Low dose X-ray speckle visibility spectroscopy reveals nanoscale dynamics in radiation sensitive ionic liquids

X-ray radiation damage provides a serious bottle neck for investigating {\mu}s to s dynamics on nanometer length scales employing X-ray photon correlation spectroscopy. This limitation hinders the investigation of real time dynamics in most soft matter and biological materials which can tolerate only X-ray doses of kGy and below. Here, we show that this bottleneck can be overcome by low dose X-ray speckle visibility spectroscopy. Employing X-ray doses of 22 kGy to 438 kGy and analyzing the sparse speckle pattern of count rates as low as 6.7x10-3 per pixel we follow the slow nanoscale dynamics of an ionic liquid (IL) at the glass transition. At the pre-peak of nanoscale order in the IL we observe complex dynamics upon approaching the glass transition temperature TG with a freezing in of the alpha relaxation and a multitude of milli-second local relaxations existing well below TG. We identify this fast relaxation as being responsible for the increasing development of nanoscale order observed in ILs at temperatures below TG.Comment: 7 pages, 5 figure

Coherent X-ray Scattering Reveals Nanoscale Fluctuations in Hydrated Proteins

Hydrated proteins undergo a transition in the deeply supercooled regime, which is attributed to rapid changes in hydration water and protein structural dynamics. Here, we investigate the nanoscale stress relaxation in hydrated lysozyme proteins stimulated and probed by X-ray Photon Correlation Spectroscopy (XPCS). This approach allows us to access the nanoscale dynamic response in the deeply supercooled regime (T = 180 K) which is typically not accessible through equilibrium methods. The relaxation time constants exhibit Arrhenius temperature dependence upon cooling with a minimum in the Kohlrausch-Williams-Watts exponent at T = 227 K. The observed minimum is attributed to an increase in dynamical heterogeneity, which coincides with enhanced fluctuations observed in the two-time correlation functions and a maximum in the dynamic susceptibility quantified by the normalised variance $\chi_T$. Our study provides new insights into X-ray stimulated stress relaxation and the underlying mechanisms behind spatio-temporal fluctuations in biological granular materials

Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection

Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8+ T cell populations in Mamu-A*01+ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8+ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8+ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection

HCV genotypes are differently prone to the development of resistance to linear and macrocyclic protease inhibitors

Because of the extreme genetic variability of hepatitis C virus (HCV), we analyzed whether specific HCV-genotypes are differently prone to develop resistance to linear and macrocyclic protease-inhibitors (PIs)

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P < 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P < 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk

Eine Nanorheologiestudie der viskoelastischen Eigenschaften von photorheologischen Flüssigkeiten mithilfe von Röntgenphoton-Korrelationsspektroskopie

Networks formed by long cylindrical or wormlike molecules appear in various shapes in nature and technology. They occur on a variety of length scales from nanometers to centimeters and determine especially the mechanical properties of a material, e.g., they control stabilization and transport, and induce interesting phenomena like viscoelasticity. By our nanorheology study on the viscoelastic properties of photorheological liquids, we gained new insight into the complex processes in microscopic networks on the nanometer length scale, in particular, the dynamics mediating the stress relaxation and determining the high-frequency rheology of the system. Photorheological fluids contain entangled networks of wormlike molecules, where the molecular structure and thereby network morphology can be altered by irradiation with light. Aqueous solutions of highly concentrated cetyl trimethylammonium bromide (CTAB) and ortho-methoxycinnamic acid (OMCA) exhibit enhanced viscoelasticity due to the self-assembly of long cylindrical (wormlike) micelles. The photoresponsivity of OMCA gives rise to the characteristic photorheological properties of those fluids that can be tailored by UV illumination. Employing passive nanorheology, the network structure and the associated stress relax- ation processes are accessible through the correlation functions of silica tracer particles measured by microsecond X-ray photon correlation spectroscopy (XPCS). The methods we developed to overcome limitations like beam damage and to analyze big datasets in the low intensity limit will be valuable for future XPCS studies on radiation sensitive systems and microsecond dynamics. We found that the nanorheology results deviate from macroscopic measurements when the confinement of the tracer particles is reduced below a certain threshold indicative of the complex network microstructure. We could further show that the functional form of the stress relaxation is reflected in the shape of the XPCS correlation functions. Anomalous diffusion, especially subdiffu- sive behavior, originates from the coupling between micelle and tracer dynamics. More precisely, we found a transition from exponential stress relaxation due to random scission of micelles to strongly non-exponential, reptation driven stress relaxation of the network, that can be tuned by UV illumination. From the short-time caging motion of the tracers, information on the local viscoelas- tic properties could be reduced on the nanometer length scale and microsecond time scales beyond the limits of classical rheology. Our results indicate high-frequency strain- stiffening of the OMCA-CTAB network due to short-range rigidity of the micelles.Netzwerke aus langen, zylindrischen oder wurmartigen Molekülen kommen in der Natur und Technik in unterschiedlichsten Formen vor. Auf Längenskalen von einigen wenigen Nanometern bis Zentimetern bestimmen sie insbesondere die mechanischen Eigenschaf- ten eines Materials. So können sie z.B. einen Stoff stabilisieren oder den Informations- transport steuern. Zusätzlich führen verschlungene Netzwerke in komplexen Fluiden zu interessanten Phänomenen wie Viskoelastizität. In der vorliegenden Arbeit untersuchen wir die viskoelastischen Eigenschaften von photorheologischen Flüssigkeiten. Wir gewan- nen neue Erkenntnisse über die komplexen Prozesse in mikroskopischen Netzwerken und die Dynamik von Relaxationsprozessen im Bereich von Mikrosekunden. Photorheologische Flüssigkeiten enthalten verschlungene Netzwerke aus wurmartigen Molekülen, wobei die Netzwerkmorphologie durch Bestrahlung mit Licht verändert wer- den kann. Wässrige Lösungen von Cetyltrimethylammoniumbromid (CTAB) und Ortho- Methoxyzimtsäure (OMCA) zeigen verstärkt viskoelastische Eigenschaften aufgrund der Formation von wurmartigen Mizellen. Durch UV-Bestrahlung kann die Mizellenlänge und damit die mikroskopische Struktur des Netzwerks verändert werden. Nanorheologie erlaubt die Netzwerkstruktur und die damit verbundenen Relaxations- prozesse zu untersuchen. Dafür werden der Lösung sphärische Nanoteilchen hinzuge- fügt, sogenannte „Tracer“. Ihre Dynamik kann mit Röntgenphoton Korrelationsspektro- skopie (XPCS) gemessen werden. Die von uns entwickelten Methoden zur Berechnung von Korrelationsfunktionen erlauben Mikrosekundendynamik von strahlensensitiven Sys- temen basierend auf großen XPCS Datensätzen zu analysieren. Unsere Ergebnisse zeigen, dass die Nanorheologie nur in einem gewissen Bereich mit den makroskopischen Rheologiemessungen übereinstimmt. Ab einer bestimmten hydro- dynamischen Korrelationslänge (oder Maschengröße) zeigen die Tracer verstärkt subdif- fusive Dynamik und eine erhöhte Mobilität. Dies ist durch eine schwache Lokalisierung der Nanoteilchen zu erklären, die anfangen sich durch die Maschen des Netzwerks hin- durchzubewegen. Wir konnten weiter zeigen, dass die Form der Spannungsrelaxationsfunktion aus dem Verhalten der XPCS Korrelationsfunktionen abgeleitet werden kann. Anomale Diffusi- on, insbesondere subdiffusive Dynamik, resultiert aus der Interaktion zwischen Mizellen und Tracer Dynamik. Genauer gesagt fanden wir einen Übergang von exponentiellem zu stark nicht-exponentiellem Verhalten. Dies ist auf die „Reptation“-Bewegung der Mizellen zurückzuführen, die durch UV-Bestrahlung zum dominanten Beitrag der Spannungsrela- xation wird. Aus der lokalisierten Bewegung der Tracer, auf Zeitskalen von Mikrosekunden, konnten wir Informationen über die lokalen viskoelastischen Eigenschaften des Netzwerks ablei- ten. Unsere Ergebnisse weisen auf eine erhöhte Steifigkeit des OMCA-CTAB-Netzwerks auf der Nanometer Längenskala hin, die mit der mikroskopischen Mizellenstruktur in Zusammenhang steht

Mechanical chest compression devices in the helicopter emergency medical service in Switzerland.

BACKGROUND Over the past years, several emergency medical service providers have introduced mechanical chest compression devices (MCDs) in their protocols for cardiopulmonary resuscitation (CPR). Especially in helicopter emergency medical systems (HEMS), which have limitations regarding loading weight and space and typically operate in rural and remote areas, whether MCDs have benefits for patients is still unknown. The aim of this study was to evaluate the use of MCDs in a large Swiss HEMS system. MATERIALS AND METHODS We conducted a retrospective observational study of all HEMS missions of Swiss Air rescue Rega between January 2014 and June 2016 with the use of an MCD (Autopulse®). Details of MCD use and patient outcome are reported from the medical operation journals and the hospitals' discharge letters. RESULTS MCDs were used in 626 HEMS missions, and 590 patients (94%) could be included. 478 (81%) were primary missions and 112 (19%) were interhospital transfers. Forty-nine of the patients in primary missions were loaded under ongoing CPR with MCDs. Of the patients loaded after return of spontaneous circulation (ROSC), 20 (7%) experienced a second CA during the flight. In interhospital transfers, 102 (91%) only needed standby use of the MCD. Five (5%) patients were loaded into the helicopter with ongoing CPR. Five (5%) patients went into CA during flight and the MCD had to be activated. A shockable cardiac arrhythmia was the only factor significantly associated with better survival in resuscitation missions using MCD (OR 0.176, 95% confidence interval 0.084 to 0.372, p < 0.001). CONCLUSION We conclude that equipping HEMS with MCDs may be beneficial, with non-trauma patients potentially benefitting more than trauma patients

Using low dose X-ray Speckle Visibility Spectroscopy to study dynamics of soft matter samples

We demonstrate the successful application of X-ray Speckle Visibility Spectroscopy (XSVS) experiments to study the dynamics of radiation sensitive, biological samples with unprecedentedly small X-ray doses of 45 Gy and below. Using XSVS, we track the dynamics of casein micelles in native, concentrated, and acidified solution conditions, while substantially reducing the deposited dose as compared to alternative techniques like sequential X-ray photon correlation spectroscopy (XPCS). The Brownian motion in a skim milk sample yields the hydrodynamic radius of the casein micelles while deviations from Brownian motion with a characteristic $q$-dependent diffusion coefficient $D(q)$ can be observed in more concentrated solution conditions. The low dose applied in our experiments allows the observation of static, frozen speckle patterns from gelled acidic milk. We show that the XSVS technique is especially suitable for tracking dynamics of radiation sensitive samples in combination with the improved coherent properties of new generation X-ray sources, emphasizing the great potential for further investigations of protein dynamics using fourth generation synchrotrons and free electron lasers

Analysis Strategies for MHz XPCS at the European XFEL

The nanometer length-scale holds precious information on several dynamical processes that develop from picoseconds to seconds. In the past decades, X-ray scattering techniques have been developed to probe the dynamics at such length-scales on either ultrafast (sub-nanosecond) or slow ((milli-)second) time scales. With the start of operation of the European XFEL, thanks to the MHz repetition rate of its X-ray pulses, even the intermediate μs range have become accessible. Measuring dynamics on such fast timescales requires the development of new technologies such as the Adaptive Gain Integrating Pixel Detector (AGIPD). μs-XPCS is a promising technique to answer many scientific questions regarding microscopic structural dynamics, especially for soft condensed matter systems. However, obtaining reliable results with complex detectors at free-electron laser facilities is challenging and requires more sophisticated analysis methods compared to experiments at storage rings. Here, we discuss challenges and possible solutions to perform XPCS experiments with the AGIPD at European XFEL; in particular, at the Materials Imaging and Dynamics (MID) instrument. We present our data analysis pipeline and benchmark the results obtained at the MID instrument with a well-known sample composed by silica nanoparticles dispersed in wate

Interplay between Kinetics and Dynamics of Liquid–Liquid Phase Separation in a Protein Solution Revealed by Coherent X-ray Spectroscopy

Microscopic dynamics of complex fluids in the early stage of spinodal decomposition (SD) is strongly intertwined with the kinetics of structural evolution, which makes a quantitative characterization challenging. In this work, we use X-ray photon correlation spectroscopy to study the dynamics and kinetics of a protein solution undergoing liquid–liquid phase separation (LLPS). We demonstrate that in the early stage of SD, the kinetics relaxation is up to 40 times slower than the dynamics and thus can be decoupled. The microscopic dynamics can be well described by hyper-diffusive ballistic motions with a relaxation time exponentially growing with time in the early stage followed by a power-law increase with fluctuations. These experimental results are further supported by simulations based on the Cahn–Hilliard equation. The established framework is applicable to other condensed matter and biological systems undergoing phase transitions and may also inspire further theoretical work