Elucidating 2D Charge-Density-Wave Atomic Structure in an MX-Chain by the 3D-ΔPair Distribution Function Method.

The front cover artwork is provided by Prof. Masahiro Yamashita's group at Tohoku University and designed by Dr. Laurent Guérin at University of Rennes 1. The image illustrates that the atomic structure of a 2D charge density wave can be revealed although the planes associated to this local 2D order are randomly stacked preventing the use of conventional structure determination techniques. Read the full text of the Research Article at 10.1002/cphc.202100857.

Elucidating 2D Charge-Density-Wave Atomic Structure in an MX-Chain by the 3D-ΔPair Distribution Function Method.

Many solids, particularly low-dimensional systems, exhibit charge density waves (CDWs). In one dimension, charge density waves are well understood, but in two dimensions, their structure and their origin are difficult to reveal. Herein, the 2D charge-density-wave atomic structure and stabilization mechanism in the bromide-bridged Pd compound [Pd(cptn)2 Br]Br2 (cptn=1R,2R-diaminocyclopentane) is investigated by means of single-crystal X-ray diffraction employing the 3D-Δpair distribution function (3D-ΔPDF) method. Analysis of the diffuse scattering using 3D-ΔPDF shows that a 2D-CDW is stabilized by a hydrogen-bonding network between Br- counteranion and the amine (NH2 ) group of the cptn in-plane ligand, and that 3D ordering is prevented due to a weak plane to plane correlation. We extract the effective displacements of the atoms describing the atomic structure quantitatively and discuss the stabilization mechanism of the 2D-CDW. Our study provides a method to identify and measure the key interaction responsible for the dimensionality and stability of the CDW that can help further progress of rational design.

Hydrogen Bonding Propagated Phase Separation in Quasi-Epitaxial Single Crystals: A Pd-Br Molecular Insulator.

In condensed matter, phase separation is strongly related to ferroelasticity, ferroelectricity, ferromagnetism, electron correlation, and crystallography. These ferroics are important for nano-electronic devices such as non-volatile memory. However, the quantitative information regarding the lattice (atomic) structure at the border of phase separation is unclear in many cases. Thus, to design electronic devices at the molecular level, a quantitative electron-lattice relationship must be established. Herein, we elucidated a PdII-PdIV/PdIII-PdIII phase transition and phase separation mechanism for [Pd(cptn)2Br]Br2 (cptn = 1R,2R-diaminocyclopentane), propagated through a hydrogen-bonding network. Although the Pd···Pd distance was used to determine the electronic state, the differences in the Pd···Pd distance and the optical gap between Mott-Hubbard (MH) and charge-density-wave (CDW) states were only 0.012 Å and 0.17 eV, respectively. The N-H···Br···H-N hydrogen-bonding network functioned as a jack, adjusting the structural difference dynamically, and allowing visible ferroelastic phase transition/separation in a fluctuating N2 gas flow. Additionally, the effect of the phase separation on the spin susceptibility and electrical conductivity were clarified to represent the quasi-epitaxial crystals among CDW-MH states. These results indicate that the phase transitions and separations could be controlled via atomic and molecular level modifications, such as the addition of hydrogen bonding.

Venous return and mean systemic filling pressure: physiology and clinical applications.

Venous return is the flow of blood from the systemic venous network towards the right heart. At steady state, venous return equals cardiac output, as the venous and arterial systems operate in series. However, unlike the arterial one, the venous network is a capacitive system with a high compliance. It includes a part of unstressed blood, which is a reservoir that can be recruited via sympathetic endogenous or exogenous stimulation. Guyton's model describes the three determinants of venous return: the mean systemic filling pressure, the right atrial pressure and the resistance to venous return. Recently, new methods have been developed to explore such determinants at the bedside. In this narrative review, after a reminder about Guyton's model and current methods used to investigate it, we emphasize how Guyton's physiology helps understand the effects on cardiac output of common treatments used in critically ill patients.

Effects of Prone Positioning on Venous Return in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVES: To examine the effects of prone positioning on venous return and its determinants such as mean systemic pressure and venous return resistance in patients with acute respiratory distress syndrome. DESIGN: Prospective monocentric study. SETTINGS: A 25-bed medical ICU. PATIENTS: About 22 patients with mild-to-severe acute respiratory distress syndrome in whom prone positioning was decided. INTERVENTIONS: We obtained cardiac index, mean systemic pressure, and venous return resistance (the latter two estimated through the heart-lung interactions method) before and during prone positioning. Preload responsiveness was assessed at baseline using an end-expiratory occlusion test. MEASUREMENTS AND MAIN RESULTS: Prone positioning significantly increased mean systemic pressure (from 24 mm Hg [19-34 mm Hg] to 35 mm Hg [32-46 mm Hg]). This was partly due to the trunk lowering performed before prone positioning. In seven patients, prone positioning increased cardiac index greater than or equal to 15%. All were preload responsive. In these patients, prone positioning increased mean systemic pressure by 82% (76-95%), central venous pressure by 33% (21-59%), (mean systemic pressure - central venous pressure) gradient by 144% (83-215)%, while it increased venous return resistance by 71% (60-154%). In 15 patients, prone positioning did not increase cardiac index greater than or equal to 15%. In these patients, prone positioning increased mean systemic pressure by 28% (18-56%) (p < 0.05 vs. patients with significant increase in cardiac index), central venous pressure by 21% (7-54%), (mean systemic pressure - central venous pressure) gradient by 28% (23-86%), and venous return resistance by 37% (17-77%). Eleven of these 15 patients were preload unresponsive. CONCLUSIONS: Prone positioning increased mean systemic pressure in all patients. The resulting change in cardiac index depended on the extent of increase in (mean systemic pressure - central venous pressure) gradient, of preload responsiveness, and of the increase in venous return resistance. Cardiac index increased only in preload-responsive patients if the increase in venous return resistance was lower than the increase in the (mean systemic pressure -central venous pressure) gradient.

Norepinephrine potentiates the efficacy of volume expansion on mean systemic pressure in septic shock.

BACKGROUND: Through venous contraction, norepinephrine (NE) increases stressed blood volume and mean systemic pressure (Pms) and exerts a "fluid-like" effect. When both fluid and NE are administered, Pms may not only result from the sum of the effects of both drugs. Indeed, norepinephrine may enhance the effects of volume expansion: because fluid dilutes into a more constricted, smaller, venous network, fluid may increase Pms to a larger extent at a higher than at a lower dose of NE. We tested this hypothesis, by mimicking the effects of fluid by passive leg raising (PLR). METHODS: In 30 septic shock patients, norepinephrine was decreased to reach a predefined target of mean arterial pressure (65-70 mmHg by default, 80-85 mmHg in previously hypertensive patients). We measured the PLR-induced increase in Pms (heart-lung interactions method) under high and low doses of norepinephrine. Preload responsiveness was defined by a PLR-induced increase in cardiac index ≥ 10%. RESULTS: Norepinephrine was decreased from 0.32 [0.18-0.62] to 0.26 [0.13-0.50] µg/kg/min (p < 0.0001). This significantly decreased the mean arterial pressure by 10 [7-20]% and Pms by 9 [4-19]%. The increase in Pms (∆Pms) induced by PLR was 13 [9-19]% at the higher dose of norepinephrine and 11 [6-16]% at the lower dose (p < 0.0001). Pms reached during PLR at the high dose of NE was higher than expected by the sum of Pms at baseline at low dose, ∆Pms induced by changing the norepinephrine dose and ∆Pms induced by PLR at low dose of NE (35.6 [11.2] mmHg vs. 33.6 [10.9] mmHg, respectively, p < 0.01). The number of preload responders was 8 (27%) at the high dose of NE and 15 (50%) at the low dose. CONCLUSIONS: Norepinephrine enhances the Pms increase induced by PLR. These results suggest that a bolus of fluid of the same volume has a greater haemodynamic effect at a high dose than at a low dose of norepinephrine during septic shock.

Oseltamivir Resistance in Severe Influenza A(H1N1)pdm09 Pneumonia and Acute Respiratory Distress Syndrome: A French Multicenter Observational Cohort Study.

In a multicenter cohort study including 22 oseltamivir-treated patients with influenza A(H1N1)pdm09 acute respiratory distress syndrome, prevalence of the H275Y substitution in the neuraminidase, responsible for highly reduced sensitivity to oseltamivir, was 23%. Patients infected with the H275Y mutant virus had higher day 28 mortality than others (80% vs 12%; P = .011).

Long-term Quality of Life in Adult Patients Surviving Purpura Fulminans: An Exposed-Unexposed Multicenter Cohort Study.

BACKGROUND: Long-term health-related quality of life (HR-QOL) of patients surviving the acute phase of purpura fulminans (PF) has not been evaluated. METHODS: This was a French multicenter exposed-unexposed cohort study enrolling patients admitted in 55 intensive care units (ICUs) for PF from 2010 to 2016. Adult patients surviving the acute phase of PF (exposed group) were matched 1:1 for age, sex, and Simplified Acute Physiology Score II with septic shock survivors (unexposed group). HR-QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36) questionnaire, the Hospital Anxiety and Depression (HAD) scale, the Impact of Event Scale-Revised (IES-R), and the activity of daily living (ADL) and instrumental ADL (IADL) scales. The primary outcome measure was the physical component summary (PCS) of the SF-36 questionnaire. RESULTS: Thirty-seven survivors of PF and 37 of septic shock were phone-interviewed at 55 (interquartile range [IQR], 35-83) months and 44 (IQR, 35-72) months, respectively, of ICU discharge (P = .23). The PCS of the SF-36 was not significantly different between exposed and unexposed patients (median, 47 [IQR, 36-53] vs 54 [IQR, 36-57]; P = .18). There was also no significant difference between groups regarding the mental component summary of the SF-36, and the HAD, IES-R, ADL and IADL scales. Among the 37 exposed patients, those who required limb amputation (n = 12/37 [32%]) exhibited lower PCS (34 [IQR, 24-38] vs 52 [IQR, 42-56]; P = .001) and IADL scores (7 [IQR, 4-8] vs 8 [IQR, 7-8]; P = .021) compared with nonamputated patients. CONCLUSIONS: Long-term HR-QOL does not differ between patients surviving PF and those surviving septic shock unrelated to PF. Amputated patients have an impaired physical HR-QOL but a preserved mental health. CLINICAL TRIALS REGISTRATION: NCT03216577.

Methodological elements for optimising the spatial monitoring design to support regional benthic ecosystem assessments.

Benthic habitat condition assessments are a requirement under various environmental directives. The Marine Strategy Framework Directive (MSFD), for example, challenges member states in a European sea region to perform comparable assessments of good environmental status and improve coherence of their monitoring programmes by 2020. Currently, North Sea countries operate independent monitoring programmes using nationally defined assessment areas. Lack of an agreed OSPAR or EU scale monitoring method and programme has been identified as a priority science need. This paper proposes a method for the development of a coherent and efficient spatial sampling design for benthic habitats on regional level and gives advice on optimal monitoring effort to get more accurate assessments. We use ecologically relevant assessment areas (strata) across national borders and test spatial sample allocation methods. Furthermore, we investigate the number of samples needed in each stratum to reduce the variance for estimating mean number of taxa and abundance. The stratification needs to take into account the spatial heterogeneity of the entire ecosystem. The total sample effort is optimal when sample allocation takes into account the size and benthic variability within those strata. Change point analysis helps to find a balance between sampling effort and precision of the benthic parameter estimate. A joint sampling design for the North Sea could be generated by combining current efforts, and where needed adapting existing national programmes. This serves a coordinated, region-wide, benthic condition status assessment and strengthens regional cooperation to fulfil multiple monitoring tasks, with a scientifically underpinned common approach.

First Step Towards a Devil's Staircase in Spin-Crossover Materials.

The unprecedented bimetallic 2D coordination polymer {Fe[(Hg(SCN)3 )2 ](4,4'-bipy)2 }n exhibits a thermal high-spin (HS)↔low-spin (LS) staircase-like conversion characterized by a multi-step dependence of the HS molar fraction γHS . Between the fully HS (γHS =1) and LS (γHS =0) phases, two steps associated with different ordering appear in terms of spin-state concentration waves (SSCW). On the γHS ≈0.5 step, a periodic SSCW forms with a HS-LS-HS-LS sequence. On the γHS ≈0.34 step, the 4D superspace crystallography structural refinement reveals an aperiodic SSCW, with a HS-LS sequence incommensurate with the molecular lattice. The formation of these different long-range spatially ordered structures of LS and HS states during the multi-step spin-crossover is discussed within the framework of "Devil's staircase"-type transitions. Spatially modulated phases are known in various types of materials but are uniquely related to molecular HS/LS bistability in this case.

Effects of passive leg raising and volume expansion on mean systemic pressure and venous return in shock in humans.

INTRODUCTION: The aim of this study was to assess how mean systemic pressure (Psm) and resistance to venous return (Rvr) behave during passive leg raising (PLR) in cases of fluid responsiveness and fluid unresponsiveness. METHOD: In 30 patients with an acute circulatory failure, in order to estimate the venous return curve, we constructed the regression line between pairs of cardiac index (CI) and central venous pressure (CVP). Values were measured during end-inspiratory and end-expiratory ventilatory occlusions performed at two levels of positive end-expiratory pressure. The x-axis intercept was used to estimate Psm and the inverse of the slope to quantify Rvr. These measurements were obtained at baseline, during PLR and after fluid infusion. Patients in whom fluid infusion increased CI by more than 15 % were defined as "fluid-responders". RESULTS: In fluid-responders (n = 15), CVP and Psm significantly increased (from 7 ± 3 to 9 ± 4 mmHg and from 25 ± 13 to 31 ± 13 mmHg, respectively) during PLR. The Psm-CVP gradient significantly increased by 20 ± 30 % while Rvr did not change significantly during PLR. In fluid-nonresponders, CVP and Psm increased significantly but the Psm-CVP gradient did not change significantly during PLR. PLR did not change the intra-abdominal pressure in the whole population (14 ± 6 mmHg before vs. 13 ± 5 mmHg during PLR, p = 0.26) and in patients with intra-abdominal hypertension at baseline (17 ± 4 mmHg before vs. 16 ± 4 mmHg during PLR, p = 0.14). In the latter group, PLR increased Psm from 22 ± 11 to 27 ± 10 mmHg (p <0.01) and did not change Rvr (5.1 ± 2.6 to 5.2 ± 3 mmHg/min/m(2)/mL, p = 0.71). In fluid-responders, Psm, CVP and the Psm-CVP gradient significantly increased during fluid infusion while the Rvr did not change. In fluid-nonresponders, CVP and Psm increased significantly during fluid infusion while the Psm-CVP gradient and Rvr did not change. CONCLUSION: PLR significantly increased Psm without modifying Rvr. This was also the case in patients with intra-abdominal hypertension. In case of fluid responsiveness, PLR increased venous return by increasing Psm to a larger extent than CVP. In patients with fluid unresponsiveness, PLR increased Psm but did not change the Psm-CVP gradient. Fluid infusion induced similar effects on Psm and Rvr.

Identifying the major intermediate species by combining time-resolved X-ray solution scattering and X-ray absorption spectroscopy.

Identifying the intermediate species along a reaction pathway is a first step towards a complete understanding of the reaction mechanism, but often this task is not trivial. There has been a strong on-going debate: which of the three intermediates, the CHI2 radical, the CHI2-I isomer, and the CHI2(+) ion, is the dominant intermediate species formed in the photolysis of iodoform (CHI3)? Herein, by combining time-resolved X-ray liquidography (TRXL) and time-resolved X-ray absorption spectroscopy (TR-XAS), we present strong evidence that the CHI2 radical is dominantly formed from the photolysis of CHI3 in methanol at 267 nm within the available time resolution of the techniques (∼20 ps for TRXL and ∼100 ps for TR-XAS). The TRXL measurement, conducted using the time-slicing scheme, detected no CHI2-I isomer within our signal-to-noise ratio, indicating that, if formed, the CHI2-I isomer must be a minor intermediate. The TR-XAS transient spectra measured at the iodine L1 and L3 edges support the same conclusion. The present work demonstrates that the application of these two complementary time-resolved X-ray methods to the same system can provide a detailed understanding of the reaction mechanism.

Extravascular lung water, B-type natriuretic peptide, and blood volume contraction enable diagnosis of weaning-induced pulmonary edema.

OBJECTIVE: We tested whether the changes in extravascular lung water indexed for ideal body weight could detect weaning-induced pulmonary edema. We also studied the diagnostic value of blood volume contraction indices and B-type natriuretic peptide variations. DESIGN: Prospective study. SETTING ICU PATIENTS: Twenty-one patients who failed a first spontaneous breathing trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We performed a second 60-minute T-tube spontaneous breathing trial. Before and at the end of spontaneous breathing trial, we recorded pulmonary artery occlusion pressure, the extravascular lung water indexed for ideal body weight, plasma B-type natriuretic peptide level, hemoglobin, and plasma protein concentrations. Weaning-induced pulmonary edema was defined by the association of signs of clinical intolerance and a pulmonary artery occlusion pressure greater than or equal to 18 mm Hg at the end of spontaneous breathing trial. Because some patients performed several spontaneous breathing trial, a primary analysis included all spontaneous breathing trial and a secondary analysis included only the first spontaneous breathing trial of each patient. In primary analysis, 36 spontaneous breathing trials were analyzed, 21 spontaneous breathing trial with weaning-induced pulmonary edema and 15 without. During spontaneous breathing trial, extravascular lung water indexed for ideal body weight increased only in cases with weaning-induced pulmonary edema (25% ± 23%). Plasma protein concentration, hemoglobin concentration, and B-type natriuretic peptide also significantly increased only in cases with weaning-induced pulmonary edema (9% ± 3%, 9% ± 4%, 21% ± 23%, respectively). The areas under the receiver operating characteristics curves to detect weaning-induced pulmonary edema were 0.89 (95% CI, 0.78-0.99) for extravascular lung water indexed for ideal body weight, 0.97 (0.93-1.01) for spontaneous breathing trial-induced changes in plasma protein concentration, 0.96 (0.90-1.01) for changes in hemoglobin concentration, and 0.76 (0.60-0.93) for changes in B-type natriuretic peptide. An increase in extravascular lung water indexed for ideal body weight greater than or equal to 14% diagnosed weaning-induced pulmonary edema with a sensitivity of 67% (95% CI, 43-85%) and a specificity of 100% (95% CI, 78-100%). The secondary analysis confirmed these results. CONCLUSIONS: Spontaneous breathing trial-induced increases in extravascular lung water indexed for ideal body weight, plasma protein concentrations, hemoglobin concentration, and B-type natriuretic peptide are reliable alternatives to the pulmonary artery catheter for diagnosing weaning-induced pulmonary edema.

Transpulmonary thermodilution enables to detect small short-term changes in extravascular lung water induced by a bronchoalveolar lavage.

OBJECTIVE: To take the opportunity of a bronchoalveolar lavage to challenge the transpulmonary thermodilution for detecting the time course of changes in extravascular lung water. DESIGN: Observational study. SETTING: Medical ICU. PATIENTS: Mechanically ventilated patients in whom a bronchoalveolar lavage by bronchoscopy was performed. INTERVENTION: Transpulmonary thermodilution before and after bronchoalveolar lavage. MEASUREMENTS AND MAIN RESULTS: Before and at different times after bronchoalveolar lavage, transpulmonary thermodilution was performed to record the value of indexed extravascular lung water. For each measurement, the values of three thermodilution measurements were averaged at the following steps: before bronchoalveolar lavage, after bronchoalveolar lavage, and 1 hour, 2 hours, 4 hours, and 6 hours after bronchoalveolar lavage. The amount of saline infusion left in the lungs after bronchoalveolar lavage was also recorded. Twenty-five patients with suspicion of pneumonia were included. Twenty-eight bronchoalveolar lavages were finally analyzed. On average, 200 mL (180-200 mL) of saline were injected and 130 mL (100-160 mL) were left in the lungs. Between before and immediately after bronchoalveolar lavage, indexed extravascular lung water significantly increased from 12 ± 4 to 15 ± 5 mL/kg, respectively, representing a 169 ± 166 mL increase in nonindexed extravascular lung water. After bronchoalveolar lavage, the value of indexed extravascular lung water was significantly different from the baseline value until 2 hours after bronchoalveolar lavage and became similar to the baseline value thereafter. CONCLUSIONS: Transpulmonary thermodilution enabled to detect small short-term changes of indexed extravascular lung water secondary to bronchoalveolar lavage.

Filming the birth of molecules and accompanying solvent rearrangement.

Molecules are often born with high energy and large-amplitude vibrations. In solution, a newly formed molecule cools down by transferring energy to the surrounding solvent molecules. The progression of the molecular and solute-solvent cage structure during this fundamental process has been elusive, and spectroscopic data generally do not provide such structural information. Here, we use picosecond X-ray liquidography (solution scattering) to visualize time-dependent structural changes associated with the vibrational relaxation of I(2) molecules in two different solvents, CCl(4) and cyclohexane. The birth and vibrational relaxation of I(2) molecules and the associated rearrangement of solvent molecules are mapped out in the form of a temporally varying interatomic distance distribution. The I-I distance increases up to ~4 Å and returns to the equilibrium distance (2.67 Å) in the ground state, and the first solvation cage expands by ~1.5 Å along the I-I axis and then shrinks back accompanying the structural change of the I(2) molecule.

Relationship of Extravascular Lung Water and Pulmonary Vascular Permeability to Respiratory Mechanics in Patients with COVID-19-Induced ARDS.

During acute respiratory distress syndrome (ARDS), the increase in pulmonary vascular permeability and lung water induced by pulmonary inflammation may be related to altered lung compliance. A better understanding of the interactions between respiratory mechanics variables and lung water or capillary permeability would allow a more personalized monitoring and adaptation of therapies for patients with ARDS. Therefore, our main objective was to investigate the relationship between extravascular lung water (EVLW) and/or pulmonary vascular permeability index (PVPI) and respiratory mechanic variables in patients with COVID-19-induced ARDS. This is a retrospective observational study from prospectively collected data in a cohort of 107 critically ill patients with COVID-19-induced ARDS from March 2020 to May 2021. We analyzed relationships between variables using repeated measurements correlations. We found no clinically relevant correlations between EVLW and the respiratory mechanics variables (driving pressure (correlation coefficient [CI 95%]: 0.017 [-0.064; 0.098]), plateau pressure (0.123 [0.043; 0.202]), respiratory system compliance (-0.003 [-0.084; 0.079]) or positive end-expiratory pressure (0.203 [0.126; 0.278])). Similarly, there were no relevant correlations between PVPI and these same respiratory mechanics variables (0.051 [-0.131; 0.035], 0.059 [-0.022; 0.140], 0.072 [-0.090; 0.153] and 0.22 [0.141; 0.293], respectively). In a cohort of patients with COVID-19-induced ARDS, EVLW and PVPI values are independent from respiratory system compliance and driving pressure. Optimal monitoring of these patients should combine both respiratory and TPTD variables.

Low versus standard calorie and protein feeding in ventilated adults with shock: a randomised, controlled, multicentre, open-label, parallel-group trial (NUTRIREA-3).

BACKGROUND: The optimal calorie and protein intakes at the acute phase of severe critical illness remain unknown. We hypothesised that early calorie and protein restriction improved outcomes in these patients, compared with standard calorie and protein targets. METHODS: The pragmatic, randomised, controlled, multicentre, open-label, parallel-group NUTRIREA-3 trial was performed in 61 French intensive care units (ICUs). Adults (≥18 years) receiving invasive mechanical ventilation and vasopressor support for shock were randomly assigned to early nutrition (started within 24 h after intubation) with either low or standard calorie and protein targets (6 kcal/kg per day and 0·2-0·4 g/kg per day protein vs 25 kcal/kg per day and 1·0-1·3 g/kg per day protein) during the first 7 ICU days. The two primary endpoints were time to readiness for ICU discharge and day 90 all-cause mortality. Key secondary outcomes included secondary infections, gastrointestinal events, and liver dysfunction. The trial is registered on ClinicalTrials.gov, NCT03573739, and is completed. FINDINGS: Of 3044 patients randomly assigned between July 5, 2018, and 8 Dec 8, 2020, eight withdrew consent to participation. By day 90, 628 (41·3%) of 1521 patients in the low group and 648 (42·8%) of 1515 patients in the standard group had died (absolute difference -1·5%, 95% CI -5·0 to 2·0; p=0·41). Median time to readiness for ICU discharge was 8·0 days (IQR 5·0-14·0) in the low group and 9·0 days (5·0-17·0) in the standard group (hazard ratio [HR] 1·12, 95% CI 1·02 to 1·22; p=0·015). Proportions of patients with secondary infections did not differ between the groups (HR 0·85, 0·71 to 1·01; p=0·06). The low group had lower proportions of patients with vomiting (HR 0·77, 0·67 to 0·89; p<0·001), diarrhoea (0·83, 0·73 to 0·94; p=0·004), bowel ischaemia (0·50, 0·26 to 0·95; p=0·030), and liver dysfunction (0·92, 0·86-0·99; p=0·032). INTERPRETATION: Compared with standard calorie and protein targets, early calorie and protein restriction did not decrease mortality but was associated with faster recovery and fewer complications. FUNDING: French Ministry of Health.

Protein structural dynamics of photoactive yellow protein in solution revealed by pump-probe X-ray solution scattering.

Photoreceptor proteins play crucial roles in receiving light stimuli that give rise to the responses required for biological function. However, structural characterization of conformational transition of the photoreceptors has been elusive in their native aqueous environment, even for a prototype photoreceptor, photoactive yellow protein (PYP). We employ pump-probe X-ray solution scattering to probe the structural changes that occur during the photocycle of PYP in a wide time range from 3.16 µs to 300 ms. By the analysis of both kinetics and structures of the intermediates, the structural progression of the protein in the solution phase is vividly visualized. We identify four structurally distinct intermediates and their associated five time constants and reconstructed the molecular shapes of the four intermediates from time-independent, species-associated difference scattering curves. The reconstructed structures of the intermediates show the large conformational changes such as the protrusion of N-terminus, which is restricted in the crystalline phase due to the crystal contact and thus could not be clearly observed by X-ray crystallography. The protrusion of the N-terminus and the protein volume gradually increase with the progress of the photocycle and becomes maximal in the final intermediate, which is proposed to be the signaling state. The data not only reveal that a common kinetic mechanism is applicable to both the crystalline and the solution phases, but also provide direct evidence for how the sample environment influences structural dynamics and the reaction rates of the PYP photocycle.

Transient photoinduced 'hidden' phase in a manganite.

Photoinduced phase transitions are of special interest in condensed matter physics because they can be used to change complex macroscopic material properties on the ultrafast timescale. Cooperative interactions between microscopic degrees of freedom greatly enhance the number and nature of accessible states, making it possible to switch electronic, magnetic or structural properties in new ways. Photons with high energies, of the order of electron volts, in particular are able to access electronic states that may differ greatly from states produced with stimuli close to equilibrium. In this study we report the photoinduced change in the lattice structure of a charge and orbitally ordered Nd(0.5)Sr(0.5)MnO(3) thin film using picosecond time-resolved X-ray diffraction. The photoinduced state is structurally ordered, homogeneous, metastable and has crystallographic parameters different from any thermodynamically accessible state. A femtosecond time-resolved spectroscopic study shows the formation of an electronic gap in this state. In addition, the threshold-like behaviour and high efficiency in photo-generation yield of this gapped state highlight the important role of cooperative interactions in the formation process. These combined observations point towards a 'hidden insulating phase' distinct from that found in the hitherto known phase diagram.

100†picosecond diffraction catches structural transients of laser-pulse triggered switching in a spin-crossover crystal.

We study by 100 picosecond X-ray diffraction the photo-switching dynamics of single crystal of the orthorhombic polymorph of the spin-crossover complex [(TPA)Fe(TCC)]PF(6), in which TPA = tris(2-pyridyl methyl)amine, TCC(2-) = 3,4,5,6-Cl(4)-Catecholate(2-). In the frame of the emerging field of dynamical structural science, this is made possible by using optical pump/X-ray probe techniques, which allow following in real time structural reorganization at intra- and intermolecular levels associated with the change of spin state in the crystal. We use here the time structure of the synchrotron radiation generating 100 picosecond X-ray pulses, coupled to 100 fs laser excitation. This study has revealed a rich variety of structural reorganizations, associated with the different steps of the dynamical process. Three consecutive regimes are evidenced in the time domain: 1) local molecular photo-switching with structural reorganization at constant volume, 2) volume relaxation with inhomogeneous distribution of local temperatures, 3) homogenization of the crystal in the transient state 100 µs after laser excitation. These findings are fundamentally different from those of conventional diffraction studies of long-lived photoinduced high spin states. The time-resolution used here with picosecond X-ray diffraction probes different physical quantities on their intrinsic time-scale, shedding new light on the successive processes driving macroscopic switching in a functionalized material. These results pave the way for structural studies away from equilibrium and represent a first step toward femtosecond crystallography.