Severe esophageal damage due to button battery ingestion: can it be prevented?

Batteries represent less than 2% of foreign bodies ingested by children, but in the last 2 decades, the frequency has continuously increased. Most ingestions have an uneventful course, but those that lodge in the esophagus can lead to serious complications and even death. Medline was used to search the English medical literature, combining “button battery” and “esophageal burn” as keywords. Cases were studied for type, size, and source of the batteries; duration and location of the battery impaction in the esophagus; symptoms; damage caused by the battery; and outcome. Nineteen cases of esophageal damage have been reported since 1979.Batteries less than 15 mm in diameter almost never lodged in the esophagus. Only 3% of button batteries were larger than 20 mm but were responsible for the severe esophageal injuries in this series. These data suggest that manufacturers should replace large batteries with smaller ones and thus eliminate most of the complications. When the battery remains in the esophagus, endoscopic examination and removal done urgently will allow assessment of the esophageal damage, and treatment can be tailored accordingly. There is a need for more public education about the dangers of battery ingestion; this information should be included as part of the routine guidelines for childproofing the home.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47164/1/383_2004_Article_1223.pd

Combining norms to prove termination

Automatic termination analyzers typically measure the size of terms applying norms which are mappings from terms to the natural numbers. This paper illustrates how to enable the use of size functions defined as tuples of these simpler norm functions. This approach enables us to simplify the problem of deriving automatically a candidate norm with which to prove termination. Instead of deriving a single, complex norm function, it is sufficient to determine a collection of simpler norms, some combination of which, leads to a proof of termination. We propose that a collection of simple norms, one for each of the recursive data-types in the program, is often a suitable choice. We first demonstrate the power of combining norm functions and then the adequacy of combining norms based on regular-types

Deleterious variants in TRAK1 disrupt mitochondrial movement and cause fatal encephalopathy

This is the author accepted manuscript. The final version is available from Oxford University Press via the DOI in this record.The corrigendum to this article is in ORE: http://hdl.handle.net/10871/33588Cellular distribution and dynamics of mitochondria are regulated by several motor proteins and a microtubule network. In neurons, mitochondrial trafficking is crucial because of high energy needs and calcium ion buffering along axons to synapses during neurotransmission. The trafficking kinesin proteins (TRAKs) are well characterized for their role in lysosomal and mitochondrial trafficking in cells, especially neurons. Using whole exome sequencing, we identified homozygous truncating variants in TRAK1 (NM_001042646:c.287-2A > C), in six lethal encephalopathic patients from three unrelated families. The pathogenic variant results in aberrant splicing and significantly reduced gene expression at the RNA and protein levels. In comparison with normal cells, TRAK1-deficient fibroblasts showed irregular mitochondrial distribution, altered mitochondrial motility, reduced mitochondrial membrane potential, and diminished mitochondrial respiration. This study confirms the role of TRAK1 in mitochondrial dynamics and constitutes the first report of this gene in association with a severe neurodevelopmental disorder.D.M.E. and J.K. are supported by the Office of Naval Research (ONR) Grant N000141410538. M.S. is supported by the BBSRC (BB/K006231/1), a Wellcome Trust Institutional Strategic Support Award (WT097835MF, WT105618MA), and a Marie Curie Initial Training Network (ITN) action PerFuMe (316723). M.C.V.M., J.S., H.P., C.F., T.V. and W.A.G. are supported by the NGHRI Intramural Research Program. G.R. is supported by the Kahn Family Foundation and the Israeli Centers of Excellence (I-CORE) Program (ISF grant no. 41/11)

Systemic AAV vectors for widespread and targeted gene delivery in rodents

We recently developed adeno-associated virus (AAV) capsids to facilitate efficient and noninvasive gene transfer to the central and peripheral nervous systems. However, a detailed protocol for generating and systemically delivering novel AAV variants was not previously available. In this protocol, we describe how to produce and intravenously administer AAVs to adult mice to specifically label and/or genetically manipulate cells in the nervous system and organs, including the heart. The procedure comprises three separate stages: AAV production, intravenous delivery, and evaluation of transgene expression. The protocol spans 8 d, excluding the time required to assess gene expression, and can be readily adopted by researchers with basic molecular biology, cell culture, and animal work experience. We provide guidelines for experimental design and choice of the capsid, cargo, and viral dose appropriate for the experimental aims. The procedures outlined here are adaptable to diverse biomedical applications, from anatomical and functional mapping to gene expression, silencing, and editing

Non-termination Analysis of Logic Programs Using Types

In recent years techniques and systems have been developed to prove non-termination of logic programs for certain classes of queries. In previous work, we developed such a system based on mode-information and a form of loop checking performed at compile time. In the current paper we improve this technique by integrating type information in the analysis and by applying non-failure analysis and program specialization. It turns out that there are several classes of programs for which existing non-termination analyzers fail and for which our extended technique succeeds in proving non-termination.status: publishe

Is It Safe to Delay Appendectomy in Adults With Acute Appendicitis?

OBJECTIVE: To examine whether delayed surgical intervention in adult patients with acute appendicitis is safe by correlating the interval from onset of symptoms to operation (total interval) with the degree of pathology and incidence of postoperative complications. SUMMARY BACKGROUND DATA: Prompt appendectomy has long been the standard of care for acute appendicitis because of the risk of progression to advanced pathology. This time-honored practice has been recently challenged by studies in pediatric patients, which suggested that acute appendicitis can be managed in an elective manner once antibiotic therapy is initiated. No such data are available in adult patients with acute appendicitis. METHODS: A retrospective review of 1081 patients who underwent an appendectomy for acute appendicitis between 1998 and 2004 was conducted. The following parameters were monitored and correlated: demographics, time from onset of symptoms to arrival at the emergency room (patient interval) and from arrival to the emergency room to the operating room (hospital interval), physical, computed tomography (CT scan) and pathologic findings, complications, length of stay, and length of antibiotic treatment. Pathologic state was graded 1 (G1) for acute appendicitis, 2 (G2) for gangrenous acute appendicitis, 3 (G3) for perforation or phlegmon, and 4 (G4) for a periappendicular abscess. RESULTS: The risk of advanced pathology, defined as a higher pathology grade, increased with the total interval. When this interval was <12 hours, the risk of developing G1, G2, G3, and G4, was 94%, 0%, 3%, and 3%, respectively. These values changed to 60%, 7%, 27%, and 6%, respectively, when the total interval was 48 to 71 hours and to 54%, 7%, 26%, and 13% for longer than 71 hours. The odds for progressive pathology was 13 times higher for the total interval >71 hours group compared with total interval<12 hours (95% confidence interval = 4.7–37.1). Although both prolonged patient and hospital intervals were associated with advanced pathology, prehospital delays were more profoundly related to worsening pathology compared with in-hospital delays (P < 0.001). Advanced pathology was associated with tenderness to palpation beyond the right lower quadrant (P < 0.001), guarding (P < 0.001), rebound (P < 0.001), and CT scan findings of peritoneal fluid (P = 0.01), fecalith (P = 0.01), dilation of the appendix (P < 0.001), and perforation (P < 0.001). Increased length of hospital stay (P < 0.001) and antibiotic treatment (P < 0.001) as well as postoperative complications (P < 0.001) also correlated with progressive pathology. CONCLUSION: In adult patients with acute appendicitis, the risk of developing advanced pathology and postoperative complications increases with time; therefore, delayed appendectomy is unsafe. As delays in seeking medical help are difficult to control, prompt appendectomy is mandatory. Because these conclusions are derived from retrospective data, a prospective study is required to confirm their validity