1,123 research outputs found
Staphylococcus aureus bloodstream infection: A pooled analysis of five prospective, observational studies
Objectives: Staphylococcus aureus bacteraemia is a common, often fatal infection. Our aim was to describe how its clinical presentation varies between populations and to identify common determinants of outcome.
Methods: We conducted a pooled analysis on 3395 consecutive adult patients with S. aureus bacteraemia. Patients were enrolled between 2006 and 2011 in five prospective studies in 20 tertiary care centres in Germany, Spain, United Kingdom, and United States.
Results: The median age of participants was 64 years (interquartile range 50–75 years) and 63.8% were male. 25.4% of infections were associated with diabetes mellitus, 40.7% were nosocomial, 20.6% were caused by methicillin-resistant S. aureus (MRSA), although these proportions varied significantly across studies. Intravenous catheters were the commonest identified infective focus (27.7%); 8.3% had endocarditis. Crude 14 and 90-day mortality was 14.6% and 29.2%, respectively. Age, MRSA bacteraemia, nosocomial acquisition, endocarditis, and pneumonia were independently associated with death, but a strong association was with an unidentified infective focus (adjusted hazard ratio for 90-day mortality 2.92; 95% confidence interval 2.33 to 3.67, p < 0.0001).
Conclusion: The baseline demographic and clinical features of S. aureus bacteraemia vary significantly between populations. Mortality could be reduced by assiduous MRSA control and early identification of the infective focus.Junta de Andalucía PI 0185/201
Serial Assessment of Cardiac Function during and following Mitoxantrone Infusion in 30 Consecutive Patients with Multiple Sclerosis
Immunosuppressive therapy is an established therapeutic option in patients suffering from multiple sclerosis (MS). In an open nonrandomized study we serially assessed cardiac function in 30 consecutive patients with MS before, during, and after mitoxantrone therapy. Mitoxantrone (12 mg/m2) was administered intravenously at 3-month intervals. Before each infusion, cardiac function was assessed by history taking, resting electrocardiogram, and echocardiography. Whereas no patient experienced clinical signs of heart failure, left ventricular pump function decreased continuously during mitoxantrone therapy and did not recover after cessation. The presented data suggest a dose-dependent and long-lasting toxic cardiac effect of low-dose mitoxantrone therapy in MS
Ocean-air N2O trace gas fluxes in Halifax Harbour derived from open-path FTIR measurements
1 online resource (133 pages) : colour illustrations, colour maps, charts (chiefly colour), graphsIncludes abstract and appendix.Includes bibliographical references (pages 112-116).Open-Path Fourier Transform Infrared (OP-FTIR) spectroscopy is an established technique
for path-average measurements of atmospheric trace gas concentrations. We describe the novel
application of OP-FTIR to measure ocean-air gas fluxes across 586 m of Halifax Harbour
(northwest Atlantic coast), also using a 3-D sonic anemometer and two vertically separated
retroreflector arrays. We present spectroscopic retrievals of nitrous oxide (N2O) concentration,
micrometeorological data characteristics, and flux-gradient method calculations of ocean-air N2O
flux. From Dec. 2020 to Apr. 2021 the calculated ocean sink of −10.81 kgN2Oha
−1
agreed broadly
with a global model of thermal (solubility-driven) N2O flux. A powerful short-term ocean source
event observed on Dec. 15-17 (+2.00 kgN2Oha
−1
) correlated with high winds and strong ocean
cooling that plausibly caused surface overturning and the upwelling of N2O-rich deeper waters.
The method presented is well suited to high frequency monitoring of coastal N2O fluxes, necessary
to resolve complex physical, chemical and biological processes
Herramientas normativas sobre la compleja realidad ambiental : sus generalidades
p.1-5El presente trabajo tiene como objetivo de sistematizar el proceso de las herramientas jurídicas básicas sobre el medio ambiente ya que, es de fundamental importancia el conocimiento normativo que va a regular las relaciones sociales para que, desde una perspectiva holística se puedan lograr resoluciones integrales. El derecho ambiental es la respuesta normativa a la creciente degradación que sugre el medio en que vivimos. Se integra con una serie de normas de diverso nivel de importancia (leyes, decretos, ordenazas, resoluciones, etc.) y diverso origen (demanadas del estado nacional, de los estados provinciales o de los municipios), que en algunos casos se superponen y en otros se contradicen. Con una visión interdisciplinaria y en la necesidad de tomar cnocimiento del derecho ambiental y poder identificar, cuál sería la normativa aplicable a una determinada organización/actividad, en una primera instancia y a modo de guía se han elaborado una serie de preguantas esenciales que pueden resultar de gran utilidad para que, la gestión ambiental de los profesionales en su hacer se ajuste a derecho
Endocortical bone loss in osteoporosis: The role of bone surface availability
Age-related bone loss and postmenopausal osteoporosis are disorders of bone
remodelling, in which less bone is reformed than resorbed. Yet, this
dysregulation of bone remodelling does not occur equally in all bone regions.
Loss of bone is more pronounced near and at the endocortex, leading to cortical
wall thinning and medullary cavity expansion, a process sometimes referred to
as "trabecularisation" or "cancellisation". Cortical wall thinning is of
primary concern in osteoporosis due to the strong deterioration of bone
mechanical properties that it is associated with. In this paper, we examine the
possibility that the non-uniformity of microscopic bone surface availability
could explain the non-uniformity of bone loss in osteoporosis. We use a
computational model of bone remodelling in which microscopic bone surface
availability influences bone turnover rate and simulate the evolution of the
bone volume fraction profile across the midshaft of a long bone. We find that
bone loss is accelerated near the endocortical wall where the specific surface
is highest. Over time, this leads to a substantial reduction of cortical wall
thickness from the endosteum. The associated expansion of the medullary cavity
can be made to match experimentally observed cross-sectional data from the
Melbourne Femur Collection. Finally, we calculate the redistribution of the
mechanical stresses in this evolving bone structure and show that mechanical
load becomes critically transferred to the periosteal cortical bone.Comment: 13 pages, 3 figures. V2: minor stylistic improvements in
text/figures; more accurately referenced subsection "Internal mechanical
stress distribution"; some improved remarks in the Discussion sectio
Bio-inspired Factories of the Future
The biological transformation of added value is seen as one of the key aspects in applied research. Bio- inspired methods and technologies will affect factories of the future and enable them to cope with changing boundary conditions and the rising necessity of sustainability. This results in a higher demand for flexibility and transformation ability of the comprised production systems.
To elaborate topics like these, Fraunhofer initiated strategic collaborative research projects. The current project aims at developing aspects of the biological transformation, whereof organic bio-inspired factories is one. Different research focal points were identified as enabling technologies on different levels of the well-established automation pyramid. The paper highlights the aspects “facility layout planning”, “behavioral modeling of production systems” and “skill-based controller programming” as enabling technologies. Solution approaches for the addressed aspects are discussed and future steps towards a flexible and sustainable production are shown
CD38-driven mitochondrial trafficking promotes bioenergetic plasticity in multiple myeloma
Metabolic adjustments are necessary for the initiation, proliferation, and spread of cancer cells. Although mitochondria have been shown to move to cancer cells from their microenvironment, the metabolic consequences of this phenomenon have yet to be fully elucidated. Here we report that multiple myeloma (MM) cells use mitochondrial-based metabolism as well as glycolysis when located within the bone marrow microenvironment (BMM). The reliance of MM cells on oxidative phosphorylation was caused by intercellular mitochondrial transfer to MM cells from neighboring non-malignant bone marrow stromal cells (BMSC). This mitochondrial transfer occurred through tumor-derived tunneling nanotubes (TNT). Moreover, shRNA mediated knockdown of CD38 inhibits mitochondrial transfer and TNT formation in-vitro and blocks mitochondrial transfer and improves animal survival in vivo. This study describes a potential treatment strategy to inhibit mitochondrial transfer for clinical benefit and scientifically expands the understanding of the functional effects of mitochondrial transfer on tumor metabolism
Early oral switch therapy in low-risk Staphylococcus aureus bloodstream infection (SABATO): study protocol for a randomized controlled trial
Background Current guidelines recommend that patients with Staphylococcus aureus bloodstream infection (SAB) are treated with long courses of intravenous antimicrobial therapy. This serves to avoid SAB-related complications such as relapses, local extension and distant metastatic foci. However, in certain clinical scenarios, the incidence of SAB-related complications is low. Patients with a low-risk for complications may thus benefit from an early switch to oral medication through earlier discharge and fewer complications of intravenous therapy. The major objective for the SABATO trial is to demonstrate that in patients with low-risk SAB a switch from intravenous to oral antimicrobial therapy (oral switch therapy, OST) is non-inferior to a conventional course of intravenous therapy (intravenous standard therapy, IST). Methods/Design The trial is designed as randomized, parallel-group, observer-blinded, clinical non-inferiority trial. The primary endpoint is the occurrence of a SAB-related complication (relapsing SAB, deep-seated infection, and attributable mortality) within 90 days. Secondary endpoints are the length of hospital stay; 14-day, 30-day, and 90-day mortality; and complications of intravenous therapy. Patients with SAB who have received 5 to 7 full days of adequate intravenous antimicrobial therapy are eligible. Main exclusion criteria are polymicrobial bloodstream infection, signs and symptoms of complicated SAB (deep-seated infection, hematogenous dissemination, septic shock, and prolonged bacteremia), the presence of a non-removable foreign body, and severe comorbidity. Patients will receive either OST or IST with a protocol-approved antimicrobial and are followed up for 90 days. Four hundred thirty patients will be randomized 1:1 in two study arms. Efficacy regarding incidence of SAB-related complications is tested sequentially with a non-inferiority margin of 10 and 5 percentage points. Discussion The SABATO trial assesses whether early oral switch therapy is safe and effective for patients with low-risk SAB. Regardless of the result, this pragmatic trial will strongly influence the standard of care in SAB. Trial registration ClinicalTrials.gov NCT01792804 registered 13 February 2013; German Clinical trials register DRKS00004741 registered 4 October 2013, EudraCT 2013-000577-77. First patient randomized on 20 December 2013
Efficacy of Integrated Social Cognitive Remediation vs. Neurocognitive Remediation in Improving Functional Outcome in Schizophrenia: Concept and Design of a Multicenter, Single-Blind RCT (The ISST Study)
Background: Although clinically effective treatment is available for schizophrenia,
recovery often is still hampered by persistent poor psychosocial functioning, which
in turn is limited by impairments in neurocognition, social cognition, and social
behavioral skills. Although cognitive remediation has shown general efficacy in improving
cognition and social functioning, effects still need to be improved and replicated in
appropriately powered, methodologically rigorous randomized controlled trials (RCTs).
Existing evidence indicates that effects can most likely be optimized by combining
treatment approaches to simultaneously address both social cognitive and social
behavioral processes.
Objectives: To assess whether Integrated Social Cognitive and Behavioral Skill Therapy
(ISST) ismore efficacious in improving functional outcome in schizophrenia than the active
control treatment Neurocognitive Remediation Therapy (NCRT).
Methods: The present study is a multicenter, prospective, rater-blinded, two-arm RCT
being conducted at six academic study sites in Germany. A sample of 180 at least partly
remitted patients with schizophrenia are randomly assigned to either ISST or NCRT. ISST
is a compensatory, strategy-based program that targets social cognitive processes and
social behavioral skills. NCRT comprisesmainly drill and practice-oriented neurocognitive
training. Both treatments consist of 18 sessions over 6 months, and participants are subsequently followed up for another 6 months. The primary outcome is all-cause
discontinuation over the 12-month study period; psychosocial functioning, quality of life,
neurocognitive and social cognitive performance, and clinical symptoms are assessed as
secondary outcomes at baseline before randomization (V1), at the end of the six-month
treatment period (V6), and at the six-month follow-up (V12).
Discussion: This RCT is part of the German Enhancing Schizophrenia Prevention and
Recovery through Innovative Treatments (ESPRIT) research network, which aims at using
innovative treatments to enhance prevention and recovery in patients with schizophrenia.
Because this study is one of the largest and methodologically most rigorous RCTs on
the efficacy of cognitive remediation approaches in schizophrenia, it will not only help
to identify the optimal treatment options for improving psychosocial functioning and thus
recovery in patients but also allow conclusions to be drawn about factors influencing and
mediating the effects of cognitive remediation in these patients
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