Expected resolution limits of x-ray free-electron laser single-particle imaging for realistic source and detector properties.

The unprecedented intensity of x-ray free-electron laser sources has enabled single-particle x-ray diffraction imaging (SPI) of various biological specimens in both two-dimensional projection and three dimensions (3D). The potential of studying protein dynamics in their native conditions, without crystallization or chemical staining, has encouraged researchers to aim for increasingly higher resolutions with this technique. The currently achievable resolution of SPI is limited to the sub-10 nanometer range, mainly due to background effects, such as instrumental noise and parasitic scattering from the carrier gas used for sample delivery. Recent theoretical studies have quantified the effects of x-ray pulse parameters, as well as the required number of diffraction patterns to achieve a certain resolution, in a 3D reconstruction, although the effects of detector noise and the random particle orientation in each diffraction snapshot were not taken into account. In this work, we show these shortcomings and address limitations on achievable image resolution imposed by the adaptive gain integrating pixel detector noise.

The music-related quality of life: Italian validation of MuRQoL into MUSQUAV questionnaire and preliminary data from a cohort of postlingually deafened cochlear implant users.

PURPOSE: Cochlear implant (CI) users do not receive much of the auditory information necessary for an accurate perception of music. This usually entails a dissatisfaction with the music they hear, so that their quality of life may potentially be affected. The main aim of this paper was to translate and validate into Italian an instrument to evaluate these aspects-The Music-Related Quality of Life Questionnaire (MuRQoL)-to help the work of clinicians and therapists. METHODS: The translation of the MuRQoL into "Questionario Musica e Qualità della Vita" (MUSQUAV) was done according to the international guidelines. The translated questionnaire was administered to normal hearing (NH) and CI users adults. Exploratory factor analysis, confirmatory factor analysis and known group method were used to confirm construct validity and applicability of MUSQUAV. RESULTS: We retrieved 225 results. The MUSQUAV questionnaire was acceptable according to the goodness-of-fit indices. The correlation between the items, evaluated using Cronbach's α coefficient, indicates a good internal consistency (> 0.80). The non-parametric Mann-Whitney test showed significant differences in the distinct populations tested. CONCLUSIONS: The MUSQUAV questionnaire is a valid, low-cost and rapid instrument for professional workers in the audiological field, especially useful in the assessment of the patients' perception and musical engagement.

An unusual case of death using a compacting machine.

ABSTRACT: In the large series of forensic injury, death from accidental me-chanical asphyxiation in adults is rare and is usually secondary to suffocation, aspiration, strangulation caused by entrapment of clothing in machinery (deaths at work) or asphyxiation in the course of erotic maneuvers. Compression asphyxia is a form of violent mechanical asphyxia in which the asphyxiated insult is produced by means of a compression and constriction mechanism of the thoracic cage. The authors report an unusual case of asphyxiated death from chest com-pression resulting from the action of a compacting machine, which occurred in a person who had fallen asleep in a waste bin.

Experimental 3D coherent diffractive imaging from photon-sparse random projections.

The routine atomic resolution structure determination of single particles is expected to have profound implications for probing structure-function relationships in systems ranging from energy-storage materials to biological molecules. Extremely bright ultrashort-pulse X-ray sources - X-ray free-electron lasers (XFELs) - provide X-rays that can be used to probe ensembles of nearly identical nanoscale particles. When combined with coherent diffractive imaging, these objects can be imaged; however, as the resolution of the images approaches the atomic scale, the measured data are increasingly difficult to obtain and, during an X-ray pulse, the number of photons incident on the 2D detector is much smaller than the number of pixels. This latter concern, the signal 'sparsity', materially impedes the application of the method. An experimental analog using a conventional X-ray source is demonstrated and yields signal levels comparable with those expected from single biomolecules illuminated by focused XFEL pulses. The analog experiment provides an invaluable cross check on the fidelity of the reconstructed data that is not available during XFEL experiments. Using these experimental data, it is established that a sparsity of order 1.3 × 10-3 photons per pixel per frame can be overcome, lending vital insight to the solution of the atomic resolution XFEL single-particle imaging problem by experimentally demonstrating 3D coherent diffractive imaging from photon-sparse random projections.

A versatile liquid-jet setup for the European XFEL.

The SPB/SFX instrument of the European XFEL provides unique possibilities for high-throughput serial femtosecond crystallography. This publication presents the liquid-jet sample delivery setup of this instrument. The setup is compatible with state-of-the-art gas dynamic virtual nozzle systems as well as high-viscosity extruders and provides space and flexibility for other liquid injection devices and future upgrades. The liquid jets are confined in a differentially pumped catcher assembly and can be replaced within a couple of minutes through a load-lock. A two-microscope imaging system allows visual control of the jets from two perspectives.

On the characterization of a 1 m long, ultra-precise KB-focusing mirror pair for European XFEL by means of slope measuring deflectometry.

Recently, the European X-Ray Free Electron Laser (XFEL) has successfully produced its first X-ray photon pulse trains. This unique photon source will provide up to 27 000 photon pulses per second for experiments in different fields of science. In order to accomplish this, ultra-precise mirrors of dedicated shape are used to guide and focus these photons along beamlines of up to 930 m in length from the source in the undulator section to the desired focal point at an experimental station. We will report on a Kirkpatrick-Baez-mirror pair designed to focus hard-X-rays in the energy range from 3 to 16 keV to a 100 nm scale at the SPB/SFX instrument of the European XFEL. Both mirrors are elliptical cylinder-like shaped. The figure error of these 1 m long mirrors was specified to be better than 2 nm pv in terms of the height domain; this corresponds to a slope error of about 50 nrad rms (at least a best effort finishing is requested). This is essential to provide optimal experimental conditions including preservation of brilliance and wavefront. Such large and precise optics represents a challenge for the required deterministic surface polishing technology, elastic emission machining in this case, as well as for the metrology mandatory to enable a precise characterization of the topography on the mirror aperture. Besides the slope errors, the ellipse parameters are also of particular interest. The mirrors were under inspection by means of slope measuring deflectometry at the BESSY-NOM slope measuring profiler at the Helmholtz Zentrum Berlin. The NOM measurements have shown a slope error of 100 nrad rms on a aperture length of 950 mm corresponding to a residual figure deviation ≤20 nm pv for both mirrors. Additionally we found a strong impact of the mirror support conditions on the mirror shape finally measured. We will report on the measurement concept to characterize such mirrors as well as to discuss the achieved results.

Live birth and multiple birth rates in US in vitro fertilization treatment using donor oocytes: a comparison of single-embryo transfer and double-embryo transfer.

OBJECTIVE: To compare live birth rates (LBRs) and multiple birth rates (MBRs) between elective single-embryo transfer (eSET) and double-embryo transfer (DET) in donor oocyte in vitro fertilization (IVF) treatments in both a cycle-level and clinic-level analysis. METHODS: Donor oocyte IVF treatments performed by US IVF clinics reporting to the Centers for Disease Control and Prevention in 2013-2014 were included in the analysis. Primary outcomes included LBR and MBR. Secondary outcomes included gestational age at delivery (GA) and birth weight (BW) of offspring. These outcomes were evaluated on an individual cycle level as well as on the clinic level. RESULTS: In multivariable models, LBR did not change significantly as clinics utilized eSET more frequently. MBR decreased significantly as utilization of eSET increased, from 39% MBR in clinics that utilized eSET 0-9% of the time to 7% MBR in clinics that used eSET 70% of the time (P < .0001). Mean BW and GA of IVF-conceived offspring both increased as clinics utilized eSET more frequently (2778 to 3185 g [P < .0001] and 37.5 to 38.5 weeks [P = .02] for clinics with the lowest and highest eSET utilization, respectively). CONCLUSIONS: US IVF clinics utilizing eSET with higher frequencies have clinically comparable LBRs and significantly lower MBRs than clinics with lower-frequency eSET utilization. Mean offspring BW and GA increased with higher eSET utilization, further confirming the improved safety of this practice.

Applying systems thinking to task shifting for mental health using lay providers: a review of the evidence.

OBJECTIVE: This paper seeks to review the available evidence to determine whether a systems approach is employed in the implementation and evaluation of task shifting for mental health using lay providers in low- and middle-income countries, and to highlight system-wide effects of task-shifting strategies in order to better inform efforts to strength community mental health systems. METHODS: Pubmed, CINAHL, and Cochrane Library databases were searched. Articles were screened by two independent reviewers with a third reviewer resolving discrepancies. Two stages of screens were done to ensure sensitivity. Studies were analysed using the World Health Organization's building blocks framework with the addition of a community building block, and systems thinking characteristics to determine the extent to which system-wide effects had been considered. RESULTS: Thirty studies were included. Almost all studies displayed positive findings on mental health using task shifting. One study showed no effect. No studies explicitly employed systems thinking tools, but some demonstrated systems thinking characteristics, such as exploring various stakeholder perspectives, capturing unintended consequences, and looking across sectors for system-wide impact. Twenty-five of the 30 studies captured elements other than the most directly relevant building blocks of service delivery and health workforce. CONCLUSIONS: There is a lack of systematic approaches to exploring complexity in the evaluation of task-shifting interventions. Systems thinking tools should support evidence-informed decision making for a more complete understanding of community-based systems strengthening interventions for mental health.

Review article: the aetiology of primary Budd-Chiari syndrome - differences between the West and China.

BACKGROUND: China may have the largest number of Budd-Chiari syndrome (BCS) cases in the world (at least 1914 original papers were published, and at least 20 191 BCS patients were reported). Considering the discrepancy in the clinical profiles and preferred treatment selection of primary BCS between the West and China, understanding its aetiology in these two different regions is very important. AIM: To review the data from large cohort studies and meta-analyses to illustrate the epidemiology of risk factors for BCS in the West and China. METHODS: Relevant papers were identified by major English- and Chinese-language databases, conference abstracts, and by manual search. RESULTS: Risk factors reviewed include myeloproliferative neoplasms (MPNs) and their related gene mutations, anti-phospholipid syndrome, paroxysmal nocturnal haemoglobinuria (PNH), hyperhomocysteinaemia and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T mutation, factor V Leiden (FVL) and prothrombin G20210A mutations, inherited anti-thrombin, protein C and protein S deficiencies, pregnancy and puerperium, poverty, and family history. CONCLUSIONS: We examined the differences in the aetiological distribution of BCS between the West and China. Several recommendations should be considered in Chinese BCS patients: (i) screening for hyperhomocysteinaemia and MTHFR mutation should be regularly performed; (ii) screening for MPNs, PNH, and anti-phospholipid syndrome should be selectively performed; (iii) inherited anti-thrombin, protein C, and protein S deficiencies should be actively explored; (iv) screening for FVL and prothrombin G20210A mutations may be unnecessary; and (v) the clinical significance of pregnancy and puerperium, poverty with bacterial infections and unsanitary environments, and family history as possible risk factors should never be neglected.

PO-40 - Real-life use of non-vitamin k antagonist oral anticoagulants in patients with cancer associated venous thromboembolism: data from a prospective cohort.

INTRODUCTION: Cancer associated thrombosis (CAT) has an increased risk of recurrent venous thromboembolism (VTE). Type, stage of cancer and chemotherapy (CHT) influence thromboembolic risk. The use of novel oral anticoagulants (NOACs) is controversial in patients with CAT. AIM: The aim of this study is to assess mortality, recurrent VTE and bleeding complications in patients with CAT and in patients without cancer receiving NOACs. MATERIALS AND METHODS: Consecutive patients with acute objectively confirmed VTE receiving NOACs within 1 month from diagnosis are included from September 2013 in an ongoing prospective cohort study. Characteristics of patients and outcome are reported according to the presence of CAT. Chi-squared test and Student' t-test are used. RESULTS: As for November 10(th) 2015, 472 patients were included in the study: 78 with CAT (16.5%). Lung, breast, gastrointestinal and genitourinary cancer was observed in 16%, 24%, 20% and 24% of patients with CAT, respectively. 31 patients with CAT (40%) were on CHT or radiotherapy (RT). 10 patients with CAT (13%) had at least an additional risk factor for VTE (4 had a CVC related thrombosis) and 34 (43.5%) were inpatients. Baseline characteristics of patients with and without CAT are reported in the Table. Pulmonary embolism was index VTE in 152 patients: 24.4% of patients with CAT and in 33.8% of those without cancer (p=0.10). DVT only was present in 320 patients and 78 had both DVT and PE. Among NOACs patients, 312 (66%) received initial loading dose: 61% of those with CAT and 67% without. 53 (11%) received reduced maintenance doses (10% with CAT, 11% without). As for nowadays, 272 patients had at least 3 months of follow-up, the mean follow-up being 8.6 months. 20 patients died (7.3%): 17 were cancer related deaths. Non cancer related death occurred in 1 patient with CAT (2%) and in 2 patients without (0.9%). No fatal bleedings or fatal VTE recurrences occurred. Patients recruitment and follow-up is currently ongoing aimed at assessing mortality, recurrent VTE and bleeding complications. Updated results on clinical outcomes will be presented at the congress. CONCLUSIONS: Patients with CAT receiving NOACs are treated as patients without CAT in terms of use of loading doses and maintenance treatment. Upper arm thrombosis is more frequently involved in CAT patients and proximal lower vein in patients without CAT. Non cancer related mortality was higher in CAT patients but no fatal recurrences or fatal bleedings were observed so far.

Tomography of a Cryo-immobilized Yeast Cell Using Ptychographic Coherent X-Ray Diffractive Imaging.

The structural investigation of noncrystalline, soft biological matter using x-rays is of rapidly increasing interest. Large-scale x-ray sources, such as synchrotrons and x-ray free electron lasers, are becoming ever brighter and make the study of such weakly scattering materials more feasible. Variants of coherent diffractive imaging (CDI) are particularly attractive, as the absence of an objective lens between sample and detector ensures that no x-ray photons scattered by a sample are lost in a limited-efficiency imaging system. Furthermore, the reconstructed complex image contains quantitative density information, most directly accessible through its phase, which is proportional to the projected electron density of the sample. If applied in three dimensions, CDI can thus recover the sample's electron density distribution. As the extension to three dimensions is accompanied by a considerable dose applied to the sample, cryogenic cooling is necessary to optimize the structural preservation of a unique sample in the beam. This, however, imposes considerable technical challenges on the experimental realization. Here, we show a route toward the solution of these challenges using ptychographic CDI (PCDI), a scanning variant of coherent imaging. We present an experimental demonstration of the combination of three-dimensional structure determination through PCDI with a cryogenically cooled biological sample--a budding yeast cell (Saccharomyces cerevisiae)--using hard (7.9 keV) synchrotron x-rays. This proof-of-principle demonstration in particular illustrates the potential of PCDI for highly sensitive, quantitative three-dimensional density determination of cryogenically cooled, hydrated, and unstained biological matter and paves the way to future studies of unique, nonreproducible biological cells at higher resolution.

Acute Invasive Fungal Rhinosinusitis: A Comprehensive Update of CT Findings and Design of an Effective Diagnostic Imaging Model.

BACKGROUND AND PURPOSE: Acute invasive fungal rhinosinusitis carries a high mortality rate. An easy-to-use and accurate predictive imaging model is currently lacking. We assessed the performance of various CT findings for the identification of acute invasive fungal rhinosinusitis and synthesized a simple and robust diagnostic model to serve as an easily applicable screening tool for at-risk patients. MATERIALS AND METHODS: Two blinded neuroradiologists retrospectively graded 23 prespecified imaging abnormalities in the craniofacial region on craniofacial CT examinations from 42 patients with pathology-proven acute invasive fungal rhinosinusitis and 42 control patients proved negative for acute invasive fungal rhinosinusitis from the same high-risk population. A third blinded neuroradiologist decided discrepancies. Specificity, sensitivity, positive predictive value, and negative predictive value were determined for all individual variables. The 23 variables were evaluated for intercorrelations and univariate correlations and were interrogated by using stepwise linear regression. RESULTS: Given the low predictive value of any individual variable, a 7-variable model (periantral fat, bone dehiscence, orbital invasion, septal ulceration, pterygopalatine fossa, nasolacrimal duct, and lacrimal sac) was synthesized on the basis of multivariate analysis. The presence of abnormality involving a single variable in the model has an 87% positive predictive value, 95% negative predictive value, 95% sensitivity, and 86% specificity (R(2) = 0.661). A positive outcome in any 2 of the model variables predicted acute invasive fungal rhinosinusitis with 100% specificity and 100% positive predictive value. CONCLUSIONS: Our 7-variable CT-based model provides an easily applicable and robust screening tool to triage patients at risk for acute invasive fungal rhinosinusitis into a disease-positive or -negative category with a high degree of confidence.