Evidence-based diagnosis

Making an accurate diagnosis is essential to ensure that a patient receives appropriate treatment and correct information regarding their prognosis. Characteristics of diagnostic tests are quantified in test accuracy studies, but many such studies have methodological flaws. The HSRC evidence-based diagnosis programme has focused on methods for systematic reviews of test accuracy studies, and the wider context in which tests are ordered and interpreted. We carried out a range of projects relating to literature searching, quality assessment, meta-analysis, presentation of results, and interactions between doctors and patients during the diagnostic process. We have shown that systematic reviews of test accuracy studies should search a range of databases and that current diagnostic filters do not have sufficient accuracy to be used in test accuracy reviews. Summary quality scores should not be used in test accuracy reviews; the Quality Assessment of Studies of Diagnostic Accuracy included in Systematic Reviews (QUADAS) tool for assessing test accuracy studies is acceptable for quality assessment. We have shown that the hierarchical summary receiver operating characteristic (HSROC) and bivariate models for meta-analysis of test accuracy are statistically equivalent in many circumstances, and have developed an add-on module for the statistical software package Stata that enables these statistically rigorous models to be fitted by those without expert statistical knowledge. Three areas that would benefit from further research are literature searching, synthesis of results from individual patient data and presentation of results.

One-year outcomes of repeated adjunctive photodynamic therapy during periodontal maintenance: a proof-of-principle randomized-controlled clinical trial

BACKGROUND: Single photodynamic therapy (PDT) has been effective in initial periodontal therapy, but only improved bleeding on probing (BoP) in maintenance patients after a single use. Repeated PDT has not been addressed. OBJECTIVES: To study the possible added benefits of repeated adjunctive PDT to conventional treatment of residual pockets in patients enrolled in periodontal maintenance. MATERIAL AND METHODS: Ten maintenance patients with 70 residual pockets [probing pocket depth (PPD)>or=5 mm] were randomly assigned for treatment five times in 2 weeks (Days 0, 1, 2, 7, 14) with PDT (test) or non-activated laser (control) following debridement. The primary outcome variable was PPD, and the secondary variables were clinical attachment level (CAL) and BoP. These were assessed at 3, 6 and 12 months following the interventions. RESULTS: Greater PPD reductions were observed in the test (-0.67 +/- 0.34; p=0.01) compared with the control patients (-0.04 +/- 0.33; NS) after 6 months. Significant CAL gain (+0.52 +/- 0.31; p=0.01) was noted for the test, but not in the control (-0.27 +/- 0.52; NS) patients after 6 months. BoP percentages decreased significantly in test (97-64%, 67%, 77%), but not control patients after 3, 6 and 12 months. CONCLUSIONS: Repeated (five times) PDT adjunctive to debridement yielded improved clinical outcomes in residual pockets in maintenance patients. The effects were best documented after 6 months.

Building silent compartments at the nuclear periphery: a recurrent theme.

In eukaryotes, the genetic material is stored in the nucleus, which is enclosed in a double lipid bilayer, the nuclear envelope (NE). It protects the genome from physical stress and separates it from the rest of the cell. On top of this physical function, growing evidence shows that the nuclear periphery contributes to the 3D organization of the genome. In turn, tridimensional organization of chromatin in the nuclear space influences genome expression. Here we review recent findings on the function of this physical barrier in gene repression and latest models on how silent subnuclear compartments at the NE are built in yeast as well as in the nematode C. elegans and mammalian cells; trying to draw parallels between the three systems.

Magnitude and frequency: challenges for the assessment of vulnerability to geomorphic hazards

In natural hazard research, risk is defined as a function of (1) the probability of occurrence of a hazardous process, and (2) the assessment of the related extent of damage, defined by the value of elements at risk exposed and their physical vulnerability. Until now, various works have been undertaken to determine vulnerability values for objects exposed to geomorphic hazards such as mountain torrents. Yet, many studies only provide rough estimates for vulnerability values based on proxies for process intensities. However, the deduced vulnerability functions proposed in the literature show a wide range, in particular with respect to medium and high process magnitudes. In our study, we compare vulnerability functions for torrent processes derived from studies in test sites located in the Austrian Alps and in Taiwan. Based on this comparison we expose needs for future research in order to enhance mountain hazard risk management with a particular focus on the question of vulnerability on a catchment scale.

Hemodynamics and Flow Characteristics of a New Dialysis Port

Renal replacement therapy by hemodialysis requires a permanent vascular access. Implantable ports offer a potential alternative to standard vascular access strategies although their development is limited both in number and extent. We explored the fluid dynamics within two new percutaneous bone-anchored dialysis port prototypes, both by in vitro experiments and computer simulation. The new port is to be fixed to bone and allows the connection of a dialysis machine to a central venous catheter via a built-in valve. We found that the pressure drop induced by the two ports was between 20 and 50 mmHg at 500 ml/min, which is comparable with commercial catheter connectors (15–80 mmHg). We observed the formation of vortices in both geometries, and a shear rate in the physiological range (<10,000s-1), which is lower than maximal shear rates reported in commercial catheters (up to 13,000s-1). A difference in surface shear rate of 15% between the two ports was obtained.

Quantitative morphometric analysis of lakes using GIS: rectangularity R , ellipticity E , orientation O , and the rectangularity vs. ellipticity index, REi

Quantitative measures of polygon shapes and orientation are important elements of geospatial analysis. These kinds of measures are particularly valuable in the case of lakes, where shape and orientation patterns can help identifying the geomorphological agents behind lake formation and evolution. However, the lack of built-in tools in commercial geographic information system (GIS) software packages designed for this kind of analysis has meant that many researchers often must rely on tools and workarounds that are not always accurate. Here, an easy-to-use method to measure rectangularity R, ellipticity E, and orientation O is developed. In addition, a new rectangularity vs. ellipticity index, REi, is defined. Following a step-by-step process, it is shown how these measures and index can be easily calculated using a combination of GIS built-in functions. The identification of shapes and estimation of orientations performed by this method is applied to the case study of the geometric and oriented lakes of the Llanos de Moxos, in the Bolivian Amazon, where shape and orientation have been the two most important elements studied to infer possible formation mechanisms. It is shown that, thanks to these new indexes, shape and orientation patterns are unveiled, which would have been hard to identify otherwise.

A serial scheme for minimizing the duration of resource-constrained projects within Microsoft Project

Microsoft Project is one of the most-widely used software packages for project management. For the scheduling of resource-constrained projects, the package applies a priority-based procedure using a specific schedule-generation scheme. This procedure performs relatively poorly when compared against other software packages or state-of-the-art methods for resource-constrained project scheduling. In Microsoft Project 2010, it is possible to work with schedules that are infeasible with respect to the precedence or the resource constraints. We propose a novel schedule-generation scheme that makes use of this possibility. Under this scheme, the project tasks are scheduled sequentially while taking into account all temporal and resource constraints that a user can define within Microsoft Project. The scheme can be implemented as a priority-rule based heuristic procedure. Our computational results for two real-world construction projects indicate that this procedure outperforms the built-in procedure of Microsoft Project

Taking a New Look at Neo-Assyrian Gates

The Assyrian capitals are not only known for their magnificent temples and palaces, but also for their monumental city walls. The most impressive and at the same time most delicate features of all the town defenses were the city gates. As they interrupted the line of defense, they were al-ways a vulnerable spot of every system of fortifications. However, the walled cities’ economic needs demanded these gateways to be built, in order to ensure the steady flow of goods and pro-visions. Apart from that, they also had a significant ideological meaning, which is emphasized by many cuneiform texts. During the excavations of the Assyrian capitals of Ashur, Dūr Šarrūkīn, and Nineveh, a fairly large number of Assyrian city gates were brought to light. By re-examining the archaeological reports and employing remote sensing, many details of these structures can still be revealed. The paper aims at illuminating the different considerations that went into constructing these gates, as well as the development Assyrian city gates underwent and what may have influenced this process.

Neo-Assyrian concepts of fortification

The major cities of the Neo-Assyrian Empire were not only home to impressive palaces and temples, but they were also equipped with strong fortifications. The city walls were not only meant to keep out potential enemies, but by demonstrating Assyria’s power to any approaching person, they served an ideological purpose, as well. However, military efficiency was just as crucial, since, over its entire history, the empire repeatedly faced internal and external threats and could not have afforded to lose any of its urban centers which were essential to maintaining control over the various provinces or geographic regions associated with them. The study of Neo-Assyrian fortifications relies on evidence provided by archaeological excavations, the study of Assyrian reliefs and information from cuneiform texts. Even though these sources help us reconstruct the appearance of the town defenses, the question of why the individual fortification systems were built in a specific way cannot be addressed by these means alone. Remote sensing offers an opportunity to view the course and placement of the city walls within their topographical context. Furthermore, geographical information systems (GIS) offer a tool to illustrate the distribution of the strongly fortified Assyrian towns, thereby allowing us to recognize patterns and functions of regional fortification systems during the Neo-Assyrian period.

Effects of biotechnology on biodiversity: herbicide-tolerant and insect-resistant GM crops

Biodiversity is threatened by agriculture as a whole, and particularly also by traditional methods of agriculture. Knowledge-based agriculture, including GM crops, can reduce this threat in the future. The introduction of no-tillage practices, which are beneficial for soil fertility, has been encouraged by the rapid spread of herbicide-tolerant soybeans in the USA. The replacement of pesticides through Bt crops is advantageous for the non-target insect fauna in test-fields. The results of the British Farm Scale experiment are discussed. Biodiversity differences can mainly be referred to as differences in herbicide application management.

Biomarker-guided personalised emergency medicine for all - hope for another hype?

Polymorbid patients, diverse diagnostic and therapeutic options, more complex hospital structures, financial incentives, benchmarking, as well as perceptional and societal changes put pressure on medical doctors, specifically if medical errors surface. This is particularly true for the emergency department setting, where patients face delayed or erroneous initial diagnostic or therapeutic measures and costly hospital stays due to sub-optimal triage. A "biomarker" is any laboratory tool with the potential better to detect and characterise diseases, to simplify complex clinical algorithms and to improve clinical problem solving in routine care. They must be embedded in clinical algorithms to complement and not replace basic medical skills. Unselected ordering of laboratory tests and shortcomings in test performance and interpretation contribute to diagnostic errors. Test results may be ambiguous with false positive or false negative results and generate unnecessary harm and costs. Laboratory tests should only be ordered, if results have clinical consequences. In studies, we must move beyond the observational reporting and meta-analysing of diagnostic accuracies for biomarkers. Instead, specific cut-off ranges should be proposed and intervention studies conducted to prove outcome relevant impacts on patient care. The focus of this review is to exemplify the appropriate use of selected laboratory tests in the emergency setting for which randomised-controlled intervention studies have proven clinical benefit. Herein, we focus on initial patient triage and allocation of treatment opportunities in patients with cardiorespiratory diseases in the emergency department. The following five biomarkers will be discussed: proadrenomedullin for prognostic triage assessment and site-of-care decisions, cardiac troponin for acute myocardial infarction, natriuretic peptides for acute heart failure, D-dimers for venous thromboembolism, C-reactive protein as a marker of inflammation, and procalcitonin for antibiotic stewardship in infections of the respiratory tract and sepsis. For these markers we provide an overview on physiopathology, historical evolution of evidence, strengths and limitations for a rational implementation into clinical algorithms. We critically discuss results from key intervention trials that led to their use in clinical routine and potential future indications. The rational for the use of all these biomarkers, first, tackle diagnostic ambiguity and consecutive defensive medicine, second, delayed and sub-optimal therapeutic decisions, and third, prognostic uncertainty with misguided triage and site-of-care decisions all contributing to the waste of our limited health care resources. A multifaceted approach for a more targeted management of medical patients from emergency admission to discharge including biomarkers, will translate into better resource use, shorter length of hospital stay, reduced overall costs, improved patients satisfaction and outcomes in terms of mortality and re-hospitalisation. Hopefully, the concepts outlined in this review will help the reader to improve their diagnostic skills and become more parsimonious laboratory test requesters.

Is sensitization to stimulants time dependent and mediated via NMDA receptors?

Chronic administration of psychomotor stimulants has been reported to produce behavioral sensitization to its effects on motor activity. This adaptation may be related to the pathophysiology of recurrent psychiatric disorders. Since disturbances in circadian rhythms are also found in many of these disorders, the relationship between sensitization and chronobiological factors became of interest. Therefore, a computerized monitoring system investigated the following: whether repeated exposure to methylphenidate (MPD) and amphetamine (AMP) could produce sensitization to its locomotor effects in the rat; whether sensitization to MPD and AMP was dependent on the circadian time of drug administration; whether the baseline levels of locomotor activity would be effected by repeated exposure to MPD and AMP; whether the expression of a sensitized response could be affected by the photoperiod; and whether MK-801, a non-competitive NMDA antagonist, could disrupt the development of sensitization to MPD. Dawley rats were housed in test cages and motor activity was recorded continuously for 16 days. The first 2 days served as baseline for each rat, and on day 3 each rat received a saline injection. The locomotor response to 0.6, 2.5, or 10 mg/kg of MPD was tested on day 4, followed by five days of single injections of 2.5 mg/kg MPD (days 5–9). After five days without injection (days 10–14) rats were re-challenged (day 15) with the same doses they received on day 4. There were three separate dose groups ran at four different times of administration, 08:00, 14:00, 20:00, or 02:00 (i.e. 12 groups). The same protocol was conducted with AMP with the doses of 0.3, 0.6, and 1.2 mg/kg given on day 4 and 15, and 0.6 mg/kg AMP as the repeated dose on days 5 to 9. In the second set of experiments only sensitization to MPD was investigated. The expression of the sensitized response was dose-dependent and mainly observed with challenge of the lower dose groups. The development of sensitization to MPD and ANT was differentially time-dependent. For MPD, the most robust sensitization occurred during the light phase, with no sensitization during the middle of the dark phase. (Abstract shortened by UMI.) ^

El obraje: una historia de explotación y despojo en dos obras de autores santiagueños

Este trabajo se propone demostrar cómo se construye la realidad representada -en este caso el obraje- en dos obras de autores santiagueño: Tolvanera, de Carlos Bernabé Gómez y Hacha y quebracho, de Raúl Dargoltz. Se analizan las obras mencionadas en relación con el contexto socio-histórico y la realidad del obraje y la explotación forestal en Santiago del Estero Las conclusiones surgirán, pues, del cruce entre historia, ficción y realidad vivida.

De la discapacidad como constructo social a las formas alternas del ser y estar en el mundo

La constitución del campo de la discapacidad expresa las condiciones históricas que responden a un concepto particular de hombre y de lo que una cultura pretende ofertar como condición de vida, sentido de vida para sus integrantes. Cada cultura instaura una promesa de proyección para que la existencia de cada uno encuentre una posición, valor y transcendencia. En esto radica el sustento filosófico de vida. Nos interesa para el caso del concepto de discapacidad ubicarla en el marco de la gestión social de su enunciado. Hay una separación abismal entre el discurso de Séguin, el apóstol de los sin razón y el discurso de Galton. Tal pareciera que Galton iba en búsqueda de ofrecer las condiciones para que el hombre alcanzara su perfectibilidad y la civilización el progreso, lo cual derivó en la comparación de los más avanzados en el proceso evolutivo y con ello se apoyó la diferenciación de umbrales de normalidad-anormalidad, en tanto que Séguin parecía seguidor de una ética de la fraternidad. Esta ética reconoce un mundo plural caracterizado por la heterogeneidad. Desde nuestra perspectiva la heterogeneidad requiere ser enfocada desde la diferencia, una diferencia que no se disuelva en los discursos de igualdad o equidad. Se trata de reconocer justamente las dimensiones de la diferencia, de explicitarla, comprenderla, investigarla y hacerla converger con el sentido originario de la educación. A cada diferencia le corresponde una posibilidad de vida dentro del mundo plural que posiblemente está por construirse. Se plantea en el trabajo un decálogo de reflexiones en los que se introduce una reconversión del significante “discapacidad" por la pluralidad de las formas de la existencia humana.

El ataque libertarista contra el igualitarismo y el marxismo : actualidad de un debate inconcluso

El presente artículo examina las principales líneas de ataque lanzadas por el libertarismo de derecha -expresado fundamentalmente en la obra de Robert Nozick-, contra el igualitarismo liberal de John Rawls y el materialismo histórico. En particular, analiza el rechazo nozickeano a la justicia distributiva, a la deseabilidad (y posibilidad) de la cooperación social, y a los esquemas distributivos contrarios al principio de autopropiedad. Asimismo, explora el impacto de este principio libertarista sobre algunos postulados fundamentales del marxismo. Desde una perspectiva que se nutre de los principales debates de la filosofía política contemporánea, y con una opción teórica por el igualitarismo, este texto presenta y procura debilitar las más audaces tesis nozickeanas, las cuales siguen ejerciendo gran influencia en círculos académicos, en algunas instancias de formulación de políticas públicas y, sobre todo, en el sentido común forjado en tiempos de hegemonía neoliberal.