Novel experimental setup for megahertz X-ray diffraction in a diamond anvil cell at the High Energy Density (HED) instrument of the European X-ray Free-Electron Laser (EuXFEL).

The high-precision X-ray diffraction setup for work with diamond anvil cells (DACs) in interaction chamber 2 (IC2) of the High Energy Density instrument of the European X-ray Free-Electron Laser is described. This includes beamline optics, sample positioning and detector systems located in the multipurpose vacuum chamber. Concepts for pump-probe X-ray diffraction experiments in the DAC are described and their implementation demonstrated during the First User Community Assisted Commissioning experiment. X-ray heating and diffraction of Bi under pressure, obtained using 20 fs X-ray pulses at 17.8 keV and 2.2 MHz repetition, is illustrated through splitting of diffraction peaks, and interpreted employing finite element modeling of the sample chamber in the DAC.

The cross-sectional association between diabetes and orthostatic hypotension in community-dwelling older people.

AIMS: Orthostatic hypotension is a recognized complication of diabetes, but studies examining prevalence in diabetes are limited. The aim of this study was to ascertain the prevalence of orthostatic hypotension and the pattern of orthostatic BP response in a cohort of people with diabetes aged ≥ 50 years, embedded within the Irish Longitudinal Study of Ageing. METHODS: Orthostatic hypotension was defined as a drop in systolic blood pressure (SBP) ≥ 20 mmHg or drop in diastolic blood pressure (DBP) ≥ 10 mmHg at 30 s after standing. Diabetes was defined by self-report but cross-checked against HbA1c and medication records. Multilevel mixed effects linear regression models were used to compare orthostatic BP in people with and without diabetes. RESULTS: Some 3222 people were included, 7% (213 of 3222) of whom had diabetes. Prevalence of orthostatic hypotension in the group with diabetes was 22% (46 of 213) vs. 13% in those without diabetes; χ2 = 12.43; P < 0.001. Multilevel models demonstrated prolonged recovery of DBP in people with diabetes, with only 41% (87 of 213) returning to baseline by 60 s. Logistic regression models demonstrated that diabetes was associated with a significantly increased likelihood of orthostatic hypotension (odds ratio 1.84, 95% confidence interval 1.30-2.59; P = 0.001) and this remained robust after controlling for covariates. CONCLUSION: Over one-fifth of older people with diabetes had orthostatic hypotension. Recovery of DBP is related to dynamic changes in total peripheral resistance and impairment of this baroreflex-mediated response may explain the higher prevalence in diabetes. Given the prognostic implications when co-existing with diabetes, orthostatic hypotension may represent a potentially modifiable risk factor for adverse outcomes in late-life diabetes.

Observation of the shock-induced ß-Sn to b.c.t.-Sn transition using time-resolved X-ray diffraction.

Time-resolved X-ray diffraction measurements have been carried out on dynamically compressed Sn up to a maximum pressure of ∼13 GPa at the European Synchrotron Radiation Facility. The phase transition from ß-Sn to body-centered tetragonal (b.c.t.) Sn has been observed using synchrotron X-ray diffraction for the first time undergoing shock compression and release. Following maximum compression, the sample releases to lower pressures for several nanoseconds until the reverse transition occurs. The data are in good agreement with previous shock boundaries that indicate that the ß-Sn phase is stable ∼2 GPa higher than the static boundary upon compression and the b.c.t.-Sn phase is stable ∼1 GPa lower upon release. The transition to the high-pressure phase reveals a loss of texture in the X-ray diffraction data from the `quasi' single-crystal ß-Sn structure to a more powder-like Debye-Scherrer ring.

Measurement of Body-Centered Cubic Gold and Melting under Shock Compression.

We combined laser shock compression with in situ x-ray diffraction to probe the crystallographic state of gold (Au) on its principal shock Hugoniot. Au has long been recognized as an important calibration standard in diamond anvil cell experiments due to the stability of its face-centered cubic (fcc) structure to extremely high pressures (P >600 GPa at 300 K). This is in contrast to density functional theory and first principles calculations of the high-pressure phases of Au that predict a variety of fcc-like structures with different stacking arrangements at intermediate pressures. In this Letter, we probe high-pressure and high-temperature conditions on the shock Hugoniot and observe fcc Au at 169 GPa and the first evidence of body-centered cubic (bcc) Au at 223 GPa. Upon further compression, the bcc phase is observed in coexistence with liquid scattering as the Hugoniot crosses the Au melt curve before 322 GPa. The results suggest a triple point on the Au phase diagram that lies very close to the principal shock Hugoniot near ∼220 GPa.

Identification of Phase Transitions and Metastability in Dynamically Compressed Antimony Using Ultrafast X-Ray Diffraction.

Ultrafast x-ray diffraction at the LCLS x-ray free electron laser has been used to resolve the structural behavior of antimony under shock compression to 59 GPa. Antimony is seen to transform to the incommensurate, host-guest phase Sb-II at ∼11 GPa, which forms on nanosecond timescales with ordered guest-atom chains. The high-pressure bcc phase Sb-III is observed above ∼15 GPa, some 8 GPa lower than in static compression studies, and mixed Sb-III/liquid diffraction are obtained between 38 and 59 GPa. An additional phase which does not exist under static compression, Sb-I^{'}, is also observed between 8 and 12 GPa, beyond the normal stability field of Sb-I, and resembles Sb-I with a resolved Peierls distortion. The incommensurate Sb-II high-pressure phase can be recovered metastably on release to ambient pressure, where it is stable for more than 10 ns.

Ferrous Iron Under Oxygen-Rich Conditions in the Deep Mantle.

Recent experiments have demonstrated the existence of previously unknown iron oxides at high pressure and temperature including newly discovered pyrite-type FeO2 and FeO2Hx phases stable at deep terrestrial lower mantle pressures and temperatures. In the present study, we probed the iron oxidation state in high-pressure transformation products of Fe3+OOH goethite by in situ X-ray absorption spectroscopy in laser-heated diamond-anvil cell. At pressures and temperatures of ~91 GPa and 1,500-2,350 K, respectively, that is, in the previously reported stability field of FeO2Hx, a measured shift of -3.3 ± 0.1 eV of the Fe K-edge demonstrates that iron has turned from Fe3+ to Fe2+. We interpret this reductive valence change of iron by a concomitant oxidation of oxygen atoms from O2- to O-, in agreement with previous suggestions based on the structures of pyrite-type FeO2 and FeO2Hx phases. Such peculiar chemistry could drastically change our view of crystal chemistry in deep planetary interiors.

UV superconducting nanowire single-photon detectors with high efficiency, low noise, and 4 K operating temperature.

For photon-counting applications at ultraviolet wavelengths, there are currently no detectors that combine high efficiency (> 50%), sub-nanosecond timing resolution, and sub-Hz dark count rates. Superconducting nanowire single-photon detectors (SNSPDs) have seen success over the past decade for photon-counting applications in the near-infrared, but little work has been done to optimize SNSPDs for wavelengths below 400 nm. Here, we describe the design, fabrication, and characterization of UV SNSPDs operating at wavelengths between 250 and 370 nm. The detectors have active areas up to 56 µm in diameter, 70 - 80% efficiency at temperatures up to 4.2 K, timing resolution down to 60 ps FWHM, blindness to visible and infrared photons, and dark count rates of ∼ 0.25 counts/hr for a 56 µm diameter pixel. These performance metrics make UV SNSPDs ideal for applications in trapped-ion quantum information processing, lidar studies of the upper atmosphere, UV fluorescent-lifetime imaging microscopy, and photon-starved UV astronomy.

Ultrafast X-Ray Diffraction Studies of the Phase Transitions and Equation of State of Scandium Shock Compressed to 82 GPa.

Using x-ray diffraction at the Linac Coherent Light Source x-ray free-electron laser, we have determined simultaneously and self-consistently the phase transitions and equation of state (EOS) of the lightest transition metal, scandium, under shock compression. On compression scandium undergoes a structural phase transition between 32 and 35 GPa to the same bcc structure seen at high temperatures at ambient pressures, and then a further transition at 46 GPa to the incommensurate host-guest polymorph found above 21 GPa in static compression at room temperature. Shock melting of the host-guest phase is observed between 53 and 72 GPa with the disappearance of Bragg scattering and the growth of a broad asymmetric diffraction peak from the high-density liquid.

Straight-to-test colonoscopy for 2-week-wait referrals improves time to diagnosis of colorectal cancer and is feasible in a high-volume unit.

AIM: We have introduced 'straight-to-test' (STT) colonoscopy as part of our 2-week-wait (2WW) pathway to address increasing numbers of urgent referrals for colorectal cancer (CRC) within the National Health Service. In this study we evaluated the ability of this initiative to shorten the time to diagnosis of CRC. METHOD: We amended our 2WW referral form to include performance status and comorbidities. General practitioners were asked to provide data on estimated glomerular filtration rate and full blood count/ferritin. Our 2WW referrals were screened by a colorectal consultant and a nurse specialist. Those deemed unsuitable for STT were offered outpatient assessment (OPA). RESULTS: Of 553 2WW referrals screened, 352 were considered suitable, 65 of whom failed a telephone assessment or were uncontactable, and accordingly 287 were offered the STT pathway. The STT group was significantly younger than the OPA group (median 65.9 years vs 78.7 years; P < 0.0001). STT colonoscopy significantly reduced the time to first test (13 days vs 22 days; P < 0.0001) and tissue diagnosis from the referral date (17 days vs 24.5 days; P < 0.0001). Thirty-seven (6.8%) CRCs were detected. Proportionately fewer patients in the STT pathway were managed with 'best supportive care only' compared with patients attending OPA (one of 15 vs six of 22, respectively). STT colonoscopy obviated the need for clinic attendance before testing in 287 patients, representing a potential net cost benefit of at least £48 500 in 4 months. CONCLUSION: STT colonoscopy was safe and effective for selecting out a group of symptomatic patients who could proceed straight to endoscopic examination and receive a diagnosis more rapidly.

Investigation and diagnostic formulation in patients admitted with transient loss of consciousness.

Several commonly completed tests have low diagnostic yield in the setting of transient loss of consciousness (T-LOC). We estimated the use and cost of inappropriate investigations in patients admitted with T-LOC and assessed if these patients were given a definitive diagnosis for their presentation. We identified 80 consecutive patients admitted with T-LOC to a university teaching hospital. Eighty-eight percent (70/80) had a computerized topography (CT) brain scan and 49% (34/70) of these scans were inappropriate based on standard guidelines. Almost half (17/80) of electroencephalograms (EEG) and 82% (9/11) of carotid doppler ultrasound performed were not based on clinical evidence of seizure or stroke respectively. Forty-four percent (35/80) of patients had no formal diagnosis documented for their presentation. Inappropriate investigation in T-LOC is very prevalent in the acute hospital, increasing cost of patient care. In addition, there is poor diagnostic formulation for T-LOC making recurrent events more likely in the absence of definitive diagnoses.

X-Ray Diffraction of Solid Tin to 1.2 TPa.

We report direct in situ measurements of the crystal structure of tin between 0.12 and 1.2 TPa, the highest stress at which a crystal structure has ever been observed. Using angle-dispersive powder x-ray diffraction, we find that dynamically compressed Sn transforms to the body-centered-cubic (bcc) structure previously identified by ambient-temperature quasistatic-compression studies and by zero-kelvin density-functional theory predictions between 0.06 and 0.16 TPa. However, we observe no evidence for the hexagonal close-packed (hcp) phase found by those studies to be stable above 0.16 TPa. Instead, our results are consistent with bcc up to 1.2 TPa. We conjecture that at high temperature bcc is stabilized relative to hcp due to differences in vibrational free energy.

Direct Observation of Melting in Shock-Compressed Bismuth With Femtosecond X-ray Diffraction.

The melting of bismuth in response to shock compression has been studied using in situ femtosecond x-ray diffraction at an x-ray free electron laser. Both solid-solid and solid-liquid phase transitions are documented using changes in discrete diffraction peaks and the emergence of broad, liquid scattering upon release from shock pressures up to 14 GPa. The transformation from the solid state to the liquid is found to occur in less than 3 ns, very much faster than previously believed. These results are the first quantitative measurements of a liquid material obtained on shock release using x-ray diffraction, and provide an upper limit for the time scale of melting of bismuth under shock loading.

In-hospital stroke: characteristics and outcomes.

In-hospital stroke (IS) made up 6.5% of strokes recorded in the Irish National Stroke Register in 2012. International research has demonstrated poorer outcomes post IS compared to out of hospital stroke (OS). We aimed to profile all IS and OS over a 22 month period and compare the two groups by gathering data from the HIPE portal stroke register. The study site is a primary stroke centre. IS represented 11% (50/458) of total strokes with over half (27/50, 54%) admitted initially with medical complaints. IS patients had a significantly longer length of stay (79.2 +/- 87.4 days vs. 21.9 +/- 45.9 days, p < 0.01) and higher mortality (13/50 vs. 39/408, p < 0.01). Patients in the IS group were also less likely to receive stroke unit care (1/50 vs. 136/408, p < 0.01). This study demonstrates the significant morbidity and mortality associated with IS and highlights the need for efforts to be made to optimize identification and management of acute stroke in this cohort.

Anabolic implants alter abundance of mRNA involved in muscle growth, metabolism, and inflammation in the longissimus of Angus steers in the feedlot.

The majority of beef cattle in the United States often receive at least one anabolic implant resulting in improved growth, feed efficiency, and environmental and economic sustainability. However, the physiological and molecular mechanisms through which anabolic implants increase skeletal muscle growth of beef cattle remain elusive. The objective of this study was to identify transcriptional changes occurring in skeletal muscle of steers receiving anabolic implants containing different steroid hormones. Forty-eight steers were stratified by weight into 1 of 4 (n = 12/treatment) implant treatment groups: (1) estradiol (ImpE2; 25.7 mg E2; Compudose, Elanco Animal Health, Greenfield, IN), (2) trenbolone acetate (ImpTBA; 200 mg TBA; Finaplix-H, Merck Animal Health, Madison, NJ), (3) combination (ImpETBA; 120 mg TBA + 24 mg E2; Revalor-S, Merck Animal Health), or (4) no implant (CON). Skeletal muscle biopsies were taken from the longissimus 2 and 10 d post-implantation. The mRNA abundance of 94 genes associated with skeletal muscle growth was examined. At 10 d post-implantation, steers receiving ImpETBA had greater (P = 0.02) myoblast differentiation factor 1 transcript abundance than CON. Citrate synthase abundance was increased (P = 0.04) in ImpETBA steers compared to CON steers. In ImpE2 steers 10 d post-implantation, muscle RING finger protein 1 decreased (P = 0.05) compared to CON steers, and forkhead box protein O4 decreased (P = 0.05) in ImpETBA steers compared to CON steers. Interleukin-6 abundance tended to be increased (P = 0.09) in ImpE2 steers compared to both ImpETBA and CON steers. Furthermore, interleukin-10 mRNA abundance tended to be increased (P = 0.06) in ImpTBA steers compared to ImpETBA steers. Leptin receptor abundance was reduced (P = 0.01) in both ImpE2 and ImpTBA steers when compared to CON steers. Abundance of phosphodiesterase 4B was increased (P = 0.04) in ImpTBA steers compared to CON steers 2 d post-implantation. Taken together, the results of this research demonstrate that estradiol increases skeletal muscle growth via pathways related to nutrient partitioning and mitochondria function, while trenbolone acetate improves steer skeletal muscle growth via pathways related to muscle growth.

Relationship among cattle breed and anabolic implant protocol relative to feedlot performance: Growth, temperament, feeding behavior, carcass traits, and economic return.

Recent research has suggested that different cattle breed types may respond differently to anabolic implant protocols of varying intensity. Therefore, the purpose of this research was to compare anabolic implant protocols in feedlot steers of 2 different breed types. Sixty steers were stratified by weight and breed in a 2 × 3 factorial design examining 2 different breeds: Angus (AN; n=38) or Santa Gertrudis influenced (SG; n=22), and 3 implant strategies: no implant (CON; n=20), a moderate intensity implant protocol (d0 implant: Revalor-G, d56 implant: Revalor-IS, d112 implant: Revalor-S; MI; n=20), or a high intensity implant protocol (d0 implant: Revalor-IS, d56 implant: Revalor-S, d112 implant: Revalor-200; HI; n=20). Steers were randomly placed into pens equipped with GrowSafe bunks to collect dry matter intake and feeding behavior. All animals were fed the same diet. Weight, chute score, exit velocity, serum, rectal temperature, hip height and 12th rib fat thickness were collected approximately every 28 d over a 196 d period. Serum urea nitrogen (SUN) was evaluated as well. Total average daily gain was increased (P < 0.0001) in both the HI and MI steers compared to the CON steers by 29.4% and 26%, respectively. A treatment × breed interaction was observed (P < 0.0001) for hip height, with AN-CON steers being shorter (P < 0.0007) than AN-HI, SG-CON, SG-MI, and SG-HI steers. A breed × treatment interaction was observed (P < 0.004) for chute score and rectal temperature, with SG-HI and SG-MI steers having increased chute scores (P < 0.001) when compared to AN-HI, AN-MI, AN-CON, and SG-CON throughout the course of the trial. Additionally, SG-HI and SG-MI steers had an increased rectal temperature (P < 0.004) compared to AN-HI, AN-MI, AN-CON, and SG-CON steers. A breed effect was observed (P = 0.002) for SUN with AN steers having increased (P = 0.002) SUN concentration compared to SG sired steers, in addition to a treatment effect (P < 0.0001), with CON steers having a higher (P < 0.0001) SUN concentration than MI and HI steers, regardless of breed. The MI implant protocol increased net return per head, on average, by $97.28, regardless of breed, while the HI implant protocol increased net return by only $80.84. Taken together, despite the cattle breed types responding differently to the different anabolic implant protocols at times, a moderate intensity anabolic implant protocol was optimal in this experiment for steers raised in a temperate climate.

A comparative analysis exposes an amplification delay distinctive to SARS-CoV-2 Omicron variants of clinical and public health relevance.

ABSTRACTMutations in the SARS-CoV-2 genome may negatively impact a diagnostic test, have no effect, or turn into an opportunity for rapid molecular screening of variants. Using an in-house Emergency Use Authorized RT-qPCR-based COVID-19 diagnostic assay, we combined sequence surveillance of viral variants and computed PCR efficiencies for mismatched templates. We found no significant mismatches for the N, E, and S set of assay primers until the Omicron variant emerged in late November 2021. We found a single mismatch between the Omicron sequence and one of our assay's primers caused a > 4 cycle delay during amplification without impacting overall assay performance.Starting in December 2021, clinical specimens received for COVID-19 diagnostic testing that generated a Cq delay greater than 4 cycles were sequenced and confirmed as Omicron. Clinical samples without a Cq delay were largely confirmed as the Delta variant. The primer-template mismatch was then used as a rapid surrogate marker for Omicron. Primers that correctly identified Omicron were designed and tested, which prepared us for the emergence of future variants with novel mismatches to our diagnostic assay's primers. Our experience demonstrates the importance of monitoring sequences, the need for predicting the impact of mismatches, their value as a surrogate marker, and the relevance of adapting one's molecular diagnostic test for evolving pathogens.

Neural bases of the foreign accent syndrome: a functional magnetic resonance imaging case study.

Foreign accent syndrome (FAS) is a rare disorder characterized by the emergence of a perceived foreign accent following brain damage. Despite decades of study, little is known about the neural substrates involved in this disorder. In this case study, MRI images of the brain were obtained during a speech task for an American English-speaking monolingual female who presented with FAS of unknown etiology and was thought to sound 'Swedish' or 'Eastern European'. On the basis of MR structural imaging, the patient was noted to have frontal lobe atrophy. An fMRI picture-naming task designed to broadly engage the speech motor network revealed predominantly left-hemisphere involvement, including activation of the (1) left superior temporal and medial frontal structures, (2) bilateral subcortical structures and thalamus, and (3) left cerebellum. The results suggest an instance of substantial brain reorganization for speech motor control.

Multicentre survey of radiologically inserted gastrostomy feeding tube (RIG) in the UK.

AIMS: To evaluate the variance in current UK clinical practice and clinical outcomes for direct percutaneous radiologically inserted gastrostomy (RIG). MATERIALS AND METHODS: A prospective UK multicentre survey of RIG performed between October 2008 and August 2010 was performed through the British Society of Gastrointestinal and Abdominal Radiology (BSGAR). RESULTS: Data from 684 patients were provided by 45 radiologists working at 17 UK centres. Two hundred and sixty-three cases (40%) were performed with loop-retained catheters, and 346 (53%) with balloon-retained devices. Sixty percent of all patients experienced pain in the first 24 h, but settled in the majority thereafter. Early complications, defined as occurring in the first 24 h, included minor bleeding (1%), wound infection (3%), peritonism (2%), and tube misplacement (1%). Late complications, defined as occurring between day 2 and day 30 post-procedure, included mild pain (30%), persisting peritonism (2%), and 30 day mortality of 1% (5/665). Pre-procedural antibiotics or anti-methicillin-resistant Staphylococcus aureus (MRSA) prophylaxis did not affect the rate of wound infection, peritonitis, post-procedural pain, or mortality. Ninety-three percent of cases were performed using gastropexy. Gastropexy decreased post-procedural pain (p < 0.001), but gastropexy-related complications occurred in 5% of patients. However, post-procedure pain increased with the number of gastropexy sutures used (p < 0.001). The use of gastropexy did not affect the overall complication rate or mortality. Post-procedure pain increased significantly as tube size increased (p < 0.001). The use of balloon-retention feeding tubes was associated with more pain than the deployment of loop-retention devices (p < 0.001). CONCLUSION: RIG is a relatively safe procedure with a mortality of 1%, with or without gastropexy. Pain is the commonest complication. The use of gastropexy, fixation dressing or skin sutures, smaller tube sizes, and loop-retention catheters significantly reduced the incidence of pain. There was a gastropexy-related complication rate in 5% of patients. Neither pre-procedural antibiotics nor anti-MRSA prophylaxis affected the rate of wound infection.