On central focusing for contrast optimization in direct electron ptychography of thick samples.

Ptychography provides high dose efficiency images that can reveal light elements next to heavy atoms. However, despite ptychography having an otherwise single signed contrast transfer function, contrast reversals can occur when the projected potential becomes strong for both direct and iterative inversion ptychography methods. It has recently been shown that these reversals can often be counteracted in direct ptychography methods by adapting the focus. Here we provide an explanation of why the best contrast is often found with the probe focused to the middle of the sample. The phase contribution due to defocus at each sample slice above and below the central plane in this configuration effectively cancels out, which can prevent contrast reversals when dynamical scattering effects are not overly strong. In addition we show that the convergence angle can be an important consideration for removal of contrast reversals in relatively thin samples.

Enhanced intrapulse difference frequency generation in the mid-infrared by a spectrally dependent polarization state.

We present a technique to optimize the intrapulse difference frequency generation efficiency for mid-infrared generation. The approach employs a multi-order wave plate that is designed to selectively rotate the polarization state of the incoming spectral components on the relevant orthogonal axes for subsequent nonlinear interaction. We demonstrate a significant increase of the mid-infrared average power generated, of a factor ≥2.5 compared with the conventional scheme, owing to an optimally distributed number of photons enrolled in the difference frequency generation process.

Event driven 4D STEM acquisition with a Timepix3 detector: Microsecond dwell time and faster scans for high precision and low dose applications.

Four dimensional scanning transmission electron microscopy (4D STEM) records the scattering of electrons in a material in great detail. The benefits offered by 4D STEM are substantial, with the wealth of data it provides facilitating for instance high precision, high electron dose efficiency phase imaging via centre of mass or ptychography based analysis. However the requirement for a 2D image of the scattering to be recorded at each probe position has long placed a severe bottleneck on the speed at which 4D STEM can be performed. Recent advances in camera technology have greatly reduced this bottleneck, with the detection efficiency of direct electron detectors being especially well suited to the technique. However even the fastest frame driven pixelated detectors still significantly limit the scan speed which can be used in 4D STEM, making the resulting data susceptible to drift and hampering its use for low dose beam sensitive applications. Here we report the development of the use of an event driven Timepix3 direct electron camera that allows us to overcome this bottleneck and achieve 4D STEM dwell times down to 100 ns; orders of magnitude faster than what has been possible with frame based readout. We characterize the detector for different acceleration voltages and show that the method is especially well suited for low dose imaging and promises rich datasets without compromising dwell time when compared to conventional STEM imaging.

Watt-scale 50-MHz source of single-cycle waveform-stable pulses in the molecular fingerprint region.

We report a coherent mid-infrared (MIR) source with a combination of broad spectral coverage (6-18 µm), high repetition rate (50 MHz), and high average power (0.5 W). The waveform-stable pulses emerge via intrapulse difference-frequency generation (IPDFG) in a GaSe crystal, driven by a 30-W-average-power train of 32-fs pulses spectrally centered at 2 µm, delivered by a fiber-laser system. Electro-optic sampling (EOS) of the waveform-stable MIR waveforms reveals their single-cycle nature, confirming the excellent phase matching both of IPDFG and of EOS with 2-µm pulses in GaSe.

Structural determinants of the interaction between influenza A virus matrix protein M1 and lipid membranes.

Influenza A virus is a pathogen responsible for severe seasonal epidemics threatening human and animal populations every year. One of the ten major proteins encoded by the viral genome, the matrix protein M1, is abundantly produced in infected cells and plays a structural role in determining the morphology of the virus. During assembly of new viral particles, M1 is recruited to the host cell membrane where it associates with lipids and other viral proteins. The structure of M1 is only partially known. In particular, structural details of M1 interactions with the cellular plasma membrane as well as M1-protein interactions and multimerization have not been clarified, yet. In this work, we employed a set of complementary experimental and theoretical tools to tackle these issues. Using raster image correlation, surface plasmon resonance and circular dichroism spectroscopies, we quantified membrane association and oligomerization of full-length M1 and of different genetically engineered M1 constructs (i.e., N- and C-terminally truncated constructs and a mutant of the polybasic region, residues 95-105). Furthermore, we report novel information on structural changes in M1 occurring upon binding to membranes. Our experimental results are corroborated by an all-atom model of the full-length M1 protein bound to a negatively charged lipid bilayer.

Long-term implant of intramuscular sensors and nerve transfers for wireless control of robotic arms in above-elbow amputees.

Targeted muscle reinnervation (TMR) amplifies the electrical activity of nerves at the stump of amputees by redirecting them in remnant muscles above the amputation. The electrical activity of the reinnervated muscles can be used to extract natural control signals. Nonetheless, current control systems, mainly based on noninvasive muscle recordings, fail to provide accurate and reliable control over time. This is one of the major reasons for prosthetic abandonment. This prospective interventional study includes three unilateral above-elbow amputees and reports the long-term (2.5 years) implant of wireless myoelectric sensors in the reinnervation sites after TMR and their use for control of robotic arms in daily life. It therefore demonstrates the clinical viability of chronically implanted myoelectric interfaces that amplify nerve activity through TMR. The patients showed substantial functional improvements using the implanted system compared with control based on surface electrodes. The combination of TMR and chronically implanted sensors may drastically improve robotic limb replacement in above-elbow amputees.

A novel mechanotronic orthosis enables symmetrical gait kinematics in a patient with a femoral nerve palsy - a case study.

The usage of stance- and swing-phase control orthoses (SSCOs) is a good option in patients with neuromuscular insufficiency of the quadriceps muscle in a broad range of musculo-skeletal disorders. The subjective sensation of improved mobility in daily life and walking comfort could be objectively confirmed by the ability to walk without crutches and by harmonization of the gait patterns in hip and knee. They could also be a considered mobility device after limb salvage surgery, which may even have an impact on preoperative decision making. IMPLICATIONS FOR REHABILITATION Symmetric gate in spite of femoral nerve palsy. Early gate improvements even after hours. High patient?s motivation to use the device.

Use of failure-to-rescue to identify international variation in postoperative care in low-, middle- and high-income countries: a 7-day cohort study of elective surgery.

BACKGROUND: The incidence and impact of postoperative complications are poorly described. Failure-to-rescue, the rate of death following complications, is an important quality measure for perioperative care but has not been investigated across multiple health care systems. METHODS: We analysed data collected during the International Surgical Outcomes Study, an international 7-day cohort study of adults undergoing elective inpatient surgery. Hospitals were ranked by quintiles according to surgical procedural volume (Q1 lowest to Q5 highest). For each quintile we assessed in-hospital complications rates, mortality, and failure-to-rescue. We repeated this analysis ranking hospitals by risk-adjusted complication rates (Q1 lowest to Q5 highest). RESULTS: A total of 44 814 patients from 474 hospitals in 27 low-, middle-, and high-income countries were available for analysis. Of these, 7508 (17%) developed one or more postoperative complication, with 207 deaths in hospital (0.5%), giving an overall failure-to-rescue rate of 2.8%. When hospitals were ranked in quintiles by procedural volume, we identified a three-fold variation in mortality (Q1: 0.6% vs Q5: 0.2%) and a two-fold variation in failure-to-rescue (Q1: 3.6% vs Q5: 1.7%). Ranking hospitals in quintiles by risk-adjusted complication rate further confirmed the presence of important variations in failure-to-rescue, indicating differences between hospitals in the risk of death among patients after they develop complications. CONCLUSIONS: Comparison of failure-to-rescue rates across health care systems suggests the presence of preventable postoperative deaths. Using such metrics, developing nations could benefit from a data-driven approach to quality improvement, which has proved effective in high-income countries.

Enhancement cavities for few-cycle pulses.

We address the challenge of increasing the bandwidth of high-finesse femtosecond enhancement cavities and demonstrate a broad spectrum spanning 1800 cm-1 (195 nm) at -10 dB around a central wavelength of 1050 nm in an EC with an average finesse exceeding 300. This will benefit a host of spectroscopic applications, including transient absorption spectroscopy, direct frequency comb spectroscopy, and Raman spectroscopy. The pulse circulating in the EC is composed of only 5.4 optical cycles, at a kilowatt-level average power. Together with a suitable gating technique, this paves the way to the efficient generation of multi-megahertz-repetition-rate isolated extreme ultraviolet attosecond pulses via intracavity high-order harmonic generation.

Stable dispersions of azide functionalized ferromagnetic metal nanoparticles.

Ferromagnetic nanoparticles are covalently modified in order to enhance the dispersion stability as well as the antifouling properties. Insertion of an azide moiety allows "click"-reaction of a relevant tag molecule. This and the high saturation magnetization of the presented nanocomposite offer a promising platform for magnetic biosensors.

Performance of a new pulse contour method for continuous cardiac output monitoring: validation in critically ill patients.

BACKGROUND: A new calibrated pulse wave analysis method (VolumeView™/EV1000™, Edwards Lifesciences, Irvine, CA, USA) has been developed to continuously monitor cardiac output (CO). The aim of this study was to compare the performance of the VolumeView method, and of the PiCCO2™ pulse contour method (Pulsion Medical Systems, Munich, Germany), with reference transpulmonary thermodilution (TPTD) CO measurements. METHODS: This was a prospective, multicentre observational study performed in the surgical and interdisciplinary intensive care units of four tertiary hospitals. Seventy-two critically ill patients were monitored with a central venous catheter, and a thermistor-tipped femoral arterial VolumeView™ catheter connected to the EV1000™ monitor. After initial calibration by TPTD CO was continuously assessed using the VolumeView-CCO software (CCO(VolumeView)) during a 72 h period. TPTD was performed in order to obtain reference CO values (COREF). TPTD and arterial wave signals were transmitted to a PiCCO2™ monitor in order to obtain CCO(PiCCO) values. CCO(VolumeView) and CCO(PiCCO) were recorded over a 5 min interval before assessment of CO(TPTD). Bland-Altman analysis, %(errors), and concordance (trend analysis) were calculated. RESULTS: A total of 338 matched sets of data were available for comparison. Bias for CCO(VolumeView)-CO(REF) was -0.07 litre min(-1) and for CCO(PiCCO)-CO(REF) +0.03 litre min(-1). Corresponding limits of agreement were 2.00 and 2.48 litre min(-1) (P<0.01), %(errors) 29 and 37%, respectively. Trending capabilities were comparable for both techniques. CONCLUSIONS: The performance of the new VolumeView™-CCO method is as reliable as the PiCCO2™-CCO pulse wave analysis in critically ill patients. However, an improved precision was observed with the VolumeView™ technique. CLINICALTRIALS.GOV IDENTIFIER: NCT01405040.

Comparison of pregnancy characteristics and outcomes between HIV-infected and HIV-non-infected women in Brazil.

The aim of this study is to evaluate the characteristics of pregnant women whether they are HIV infected or not and their prenatal care. It is a cross-sectional study. HIV-infected women were derived from a cohort study of all HIV-infected pregnant women followed from 1995 to 2005, at the Instituto de Puericultura e Pediatria Martagão Gesteira - Rio de Janeiro. HIV-non-infected women were derived from a random sample of all pregnant women who gave birth at Rio de Janeiro municipality between 1999 and 2001. All relevant sociodemographic, clinical, and pregnancy outcomes data were retrieved from both studies. To evaluate the prenatal care, we calculated the Kotelchuck Modified Index (KMI). The index is based on the months of initiation of prenatal care and the proportion of visits observed in each trimester, according to gestational age at birth. Comparisons were performed using Student t- and chi-square tests. Variables with p-value < 0.25 were included in an unconditional logistic regression model. There were 713 HIV-infected women and 2145 HIV-non-infected women. Variables independently associated with HIV status were: inadequate KMI (OR=4.08, 95% CI=3.17-5.24); lower educational level (OR=1.32, 95% CI=1.04-1.68); does not live with a partner (OR=3.54, 95% CI=2.66-4.64); lower family income (OR=4.71, 95% CI=3.62-6.14); tobacco use (OR=2.17, 95% CI=1.63-2.88); and hypertension (OR=1.47, 95% CI=1.01-2.17). Prematurity was not independently associated with HIV status. Although in Brazil, the HIV care is free of charge, pregnant women are still having difficulty to reach the specialized care. Better access to care must be offered to this population and studies of prematurity in the HIV-infected women must evaluate their prenatal care.

[Principles of perioperative coagulation management]. / Prinzipien des perioperativen Gerinnungsmanagements.

The coagulation system is a complex network of interacting proteins and cells with extensive sensitivity, amplification and control pathways. The system represents a delicate balance between procoagulant and anticoagulant as well as profibrinolytic and antifibrinolytic activities. Clinically relevant phenotypes, e.g. bleeding and thrombosis, occur immediately when this balance is no longer in equilibrium. A correct understanding of the complex coagulation pathophysiology in the perioperative setting is essential for an effective treatment. In a bleeding patient, patient's history, clinical findings, routine and advanced laboratory coagulation testing as well as point-of-care coagulation monitoring help to reliably and readily identify the underlying coagulation disorder. Modern coagulation management is proactive, individualized, balanced and follows clearly defined algorithms. Coagulopathic bleeding can be successfully controlled with specific interventions in the coagulation system.

[Lichen sclerosus in the genitourinary region]. / Lichen sclerosus im Urogenitalbereich.

Lichen sclerosus (LS) is a chronic inflammatory disorder of the skin and mucosa, presenting to genitourinary physicians, pediatricians, and dermatologists. It affects both sexes with a lower incidence in men than in women. Autoimmune factors, infections, and genetic disposition are implicated in its pathogenesis. The classic clinical picture is of atrophic white plaques in the anogenital region. Pruritus, soreness, difficulty retracting the foreskin, and obstructive urinary symptoms are frequent complaints. Early histological confirmation by biopsy is recommended. The disorder is usually highly responsive to ultrapotent topical steroids. This may help arrest or delay the progressive nature of this disorder. Surgical treatment may be needed in cases of disease progression despite medical therapy. Circumcision is a successful treatment, if LS is limited to the glans and foreskin. In cases of meatal stenosis meatoplasty and in cases of urethral involvement one- or two-stage oral graft urethroplasty is necessary.

[Principles of perioperative coagulation management]. / Prinzipien des perioperativen Gerinnungsmanagements.

The coagulation system is a complex network of interacting proteins and cells with extensive sensitivity, amplification and control pathways. The system represents a delicate balance between procoagulant and anticoagulant as well as profibrinolytic and antifibrinolytic activities. Clinically relevant phenotypes, e.g. bleeding and thrombosis, occur immediately when this balance is no longer in equilibrium. A correct understanding of the complex coagulation pathophysiology in the perioperative setting is essential for an effective treatment. In a bleeding patient, patient's history, clinical findings, routine and advanced laboratory coagulation testing as well as point-of-care coagulation monitoring help to reliably and readily identify the underlying coagulation disorder. Modern coagulation management is proactive, individualized, balanced and follows clearly defined algorithms. Coagulopathic bleeding can be successfully controlled with specific interventions in the coagulation system.

[Male breast cancer: a challenge for urologists]. / Das Mammakarzinom beim Mann : Eine Herausforderung für den Urologen.

Male breast cancer (male BC) accounts for <1% of all cancers in men, showing an increasing incidence with a peak in the sixth decade. Overall, men experience a worse prognosis than women, probably due to an advanced stage together with the higher age at diagnosis of male patients. Major risk factors for developing male BC include clinical disorders involving hormonal imbalances (excess of estrogen or a deficiency of testosterone as seen in patients with Klinefelter syndrome) and a positive family history for breast cancer. About 90% of male BC are invasive ductal carcinomas. Standard treatment for localized cancer is surgical removal. Adjuvant radiation and systemic therapy are the same as in women with breast cancer. Male BC expresses hormone receptors in about 90% of cases; therefore, tamoxifen is a therapeutic option. A future challenge for the urologist or andrologist is to diagnose the disease at an early stage to improve prognosis.

Thrombelastography in the surgical patient.

Coagulopathy in surgical patients is an important factor in triggering major perioperative complications, i.e., intra- or postoperative bleeding and thrombo-embolic events associated with an increased mortality and morbidity. Different methods exist to assess the coagulation status of patients before, during and after surgery. Routine coagulation tests have long been considered to be the clinical standard. However, these tests have considerable limitations. Information regarding the kinetics of clot formation, clot strength, interaction of the coagulation components, platelet function and fibrinolysis is not available. Moreover, there is an important delay in obtaining test results. In contrast, thrombelastography and thrombelastometry, which both measure the visco-elastic properties of whole blood, allow the dynamic assessment of a developing clot, from fibrin formation to clot strengthening and clot lysis. Both techniques are increasingly being used in daily clinical practice in order to detect perioperative coagulopathy and to guide predominantly pro-coagulant therapy in different settings. This article provides an overview of both techniques, thrombelastography (TEG) and thrombelastometry (ROTEM), and their field of perioperative application considering of recently published data.