Terahertz All-Optical Modulation in a Silicon-Polymer Hybrid System

Although Gigahertz-scale free-carrier modulators have been previously demonstrated in silicon, intensity modulators operating at Terahertz speeds have not been reported because of silicon's weak ultrafast optical nonlinearity. We have demonstrated intensity modulation of light with light in a silicon-polymer integrated waveguide device, based on the all-optical Kerr effect - the same ultrafast effect used in four-wave mixing. Direct measurements of time-domain intensity modulation are made at speeds of 10 GHz. We showed experimentally that the ultrafast mechanism of this modulation functions at the optical frequency through spectral measurements, and that intensity modulation at frequencies in excess of 1 THz can be obtained in this device. By integrating optical polymers through evanescent coupling to high-mode-confinement silicon waveguides, we greatly increase the effective nonlinearity of the waveguide for cross-phase modulation. The combination of high mode confinement, multiple integrated optical components, and high nonlinearities produces all-optical ultrafast devices operating at continuous-wave power levels compatible with telecommunication systems. Although far from commercial radio frequency optical modulator standards in terms of extinction, these devices are a first step in development of large-scale integrated ultrafast optical logic in silicon, and are two orders of magnitude faster than previously reported silicon devices.Comment: Under consideration at Nature Material

Lymph node infarction – a rare complication associated with disseminated intra vascular coagulation in a case of dengue fever

BACKGROUND: Lymph node infarction is known to occur in association with many non-neoplastic and neoplastic conditions however its occurrence in association with DIC is not reported hitherto in the literature. CASE PRESENTATION: We describe an unusual case of lymph node infarction in a twenty seven year old male following disseminated intravascular coagulation (DIC) in a case of dengue fever. Multiple sections of the infarcted and the surrounding non-infarcted lymph nodes failed to reveal any predisposing condition. How ever the parahilar vessels showed thrombotic occlusion, which must have been responsible for the infarction. CONCLUSION: Global infarction of the lymph node may mask the underlying pathology. Any malignancy especially lymphoma may coexist or follow lymph node infarction, therefore the patient needs constant surveillance

Burden of typhoid and paratyphoid fever in India.

BACKGROUND: In 2017, more than half the cases of typhoid fever worldwide were projected to have occurred in India. In the absence of contemporary population-based data, it is unclear whether declining trends of hospitalization for typhoid in India reflect increased antibiotic treatment or a true reduction in infection. METHODS: From 2017 through 2020, we conducted weekly surveillance for acute febrile illness and measured the incidence of typhoid fever (as confirmed on blood culture) in a prospective cohort of children between the ages of 6 months and 14 years at three urban sites and one rural site in India. At an additional urban site and five rural sites, we combined blood-culture testing of hospitalized patients who had a fever with survey data regarding health care use to estimate incidence in the community. RESULTS: A total of 24,062 children who were enrolled in four cohorts contributed 46,959 child-years of observation. Among these children, 299 culture-confirmed typhoid cases were recorded, with an incidence per 100,000 child-years of 576 to 1173 cases in urban sites and 35 in rural Pune. The estimated incidence of typhoid fever from hospital surveillance ranged from 12 to 1622 cases per 100,000 child-years among children between the ages of 6 months and 14 years and from 108 to 970 cases per 100,000 person-years among those who were 15 years of age or older. Salmonella enterica serovar Paratyphi was isolated from 33 children, for an overall incidence of 68 cases per 100,000 child-years after adjustment for age. CONCLUSIONS: The incidence of typhoid fever in urban India remains high, with generally lower estimates of incidence in most rural areas. (Funded by the Bill and Melinda Gates Foundation; NSSEFI Clinical Trials Registry of India number, CTRI/2017/09/009719; ISRCTN registry number, ISRCTN72938224.)

The value of health care – a matter of discussion in Germany

BACKGROUND: Interest in assessing the value of health-care services in Germany has considerably increased since the foundation of the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG (Institute for Quality and Efficiency in Health Care). The practical application of value assessment illustrates how problematic the process can be. In all decisions made for the provision of health care, data concerning the measurable dimensions (quantity and quality of efficacy and effectiveness, validity of the results and costs) flow into a complex and not yet standardized decision-making process concerning public financing. Some of these decisions are based on data of uncertain validity, unknown reproducibility and unclear appropriateness. DISCUSSION: In this paper we describe the theoretical aspects of value from psychological and economic viewpoints and discuss national and international approaches. Methodic details and difficulties in assessing the value of health-care services are analysed. A definition of the intangible value of health-care services will be proposed which contains only three factors: the absolute risk reduction (usually a measure of efficacy), the validity of the scientific papers examined and the type of the expected effectiveness (prevention of death and disability, restitution of well-being). The intangible value describes the additional benefit when comparing two possible actions, like treatment or observation only. CONCLUSION: The description of intangible value from the viewpoint of different stakeholders is a useful measure for subsequent steps (not discussed here) – the evaluation of costs and of patient benefit. A standardised, transparent, fair and democratic evaluation is essential for the definition of a basic benefit package

High-temporal-resolution electron microscopy for imaging ultrafast electron dynamics

Ultrafast Electron Microscopy (UEM) has been demonstrated to be an effective table-top technique for imaging the temporally-evolving dynamics of matter with subparticle spatial resolution on the time scale of atomic motion. However, imaging the faster motion of electron dynamics in real time has remained beyond reach. Here, we demonstrate more than an order of magnitude (16 times) enhancement in the typical temporal resolution of UEM by generating isolated 30 fs electron pulses, accelerated at 200 keV, via the optical-gating approach, with sufficient intensity for efficiently probing the electronic dynamics of matter. Moreover, we investigate the feasibility of attosecond optical gating to generate isolated subfemtosecond electron pulses, attaining the desired temporal resolution in electron microscopy for establishing the Attomicroscopy to allow the imaging of electron motion in the act.Comment: 19 Pages, 4 Figure

Antioxidants Protect Keratinocytes against M. ulcerans Mycolactone Cytotoxicity

BACKGROUND: Mycobacterium ulcerans is the causative agent of necrotizing skin ulcerations in distinctive geographical areas. M. ulcerans produces a macrolide toxin, mycolactone, which has been identified as an important virulence factor in ulcer formation. Mycolactone is cytotoxic to fibroblasts and adipocytes in vitro and has modulating activity on immune cell functions. The effect of mycolactone on keratinocytes has not been reported previously and the mechanism of mycolactone toxicity is presently unknown. Many other macrolide substances have cytotoxic and immunosuppressive activities and mediate some of their effects via production of reactive oxygen species (ROS). We have studied the effect of mycolactone in vitro on human keratinocytes--key cells in wound healing--and tested the hypothesis that the cytotoxic effect of mycolactone is mediated by ROS. METHODOLOGY/PRINCIPAL FINDINGS: The effect of mycolactone on primary skin keratinocyte growth and cell numbers was investigated in serum free growth medium in the presence of different antioxidants. A concentration and time dependent reduction in keratinocyte cell numbers was observed after exposure to mycolactone. Several different antioxidants inhibited this effect partly. The ROS inhibiting substance deferoxamine, which acts via chelation of Fe(2+), completely prevented mycolactone mediated cytotoxicity. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that mycolactone mediated cytotoxicity can be inhibited by deferoxamine, suggesting a role of iron and ROS in mycolactone induced cytotoxicity of keratinocytes. The data provide a basis for the understanding of Buruli ulcer pathology and the development of improved therapies for this disease

Using enhanced number and brightness to measure protein oligomerization dynamics in live cells

Protein dimerization and oligomerization are essential to most cellular functions, yet measurement of the size of these oligomers in live cells, especially when their size changes over time and space, remains a challenge. A commonly used approach for studying protein aggregates in cells is number and brightness (N&B), a fluorescence microscopy method that is capable of measuring the apparent average number of molecules and their oligomerization (brightness) in each pixel from a series of fluorescence microscopy images. We have recently expanded this approach in order to allow resampling of the raw data to resolve the statistical weighting of coexisting species within each pixel. This feature makes enhanced N&B (eN&B) optimal for capturing the temporal aspects of protein oligomerization when a distribution of oligomers shifts toward a larger central size over time. In this protocol, we demonstrate the application of eN&B by quantifying receptor clustering dynamics using electron-multiplying charge-coupled device (EMCCD)-based total internal reflection microscopy (TIRF) imaging. TIRF provides a superior signal-to-noise ratio, but we also provide guidelines for implementing eN&B in confocal microscopes. For each time point, eN&B requires the acquisition of 200 frames, and it takes a few seconds up to 2 min to complete a single time point. We provide an eN&B (and standard N&B) MATLAB software package amenable to any standard confocal or TIRF microscope. The software requires a high-RAM computer (64 Gb) to run and includes a photobleaching detrending algorithm, which allows extension of the live imaging for more than an hour