Design of a suspended germanium micro-antenna for efficient fiber-chip coupling in the long-wavelength mid-infrared range.

Recent developments of photonic integrated circuits for the mid-infrared band has opened up a new field of attractive applications for group IV photonics. Grating couplers, formed as diffractive structures on the chip surface, are key components for input and output coupling in integrated photonic platforms. While near-infrared optical fibers exhibit large mode field diameters compared to the wavelength, in the long-wave regime commercially available single-mode optical fibers have mode field diameters of the order of the operating wavelength. Consequently, an efficient fiber-chip surface coupler designed for the long-wave infrared range must radiate the power propagating in the waveguide with a higher radiation strength than a conventional grating coupler in the near-infrared range. In this article, we leverage the short electrical length required for long-wave infrared couplers to design a broadband all-dielectric micro-antenna for a suspended germanium platform at 7.67 µm. The design methodology is inspired by fundamental grating coupler equations, which remain valid even when the micro-antenna has only two or three diffractive elements. A simulated coupling efficiency of ~ 40% is achieved with a 1-dB bandwidth broader than 430 nm, which is almost twice the typical fractional bandwidth of a conventional grating coupler. In addition, the proposed design is markedly tolerant to fiber tilt misalignments of ±10°. This all-dielectric micro-antenna design paves the way for efficient fiber-chip coupling in long-wavelength mid-infrared integrated platforms.

Suspended silicon waveguides for long-wave infrared wavelengths.

In this Letter, we report suspended silicon waveguides operating at a wavelength of 7.67 µm with a propagation loss of 3.1±0.3 dB/cm. To our knowledge, this is the first demonstration of low-loss silicon waveguides at such a long wavelength, with loss comparable to other platforms that use more exotic materials. The suspended Si waveguide core is supported by a sub-wavelength grating that provides lateral optical confinement while also allowing access to the buried oxide layer so that it can be wet etched using hydrofluoric acid. We also demonstrate low-loss waveguide bends and s-bends.

Suspended silicon mid-infrared waveguide devices with subwavelength grating metamaterial cladding.

We present several fundamental photonic building blocks based on suspended silicon waveguides supported by a lateral cladding comprising subwavelength grating metamaterial. We discuss the design, fabrication, and characterization of waveguide bends, multimode interference devices and Mach-Zehnder interferometers for the 3715 - 3800 nm wavelength range, demonstrated for the first time in this platform. The waveguide propagation loss of 0.82 dB/cm is reported, some of the lowest loss yet achieved in silicon waveguides for this wavelength range. These results establish a direct path to ultimately extending the operational wavelength range of silicon wire waveguides to the entire transparency window of silicon.

The TWEAK receptor Fn14 is a potential cell surface portal for targeted delivery of glioblastoma therapeutics.

UNLABELLED: Fibroblast growth factor-inducible 14 (Fn14; TNFRSF12A) is the cell surface receptor for the tumor necrosis factor (TNF) family member TNF-like weak inducer of apoptosis (TWEAK). The Fn14 gene is normally expressed at low levels in healthy tissues but expression is significantly increased after tissue injury and in many solid tumor types, including glioblastoma (GB; formerly referred to as 'GB multiforme'). GB is the most common and aggressive primary malignant brain tumor and the current standard-of-care therapeutic regimen has a relatively small impact on patient survival, primarily because glioma cells have an inherent propensity to invade into normal brain parenchyma, which invariably leads to tumor recurrence and patient death. Despite major, concerted efforts to find new treatments, a new GB therapeutic that improves survival has not been introduced since 2005. In this review article, we summarize studies indicating that (i) Fn14 gene expression is low in normal brain tissue but is upregulated in advanced brain cancers and, in particular, in GB tumors exhibiting the mesenchymal molecular subtype; (ii) Fn14 expression can be detected in glioma cells residing in both the tumor core and invasive rim regions, with the maximal levels found in the invading glioma cells located within normal brain tissue; and (iii) TWEAK: Fn14 engagement as well as Fn14 overexpression can stimulate glioma cell migration, invasion and resistance to chemotherapeutic agents in vitro. We also discuss two new therapeutic platforms that are currently in development that leverage Fn14 overexpression in GB tumors as a way to deliver cytotoxic agents to the glioma cells remaining after surgical resection while sparing normal healthy brain cells.

Sap fluxes from different parts of the rootzone modulate xylem ABA concentration during partial rootzone drying and re-wetting.

Previous studies with partial rootzone drying (PRD) irrigation demonstrated that alternating the wet and dry parts of the rootzone (PRD-Alternated) increased leaf xylem ABA concentration ([X-ABA]leaf) compared with maintaining the same wet and dry parts of the rootzone (PRD-Fixed). To determine the relative contributions of different parts of the rootzone to this ABA signal, [X-ABA]leaf of potted, split-root tomato (Solanum lycopersicum) plants was modelled by quantifying the proportional water uptake from different soil compartments, and [X-ABA]leaf responses to the entire pot soil-water content (θpot). Continuously measuring soil-moisture depletion by, or sap fluxes from, different parts of the root system revealed that water uptake rapidly declined (within hours) after withholding water from part of the rootzone, but was rapidly restored (within minutes) upon re-watering. Two hours after re-watering part of the rootzone, [X-ABA]leaf was equally well predicted according to θpot alone and by accounting for the proportional water uptake from different parts of the rootzone. Six hours after re-watering part of the rootzone, water uptake by roots in drying soil was minimal and, instead, occurred mainly from the newly irrigated part of the rootzone, thus [X-ABA]leaf was best predicted by accounting for the proportional water uptake from different parts of the rootzone. Contrary to previous results, alternating the wet and dry parts of the rootzone did not enhance [X-ABA]leaf compared with PRD-Fixed irrigation. Further work is required to establish whether altered root-to-shoot ABA signalling contributes to the improved yields of crops grown with alternate, rather than fixed, PRD.

Wavelength independent multimode interference coupler.

We propose an ultra-broadband multimode interference (MMI) coupler with a wavelength range exceeding the O, E, S, C, L and U optical communication bands. For the first time, the dispersion property of the MMI section is engineered using a subwavelength grating structure to mitigate wavelength dependence of the device. We present a 2 × 2 MMI design with a bandwidth of 450nm, an almost fivefold enhancement compared to conventional designs, maintaining insertion loss, power imbalance and MMI phase deviation below 1dB, 0.6dB and 3°, respectively. The design is performed using an in-house tool based on the 2D Fourier Eigenmode Expansion Method (F-EEM) and verified with a 3D Finite Difference Time Domain (FDTD) simulator.

Colorless directional coupler with dispersion engineered sub-wavelength structure.

Directional couplers are extensively used devices in integrated optics, but suffer from limited operational wavelength range. Here we use, for the first time, the dispersive properties of sub-wavelength gratings to achieve a fivefold enhancement in the operation bandwidth of a silicon-on-insulator directional coupler. This approach does not compromise the size or the phase response of the device. The sub-wavelength grating based directional coupler we propose covers a 100 nm bandwidth with an imbalance of ≤ 0.6 dB between its outputs, as supported by full 3D FDTD simulations.

High-performance 90° hybrid based on a silicon-on-insulator multimode interference coupler.

We propose a multimode interference coupler (MMI) design for high-index-contrast technologies based on a shallowly etched multimode region, which is, for the first time to our knowledge, directly coupled to deeply etched input and output waveguides. This reduces the phase errors associated with the high-index contrast, while still allowing for a very compact layout. Using this structure, we fabricate a 2 × 4 MMI operating as a 90° hybrid, with a footprint of only 0.65 mm × 0.53 mm, including all the structures necessary to couple light to a fiber array. We experimentally demonstrate a common mode rejection ratio better than -20 dBe and phase errors better than ±5° in a ~50 nm bandwidth.

Characterization of integrated photonic devices with minimum phase technique.

Spurious reflections can preclude the accurate experimental characterization of integrated optical devices. This is particularly important for facet reflections in high refractive index platforms such as Indium Phosphide (InP) or Silicon-on-Insulator (SOI) when no anti-reflective (AR) coating is used. In this paper we present a novel method to recover the original device characteristics from the measured power transmission in the presence of such reflections. Our approach uses minimum phase techniques to reconstruct time domain information which is filtered to remove the reflection artifacts. A criterion to assess if a certain device exhibits the minimum phase characteristics required to apply the technique is given. Simulated and experimental results for multi-mode interference couplers (MMICs) in SOI without AR coating validate the technique.

Removal of the Gibbs phenomenon and its application to fast-Fourier-transform-based mode solvers.

A simple strategy for accurately recovering discontinuous functions from their Fourier series coefficients is presented. The aim of the proposed approach, named spectrum splitting (SS), is to remove the Gibbs phenomenon by making use of signal-filtering-based concepts and some properties of the Fourier series. While the technique can be used in a vast range of situations, it is particularly suitable for being incorporated into fast-Fourier-transform-based electromagnetic mode solvers (FFT-MSs), which are known to suffer from very poor convergence rates when applied to situations where the field distributions are highly discontinuous (e.g., silicon-on-insulator photonic wires). The resultant method, SS-FFT-MS, is exhaustively tested under the assumption of a simplified one-dimensional model, clearly showing a dramatic improvement of the convergence rates with respect to the original FFT-based methods.

Leaf water relations and net gas exchange responses of salinized Carrizo citrange seedlings during drought stress and recovery.

BACKGROUND AND AIMS: Since salinity and drought stress can occur together, an assessment was made of their interacting effects on leaf water relations, osmotic adjustment and net gas exchange in seedlings of the relatively chloride-sensitive Carrizo citrange, Citrus sinensis x Poncirus trifoliata. METHODS: Plants were fertilized with nutrient solution with or without additional 100 mm NaCl (salt and no-salt treatments). After 7 d, half of the plants were drought stressed by withholding irrigation water for 10 d. Thus, there were four treatments: salinized and non-salinized plants under drought-stress or well-watered conditions. After the drought period, plants from all stressed treatments were re-watered with nutrient solution without salt for 8 d to study recovery. Leaf water relations, gas exchange parameters, chlorophyll fluorescence, proline, quaternary ammonium compounds and leaf and root concentrations of Cl(-) and Na(+) were measured. KEY RESULTS: Salinity increased leaf Cl(-) and Na(+) concentrations and decreased osmotic potential (Psi(pi)) such that leaf relative water content (RWC) was maintained during drought stress. However, in non-salinized drought-stressed plants, osmotic adjustment did not occur and RWC decreased. The salinity-induced osmotic adjustment was not related to any accumulation of proline, quaternary ammonium compounds or soluble sugars. Net CO(2) assimilation rate (A(CO2)) was reduced in leaves from all stressed treatments but the mechanisms were different. In non-salinized drought-stressed plants, lower A(CO2) was related to low RWC, whereas in salinized plants decreased A(CO2) was related to high levels of leaf Cl(-) and Na(+). A(CO2) recovered after irrigation in all the treatments except in previously salinized drought-stressed leaves which had lower RWC and less chlorophyll but maintained high levels of Cl(-), Na(+) and quaternary ammonium compounds after recovery. High leaf levels of Cl(-) and Na(+) after recovery apparently came from the roots. CONCLUSIONS: Plants preconditioned by salinity stress maintained a better leaf water status during drought stress due to osmotic adjustment and the accumulation of Cl(-) and Na(+). However, high levels of salt ions impeded recovery of leaf water status and photosynthesis after re-irrigation with non-saline water.

Medical examiner samples: a source for dengue surveillance

Post-mortem medical examiner samples may be useful for sentinel surveillance of disorders usually detected by antibody determinations on specimens from ill patients or from surveys. We found anti-dengue IgM positivity in 3(23/780) and anti-dengue IgG positivity in 77(597/777) of sera obtained at the Puerto Rico medical examiner (Institute of Forensic Sciences) in December 2000, April 2001, and October 2001. This approach may be a useful alternative for estimating the population prevalence of serologic markers for dengue and other infectious diseases.

Leptospirosis among patients presenting with dengue-like illness in Puerto Rico.

Leptospirosis is difficult to distinguish from dengue fever without laboratory confirmation. Sporadic cases/clusters of leptospirosis occur in Puerto Rico, but surveillance is passive and laboratory confirmation is rare. We tested for leptospirosis using an IgM ELISA on sera testing negative for dengue virus IgM antibody and conducted a case-control study assessing risk factors for leptospirosis, comparing clinical/laboratory findings between leptospirosis (case-patients) and dengue patients (controls). Among 730 dengue-negative sera, 36 (5%) were positive for leptospirosis. We performed post mortem testing for leptospirosis on 12 available specimens from suspected dengue-related fatalities; 10 (83%) tested positive. Among these 10 fatal cases, pulmonary hemorrhage and renal failure were the most common causes of death. We enrolled 42 case-patients and 84 controls. Jaundice, elevated BUN, hyperbilirubinemia, anemia, and leukocytosis were associated with leptospirosis (p < .01 for all). Male sex, walking in puddles, rural habitation, and owning horses were independently associated with leptospirosis. Epidemiological, clinical, and laboratory criteria may help distinguish leptospirosis from dengue and identify patients who would benefit from early antibiotic treatment.

La real Expedición filantrópica de la Vacuna de viruela: monarquía y modernidad en 1803 / The real philanthropic expedition of the smallpox vaccine: monarchy and modernity in 1803

Smallpox resulted in the death of 30 % of those who acquired it, so the preventive method discovered by Edward Jenner (London, 1798) spread very quickly. At the request in 1803 of Carlos IV, king of Spain, his government evaluated offers to carry smallpox vaccine to the colonies. The selected proposal, by doctor Francisco Xavier de Balmis, sought to take the lymph to America and Asia in a chain of arm to arm vaccination of foundlings. The Expedition set sail from Corunna on November 30, 1803, stopped in the Canary Isles, Puerto Rico, and Venezuela and after Caracas (1804) split in two groups. Balmis led some members of the Expedition to Cuba and Mexico. For the trip to the Philippines, in 1805, parents lent their children in exchange for economic compensation and the promise that the boys would be returned home. The Expedition returned to Mexico in August, 1807, but Balmis separately took vaccine to China and returned to Spain. Another contingent of the Expedition, under vice-director José Salvany, took vaccine to what we know as Colombia, Ecuador, Peru and Bolivia. His assistant Manuel Grajales reached the Chilean Patagonia in 1811. This article also comments on three principal themes - the institutional management of the scientific project, the conflicts that characterized its course, and the children's experience. The Vaccine Expedition was a brave and humanitarian endeavor, but also an extraordinary sanitary and administrative success. It was not until the twentieth century that a global eradication campaign eliminated smallpox in the world.

Consultant supported intermediate care--a model for remote and island hospitals.

INTRODUCTION: Providing local consultant-delivered hospital services in remote and island communities in the United Kingdom is increasingly problematic due to difficulties with recruitment and retention of staff, statutory restrictions to hours worked by health professionals and the expectation each clinician must manage an externally defined volume of cases to maintain clinical standards. This article describes a before-and-after evaluation of a novel method of providing consultant support for acute internal medicine to an island grouping off the Scottish coast. Under the scheme, local GPs provided acute medical care of inpatients. A consultant general physician was appointed in a district general hospital on the mainland, approximately 100 miles from the island group, to provide a lead clinician role for inpatient services at the island hospital, visiting the island on a twice-monthly basis, undertaking educational sessions and developing local guidelines and care pathways for the management of individual medical conditions. In addition, two junior doctors were appointed to the island hospital to support inpatient care. METHODS: A prospective recording system for case mix was established with agreed evidence-based protocols, developed as integrated care pathways (ICP), for indicator conditions. General case mix was determined during two 6-month periods, June-November 2001 and June-November 2002, before and after implementation of the new arrangements. Performance against an ICP for management of suspected cardiac chest pain was evaluated in detail, examining the process of management, clinical outcome and economics. Data from the clinical literature were used to estimate the potential health gains from observed changes in clinical practice. RESULTS: Total admissions rose by 25% in the second time period, with particular increases noted for cardiovascular, cerebrovascular disease, and cancer. Total air ambulance transfers between the islands and the mainland within these time periods increased by 31%, from 88 to 115 transfers. Recording specific details from the history and frequency of appropriate blood investigations increased and initial steps in management changed considerably after introduction of the ICP. The number of transfers to the mainland teaching hospital increased from 3/37 (8%) in 2001 to 15/56 (27%) in 2002. Based on an estimated 100 patients per year, of whom 15 would receive thrombolysis, total additional patient costs would be 64,000 pounds sterling. The annual cost of the additional resource input into the medical service was 148,000 pounds sterling. Approximately 16 adverse events would be avoided at a combined cost of 212,000 pounds sterling (148,000 pounds sterling direct costs of intervention + 64,000 pounds sterling additional treatment costs) or 13,250 pounds sterling per event avoided. This is a conservative estimate of benefit as all the direct costs of the intervention have been included. CONCLUSIONS: This study shows that appropriate standards of care can be delivered in the setting described. Costs of care increased, but the level of service provided increased concomitantly, and the health benefits were achieved at costs that compare favourably with other interventions recommended by health technology assessment groups. An estimate of notional costs involved in alternative models for the delivery of hospital medical services in a remote area suggests that costs would be similar for a three-consultant service, the present model, and a triage and transfer system. In the future, the models chosen by remote and island communities and healthcare providers are therefore likely to be determined by viability, sustainability and public acceptability rather than cost. Our study indicates that consultant supported intermediate care is a viable model.

Developing a scoring system to quality assess economic evaluations.

The number of economic evaluations is constantly increasing. The need to establish a framework with which to assess the validity of the studies has led to the development of checklists and scoring systems to compare the quality of different studies and ensure that decisions made by decision makers and researchers are based on solid evidence. The most prominent of these checklists is that produced by Drummond et al. Their checklist aims to answer two important questions: is the methodology employed in the study appropriate and are the results valid? In this paper three methods using the checklist of Drummond et al. are developed to assess the quality of a random sample of 50 papers selected from the NHS Economic Evaluation Database. Method 1, a direct application of the checklist calculates an average score with each of the ten items weighted equally, this method proves to be good at identifying low quality studies but is a rather a blunt tool for differentiating between high-quality studies. Method 2, also using an additive score, introduces a hierarchy of the effectiveness data and also adds a new item with respect to the transferability of the results. With this method the number of papers scoring top marks decreases dramatically in comparison to method 1. Method 3 involves a multiplicative rather than additive scoring system, which is better at distinguishing between good quality studies but appears to reduce discrimination between poor-quality studies. Overall, the ten-point checklist of Drummond et al. is a useful and quick tool with which to assess the quality of economic evaluations and to enable decision makers and researchers to focus upon the most relevant studies.

The dengue and dengue hemorrhagic fever epidemic in Puerto Rico, 1994-1995.

From June 1, 1994 to May 31, 1995 a total of 24,700 cases of dengue (7.01/1,000 population) were reported to the laboratory-based surveillance system in Puerto Rico (1991-1994, annual average: 2.55/1,000). Dengue virus 2 predominated. The earliest indicator of epidemic activity was the virus isolation rate in May 1994 (14.0% versus 5.7% average). The male-to-female ratio among cases was 1:1.1; 65.4% were younger than 30 years (the 10 to 19 year age group had the highest incidence, 11.8/1,000). At least 5,687 cases (23.0%) showed a hemorrhagic manifestation; 4,662 (18.9%) were hospitalized, and 40 died (0.2%; 10 laboratory-positive). Two cases documented by laboratory were transmitted by unusual routes--intrapartum and through a bone marrow transplant. Among 2,004 hospitalized cases reported by infection control nurses, 139 (6.9%) fulfilled the criteria for dengue hemorrhagic fever (DHF) and another 13 cases (0.6%) had dengue shock syndrome. This epidemic produced the largest number of hospitalizations, DHF cases, and deaths from any dengue epidemic in Puerto Rico. Severity did not change throughout the year. Surveillance capabilities were maintained by temporary, simplified reporting methods, none of which could be recommended as the single method of choice for surveillance; each must be used (on site, or as a service available from a reference laboratory) at the right time in the epidemic cycle. The utility of comparisons of current and previous data underscores the value of long-term surveillance. Our analysis was unable to document whether significantly increased transmission occurred more often in cities where the water supply was rationed or where the local landfill was closed.

Dengue activity in Puerto Rico during an interepidemic period (1995-1997).

From 1995 to 1997 dengue was reported in Puerto Rico at an average annual rate of 1.75/1,000 population, compared to 6.73 in 1994, an epidemic year. Dengue virus serotypes 1 (DEN-1), -2, and -4 were isolated each year, with DEN-2 predominating in 1995 and 1996, and DEN-4 in 1997. From 1995 through 1997 incidence was highest (0.61-0.77/1,000) in persons under 30 years of age; males and females were equally affected. Among positive cases, 28.3% to 37.9% were hospitalized; 28.9% to 35.2% had hemorrhagic manifestations; at least 1.1% to 1.6% fulfilled the criteria for dengue hemorrhagic fever/dengue shock syndrome; and 0.2% to 0.3% died. Neither hurricane preparations (1995) nor widespread floods (1996) seem to have affected dengue incidence. Most municipalities with the highest laboratory-diagnosed dengue rates in 1995 were in the eastern foothills of the central mountains, an area relatively spared by the 1994 epidemic. In the next two years, at least half of the municipalities with the highest laboratory-diagnosed dengue rates were in the west. The most intense municipal outbreak of this period (DEN-2, Villalba, 1995, rate of 11.67/1,000) is described to highlight the importance of local conditions and epidemiologic history in determining the risk of dengue.

[Bailey K. Ashford, more in his remembrance]. / Bailey K. Ashford, más allá de sus memorias.

The military physician Bailey K. Ashford (Washington, D. C., September 18, 1873--San Juan, Puerto Rico, November 1, 1934) is mostly remembered for having identified in 1899 the cause of fatal anemia prevalent among Puertorican peasants, but he was also a distinguished investigator of other diseases, and organizer of mass medical services, in peace and in war. In spite of Ashford's own sober statements, the great influence of his scientific work in Puerto Rico and the impact of his personality in patients and colleagues have helped cast him as a mythical figure. His personal archives (kept at the library of the University of Puerto Rico's Medical Sciences Campus) make clear that his autobiography presents only a selection among the episodes that would form a complete biography.