Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end‐stage renal disease die because they cannot ...afford renal replacement therapy—even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed‐world patient–donor pairs with immunological barriers and developing‐world patient–donor pairs with financial barriers. By making developed‐world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange—a modality equally benefitting rich and poor. We report the 1‐year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow‐up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable.
The authors propose a system of kidney exchange between developed‐world patient–donor pairs with immunological barriers and developing‐world patient–donor pairs with financial barriers in which the savings from transplantation over continued dialysis fund the cost of transplantation, donor and recipient follow‐up, and long‐term recipient immunosuppression for the developing‐world pair. See Wiseman and Gill's editorial on page 597.
The genetic architecture of schizophrenia is complex, involving risk alleles ranging from common alleles of weak effect to rare alleles of large effect, the best exemplar of the latter being large ...copy number variants (CNVs). It is currently unknown whether pathophysiology in those with defined rare mutations overlaps with that in other individuals with the disorder who do not share the same rare mutation. Under an extreme heterogeneity model, carriers of specific high-penetrance mutations form distinct subgroups. In contrast, under a polygenic threshold model, high-penetrance rare allele carriers possess many risk factors, of which the rare allele is the only one, albeit an important, factor. Under the latter model, cases with rare mutations can be expected to share some common risk alleles, and therefore pathophysiological mechanisms, with cases without the same mutation. Here we show that, compared with controls, individuals with schizophrenia who have known pathogenic CNVs carry an excess burden of common risk alleles (P=2.25 × 10(-17)) defined from a genome-wide association study largely based on individuals without known CNVs. Our finding is not consistent with an extreme heterogeneity model for CNV carriers, but does offer support for the polygenic threshold model of schizophrenia. That this is so provides support for the notion that studies aiming to model the effects of rare variation may uncover pathophysiological mechanisms of relevance to those with the disorder more widely.
Purpose
Early central venous catheter (CVC) insertion in Ebola virus disease (EVD) is a novel approach and has not previously been described. This report delineates the safety, feasibility and ...clinical implications of early CVC insertion as the optimum means of vascular access in patients with EVD, in the setting of a deployed military Ebola virus disease treatment unit in Sierra Leone.
Methods
In the gastrointestinal phase of EVD, a 7-French 20-cm triple-lumen CVC was inserted using aseptic technique. Data were collected prospectively on all cases to include baseline and subsequent blood test variables, insertion site and technique, and complications associated with CVC placement.
Results
Twenty-three patients underwent CVC insertion as follows: subclavian, 21 (88 %); internal jugular, 2 (8 %); axillary, 1 (4 %). The mean duration of CVC placement was 5 days. There were no significant procedure-related adverse events. Despite coagulopathy being present in 75 % of cases, CVC insertion was safe, and there was only 1 case of significant catheter site bleeding. A total of 152 needle venepunctures were avoided owing to the presence of a CVC, a mean of 7 (±3.8) per case over the average stay.
Conclusion
The early use of CVCs in Ebola virus disease is safe, effective and facilitates patient care. It should be considered a feasible additional route of venous access, where physician expertise and resources allow.
Summary
Here, we describe the development of a method that exploits bacteriophage D29 as a lysis agent for efficient DNA extraction from low numbers of mycobacterial cells. This method (Actiphage®) ...used in combination with PCR achieved rapid and sensitive (LOD ≤ 10 cell ml−1) detection and identification of viable, pathogenic mycobacteria in blood samples within 6 h. We demonstrate that mycobacteriophage D29 can be used to detect a range of mycobacteria from clinical blood samples including both Mycobacterium tuberculosis complex and Mycobacterium avium subsp. paratuberculosis without the need for culture and confirms our earlier observations that a low‐level bacteraemia is associated with these infections in cattle. In a study of M. bovis‐infected cattle (n = 41), the sensitivity of the Actiphage® method was 95 % (95 % CI; 0.84–0.99) and specificity was 100 % (95% CI; 0.92–1). We further used Actiphage® to demonstrate viable Mycobacterium avium subsp. paratuberculosis is present in the blood of Johne’s infected cattle. This method provides a revolutionary new tool for the study of infections caused by these difficult to grow pathogens.
Actiphage has the ability to rapidly and sensitivity detect pathogenic mycobacteria from the blood of cattle infected with bovine TB and Johne's disease.
Currently, there is no comprehensive picture of the global surveillance landscape. This survey examines the current state of surveillance systems, levels of integration, barriers and opportunities ...for the integration of surveillance systems at the country level, and the role of national public health institutes (NPHIs).
This was a cross-sectional survey of NPHIs.
A web-based survey questionnaire was disseminated to 110 NPHIs in 95 countries between July and August 2022. Data were descriptively analysed, stratified by World Health Organization region, World Bank Income Group, and self-reported Integrated Disease Surveillance (IDS) maturity status.
Sixty-five NPHIs responded. Systems exist to monitor notifiable diseases and vaccination coverage, but less so for private, pharmaceutical, and food safety sectors. While Ministries of Health usually lead surveillance, in many countries, NPHIs are also involved. Most countries report having partially developed IDS. Surveillance data are frequently inaccessible to the lead public health agency and seldomly integrated into a national public health surveillance system. Common challenges to establishing IDS include information technology system issues, financial constraints, data sharing and ownership limitations, workforce capacity gaps, and data availability.
Public health surveillance systems across the globe, although built on similar principles, are at different levels of maturity but face similar developmental challenges. Leadership, ownership and governance, supporting legal mandates and regulations, as well as adherence to mandates, and enforcement of regulations are critical components of effective surveillance. In many countries, NPHIs play a significant role in integrated disease surveillance.
Article in a tweet: Our multicountry survey found disease surveillance systems globally are at different levels of maturity but face similar challenges, for example, in leadership, governance, legal mandates, and resourcing. In many countries, NPHIs play a key role in supporting integrated disease surveillance.
Abstract
The haematogenous dissemination of Mycobacterium tuberculosis (Mtb) is critical to the pathogenesis of progressive tuberculous infections in animal models. Using a novel, phage-based blood ...assay, we report the first concordant evidence in well-characterized, immunocompetent human cohorts, demonstrating associations of Mtb bacteremia with progressive phenotypes of latent infection and active pulmonary tuberculosis.
The Swift Gamma-Ray Burst Mission Gehrels, N; Chincarini, G; Giommi, P ...
The Astrophysical journal,
08/2004, Letnik:
611, Številka:
2
Journal Article
Recenzirano
The Swift mission, scheduled for launch in 2004, is a multiwavelength observatory for gamma-ray burst (GRB) astronomy. It is a first-of-its-kind autonomous rapid-slewing satellite for transient ...astronomy and pioneers the way for future rapid-reaction and multiwavelength missions. It will be far more powerful than any previous GRB mission, observing more than 100 bursts yr super(-1) and performing detailed X-ray and UV/optical afterglow observations spanning timescales from 1 minute to several days after the burst. The objectives are to (1) determine the origin of GRBs, (2) classify GRBs and search for new types, (3) study the interaction of the ultrarelativistic outflows of GRBs with their surrounding medium, and (4) use GRBs to study the early universe out to z > 10. The mission is being developed by a NASA-led international collaboration. It will carry three instruments: a new-generation wide-field gamma-ray (15-150 keV) detector that will detect bursts, calculate 1arcmin-4arcmin positions, and trigger autonomous spacecraft slews; a narrow-field X-ray telescope that will give 5arc sec positions and perform spectroscopy in the 0.2-10 keV band; and a narrow-field UV/optical telescope that will operate in the 170-600 nm band and provide 0!!3 positions and optical finding charts. Redshift determinations will be made for most bursts. In addition to the primary GRB science, the mission will perform a hard X-ray survey to a sensitivity of approx1 mcrab (approx2 x 10 super(-11) ergs cm super(-2) s super(-1) in the 15-150 keV band), more than an order of magnitude better than HEAO 1 A-4. A flexible data and operations system will allow rapid follow-up observations of all types of high-energy transients, with rapid data downlink and uplink available through the NASA TDRSS system. Swift transient data will be rapidly distributed to the astronomical community, and all interested observers are encouraged to participate in follow- up measurements. A Guest Investigator program for the mission will provide funding for community involvement. Innovations from the Swift program applicable to the future include (1) a large-area gamma-ray detector using the new CdZnTe detectors, (2) an autonomous rapid-slewing spacecraft, (3) a multiwavelength payload combining optical, X-ray, and gamma-ray instruments, (4) an observing program coordinated with other ground-based and space-based observatories, and (5) immediate multiwavelength data flow to the community. The mission is currently funded for 2 yr of operations, and the spacecraft will have a lifetime to orbital decay of approx8 yr.
Bacteriophages D29 and TM4 are able to infect a wide range of mycobacteria, including pathogenic and non-pathogenic species. Successful phage infection of both fast- and slow-growing mycobacteria can ...be rapidly detected using the phage amplification assay. Using this method, the effect of oxygen limitation during culture of mycobacteria on the success of phage infection was studied. Both D29 and TM4 were able to infect cultures of M. smegmatis and Mycobacterium avium subspecies paratuberculosis (MAP) grown in liquid with aeration. However when cultures were grown under oxygen limiting conditions, only TM4 could productively infect the cells. Cell attachment assays showed that D29 could bind to the cells surface but did not complete the lytic cycle. The ability of D29 to productively infect the cells was rapidly recovered (within 1 day) when the cultures were returned to an aerobic environment and this recovery required de novo RNA synthesis. These results indicated that under oxygen limiting conditions the cells are entering a growth state which inhibits phage D29 replication, and this change in host cell biology which can be detected by using both phage D29 and TM4 in the phage amplification assay.
The FASTPlaqueTB assay is an established diagnostic aid for the rapid detection of Mycobacterium tuberculosis from human sputum samples. Using the FASTPlaqueTB assay reagents, viable Mycobacterium ...avium subsp. paratuberculosis cells were detected as phage plaques in just 24 h. The bacteriophage used does not infect M. avium subsp. paratuberculosis alone, so to add specificity to this assay, a PCR-based identification method was introduced to amplify M. avium subsp. paratuberculosis-specific sequences from the DNA of the mycobacterial cell detected by the phage. To give further diagnostic information, a multiplex PCR method was developed to allow simultaneous amplification of either M. avium subsp. paratuberculosis or M. tuberculosis complex-specific sequences from plaque samples. Combining the plaque PCR technique with the phage-based detection assay allowed the rapid and specific detection of viable M. avium subsp. paratuberculosis in milk samples in just 48 h.
Failure to convert computer‐identified possible kidney paired donation (KPD) exchanges into transplants has prohibited KPD from reaching its full potential. This study analyzes the progress of ...exchanges in moving from “offers” to completed transplants. Offers were divided into individual segments called 1‐way transplants in order to calculate success rates. From 2007 to 2014, the Alliance for Paired Donation performed 243 transplants, 31 in collaboration with other KPD registries and 194 independently. Sixty‐one of 194 independent transplants (31.4%) occurred via cycles, while the remaining 133 (68.6%) resulted from nonsimultaneous extended altruistic donor (NEAD) chains. Thirteen of 35 (37.1%) NEAD chains with at least three NEAD segments accounted for 68% of chain transplants (8.6 tx/chain). The “offer” and 1‐way success rates were 21.9 and 15.5%, respectively. Three reasons for failure were found that could be prospectively prevented by changes in protocol or software: positive laboratory crossmatch (28%), transplant center declined donor (17%) and pair transplanted outside APD (14%). Performing a root cause analysis on failures in moving from offer to transplant has allowed the APD to improve protocols and software. These changes have improved the success rate and the number of transplants performed per year.
This analysis of the reasons for failure to progress from computer‐generated kidney exchanges to actual transplants in a multi‐center kidney paired donation program identifies obstacles in matching incompatible donor/recipient pairs and discusses implications for a national kidney paired donation program. See related articles from Gentry and Segev on page 2539, Bray et al on page 2636, and Flechner et al on page 2712.
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