Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-α/β

To understand how virulent mycobacteria subvert host immunity and establish disease, we examined the differential response of mice to infection with various human outbreak Mycobacterium tuberculosis clinical isolates. One clinical isolate, HN878, was found to be hypervirulent, as demonstrated by unusually early death of infected immune-competent mice, compared with infection with other clinical isolates. The differential effect on survival required lymphocyte function because severe combined immunodeficiency (SCID) mice infected with HN878 or other clinical isolates all died at the same rate. The hypervirulence of HN878 was associated with failure to induce M. tuberculosis-specific proliferation and IFN-γ production by spleen and lymph node cells from infected mice. In addition, 2- to 4-fold lower levels of tumor necrosis factor-α (TNF-α), IL-6, IL-12, and IFN-γ mRNAs were observed in lungs of HN878-infected mice. IL-10, IL-4, and IL-5 mRNA levels were not significantly elevated in lungs of HN878 infected mice. In contrast, IFN-α mRNA levels were significantly higher in lungs of these mice. To further investigate the role of Type 1 IFNs, mice infected with HN878 were treated intranasally with purified IFN-α/β. The treatment resulted in increased lung bacillary loads and even further reduced survival. These results suggest that the hypervirulence of HN878 may be due to failure of this strain to stimulate Th1 type immunity. In addition, the lack of development of Th1 immunity in response to HN878 appears to be associated with increased induction of Type 1 IFNs.

The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing.

In late 1994 and early 1995, Ebola (EBO) virus dramatically reemerged in Africa, causing human disease in the Ivory Coast and Zaire. Analysis of the entire glycoprotein genes of these viruses and those of other EBO virus subtypes has shown that the virion glycoprotein (130 kDa) is encoded in two reading frames, which are linked by transcriptional editing. This editing results in the addition of an extra nontemplated adenosine within a run of seven adenosines near the middle of the coding region. The primary gene product is a smaller (50-70 kDa), nonstructural, secreted glycoprotein, which is produced in large amounts and has an unknown function. Phylogenetic analysis indicates that EBO virus subtypes are genetically diverse and that the recent Ivory Coast isolate represents a new (fourth) subtype of EBO virus. In contrast, the EBO virus isolate from the 1995 outbreak in Kikwit, Zaire, is virtually identical to the virus that caused a similar epidemic in Yambuku, Zaire, almost 20 years earlier. This genetic stability may indicate that EBO viruses have coevolved with their natural reservoirs and do not change appreciably in the wild.

Financial fragility, trade credit and contagion effects during the crisis: a spatial econometric approach to firm-level data

The number of distressed manufacturing firms increased sharply during recessionary phase 2009-13. Financial indebtness traditionally plays a key role in assessing firm solvency but contagion effects that originate from the supply chain are usually neglected in literature. Firm interconnections, captured via the trade credit channel, represent a primary vehicle of individual shocks’ propagation, especially during an economic downturn, when liquidity tensions arise. A representative sample of 11,920 Italian manufacturing firms is considered to model a two-step econometric design, where chain reactions in terms of trade credit accumulation (i.e. default of payments to suppliers) are primarily analyzed by resorting to a spatial autoregressive approach (SAR). Spatial interactions are modeled based on a unique dataset of firm-to-firm transactions registered before the outbreak of the crisis. The second step in instead a binary outcome model where trade credit chains are considered together with data on the bank-firm relationship to assess determinants of distress likelihoods in 2009-13. Results show that outstanding trade debt is affected by the liquidity position of a firm and by positive spatial effects. Trade credit chain reactions are found to exert, in turn, a positive impact on distress likelihoods during the crisis. The latter effect is comparable in magnitude to the one exerted by individual financial rigidity, and stresses the importance to include complex interactions between firms in the analysis of the solvency behavior.

On the time to reach a critical number of infections in epidemic models with infective and susceptible immigrants.

In this paper we examine the time T to reach a critical number K0 of infections during an outbreak in an epidemic model with infective and susceptible immigrants. The underlying process X, which was first introduced by Ridler-Rowe (1967), is related to recurrent diseases and it appears to be analytically intractable. We present an approximating model inspired from the use of extreme values, and we derive formulae for the Laplace-Stieltjes transform of T and its moments, which are evaluated by using an iterative procedure. Numerical examples are presented to illustrate the effects of the contact and removal rates on the expected values of T and the threshold K0, when the initial time instant corresponds to an invasion time. We also study the exact reproduction number Rexact,0 and the population transmission number Rp, which are random versions of the basic reproduction number R0.

Numerical modeling of electromagnetic coupling phenomena in the vicinities of overhead power transmission lines.

Electromagnetic coupling phenomena between overhead power transmission lines and other nearby structures are inevitable, especially in densely populated areas. The undesired effects resulting from this proximity are manifold and range from the establishment of hazardous potentials to the outbreak of alternate current corrosion phenomena. The study of this class of problems is necessary for ensuring security in the vicinities of the interaction zone and also to preserve the integrity of the equipment and of the devices there present. However, the complete modeling of this type of application requires the three- -dimensional representation of the region of interest and needs specific numerical methods for field computation. In this work, the modeling of problems arising from the flow of electrical currents in the ground (the so-called conductive coupling) will be addressed with the finite element method. Those resulting from the time variation of the electromagnetic fields (the so-called inductive coupling) will be considered as well, and they will be treated with the generalized PEEC (Partial Element Equivalent Circuit) method. More specifically, a special boundary condition on the electric potential is proposed for truncating the computational domain in the finite element analysis of conductive coupling problems, and a complete PEEC formulation for modeling inductive coupling problems is presented. Test configurations of increasing complexities are considered for validating the foregoing approaches. These works aim to provide a contribution to the modeling of this class of problems, which tend to become common with the expansion of power grids.

Antecedentes históricos de la nutrición comunitaria en España: los trabajos de la Escuela Nacional de Sanidad, 1930-36

El trabajo analiza los antecedentes históricos de la nutrición comunitaria española a través del estudio de los primeros intentos de institucionalización que tuvieron lugar en la Sección de Higiene de la Alimentación y Nutrición de la Escuela Nacional de Sanidad (ENS), limitando la búsqueda al período 1930-1936. Junto a la formación de los profesionales de la salud pública en las materias relacionadas con la nutrición y la alimentación se desarrolló un programa de investigación que contemplaba tres grandes áreas de trabajo. Para poder conocer cuál era la alimentación media habitual de los españoles y orientar las medidas preventivas encaminadas a conseguir una adecuada alimentación se llevaron a cabo estudios y encuestas sobre consumo. Se estudió la composición química de los alimentos españoles, con el objeto de determinar las posibles carencias. Por último, se analizaron los problemas de salud que acarreaba una alimentación deficiente en grupos de riesgo como las personas diabéticas. Los resultados de las investigaciones pusieron de manifiesto que la alimentación media de los españoles, especialmente la de las clases trabajadoras, estaba muy lejos de poder ser considerada equilibrada desde el punto de vista nutricional. Los mayores problemas residían en un déficit de proteínas animales, así como importantes deficiencias en aportes de minerales y vitaminas. El estallido de la guerra civil en julio de 1936 interrumpió el desarrollo del proceso de institucionalización. Sólo en la década de 1960, tras el paréntesis del primer franquismo, se recuperó el interés sanitario por los problemas de la alimentación.

El año de la primera campaña de vacunación oral contra la poliomielitis según la prensa de Santander (1963)

La poliomielitis emergió como una devastadora epidemia en los países desarrollados durante la primera mitad del siglo XX. Los hallazgos de una vacuna inactivada por Salk (1955) y otra atenuada por Sabin (1957) ofrecieron una solución para eliminarla, coincidiendo con el periodo de mayor incidencia de la enfermedad en España (1950-1963). La respuesta de las autoridades sanitarias españolas no se concretó hasta el año de 1963, cuando el Ministerio de Fomento organizó una campaña nacional de inmunización con vacuna inactivada. Estudios epidemiológicos realizados por investigadores de la Escuela Nacional de Sanidad llevaron al convencimiento de utilizar la vacuna atenuada y a un cambio de estrategia que originó en otoño del mismo año una nueva campaña nacional a cargo del Ministerio de la Gobernación. Este estudio de caso analiza la difusión mediática de ambas campañas en Santander, mediante una revisión de las noticias de prensa publicadas en 2 diarios de ámbito provincial.

Un médico rural contra la viruela, la epidemia de 1891-92 en Huércanos (Logroño)

La práctica inconstante de la vacunación contra la viruela durante el siglo xix tuvo como consecuencia la aparición de varias oleadas epidémicas en España. La baja aceptación de la vacuna entre la población, unida a la incapacidad del estado para organizar campañas y suministrar vacuna, contribuyeron a perpetuar la enfermedad. Durante la segunda mitad del siglo se abrió un debate sobre la necesidad de hacer obligatoria la vacunación y revacunación, incorporándose, además, el uso de la vacuna animalizada. Un texto de Emilio Casas Arriola, médico de Huércanos (Logroño), describe el brote epidémico sufrido entre 1891 y 1892 en este municipio. La obra tiene la estructura de una topografía médica y fue redactada con la intención de concurrir a un premio de la Real Academia Médica de Madrid. Se analizan las dificultades, vicisitudes y medidas adoptadas para afrontar la epidemia en un entorno aislado y rural.

Annotated almanac, 1756

Almanac containing two laid-in leaves and calendar pages with sporadic annotations of measurements, on the May page an annotation listing towns where Winthrop lodged. The first laid-in leaf has a short entry with structural measurements relating to an inclination of Old Stoughton College (January 21), and the second laid-in leaf has entries including notes on deaths in the community, the weather, an outbreak of dysentery (September 4), and the raising of a new Cambridge meeting house (November 12-17).

Annotated almanac, 1759

Almanac containing a laid-in leaf and calendar pages with sporadic annotations of measurements, a note of the printer's markings on Winthrop and his wife's watches (January). The laid-in leaf includes personal entries about a measles outbreak (January), the death of his "negro man George" (May 13), the presence of bears in the area (September), the surrender of Quebec (October 16), the heights of Winthrop's son Jemmy and a "new negro boy" named Scipio, and deaths in the community including the burial and baptism statistics for Boston.

Annotated almanac, 1759

Almanac with three notations scattered among the calendar pages and one laid-in leaf containing entries about the weather, a list of deaths in the community arranged by date and containing names, age, and cause, a measles outbreak (January 5), an earthquake (February 2), and a bill of mortality for the first parish of Cambridge. Most entries appear to be in the hand of Hannah Winthrop; part of the list of deaths in the community and the bill of mortality appear to be in John Winthrop's hand.

Interleaved almanac, 1744

The 1744 diary is interleaved in Poor Richard's An almanack for the year of Christ 1744. The thin paper-covered book holds brief notes about Holyoke’s daily life as an undergraduate at Harvard, written on blank pages bound with the almanac. The entries focus on Holyoke’s life as a college student with mention of his professors and daily events. The months of May, July, October, November, and December have no entries. The diary records the outbreak of King George's War: "War with France Proclamed [sic]" (June 2), as well as his new hobby of painting.

Letter from David Phips to Colonel Jonathan Snelling regarding escort of Governor Hutchinson to Harvard Commencement, 1773 July 12

David Phips wrote this letter to Colonel Jonathan Snelling from Cambridge on July 12, 1773, to inform him that Massachusetts Governor Thomas Hutchinson had requested the accompaniment of guards during his travels from Milton to Cambridge on July 21, 1773, to attend the Harvard College Commencement exercises. In the letter, Phips informs Snelling that he has issued warrants to the guards, instructing them to congregate at the Sign of the Grey Hound in Roxbury, Massachusetts at eight o'clock on the morning of the 21st. He explains that twelve other men will march, under the command of Sub-Brigadier Sumner, to the Governor's home in Milton to escort him to Roxbury, where the larger party will assemble. These heightened security measures were certainly prompted by political unrest, although this is not stated explicitly in the letter. Phips concludes by saying: "I shall order a dinner for us at Bradish's, where I hope to have the pleasure to dine with you."

Restrictions on Aliens in the United Kingdom, 1914-1919 : a Study of the Origins and Political Background of the Aliens Restrictions Acts of 1914 and 1919.

At first glance the Aliens Restriction Act of 1914, which was introduced and passed on the first day of World War One, seems a hasty and ill-prepared piece of legislation. Actually, when examined in the light of Arthur Marwick's thesis that war is a forcing house for pre-existent social and governmental ideas, it becomes clear that the act was not after all the product of hastily formed notions. In point of fact it followed the precedent of detailed draft clauses produced in 1911 by a sub-committee of the Committee of Imperial Defence established to consider the treatment of aliens in the event of war. Indeed the draft clauses and the restrictions embodied in the 1914 act were strikingly similar to restrictions on aliens legislated in 1793. Hostility to aliens had been growing from 1905 to 1914 and this hostility blossomed into xeno-phobia on the outbreak of war, a crucial precondition for the specifically anti-enemy fears of the time. In 1919 the Aliens Restriction (Amendment) Bill was introduced into parliament to extend temporarily the provisions of the 1914 act thus permitting the Home Secretary to plan permanent, detailed legislation. Two minority groups of MPs with extreme views on the treatment of aliens were prominent in the debates on this bill. The extreme Liberal group which advocated leniency in the treatment of aliens had little effect on the final form of the bill, but the extreme Conservative group, which demanded severe restrictions on aliens, succeeded in persuading the government to include detailed restrictions. Despite its allegedly temporary nature, the Aliens Restriction (Amendment) Act of 1919 was renewed annually until 1971.

Infeções associadas aos cuidados de saúde e surtos infeciosos em unidades de cuidados intensivos neonatais e protocolos de seguimento

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014