Practical recommendations for diagnosis and management of respiratory muscle weakness in late-onset Pompe disease

Pompe disease is an autosomal-recessive lysosomal storage disorder characterized by progressive myopathy with proximal muscle weakness, respiratory muscle dysfunction, and cardiomyopathy (in infants only). In patients with juvenile or adult disease onset, respiratory muscle weakness may decline more rapidly than overall neurological disability. Sleep-disordered breathing, daytime hypercapnia, and the need for nocturnal ventilation eventually evolve in most patients. Additionally, respiratory muscle weakness leads to decreased cough and impaired airway clearance, increasing the risk of acute respiratory illness. Progressive respiratory muscle weakness is a major cause of morbidity and mortality in late-onset Pompe disease even if enzyme replacement therapy has been established. Practical knowledge of how to detect, monitor and manage respiratory muscle involvement is crucial for optimal patient care. A multidisciplinary approach combining the expertise of neurologists, pulmonologists, and intensive care specialists is needed. Based on the authors’ own experience in over 200 patients, this article conveys expert recommendations for the diagnosis and management of respiratory muscle weakness and its sequelae in late-onset Pompe disease

Living alone is a risk factor for mortality in men but not women from the general population: a prospective cohort study

During the past decades a rising trend of living alone can be observed in the population especially in urban areas. Living alone is considered a psychosocial risk factor. We studied the relationship between living alone, cardiovascular risk factors and mortality. We analysed data from the population-based MONICA/KORA cohort study including 3596 men and 3420 women of at least one of three surveys carried out between 1984 and 1995 in the region of Augsburg, Germany. They were between 45 and 74 years old and were followed-up until 31 December 2002. During follow-up 811 men and 388 women died. Cox proportional hazards analysis was used to examine the association between living alone and mortality

Unilateral versus coordinated effects:comparing the impact on consumer welfare of alternative merger outcomes

The nature of tacitly collusive behaviour often makes coordination unstable, and this may result in periods of breakdown, during which consumers benet from reduced prices. This is allowed for by adding demand uncertainty to the Compte et al. (2002) model of tacit collusion amongst asymmetric rms. Breakdowns occur when a rm cannot exclude the possibility of a deviation by a rival. It is then possible that an outcome with collusive behaviour, subject to long/frequent break downs, can improve consumer welfare compared to an alternative with sustained unilateral conduct. This is illustrated by re-examining the Nestle/Perrier merger analyzed by Compte et al., but now also taking into account the potential for welfare losses arising from unilateral behaviour

Civil Aircraft for the regular investigation of the atmosphere based on an instrumented container: The new CARIBIC system

An airfreight container with automated instruments for measurement of atmospheric gases and trace compounds was operated on a monthly basis onboard a Boeing 767-300 ER of LTU International Airways during long-distance flights from 1997 to 2002 (CARIBIC, Civil Aircraft for Regular Investigation of the Atmosphere Based on an Instrument Container, http://www.caribic-atmospheric.com). Subsequently a more advanced system has been developed, using a larger capacity container with additional equipment and an improved inlet system. CARIBIC phase #2 was implemented on a new long-range aircraft type Airbus A340-600 of the Lufthansa German Airlines (Star Alliance) in December 2004, creating a powerful flying observatory. The instrument package comprises detectors for the measurement of O3, total and gaseous H2O, NO and NOy, CO, CO2, O2, Hg, and number concentrations of sub-micrometer particles (>4 nm, >12 nm, and >18 nm diameter). Furthermore, an optical particle counter (OPC) and a proton transfer mass spectrometer (PTR-MS) are incorporated. Aerosol samples are collected for analysis of elemental composition and particle morphology after flight. Air samples are taken in glass containers for laboratory analyses of hydrocarbons, halocarbons and greenhouse gases (including isotopic composition of CO2) in several laboratories. Absorption tubes collect oxygenated volatile organic compounds. Three differential optical absorption spectrometers (DOAS) with their telescopes mounted in the inlet system measure atmospheric trace gases such as BrO, HONO, and NO2. A video camera mounted in the inlet provides information about clouds along the flight track. The flying observatory, its equipment and examples of measurement results are reported

Twenty Years of SUGRA

A brief review is given of the developments of mSUGRA and its extensions since the formulation of these models in 1982. Future directions and prospects are also discussed.Comment: Invited talk at the International Conference BEYOND-2003, Schloss Ringberg, Germany, June 10-14, 2003; 21 pages, Late

UK guidelines on oesophageal dilatation in clinical practice

These are updated guidelines which supersede the original version published in 2004. This work has been endorsed by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG) under the auspices of the oesophageal section of the BSG. The original guidelines have undergone extensive revision by the 16 members of the Guideline Development Group with representation from individuals across all relevant disciplines, including the Heartburn Cancer UK charity, a nursing representative and a patient representative. The methodological rigour and transparency of the guideline development processes were appraised using the revised Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. Dilatation of the oesophagus is a relatively high-risk intervention, and is required by an increasing range of disease states. Moreover, there is scarcity of evidence in the literature to guide clinicians on how to safely perform this procedure. These guidelines deal specifically with the dilatation procedure using balloon or bougie devices as a primary treatment strategy for non-malignant narrowing of the oesophagus. The use of stents is outside the remit of this paper; however, for cases of dilatation failure, alternative techniques—including stents—will be listed. The guideline is divided into the following subheadings: (1) patient preparation; (2) the dilatation procedure; (3) aftercare and (4) disease-specific considerations. A systematic literature search was performed. The Grading of Recommendations Assessment, Develop­ment and Evaluation (GRADE) tool was used to evaluate the quality of evidence and decide on the strength of recommendations made

Relationships of Cetacea (Artiodactyla) Among Mammals: Increased Taxon Sampling Alters Interpretations of Key Fossils and Character Evolution

BACKGROUND: Integration of diverse data (molecules, fossils) provides the most robust test of the phylogeny of cetaceans. Positioning key fossils is critical for reconstructing the character change from life on land to life in the water. METHODOLOGY/PRINCIPAL FINDINGS: We reexamine relationships of critical extinct taxa that impact our understanding of the origin of Cetacea. We do this in the context of the largest total evidence analysis of morphological and molecular information for Artiodactyla (661 phenotypic characters and 46,587 molecular characters, coded for 33 extant and 48 extinct taxa). We score morphological data for Carnivoramorpha, Creodonta, Lipotyphla, and the raoellid artiodactylan Indohyus and concentrate on determining which fossils are positioned along stem lineages to major artiodactylan crown clades. Shortest trees place Cetacea within Artiodactyla and close to Indohyus, with Mesonychia outside of Artiodactyla. The relationships of Mesonychia and Indohyus are highly unstable, however--in trees only two steps longer than minimum length, Mesonychia falls inside Artiodactyla and displaces Indohyus from a position close to Cetacea. Trees based only on data that fossilize continue to show the classic arrangement of relationships within Artiodactyla with Cetacea grouping outside the clade, a signal incongruent with the molecular data that dominate the total evidence result. CONCLUSIONS/SIGNIFICANCE: Integration of new fossil material of Indohyus impacts placement of another extinct clade Mesonychia, pushing it much farther down the tree. The phylogenetic position of Indohyus suggests that the cetacean stem lineage included herbivorous and carnivorous aquatic species. We also conclude that extinct members of Cetancodonta (whales+hippopotamids) shared a derived ability to hear underwater sounds, even though several cetancodontans lack a pachyostotic auditory bulla. We revise the taxonomy of living and extinct artiodactylans and propose explicit node and stem-based definitions for the ingroup

Red blood cell-derived semaphorin 7A promotes thrombo-inflammation in myocardial ischemia-reperfusion injury through platelet GPIb.

Myocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet-neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here, we show that platelet-neutrophil complexes (PNCs) are increased in patients with acute myocardial infarction and that this is associated with increased levels of neuronal guidance protein semaphorin 7A (SEMA7A). To investigate this further, we injected WT animals with Sema7a and found increased infarct size with increased numbers of PNCs. Experiments in genetically modified animals identify Sema7a on red blood cells to be crucial for this condition. Further studies revealed that Sema7a interacts with the platelet receptor glycoprotein Ib (GPIb). Treatment with anti-Sema7a antibody protected from myocardial tissue injury. In summary, we show that Sema7a binds to platelet GPIb and enhances platelet thrombo-inflammatory activity, aggravating post-ischemic myocardial tissue injury