reconfigurable integrated photonic circuit comprising integrated quantum dots (QDs), a Mach-Zehnder interferometer (MZI) and surface acoustic wave (SAW) transducers directly fabricated on a monolithic semiconductor platform. We demonstrate on-chip single photon generation by the QD and its sub-nanosecond dynamic on-chip control. Two independently applied SAWs piezo-optomechanically rotate the single photon in the MZI or spectrally modulate the QD emission wavelength. In the MZI, SAWs imprint a time-dependent optical phase and modulate the qubit rotation to the output superposition state. This enables dynamic single photon routing with frequencies exceeding one gigahertz. Finally, the combination of the dynamic single photon control and spectral tuning of the QD realizes wavelength multiplexing of the input photon state and demultiplexing it at the output. Our approach is scalable to multi-component integrated quantum photonic circuits and is compatible with hybrid photonic architectures and other key components for instance photonic resonators or on-chip detectors

Hepcidin Is an Antibacterial, Stress-Inducible Peptide of the Biliary System

BACKGROUND/AIMS: Hepcidin (gene name HAMP), an IL-6-inducible acute phase peptide with antimicrobial properties, is the key negative regulator of iron metabolism. Liver is the primary source of HAMP synthesis, but it is also produced by other tissues such as kidney or heart and is found in body fluids such as urine or cerebrospinal fluid. While the role of hepcidin in biliary system is unknown, a recent study demonstrated that conditional gp130-knockout mice display diminished hepcidin levels and increased rate of biliary infections. METHODS: Expression and localization of HAMP in biliary system was analyzed by real time RT-PCR, in-situ hybridization, immunostaining and -blotting, while prohepcidin levels in human bile were determined by ELISA. RESULTS: Hepcidin was detected in mouse/human gallbladder and bile duct epithelia. Biliary HAMP is stress-inducible, in that it is increased in biliary cell lines upon IL-6 stimulation and in gallbladder mucosa of patients with acute cholecystitis. Hepcidin is also present in the bile and elevated prohepcidin levels were observed in bile of primary sclerosing cholangitis (PSC) patients with concurrent bacterial cholangitis compared to PSC subjects without bacterial infection (median values 22.3 vs. 8.9; p = 0.03). In PSC-cholangitis subjects, bile prohepcidin levels positively correlated with C-reactive protein and bilirubin levels (r = 0.48 and r = 0.71, respectively). In vitro, hepcidin enhanced the antimicrobial capacity of human bile (p<0.05). CONCLUSION: Hepcidin is a stress-inducible peptide of the biliary epithelia and a potential marker of biliary stress. In the bile, hepcidin may serve local functions such as protection from bacterial infections

Discovery of water vapour in the carbon star V Cygni from observations with Herschel/HIFI

We report the discovery of water vapour toward the carbon star V Cygni. We have used Herschel's HIFI instrument, in dual beam switch mode, to observe the 1(11) - 0(00) para-water transition at 1113.3430 GHz in the upper sideband of the Band 4b receiver. The observed spectral line profile is nearly parabolic, but with a slight asymmetry associated with blueshifted absorption, and the integrated antenna temperature is 1.69 \pm 0.17 K km/s. This detection of thermal water vapour emission, carried out as part of a small survey of water in carbon-rich stars, is only the second such detection toward a carbon-rich AGB star, the first having been obtained by the Submillimeter Wave Astronomy Satellite toward IRC+10216. For an assumed ortho-to-para ratio of 3 for water, the observed line intensity implies a water outflow rate ~ (3 - 6) E-5 Earth masses per year and a water abundance relative to H2 of ~ (2-5) E-6. This value is a factor of at least 1E+4 larger than the expected photospheric abundance in a carbon-rich environment, and - as in IRC+10216 - raises the intriguing possibility that the observed water is produced by the vapourisation of orbiting comets or dwarf planets. However, observations of the single line observed to date do not permit us to place strong constraints upon the spatial distribution or origin of the observed water, but future observations of additional transitions will allow us to determine the inner radius of the H2O-emitting zone, and the H2O ortho-to-para ratio, and thereby to place important constraints upon the origin of the observed water emission.Comment: Accepted for publication in A&A (HIFI special issue

First detection of ND in the solar-mass protostar IRAS16293-2422

In the past decade, much progress has been made in characterising the processes leading to the enhanced deuterium fractionation observed in the ISM and in particular in the cold, dense parts of star forming regions such as protostellar envelopes. Very high molecular D/H ratios have been found for saturated molecules and ions. However, little is known about the deuterium fractionation in radicals, even though simple radicals often represent an intermediate stage in the formation of more complex, saturated molecules. The imidogen radical NH is such an intermediate species for the ammonia synthesis in the gas phase. Herschel/HIFI represents a unique opportunity to study the deuteration and formation mechanisms of such species, which are not observable from the ground. We searched here for the deuterated radical ND in order to determine the deuterium fractionation of imidogen and constrain the deuteration mechanism of this species. We observed the solar-mass Class 0 protostar IRAS16293-2422 with the heterodyne instrument HIFI as part of the Herschel key programme CHESS (Chemical HErschel Surveys of Star forming regions). The deuterated form of the imidogen radical ND was detected and securely identified with 2 hyperfine component groups of its fundamental transition in absorption against the continuum background emitted from the nascent protostar. The 3 groups of hyperfine components of its hydrogenated counterpart NH were also detected in absorption. We derive a very high deuterium fractionation with an [ND]/[NH] ratio of between 30 and 100%. The deuterium fractionation of imidogen is of the same order of magnitude as that in other molecules, which suggests that an efficient deuterium fractionation mechanism is at play. We discuss two possible formation pathways for ND, by means of either the reaction of N+ with HD, or deuteron/proton exchange with NH.Comment: Accepted; To appear in A&A Herschel/HIFI Special Issu

Herschel-HIFI detections of hydrides towards AFGL 2591 (Envelope emission versus tenuous cloud absorption)

The Heterodyne Instrument for the Far Infrared (HIFI) onboard the Herschel Space Observatory allows the first observations of light diatomic molecules at high spectral resolution and in multiple transitions. Here, we report deep integrations using HIFI in different lines of hydrides towards the high-mass star forming region AFGL 2591. Detected are CH, CH+, NH, OH+, H2O+, while NH+ and SH+ have not been detected. All molecules except for CH and CH+ are seen in absorption with low excitation temperatures and at velocities different from the systemic velocity of the protostellar envelope. Surprisingly, the CH(JF,P = 3/2_2,- - 1/2_1,+) and CH+(J = 1 - 0, J = 2 - 1) lines are detected in emission at the systemic velocity. We can assign the absorption features to a foreground cloud and an outflow lobe, while the CH and CH+ emission stems from the envelope. The observed abundance and excitation of CH and CH+ can be explained in the scenario of FUV irradiated outflow walls, where a cavity etched out by the outflow allows protostellar FUV photons to irradiate and heat the envelope at larger distances driving the chemical reactions that produce these molecules.Comment: Accepted for publication in Astronomy and Astrophysics (HIFI first results issue

Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker.

Background -Preeclampsia (PE) is a complex and common human-specific pregnancy syndrome associated with placental pathology. The human-specificity provides both intellectual and methodological challenges, lacking a robust model system. Given the role of imprinted genes in human placentation and the vulnerability of imprinted genes to loss of imprinting changes, there has been extensive speculation, but no robust evidence, that imprinted genes are involved in PE. Our study aims at investigating whether disturbed imprinting contributes to PE. Methods -We first aimed at confirming that PE is a disease of the placenta by generating and analysing genome-wide molecular data on well-characterized patient material. We performed high-throughput transcriptome analyses of multiple placenta samples from normal and PE patients. Next, we identified differentially expressed genes (DEGs) in PE placenta, and intersected them with the list of human imprinted genes. We employed bioinformatics/statistical analyses to confirm association between imprinting and PE, and to predict biological processes affected in PE. Validation included epigenetic and cellular assays. Regarding human-specificity, we established an in vitro invasion-differentiation trophoblast model. Our comparative phylogenetic analysis involved single-cell transcriptome data of human, macaque and mouse preimplantation embryogenesis. Results -We found disturbed placental imprinting in PE and revealed potential candidates, including GATA3 and DLX5, with poorly explored imprinted status and no prior association with PE. Due to loss of imprinting DLX5 was upregulated in 69% of PE placentas. Levels of DLX5 correlated with classical PE marker. DLX5 is expressed in human, but not in murine trophoblast. The DLX5(high) phenotype resulted in reduced proliferation, increased metabolism and ER stress-response activation in trophoblasts in vitro The transcriptional profile of such cells mimics the transcriptome of PE placentas. Pan-mammalian comparative analysis identified DLX5 as a part of the human-specific regulatory network of trophoblast differentiation. Conclusions -Our analysis provides evidence of a true association between disturbed imprinting, gene expression and PE. Due to disturbed imprinting, the upregulated DLX5 affects trophoblast proliferation. Our in vitro model might fill a vital niche in PE research. Human-specific regulatory circuitry of DLX5 might help to explain certain aspects of PE

Herschel/HIFI observations of spectrally resolved methylidyne signatures toward the high-mass star-forming core NGC6334I

In contrast to extensively studied dense star-forming cores, little is known about diffuse gas surrounding star-forming regions. We study molecular gas in the high-mass star-forming region NGC6334I, which contains diffuse, quiescent components that are inconspicuous in widely used molecular tracers such as CO. We present Herschel/HIFI observations of CH toward NGC6334I observed as part of the CHESS key program. HIFI resolves the hyperfine components of its J=3/2-1/2 transition, observed in both emission and absorption. The CH emission appears close to the systemic velocity of NGC6334I, while its measured linewidth of 3 km/s is smaller than previously observed in dense gas tracers such as NH3 and SiO. The CH abundance in the hot core is 7 10^-11, two to three orders of magnitude lower than in diffuse clouds. While other studies find distinct outflows in, e.g., CO and H2O toward NGC6334I, we do not detect outflow signatures in CH. To explain the absorption signatures, at least two absorbing components are needed at -3.0 and +6.5 km/s with N(CH)=7 10^13 and 3 10^13 cm^-2. Two additional absorbing clouds are found at +8.0 and 0.0 km/s, both with N(CH)=2 10^13 cm^-2. Turbulent linewidths for the four absorption components vary between 1.5 and 5.0 km/s in FWHM. We constrain physical properties of our CH clouds by matching our CH absorbers with other absorption signatures. In the hot core, molecules such as H2O and CO trace gas that is heated and dynamically influenced by outflow activity, whereas CH traces more quiescent material. The four CH absorbers have column densities and turbulent properties consistent with diffuse clouds: two are located near NGC6334, and two are unrelated foreground clouds. Local density and dynamical effects influence the chemical composition of physical components of NGC6334, causing some components to be seen in CH but not in other tracers, and vice versa.Comment: Accepted by A&A Letters; 5 pages, 1 figure; v2: minor textual and typographical change

Ortho-to-para ratio of interstellar heavy water

Despite the low elemental deuterium abundance in the Galaxy, enhanced molecular D/H ratios have been found in the environments of low-mass star forming regions, and in particular the Class 0 protostar IRAS 16293-2422. The CHESS (Chemical HErschel Surveys of Star forming regions) Key Program aims at studying the molecular complexity of the interstellar medium. The high sensitivity and spectral resolution of the HIFI instrument provide a unique opportunity to observe the fundamental 1,1,1 - 0,0,0 transition of the ortho-D2O molecule, inaccessible from the ground, and to determine the ortho-to-para D2O ratio. We have detected the fundamental transition of the ortho-D2O molecule at 607.35 GHz towards IRAS 16293-2422. The line is seen in absorption with a line opacity of 0.62 +/- 0.11 (1 sigma). From the previous ground-based observations of the fundamental 1,1,0 - 1,0,1 transition of para-D2O seen in absorption at 316.80 GHz we estimate a line opacity of 0.26 +/- 0.05 (1 sigma). We show that the observed absorption is caused by the cold gas in the envelope of the protostar. Using these new observations, we estimate for the first time the ortho to para D2O ratio to be lower than 2.6 at a 3 sigma level of uncertainty, to be compared with the thermal equilibrium value of 2:1.Comment: 5 pages, 5 figures, accepted the A&A HIFI Special Issue as a lette